Bec aus es he co u ... wers ans or uf yo
fact
n so nt
progesterone
Only ONE works with one daily dose It’s a fact. CRINONE is the only once-daily vaginal progesterone gel approved for ART through 12 weeks of pregnancy. The vaginal insert requires three daily applications to achieve similar efficacy rates.1 And this dosing schedule can reduce patient convenience dramatically. When she asks about progesterone, give her the facts.
The only ONE CRINONE 8% (progesterone gel) is indicated for progesterone supplementation or replacement as part of an Assisted Reproductive Technology (ART) treatment for infertile women with progesterone deficiency. Important Safety Information The most common side effects of CRINONE 8% include breast enlargement, constipation, somnolence, nausea, headache, and perineal pain. CRINONE 8% is contraindicated in patients with active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders, missed abortion, undiagnosed vaginal bleeding, liver dysfunction or disease, and known or suspected malignancy of the breast or genital organs. Please see brief summary of full prescribing information on the following page.
Reference: 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. Š 2009, Columbia Laboratories, Inc.
Printed in USA
www.crinoneusa.com CRI8-PAD-004
OBGYN_1209:OBGYN 12/10/09 5:53 PM Page 3
Clinical News Gardasil for Prevention of Genital Warts in Males In October 2009, the FDA approved the use of Gardasil—human papillomavirus (HPV) quadrivalent (types 6, 11, 16, and 18) vaccine, recombinant— for men and boys for the prevention of genital warts (condyloma acuminate) from HPV. The new approval is for boys
and men ages 9 years through 26 years for the prevention of genital warts from HPV types 6 and 11 (www.fda.gov). The manufacturer will conduct a postmarketing study to ensure the safety of this vaccine in this male population. Until then, Gardasil had only been approved for girls and women ages 9 through 26 years for the prevention of
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%).
cervical cancer caused by HPV types 6, 11, 16, and 18, and genital warts. About 2 of 1000 American men are diagnosed with genital warts each year. HPV is the most common sexually transmitted infection in the United States, and the majority of genital warts are caused by HPV. Preventing the infection in men may also help reduce
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%). 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 CRI8-XBS-001
Columbia Laboratories, Inc. Livingston, NJ 07039
the rate of infection in young women, who are often being infected by their male sexual partners. Types 6 and 11 are the most common causes of HPV.
Immobilization Post-IUI Increases Pregnancy Rate Women who remain lying down for 15 minutes after they receive artificial intrauterine insemination (IUI) are 9.4% more likely to become pregnant than women who stand up and walk immediately (Ledger WL. BMJ. 2009; 339:b4274). Most fertility centers have the women move out of the fertilization room as soon as IUI is completed. This study randomized 199 couples to immediate post-IUI immobilization and 192 couples to immediate mobilization. The procedures took place in the Netherlands between September 2005 and October 2007. The pregnancy rate per couple was 27% in the immobilization group and 18% in the control group. This translates into a 50% increased relative chance of becoming pregnant among women in the immobilization group. Live birth rates were 27% and 18%, respectively, or a 60% increased chance of a live birth with rest. The researchers suggest that immobilization should be incorporated routinely into IUI procedures.
High Testosterone in Postmenopause a Risk for Heart Disease Postmenopausal women with elevated testosterone levels are at risk for heart disease, metabolic syndrome, and insulin resistance according to a new study (Patel, SM , et al. J Clin Endocrinol Metab. 2009;94:4776-4784). Among 344 postmenopausal women (ages 65-98 years), those with the highest testosterone levels were 3-fold more likely to have heart disease than those with lower levels. They were also 3 times more likely to have the metabolic syndrome. This link may be the result of the increased insulin resistance risk found in the women with highest testosterone levels. “For many years, androgens like testosterone were thought to play a significant role in men only and to be largely irrelevant to women,” said principal investigator, Anne Cappola, MD. “It is now largely accepted that young women with polycystic ovarian syndrome, a condition in which androgens are elevated, have increased health risks. However, the clinical relevance of testosterone in women over the age of 65 had remained uncertain until this recent study.”
Early-Stage HER2 Breast Cancer Increases Recurrence Risk Women with early-stage HER2-positive breast cancer (tumor <1 cm) are at Continued on page 27
www.obgyn-infertility-nurse.com
december 2009 I Vol 1, no 2
3
OBGYN_1209:OBGYN 12/10/09 5:53 PM Page 4
The OB/GYN and
INFERTILITY Nurse
TM
T
PUBLISHING STAFF Managing Director Jack Iannaccone jack@infertilitynurse.org 732-992-1537 Editorial Director Dalia Buffery dalia@greenhillhc.com 732-992-1889 Associate Editor Lara J. Reiman lara@greenhillhc.com Director, Client Services Russell Hennessy russell@greenhillhc.com 732-992-1888 Mark Timko mark@greenhillhc.com Senior Production Manager Lynn Hamilton Business Manager Blanche Marchitto Editorial Contact: Telephone: 732-992-1892 Fax: 732-656-7938 EDITORIAL BOARD Co-Editor-in-Chief Debra Moynihan, WHNP-BC, MSN Women’s Health Nurse Practitioner Carolina OB/GYN, NC Co-Editor-in-Chief Sue Jasulaitis, RN, MS Clinical Research Manager Fertility Centers of Illinois, Chicago Donielle Abbruscato, 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 Kit Devine, MSN, ARNP Advanced Nurse Practitioner Fertility & Endocrine Associates, Kentucky Gina Paoletti-Falcone, RN, BSN Clinical Services Manager Freedom Fertility Pharmacy, Mass Sandra Fernandez, RPh, PharmD Pharmacist Mandell’s Clinical Pharmacy Jennifer Iannaccone, RNC Nursing Manager IVF Coordinator, IVF New Jersey Donna Makris, RN, BSN, IBCLC Parent Education Coordinator St. Peter’s Medical Center, NJ Jill Marchetti, RN Director, Egg Donor Program IVF New Jersey Mary McGregor, RN IVF Coordinator The Fertility Institute of New Orleans Patricia Rucinsky, RN, BSN Clinical Nurse Manager IRMS, St. Barnabas, NJ Joan Zaccardi, MS, DrNP Administrative Practice Manager Urogynecology Arts of New Jersey 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.
4
december 2009 I Vol 1, no 2
CONTENTS
december 2009
Vol 1, no 2
CLINICAL NEWS
3 Gardasil for Prevention of Genital Warts in Males High Testosterone in Postmenopause a Risk for Heart Disease 27 Long-Term Use of Some Gonadotropins Linked to Uterine Cancer 6
THE OB/GYN NURSE
9 After the Miracle of Birth, Why Is She So Unhappy? 10 Postmenopausal Osteoporosis a Major Cause of Fractures 11 Oral Glucose Tolerance Test Not Needed in Lean Women with PCOS Combination Therapy Better than Monotherapy for Osteoporosis 12 Hypoactive Sexual Desire Disorder in Women 7
INFECTIOUS DISEASES
13 Seasonal Flu Vaccine in Pregnant Women Protects Fetus/Infant PHARMACY CORNER
14 Prescription Prenatal Vitamin Supplementation 2009 ASRM HIGHLIGHTS
15 Predictors of Low Birth Weight in Singleton Pregnancies Identified 8
Women with Low Ovarian Reserve Have 40% Chance of Conceiving 16 Switching from IM to Oral/Vaginal Progesterone Regimen Maintains ART Success ASRM Releases New Guidelines on Number of Embryos to Transfer
REPRODUCTIVE MEDICINE
17 Drug Therapy for Women with Polycystic Ovarian Syndrome THE INFERTILITY NURSE
10
18 Age, Fertility, and Ovarian Reserve 19 Survival Strategies for the Holidays for Patients Dealing with Infertility 20 Pregnancies with Multiples Increase Fetal and Infant Risks Mind-Body Program for Stress Management Improves IVF Success
REPRODUCTIVE RESOURCES 18
21 Psychological Aspects of Fertility 22 Holistic Nursing for Patients Undergoing Fertility Treatment THE UROLOGY NURSE
24 Repair of Clinical Varicocele Improves Fertility/Spontaneous Pregnancies 25 Considering Sperm Cryopreservation NUTRITION
26 High-Fiber Diet Counterproductive for Women Trying to Become Pregnant
25
Correction In October, in the Table on Page 14, “Gonal-fRFF 75 IU” was incorrectly identified as a syringe. It is available as a vial, not a syringe.
The OB/GYN and Infertility Nurse, ISSN 2151-8394 (print); ISSN 2151-8408 (online), is published 6 times a year by Greenhill Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205D, Monroe Twp, NJ 08831. Copyright ©2009 by Greenhill Healthcare Communications, LLC. All rights reserved. The OB/GYN and Infertility Nurse is a trademark of Greenhill 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. 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
OBGYN_1209:OBGYN 12/10/09 5:53 PM Page 5
From the Editors
Co-Editor-in-Chief Debra Moynihan, WHNP-BC, MSN Carolina OB/GYN
Co-Editor-in-Chief Sue Jasulaitis, RN, MS Fertility Centers of Illinois
The Mind-Body Connection in Pregnancy Keeping Up with Your Colleagues
I
f, like us, you were unable to attend the 2009 American Society of Reproductive Medicine (ASRM) meeting, this second issue of our new publication gives you the opportunity to catch up with your colleagues and explore key developments and new findings in gynecology and infertility presented at the meeting. Several presentations from the Nurses Professional Group and other nurses are featured in this issue. For example, Loretta Camarano, RN, PhD, Clinical Nurse Manager at a fertility center in California, and her team, identified a set of predictors for delivering a lowweight baby by women with a history of infertility (page 15). Kriston Ward, MS, RN, NP-C, found that young women with diminished ovarian reserve still have a 40% chance of becoming pregnant with the help of reproductive technologies (page 15). The topic of aging, fertility, and ovarian reserve is further
explored in another article by Dr Uhler (page 18). Jenessa Klein, RN, BSN, discusses her fertility clinic’s findings that switching from intramuscular progesterone to an oral/vaginal progesterone regimen does not diminish its therapeutic effect (page 16). Gynecologic and reproductive nurses can incorporate these new findings to better inform their patients and their own clinical decisions. In addition, new guidelines for embryo transfer released at the ASRM meeting (page 16) are of concern to all nurses involved in women’s health and fertility treatment. We would love to hear your thoughts on this subject, as well as about where you stand regarding the debate on oocyte cryopreservation presented at ASRM (pages 1, 6). A recurrent theme in this issue is the mind-body connection in pregnancy and sexuality. Dr Domar’s findings from her Mind/Body Program in Boston won
Happy Holidays to All Our Readers!
FREE SUBSCRIPTION
1
VOL 1, NO
the best research award at the ASRM meeting. She found a significant link between personal stress and fertility treatment success, showing that a holistic approach to fertility can lead to improved pregnancy outcomes (page 20). The topic is also the focus of Barbara Alice, RN, APN-C, MSN, in this month’s featured Clinic Profile. Ms Alice describes her own initiative to promote a holistic approach to fertility treatment at her South Jersey center (pages 1, 7), accompanied by a discussion of the psychological aspects of infertility (page 21) and holistic nursing (page 22). This theme is further highlighted by an article on postpartum depression (page 9) and on drug therapies for hypoactive sexual desire disorder (page 12), topics that reinforce the mind-body connection in human reproduction.
E.COM ILITY-NURS YN-INFERT WWW.OBG 2009 OCTOBER
S
ION G QUEST e ld We Advis How ShouWomen Regarding Pregnant Flu Vaccine? k, NJ N1 New Brunswic the H1RN, C ical Center, BSN, IBCL Jersey, we t Peter’s Med
EMERGIN PROFILE
JerseNuyrsing IVFitioNninegw to Infertility
CLINIC
Trans
Interview with
accone, RN Jennifer Iann
ris, Donna Mak ation Coordinator, Sain Parent Educ and nurse
midwives, ed bstetricians, in the Unit practitioners with the recent States agree that pregmendations national recom ld have priority once shou ennant women the novel H1N1 influ for swine flu) a vaccine known as the za virus (also able. ital becomes avail r’s University Hosp At Saint Pete
O
FREE SUBSCRIPTION REQUEST
swick, New for expeces in New Brun array of class the Parent offer a wide as in lies, and, I am certa tant fami Coordinator, ts will be Education our participan ine this of that many flu vacc t the H1N1 other nurses abou g askin and YN nurses women should fall. OB/G ant pregn to working with provide information to on page 7 be prepared Continued
K K
Illinoirchs CentecersInfeof rtility Resea Fertilirsety s Can Influen
YES! I would like to receive The OB/GYN and Infertility Nurse as well as related educational supplements FREE! NO. Please discontinue my subscription. TM
OTLIGHT CLINIC SP
How Nu
Interview with
, RN, MS Sue Jasulaitis
Research is Clinical ers of ue Jasulaitis Fertility Cent h, in Manager at ), River Nort Illinois (FCI view she discussthis inter how Chicago. In center and res of the by sugfeatu care key rate. nt patie e- es ager at IVF has a lower success based on an IVF proc s can improve Clinical Man accone has the couple then tries good success nurse problem areas to study n her role as Jennifer Iann of gesting a very experience. New Jersey, y nurses to the field which has daily , dure own their precepted man this interview, she rate at our center. who coordispecial In is the one at her clinsome of the infertility. cycle. She The nurse What are ? steps she takes liar with patient’s IVF describes the get fami nd the IVF protocol. nates the res of FCI new nurse ca- featu has 10 offices arou the patient’s . ic to help a writes up staffed in dates of medi FCI of this field with 2 fully n the start deter is the demands North. es We assig once a protocol is tation Chicago area, n (IVF) centers. FCI edur proc Inside River in and tions only IVF her IVF orien e all vitro fertilizatio st fertility centers as well as 120 Do you do large rgon d, schedule treat the ey? unde mine clinical staff, FCI. of ided Jers les has prov mately 60 at sure she has coor- one at IVF New have a lot more coup and make country, and during the g. We also staff employedcombine the best Actually we intrauterine insemina- the appropriate testin and to have his the t to >100,000 patients physicians support is to g Our main goal expertise, technology, ization have 11 the husb the men fertil We on a with . who are doin if te vitro years cine, used dina 25 than in ive medi ty care that on page 8 is a more n, which is le to produce past tion (IUI) Continued d in reproduct ists, approxi- quali is that IVF semen froze alize n unab is speci reaso prohe new set retrieval (IVF). The edure; it is a surgical of embryolog involves a a day of large team intrusive proc ires general anesthesi , a specimen. All this infertility may be requ Therefore ies ledge. Basic cedure that on page 6 more risk. Polar Bod e- of know Continued and involves begin with an IUI proc Screening s enhance les coup more New technique
as, Ella Jamie Thom z, Jill Marchetti, (from left): de the clinic Mancera, Cathy Ovac nurses outsi e, Zofia IVF New Jersey Jennifer Iannaccon Nelson. cke, Terri Roychowdhury, sive but also e, Leslie Mein h is less intru the IUI fails, Lauren Nobl If dure, whic
Specialty
Date (Required)
Address
Name
City/State/ZIP
Company
Title
Phone
S
I
Inside cy Corner
drugs Pharma in infertility Latex allergies Page 14
Umbilical Newborn Cord Blood e Levine The case of Chlo
nosis
genetic diag Page 17
on Reproducti Obesity and need to know What nurses Page 24
Page 15
Hill ©2009 Green
Signature (Required)
tions, LLC Communica Healthcare
Subscribe online at www.obgyn-infertility-nurse.com
www.obgyn-infertility-nurse.com
1 VOL 1, NO
Fax to: 732.656.7938
"
!
!
december 2009 I Vol 1, no 2
5
OBGYN_1209:OBGYN 12/10/09 5:53 PM Page 6
Emerging Questions
Is Routine Oocyte Cryopreservation for Young Women... Continued from page 1 freezing meets the criteria for a safe and effective procedure. It is currently accepted for preserving fertility for cancer patients and is increasingly offered in fertility centers to patients undergoing in-vitro fertilization (IVF). Dr Jain argues that pregnancy rates have been improving with oocyte cryopreservation for more than a decade, and IVF success rates with either slow freezing or vitrification now exceed 30%. In 2 studies published earlier this year on ongoing pregnancies or live birth rates with oocyte cryopreservation, the success rate for embryo transfer was 57% in one study and 75% in the other. As for safety, more than 150,000 births have resulted from cryopreserved embryos, with no increase in the number of congenital anomalies compared with spontaneous pregnancies, and no increase in chromosomal abnormalities have been found in embryos obtained from cryopreserved oocytes, according to Dr Jain. In contrast, Claria R. Gracia, MD, Assistant Professor of Obstetrics and Gynecology at the University of Pennsylvania, argues that the IVF success rates for pregnancy, live birth or embryo transfer, and implantation are superior with fresh eggs compared with either slow freezing or vitrification. In fact, the success rate of pregnancy with slow freezing eggs in a 33-year-old woman correspond to the success rate of IVF with a fresh egg in a 40-year-old woman. Dr Gracia says that the best recent evidence on outcomes of egg and oocyte cryopreservation comes from a study of 20 women (mean age, 31.5 years) who were candidates for IVF and donor egg cycles, in which half of 322 oocytes retrieved underwent slow feezing and half underwent vitrification. The mean number of embryos transferred per patient was 2.3 and the number of viable births was 13 (4%) in the overall group. Existing data on which to judge the safety and efficacy of cryopreservation have limitations, Dr Gracia says. Most of the data have been generated from women much younger than age 35 years, who have many eggs, which is not representative of the population of women who want to freeze eggs or those with decreased ovarian reserve. In addition, it is not yet clear which method is the best—slow freeze or vitrification. Dr Jain admits that more safety and efficacy data are needed, but he notes that in 2005-2006, the risk to benefit ratio of oocyte cryopreservation was already deemed to be reasonable for patients with cancer, and that the risk to benefit ratio has only improved since then.
6
december 2009 I Vol 1, no 2
Experimental or Established Procedure? Dr Gracia says that cryopreservation of eggs should still be considered experimental, and thus is not appropriate for universal application. The field of assisted reproductive technology is littered with examples of technology that
lead to a backlash,” she says. “I believe it should be offered as an investigational procedure under the auspices of an institutional review board.” Dr Jain agrees that more efforts should be made to control the marketing of oocyte freezing or vitrification, even though his own clinic (and many
“Oocyte cryopreservation should be considered an established medical practice and be available for wider applications.” —John K. Jain, MD
failed to live up to their hype, she says. One such example is preimplantation genetic screening, which was being offered in more than two thirds of US fertility clinics in an effort to improve the success rates of pregnancy failures associated with advanced maternal age, recurrent pregnancy loss, and IVF. It ultimately proved to lower pregnancy and live birth rates. In contrast, Dr Jain believes that “oocyte cryopreservation should be considered an established medical practice and be available for wider applications.” He noted that 54% of fertility clinics already offer oocyte cryopreservation, which is evidence of its wide acceptance. Marketing False Hopes? The marketing of oocyte freezing as “egg-surance” is premature, argues Dr Gracia. Perhaps her major complaint is the false hope that egg or oocyte freezing offers to a vulnerable population. Marketing of this technology plays on patients’ fears and provides them with a false sense of security. The ramifications are that “widespread freezing with low success and a presumed guarantee might
others) markets oocyte cryopreservation on its website. Birth Outcomes Birth outcomes for frozen oocytes are favorable, argues Dr Jain. Data from a registry of 200 infants from vitrified oocytes showed no difference in median birth weight or the incidence of congenital anomalies compared with
child development are limited, he acknowledges, but they appear favorable for children conceived with oocyte cryopreservation. Practical Suggestions Dr Jain recommends leaving oocyte cryopreservation in the hands of reproductive specialists, as is the case with intracytoplasmic sperm injection. He calls for obtaining valid informed consent from each patient before proceeding with the procedure. To be valid, informed consent must involve a qualified mental health professional, it must emphasize that oocyte cryopreservation does not guarantee a pregnancy, and it must provide specific outcomes data. Fertility centers should obtain clinic-specific outcomes to offer the patient, he suggests. In addition, the risks of freezing eggs and oocytes must also be considered, says Dr Gracia. The risk of major complications—including ovarian hyperstimulation syndrome (OHSS) requiring hospitalization, intra-abdominal bleeding, and ruptured ovarian cyst— was 0.7% in one study of 587 egg donors, and the risk of minor compli-
“Widespread freezing with low success and a presumed guarantee might lead to a backlash….It should be offered as an investigational procedure under the auspices of an institutional review board.” —Claria R. Gracia, MD
infants from spontaneous pregnancies. In addition, no increase in congenital anomalies was found in 936 babies from cryopreserved oocytes compared with information on natural conceptions from the Centers for Disease Control and Prevention. The data on
cations, mild OHSS, was almost 6%. In addition, oocyte freezing for future use is an expensive gamble. The cumulative cost is $22,000 to delay having children for 5 years. “The best advice is to have a child now,” Dr Gracia suggests. ■
www.obgyn-infertility-nurse.com
OBGYN_1209:OBGYN 12/10/09 5:53 PM Page 7
Clinic Profile South Jersey Fertility Center... Continued from page 1 • Reduce stress and anxiety • Increase energy level • Improve blood flow to the pelvic organs. Acupuncture treatments are designed to benefit the individual patient in a customized manner. Finally, Barbara “Ted” Piotrowski, a board-certified holistic nurse, offers relaxation and meditation techniques with her Greater Harmony program, focusing on the mind-body balance by using meditation, Reiki, yoga, and shiatsu (see article, page 22). Barbara Alice, RN, APN-C, MSN
fessional people in the area, and we now offer referrals for counseling, nutrition, acupuncture, yoga, acupressure, massage, and meditation to augment the fertility treatments. Our Infertility Counseling Program is offered by Pressman and Associates (see article, page 21). They offer free educational seminars to our patients each month to help women and couples through the challenges of fertility treatments. Some of the seminar topics have been: • Dealing with the disappointment of a negative pregnancy test • Developing coping skills to reduce stress during fertility treatment • Handling changes in sexual intimacy during fertility treatment • Managing social obligations that require being around children • Talking to family and friends about fertility treatment. This past November, Pam Pressman offered a session on dealing with the coming holidays and how the stress of fertility treatment compounds the stress associated with the holidays. Their office is very close to our Marlton office and provides a confidential setting for those seeking support services, such as individual and couples counseling; group infertility counseling; biofeedback and hypnotherapy for stress management; and diagnostic evaluation for egg donor cycles. In addition, a board-registered dietitian, Mary Ellen DiMatteo, RD, helps patients to make lifestyle changes for balanced nutrition. She offers free nutrition programs, as well as detailed nutrition programs and one-on-one nutrition counseling for a fee. We also offer referrals to licensed acupuncturists who are experienced in female and male infertility. There is growing evidence that acupuncture has a positive impact on fertility. Specifically, acupuncture has been shown to: • Help regulate menstrual cycles
www.obgyn-infertility-nurse.com
At what stage do you recommend these services? Every new patient is given information on our balanced approach and the opportunities to take advantage of these resources. Throughout their treatment, we make reference to this support system and reach out to them if
I believe that stress definitely has an impact on patients’ approach to treatment. It affects how much they can handle and how far they will go with treatment. they are having a stressful day. We remind them that Pam is available for a one-on-one session, that a free seminar may be coming up that they may want to attend, or that they can take advantage of a meditation class with Ted. We hope to help ground them. Each patient will decide the best approach to augment her treatment. During the IVF lecture for patients, we explain that the treatment is
becoming more intense and now may be the time to consider these alternative approaches. During the embryo transfer, we play a CD in the transfer room with meditative music. In January we plan to expand our program again by sending the meditation CD home with each patient to play when they feel stressed. So stress could be an obstacle to treatment success? Yes. Many patients worry how much stress actually affects their overall success, which is a common thread in the medical literature. It is hard to measure its exact impact, but I believe that stress definitely has an impact on patients’ approach to treatment. It affects how much they can handle and how far they will go with treatment. It may possibly affect the overall treatment success. Our goal is to help them manage stress as they proceed on their journey to parenthood. What is involved in your role as a nurse practitioner? As nurse practitioners, Tracy Krause and I evaluate and treat patients in all 4 of our facilities. I coordinate the PGD program, and Tracy coordinates all third-party reproduction. As the nurse manager of SJFC, I oversee all the nursing and the medical assistant staff at all our facilities. I also coordinate the quarterly IVF protocol meetings with our physicians and the embryology staff, in which we review patient care protocols to maximize IVF success. Do fertility nurses get trained in stress management? Ted and Pam have both done in-services for our nursing staff to make them aware of how they can best approach these issues, the services Ted and Pam
(From left) back row: Tracy Hunter, CMA; Tammy Selwood, CMA; Lisa Mangini, CMA; Jennifer Bond, CMA; front row: Katrina Granger, CMA; Barbara Alice, RN, APN-C, MSN.
offer, and to help nurses acknowledge that this is a very stressful time in each patient’s life. It is important that nurses support the patients as much as they can, but they are not doing counseling themselves. They need to know what resources are available for the patients. If I am performing an ultrasound and the patient is expressing her frustration with treatment and is getting discouraged, I will take the extra time and talk to her about the resources that are available. I have even done a mini meditation session with the patient in the office. But our main goal is to encourage patients to take advantage of the alternative services we offer. Costs and insurance coverage must be other sources of stress? Obviously, fertility treatment can be very expensive. So for those who have coverage, a lot of stress is removed. For those who do not have insurance, it is clearly a source of additional stress. Many states today, including New Jersey, have mandatory insurance coverage for IVF.
15 States Mandate Fertility Coverage Arkansas California Connecticut Hawaii Illinois Louisiana Maryland Massachusetts Montana New Jersey New York Ohio Rhode Island Texas West Virginia New Jersey enacted the Family Building Act in 2001 that mandated that all New Jersey residents whose insurance is based in the state must be covered for fertility treatment. Each individual insurance policy may have exemptions to this coverage, and we encourage patients to check directly with their insurance carrier to verify coverage. Exemptions could include patient age or having had a previous tubal ligation. Those patients who conceive successfully often come back to have a second or third child. Many times patients have frozen embryos, making the treatment a lot easier and less expensive, which in turn is less stressful. ■
december 2009 I Vol 1, no 2
7
OBGYN_1209:OBGYN 12/10/09 5:53 PM Page 8
Clinic Spotlight Starting CAREN... Continued from page 1 • Duke Fertility • UNC Division of Reproductive Endocrinology and Fertility • North Carolina Center for Reproductive Medicine • Our own center—Carolina Conceptions. Why Start a Nurses Group? With 4 centers serving this small Triangle region, each with several nurses, embryologists, andrologists, and many medical assistants, the need for an organization to provide field-specific continuing education (CE) credits became increasingly apparent. It dawned on us that with current CE requirements for updating licensure in the state of North Carolina, it would be beneficial to establish an organization for nurses that could provide area-specific training to target the infertility patient population, with whom nurses like us deal with most often in their
practices. In addition, providing consistent printed materials for each patient rather than materials yielded by a Google search at 2 AM (because of a lack of sleep) has a clear advantage. These reasons did not require a second thought, but getting started required some organization. Getting Started Armed with resources made available to us by Columbia Laboratories and Mandell’s Pharmacy, a group of nurses from each of the 4 centers got involved in our efforts to establish our first dinner meeting, which also incorporated a brief presentation. The designated speaker had approved CE content and is credentialed to provide CE credits based on the infertility-specific approved topics. A total of 12 nurses attended our first meeting, which took place in April 2009 and was very well received.
Helping new nurses to get comfortable in this new environment and get acclimated sooner can reduce some of these difficulties for them.
practices. After all, providing education and resource information to the nursing staff ultimately benefits the patients. Having practiced in the areas of infertility and women’s health since 1997, I came to realize the demands of the task associated with bringing new nurses to the specialty field of infertility and of getting them “up and running” in this specific area of knowledge. Local Nurses Establish CAREN It could sometimes take months for the newly hired nurse to get comfortable in triage, with patient care, and to be able to provide the specific education necessary for this patient population. Helping new nurses to get comfortable in this new environment and get acclimated sooner can reduce some of these difficulties for them. Realizing the need for subspecialty education was one of the motivating factors for us in forming our group— Carolina Association of Reproductive Endocrinology Nurses (CAREN). Another factor, of course, was the benefit that such a group would have for us, the nurses, and our patients. The licensure accreditation was a great motivation, but establishing our organization also has the added bonus of being able to have resources and printed materials for our centers and to integrate these into our individual
Its success was also evident by our ability to get additional support from those in attendance to help launch CAREN. A second meeting took place in September 2009, and the number of attendees was twice as large. Ultimately, we intend to spread our base to include the entire state of North Carolina, but for now we have decided to focus on our local centers. Membership dues will officially be collected
Our embryologist, Heather Blackmon, performing intracystoplasmic sperm injection.
for the first time at our next meeting, in January 2010, although so far 10 members have already paid their membership fee. A holidays’ social evening that will not incorporate any educational topic is scheduled to take place before the end of the year. First Accomplishments While still in the fledgling state— this is only the first year of our organization—CAREN can already score a few accomplishments: • We have established a mission statement, which defines our goals: “Educating members regarding reproductive endocrinology and serving as a mentor for new nurses.” In addition, we are currently reviewing potential bylaws that were provided to us by a similar organization in New Jersey. • We will soon establish a financial account for handling membership dues, as well as to help offset expens-
Carolina Conceptions staff (left to right) back row: Leanne Ritter, CMA; Heather Blackmon, Embryologist; Mary Alice Goode, CRNA; Terry Hunter, RN; Susan Griffith; Angela Lovingood, RN; Michelle Roden; middle row: Sheridan Robinson; Angela Ashley; Elisa Miller, CMA; Tracy Coil, RN; Anthony Purter; Michelle Moyer, Embryologist; front row: John Park, MD; Grace Couchman, MD; Bill Meyer, MD.
es for meeting speakers, meals provided at meetings, and similar occasions. • We have consulted with an attorney regarding the incorporation of our group, but have decided to hold it off until we become better organized and grow in membership. • Our latest meeting in September included 25 nurses and ancillary care providers from the 4 centers in the area, as well as guests from our counterpart group in New Jersey. With a clear purpose in mind and a targeted population in need, we intend to move forward with strengthening the support network of our organization and increasing our base in 2010. Carolina Conceptions: The Baby Boom Open since 2006, Carolina Conceptions (www.carolinaconceptions.com) may be the new kid on the block, but the center has quickly garnered attention as the fastest growing infertility clinic in the Southeast. With more than 1000 pregnancies to date, the practice has been keeping the labor and delivery wards bustling thanks to some of the highest success rates not only in the region but in the country (Table). Although one of the newest infertility clinics in the country, Carolina Conceptions’ physicians are not strangers to the field itself. Together, Drs Bill Meyer, Grace Couchman, and John Park share more than 45 years’ experience in the infertility specialty. Our clinic is also the only private practice of its kind in the region in which all the physicians are board certified in OB/GYN and reproductive endocrinology and infertility. Committed to “Making Families a Reality,” as our motto states, the practice is at the forefront of innovative technologies this specialty has to offer. Our in-vitro fertilization (IVF) laboratory uses a 3-gas system to incubate Continued on page 9
8
december 2009 I Vol 1, no 2
www.obgyn-infertility-nurse.com
OBGYN_1209:OBGYN 12/10/09 5:53 PM Page 9
The OB/GYN Nurse
After the Miracle of Birth, Why Is She So Unhappy? The Toll of Postpartum Depression Debra Moynihan, WHNP-BC, MSN Carolina OB/GYN
M
any people find it hard to understand how a new mother could be depressed. She has created life and journeyed through one of the most rewarding experiences life could offer. According to the Centers for Disease Control and Prevention, the incidence of postpartum depression (PPD) in the United States is between 11.7% and 20.4%. Age or parity has no influence on the incidence of PPD. A woman can have no problems after the birth of her first 2 children and then experience PPD after the birth of her third child. PPD has no boundaries: it can be found in all races, cultures, and socioeconomic groups. Recognizing the Symptoms The symptoms of PPD are similar to those of most depressive disorders. Women will report episodes of tearfulness and feelings of sadness. They tend to lose interest in things that they once found pleasurable. They may also have feelings of guilt, shame, and helplessness. These feelings often intensify with time and can begin to interfere with activities of daily living. Changes in appetite and sleep disturbances lend themselves to increased irritability. Complaints of fatigue and poor concentration are common. But in addition to the usual symptoms of depression, the patient with PPD has a concern over ambivalent or
negative feelings toward her baby. The woman may be having thoughts of harming the baby or herself. She may express fear of being alone with the baby. These symptoms can appear anytime within the first year after delivery and will persist for more than 2 weeks, even for months. Risk Factors PPD is more likely to occur in women who have a personal or family history of psychiatric disorders than in other women. Studies have consistently
birth or a recent episode of stress, such as a death in the family or loss of a job. Other risk factors include: • Lack of social support • Adolescent mothers • Unplanned pregnancy • Previously infertile mothers • Women with a history of recurrent pregnancy loss • Mothers of infants requiring hospitalization after birth • Fetal anomalies • New mothers experiencing difficulty with breastfeeding.
A woman can have no problems after the birth of her first 2 children and then experience PPD after her third child. Nurses can make a difference by educating the patient and assisting her in setting up a support system. shown that women who experience depression or anxiety during pregnancy are at increased risk for developing PPD. The American College of Obstetricians and Gynecologists suggests that the treatment of depression during pregnancy must be individualized. If a woman is being treated with a selective serotonin reuptake inhibitor (SSRI) during pregnancy, tapering or discontinuing that medication is controversial. Continuing these medications should be considered as opposed to subjecting the patient to the risk of PPD. Other at-risk patients are women who have had PPD with a previous
Screening for PPD Prompt recognition and treatment of PPD is important, because this condition not only affects the patient but also her partner and infant. Those who experience PPD are at increased risk for substance abuse and are less likely to adhere to recommendations of their healthcare provider. Up to 50% of spouses of a wife who has PPD will also develop depression. Infants of mothers with PPD have demonstrated attachment difficulties and developmental delays. Some patients may voluntarily speak with their healthcare provider regarding their symptoms, whereas others may be
reluctant or embarrassed. Screening for PPD should be done on all patients when they come in for their postpartum visit, to identify PPD as early as possible. The Postpartum Depression Screening Scale and the Edinburgh Postnatal Depression Scale are among the most common screening tools. These questionnaires are completed by patients in the office and are used to identify PPD. Treatment Once the patient is diagnosed with PPD, treatment options should be discussed and initiated promptly. Psychotherapy is generally the first-line treatment, but in many cases this is cost prohibitive to the patient. Medications such as SSRIs or serotonin-norepinephrine reuptake in hibitors, even in generic forms, are usually affordable to the patient. The use of medication in combination with psychotherapy usually yields the best results. If the patient is severely depressed, she will most likely need to be referred to a mental health professional that specializes in major depressive disorders. The most important thing to remember when treating a woman with PPD is that she needs to understand that she is not “crazy.” PPD is a treatable condition. Nurses can make a difference by educating the patient and assisting her in setting up a support system that she can turn to when she feels overwhelmed. Even telephone support by a nurse has often proved helpful. With proper treatment options and cooperation of the patient, most women will recover and be able to enjoy their baby. ■
Starting CAREN... Continued from page 8
www.obgyn-infertility-nurse.com
Pregnancies
Table Pregnancy Rates per Embryo Transfer, Carolina Conceptions, 2006-2009 80%
8
70%
7
60%
6
50%
5
40%
4
30%
3
20%
2
10%
1
0%
< 35 (n = 128)
35-37 (n = 52)
Age, y
38-40 (n = 39)
>40 (n = 8)
Frozen embryos (n = 53)
Donor egg (n = 41)
0
Average number of embryos transferred
embryos instead of the standard 2-gas system still used in many laboratories. This approach decreases oxygen levels to create a more accurate representation of the woman’s reproductive system, and is believed to increase pregnancy rates. Other state-of-the-art treatments we offer include robotic surgery, oocyte cryopreservation, and on-site acupuncture services. We have also recently installed a Siemens Compact L arm to provide in-office hysterosalpingograms to our patients, as well as to other patients referred by the medical community at large. Behind every great physician is a great support staff, and that is no
exception at Carolina Conceptions. We have a highly trained and caring team of seasoned laboratory personnel, experienced infertility nurses, knowledgeable financial counselors, friendly administrative staff, and easy access to a reproductive urologist, infertility counselor, and acupuncturist. The 4 nurses at the clinic dedicate their attention to patients undergoing IVF and various forms of controlled ovarian hyperstimulation. My roles involve coordinating the Egg Donor Program (from donor recruitment and screening to education for donors and the recipient couple), as well as coordination of frozen embryo transfer cycles. ■
december 2009 I Vol 1, no 2
9
OBGYN_1209:OBGYN 12/10/09 5:53 PM Page 10
The OB/GYN Nurse
Postmenopausal Osteoporosis a Major Cause of Fractures Emerging Trends in Management By Wayne Kuznar
T Score and Fracture Risk The relationship between BMD T score and fracture risk is strong, said Dr Watts. Routine screening with a BMD test for osteoporosis should begin at age 65 years, and at age 60 if the woman weighs <70 kg, lacks estrogen, or has other risk factors for osteoporosis. The T score is the number of standard deviations below or above the average peak bone mass in young adults. Osteopenia (low bone mass) is defined as a T score between –1 and –2.5. Normal bone mass is up to 1 standard deviation below the normal mean. The World Health Organization (WHO) criterion for postmenopausal osteoporosis is a bone density of more than 2.5 standard deviations below the normal mean for young women, or a T score of –2.5 or less. Drug therapy is rarely indicated with T scores of –1.5 or better, and patients with a T score of –2.5 or below are sufficient candidates for drug treatment. “But considerable disagreement exists for patients between –1.5 and –2.5,” Dr Watts said. He noted that more than half of all fractures occur in women with
T scores that are better than –2.5. “It’s purely a numbers game,” because the number of women with T scores better than –2.5 is substantially greater than the number of women with T scores worse than –2.5, although the latter group is at higher risk of fracture. “We can’t afford to treat all women with a T score better than –2.5,” he said, so a strategy is needed to select those for treatment.
weight-bearing exercise (ie, walking or resistance exercises), stated Dr Watts. Calcium and Vitamin D Optimal calcium intake is 1200 mg/day from all sources. On average, women aged ≥50 years get only about 500 mg/day of calcium from their diet, “and therefore would benefit from a supplement on the order of 700 mg/day to 1000 mg/day,” Dr Watts said. There is
“Bone density remains our best tool for identifying patients with osteoporosis before they fracture, for determining the risk of fracture, and for monitoring the response to treatment.” —Nelson B. Watts, MD The National Osteoporosis Foundation updated its treatment guidelines for postmenopausal women in 2008, and now recommends pharmacotherapy for women with a previous hip or vertebral fracture; those with a T score of –2.5 or worse at the femoral neck (cervical hip), total hip, or spine; and those with low bone mass (T score between –1.0 and –2.5 at the femoral neck, total hip, or spine) who have a 10-year fracture risk of ≥3% at the hip or ≥20% for major osteoporosis-related fractures as assessed by FRAX (www. shef.ac.uk/FRAX). According to Dr Watts, “FRAX provides appropriate targeting of treatment; fewer younger patients who don’t have risk factors will be offered therapy, and older patients, or younger patients with higher risk, will be targeted.” The fundamental measures for bone health are calcium, vitamin D, and Table 1 Drugs Approved for Postmenopausal Osteoporosis Drug Prevention Treatment Estrogen √ Calcitonin √ Raloxifene √ √ Ibandronate √ √ Alendronate √ √ Risedronate √ √ Zoledronic √ √ acid Teriparatide √
no benefit to consuming >1500 mg/day calcium, and the safety of such amounts cannot be guaranteed. Vitamin D has important skeletal and extraskeletal effects and also has been shown to reduce the risk of falling among the elderly. Most people are vitamin D deficient, he said. The desirable range of 25-hydroxyvitamin D is blood levels between 30 ng/mL and 60 ng/mL; most women will require 1000 IU to 2000 IU of vitamin D daily to achieve this level. On average, adding 1000 IU/day of vitamin D will raise the blood level by 10 ng/mL. A safe upper level is 2000 IU/day. Drug Therapy Several medications are indicated for the treatment or prevention of postmenopausal osteoporosis (Table 1). Agents can be divided based on mechanism of action: antiresorptive versus anabolic.
Copyright 2009 iStockphoto LP.
O
steoporotic fractures in older women are more common than stroke, heart attack, and breast cancer combined, and thus screening, prevention, and treatment of this disease is critically important, said Nelson B. Watts, MD, Director, University of Cincinnati Bone Health and Osteoporosis Center, at the 2009 annual meeting of the American Society for Reproductive Medicine. The cost of treating fractures in 2005 was $16.9 billion. Some 1.4 million fractures occur annually in women 50 years or older; and about 75% of them are at nonvertebral sites. As defined by the National Institutes of Health, osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. “For now and for the foreseeable future, bone density remains our best tool for identifying patients with osteoporosis before they fracture, for determining the risk fracture, and for monitoring the response to treatment,” Dr Watts said. The technology used is central dual-energy x-ray absorptiometry, which measures bone mineral density (BMD) at the central skeletal spine and hip.
Femoral neck (cervical hip) fracture.
Antiresorptive agents change the balance of remodeling in favor of bone formation over resorption, “allowing you to keep more of the bone that you’re making,” Dr Watts explained. By slowing the process of remodeling, they also allow for improvement in the material properties of bone. They increase BMD and have a robust effect on reducing fracture risk. Evidence shows that all medications approved for fracture reduction lessen the risk of vertebral fracture, but only the bisphosphonates alendronate, risedronate, and zoledronic acid have been demonstrated to reduce the risk of nonvertebral fracture and hip fracture (Table 2). Oral vs intravenous bisphosphonates. Musculoskeletal pain, oversuppression of bone turnover, and osteonecrosis of the jaw with bisphosphonates have received considerable attention in the media, “but they appear to be extremely rare,” Dr Watts said. Osteonecrosis of the jaw is a problem for patients with cancer, who use intravenous bisphosphonate, but it is very rare for those taking oral bisphosphonates, he said. Long-term treatment of bisphosphonates appears to be safe for most patients. Lower-risk patients can probably take a drug holiday of 1 to 2 years after 5 years of treatment (consistent with data from the long-term extension of the Fracture Intervention
Table 2 Evidence for Fracture Reduction with Drug Therapy Drug Calcitonin Raloxifene Ibandronate Alendronate Risedronate Zoledronic acid Teriparatide
Vertebral fracture
Nonvertebral fracture
Hip fracture
√ √ √ √ √ √
No effect demonstrated No effect demonstrated No effect demonstrated Xa √ √
No effect demonstrated No effect demonstrated No effect demonstrated √ Xa √
√
√
No effect demonstrated
a
Evidence for an effect but not an approved indication. Continued on page 11
10
december 2009 I Vol 1, no 2
www.obgyn-infertility-nurse.com
OBGYN_1209:OBGYN 12/10/09 5:54 PM Page 11
The OB/GYN Nurse
Oral Glucose Tolerance Test Not Needed in Lean Women with PCOS By Wayne Kuznar
L
ean women with polycystic ovarian syndrome (PCOS) are unlikely to have impaired glucose tolerance or insulin resistance, reported Dale W. Stovall, MD, Professor of Obstetrics and Gynecology and Director, Division of Reproductive Endocrinology, University of Virginia, Charlottesville, at the 2009 American Society of Reproductive Medicine annual meeting. Dr Stovall and colleagues studied 78 women (age, 18-43 years) with a diagnosis of PCOS; all weighed ≤113 kg and had a fasting blood glucose level of <126 mg/dL. Serum glucose levels and insulin levels were measured at baseline and again at 30 minutes, 60 minutes, 90 minutes, and 120 minutes after a 75-g glucose load. None of the women were
being treated with oral hypoglycemic agents or with hormonal contraceptives for their PCOS. Lean woman was defined as a body mass index (BMI) <25 g/m2. None of
of insulin resistance, but age was not. Based on these findings, Dr Stovall said that “it is unnecessary to perform a 2-hour oral glucose tolerance test in lean women with PCOS for the assess-
“It is unnecessary to perform a 2-hour oral glucose tolerance test in lean women with PCOS for the assessment of either insulin resistance or impaired glucose tolerance, if their fasting blood glucose is <126 mg/dL.” —Dale W. Stovall, MD the lean women had impaired glucose tolerance or insulin resistance; in contrast, 15% of the non-lean women had insulin resistance (but none had impaired glucose tolerance). In this study, BMI level was found to be a significant independent predictor
ment of either insulin resistance or impaired glucose tolerance if their fasting blood glucose is <126 mg/dL.” This supports previous practice guidelines at his institution. In another study, elevations in serum levels of alanine aminotransferase
(ALT) were found to correlate independently with the severity of insulin resistance in women with PCOS, said researchers at Texas Tech University Health Science Center, Amarillo. They studied 45 women with PCOS who underwent oral glucose tolerance tests. BMI, free androgen index, and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Insulin resistance, as determined using HOMA-IR, was the only factor that was associated with serum ALT concentration when controlling for age, BMI, androgen levels, and other metabolic factors. ■ See also Drug Therapy for PCOS, page 17.
Combination Therapy Better than Monotherapy for Postmenopausal Osteoporosis in Women with Other Risk Factors By Alice Goodman
T
he combination of a drug that builds bone, teriparatide (Forteo), with a drug that prevents bone resorption, zoledronic acid (Zometa), may be better than either drug alone in postmenopausal women with osteoporosis plus rheumatoid arthritis, according to results of a study presented at the American College of Rheumatology/Alliance for Human Research Protection 2009 meeting. Combination treatment with the once-yearly injection of the bisphosphonate zoledronic acid and the parathyroid hormone teriparatide showed modest, but more rapid, increases in bone mineral density
(BMD) levels at the spine and hip compared with either drug alone. “The combination of zoledronic acid
“The combination of zoledronic acid and teriparatide can be considered in selected high-risk patients, including those with low hip BMD, previous fractures, and rheumatoid arthritis, and other serious conditions where we want to achieve a more rapid response.” —Kenneth Saag, MD
and teriparatide can be considered in selected high-risk patients, including
Postmenopausal Osteoporosis... Continued from page 10
Trial), whereas higher-risk patients should probably continue treatment for 10 years, and then consider a 1- to 2-year holiday. Parathyroid hormone. Intermittent injections of parathyroid hormone (teriparatide) improve bone microarchitecture and increase spine BMD dramatically—3 times as much as bisphosphonates. It has been demonstrated to reduce the incidence of vertebral and nonvertebral fractures but not hip
www.obgyn-infertility-nurse.com
those with low hip BMD, previous fractures, and rheumatoid arthritis, and other serious conditions where we want
fracture. Given its greater expense compared with other agents for the treatment of osteoporosis and its more difficult administration, teriperatide should be reserved for patients with severe osteoporosis, “or those losing ground on bisphosphonate therapy,” according to Dr Watts. Its use has been approved for up to 2 years, because an increased risk for bone cancer has been associated with teriparatide in animal studies. ■
to achieve a more rapid response,” said Kenneth Saag, MD, Jane Knight Lowe Professor of Medicine, University of Alabama, Birmingham. Previous studies of the combination of alendronate (Fosamax)—a less potent bisphosphonate than zoledronic acid— and teriparatide showed no improvement in BMD in postmenopausal women, presumably because the more frequent dosing of alendronate suppressed new bone formation. This new study suggests that the once-yearly treatment with zoledronic acid does not inhibit the bone-forming effects of teriparatide. This 1-year, partial double-blind study included 412 postmenopausal women (age >65 years) with osteoporo-
sis or osteopenia and 1 previous bone fracture. Patients were randomized to receive 1 intravenous injection of 5 mg zoledronic acid on day 1, plus subcutaneous teriparatide 20 mg/day versus either agent alone at the same doses. At week 52, increase in spine BMD was similar for the combination and for teriparatide alone (7.51% and 7.05%, respectively) compared with an increase of 4.37% in the zoledronic acid arm (P <.001 for combination vs teriparatide or zoledronic acid alone). In addition, the combination therapy and zoledronic acid alone significantly increased total hip BMD at 52 weeks compared with teriparatide alone (P <.005). However, Dr Saag said that the combination therapy achieved faster increases in BMD than either drug alone, based on BMD measurements taken at different intervals. The radiographic results of the study have not yet been analyzed; this analysis, expected later this year, will determine the actual effects of these 3 treatment arms on erosive joint damage. BMD is a surrogate end point for fracture rates, and this study was too small to show a significant difference in fracture rate. No significant differences in deaths, serious adverse events, or study discontinuations because of adverse events were reported for any of the 3 arms. ■
december 2009 I Vol 1, no 2
11
OBGYN_1209:OBGYN 12/10/09 5:54 PM Page 12
The OB/GYN Nurse
Hypoactive Sexual Desire Disorder in Women: Approved Therapies Are Limited Hormonal Options Include Vaginal Estrogen, Oral/Intramuscular Testosterone By Wayne Kuznar
D
ealing with low sexual desire in women remains a challenge for patients and for clinicians, with most options currently limited to hormonal therapies, based on the assumption that hypoactive sexual desire disorder (HSDD) in women is often linked to low sex hormone levels. The causes for HSDD are complex, including physiologic as well as emotional etiologies. At a recent conference on female sexuality at the Cleveland Clinic, Holly L. Thacker, MD, FACP, Director, Center for Women’s Specialized Health at the Cleveland Clinic, discussed the various hormonal options available for women with HSDD.
Low-Dose Vaginal Estrogen In women with HSDD and vaginal atrophy in whom nonohormonal options have failed to reverse atrophic changes and relieve symptoms, lowdose prescription vaginal estrogen is an effective and well-tolerated therapy, according to Dr Thacker. By the time a woman presents to her physician with vaginal atrophy, she has likely already tried nonhormonal vaginal lubricants and moisturizers. For these women, several low-dose, local vaginal estrogen products are currently approved by the Food and Drug Administration. “Vaginal estrogen is the female ‘Viagra’ equivalent, because vaginal estrogen improves blood flow to the genitals in women,” Dr Thacker said. “I can’t emphasize enough that estrogen therapy is required for most symptomatic vaginal atrophy. It is the only thing that restores the integrity of the vagina.” Systemic absorption of vaginal estrogen products is very limited, and all products appear to be equally effective for the treatment of vaginal atrophy at the doses recommended. The choice of treatment “depends on primarily patient preference as well as your clinical judgment,” in addition to the cost, she said. When using low-dose vaginal estrogen, concomitant use of progestogen is generally not indicated in women with an intact uterus. The duration of vaginal estrogen therapy should be based on the presence of distressful symptoms.
Endometrial Surveillance The data are insufficient to recommend annual endometrial surveillance in asymptomatic women who use low-
12
december 2009 I Vol 1, no 2
dose vaginal estrogen, although certain patients may require closer surveillance. These include women at high risk for endometrial cancer, those who use a greater dose of vaginal estrogen, and those who have symptoms such as spotting or breakthrough bleeding.
ty of testosterone in women with intact uterus who are not using concomitant estrogen. Testosterone gets aromatized to estradiol, reminded Dr Thacker, “so if you have a uterus and you’re given some estradiol, not directly but indirectly, you have to still worry about it.”
“Vaginal estrogen is the female ‘Viagra’ equivalent, because vaginal estrogen improves blood flow to the genitals in women….I can’t emphasize enough that estrogen therapy is required for most symptomatic vaginal atrophy.” —Holly L. Thacker, MD Cancer Therapy and Vaginal Atrophy Cancer therapy affects female hormone levels and often results in vaginal atrophy, which can cause sexual difficulties later on for the woman. For women who are treated for a non–hormone-dependent cancer, “I like to start vaginal estrogen therapy before they get atrophic on their cancer therapy,” Dr Thacker said. “We see so many breast cancer survivors who are put on aromatase inhibitors that wiped out cellular estrogen, and we see a lot of cases of severe vaginal atrophy in otherwise healthy people. I like to intervene before they get to that stage, if possible.”
Contraindications to testosterone are similar to those to estrogen therapy. Appropriate Testing Laboratory testing of testosterone levels should not be used to diagnose testosterone deficiency, only to monitor for supraphysiologic levels before and during testosterone therapy. “Salivary levels are not validated and are a waste of time,” said Dr Thacker. “It’s not what’s in your spit that matters but what’s inside your tissues.” The free testosterone index is the simplest and most readily available clinical estimate of free testosterone. It
“Start vaginal estrogen therapy before they get atrophic on their cancer therapy….We see so many breast cancer survivors who are put on aromatase inhibitors that wiped out cellular estrogen.” —Holly L. Thacker, MD
Testosterone Therapy Testosterone therapy may be an option for women who present with symptoms of decreased sexual desire associated with emotional distress and who have no other identifiable cause for their sexual concerns, Dr Thacker suggests. Testosterone therapy without concomitant estrogen therapy is not recommended, according to the North Ameri can Menopause Society, although the APHRODITES study (N Engl J Med. 2008;359:2005-2007) demonstrated that testosterone alone improves sexual function. There are no data on the safe-
is calculated from total testosterone and serum hormone-binding globulin. Before initiating testosterone therapy, baseline levels for lipids and liver function tests should be established, she advised, and consider retesting at 3 months. IM Formulations Only oral and intramuscular (IM) testosterone products are approved for use in women in the United States. The IM formulation carries the risk of excessive dosing in women, but so do the testosterone products formulated for men. ■
New Drug for Low Sexual Desire in Women The treatment of low sexual desire in women has puzzled experts involved in women’s health and sexuality ever since Viagra (sildenafil citrate) first took the American sexuality scene by storm in treating erectile dysfunction. At the time, sexuality experts had hoped that it would also prove beneficial for women with sexual dysfunction, specifically those with hypoactive sexual desire disorder (HSDD). But large clinical trials failed to show such benefits. Now, an investigational drug targeting HSDD in women may offer a new direction for treating this condition. Known as flibanserin, the drug is being developed by Boehringer Ingelheim and is awaiting FDA review. Flibanserin represents a departure from current hormonal therapies used for the treatment of HSDD in women, or from Viagra, which works by boosting the body’s blood flow, including to the genital area (a crucial mechanism in men’s erectile function). Flibanserin is a nonhormonal medication that activates neurotransmitters in the brain. The brain (in addition to sex hormones) is considered central to sexual response, especially in women. Flibanserin is a serotonin 2A receptor antagonist and serotonin 1A agonist and dopamine D4 receptor, which was originally investigated as an antidepressant. Although it failed to reduce depressive symptoms, it showed unexpected benefits in increasing sexual desire in women. According to John Thorp, MD, University of North Caroline at Chapel Hill, results from clinical trials with flibanserin provide the first evidence that targeting the central nervous system can successfully treat sexual dysfunction in women. If approved, flibanserin may provide the first true help for the many women with HSDD.
Share Your Questions with Colleagues We invite you to share your professional questions with your colleagues and have them discussed in the pages of The OB/GYN and Infertility Nurse. Fax: 732-656-7938.
www.obgyn-infertility-nurse.com
OBGYN_1209:OBGYN 12/10/09 5:54 PM Page 13
Infectious Diseases
Seasonal Flu Vaccine in Pregnant Women Protects Fetus/Infant Reduces Low Birth Weight Rates and Prematurity By Alice Goodman
A
t the 2009 Infectious Diseases Society of America annual meeting, 3 separate studies demonstrated that seasonal flu immunization of pregnant women also protects their fetuses and infants. Infants whose mothers received the seasonal flu vaccine had reduced rates of flu-related hospitalizations, prematurity, and low birth weight. These findings add to the substantial evidence for maternal and infant benefits from the seasonal flu vaccine. Infectious diseases experts expressed deep concern about the dismal rate of vaccinations among pregnant women in the United States. Currently, fewer than 1 of 4 pregnant women get the vaccine. Many experts blame the low rates of maternal immunizations on perceived fears that vaccines can cause autism, which have been exacerbated by media coverage. “Mothers don’t want to take anything that they think will harm the baby, but it is clear that the virus is far more harmful than the vaccine,” said Paul Offit, MD, Director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.
nificant difference. Flu-related hospitalization was prevented in 85.3% of infants younger than 6 months old whose mothers were vaccinated. Reduced Prematurity and Low Birth Weight A second study showed that mothers who were vaccinated against seasonal flu gave birth to infants with reduced rates of prematurity and low birth weight compared with unvaccinated mothers. The study was based in the Georgia Pregnancy Risk Assessment Monitoring System from June 2004 through September 2006. Of the 6140 live births during that period, 921 (15%) of the pregnant women received the flu vaccine. Infants born to vaccinated mothers at the peak of the flu season were: • 70% less likely to be premature • 60% less likely to have low birth weight.
Infants born to vaccinated mothers in the period of least flu activity were: • 50% less likely to be premature • 30% less likely to be of low birth weight. Birth Weight: Flu vs Pneumococcal Vaccine A subanalysis of a large randomized controlled study conducted in Bangladesh demonstrated that mothers who got the seasonal flu vaccine in the third trimester of pregnancy gave birth to infants who weighed approximately 0.5 lb more compared with mothers who got the pneumococcal vaccine. “These are unique and robust data from a randomized controlled trial showing a beneficial effect of the flu vaccine on the fetus,” said Mark C. Steinhoff, MD, Cincinnati Children’s Medical Center, Ohio. A total of 340 pregnant women were randomized to receive the inactivated
seasonal flu vaccine or the pneumococcal vaccine (ie, controls) during the flu season. Infants of mothers who got the flu vaccine had a 50% reduction of
“The flu vaccine is not approved for infants under 6 months old, yet these are the most vulnerable children. ” —Marietta Vázquez, MD
febrile respiratory illness and a mean birth weight that was 214 g higher compared with those whose mother got the pneumococcal vaccine. The percentage of small, low birth weight infants was 17% in infants born to mothers who got the flu vaccine compared with 41% in the controls, a significant difference. ■
“Mothers don’t want to take anything that they think will harm the baby, but it is clear that the virus is far more harmful than the vaccine.” —Paul Offit, MD
Dr Offit and colleagues note that obstetrician/gynecologists should be more proactive in offering immunization to pregnant patients, including the seasonal flu and H1N1 vaccine. Fewer Infant Hospitalizations In one study, maternal seasonal flu vaccine was effective in preventing flurelated hospitalizations in infants. “The flu vaccine is not approved for infants under 6 months old, yet these are the most vulnerable children. This study suggests that the maternal flu vaccine can prevent very young infants from getting really sick with the flu,” said Marietta Vázquez, MD, Yale University School of Medicine. The study included 119 infants up to 12 months old hospitalized with flu and 172 matched controls hospitalized without the flu. A total of 5% of infants with flu compared with 16% of the controls (without flu) had mothers who received the flu vaccine during pregnancy, a sig-
www.obgyn-infertility-nurse.com
WISHES TO THANK Gold Founding Member Supporter Columbia Laboratories, Inc.
We thank you for your support and commitment to the academy
december 2009 I Vol 1, no 2
13
OBGYN_1209:OBGYN 12/10/09 5:55 PM Page 14
Pharmacy Corner
Prescription Prenatal Vitamin Supplementation @Copyright iStockphotos.com/drbouz
Not All Supplements Are Created Equal Sandra Fernandez, RPh, PharmD Pharmacist, Mandell’s Clinical Pharmacy, Somerset, NJ
P
renatal vitamin supplements are intended to be taken by women of childbearing age before, during, and after pregnancy to provide
them the nutrients they need to ensure proper fetal growth and development. These vitamins are formulated to provide expectant mothers and the fetus
with the key nutrients that women may not be getting from their diet. Although similar to most standard adult multivitamins, prenatal vitamin
Table Characteristics of US Prescription Prenatal Vitamins Stool Kosher Brand name Folic acida Irona Calciuma DHA softener certified Chewable Other components Advanced NatalCare √ √ √ √ √ Advanced-RF NatalCare √ √ √ √ √ Cal-Nate √ √ √ √ CareNatal DHA √ √ √ √ CitraNatal Assure √ √ √ √ √ Life’s DHAb CitraNatal DHA √ √ √ √ √ Life’s DHAb CitraNatal 90 DHA √ √ √ √ √ Life’s DHAb CompleteNate Chewable √ √ √ Wildberry flavor Duet DHA with Ferrazone √ √ √ √ Enteric-coated DHA softgel Duet Chewable √ √ √ √ Citrus flavor Gesticare √ √ √ Gesticare DHA √ √ √ √ Life’s DHAb NataChew √ √ √ Wildberry flavor Natafort √ √ Natelle-ez √ √ √ Natelle Plus w/DHA √ √ √ √ Life’s DHAb Neevo √ √ √ Lactose, yeast, and gluten free Neevo DHA √ √ √ √ √ Life’s DHAb NutriNate Chewable √ √ √ √ Wildberry flavor OB Complete √ √ OB Complete DHA √ √ √ OB NatalOne √ √ √ √ Prefera OB √ √ Prenatal Plus √ √ √ Prenate DHA √ √ √ √ Prenate Elite √ √ √ Select OB √ √ √ Mixed berry flavor Lactose, gluten, and iodine free Select OB DHA √ √ √ √ Natural berry-flavored caplet; orange-flavored DHA gelcap Lactose, gluten, and fishbyproduct free Life’s DHAb Ultra NatalCare √ √ √ √ √ Vitafol OB
√
√
√
Vitafol OB + DHA
√
√
√
a
√
Gluten, lactose, iodine, and sugar free Orange-flavored DHA capsule (to avoid aftertaste) Gluten, lactose, iodine, and sugar free Life’s DHAb
The following components of folic acid, iron, and calcium may appear in any of the products in this table: calcium carbonate, calcium citrate, carbonyl iron, docusate sodium, sodium feredetate, bis-glycine chelate, ferronyl iron, ferrous bis-glycinate, ferrous(II) bis-glycinate chelate, ferrous fumarate, ferrous gluconate, ferrous sodium, ferrous sulfate, heme iron polypeptide, calcium L-methylfolate, polysaccharide iron complex, tricalcium phosphate. b Life’s DHA from algae is a vegetarian source of DHA. It is produced, from start to finish, in an FDA-inspected facility, with controls in place to ensure the highest quality. Because it is not derived from fish, there is no risk of ocean-borne pollutants. Life’s DHA comes from a source that has not been genetically modified and is both Kosher and Halal. Life’s DHA is approved by the FDA for use in infant formulas and is the only DHA currently used in US infant formulas. Note: Call your pharmacy to be sure that the specific prenatal supplement prescribed to your patient is still available; manufacturers are constantly reformulating their vitamins based on newly published data. Ask your pharmacist for specifications on doses and salt forms if you are concerned with particular criteria. DHA indicates docosahexaenoic acid. Source: http://www.lifesdha.com/Pregnant-and-Nursing-Women/About-lifesDHA-.aspx.
14
december 2009 I Vol 1, no 2
supplements contain higher concentrations of folic acid, calcium, and iron, which are the most important nutrients for expectant mothers. Over-the-counter (OTC) prenatal vitamins differ from prescription prenatal vitamins in that they are typically manufactured with lower doses of both folic acid and iron and are not required to adhere to safety and efficacy regulations by the Food and Drug Administration (FDA).
The latest trend in prescription prenatal vitamins is to include DHA, an omega-3 fatty acid essential for infant brain, eye, and nervous system development. Because OTC supplements are not monitored by the FDA, some of them contain extra ingredients, such as herbs, that are claimed to support reproductive health and are not found in prescription formulations. Women should consult their healthcare provider or pharmacist when choosing an OTC prenatal vitamin, because some of the herbs have been shown to be unsafe in pregnancy. The latest trend in prescription prenatal formulations is to include docosahexaenoic acid (DHA), an omega-3 fatty acid that is essential for optimal infant brain, eye, and nervous system development. Because fish is a primary source of DHA, and pregnant women are often instructed to limit their intake of fish, which has high content of mercury, many pregnant women are deficient in DHA. For this reason, DHA supplementation during pregnancy ensures the availability of this vital nutrient to the fetus, thereby supporting healthy fetal growth and development. Prenatal vitamins are available in different types (Table). When choosing a prenatal vitamin to prescribe, there are many factors that healthcare professionals should consider, such as cost, ingredients, and the patient’s needs. Nurses and physicians should always keep in mind that a specific prenatal vitamin supplement that is best for one woman may not be the best choice for another woman. ■
www.obgyn-infertility-nurse.com
OBGYN_1209:OBGYN 12/10/09 5:55 PM Page 15
2009 ASRM Highlights THE NURSES PROFESSIONAL GROUP The following articles focus on nurses’ presentations at the American Society of Reproductive Medicine (ASRM) annual meeting.
Predictors of Low Birth Weight in Singleton Pregnancies Identified But No Effect on Preterm Delivery Rates By Wayne Kuznar
W
omen conceiving a singleton pregnancy who have a history of infertility and undergo infertility treatment were found to have an increased risk of delivering a low birth weight (LBW) baby, defined as <2500 g, said Loretta Camarano, RN, PhD, Clinical Nurse Manager, Fertility Physicians of Northern California, and Assistant Professor, School of Nursing, University of California, San Francisco, at the ASRM. However, no increased risk for preterm babies was found. This retrospective cohort study, Dr Camarano said, does not implicate infertility treatments but rather highlights differences in health status between women with a history of infertility who undergo infertility treatment, those with a history of infertility who conceive without treatment, and fertile women. Her team’s research, conducted at 11 infertility clinics in northern California, had 2 principal goals. The first was to identify differences in health status, index pregnancy conditions, and the risks of preterm delivery or LBW between 3 groups of women: (1) fertile women who conceive spontaneously, (2) women with a history of infertility who conceive without treat-
ment, and (3) women with a history of infertility who use infertility treatment to continue pregnancy. The second goal was to determine whether there is a relationship between fertility conception status, LBW, and preterm delivery when controlling for maternal age, parity, gestational diabetes, and obesity.
The risk of delivering a low birth weight baby increased by 55% with infertility treatment resulting in a singleton pregnancy; however, “We did not find a difference in preterm delivery rates between the groups.” —Loretta Camarano, RN, PhD
Of the 983 women in the study who carried singleton pregnancies to ≥20 weeks gestation, 44% conceived naturally after a history of infertility and 55% conceived using either ovulationinducing medications, intrauterine insemination, or in-vitro fertilization/
intracytoplasmic sperm injection. The comparator group included 1008 fertile women who were matched on singleton status, maternal age, and county of delivery. In pregnancies not associated with multiple births, LBW occurred in: • 10.8% of women with a history of infertility who underwent infertility treatment • 8.6% in women with a history of infertility who conceived naturally • 6.4% in the fertile comparators. Independent predictors of LBW were (1) undergoing infertility treatment, which increased the risk by 55%, and (2) nulliparity, which increased the risk by 51%. However, the effect size of these 2 predictors was small, said Dr Camarano, barely achieving significance. She noted that, “We did not find a difference in preterm delivery rates between the groups.” Preterm delivery, defined as <37 weeks gestation, occurred at a rate of 6.6% in fertile women and 8.1% in women with a history of infertility who received infertility treatment. Differences in Health Status Almost 6% of the women with a his-
tory of infertility who underwent infertility treatment were obese—significantly more than the rate of obesity in the other 2 groups. There was no difference between the groups in the history of other health measures. But, Dr Camarano noted, “We did find a few more differences between the groups in index pregnancy conditions.” Some 29% of the women with a history of infertility who underwent infertility treatment were nulligravida, and 60% were nulliparous—both significantly higher than in the other 2 groups. That group also developed gestational diabetes significantly more often than the fertile women or those with a history of infertility who conceived naturally. Women with a history of infertility who underwent infertility treatment had a lower rate of smoking and alcohol consumption during the index pregnancy than the other groups. There were no differences between the groups in the rates of neonatal sepsis or fetal or neonatal death. Dr Camarano’s team will next attempt to identify if any particular infertility treatment was associated with an increased risk for delivering a LBW infant. ■
Young Women with Low Ovarian Reserve Still Have 40% Chance of Conceiving omen age ≤35 years with a diagnosis of diminished ovarian reserve (DOR) still have a 40% chance of conceiving with fertility treatments (clomiphene citrate and gonadotropin hormone), according to data presented at ASRM by Kriston Ward, MS, RN, NP-C, Adult Nurse Practitioner at Strong Fertility Center, Rochester Medical Center, NY. “Care providers can offer some reassurance to this patient population that they have a reasonable chance of conceiving,” said Ms Ward. “They therefore may decide to go forward with fertility treatments.” Women older than age 35 with a diagnosis of DOR did not fare as well, however. In a retrospective chart review of
W
www.obgyn-infertility-nurse.com
women presenting to Strong Fertility Center from 2003 to 2007, Ms Ward compared pregnancy outcomes in women with DOR between 52 women age
cessful pregnancy outcome. Pregnancy rates were 69% with follicle-stimulating hormone (FSH), 25% with clomiphene, and 6% with natural cycles. Contrary
“Care providers can offer some reassurance to this patient population that they have a reasonable chance of conceiving….Putting it into perspective, you have this diagnosis, but your age is working for you.” — Kriston Ward, MS, RN, NP-C
≤35 years and 201 women age >35 years. Overall, 21 of the 52 women (40%) in the younger group, age ≤3, had a suc-
to published literature, the rate of miscarriage was not high, said Ms Ward. Only 2 women (4%) in that age group
had a pregnancy loss. In contrast, only 46 of the 201 (23%) women age >35 years had a successful pregnancy, and 20 (10%) of them had pregnancy loss. In this age group, pregnancy rates were 39% with clomiphene, 58% with FSH, and 3% with natural cycles. “A diagnosis of DOR is a pretty hard diagnosis for younger women. I did the study so that I could tell them that even though you have this diagnosis, your chances of conceiving are still pretty good, especially when compared with their older counterparts, and I have the data to support that statement,” said Ms Ward. “Putting it into perspective, you have this diagnosis, but your age is working for you.”—W.K. ■
december 2009 I Vol 1, no 2
15
OBGYN_1209:OBGYN 12/10/09 5:55 PM Page 16
2009 ASRM Highlights
Switching from IM to Oral/Vaginal Progesterone Regimen Maintains ART Success By Wayne Kuznar
N
ew findings from a retrospective analysis presented at ASRM show that switching from intramuscular (IM) progesterone to a combination of oral/vaginal progesterone for the luteal phase support does not diminish the success rate of assisted reproductive technologies (ART), said Jenessa Klein, RN, BSN, of Reproductive Medicine Associates of New York. Previous studies have shown that corpus luteum function may be deficient in patients who undergo oocyte aspiration, and that progesterone supplementation may decrease pregnancy loss. Progesterone supplementation comes in various forms, only some of which are approved by the Food and Drug Administration (FDA) for use in in-vitro fertilization (IVF) cycles. In their clinic, said Ms Klein, it is the practice to use IM progesterone to support the luteal phase, but no data have supported this use. The most frequently used form of progesterone for IVF is IM progesterone in oil base, but IM progesterone is associated with patient complaints, including injection-site soreness and redness, infection, cyst formation
from accumulation of progesterone, muscle soreness, the inability to inject oneself or find somebody to give the injection, and sciatic injury. Many of these complaints make tolerating long courses of progesterone
pounded suppositories, tablets that contain micronized progesterone (manufactured principally for oral use), an 8% progesterone gel, or a micronized progesterone vaginal insert. Only the 8% gel and vaginal inserts are approved by the FDA for luteal-phase support in IVF cycles.
“We can assure patients who have to switch from the IM to the oral/vaginal form…that switching will not diminish the effect [of progesterone]…and may increase satisfaction with the IVF process.” —Jenessa Klein, RN, BSN
therapy difficult and can lead to patient dissatisfaction and many office visits to examine the injection site or to review the injection technique, which increase demands on the nursing staff, according to Ms Klein. The goal of this study was to provide some evidence-based information for clinicians and patients. Oral progesterone is poorly absorbed, unless it is micronized in oil, and its use has not been approved for use in ART. Vaginal delivery of progesterone, which is also used in IVF cycles, can be administered using com-
New Findings In this analysis, Ms Klein’s group compared outcomes between 3 groups of patients in their practice: (1) those who had used only IM progesterone (n = 20), (2) those who used only oral/vaginal progesterone (8% gel) supplementation (n = 12), and (3) those who switched from IM injection to combination of oral/vaginal delivery (n = 9). The analysis included 41 IVF cycles. IM progesterone replacement consisted of a 50-mg daily dose solubilized
in water. Oral/vaginal progesterone was supplied as 100 mg of oral micronized progesterone taken 4 times daily and 100 mg of vaginal progesterone suppositories used twice daily. The rates of clinical pregnancy/pregnancy loss were not significantly different between the 3 groups: • IM progesterone: 50% (10/20) pregnancy; 25% (2/10) loss • Oral/vaginal: 66% (8/12) pregnancy; 12.5% (1/8) loss • IM to oral/vaginal: 89% (8/9) pregnancy; 25% (2/8) loss. Bleeding occurred more with the IM to oral/vaginal progesterone regimen (33%) compared with the oral/vaginal progesterone only (8%); no bleeding occurred with IM progesterone only. “We can assure patients who have to switch from the IM to the oral/vaginal form due to complications or inability to tolerate the medication or inject oneself, that switching will not diminish the effect [of progesterone]…and may increase satisfaction with the IVF process,” Ms Klein said. She added that, “The live birth rate was nearly identical in one study in which intravaginal and IM progesterone were compared during pregnancy.” ■
ASRM Releases New Guidelines on Number of Embryos to Transfer
O
n October 19, 2009, the first day of its annual meeting, the American Society of Reproductive Medicine (ASRM) released the newly revised guidelines on the number of embryos to transfer with in-vitro fertilization (IVF) cycles. The guidelines were developed by ASRM and by the Society for Assisted Reproductive Technology (SART). The ASRM first published guidelines for embryo transfer more than a decade ago.
“This latest revision is our most recent effort to help our members provide their patients with the best, safest care possible.” —R. Dale McClure, MD
The new guidelines represent an ongoing effort to limit the number of embryos transferred in IVF cycles to reduce the number of pregnancies with multiple births, which are becoming prevalent with the rise in IVF procedures performed throughout the country.
16
december 2009 I Vol 1, no 2
The guidelines say that regardless of the patient prognosis, only 1 more embryo than the number suggested in the guidelines should be transferred in any patient. They advise fertility clinicians that pregnancies with multiples (≥3 implanted embryos) are an undesirable consequence of IVF technologies and can result in complications to fetus and to mother. Furthermore, fetal reduction carries its own risks for the other fetuses as well as for the mother. Fertility clinics are now encouraged to collect their own data on embryo transfers. Programs with high-order multiple pregnancies >2 standard deviations above the mean rate for SART reporting clinics for 2 years may be audited by SART. In addition, patients must be advised on the risks associated with pregnancies with multiple embryos/fetuses, and all exceptions from the guidelines and counseling should be signed by patients and documented in the patient’s records. The following recommendations indicate the number of embryos to transfer, which vary according to the woman’s prognosis:
• 1-2 for women age <35 yrs • 2-3 for women age 35-37 yrs • 2-4 for women age 38-40 yrs • 3-5 for women age 41-42 yrs. Commenting on the new guidelines, R. Dale McClure, MD, President of ASRM, said, “It is clear that these guidelines have a terrific impact on clinical practice. Over the years we have seen a reduction in the number of high-order multiple births while main-
taining strong success rates. This latest revision is our most recent effort to help our members provide their patients with the best, safest care possible.” The new guidelines were published in November in Fertility and Sterility (2009;92:1518-1519). ■ See also Pregnancies with Multiples, page 20.
Our Booth at ASRM.
www.obgyn-infertility-nurse.com
OBGYN_1209:OBGYN 12/10/09 5:55 PM Page 17
Reproductive Medicine
Drug Therapy for Women with Polycystic Ovarian Syndrome Aaron S. Lifchez, MD, and Sue Jasulaitis, RN, MS Dr Lifchez is Clinical Assistant Professor, University of Illinois, Chicago, and Medical Director, Fertility Centers of Illinois, Center for Collaborative Reproduction; Ms Jasulaitis is Clinical Research Manager, Fertility Centers of Illinois, Chicago
See also Glucose Tolerance Test in PCOS, page 11.
I
n October we discussed the diagnosis and lifestyle recommendations for women with polycystic ovarian syndrome (PCOS), a serious medical condition with important reproductive implications. This article focuses on the many drug options for PCOS, highlighting the correct use of each drug class. Because patients are at risk for impaired glucose tolerance and other complications, including elevated lipid levels, type 2 diabetes, hypertension, and obesity, the treatment of PCOS is centered on controlling insulin function and correcting reproductive problems. Controlling insulin function aims at reducing the risk for diabetes, thereby also improving reproductive function. Drug Options for PCOS Many medications are used for the treatment of PCOS. Although treatment is directed at the symptoms of PCOS (such as irregular menstrual periods or hirsutism) rather than infertility, many of the treatments can also improve fertility. Oral Contraceptives Oral contraceptives (OCs) are often the first line of treatment for women who have irregular menstruation or hirsutism who are not interested in pregnancy at that time. OCs will regulate their menstruation and can also protect against endometrial carcinoma. In addition, OCs can improve fertility by reducing the production of ovarian androgens and the production of male sex hormone–binding globulin by the liver, thereby decreasing the level of circulating androgens.
Antiandrogens Antiandrogens work by blocking the androgen receptors, competing for androgen-binding sites on the cell’s surface, or blocking the production of androgens. Antiandrogens are typically slow to produce results, and improvement is often not seen for 6 to 9 months. These agents are contraindicated in pregnancy and have not yet been approved by the Food and Drug Administration (FDA) for the treatment of symptoms of PCOS, such as hirsutism. Spironolactone (Aldactone), in doses up to 200 mg/day, is the most widely
used of these drugs. Spironolactone is an antihypertensive medication and is not FDA-approved for PCOS. However, its use for hirsutism is safe, although off-label. Spironolactone is not safe in pregnancy and should only be given to patients with PCOS who are not interested in becoming pregnant. It is best given in combination with an OC. Flutamide (Eulexin) and finasteride (Propecia) are occasionally used to treat hirsutism in patients with PCOS. Their use is also off-label, and they are also contraindicated in pregnancy.
Oral contraceptives are often the first line of treatment for women who have irregular menstruation or hirsutism who are not interested in pregnancy at that time. Insulin-Sensitizing Agents Drugs used for type 2 diabetes are very effective for the treatment of PCOS. These drugs, known as insulinsensitizing agents, improve the body’s response to insulin, thereby reducing the need for excess insulin and restoring insulin levels to normal. At present, many reproductive endocrinologists believe that insulinsensitizing agents represent first-line therapy for women with PCOS interested in achieving pregnancy. These agents need to be prescribed in conjunction with a carbohydrate-restricted diet, exercise, as well as a weight-loss plan for those who are obese. Although results from clinical trials have been very encouraging, the use of insulinsensitizing agents for PCOS is not FDA approved and is still off-label. The data clearly confirm that the use of insulin-sensitizing agents for ovulation induction in patients with PCOS who want to conceive is appropriate. Because these agents correct the underlying metabolic abnormalities associated with PCOS, it is more than likely that their long-term use may delay or prevent the development of type 2 diabetes, elevated cholesterol
levels, high blood pressure, and cardiovascular disease. Because long-term data are lacking, long-term use of these agents for PCOS cannot be recommended at present; however, early studies are very encouraging. Metformin (Glucophage) is the best studied insulin-sensitizing agent available in the United States for women with PCOS; it is a biguanide that has been available for 40 years. It reduces circulating insulin and androgen levels and restores normal ovulation in some women with PCOS. Even if metformin alone does not restore regular ovulation, it often improves a woman’s response to fertility drugs. Gastrointestinal (GI) side effects, including diarrhea, nausea/vomiting, flatulence, or abdominal discomfort, are common. GI symptoms usually improve after a few weeks, particularly when starting with a low dose and gradually increasing it to the full dose. Lactic acidosis is a rare but serious adverse effect of metformin. Metformin is available in 3 tablet strengths (500 mg, 850 mg, 1000 mg) and is generally prescribed in a daily divided dose ranging from 1500 mg to 2000 mg. Metformin is also available in 2 tablet strengths of an extendedrelease form (Glucophage XR; 500 mg and 750 mg). Metformin ER is taken in a single dose and causes fewer GI symptoms. It must be swallowed whole and never crushed or chewed. Occasionally, the inactive component of metformin ER can be eliminated as a soft mass in stool that may look like the original tablet; this is not harmful and will not affect the drug action. Clinicians should discuss the appropriate dose regimen with patients. Metformin is not recommended for patients with kidney, lung, liver, or heart disease. Thiazolidinediones are used to treat diabetes and are also FDA approved for the treatment of women with PCOS. The 2 available thiazolidinediones are rosiglitazone (Avandia; 4 mg twice daily) and pioglitazone (Actos; 15 mg/day to 30 mg/day). Thiazolidinediones have been shown to reduce hyperandrogenism and restore ovulation in some patients with PCOS. Liver toxicity is the main concern with these agents. Liver tests should be performed frequently during the first year and periodically there-
after in patients using these agents. These medications should not be started in women with any evidence of liver disease. Use in pregnancy. The FDA classifies metformin as a pregnancy class B drug (no evidence of risk in humans); the thiazolidinediones are classified as pregnancy class C drugs (risk in pregnancy cannot be ruled out). Therefore metformin is the insulin-sensitizing agent of choice. Thiazolidinediones may be considered if metformin is ineffective or not tolerated by the patient. Metformin should be temporarily stopped several days before having surgery or an x-ray that uses intravenous contrast. Unlike ovulation-inducing drugs, the use of insulin-sensitizing agents is not associated with an increased risk of multiple pregnancies. Present data suggest that the continued use of metformin during the first trimester of pregnancy decreases the slightly increased incidence of firsttrimester spontaneous abortion associated with PCOS. Therefore, once pregnant, patients are advised to continue to take metformin until instructed to discontinue. Emerging data also suggest that the continued use of metformin throughout pregnancy may decrease the incidence of gestational diabetes. Ovulation-Inducing Agents Initially the use of ovulation-inducing medication was the most common infertility treatment in patients with PCOS. Clomiphene (Clomid) is still the gold standard in this category. Clomiphene is an anti-estrogen that stimulates the pituitary gland to increase the release of gonadotropins, which in turn stimulates the ovaries. Approximately 33% to 50% of patients who take clomiphene will conceive. Conception generally will occur within 3 to 4 treatment cycles, given at doses of 50 mg/day or 100 mg/day for 5 days. Clomiphene at these doses has minimal side effects but does increase the incidence of multiple pregnancies to 3% to 5%. Gonadotropins (Follistim, Gonal-F, Bravelle, Menopur). These folliclestimulating hormone agents can be used to induce ovulation. The gonadotropins are given as daily injections, usually for 7 to 10 days, and safe administration requires frequent monitoring to avoid Continued on page 18
www.obgyn-infertility-nurse.com
december 2009 I Vol 1, no 2
17
OBGYN_1209:OBGYN 12/10/09 5:55 PM Page 18
The Infertility Nurse
Age, Fertility, and Ovarian Reserve IVF Rates also Affected by Increasing Age Meike L. Uhler, MD Reproductive Endocrinologist, Fertility Centers of Illinois, Naperville, IL
T
he most significant factor that influences pregnancy rate is the age of the woman. As a woman’s age increases, there is a gradual and steady decline in pregnancy rates. This was first noted by a classic report of the Hutterite population, which does not use contraception, and was later confirmed in normal women with azoospermic husbands undergoing donor insemination.1 More recently, pregnancy rates reported with in-vitro fertilization (IVF) clearly show a decrease in clinical pregnancy and live birth rates with increasing age of the female partner. Fecundity declines gradually but significantly beginning with a woman’s early 30s and more rapidly after age 35. Subtle changes in day 3 folliclestimulating hormone (FSH) and inhibin levels occur before the appearance of clinical symptoms of menstrual cycle irregularities or ovarian steroid secretion.
Premature Decline in Ovarian Reserve Risk factors for the premature decrease in ovarian reserve include: • Smoking • Family history of premature ovarian failure • Significant ovarian pathology • Previous ovarian surgery. In addition, as the woman’s age increases, the risk of other disorders
IVF Treatment for PCOS In-vitro fertilization (IVF) may also be offered to women with PCOS after
18
december 2009 I Vol 1, no 2
Fertility Evaluation Consequently, an infertility evaluation should be initiated after 6 months of failed attempts to conceive in women older than 35 years. Several tests are available for the
Ovary of a menopausal woman.
Fecundity declines gradually but significantly beginning with a woman’s early 30s and more rapidly after age 35. The most successful treatment for women with diminished ovarian reserve is oocyte donation. that may adversely affect fertility, such as fibroids, endometriosis, and tubal disease, also increases. Advancing Age The decline in fertility with advancing age is accompanied with increases in spontaneous abortion and the rate of chromosomal abnormality in live birth. These findings are attributable
Drug Therapy for PCOS... ovulation overstimulation. The drugs themselves are costly, as is the frequent monitoring with required blood tests and pelvic ultrasounds. In addition, the incidence of multiple pregnancy is only 20% when these drugs are used. However, gonadotropins often result in pregnancy when clomiphene fails. (See also article on page 27.) Letrozole (Femara) was developed for and is FDA approved for the treatment of breast cancer; its use for ovulation induction is off-label. Letrozole interferes with the production of estrogen, which in turn stimulates the pituitary gland to increase the release of gonadotropins in a manner similar to clomiphene, thereby stimulating the ovaries. Some controversial studies suggest that letrozole may increase the incidence of birth defects. For this reason, many reproductive endocrinologists are reluctant to prescribe letrozole to pregnant women.
to the meiotic spindle in the oocyte, which frequently exhibits irregular chromosome alignment and microtubular matrix composition.
Continued from page 17
other treatment strategies have failed. Success rates with IVF in PCOS patients are generally excellent, although this is accompanied by an increased risk for ovarian hyperstimulation syndrome (OHSS). Careful patient monitoring during the IVF cycle is therefore critical. Extensive research has been conducted in women with PCOS, because of the inherent complications in this population. A new national study, funded by Ferring Pharmaceuticals, is looking at the rate of OHSS in patients with PCOS undergoing IFV. This ongoing study is comparing the use of Menopur and Follistim in this patient population to determine the rate of IVF cycle cancellation as a result of OHSS risk. Data analysis is pending completion of the study. Pharmacologic management of the patient with PCOS remains a challenge. As new treatment options and drug protocols become available, successful management will maximize treatment outcomes while providing safe clinical care. ■
evaluation of ovarian reserve. The measurement of serum FSH and estradiol on day 3 of the follicular phase is often used to test ovarian reserve. Common criteria for normal ovarian function are d3 FSH <10 mIU/mL and estradiol level <80 pg/mL.2 When d3 FSH levels are elevated, particularly FSH levels >20 mIU/mL, the prognosis for successful pregnancy is poor. Other tests for ovarian reserve include the clomiphene citrate challenge test, inhibin B level, antimullerian hormone, and antral follicle count and ovarian volume by transvaginal ultrasound. Treatment Treatment options for diminished ovarian reserve include: • Ovulation induction with controlled ovarian hyperstimulation (COHS) • IVF • IVF with donor oocyte. Ovulation induction with COHS has limited efficacy in older women, and in women with demonstrated laboratory evidence of decreased ovarian function. Pregnancy rates with IVF are higher than with ovulation induction with COHS, but they also decline significantly with increasing age. At Fertility Centers of Illinois, our current pregnancy rates with IVF are more than 60% in women younger than 35 years, but they steadily decline with increasing age; in women older than 40 years, the approximate pregnancy rate is 20% to 25%. These rates are consistent with other national IVF centers. In con-
Ovary of a nonresponder.
Ovary of a good responder.
trast, our pregnancy rate with donor oocyte is 65%, regardless of the age of the recipient. Practical Implications The decline in fertility with increasing age is related to oocyte abnormalities. Clinical tests to estimate ovarian reserve include day 3 FSH and estradiol levels or clomiphene citrate challenge test. Prompt evaluation and treatment of infertility should be undertaken in women age ≥35 years. The most successful treatment for women with diminished ovarian reserve is oocyte donation. ■ References 1. The Committee on Gynecologic Practice of American College of Obstetricians and Gynecologists: Practice Committee of American Society for Reproductive Medicine. Age-related fertility decline: a committee opinion. Fertil Steril. 2008;90(5 suppl 3): S154-S155. 2. The Practice Committee of the American Society for Reproductive Medicine. Aging and infertility in women. Fertil Steril. 2006;86(5 suppl 1):S248-S252.
See also Young Women with Low Ovarian Reserve, page 15.
www.obgyn-infertility-nurse.com
OBGYN_1209:OBGYN 12/10/09 5:55 PM Page 19
The Infertility Nurse
Survival Strategies for the Holidays for Patients Dealing with Infertility Lawrence A. Jacobs, MD Section Head, Division of Reproductive Endocrinology, Lutheran General Hospital, Buffalo Grove, IL
My wife and I have struggled with infertility for the past year. It has been a very stressful ordeal for both of us. We are supposed to go to Michigan to be with family over the Christmas holiday. We know the holidays are going to be very stressful for us and we are reluctant to go. We dread the inevitable questions such as, “Isn’t it time you started a family?” Could you give us advice on how to cope with our infertility during the holidays? This is a typical question fertility nurses and doctors may encounter during the holidays. The holidays can be stressful for anyone. Many people dread the holidays, but those times can be particularly difficult for couples
with infertility issues. The holiday hype is often focused on kids and family, leaving people vulnerable to frustrating family dynamics. At holiday gatherings, well-meaning friends or family members often inquire
about a couple’s plans for having children, not knowing about their fertility struggles. In other situations, if they are aware of the couple’s fertility problems, they are often at a loss as to how to behave or what to say. Honest discus-
The OB/GYN and
INFERTILITY Nurse
TM
THE OFFICIAL PUBLICATION OF THE AMERICAN ACADEMY OF OB/GYN AND INFERTILITY NURSES
Request your
FREE SUBSCRIPTION AT www.obgyn-infertility-nurse.com
FOCUS ON u OB/GYN and Reproductive Nursing u Women's Health, Nutrition,
Drug Therapy u Medical Aspects of Human Sexuality
www.obgyn-infertility-nurse.com
u Aging, Chronic Diseases u Clinical Updates from Professional
Meetings/Literature
www.obgyn-infertility-nurse.com
sion about the couple’s emotions and fertility problems may lessen some of the awkwardness. Suggest to your patients some of the following coping strategies for the holidays: • One way to alleviate the stress of painful holiday family gatherings is to stay home—don’t go. Avoiding painful family situations may lead to other problems, but in fact may be the best solution under certain circumstances, such as a recent failed in-vitro fertilization attempt. Decline invitations if you think it will be too much of an emotional strain to be around someone’s new baby or obvious pregnancy. Protect yourself. • Take control over some of the celebration and limit the time you do spend. Decide when you want to go there, and when you want to leave. • Communicate with your spouse about these decisions. Your spouse may have a different attitude, and you need to try to be on the same page. Just talk about your feelings. Support each other. Talk and compromise; be a team and make it work. • Plan some quality time with family and friends with whom you know you will feel comfortable. Or, better yet, plan a lovely vacation by yourselves, away from everyone. Remember, the two of you are a family. • Prepare yourself ahead of time for the inevitable awkward questions, such as, “When are you going to start a family?” Have a comeback answer ready. For example, “Thanks for asking, but it’s a painful subject, and I don’t feel like talking about it” will usually end the discussion. • Get information about dealing with the stress of holidays and infertility from well-respected support groups. National resources that can be helpful include the American Fertility Association (www.theafa.org) and Resolve (www.resolve.org). • Do something nice for other people. It will take your mind off your problems if you focus on helping others. Remember, there are always others less fortunate than you. Volunteer at a homeless shelter, or visit the elderly in a nursing home or a veteran at a local VA hospital. Or donate your time as a volunteer in a hospital or a residence of children/adults with developmental disabilities. Helping others will change you forever—for the better. ■
december 2009 I Vol 1, no 2
19
OBGYN_1209:OBGYN 12/10/09 5:55 PM Page 20
The Infertility Nurse
Pregnancies with Multiples Increase Fetal and Infant Risks New Guidelines Call for Reduced Embryos Transferred
See also New Guidelines, page 16.
By Wayne Kuznar
W
e are living in an epidemic of multiples,” said Mark Evans, MD, Professor of Obstetrics/ Gynecology, Mt. Sinai School of Medicine, New York City, at the 2009 American Society of Reproductive Medicine (ASRM) meeting. Many patients and doctors underestimate the risks of pregnancies with multiples, including fetal loss, infant mortality, and long-term risks, Dr Evans said. Angela Smith, NP, EdD, Nurse Practitioner and Clinical Supervisor, American Fertility Services, Hackensack, NJ, noted that 1 of 5 women aged ≥45 years who become pregnant through assisted reproductive technologies delivers twins. “We still have our patients coming to us with a sense of urgency…they are tired of not being pregnant. They want solutions,” said Dr Smith. “This sense of urgency is shared by practitioners in the field; they want to help the women achieve their goals.” The ASRM and the Society for Assisted Reproductive Technology (SART) have just released new guidelines on the number of embryo transfers during in vitro fertilization (IVF), Dr Smith noted. According to the guidelines, no more than 2 embryos are to be transferred in women aged <35 years, and transferring only 1 embryo should be considered. More centers today are offering single-embryo transfer, but “we are not all there,” she said. In addition, IVF cycles cost between $10,000 and $20,000 each, making single-embryo transfer cost-prohibitive for many patients, according to Dr Evans.
“
Risk of Fetal/Infant Complications Since the 1980s, twin births have
“We still have our patients coming to us with a sense of urgency.” —Angela Smith, NP, EdD
increased by 48% and triplets by 146%. More than half the babies born in the United States via IVF are part of a multiple pregnancy. Conservative estimates for fetal loss in multiple pregnancies are 8% for twins and 15% for triplets, and rises exponentially from there, Dr Evans said. Infant mortality also rises exponentially with the number of pregnancies, from 0.5% with a singleton to 3% per baby of twins, and 6% per baby of triplets. “If you’re a quadruplet baby, the chance of not living to your first birthday is about 10%,” he said. These numbers “are not understood by our patients and frankly by most of our doctors who are dealing with these patients.” He tells patients “that there are 2 kinds of bad outcomes you can have with a pregnancy. You can lose it so early, <24 weeks, and you go home with nothing, or there’s a window between about 24 and 27 weeks, where the odds of survival are very good but the odds of impairment are very high.” The chance of a baby having cerebral palsy when delivered during this window is about 20%. The risk of cerebral palsy is approximately 1 of 700 with a singleton pregnancy but rises to 1 of 100 with twins and 1 of 30 births with triplets. Delivery at <32 weeks is 1.6% with singleton pregnancies. “By the time
you are at twins, the number is 8 to 10 times higher; more than 10%,” said Dr Evans. Long-term outcomes of prematurity include: • Cerebral palsy • Asthma • Poor vision • Low intelligence • Poor motor skills. Negative outcomes are 3 to 5 times more common in babies weighing <1000 g at delivery compared with those weighing >1000 g. More than 50% of babies weighing <750 g at birth have learning disabilities. Low birthweight has also been linked to increased cardiovascular risk factors as adults.
“We are living in an epidemic of multiples.” —Mark Evans, MD
Fetal Reduction and PGD Assuming that the guidelines on embryo transfer are being followed, many women will still require pregnancy reduction. Because the average age of women undergoing IVF is 38 years, more embryo transfers are recommended for them.
According to 2005 data from SART, >50% of 90,000 fresh nondonor cycles were in women age >35 years, of whom 59% underwent intracytoplasmic sperm injection, which increases the risk of cytogenetic abnormalities, and 4% used preimplantation genetic diagnosis (PGD). “Every patient who is pregnant who is using PGD or preimplantation genetic aneuploidy screening for chromosomes needs to have chorionic villi sampling [CVS] or amniocentesis, preferably a CVS,” Dr Evans advised. “The mistake rate on the single cell is 2% to 3% and on the chromosome is 3% to 5%. PGD and preimplantation genetic aneuploidy screening for chromosomes are good screening tests but not good diagnostic tests.” CVS rather than amniocentesis is preferred for any patient with twins (or more) who is interested in PGD testing. “It’s much better medically, psychologically, and in every other way to confront this at 12 weeks than to have to confront it at 17 weeks,” he noted. In his practice, when a fetal reduction is desired, most women undergo CVS and fluorescence in situ hybridization (FISH) before the reduction. The results from FISH testing are available in <24 hours, and accuracy is >99% in detecting chromosomal abnormalities. “In the 1% of cases in which there is a discordance between the FISH and the karyotype, in more than half of those, it turns out that the FISH was correct and the culture was wrong,” Dr Evans said. “That dogma has to change. I counsel everybody that the residual risk of acting based on the FISH alone…is less than 1 in 400.” ■
Mind-Body Program for Stress Management Improves IVF Pregnancy Rates
A
ccording to Alice Domar, PhD, Executive Director, Domar Center for Mind/Body Health, and Director, Mind/Body Services, Boston IVF, 22 studies looking at baseline distress and pregnancy have shown that patients with more distress are less likely to get pregnant; patients with the most distress are 93% less likely to get pregnant than those with the least distress. Presenting her award-winning study of her body-mind program at the American Society of Reproductive Medicine (ASRM) annual meeting, Dr Domar said that women who participate in a stress management program con-
20
december 2009 I Vol 1, no 2
sisting of 10 sessions before or during their second in-vitro fertilization (IVF) cycle were more than twice as likely to get pregnant than those not participating in such a program. Women age ≤40 years who were scheduled to begin their first IVF cycle were randomized to a 10-session mindbody program or to a control group that did not use that approach. A total of 97 women completed the study. The pregnancy rate for the first IVF cycle was 43% in both groups. Before beginning their second IVF cycle 76% attended 6 to 10 sessions. Pregnancy rates for the second IVF cycle were 52% for those participating
in the mind-body program compared with only 20% among those not using the mind-body program.
Patients with the most distress are 93% less likely to get pregnant than those with the least distress. The mind-body sessions were 2 hours each, and consisted of relaxation, cognitive-behavioral strategies, and participation in group support, reported Dr Domar. The session took place over 9
weeks; partners were allowed to attend 3 of the 10 sessions. Each group had 12 to 16 women. Women who had moderate symptoms of depression at baseline were analyzed separately. In this group of women, pregnancy rates were: • 62% in the mind-body group; 39% in the control group for cycle 1 • 67% in the mind-body group; 0% in the control group for cycle 2. “It’s clear, based on this carefully designed study, that a holistic approach to infertility care leads to better outcomes for patients,” commented R. Dale McClure, MD, President of ASRM. —W.K. ■
www.obgyn-infertility-nurse.com
OBGYN_1209:OBGYN 12/10/09 6:23 PM Page 21
Reproductive Resources
Psychological Aspects of Infertility Pamela Fawcett Pressman, MEd, LPC Director of the Infertility Counseling Program, at Pressman and Associates, Voorhees, NJ, www.pressmanandassociates.com. Ms Pressman spent 15 years with the University of Pennsylvania Department of Psychiatry and has been in private practice since 1989. After resolving her own infertility through adoption, she incorporated infertility treatment into her practice. She is a member of Resolve, ASRM, and AFA.
I
nfertility may be one of the most difficult experiences a woman can have in her lifetime. The emotional consequences of an infertility diagnosis can be devastating, which may be little known to patients and medical personnel. As a psychotherapist, I have seen very few life problems more emotionally painful and challenging than infertility. Understanding and treating infertile women and couples has been an ongoing area of interest for mental health professionals in the field of reproductive medicine. From a psychological standpoint, infertility has similarities to other chronic illnesses. For many patients, a diagnosis of infertility is shocking. Healthy women in their 30s and 40s are frequently unaware that they are at high risk for infertility. As with other medical illnesses, the treatment and prognosis for infertility is often unknown to them. This leaves women and couples in a constant state of ambiguity until they achieve a successful pregnancy. Learning to live with uncertainty about something as important as having a child is a challenge even for the most well-adjusted person.
Emotional Distress Women (rather than men) almost always experience a greater degree of emotional distress with infertility. This is not to minimize the anguish a man may feel in response to an infertility diagnosis, because naturally men can long for parenthood as well. A man’s distress, however, tends to be more focused on how to support his distraught female partner and infuse her with his optimism for a successful outcome. Emotional reactions to infertility are often independent of a patient’s medical diagnosis or likelihood of pregnancy. The intensity of emotional distress a woman may experience is often surprising, even to her. She may feel distraught each month that she has a failed attempt at pregnancy. Once a woman has made the emotional shift to motherhood, each month without a child may feel empty. Women describe it as “an aching in my heart.” For many women, each month without a baby is a painful loss, similar to grieving a deceased loved one. Feelings of sadness, depression, anxiety, and preoccupation with infertility are common. In the literature this is referred to, in part, as “anticipatory grief.” I often tell patients, “We are mothers in our hearts before our babies
www.obgyn-infertility-nurse.com
The emotional consequences of an infertility diagnosis can be devastating, which may be little known to patients and medical personnel. As a psychotherapist, I have seen very few life problems more emotionally painful and challenging than infertility. find us.” This phenomenon occurs even with otherwise happy, welladjusted women. Feeling of Inadequacy Women may also experience shame, guilt, or a feeling of inadequacy. Pregnancy has long been associated with womanhood, and failing at something so fundamental to a woman’s identity can be a terrible blow. A woman may search her mind for what she “did” to cause the infertility and unfairly blame herself. Often, women and couples “hide” their infertility struggles as they continue to fulfill daily obligations, carrying the secret burden of a life crisis. This brave front exacerbates the stress women and couples are already enduring as they struggle to feel “normal.” In keeping the secret, they inadvertently maintain a false belief that they are alone in their struggle. They are often unaware of how many other people are coping with infertility and/or pregnancy loss. They also may not hear of the many successful outcomes that infertility treatments afford. The Roller Coaster of Fertility Treatment Infertility treatment can place a heavy burden on couples who at times must adhere to timed lovemaking to fulfill medical protocol requirements. This can leave men feeling like “sperm donors,” in part because women often lose their libido during treatment and are therefore often not interested in sexual intimacy at spontaneous times. Diagnostic and treatment procedures will often require more effort on the part of the woman who may be experiencing physical discomforts, as well as hormonal changes. Couples must be supported in knowing that these changes in their sexual intimacy are only temporary and will return to nor-
mal after infertility treatment ends. The treatment for infertility is often referred to as an “emotional roller coaster,” because of the inherent ups and downs associated with the process. Couples must be at once optimistic about the outcome and also realistic about the possibility of not having the desired outcome. For every month that does not result in a pregnancy there will have been many hours of hopefulness, followed by, at best, disappointment or, at worst, despair. The Signs of Distress Usual coping strategies, such as hard work and perseverance, are inadequate to manage the crisis of infertility, which leaves many women and couples unsure of how to cope and feeling a loss of control. This loss of control is what many women find most difficult to handle. It is also the reason why patients can be irritable or angry at treatment staff. Frequent calls or badgering of the front desk or nursing staff are indications that the patient is exhibiting more anxiety than she can tolerate. Tearfulness and reports that a patient is having trouble thinking of anything besides pregnancy are other signs that her level of distress may warrant the support of a mental health professional/ infertility counselor. Intervention Much can be done to support women and couples who are experiencing infertility or pregnancy loss. Early referral to an infertility mental health professional provides an opportunity for assessment and intervention, which can help the woman or the couple be more prepared for the journey they are about to embark on. Mental health professionals are able to assess the person’s or the couple’s strengths and vulnerabilities, and
explore coping styles and belief systems. They can identify expectations about treatment and discuss moral and ethical issues that may arise during the treatment process. Couples can learn ways to understand each other better and communicate more effectively. They have a forum in which to process grief and integrate the infertility experience. Ultimately, the goal of infertility counseling is to increase resiliency, which will support patients and couples throughout their infertility journey, regardless of where it takes them. In addition to psychotherapy, patients can learn stress management techniques, such as progressive relaxation, deep breathing, and meditation, which are especially useful during medical procedures and anytime a patient is experiencing stress. Infertility organizations such as Resolve, the American Society of Reproductive Medicine (ASRM), and the American Fertility Association (AFA) help to educate patients and medical professionals about all aspects of infertility, including mental health. Members of these organizations who are mental health professionals are committed to providing the highest quality psychological support to women and men as they strive to become parents. ■
Coming in February • Continuing Education Credit • Ectopic Pregnancy • Female Sexual Dysfunction Diagnosis • Gonadotoxins that Affect Male Fertility • Ovarian Hyperstimulation Syndrome: A Nurse’s Perspective • Endometriosis Management • Alternative Therapies in Infertility Treatment • Lifestyle Choices that Influence Fertility • Controversies in Mammography • The Pap Smear Debate
december 2009 I Vol 1, no 2
21
OBGYN_1209:OBGYN 12/10/09 6:23 PM Page 22
Reproductive Resources
Holistic Nursing for Patients Undergoing Fertility Treatment Barbara “Teddy” Piotrowski, RN, BA, HNB-BC, Dipl. ABT, E-RYT, CMS Board-certified Holistic Nurse, Cherry Hill, NJ (www.greaterharmony.net)
I
commend South Jersey Fertility Center (SJFC) for recognizing the importance of emotional, as well as physical, well-being of their patients. They integrate a holistic style to provide a balanced method to the rigors of fertility treatment (See page 1). As a registered nurse with more than 30 years’ experience, I have come to appreciate the many different types of healing. My goal as a holistic nurse is to guide individuals in their journey toward self-healing, by integrating Western and Eastern approaches to health. The Mind-Body Connection The mind-body connection focuses on the brain, mind, and body as they interact with other factors such as emotional, mental, social, spiritual, and behavioral cues that directly affect health. Such a method respects and enhances each person’s capacity for growth through self-knowledge and selfcare, and emphasizes techniques that are grounded in individual empowerment. Mind-body modalities offer many health benefits. The regular use of these interventions brings the parasympathetic nervous system to the forefront (the “relaxation response”) in contrast to the sympathetic nervous system (the “fight or flight” reaction). Activating our parasympathetic nervous system calms the body and slows down the heart rate and breathing. This allows the blood vessels to dilate, thereby decreasing blood pressure and improving blood flow to many parts of the digestive tract, as well as the reproductive system. There is clear evidence for the direct connection between the function of our mind and our body, which is the basis of many Eastern healing arts that are increasingly being incorporated into Western medicine. Holistic Nursing Holistic nurses view healing as a therapeutic partnership with the people in their care. We realize that if we can keep our foundation strong and stable, people will be able to maintain balance and harmony in everyday life, and fend off life’s storms. During the first session, I introduce relaxation techniques and provide handouts that give clients information they can use to practice at home. The
22
december 2009 I Vol 1, no 2
key is to help people help themselves. Services are tailored to meet the individual’s needs, depending on where they are in their cycle, as well as their personal requests. Because I emphasize self-care, my handouts and homework give patients tools they can use for everyday living. The holistic modalities I offer are based on Asian Bodywork Therapy (ABT): shiatsu, acupressure, Reiki, yoga, relaxation techniques, and meditation. These modalities help patients increase clarity, maintain healthy circulation, and bring homeostasis to the body. They also provide a vehicle to increased balance as patients go through the rigorous demands of treatment.
energy and blood flow. Acupressure uses the fingers to press key points on the surface of the skin to stimulate the body’s energy. When these points are pressed, they release muscular tension and promote the circulation of blood and the body’s life force, or Qi. The healing touch of acupressure reduces tension, increases circulation, and enables the body to deeply relax. By relieving stress, acupressure strengthens the body and promotes wellness. Reiki is a gentle but powerful technique that addresses chronic and acute conditions. It is a regenerative process of body and mind. I apply a series of hand positions to areas where comfort
Activating our parasympathetic nervous system...allows the blood vessels to dilate, thereby decreasing blood pressure and improving blood flow to many parts of the digestive tract, as well as the reproductive system. When we are aware our bodies are out of balance, we are either not eating healthy, are stressed out, or our breathing is shallow. These are all signs that we need to relax. I offer the following services designed to meet the individual’s needs. Asian Bodywork Therapy. ABT helps to bring vital energy into the body and restores balance by moving and nourishing the free flow of energy or Qi. ABT is based on Chinese medical principles for assessing and evaluating the body’s energy system. My expertise is in shiatsu and acupressure. Shiatsu involves applying gentle pressure usually with the thumb and fingers along the energy pathways. Gentle joint rotation and stretching may be included in a session. Releasing the tension blocks in the client affects the mind, as well as the body. The lack of free flow of energy causes discomfort and imbalances. Working with the meridians releases the energy flow through the entire body, not just the specific area of discomfort. The treatment brings a sense of relaxation while stimulating
and balance are needed, resulting in flowing energy and deep relaxation. It is a tangible form of relaxation that is best understood only by experiencing it. Meditation helps the person find a distinct point of mind-body balances. Through the centuries, meditation has been proved to be a powerful tool to still the mind. Studies have shown that those who meditate are better able to face life with inner strength and balance. Yoga consists of a series of stretching postures (called asanas), breathing exercises, and meditative practices. It increases flexibility, improves muscle tone, and is helpful in the reduction of stress. Yoga can be used as an efficient system to maintain health and balance and revitalize the body systems. Collaborating with SJFC During the past 2 years I have been working with the nurses at SJFC in introducing these much-needed adjunct services to their patients. We began by disseminating information and providing workshops to the nursing staff, and short relaxation sessions
at the center for patients. After reviewing patients’ feedback, SJFC began to refer patients to me as a holistic nurse. The key is that the client has to initiate the initial contact with me. As patients discover increased clarity and thinking, it aids them in following a healthier lifestyle and increases sensitivity about their bodies and body processes. This empowerment may also help them to better communicate their symptoms to their physician and become a more active participant in their own care, as well as have a higher level of self-esteem. Self-Care for Nurses This aspect of self-care is important for everyone, especially nurses, who normally focus on caring for others first. As a registered nurse, I know that selfcare is important for all of us; we all need to take time to go into a quiet place, bringing balance and homeostasis to our nervous system and bodies. The goal is to heal the whole person by recognizing the inner-connectivity of body, mind, spirit, and the environment. This is something that everyone could benefit from, not just those who are going through treatment. In nursing school we were taught how to take care of our patients, but we were not taught how to care for ourselves. As caregivers, it is critical to take time each day to promote wholesome behavior and renew and nourish ourselves. Only by being positive role models can we better serve the people we care for. ■
Holistic Resources American Holistic Nurses Association AHNA (www.ahna.org) promotes the education of nurses, other healthcare professionals, and the public on holistic care and healing, serving as a bridge between conventional medicine and complementary/alternative healing practices. Holistic nursing is recognized by the American Nurses Association as an official nursing subspecialty with standards of practice. The National Certification Commission for Acupuncture and Oriental Medicine (www.nccaom.org). Reiki (http://nccam.nih.gov/health/ reiki/). Yoga Alliance (www.yogaalliance.org). Meditation Specialists (www.meditation specialists.com/cms).
www.obgyn-infertility-nurse.com
OBGYN_1209:OBGYN 12/10/09 6:23 PM Page 23
Join the Academy at
www.obgyn-infertility-nurse.org First-year membership $39.95 includes more than $200 off future Annual Meeting registration for Full Members. Membership is open to all OB/GYN, Infertility, and Urology Nursing Professionals. As a member you will receive resources on patient care best practices, continuing education, and opportunities to interact with your peers.
OCTOBER 200 9 WWW.OBGY N-INFERTILIT Y-NURSE.CO M VOL 1, NO 1
Member Benefits Include:
CLINIC PRO FILE
IVF New Jers ey
Transitioning
EMERGING QUESTIO
How Should NS Pregnant WoWe Advise the H1N1 Flu men Regarding Vaccine? Donna Makris, RN, BSN, IBCLC Paren
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).
•
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 expecmend ies, and, as nant women shoul ations that preg- Educa tion Coordinator the Parent a vaccine for the d have priority once that many of our partic, I am certain novel H1N1 influe za virus (also know ipants will be n- asking about 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
O
How Nurses Can
I
•
for issues such as coverage and reimbursement.
Research
S
Inside
Pharmacy Corn Latex allergies in er infertility drugs
Page 14
• 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
7
Fertility Center s of Illinois Influence Infertilit y
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. Interview with , Jill Marchetti, Sue Jasulaitis, RN, MS n her role as Clinic ue Jasulaitis is New Jersey, Jennif al Manager at IVF dure, which Clinic er Ianna is less intrusive Manager at Fertil al Research ccone has has precepted many but also ity Centers of a lower success nurses to the field rate. infertility. In If the of the coupl IUI fails, Chica Illinois (FCI), River North this interview, e , in go. In this interv describes the steps she dure, which then tries an IVF proceiew she discusses key features has a very good ic to help a new she takes at her clin- rate of the center success nurse at our center. nurse get famili and how s can improve ar with the demands of patient care by The nurse is this field. gesting problem sugthe areas to nates the patien one who coordi- their own daily exper study based on t’s IVF cycle. Do you do only ience writes She . up the patien t’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 vitro priate that fertilization (IVF) IVF is a more testing. We also intrusive proce dinate with the coor- one of centers. FCI is dure; husband to have the cedure that requir it is a surgical pro- semen his the count largest fertility centers in frozen es general anesth ry, and has provid and involves esia day of retrie , which is used if on the more ed treatInside River North more couples begin risk. Therefore, a specim val he is unable to produce ment to >100,000 patients . durin en. past with an IUI proce g the matel All 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,
©2009 Green
Newborn Umb Cord Blood ilical The case of Chloe Levine
Hill Healthcare
Communications, LLC
Page 15
Continued on page
Polar Bodies Screening New techniques enhance genetic diagnosis
Page 17
Obesity and Reproduction What nurses need to know
Page 24
VOL 1, NO 1
The official pu blication of the American Academy of OB/GYN and Infertility Nu rses
8
OBGYN_1209:OBGYN 12/10/09 6:23 PM Page 24
Urology Nurse
Repair of Clinical Varicocele Improves Fertility and Spontaneous Pregnancies By Wayne Kuznar
S
ince varicocele was first discovered as a cause of male infertility more than 50 years ago, the role of treatment for male subfertility has been controversial. In building a case for the treatment of varicocele, evidence indicates that repair of clinical varicocele improves the rate of spontaneous pregnancies, and in men with oligospermia or azoospermia, varicocele repair can improve outcomes associated with assisted reproductive technologies (ART), said Lawrence S. Ross, MD, Professor of Urology at the University of
Illinois, Chicago, during the 2009 American Society of Reproductive Medicine annual meeting.
a second pregnancy, almost 70% [of the time] the male’s varicocele is noted as an underlying cause,” said Dr Ross.
“When one looks at secondary infertility, almost 70% [of the time] the male’s varicocele is noted as an underlying cause.” —Lawrence S. Ross, MD Recent estimates of varicocele in a population of infertile men are as high as 50%. “When one looks at secondary infertility, couples who produce 1 pregnancy but are having trouble producing
The effect of varicocele on semen parameters was analyzed by the World Health Organization in 1992, showing varicocele in 25.4% of men with abnormal semen and in only 11.7% of men
CLASSIFIED ADVERTISEMENTS TO PLACE AN ADVERTISEMENT Call Mark Timko: 732.992.1897 se.com r u n y it il t r e f in www.obgynUS $185.00 1x RATES
per ent is priced An advertisem .25”) lumn width, 2 o (c h c in n m colu $185.00 mn inch, US Cost per colu
Increase ! re Your Exposu For more information ko: Call Mark Tim 7 732.992.189
RATES An advertisement is priced per column inch (column width, 2.25”) Cost per column inch, US $185.00
6x 12x 18x
US $165.00 US $145.00 US $130.00
YOUR AD HERE dAy! Advertise to 97 18 299 CAll: 732Y-NURSE.COM IT IL RT FE -IN WWW.OBGYN
g
Advertisin thAt Works
an Reach more th s 20,000 Nurse and PAs odAy! Advertise t CAll: 97 732-992-18
online d a r u o y e c Pla nse rate o p s e r r u o y t and boos 1x 6x 12x 18x
US $185.00 US $165.00 US $145.00 US $130.00
Additional Charges: • One color–$75.00 • Full color–$250.00 • Internet exposure www.obgyn-infertility-nurse.com (with print ad)–$75
with normal semen. Varicocele was accompanied by decreased testes volume, sperm quality, and hormonal function. “The conclusion…was that varicocele is clearly associated with impairment of testicular function and infertility,” he said. A second study around the same time showed that untreated men with varicocele had progressive deterioration of semen parameters. “When the varicocele is not treated in men who have abnormal semen, the sperm count continues to decline,” Dr Ross pointed out. “Many of us have seen patients who progress to azoospermia.” Adolescents with clinical varicocele (grade 2 or 3) show retardation of testes growth on the side of the lesion; testes growth resumes when the varicocele is repaired. The treatment of varicocele falls into 2 categories: transvenous procedures that occlude with coils or use sclerotherapy to obstruct the vein and surgical ablation. “The preferred method is surgical correction using microsurgical techniques,” noted Dr Ross. “If we treat varicocele, how do we measure the results? Ultimately what’s important to our patients is the pregnancy and fertility outcomes.” Varicocele repair has been demonstrated to improve sperm count, motility, and morphology, and some studies have shown improvement of the hormonal milieu of the testis. A review of almost 2300 men who underwent vari cocele repair found a pregnancy rate of about 35%. By comparison, in untreated series, the pregnancy rate is approximately 20%. Other meta-analyses seem to counter the notion that varicocele repair improves spontaneous pregnancy rate, according to Dr Ross. These inconsistences may result from heterogeneity of studies and poor methodology of studies included in meta-analyses, in addition to selection bias. “Perhaps the most important problem is that a large number of these studies included subclinical varicoceles,” he noted. A clinical varicocele is one that can either be seen with the patient in a standing position (grade 3) or one that is easily palpated (grade 2). In contrast, subclinical varicoceles are detected using the Valsalva maneuver or on ultrasound or other types of radiologic studies, and these probably have no clinical effect. When the study population is confined to infertile men with clinical varicoceles, spontaneous pregnancy Continued next page
24
december 2009 I Vol 1, no 2
www.obgyn-infertility-nurse.com
OBGYN_1209:OBGYN 12/10/09 6:23 PM Page 25
Urology Nurse
Considering Sperm Cryopreservation One Less Worry Evelina M. Pawlowska, BS, MS Andrologist, Fertility Centers of Illinois, Chicago
T
he number of individuals affected by infertility is increasing every year, as does the number of people who are seeking infertility treatments that would fulfill their dream of a family. Once established as fertility patients, couples are subjected to fertility evaluation testing, to help clinicians develop a treatment plan. As a part of their fertility evaluation, the andrology laboratory performs multiple procedures and tests for the couple. The Reasons for Sperm Freezing A common andrology procedure is the freezing of sperm (or sperm cryopreservation) for insemination, for invitro fertilization (IVF) procedures, and/or storage for future use. Sperm cryopreservation can be incorporated into the couple’s treatment plan to simply accommodate patients or to allow them additional treatment options. There are many reasons why couples or individuals choose to freeze sperm. Some patients prefer to freeze sperm as a back-up before insemination or IVF to ensure that the specimen is ready when it is needed for treatment. Other patients have very demanding work schedules that require constant travel; therefore, freezing sperm would be the safest option for them when starting fertility treatment.
Repair of Clinical Varicocele... Continued from page 24
rates are 2 to 3 times higher with varicocele repair versus untreated varicocele. Spontaneous pregnancy is not the only outcome that measures the success of varicocele repair. Seven studies in the literature document a return of sperm to the ejaculate in azoospermic men with varicocele repair. It may also restore sufficient sperm for ART in azoospermia. Stacking varicocele repair and intrauterine insemination or intracytoplasmic sperm injection in men with oligospermia or azoospermia appears to improve outcomes associated with ART, Dr Ross concluded. ■
www.obgyn-infertility-nurse.com
Another reason is to decrease the potential for treatment cycle cancellation. It is strongly recommended that couples freeze a sperm back-up when the man has a history or a concern of inability to produce a sperm specimen on demand. In such incidences, the pressure and anxiety caused by the timed need for the sperm specimen causes some men to be unable to produce the specimen altogether, thus cancelling the treatment cycle. Sperm cryopreservation is also used for the increasing number of cases of military deployment. Additional reasons to cryopreserve sperm are donor-directed sperm cases— derived from either anonymous or known donors—as well as sperm freezing before toxic medical treatments, such as chemotherapy. Finally, some patients decide on sperm cryopreservation because of their age. We know that with age, the body (men’s as well as women’s) changes and loses its viability and capability to reproduce. When choosing to cryopreserve sperm, patients ensure that as time progresses, their reproductive status remains intact, because frozen reproductive cells (ie, gametes) will remain in the same age and condition as on the day they were frozen. Correctly maintained by andrology laboratories, cryopreserved specimens are viable for years. Sperm Quality Control Andrology laboratories maintain a stringent environment to optimize the condition and longevity of the sperm samples. Sperm is stored in tanks filled with liquid nitrogen, which require daily supervision, as well as weekly and monthly maintenance. If all these conditions are met, sperm quality will not be jeopardized. To ensure quality control in the andrology laboratory, a quality control check for automated (Hamilton Thorne analyzer) and manual sperm-counting chambers should be performed daily. Accu-Beads+ is a quality control product used to validate the accuracy of sperm-counting methods. In accordance with the Clinical and Laboratory Improvement Amendments (CLIA) regulation for cryopreservation, each test is composed of 2 levels—18 M/mL (low) and 35 M/mL (high). The low level range is between 15.5 M/mL and 20.5 M/mL, and the variation in the high level is between 30 M/mL and 40 M/mL. The Accu-Beads+ solution
consists of small latex spheres that are swimming in an isopycnic medium (photo). The physical composition of the medium allows beads to spread evenly throughout the solution. The Procedure The cryopreservation process is a combination of freezing and low-temperature storage of living reproductive cells. This procedure allows clinicians to better manage the woman’s ovulation cycle, since ovulation may occur when the man is not able to provide a
ensure sperm survivability. Sperm freezing requires multiple steps to complete. To begin the process, equal volume of freezing media is added to the sperm sample in a drop-wise fashion, so there is no significant distortion to the sample. Cryopreservation vials are then filled with the prepared sperm specimen and freezing media mixture and are vaporized in a tank. After some incubation in this vapor phase, samples are quickly removed from the tank’s freezing rack and transferred to a prelabeled cryocane (holder). Next, the cryocane and sample
It is strongly recommended that couples freeze a sperm back-up when the man has a history of or a concern with inability to produce a sperm specimen on demand. specimen. Cryopreservation is considered successful when live and functionally competent sperm is obtained after thawing. Preventing Cell Death The formation of ice crystals during the freezing process must be very carefully regulated to avoid bursting the cell’s surface during the thawing procedure. When the ice forms in the intracellular matrix of the cell, it causes a disruption in the cell membrane. The formation of intra- and extracellular ice disturbs the osmotic gradient and causes the flow of water out of the cell during the dehydration process. In such cases, the end result is cellular death. To prevent this, a cryoprotectant (freezing medium) is applied to sperm in the preliminary freezing steps. This cryoprotectant is comprised of a testyolk buffer designed to shield sperm cells from potential cellular disruptions caused by ice crystal formation, by giving them a safety coating. The freezing medium is a membrane filtered and aseptically processed. Each of the freezing media lots is tested for endotoxins, sperm motility recovery assay, and sterility before it is made available for sale. When needed, the freezing media is removed from the freezer and warmed in the incubator for about 20 to 30 minutes at 37°C. Sperm Freezing A unique body of knowledge is required when establishing and maintaining an andrology laboratory. The laboratory technicians are trained in the correct method of sperm freezing to
are slid onto a cryosleeve and plunged into a liquid nitrogen–filled canister in a tank. Optimally, samples need to be incubated in a liquid nitrogen tank for at least 2 days before they can undergo the thawing procedure. Conclusion It is a great advantage for patients and clinicians to know that there are many options that could help in the fertility treatment process. Freezing sperm for future use enhances fertility treatment options and allows for decreased stress and anxiety on the part of the couple. Cryopreservation gives patients the ability to better manage their treatment cycle, and when they need to use the frozen sperm, they can be assured that their frozen vials are professionally prepared and maintained by the andrology laboratory. ■
Accu-Beads+ solution: small latex spheres swimming in media.
december 2009 I Vol 1, no 2
25
OBGYN_1209:OBGYN 12/10/09 6:23 PM Page 26
Nutrition
High-Fiber Diet Counterproductive for Women Trying to Become Pregnant By Rosemary Frei, MSc
A
n apple a day may keep the doctor away, but it may also keep a baby away. Results of a new study show that increasing the intake of dietary fiber by just 5 g/day—equivalent to about 1 large apple or 2 slices of brown bread—can increase a woman’s risk of anovulation by as much as 78% (Gaskins AJ. Am J Clin Nutr. 2009;90: 1061-1069). The members of the BioCycle Study Group followed 259 women through 2 menstrual cycles. These were regularly menstruating, premenopausal, healthy women with an average age of 27.5 years, living in the western New York area. The women were not pregnant or breastfeeding within the past 6 months before the study and were not taking oral contraceptives, vitamin or mineral supplements, or prescription medications during the study period. Investigators measured the subjects’ reproductive hormones at short intervals during their menstrual cycles, and collected 24-hour dietary recall information 4 times per cycle. Results showed that the women’s adjusted odds ratio for anovulation was 1.78 for each 5-g increase in their daily fiber intake. When separate analyses were performed according to the source of the fiber, fruit fiber had the strongest association with stopping ovulation. Every 5-g increase in daily fruit fiber intake increased the risk by more than 3-fold. Similar increases in daily grain or vegetable fiber intake did not significantly increase the risk for anovulation.
In addition, 22% of the menstrual cycles were anovulatory among women who consumed at least the daily recommended intake of ≥22 g of fiber. This anovulatory rate is significantly higher than the 7.1% of anovulatory cycles among women who ingested no more than 10 g/day of fiber. The women in the higher fiber consumption group had an adjusted odds ratio of 10.98 for anovulation compared with the women in the lower group.
Fiber, g 2.3 2.1 2.7 8.7 8.4 1.2 4.2 7.5 2.0 2.3 5.3 2.1 0.6 1.8 1.4 2.1 2.2
Source: Nevo table 1996, Nevo Foundation, Netherland Nutrition Centre. www.thefruitpages.com/contents.shtml.
26
december 2009 I Vol 1, no 2
conducted such analyses. “We are continuing to look into the effect of other dietary nutrients on reproductive-hormone regulation and anovulation risk in this same cohort of women,” said lead investigator Audrey Gaskins, BSE, of the National Institute of Child Health and Human Development, Rockville, MD. Much of the fiber in fruit is stored in the skin. Apples in particular contain much soluble fiber. ■
Presents The Second Annual 2009 Curriculum for
CONSIDERATIONS IN MULTIPLE MYELOMA A Newsletter Series for Cancer Care Professionals Center of Excellence Media, along with Editor-in-Chief Sagar Lonial, MD, of Emory University, are pleased to offer your multidisciplinary cancer team with this series of newsletters focusing on the challenges in treating patients with multiple myeloma.
SAGAR LONIAL, MD Associate Professor of Hematology and Oncology Emory University
# Earn Continuing Education Credits # Eight part newsletter series
CLINICAL TOPICS: • Retreatment Settings • Maintenance Therapy • Do CRs Correlate with Clinical Benefit?
• Perspectives on Relevant Endpoints of Clinical Trials • Stem Cell Mobilization • Cytogenic Testing in the MM Patient
• To Transplant or Not to Transplant…That is the Question • Sequencing Strategies in MM: Treatment with Case Studies
Each newsletter will feature: • Contributions from thought-leading physicians, pharmacists, and nurses
Table Fiber Content in Some Fruit Fruit (100 g) Apple Apricot Banana Blackberry Blueberry Cherry Cranberry Date Fig Grapes Guava Kiwi Melon (cantaloupe) Orange Peach Pear Strawberry
In addition, increased fiber intake was associated with significantly decreased levels of estradiol and lutealphase progesterone. Furthermore, soluble fiber had a stronger negative association with estradiol concentration than insoluble fiber, and fruit fiber had a much stronger negative association than grain or vegetable fiber. Investigators did not include analyses stratified by age because they did not observe any differences when they
• Continuing Education credits available to physicians, pharmacists, and nurses
PARTICIPATE TODAY at www.COEXM.com Stem Cell Mobilization Statement of Need
Physician Credit Designation
The purpose of this activity is to enhance knowledge concerning the treatment of patients with multiple myeloma (MM).
Global Education Group designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Target Audience This activity was developed for physicians, nurses, and pharmacists.
Learning Objectives At the completion of this activity participants should be able to: • Explain how various agents and combination regimens used in induction regimens for multiple myeloma (MM) may affect stem cell mobilization • Describe the safety and efficacy of standard agents used for stem cell mobilization in patients with MM • Interpret data from clinical trials evaluating novel approaches to stem cell mobilization as reported at the 2008 ASH meeting
Physician Accreditation This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Global Education Group (Global) and Medical Learning Institute, Inc. (MLI). Global is accredited by the ACCME to provide continuing medical education for physicians.
Registered Nurse Designation Medical Learning Institute, Inc. Provider approved by the California Board of Registered Nursing, Provider 15106, for 1.0 contact hour.
Registered Pharmacy Designation MLI is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. Completion of this activity provides for 1.0 contact hour (0.1 CEU) of continuing education credit. The universal program number for this activity is 468-999-09-027-H01-P.
Agenda: 1 hour Articles/Commentaries: 45 minutes Evaluation/Posttest: 15 minutes Date of original release: August 31, 2009 Valid for CME credit through: August 31, 2010
This activity is jointly sponsored by
This activity is supported by an educational grant from Millennium Pharmaceuticals, Inc.
www.obgyn-infertility-nurse.com
OBGYN_1209:OBGYN 12/10/09 6:23 PM Page 27
Clinical News Continued from page 3
Early-Stage HER2... increased risk for tumor recurrence compared with patients with this disease but no HER2 expression according to data from a new study (GonzalezAngulo AM, et al. J Clin Oncol. 2009; 27:5700-5706). These findings represent the first analysis of this patient population group and suggest a shift in the way women with early-stage HER2-positive breast cancer should be evaluated for the risk of tumor recurrence, as well as their need for early, aggressive treatment, according to lead investigator Ana M. Gonzalez-Angulo, MD, Associate Professor, M.D. Anderson Cancer Center, Texas. In this first-of-its-kind study, the 5year recurrence-free survival rate in women with HER2-positive breast cancer tumors was 77.1% compared with 93.7% in those with HER2-negative tumors, a significant difference. “Our findings show that women with early-stage HER2-positive breast cancer have a 23% chance of recurrence. These findings indicate that physicians need to consider offering these women Herceptin-based therapy in the postoperative, or adjuvant, setting,” said Dr Gonzalez-Angulo.
Long-Term Use of Some Gonadotropins Linked to Uterine Cancer A set of studies by a Danish team has suggested a possible link between cancer and some drugs used in fertility treatments. New findings suggest that the use of some gonadotropins increases the risk for uterine cancer (Jensen A, et al. Am J Epidemiol. 2009;170: 14081414). This cohort included 56,362 Danish women who visited infertility clinics between 1965 and 1998. Women who had used follicle-stimulating hormone or human menopausal gonadotropin at some point in their lives had a 2.21 relative risk for uterine cancer. The increased risk occurred largely after 10 years of follow-up. “This gives us a hint that there is a latency effect,” said Allan Jensen, MD, of the Danish Cancer Society Institute of Cancer Epidemiology. And women who had taken clomiphene and human chorionic gonadotropin at some point had a relative risk of 1.36 for developing uterine cancer. However, other studies have shown no link between these drugs and breast cancer (Jensen A, et al. Cancer Epidemiol Biomarkers Prev. 2007;16:1400-1407) or ovarian cancer (Jensen A, et al. BMJ. 2009;338:b249).
IVF-Conceived Children at Risk for CV Events A Dutch study indicates that children born by in-vitro fertilization (IVF)
www.obgyn-infertility-nurse.com
have a growth spurt during late infancy and another spurt during early childhood (Ceelan M, et al. Hum Reprod. 2009; 24:2788-2795). The second growth spurt is associated with increased blood pressure (BP) and increased skin fold thickness, putting the children at risk for cardiovascular (CV) events. The study compared 233 children
conceived with IVF procedures and 233 children who were spontaneously conceived. The IVF children were smaller than controls at birth and had significantly greater gains in weight, height, and body mass index than the controls during late infancy. Some IVF children also had rapid weight gain during early infancy and had more skin
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%).
folds than the controls, as well as higher BP in later years, independent of birth weight, gestational age, and height at follow-up. Researchers suggest it may be wise to moderate early postnatal growth of IVF children to mitigate potential CV and metabolic events. These results must first be reproduced in long-term studies. ■
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%). 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 CRI8-XBS-001
Columbia Laboratories, Inc. Livingston, NJ 07039
december 2009 I Vol 1, no 2
27
Bec aus es he co u ... wers ans or uf yo
fact
n so nt
progesterone
Only ONE works with one daily dose Itâ&#x20AC;&#x2122;s a fact. CRINONE is the only once-daily vaginal progesterone gel approved for ART through 12 weeks of pregnancy. The vaginal insert requires three daily applications to achieve similar efficacy rates.1 And this dosing schedule can reduce patient convenience dramatically. When she asks about progesterone, give her the facts.
The only ONE CRINONE 8% (progesterone gel) is indicated for progesterone supplementation or replacement as part of an Assisted Reproductive Technology (ART) treatment for infertile women with progesterone deficiency. Important Safety Information The most common side effects of CRINONE 8% include breast enlargement, constipation, somnolence, nausea, headache, and perineal pain. CRINONE 8% is contraindicated in patients with active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders, missed abortion, undiagnosed vaginal bleeding, liver dysfunction or disease, and known or suspected malignancy of the breast or genital organs. Please see brief summary of full prescribing information on the following page.
Reference: 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. Š 2009, Columbia Laboratories, Inc.
Printed in USA
www.crinoneusa.com CRI8-PAD-004