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CONTENTS

June 2010

Vol 2, no 3

PUBLISHING STAFF

Managing Director Jack Iannaccone jack@infertilitynurse.org 732-992-1537 Editorial Director Dalia Buffery dalia@novellushc.com 732-992-1889 Associate Editor Lara J. Reiman lara@novellushc.com 732-992-1892 Editorial Assistant Jessica A. Smith Director, Client Services Russell Hennessy russell@novellushc.com 732-992-1888 Director, Client Services Mark Timko mark@novellushc.com 732-992-1897 Senior Production Manager Lynn Hamilton Business Manager Blanche Marchitto Editorial Contact: Telephone: 732-992-1892 Fax: 732-656-7938 MISSION STATEMENT The OB/GYN and Infertility Nurse is the official publication of the American Academy of OB/GYN and Infertility Nurses. The OB/GYN and Infertility Nurse provides practical, authoritative, cutting-edge information on the physiologic, medical, and psychological aspects of human reproduction, focusing on the role of the OB/GYN, infertility, and urology nurse in patient care.

Our journal offers a forum for nurses, nurse practitioners, physician assistants, administrators, researchers, and all others involved in OB/GYN, infertility, and urology to discuss the entire scope of current and emerging diagnostic and therapeutic options, as well as counseling and patient follow-up for men and women throughout their reproductive years and beyond.

Written by nurses for nurses, The OB/GYN and Infertility Nurse promotes peer-to-peer collaboration among all nursing professionals toward the advancement of integrated services for optimal care delivery.

The journal offers continuing education for all nurses involved in these interrelated fields of patient management.

The OB/GYN and Infertility Nurse, ISSN 2151-8394 (print); ISSN 2151-8408 (online), is published 6 times a year by Novellus Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205D, Monroe Twp, NJ 08831. Copyright ©2010 by Novellus Healthcare Communications, LLC. All rights reserved. The OB/GYN and Infertility Nurse is a trademark of Novellus Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher. Printed in the United States of America.

The ideas and opinions expressed in The OB/GYN and Infertility Nurse do not necessarily reflect those of the Editorial Board, the Editors, or the Publisher.

Publication of an advertisement or other product mentioned in The OB/GYN and Infertility Nurse should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturers about any features or limitations of products mentioned.

Neither the Editors nor the Publisher assume any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material mentioned in this publication.

ASK THE EXPERT

4 Nutrition Advice for Pregnant Women CLINICAL NEWS

5 Pelvic Floor Muscle Training May Reverse Prolapse Long-Term Metformin Use Linked to B12 Deficiency Mirena Approved for Heavy Menstrual Bleeding 27 Jury Still Out on Dangers of Yaz, Yasmin Birth Control Pill at 50, but Unplanned Pregnancies Abound Oklahoma Issues Major Blocks to Abortion Rights

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PHARMACY CORNER

7 Medication Use in Pregnancy: What Your Patients Need to Know CONTINUING EDUCATION

10 Elective Single-Embryo Transfer Success 12 Commentary: Elective Single-Embryo Transfer: Its Time Has Come 16

THE OB/GYN NURSE

14 Heartburn, Nausea, and Vomiting in Pregnancy 15 2010 a New Decade in Women’s and Children’s Health 16 Interstitial Cystitis More Common than Previously Thought 58TH ANNUAL CLINICAL MEETING

MSSA Infections in Infants More Common, Dangerous than Many Realize 18 Teenaged Girls Lose Bone Density with DMPA Contraceptive Injections 19 Childbirth after Breast Cancer Affects a Woman’s Mortality Risk

THE AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS

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NUTRITION

19 Optimal Weight Gain during Pregnancy for Obese Women Depends on Obesity Severity

ACOG HIGHLIGHTS

20 Hormone Therapy Still Gold Standard for Hot Flushes Careful Risk–Benefit Balance Necessary When Prescribing Hormone Therapy 21 Gestational Diabetes Developing into Type 2 Diabetes Postpartum ACOG Poll on OB/GYN Practices

THE INFERTILITY NURSE

22 Endometriosis and Infertility 24 Fetal Reduction in Multiple Pregnancy 25 Infertility Is a Disease: CDC Marks National Fertility Awareness Week THE UROLOGY NURSE

26 Intensive Nonmedical Program Improves Male Pelvic Pain Condition Nerve Stimulation Device a Good Option for Overactive Bladder PSA Screening Not Recommended in Frail, Elderly Men

YEARLY SUBSCRIPTION RATES: United States and possessions: individuals, $105.00; institutions, $135.00; single issue, $17.00. Orders will be billed at individual rates unless proof status is confirmed.

SUBSCRIPTIONS/CHANGE OF ADDRESS should be directed to CIRCULATION DIRECTOR, The OB/GYN and Infertility Nurse, 241 Forsgate Drive, Suite 205D, Monroe Twp, NJ 08831; Fax: 732-656-7938.

www.obgyn-infertility-nurse.com

June 2010 I Vol 2, no 3

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From the Editors

Co-Editor-in-Chief Debra Moynihan, WHNP-BC, MSN Carolina OB/GYN

Ask the Expert

Co-Editor-in-Chief Sue Jasulaitis, RN, MS Fertility Centers of Illinois

By Debra Moynihan

Question: When you tell a woman she is pregnant, what advice do you offer her on appropriate nutrition during pregnancy?

Answer: Nurses working in infertility have the advantage of providing this information to patients before pregnancy. This offers the patients a jump start on eating right. Nurses working in an OB/GYN office normally do not see the patient until pregnancy has been achieved and confirmed by a pregnancy test. But whatever the case, it is never too late to provide the patient with nutritional guidance.

First, I suggest starting with information regarding healthy weight gain.

It is normal to gain weight during pregnancy. This is not the time to try to lose weight or to follow a fad diet. It is important to eat a variety of healthy foods while pregnant. Women of average height and weight should expect a weight gain between 25 and 35 pounds. During the first trimester (12 weeks), the patient should gain 4 to 5 pounds. Once she has entered the second trimester, a weight gain of 1 pound per week is average.

EDITORIAL BOARD Co-Editor-in-Chief Debra Moynihan, WHNP-BC, MSN Women’s Health Nurse Practitioner Carolina OB/GYN, SC Co-Editor-in-Chief Sue Jasulaitis, RN, MS Clinical Research Manager Fertility Centers of Illinois, Chicago Donielle Farrington, RNC Clinical Nursing Manager Brunswick Hills OB/GYN, NJ Barbara Alice, RN, APN-C, MSN Nursing Manager, IVF Coordinator South Jersey Fertility Center Monica R. Benson, BSN, RNC Nurse Manager Third Party Reproduction, RMA New Jersey

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June 2010 I Vol 2, no 3

Nurses should review the 5 food groups with patients. These include grain products, fruits, vegetables, milk and milk products, and meat and/or other protein-rich foods. Patients should be choosing foods from each group on a daily basis. It is very important to limit sweets and fatty foods.

These are “empty” calories that do not have any nutritive value. Most women require an extra 300 calories daily for proper nutrition during pregnancy.

Foods that must be avoided, because of the potential to make the mother and baby sick, should also be discussed with the patient. Examples include raw fish, especially shellfish, and fish that is high in mercury, such as shark, swordfish, tile fish, and king mackerel. Local health departments can also share information on local game fish. Otherwise, it is recommended that pregnant women eat 12 oz of fish per week. Undercooked meats, poultry, and hot dogs can cause food poisoning. Pregnant women should not

eat soft scrambled eggs, uncooked yolks, or raw eggs, because this could lead to salmonella. Soft cheeses, such as feta, goat, Brie, Camembert, and other unpasteurized cheeses can also cause food poisoning.

Hydration is also very important. A pregnant woman should be instructed to drink a minimum of 6 to 8 glasses of fluid daily. This can include water, milk, juice, and lemonade. Encourage the patient to drink juice that comes in a “light” form, because most juices are loaded with sugar, which can add to unnecessary weight gain. Caffeinated beverages and foods should be limited to 12 oz per day. Too much caffeine has been linked to miscarriage, decreased iron absorption from diet, and low-birth-weight infants. Remind patients that caffeine is found not only in coffee, but also in tea, soda, and chocolate.

Also, do not forget to mention that prenatal vitamins should be continued

throughout the entire pregnancy.

Preconception and in the early weeks of pregnancy, 400 µg/day of folic acid is needed to help prevent birth defects of the spinal cord and brain. During the rest of pregnancy, folic acid should be increased to 600 µg/day. Most prenatal vitamins have at least 1 mg of folic acid. In addition, folic acid can be found in peanuts, beans, peas, citrus fruits and juices, and leafy green vegetables. A mother’s need for iron doubles during pregnancy. Therefore, she should be encouraged to each plenty of iron-rich foods, which include leafy green vegetables, beans, whole grains, meats, and dried fruits.

Some helpful websites for nurses and patients include The March of Dimes (www.modimes.org), and the US Food and Drug Administration website for fish and food safety (www.cfsan.fda.gov/seafood1.html).

These are informative, accurate, and user-friendly.

Melissa B. Brisman, Esq Owner Reproductive Possibilities, LLC Surrogate Fund Management, LLC

Donna Makris, RN, BSN, IBCLC Parent Education Coordinator OB/GYN, St. Peter’s Medical Center, NJ

Cyndi Gale Roller, PhD, RN, CNP, CNM Program Director Women’s Health College of Nursing Kent State University, OH

Kit Devine, MSN, ARNP Advanced Nurse Practitioner Fertility & Endocrine Associates, Kentucky Gina Paoletti-Falcone, RN, BSN Clinical Services Manager Freedom Fertility Pharmacy Byfield, MA Sandra Fernandez, RPh, PharmD Pharmacist Mandell’s Clinical Pharmacy, NJ Jennifer Iannaccone, RNC

Nursing Manager IVF Coordinator IVF New Jersey

Jill Marchetti, RN Director, Egg Donor Program IVF New Jersey Mary McGregor, RN IVF Coordinator The Fertility Institute of New Orleans Norah S. Nutter, MSN, WHNP-BC, IBCLC Women’s Health Nurse Practitioner Magnolia OB/GYN Myrtle Beach, SC Kutluk Oktay, MD, FACOG Professor of Obstetrics & Gynecology Director, Division of Reproductive Medicine & Infertility, Department of Obstetrics & Gynecology; Medical Director, Institute for Fertility Preservation, New York

Patricia Rucinsky, RN, BSN Clinical Nurse Manager IRMS, St. Barnabas, NJ Kriston Ward, RN, MS, NP-C Strong Fertility Center University of Rochester Medical Center, Rochester, NY Joan Zaccardi, MS, DrNP Administrative Practice Manager Urogynecology Arts of New Jersey

www.obgyn-infertility-nurse.com

Clinical News Pelvic Floor Muscle Training May Reverse Prolapse Performing exercises to increase the strength of pelvic floor muscles (PFM) can reduce prolapse symptoms in women and potentially prevent the need for surgery, according to a recent study (Am J Obstet Gynecol. 2010 April 20. Epub ahead of print).

Norwegian researchers randomized

59 women with stage I, II, or III prolapse to PFM training. Another 50 women served as controls and were asked not to start or change their frequency of PFM training.

Women in both groups were asked to avoid straining and were taught how to contract their PFM before and during increases in abdominal pressure. Women randomized to PFM training were asked

to do 3 sets of 8 to 12 PFM contractions at close to their maximum ability 3 times daily and to record their adherence in an exercise diary. They also received a booklet and DVD showing the exercise program.

Significantly more women in the PFM training group improved their Pelvic Organ Prolapse Quantification System stage by at least 1, at 19% (n =

11) versus 8% (n = 4) in the control group. In addition, significant elevation of the bladder and rectum was more common in those who performed PFM training than in controls. PFM training participants also had fewer and less bothersome prolapse symptoms than controls.

Long-Term Metformin Use Linked to B12 Deficiency Patients with type 2 diabetes who receive long-term treatment with metformin face a risk of vitamin B12 deficiency (BMJ. 2010;340:c2181). Vitamin B12 insufficiency (<150 pmol/L) results in increased homocysteine concentration, a risk for coronary heart disease and stroke.

This multicenter, placebo-controlled trial randomized 390 patients with diabetes to 850-mg metformin or to placebo, 3 times daily, for 4.3 years. Metformin treatment was associated with a 19% mean decrease in vitamin B12 concentration, a 5% mean decrease in folate concentration, and a 5% increase in homocysteine concentration compared with placebo.

Vitamin B12 deficiency risk was 7.2% higher at study end in the metformin group compared with placebo; the risk of low vitamin B12 was 11.2% higher with metformin compared with placebo. After 4.3 years, patients with vitamin B12 deficiency had a mean homocysteine level of 23.7 µmol/L, versus 18.1 µmol/L in those with a low vitamin B12 concentration, and 14.9 µmol/L in patients with a normal vitamin B12 level.

Mirena Approved for Heavy Menstrual Bleeding The Food and Drug Administration (FDA) approved Mirena (levonorgestrel intrauterine [IU] system) late last year for the treatment of menorrhagia.

Mirena is the first IU device to be FDAapproved for this indication.

“Women who suffer heavy, prolonged menstrual periods find the condition unpleasant, disabling, and frightening,” said Kathleen Uhl, MD, Director of the FDA’s Office of Women’s Health. “Bleeding can be so heavy that women must miss work, school, or social activities.”

First approved as a contraceptive in 2000, Mirena is a small, flexible hormone-releasing device consisting of a Tshaped polyethylene frame with a steroid reservoir containing 52-mg levonorgestrel packaged within a sterile inserter. Mirena releases 20-µg/day levonorgestrel for the first 5 years; this rate is then reduced by about half, at which time the device should be replaced.

Mirena treats heavy menstrual bleeding by reducing monthly thickening of uterine walls, thereby reducing, or sometimes completely stopping, menstruation. It is recommended for use in Continued on page 27 www.obgyn-infertility-nurse.com

June 2010 I Vol 2, no 3

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Clinic Spotlight

Patient-Friendly Treatment...

Continued from page 1

An area of special interest to me is the commitment of our physicians to a patient-friendly approach to IVF, as long as it does not compromise outcome. We were among the first centers in the country to popularize the mixing of fertility medications in a single injection and adopt vaginal progesterone for replacement and supplementation in our protocols. This has greatly simplified the experience for our patients and our nurses, and patient feedback is overwhelmingly positive.

Nurses Prefer Patient-Friendly Medications As nurses, we are aware that new patients are concerned with the medication regimen. Patients are worried that the injections will be painful, that they will not be able to self-inject, or that they might do something wrong that could cause them harm or cause their cycle to fail. Reproductive endocrinology nurses are adept at teaching patients a variety of medication protocols. Many hours are spent answering questions that focus on medication concerns. Simplifying the regimen lessens frustration for patients and for nurses.

Several studies have shown equivalency in outcome with the patientfriendly approach of mixing medications. From our vast experience we know that mixing gonadotropins in a single shot does not diminish oocyte yield or quality, and does not compromise cycle outcome. We offer our Boston IVF patients this approach, and a majority opts to combine medications into a single evening shot. We started this practice about 15 years ago and it has become our standard.

At the same time, we stopped using intramuscular (IM) progesterone injections and have relied on vaginal preparations for supplementation in ART cycles, as well as replacement for frozen embryo transfers and donor egg cycles.

It has been encouraging to see more centers adopt this approach, but this is still far from the mainstream.

In fact, until recently we were the only IVF center in the area to use vaginal progesterone as a standard approach. Therefore, it was very gratifying when our colleague, Dr Elena Yanushpolsky, from the neighboring IVF center at Brigham and Women’s Hospital, recently published a prospective study, concluding that vaginal progesterone (Crinone 8%) was equally effective and better tolerated than IM progesterone (Fertil Steril. 2010, March 26 [Epub ahead of print]).

Thanks to her diligent work, a greater percentage of patients undergoing IVF

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June 2010 I Vol 2, no 3

insert vaginal progesterone tablets 2 or 3 times a day. As with all medications, patients can have distinct preferences.

When nurses explain the differences in these 2 products, pointing out that their efficacy is the same, many patients opt for once-daily dosing for cycles that require supplementation. Crinone is the only FDA-approved supplement for women aged ≥35 years, and that sways some physicians to prescribe it for that patient population. For those who prefer tablets to gel, Endometrin is available in dosing of 2 or 3 times daily.

From left: Heather Todd, RN; Kristin MacCutcheon, RN; Ilana Seriac, RN; Carol Lesser, NP.

can now avoid the uncomfortable side effects associated with these unpopular injections. Although we do not suggest that vaginal progesterone is better than IM progesterone in terms of outcomes, we maintain—because our patients have told us loud and clear— that vaginal progesterone is better for, and preferred by, our patients.

When nurses convey confidence in a medication’s efficacy, it puts patients at ease. In the end, allaying patient concerns regarding efficacy is the most important nursing intervention.

As noted above, we have used vaginal progesterone for close to 2 decades.

Although all progesterone supplements can have side effects, vaginal products are preferred by patients overwhelmingly. The pain associated with weeks of IM injections is well-known to patients and nurses, and there are more systemic complaints with IM injections.

Switching to vaginal preparations helps minimize patient complaints.

There are 2 popular vaginal progesterone preparations—Crinone (progesterone gel 8%) vaginal gel and Endometrin vaginal insert tablets.

Both products are preferred by patients over IM progesterone. Clearly, teaching vaginal progesterone administration is easier than teaching IM progesterone injection, which is why nurses also prefer it.

When prescribing vaginal progesterone, patients must be informed of possible side effects. Patients must be prepared for potential vaginal discharge from the cumulative buildup of the residue left behind after the progesterone is absorbed. Cumulative buildup

will generally occur after days or weeks of use, not initially. When nurses prepare patients for this, the number of calls/complaints falls drastically.

Boston IVF nurses have learned to anticipate patients’ concerns and address them before the start of the cycle. Our patients are taught to expect discharge, and how to remove vaginal residue if it should accumulate. More important, they are taught that efficacy is not compromised by the leakage.

When nurses convey confidence in a medication’s efficacy, it puts patients at ease. In the end, allaying patient concerns regarding efficacy is the most important nursing intervention.

Our patients are also prepared for possible bleeding before a pregnancy test. We explain in advance that bleeding is common with IVF cycles.

Bleeding may signal a failed cycle, a successful implantation, a subchorionic hematoma, or a successful pregnancy along with a vanishing twin. The cause of bleeding is easier to explain when the cycle outcome is known. Successful and failed cycles can exhibit bleeding before a pregnancy test.

The important distinction to explain to patients is that although bleeding may signal a failed cycle, the outcome was not caused by the type of progesterone used. Although IM progesterone may be associated with less luteal bleeding, the pregnancy rate is the same.

From this perspective, it appears that IM progesterone may delay the inevitable period when pregnancy has not occurred. Preparing patients for this substantially reduces the number of distressed calls.

When given a choice between progesterone products, many patients prefer the gel, because of its once-daily dosing. For busy women who want to simplify their medication regimen, progesterone gel is ideal. Patients are asked to insert the prefilled applicator of vaginal gel in the morning, when they tend to be active. The other option is to

Advances in Reproductive Medicine We are proud that substantial advances in reproductive medicine afford a significantly higher chance of success to more individuals and couples. Our ability to diagnose and treat a range of disorders has improved even further in the 2 decades I have worked in this field. Less well appreciated, however, is that only a fraction of those in need of care actually make an appointment to receive help. Although there are many barriers to establishing care, several common myths about IVF continue to be problematic.

First, public perception is that fertility shots are painful and hard to inject; second, that the costs of treatment are prohibitive; and third, that success rates are too low to be worth the effort.

Reaching out to better educate the public about the vast improvements in success rates and established patientfriendly medications is one way to increase the number of patients we can help in their quest to have a baby.

Nurses often find themselves in a patient advocacy role. Encouraging their physicians and teams to adopt more patient-friendly approaches benefits patients and staff and is part of nursing’s mandate.

Looking back over more than 2 decades in the IVF field, I am pleased that the medications fundamental to the orchestration of the successful IVF cycle have improved so notably. Mixing gonadotropins in a single shot, reliance on short-acting antagonists over long agonist protocols, and reliance on vaginal progesterone represent prime examples of patient-friendly improvements.

Humanizing the IVF cycle in every way possible, including medication selection, can encourage more patients to avail themselves of the services we have to offer. It is the responsibility of us, nurses, to encourage progressive changes in this area of cycle management. By doing so, we will substantially improve the experience for our patients as well as for ourselves. ■

www.obgyn-infertility-nurse.com

Pharmacy Corner

Medication Use in Pregnancy What Your Patients Need to Know Sandra Fernandez, PharmD Pharmacist, Mandell’s Clinical Pharmacy, Somerset, NJ

P

regnant women and women considering pregnancy should be told that anything they ingest will ultimately reach the fetus by crossing the placenta, the same route taken by oxygen and nutrients needed for fetal growth and development. The fetus is most vulnerable to birth defects in the first 8 weeks after fertilization, because its organs are developing. It is therefore particularly important for pregnant women to avoid all medications during this crucial time in the fetus’s development.

However, although some drugs are not safe for some pregnant women, they are essential for the health of other pregnant women and their fetuses. A woman should always consult with her healthcare provider or pharmacist about the risks and benefits of taking medications during pregnancy, including over-the-counter medications, vitamins, and dietary supplements.

In 1979, the US Food and Drug Administration (FDA) introduced a classification system for fetal risk of pharmaceuticals used during pregnancy (Table 1). The list does not include potential risks associated with medications that may be present in breast milk.

This system does not address many concerns, such as the risks of not treating a disease versus the risk of using the medication during pregnancy. Case-specific consideration should be used when choosing a medication based on the FDA pregnancy categories, because most of the information about drug safety in pregnancy is derived from animal studies. Despite oversimplification of this system, it continues to serve as a primary reference for prescribers, pharmacists, and patients when selecting drug therapy during pregnancy.

Common medications with known or suspected teratogenic effects (ie, adversely affecting fetal growth) are listed in Table 2.

Changes to FDA Pregnancy Drug Classification Last year, the FDA proposed major prescription drug labeling revisions to provide greater information to clinicians regarding the effects of medications if used during pregnancy or breastfeeding.

The proposed changes would bring 2 new features to the pregnancy and lactation subsections of drug labels—a summary explaining the risks a medication could pose to the fetus or breastfeeding infant, and a discussion of the data that support the risk summary. An additional change would be the inclusion of clinical information to aid clinicians in prescribing, managing, and counseling patients about the medications.

In addition, the FDA would eliminate the current pregnancy categories. The subsection entitled “Labor and Delivery” would be eliminated, and information on labor and delivery would be included in the “Pregnancy” subsection.

Table 1 FDA Pregnancy Category Classification Category A Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of

pregnancy (and there is no evidence of risk in later trimesters) Category B Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and

well-controlled studies in pregnant women OR animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester Category C Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-con-

trolled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite risks Category D There is positive evidence of human fetal risk based on adverse reaction data from investigational or market-

ing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks Category X Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human

fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits

Table 2 Common Medications with Known or Suspected Teratogenic Effects Drug name generic (trade) Thalidomide (Thalomid) Androgens: eg, testosterone, fluoxymesterone, methyltestosterone Danazol (Danocrine) Isotretinoin (Accutane) Acitretin (Soriatane) Coumarins (Coumadin) Misoprostol (Cytotec) Methotrexate (Rheumatrex, Trexall) Diazepam (Valium) Tetracyclines: various antibiotics Lithium (Lithobid) Streptomycin (Streptomycin) Valproate (Depakote, Depakote ER, Depacon, Depakene, Stavzor) Phenytoin (Dilantin, Phenytek) Methimazole (Tapazole) Fluoroquinolones (Cipro, Avelox, Floxin, Levaquin, Noroxin) Sulfamethoxazole-trimethoprim (Bactrim) Chloramphenicol ACE inhibitors (Prinivil, Lotensin, Altace, Vasotec, Aceon, Accupril, Univasc) NSAIDs: eg, aspirin, ibuprofen, naproxen sodium

Live virus vaccines: eg, measles, mumps, rubella, varicella

FDA pregnancy category X X X X X X X X D D D D D D

Associated congenital abnormalities Severe birth defects, fetal death Masculinized external genitalia in girls Androgenic effects on female fetus Small ears, heart defects, hydrocephalus, mental retardation Malformations of hip, ankle, and forearm, cardiovascular malformation, alterations of skull and cervical vertebrae Birth malformations, fatal hemorrhage, depressed nasal bridge Skull defects, cranial nerve palsies, facial malformations, limb defects Severe birth defects Respiratory and feeding, difficulties, exaggerated reflexes, withdrawal symptoms Slowed bone growth, permanent discoloration of teeth Heart defects, lethargy, reduced muscle tone Deafness Neural tube defects

D C

Orofacial clefts, cardiac defects, growth abnormalities, mental defects, bleeding problems Enlarged/underactive thyroid gland in fetus Possibility of joint abnormalities

C

Cleft palate

C C (first trimester) D (second and third trimester), but Aceon is always D These are all OTC drugs, not classified but are contraindicated in pregnancy C

Gray baby syndrome Kidney damage, reduction in amniotic fluid

In large doses: Delay the start of labor, prematurely close the connection between the aorta and artery to the lungs, jaundice, brain damage Transmission of the vaccine virus to the fetus

NOTE: This list is not all-inclusive.

ACE indicates angiotensin-converting enzyme; NSAID, nonsteroidal anti-inflammatory drug; OTC, over the counter.

Continued on page 8

www.obgyn-infertility-nurse.com

June 2010 I Vol 2, no 3

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Clinic Profile

Women’s Health Nurse Practitioner Program... Continued from page 1 Health Nurse Practitioner (WHNP) Program at Kent State, we offered a master’s in the concentration of parent–child nursing. Students could follow either the clinical nurse specialist track or WHNP track. Because there is no longer a certifying examination for women’s health clinical nurse specialists, we only have WHNP. Our program is focused on primary healthcare for women. Primary care provides the first access to comprehensive care for women. Our patients are no longer coming in just for their Pap smears; they present with complaints of sinus infections, sore throats, the flu, and gastrointestinal problems. Many times, women come to us because they only want a woman care provider, not a male provider.

As WHNPs, we want to be able to give broad, comprehensive care to women across the life span. We are seeing women from adolescence through old age and postmenopause, until the grave. We prepare our students to work in different settings—medical centers, physicians’ private offices, free clinics, and Planned Parenthood. This has really changed over the years. Next year we will be enrolling students in the doctor of nursing practice program at Kent State.

Do you still provide the traditional OB/GYN education?

Yes, we do, but my students are taught that when a woman comes to the ambulatory setting, the WHNP has to consider the whole person. It is not just about a breast and pelvic exam; they are taught to look at the whole person today.

The clinical sequence of our program begins with healthcare of the well woman, followed by healthcare of the reproductive-age woman, and then primary healthcare of women. With primary care of women, the students go

into clinical settings that provide care to women with cardiac problems, autoimmune disorders, endocrine disorders, gastrointestinal disorders, and urogenital disorders, to name only a few.

The scope of practice for WHNPs has grown over the past decade.

In certain settings, however, like in family planning clinics, WHNPs’ practice is more focused to include contraception and screening for sexually transmitted infections.

As WHNPs, we want to be able to give broad, comprehensive care to women across the life span. We are seeing women from adolescence through old age and postmenopause, until the grave.

Education has changed drastically over the past decade, as a result of economic demands and advancing technology. Students no longer can afford to give up their jobs to come to a campus for full-time schooling. My students all work full-time and have families, so our online program meets their needs. This year, we graduated our first group of stu-

Medication Use in Pregnancy...

Continued from page 7

“The proposed rule is intended to create a consistent format for providing information about the risks and benefits of medicine use during pregnancy and lactation,” the FDA stated.

“In doing so, the proposed rule would enhance well-informed decision making by healthcare practitioners and women of childbearing age.” It remains to be seen when the proposed changes would take hold.

Keep Your Pregnant Patients Informed Pregnant women should also be aware that an unhealthy lifestyle is an

immense hazard for the development of the fetus. Alcohol, tobacco, and illicit-drug use during pregnancy increase the risks of birth defects, miscarriages, stillbirths, and premature births. It is important for all women to make healthy lifestyle changes during pregnancy. For some women, this may include adjusting an exercise schedule, resting, and eating a healthier diet; for others, it may include overcoming a smoking or drinking habit. These changes, along with the proper prenatal care, will promote a healthy pregnancy, as well as a healthy baby. ■

dents who have come through the online WHNP program. In the online program, students can continue with their jobs and their families while studying to become a nurse. This puts more stress on them, but I have scheduled the courses so that they have the weekends to do their readings and online postings.

Online education is very exciting when done well. I have much more contact with my students in an online course. It is different from standing up in front of a class and lecturing. In a lecture course, the entire semester can go by without the faculty interacting with every student. When teaching online, I interact with each student at a minimum of twice a week, but usually every day and sometimes a few times a day. I really get to know each student, and I can facilitate learning nuances that are specific for each student. Education is very exciting today and the online environment allows me to be creative in ways I never could when teaching faceto-face.

How do online NP students get hands-on experience?

Each clinical course has a clinical component. Students are in the clinical setting with a preceptor at a minimum of 1 day per week and a maximum of 3 days per week (during their Capstone course at the end of the program).

Currently most of my students are from Ohio, but I am now getting calls from potential students from as far away as Texas. Some of the students come to the program with preceptors from their communities. Often, they have preceptors who are looking to expand their practices. These students not only create a preceptor site for themselves, but also open the opportunity for job placement upon graduation. Our online students come to the Kent campus when they start the first clinical course of the clinical sequence. During that time, they have 2 days of orientation and then we do hands-on learning, in which the students are doing pelvic exams and breast exams.

What is the range of patients you see?

In my practice, my patients range from about age 14 years up until 80 years of age—I have not seen a 90-yearold woman, but my partner has. We see patients across the lifespan. Increasingly, we see younger girls come in with problems; I have recently seen an 11year-old girl with issues that suggested she may be sexually abused. We now start seeing young adolescents or patients in late childhood who are coming in with different types of vaginitis, which can indicate sexual abuse.

But we see women of all ages,

Nursing students at Kent State WHNP program.

through old age, for regular healthcare.

I have many elderly women patients who come in when they become menopausal; other common problems include postmenopausal bleeding, problems with prolapsed uterine or prolapsed bladder, cystoceles, or rectoceles.

We deal with the full range of issues in the older woman.

And today, we do new things in our practices. The physician I work with does laser hair removal, Botox, and laser resurfacing. It is sort of “one-stop shopping” for women’s health—get your Pap smear test and get your face resurfaced.

Do you manage patients with hypertension in pregnancy or gestational diabetes?

Yes, we do. It depends on the practice and on the standard care agreement in each practice, according to the state’s nurse practitioner (NP) protocol that outlines what they can and cannot do, and what medications they can prescribe. Ohio NPs have prescriptive privileges.

In my previous practice, I provided care for pregnant women and managed, in collaboration with a perinatologist, women with gestational diabetes, gestational hypertension, preeclampsia, multiple gestation, and women undergoing fertility treatment. In my current practice, which is primary healthcare for women, I do more endometrial biopsies, colposcopies, cervical biopsies, and urodynamic testing (for urinary incontinence).

Based on your expertise in sexual abuse, do women tend to open up about sexuality?

If asked the right question, and if they feel safe, women will share their experiences of violence. I have seen women who present with complaints of sexual dysfunction or other issues related to their sexuality, and often sexual violence is at the core of their problem. However, I have found that clinicians often avoid asking the questions that can elicit answers regarding sexual problems. Many providers have told me, “I do not have time. I have to Continued on page 9

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Nutrition

Women’s Health Nurse Practitioner Program... Continued from page 8 be productive. I have to see so many patients in a short time, and I barely have enough time to do the things I need to do.”

When practitioners use those excuses, they are not providing the best healthcare to their patients. Practitioners need to incorporate questions about sexuality, including sexual violence, into the time allotted for each patient.

Research supports that many clinicians do not ask questions about sexual violence, because they do not know what to do if they get an affirmative answer. They ask, “Now that I know, what do I do?”

A young woman came to me after about 8 years of having seen many doctors, with a complaint of pelvic pain.

They did laparoscopic procedures on her and found no pathology. When she came to see me, I did a physical exam and found no abnormalities.

When I finished, I asked her straightforward, “As a child, were you ever sexually abused?” She looked at me and said, “No one has ever asked me that

When I finished, I asked her straightforward, “As a child, were you ever sexually abused?”

She looked at me and said, “No one has ever asked me that question, and yes, I was.”

question, and yes, I was.” I referred her to a trauma therapist.

Another patient, 24 years old, shared for the first time that she was sexually abused by a healthcare provider during her first well woman exam as a teenager.

We spent time talking about what had happened to her. I confirmed that what she experienced was sexual violence.

She cried and then allowed me to complete the examination.

After that, I referred her to a trauma therapist. The following week, her Pap test revealed “high-grade SIL [squamous intraepithelial lesion].” This woman needed colposcopy. I called her to discuss the results and the need for followup, but she never returned my calls. Unfortunately, she never followed up with the trauma therapist or the colposcopy.

This young woman is at risk for cervical cancer, and not only is she not getting the care needed to help prevent cervical cancer, but she is not getting the care necessary to help heal her life experience of sexual violence.

But if practitioners do not ask the

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questions, they do not get the answers.

Practitioners can often tell if a woman has experienced sexual violence during an exam, as I did with the aforementioned patient. Women who have experienced sexual violence tend to be hypervigilant about the exam. They want to know what you are going to do; they are very anxious and jumpy, and

when you touch them to do a pelvic exam, they tend to jump up off the table or even dissociate.

These exaggerated responses to the pelvic exam are a clear sign of sexual violence. Women survivors of sexual violence feel out of control. When anybody does an invasive procedure, it triggers flashbacks and other symptoms

of posttraumatic stress disorder. They sometimes have panic attacks. But experienced NPs can see that and identify it in practice. It is not enough to send these women to any therapist; they need to be referred to a trauma therapist.

(A follow-up article on survivors of sexual abuse will appear in August.) ■

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Elective Single-Embryo Transfer Success The Ultimate Measure of Safety and Efficacy for an IVF Center Juergen Liebermann, PhD, HCLD Director of Laboratory, Fertility Centers of Illinois, River North, Chicago, IL STATEMENT OF NEED The goal of in-vitro fertilization (IVF) “is the birth of 1 single healthy child, with a twin pregnancy being regarded as a complication.” The Fertility Centers of Illinois (FCI), Chicago, report how they have optimized the IVF cycle by maintaining a balance between the end result and the efforts, costs, and complications of the IVF cycle, and have implemented elective single-embryo transfer (eSET) as a viable alternative to multiple-embryo transfers. Based on the experience of FCI and others, steps can be implemented that support successful eSET, thus achieving a healthy outcome for mother and child.

TARGET AUDIENCE Advanced practice nurses, registered nurses, and other interested healthcare professionals.

LEARNING OBJECTIVES After completing this activity, the reader should be better able to: • Assess the potential benefits gained through elective singleembryo transfer (eSET) • Discuss practices that support successful eSET as a viable alternative to multiple-embryo transfers • Encourage women and couples undergoing IVF treatment to consider using single-embryo transfer rather than multiple-embryo transfer EDITORIAL BOARD Juergen Liebermann, PhD, HCLD Chicago/River North IVF Center 900 N. Kingsbury, Ste RW6 Chicago, IL 60610 Amy E.T. Sparks, PhD, HCLD UI Hospitals and Clinics 200 Hawkins Drive, 3RCP Iowa City, IA 52242-1089 PLANNING COMMITTEE Gloria Mui Medical Director Veritas Institute for Medical Education, Inc. 611 Route 46 West Hasbrouck Heights, NJ 07604 Julie Ann Tagliareni CME Director Veritas Institute for Medical Education, Inc. 611 Route 46 West Hasbrouck Heights, NJ 07604 Anne L. Finger President Veritas Institute for Medical Education, Inc. 611 Route 46 West Hasbrouck Heights, NJ 07604 Dalia Buffery Editorial Director Novellus Healthcare Communications, LLC 241 Forsgate Drive Monroe Twp, NJ 08831

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n 1996, the Centers for Disease Control and Prevention (CDC) initiated data collection on assisted reproductive technology (ART). In 2006, the CDC reported a national multiple pregnancy rate with ART or in-vitro fertilization (IVF) of 48%, with a 43% rate for twin pregnancies and 4% for triplet or higher-order multiples.1 In the early days of IVF, the goal of treatment was to maximize the chance of achieving a pregnancy by transferring several embryos, regardless of any known complications created by multiple-order pregnancies.1,2 It has since been shown that the risk of multipleorder births increases with the number of embryos being transferred, which is associated with shifting from pregnancy success to complications.1,3 The increased risk of multiple pregnancies is therefore associated with potential complications, which are attributed to an increase in maternal and perinatal mortality and morbidity and increased costs for all parties involved.4,5 Multiple pregnancies always cause iatrogenic effects.4,5 Ombelet and colleagues reported stepped increases in neonatal morbidity after assisted reproduction treatment in twins and triplets compared with singletons.5 Their results indicate that there was an increased incidence of congenital malformations—3.0%, 3.5%, and 2.0%—and a higher incidence of respiratory distress syndrome—8.0%, 20.4%, and 1.6%— in twins and triplets compared with sin-

These data show that successful implementation of eSET for clinical application can be achieved by using basic embryonic knowledge rather than relying on expensive equipment and complex technology that is still under scientific development. gleton births, respectively.5 The risk of perinatal death for twin pregnancies is 3 to 4 times higher than for singletons, and 6 to 10 times for triplets and quadruplets.4-6 Over the past decade, ART has made progress worldwide in terms of greater infertility treatment success.1,3 This can be attributed to the availability of complex culture media, a better understanding of in-vitro culture conditions for human embryos, which allow use of culture until the blastocyst stage, and improved cryopreservation techniques for surplus embryos not chosen for transfer.3 To increase the success rate of an IVF cycle, it has become an accepted practice to transfer more than 1 embryo to the uterus.

Therefore, ART (including IVF) is associated with a greater number of multiple-order pregnancies compared with natural conception.1,3,5 But clinical experience also shows that many patients are confronted with dilemmas when deciding whether to

CONTINUING NURSING EDUCATION ACCREDITATION AND CONTACT HOURS STATEMENT Veritas Institute for Medical Education, Inc., is approved by the California Board of Registered Nursing Provider #13986 for 1.0 Contact Hour.

METHOD OF PARTICIPATION 1. Read the article in its entirety 2. Log on to www.obgyn-infertility-nurse.com 3. Click on “CE Credits” 4. Click on “Click here to complete the posttest and obtain a CE certificate online” 5. Register to participate 6. Enter program number OGI3 7. Complete and submit the CE posttest and CE Activity Evaluation and Request for Credit Form online 8. Print your Statement of Completion This activity is provided free of charge to participants.

FINANCIAL DISCLOSURES Veritas Institute for Medical Education, Inc., is required to disclose to the activity audience

choose 1 or 2 embryos for embryo transfer. The nature of some of these dilemmas may lie in: • The emotional stress that a patient may be undergoing (urgency to get pregnant) • The financial aspects of the treatment (cost to the infertile couple, which increases with no IVF insurance coverage) • Educational issues (lack of information about the risks of multiple gestation) • Statistical concerns (being aware of the low ongoing pregnancy rate per treatment cycle from national data).

International meetings, such as the Bertarelli Foundation Conference3 or the European Society of Human Reproduction and Embryology Consensus Conference,7 raised awareness of the problem of infertility therapy–associated multiple pregnancies, suggesting that the goal of IVF “is the birth of 1 single healthy child, with a twin pregnancy being regarded as a complication.”7

the relevant financial relationships of the planners and faculty involved in the development of CE content. An individual has a relevant financial relationship if he or she has a financial relationship in any amount occurring in the last 12 months with a commercial interest whose products or services are discussed in the CE activity content over which the individual has control. In addition, all faculty are expected to openly disclose any unlabeled/unapproved/investigational uses of drugs or devices discussed in this activity. Disclosures are as follows: • Juergen Liebermann, PhD, HCLD, is a consultant to Origio.

• Amy E.T. Sparks, PhD, HCLD, is a consultant to the Center for Reproductive Medicine, Wichita, KS. • The staffs of Veritas Institute for Medical Education, Inc., and Novellus Healthcare Communications, LLC, have nothing to disclose.

DISCLAIMER The opinions expressed in this activity are those of the presenters and do not necessarily reflect the opinions or recommendation of Veritas Institute for Medical Education, Inc. Copyright © 2010 Veritas Institute for Medical Education, Inc. All rights reserved.

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One way to move away from “maximizing” an IVF cycle (ie, achieving a pregnancy at all costs) is to optimize the cycle by maintaining a balance between the end result (ie, efficacy) and the efforts, costs, and complications (ie, safety) of the IVF cycle. In an effort to reduce high-order multiple pregnancies, a growing body of evidence supports reducing the number of embryos transferred and moving toward elective single-embryo transfer (eSET) as a viable alternative to multiple-embryo transfers.8-15 The success of eSET, if applied during an IVF cycle, requires the ability to select a good-quality embryo and the careful selection of the right patient and the right cycle.16,17 These benefits will reduce the risk of a multiple-order pregnancy, with only a slight, but not significant, drop in the live birth rate.14,18 Embryo selection remains a point of controversy and is still under scientific development. Identifying the features that characterize a top-quality embryo is crucial for achieving success with eSET. The current established method for embryo selection in clinical application is based on morphologic and physical characteristics identified by using light microscopy. However, increasing voices in the clinical community argue that morphology is not only subjective but also a relatively poor indicator of developmental potential. In turn, a variety of minimally invasive approaches to assess embryonic developmental potential (ie, biological processes, such as metabolism) are currently being developed. Most of these approaches are still under scientific development, and many IVF clinics are unable to afford proteomic/metabolomic studies, or financially unable to equip a laboratory with expensive equipment necessary to perform such studies. In addition, most of these so-called noninvasive assays require major changes in existing gamete/embryo culture and handling methods.

Successful Application of eSET in Clinical Practice In 2007, Fertility Centers of Illinois (FCI) started to implement eSET as a clinical application. For embryo selection, FCI went back to the basics of embryology, using morphologic criteria for the selection of good-quality embryos, combined with careful selection of patients, without changing the existing, and very successful, culture system. The following report summarizes the results of our study with eSET at FCI. Between 2007 and 2009, we performed 4081 autologous cycles with embryo transfer, of which 1783 (44%) embryo transfers were performed on day 3 without eSET, and 2298 (56%) embryo transfers were done on day 5. Records of

a total of 314 autologous eSETs on day 5 (14% of all blastocyst transfers— 314:2298) were reviewed. The CDC reported a national average of 4.5% for eSET cycles in their 2007 report.19 For FCI patients with good prognosis, we recommended using eSET. The criteria for this recommendation included: • Age <37 years • Having conceived in a first IVF cycle • Availability of 1 or more high-quality blastocysts.

Oocytes underwent intracytoplasmic sperm injection and were cultured in SAGE media for extended culture. On day 5, eSET cases were identified by using a scoring system that takes into account embryo morphology based on the size of the inner cell mass and the number of trophectoderm cells, as well as whether there were 1 or more blastocysts suitable for cryopreservation.

The mean age of the patient population was 31.1 ± 3.3 years. On average, 18 oocytes per patient were retrieved.

Of a total of 5738 oocytes retrieved, 79.5% were injected. The majority (98.1%) of the fertilized oocytes cleaved on day 2, 74.3% of the fertilized oocytes progressed to blastocysts, and 53.3% of them were suitable for cryopreservation (Table).

In 314 eSET cases, 224 positive pregnancies (71.3%) were achieved, with 205 clinical pregnancies (65.3%).

The implantation rate was 67.2% (211/314), with 188 ongoing pregnancies, yielding a 59.9% ongoing pregnancy rate. Furthermore, of the 73 patients that came back for a frozen embryo transfer, 75.3% achieved a positive pregnancy, with a clinical and ongoing pregnancy rate of 67.1% (49/73). That leads to a cumulative ongoing pregnancy rate (fresh and frozen transfers combined) of 75.5% (237:314) per oocyte retrieval. The added value of cryopreservation is 15.3%. So far, 124 healthy babies have been born from eSET (59 boys, 65 girls). At FCI, extended culture generates high pregnancy and implantation rates, even when we are transferring single embryos. A large cohort of goodquality blastocysts, with a high percentage of them suitable for cryopreservation, is usually what also qualifies patients for eSET. After 314 eSETs at FCI, we did not observe a decrease in the overall ongoing pregnancy rate of our program, but we did find a dramatic reduction of twins (from a rate of 50.4% with transfer of 2 blastocysts to less than 3% with eSET) and a complete disappearance of high-order multiple pregnancies.

Combining the ongoing pregnancy rate of fresh and frozen embryo transfers at FCI yields a cumulative ongoing pregnancy rate of 75%.

Table Retrospective Outcome Data from Autologous Elective Single-Embryo Transfers on Day 5 Patients, N

314

Patients’ age, y

31.3 ± 3.3

Oocytes retrieved, N

5738

Oocytes injected, N

4559

Oocytes fertilized, N (%)

3494 (76.6 ± 5.1, 75.8-78.8a)

Embryos cleaved on day 2, N (%)

3429 (98.1 ± 5.0,b 97.9-98.9a)

Embryos with ≥6 blastomeres on day 3, N (%)c

2934 (84.0 ± 4.6,b 82.6-86.4a)

Compacting embryos on day 4, N (%)c

2570 (73.6 ± 4.4,b 71.5-76.3a)

Blastocysts on day 5, N (%)c

2597 (74.3 ± 4.1,b 72.6-76.6a)

Blastocysts cryopreserved, N (%)

1385 (53.3 ± 3.0)

Patients who underwent eSET, N

314

Implantations, N (%)

211 (67.2)

Positive pregnancy/eSET, N (%)

224 (71.3)

Clinical pregnancy/eSET, N (%)

205 (65.3)

Ongoing/delivered pregnancies/eSET, N (%)

188 (59.9)

Live births, N

124

a

95% confidence interval. ± SEM. %/2 pns. eSET indicates elective single embryo transfer; SEM, standard error of mean. bMeans c

Conclusion These data show that successful implementation of eSET for clinical application can be achieved by using basic embryonic knowledge rather than relying on expensive equipment and complex technology that is still under scientific development. In addition, aside from a wider acceptance of eSET in the IVF patient population, as well as among physicians and embryologists,20 an active and effective cryopreservation program is essential for implementing eSET successfully and for effectively reducing the rate of multiple gestations associated with ART. In general, based on the data achieved at FCI, eSET has been demonstrated to be a valuable tool, not to maximize but rather to optimize pregnancy rates. ■ Acknowledgments The author thanks all the physicians at the FCI (Angelina Beltsos, MD; Christopher Sipe, MD; Meike Uhler, MD; Kevin Lederer, MD; Aaron Lifchez, MD; Jane Nani, MD; Eve Feinberg, MD; Laurence Jacobs, MD; John Rapisarda, MD) and the embryologists at the FCI IVF Laboratory River North (Elissa Pelts, BS; Jill Matthews, BS; Sara Sanchez, BS; Yuri Wagner, BS; Amanda Erman, BS; Rebecca Brohammer, BS) for their invaluable contributions and support with this study.

References 1. Sunderam S, Chang J, Flowers L, et al. Assisted reproductive technology surveillance—United States, 2006. MMWR Surveill Summ. 2009;58:1-25.

2. Faber K. IVF in the US: multiple gestation, economic competition, and the necessity of excess. Hum Reprod.

1997;12:1614-1616.

3. Adashi EY, Barri PN, Berkowitz R, et al. Infertility therapy-associated multiple pregnancies (births): an ongoing epidemic. Reprod Biomed Online. 2003;7:515-542.

4. Oleszczuk AK, Oleszczuk JJ, Keith LG. Defining the

high-risk nature of triplet pregnancies. Int J Fertil Women’s Med. 2002;47:182-190.

5. Ombelet W, Martens G, De Sutter P, et al. Perinatal outcome of 12,021 singleton and 3108 twin births after non-IVF-assisted reproduction: a cohort study. Hum Reprod. 2006;21:1025-1032.

6. Doyle P. The outcome of multiple pregnancy. Hum Reprod. 1996;11(suppl 4):110-117.

7. Land JA, Evers JL. Risks and complications in assisted reproduction techniques: report of an ESHRE consensus meeting. Hum Reprod. 2003;18:455-457.

8. Martikainen H, Tiitinen A, Tomás C, et al. One versus two embryo transfer after IVF and ICSI: a randomized study. Hum Reprod. 2001;16:1900-1903.

9. Tiitinen A, Unkila-Kallio L, Halttunen M, HydenGranskog C. Impact of elective single embryo transfer on the twin pregnancy rate. Hum Reprod. 2003;18: 1449-1453.

10. Gerris J, De Neubourg D, Mangelschots K, et al.

Elective single day 3 embryo transfer halves the twinning rate without decrease in the ongoing pregnancy rate of an IVF/ICSI programme. Hum Reprod.

2002;17:2626-2631.

11. Gerris J, De Sutter P, De Neubourg D, et al. A reallife prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles. Hum Reprod. 2004;19:917-923.

12. Van Landuyt L, Verheyen G, Tournaye H, et al.

New Belgian embryo transfer policy leads to sharp decrease in multiple pregnancy rate. Reprod Biomed Online. 2006;13:765-771.

13. De Sutter P, Van der Elst J, Coetsier T, Dhont M. Single embryo transfer and multiple pregnancy rate reduction in IVF/ICSI: a 5-year appraisal. Reprod Biomed Online. 2003;6:464-469.

14. Criniti A, Thyer A, Chow G, et al. Elective single blastocyst transfer reduces twin rates without compromising pregnancy rates. Fertil Steril. 2005;84:1613-1619.

15. Gerris J. Single-embryo transfers versus multipleembryo transfer. Reprod Biomed Online. 2009;18:63-70.

16. Hunault CC, Eijkemans MJ, Pieters MH, et al. A prediction model for selecting patients undergoing in vitro fertilization for elective single embryo transfer.

Fertil Steril. 2002;77:725-732.

17. Gardner DK, Surrey E, Minjarez D, et al. Single blastocyst transfer: a prospective randomized trial. Fertil Steril. 2004;81:551-555.

18. Thurin A, Hausken J, Hillensjö T, et al. Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization. N Engl J Med. 2004;351:2392-2402.

19. US Department of Health and Human Services and Centers for Disease Control and Prevention. Assisted Reproductive Technology Success Rates: National Summary and Fertility Clinic Reports 2007.

20. Henman M, Catt JW, Wood T, et al. Elective transfer of single fresh blastocysts and later transfer of cryostored blastocysts reduces the twin pregnancy rate and can improve the in vitro fertilization live birth rate in younger women. Fertil Steril. 2005;84:1620-1627.

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COMMENTARY

Elective Single-Embryo Transfer Its Time Has Come Amy E.T. Sparks, PhD, HCLD University of Iowa Hospitals and Clinics, Department of Obstetrics and Gynecology, Center for Advanced Reproductive Care, Iowa City, IA

E

lective single-embryo transfer (eSET) is an approach to the procedure that is frequently discussed but is rarely practiced in the United States.1 Recognized as the safest way to achieve optimal outcomes from in-vitro fertilization (IVF), eSET is often practiced throughout Europe and, in some countries, has been proposed to be the standard of care.2-5 I congratulate Dr Juergen Liebermann and his colleagues at Fertility Centers of Illinois, Chicago, for identifying a good prognosis patient population and convincing many of those patients to electively transfer a single embryo.

A Tale of 2 Additional eSET Experiences Other infertility centers in the United States, while taking different approaches to patient selection and eSET promotion, have reported similar pregnancy and delivery rates.6,7 Stillman and colleagues describe their rigorous efforts to increase the proportion of patients who underwent eSET.6 After establishing a goal to reduce the risks of twin gestations in 2004, they took a series of steps to encourage patients to undergo eSET. Patient selection criteria for eSET included women aged 37 years or less who had ≥2 high-quality blastocysts.6 These efforts led to a 6-fold increase (from 1.5% in 2002 to 8.6% in 2007) in the percentage of autologous oocyte embryo transfers that were eSETs. They reported a significant decrease in the average number of

embryos transferred (2.16 in 2007 vs 2.45 in 2002), maintenance of pregnancy rates, and a 19% decrease in the twin pregnancy rate (30% vs 37%).6 The authors admitted that although their results were encouraging, significantly more patients need to be convinced to undergo eSET to substantially decrease the program’s twin pregnancy rate.

Multifetal gestations continue to be a significant complication of IVF in the United States. We need to limit the number of embryos transferred to the minimum required to achieve a healthy outcome.

Our IVF program at the University of Iowa took a slightly different approach, by establishing a mandatory eSET policy.7 Similar to Stillman and colleagues, we took action to decrease our rate of multiple pregnancies. In June 2004, we implemented a 2-pronged strategy that included a patient education campaign and a program-wide policy of mandatory single-blastocyst transfer in patients who were at high risk for twins.7 All patients aged <38 years with no previous failed fresh cycles in our program, >7 zygotes, and the availability of 1 good-quality blastocyst underwent eSET.7

The use of this policy led to a slightly, but not statistically significant, different ongoing pregnancy rate, and a significant decrease in our multiple pregnancy rate—from 35% to 19%.

As we celebrate our 6-year anniversary of this policy, eSET is performed for one third of all autologous oocyte embryo transfers at our IVF center. We continue to celebrate with patients who qualify for our eSET policy, and the live-birth rate after the fresh transfer remains at 66%. More than 80% of our patients take home a baby after cryoaugmentation.

Where to Begin?

Based on the experiences of these and other centers, the path to eSET requires the following steps: • Developing patient-selection criteria, by identifying factors that are characteristic of patients who are at risk for a multifetal gestation • Educating physicians and other staff members about your current outcomes, the risks of multifetal gestations, and the potential benefits gained through eSET • Initiating a patient education program6,8 • Confirming that your center has a reliable blastocyst cryopreservation program • Having a quality management program in place to ensure consistency throughout all aspects of clinical IVF, from controlled ovarian hyperstimulation to embryo grading.

Multifetal gestations continue to be a significant complication of IVF in the United States.9 We need to limit the number of embryos transferred to the minimum required to achieve a healthy outcome for mother and child. For many patients, this means that we should transfer only 1 embryo, because the optimal outcome of an IVF cycle is a single, healthy baby. ■ References 1. Luke B, Brown MB, Grainger DA, et al. Practice patterns and outcomes with the use of single embryo transfer in the United States. Fertil Steril. 2010;93:490-498.

2. Gordts S, Campo R, Puttemans P, et al. Belgian legislation and the effect of elective single embryo transfer on IVF outcome. Reprod Biomed Online. 2005;10:436-441.

3. Prevention of twin pregnancies after IVF/ICSI by single embryo transfer. ESHRE Campus Course Report.

Hum Reprod. 2001;16:790-800.

4. Andersen AN, Goossens V, Gianaroli L, et al. Assisted reproductive technology in Europe, 2003. Results generated from European registers by ESHRE. Hum Reprod. 2007;22:1513-1525.

5. Practice Committee, Society for Assisted Reproductive Technology and the American Society for Reproductive Medicine. Guidelines on the number of embryos transferred. Fertil Steril. 2004;82:773-774.

6. Stillman RJ, Richter KS, Banks NK, Graham JR. Elective single embryo transfer: a 6-year progressive implementation of 784 single blastocyst transfers and the influence of payment method on patient choice.

Fertil Steril. 2009;92:1895-1906.

7. Ryan GL, Sparks AE, Sipe CS, et al. A mandatory single blastocyst transfer policy with educational campaign in a United States IVF program reduces multiple gestation rates without sacrificing pregnancy rates. Fertil Steril. 2007;88:354-360. Epub 2007 May 9.

8. Hope N, Rombauts L. Can an educational DVD improve the acceptability of elective single embryo transfer? A randomized controlled study. Fertil Steril.

2009 May 12. [Epub ahead of print].

9. Centers for Disease Control and Prevention. American Society for Reproductive Medicine, Society for Reproductive Technology. 2005 Assisted Reproductive Technology: Success Rates. October 2007. www.cdc. gov/art/art2005/508PDF/2005ART508.pdf. Accessed May 24, 2010.

EMERGING QUESTIONS

How Old Is Too Old to Have a Baby?...

1992, from 0.2 live births per 1000 women in the 1970s and 1980s to 0.6 in 2005.2 Before any discussion on the ethics of AMA and pregnancy can begin, it is important to understand the relative medical risks to mother and child.

Pregnancy Complications in Older Age It is well-established that pregnancy-related complications increase dramatically in older women, including the risk for: • Cesarean section • Gestational diabetes

• Maternal and infant mortality • Pregnancy-induced hypertension/ preeclampsia • Preterm birth • Small fetus for gestation age • Low birth weight.

Much of the increase in delivery rates in this population is the result of the use of donor eggs; therefore, the focus of this article is on pregnancy itself (rather than the risks inherent in the aging egg, including chromosomal abnormalities, congenital anomalies, and miscarriage).

Researchers have investigated the increased risks associated with older age

Continued from page 1

in pregnancy. For example, a 2009 analysis of 16 studies published between 1990 and June 2009 of pregnant women aged ≥44 years showed significant increases in complications in this agegroup (>44 years at time of delivery) compared with the younger control group (age varied, 20-29 years).2 Pregnancy-induced hypertension was more likely to occur in the older agegroup, with a relative risk of 2.8. In this analysis, the 2 diagnoses of gestational hypertension and preeclampsia are included in the term “pregnancyinduced hypertension.”2 Cesarean section was more common

and prenatal mortality increased in the older age-group. Birth weights in the older group and the controls were 3126 g and 3178 g, respectively.2 But although these differences were statistically significant, they were not clinically significant.2 The risk for gestational diabetes was very high for women who delivered after age 44 years (relative risk, 11.2).2 However, none of the studies included in this analysis discussed whether the study population had increased risk factors (eg, family history of diabetes, excess maternal weight, or gestational diabetes with a previous pregnancy).

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Emerging Questions

How Old Is Too Old to Have a Baby?...

This study showed that women giving birth after age 44 can expect complications. Therefore, patients should be adequately counseled about the risks for these complications. They should also be made aware of the risk for perinatal mortality. Although significant, this latter risk is still generally low, and healthy 44-year-old women can expect largely positive pregnancy outcomes.2 In 2007, Delbaere and colleagues controlled confounding factors and established that after adjusting for hypertension, diabetes, mode of conception, and level of education, rates of most adverse events remained significantly higher in older primiparae. They reported increased rates of very preterm birth, extreme preterm birth, low birth weight, very low birth weight, extreme low birth weight, perinatal death, and an increase in caesarean section rate in the primiparae of AMA.3 Even after adjusting for the confounding factors, maternal age was an independent risk factor for adverse pregnancy outcome.

The results also showed that women with hypertension have a 3-fold increased risk of preterm birth and a 3to 4-fold increased risk for delivering a low-birth-weight child.3 In another randomized, prospective, multicenter investigation of singleton pregnancies, Cleary-Goldman and colleagues controlled for race, parity, body mass index, education, marital status, smoking, medical history, use of assisted conception, and patient’s study site.4 AMA (aged 35-39 years and ≥40 years) was associated with an increase in the risk of miscarriage, chromosomal abnormalities, gestational diabetes, placenta previa, and cesarean delivery.4 In addition, patients aged ≥40 years at delivery were at increased risk of placental abruption, preterm delivery, low birth weight, and perinatal mortality.4 No significant differences were noted for gestational hypertension, preeclampsia, or preterm labor.4 An interesting aspect of this study was the lack of association between AMA and the risk for gestational hypertension, which stands in contrast to many reports. The study controlled for covariates associated with gestational hypertension and preeclampsia, including parity, history of medical conditions, and use of ART.4 Although chronic hypertension is more common with advancing maternal age, age alone is not responsible for gestational hypertensive complications.4 There can also be risks to the infant.

In 2001, US infant mortality rates rose for the first time in more than 40 years—to 6.8 deaths per 1000 live births; in 2002, that rate was 7.0.5 It has been suggested that one of the main

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reasons for this is delaying pregnancy to older age, and the use of fertility treatment that is linked to multiple births.5 Multiple birth is associated with serious complications, including premature birth; 50% of all twins and 90% of all triplets are born prematurely.6 Other serious risks include impaired brain development, such as cerebral palsy and impaired lung development.6

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their advanced chronological age, they potentially violate the ADA. However, a review of the cases litigated under the ADA suggests that advocates, regulators, and elders have not used the ADA to address even the most blatant age discrimination practices in healthcare.

Fertility treatment is generally considered elective and is seldom federally funded. Therefore, reproductive endo-

Responsible reproductive centers typically have guidelines regarding age limitations, but in the end, individuals must decide for themselves whether they are capable of enduring the rigors of pregnancy and are prepared for parenting.

Ethical and Social Concerns At the forefront of the ethical issues involved in AMA and pregnancy is age discrimination, specifically whether it is legal to limit access to “medical treatment.” Other concerns involve laws stipulating that healthcare providers cannot set limits on age, and whether it can be considered age discrimination to set guidelines based on age alone.

The Age Discrimination Act (ADA) of 1975 prohibits discrimination on the basis of age in programs or activities receiving federal financial assistance. The ADA applies to people of all ages, but it does not cover employment discrimination.

At the forefront of the ethical issues involved in AMA and pregnancy is age discrimination, specifically whether it is legal to limit access to “medical treatment.”

The Office of Civil Rights of the US Department of Health and Human Services (HHS) enforces federal laws that prohibit discrimination by healthcare and human service providers that receive funds from HHS.7 The problem of clinicians making age-based decisions for older patients has received considerable attention and condemnation from medical and social science researchers in relation to the treatment of chronic and acute illness. When clinicians offer inappropriate or less care to patients because of

crinology centers would seem even less vulnerable to such litigation. Several states limit infertility coverage mandates based on age.

Presently, 4 states have infertility coverage mandates that include a maximum patient age: • New Jersey permits insurers to limit surgical treatment of infertility to people aged ≤45 years • New York requires insurers to cover infertility treatment (excluding IVF) for people aged 21 to 44 years, but permits insurers to provide coverage to patients of other ages • Rhode Island requires coverage for women aged 25 to 42 years (in 2007 the coverage limit was extended from age 40 to 42) • Connecticut law requires health insurance policies to cover medically necessary expenses incurred for the diagnosis and treatment of infertility but allows policies to limit the coverage to patients aged ≤40 years.

Determining eligibility for fertility treatment based on age alone—although perhaps ethically problematic—is not illegal. Centers should protect themselves by having well-written protocols on age requirements and limitations.

Patients should be counseled on topics such as cutoffs at initiation of treatment regimens.

In a 2007 study, 49 women who conceived and delivered after age 50 with the help of ART were matched with 129 women in their 30s and 40s who also conceived via ART. The women were mailed questionnaires on parenting stress and physical and mental well-being. Approximately 50% of the women completed the question-

naire. Their self-reported results showed that the older women had slightly lower physical functioning scores than the younger women, but their mental functioning scores were higher. There was no difference between the older and younger women in overall parenting stress.8 It is also relevant to consider current life expectancy, which has increased in the United States over the past few decades, from 69.8 in 1960 to 78.4 in 2008.9 Practical Implications The most basic tenet of healthcare providers is “to do no harm.” One must evaluate the relative risks of AMA for each patient individually as it relates to pregnancy and the health of the child.

Patients need to be educated on the increased risks of fertility treatments in older women. Many infertility patients are anxious and overloaded with information, and they do not retain all the information given to them at any given time. This is especially true during a new patient consultation, which can be very overwhelming. Therefore it is crucial to ensure that patients comprehend the increased risks of pregnancy complications on their lives.

Some consideration should also be given to potential offspring and the potential consequences of having elderly parents, including the potential burden of taking care of an elderly parent, potentially growing up without parents, as well as the social impact. Responsible reproductive centers typically have guidelines regarding age limitations, but in the end, individuals must decide for themselves whether they are capable of enduring the rigors of pregnancy and are prepared for parenting. ■ References 1. Martin JA, Hamilton BE, Ventura SJ, et al. Births: final data from 2001. Nat Vital Stat Rep. 2002;51:1-102.

2. Schoen C, Rosen T. Maternal and perinatal risks for women over 44—a review. Maturitas. 2009;64:109-113.

3. Delbaere I, Verstraelen H, Goetgeluk S, et al.

Pregnancy outcome in primiparae of advanced maternal age. Eur J Obstet Gynecol Reprod Biol. 2007;135:41-46.

4. Cleary-Goldman J, Malone FD, Vidaver J, et al.

Impact of maternal age on obstetric outcome. Obstet Gynecol. 2005;105:983-990.

5. Infant mortality rate rises in USA, first time in 45 years. February 11, 2004. www.medicalnewstoday.com/ articles/5846.php. Accessed May 28, 2010.

6. American Society for Reproductive Medicine.

Patient Fact Sheet: Fertility Drugs and the Risk of Multiple Births. 2008. www.asrm.org/uploadedFiles/ ASRM_Content/Resources/Patient_Resources/Fact_ Sheets_and_Info_Booklets/fertilitydrugs_multiple births.pdf. Accessed May 28, 2010.

7. US Department of Health & Human Services, Office of Civil Rights. Your rights under the Age Discrimination Act. www.hhs.gov/ocr/age.html. Accessed May 28, 2010.

8. Steiner AZ, Paulson RJ. Motherhood after age 50: an evaluation of parenting stress and physical functioning.

Fertil Steril. 2007;87:1327-1332.

9. The World Bank Group. World Development Indicators. Health Nutrition and Population Statistics. http://databank.worldbank.org/ddp/home.do?Step=3& id=4. Accessed May 28, 2010.

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The OB/GYN Nurse

NAMS Issues New Guidelines... ease (CHD) and stroke—and HT discontinuance. New sections on ovarian cancer and lung cancer were added.

In its statement, NAMS calls for individualization of HT based on a woman’s risk profile and the number of years since entering menopause, noting that “it cannot be assumed that benefits and risks of HT apply to all age ranges and durations of therapy.” The risk-benefit ratio for HT “is more likely to be acceptable for short-term use for symptom reduction in a younger population.

In contrast, long-term HT or initiation in older women may have a less acceptable ratio.”

The risk-benefit ratio for an individual woman will change as she ages and as her menopause-related symptoms change, the document states.

The NAMS statement places special emphasis on the timing of HT initiation and how it affects the risk-benefit ratio, noting that initiation by younger women (aged 50-59 years) or within 10 years after menopause does not seem to raise the risk of CHD. In fact, NAMS points out that evidence is emerging to suggest that HT initiation early in menopause may lower CHD risk. HT, however, is not recommended for the prevention of heart disease, according to the position statement.

Among the most prominent revisions is the section on CV effects of HT. Cardiovascular Risk Reassessed NAMS says that the discordance in findings between observational studies, which support the use of HT in lowering CHD risk, and randomized controlled trials, which have found an excess of CHD risk with HT use, is a function of the different characteristics of the women participating in each.

Women in observational studies in which CV end points were recorded were younger than 55 years and only 2 to 3 years beyond menopause when HT was initiated, whereas those in the ran-

domized controlled trials were an average of 63 to 64 years old and an average of >10 years beyond menopause.

In the WHI, a reduction in composite CV end point consisting of heart attack, a revascularization procedure, and coronary death was found in women aged 50 to 59 years who were randomized to the estrogen therapy (ET) arm compared with placebo.

Short-term use of HT is associated with an increase in CHD risk in women who are distant from menopause at the time they start HT.

“It cannot be assumed that benefits and risks of HT apply to all age ranges and durations of therapy.”—North American Menopause Society

The risk of ischemic stroke in HT users is equally complex, says the NAMS panel: HT is associated with excess ischemic stroke risk overall, but there is no significant increase in risk among women initiating HT within 5 years of menopause.

Oral HT is associated with an increased risk of venous thromboembolism, regardless of age or timing of initiation; the risk emerges soon after initiation.

Breast Cancer Risk Women in the WHI who started combined estrogen-progestin therapy shortly after menopause had an increased risk of breast cancer over the next 5 years, whereas those who started >5 years after menopause had no increased risk.

There was no increase in breast cancer risk in women randomized to ET alone in the WHI. In breast cancer survivors, ET has not been proved to be safe and may raise the risk of recurrence.

See also page 20.

Continued from page 1

Lung Cancer Risk The estrogen-progestin therapy arm of the WHI showed an increase in the number of deaths from non–small-cell lung cancer and the number of poorly differentiated and metastatic tumors (87% increase), which appeared to be limited to past and current smokers and women aged >60 years.

An Oncologist’s Perspective Rowan Chlebowski, MD, PhD, a lead investigator of the WHI, Professor and Chief, Department of Internal Medicine, Medical Oncology/Hematology, Harbor UCLA Medical Center, Torrance, CA, told the OB/GYN & Infertility Nurse, “We have presented post-hoc evidence of less harm or maybe no harm for EPT [estrogen-progestin therapy] for CHD started closer to menopause. It wasn’t cardioprotective, but it didn’t have evidence of harm. To make the suggestion that CHD could be cardioprotective in early initiators of EPT, you have to move away from the randomized clinical trial, because in the combined EPT group, there wasn’t a suggestion of benefit.”

On the flip side, estrogen-progestin therapy started closer to menopause was associated with a greater risk of invasive breast cancer, muddying the risk-benefit ratio of early initiation.

“As an oncologist, as a general rule, I believe that…the increased risk of breast cancer and the increased risk of lung cancer mortality in the EPT are not fully engaged by any of the statements that have come out,” Dr Chlebowski said.

“Breast cancer is the leading cause of cancer in women and the second leading cause of cancer death, and lung cancer is the leading cause of cancer death in women. If you have a therapy that is increasing significantly both of those, I would think it would be a bigger part of the risk-benefit discussion.”

Half the women in the United States

are current and past smokers, he said, referring to the increased risk of lung cancer deaths in this group that was assigned to estrogen-progestin therapy compared with placebo. According to the WHI, a current smoker who takes estrogen-progestin therapy for 5.6 years has a 1 in 100 risk of avoidable death from lung cancer. “That’s a big number,” said Dr Chlebowski.

The WHI was not designed to look at lung cancer risk; therefore, caution must be used when interpreting the lung cancer data, said Jani Jensen, MD, Assistant Professor of Obstetrics/Gynecology, Mayo Clinic, Rochester, MN. Although breast cancer risk was increased in the estrogen-progestin therapy group in the WHI, “the risk is moderate” and similar to the excess risk conferred by 2 glasses of wine daily or a later age at menopause, she said.

“The risk-benefit ratio is always a moving target,” said Dr Jensen—a target that depends on age at initiation of HT and the woman’s personal risk profile, as the NAMS statement emphasizes. She said that the new statement offers stronger support to the benefit of HT in the right women (early after menopause). ■

Other Recommendations from NAMS

• HT is not recommended for women with histories of endometrial cancer • Unopposed ET in women with an intact uterus is associated with an increased risk of endometrial cancer • Intrauterine systems are not recommended for endometrial protection in users of ET • When HT is discontinued after several years of use, bone mineral density should be measured, and fracture prevention medications should be initiated, if appropriate.

Heartburn, Nausea, and Vomiting in Pregnancy Finally, Some Statistics

By Caroline Helwick

H

eartburn and nausea/vomiting are common symptoms in pregnancy, but formal studies are lacking. Several studies presented at the 2010 Digestive Disease Week offered insights.

Heartburn is believed to occur approximately 4 times more often in pregnant women than in the general population, but are there risk factors?

Investigators from the University of Washington, Seattle, studied the occurrence of heartburn in 2731 pregnant women attending an obstetrics orientation class. They administered 3 questionnaires at study entry (10-13 weeks gestation), early in the third trimester, and at 4 to 6 weeks postpartum. Participants were questioned regarding meal frequency, pharmaco-

logic therapy, maternal and obstetric variables, and demographics.

Approximately 83% of the women reported having symptoms of heartburn at some time during their pregnancy, Christopher Naumann, MD, reported at the meeting.

The prevalence of heartburn increased each trimester, from 42.7% during the first trimester to 69.8% by

the second trimester and to 71.7% by the third trimester. More than 50% of the women had a history of heartburn before becoming pregnant, and 40% reported their first symptoms during pregnancy.

Several factors independently predicted the occurrence of heartburn— primarily a history of heartburn before pregnancy, which increased the risk Continued on page 15

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The OB/GYN Nurse

2010 a New Decade in Women’s and Children’s Health Debra Moynihan, WHNP-BC, MSN Carolina OB/GYN, SC

L

arge conferences may seem more attractive to some, especially when there is an opportunity to travel, but many 1-day seminars offered on a more local level can be very interesting as well. A recent example was the 2010 A New Decade in Women’s and Children’s Health, which was jointly presented by the South Carolina Nurses Association Women’s and Children’s Health Chapter and the South Carolina Section of the Association of Women’s Health, Obstetric and Neonatal Nurses (AWHONN). A total of 85 nurses attended the full-day workshop on April 30, 2010, in Columbia, SC. I presented one of the breakout sessions, “Fertility Basics: What Every

Nurse Should Know.” Other topics presented during breakout sessions included labor support and AWHONN guidelines for second-stage labor, breastfeeding protocols, obstetric emergencies, a pharmacology update for neonatal and pediatric patients, and pediatric asthma for pediatric nurses. The general sessions “Taking Care of Ourselves, the Most Recent Research,” “Discovering Perinatal Core Measures & Quality Initiatives,” and “the Ramifications of Child Abuse and Drug Abuse on the Pregnant and the Neonate/Pediatric Patient” were real eye openers.

For those who are unfamiliar with the perinatal core measures that have

Heartburn, Nausea and Vomiting... more than 5-fold. Heartburn was also more common among women who were overweight or obese before pregnancy, Dr Naumann said (Table).

Although heartburn was common, treatment was not. Only 47% of women with heartburn used medications.

Interestingly, infants born to women with heartburn had significantly higher birth weights (mean 3442 g vs 3379 g), although they were of similar gestational age (39 weeks).

After giving birth, 12.6% of the women with heartburn continued to have symptoms. “We think that pregnancyinduced heartburn predisposes to early postpartum heartburn and may be a risk factor for heartburn later in life,” Dr Naumann said.

PPIs in Pregnancy Associated with Cardiac Defects in Offspring Only 1% of patients in the University of Washington study received proton pump inhibitors (PPIs), such as omeprazole, but these agents are a standard treatment for gastroesophageal reflux disease (GERD) in the general population. Another study presented at the meeting suggested that PPIs may not be completely safe in pregnant women.

University of Pennsylvania investigators found a doubling in risk for cardiac defects in babies born to mothers who took PPIs during the first trimester of their pregnancies. The study is based on 208,951 pregnancies from The Health Improvement Network database in the United Kingdom, of

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become effective as of April 1, 2010, these are a few measures of special interest: • Decrease the number of elective deliveries before 39 completed weeks of gestation • Decrease the cesarean section rate in nulliparous women with a term singleton baby in the vertex position • Increase the rate of antenatal steroid administration to patients at risk for preterm delivery at 24 to 32 weeks • Increase the rate of exclusive breast milk feeding during the newborn hospitalization; the goal is to have newborns fed breast milk exclusively from birth, and it will be necessary for physicians to document a reason for mothers not breastfeeding.

The children and drug abuse presentation was delivered by the coroner’s office. Did you know that nurses can be elected as a coroner or deputy coroner? The 2 nurses who presented the material were elected into these positions. They said that it was much easier to teach nurses the law than to teach medical information to law enforcement officials. Many of us found that quite interesting. After listening to their presentation, however, I wonder how many of us felt we were up to the task. Their information was extremely interesting and challenging.

Nursing organizations that have local and regional chapters work very hard to bring up-to-date information right into our own backyards. Please take advantage of these opportunities and show your support of their efforts. ■

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which 2445 cases of cardiac malformations in newborns were identified and matched to 19,530 controls.

The 2-fold increased risk associated with maternal PPI use in pregnancy was significant even after adjustments for numerous confounders, reported Andrew D. Rhim, MD, of the University of Pennsylvania School of Medicine, Philadelphia. Dr Rhim noted that the safety of PPIs has not been clearly established in pregnancy; nevertheless, these drugs are increasingly being prescribed.

“These findings, if confirmed, may have direct clinical implications in the treatment of millions of women worldwide, since GERD is common during

Table Independent Predictors of Heartburn During Pregnancy Variable Race, vs white African American Asian/Pacific Islander American Indian Mixed/other/unknown Prepregnancy BMI, vs <25 kg/m2 25-25.9 kg/m2 ≥30 kg/m2 Prepregnancy gravidity Prepregnancy heartburn

1.50 1.86 1.10 5.28

BMI indicates body mass index.

“These findings, if confirmed, may have direct clinical implications in the treatment of millions of women worldwide, since GERD is common during pregnancy.”—Andrew D. Rhim, MD pregnancy,” he said. He emphasized, however, that cardiac malformations are still extremely rare.

Deborah Proctor, MD, of Yale University, who moderated the press conference, emphasized the need for pregnant women to consume enough folate, which has been shown to protect against neurologic and cardiac defects in newborns.

Odds ratio 0.66 0.52 1.65 0.63

Nausea and Vomiting in 75% of Pregnant Women The University of Washington investigators also evaluated nausea and vomiting during pregnancy, not surprisingly finding it to be extremely common, with a prevalence of 75.2% in the first trimester, dropping to 55.6% in the second trimester and 28% in the third trimester.

The greatest predictor of nausea and vomiting was a history of nausea and vomiting before pregnancy, which more than doubled the risk. Other digestive problems also increased the risk.

“Morning sickness” proved to be something of a misnomer, Dr Naumann said. Approximately 35% of the affected women reported having nausea and vomiting throughout the day, compared with approximately 20% in the morning and 10% in the evening. During the second trimester, more than 40% of women felt symptoms throughout the day, compared with about 12% in the morning and 7% in the evening.

It is often recommended that women with nausea and vomiting during pregnancy eat small, frequent meals, but this did not seem to alter the occurrence of these symptoms, Dr Naumann noted. ■

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The OB/GYN Nurse

Interstitial Cystitis More Common than Previously Thought Nurses Can Help Raise Awareness to This Painful Condition

I

nterstitial cystitis (IC), or chronic inflammation of the bladder, has been largely associated with middle-aged women and men, but researchers now suggest that this condition can strike at any age and is more prevalent than many health practitioners think.

Richard Heaton, MD, President of the Heart of Georgia Women’s Center, Warner Robins, told the OB/GYN and Infertility Nurse that nurses can help raise awareness among women about this poorly understood and likely underdiagnosed condition. “They should let the patients know that their condition is treatable, and that they should persist in seeking treatment until they find a physician who is knowledgeable and interested in the field.”

The common symptoms of IC include chronic pelvic pain and frequent urination, 2 symptoms that are often misdiagnosed. The condition appears quite common in young adolescents (photo).

In addition, 60% of patients with IC have endometriosis and/or adenomyosis, according to Dr Heaton and M. Sami Walid, MD, research fellow at the Medical Center of Central Georgia,

© Nova Science Publishers. Used with permission.

By Rosemary Frei

“Let the patients know that their condition is treatable, and that they should persist in seeking treatment until they find a physician who is knowledgeable…in the field.”

—Richard Heaton, MD Macon. For their new study (Gynecol Surg. 2010 May 12 [Epub ahead of print]), they reviewed the records of 116 women with symptoms suggestive of IC. Typical IC findings were determined in 62 women, and 38 fit the criteria for atypical IC. Based on pathology reports, Drs Heaton and Walid determined that 67.74% of women with typical IC had endometriosis and/or adenomyosis and that the rate was 47.4% among those with atypical cystitis.

In another study (to be published in Int J Child Adolesc Health. 2010;3), Dr Heaton diagnosed 6 females, aged 14 to 19 years, with IC in a single year. Health practitioners should be alert for the presence of IC even in adolescent female patients, sug-

gested Dr Walid.

Glomerulations and Hunner’s ulcer in the bladder of a 16-year-old girl.

“We need to diagnose it objectively, with reliable • Plus daytime urinary frequency ≥10 methods, such as cystoscopy combined • Or urgency because of pain, pressure, or with hydrodistension…and treat it effecdiscomfort rather than fear of wetting. tively with oral and intravesical theraA second definition showed 79% pies,” Dr Walid said. “If it is left undiag- specificity: nosed and untreated, it may cause a lot of • Pain, pressure, or discomfort in the confusion in the woman’s gynecological pelvic area anamnesis, even up to unnecessary surgi- • Plus daytime urinary frequency ≥10 • Or urgency as a result of pain, pressure, cal intervention.” or discomfort rather than fear of wetting Sandra Berry and colleagues developed an approach to diagnosing IC accurately • Symptoms did not resolve after treatment with antibiotics (J Urol. 2010;183:1848-1852). Their definition of IC, based on the following char- • No treatment with hormone injection therapy for endometriosis. acteristics, had 91% sensitivity: Using these 2 definitions may help • Pain, pressure, or discomfort in the diagnose IC more accurately. ■ pelvic area

MSSA Infections in Infants More Common, Dangerous than Many Realize Linked to High Rates of Mortality, Morbidity

N

early 75% of Staphylococcus aureus infections in a group of very-low-birth-weight infants were methicillin-susceptible S aureus (MSSA), and the remainder were methicillin-resistant S aureus (MRSA), a new study conducted between 2006 and 2008 has shown.

According to new data presented at the Pediatric Academic Societies 2010 annual meeting, the mortality rates for MSSA and MRSA were 26% and 24%, Table Risk of Neonatal MRSA or MSSA Infection, by Gestational Age Gestational age, wks Relative risk <25a 5.60 b 25-28 3.20 ≥29 1.0 a

P <.001.

P >.05.

MRSA indicates methicillin-resistant S aureus; MSSA, methicillin-susceptible S aureus. b

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respectively, with similar morbidity rates.

Practices in many neonatal intensive care units and “inpatient settings specify contact isolation for infants with MRSA infections, yet not for infants with MSSA infection,” noted lead investigator Andi Shane, MD, MPH, MSc, Assistant Professor of Pediatric Infectious Diseases, Emory University School of Medicine, Atlanta, GA. “Since we observed comparable morbidity and mortality from MRSA and MSSA infections, this practice seems questionable. The management of infants with MRSA and MSSA should be comparable.”

Dr Shane and colleagues from the National Institute of Child Health and Human Development Neonatal Research Network gathered data on 4392 babies weighing ≤1.5 kg who survived for more than 3 days after birth and who developed an invasive infection during their birth hospitalization.

Some 228 babies had MSSA infections and 88 had MRSA infections.

Mortality rates during the birth hospitalization were similar in the 2 groups.

In addition, the rates were similar for respiratory distress syndrome, patent

Extreme prematurity was the greatest risk factor for MRSA and MSSA infections. ductus arteriosis, necrotizing enterocolitis, severe intraventricular hemorrhage, retinopathy of prematurity, and bronchopulmonary dysplasia.

The team found that extreme prematurity was the greatest risk factor for MRSA and MSSA infections (Table).

An initial analysis indicated that non-Hispanic black race was associated with a significantly elevated risk of

developing MRSA or MSSA. However, a second analysis showed that the increased risk of MRSA in this group was confounded by the center where the birth took place. After the researchers adjusted for this factor, the significant difference was no longer present.

Investigators also found that infection risk was not significantly influenced by antibiotic use of the mother, sex of the newborn, or presence of a major birth defect.

Dr Shane recommended that healthcare providers practice “meticulous hygiene at the bedside, judicious use of antimicrobial therapy, and minimizing invasive procedures” to prevent these infections. She added that “correlating neonatal [intensive care unit]–specific practices with a prevalence of MRSA and MSSA infections could provide information regarding effective strategies for prevention of invasive staphylococcal infections.”—RF ■

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is proven to work in women of all ages above and

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Teenaged Girls Lose Bone Density with DMPA Contraceptive Injections Loss of Estrogen the Culprit, Bone Is Regained after Discontinuation

By Wayne Kuznar

A

dolescent girls who use depot medroxyprogesterone acetate (DMPA) injections for contraception lose bone mineral density (BMD), which directly affects bone health. However, this loss is reversible

after stopping the injections, and recovery is faster at the lumbar spine than at the hip, according to results of a recent study (Contraception. 2010;81:281-291).

“The data are reassuring in terms of the spine, although there is some concern at

CRINONE® 4% CRINONE® 8% (progesterone gel)

See package insert for full prescribing information.

INDICATIONS AND USAGE Assisted Reproductive Technology Crinone 8% is indicated for progesterone supplementation or replacement as part of an Assisted Reproductive Technology (“ART”) treatment for infertile women with progesterone deficiency.

Secondary Amenorrhea Crinone 4% is indicated for the treatment of secondary amenorrhea. Crinone 8% is indicated for use in women who have failed to respond to treatment with Crinone 4%.

CONTRAINDICATIONS Crinone should not be used in individuals with any of the following conditions: known sensitivity to Crinone, progesterone or any of the other ingredients; undiagnosed vaginal bleeding; liver dysfunction or disease; known or suspected malignancy of the breast or genital organs; missed abortion; active thrombophlebitis or thromboembolic disorders; or a history of hormoneassociated thrombophlebitis or thromboembolic disorders.

WARNINGS The physician should be alert to the earliest manifestations of thrombotic disorders (thrombophlebitis, cerebrovascular disorders, pulmonary embolism, and retinal thrombosis). Should any of these occur or be suspected, the drug should be discontinued immediately.

Progesterone and progestins have been used to prevent miscarriage in women with a history of recurrent spontaneous pregnancy losses. No adequate evidence is available to show that they are effective for this purpose.

PRECAUTIONS General 1. The pretreatment physical examination should include special reference to breast and pelvic organs, as well as Papanicolaou smear.

2. In cases of breakthrough bleeding, as in all cases of irregular vaginal bleeding, nonfunctional causes should be considered. In cases of undiagnosed vaginal bleeding, adequate diagnostic measures should be undertaken.

3. Because progestogens may cause some degree of fluid retention, conditions which might be influenced by this factor (e.g., epilepsy, migraine, asthma, cardiac or renal dysfunction) require careful observation.

4. The pathologist should be advised of progesterone therapy when relevant specimens are submitted.

5. Patients who have a history of psychic depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree.

6. A decrease in glucose tolerance has been observed in a small percentage of patients on estrogen-progestin combination drugs. The mechanism of this decrease is not known. For this reason, diabetic patients should be carefully observed while receiving progestin therapy.

Information for Patients The product should not be used concurrently with other local intravaginal therapy. If other local intravaginal therapy is to be used concurrently, there should be at least a 6-hour period before or after Crinone administration. Small, white globules may appear as a vaginal discharge possibly due to gel accumulation, even several days after usage.

Drug Interactions No drug interactions have been assessed with Crinone.

Carcinogenesis, Mutagenesis, Impairment of Fertility Nonclinical toxicity studies to determine the potential of Crinone to cause carcinogenicity or mutagenicity have not been performed. The effect of Crinone on fertility has not been evaluated in animals.

Pregnancy Crinone 8% has been used to support embryo implantation and maintain pregnancies through its use as part of ART treatment regimens in two clinical studies (studies COL1620-007US and COL1620-F01). In the first study (COL1620-007US), 54 Crinone-treated women had donor oocyte transfer procedures, and clinical pregnancies occurred in 26 women (48%).

The outcomes of these 26 pregnancies were as follows: one woman had an elective termination of pregnancy at 19 weeks due to congenital malformations (omphalocele) associated with a chromosomal abnormality; one woman pregnant with triplets had an elective termination of her pregnancy; seven women had spontaneous abortions; and 17 women delivered 25 apparently normal newborns.

In the second study (COL1620-F01), Crinone 8% was used in the luteal phase support of women undergoing in vitro fertilization (“IVF”) procedures. In this multi-center, open-label study, 139 women received Crinone 8% once daily beginning within 24 hours of embryo transfer and continuing through Day 30 post-transfer.

Clinical pregnancies assessed at Day 90 post-transfer were seen in 36 (26%) of women. Thirty-two women (23%) delivered newborns and four women (3%) had spontaneous abortions. Of the 47 newborns delivered, one had a teratoma associated with a cleft palate; one had respiratory distress syndrome; 44 were apparently normal and one was lost to follow-up.

Geriatric Use The safety and effectiveness in geriatric patients (over age 65) have not been established.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

Nursing Mothers Detectable amounts of progestins have been identified in the milk of mothers receiving them. The effect of this on the nursing infant has not been determined.

ADVERSE REACTIONS Assisted Reproductive Technology In a study of 61 women with ovarian failure undergoing a donor oocyte transfer procedure receiving Crinone 8% twice daily, treatment-emergent adverse events occurring in 5% or more of the women were: bloating (7%), cramps not otherwise specified (15%), pain (8%), dizziness (5%), headache (13%), nausea (7%), breast pain (13%), moniliasis genital (5%), vaginal discharge (7%), pruritus genital (5%).

In a second clinical study of 139 women using Crinone 8% once daily for luteal phase support while undergoing an IVF procedure, treatment-emergent adverse events reported in 5% or more of the women were: abdominal pain (12%), perineal pain female (17%), headache (17%), constipation (27%), diarrhea (8%), nausea (22%), vomiting (5%), arthralgia (8%), depression (11%), libido decreased (10%), nervousness (16%), somnolence (27%), breast enlargement (40%), dyspareunia (6%), nocturia (13%).

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the hip. Those who lose more than 5% of bone from baseline find it more difficult to recover at the hip,” said lead investigator Zeev Harel, MD, Associate Professor of Pediatrics, Warren Alpert Medical School of Brown University, Providence, RI.

Secondary Amenorrhea In three studies, 127 women with secondary amenorrhea received estrogen replacement therapy and Crinone 4% or 8% every other day for six doses. Treatment-emergent adverse events reported in 5% or more of women treated with Crinone 4% or Crinone 8% respectively were: abdominal pain (5%, 9%), appetite increased (5%, 8%), bloating (13%, 12%), cramps not otherwise specified (19%, 26%), fatigue (21%, 22%), headache (19%, 15%), nausea (8%, 6%), back pain (8%, 3%), myalgia (8%, 0%), depression (19%, 15%), emotional lability (23%, 22%), sleep disorder (18%, 18%), vaginal discharge (11%, 3%), upper respiratory tract infection (5%, 8%), and pruritus genital (2%, 6%).

Additional adverse events reported in women at a frequency of less than 5% in Crinone ART and secondary amenorrhea studies and not listed above include: autonomic nervous system–mouth dry, sweating increased; body as a whole– abnormal crying, allergic reaction, allergy, appetite decreased, asthenia, edema, face edema, fever, hot flushes, influenza-like symptoms, water retention, xerophthalmia; cardiovascular, general–syncope; central and peripheral nervous system–migraine, tremor; gastro-intestinal–dyspepsia, eructation, flatulence, gastritis, toothache; metabolic and nutritional–thirst; musculo-skeletal system–cramps legs, leg pain, skeletal pain; neoplasm–benign cyst; platelet, bleeding & clotting–purpura; psychiatric–aggressive reactions, forgetfulness, insomnia; red blood cell–anemia; reproductive, female–dysmenorrhea, premenstrual tension, vaginal dryness; resistance mechanism–infection, pharyngitis, sinusitis, urinary tract infection; respiratory system–asthma, dyspnea, hyperventilation, rhinitis; skin and appendages–acne, pruritus, rash, seborrhea, skin discoloration, skin disorder, urticaria; urinary system–cystitis, dysuria, micturition frequency; vision disorders–conjunctivitis.

OVERDOSAGE There have been no reports of overdosage with Crinone. In the case of overdosage, however, discontinue Crinone, treat the patient symptomatically, and institute supportive measures.

As with all prescription drugs, this medicine should be kept out of the reach of children.

DOSAGE AND ADMINISTRATION Assisted Reproductive Technology Crinone 8% is administered vaginally at a dose of 90 mg once daily in women who require progesterone supplementation.

Crinone 8% is administered vaginally at a dose of 90 mg twice daily in women with partial or complete ovarian failure who require progesterone replacement. If pregnancy occurs, treatment may be continued until placental autonomy is achieved, up to 10-12 weeks.

Secondary Amenorrhea Crinone 4% is administered vaginally every other day up to a total of six doses. For women who fail to respond, a trial of Crinone 8% every other day up to a total of six doses may be instituted.

It is important to note that a dosage increase from the 4% gel can only be accomplished by using the 8% gel. Increasing the volume of gel administered does not increase the amount of progesterone absorbed.

This brief summary is based on the current Crinone package insert (Version 40405010007, Revised December 2006).

How Supplied Crinone is available in the following strengths: 8% gel (90 mg) in a single use, one piece, disposable, white polyethylene vaginal applicator with a twist-off top. Each applicator contains 1.45 g of gel and delivers 1.125 g of gel.

NDC-55056-0806-2 - 6 Single-use prefilled applicators.

NDC-55056-0818-2 - 18 Single-use prefilled applicators.

Each applicator is wrapped and sealed in a foil overwrap.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).

Rx only.

U.S. Patent Number 5,543,150.

Manufactured for: Columbia Laboratories, Inc. Livingston, NJ 07039 Manufactured by: Fleet Laboratories Ltd., Watford, United Kingdom © 2007, Columbia Laboratories, Inc. Printed in USA 6/07

References: 1. Doody KJ, Schnell VL, Foulk RA, et al. Endometrin for luteal phase support in a randomized, controlled, open-label, prospective in-vitro fertilization trial using a combination of Menopur and Bravelle for controlled ovarian hyperstimulation. Fertil Steril. 2009;91:1012–1017. 2. Berger BM, Ezcurra D, Phillips JA, Zubovskiy KY. Efficacy of three different progesterones for luteal phase and early pregnancy support in older women with high implantation potential embryos undergoing IVF-ET. Fertil Steril. 2009;92(suppl). Abstract O-76. 3. Endometrin® prescribing information.

Parsippany, NJ: Ferring Pharmaceuticals Inc; 2008.

Columbia Laboratories, Inc. Livingston, NJ 07039

A total of 98 healthy adolescents (aged 12-18 years) were started on DMPA injections for contraception. Their BMD measurements were available for up to 240 weeks while receiving DMPA and for up to 300 weeks after stopping it.

At the time of their last DMPA injections, BMD declined a mean of 2.7% at the spine, 4.1% at the total hip, and 3.9% at the femoral neck. Mean BMD at the spine returned to baseline within 60 weeks of discontinuing DMPA, but took 180 weeks to recover at the femoral neck and 240 weeks at the hip.

By 240 weeks after discontinuation, 84% of the adolescents had a lumbar spine BMD that exceeded baseline.

The main reason for bone loss with DMPA injection, a progestin-only contraceptive, is insufficient estrogen. The observed recovery of bone health was consistent with an increase in serum estradiol levels after discontinuing this contraception.

“Those on DMPA who lose >5% from baseline find it more difficult to recover, specifically at the hip….To minimize bone density loss, emphasize calcium and maybe vitamin D.”—Zeev Harel, MD “Fifty-three percent lost more than 5% at the hip,” said Dr Harel. “The bottom line is that those on DMPA who lose >5% from baseline find it more difficult to recover, specifically at the hip. We have to make some efforts to minimize the bone density loss in the hip….To minimize bone density loss, emphasize calcium and maybe vitamin D.” In a separate study (to be published in October 2010), “we showed that we could not distinguish between the group that lost <5% and the group that lost >5% based on the estradiol level in the blood,” he said. “That prompted us to take a look at more mechanisms that could be involved in BMD loss. That’s what brought us to calcium and vitamin D.” Among the adolescents with adequate calcium intake (≥28 servings weekly), the degree of BMD loss decreased significantly at the total hip and femoral neck but not in the spine. Adequate intake of calcium is at least 1300 mg/day in this age-group and at least 400 IU/day of vitamin D. Routine measurement of BMD may be warranted for those with a family history of osteoporosis or a chronic disease that affects bone loss, or those who have been treated with steroids, said Dr Harel. ■

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Nutrition

Optimal Weight Gain during Pregnancy for Obese Women Depends on Obesity Severity Very Low Weight Gain or Loss Not Recommended

By Wayne Kuznar

W

eight gain is appropriate for obese women during pregnancy, and the proper amount of gestational weight gain may vary by the severity of obesity, according to the results of a new study (Am J Clin Nutr.

[Epub March 31, 2010]). The findings run contrary to some clinicians’ recommendation of weight restrictions for all pregnant women who are obese.

In 2009, the Institute of Medicine (IOM) revised its guidelines for optimal weight gain in obese women, recommending a gain of 5 to 9 kg (approximately 11-20 lbs) at the end of pregnancy for women with a pregravid body mass index (BMI) ≥30 kg/m2, but the IOM lacked enough data to make recommendations for each specific class of obesity.

The researchers of this new study, led

by Barbara Adams, DrPH, RD, Professor of Epidemiology, Maternal and Child Health, and Public Health Nutrition at the University of California, Berkeley, retrospectively analyzed birth outcomes for 5550 women with different classes of obesity who delivered singleton live-

born infants. Outcomes assessed were: • The risk of preterm delivery • Small-for-gestational-age (SGA) deliveries • Large-for-gestational-age (LGA) deliveries • Spontaneous preterm births • Medically indicated preterm births.

The adjusted risk for SGA delivery decreased with increasing weight gain among the infants born to mothers in class 1 obesity but not in class 2 obesity, and very high weight gain did not protect against SGA deliveries.

These outcomes were compared with those from 18,950 normal-weight women.

Among the obese women, 3254 had class 1 obesity (BMI, 30-34.9 kg/m2),

1451 had class 2 obesity (BMI, 35-39.9 kg/m2), and 845 had class 3 obesity (BMI, ≥40 kg/m2).

Of the weight recommended by the IOM in 2009, 25% of the women in obesity class 1, 22.4% in class 2, and 20.8% in class 3 gained 141% to <211%. With more severe obesity, the amount of weight gain declined and the number of women who lost weight increased.

The adjusted risk for SGA delivery decreased with increasing weight gain among the infants born to mothers in class 1 obesity but not in class 2 obesity, and very high weight gain did not protect against SGA deliveries. In all classes of obesity, the risk for LGA delivery increased as weight gain increased.

Specific ranges of weight gain in each obesity class were associated with the lowest risks for adverse birth outcomes: • For women in class 1 obesity, a weight gain of 9.1 to 13.5 kg was associated with <10% probability of SGA or LGA delivery and a small risk of medically indicated preterm birth and spontaneous preterm birth

• For women in class 2 obesity, these probabilities were similar with a weight gain of 2.2 to 9 kg • For women in class 3 obesity, a weight gain of 2.2 to <5 kg was associated with the best birth outcomes; women in the class 3 obesity group who lost weight or had minimal weight gain had the lowest risk of medically indicated preterm birth.

At weight gains ≥352% of the IOM recommendation, the risk for medically indicated preterm birth increased for women in the class 1 obesity group, and the risk of spontaneous preterm birth increased for women in the class 2 obesity group, but neither risk increased among women with class 3 obesity who gained ≥352% of the IOM-recommended weight gain.

The authors strongly recommend nutrition counseling for all obese women during their pregnancies. ■

See also “Ask the Expert,” page 4.

The OB/GYN Nurse

Childbirth after Breast Cancer Affects a Woman’s Mortality Risk Timing Is Also Important, but the Reasons Remain Unclear

By Caroline Helwick

D

espite being in good health otherwise, women who give birth after having breast cancer have a substantially greater risk of dying within 10 years than women without breast cancer but a lower risk than those with breast cancer who do not give birth, according to a recent, large study.

Women with breast cancer who give birth are therefore assumed to be in better health than those who do not have children within 10 years after cancer diagnosis. After 10 years, the relative mortality risks are similar for patients with breast cancer whether they give birth or not, probably because patients with advanced disease have died, said principal investigator Mikael Hartman, MD, PhD, of the Karolinska Institute, Stockholm, Sweden.

“Our study shows that women who give birth after breast cancer have a considerably higher risk of premature death as compared with the general popula-

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tion, despite of the fact that their mortality risk is less than half that of patients who do not give birth after diagnosis,” Dr Hartman said.

Previous studies have shown that pregnancy during or shortly after a breast cancer diagnosis is unlikely to have a negative impact on breast cancer out-

ing their child grow up.”

The study linked the Singapore Birth Register of 319,437 women and the Swedish Multi-Generation Register of 11 million women with the respective population-based cancer registries, identifying 492 women who gave birth at least 1 year after a diagnosis of inva-

“Breast cancer patients were 32 times more likely to die if they did not give birth after diagnosis, and nearly 14 times more likely to die if they did, compared with the noncancer population.”

—Mikael Hartman, MD, PhD comes, Dr Hartman noted. “But to make a completely informed decision about having a child, young women should also be counseled on their risk of premature death in comparison to other young women without a history of breast cancer,” he added. “In other words, they may want to consider the chance of not see-

sive breast cancer (“mothers”). Cumulative all-cause mortality risks and standardized mortality ratios were compared with the background population without cancer. Similar parameters were calculated for 8529 patients with breast cancer aged <40 years without subsequent childbirth.

Mothers had a lower 15-year overall mortality rate than other patients with breast cancer who did not deliver children: 16.8% versus 40.7%. However, their relative risk of death was substantially higher than that of the background population.

“Breast cancer patients were 32 times more likely to die if they did not give birth after diagnosis, and nearly 14 times more likely to die if they did, compared with the noncancer population,” Dr Hartman said.

The timing of the delivery was also important, he added. Women who gave birth within 2 years of diagnosis had a more than 3-fold increased risk of death compared with those who delivered more than 4 years after breast cancer diagnosis.

“Although these young women are healthy, they are still at an increased risk of dying, and this persists at a constant rate. At 15 years, close to 20% of these women have died,” Dr Hartman said, but the reasons remain unclear. ■

June 2010 I Vol 2, no 3

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ACOG Highlights

Hormone Therapy Still Gold Standard for Hot Flushes

By Jessica A. Smith

V

asomotor flushes, better known as hot flushes, can be the bane of a woman’s existence during menopause, but treating these symptoms should not put her at risk for other health problems. Despite the Women’s Health Initiative (WHI) findings regarding hormone therapy (HT), it is still the “gold standard” for the treatment of hot flushes, said Isaac Schiff, MD, Chief, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, and Joe Vincent Meigs Professor of Gynecology, Harvard Medical School, Boston, MA. “Hormone therapy remains an appropriate treatment option for women with moderate-to-severe vasomotor symptoms,” Dr Schiff said at the ACOG meeting.

Acknowledging the concern surrounding HT in the wake of the WHI as well as the complexity of HT treatment decisions, he discussed options for practitioners, including modes of administration for, and alternatives to, HT. “There is no right answer—it has to be individualized,” he said.

According to Dr Schiff, the prevalence of hot flushes tends to occur between 1 and 2 years of menopause but can continue up to 10 years after onset.

Despite past belief that only thin women experienced hot flushes, the Study of Women’s Health Across the Nation (SWAN) showed that hot flushes actually increase with higher body mass index, he said.

Although SWAN showed that hot flushes are associated with increased aortic calcification, other studies have shown differing results. “All across the board, women who had vasomotor symptoms tended to have lower bone density,” Dr Schiff said.

According to Dr Schiff, menopausal women are the best candidates for HT, and health practitioners should use the lowest possible dose for the shortest duration. High doses of estrogen can cause breakthrough bleeding, he said, and when using estrogen in combination, the dose should be lowered.

Patients should be evaluated annually during treatment with HT to weigh the risks and benefits.

In discussing delivery modes for HT, Dr Schiff said a low-dose transdermal patch can be an attractive option, because it reduces hot flushes while helping to increase bone mineral density. “It appears that the transdermal patch will result in fewer cases of phlebitis,” he said, because it bypasses

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the liver. In addition, oral HT confers a higher risk of venous thromboembolism compared with the patch.

Other good options for low-dose HT are cream or gel formulations.

“Hormone therapy remains an appropriate treatment option for women with moderateto-severe vasomotor symptoms.”

—Isaac Schiff, MD

The vaginal tablet comes in such a low dose that a blood estradiol level can hardly be measured with its use. “You can’t really see a change,” Dr Schiff said. Because it is a low dose, however, it is not thought to cause endometrial cancer, and combination therapy with progestin is not necessary, he said.

Although not as effective as estrogen for treating the symptoms of menopause, Replens (an over-the-counter polycarbophil-based vaginal moisturizer) confers the same benefits as estrogen in increasing vaginal moisture, fluid volume, and elasticity, he said.

For dispareunia (pain during intercourse) or vaginal dryness, a low-dose topical formulation of estrogen is appropriate, he said; vaginal dryness is a significant problem that is often unaddressed. “As obstetricians and gynecologists, it is really critical that we ask our patients about this,” Dr Schiff said.

For assessing whether to use HT for fracture prevention, Dr Schiff recommended using the World Health Organization Fracture Risk Assessment Tool (FRAX). Accessible online, FRAX offers risk calculators that help practitioners determine whether medical therapies are needed to prevent fractures in postmenopausal women, as well as in men aged ≥50 years.

58TH ANNUAL CLINICAL MEETING

THE AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS

A number of complementary and alternative therapies are available for menopausal women, but in most cases, there is insufficient research to prove their efficacy. According to Dr Schiff, white and Japanese women are most likely to use treatments, such as Bellergal, black cohosh, dong quai, vitamin E, evening primrose oil, ginseng, red clover, acupuncture, mind/body therapies, and yoga.

A natural aid for women with dispareunia or vaginal dryness is regular copulation, because it promotes vaginal elasticity and lubrication, he said.

Although paroxetine has been shown to reduce hot flushes, it should not be used in combination with tamoxifen because of the increased risk for breast cancer. ■

Careful Risk–Benefit Balance Necessary When Prescribing Hormone Therapy

O

f many lessons gleaned from the Women’s Health Initiative (WHI), one in particular rings true when considering treatment with hormone therapy (HT)—“Accept and embrace complexity,” according to JoAnn E. Manson, MD, DrPH, Chief, Division of Preventive Medicine, Brigham and Women’s Hospital, Professor of Medicine and the Elizabeth F. Brigham Professor of Women’s Health, Harvard Medical School, Boston, MA. There is “no simple one-size-fitsall” formula when it comes to prescribing hormone therapy, said Dr Manson, who was a lead investigator of the WHI. The risks and benefits for individual patients must be carefully weighed before initiating HT, and many patient factors should be considered, she said. At the recent ACOG annual meeting she discussed the results of the WHI, and the use of HT in postmenopausal women.

“There have been major discrepancies between observational studies and clinical trials,” Dr Manson said, adding that observational studies have

There is “no simple one-size-fits-all” formula when it comes to prescribing hormone therapy.

—JoAnn E. Manson, MD, DrPH

overstated the benefits of HT, particularly for cardiovascular health. Part of that perceived benefit, she said, is because women who use HT are typically healthier than those who do not, as a result of better access to healthcare, being nonsmokers, and other lifestyle factors.

The results of the WHI show that women between the ages of 50 and 59 years who received estrogen alone or estrogen plus progestin had a 30% reduced mortality risk, whereas women between the ages of 70 and 79 years had a 14% increase in mortality risk. In all the WHI subanalyses, older women faced more risks associated with HT, including cardiovascular risks, cancer, and stroke, Dr Manson said.

Her recommendations for the use of HT largely mirrored those of the North American Menopause Society (NAMS): • HT should not be used long-term and should not be used for the express purpose of preventing diseases • If there is no quality-of-life benefit for the patient, HT should not be used • If a patient’s quality-of-life will benefit from the use of HT, balance the time since menopause with the patient’s overall risk of cardiovascular disease.—JS ■

See also page 14 for NAMS’ updated position statement on HT.

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ACOG Highlights

Gestational Diabetes Developing into Type 2 Diabetes Postpartum: A Growing Problem

By Jessica A. Smith

G

estational diabetes mellitus can have lasting implications for the pregnant woman and her baby. Steven G. Gabbe, MD, Senior Vice President for Health Sciences and CEO, Ohio State University Medical Center, discussed gestational diabetes at the 2010 American College of Obstetricians and Gynecologists (ACOG) annual meeting.

“Alarmingly, type 2 diabetes is increasing rapidly in pregnancy—especially in young women,” he said.

“We’re seeing more teenage women who are pregnant and have diabetes.”

Dr Gabbe stressed the importance of screening for gestational diabetes, stating that it is wrong to take a lax approach and think that the condition will go away when the woman delivers.

Instead, gestational diabetes provides a “sneak peek for us into the future of the woman’s metabolic problems,” he said.

Risks for Mother and Baby Between 35% and 60% of women with gestational diabetes will develop type 2 diabetes, especially within the first decade postpartum. In terms of risk, women with gestational diabetes face a 7-fold higher risk of developing type 2 diabetes compared with their non–gestational diabetes counterparts.

These women also have a shorter life expectancy, he said.

“We have to screen for gestational diabetes mellitus,” Dr Gabbe said. “If we don’t, we can’t treat it.”

When gestational diabetes is untreated, the consequences for the newborn can be: • Macrosomia • Large fetus for gestational age • Trauma, including shoulder dystocia • Hypoglycemia • Hypocalcemia • Jaundice.

In addition, the neonate born to a mother with gestational diabetes can develop other problems—including type 2 diabetes—later in life, he said.

Screening Women who are severely obese and have a history of gestational diabetes or a strong family history of diabetes are considered at high risk for gestational diabetes and should be tested at the first opportunity.

Those who have 1 or 2 risk factors are at average risk and should be tested between 24 and 28 weeks of gestation.

Low risk for gestational diabetes includes: • Age <25 years

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“Alarmingly, type 2 diabetes is increasing rapidly in pregnancy—especially in young women. . . we’re seeing more teenage women who are pregnant and have diabetes.”—Steven G. Gabbe, MD • Normal weight • No first-degree relative with diabetes, personal history of diabetes, or poor obstetric outcome • Not of an ethnicity that places them at higher risk for diabetes (ie, African American, American Indian, Asian American, Hispanic, or Pacific Islander).

Health practitioners should screen patients using a 50-g glucose load, or in high-risk women, a diagnostic oral glucose tolerance test, he said.

Changing Guidelines The diagnostic criteria for gestational diabetes have changed over the years, establishing lower cutoff levels.

The glucose level thresholds for a diagnosis of gestational diabetes recommended by the American Diabetes Association and ACOG are: • Fasting plasma glucose ≥95 mg/dL • 1-hour plasma glucose ≥180 mg/dL • 2-hour plasma glucose ≥155 mg/dL • 3-hour plasma glucose ≥140 mg/dL. An even higher prevalence of gestational diabetes could emerge if results of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study are used to create new standards, Dr Gabbe said. The HAPO study demonstrated a strong relationship between maternal glucose levels that fell below the current threshold for gestational diabetes and birth weight and body fat percentage >90th percentile, cesarean delivery, neonatal hypoglycemia, and cord C-peptide >90th percentile.

Dr Gabbe said he was unsure when these new standards may be adopted.

“I just think it is going to be some time before folks agree, because it does increase the number of women with gestational diabetes dramatically,” he said.

Gestational diabetes currently affects 7% of all pregnancies in the United States, and that number would more than double if the HAPO standards are adopted, he said. Recommendations resulting from the HAPO study’s findings would entail: • Fasting plasma glucose ≥92 mg/dL • 1-hour plasma glucose ≥180 mg/dL • 2-hour plasma glucose ≥153 mg/dL.

Treatment during Pregnancy The good news is that “treatment does work,” Dr Gabbe said. Lifestyle recommendations include a diet consisting of 3 balanced meals and a bedtime snack, plus 30 minutes of daily exercise.

If lifestyle modifications alone do not keep gestational diabetes under control, oral agents can be used.

Glyburide is an option, but it has been shown to get through the placenta, with 70% of the level in the mother being detected in the fetus, Dr Gabbe said. He therefore recommended not exceeding 20 mg/day of glyburide for the treatment of gestational diabetes.

Studies have shown that women with gestational diabetes receiving treatment with metformin, the common diabetes medication, had an increased rate of preterm birth, and 46.3% needed supplemental insulin. Other studies, however, have shown no evidence of adverse maternal or neonatal outcomes with this drug, Dr Gabbe pointed out.

Overall, diet and exercise are the best and safest treatments, but glyburide, insulin, or metformin can all be safely used, he said. It is also crucial to check fasting and 1- and 2-hour postprandial glucose levels daily.

Postpartum Follow-up Monitoring plasma glucose levels remains important after the woman gives birth, Dr Gabbe said. Fasting plasma glucose levels should be checked after delivery, at 1 year postpartum, and then every 3 years, although some recommend annual checks, he added. “We have to continue to follow the patient,” Dr Gabbe said. ■

ACOG Poll on OB/GYN Practices

M

ore than 600 OB/GYNs attended the President’s Program to kick off the 2010 American College of Obstetricians and Gynecologists (ACOG) annual meeting in San Francisco, May 15-19. Using an electronic polling system, President Gerald F. Joseph, Jr, received the following responses from attendees: Obstetrics 82% practice obstetrics Perinatal depression 52% screen for perinatal depression; of these: • 7% use the Edinburgh Postnatal Depression Scale • 50% use another tool Cosmetic procedures 93% do not offer cosmetic procedures in their practices; of those who do: • 1% offer laser hair removal • 1% offer Botox • 0% offer spider vein removal • 5% offer some other cosmetic treatment or a combination of these Natural supplements 89% do not offer natural supplements in their practice; of the 3% who do offer them: • 2% offer skinceuticals • 3% offer prescription products • 3% offer some combination of these Smartphones and PDAs 45% do not use a PDA or smartphone at the point of care; of those who do: • 15% use a BlackBerry • 25% use an iPhone • 7% use a Palm • 8% use another type of smartphone Electronic medical records • 65% have implemented electronic medical records (EMRs) in their practices • 14% plan to implement EMRs in their practices within the next year

June 2010 I Vol 2, no 3

21

The Infertility Nurse

Endometriosis and Infertility

By Carol Drury (carol@endometriosisassn.org) Education Program Coordinator/Associate Director, Endometriosis Association

E

ndometriosis and infertility are intertwined for too many women.

Most women with this condition know that they need to be concerned about fertility as they consider treatment options. Others may learn they have it as part of an infertility workup.

The Endometriosis Association (www.EndometriosisAssn.org) estimates that 7.3 million women and girls in the United States and Canada have the disease. For women with endometriosis, infertility can develop as the disease progresses; therefore, early diagnosis and treatment are critical.

Approximately 30% to 40% of women with endometriosis are infertile, and endometriosis is the cause of infertility in about 30% of all infertile women.1 Those with endometriosis who have given birth to 1 child may still struggle with infertility—only 20% conceive again.

A woman’s partner, of course, also factors into the equation. If a patient with endometriosis has been diagnosed with severe (stage IV) endometriosis, and her partner has a male factor (eg, low sperm count or low sperm motility), she has a 7% chance of conceiving.2 If the condition is minimal (stage I), and no male factor is involved, the odds of conceiving are as high as 82%.2 Laparoscopy is warranted in women who do not have a surgical diagnosis for infertility, regardless of pain symptoms or transvaginal ultrasound results.3

The Link to Infertility Why endometriosis results in infertility is largely unknown. Potential reasons may be irregular periods, pain with intercourse (which could lead to less sex), or biologic mechanisms. In a recent study comparing proteins present in the follicular fluid in women with endometriosis and in pregnant women without endometriosis, 62 proteins that affected immune response, cell division, and cellular metabolism were expressed differently between the 2 groups.4 One group of proteins, “integrins,” which are produced by the endometrium for a few days each month, are critical to embryo implantation. Some women with endometriosis do not produce the beta-3 integrin.5 The expression of the HOXA-10 gene has been found to be altered in the endometrial stromal cells during the window of implantation in patients with only superficial endometriosis, suggesting that even mild endometriosis can interfere with normal fertility.6

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Immune system abnormalities may also be a factor. Some women with endometriosis have been found to have elevated disease-fighting proteins in the endometrium, which may affect their receptivity and ability to implant an embryo. Another reason may be increased autoantibodies.7 High levels of cytokines in the fluid of the pelvis of a patient with endometriosis may be toxic to sperm.

They and other activated immune cells may damage the ovary and/or the eggs, or the antibodies produced against the endometrial cells and/or their cellular components may cause the immune system to react against the blastocyst or the endometrium, thereby preventing implantation.

adhesions or the presence of endometriomas is another cause of infertility.

The Treatment Conundrum A woman experiencing significant pain or other symptoms associated with endometriosis who wants to become pregnant has a difficult choice to make. Medical treatments for endometriosis delay conception, because they are contraceptive in nature, designed to suppress the estrogen that feeds endometriosis, as well as ovulation. If she uses pain medication for endometriosis and wishes to become pregnant, she will need to stop taking the drugs and wait for her body to recover from the effects of the medication before trying to get pregnant.

Approximately 30% to 40% of women with endometriosis are infertile, and endometriosis is the cause of infertility in about 30% of all infertile women.

Hormonal and ovulation abnormalities that reduce fertility in women with or without endometriosis include luteinized unruptured follicle syndrome, luteal phase dysfunction, abnormal follicular growth, and premature or multiple luteinizing hormone surges.8 Environmental factors can be at play as well. Many toxins mimic estrogen when absorbed into the body. Toxins such as DDE (a form of the pesticide DDT) remain in the soil contaminating the food chain, even though they were banned 35 years ago. In women with infertility, one study found levels of DDE 90 times higher than in women who conceived.9 Conditions common in women with endometriosis, including hypothyroidism and Hashimoto’s thyroiditis (autoimmune thyroid disease), can also affect fertility.

Moderate-to-severe endometriosis can cause damage to 1 or more reproductive organs. If the ovaries are covered in thick adhesions, for example, the egg may not be able to escape from the ovary. Adhesions may “pull” the ovaries or fallopian tubes away from their normal locations, causing an egg that is released from the ovary to not reach the fallopian tube.10 Damage to the fallopian tubes and ovaries from

Progestin-based drugs administered by injection may suppress ovulation for many months after they are discontinued. Furthermore, drugs used to increase the odds of conception exacerbate endometriosis.

Multiple surgeries for endometriosis put a woman at risk of developing adhesions that can distort pelvic anatomy.

However, surgery for advanced endometriosis may alleviate pain and/or restore pelvic anatomy. One study has shown that surgical treatment for endometriosis approximately doubles fecundity (pregnancy rate).11 Surgery on the ovaries, however, one of the most common sites for endometriosis, can compromise blood supply to them.

Surgery for ovarian endometriomas resulted in 13% severe ovarian damage, making it “not a rare event,” according to a recent study.12 For women with mild endometriosis and no pain, research indicates that endometrial surgery may still be warranted, but the effect on fertility is likely to be small.13 After endometrial surgery, there appears to be a fertility “window of opportunity” for 6 to 9 months. At the beginning of this window, the disease is probably fairly quiet, giving a patient the best opportunity for pregnancy.

Experts disagree on whether endo-

metriosis in a woman with infertility should be treated before pursuing infertility treatment. Infertility options, such as controlled ovarian hyperstimulation combined with intrauterine insemination, appear to be the most promising fertility treatment for women with endometriosis. Two randomized trials have shown this combination to increase fertility compared with no treatment.14,15 IVF procedures have also been found to be effective in improving fertility in women with endometriosis.16 IVF procedures—number of IVF cycles and the responsiveness to ovarian hyperstimulation—do not seem to influence the likelihood of endometriosis recurrence.17 Finally, the anguish experienced by all women longing for a baby is further deepened for the woman with endometriosis who may also be dealing with severe pain and other complications of this insidious disease. ■ References 1. Diamond MP, Osteen KG, eds. Endometrium and Endometriosis. New York, NY: Wiley-Blackwell;1997.

2. Ballweg M. The Endometriosis Sourcebook. New York, NY: McGraw-Hill;1995.

3. Meuleman C, Vandenabeele B, Fieuws S, et al. High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil Steril. 2009;92:68-74. Epub 2008 Aug 5.

4. Lo Turco E, Souza GH, Garcia JS, et al. Effect of endometriosis on the protein expression pattern of follicular fluid from patients submitted to controlled ovarian hyperstimulation for in vitro fertilization. Hum Reprod. 2010 Apr 28. [Epub ahead of print.]

5. Lessey BA. Implantation defects in infertile women with endometriosis. Ann N Y Acad Sci. 2002;955:265-280.

6. Matsuzaki S, Canis M, Darcha C, et al. HOXA-10 expression in the mid-secretory endometrium of infertile patients with either endometriosis, uterine fibromas or unexplained infertility. Hum Reprod. 2009;24:31803187. Epub 2009 Sep 7.

7. Lebovic DI, Mueller MD, Taylor, RN. Immunobiology of endometriosis. Fertil Steril. 2001;75:1-10.

8. Mahmood TA, Templeton A. Folliculogenesis and ovulation in infertile women with mild endometriosis.

Hum Reprod. 1991;6:227-231.

9. Foster WG. Environmental toxicants and human fertility. Minerva Ginecol. 2003;55:451-457.

10. American Society for Reproductive Medicine.

Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997; 67:817-821.

11. Marcoux S, Maheux R, Bérubé S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. N Engl J Med. 1997;337:217-222.

12. Benaglia L, Somigliana E, Vighi V, et al. Rate of severe ovarian damage following surgery for endometriomas. Hum Reprod. 2010;25:678-682. Epub 2010 Jan 17.

13. Olive DL, Pritts EA. The treatment of endometriosis: a review of the evidence. Ann N Y Acad Sci. 2002; 995:360-372.

14. Deaton JL, Gibson M, Blackmer KM, et al. A randomized, controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis. Fertil Steril. 1990;54:1083-1088.

15. Tummon IS, Asher LJ, Martin JS, Tulandi T. Randomized controlled trial of superovulation and insemination for infertility associated with minimal or mild endometriosis. Fertil Steril. 1997;68:8-12.

16. Buyalos RP, Agarwal SK. Endometriosis-associated infertility. Curr Opin Obstet Gynecol. 2000;12:377-381.

17. Benaglia L, Somigliana E, Vercellini P, et al. The impact of IVF procedures on endometriosis recurrence.

Eur J Obstet Gynecol Reprod Biol. 2010;148:49-52.

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CLINIC PRO FILE

IVF New Jers ey

EMERGING QUESTIONS

How Should Pregnant WoWe Advise the H1N1 Flu men Regarding Vaccine?

Donna Makris, RN, BSN, IBCLC Paren

Transitioning to Infertility Nu rsing

Interview with Jennifer Ianna ccone, RN

• A

to The OB/GYN and Infertility Nurse, . Written for nurses by nurses, it covers current and pertinent information on the physiologic, medical, and psychological aspects of human reproduction, with special emphasis on the nurse’s role in patient care ($150 value).

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on all American Academy of OB/GYN and Infertility Nurses™ educational activities, including more than $200 off future Annual Meeting registration fees.

t Education Coord inator, Saint Peter’ s Medical Cente bstetricians, midwi r, New Brunswick, ves, and nurse NJ practitioners in New Bruns in the Unite wick, New Jersey d offer a wide States agree , we with the recen array of classes national recom t tant famil for expecmendations that ies, and, as nant women shoul preg- Educa tion Coordinator the Parent a vaccine for the d have priority once that , I am certain many of novel H1N1 influe za virus (also know n- asking about our participants will be n as the swine becomes availa flu) fall. OB/G the H1N1 flu vaccine this ble.

YN nurses and At Saint Peter’ other working with s University Hospi pregnant wome nurses tal be prepa n should red to provide information to

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Research

Interview with Sue Jasulaitis, RN, MS n her role as Clinic ue Jasulaitis is New Jersey, Jennif al Manager at IVF dure, which Clinic Manager at Fertil al Research precepted many er Iannaccone has has a lower is less intrusive but also ity Centers of nurses to the field success rate. If Illinois (FCI), infertility. In the IUI fails, of the coupl River North, this interview, Chica e then in go. tries an IVF In this interview describes the steps she dure, which she discusshas a very good proce- es key features of ic to help a new she takes at her clin- rate the center and success nurse at our center. nurse get famili how s can improve ar with the demands of patient care by The nurse is this field. gesting problem the areas to study basedsugnates the patien one who coordi- their on own daily exper t’s IVF cycle.

Do you do only ience. writes up the She patient’s IVF at IVF New Jerse IVF procedures We assign y? the start dates protocol.

What are some Actually we have of medicaof the special tions and once features of FCI? a lot more coupl a protocol is who are doing deterintrauterine insem es mined, schedule her FCI has 10 IVF orientation tion (IUI) than ina- and make offices aroun in d the (IVF). The reason vitro fertilization the appro sure she has undergone all Chicago area, with 2 fully staffed in is that IVF is a priate testing. vitro fertilization intrusive proce more We (IVF) also dinate coorcenters. FCI is dure; with the husba cedure that requir it is a surgical pro- semen nd to have his one of the largest fertility centers in frozen, which es general anesth is used if on the the country, and has provid and involves more risk. There esia day of retrieval he is ed treatment to Inside River North >100, unabl more couples begin fore, a specim 000 patients durin e to produce . en. All past with an IUI proce g the matel y 60 - of knowledge. this involves a new set specia25 years. We have 11 physic ians support clinical staff, as well as 120 Basic infertility lized in reprod staff employed uctive medicine, may be large at FCI. a team of embry Our main Continued on page ologists, appro 6 xi- quality care goal is to combine the best that expertise, technology,

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Inside

Pharmacy Corn Latex allergies in er infertility drugs

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for issues such as coverage and reimbursement.

©2009 Green

Newborn Umb Cord Blood ilical The case of Chloe Levine

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Fertility Ce How Nurses Can nters of Illinois Influence Infertilit y

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• Obtain to the enhanced, member-only sections at www.obgyn-infertility-nurse.org to network with your peers in a community of OB/GYN, Infertility, and Urology Nursing Professionals. Discuss current and emerging diagnostic and therapeutic options, as well as strategies for counseling and follow-up of patients.

Continued on page

CLINIC SPO TLIGHT

IVF New Jersey Roychowdhury, nurses outside the clinic (from left): Jamie Thom Lauren Noble, Jennifer Iannaccone, Zofia Mance as, Leslie Meincke, ra, Cathy Ovacz Ella Terri Nelson. , Jill Marchetti,

Page 15

Continued on page

Polar Bodies Screening New techniques enhance genetic diagnosis

Page 17

Obesity and Reproduction What nurses need to know

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VOL 1, NO 1

The official pu blication of the American Academy of OB/GYN and Infertility Nu rses

8

The Infertility Nurse

Fetal Reduction in Multiple Pregnancy The Dreaded Decision Debra Moynihan, WHNP-BC, MSN, Carolina OB/GYN, SC

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he incidence of multifetal pregnancies has dramatically increased over the decades, as a result of the use of gonadotropins and assisted reproductive techniques.

Normally, the incidence of spontaneous twins is 1 in 90, and the incidence of triplets is 1 in 8100 pregnancies. In the United States alone, however, between 1973 and 1990 twin births have increased from 1 in 55 to 1 in 40, and triplets and high-order multiples (4 or more) have soared from 1 in 3323 to 1 in 1343. In many cases, couples are prepared to handle a twin pregnancy, but when the number grows higher, a heart-wrenching decision must be made, and there is little time to spare.

Fetal reduction is a procedure used to reduce a high-order multiple pregnancy of ≥3 fetuses to a twin or singleton pregnancy. This may be done in a twin pregnancy, but it is much less common. The main objective is to improve the chances of delivering 1 or 2 healthy babies as opposed to ≥3 premature, and possibly compromised, babies.

A Complicated Choice The decision to reduce a pregnancy is very difficult for the couple. In addition to being counseled by the reproductive endocrinologist who is caring for them, they need to consult with a specialist who deals with multiple pregnancies on a daily basis. In some cases, even though time is crucial, couples need extra psychological counseling with a professional. Although the risk of high-order multiples is discussed before fertility treatment, people tend to think that it is not going to happen to them. If and when it does, they are in total shock.

First, the couple needs to be aware of the variety of risks involved in a multiple pregnancy. Fetal risks include intrauterine growth restriction and an increased risk of congenital abnormalities. Anomalies are 2 to 4 times greater in multiples than in singleton pregnancies. If there is monozygotic twinning, cord entanglement and twin-to-twin transfusion may complicate the pregnancy.

Fetal demise is 5 times greater in twins and 6 times greater in triplets than in singletons. The rates are higher for monochorionic twins than for dichorionic twins. Prematurity is also a factor. The mean gestation length for twins is 37 weeks, whereas for triplets it is only 31 weeks. Premature births often result in increased rates of cerebral palsy, language and speech delays, cog-

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June 2010 I Vol 2, no 3

nitive delays or motor problems, and behavioral problems.

Multiple pregnancies do not come without a risk to the mother. She may need to deal with hyperemesis gravidarum, anemia, polyhydramnios, or placenta previa. Increased strain on the maternal cardiovascular system lends itself to pregnancy-induced hypertension and preeclampsia. She may also have a difficult delivery. Because of overdistention of the uterus, there is an increased risk for preterm labor, prema-

The main objective is to improve the chances of delivering 1 or 2 healthy babies as opposed to ≥3 premature, and possibly compromised, babies. ture rupture of membranes, slow progress in labor, and the risk of postpartum hemorrhage. Less than half (approximately 45%) of twins are both in the cephalic presentation. Any malpresentation of twins, or any high-order multiple pregnancy, disqualifies a woman for vaginal delivery; therefore, she will most likely deliver by cesarean section.

Socioeconomic Factors In addition to the physical risks involved, we must consider the socioeconomic factors associated with multiple pregnancies. In 2003, a full-term birth cost $1700 and a premature birth cost $77,000. The total cost for all births in 2003 was $36.7 billion, with $18.1 million attributed to prematurity.

The average hospital stay for a fullterm pregnancy is 2 days. For a birth with any diagnosis of prematurity or low birth weight, the average stay for the baby is 13.6 days. If the primary diagnosis is preterm or low birth weight, the stay increases to 24.2 days.

A total of 25% of the babies who “graduate” from the neonatal intensive care unit (NICU) leave with longterm disabilities, such as blindness, cerebral palsy, and other chronic conditions. The healthcare costs for such babies are astronomical.

Raising multiples brings on other challenges. In addition to the physical demands of caring for more than 1 infant at a time, there may be the emotional strain of caring for handicapped children. Financial strains grow as the family grows. Early on, there is the cost of supplies, such as diapers, formula,

and vaccinations. Later on, the longterm expenses of clothing, sports and activities, and then college education may be more than a family can handle.

These all need to be considered when speaking with the couple.

What to Remind the Couple So now a decision must be made “to reduce or not to reduce.” The couple needs to be reminded of the following advantages of fetal reduction: • Increased duration of pregnancy • Increased birth weight • Reduced neonatal mortality • Shorter stay in the NICU. In contrast, some of the disadvantages of fetal reduction are: • The pregnancy loss rate before 20 weeks gestation after fetal reduction is approximately 2% to 10% • Possible ethical issues to deal with, maybe with family and friends.

If the couple has weathered a course of prolonged infertility, their decision will be met with ambivalence, guilt, and bereavement. This leaves the couple with 2 options. They can opt to continue the pregnancy without fetal reduc-

tion, with the understanding that with quadruplets or quintuplets survival of all or just some fetuses is realistic but quite problematic. If there are sextuplets or more, the chance of survival is very low.

The more realistic approach is to consider multifetal reduction.

The Procedure Fetal reduction is a transabdominal procedure performed under ultrasound guidance. A needle with potassium chloride is injected into the thorax of the targeted fetus(es). It is done between 10 and 13 weeks gestation, and is usually performed on 2 fetuses at a time. If there are more than 2 fetuses, a repeated procedure is usually done 1 week later. Once the procedure is completed, the patient will need a second ultrasound in 1 week to confirm the viability of the surviving fetus(es).

Before the procedure, have a detailed discussion with the couple about how the procedure is performed.

Confirm that they understand the risks involved, and that follow-up care is necessary. Also, allow the couple to voice their ethical concerns. ■

Failed IVF and Use of GnRH Agonists Linked to Risk of MS Relapse

By Alice Goodman

W

omen with multiple sclerosis (MS) who have difficulty conceiving and giving birth naturally should be encouraged to try assisted reproductive technology (ART), including IVF. However, patients should be informed of the risk of MS relapse within the first 3 months after a failed IVF. In a recent study presented at the annual meeting of the American Academy of Neurology, failed IVF increased the risk of MS relapse during the next 3 months, and the relapse risk was influenced by the use of luteinizing hormone-releasing hormone (LHRH) agonists, also known as gonadotropin-releasing hormone (GnRH) agonists in the IVF context.

Lead investigator, Laure Michel, MD, of Nantes Hospital, France, said, “Successful IVF seems to be protective against relapse in MS patients, while use of LHRH antagonists did not appear to increase risk of relapse.”

This trial included 32 women with MS. All patients underwent at least 1 IVF session after the onset of MS—18 patients did not receive any treatment for MS during the study, 4 patients were treated with MS drugs

during the study, and the other 10 patients stopped immunomodulatory treatment at a mean of 19 months before their first IVF cycle.

A total of 79 IVF cycles were performed, resulting in 21 pregnancies and 18 live births. An LHRH agonist protocol was used in 48 IVF procedures, and an LHRH antagonist protocol was used in 19 IVF procedures.

The drug protocol for 3 of the IVF procedures was unknown.

In the 3 months after IVF, relapse rates increased compared with the period preceding IVF and compared with the 1-year control period. After 6 months, relapse rates were almost down to the level of the period preceding IVF. Both failed IVF and use of LHRH antagonists significantly increased the risk of relapse.

“We believe that patients and the treating gynecologist should be informed at the risk of relapse if IVF procedure fails and about the potential detrimental effect of LHRH agonists during IVF. In fact, the findings of our study may be more important for gynecologists who treat MS patients than for neurologists,” Dr Michel stated. ■

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The Infertility Nurse

Infertility Is a Disease: CDC Marks National Infertility Awareness Week Barbara Collura, Executive Director, RESOLVE: The National Infertility Association

O

n a spring afternoon in April 2010, legislators, healthcare professionals, government officials, and patient advocates gathered on Capitol Hill for a briefing to discuss the complexities of the disease of infertility, and how best to handle this growing public health issue. The briefing was held during National Infertility Awareness Week, which educates the public, media, and legislators about infertility being a disease that affects 1 in 8 American women and men of reproductive age.

Rep Debbie Wasserman Schultz (DFL) was the first to speak. She reiterated that yes, indeed, infertility is a disease, and she challenged everyone to explore ways to beat this disease. She highlighted the National Action Plan put forward by the Centers for Disease Control and Prevention (CDC) as an example of the nation’s public health agency partnering with all of the stakeholders in this fight to advance our common goals.

Rep Schultz also asked for support of the Family Building Act (HR 697), a bill now in Congress. Infertility patients deserve this legislation so they can receive the care they need.

As those struggling with this disease know, more information must be given to women and men struggling with infertility. Diedre Bennett, health legislative assistant for Sen Kirsten Gillibrand (DNY), said that infertility is rampant, and that our goal should be to get information into the patients’ hands.

Melissa Ford, a blogger and author, and a woman who fought this disease, could not agree more about the lack of information available. She thanks an unknown 27-year-old newly married woman whose husband was tragically killed in 9/11 for sharing her story, which encouraged Ms Ford and her husband to begin trying to have a baby earlier than they had planned. “Life is too short to wait; look at this woman who lost everything,” she said.

Ms Ford’s message is simple—infertility is secretive, and we need to “talk more about infertility...learn more about infertility,” and “do more about infertility.” Because of her own battle with infertility, Ms Ford took action and began a blog (www.stirrup-queens.com), and authored a book titled Navigating the Land of If. Bringing infertility to the forefront of discussions is vitally important, so that no one has to suffer in silence.

Rafat Abbasi, MD, a reproductive endocrinologist from Columbia Fertility Associates, Washington, DC, described

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her feelings of helplessness when she sits across from patients and has to tell them that they are infertile. Each patient sitting there thinks they are flawed. She pointed out that time is not your friend when dealing with infertility. It is also not just a female problem; male infertility is on the rise. Finally, she encouraged insurance companies to cover infertility treatments and help the 1 in 8 couples struggling with this disease to build their families.

Maurizio Macaluso, MD, DrPH, Chief of the Women’s Health and Fertility Branch at the CDC, spoke about infertility becoming an emerging public health problem in our nation.

The financial barriers and the health disparities make measuring infertility difficult. Dr Macaluso discussed the CDC’s role in leading the National Action Plan to address infertility as a public health issue. All stakeholders on this issue, including government, non-

governmental organizations, industry, physicians—gynecologists as well as specialists—nurses, and patients need to work together in this effort.

As healthcare professionals treating women or men struggling with infertility, remember that knowledge is power, and that knowledge can help each patient on their family-building journey. For professional and patient resources, visit RESOLVE’s website (www.resolve.org) to be a part of the solution. ■

CONTINUING EDUCATION CREDITS Current activities at www.COEXM.com include:

June 2010 I Vol 2, no 3

25

The Urology Nurse

Intensive Nonmedical Program Improves Chronic Pelvic Pain Syndrome in Men

By Jill Stein

N

ew research is showing that men with severely refractory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) may benefit from a 6-day immersion program involving myofascial trigger point therapy, cognitive behavioral therapy, and relaxation training.

Researchers described the program at the American Urological Association 2010 annual meeting.

“Effective treatment options for CP/CPPS remain elusive,” said Rodney Anderson, MD, Professor of Urology at Stanford University School of Medicine, Palo Alto, CA, where the new treatment protocol was developed.

“Patients typically report longstanding pain and dysfunction along with repeated failure with a host of oral agents, including antibiotics, nonsteroidal antiinflammatory agents, and alpha blockers, among others.”

The Stanford approach is based on research showing that CP/CPPS is not caused by prostate or organ pathology but rather by chronically tense myofas-

cial tissue in and around the male pelvic floor.

“Roughly 8% of the male population has CP/CPPS, so it’s fairly common in a urologic practice,” Dr Anderson said.

“Unfortunately, treatments to date haven’t worked.”

training (3-4 hours) with a psychologist to learn how to perform paradoxical relaxation therapy and are provided with a series of relaxation tapes. Cognitive behavioral therapy sessions are held daily to help patients manage the anxiety and catastrophic thinking about their symp-

“Patients typically report longstanding pain and dysfunction along with repeated failure with a host of oral agents, including antibiotics, nonsteroidal anti-inflammatory agents, and alpha blockers, among others.”—Rodney Anderson, MD Men referred for the Stanford treatment protocol are typically examined by a urologist and then complete pain symptom questionnaires. During the 6day program, patients undergo daily manual physiotherapy and are taught by a physical therapist how to self-administer external and internal myofascial trigger point release.

They also undergo daily intensive

toms that commonly occur with chronic pelvic pain syndromes.

Follow-up assessments are performed from 3 to 42 months after the training/treatment program.

Dr Anderson reported results for 116 men (average age, 48 years) who had symptoms for nearly 5 years. The most common pain site was the penis, followed by the perineum and rectum.

Investigators documented a significant improvement (P <.001) in scores on the National Institutes of Health Chronic Prostatitis Symptom Index, an accepted tool for the symptomatic evaluation of men with CP/CPPS, after 6 months of follow-up. Scores on the Global Response Assessment, a patient selfreport measure, showed that patients perceived significant improvement.

“We have been able to make some strides in improving the lives of these patients,” Dr Anderson said. “There is no cure for this disorder, but we think that anything that gets up into the 60% to 70% improvement range is worthwhile, and that’s what we found in our study.”

Finally, he emphasized that an important goal of the immersion protocol is to prepare patients to be able to selfadminister internal and external trigger point massage and to continue relaxation therapy at home. A reduction in symptoms is maintained, or in some cases improved, with continued use of the protocol, he added. ■

Nerve Stimulation Device a Good Option for Overactive Bladder

P

ercutaneous tibial nerve stimulation (PTNS) is safe and effective for patients with overactive bladder (OAB) in whom conservative therapy has failed, researchers reported at the 2010 American Urological Association annual meeting.

Kenneth M. Peters, MD, Professor and Chair of Urology, Oakland University William Beaumont School of Medicine, Royal Oak, MI, presented results for 220 patients randomized after a 2-week antimuscarinic washout to nerve stimulation or sham intervention.

The trial included men and women aged ≥18 years who had OAB symptoms for at least 3 months that had not responded to multiple conservative treatments.

PTNS, which is intended for use in a urologist’s office, is a neuromodulation therapy that uses electrical stimulation to target the sacral plexus from an accessible, minimally invasive entry point into the nervous system—the posterior tibial nerve.

Patients in the study completed 12 consecutive weekly 30-minute intervention sessions.

Results showed that on a widely validated patient self-report measure of overall treatment effectiveness, 54.5% of patients receiving PTNS and 20.9% of patients who had the sham procedure reported moderate or marked improve-

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June 2010 I Vol 2, no 3

ment (P <.001) in bladder symptoms after 13 weeks.

Also, nerve stimulation therapy was associated with significant improvements in all individual components of the self-report measure, including urgency, frequency, and urge incontinence compared with sham therapy.

This noninvasive treatment also improved voiding diary parameters, including frequency, nighttime voids, moderate-to-severe urgency, and urge incontinence compared with sham therapy, as well as quality-of-life scores on a widely validated OAB questionnaire.

Side effects with PTNS were infrequent and included ankle bruising, discomfort and bleeding at the needle site, and tingling in the leg.

The follow-up period in this study was 12 weeks, which is in line with the recommended treatment protocol for PTNS. Approximately 34 million people in the United States have OAB, and this is expected to increase with the aging of the baby boomers, Dr Peters noted.

OAB reduces quality of life, promotes social isolation, and increases the rate of falls and fractures.

Treatment Options for OAB Initial treatment for OAB involves behavioral and pelvic floor therapies, followed by antimuscarinic agents, according to Dr Peters. More than 75%

of patients with OAB quit taking these medications within 1 year after starting treatment, because of a lack of efficacy, side effects, and cost.

Surgical treatment is invasive and usually infrequent. Dr Peters said that nerve stimulation therapy should be considered in patients who: • Are unwilling or unable to tolerate systemic antimuscarinic side effects,

such as dry mouth, constipation, or central nervous system effects • Have conditions refractory to medical and behavioral treatments • Do not wish to undergo surgery or are not candidates for surgery.

Patients with primary stress urinary incontinence and pregnant women are not suitable candidates for nerve stimulation therapy. —JS ■

PSA Screening Not Recommended in Frail, Elderly Men

A

t the 2010 annual meeting of the American Geriatrics Society, researchers indicated that frail or ill elderly men in the United States are undergoing too many prostate-specific antigen (PSA) tests. Louise Walter, MD, Associate Professor, Division of Geriatrics, University of California at San Francisco, presented the results of her recent study at the meeting.

Her team conducted this study to assess the frequency of PSA screening in elderly, unwell men, who may have less than 10 years to live. “PSA is not recommended for very elderly men who are ill,” Dr Walter said. A complicating factor is that older men have a high percentage of benign prostate hypertrophy (BPH), which elevates PSA levels.

In addition, PSA testing in this pop-

ulation can often reveal prostate cancer, which at this stage of their lives is not expected to affect them in the remaining years of their lives. Therefore, treating such cancers, or mistaking BPH for prostate cancer, can cause more harm than good.

Dr Walter and her team evaluated 622,262 men aged >70 years from 104 Veteran Affairs (VA) hospitals who were eligible for PSA screening. They found that even among those aged >80 years, PSA screening was performed at a rate of 17% to 72%, depending on the facilities.

Dr Walter noted that overutilization of testing in elderly people is a great concern, not only in the VA system but universally in the United States, and this is particularly the case when screening can cause more harm than good.

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Clinical News Mirena..Continued from page 5 women who have had at least 1 child. A meta-analysis of 6 randomized clinical trials demonstrated that the levonorgestrel IU system shows efficacy similar to that of endometrial ablation up to 2 years after treatment (Obstet Gynecol. 2009;113:1104-1116).

Jury Still Out on Dangers of Yaz, Yasmin Bayer HealthCare is facing at least 1100 lawsuits alleging health risks associated with its Yaz and Yasmin oral contraceptives (OCs). Both include a combination of ethinyl estradiol and drospirenone, a synthetic progestin believed to cause deep-vein thrombosis (DVT), stroke, heart attack, and gallbladder disease.

Last year, 2 separate studies raised red flags about drospirenone. One assessed DVT risk in healthy premenopausal Danish women (aged 15-49 years) receiving hormonal contraception (BMJ. 2009;339:b2890). During a 10year period, a total of 4213 DVT events occurred in 2045 OC users. OCs with desogestrel, gestodene, or drospirenone were associated with an increased risk of DVT compared with contraceptives containing levonorgestrel.

The second study (BMJ. 2009;339: b2921) assessed thrombotic risk in 1524 premenopausal women using OCs across 6 anticoagulation clinics in the Netherlands. Results showed a 6.3-fold increased risk of thrombosis compared with nonuse of OCs. Two Bayer-sponsored prospective observational studies conducted in 2001, including more than 120,000 combination OC users in the United States and Europe, showed drospirenone to be as safe as other progestins.

A labeling change in April added a warning box for Yaz and Yasmin regarding “thromboembolic disorders and other vascular problems.”

Birth Control Pill at 50, but Unplanned Pregnancies Abound May 2010 marked the 50th anniversary of the birth control pill, which revolutionized women’s healthcare. Early versions of the pill contained nearly 4 times estrogen and nearly 10 times progestin levels found in current formulations. Today, >40 branded/generic pills are FDA approved, on top of the plethora of other forms of contraception.

Despite the control the pill offered women over their reproductive lives, the Centers for Disease Control and Prevention’s 2006-2008 National Survey of Family Growth indicates that 50% of all pregnancies in the United States are unintended. The average likelihood of an unintended pregnancy within 12 months of contraceptive use in the United States is 12%, the same as

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in 1995. The cause is often incorrect or inconsistent use of contraception, not failure of the contraceptive method itself

Oklahoma Issues Major Blocks to Abortion Rights Legislators in Oklahoma have voted to override 3 of 4 vetoes by Gov Brad Henry to measures aimed at discouraging abortion in the state.

The first 2 measures were passed in April 2010. One mandates that before

an abortion, women—including victims of rape and incest—undergo an ultrasound and view the fetus on a monitor while the practitioner provides a required detailed description of the fetus and its features. The second measure prevents women from suing their health practitioners for withholding information about birth defects while the child was in utero.

In late May, the third veto was overridden to pass a law requiring women

CRINONE® 4% CRINONE® 8% (progesterone gel)

See package insert for full prescribing information.

INDICATIONS AND USAGE Assisted Reproductive Technology Crinone 8% is indicated for progesterone supplementation or replacement as part of an Assisted Reproductive Technology (“ART”) treatment for infertile women with progesterone deficiency.

Secondary Amenorrhea Crinone 4% is indicated for the treatment of secondary amenorrhea. Crinone 8% is indicated for use in women who have failed to respond to treatment with Crinone 4%.

CONTRAINDICATIONS Crinone should not be used in individuals with any of the following conditions: known sensitivity to Crinone, progesterone or any of the other ingredients; undiagnosed vaginal bleeding; liver dysfunction or disease; known or suspected malignancy of the breast or genital organs; missed abortion; active thrombophlebitis or thromboembolic disorders; or a history of hormoneassociated thrombophlebitis or thromboembolic disorders.

WARNINGS The physician should be alert to the earliest manifestations of thrombotic disorders (thrombophlebitis, cerebrovascular disorders, pulmonary embolism, and retinal thrombosis). Should any of these occur or be suspected, the drug should be discontinued immediately.

Progesterone and progestins have been used to prevent miscarriage in women with a history of recurrent spontaneous pregnancy losses. No adequate evidence is available to show that they are effective for this purpose.

PRECAUTIONS General 1. The pretreatment physical examination should include special reference to breast and pelvic organs, as well as Papanicolaou smear.

2. In cases of breakthrough bleeding, as in all cases of irregular vaginal bleeding, nonfunctional causes should be considered. In cases of undiagnosed vaginal bleeding, adequate diagnostic measures should be undertaken.

3. Because progestogens may cause some degree of fluid retention, conditions which might be influenced by this factor (e.g., epilepsy, migraine, asthma, cardiac or renal dysfunction) require careful observation.

4. The pathologist should be advised of progesterone therapy when relevant specimens are submitted.

5. Patients who have a history of psychic depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree.

6. A decrease in glucose tolerance has been observed in a small percentage of patients on estrogen-progestin combination drugs. The mechanism of this decrease is not known. For this reason, diabetic patients should be carefully observed while receiving progestin therapy.

Information for Patients The product should not be used concurrently with other local intravaginal therapy. If other local intravaginal therapy is to be used concurrently, there should be at least a 6-hour period before or after Crinone administration. Small, white globules may appear as a vaginal discharge possibly due to gel accumulation, even several days after usage.

Drug Interactions No drug interactions have been assessed with Crinone.

Carcinogenesis, Mutagenesis, Impairment of Fertility Nonclinical toxicity studies to determine the potential of Crinone to cause carcinogenicity or mutagenicity have not been performed. The effect of Crinone on fertility has not been evaluated in animals.

Pregnancy Crinone 8% has been used to support embryo implantation and maintain pregnancies through its use as part of ART treatment regimens in two clinical studies (studies COL1620-007US and COL1620-F01). In the first study (COL1620-007US), 54 Crinone-treated women had donor oocyte transfer procedures, and clinical pregnancies occurred in 26 women (48%).

The outcomes of these 26 pregnancies were as follows: one woman had an elective termination of pregnancy at 19 weeks due to congenital malformations (omphalocele) associated with a chromosomal abnormality; one woman pregnant with triplets had an elective termination of her pregnancy; seven women had spontaneous abortions; and 17 women delivered 25 apparently normal newborns.

In the second study (COL1620-F01), Crinone 8% was used in the luteal phase support of women undergoing in vitro fertilization (“IVF”) procedures. In this multi-center, open-label study, 139 women received Crinone 8% once daily beginning within 24 hours of embryo transfer and continuing through Day 30 post-transfer.

Clinical pregnancies assessed at Day 90 post-transfer were seen in 36 (26%) of women. Thirty-two women (23%) delivered newborns and four women (3%) had spontaneous abortions. Of the 47 newborns delivered, one had a teratoma associated with a cleft palate; one had respiratory distress syndrome; 44 were apparently normal and one was lost to follow-up.

Geriatric Use The safety and effectiveness in geriatric patients (over age 65) have not been established.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

Nursing Mothers Detectable amounts of progestins have been identified in the milk of mothers receiving them. The effect of this on the nursing infant has not been determined.

ADVERSE REACTIONS Assisted Reproductive Technology In a study of 61 women with ovarian failure undergoing a donor oocyte transfer procedure receiving Crinone 8% twice daily, treatment-emergent adverse events occurring in 5% or more of the women were: bloating (7%), cramps not otherwise specified (15%), pain (8%), dizziness (5%), headache (13%), nausea (7%), breast pain (13%), moniliasis genital (5%), vaginal discharge (7%), pruritus genital (5%).

In a second clinical study of 139 women using Crinone 8% once daily for luteal phase support while undergoing an IVF procedure, treatment-emergent adverse events reported in 5% or more of the women were: abdominal pain (12%), perineal pain female (17%), headache (17%), constipation (27%), diarrhea (8%), nausea (22%), vomiting (5%), arthralgia (8%), depression (11%), libido decreased (10%), nervousness (16%), somnolence (27%), breast enlargement (40%), dyspareunia (6%), nocturia (13%).

to complete a preabortion questionnaire, which includes questions about relationships, education, income, race, and reasons for seeking the abortion.

Gov Henry vetoed a fourth bill 2 days before legislators adjourned on May 28.

The bill would have placed stringent limits on abortion coverage by health insurance companies and would have required women seeking abortions to obtain a separate health insurance policy to cover the procedure. ■

Secondary Amenorrhea In three studies, 127 women with secondary amenorrhea received estrogen replacement therapy and Crinone 4% or 8% every other day for six doses. Treatment-emergent adverse events reported in 5% or more of women treated with Crinone 4% or Crinone 8% respectively were: abdominal pain (5%, 9%), appetite increased (5%, 8%), bloating (13%, 12%), cramps not otherwise specified (19%, 26%), fatigue (21%, 22%), headache (19%, 15%), nausea (8%, 6%), back pain (8%, 3%), myalgia (8%, 0%), depression (19%, 15%), emotional lability (23%, 22%), sleep disorder (18%, 18%), vaginal discharge (11%, 3%), upper respiratory tract infection (5%, 8%), and pruritus genital (2%, 6%).

Additional adverse events reported in women at a frequency of less than 5% in Crinone ART and secondary amenorrhea studies and not listed above include: autonomic nervous system–mouth dry, sweating increased; body as a whole– abnormal crying, allergic reaction, allergy, appetite decreased, asthenia, edema, face edema, fever, hot flushes, influenza-like symptoms, water retention, xerophthalmia; cardiovascular, general–syncope; central and peripheral nervous system–migraine, tremor; gastro-intestinal–dyspepsia, eructation, flatulence, gastritis, toothache; metabolic and nutritional–thirst; musculo-skeletal system–cramps legs, leg pain, skeletal pain; neoplasm–benign cyst; platelet, bleeding & clotting–purpura; psychiatric–aggressive reactions, forgetfulness, insomnia; red blood cell–anemia; reproductive, female–dysmenorrhea, premenstrual tension, vaginal dryness; resistance mechanism–infection, pharyngitis, sinusitis, urinary tract infection; respiratory system–asthma, dyspnea, hyperventilation, rhinitis; skin and appendages–acne, pruritus, rash, seborrhea, skin discoloration, skin disorder, urticaria; urinary system–cystitis, dysuria, micturition frequency; vision disorders–conjunctivitis.

OVERDOSAGE There have been no reports of overdosage with Crinone. In the case of overdosage, however, discontinue Crinone, treat the patient symptomatically, and institute supportive measures.

As with all prescription drugs, this medicine should be kept out of the reach of children.

DOSAGE AND ADMINISTRATION Assisted Reproductive Technology Crinone 8% is administered vaginally at a dose of 90 mg once daily in women who require progesterone supplementation.

Crinone 8% is administered vaginally at a dose of 90 mg twice daily in women with partial or complete ovarian failure who require progesterone replacement. If pregnancy occurs, treatment may be continued until placental autonomy is achieved, up to 10-12 weeks.

Secondary Amenorrhea Crinone 4% is administered vaginally every other day up to a total of six doses. For women who fail to respond, a trial of Crinone 8% every other day up to a total of six doses may be instituted.

It is important to note that a dosage increase from the 4% gel can only be accomplished by using the 8% gel. Increasing the volume of gel administered does not increase the amount of progesterone absorbed.

This brief summary is based on the current Crinone package insert (Version 40405010007, Revised December 2006).

How Supplied Crinone is available in the following strengths: 8% gel (90 mg) in a single use, one piece, disposable, white polyethylene vaginal applicator with a twist-off top. Each applicator contains 1.45 g of gel and delivers 1.125 g of gel.

NDC-55056-0806-2 - 6 Single-use prefilled applicators.

NDC-55056-0818-2 - 18 Single-use prefilled applicators.

Each applicator is wrapped and sealed in a foil overwrap.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).

Rx only.

U.S. Patent Number 5,543,150.

Manufactured for: Columbia Laboratories, Inc. Livingston, NJ 07039 Manufactured by: Fleet Laboratories Ltd., Watford, United Kingdom © 2007, Columbia Laboratories, Inc. Printed in USA 6/07

Reference: Data on file, Columbia Laboratories, Inc., Livingston, NJ.

Columbia Laboratories, Inc. Livingston, NJ 07039

June 2010 I Vol 2, no 3

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Because they trust your judgment...

Progesterone Fact #4 Patients prefer CRINONE vs Endometrin速 2 to 1

The only