Ajog oct dec 2013 by IJCP

Volume : 4 October-December 2013

Asian Journal of

Online Submission

Volume 4, October-December 2013

An IJCP Group Publication Corporate Panel Dr Sanjiv Chopra Prof. of Medicine and Faculty Dean Harvard Medical School Group Consultant Editor Dr Deepak Chopra Chief Editorial Advisor Padma Shri and Dr BC Roy National Awardee Dr KK Aggarwal Group Editor-in-Chief Dr Veena Aggarwal MD, Group Executive Editor AJOG Specialty Panel

Dr Alka Kriplani Editor Consultant Editor Dr Urmil Sharma Assistant Editors Dr Nutan Agarwal (Delhi) Dr Neera Aggarwal (Delhi) Dr A Biswas (Singapore) Dr CS Dawn (Kolkata) Dr Gauri (Delhi) Dr Suneeta Mittal (Delhi) Dr S Mehra (Delhi) Dr Prashant Mangeshikar (Mumbai) Dr Prakash Trivedi (Mumbai) Dr Gita Ganguly Mukherjee (Kolkata)

Dr (Mrs) Prabha Arora (Delhi) Dr Hema Divakar (Bangalore) Dr Kamini A Rao (Bangalore) Dr Deepti Goswami (Delhi) Dr Neerja Bhatla (Delhi) Dr Bhawna Malhotra (Delhi) Dr Biswas Nicholas (Australia) Dr Sudhaa Sharma (Jammu) Dr Jaibhagwan Sharma (Delhi) Dr Veena Mathur (Agra) Dr Garima Kachhawa

Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma Dr Kamala Selvaraj

ENT Dr Jasveer Singh

Cardiology Dr Praveen Chandra Dr SK Parashar

Gastroenterology Dr Ajay Kumar

Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses Dr Sidhartha Das Dr A Ramachandran Dr Samith A Shetty

Dentistry Dr KMK Masthan Dr Rajesh Chandna

Dermatology Dr Hasmukh J Shroff

CONTENTS FROM THE ISSUE EDITOR

Alka Kriplani

FROM THE DESK OF GROUP EDITOR-IN-CHIEF

What is New in Obstetrics and Gynecology ?

KK Aggarwal

CLINICAL STUDY

A Study of Outcome of Induction of Labor: Medical Versus Surgical

P Kaur, M Kaur, K Kaur, MK Manjit, P Goel

Randomized Control Study of Oral Versus Vaginal and Sublingual Misoprostol with Mifepristone for First-Trimester MTP

RR Sahu, AA Soni, VS Raut

Comparative Study of Obstetric Outcome Between Scarred and Unscarred Uterus in Placenta Previa Cases

Gayatri Mathuriya, Pallavi Lokhande

Accuracy in Estimation of Gestational Age in Third Trimester by Fetal Kidney Length in Indian Women

DP Gupta, Hem Prabha Gupta, Zeeshan Zaidi, DK Saxena, Ratna Prabha Gupta

Neurology Dr V Nagarajan Journal of Applied Medicine and Surgery Dr SM Rajendran Dr Jayakar Thomas

Anand Gopal Bhatnagar Editorial Anchor Advisory Body Heart Care Foundation of India Non-Resident Indians Chamber of Commerce and Industry World Fellowship of Religions

The Effect of Conventional Hormone Therapy and Tibolone on Tear Composition and Function in Postmenopausal Women Mhaleneinuo Modesta Belho, Ritu Khatuja, Neerja Goel, Jolly Rohatgi, Satendra Sharma, Shalini Rajaram, Sumita Mehta

Asian Journal of Volume 4, October-December 2013

CONTENTS

Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E - 219, Greater Kailash, Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com

CLINICAL STUDY

Medical Management of Ectopic Pregnancy with Methotrexate

Sandip Sonara, Sumant R Shah, Bhavesh Patel, Nidhi Patel

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CASE REPORT

Unusual Presentation of Acrochordon

Disha A Rajput, Jaya K Gedam, Arti Patel, Meenal Bhalerao

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An Experience of Chronic Inflammatory Demyelinating Polyradiculoneuropathy with Pregnancy 43 Debasmita Mandal, Chaitalli Dattaray, Mousumi Datta, Alok Pandit, Saroj Mandal, Shyamal Das

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FROM THE ISSUE EDITOR

Dr Alka Kriplani Professor and Head of Unit II Dept. of Obstetrics and Gynecology AIIMS, New Delhi E-mail: kriplanialka@gmail.com

Dear Reader This first issue of the New Year wishes you a bright year ahead. It also reminds us to renew our pledge to bring to you every new development that is born of this field, obstetrics and gynecology. Smoking tobacco or marijuana, taking prescription painkillers, or using illegal drugs during pregnancy is associated with double or even triple the risk of stillbirth, according to research funded by the National Institutes of Health. Researchers based their findings on measurements of the chemical byproducts of nicotine in maternal blood samples; and cannabis, prescription painkillers and other drugs in umbilical cords. Taking direct measurements provided more precise information than did previous studies of stillbirth and substance use that relied only on women’s self-reporting. The study findings appear in the journal Obstetrics and Gynecology. “Smoking is a known risk factor for stillbirth, but this analysis gives us a much clearer picture of the risks than before,” said senior author Uma M. Reddy, M.D., MPH, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH institute that supported the study. “Additionally, results from the latest findings also showed that likely exposure to secondhand smoke can elevate the risk of stillbirth.” Stillbirth occurs when a fetus dies at or after 20 weeks of gestation. The researchers tested the women’s blood for cotinine, a derivative of nicotine, and tested fetal umbilical cords

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

for evidence of several types of drugs. They looked for evidence of the stimulants cocaine and amphetamine; prescription painkillers, such as morphine and codeine, and marijuana. These tests reflect exposure late in pregnancy. Among the women who had experienced a stillbirth, more than 80% showed no traces of cotinine and 93% tested negative for the other drugs. In comparison, about 90% of women who gave birth to a live infant tested tobacco-free and 96% tested negative for other drugs. Based on the blood test results and women’s own responses, the researchers calculated the increased risk of stillbirth for each of the substances they examined: • Tobacco use: 1.8 to 2.8 times greater risk of stillbirth, with the highest risk found among the heaviest smokers • Marijuana use: 2.3 times greater risk of stillbirth • Evidence of any stimulant, marijuana or prescription painkiller use: 2.2 times greater risk of stillbirth • Passive exposure to tobacco: 2.1 times greater risk of stillbirth The researchers noted that they could not entirely separate the effects of smoking tobacco from those of smoking marijuana. Only a small number of women tested positive for prescription painkiller use, but there was a trend towards an association of these drugs with an elevated stillbirth risk.

FROM THE DESK OF GROUP EDITOR-IN-CHIEF

What is New in Obstetrics and Gynecology? Dr KK Aggarwal

Padma Shri and Dr BC Roy National Awardee Sr. Physician and Cardiologist, Moolchand Medcity, New Delhi President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS National Vice President, IMA Member, Ethics Committee, MCI Chairman, Ethics Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) emedinews@gmail.com http://twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook)

In 2013, the American College of Obstetricians and Gynecologists removed proteinuria as an essential diagnostic criterion for preeclampsia. Preeclampsia can now be diagnosed based on new onset of hypertension with either proteinuria or end-organ dysfunction after 20 weeks of gestation.1 Massive proteinuria and fetal growth restriction have also been removed as characteristics of severe disease. In a randomized trial of over 800 women with twin gestations, use of a cervical pessary inserted between 16 and 20 weeks gestation compared to no pessary, did not reduce preterm birth or a composite of poor perinatal outcomes.2 The Twin Birth Study showed that planned cesarean delivery does not significantly improve neonatal outcome as compared with planned vaginal delivery when the first twin is in vertex presentation.3 In 2013, the WHO updated its guidelines on the prevention and treatment of HIV in resourcelimited settings to recommend initiation of antiretroviral therapy (ART) for HIV-infected patients with CD4 cell counts ≤ 500 cells/L.4 These guidelines also recommend initiation of a combination antiretroviral regimen for all pregnant women with HIV infection, regardless of CD4 cell count, to continue at least throughout the period of mother-to-child transmission risk, which includes the breastfeeding period. For all HIV-infected individuals in resource-limited settings, efavirenz/tenofovir/emtricitabine is the WHO preferred first-line regimen.

In a change from previous guidelines, a practice bulletin by the American College of Obstetricians and Gynecologists endorsed the use of oral antihyperglycemic agents (glyburide) as an alternative to insulin for treatment of gestational diabetes mellitus (GDM).5 In a large study, first-trimester use of fluconazole (most commonly a single dose of 150 mg) in 7,352 pregnancies was not associated with an increased risk of birth defects overall.6 A population-based cohort study from Sweden including over 1.5 million singleton deliveries confirmed that overweight and obese women were not only at increased risk for medically indicated preterm deliveries at all gestational ages but also observed a significant dose-response relationship between severity of obesity and risk of spontaneous extremely preterm birth (22-27 weeks).7 In a 2013 systematic review and meta-analysis of randomized trials for the US Preventive Services Task Force, appropriate management of gestational diabetes mellitus (nutritional therapy, self blood glucose monitoring, and administration of insulin if target blood glucose concentrations are not met with diet alone) resulted in reductions in preeclampsia, birthweight > 4,000 g, and shoulder dystocia.8 A United States Preventive Services Task Force (USPSTF) systematic review of cohort studies of screening tests for GDM concluded that the glucose challenge test performed well at both the 130 mg/dL (7.2 mmol/L) and 140 mg/dL Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

FROM THE DESK OF GROUP EDITOR-IN-CHIEF

(7.8 mmol/L) thresholds and performed better than fasting plasma glucose level at a threshold of 85 mg/dL (4.7 mmol/L) for identifying women who were ultimately diagnosed with GDM.9 The Society of Radiologists in Ultrasound has added criteria for early gestations (gestational sac < 25 mm or embryo 7 mm) based upon lack of development over time.10 These stipulate that a spontaneous abortion may be diagnosed if the appropriate findings (yolk sac or fetal cardiac activity) are not visualized in a follow-up ultrasound in 11-14 days.

References 1. American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Obstet Gynecol 2013;122:1122. 2. Liem S, Schuit E, Hegeman M, et al. Cervical pessaries for prevention of preterm birth in women with a multiple pregnancy (ProTWIN): a multicentre, open-label randomised controlled trial. Lancet 2013;382:1341. 3. Barrett JF, Hannah ME, Hutton EK, et al. A randomized trial of planned cesarean or vaginal delivery for twin pregnancy. N Engl J Med 2013;369:1295.

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

4. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach, June 30, 2013. Available at: http://www.who.int/hiv/pub/ guidelines/arv2013/download/en/index.html 5. American College of Obstetricians and Gynecologists. Practice bulletin no. 137: gestational diabetes mellitus. Obstet Gynecol 2013;122:406. 6. MĂ¸lgaard-Nielsen D, Pasternak B, Hviid A. Use of oral fluconazole during pregnancy and the risk of birth defects. N Engl J Med 2013;369:830. 7. Cnattingius S, Villamor E, Johansson S, et al. Maternal obesity and risk of preterm delivery. JAMA 2013;309:2362. 8. Hartling L, Dryden DM, Guthrie A, et al. Benefits and harms of treating gestational diabetes mellitus: a systematic review and meta-analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research. Ann Intern Med 2013;159:123. 9. Donovan L, Hartling L, Muise M, et al. Screening tests for gestational diabetes: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2013;159:115. 10. Doubilet PM, Benson CB, Bourne T, et al. Diagnostic criteria for nonviable pregnancy early in the first trimester. N Engl J Med 2013;369:1443.

CLINICAL STUDY

A Study of Outcome of Induction of Labor: Medical Versus Surgical P Kaur*, M Kaur*, K Kaur†, MK Manjit‡, P Goel§

ABSTRACT The aim of this article is to study the outcome of induction of labor using medical and surgical methods. Two hundred twelve patients with > 28 weeks pregnancy requiring induction of labor were studied for a period of 1 year in the Government Medical College and Rajindra Hospital, Patiala, Punjab. In 25 patients (Group 1), artificial rupture of membranes was done to induce labor, 52 patients were induced with oxytocin, and 83 patients were induced with misoprostol (Group 2). In 52 patients (Group 3), medical and surgical methods were used in combination. The incidence of labor induction came out to be 13.86%. The induction delivery interval was shortest in Group 3 (85.42% delivered within 12 hours) compared to 62.72% and 64.60% in Groups 1 and 2, respectively. The lower segment cesarean section rate was least in Group 3 (7.69% vs 12% and 16.30%, respectively). Postpartum hemorrhage and maternal pyrexia were observed more in Group 1 (20% and 8%) than in Group 2 (2.96% and 0.74%) and Group 3 (5.77% and 3.85%). All methods were equally effective in induction of labor in terms of induction delivery interval and mode of delivery. Key words: Induction of labor, misoprostol, oxytocin

nduction of labor (IOL) implies stimulation of uterine contractions before the spontaneous onset of labor with or without ruptured fetal membranes for the purpose of accomplishing delivery.1 IOL is indicated when the benefit to either the mother or fetus outweighs that of continuing the pregnancy.2 However, all inductions are not successful and some may develop complications. In nullipara with an unfavorable cervix undergoing labor induction, cesarean delivery rate is more than 30%.3 This study was carried out to find out the incidence of IOL in our institution, to find the indications for which IOL is performed, to find out the most effective method for IOL, to study the complications of induced labor, and to find out the failure rate of IOL.

*Associate Professor † Professor ‡ Professor and Head § Junior Resident Dept. of Obstetrics and Gynecology Government Medical College and Rajindra Hospital Patiala, Punjab Address for correspondence Dr Parneet Kaur House No. 151, Punjabi Bagh Near Klair Orthopedic Centre Patiala 147 001, Punjab E-mail: parneetkd@yahoo.co.in

Methods The present study was conducted for a period of 1 year from January 1, 2009 to December 31, 2009 in the labor room of the Department of Obstetrics and Gynecology, Government Medical College and Rajindra Hospital, Patiala. A total of 212 patients were studied and were divided into three groups according to the method of induction employed. • Group 1: Cases in which mechanical or surgical IOL, that is, artificial rupture of membranes (ARM) was done (25 patients). Patients in this group were less as in most patients either the os was closed or the head was high up; therefore, induction by ARM could not be done. • Group 2: Cases in which medical induction was done. This group was subdivided into two subgroups: (A) Oxytocin by intravenous infusion (52 patients). (B) Misoprostol sublingual or per vaginum given (83 patients). • Group 3: Cases in which medical and surgical methods were used in combination (52 patients).

This study was performed based on two criteria:

• Inclusion criteria: Cases with singleton pregnancy, of > 28weeks gestation and parity ≤ 4 were included in this study. • Exclusion criteria: Cases with previous cesarean section, myomectomy, hysterotomy, or any other Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY Table 1. Indications for Induction of Labor Group 1

Group 2

Group 3

Total

%age

HDP

28.77

Postdated pregnancy

29.72

PROM/LPV

–

15.09

APH

6.13

Congenital malformation

–

4.72

BOH

3.30

Nonreactive NST

–

1.89

Hydraminos

–

1.89

IUD

–

8.49

Total

135

212

100

BOH = Bad obstetric history; HDP = Hypertensive disorders of pregnancy; IUD = Intrauterine death; LPV = Leaking per vaginum; NST = Nonstress test; PROM = Premature rupture of membranes.

Table 2. Induction-Delivery Interval Induction-Delivery interval (in Hours)

Successful no. of patients (%age) (Vaginal delivery) Group 1

Group 2

Group 3

0-6

10 (45.45)

25 (22.12)

21 (43.75)

6-12

6 (27.27)

48 (42.48)

20 (41.67)

12-18

3 (13.64)

21 (18.58)

4 (8.33)

18-24

2 (9.09)

12 (10.62)

3 (6.25)

> 24

1 (4.54)

7 (6.19)

0 (0)

Total

113

χ2 = 2.87; p = 0.5798 (not significant).

scar on the uterus, contracted pelvis, cephalopelvic disproportion (CPD), malpresentation, active herpes simplex infection, and placenta previa, any clinical evidence of fetal distress, or history of allergy to prostaglandins were excluded from the study. On admission of the patient to the hospital, the particulars of the patient, such as name, age, parity, detailed history of pregnancy, menstrual history with last menstrual period, and obstetric history, were recorded. Family history, past history, and drug history was also noted. A thorough general physical examination was done followed by local examination, which included per abdomen examination and per vaginal examination. The indication for IOL of each case was noted (Table 1) and the method of induction was chosen according to the individual case. In cases where the Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

Bishop Score was five or less, that is, unfavorable cervix, ripening of cervix was done by intracervical (0.5 mg)/intravaginal (1 mg) instillation of prostaglandin gel or intravenous oxytocin drip. Cervical scoring was repeated after 6 hours In cases where cervix was ripe, IOL was started by any of the method described above. In those cases where cervix was unripe even after 12 hours of first instillation, second dose of prostaglandin was instilled. Time of onset of regular painful uterine contractions was taken as time of initiation of labor. Observations The following observations were made in all the cases: (1) progress of labor, (2) mode of delivery, and (3) any maternal complications. The observations were recorded and analyzed, and conclusions were drawn. The incidence of IOL in the present study group was 13.86%. The most common indications for IOL were postdated pregnancy (29.72%) and hypertensive disorders of pregnancy (28.77%). Table 2 shows that maximum number of patients (85.42%) in Group 3 were delivered vaginally within 12 hours, 14.58% were delivered in 12-24 hours, and none had induction-delivery interval > 24 hours. In Group 1 and Group 2, delivery within 12 hours was accomplished in 62.72% and 64.60% cases, respectively, while 22.73% and 29.2%, respectively, took 12-24 hours to deliver; but this difference was not statistically significant. 9

CLINICAL STUDY Table 3. Mode of Delivery Mode of delivery Spontaneous vaginal delivery

Group 1

Group 2

Group 3

Total No. of patients

%age

22 (88%)

111 (82.22%)

47 (90.39%)

180

84.90

–

2 (1.48%)

1 (1.92%)

1.89

LSCS

3 (12%)

22 (16.30%)

4 (7.69%)

13.68

Total

135

212

100

Outlet forceps delivery

χ2 = 2.87; p = 0.5798 (not significant). LSCS = Lower segment cesarean section.

Table 4. Maternal Complications in Different Study Groups Maternal complications PPH

Group 1

Group 2

Group 3

Total No. of patients

%age

5 (20%)

4 (2.96%)

3 (5.77%)

5.66

–

1 (0.74%)

2 (3.85)

1.42

2 (8%)

1 (0.74%)

2 (3.85%)

2.36

Cervical tear

–

4 (2.96%)

1 (1.92%)

2.36

Cesarean hysterectomy

–

Total

11.80

Retained placenta Maternal pyrexia

PPH = Postpartum hemorrhage.

Table 5. Indications for Cesarean Section in Cases of Induced Labor Maternal complication

Group 1

Group 2

Group 3

Total No.

%age

Cervical dystocia

0.47

NPOL

1.42

Failed induction

0.94

Undiagnosed CPD

0.47

Fetal distress

8.02

Malposition

0.94

Abnormal uterine action

0.94

HELLP

0.47

Total

13.68

APH = Antepartum hemorrhage; HELLP = Hemolysis, elevated liver enzymes, low platelet count; NPOL = Nonprogress of labor.

The maximum number of patients (90.39%) delivered vaginally were in Group 3, whereas 88% and 82.22% of the patients were delivered vaginally in Group 1 and Group 2, respectively; but the difference was not statistically significant. The LSCS rate in Group 1, Group 2, and Group 3 was 12%, 16.30% and 7.69%, respectively (Table 3). 10

In the present study, the most common maternal complication was PPH that occurred in 5.66% of the patients (Table 4). The most common indications for LSCS were fetal distress (8.02%) and NPOL (2.36%). The rate of failed induction was 0.94% (Table 5). Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY Discussion

Conclusion

IOL is a valuable procedure in obstetrics, often undertaken in the interest of the mother or of the fetus or both. An ideal method of induction must be cost effective, must ensure efficacy and safety for the mother and the fetus with minimal induction delivery interval, and should be convenient for the patient and the medical staff.

All methods were equally effective in IOL in terms of induction delivery interval and mode of delivery but the combined method, that is, medical and surgical, had the best results.

The incidence of IOL in the present study (13.86%) is higher as compared to that reported by Arulkumaran et al (10% and 9.8%).4 In the present study, the most common indications for IOL were postdated pregnancy (29.72%) and HDP (28.77%). Boulvain et al5 also reported these two as the most common indications for IOL. In the present study, medical and surgical methods when used in combination gave the best results in terms of both induction-delivery interval (85.42% of the patients delivered within 12 hours) and successful vaginal delivery (92.31%) as compared to when either of these methods were used individually; 72.72% and 65.18% of the patients were delivered within 12 hours when induced by surgical methods and medical methods, respectively, and 88% and 83.7% of the patients delivered vaginally when induction was done by surgical and medical methods, respectively. Out of total, 86.32% of the patients delivered vaginally and 13.68% underwent cesarean section, which is comparable to the study of Boulvain et al5 who reported vaginal delivery and cesarean in 87.88% and 12.12% of the patients, respectively. PPH and maternal pyrexia were the most common maternal complications observed and occurred in 5.66% and 2.36%, respectively, whereas the study by Tan et al6 reported PPH and maternal pyrexia in 13.3% and 21%, respectively.

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

Acknowledgment The authors would like to thank Dr Surjit Kaur Bajwa, our Ex-Professor and Head, for her continuous guidance and support during the study.

References 1. American College of Obstetricians and Gynecologists. Technical Bulletin Number 157-July 1991. Induction and augmentation of labor. Int J Gynecol Obstet 1992;39:139. 2. Abramovici D, Goldnasser S, Mabie BC, Mercer BM, Goldwasser RN, Sibai BM. A randomized comparison of oral misoprostol versus Foley catheter and oxytocin for induction of labor at term. Am J Obstet Gynec 1999;181:1108-12. 3. Johnson DP, Davis NR, Brown AJ. Risk of cesarean delivery after induction at term in nullipaous women with an unfavourable cervix. Am College Obstet Gynecol 2003;188:1565-9. 4. Arulkumaran S, Gibb DM, Tambyraja RL, Heng SH, Ratnam SS. Failed induction of labor. Aust N Z J Obstet Gynaecol 1985;25(3):190-3. 5. Boulvain M, Fraser WD, Marcoux S, Fontaine JY, Bazin S, Pinautt JJ, et al. Does sweeping of the membranes reduce the need for formal induction of labor? A randomized controlled trial. Br J Obstet Gynecol 1998;105:34-40. 6. Tan PC, Valiapan SD, Tay PYS, Omar SZ. Concurrent oxytocin with dinoprostone pessary versus dinoprostone pessary in labor induction of multiparas with infavourable cervix: a randomized placebo-controlled trial. Br J Obstet Gynaec 2007;114:824-32.

CLINICAL STUDY

Randomized Control Study of Oral Versus Vaginal and Sublingual Misoprostol with Mifepristone for First-Trimester MTP RR Sahu*, AA Soni*, VS Raut*

ABSTRACT Objective: To compare the outcome of two regimes of mifepristone and misoprostol (oral vs vaginal and sublingual administration of misoprostol) for medical termination of early pregnancy (within 49 days). Study design: A randomized controlled study was conducted. On 75 women undergoing medical termination of pregnancy (MTP) within 49 days of amenorrhea (7 weeks). These women were divided into two groups â&#x20AC;&#x201C; Group 1: received tablet mifepristone 200 mg orally followed by tablet misoprostol 600 mcg oral after 48 hours Group 2: received tablet Mifepristone 200 mg orally followed by misoprostol tablet 800 mcg, two tablets administered per vaginum and two tablets advised to be taken sublingually after 12 hours An ultrasonography pelvis was performed on all patients pre-MTP to confirm the location and age of gestation and post-MTP on Day 15 to confirm no retained products of conception. Statistical analysis was done by two proportion tests for individual side effect with the null hypothesis. Results: The complete abortion rates in Group 1 were 91.4% as compared to 90% in Group 2. Only 11.4% of women in Group 1 and 12.5% in Group 2 had bleeding for more than 15 days. The duration and amount of bleeding were statistically similar in both groups. Conclusion: We concluded that after 48 hours of administration of mifepristone, oral 600 mcg of misoprostol is as efficient as 800 mcg of misoprostol (administered vaginally, 400 mcg and sublingually, 400 mcg) in inducing medical abortion of pregnancy within 49 days of amenorrhea. Key words: Mifepristone, misoprostol, medical termination of pregnancy

n India, 6.7 million induced abortions are performed per year, with a ratio of 60 induced abortions per 1,000 women of child-bearing age.1 In spite of legalization of medical termination of pregnancy (MTP) in India, the incidence of illegal abortion is at times more common than legal abortion. Unsafe abortions are a major cause of mortality among women in India accounting for 12% of all maternal deaths. Medical abortion using combination of mifepristone and misoprostol offers a potentially simple and safe method than surgical abortion. Mifepristone was approved for abortion in the United States by the Food and Drug Administration (FDA) in September 2000. In India, medical method of termination was approved only in 2002, for pregnancies up to 49 days after the last menstrual period. Later, the Drug Controller in the year 2010 approved the use of

* Consultant Dr LH Hiranandani Hospital, Powai Mumbai, Maharashtra Address for correspondence Dr Rakhee R Sahu C-202, Blooming Heights, Pacific Enclave CHSL G.L. Compound, Powai - 400 076 Mumbai, Maharashtra E-mail: rakhee.sahu@hiranandanihospital.org

MTP pill up to 63 days of pregnancy. Various regimes and combination of mifepristone and misoprostol have been experimented to achieve complete abortion rates with low doses and least side effects. We conducted this study for medical abortion using two regimes of mifepristone with misoprostol in different doses and different routes of administration of misoprostol. This study was conducted to find an optimally effective regime for medical termination of early pregnancy. Mifepristone, a 19-nor-steroid, is a derivative of the synthetic progestin norethindrone. Mifepristone acts as a competitive receptor antagonist and binds to the progesterone receptors with three to four times greater affinity resulting in necrosis of the endometrium and deciduas. It also causes softening of cervix and mild uterine contractions. Mifepristone also sensitizes the uterus to prostaglandins and increases the efficacy of prostaglandins. It also acts as a competitive antagonist at the glucocorticoid receptor. Misoprostol is a synthetic analogue of prostaglandin E1 (PGE1). It was approved by the US FDA for the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers. The action of misoprostol on the pregnant uterus was first described Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY by Rabe et al in 1987; they discovered that it binds to the EP-2/EP-3 prostanoid receptors and induces effective uterine contraction. Although misoprostol is licensed for oral administration, it is now often used vaginally and also sublingually.

Table 1. Basic Characteristics of the Patients Included in the Study

Aim

Total patients

The patients were clinically examined for pallor, systemic examination, and per vaginal examination to assess the size of uterus and exclude ectopic pregnancy. Anti-D injections were administered if the pregnant women had Rh negative blood group. Ultrasonography pelvis was performed for all patients to confirm intrauterine pregnancy and weeks of gestation. The basic characteristics of the patients are shown in Table 1 and Figure 1. Patients of Group 1 received mifepristone tablet 200 mg orally on Day 1. On Day 3, that is, after 48 Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

21-42

Multigravida

4-6.6

5-6.3

Weeks of gestation (ultrasonography) Previous LSCS

Group 1 Group 2

25 20 15 10

CS sL S iou ev Pr

ltig

rav

ida

We ge eks sta of tio n

The study was conducted at Dr LH Hiranandani Hospital, Mumbai, from November 2011 to August 2012. The study included women who requested for MTP within 49 days of amenorrhea, that is, seven weeks of pregnancy. Exclusion criteria were women with severe anemia, suspected ectopic pregnancy, known case of coagulopathy or on anticoagulant therapy, cardiovascular diseases such as uncontrolled hypertension, angina, valvular disease, and arrhythmia, severe renal, liver, or respiratory disease, uncontrolled seizure disorder, inherited porphyria, and allergic to mifepristone or misoprostol. Women who opted for MTP gave written informed consent and agreed for suction evacuation if there was heavy bleeding and incomplete abortion.

20-38

igr

Material and Methods

Age (years)

Women seeking MTP were given option of medical as well as surgical termination of pregnancy. Women who opted for medical termination using pills were further counseled regarding the procedure and visits for MTP and written valid consent was taken. All the patients were explained that in case of incomplete abortion or continuation of pregnancy, surgical uterine evacuation was advised.

Group 2 Group 1 (Mifepristone 200 mg (Mifepristone 200 + Oral misoprostol mg + Misoprostol 800 mcg) 600 mcg)

Primigravida

This study was conducted to evaluate the efficacy of two regimes of MTP using different dosage and route of misoprostol administration.

Parameter

Figure 1. Basic characteristics of the patients included in the study.

hours of mifepristone, patients were advised to take misoprostol tablet 600 mg orally. Patients of Group 2 received mifepristone tablet 200 mg orally on Day 1. On Day 3, patients were advised to insert misoprostol tablet 400 mcg per vaginum followed by misoprostol tablet 400 mcg sublingually (total 800 mcg misoprostol). Statistical Analysis The data was managed in Microsoft Excel spreadsheet. Demographics were described as average, standard deviation, minimum and maximum observation, and median (middle value). Demographics and general information for various parameters with all permutations and combinations were calculated in Microsoft Excel. Two proportion tests with null hypothesis of equal proportion was used to investigate 13

CLINICAL STUDY Table 2. Amount of Bleeding in Both Groups Amount of bleeding

Group 1

Group 2

Heavy bleeding

Moderate bleeding

Comparison of amount of bleeding between Groups 1 and 2.

Complete abortion

Incomplete abortion

15 10

Test and CI for Two Proportions Sample

Sample p

0.885714

0.925000

Difference = p (1) p (2); Estimate for difference: −0.0392857

Group 1

Group 2

Figure 2. Comparison of outcome of MTP between Groups 1 and 2.

95% CI for difference: (−0.172599, 0.0940279); Test for difference = 0 (vs not = 0): Z = −0.58; p-value = 0.564. Conducted two proportion tests with the null hypothesis: “Moderate bleeding (in amount of bleeding) in Group 1 is equal to Group 2.” Conclusion: As the p value is > 0.05, there is no significant difference in moderate bleeding for amount of bleeding between Groups 1 and 2.

and model impact of various parameters like result of outcome of MTP, duration of bleeding, and side-effects between the two groups. A p value < 0.05 was considered statistically significant (Table 2). All graphs were drawn and all statistical analysis was done using Minitab 16. All patients were asked to note the onset of bleeding after medication, and the amount and duration of bleeding. Patients reported any of the side-effects of medications like nausea, vomiting, giddiness, diarrhea, painful cramps in abdomen, rash, or allergic reaction. All patients were advised to follow-up after 14 days of mifepristone tablets for clinical examination and ultrasound confirming no retained products of conception. Post-MTP ultrasonography was done for all patients in our study to look for complete expulsion of products of conception. On day 15 of follow-up, the amount and duration of bleeding and any of the side effects were noted. Few patients reported mild bleeding on day 2 after oral mifepristone, 8.5% in Group 1 and 8.8 % in Group 2. Most of the patients reported onset of bleeding usually 4-6 hours after misoprostol tablets ingestion. All the parameters and abortion rates were statistically analyzed by the two proportion test with null hypothesis of equal proportion. A p value < 0.05 was considered statistically significant. Successful outcome of medical termination was considered when there were no retained products of conception seen in 14

Table 3. Treatment Outcome of the Regimes Outcome of MTP

Group 1 (Total = 35)

Group 2 (Total = 40)

Complete abortion

Incomplete abortion

Dilation and curettage required

Test and CI for Two Proportions Sample

Sample p

0.085714

0.125000

Difference = p (1) p (2); Estimate for difference: −0.0392857; 95% CI for difference: (−0.177508, 0.0989361); Test for difference = 0 (vs not = 0): Z = −0.56; p value = 0.577 Conducted two proportion tests with the null hypothesis: “The percentage defective in outcome of MTP is equal for Groups 1 and 2.” Conclusion: As the p value is > 0.05, the null hypothesis is accepted at 95% CI. This means that there is a no significant difference in outcome of MTP between Groups 1 and 2.

post-MTP ultrasonography and when there was no need for surgical intervention of suction evacuation for heavy bleeding or retained products of conception. The abortion rate in Group 1, which was treated with mifepristone tablet 200 mg followed by misoprostol tablet 600 mcg orally, was 91.4% (Table 3). The complete abortion rate in Group 2, which was treated with 200 mg of mifepristone followed by misoprostol tablet 400 mcg vaginally and 400 mcg sublingually, 12 hours apart on Day 3, was 90% (Table 3). The comparison of outcome of MTP between Group 1 and 2 is shown in Figure 2. The p value was > 0.05, the null hypothesis is accepted at 95% confidence interval Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY

Conducted two proportion tests for individual duration with the null hypothesis: “The duration of bleeding is equal between Groups 1 and 2.”

in duration of bleeding between Group 1 and Group 2. Oral misoprostol 600 mcg was tolerated well by patients and lowering the dose did not reduce the abortion rates and the amount or duration of bleeding when compared with total 800 mcg of misoprostol. The incidence of nausea and vomiting was lesser with vaginal and oral misoprostol as compared to sublingual route (Table 5, Fig. 3).

Conclusion: As the p value is > 0.05 for all the parameters, there is no significant difference in duration of bleeding between Groups 1 and 2.

Pharmacokinetics of Mifepristone

Table 4. Duration of Bleeding Duration of Bleeding

Group 1

Group 2

< 7 days

7-10 days

> 14 days

Comparison between Groups 1 and 2 for duration of bleeding.

Table 5. Side Effects of Misoprostol Side effects of misoprostol

Group 1

Group 2

Nausea

Vomiting

Pain in lower abdomen requiring analgesic

Fainting

Rash and allergic reaction

Emergency services required

Comparison between Groups 1 and 2 for various side-effects. Conducted two proportion tests for individual side-effect with the null hypothesis: “The proportion of side-effect for Group 1 is equal to the proportion of Group 2.” Conclusion: As the p value is > 0.05 and t test of mean difference 0 is within the CI, the null hypothesis is accepted at 99% CI. This means there is a no significant difference in side-effects between Groups 1 and 2.

6 5 4 3 2 1 0

Fa R in tin re ash ac a g tio n n da E lle re me rg qu rg ic ire en d cy se rv ic es

iti ng P ab ain do in m lo en w er

Vo m

au s

Group 1 Group 2

Figure 3. Comparison of outcome of MTP between Groups 1 and 2.

(CI), and there is no statistical difference in outcome of MTP between Groups 1 and 2. The duration and amount of bleeding were similar in both groups (Table 4). As the p value is > 0.05 for all the parameters, there is no significant difference Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

In the presence of progestins, mifepristone acts as a competitive receptor antagonist for progesterone receptors. When administered in early pregnancy, it causes decidual breakdown by blockade of uterine progesterone receptors, which leads to detachment of blastocyst resulting in decrease of human chorionic gonadotropin production. This, in turn, decreases the progesterone from the corpus luteum, softens the cervix, and enhances uterine contractions. The bioavailability of mifepristone is approximately 60% of the administered dose, with 85% of the drug being absorbed after oral administration and peak serum levels occurring 1-2 hour later. Concentrations remain stable for 12 hours and then start to decline with a half-life of approximately 24 hours in pregnant or nonpregnant women. Mifepristone causes endometrial shedding by direct inhibition of the endometrial progesterone receptor, leading to decreased glandular secretion activity and accelerated degenerative changes that usually occur within 48-72 hours of drug administration. Pharmacodynamics and Pharmacokinetics of Misoprostol Misoprostol is a synthetic PGE1. PGE1 causes myometrial contractions by interacting with specific receptors on myometrial cells. This interaction results in a change in calcium concentration, thereby initiating muscle contractions. By interacting with prostaglandin receptors, misoprostol causes the cervix to soften and the uterus to contract, resulting in expulsion of uterine contents. Misoprostol is extensively absorbed and undergoes rapid de-esterification to its free acid, which is responsible for its clinical activity, and unlike the parent compound, is detectable in plasma. The alpha chain undergoes beta oxidation and the beta side chain undergoes omega oxidation followed by reduction of the ketones to give prostaglandin F analogs. The compound is a lipophilic methyl ester prodrug and 15

CLINICAL STUDY is readily metabolized to the free acid, which is the biologically active form. Following oral administration, the plasma concentration increased rapidly with a peak of 30 min, declined rapidly by 120 min, and remained low thereafter. In contrast, after vaginal administration, the plasma concentration gradually increased, reaching maximum levels after 70-80 min and slowly declined with detectable levels present after 6 hours Vaginal misoprostol was present in the circulation longer than oral misoprostol and hence its duration of stimulation of the uterus exceeds that of oral misoprostol.2 Vaginal application of misoprostol results in slower increase and lower plasma concentrations of misoprostol acid than does oral administration, but overall exposure to drug is increased. Misoprostol inhibits gastric acid secretion in humans and there is also some evidence that it limits the extent of gastrointestinal damage induced by ulcerogenic agents in animals and healthy volunteers at doses lower than those required to inhibit acid secretion. NSAIDs inhibit prostaglandin synthesis and a deficiency of prostaglandin within the gastric mucosa may lead to diminishing bicarbonate and mucus secretion and may contribute to the mucosal damage caused by these agents. Misoprostol increases bicarbonate and mucus production, but in man it has been shown that at doses 200 mcg and above they are antisecretory. It is therefore not possible to tell whether the ability of misoprostol to reduce the risk of gastric ulcer is the result of its antisecretory effect or its mucosal effect, or both. The recommended adult dose for reducing the risk of NSAID-induced ulceration is 100-200 mcg four times a day with food. If the patient becomes pregnant on misoprostol therapy, she has to be appraised of potential harm to the fetus and should be advised abortion. The use of misoprostol in first trimester of pregnancy has been associated with a specific type of moebius sequence with or without limb deficiency.3,4 Discussion Medical abortion offers great potential for improving abortion access and safety, as it requires less extensive infrastructure than surgical abortion. Also there is, no need for anesthesia and operation theater facilities, and maintains patientâ&#x20AC;&#x2122;s need for privacy. The disadvantages would be that the women requires at least three visits to the hospital, unpredictable outcome in few patients, 16

longer duration of bleeding, and potential risk of fetal malformation if it fails to cause abortion. The factors that may prevent the women from accepting the medical method of termination of pregnancy is the abdominal cramps and heavy bleeding, duration of bleeding (average 7-10 days), and the need to follow-up after 2 weeks for clinical examination and sonography. We conducted this study to find the efficacy of the regime of pretreatment with mifepristone followed by low-dose misoprostol administered orally along with vaginal and sublingual route. The abortion rate in Group 1 (600 mcg misoprostol orally) was 91.4% and in Group 2 (400 mcg vaginally and 400 mcg sublingually 12 hours apart) was 90%. Most of the patients would start bleeding within 6 hours of misoprostol tablets. The incidence of minimal bleeding on Day 2 after mifepristone was observed in 8.8% of patients in Group 1 and 8.5% in Group 2. There is evidence that it is beneficial to perform a routine ultrasonography at the time when a patient is seen for the first time for a termination of pregnancy.5 The scan allows the exact determination of the gestational age, especially in women with irregular cycles, which is important for advising the patient about the most appropriate method of termination. It also helps to diagnose multiple pregnancies, exclude/diagnose ectopic pregnancy, diagnose a molar pregnancy, and diagnose coincidental pelvic pathology like fibroid or ovarian cyst. Multicentric trails conducted by the World Health Organization demonstrated that the effectiveness of 600 mg of mifepristone can be compared with 200 mg dosage.6 Chuni and Chandrashekhar7 conducted a study on 112 women for MTP of 63 days duration with oral mifepristone 200 mg followed by oral misoprostol 400 mcg 48 hours apart. The rates of complete abortion were 92.8%, 83%, and 80% in the < 49 days group, 50-59 days group, and 57-63 days group, respectively. Mittal et al8 conducted a study comparing oral versus vaginal misoprostol and continued use of misoprostol after mifepristone for early medical abortion. Women within 9 weeks of pregnancy were included and all were given mifepristone 200 mg on Day 1 followed by misoprostol after 48 hours In this study, patients were divided into three groups: Group 1 received 800 mcg misoprostol orally and placebo vaginally; Groups 2 and Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY 3 received misoprostol 800 mcg vaginally and placebo orally. Those in Groups 1 and 2 received oral misoprostol 400 mcg twice a day from Day 4 for 7 days, while Group 3 took placebo. The abortion rates were 100%, 98% and 96% in Groups 1, 2 and 3, respectively. The addition of misoprostol for 7 days from Day 4 did not help in decreasing the abortion rates nor the duration or the amount of bleeding. Since misoprostol also has protective action on the gastric mucosa, there was no increased incidence of nausea and vomiting in the oral group. A study was conducted by the World Health Organization (WHO),9 Geneva, on 1589 pregnant women with menstrual delay of less than or equal to 35 days requesting for nonsurgical abortion. A double-blinded study assigned a single oral dose of mifepristone, either 200 mg or 600 mg, followed by oral misoprostol 400 mcg. The complete abortion rate with the lower dose of mifepristone was similar to that of higher dose (89.3% vs 88.1%). The efficacy of the mifepristone prostaglandin regime was not reduced by decreasing the dose of mifepristone from 600 to 200 mg. However, it was noted that this regime was not sufficiently efficient in inducing complete abortion when the length of pregnancy was more than seven weeks. A clinical study of medical termination on 263 women with up to nine weeks of pregnancy showed that vaginal administration of 800 mcg after pretreatment with mifepristone resulted in higher complete abortion rate (95%) than with oral route (87%). The WHO multinational study10 of mifepristone combined with three different misoprostol regimes – (a) 800 mcg vaginally on Day 3 only; (b) 800 mcg vaginally on Day 3 followed by 400 mcg orally twice a day daily for 7 days; or (c) 800 mcg orally on Day 3 followed by 400 mcg orally twice a day orally daily for 7 days; n = 2,219. This study found that in women with gestation periods more than 59 days, the risk of failure was higher in group (c) compared to group (b) (RR 2.8, CI 1.3-5.8), but there were no significant differences in efficacy in women with gestation periods less than 59 days. A study was conducted by el-Refaey et al11 on induction of abortion with mifepristone (600 mg) and oral or vaginal misoprostol (800 mcg) in 270 pregnant women within 63 days from onset of amenorrhea. The rate of Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

complete abortion was 87% in the oral misoprostol group and 95% in the vaginal group (p = 0.03). Vomiting and diarrhea were reported more frequently by the women who received oral misoprostol than by those who received vaginal misoprostol. They concluded that vaginal administration of misoprostol is more effective and better tolerated than oral administration for induction of first-trimester abortion. A study by Ashok et al12 showed an efficacy of 98% in a series of 2,000 women up to 63 days from last menstrual period with 200 mg mifepristone orally, followed by 2 days later by 800 mcg misoprostol vaginally. Conclusion The complete abortion rate with mifepristone followed by oral misoprostol (600 mcg) (91.4%) was comparable to that with mifepristone followed by vaginal and sublingual misoprostol (800 mcg) (90%). The amount and the duration of bleeding were comparable in both the groups. The patients were more comfortable with oral tablets of misoprostol rather than the vaginal insertion. Access to safe abortion is limited in many developing countries because of legal restrictions, administrative and financial barriers, and lack of adequately trained providers. More trails are needed to find a method of medical termination that is efficient and acceptable with minimal side-effects. There is a need to examine the different dosages, routes, and timings of administration of mifepristone and misoprostol to determine the most appropriate treatment protocol. Acknowledgment The authors would like to thank Dr Sujit Chatterjee, CEO, Dr LH Hiranandani Hospital, Mumbai, for allowing to conduct and publish the study.

References 1. Chhabra R, Nuna SC. Abortion in India: an overview. Delhi: Ford Foundation; 1994. 2. Zeiman M, Fong SK, Benowitz NL, Banskter D, Darney PD. Absorption kinetics of misoprostol with oral or vaginal administration. Obstet Gynecol 1997;90(1):88-92. 3. Paustuszak AI, Schuler L, Speck-Martins CE. Use of misoprostol during pregnancy and Möbius syndrome in infants. N Engl J Med 1998;338:1881-5. 4. Gonealez CH, Vargas FR, Perez AB, et al. Limb deficiency with or without Möbius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy. Am J Med Genet 1993;47:59.

CLINICAL STUDY 5. McGalliard C, Gaudoin M. Routine ultrasound for pregnancy termination request increases womenâ&#x20AC;&#x2122;s choice and reduces inappropriate treatments. Br J Obstet Gynecol 2004;111:79-82. 6. World Health Organisation Task Force on Post-ovulatory Methods of Fertility Regulation; Special Programme of Research, Development and Research Training; World Health Organisation. Comparison of two doses of mifepristone in combination with early medical abortion: a randomized trial. Br J Obstet Gynecol 2000;107:524-30. 7. Chuni N, Chandrashekhar TS. Early pregnancy termination with a simplified mifepristone: medical abortion outpatient regimen. Kathmandu Univ Med J 2009;7(27):209-12. 8. Mittal S, Agarwal S, et al. Comparison of oral versus vaginal misoprostol and continued use of misoprostol after mifepristone for early medical abortion. Indian J Med Res 2005;122:132-6.

9. World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation. Medical abortion at 57 to 63 days gestation with a lower dose of mifepristone and gemeprost. A randomized controlled trial. Acta Obstet Gynecol Scand 2001;80:447-51. 10. von Hertzen H, Honkanen H, Piaggio G, et al; WHO Research Group on Post-ovulatory Method for Fertility Regulation. WHO multinational study of three misoprostol regimen after mifepristone for early medical abortion. I: efficacy. Br J Obstet Gynecol 2003;110(9):808-18. 11. el-Refaey H, Rajasekar D, Abdalla M, Calder L, Templeton A. Induction of abortion with mifepristone and oral or vaginal misoprostol. N Engl J Med 1995;332 (15):983-7. 12. Ashok PW, Penney GC, Flett GM, Templeton A. An effective regime for early medical abortion: a report of 2000 consecutive cases. Hum Reprod 1998;13:2962-5.

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY

Comparative Study of Obstetric Outcome Between Scarred and Unscarred Uterus in Placenta Previa Cases Gayatri Mathuriya*, Pallavi Lokhande**

ABSTRACT Objective(s): To compare the incidence of placenta previa, associated factors, complications, placental position, mode of delivery and fetal and maternal outcome in scarred (Group A) and unscarred uterus (Group B) in 20 months of hospital-based study. Material and methods: In a prospective study, 140 cases of pregnancies beyond 28 weeks of gestation complicated by placenta previa were identified. These cases were divided into two groups, scarred uterus (Group A, n = 34) and unscarred uterus (Group B, n = 106). Total number of deliveries were 16,784 out of which 2,354 patients had cesarean section and 140 patients had placenta previa. Results: The incidence of placenta previa in scarred cases is significantly higher (1.2%) than overall incidence (0.6%). Majority of scarred cases had anterior placenta (85.2%) and majority of unscarred cases had posterior placenta (63.2%) (p = 0.00, HS). The number of unbooked cases in both Groups A and B was high (p = 0.404, NS). A significant association of placenta previa following curretage in Group B was observed (p = 0.002, S). There was only one maternal mortality in Group B and none in Group A. Results showed a favorable fetal outcome in both groups. (Group A-70.6%, Group B-64.2%, p = 0.08, NS). Conclusion(s): An increase in the incidence of prior cesarean section and advanced maternal age probably contribute to a rise in the number of pregnancies complicated with placenta previa and its association with adverse maternal and perinatal outcome. Key words: Placenta previa, incidence, maternal outcome, fetal outcome

lacenta previa is an obstetric complication in which the placenta is inserted partially or wholly in lower uterine segment.1 It can sometimes occur in later part of the first trimester, but usually occurs during the second or third. It is a leading cause of antepartum hemorrhage (vaginal bleeding). It affects approximately 0.4-0.5% of all labors.2 Exact etiology of placenta previa is unknown. It is hypothesized to be related to abnormal vascularization of the endometrium caused by scarring or atrophy from previous trauma, surgery or infection. These factors may reduce differential growth of lower segment, resulting in less upward shift in placental position as pregnancy advances.3

The traditional classification of placenta previa describes the degree to which the placenta encroaches upon the cervix in labor and is divided into low lying, marginal, *Assistant Professor Dept. of Obstetrics and Gynecology MGM Medical College and MY Hospital, Indore, Madhya Pradesh **Resident Dept. of Obstetrics and Gynecology MGM Medical College, Indore, Madhya Pradesh Address for correspondence Dr Gayatri Mathuriya 48, Kalindi Kunj, Indore - 452 001, Madhya Pradesh E-mail: drgayatrimathuriya@gmail.com

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

partial or complete placenta previa.4 In recent years due to the increased value of transvaginal ultrasound in diagnosis of placenta previa, the traditional classification is rendered obsolete.4 Diagnosis is made on history, clinical examination and few investigations that include ultrasound (transabdominal, transvaginal) and megnetic resonance imaging (MRI).5 Although the etiology the placenta previa remains speculative, several risk factors associated with this condition have been established. These include advanced maternal age, multiparity, multiple gestation, previous abortion, previous cesarean section and placenta previa in previous pregnancy.6 Myometrial damage due to cesarean section and dilation curettage are main predisposing factors. 7 Also, risk factors are previous cesarean section, history of abortion and complete previa.8 Most obstetricians have concerns about massive hemorrhage not only when complete previa exists but also when placenta is located on the anterior position of the uterus, beneath the cesarean incision site.9,10 Patients with placenta previa are at increased risk of spontaneous abortion, fetal malpresentation, cesarean section, increased loss of blood, peripartum hysterectomy and prolonged hospitalization. 19

CLINICAL STUDY The infants of these patients are also at increased risk of premature deliveries, increased perinatal mortality than in general population. The frequency of this condition may be on the rise so we need to identify and target preventive interventions among women at increased risk of placenta previa. Material and Methods This study was conducted in the Dept. of Obstetrics and Gynecology, MGM Medical and MY Hospital, Indore, from May 2011 to December 2012. A total number of 140 patients beyond 28 weeks gestation, complicated by placenta previa alone or with previous myomectomy, cesarean section and uterine repair were identified. All types of placenta previa were included. The subjects were divided into two groups: Group A in which placenta previa occurred in scarred uterus and Group B in which placenta previa occurred in unscarred uterus. Transabdominal sonography was done for obstetrical reasons as well as for exact location of placenta. The following potential risk factors such as maternal age, parity, previous abortion, prior cesarean section and multiple pregnancies were examined in both the groups and were compared. Table 1. Maternal Characteristics Scarred uterus (Group A)

Unscarred uterus (Group B)

No.

20-25

23.6

65.0

26-30

67.6

22.6

> 30

8.8

12.4

P value

Age in years 0.00 (HS)

Parity 0.002 (S)

21.6

5.8

6.6

â&#x2030;Ľ4

7.6

History of curettage

3.8

0.002 (S) 0.23 (NS)

20.58

Gestational age (weeks)

< 37

> 37

Table 2. Relative Frequency Scarred uterus (Group A)

Unscarred uterus (Group B)

No.

67.8

47.2

17.6

33.0

III

5.8

11.4

8.8

8.4

85.3%

36.8%

Posterior

17.7

63.2

P value

Grading 0.17 (NS)

Type

The association malpresentation, hemorrhage and evaluated in both

0.00 (HS)

of placenta previa with fetal abruptio placenta, postpartum maternal fetal outcome were also the groups and compared.

Chi-square test and chi-square test with Yateâ&#x20AC;&#x2122;s correction was used to compare different quantitative data variable. Results Maternal characteristics of the two groups are given in Table 1. Majority of the patients in the study were between the age range of 26-30 years in Group A (67.6%) and 20-25 years in Group B (65%) (p = 0.00, HS). Primipara with placenta previa were 0 in Group A and 31 (29.2%) in Group B (p = 0.002, S). A definite association of placenta previa following curretage was observed (Group A-20.58%, Group B-3.8%, p = 0.002, S). Table 2 shows that majority of cases had Grade I or low lying placenta, which is 47.2% in unscarred and 67.8% in scarred cases (p = 0.17, NS). Majority of patients with scarred uterus had anterior placenta, that is 85.3% and majority of patients with unscarred cases had posterior placenta, that is 63.2% (p = 0.00, HS). Table 3 compares the related complications between the two groups. There was only one maternal mortality in Group B and none in Group A (p = 0.001, S). Results showed a favorable fetal outcome in both groups (Group A-70.6%, Group B-64.2%, p = 0.08, NS) (Table 4). Both Groups A and B had a high number of unbooked patients (A-94.11%, B-97.2%, p = 0.404, NS) (Table 5). Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY Table 3. Related Complications Complications

Scarred uterus (Group A)

Table 6. Relative Incidence Unscarred uterus (Group B)

P value

No.

Fetal malpresentation

8.4

0.001

Postpartum hemorrhage

47.05

71.6

(S)

Cesarean section with uterine artery ligation

20.5

5.6

Cesarean section with internal iliac artery ligation

0.94

Cesarean hysterectomy

8.8

Placenta accreta

2.9

Placenta percreta

2.9

Maternal mortality

0.94

Blood transfusion

71.6

Table 4. Fetal Outcome Scarred uterus (Group A)

Unscarred uterus (Group B)

P value

No.

Alive

70.6

64.2

0.08

Stillbirth

24.4

(NS)

Neonatal death

20.4

11.4

Table 5. Booking Status Status

Scarred uterus (Group A)

Unscarred uterus (Group B)

P value

No.

Booked

5.88

2.8

0.404

Emergency

94.11

103

97.2

(NS)

Discussion The incidence of placenta previa in present study is 0.62%, which is comparable to study of Hemmadi et al11 and Reddy et al,12 which is 0.4% and 0.5%, respectively. Incidence of placenta previa is significantly higher in patients with previous cesarean section (1.2%) than overall incidence of 0.6%. Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

Overall incidence of placenta previa

Incidence in scarred cases

Incidence in unscarred cases

0.6%

1.2%

0.47%

Placenta previa is more common among increasing age group, which is 68% in 26-30 years in scarred cases and in unscarred cases 65% in the age group 20-25 years, as comparable to Reddy et al.12 who reported 73% incidence in 20-29 years age group and also comparable to Rasmussen13 who showed increase incidence with increasing maternal age (20-29 years). Our study shows increasing parity increases with risk of placenta previa, Para 3 in scarred uterus, which is 45% and in unscarred cases increased incidence is found in Para 2 cases, which is 30%. The results are consistent with Reddy et al12 in which 69% were multiparous. In our study, we found 7.8% association of placenta previa with previous history of curettage, comparable to study of Taylor et al14 who found that women with one or more spontaneous abortion or induced abortion are 30% more likely to have placenta previa in subsequent pregnancy. Incidence of placenta accreta is greater in patients with prior cesarean section than in unscarred uterus. In our study, 5.8% out of the scarred uterus constitute placenta accreta and percreta, which is consistent with the study of Clark et al15 who concluded that probability of placenta accreta is greater in patients with prior cesarean section. In evaluation of the related complications, we found that women with placenta previa were more likely to have postpartum hemorrhage, cesarean hysterectomy as diminished muscle content in lower uterine segment causes less effective contraction to control bleeding. The associated malpresentation with placenta previa increases the number of cesarean section, deliveries even in cases where placenta previa is marginal. Anterior previa is more common in patients with prior cesarean section compared to no prior cesarean section and it is more dangerous than posterior previa in view of increasing maternal morbidity such as excessive blood loss, massive transfusion, placenta accreta and hysterectomy.16 In our study, also 85.3% cases have anterior previa in scarred uterus and only 36.8% cases in unscarred uterus (p = 0.00 HS). 21

CLINICAL STUDY Prematurity due to placenta previa accounts for 60% of perinatal morbidity.17 In our study, 50% of cases delivered premature babies. Conclusion This study concludes that efforts should be made to reduce the rates of operative deliveries because there is greater likelihood of placenta previa in scarred uterus in subsequent pregnancies. Sonographic detection of anterior placenta is very important to predict maternal outcome in placenta previa and in such cases obstetricians should be aware of maternal massive hemorrhage. The family planning services should be further improved to attain a decline in the number of women of high parity. The morbidity associated with placenta previa can be reduced by detecting the condition in the antenatal period by ultrasound, before it becomes symptomatic. This calls for educating our patients and making them aware of the importance of antenatal care and its availability. References 1. Kumaran A, Warren R, Sabaratnam. Best Practice in Labour and Delivery. 1st edition, 3rd printing edition, Cambridge University Press: Cambridge 2009:p.142-6. 2. Faiz AS, Ananth CV. Etiology and risk factors for placenta previa: an overview and meta-analysis of observational studies. J Matern Fetal Neonatal Med 2003;13(3):175-90. 3. Dashe JS, McIntire DD, Ramus RM, Santos-Ramos R, Twickler DM. Persistence of placenta previa according to gestational age at ultrasound detection. Obstet Gynecol 2002;99(5 Pt 1):692-7. 4. Oppenheimer L; Society of Obstetricians and Gynaecologists of Canada. Diagnosis and management of placenta previa. J Obstet Gynaecol Can 2007;29(3):261-73.

5. Razia A, Alyia B, Asma G, Rabia N, Chohan A. Frequency of placenta praevia with previous caesarean section. Ann King Edward Med Coll 2005;1:299-300. 6. Hung TH, Hsieh CC, Hsu JJ, Chiu TH, Lo LM, Hsieh TT. Risk factors for placenta previa in an Asian population. Int J Gynaecol Obstet 2007;97(1):26-30. 7. Palacios-Jaraquemada JM. Diagnosis and management of placenta accreta. Best Pract Res Clin Obstet Gynaecol 2008;22(6):1133-48. 8. Choi SJ, Song SE, Jung KL, Oh SY, Kim JH, Roh CR. Antepartum risk factors associated with peripartum cesarean hysterectomy in women with placenta previa. Am J Perinatol 2008;25(1):37-41. 9. Ogawa M, Sato A, Yasuda K, Shimizu D, Hosoya N, Tanaka T. Cesarean section by transfundal approach for placenta previa percreta attached to anterior uterine wall in a woman with a previous repeat cesarean section: case report. Acta Obstet Gynecol Scand 2004;83(1):115-6. 10. Boehm FH, Fleischer AC, Barrett JM. Sonographic placental localization in the determination of the site of uterine incision for placenta previa. J Ultrasound Med 1982;1(8):311-4. 11. Hemmadi SS, Shenyar NK Walvekar. J Obstet Gynecol India 1995,4:365. 12. Reddy R, Latha C. Placenta previa: an analysis of 4 year experience. J Obstet Gynecol India 1999;53-56. 13. Rasmussen S, Albrechtsen S, Dalaker K. Obstetric history and the risk of placenta previa. Acta Obstet Gynecol Scand 2000;79(6):502-7. 14. Taylor VM, Kramer MD, Vaughan TL, Peacock S. Placental previa in relation to induced and spontaneous abortion: a population-based study. Obstet Gynecol 1993;82(1):88-91. 15. Clark SL, Koonings PP, Phelan JP. Placenta previa/accreta and prior cesarean section. Obstet Gynecol 1985;66(1): 89-92. 16. Jang DG, We JS, Shin JU, Choi YJ, Ko HS, Park IY, et al. Maternal outcomes according to placental position in placental previa. Int J Med Sci 2011;8(5):439-44. 17. Decherney AH, Pernoll ML. Current Obstetrics and Gynecology. Diagnosis and Treatment Third Trimester Hemorrhage. 8th edition, 1994:p.404-9.

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY

Accuracy in Estimation of Gestational Age in Third Trimester by Fetal Kidney Length in Indian Women DP Gupta*, Hem Prabha Gupta**, Zeeshan Zaidi†, DK Saxena‡, Ratna Prabha Gupta¶

ABSTRACT Introduction: Accuracy in estimation of gestational age (GA) has become more demanding as technology used in sonography has become more advanced. Patient’s expectations have also increased and they expect exact estimations to plan their pregnancies. Fetal kidney length (FKL) alone or in combination with other biometric indices can be used in estimating GA more precisely. Objective: The study aimed in measuring FKL and calculating GA using it as a single parameter and comparing the accuracy when combined with other biometric parameters used in estimation of GA on ultrasonography in third trimester in Indian women. Material and methods: Healthy pregnant women in third trimester with single live fetus with no maternal or fetal complications were selected for the study. FKL along with other biometric parameters were measured. The results were analyzed for finding if FKL could be used as a single parameter in estimation of GA and if the accuracy improved if combined with other indices. Results: GA was estimated in 715 cases by all four parameters in the women who came in the third trimester for ultrasonography. FKL was also measured simultaneously in these women. It was observed that average FKL increased linearly from 30.7 mm at 27 weeks to 39.4 mm at 38 weeks. Mean left kidney length was slightly but significantly more than the right kidney. GA was estimated by FKL alone and it gave results with SE ± 10.45 days and when combined with other indices accuracy improved to SE ± 5.45 days. Conclusion: FKL can be a single lone parameter in estimation of GA to give an accuracy of SE ± 10.45 days, but when used in combination with other four indices the accuracy increased to SE ± 5.5 days. Key words: Gestational age, fetal kidney length

ltrasonography in obstetrics has changed the way gestational age (GA) is determined. It has completely altered the method in which the obstetrician queries, examines and announces the due date of delivery. Dating by last menstrual period (LMP) is inaccurate as most of the women do not remember the date, or they calculate their dates by the Indian Calendar e.g., Sawan ki Ekadashi or before holi and the muslim ladies calculate their LMP by the Islamic Calendar e.g., fifth day after Muharram or Bakri-Id. This is too cumbersome for the obstetrician *Associate Professor Dept. of Radiology **Professor Dept. of Obstetrics and Gynecology † Statistician-cum-Lecturer Dept. of Community Medicine ‡ Assistant Professor Dept. of Radiology Era’s Lucknow Medical College Lucknow, Uttar Pradesh ¶ Consultant Pathologist New X-ray and Pathology, Thakurganj Lucknow, Uttar Pradesh Address for correspondence Dr DP Gupta MIG-2, Napier Road Part II, LDA Colony Thakurganj, Lucknow - 226 003, Uttar Pradesh E-mail: dp_gupta2007@yahoo.co.in

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

and the exact date of LMP is miscalculated. Andersen et al1 demonstrated that only 71% women could accurately tell the date of their LMP. Factors such as menstrual irregularities, conception during lactational amenorrhea and spotting in early pregnancy also lead to miscalculated LMP. An accurate GA has become a necessity in the management of high-risk pregnancies. An accurate GA is of importance in cases, where early termination is necessary as soon as the fetus becomes mature e.g., pre-eclampsia, chronic renal disease, severe intrauterine growth restriction (IUGR), diabetes, central placenta previa and where mothers are Rh-ve. Accurate GA estimation is also necessary, where certain tests need to be performed for example amniotic fluid and serum assays, chorionic villus sampling and to plan fetal therapies. A recent trend can also be included in this list, where women want an elective cesarean section on a certain date e.g., 11.11.11. or 12.12.12 or the new year day and also the date suggested by the astrologer. A sudden increase in operation were witnessed on these dates. In routine ultrasonography, the ultrasonologist measures the biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur 25

CLINICAL STUDY

Average kidney length (mm)

length (FL) in estimating the GA and estimated date of delivery.2 The use of all four biometric indices are recommended for all pregnancies beyond 20 weeks for reduction of variabilities.3 In second trimester BPD, HC, AC and FL can predict GA with fair accuracy (± 10-14 days). As pregnancy advances these parameters become increasingly unreliable in estimation of GA.4 Previous studies have demonstrated that fetal kidney length (FKL) is a more accurate method of GA estimation than BPD, HC, AC and FL after 24 weeks of gestation.5-8 Cohen et al9 demonstrated a strong relation between GA and kidney length (KL) in 397 consecutive women examined at various stages of pregnancy. Konje et al5 have also reported that KL is a more accurate method of determining GA than the fetal biometric indices of BPD, HC, AC and FL between 24 and 38 weeks of gestation. In this study, we have measured the KL in normal pregnancies and y = 0.863x + 7.208 R2 = 0.615

45 40 35 30 25 20

GA (weeks)

Figure 1. Scatter plot of kidney length with gestational age.

calculated the normal range during third trimester in Indian women during different weeks of gestation. An attempt has been made to calculate if FKL alone can be the criteria in estimation of GA, or it gives more accurate results when combined with other biometric indices. Material and Methods The study was conducted in the Dept. of Radiology, Era’s Lucknow Medical College, Lucknow during the period from October 2011 to April 2013 on pregnant women who came for ultrasonography with a single live fetus in the third trimester. All women were screened for any complication during pregnancy, any disease e.g., tuberculosis, diabetes, hypertension, obesity, IUGR and suspected fetal anomalies. Only those fetuses were included in the study in whom the kidney was clearly visualized and no abnormal renal morphology was observed. Seven hundred fifteen pregnant women were screened for BPD, HC, AC and FL. In all these cases, KL was also measured simultaneously. Accuracy of estimation of GA by BPD alone was calculated using it as a single parameter (Table 2) and also GA was estimated by FKL. The accuracy in the prediction of GA was compared to the values obtained when KL was combined with FL, KL with FL and BPD, KL with FL and AC and KL with FL and HC. All these values were compared to the values obtained when all the five parameters i.e. KL, FL, AC, HC, BPD were used (Table 2).

Table 1. Summary of Kidney Length in mm with Gestational Age GA weeks

RKL Mean

LKL SD

Mean

Mean (LKLRKL)

Paired P ‘t’ value value

Mean

Minimum

Maximum

30.093

1.957

31.330

2.160

1.237

-9.268

0.000

30.712

28.600

34.400

2.028

30.254

2.234

31.529

2.056

1.276

-4.364

0.000

30.892

27.500

35.250

1.933

31.256

1.260

32.428

1.814

1.172

-7.350

0.000

31.842

29.450

35.850

1.486

32.843

1.660

33.716

1.968

0.872

-4.334

0.000

33.279

30.850

37.350

1.651

34.000

1.880

35.093

1.758

1.093

-7.261

0.000

34.547

31.900

38.550

1.750

34.516

1.787

35.242

2.139

0.726

-3.484

0.001

34.879

31.700

39.200

1.792

35.526

1.691

36.501

1.770

0.975

-7.477

0.000

36.014

32.450

40.000

1.639

35.445

0.852

36.670

0.817

1.225

-8.264

0.000

36.058

33.450

37.400

0.690

36.519

0.567

37.794

1.134

1.275

-6.494

0.000

37.156

35.850

39.150

0.806

37.463

0.684

38.488

0.714

1.025

-12.204

0.000

37.975

36.700

38.800

0.689

38.500

0.141

38.800

0.566

0.300

-0.600

0.656

38.650

38.500

38.800

0.212

39.500

0.707

39.450

0.636

0.050

0.053

0.967

39.457

39.450

39.500

0.035

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY Table 2. Regression Models of Relationship Between GA with Parameters KL, BPD, FL, AC and HC Parameters

Equation

AIC

SE (days)

GA = 6.897 + 0.712*KL

1895.08

61.5

10.451

KL, FL

GA = 5.648 + 0.0401*KL + 0.192*FL

1669.43

77.8

7.938

KL, FL, BPD

GA = 3.701 + 0.311*KL + 0.146*FL + 0.098*BPD

1592.67

81.7

7.224

KL, FL, AC

GA = 4.562 + 0.211*KL + 0.149*FL + 0.037*AC

1469.86

86.4

6.233

KL, FL, HC

GA = 2.957 + 0.285*KL + 0.177*FL + 0.026*HC

1581.42

82.1

7.126

KL, FL, AC, HC, BPD

GA = 2.206 + 0.134*KL + 0.125 FL + 0.015*HC + 0.030*AC + 0.049*BPD

1376.36

89.1

5.554

BPD

GA = 9.749 + 0.269*BPD

1917.78

59.8

10.689

Kidney length was the most single accurate parameter in predicting GA with standard error of ± 10.451 days. The coefficient of determination corresponding to this parameter observed is 0.615 (61.5%).

The length of fetal kidney was measured from outer to outer margin using a gray scale real time ultrasonographic scanner, a Elpro GE Logic 200 pro and a 3.5 MHz sector transducer was used. The method described by Konje5 was followed i.e., the fetus was scanned in transverse plane until the kidney were visualized just below the stomach. The probe was rotated through 90° to outline the longitudinal axis of the kidney during apnea. The right and left KL was measured by a single investigator on a single ultrasound machine. Both the kidney lengths were measured and a comparison was made between the increase in length of right and left kidney and if the increase occurred linearly. Women who had any pregnancy-related complication, fetal growth disorder, amniotic fluid abnormality, abnormal renal morphology and in whom adrenal and renal borders could not be visualized were excluded from the study. The data thus compiled was analyzed using computer software MS Excel and SPSS 14.0 version software. At each GA, FKL and other biometric indices were reported as mean standard deviation (SD). Correlation between GA and FKL as well as correlation between GA and other parametric indices were calculated and assessed by using Pearson’s product moment correlation coefficient. To predict GA by using FKL measurements and other biometric indices, multiple linear regression analysis was performed using linear mixed model approach taking GA as dependent variable and fetal biometric indices as independent variables. New models were constructed by including BPD, FL, HC and average of left and right kidney in various combinations. Determination of best model Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

was based on Akaike information criterion (AIC), r2 and standard error (SE) of prediction. For each model the SE of prediction in days was calculated. Level of significance was expressed as ‘p’ value (0.05 was taken as significant.) Results A total of 715 pregnant ladies between 19 years and 40 years, regardless of parity, who came for sonography during the period from October 2011 to April 2013 were examined for all the four parameters BPD, HC, AC and FL to calculate the composite ultrasonographic age (CUA). The BPD increased linearly from a mean of 69.54 mm at 27 weeks to 93.85 mm at 38 weeks of gestation. GA was estimated by this parameter alone by regression model and a SE of ± 10.68 days (r2 = 59.8) was seen. These pregnant women were also examined for FKL along with the other parameters. Care was taken to exclude those cases, where there was any pregnancy-related complication or any other maternal disease e.g., tuberculosis, diabetes, hypertension, obesity or any fetal abnormality, IUGR, oligohydramnios or polyhydramnios. Both the right and left kidney were measured. Any fetus in whom the kidney borders were not clearly visualized or any renal abnormality was detected, was excluded from the study. Average FKL increased from 30.7 mm at 27 weeks to 39.4 mm at 38 weeks of gestation. The KL increased linearly as pregnancy advanced as seen in Figure 1. Mean fetal left KL was slightly but significantly more than right FKL within all the gestational weeks till 37 weeks (Table 1). GA was calculated by regression 27

CLINICAL STUDY model of relationship between GA with other parameters. Table 2 shows that when GA was calculated by KL alone the SE was ± 10.45 days, fetal FL was added to KL and calculation done the SE was reduced to ± 7.93 days. As more parameters were clubbed together e.g., AC, the SE was ± 6.22 days. When all the five parameters were included in the calculation the accuracy increased and the SE was only ± 5.5 days. Thus, it was observed that calculation by regression model relationship between GA with KL the coefficient of determination corresponding to this parameter was r2 = 61.5%, which was better than BPD alone r2 = 59.8%. When all the five parameters were included the accuracy improved and the coefficient was r2 = 89.1% corresponding to SE of only ± 5.45 days. Discussion The fetal biometric indices measured and used for calculation of GA during second trimester are also used during the third trimester inspite of the fact that accuracy decreases as GA progresses.4 In this study, we evaluated the role of FKL in estimation of GA and compared its accuracy with other fetal biometric indices, alone and in combination with other indices. In all the cases, both the kidneys were visualized with a little manipulation of the transducer position and angle insonation relative to the kidney plane, both the kidneys could be identified easily, which is in agreement with Konje et al.5 All four biometric indices were measured in 715 cases along with KL. We observed that by BPD alone the GA was estimated with SE of ± 10.68 days (Table 2). Our measurement were in accordance with Konje et al4 who reported a SE ± 11.62 days. The minimum KL corresponds well with GA as seen in Table 1. At 27 weeks it was 28.6, at 30 weeks 30.85 at 34 weeks 33.45 mm and at 38 weeks it was 39.45 mm. Ansari et al10 had also found an excellent correlation between GA and FKL, they also found FKL of 29 mm at 29 weeks, 39.5 mm at 40 weeks. Rahman et al11 have also reported mean FKL of 28.8 mm at 29 weeks and 40.23 mm at 40 weeks. Lawson et al12 and Fong and Ryan13 also reported that measurements of FKL in mm is approximately the same as GA in weeks. Similar results have been reported by Scott et al.14 28

In our study, when FKL was used for calculating GA values were with SE ± 10.45 days, which is in accordance with the values calculated by Konje et al5 of SE ± 10.29 days. When all four parameters (HC, BPD, AC, FL) were incorporated the accuracy was SE ± 6.22 days, which differed slightly from values obtained by Konje et al4 of SE ± 9.45 days. When FKL was combined with other four indices the accuracy increased to SE ± 5.54 days. Though FKL can be used as a single parameter in estimation of GA, very accurate results can be obtained by using all five biometric indices. FKL determination would also help in early detection of renal malformation when renal lengths can be compared with normal values. We found that the most precise way of estimating GA was when all five indices were included, which was SE ± 5.54 days, which is also in accordance with study of Konje et al5 ± 8.4 days and Indu et al8 ± 7.41 days. Conclusion Both the kidneys can be easily visualized on ultrasonography in third trimester and can be easily and accurately measured. This parameter alone can estimate the GA. The FKL in mm collaborates nicely with GA in weeks. When the traditionally used four parameters (BPD, HC, AC, FL) alone give unreliable results in third trimester, FKL can be combined to give more accurate estimation of GA. References 1. Andersen HF, Johnson TR Jr, Flora JD Jr, Barclay ML. Gestational age assessment. II. Prediction from combined clinical observations. Am J Obstet Gynecol 1981;140(7):770-4. 2. Pearce JM, Chazal RD. Establishing gestational age. In: Ultrasound in Obstetric and Gynecology. 1st edition, Dewbury K, Meire H, Cosgrove D (Eds.), Churchill Livingstone: Edinburg 1993:p.211-21. 3. Hadlock FP, Deter RL, Harrist RB, Park SK. Estimating fetal age: computer-assisted analysis of multiple fetal growth parameters. Radiology 1984;152(2):497-501. 4. Benson CB, Doubilet PM. Sonographic prediction of gestational age: accuracy of second- and third-trimester fetal measurements. AJR Am J Roentgenol 1991;157(6):1275-7. 5. Konje JC, Abrams KR, Bell SC, Taylor DJ. Determination of gestational age after the 24th week of gestation from fetal kidney length measurements. Ultrasound Obstet Gynecol 2002;19(6):592-7. 6. Yousuf N, Moslem F, Haque JA. Fetal kidney length: can be a new parameter for determination of gestational age in third trimester. TAJ 2007;20(2):147-50. Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY 7. Cannie M, Neirynck V, De Keyzer F, Dymarkowski S, Bogaert GA. Prenatal magnetic resonance imaging demonstrates linear growth of the human fetal kidneys during gestation. J Urol 2007;178(4 Pt 2):1570-4. 8. Kaul I, Memia V, Anand AK, Gupta R. Role of fetal kidney length in estimation of gestational age. JK Science 2012;14(2):65-69. 9. Cohen HL, Cooper J, Eisenberg P, Mandel FS, Gross BR, Goldman MA, et al. Normal length of fetal kidneys: sonographic study in 397 obstetric patients. AJR Am J Roentgenol 1991;157(3):545-8. 10. Ansari SM, Saha M, Paul AK, Mia SR, Sohel A, Karim R. Ultrasonographic study of 793 foetuses: measurement of normal foetal kidney lengths in Bangladesh. Australas Radiol 1997;41(1):3-5.

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

11. Rahman H, Sadeque A, Al Azad S, Zakir Hussain A, Nazrul Islam, Islam S, et al. Ultrasonographic evaluation of fetal kidney length in third trimester: correlation with gestational age. Bangladesh Journal of Radiology and Imaging 2008;16(1):6-10. 12. Lawson TL, Foley WD, Berland LL, Clark KE. Ultrasonic evaluation of fetal kidneys. Radiology 1981;138(1):153-6. 13. Fong KW, Ryan G. Fetal urogenital tract. In: Diagnostic Ultrasound. 2nd edition, Rumack CM, Wilson SR, Charboneau, JW (Eds.), Mosby Year Book Inc.: New York 1998(2):p.1093-121. 14. Scott JE, Wright B, Wilson G, Pearson IA, Matthews JN, Rose PG. Measuring the fetal kidney with ultrasonography. Br J Urol 1995;76(6):769-74.

CLINICAL STUDY

The Effect of Conventional Hormone Therapy and Tibolone on Tear Composition and Function in Postmenopausal Women Mhaleneinuo Modesta Belho*, Ritu Khatuja**, Neerja Goel†, Jolly Rohatgi‡, Satendra Sharma#, Shalini Rajaram†, Sumita Mehta¶

ABSTRACT Objective: To compare the effects of conventional hormonal therapy (HT) and tibolone on tear composition and tear function. Material and methods: Prospective randomized study in 60 postmenopausal women who received conventional HT versus tibolone for postmenopausal symptoms. Response assessed on Kupperman index, eye symptoms and qualitative and quantitative tests for tears at six months follow-up. Quantitative data analyzed using Student’s t-test, ANOVA test, Fisher’s exact test and qualitative data by using McNemar-Bowker test with Bonferroni correlation and Kappa test. Results: There was a significant improvement in the mean Kupperman scores with conventional HT and tibolone (p < 0.01). Tibolone effectively reduced foreign body sensation but there was no appreciable change in other eye symptoms with both therapies. P value did not show any significant change in quantitative tests (Schirmer’s I and II) and qualitative tests (break-up time) for tear secretion. Tear immunoglobulin A level was significantly elevated with both therapies. Conclusion: Conventional HT or tibolone did not have any significant beneficial effect on tear composition and tear function. A larger study can be undertaken using systemic or topical estrogen or androgen containing preparation for further evaluation for dry eye symptoms. Key words: Conventional hormonal therapy, tibolone, tear composition, tear function, postmenopausal women

enopause is a remarkable event in the reproductive life of a woman. The dramatic fall in circulating estradiol levels at menopause impacts many tissues, the eye being one of the target organs. Dry eye complaint is commonly seen in postmenopausal women than men of the same age group, which may be attributed to androgen or estrogen deficiency in them or just an imbalance between the two hormones.1 The treatment of deficiencies at the target organs bears no definite consensus. If a causal treatment is to be proposed, hormone therapy containing either estrogen or androgenic preparations could provide symptomatic relief in dry eye. Taking account of this fact, we planned our study to evaluate the effect of conventional hormone therapy and synthetic androgenic steroid, tibolone on tear composition and tear function. *Postgraduate **Senior Resident † Director Professor, Dept. of Obstetrics and Gynecology ‡ Professor, Dept. of Ophthalmology # Professor, Dept. of Pathology ¶ Specialist, Dept. of Obstetrics and Gynecology University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi Address for correspondence Dr Ritu Khatuja Senior Resident Dept. of Obstetrics and Gynecology University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi-110 095 E-mail: rituneeraj36@rediffmail.com

Material and Methods A randomized prospective study conducted in the Dept. of Obstetrics and Gynecology, Ophthalmology and Pathology, University College of Medical Sciences and Guru Teg Bahadur (GTB) Hospital, Delhi, from November 2009 to April 2011. Sixty postmenopausal women attending Menopausal HT Clinic at GTB Hospital were recruited. The inclusion criteria were age between 40-65 years, either surgical or natural menopause and women who had never received any hormonal treatment (HT) in past. Women with Sjogren’s syndrome, contact lens user, unexplained vaginal bleeding, any chronic illness, blood dyscrasias and carcinoma breast or endometrium in past were excluded. Study Groups

After taking informed consent, 60 selected women were randomized into two groups of 30 each by using computer generated random tables and put on different regimens of HT for the study. One group was put on continuous combined conventional HT conjugated equine estrogen (CEE) 0.625 mg and medroxyprogesterone acetate (MPA) 2.5 mg/CEE alone 0.625 mg in hysterectomized women and the other on tibolone (2.5 mg) for six months. Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY Methodology

Statistical Analysis

Women participating in the study underwent a detailed history taking and complete examination. Parameters like assessment of menopausal symptoms, eye symptoms and eye tests were done and recorded both before initiation of therapy (0 months) and after completion of therapy (6 months later).

Quantitative data analyzed using Student’s t-test, ANOVA test, Fisher’s exact test and qualitative data by using McNemar-Bowker test with Bonferroni correlation and Kappa test.

Kupperman Index

Assessment of clinical symptomatology of menopause grading from 0 to 4 (none-severe).2 Dry eye symptoms assessed were foreign body sensation, excessive tear secretion, irritation/burning sensation, redness, diminution of vision. Symptoms were graded according to their severity into: None = Grade 0, Mild = Grade 1, Moderate = Grade 2 and Severe = Grade 3. Eye Tests

A routine eye examination of all the patients included in study was carried out. zz

Schirmer’s I test: It measures reflex and basal tear secretion. The test was done using a 5 mm broad and 35 mm long Whatman No. 41 paper. A value of > 10 mm wetting was considered normal and ≤10 mm was considered abnormal.3,4 Schirmer’s II test: It measures basal tear secretion volume.3,4 Same procedure repeated after anesthetizing with topical anesthetic and value > 10 mm was considered normal. Tear break-up time: It is to assess quality of tears. Appearance of the first dry spot after application of fluorescein dye was measured three times and the mean value recorded. Tear break-up time of < 10 seconds was be taken as abnormal.3,4 Tear immunoglobulin A (IgA) analysis: Tear IgA is the major tear immunoglobulin, which is secreted from lacrimal gland and it contributes to the local immunity in the eye.5 Levels in tears are age and tear volume-dependent. Tears were sampled from the eyes using 3-4 filter papers Whatman No. 1, 5 mm diameter sized discs and tested by radial immunodiffusion (RID) technique. The IgA in the patient sample was measured using the standard curve.

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

Results The mean age of the women participating in the study was 49.55 years, the range being 40-65 years. Maximum women were in the age group of 46-50 years. Kupperman Index

The common menopausal symptoms in order of frequency were hot flashes (75%), insomnia (65%), arthralgia/myalgia (63.33%), weakness (61.67%) and paresthesia (50%). The less common symptoms were palpitations (18.33%), vertigo (20%), melancholia (35%) and headache (35%). There was a significant improvement in the mean Kupperman scores with both the types of therapy (p < 0.01) (Fig. 1) and also in Kupperman score grading. Eye Symptoms

The common eye symptoms were diminution of vision (31.6%) followed by foreign body sensation (30%). Tibolone reported relief in symptom of foreign body sensation, which was statistically significant. The symptom of diminution of vision was also relieved by tibolone but it is not statistically significant. The symptom of irritation in the eye was relieved with both 14

13.9

12.23

12 10 8 6

4.57

4.73

4 2 0

Conventional HT Before therapy

Tibolone After therapy

Figure 1. Mean Kupperman scores before and after therapy.

CLINICAL STUDY Table 1. Eye Symptoms Grading in Conventional HT and Tibolone Groups Symptoms

Grades

Foreign body sensation

Tearing

Irritation

Redness

Diminution of vision

Before therapy (n)

P value*

After therapy (n)

Conventional HT

Tibolone

Conventional HT

Tibolone

Conventional HT

Tibolone

None

0.38

0.02

Mild

Moderate

Severe

0 0.18

0.31

1.00

0.18

0.45

0.42

1.00

0.29

None

Mild

Moderate

Severe

None

Mild

Moderate

Severe

None

Mild

Moderate

Severe

None

Mild

Moderate

Severe

*McNemar = Bowker test with Bonferroni adjustment.

Conventional HT 10.5 11.3

12.28 10.5

16.85 16.83

20.62 16.86

15.87 18.47

12.1 13.83

12.13 12.43

19.17 15.87

Tibolone

5 0

Schirmer I Schirmer II Schirmer I Schirmer II Schirmer I Schirmer II Schirmer I Schirmer II Right eye before Right eye after therapy Left eye before Left eye after therapy therapy therapy

Figure 2. Comparison of Schirmer’s I and II mean values (mm) before and after in the conventional HT and tibolone groups.

the therapies but was not statistically significant. Both

Eye Tests

therapies did not improve symptoms of excessive tearing

Schirmer’s I: The mean values of Schirmer’s I did not undergo statistical significant changes in both the group.

and redness of eyes after six months treatment (Table 1). 32

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY Table 2. Comparison of Mean Tear IgA Levels in Conventional HT and Tibolone Groups Groups

Before therapy (mg%)

After therapy (mg%)

P value*

< 0.01

Conventional HT

51.00

71.17

Tibolone

54.67

73.83

*Repeated measures ANOVA with Tukey test at 5% level of significance.

The mean Schirmer’s I value before therapy was s19.17 mm and 20.62 mm in right and left eye and after therapy it was 15.87 mm and 16.83 mm, respectively in conventional HT group. While it was 15.87 mm and 16.86 mm in right and left eye and after therapy, and 18.47 mm and 16.83 mm, respectively in tibolone group (Fig. 2). zz Schirmer’s II: Its mean values in right and left eye was 12.13 mm and 12.28 mm before therapy and after therapy it was 12.1 mm and 10.5 mm, respectively in conventional HT group, while it was 12.43 mm and 10.5 mm in right and left eye before therapy and after therapy 13.83 mm and 11.3 mm, respectively in tibolone group (Fig. 2). The mean values of Schirmer’s II did not undergo statistical significant changes in both the groups. zz

There was no improvement in the grading of Schirmer’s I and II in both groups. Break-up time: The mean break-up time was 10.44 seconds and 11.08 seconds before and after therapy, respectively in conventional HT group and 11.82 seconds and 11.31 seconds, respectively before and after therapy in tibolone group and this was not statistically significant. The mean tear break-up time values fell in the normal range before and after therapy. Tear IgA analysis: Both groups of therapies increased the tear IgA level post therapy. At the end of six months therapy, there was a significant change in both the groups (Table 2).

Discussion The mean age at onset of menopause of the women in this study was 44.48 years lower than the average age of onset of menopause in India, which is 47.5 years.6 Most studies in India and outside have found the most common menopausal symptoms to be fatigue and arthralgia/myalgia but vasomotor symptoms still figure among the commonest symptoms in postmenopausal women.7,8 In our study, we found hot flashes to be the common symptom followed by insomnia and myalgia. Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

The majority of women in our study were < 5 years since menopause, which can explain the symptom of hot flashes and insomnia to be more common. Also 33.33% of the women in our study had surgical menopause, which is known to present acutely and more commonly with vasomotor symptoms. Some studies found diminution of vision to be the most common menopausal complaint9,10 but in our study, eye symptoms were not the presenting complaints in any of the women but on asking a leading question about the eye symptoms, diminution of vision was the most common eye symptom (31.6%), followed very closely by foreign body sensation (30%). Response to HT in regard to eye symptoms is controversial. Erdem and associates in their study advocated that the duration of menopause and the use of HT is a risk factor for developing dry eye;11 while other studies have proved that HT has beneficial effect on the dry eye symptoms.12,13 Tests done to assess the quantity and quality of tears did not show any statistically significant response to either conventional HT or tibolone therapy but the mean Schirmer’s I and II values, break-up time values were in the normal range before and after therapy. Hence, the present study also supports that conventional HT or tibolone is not a causative factor for dry eyes in postmenopausal women. So, the use of hormone therapy, either estrogen- or androgen-based could be a promising modality for treatment of dry eye, which is hormone-dependent.1 Both conventional HT and tibolone had a significant impact on the tear IgA levels. Post therapy a significant increase in the tear IgA levels was appreciated, with higher mean levels in the tibolone group. Conclusion Kupperman index, the 11-item menopausal symptomatology index assessed before and after six months of therapy found that both conventional 33

CLINICAL STUDY HT and tibolone effectively relieves the symptoms assessed and are equally effective in reducing the severity of these symptoms. A positive effect of both the groups of therapy over quantitative (Schirmerâ&#x20AC;&#x2122;s I and II) and qualitative tests break-up time for tears could not be found, with the mean levels of the quantitative and qualitative tests for tears were in the normal range. Both therapies did improve eye symptoms. Foreign body sensation in the eyes was effectively treated in the tibolone group, while conventional HT group reported lesser irritation in eyes after six months therapy. Tear IgA levels were significantly increased by both form of therapy and this appreciable rise was more in the tibolone treated group. Thus, both the therapies showed no detrimental effect on dry eye and as the route of administration of our therapy was systemic and sample size was small, topical estrogen or androgen containing preparations and large sample size can be studied on postmenopausal women to see their effect on dry eye. References 1. Versura P, Campos EC. Menopause and dry eye. A possible relationship. Gynecol Endocrinol 2005;20(5):289-98. 2. Han KK, Soares JM Jr, Haidar MA, de Lima GR, Baracat EC. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol 2002;99 (3):389-94.

3. McCulley JP, Shine WE. Meibomian gland and tear film lipids: structure, function and control. Adv Exp Med Biol 2002;506(Pt A):373-8. 4. Shapiro A, Merin S. Schirmer test and break-up time of tear film in normal subjects. Am J Ophthalmol 1979;88 (4):752-7. 5. Sen DK, Sarin GS, Mani K, Saha K. Immunoglobulins in tears of normal Indian people. Br J Ophthalmol 1976;60(4):302-4. 6. Kaw D, Vashistha K. Factors influencing the age at menopause. J Obstet Gynecol India 1994;44:273-7. 7. Sharma S, Tandon VR, Mahajan A. Menopausal symptoms in urban women. JK Science 2007;9(1):13-7. 8. Kim YH, Ha EH, Shin SJ. A study on the menopausal symptoms and quality of life in middle aged women. Taehan Kanho Hakhoe Chi 2003;33(5):601-8. 9. Kaur S, Walia I, Singh A. How menopause affects the lives of women in suburban Chandigarh, India. Climacteric 2004;7(2):175-80. 10. Singh A, Arora AK. Profile of menopausal women in rural north India. Climacteric 2005;8(2):177-84. 11. Erdem U, Ozdegirmenci O, Sobaci E, Sobaci G, GĂśktolga U, Dagli S. Dry eye in post-menopausal women using hormone replacement therapy. Maturitas 2007;56 (3):257-62. 12. Jensen AA, Higginbotham EJ, Guzinski GM, Davis IL, Ellish NJ. A survey of ocular complaints in postmenopausal women. J Assoc Acad Minor Phys 2000;11 (2-3):44-9. 13. Lang Y, Lang N, Ben-Ami M, Garzozi H. The effects of hormone replacement therapy (HRT) on the human eye. Harefuah 2002;141(3):287-91, 313, 312.

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY

Medical Management of Ectopic Pregnancy with Methotrexate Sandip Sonara*, Sumant R Shah**, Bhavesh Patel†, Nidhi Patel*

ABSTRACT Objective: The aim of this study is to determine the efficacy of methotrexate treatment for ectopic pregnancies in our settings which will in-turn help us reduce maternal mortality and morbidity. Material and methods: This was a retrospective study of 40 cases of unruptured ectopic pregnancy treated with methotrexate in civil hospital, Ahmedabad. Clinical presentation, treatment, progress, outcome, side effects and future fertility follow-up were analyzed using database from May 2008 to June 2012. Results: The success rate of methotrexate therapy in our study was 85% (n = 35) and 15% (n = 06) required surgical intervention compared to reported success rate of 67-100% published in various studies. The mean average time of resolution of ectopic pregnancy was 32 days for a single dose and 58 days for repeat second doses. Successful fertility outcome with intrauterine pregnancy was observed in three patients. Conclusion: Methotrexate treatment of ectopic pregnancies is safe and effective with no major side-effects. Intramuscular methotrexate has the advantage of tubal conservation and saves patients from surgical intervention. Our study showed single dose methotrexate to be an effective treatment option for selected patients with unruptured tubal ectopic pregnancy. Key words: Methotrexate, maternal mortality, ectopic pregnancy

ctopic pregnancy is an acute emergency if not timely diagnosed and treated. Timely diagnosis and appropriate treatment can reduce the risk of maternal mortality and morbidity related to ectopic pregnancy. It is an important diagnosis to exclude when a woman presents with bleeding in early pregnancy. A report of the incidence from elsewhere is showing a rise from 0.5-1-2%. There has been a rise of 3-5% in pregnancies from assisted reproductive techniques. The clinical presentation of ectopic pregnancy has changed from a life threatening disease to a more benign condition for which nonsurgical treatment options are available with systemic methotrexate (MTX) or expectant management. Medical management with methotrexate fulfiling the criteria in selected cases were tried and found to be equally successful. Medical management was found to be equally effective as surgical management particularly taking consideration of future fertility.

Methotrexate can be administered systemically as a single dose regimen; this was introduced to minimize side *Resident (IIIrd year) **Professor Dept. of Obstetrics and Gynecology Head of Unit, BJ Medical College and Civil Hospital Ahmedabad † Consultant Gynecologist Address for correspondence Dr Sandip Sonara Dept. of Obstetrics and Gynecology BJ Medical College, Civil Hospital, Ahmedabad

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

effects, to improve patient compliance and to reduce the overall costs. Methotrexate has been shown to be safe with virtually no adverse effects reported on reproductive outcome. Careful follow-up and assessment are required for all women presenting with pain in the few days following methotrexate therapy before assuming that the treatment has failed and if there is need for surgical intervention. Material and Methods Between May 2008 and June 2012, n = 40 patients of diagnosed ectopic pregnancy treated as in-patients with methotrexate regimen were retrospectively identified from hospital records of the Dept. of Obstetrics and Gynecology, Civil Hospital, Ahmedabad. The diagnosis of ectopic pregnancy was made using both transvaginal ultrasound and measurement of b-hCG All cases selected for medical management gave their informed written consent before starting the treatment. The selection criteria for patients suspected to have ectopic pregnancy but with low serum b-hCG, or cases of pregnant women patients who were hemodynamically stable with beta human chronic gonadotrophin (b-hCG) level of ≤ 10,000 mIU/mL and if clinically feasible > 10,000 mIU/mL, adnexal mass ≤ 4 cm and if clinically feasible > 4 cm, absent cardiac activity and the presence of hemoperitoneum less than 100 mL. Baseline investigations such as full blood count, b-hCG, renal and 35

CLINICAL STUDY liver functions tests, and blood group RH factor were done on Day 1 and single dose of 50 mg/m MTX was administered. Serial b-hCG was repeated on Days 4 and 7. If b-hCG on Day 7 was at least 15% lower than that on Day 4, the patient was discharged and followed up as an outpatient. If the b-hCG level on Day 7 was the same or higher than that on Day 4, the patient received a second dose of 50 mg/m MTX. Follow-up serum b-hCG was performed weekly. Single dose MTX treatment was considered successful when b-hCG levels became negative without further administration of MTX dose or surgery. The ultrasound examination was performed. Cases with persistent plateauing serum b-hCG concentration were defined as 15% fall or < 15% rise in serum b-hCG concentrations. Second dose of MTX was installed in both cases of either increasing b-hCG or plateauing b-hCG. Follow-up b-hCG was performed weekly until negative with value of b-hCG < 5mIU/mL. For patients with hemodynamic instability, signs of tubal rupture, increasing abdominal pain, falling hemoglobin level surgical intervention were considered. The toxicity of MTX treatment was evaluated by noting side effects such as lower abdominal pain, vaginal bleeding, mouth ulcers, sore throat, gastrointestinal side-effects or complaints of any rashes. Nonsensitized Rhesus negative women received anti-D immunoglobulins 250 μgms as per the department protocol. Women treated with MTX were advised to refrain from sexual intercourse until serum b-hCG was negative, and not to conceive within three months of treatment.

in the Day 4 value was observed in some cases, mainly due to the trophoblastic tissue breakdown releasing the hormone (Table 5). Methotrexate has a cytotoxic effect on trophoblastic tissue. Although it arrests mitosis in cytotrophoblast, the syncytiotrophoblast mass may still increase and produce β-hCG. The average time of resolution for serum b-hCG level was 32 days for single dose of methotrexate and 58 days for those receiving two doses. Time of resolution for serum b-hCG was defined as the total number of days from the beginning of treatment until β-hCG level became negative (< 5 mIU/mL). The total number of women treated with single dose was (n = 35) 87.5% and n = 5 (12.5%) received two doses. Success rate in group of patient given single dose methotrexate is 82.85% and in patients with two dose methotrexate 100%. The overall success rate of treatment in our study was 85% (n = 34). Surgical intervention was required for 15% (n = 6) of patients with tubal rupture and abdominal pain (Table 6). One patient complained of lower abdominal pain between Days 2 to 7 and early surgical intervention by laparotomy followed by salpingectomy. Two cases were managed by laparoscopic salpingotomy. Mild vaginal bleeding, not more than the initial bleeding was noted with no reported case of gastrointestinal side effects. Fifteen percent (n = 6) women had history of previous ectopic pregnancy, three women had history of pelvic tuberculosis and 40% (n = 16) had history of miscarriages. Three women reported successful intrauterine pregnancy outcome after one year.

Results

Discussion

In this study, the majority of patient (45%) were between 20-25 years (n = 18) (Table 1). The success rate of MTX decreased as maternal age increased. Gravidity was between one and six with 40% (n = 12) primipara. The majority of patient with gestation age at diagnosis was < 6 weeks (n = 25) 62.5% (Table 2). The success rate of MTX decreased with increasing gestational age. Adnexal mass ranged from 2-4 cm. In patients with adnexal mass more than 4 cm, the success rate was less. In women with 2-3 cm adnexal mass success rate is (n = 28) 82.1% (Table 3).There was no marked difference in the site of ectopic gestation. The average value of b-hCG on Day 1 in patients treated with single dose of MTX was 3,000 mIU/mL (range 100-8,847) and those treated with two doses or more was 10,000 mIU/mL (Table 4). An increase

Ectopic pregnancy occurs in around 1% of pregnant women and may seriously compromise women’s health and future fertility. With increase in the artificial reproduction technique and increase in pelvic inflammatory disease due to increased sexual promiscuity incidence of ectopic pregnancy has increased. Ectopic pregnancy can be diagnosed before the patient’s condition has deteriorated and the cornerstone of diagnosis is the use of transvaginal ultrasound and serum human chorionic gonadotropin measurement. Single dose methotrexate appears effective and has better patient compliance. Treatment success is inversely correlated to β-hCG concentration. The most important selection criteria for medical management is the absence of pain and the prediction that the pregnancy will not rupture before its resolution. Surgery and medical management Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY are the two ways to treat ectopic pregnancy. Both are effective and the choice depends on clinical situation, site of ectopic mass and access to technology. Systemic single dose methotrexate seems to offer the greatest benefits in terms of efficacy and tolerability. It has proved to be a good alternative to laparoscopy in selected cases. The success rate of systemic MTX in our study was 85% (n = 34), 12.5% (n = 5) were treated with two doses of MTX 15% and (n = 6) required surgical intervention. Patients with small unruptured ectopic pregnancies achieved a success rate of 82.1% with five women requiring a second dose. Srivichai et al reported a success rate of 90.6% in 96 out of 106 patients who were successfully treated with methotrexate though four required a second dose. In all comparative studies, the success rate was found to be same as in our study. The reason being that at the beginning of starting the methotrexate regimen in our institution women with increasing β-hCG values and complaints of abdominal pain were taken early for surgical intervention for fear of rupture of the ectopic pregnancy. With more experience of using the drug the success rate improved. Treatment

Table 4. b-hCG Level on Day 1 On admission b-hCG level

No of Percentage No of Success patients successful rate patients

< 10,000

87.5%

80%

> 10,000

12.5%

40%

Table 5. Fall in b-hCG Level on Day 4 & Day 7 and Outcome Total No of patients

Percentage

No of Success successful rate patients

> 15%

80%

90.6%

< 15%

20%

62.5%

Table 6. Success Rate No of patients

Percentage

Sucessful

85%

Unsucessful

15%

No of patients

Percentage

Table 1. Age of Patients Age

No of patients

Percentage

20-25 years

45%

25-30 years

37.5%

Present

2.5%

31-35 years

10%

Absent

97.5%

35-40years

7.5%

100%

Table 2. Month of Amenorrhoea Month of amenorrhoea

No of patients

Percentage

< 1 ½ MA

62.5%

> 1 ½ MA

22.5%

No MA

15%

Table 3. Size of Ectopic Mass and Outcome Size of mass

No of patients

Percentage

< 4 cm

70%

82.1%

> 4 cm

30%

91.1%

No of Success successful rate patients

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

Table 7. Cardiac Activity

failure based strictly on a high increase in β-hCG level from Day 4-7 may be a hasty judgment. Pain after MTX treatment could be due to tubal abortion or stretching of the tube by hematoma contributing to increased failure rate in most of the medical management. Differentiating ‘separation pain’ due to tubal abortion from pain due to tubal rupture can be difficult and may lead to early surgical intervention. Mahboob reported a success rate of 80% by treating 12 out of 15 women with single dose MTX with initial β-hCG levels equal to 5,000 mIU/mL. In the same series, an increase in the treatment failure group with advanced maternal age ≥ 35 years and history of spontaneous abortions was noted corresponding to our study where success rate of MTX treatment decreased as maternal age increased. In our study, nine women aged over 30 years had a failure rate of (n = 4). Lee reported a success rate of 96% with β-hCG 37

CLINICAL STUDY < 6,000 mIU/mL and 58% when β-hCG was > 6,000 mIU/mL. He noted that initial β-hCG is the only predictor of success for repeated injection of MTX in single dose regimen. The incidence of infertility as a risk factor reported in literature was 30% for ectopic pregnancy. However, it accounted for 15% (n = 9) in our study (primary-7 and secondary-2). Many studies have identified the risk factors for ectopic pregnancy. A third of cases are associated with tubal damage caused by infection or surgery and another third with appendicectimy which is a rare factor. No cause can be established for the remaining third. Techniques of assisted reproduction increase the risk of ectopic pregnancy by 2-4%. Multiple dose regimen for hemodynamically stable women with an unruptured tubal ectopic pregnancy with serum hCG concentrations < 3,000 mIU/mL and a single-dose MTX for serum hCG < 1,500 mIU/mL is recommended. Women with a pretreatment β-hCG level of 3,000-4,000 mIU/mL have a greater probability of surgery or multiple dose treatment. The time of resolution of serum b-hCG in our study was 32 days with a single dose and 58 days with two doses of methotrexate as compared to 27.3 days and 35 days respectively in other series. Thia noted the time of resolution was 33 days with one dose and 55 days with two doses, similar to our study. Erdem reported the mean time of resolution as 26.5 (10-37) days in patients who were successfully treated with MTX. These results are consistent with other studies. Methotrexate regimen reduces the incidence of persistent trophoblast. Persistent trophoblast is detected by the failure of serum hCG levels to fall as expected after initial treatment, often a problem occurring after salpingotomy rather than salpingectomy. In 12 cases treated with laparoscopy, one case of persistent trophoblast was observed and this could have been prevented with medical management of ectopic pregnancy and β-hCG follow-up to avoid complications such as delayed hemorrhage owing to persistent trophoblast. In our study cardiac activity was absent in (n = 39) 97.5% patients and (n = 1) 2.5% patient cardiac activity was present which required surgical intervention (Table 7). In our study, 37.5% (n = 15) of women complained of lower abdominal pain and 15% (n = 6) were treated surgically due to increasing hemoperitoneum. 38

Most studies showed increased lower abdominal pain between 2-7 days after treatment. This complication of methotrexate is disturbing in an outpatient with an ectopic pregnancy. No other side-effect of methotraxate was observed in our study. In Thia’s series, 40% (n = 4) of patients were hospitalized for pelvic pain two days after treatment and their pain regressed without surgery. One patient developed mild rash in light exposed skin areas. No such complaint was observed in the studied patients managed as inpatients. In the same study, 28.2% (n = 9) of patients complained of abdominal pain between Days 4 and 8 and one patient was found to have a ruptured cornual ectopic pregnancy at laparoscopy. Minor side-effects reported in the same series were mucositis in 19.1% (n = 21) and 10.9% (n = 12) of the patients suffered gastric pain and diarrhea. No side-effects were reported with single dose treatment in a series of 30 patients with a success rate of 97%. Increased abdominal pain on Days 5-10 after medical management of ectopic pregnancy has to be closely monitored for possible rupture. Methotrexate therapy was associated with high rates (80%) of subsequent fertility compared to our study, successful intrauterine pregnancy following methotrexate was observed in three women. Conclusion Methotrexate has proven to be an effective medical management for ectopic pregnancies in a society where tubal conservation is of utmost importance. The medical management by MTX seems to offer several benefits over surgical treatment. It is less invasive, less expensive and does not need expertise like laparoscopy. Future reproductive expectations are better with methotrexate with higher intrauterine pregnancy rates and lower ectopic rates subsequently. However the risk of tubal rupture after medical treatment combined with a prolonged follow-up for an ectopic pregnancy to resolve requires monitoring for rupture and methotrexate side-effects making compliance important in patient selection. The predictors of success in our study are low β-hCG and adnexal mass < 4 cm. Single dose methotrexate offers a safe and effective nonsurgical method of treating selected patients and one important advantage of medical therapy is the potential for considerable savings in treatment costs. Suggested Readings 1. Thia EW, Loi K, Wang JJ, Siow A. Methotrexate treatment for ectopic pregnancy at the KK Women’s and

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CLINICAL STUDY Children’s Hospital, Singapore. Singapore Med J 2009;50 (11):1058-61.

analysis based on a large casecontrol, population-based study in France. Am J Epidemiol 2003;157(3):185-94.

2. Merisio C, Anfuso S, Berretta R, Gualdi M, Pultrone D, et al. Single-dose methotrexate for Ectopic pregnancy treatment: preliminary data Acta Bio Med 2005;76:33-36.

10. Fernandez H, Gervaise A. Ectopic pregnancies after infertility treatment: modern diagnosis and therapeutic strategy. Hum Reprod Update 2004;10(6):503-13.

3. Zargar M, Razi T, Barati M. Comparison of single and multidose of methotrexate in medical treatment of ectopic pregnancy. Pak J Med Sci 2008;24:586-9.

11. Erdem M, Erdem A, Arslan M, Oc A, Biberoğlu K, Gursoy R. Single-dose methotrexate for the treatment of unruptured ectopic pregnancy. Arch Gynecol Obstet 2004;270 (4):201-4.

4. Kirk E, Condous G, Bourne T. The non-surgical management of ectopic pregnancy. Ultrasound Obstet Gynecol 2006;27(1):91-100. 5. Hajenius PJ, Mol BW, Bossuyt PM, Ankum WM, van der Veen F: Interventions for tubal ectopic pregnancy. Cochrane Database of Syst Rev 2007;(1):CD000324. 6. Barnhart KT, Gosman G, Ashby R, Sammel M. The medical management of ectopic pregnancy: a meta-analysis comparing “single dose” and “multidose” regimens. Obstet Gynecol 2003;101(4):778-84.

12. Tawfiq A, Agameya AF, Claman P. Predictors of treatment failure for ectopic pregnancy treated with single-dose methotrexate. Fertil Steril 2000;74(5):877-80. 13. The Management of tubal pregnancy. Royal college of obstetricians and gynaecologists guidelines 2004;21:1-10. 14. Tawfiq A, Agameya AF, Claman P. Predictors of treatment failure for ectopic pregnancy treated with single-dose methotrexate. Fertil Steril 2000;74(5):877-80.

7. Lipscomb GH, Puckett KJ, Bran D, Ling FW. Management of separation pain after single-dose methotrexate therapy for ectopic pregnancy. Obstet Gynecol 1999;93(4):590-3.

15. Slaughter JL, Grimes DA. Methotrexate therapy. Nonsurgical management of ectopic pregnancy. West J Med 1995;162(3):225-28.

8. Cho GJ, Lee SH, Shin JW, Lee NW, Kim T, Kim HJ, et al. Predictors of success of repeated injections of single-dose methotrexate regimen for tubal ectopic pregnancy. J Korean Med Sci 2006;21(1):86-89.

16. Stovall TG, Ling FW, Gray LA. Single-dose methotrexate for treatment of ectopic pregnancy. Obstet Gynecol 1991; 77(5):754-57.

9. Bouyer J, Coste J, Shojaei T, Pouly JL, Fernandez H, Gerbaud L, et al. Risk factors for ectopic pregnancy: a comprehensive

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

17. Stovall TG, Ling FW, Gray LA, Carson SA, Buster JE. Methotrexate treatment of unruptured ectopic pregnancy: a report of 100 cases. Obstet Gynecol 1991;77(5):749-53.

CASE REPORT

Unusual Presentation of Acrochordon Disha A Rajput*, Jaya K Gedam*, Arti Patel**, Meenal Bhaleraoâ&#x20AC;

ABSTRACT Objective: An acrochordon, is a small, soft, common, benign, usually pedunculated neoplasm that is found particularly in persons who are obese. Acrochordons have been reported to have an incidence of 46% in the general population. Most acrochordons vary in size from 2-5 mm in diameter, although larger acrochordons upto 5 cm in diameter are sometimes evident. They may occur singly or in multiples and they are most often found in intertriginous areas (e.g., axillae, neck, eyelids). We report an unusual presentation of acrochordon in a 38-year-old multipara who presented with complains of some mass in the private parts since three months. She was diagnosed to have acrochordon of the clitoris. Key words: Acrochordon, skin tag, intertrignous areas, benign tumors

n acrochordon, also known as a (cutaneous) skin tag,1 or fibroepithelial polyp (FEP), is a small, soft, common, benign, usually pedunculated neoplasm that is found particularly in persons who are obese. It is usually skin colored or hyperpigmented, and it may appear as a surface nodule or papilloma on healthy skin. Most acrochordons vary in size from 2-5 mm in diameter, although larger acrochordons up to 5 cm in diameter are sometimes evident. They may occur singly or in multiples and they are most often found in intertriginous areas (e.g., axillae, neck, eyelids). They are also commonly located on the trunk, the groin, the abdomen and the back. Pathophysiology Frequent irritation seems to be an important causative factor, especially in persons who are obese. An opinion also exists that acrochordons are simply the effect of skin aging, with many factors responsible for their development. Hormone imbalances may facilitate the development of acrochordons (e.g., high levels of estrogen and progesterone during pregnancy, high levels of growth hormone in acromegaly). Epidermal growth factor (EGF) and *Associate Professor **Senior Resident â&#x20AC; Registrar Dept. of Obstetrics and Gynecology ESIC, PGIMSR, MGM, Hospital, Parel, Mumbai -12 Address for correspondence Dr Disha A Rajput Associate Professor Dept. of Obstetrics and Gynecology

alpha-tissue growth factor (a-TGF) have also been implicated in the development of tumors such as these. Whether any infective factors initiate acrochordon growth is still not clear. Human papillomavirus (HPV) types 6/11 DNA were found in a high percentage of skin tag biopsy samples obtained from 49 white patients. According to the authors of the study, viral infection should be considered as a pathogenic cofactor.2 Acrochordons associated with fibrofolliculomas and trichodiscomas have been described as components of BirtHogg-DubĂŠ (BHD) syndrome, an autosomal dominant disorder. They have been reported to accompany other neoplasms, especially tumors of the gastrointestinal tract and kidneys. Neoplasms are suggested to produce and release growth factors that cause acrochordon growth into the circulation. The results of a recent study refute the theory that an association of acrochordons and colonic polyps actually exists. An association with type 2 diabetes mellitus has been observed.3 A study of 118 research subjects with acrochordon reported an incidence of 40.6% of either overt type 2 diabetes mellitus or impaired glucose tolerance. Reports exist suggesting that the mechanism is through the effect of insulin and glucose starvation.4 The previous study showed no correlation between the location, size, color or number of acrochordons with impairment of glucose tolerance. Three types4 of acrochordons are described, as follows: zz Small, furrowed papules of approximately 1-2 mm Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CASE REPORT

in width and height, located mostly on the neck and the axillae. Single or multiple filiform lesions of approximately 2 mm in width and 5 mm in length occurring elsewhere on the body. Large, pedunculated tumors or nevoids, bag-like, soft fibromas that occur on the lower part of the trunk.

Case Report

Figure 1. Showing acanthotic, flattened or frond-like epithelium.

A 38-year-old multipara reported to Gynecology OPD of ESIC-PGIMSR MGM Hospital, Parel, Mumbai, with complaints of some mass in the private parts since three months and slight pain since seven days. Mass was small in size to begin, with no complaints. It gradually increased in size over a period of three months. There was no itching, discharge or bleeding from the mass. Her menstrual cycle was regular 4-5/30 days. There was no history of diabetes mellitus, hypertension, tubercular or any other medical or surgical illness. On general examination; patient was average built, weight 60 kg, pulse 80/min, blood pressure 120/80 mmHg. No pallor, edema. Lymphadenopathy noted. On local examination; a pedunculated, soft, skincolored polypoidal structure of 6 Ă&#x2014; 6 Ă&#x2014; 4 cm in size was seen hanging from clitoris. Surface was smooth with no discharge or bleeding. Mass was nontender but peduncle was tender. There was no other such mass in the vulva, anus or groin region. P/S â&#x20AC;&#x201C; cervix, vagina heathy, no discharge seen through the cervix. Paps smear taken. P/V- Uterus anteverted, multiparous size, fornices free and nontender. Patient was posted for excision of the mass. Her routine investigations were done and found normal. In operation theater under local and intravenous (IV) sedation pedunculated mass was cut and ligated. Mass was sent for histopathological examination. Patient was kept on antibiotics and anti-inflammatory drugs and discharged on the same day. She came back after 15 days for follow-up with Paps smear and histopathological report. Symptomatically, patient had improved and on local examination, the site of surgery was found to be completely healed. Paps smear report showed no abnormality. Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

Figure 2. Showing a hyperplastic epidermis papillomatosis, hyperkeratosis and acanthosis.

Histologic Findings

Figure 1 showing acanthotic, flattened or frond-like epithelium. A papillary-like dermis composed of loosely arranged collagen fibers and dilated capillaries and lymphatic vessels was seen. Appendages were absent. A hyperplastic epidermis showing papillomatosis, hyperkeratosis and acanthosis overlying loosely arranged collagen fibers and many capillaries was seen (Fig. 2). A higher-power view demonstrated to better advantage loosely arranged collagen fibers and many capillaries. Discussion Acrochordons have been reported to have an incidence of 46% in the general population.4 Acrochordons are benign tumors. On rare occasions, histologic examination of a clinically diagnosed FEP reveals a basal or squamous cell carcinoma. In a recent study, of 1,335 clinically diagnosed FEP specimens were malignant. Four were basal cell carcinomas and one was a squamous cell carcinoma in situ. None of these specimens submitted by a dermatologist. This 41

CASE REPORT study concluded that clinically diagnosed FEPs have a low probability of having malignant characteristics on histologic examination. An equal prevalence of acrochordons exists in males and females. When present, acrochordons increase in frequency up through the fifth decade. As many as 59% of persons may have acrochordons by the time they are aged 70 years.4 Acrochordons are flesh-colored pedunculated lesions that tend to occur in areas of skin folds. A family history sometimes exists of acrochordons. These tumors are usually asymptomatic, and they do not become painful unless inflamed or irritated. Patients may complain of pruritus or discomfort when an acrochordon is snagged by jewellery or clothing. Acrochordons may occur at unusual sites of the body. Genital skin tags appear on genitals, i.e., the penis (penis in men) and vagina (vaginal skin tags in women). They may be the cause of more embarrassment than skin tags on other parts of the body. The reason is that genital skin tags are felt during sex and it is not uncommon for both the person and his/her sex partner to suspect them of some contagious disease, especially of sexually-transmitted diseases (STDs). Another reason for concern over genital skin tags is their risk of hosting infections. But on the whole, groin skin tags themselves are not infectious or malignant. They are just skin tags of the genitalia in men and women of various age groups. In women, genital skin tags appear mostly in the vagina, especially in the folds of the outer layer called vulva.5 Unlike men, women mostly get female skin tags in the vaginal area after pregnancy. However, in some women they may appear at any age, more during the adult life. Their appearance is the same as other skin tags on the body i.e., small floppy growths of skin that are a little darker in color than the surrounding skin. In some women having vaginal skin tags, the size of the tags is increased during menstrual periods. However, after the period is over, the tags resume their normal size. Pedunculated lesions may become twisted, infarcted and fall off spontaneously. Acrochordon of clitoris is never reported in literature. A huge acrochordon has been described on the penis.6 A lymphedematous acrochordon of the glans penis unassociated with condom catheter use also has been described.7 An acrochordon may be associated with 42

vulval itching without the symptom being the result of fungal infection. Endoscopy may reveal FEPs arising in a ureter.8 Multiple skin tags are often linked with type 2 diabetes mellitus and with obesity, prompting a study of 58 people with skin tags. It showed that people with skin tags had significantly higher serum cholesterol and low-density lipoprotein levels, but not serum leptin levels, when compared with a healthy control group lacking skin tags.9 Skin tags are generally treated for cosmetic reasons. Small, pedunculated acrochordons may be removed with curved or serrated blade scissors, while larger skin tags may simply require excision. For small acrochordons, application of aluminium chloride prior to removal will decrease the amount of minor bleeding. Anesthesia prior to electrodesiccation is another option. Other methods of removal include cryotherapy and ligation with a suture or a copper wire; however, freezing of the surrounding skin during liquid nitrogen cryotherapy may result in dyschromic lesions. Taking hold of the acrochordon with forceps and applying cryotherapy to the forceps may provide superior results. References 1. Cutaneous skin tags: MedlinePlus Medical Encyclopedia. http://www.nih.gov/medlineplus/ency/article/000848.htm 2. Dianzani C, Calvieri S, Pierangeli A, Imperi M, Bucci M, Degener AM. The detection of human papillomavirus DNA in skin tags. Br J Dermatol 1998;138(4):649-51. 3. Thappa DM. Skin tags as markers of diabetes mellitus: an epidemiological study in India. J Dermatol 1995;22 (10):729-31. 4. Acrochordonemedicine.medscape.com/article/1060373overview. 5. Vaginal Skin Tags, Genital Skin Tag Treatment. www. skintagsolution.com/vaginal-skin-tags.html 6. Emir L, Ak H, Karabulut A, Ozer E, Erol D. A huge unusual mass on the penile skin: acrochordon. Int Urol Nephrol 2004;36(4):563-5. 7. Mason SE, DeVilliers P, Andea AA. Lymphedematous fibroepithelial polyps of the penis associated with longterm condom catheter use: case report and review of the literature. J Cutan Pathol 2009;36(8):906-9. 8. Carey RI, Bird VG. Endoscopic management of 10 separate fibroepithelial polyps arising in a single ureter. Urology 2006;67(2):413-5. 9. Gorpelioglu C, Erdal E, Ardicoglu Y, Adam B, Sarifakioglu E. Serum leptin, atherogenic lipids and glucose levels in patients with skin tags. Indian J Dermatol 2009;54(1):20-2.

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CASE REPORT

An Experience of Chronic Inflammatory Demyelinating Polyradiculoneuropathy with Pregnancy Debasmita Mandal*, Chaitalli Dattaray**, Mousumi Datta†, Alok Pandit*, Saroj Mandal‡, Shyamal Das¶

ABSTRACT Pregnancy with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a very rare association. Although pregnancy influences the clinical outcome of CIDP, whether the opposite also occurs is yet to be proved. We have described here successful outcome of a pregnancy experienced with CIDP and tried to emphasize on important management options during gestation. Key words: Pregnancy, chronic inflammatory demyelinating polyradiculoneuropathy, outcome

hronic inflammator y demyelinating polyradiculoneuropathy (CIDP) was first described by Dyck et al in 1975.1 It is a chronic polyradiculoneuropathy, autoimmune in nature of at least 2-month duration, which affects motor and sensory nerves by destroying the myeline sheath surrounding the nerves. CIDP is usually associated with albuminocytological dissociation and where adult males are affected commonly. This disease is mainly characterized by slowly progressive, symmetrical limb weakness, widespread are flexia and loss of large fiber sensibility, while sensory symptoms are parasthesia and numbness and resultant respiratory weakness may require mechanical ventilation. Thorough MEDLINE search revealed instances of women with CIDP experiencing pregnancy. Hence, we have discussed our experience of this disease during the course of a pregnancy, as awareness regarding the disease and its required management is necessary because of its debilitating consequences.

*Assistant Professor **Associate Professor † Rmo-Cum Clinical Tutor ¶ Professor Dept. of Obstetrics and Gynecology IPGME & R, SSKM Hospital, 244 AJC Bose Road Kolkata, West Bengal Address for correspondence Dr Debasmita Mandal C/11 SSKM Hospital Campus 242, AJC Bose Road, Kolkata - 700 020, West Bengal E-mail: drdebasmitamondal@yahoo.com

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

Case Report A 28-year-old G2P1L1 (post-cesarean) with five months gestation attended Obstetrics and Gynecology OPD with chief complaints of tingling sensation and tenderness over both plantar regions. These symptoms were progressive in nature: Starting from left foot, involving the left leg and thereafter affecting the right leg within a span of one month. On examination, she was 156 cm tall, 43 kg in weight with an average nutritional status. The woman was normotensive with normal respiratory and cardiovascular parameters. Uterine height corresponded to 22 weeks gestation. Ultrasonography conducted at 10 and 24 weeks gestation confirmed the gestational age and excluded any gross congenital anomaly. Her Hb% was 11.3 gm% with 34% packed cell volume. Liver function tests, renal function tests and coagulation profile were within normal range. Central nervous system examination showed a normal level of higher function, speech, spine, cranium and cranial nerves with no evidence of motor atrophy and fasciculation. On the other hand, motor system examination showed both distal and proximal weakness around Grade IV/V without any atrophy, but deep tendon reflexes (DTR) were absent. Motor nerve study diagnosed a grossly reduced compound motor action potential (CMAP) amplitude in bilateral median, ulnar, tibial and peroneal nerves, with grossly reduced conduction velocity (CV) and delayed distal latencies. These led to a suspicion of acquired demyelinating (with secondary axonal) type of sensorimotor polyradiculoneuropathy 43

CASE REPORT involoving all four limbs. Nerve conduction velocity (NCV) and cerebrospinal fluid (CSF) study confirmed the diagnosis of CIDP. Sural nerve biopsy suggested the etiopathogenesis to be of vasculitis origin. Simultaneously antinuclear factor was in higher titer (> 1:320) and autoantibodies i.e., SS-A, Ro-52 were strongly positive and proliferating cell nuclear antigen (PCNA) was of borderline significance. These investigations excluded the secondary cause of CIDP as systemic lupus erythematosus (SLE). Considering the risk of sudden respiratory failure in such patients, she was shifted to a respiratory care unit. Regular monitoring and supplementation of antenatal iron, protein and calcium were continued. Physiotherapy and low-dose prednisolone (40 mg) constituted the neurological management. Fetal growth restriction became evident from 32 weeks onwards along with oligohydramnios, which failed to improve. Intravenous (IV) immunoglobulin was unaffordable by the patient. At the onset of 32 weeks gestation she had intrauterine growth restriction (IUGR) and oligohydramnios. Consequently pregnancy was electively terminated at 33 weeks four days gestation by lower-segment cesarean section under general anesthesia. A female baby weighing 2.14 kg was delivered with Apgar score of 9/10 and 10/10 in one and five minutes. Postpartum routine investigations were within normal limit except a raised serum glutamic oxaloacetic transaminase (SGOT) (450 IU) and serum glutamic pyruvic transaminase SGPT (290 IU), probably as a result of amytriptylline therapy. Typically, her existing neurological symptoms aggravated from third postpartum day and examination revealed motor quadriparesis (UL-3/5, LL-2/5) with grossly reduced DTR in all four limbs. Prednisolone dose was increased to 60 mg. Patient was taken over by neurology team after removal of stiches. Systemic examinations and investigations of baby revealed no abnormality. Neurological status appeared to have improved during her follow-up visits at sixth and 12 weeks.

coincidental pregnancy with CIDP. The disease mostly starts insidiously and evolves slowly either in a progressive (> 60%) or relapsing manner (one-third of all CIDP patients) with partial or complete recovery between recurrences.2 Physical examination usually reveals proximal symmetric muscle weakness with or without distal sensory loss and deep tendon reflexes are generally reduced or absent without any central nervous system (CNS) manifestations. The present case typically presented with similar findings. She had worsened LL weakness from late second trimester onwards to few weeks of puerperal period. Many authors have suggested that in CIDP, there is an increased frequency of relapse during the last trimester and pureperium compared to nonpregnant state.3 McCombe et al studied nine women with CIDP who had 30 pregnancies and observed five of the eight relapses (62.5%) were during third trimester of pregnancy or three months postpartum.4 Oral contraceptives can also worsen the symptoms of CIDP.3 From these data it can be concluded that probably, conditions, which cause hormonal alteration, whether pregnancy itself or drugs like oral contraceptives can precipitate the aggravation of symptoms of CIDP. So, a nonhormonal contraception is desirable if required. Although etiopathogenesis of relapses of CIDP in pregnancy is uncertain immunological studies of pregnancy have implicated the mechanism of protection of fetus from maternal rejection.5 McCombe et al enumerated probable existence of cross reactivity between fetal and maternal neural antigens or an immune response in pregnancy that provokes an anamnestic response to neural antigen.4 Treatment of CIDP includes IV immunoglobulin, plasmapheresis and steroids.3

Discussion

As safety and efficacy of plasmapheresis is still not well-proven during pregnancy and lactation, in the present case titrated low-dose of oral steroid was preferred as the main stay of treatment. Long-term immunosuppressive therapy is common in CIDP, so patients in reproductive age group must be counseled regarding teratogenecity.

Recent data shows CIDP to be relatively uncommon with an estimated prevalence in populations from UK, Australia, Italy, Norway and Japan of 0.8-7.7 per 1,00,000.2 We found limited literature showing

No literature has stressed on the effect of CIDP on pregnancy outcome. The present case had IUGR and oligohydramnious, which might be coincidental. Thus, while dealing with CIDP in

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

CASE REPORT pregnancy vigilant antenatal care is also necessary to avoid associated fetal morbidity. In this case, during the LSCS, general anesthesia was administered in order to avoid any respiratory catastrophe. Regional anesthesia administration to patients with neurological dysfunction can be of concern because of their impaired respiratory function. High sensory levels required for adequate anesthesia during cesarean delivery might paralyze the intercostals muscles and trigger respiratory distress in patients dependant on intercostals function for adequate respiration.6 An adequate counseling of the patient and her family is important so that the progressive nature and probable chance of respiratory failure are well-understood. In a country like ours, where regular antenatal supervision is commonly regarded as superfluous this ensures a timely follow-up and may prevent the patient from presenting at a stage when the process has already exacerbated.

Asian Journal of Obs and Gynae Practice, Vol. 4, October-December 2013

References 1. Dyck PJ, Lais AC, Ohta M, et al. Chronic inflammatory polyradiculoneuropathy. Mayo Clin Proc 1975;50:621-37. 2. Lewis RA. Chronic inflammatory demylinating polyradiculoneuropathy. eMedicine article (cited on 26th april, 2010). Available from URL:http://eMedicine. medscape.com/article/1172965-overview. 3. Shamer DM, Bradley WG, Daroff RB, Fenichel GM, Jankovic J. Neurological problems of pregnancy, Neurology in clinical practice, Fourth edition, Philadelphia, Elsevier Inc. 2004:2535. 4. Combe MC, Frith JA, McLeod JG. Chronic inflammatory demylinating polyradiculoneuropathy associated with pregnancy. Ann Neurol 1987;21:102-4. 5. Jacoby DR, Olding LB, Oldstone MBA. Immunological regulation of fetal-maternal balance. Adv Immunol 1984; 35:157-208. 6. Harrop- Griffiths AW, Ravalia A, Brown DA, et al. Regional anesthesia and cough effectiveness. Anesthesia 1991;46:173.

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