Ajog July-September 2013 by IJCP

Asian Journal of

Online Submission

Volume 3, July-September 2013

CONTENTS

An IJCP Group Publication Corporate Panel Dr Sanjiv Chopra Prof. of Medicine & 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

FROM THE ISSUE EDITOR

FROM THE DESK OF GROUP EDITOR-IN-CHIEF

Facts About Teen Pregnancy

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 Pradeep Garg (Delhi)

Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma Dr Kamala Selvaraj Cardiology Dr Praveen Chandra Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses Dr Sidhartha Das Dr A Ramachandran Dr Samith A Shetty ENT Dr Jasveer Singh Dr Chanchal Pal Nephrology Dr Georgi Abraham

Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dr Rajiv Khosla Dermatology Dr Hasmukh J Shroff Dr Pasricha Dr Koushik Lahiri Neurology Dr V Nagarajan Dr Vineet Suri Journal of Applied

Medicine & Surgery Dr SM Rajendran Dr Jayakar Thomas Orthopedics Dr J Maheshwari

CLINICAL STUDY

Evaluation of PO by Antenatal CTG and UA Doppler in Pre-eclamptic Mothers

Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

Barunoday Chakraborty, Tamal Kumar Mondal, Sannyasi Charan Barman, Biswa Pratim Rudra, Ramkrishna Sahana, Prabhat Chandra Mondal

Fetal FL in Assessment of GA in 3rd Trimester in Women of Northern India and a Comparative Study with Western and Other Asian Countries 14 DP Gupta, DK Saxena, Hem Prabha Gupta, Zaidi Zeeshan, RP Gupta

Evaluation of Mifepristone and Misoprostol for Medical Termination of Pregnancy Between 13-20 Weeks of Gestation

Neha Agarwal, Gauri Gandhi, Swaraj Batra, Rachna Sharma

Systolic and Diastolic Ratio and Rate Pressure Product in Anemia

K Singh

Effect of Rosiglitazone on Spontaneous and Clomiphene Citrate-induced Ovulation in Polycystic Ovary Syndrome

Sandhya Mittal, Anupama Goel, Ajay Mittal, Bal K Taneja, Praveen Gupta

Anand Gopal Bhatnagar Editorial Anchor Advisory Body Heart Care Foundation of India

KK Aggarwal

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)

Alka Kriplani

CASE REPORT

A Case Report of Yolk Sac Tumor Bratati Moitra

Asian Journal of Volume 3, July-September 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

CASE REPORT

Rare Coexisting Primary Hydatid Cyst and Mucinous Cyst Adenoma of Right Ovary

Bandana Biswas, Palash Mondal, Tanuka Das, Thejavinuo Keditsu

Printed at Nikeda Art Printers Pvt. Ltd., Mumbai ÂŠ Copyright 2013 IJCP Publications Ltd. All rights reserved. The copyright for all the editorial material contained in journal, in the form of layout, content including images and design, is held by IJCP Publications Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.

Heterologous Malignant Mixed Mullerian Tumor of Uterus: An Uncommon Tumor with Uncommon Presentation

Bhavana S

Mixed Autoimmune Disorder in Pregnancy

Editorial Policies

Pawaskar Naresh T, DA Hiremath

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Subseptate Uterus Presenting as an Unstable Lie at Term

Shikha Singh, Saroj Singh, Ankita Kumari, Ruchita Sinha

PHOTO QUIZ

Nutan Aggarwal

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Female Genital Tuberculosis

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FROM THE ISSUE EDITOR

Dr Alka Kriplani

MD, FRCOG, FAMS, FICOG, FICMCH, FIMSA, FCLS Professor and Head Dept. of Obstetrics and Gynecology Director in-charge WHO HRRC and Family Planning AIMS, Ansari Nagar, New Delhi - 110 029 E-mail:kriplanialka@gmail.com

se of selective serotonin reuptake inhibitors (SSRIs) to treat pregnant patients does not appear to be associated with stillbirth or infant mortality.1 The United States Advisory Committee on Immunization Practices (ACIP) recommends that all pregnant women receive the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine during each pregnancy, optimally between 27 and 36 weeks of gestation, regardless of prior vaccination status, to increase the likelihood of optimal protection against pertussis for both the mother and her infant during the first few months of the infant’s life.2 Previously, Tdap was recommended only for pregnant women who had not previously received the acellular pertussis vaccine during adulthood. Vaccination during pregnancy substantially reduced the risk of a maternal influenza diagnosis (adjusted hazard ratio, 0.30) and was associated with a trend in reduction of fetal death. All women who are pregnant or will be pregnant during influenza season should receive the inactivated influenza vaccine, regardless of pregnancy trimester.3 A December 2012 American College of Obstetricians and Gynecologists (ACOG) committee opinion concluded that the decision to perform early versus delayed cord clamping in term deliveries should be based on patientspecific factors, particularly the infant’s risk of developing iron deficiency anemia.4 For preterm deliveries, they recommended delayed cord clamping given the significant reduction in intraventricular hemorrhage associated with this intervention.4 In a prospective study of mothers who used benzodiazepines (primarily lorazepam, clonazepam and midazolam); while breastfeeding, central nervous system depression (defined as sleepiness, poor latching, limpness or lack of response to stimuli) in infants was an infrequent finding (affecting 2 out of 124, or 1.6%).5 References 1. Stephansson O, Kieler H, Haglund B, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality. JAMA 2013;309(1):48-54. 2. Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccine (Tdap) in Pregnant Women — Advisory Committee on Immunization Practices (ACIP), 2012. Available at: http://www.cdc.gov/mmwr/ preview/mmwrhtml/mm6207a4.htm?s_cid=mm6207a4_e (Accessed on February 21, 2013). 3. Håberg SE, Trogstad L, Gunnes N. et al. Risk of fetal death after pandemic influenza virus infection or vaccination. N Engl J Med 2013;368(4):333-40. 4. Rabe H, Diaz-Rossello JL, Duley L, et al. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database Syst Rev 2012;8:CD003248. 5. Kelly LE, Poon S, Madadi P, et al. Neonatal benzodiazepines exposure during breastfeeding. J Pediatr 2012;161(3):448-51.

Dr Alka Kriplani Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

FROM THE DESK OF GROUP EDITOR-IN-CHIEF

Facts About Teen Pregnancy

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 Elect, 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)

zz zz zz zz

Ten percent of all women aged 15-19, and 19% of those who have sexual intercourse, become pregnant. One-quarter of adolescent mothers have a second child within two years of their first. A pregnant adolescent may complain of missing her periods or of irregular periods. Pregnant adolescents may present with vague complaints and may or may not have considered the possibility of pregnancy. It is important to ask the teenager what she would do if her pregnancy test were positive before the test is performed. When the results of a positive pregnancy test are disclosed to the adolescent, her thoughts and feelings about the test result should be elicited, and emotional support provided. Factual information regarding the duration of pregnancy and estimated date of confinement (EDC) should be provided. It is also important to determine how the adolescent wants to go about informing her parent(s) and the father of the baby. Options regarding the pregnancy should be discussed in a nonjudgmental manner and the adolescent referred as soon as possible to a clinician or clinic where comprehensive pregnancy counseling is provided. The healthcare provider should contact the adolescent about one week after the scheduled referral for followup information, to demonstrate concern for the adolescent and to ensure appropriate care. Adolescents appear to be at increased risk for adverse pregnancy outcomes, such as low-birth-weight babies and infant deaths. Adolescent pregnancy is associated with several adverse socioeconomic outcomes for the mother, father and child. ■■■■

Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CLINICAL STUDY

Evaluation of PO by Antenatal CTG and UA Doppler in Pre-eclamptic Mothers Barunoday Chakraborty*, Tamal Kumar Mondal**, Sannyasi Charan Barman†, Biswa Pratim Rudra‡, Ramkrishna Sahana¶, Prabhat Chandra Mondal¶

ABSTRACT This was a well-controlled hospital-based longitudinal prospective randomized study with a sole focus on pre-eclampsia cases, where cardiotocography (CTG) and colored Doppler were the two special investigative tools applied to examine the perinatal outcome (PO). The study concluded with a note that antenatal CTG is a useful objective test to know the intrauterine fetal status but it cannot forecast the fetal behavior during labor, neither does it provide a guide to optimize the timing of induction of labor (IOL) or termination by cesarean section. Color Doppler indices done after 34 weeks definitely give a qualitative assessment of fetoplacental perfusion but it cannot predict the said perfusion during labor - when there occurs a degree of compromise with the uterus contracting repetitively. Ultrasonography (USG) for fetal biometry and liquor volume is a good test to determine small for gestational age or intrauterine growth restriction (IUGR) as the case may be taking cognizance of other factors e.g., pre-eclampsia, fetal congenital anomaly, etc. Every mother with pre-eclampsia needs to be evaluated both clinically, biochemically and ultrasonologically. Understanding the limitation of antenatal CTG and color Doppler indices, these should be applied in a few selected cases e.g., increased fetal movement, IUGR, which is reassuring to both the patient and the doctor who can wait till a reasonable degree of fetal maturity occurs before one goes for IOL or a cesarean section. Patients with a suspicious CTG should undergo continuous CTG during labor - otherwise there is always a tendency to go for an early lower-segment cesarean section (LSCS). For a pre-eclamptic mother with a pathological CTG the decision is an elective LSCS; whereas, cases with pathological CTG but normal Doppler indices the judgment is too difficult. The answer then would lie on factors like whether the pre-eclampsia is controlled and whether the biochemical and hematological parameters are within normal limits. Of course thanks to the presence of a special newborn care unit (SNCU) nearby. Key words: CTG, Doppler, pre-eclampsia

Introduction, Review of Literature and Objectives Pre-eclampsia is a multisystem, highly variable disorder, unique to pregnancy and a leading cause of maternal and perinatal mortality and morbidity.1,2 It is a syndrome defined by hypertension and proteinuria that also may be associated with a

*Associate Professor Dept. of Obstetrics and Gynecology BS Medical College, Bankura, West Bengal **Resident Dept. of Obstetrics and Gynecology RG Kar Medical College, Kolkata † RMO-cum Clinical Tutor ‡ Senior Resident ¶ Assistant Professor Dept. of Obstetrics and Gynecology BS Medical College, Bankura, West Bengal Address for correspondence Dr Barunoday Chakraborty G5/26, College Quarter, BS Medical College, Gobindanagar Bankura, West Bengal -722 102 E-mail: asmp80@rediffmail.com

Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

myriad of other signs and symptoms such as edema, visual disturbances, headache and epigastric pain.3 The increased incidence of perinatal morbidity and mortality seen in pregnancies complicated by pre-eclampsia is primarily due to the need for premature delivery and uteroplacental insufficiency resulting in a compromised blood flow to the fetus.4 The primary adoptive response of the fetus to placental insufficiency is a decrease in growth. Persistent placental insufficiency will result in decreased fetal movement to conserve energy, hemodynamic redistribution to favor the oxygenation of organs critical to the economy such as the brain, heart, suprarenal and attempt to improve the efficiency of the placental gas exchange by increasing the heart rate and the synthesis of red cells. Progressive decompensation like this will lead to a metabolic and respiratory acidosis, increased impedance to fetoplacental circulation, renal insufficiency with decreased amniotic fluid volume; myocardial compromise, absent or reversed atrial flow in ductus venosus, late deceleration in the fetal heart 7

CLINICAL STUDY rate (FHR) tracing and fetal death. It would be ideal that this sequence of pathological changes elicited by placental insufficiency and fetal hypoxia could be identified in each of its different stages by a single test, which has not been achieved so far. In an attempt to stratify risk, a variety of antepartum screening tests are performed, which include few laboratory tests and sonographic assessments, besides history taking and clinical examination including serial symphysiofundal height measurement. Antenatal cardiotocography (CTG) is a special test for evaluation of fetal status. Prof. Essar GS Dows and Prof. C Redman of United Kingdom were two pioneers in the eighties who devised the computer program to evaluate CTG. The basic objective of CTG is to assess co-ordination between fetal central nervous system (CNS) and the cardiovascular system based on the fact that a well-oxygenated healthy fetus with functionally intact CNS-cardiac axis will show accelerations (rise of FHR 15 beats/minute for 15 seconds above baseline) with fetal movements - the so called reactive CTG. In addition, good FHR variability (≥5 bpm) suggest normal balance of sympathetic-parasympathetic activity, an indirect evidence of adequate oxygenation of fetal regulatory centers; indeed, a normal FHR variability is the hallmark of fetal well-being. Accepted normal parameters for term fetus are: zz

Baseline FHR 110-160 beats/minute

Baseline variability should be >5 beats/minute

Presence of two or more accelerations of FHR exceeding 15 beats/minute, sustained for at least 15 seconds in a 20-minute period. This pattern is termed as ‘Reactive.’ Absence of deceleration.

However, the Cochrane meta-analysis of randomized controlled trials (RCTs) involving 1,558 high/ intermediate risk pregnancies suggests antepartum CTG alone has no significant impact on perinatal outcome.5 Though, initial studies have shown a strong correlation between abnormal CTG and poor perinatal outcome,6 when CTG is used alone significant interobserver variations, poor specificity and high false-positive rates causing increased number of lower-segment cesarean section (LSCS) are other problems. 8

The change in behavior of ultrasound waveform reflecting from a moving object - the Doppler effect was introduced in the assessment of umbilical artery flow at Dubling in 1977. Longitudinal Doppler studies of the umbilical artery show that the systolic/diastolic (S/D) ratio decreases as gestation progresses. This is an indirect evidence of decreasing placental resistance with advancing gestation.7 However, there is no definite agreement as to what constitutes an abnormal Doppler study. Most authors have accepted as S/D ratio >3.0 as the cut-off beyond 30 weeks gestation. Gradual increase in umbilical artery resistance leads to absent and subsequently reversed end-diastolic flow, which is associated with progressively worse perinatal outcome. The Doppler indices are calculated as ratios between peak systolic velocity (A), end-diastolic peak velocity (B) and mean velocity (mean). The indices most common in clinical practice, are pulsatility index (PI) = (A-B)/mean, and resistant index (RI) = (A-B)/A. With normal placental perfusion, the umbilical artery waveform has a pattern compatible with a low-resistance system displaying forward blood flow throughout the cardiac cycle.8 Inadequate placental perfusion causes progressive changes in the Doppler flow pattern of umbilical artery starting from absent or reversed end-diastolic flow, increase in resistance index, which correlate well with fetal acidosis.9 The first meta-analysis of umbilical artery Doppler in high-risk pregnancies published in 1995 demonstrated significant reduction in perinatal death.10 Two large RCTs- one from South Africa and other from Canada, and one Cochrane review of routine Doppler studies of umbilical artery in high-risk pregnancies have shown conflicting reports of benefit regarding perinatal outcome. However, evidence from small RCTs does indicate less requirement of emergency cesarean section for fetal distress if Doppler velocity was used (NICE Guideline, 2010). The ongoing TRUFFLE study has been designed to compare reduced short-term variations on CTG and Doppler velocimetry of ductus venosus to determine optimum timing of delivery of growth restricted fetus.11 In this study, spanning six months we tried to evaluate perinatal outcome in pre-eclampsia in term of mode of delivery (vaginal/instrumental/LSCS), need for induction of labor (IOL), neonatal status according to specific parameters by means of antenatal CTG and Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CLINICAL STUDY umbilical artery Doppler in late third trimester at our institution, which is a tertiary maternity care center with an annual delivery rate of >20,000, delivering optimal care free of cost to a large population from three districts namely Bankura, Purulia and Paschim Medinipur in West Bengal. Our objective was to ascertain an optimum and cost-effective way to treat pre-eclamptic mothers and to obviate special investigations like CTG and umbilical artery Doppler in each and every case and thereby save some cost as well as manpower. Material and Methods This was a prospective longitudinal study carried out in our department during six months period from April 2012 to September 2012. All pre-eclamptic mothers of >34 weeks of gestation with a single intrauterine fetus presenting cephalic presentation without any congenital anomaly were included in the study. Patients with prelabor rupture of membrane, antepartum hemorrhage (APH), bad obstetric history, elderly primi (>35 years), multifetal pregnancy, malpresentation, history of systemic illness e.g., antiphospholipid syndrome, chronic renal disease, heart diseases, psychiatric illness were excluded. Known cases of pre-eclampsia were evaluated with history, examination and laboratory investigations including urine albumin, serum uric acid, platelet count, clotting time, renal and liver function tests.

The cases were then randomized and allocated in the study group and control group. The study group had undergone an antenatal CTG for 40 minutes and umbilical artery Doppler study. Categorization of FHR traces was done following Royal College of Obstetricians and Gynecologist (RCOG) criteria 2001 as normal, suspicious and pathological. Normal implied a fetal well-being and as such a conservative approach; whereas, suspicious implied continued observation and additional test e.g., vibroacoustic stimulation (VAS) and pathological indicated an urgent delivery. Our CTG equipment was Schiller, Argus AFM, SN = SA0702-0009; manufacturer: Biostos Co. Ltd. Korea: 2005. The study group had also undergone assessment of fetoplacental profile and a Doppler assessment of umbilical artery. S/D ≤3 and RI ≤0.6 were considered normal; raised indices, absent or reversed end-diastolic flows were taken as signs of fetal distress. The decision to deliver the baby at an optimum time through an appropriate route (vaginal/LSCS) was taken considering the gestational age and the results of CTG and umbilical artery Doppler indices. The control group was followed up by daily clinical monitoring and routine USG for fetoplacental profile and liquor volume. They were delivered by appropriate route at an optimum gestational age according to these findings and consultant decision.

Table 1. No. of Patient Showing Reactive or Nonreactive CTG in the Study Population CTG Reactive (n = 24) Nonreactive (n = 11) Total (n = 35)

Mode of delivery

Apgar score at 1 min

Normal

LSCS

Forceps

≥7

22 (91.6%)

1 (4.2%)

18 (75%)

6 (25%)

5 (45.5%)

6 (54.5%)

3 (27.3%)

8 (72.8%)

27 (77.14%)

7 (20%)

21 (60%)

14 (40%)

P = 0.002

P = 0.003

Table 2. Umbilical Artery Doppler Indices of the Study Population Umbilical artery Doppler indices Normal (n = 10) Raised (n = 25) Total (n = 35)

Mode of delivery

Apgar score at 1 min

Normal

LSCS

Forceps

≥7

8 (80%)

1 (10%)

9 (90%)

1 (10%)

19 (76%)

6 (24%)

12 (48%)

13 (52%)

27 (77.14%)

7 (20%)

21 (60%)

14 (40%)

P = 0.2004

Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

P = 0.01

CLINICAL STUDY Study group, where a conservative approach was taken till maturity (37 weeks) were followed up by twice in a week CTG and another Doppler study after two weeks. Control group, in similar situation had another routine USG for FPP after two weeks. The neonatal outcomes of both groups were recorded in predesigned proforma and compared using Chi-square test and Student’s t-test and statistical software Medcalc 12.3.0. Ethical clearance was obtained from College Ethical Committee and due consent was taken from patients and their husbands or a near relative.

Observation and Discussion Two-third of our study population (n = 35) had a reactive CTG and one-third showed a nonreactive type (Table 1). Nearly, 92 patients of reactive CTG against 45% of those with nonreactive type had a normal delivery and 56% with nonreactive CTG had a cesarean delivery against only 3% of reactive type - the difference of picture is definitely significant (p < 0.05). Random application of CTG has increased the number of LSCS whenever CTG tracing gets

Table 3. Perinatal Outcome in the Study and Control Group Parameters

Study group

Control group

P value

38.6, 1.77

38.92, 1.88

t-test

34-37

p = 0.792

>37

IOL

Chi-sq. t-test

SOL

p = 0.298

Chi-sq. t-test

LSCS

p = 0.537

Forceps

Mean, SD

6.51, 1.90

6.69, 1.683

Chi-sq. t-test

≥7 at 1 min

p = 0.147

<7 at 1 min

Mean, SD

7.46, 0.99

7.86, 1.29

Chi-sq. t-test

≥7 at 5 min

p = 0.125

<7 at 5 min

Gestational age at birth (weeks) Mean, SD

Labor events

Mode of delivery

Apgar score

Birth weight (g) Mean, SD

2691, 392

2670, 356

Chi-sq. t-test

1,500-2,500

p = 0.816

>2,500

Yes with Bag Mask (BM)

Chi-sq. t-test

p = 0.404

Yes

Chi-sq. t-test

p = 0.285

Need for resuscitation

SNCU admission

IOL = Induction of labor; SOL = Spontaneous of labor; ND = Normal delivery; LSCS = Lower-segment cesarean section; SD = Standard deviation; SNCU = Special newborn care unit.

Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CLINICAL STUDY

100%

Apgar ≥7

90%

Apgar ≤7

80% 70% 60% 50% 40% 30% 20% 10% 0%

Reactive CTG

Nonreactive CTG

Normal Doppler indices

Raised Doppler indices

Figure 1. Association of low Apgar score with raised Doppler indices.

abnormal has been supported by other authors in the past: Khursheed et al showed a 72% LSCS rate when CTG was of pathological pattern.12 Overall, the incidence of vaginal delivery (normal and instrumental) among the study group was 80% (28 out of 35) and LSCS was 20%. In a tertiary care center 20% LSCS rate among pre-eclampsia cases was quite acceptable against World Health Organization (WHO) standard of 15%. So, CTG in this study has favored decision towards cesarean section but it has not pushed the number to an unacceptably high rate, which needed an audit. The message here is that CTG in pre-eclampsia is an useful investigation that allows judicious decision, making and does not cause unnecessary panic among obstetricians to take hasty decisions of LSCS which is obvious from the fact that 44% (5 out of 11) of nonreactive CTG cases were allowed a normal delivery. Though, a significantly higher incidence (p = 0.003) of low Apgar score was noted among nonreactive CTG, there was no perinatal death. Similar findings of increased neonatal hypoxia were noted by Khursheed and Chew et al in 2009.13 So, CTG can predict a low Apgar neonate but not enough to predict a perinatal death. More than two-third (25 out of 35, Table 2) of the study group had high umbilical artery Doppler indices (Table 2) but incidence of LSCS was not significantly Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

higher (p = 0.24). However, among the neonates the low Apgar score was significantly associated with raised Doppler indices, 52% against 10% (p = 0.01): (Fig. 1). This finding validates the fact that umbilical artery Doppler shows the extent of fetoplacental perfusion during fetal diastole and is a recognized tool to show intrauterine fetal status. Sharma et al got almost similar findings in their study in 2010.14 The mean gestational age at birth of the study group and control group were not statistically different (p = 0.792). The labor events; the incidence of IOL versus spontaneous onset labor, incidence of vaginal delivery versus LSCS; Apgar score at one minute and five minutes; mean neonatal birth weight, number of hypoxic neonates requiring Bag Mask (BM) resuscitation and special newborn care unit (SNCU) admission when compared vis-a-vis with the control group had shown quite similar results with p value ranging from 0.125 to 0.816 (Table 3). A range of well-defined studies including one evidence-based meta-analysis from 1992 to 2001 could find no significant difference in neonatal outcome and LSCS rate with Doppler velocimetry.15 In 2010, Alfirevic et al in a Cochrane review on “Fetal and umbilical Doppler ultrasound in high-risk pregnancies” could not identify a difference in the requirement of intubation and assisted ventilation among neonates between Doppler velocimetry group and control group without Doppler velocimetry.16 Conclusion Therefore, universal application of antenatal CTG and umbilical artery Doppler does not do anything better than a routine USG among mature fetuses to forecast perinatal outcome. It is the labor monitoring and 24 hours cesarean section facility that matters when emergency arises in the form of prolonged labor, meconium staining and fetal bradycardia. Over the years, scientists have explored this area to determine the postnatal events with antenatal CTG and Doppler, which has remained a grey area even today because beyond 34-36 weeks of gestation, it is uncommon to find absent or reversed EDF in the umbilical arteries caused by uteroplacental insufficiency. Abnormal umbilical artery Doppler after 35 weeks should prompt consideration of other causes specially aneuploidy (Trisomies 18, 21). 11

CLINICAL STUDY

Baseline FHR 130 bpm Variability >5 4 accelerations No deceleration

Normal CTG; Crying Boy BW - 2.8 kg (LSCS)

Baseline FHR 140 bpm Variability >5 3 accelerations No deceleration

Normal CTG; Crying Girl BW - 2.8 kg (ND)

Baseline FHR 155 bpm Variability >5 No acceleration 2 late decelerations

Suspicious CTG; Asphyxiated Boy BW - 1.75 kg (LSCS)

Baseline FHR 130 bpm Variability <5 No acceleration No deceleration

Suspicious CTG; Asphyxiated Girl BW - 2.7 kg (LSCS)

Baseline FHR 145 bpm Variability >5 First 2 mts <5 rest of tracing No acceleration 1 deceleration Pathological CTG; Asphyxiated Girl BW - 2.9 kg (LSCS) Figure 2. CTG findings of the study population.

Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CLINICAL STUDY In absence of aneuploidy assessment of intrauterine growth restriction (IUGR) in late pregnancy is challenging because umbilical artery Doppler has a limited value in this setting. The timing of delivery is contentions because a favorable perinatal outcome is expected even with early delivery once diagnosis of IUGR has been made by fetal ultrasound biometry, amniotic fluid index, umbilical and middle cerebral artery Doppler indices. Elective induction of labor with continuous FHR monitoring may result in successful vaginal delivery although fetal distress and meconium staining in labor are common complications. No study exist to provide recommendation in these circumstances regarding early delivery versus antepartum monitoring and delayed delivery.17 The current study though conducted on a small sample can be considered as a pamphlet that speaks the need of careful clinical monitoring along with a routine USG after 34 weeks thanks to the presence of SNCU attached to the maternity ward. Control of blood pressure by labetalol or nifedipine (both the drugs are freely available at our ward); sending blood samples for Hb%, hematocrit, platelet count, serum urate, liver enzymes and 24 hours urine for protein; with or without the presence of IUGR on USG provide valuable clue to choose between immediate delivery by LSCS; IOL followed by fetal monitoring and trial of labor for at least six hours and/or prophylactic MgSO4 injection followed by emergency LSCS. References 1. Ness RB, Roberts JM. Heterogeneous causes constituting the single syndrome of preeclampsia: a hypothesis and its implications. Am J Obstet Gynecol 1996;175(5):1365-70. 2. Douglas KA, Redman CW. Eclampsia in the United Kingdom. BMJ 1994;309(6966):1395-400. 3. ACOG Committee on Obstetric Practice. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 2002;77(1):67-75. 4. Dekker GA, Sibai BM. Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol 1998;179(5):1359-75.

5. Pattison N, McCowan L. Cardiotocography for antepartum fetal assessment. Cochrane Database Syst Rev 2000;(2):CD001068. Update in: Cochrane Database Syst Rev 2010;(2):CD001068. 6. Freeman RK, Anderson G, Dorchester W. A prospective multi-institutional study of antepartum fetal heart rate monitoring. I. Risk of perinatal mortality and morbidity according to antepartum fetal heart rate test results. Am J Obstet Gynecol 1982;143(7):771-7. 7. Divon MY, Ferber A. Doppler evaluation of the fetus. Clin Obstet Gynecol 2002;45(4):1015-25. 8. Neilson JP. Doppler ultrasound. Br J Obstet Gynaecol 1987;94(10):929-32. 9. Bilardo CM, Nicolaides KH, Campbell S. Doppler measurements of fetal and uteroplacental circulations: relationship with umbilical venous blood gases measured at cordocentesis. Am J Obstet Gynecol 1990;162(1): 115-20. 10. Neilson JP, Alfirevic Z. Doppler ultrasound for fetal assessment in high risk pregnancies. Cochrane Database Syst Rev 2000;(2):CD000073. Update in: Cochrane Database Syst Rev 2010;(1):CD000073. 11. Cambridge Consortium. Trial of Umbilical and Fetal Flow in Europe (TRUFLE). Ultrasound Obstet Gynecol 2005;25105-7. 12. Khursheed F, Das CM, Jatoi N. Cardiotocography: obstetric and neonatal outcome. J Rawalpindi Med Coll 2009;13(2):86-8. 13. Chew FT, Drew JH, Oats JN, Riley SF, Beischer NA. Nonstressed antepartum cardiotocography in patients undergoing elective cesarean section - fetal outcome. Am J Obstet Gynecol 1985;151(3):318-21. 14. Sharma U, Bhatnagar B. Triple vessel wave pattern by Doppler studies in normal and high risk pregnancies and perinatal outcome. J Obstet Gynaecol India 2010; 60(4):312-6. 15. Pattinson RC, Norman K, Odendaal HJ. The role of Doppler velocimetry in the management of high risk pregnancies. Br J Obstet Gynaecol 1994;101(2):114-20. 16. Alfirevic Z, Stampalija T, Gyte GM. Fetal and umbilical Doppler ultrasound in high-risk pregnancies. Cochrane Database Syst Rev 2010;(1):CD007529. 17. Rumack CM, Wilson SR, Charbonean JW, Jo-Ann M, Johnson. Diagnostic ultrasound. Elsevier: Mosby 2005;3e(2):1542.

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Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CLINICAL STUDY

Fetal FL in Assessment of GA in 3rd Trimester in Women of Northern India and a Comparative Study with Western and Other Asian Countries DP Gupta*, DK Saxena**, Hem Prabha Gupta†, Zaidi Zeeshan‡, RP Gupta#

ABSTRACT Introduction: Gestational age (GA) estimation is the most important part of obstetric practice and ultrasonic study plays an important role in its accurate estimation. Fetal femur length (FL) is one of the parameters used for estimation of GA along with biparietal diameter, head circumference and abdominal circumference (AC). Objective: This study is an attempt to correlate fetal FL with GA and to ascertain if fetal FL can be used as a parameter to calculate the GA in third trimester of pregnancy in Indian women with moderate accuracy. Findings have been compared with the work of sonologists from other countries. Material and methods: Pregnant women in the third trimester of pregnancy with single live fetus and having no other complication either in mother or fetus, were selected for the study, fetal FL along with other parameters was measured. The results were analyzed for accuracy in estimation of GA by FL and were compared with findings of other workers. Result: GA estimated from FL in 512 cases between 27-39 weeks of gestation showed that quadratic model has a good fit to the data and r2 = 0.785 with standard error + 8 days. There was a significant difference with Iranians and Bangladesh women in comparison to our findings. The paired t-test between Indian and Bangladesh, women was significant, (p < 0.001). The findings in our study were similar to the results of Western fetal FLs. Conclusion: The data can be useful in estimation of GA by FL. Our error was + 8 days. A bigger study involving same number of cases in each week of gestation in third trimester is necessary to get an accurate formula for assessment of GA by FL. Key words: Gestational age, femur length, estimation

ost of the ultrasonic studies have been reported in second trimester using a single parameter biparietal diameter (BPD)1 or multiple parameters head circumference + abdominal circumference (HC + AC) or (HC + FL) or (HC + AC + FL [femur length]). Multiple parameters were found to be slightly superior to HC or BPD alone in the estimation of fetal age. On the basis of the data derived from pregnancies with known conception dates, ultrasound determines the fetal age to within <5 days

*Associate Professor **Assistant Professor Dept. of Radiology † Professor Dept. of Obstetrics and Gynecology ‡ Statistician-cum-Lecturer Dept. of Community Medicine 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 E-mail: dp_gupta2007@yahoo.co.in

in first trimester and <7 days in second trimester in >95% of cases.2 Ultrasonic studies have proven useful in determination of gestational age (GA) in first and second trimester, but their accuracy in third trimester is not reliable because of biologic variations like racial differences in fetal biometric measurements and inter population variations.11 Aims and Objective This study was conducted to evaluate if fetal FL can be used as a parameter in GA determination in third trimester in Indian women and to compare it with the other study in Bangladesh women.3 In Iranian population, it has been reported to be an accurate indicator of GA and has a stronger correlation with GA than BPD.4 The accuracy of fetal FL in the estimation of GA has been mentioned in various studies.5 Material and Methods The study was conducted in 512 pregnant women who came for ultrasonography in the Dept. of Radiology, Era’s Lucknow Medical College and Hospital, Lucknow Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CLINICAL STUDY in between October 2011 to October 2012. Only women with >27 weeks CUA (composite ultrasonographic age) till term were included in this study. All patients were examined for any other complication. Gravid females with single live fetus with no complication i.e., congenital anomaly, or growth restriction were included. Women who participated in the study were selected on following criteria: zz Regular menstrual cycles, known date of last menstrual period zz Previous live normal neonates in multipara zz No history of taking tobacco, gutka zz No history of drug abuse zz No history of diabetes, hypertension, tuberculosis zz No uterine anomaly. All scans were performed by a single ultrasonologist on one ultrasound machine, a Elpro GE logic 200 and a 3.5 MHz sector transducer was used. The long axis of femur was aligned with transducer measuring only the osseous portion of diaphysis and metaphysis of the proximal femur. The entire osseous femur was measured without foreshortening or elongation as described by Filly et al.7,8 Femoral epiphysis is visible after 32 weeks and was not included in measurement. Statistical analysis were conducted by using SPSS version 14.0 software. At each GA, FL indices were reported as mean ± SD (standard deviation). Pearson’s correlation between GA and FL is presented in the form of scatter plot and assessed by Pearson’s product moment correlation coefficient. Its significance was assessed by using t-test. To predict GA by using FL measurements, linear regression analysis was performed using linear mixed model approach taking GA as dependent variable and FL as independent and also FL as dependent and GA as independent. Result The study was conducted in 512 women who came for ultrasonography in the third trimester. The maternal age was between 18-38 years with a mean maternal age of 24.79 ± 4. About 37.5% women were from low socioeconomic group and the rest were from middle income group. It was observed that FL increased gradually from a minimum of 50 mm at the 27.25 weeks GA to 76 mm in the 37.43 weeks (Table 1). In 36-38 weeks the increase in FL was slow Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

Table 1. Comparison of Mean GA in Indian, Western and Bangladesh with Regard to Fetal FL FL in MM

Gestational age in weeks Mean (Indian)

2 SD

Mean (Western)

Mean (Bangladesh)

27.25

0.42

27.54

1.13

27.0

27.6

27.68

1.19

27.4

28.1

28.51

2.10

27.8

28.5

28.10

1.06

28.2

29.0

28.75

1.84

28.7

29.5

29.14

2.74

29.1

30.0

29.49

2.30

29.6

30.4

30.24

2.34

30.0

30.9

30.60

2.45

30.5

31.4

30.63

1.28

30.9

31.9

31.13

2.05

31.4

32.4

31.58

2.41

31.9

32.9

31.16

2.07

32.0

33.5

32.52

1.81

33.0

34.0

32.66

1.82

33.0

34.5

33.47

2.60

33.8

35.6

33.09

1.90

34.2

35.9

33.94

2.73

34.2

36.1

34.08

2.23

34.7

36.7

31.18

1.83

35.2

37.2

34.61

2.02

35.7

37.8

35.47

1.59

36.2

38.4

35.98

2.25

37.2

36.9

35.88

3.79

37.4

39.5

36.53

1.64

38.3

37.43

2.32

38.8

36.40

0.00

39.8

(Table 2). Data were prepared for FL in different weeks of gestation in form of Tables and Graphs. Graphs based on quadratic function were prepared. There is high correlation seen between FL and CUA -r2 = 0.785 p < 0.001. Taking CUA as dependent and FL as independent, the coefficient of determination r2 was 0.78625, and the error in estimation of CUA using FL is ± 1.146 weeks or ± 8 days. Taking FL as dependent and CUA as independent the coefficient of determination was r2 = 0.74691. 15

CLINICAL STUDY Table 2. Comparison of FL of Indian Women in Percentile GA in weeks

No. of cases

Mean FL in mm

FL in mm percentiles

2 SD

56.4

2.822

5.645

0.484

58.3

3.806

7.612

0.574

57.1

62.015

2.477

4.953

0.438

59.4

62.9

2.378

4.757

0.297

60.85

55.525

62.3

66.64

4.944

9.889

3.638

63.80

57.975

63.8

68.02

3.687

7.374

0.372

5th

50th

95th

52.03

46.5

51.85

54.11

45.95

54.8

57.07

52.825

59.43

65.94

61.165

65.9

70.68

2.716

5.431

0.325

67.99

62.73

71.42

2.418

4.836

0.332

70.92

66.96

71.3

74.48

2.074

4.149

0.367

71.96

77.6

3.322

6.644

0.959

72.98

76.3

3.365

6.731

1.064

70.30

70.3

72.6

3.253

6.505

2.300

76.00

Present study

65 60 55

60 50 40 30 20 10

50 27 28 29 30 31 32 33 34 35 36 37 GA in weeks

27 28 29 30 31 32 33 34 35 36 37 38 39 CUA in weeks

Figure 1. Femur length value at specific weeks of gestation (confidence interval [CI]).

Figure 2. Comparison with Iranian and Bangladesh studies.

The error in estimation of FL using CUA is ± 3.25. The equation of fitted quadratic curves are:

Bangladesh measurements for the corresponding GA. In the early weeks of gestation, there was less difference, but as age advanced the difference increased. Our study showed accordance with the study of Rashid3 who also reported that Indian fetal FL for a particular GA was more than Bangladesh women, but in our study we found that the Indian fetal FL were similar to the western study (Fig. 3).

CUA = 0.0074 FL2 – 0.565 FL ± 38.04 FL = 0.046 CUA2 + 5.172 CUA – 55.41 Table 1 shows the mean GA in relation to FL in western, Indian and Bangladesh women. An effort was made to compare the pattern in increase in FL according to GA in the three groups. (Figs. 2 and 3). Our results showed that mean FL was similar to the Western measurements and more than 16

Bangladesh Study

70 Femur length (mm)

95% CI femur length

Iranian Study

Comparing our results with Iranian and Bangladesh study we observed that FL was more in each gestation age as compared to the Iranian and Bangladesh fetus (Fig. 2). Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CLINICAL STUDY

Femur length (mm)

Present study

90 85 80 75 70 65 60 55 50 45 40

Western Study

Bangladesh Study

calculation of GA by FL and each population needs different growth charts for accurate calculations. References 1. Campbell S. The prediction of fetal maturity by ultrasonic measurement of the biparietal diameter. J Obstet Gynaecol Br Commonw 1969;76(7):603-9.

27 28 29 30 31 32 33 34 35 36 37 38 39 CUA in weeks

Figure 3. Comparison with Western and Bangladesh studies.

Discussion In our study of 512 cases between 27-39 weeks, Table 2 shows the details of number of cases in each GA and the mean FL and its percentile in relation to the percentile table. Accordingly the values matched 5th, 50th and 95th percentile table. In the study of Hadlock et al9 they found error of ± 9.5 days between 12-23 weeks and ± 22 days between 23-40 weeks. Yeh et al10 reported a 95% confidence interval of ± 5 days during the period of 22-35 weeks with a maximum variation of ± 6 days, these values are based on analysis of 150 fetuses. While Hadlock et al9 and Hoeler et al12 analyzed over 300 fetuses and they reported the variability during this period to be higher that is ± 3-3.5 weeks. In another study of 900 fetuses by Honarvar4 there is a variability of ± 5 days during 23-40 weeks of gestation. Our study of 512 cases the variability in estimation of GA by using FL is ± 8 days. The results have shown differences with other studies because out of 512 cases, 345 cases were in the 30-34 weeks of gestation and it is during this period increase in FL is maximum. Furthermore, it is during this period of gestation that variations in FL is more between cases in the same week of gestation (Table 2). Kovac et al13 had concluded that Asian groups had a less than – expected FL as compared to Western studies, but in our study FL was similar to the Western studies (Fig. 3). Further studies with equal number of cases in each week of gestation would give a better calculation formula for the estimation of GA by FL. The difference in mean values with other ethnic groups indicates that single formula can not be used for Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

2. Wisser J, Dirschedl P, Krone S. Estimation of gestational age by transvaginal sonographic measurement of greatest embryonic length in dated human embryos. Ultrasound Obstet Gynecol 1994;4(6):457-62. 3. Rashid SQ. Gestational age predicted by femur length in Bangladesh. J Bangladesh Coll Physicians Surg 2010;3: 163-6. 4. Honarvar M, Allahyari M. Assessment of gestational age based on ultrasonic femur length in fetus. Acts Medica Iranica 1999;37(3):134-8. 5. O’Brien GD, Queenan JT, Campbell S. Assessment of gestational age in the second trimester by real-time ultrasound measurement of the femur length. Am J Obstet Gynecol 1981;139(5):540-5. 6. Chervenak FA, Skupski DW, Romero R, Myers MK, Smith-Levitin M, Rosenwaks Z, et al. How accurate is fetal biometry in the assessment of fetal age? Am J Obstet Gynecol 1998;178(4):678-87. 7. Filly RA, Hadlock FP. Sonographic determination of menstrual age. In: Ultrasonography in Obstetrics and Gynecology. Callen PW (Ed.), WB Saunders: Philadelphia 2000:p.146-70. 8. Goldstein RB, Filly RA, Simpson G. Pitfalls in femur length measurements. J Ultrasound Med 1987;6(4):203-7. 9. Hadlock FP, Harrist RB, Deter RL, Park SK. Fetal femur length as a predictor of menstrual age: sonographically measured. AJR Am J Roentgenol 1982;138(5):875-8. 10. Yeh MN, Barron B, Bracero L, Murtha L, Aboulafia M, Reilly K. Ultrasound measurement of femur length as a Index of fetal growth and development. Proceeding of the 26th Annual Meeting if the American Institute of Ultrasound in Medicine. 1981:35. 11. Brooke OG, Butters F, Wood C, Bailey P, Tukmachi F. Size at birth from 37-41 weeks gestation: ethnic standards for British infants of both sexes. J Hum Nutr 1981;35(6): 415-30. 12. Hoeler EW, Quetel TA. The relationship between fetal femur length and biparietal diameter in last half of pregnancy. Am J Obstet Gynaecol 1981;141:759-62. 13. Kovac CM, Brown JA, Apodaca CC, Napolitano PG, Pierce B, Patience T, et al. Maternal ethnicity and variation of fetal femur length calculations when screening for Down syndrome. J Ultrasound Med 2002;21(7):719-22; quiz 724-5.

CLINICAL STUDY

Evaluation of Mifepristone and Misoprostol for Medical Termination of Pregnancy Between 13-20 Weeks of Gestation Neha Agarwal*, Gauri Gandhi**, Swaraj Batra†, Rachna Sharma‡

ABSTRACT Aim: To assess the efficacy, safety and acceptability of mifepristone followed by vaginal misoprostol for medical termination of pregnancy (MTP) between 13-20 weeks of gestation. Material and methods: Forty women who fulfilled the criteria of MTP Act of India, were given 200 mg oral mifepristone, followed after 36-48 hours by 800 µg vaginal misoprostol and subsequently 400 µg vaginal misoprostol 3-hourly (maximum 2,400 µg). Success was taken as complete expulsion of fetus and placenta within 15 hours of first dose of misoprostol. Results: Success rate of complete abortion was 92.5%, which increased to 95% at 24 hours and successful expulsion of fetus was seen in 100% cases within 24 hours of first dose of misoprostol. Median induction-abortion interval was six hours. There were no major side effects. Nulliparous women took significantly longer time to abortion and required more analgesia than multiparous women. Conclusion: Mifepristone followed by vaginal misoprostol is a safe, effective and acceptable method for second trimester termination of pregnancy. Key words: Mifepristone, misoprostol, second trimester termination of pregnancy

id-trimester (13-20 weeks) abortion constitutes 10-15% of all induced abortions.1 There has been a gradual increase in second trimester termination of pregnancies because of the widespread introduction of prenatal screening programs, which detect serious fetal anomalies. The Medical Termination of Pregnancy (MTP) Act of India (1971) provides for the termination of certain pregnancies upto 20 weeks of gestation, by a registered medical practitioner, provided all the prerequisites are fulfilled. The medical methods for mid-trimester abortion, especially prostaglandins, have become increasingly popular as they avoid the risks of surgical methods. When prostaglandin E1 analogs gemeprost or misoprostol are used alone for second trimester MTP, the mean induction-abortion interval (IAI) can be as long as 12-16 hours.2,3 Pretreatment with mifepristone, an antiprogesterone,

prior to prostaglandin administration, reduces the IAI, the total dose of prostaglandins required as well as the analgesia requirement.3,4 The combination of mifepristone followed by misoprostol has been found safe and effective for first trimester termination of pregnancy. In the last decade, this combination has been studied for second trimester MTP.3-8 Among the various routes of misoprostol, vaginal route has better systemic bioavailability, is more sustained and has lower side effects than oral route.9 The ideal dose schedule of this combination is still being investigated. Aim To assess the efficacy, acceptability and side effects of this combination of mifepristone and vaginal misoprostol for MTPs between 13-20 weeks of gestation. Material and Methods

*Ex-Resident **Director Professor † Director Professor and Ex-Head ‡ Senior Specialist Dept. of Obstetrics and Gynecology Maulana Azad Medical College, New Delhi Address for correspondence Dr Neha Agarwal F-56, Professor Colony, Kamla Nagar, Agra, Uttar Pradesh E-mail: its_my_ishtyle@yahoo.com

Forty women presenting to the Family Planning Clinic, seeking MTP between 13-20 weeks of gestation and fulfilling the prerequisites specified in the MTP Act were included in this prospective clinical study after proper informed consent. The exclusion criteria were anemia (hemoglobin <9 g/dl), multiple pregnancy, previous cesarean section or previous surgery on uterus or cervix, history of coagulation disorder, anticoagulant and Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CLINICAL STUDY corticosteroid therapy, history of thromboembolism, cardiac disease or severe hypertension and allergy to misoprostol or mifepristone. Ethical approval was taken from the Institutional Ethical Committee.

nonparametric Mann-Whitney U-test. The Chi-square and Fisher’s exact test were used as appropriate for independent nominal data. Statistical significance was taken at p ≤ 0.05.

All women were given 200 mg mifepristone, to be swallowed under supervision. They were allowed to go home and were admitted to the hospital after 36-48 hours, when 800 µg misoprostol was inserted in the posterior vaginal fornix.

Observations and Results

This was followed by 3-hourly vaginal insertion of 400 µg misoprostol till the woman aborted or for a maximum of four doses of 400 µg (total 5). Maximum misoprostol inserted if required was 2,400 µg. The women were given sterile vulval pads weighed previously and were told to save all pads and any expelled products. The time of onset of expulsion of fetus and placenta was noted. Any side effects observed were recorded. After abortion, the placenta was checked for its completeness. Blood loss was estimated by weighing the soaked pads and subtracting the original weight of the pads used, plus the estimated additional blood loss during abortion. The hemoglobin and hematocrit levels were repeated the next day. All the women aborted within 24 hours. Follow-up was done after 15 days when duration of bleeding, any side effects observed and acceptability of the regimen were noted. The primary outcome measures were: zz Success rate, defined as complete abortion occurring with a maximum of total 5 doses of misoprostol, i.e., within 15 hours of first dose. zz Induction-abortion interval (IAI), calculated from the time of administration of first dose of misoprostol to complete expulsion of fetus and placenta. Secondary outcome measures were amount of blood loss, duration of bleeding, fall in hemoglobin and hematocrit levels, side effects and acceptability of this regimen. Statistical Analysis

All continuous efficacy parameters were presented as mean ± standard deviation and median (range) and were analyzed using the independent t-test or Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

The mean age of women included in the study was 29.9 years and the mean parity was 3.2. The mean period of gestation was 15.9 weeks. The women were distributed in two equal groups according to their gestational age; Group A with gestational age 13-16 weeks and Group B with gestational age 16.1-20 weeks. Both these groups were similar with respect to baseline characteristics (Table 1). Success rate (complete abortion within 15 hours of first dose of misoprostol) of the study was 92.5%. In Group A, success rate was 95%. One woman was considered as failure because she required surgical evacuation of retained placental bits, although the fetus aborted within 15 hours. In Group B, success rate was 90%. Two cases were considered as failure because they aborted later at 18.5 and 19.8 hours. One of these also needed surgical evacuation. The total success rate for complete abortion increased to 95% at 24 hours and successful expulsion of fetus was in 100% cases within 24 hours of first dose of misoprostol (Table 2). The median IAI of the study was 6.0 hours. Most women (67.5%) required 2 or 3 doses (1,200 or 1,600 µg) of misoprostol. One woman aborted with only mifepristone, prior to administration of misoprostol. The mean blood loss was 186.5 ml and none of the women required blood transfusion. The mean fall in hemoglobin and hematocrit was 0.72 gm% and 2.7%. The mean duration of bleeding was 8.6 days. There was no statistically significant effect of gestational age on any outcome (Table 1). The regimen was acceptable to all the women in the study. Effect of Nulliparity

The study included two nulliparous women at 18 weeks and 19.4 weeks gestation with ultrasound diagnosis of congenital anomalies in the fetus. They took significantly longer time to abortion, with a median IAI of 15.17 hours compared to 5.75 hours by multiparous women (p = 0.030) and required significantly higher number of doses of misoprostol 19

CLINICAL STUDY Table 1. Outcome Measures in Relation to Period of Gestation Total (n = 40)

Group A (13-16 weeks) (n = 20)

Group B (16.1-20 weeks) (n = 20)

P value between Group A and B

Mean age (years)

29.9

30.4

29.5

0.546

Mean parity

3.2

3.4

3.1

0.613

92.5%

95%

90%

0.548

Success rate (complete abortion in 15 hours) Surgical intervention Median IAI Mean no. of doses of misoprostol Blood loss

6.0 hours

5.0 hours

6.9 hours

0.106

2.5

2.1

2.9

0.054

186.5 ml

199.8 ml

173.3 ml

0.198

Fall in hemogram (gm%)

0.72

0.74

0.71

0.989

Fall in hematocrit (%)

2.7

2.9

2.5

0.473

Duration of bleeding (days)

8.6

7.9

9.3

0.099

Table 2. Cumulative Rate of Complete Abortion and Fetal Expulsion According to IAI IAI (hours)

Complete abortion

Fetal expulsion

Cumulative (%)

No. (n = 40)

Cumulative (%)

0-3

12.5

3-6

57.5

6-9

77.5

9-12

92.5

12-15

92.5

2.5

15-24

2.5

100

Total

100

18.72

No. (n = 38)

Multiparous women (n = 38) 15.17

15.75

Nulliparous women (n = 2)

14 12 10 5.75

Mean gestational age (weeks)

Mean no. of doses of misoprostol

Median of IAI (h)

Success rate

Surgical evacuation

100%

31.50%

5.30%

94.70%

2.38

50%

4.5

Analgesia requirement

Figure 1. Outcome in relation to parity.

Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CLINICAL STUDY (4.50 vs 2.38; p = 0.004) as well as more analgesia. None of the two nulliparous women required surgical evacuation, which is a big advantage because chances of infection are minimized if there is no surgical intervention (Fig. 1). Side Effects

There were no major side effects. Pain was an unavoidable component of natural abortion process. Most women had mild pain not requiring any analgesia. About 25% women had moderate pain, which settled with oral analgesic and 10% had severe pain requiring injectable analgesia. Fever (25%), headache (7.5%) and vomiting (5%) were the other side effects seen, but they were temporary and subsided as the effect of misoprostol weaned off. Discussion Several dose schedules of the combination of mifepristone and misoprostol have been studied for second trimester termination of pregnancy. The present study was compared with other studies using a similar protocol of 200 mg mifepristone with minor variations in routes of misoprostol. Gupta et al5 gave the second dose of misoprostol vaginally or sublingually after 4-6 hours of first dose. The success rate was 91.42% at 15 hours, which is very close to our success rate of 92.5%. Ashok et al3 used vaginal route for the first dose and oral for subsequent doses of misoprostol. Success rate, taken as expulsion of fetus with or without placenta within 15 hours, was 97.1%, which remained the same at 24 hours. Taking the same criteria, our success rate would be 95% at 15 hours and 100% at 24 hours. Bartley et al8 used similar routes of misoprostol as Ashok et al.3 About 94% women aborted the fetus within 24 hours versus 100% in the present study. Thus, there is a slightly higher success rate at 24 hours if all the doses of misoprostol are given vaginally. Hamoda et al6 and Goh et al7 used the same protocol as the present study and got a similar fetus expulsion rate of 100% and 97.9% at 24 hours, respectively. In the present study on increasing the period of observation to 24 hours, complete expulsion is increased from 92.5 to 95% and expulsion of fetus with or without placenta is seen in 100% women. Thus, Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

if more observation time is given with this five dose (total 2,400 Âľg) schedule, the success rate increases. The IAI in these studies ranges from 5.4 to 6.7 hours, which is comparable to six hours in the present study.3,5-8 The mean number of doses of misoprostol required for complete abortion (2.49) was also comparable.3,6 In the present study, one woman (2.5%) aborted completely with only mifepristone, prior to administration of misoprostol. She was multiparous with a gestational age of 13 weeks one day. Other studies have reported that 0.2-0.5% women abortion with mifepristone alone.3,5,6 Similar to the present study, Ashok et al3 and Goh et al7 also found that nulliparous women had a longer IAI than multiparous women, requiring higher number of doses of misoprostol as well as higher analgesia requirement. There is a slightly lower incidence of surgical intervention in nulliparous women possibly due to more efficient establishment of pregnancy in multiparous women. This further emphasizes the advantage of this medical method in nulliparous women. Conclusion It is concluded that for MTP between 13-20 weeks gestation, the drug protocol of mifepristone and misoprostol used in the present study is highly effective and has 92.5% complete abortion rate at 15 hours and 95% complete abortion rate at 24 hours. It is an acceptable and safe method and has only few minor side effects. There are no major side effects and blood loss is within acceptable limits. Surgical intervention with its risk of subsequent infection is avoided in 95% women, which is of special importance in nulliparous women. References 1. Lalitkumar S, Bygdeman M, Gemzell-Danielsson K. Midtrimester induced abortion: a review. Hum Reprod Update 2007;13(1):37-52. 2. Hammond C. Recent advances in second-trimester abortion: an evidence-based review. Am J Obstet Gynecol 2009;200(4):347-56. 3. Ashok PW, Templeton A, Wagaarachchi PT, Flett GM. Midtrimester medical termination of pregnancy: a review of 1002 consecutive cases. Contraception 2004;69(1):51-8.

CLINICAL STUDY 4. Nagaria T, Sirmor N. Misoprostol vs mifepristone and misoprostol in second trimester termination of pregnancy. J Obstet Gynaecol India 2011;61(6):659-62.

7. Goh SE, Thong KJ. Induction of second trimester abortion (12-20 weeks) with mifepristone and misoprostol: a review of 386 consecutive cases. Contraception 2006;73(5):516-9.

5. Gupta N, Mittal S. Is mifepristone needed for second trimester termination of pregnancy? J Turkish-German Gynecol Assoc 2007;8(1):58-62.

8. Bartley J, Baird DT. A randomised study of misoprostol and gemeprost in combination with mifepristone for induction of abortion in the second trimester of pregnancy. BJOG 2002;109(11):1290-4.

6. Hamoda H, Ashok PW, Flett GM, Templeton A. A randomized trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion at 13-20 weeks gestation. Hum Reprod 2005;20(8):2348-54.

9. Tang OS, Schweer H, Seyberth HW, Lee SW, Ho PC. Pharmacokinetics of different routes of administration of misoprostol. Hum Reprod 2002;17(2):332-6.

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Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CLINICAL STUDY

Systolic and Diastolic Ratio and Rate Pressure Product in Anemia K Singh

ABSTRACT Anemia, a common clinical entity is associated with hyperdynamic circulation and may be involved in etiopathology of heart failure. So, the current study was carried out in 30 patients in the age group 20-40 years with hemoglobin level < 6 g/dl and of at least 3-month duration of anemia (using WHO definition) and compared with 30 age- and sex-matched healthy subjects. Duration of systole and diastole was estimated by recording of electrocardiogram, apex-cardiogram and phonocardiogram on polyrite with the paper speed of 50 mm/sec. Duration of cardiac cycle was reduced (18.22%) and heart rate was increased (p < 0.001) in anemia compared to controls. On comparison of duration of systole and diastole, there was more decrement in diastole (26.76%, p < 0.001) compared to systole (6.45%, p < 0.01) in anemia versus healthy subjects. Similarly, when fraction occupied by systole and diastole in cardiac cycle were compared, the systolic fraction was increased, diastolic fraction in cardiac cycle was reduced and systole/diastole ratio was increased (p < 0.001) in anemics compared to controls. Rate pressure product and double product were elevated (p < 0.001) in anemia versus controls, imposing mechanical load on heart. So, it is concluded that patients of severe anemia are at the brink of heart failure and should be treated promptly. Key words: Systole, diastole, cardiac cycle, anemia

ystole and diastole are the fundamental periods of cardiac cycle. Intervals of cardiac cycle as measured by echocardiography, apex-cardiography, i.e., isovolumic contraction time, isovolumic relaxation time are used to assess ventricular function.1 Recently, importance of duration of systole and diastole is emphasized and it is advocated that they can be used to assess cardiac functions as prognosis of patients suffering from diastolic heart failure (DHF) is as ominous as prognosis of patients suffering from systolic heart failure (SHF).2 Anemia, a frequently encountered clinical entity, said to be a risk factor for functional and cognitive disease3 imposes mechanical load on heart and may be involved in pathogenesis and progression of heart failure,4 chronic angina5 and acute coronary syndrome.6 Moreover, it is associated with ventricular hypertrophy, ischemia

Professor Dept. of Physiology Pt. BD Sharma, Postgraduate Institute of Medical Sciences (PGIMS), University of Health Sciences Rohtak (UHSR), Rohtak, Haryana Address for correspondence Dr K Singh 6J-11, Medical Campus, Rohtak - 124 001, Haryana E-mail: dr_rb_singh@rediffmail.com

Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

and increased heart rate.6 So, the current study was planned to evaluate the duration of cardiac cycle, ratio of systole/diastole (S/D ratio), rate pressure product (RPP - since, it is an easy measurable index of myocardial oxygen consumption and load on heart)7 and double product (DoP) in patients of anemia. Methods The study was carried out in 30 patients of anemia (hemoglobin level was >6 g/dl for at least 3-month duration)8 using World Health Organization (WHO) definition of anemia - hemoglobin <13 g/dl for men and <12 g/dl in women9 in the age group of 20-40 years (mean age 32.65 ± 1.62) with body mass index (BMI) 22.9 ± 0.33 without clinical evidence of cardiac decompensation, and 30 age(mean 31.49 ± 3.34 years) and sex-matched healthy subjects (hemoglobin level 11-14.02 g/dl) having BMI 22.2 ± 0.36. Electrocardiogram (ECG), apexcardiogram (ACG) and phonocardiogram (PCG) were recorded with the paper speed of 50 mm/sec on polyrite (INCO). Systole was measured from onset of ventricular depolarization to first high frequency vibration of aortic sound. Diastole was measured from beginning of first high frequency of second heart sound to the beginning of sudden upstroke of ACG (Fig. 1). 25

CLINICAL STUDY Duration of cardiac cycle, proportion of cardiac cycle occupied by systole and diastole, and S/D ratio were evaluated. Heart rate (HR) was assessed from ECG (lead II). Blood pressure (BP) was recorded manually by using sphygmomanometer. RPP was calculated as SP × HR × 10-2, where SP is systolic pressure and value obtained was expressed as mmHg beats/min.7 Similarly, DoP was calculated as MP × HR, where MP is mean pressure and it was expressed in mmHg beats/min.10 Statistical analysis was done by unpaired t-test. Values were expressed as mean ± SD. A p value of <0.05 was accepted as significant. Result Duration of cardiac cycle was 884.76 ± 87.54 msec. in normal healthy controls at the HR of 75.4 ± 12.5 beats/min in contrast to 723.5 ± 55.02 msec at the HR of 92.08 ± 18.19 beats/min in anemia. This reduction in duration of cardiac cycle (18.22%) was significant (p < 0.001). Duration of systole and diastole was 372.06 ± 29.41 versus 512.70 ± 110.14 msec, respectively in controls compared to duration of systole and diastole 348.04 ± 39.46 versus 375.46 ± 107.40 msec, respectively in anemic patients. On comparison of systole and diastole, there was more decrement in diastole (26.76%, p < 0.001) compared to systole (6.45%, p < 0.001) in anemic patients versus healthy controls (Fig. 2). In healthy subjects systole and diastole constitute 42.05% and 57.94% fraction of cardiac cycle, respectively. While in anemia systole and diastole constitute 48.1% and 51.89% fraction of cardiac cycle, respectively, indicating fraction of systole was increased and diastole was reduced in anemia (Table 1). S/D ratio was lengthened (p < 0.001) in anemia, i.e., 1.04 ± 0.23 versus 0.71 ± 0.06 in controls (Fig. 2). RPP and DoP were significantly (p < 0.001) elevated in anemia compared to controls (Table 1). Discussion Anemia is said to be involved in the pathogenesis of heart failure (HF).4 It is hypothesized that relative duration of systole and diastole are altered and S/D ratio increases in HF.1 Duration of cardiac cycle in present study is about 0.88 second at normal HR in controls, which is in agreement with other authors.11 26

Electrocardiogram

Apex-cardiogram

Phonocardiogram Systole Diastole

Figure 1. Simultaneous recording of ECG, ACG and PCG in controls.

Electrocardiogram

Apex-cardiogram

Phonocardiogram

Figure 2. Simultaneous recording of ECG, ACG and PCG in anemia.

But in anemia, duration of cardiac cycle is shortened, which may be explained by hyperkinetic circulation. Reduction in duration of diastole is more (26%) than systole (6.4%), may be due to tachycardia. Tachycardia adversely affects the diastolic function by several mechanisms, as it diminishes the left ventricular filling, coronary perfusion time, increases myocardial oxygen demand, raises myocardial oxygen consumption and causes incomplete relaxation.12 It has to be noted that although duration of systole as such is reduced, proportion of cardiac cycle occupied by systole is lengthened from 42.05% in controls to 48% in anemics. In contrast proportion of cardiac cycle occupied by diastole is more reduced in anemia, from 57.9% to 51% in controls and anemics, respectively. All these changes result in enhanced S/D ratio in anemia in current study, which is consistent with the findings described by Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CLINICAL STUDY Table 1. Comparison of Parameters in Control and in Anemia (Mean ± SD) Parameters

Heart rate (beat/ min)

Systolic Diastolic BP BP (mmHg) (mmHg)

Cardiac cycle length (msec)

Duration of systole (msec)

Duration of diastole (msec)

Proportion of systole and diastole (%) in cardiac cycle

S/D ratio

RPP mmHg, beat/min

DoP mmHg beat/min

Controls

75.4 ± 12.5

120.80 ± 8.90

71.10 ± 9.20

884.76 ± 87.54

372.06 ± 29.41

512.70 ± 110.14

42.05 and 57.94

0.71 ± 0.06

91.06 ± 12.32

7609.56 ± 190.5

Anemia

92.08** ± 18.19

111.04** ± 10.21

70.80 ± 9.27

723.5** ± 55.02

348.04* ± 39.46

375.46** ± 107.40

48.1 and 51.89

1.04** ± 0.23

102.24** ± 15.21

9029.37** ± 260.1

Difference or p value

< 0.001

P< 0.001

18.22%

6.45%

26.76%

<0.001

0.001

< 0.001

p value * = < 0.01, **= < 0.001. BP = Blood pressure; S/D ratio = Systolic/Diastolic ratio; RPP = Rate pressure product; DoP = Double product.

other authors in patients of HF. Myocardial perfusion occurs primarily in diastole. Myocardial blood flow in patients of left ventricular hypertrophy (LVH) (anemia can be associated with LVH) may depend upon diastolic perfusion time and perfusion pressure. Myocardial remodeling induced by renin-angiotensin system activated due to decreased renal perfusion and increased catecholamine secretion in anemia predisposes the ischemic damage.13 Reduced oxygen carrying capacity of blood, increase in circulation time and HR with reduction in diastolic time may further complicate coronary perfusion and still worsen the cardiac function.1 But clinical signs and symptoms pointing to HF were not evident in these patients.14 They were not taking treatment of it inspite of enhanced RPP and DoP in anemia indicating increase in O2 consumption and load on the heart. Enhanced O2 consumption of cardiac muscles in severe anemia is demonstrated by other authors also.15 But it is difficult to explain the reason for absence of features of HF, may be at this HR filling of LV is adequate enough to maintain cardiac output.11 As it is also stated that DHF is referred to as HF with normal left ventricular ejection fraction (LVEF), i.e. HFNLVEF.12 Moreover, onsets of symptoms also depend on the rapidity with which the anemia develops as well as physical activity of patient. So, our findings as lengthened systole, enhanced systolic and diastolic ratio and reduction in duration of diastole pointed out that patients of anemia are at the brink of HF. So, while treating the patient of HF and coronary artery disease, we should also have a look for anemia as treatment of systole and diastole failure is different. Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

References 1. Friedberg MK, Silverman NH. Cardiac ventricular diastolic and systolic duration in children with heart failure secondary to idiopathic dilated cardiomyopathy. Am J Cardiol 2006;97(1):101-5. 2. Aurigemma GP. Diastolic heart failure: a common and lethal condition by any name. N Engl J Med 2006;355(3):308-10. 3. Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med 2006;119(4):327-34. 4. de Silva R, Rigby AS, Witte KK, Nikitin NP, Tin L, Goode K, et al. Anemia, renal dysfunction, and their interaction in patients with chronic heart failure. Am J Cardiol 2006;98(3):391-8. 5. Sharma S, Gage BF, Deych E, Rich MW. Anemia: an independent predictor of death and hospitalizations among elderly patients with atrial fibrillation. Am Heart J 2009;157(6):1057-63. 6. Meneveau N, Schiele F, Seronde MF, Descotes-Genon V, Oettinger J, Chopard R, et al; Reseau de Cardiologie de Franche Comte. Anemia for risk assessment of patients with acute coronary syndromes. Am J Cardiol 2009;103(4):442-7. 7. Gobel FL, Norstrom LA, Nelson RR, Jorgensen CR, Wang Y. The rate-pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation 1978;57(3): 549-56. 8. Agarwal V, Sachdev A, Lehl S, Basu S. Unusual haematological alterations in rheumatoid arthritis. J Postgrad Med 2004;50(1):60-1. 9. Felker GM, Gattis WA, Leimberger JD, Adams KF, Cuffe MS, Gheorghiade M, et al. Usefulness of anemia as a predictor of death and rehospitalization in patients with decompensated heart failure. Am J Cardiol 2003;92(5): 625-8. Cont’d on page 32...

CLINICAL STUDY

Effect of Rosiglitazone on Spontaneous and Clomiphene Citrateinduced Ovulation in Polycystic Ovary Syndrome Sandhya Mittal*, Anupama Goel*, Ajay Mittal**, Bal K Tanejaâ&#x20AC; , Praveen Gupta**

ABSTRACT Objective: The aim of this study was to evaluate the effect of rosiglitazone on spontaneous and clomiphene-induced cycle in polycystic ovary syndrome (PCOS) women. Methods: A randomized controlled trial was carried out on 30 women of PCOS divided into two groups of 15 each. Group I women received rosiglitazone and Group II women received both rosiglitazone and clomiphene citrate for three months. Main outcome measures: Primary outcome measures were improvement in body mass index (BMI), Hirsutism scoring and ovulation rate. Secondary outcome measures included conception rate and changes in hormonal profile. Results: Overall 20 of 30 (66.67%) women ovulated successfully. Ovulation occurred in nine of 15 women (60.00%) in Group I as compared to 11 of 15 (73.33%) in Group II (p value 0.6). Out of 30, total 53.33% became pregnant, 40% from Group I and 66.67% from Group II (p value 0.14). No significant improvement in follicle-stimulating hormone (FSH) and Hirsutism score was observed. Mean BMI of patient improved significantly and fasting insulin declined but not statistically significant. The hormonal profile showed improvement in both the groups, with decline in luteinizing hormone (LH), LH/FSH ratio and testosterone. Conclusion: Thus rosiglitazone, a wonderful insulin sensitizer, plays a significant role alone as well as in adjunct with clomiphene citrate in PCOS women. Key words: Polycystic ovary syndrome, anovulatory infertility, rosiglitazone, clomiphene citrate, insulin resistance

olycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting approximately 5-10% of women of reproductive age1 and is the most common cause of female anovulatory infertility.2 PCOS is a heterogeneous disorder characterized by any two of the following three features: zz

Oligo-ovulation or anovulation

Clinical or biochemical signs of hyperandrogenism

Polycystic ovaries (either 12 or more follicles measuring 2-9 mm in diameter or an ovarian volume of <10 cm3).3

These women have hyperandrogenism, and inappropriate gonadotropin secretion and approxi-

*Assistant Professor Dept. of Obstetrics and Gynecology **Associate Professor Dept. of Medicine â&#x20AC; Professor Dept. of Obstetrics and Gynecology

MMIMSR, Mullana (Ambala), Haryana Address for correspondence Dr Sandhya Mittal 344/5, Urban Estate, Kurukshetra, Haryana - 136 118 E-mail: sandhya81969@yahoo.com

mately 44% of them are obese and 60% display insulin resistance.4 Insulin resistance is an intrinsic, virtually universal feature of PCOS and is independent of obesity as evidence by the presence of insulin resistance even in lean women with PCOS.4 Correction of hyperinsulinemia enhances spontaneous ovulation or alternatively the responsiveness to ovulation inducing agents such as clomiphene citrate. Hyperinsulinemia is due to point mutation of insulin receptors gene5 and is known to be associated with increased cardiovascular risk and development of diabetes mellitus.6 Because of the link between insulin resistance and PCOS, metformin either alone or in combination with clomiphene citrate is now the most widely used insulin sensitizer.7-9 On the other hand rosiglitazone, another insulin sensitizer, a member of the thiazolidinedione family has been shown to be effective in type 2 diabetics and has been in trial for PCOS.10 No significant change in lipid profile including total cholesterol, low-density lipoprotein (LDL) high-density lipoprotein (HDL) and triglycerides was observed after treatment with rosiglitazone.10-12 Kaul and Diamond on their metaanalysis on 42 clinical trials found that the data showing Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CLINICAL STUDY the increased risk for myocardial infarction and death from cardiovascular disease for diabetic patients taking rosiglitazone are inconclusive.13 Further in patients with nonalcoholic steatohepatitis, rosiglitazone improves steatosis and transaminase level.14 Our study was to evaluate the effect of rosiglitazone on ovulation and conception in spontaneous as well as clomiphene-induced cycles. Methods A randomized controlled trial was conducted on 30 subjects who received the diagnosis of PCOS-based on clinical features and laboratory findings. Written informed consent was obtained from all the women and the Departmental Ethical Committee approved the study. All the subjects were of reproductive age and desired to be pregnant. By systemic random sampling subjects were randomly put into two treatment groups. Subjects in Group I (n = 15) received rosiglitazone 4 mg b.i.d. from Day 1 of cycle for three months continuously. Group II (n = 15) women received rosiglitazone 4 mg b.i.d. from Day 1 of cycle and clomiphene citrate 50 mg o.d. added on Days 2-6 of cycle for a maximum of three months. The patients with secondary amenorrhea were given progesterone for withdrawal bleeding followed by the administration of the drugs as per our protocol in both the groups. Inclusion Criteria

All subjects have confirmed PCOS either on USG or hormonal assay and were in good health with no major medical illness. Other causes of infertility including local, uterine or adnexal were ruled out by performing per speculum examination, bimanual vaginal examination and hysterosalpingography. Male factor of infertility was ruled out by doing husband semen analysis, performed within one year of participation in the study and sperm concentration at least 20 millions/ml was required.15 Exclusion Criteria

Subjects were excluded from the study if they had hyperprolactinemia, congenital adrenal hyperplasia, thyroid diseases or other cause of amenorrhea including Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

premature ovarian failure. Clinically suspected Cushing syndrome and androgen secreting neoplasm were also excluded from the study. Fasting blood sugar and insulin level were done by using enzymatic methods and serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) by immunoradiometric assay on 2nd or 3rd day of first menstrual cycle.16 Serum testosterone was estimated by radioimmunoassay.17 Body mass index (BMI) was calculated by BMI equation and Hirsutism scoring was done by Ferriman-Gallwey scale.18,19 Assessment of the ovulatory rate was done by transvaginal sonography from the 10th day of the menstrual cycle. All the tests were repeated in last treatment cycle to find out the effect of treatment. Primary outcome measures were improvement in clinical picture of PCOS including changes in BMI and Hirsutism scoring as well as ovulation rate. Secondary outcome measures included conception rate and changes in hormonal profile like serum LH, LH/FSH ratio, fasting blood sugar and fasting insulin level as well as serum testosterone. Data for all subjects before and after treatment was statistically analyzed using paired students t-test and Chi-square test and Z-test was used for comparison of outcome. The level of statistical significance was set at p < 0.05. P value ∞ denotes highly significant. Results All the women were in reproductive age group between 20-35 years of age. Out of 30, 20 women had primary and 10 had secondary infertility and were equally distributed in both the groups. Out of five patients of secondary infertility in Group I only one patient was para 1 and rest four had previous abortions. In Group II, two patients were primipara and rest three had previous abortions (Table 1). The overall compliance was good. We found a significant effect of rosiglitazone on clinical features. Six patients who had normal Table 1. Shows Age and History of Abortions in the Two Groups Parameter

Group I (n = 15)

Group II (n = 15)

P value

Age

22.53 ± 8.14

24.73 ± 3.419

0.32

Previous abortions

4 (26.67%)

3 (0.20%)

0.66

CLINICAL STUDY Table 2. Effect of Rosiglitazone on Clinical Features and Laboratory Parameters Parameters

Before treatment (Mean ± SD range)

After treatment (Mean ± SD range)

Z value

P value

Menstrual pattern zz

Oligomenorrhea

12 (40%)

10 (34.48%)

0.66

Amenorrhea

9 (30%)

0 (0%)

0.001

Polymenorrhea

3 (10%)

0 (0%)

0.08

Normal

6 (20%)

20 (66.66%)

0.0006

Acne

14 (46.67%)

8 (27.58%)

0.12

BMI

25.9 ± 5.3

23.5 ± 4.9

5.15

∞

Hirsutism score

15.9 ± 6.3

14.1 ± 5.1

1.27

0.1020

LH (mIU/ml)

13.67 ± 6.2

9.4 ± 4.3

7.2

∞

FSH (mIU/ml)

7.15 ± 8.9

9.9 ± 12.2

0.20

0.4207

LH/FSH ratio (mIU/ml)

2.0 ± 0.9

1.2 ± 0.65

5.7

∞

Testosterone (ng/dl)

0.78 ± 0.2

0.66 ± 0.16

1.85

0.0322

FBS (mg/dl)

86.0 ± 10.0

85.16 ± 8.54

0.41

0.3409

Fasting insulin level (mg/dl)

8.85 ± 6.8

7.84 ± 5.0

0.02

0.4920

Table 3. Ovulation Rate and Conception Rate Group I (n = 15)

Group II (n = 15)

Ovulation rate

Conception rate

Ovulation rate

Conception rate

First cycle

2 (13.33%)

5 (33.33%)

4 (26.67%)

Second cycle

3 (20.00%)

2 (13.33%)

4 (26.67%)

Third cycle

4 (26.67%)

2 (13.33%)

Total

9 (60.00%)

6 (40.00%)

11 (73.33%)

10 (66.67%)

P value of ovulation was 0.6 and of pregnancy was 0.14.

menstruation before treatment remained unchanged after treatment. Out of 12 patients who had oligomenorrhea, seven resumed normal cycles with rosiglitazone. Nine patients who presented with amenorrhea, five developed oligomenorrhea and four resumed normal menstruation after treatment. Among the three patients who presented with polymenorrhea, all resumed normal cycles. No significant improvement in acne was observed (Table 2). Mean BMI of patient improved highly significantly from 25.9 ± 5.3 to 23.5 ± 4.9 (p value ∞) after treatment. No significant change in Hirsutism score was observed. It was 15.9 ± 6.3 before and 14.1 ± 5.1 after treatment with rosiglitazone (Table 2). Overall 20 of 30 (66.67%) women ovulated successfully. Ovulation occurred in nine of 15 women (60.00%) in Group I as compared to 11 of 15 (73.33%) in Group II (p value 0.6). Out of 30, 16 women (53.33%) became 30

pregnant. Pregnancy rate was 40% and 66.67% in Group I and II, respectively (p value 0.14) (Table 3). Among the six pregnancies in Group I, one landed in missed abortion. Rest five had successful pregnancy outcome, one delivered by cesarean section and four vaginally. Out of 10 conceptions in Group II, two had missed abortion, one had twin pregnancy who was delivered by cesarean section and rest seven delivered at term vaginally. The hormonal profile showed improvement in both the groups after treatment with rosiglitazone with decline in LH, LH/FSH ratio, which was statistically highly significant. There was decrease in LH hormone from 13.67 ± 6.2 to 9.4 ± 4.3 (p value ∞) and LH/FSH ratio from 2.0 ± 0.9 to 1.2 ± 0.65 (p value ∞). No significant difference in FSH level was noted. Level of serum testosterone had decreased after treatment but difference was not statistically significant. Fasting insulin level improved from 8.8 5 ± 6.8 to 7.84 ± 5.1 (p value 0.4920), while Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CLINICAL STUDY fasting blood sugar (FBS) did not show any significant change (Table 2). Discussion PCOS is a very common disorder and is the most common cause of chronic anovulation and menstrual irregularity in infertile women. In current infertility practice, ovarian surgery for PCOS is not frequently recommended because of the risk of scar tissue formation that can profoundly impair tubal function thereby creating a new, very serious fertility problem that the woman did not previously has. Clomiphene is the traditional first-choice treatment for induction of ovulation in PCOS women. Though it leads to ovulation induction in 90% cases, the number of pregnancies achieved is much lower than expected.10 Combining clomiphene with one of the wonderful new insulin sensitizing drugs, metformin or rosiglitazone may convert these patients to a responsive one. The ovulation rate in our study was 60% in women who received rosiglitazone alone and 73.33% with combination (p value 0.6), while Ghazeeri et al11 had found a comparatively lower ovulation rate i.e., 33% and 77%, respectively. These findings support the fact that hyperinsulinemia impedes ovulation and decreasing insulin resistance facilitates ovulation spontaneously as well as by induction with clomiphene.10,20 There is a significant difference in conception rate in both the groups (40% in Group I vs 66.67% in Group II) with overall rate being 53.33%. Our results are higher than the results reported by Ghalaut et al10 and Ghazeeri et al.11 Regularity in the menstrual cycle was observed after treatment with rosiglitazone. Another randomized controlled trial21 studied the use of rosiglitazone in combination with clomiphene citrate and reported improvement in menstrual regularity (92% with combination therapy vs 68% with rosiglitazone). Similar results were also reported by other authors.10,12 Rosiglitazone therapy resulted in highly significant improvement in weight and BMI (p value ∞), while other authors4,11 reported no improvement in weight and BMI after treatment with rosiglitazone. No significant change in Hirsutism score was observed in our study, which was comparable to another study.10 Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

We had observed a highly significant decrease in LH hormone and LH/FSH ratio in both groups (p value ∞) with no change in FSH levels after treatment with rosiglitazone. Similar results were reported by other authors.10,11 While Sepilian et al4 did not find any significant change in LH levels and Shobokshi et al21 had found a significant decrease in FSH level. The level of serum testosterone had decreased in both the groups after treatment but statistically nonsignificant with p value 0.032. Our results were similar to another study.21 Serum testosterone level decreased after treatment due to raised level of sex hormone-binding globulin (SHBG).12 While no significant decrease was noted in level of serum testosterone by Ghalaut10 and Ghazeeri et al.11 In present study, fasting insulin declined from 8.85 ± 6.8 to 7.84 ± 5.0 after rosiglitazone (p value 0.492). Belli et al12 has also reported similar results. Unlike other study,4 we did not find any significant change in FBS level after treatment with rosiglitazone. Our findings were consistent with other studies.10,11,17,20 Conclusion Combing clomiphene with one of the wonderful new insulin sensitizing drug rosiglitazone may convert the resistant women to a responsive one. Rosiglitazone is well-tolerated with minimum side effects but should be discontinued when pregnancy occurs due to its teratogenicity. References 1. Moll E, Korevaar JC, Bossuyt PM, van der Veen F. Does adding metformin to clomifene citrate lead to higher pregnancy rates in a subset of women with polycystic ovary syndrome? Hum Reprod 2008;23(8):1830-4. 2. Barbieri RL. Clomiphene versus metformin for ovulation induction in polycystic ovary syndrome: the winner is .... J Clin Endocrinol Metab 2007;92(9):3399-401. 3. Shokeir T, El-Kannishy G. Rosiglitazone as treatment for clomiphene citrate-resistant polycystic ovary syndrome: factors associated with clinical response. J Womens Health (Larchmt) 2008;17(9):1445-52. 4. Sepilian V, Nagamani M. Effects of rosiglitazone in obese women with polycystic ovary syndrome and severe insulin resistance. J Clin Endocrinol Metab 2005;90(1):60-5. 5. Hershlag A, Peterson CM. Endocrine disorders. In: Novak’s Gynaecology. 13th edition, Rebecca DR, Paula AH, Eli YA (Eds.), Williams and Lippincott Wilkins: Philadelphia 2002:p876-9.

CASE REPORT CLINICAL STUDY 6. Lord JM, Flight IHK, Norman RJ. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome. Cochrane Database Syst Rev 2003;(3):CD003053.

Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology 2008;135(1):100-10.

7. Nestler JE. Should patients with polycystic ovarian syndrome be treated with metformin?: an enthusiastic endorsement. Hum Reprod 2002;17(8):1950-3.

15. Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, et al; Cooperative Multicenter Reproductive Medicine Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007;356(6):551-66.

8. Glueck CJ, Papanna R, Wang P, Goldenberg N, SieveSmith L. Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. Metabolism 2003;52(7):908-15. 9. Practice Committee of the American Society for Reproductive Medicine. Use of insulin sensitizing agents in the treatment of polycystic ovary syndrome. Fertil Steril 2004;82 (Suppl 1):S181-3. 10. Ghalaut VS, Sharma D, Dahiya K, Dora A, Dahiya P. Rosiglitazone: Effect of clomiphene citrate induced ovulation in polycystic ovary syndrome. J Obstet Gynecol India 2008;58(1):53-6. 11. Ghazeeri G, Kutteh WH, Bryer-Ash M, Haas D, Ke RW. Effect of rosiglitazone on spontaneous and clomiphene citrate-induced ovulation in women with polycystic ovary syndrome. Fertil Steril 2003;79(3):562-6. 12. Belli SH, Graffigna MN, Oneto A, Otero P, Schurman L, Levalle OA. Effect of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome. Fertil Steril 2004;81(3):624-9. 13. Kaul S, Diamond GA. Rosiglitazone and cardiovascular risk. Curr Atheroscler Rep 2008;10(5):398-404. 14. Ratziu V, Giral P, Jacqueminet S, Charlotte F, HartemannHeurtier A, Serfaty L, et al; LIDO Study Group.

16. Woodhead JS, Addison GM, Hales CN. Radio-immunoassay and saturation analysis. The immunoradiometric assay and related techniques. Br Med Bull 1974;30(1):44-9. 17. Abraham GE, Manlimos FS, Garza R. Radioimmunoassay of steroids. In: Handbook of Radioimmunoassay. Marcel Dekker: New York 1977:p.597-620. 18. Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961;21: 1440-7. 19. Wild RA, Vesely S, Beebe L, Whitsett T, Owen W. Ferriman Gallwey self-scoring I: performance assessment in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005;90(7):4112-4. 20. Rouzi AA, Ardawi MS. A randomized controlled trial of the efficacy of rosiglitazone and clomiphene citrate versus metformin and clomiphene citrate in women with clomiphene citrate-resistant polycystic ovary syndrome. Fertil Steril 2006;85(2):428-35. 21. Shobokshi A, Shaarawy M. Correction of insulin resistance and hyperandrogenism in polycystic ovary syndrome by combined rosiglitazone and clomiphene citrate therapy. J Soc Gynecol Investig 2003;10(2):99-104.

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10. Madanmohan, Udupa K, Bhavanani AB, Vijayalakshmi P, Surendiran A. Effect of slow and fast pranayams on reaction time and cardiorespiratory variables. Indian J Physiol Pharmacol 2005;49(3):313-8. 11. Ganong WF. Heart as a pump. Chapter 29. In: Review of Medical Physiology. 21st edition, A Lange Medical Book: McGraw-Hill, New Delhi 2010;Chap. 31, Sec.VI, p.570. 12. Chopra HK. Diastolic heart failure: a clinical challenge early recognition and timely intervention is the need of the hour. Indian Heart J 2009;61(2):138-45.

13. Schrier RW, Abraham WT. Mechanism of disease: Hormones and haemodynamics in heart failure. N Engl J Med 1999;341:577-85. 14. Braunwald E. Heart failure and corpulmonale. Chapter 216. In: Harrison’s Principle of Internal Medicine. Vol. II, 6th edition, McGraw-Hill: New York 2005:p.1370. 15. Levy PS, Quigley RL, Gould SA. Acute dilutional anemia and critical left anterior descending coronary artery stenosis impairs end organ oxygen delivery. J Trauma 1996;41(3): 416-23.

Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CASE REPORT

A Case Report of Yolk Sac Tumor Bratati Moitra

ABSTRACT Malignant ovarian germ cell tumors are rare but aggressive, accounting for approximately 1-2% of all ovarian malignancies. The peak incidence is found in young women or adolescent girls. Yolk sac tumor (YST) is the second most common tumor in ovarian tumors of this group. YST is a highly malignant tumor that metastasises early and invades all intra-abdominal structures. Before the advent of combination chemotherapy, YST was almost universally fatal. We report a case of a 21-yearold female who presented with complaints of pain all over abdomen and lump in lower abdomen since past three months. She was investigated and found to have YST. Key words: Yolk sac tumor, mixed inhomogenous echodensity, a-fetoprotein, lactic dehydrogenase, b-hCG

Case Report A young patient named Madhuri Devi of 21 years wife of Kapil Dev Singh of Giridih presented in Gyne OPD of Rajendra Institute of Medical Sciences, Ranchi on 07.12.2011 (Reg. no-G/1350) with complaints of pain all over abdomen and lump in lower abdomen for three months. Her last menstrual period (LMP) was on 02.12.2011. Her cycle was regular with scanty flow. She was Para 1 + 0 with fullterm normal vaginal delivery one and half year back at home. She had a past history of laparotomy with right-sided oophorectomy done on 12.09.2010 at Hirapur, Dhanbad. Her previous discharge summary showed that during laparotomy multinodular rightsided ovarian cyst with torsion was removed. No histopathological examination (HPE) report was available.

solid lump was felt in suprapubic region, more towards left side, size-about 10 × 12 cm. It was well-defined hard lamp with an irregular outline and was fixed. On percussion fluid thrill was present. Per vaginal examination, an irregular hard fixed lump was palpated in posterior fornix. Lump could be palpated through all fornices except anterior fornix. Uterus could not be felt separate from lump. Patient was investigated and USG was done. Reports were as follows: Patient is B+, Hb is 9.9 gm%, TLC-4,600, DLC: N-62%, L-34%, E-1%, BT-4’, CT-2’5”, blood urea31mg/dl, serum creatinine-.8 mg/dl, SGOT-40

On examination, patient was thin built, had moderate pallor and hemodynamically stable. In per abdominal examination, transverse suprapubic sear was present with distension of abdomen. On deep palpation, a

Assistant Professor Dept. of Obstetrics and Gynecology Rajendra Institute of Medical Sciences, Ranchi, Jharkhand Address for correspondence Dr Bratati Moitra 24, Bardhwan Compound, Lalpur Ranchi - 834 001, Jharkhand

Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

Figure 1. Tumor mass of 15 × 12 cm removed from uterovesical pouch of peritoneum.

CASE REPORT

Figure 2. HPE report showing yolk sac tumor.

IU/ml, SGPT-36 IU/ml and alkaline phosphatase84 IU/ml. USG - Left adnexa shows two inhomogenous mixed density mass 6 × 5 cm of it. Ovarian origin and a large heterogenous mass with irregular outline of size 13 × 10 cm. Tumor markers: zz

Serum AFP >400 mIU/ml

Serum LDH - 477 Units/lr.

Serum b-hCG- .585 mIU/ml

was done from uterovesical pouch of peritoneum (Fig. 1). There was metastasis in omentum. Omentectomy was done. All tissues were sent for HPE. Report of HPE showed yolk sac tumor (Fig. 2). Patient was discharged on 10th postoperative day and was referred to oncology department for further chemotherapy. Suggested Reading 1. Kurman RJ, Shih IeM. Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications. Int J Gynecol Pathol 2008;27(2):151-60.

Peritoneal fluid tapping was done on 14.12.2011-600 cc hemorrhagic peritoneal fluid taken out. Ascitic fluid was sent for chemical and cytological examination. Smear showed predominantly lymphocytes with few polymorphs, mesothelial cells against hemorrhagic background. On 20.12.2011 under spinal anesthesia total abdominal hysterectomy with left-sided salpingo-oophorectomy with removal of a friable tumor mass of 15 × 12 cm

2. Pecorelli S, Odicino F, Maisonnenve P, et al. Carcinoma of the ovary. Annual report on the results of treatment of gynecological cancer, Vol. 23. IFGO 1998;3:75-102. 3. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011;61(4):212-36. 4. Einhorn N, Sjövall K, Knapp RC, Hall P, Scully RE, Bast RC Jr, et al. Prospective evaluation of serum CA 125 levels for early detection of ovarian cancer. Obstet Gynecol 1992;80(1):14-8.

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CASE REPORT

Rare Coexisting Primary Hydatid Cyst and Mucinous Cyst Adenoma of Right Ovary Bandana Biswas*, Palash Mondal**, Tanuka Das†, Thejavinuo Keditsu‡

ABSTRACT The human hydatid cyst is caused by different species of the tapeworm of genus Echinococcus. In past literatures, the existence of hydatid cysts in various organs has been documented, but one pertaining to the ovary, especially with a coexisting mucinous cystadenoma is an enigma, with an incidence between 0.2 and 2.25%. In our case, a 70-year-old lady presented with a huge ovarian cyst, which was macroscopically and histopathologically proven to be the concomitant existence of a mucinous cyst of ovary and a cluster of mother and daughter hydatid cysts. In this case, no other organ showed evidence of hydatid cysts, notably the liver and lungs, the two commonest sites of involvement. Key words: Hydatid cysts, primary ovarian involvement, mucinous cystadenoma, concomitant coexistence

ydatid disease is caused by different species of the tapeworm of genus Echinococcus. The parasite, during its larval stage, can thrive in many parts of the body mainly the liver (63%) followed by the lungs (25%), muscles (5%), bones (5%) and rarely, in the kidney, brain and spleen.1 However, hydatid cyst in the pelvis, especially as a primary localization, is rare2-4 with a minuscule incidence of 0.25-2.25% of all locations of hydatid cyst.5 Few cases of ovarian involvement secondary to a cyst’s dissemination from another site have been reported till date in literature,6-9 but rarely has there been a case of primary ovarian hydatid cysts and never has a case of primary ovarian hydatid cysts with coexisting ovarian tumor been reported. Our illustrated case of hydatid cysts is particularly fascinating not only due to its uncommon primary site of involvement, but also due to the concurrent presence of histologically proven mucinous cystadenoma. Case Report A 70-year-old, postmenopausal, woman presented with the complaint of heaviness and swelling in her

*Professor Dept. of Obstetrics and Gynecology **Assistant Professor † Senior Resident ‡ Postgraduate Resident Medical College and Hospital, Kolkata, West Bengal Address for correspondence Dr Bandana Biswas 69, Chandi Ghosh Road, Kolkata, West Bengal - 700 040

Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

lower abdomen, loss of appetite and progressive weight loss over the period of six months. In the past, she had five full-term normal vaginal deliveries; all healthy, viable offsprings. There was no history of surgical intervention of any kind. Being from a farming village, she gave a history of having direct contact with cattle, dogs and cats throughout the past 25 years. She was a known hypertensive, now normotensive due to regular medication. On general examination, the lady was thinly built and malnourished. There was no palpable lymphadenopathy. On palpation, per abdominally, a cystic space occupying lesion was noted, extending upto the epigastrium. The surface was smooth, had restricted mobility (lower pole not palpable). Per vaginal examination corroborated with the abdominal findings. No other systematic abnormality could be detected. Abdominal sonography (Fig. 1) revealed a huge cystic space occupying lesion (SOL) measuring 21.7 × 16.6 × 17.1 cm, occupying the epigastric region, displacing the gut superiorly and laterally. There were no other abnormalities detected in the abdomen. Computed tomography (CT) scan (Fig. 2) showed a complex cystic SOL within the peritoneal cavity of abdomen with the uterus being compressed by the cystic SOL. There were no other abnormalities detected in the abdomen. The CT scan findings led the radiologist to differentially diagnose 35

CASE REPORT

Figure 1. Ultrasound showing cystic SOL.

Figure 4. Hydatid cyst with mucinous cyst of ovary.

Figure 2. CT scan showing huge SOL extending upto epigastrium.

Figure 5. Hydatid cyst with brood capsules (H&E X100).

Figure 3. Intraoperative finding showing cut section of cyst containing clear fluid and daughter cyst-like structures.

the mass as an ovarian SOL, hydatid cyst or mesenteric cyst. Serological investigations revealed a cancer antigen 125 (CA-125) level of 75 mIU/ml and carcinoembryonic antigen (CEA) level of 2.3 mg/ml, which did not rule the diagnosis of an ovarian malignancy. Due to its rapid growing nature, decision was taken for a laparotomy, which revealed a huge cyst of the left ovary, which contained straw colored fluid. Aspiration of the fluid was done with utmost care and precaution so as to avoid spillage. On careful inspection of the ovarian cyst, it was seen to contain within it, multiple lemon-sized cysts, which in turn contained multiple grape-like clusters of smaller cysts (Fig. 3). The right ovary and fallopian tubes were found to be normal. No other abnormalities could be found, macroscopically on exploration of abdomen. We ended the surgery by performing a total abdominal hysterectomy and Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CASE REPORT bilateral salpingo-oophorectomy. To reinforce our rare intraoperative finding, we sent sample for an echinococcal titer of the patient, which was found to be a high 66.6. Postoperatively, she received tablet albendazole 200 mg for four weeks followed by 400 mg for another four weeks. Patient made an uneventful recovery and was discharged on the 10th postoperative day. Histopathological examination of the specimen showed it to be a mucinous cystadenoma of the ovary with co-existing hydatid cyst (Figs. 4 and 5). Discussion Humans are accidental intermediate hosts in the life cycle of the parasitic tapeworm genus Echinococcus. This infection is prevalent in those countries where people keep cattle, sheep and dogs in their vicinities, such as the Mediterranean region, Middle Europe, South America, Middle East, East Africa and Australia.1 Humans become infected by handling soil, dirt, animal feces or hair that contains eggs. The egg reaches the human small intestine and releases an embryo (also called an oncosphere or hexacanth) that penetrates the intestinal wall and via portal circulation, reaches the liver. The liver being the first filter, thus, is the commonest site of development. The embryo then passes through a second filter, the lungs, before finally entering the systemic circulation and various other organs. Once it has invaded these organs, the embryo develops into a hydatid cyst, which grows to about 5-10 cm within the first year and is able to survive within organs for years. Once a cyst has reached a diameter of 1 cm, its wall differentiates into a thick outer, noncellular membrane, which covers the thin germinal epithelium. From this epithelium, cells begin to grow within the cyst. These cells then become vacuolated and are known as brood capsules, which are the parts of the parasite from which protoscolices bud. Often, daughter cysts will also form within cysts. Slowly enlarging echinococcal cysts generally remain asymptomatic. Pelvic organs are almost always affected secondary to the affection of the liver and lungs, for instance, transcoelomic spread from rupture of liver cyst has been reported. Pelvic echinococcosis is symptomatically nonspecific, with complaints like abdominal tumefactions, abdominal pain and menstrual irregularities, infertility and urinary disturbances.8 In some cases, ovarian echinococcosis can simulate either polycystic disease or Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

malignancy. Correct diagnosis can be difficult due to the vague clinical symptomatology, along with atypical ultrasonographic and radiological images, which merely show a solid ovarian mass. The treatment of choice in ovarian hydatid cysts is surgery, which could be either radical or conservative. Ovarian cystectomy, when possible, represents the gold standard treatment.6 In this case, the diagnosis of ovarian echinococcosis was dubious as the case simulated malignancy both in symptomatology, radiological features and serology, and was in retrograde found to have coexisted with one. The ultimate confirmation was made by intraoperative findings. As there was no evidence of involvement of other organs and no past history of echinococcosis, it can be concluded that this was a rare case of primary ovarian echinococcosis. Despite gold standards, our decision to perform total abdominal hysterectomy with bilateral salpingo-oophorectomy proved to be contributory to our final diagnosis of a concomitant ovarian mucinous cystadenoma making our case all the more rare. References 1. Aksu MF, Budak E, Ince U, Aksu C. Hydatid cyst of the ovary. Arch Gynecol Obstet 1997;261(1):51-3. 2. BaĹ&#x;aranoÄ&#x;lu M, Sonsuz A, Perek A, Perek S, Akin P. Primary pelvic hydatid cyst. J Clin Gastroenterol 1998;26(2):157-8. 3. Adewunmi OA, Basilingappa HM. Primary ovarian hydatid disease in the Kingdom of Saudi Arabia. Saudi Med J 2004;25(11):1697-700. 4. Gaym A, Abebe D, Degefe DA. Hydatid cyst an unusual cause of ovarian enlargement. Ethiop Med J 2002;40(3): 283-91. 5. Tampakoudis P, Assimakopoulos E, Zafrakas M, Tzevelekis P, Kostopoulou E, Bontis J. Pelvic echinococcus mimicking multicystic ovary. Ultrasound Obstet Gynecol 2003;22(2):196-8. 6. Cattorini L, Trastulli S, Milani D, Cirocchi R, Giovannelli G, Avenia N, et al. Ovarian hydatid cyst: a case report. Int J Surg Case Rep 2011;2(6):100-2. 7. Maharlooei MK, Attar A, Goran A, Amuee S, Dehghan A, Monabati A. Hydatid cyst of ovary: a case report. Iran J Med Sci 2009;34(2):76-9. 8. Dede S, Dede H, Caliskan E, Demir B. Recurrent pelvic hydatid cyst obstructing labor, with a concomitant hepatic primary. A case report. J Reprod Med 2002;47(2):164-6. 9. Konar K, Ghosh S, Konar S, Bhattacharya S, Sarkar S. Bilateral ovarian hydatid disease - an unusual case. Indian J Pathol Microbiol 2001;44(4):495-6.

CASE REPORT

Heterologous Malignant Mixed Mullerian Tumor of Uterus: An Uncommon Tumor with Uncommon Presentation Bhavana S

ABSTRACT Uterine malignant mixed mullerian tumor (MMMT), an uncommon neoplasm, is having extremely poor prognosis. Some of its predisposing factors include nulliparity, obesity, diabetes and hypertension. Five-year survival rate considerably decreases when tumor extends to cervix, vagina or parametrium. In this article, we report a case of a 65-year-old elderly woman presented with acute retention of urine, which was later diagnosed as MMMT of uterus. Key words: Malignant mixed mullerian tumor, heterologous

he uterine malignant mixed mullerian tumor (MMMT) is an uncommon neoplasm with biphasic pattern, consisting of both mesenchymal and epithelial component. They are very aggressive tumors with extremely poor prognosis, presenting in elderly menopausal women.

Case Report A 65-year-old P8L8 elderly woman presented to gynec OPD with complaints of difficulty in passing urine for the past one month and acute retention of urine for the past two days. She attained menopause 15 years back. On examination, patient was averagely built and poorly nourished. Weight-35 kg, height-136 cm, body mass index (BMI)-18.9 kg/m2. After catheterization, on per abdomen examination, a suprapubic mass was felt corresponding to uterus of 16-18 weeks, with irregular borders, firm in consistency, dullness on percussion, with grossly reduced mobility and no free fluid in the abdomen. On per speculum examination, cervix appeared healthy. On per vaginum examination, uterine mass of 16-18 weeks was felt, which was firm

Assistant Professor Dept. of Obstetrics and Gynecology Sree Mookambika Institute of Medical Sciences, Kulasekharam, Kanyakumari, Tamil Nadu Address for correspondence Dr Bhavana S W/o: Dr Rakesh Kumar Gupta No. 27, Karthik Nilaya, C-Layout, 2nd Cross Hanumanthanagar, Bannimantap, Mysore - 570 015, Karnataka E-mail: bhavana_yajat@yahoo.com

in consistency, impacted in pelvis, with gross reduction in mobility. The ultrasound revealed markedly enlarged uterus due to large mass filling the uterus 10.9 × 11.4 × 9.6 cm3 with multiple cystic areas within the lesion. No breech of surface, no ascites, no definite adjacent organ infiltration. There was mechanical bladder outlet obstruction with left sided hydronephrosis. The patient was diabetic on routine investigation and insulin therapy was started. The patient was posted for laparotomy. Intraoperatively, uterus was 18 weeks size; ovaries, parametrium, peritoneum, omentum were normal with no ascites/adhesions. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was done. The cut section of the uterus showed a large 12 × 12 × 8 cm3 broad-based pedunculated polyp arising from the fundus, distending into the entire cavity of the uterus (Fig. 1). Cross-section of the tumor showed pinkish, white, solid mass with areas of extensive necrosis. The histopathology of the tumor showed carcinomatous component composed of adenocarcinomatous, clear cell and undifferentiated areas. Sarcomatous areas with elongated spindle cells. Focal areas with malignant cartilaginous differentiation with extensive areas of tumor necrosis—MMMT with heterologous elements. (Figs. 2-4). The clinical and pathological staging was Stage 1B MMMT of uterus. The patient and the family were counseled and prognosis was explained and the option Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CASE REPORT

Figure 1. Cut section of uterus with the large pedunculated tumor arising from the fundus.

Figure 3. Sarcomatous component of malignant mixed mullerian tumor (H&E stain* high power).

Figure 2. Carcinomatous component with necrotic areas of malignant mixed mullerian tumor (H&E stain* high power).

Figure 4. Heterologous component showing cartilaginous areas of malignant mixed mullerian tumor (H&E stain* high power).

of adjuvant radiotherapy/chemotherapy was advised. But patient refused further treatment, so she was discharged on the 10th day and follow-up was advised.

there was no predisposing factors except that she was diagnosed to be diabetic after routine investigation. The MMMT’s contain admixture of carcinomatous and sarcomatous elements. The epithelial component may be of any type of mullerian carcinoma: Mucinous, squamous, endometroid, high grade papillary, clear cell or undifferentiated. On the basis of the appearance of sarcomatous component, the neoplasm is classified into homologous (leiomyosarcoma, stromal sarcoma, fibrosarcoma) or heterologous (chondrosarcoma, rhabdomyosarcoma, osteosarcoma, liposarcoma).1

Discussion The MMMT’s account for 2-5% of all malignant neoplasms of the uterine corpus. The tumor presents in postmenopausal women, in 5-7th decade of life. The reported median interval from menopause to presentation is 15-17 years.1,2 Nulliparity, obesity, diabetes and hypertension are recognized to be predisposing factors for MMMT’s. The neoplasm has been associated with previous pelvic radiation therapy.1,2 Some patients have developed MMMT, while taking tamoxifen and raloxifene.1 In our case, Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

The commonest symptoms are postmenopausal bleeding, lower abdominal pain, loss of weight, abdominal mass.1,3,4 The MMMT’s are highly aggressive neoplasms. Staging is the most important

Cont’d on page 42...

CASE REPORT

Mixed Autoimmune Disorder in Pregnancy Pawaskar Naresh T*, DA Hiremath**

ABSTRACT Patient by name Nikita aged 27 years, primigravida presented with five months amenorrhea with chief complaints of swelling all over body and weakness since eight days. It was spontaneous conception, had threatened abortion at eight weeks with blood pressure (BP) 130/90 mmHg, at 13 weeks her BP was 160/106 mmHg and was on antihypertensive medication. In view of all these, she was investigated with routine as well as special investigations. Her hemoglobin (Hb) was 9 g/dl, platelet 8,000/mm3, urine albumin positive, TFT; raised TSH, antiphospholipid antibody (APLA) profile; anticardiolipin antibody positive, KCT ratio; 1.20 positive, ANA profile positive and positive antiplatelet antibody. USG revealed 16 weeks gestation. Patient had spontaneous abortion at 16th week. It was diagnosed: Primigravida with 16 weeks with mixed autoimmune disorder including secondary APLA syndrome, hypothyroidism, thrombocytopenia and SLE. This case has been presented because of its unusual presentation with sudden onset following conception without past and family history. The case was treated accordingly. Key words: Mixed autoimmune, APLA syndrome, hypothyroidism, thrombocytopenia, threatened abortion

ixed autoimmune disorder consists of systemic lupus erythematosus (SLE), antiphospholipid antibody (APLA) syndrome and other autoimmune disorders including antibodies against thyroid gland and thrombocytes resulting in diseases pertaining to the particular systems. Autoimmune diseases arise from an inappropriate immune response of the body against substances and tissues normally present in the body. This may be restricted to certain organs in the body or it may involve a particular tissue in different places like basement membrane of the lung and the kidney. For diseases to be recognized as autoimmune they should fulfil the criteria’s such as Witebsky’s postulates. There are more than 80 illnesses caused by autoimmunity.1

This case has been presented because of its unusual presentation with sudden onset following conception

*Associate Professor Dept. of Obstetrics and Gynecology Navodaya Medical College and Hospital, Raichur, Karnataka **Professor Dept. of Anesthesiology SN Medical College, Bagalkot, Karnataka Address for correspondence Dr DA Hiremath Professor Dept. of Anesthesiology SN Medical College, Bagalkot - 587 102, Karnataka

without any past and family history. Patient had generalized edema, hypertension, productive cough, with thrombocytopenia. APLA syndrome is also called ‘PAPS’ (primary antiphospolipid antibody syndrome),2 consisting lupus anticoagulant and anticardiolipin antibody (ACLA) in patients serum and other rare antibodies like phosphatidylserine and phosphatidylethanolamine.3 These antibodies are directed against negatively charged phospholipids on the cell membrane. They may be IgG, IgM or IgA class antibodies, either alone or in combination. Lupus anticoagulant characterized by a prolonged partial thromboplastin time (PTT) is a powerful thrombotic agent.4 The prevalence of lupus anticoagulant3 in low-risk population is <1% with BOH 9.1%, early PET 16%, abruption 33% and SLE 34%. Lupus anticoagulant interferes with platelet functions causing platelet aggregation and thrombosis.5 It alters endothelial functions causing procoagulant activation and thrombosis.6 Primary APLA can be asymptomatic or symptomatic with various clinical presentation.7 Case History Patient named Nikita, aged 27 years, housewife by occupation, wife of Nilesh Takkar, farmer by occupation resident of Raichur was admitted on 28/12/2011. Primigravida with five months amenorrhea, with chief complaints of generalized body swelling and weakness Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CASE REPORT since eight days. She had conceived spontaneously and was having regular antenatal check-up. At eight weeks, she was found to have blood pressure (BP) 130/90 mmHg with features of threatened abortion but again at 13 weeks, she had BP 160/106 mmHg with mild headache; in view of that she admitted to a hospital and managed on tablet aldomat 250 mg 8th hourly and tablet depin 5 mg SOS. As her condition was worsening she was referred to a higher center. OBHPrimigravida, ML nine months, nonconsanguineous marriage, last menstrual period (LMP) 17/8/11, with regular past cycles and normal flow. No significant medical or surgical history in the past. No family history of hypertension, diabetes mellitus or any autoimmune disorder. Physical examination conscious obese patient, afebrile, pulse rate 88/min, BP 140/100 mmHg, with bilateral pedal pitting edema above knee joint. On per abdomen examination, uterus ~16 weeks with all other systems normal. Probable diagnosis was pregnancy with chronic hypertension. In view of above mentioned history and clinical findings, routine and specific laboratory investigations done. Hemoglobin (Hb) 9 g/dl, blood group B+ve, HIV-negative, HBsAg-positive, VDRLnegative, platelet count 8000/mm3, peripheral smearRBC’s has mild sparse distribution, normocytic normochromic appearance; anisocytosis was present. WBC’s normal and platelet number markedly reduced. Urine routine normal. RFT normal, LFT normal, QBC malaria negative. TFT; TSH >100 µIU/ml; free T3 1.53 pg/ml, free T4 0.38 ng/ml. Antiplatelet antibody positive. APLA profile; anticardiolipin antibody IgM+ve, IgG-negative, Dilute Russell’s Viper Venom Time (DRVVT) ratio 1.77 positive, KCT ratio 1.20 positive, APTT 45.4 secs control, 32.2 secs. ANA profile positive. Ultrasonography showed single live intrauterine gestation of 16 weeks with AFI 12 and fundal placenta. Course of treatment: In view of hypertension, she was put on tablet aldomat 500 mg q.i.d. and tablet amlodep 5 mg b.i.d., 4 units platelet transfusion done for severe thrombocytopenia, tablet thyronorm for hypothyroidism. Since, antiplatelet antibody was positive, tablet wysolone 60 mg daily started. As her urine protein was increasing physician consultation Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

done and advised injection methylprednisolone 500 mg IV pulse dose and tablet azathioprine 100 mg o.d. Platelet count and CBC repeated weakly. Patient had spontaneous abortion, expelled fetus weighting 200 g. Physician and nephrologists advised her to continue all above mentioned medicine. As she is on immunosuppressant drug renal biopsy was advised, but patient wants to come after two weeks for renal biopsy. She was discharged on 13/1/2012. Discussion SLE is an autoimmune disease, nine times more common in females during childbearing period.8 It is type ΙΙΙ hypersensitivity reaction, can attack any part of the body through immune system resulting in inflammation and tissue damage. Currently there is no cure, some time it is fatal, that can be reduced by recent medical modalities of treatment using immunosuppressant drugs like cyclophosphamide, azathioprine and corticosteroids. As it mimics or often mistaken for many illnesses it is known as ‘the great imitator’. Women with SLE have an association with APLA syndrome,9 making screening mandatory for the same in SLE woman. Antibodies against phospholipids resulting in changes in DRVVT time, prolonged PTT and positive antibodies is called lupus anticoagulant antibody. This is responsible for hemorrhagic disorder. Another antibody found is anticardiolipin antibody. These two types of antibodies are responsible for clinical manifestation pertaining to individual system. The symptoms vary widely, they may appear and go unpredictably, sometime flare-up by triggering factors or strong genetic factors. Anemia may develop in upto 50% of cases, low platelet count and WBC count may be due to disease or it can be the side effect of the treatment.9 Thirty percent sufferers have dermatological symptoms like malar rashes, thick red scaly patches on skin and ulcers on mucus membranes.9 Sometime pregnancy may flare-up the disease, exacerbation occurs in 20-30% of pregnancies and it is due to increase in estrogen, prolactin and certain cytokines. Renal disease flare-up is most common clinical presentation in SLE pregnancy.10 The worsening proteinuria in pregnancy could herald a lupus flare-up and it is impossible to predict when patient will flare-up and may cause an increase in rate 41

CASE REPORT of intrauterine fetal death and spontaneous abortion, but overall live birth rate is 72%.11 Pregnancy outcome is worse if it flares up during pregnancy.12 Long time remission before pregnancy decreases risk of aggravation depending upon the period of remission. General preventive measures include continuation of glucocorticoids in lowest effective dose and continuous use of azathioprine may be preferred in some patient with due precautions and monitoring. Most women with lupus are able to have children. Neonatal lupus occurs in baby of the SLE mother is usually benign and self-limiting but their pregnancies need careful medical monitoring because of the risk of complication. Advice for the patient is to plan for the subsequent pregnancy after reasonable period of remission at least six months and management strategy should be agreed in full consultation with the specialist prior to conception. References 1. Rose NR, Mackey IR. The Autoimmune Disease. 4th edition, 2006. 2. Harris EN. Syndrome of the black swan. Br J Rheumatol 1987;26(5):324-6. 3. Chard YA. The effectiveness of current antenatal care. In: Progress in Obstetrics and Gynecology. Studd J (Ed.), Churchill Livingstone: Edinburgh 1996;12:3-18.

4. Williams Obstetrics “Chapter 20”. Diseases and Injuries of the Fetus and Newborn 20. Appleton & Lange: Stamford, CT 1997:p.997-8. 5. Khamashta MA, Harris EN, Gharavi AE, Derue G, Gil A, Vázquez JJ, et al. Immune mediated mechanism for thrombosis: antiphospholipid antibody binding to platelet membranes. Ann Rheum Dis 1988;47(10):849-54. 6. Keeling DM, Campbell SJ, Mackie IJ, Machin SJ, Isenberg DA. The fibrinolytic response to venous occlusion and the natural anticoagulants in patients with antiphospholipid antibodies both with and without systemic lupus erythematosus. Br J Haematol 1991;77(3):354-9. 7. Berady S, et al. Arch intern Med 1988;48:1647. 8. Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med 2008;358(9):929-39. 9. Syuto T, Shimizu A, Takeuchi Y, Tanaka S, Hasegawa M, Nagai Y, et al. Association of antiphosphatidylserine/ prothrombin antibodies with neuropsychiatric systemic lupus erythematosus. Clin Rheumatol 2009;28(7):841-5. 10. Khurana R, Chelmow D. Systemic lupus erythematosus and pregnancy. Medscape. Updated: Sep. 20, 2010. 11. Smyth A, Oliveira GH, Lahr BD, Bailey KR, Norby SM, Garovic VD. A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis. Clin J Am Soc Nephrol 2010;5(11):2060-8. 12. Cortés-Hernández J, Ordi-Ros J, Paredes F, Casellas M, Castillo F, Vilardell-Tarres M. Clinical predictors of fetal and maternal outcome in systemic lupus erythematosus: a prospective study of 103 pregnancies. Rheumatology (Oxford) 2002;41(6):643-50.

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...Cont’d from page 39

predictive factor in prognosis.1-3 International Federation of Gynecology and Obstetrics (FIGO) staging of MMMT’s of the uterus is the same as for endometrial carcinoma. Five-year survival rate are about 30-40% in Stage I disease (confined to uterine corpus) and considerably less in Stage II and III (when disease extends to cervix, vagina or parametrium) and there were no survivors in those with disease outside the pelvis (Stage IV).1 Due to aggressive nature of MMMT’s and its poor prognosis, various modalities of treatment have been employed. Surgery in the form of abdominal hysterectomy and bilateral salpingo-oophorectomy remains the principle treatment.1,4 Adjuvant radiotherapy 42

and chemotherapy (cisplatin and ifosfamide) has been shown to be beneficial.4 References 1. Ho SP, Ho TH. Malignant mixed mullerian tumours of the uterus: a ten-year experience. Singapore Med J 2002;43(9): 452-6. 2. Afsharrmaghaddam N, Pooralborzi F, Aram S, Moghaddas D. Heterologous malignant mixed mullerian tumor in a diabetic patient. JRMS 2008;13(6):349-53. 3. Rosai J. Uterus-corpus. In: Rosai and Ackerman’s Surgical Pathology. Rosai J (Ed.), Mosby: Philadelphia 2004: p.1599-602. 4. Wong L, See HT, Khoo-Tan HS, Low JS, Ng WT, Low JJ. Combined adjuvant cisplatin and ifosfamide chemotherapy and radiotherapy for malignant mixed mullerian tumor of the uterus. Int J Gynecol Cancer 2006;16(3):1364-9.

Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

CASE REPORT

Subseptate Uterus Presenting as an Unstable Lie at Term Shikha Singh*, Saroj Singh**, Ankita Kumari†, Ruchita Sinha‡

ABSTRACT Subseptate uterus presenting as an unstable lie at term is uncommon. In this article, we report two rare cases; first where presentation of the baby changed four times, and in other, lie of the fetus changed twice in a short period of time. On exploration of uterus at the time of cesarean section it was found to be subseptate. Key words: Subseptate uterus, unstable lie, mullerian abnormalities

n the past, anomalies of genital tract have aroused interest as anatomical curiosity because of the relative infrequency with which they are thought to occur. In recent years, several investigators have focused attention upon these abnormalities because of their important bearing upon the frequency of abortion, premature labor, abnormal presentation of the fetus and complications of labor and of the immediate postpartum period. Among the mullerian anomalies subseptate uterus is the most common congenital uterine anomaly with an incidence of 33.6% worldwide.1 Case History Case 1

A 22-year-old multiparous (G3P1L0A1) woman presented on 3/3/2010 36 weeks of gestational age (according to her ultrasonography [USG] report done four days back, exact last menstrual period [LMP] was not known) for routine antenatal check-up. Her obstetric history had unsuccessful outcome with history of emergency lower-

* Assistant Professor **Professor and Head † Senior Resident ‡ Postgraduate Student Dept. of Obstetrics and Gynecology SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Shikha Singh Assistant Professor Dept. of Obstetrics and Gynecology SN Medical College, Agra - 282 002, Uttar Pradesh E-mail: drshikhasingh.shikha@gmail.com

Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

segment cesarean section (LSCS) done for cord prolapse and resulting in an intrauterine device (IUD) baby about 2.5 years back and one spontaneous abortion at three months of gestational age 1.5 years back. Her medical history was unremarkable. She had an USG done four days back, which showed a single live intrauterine fetus with mean gestational age of 35 weeks four days with breech presentation. Abdominal examination at the time of presentation revealed a fundal height of 34 weeks with cephalic presentation. She was advised a repeat USG, which revealed a single live intrauterine fetus of gestational age 35 weeks four days with cephalic presentation and scar thickness of 2.2 mm and placenta of Grade III maturity. In view of thin scar, persistent mild but infrequent uterine contractions and Grade III placenta she was admitted and kept under observation. During observation, her lie kept on changing from breech to transverse or cephalic. Because of thin uterine scar an elective cesarean section was decided at 37 weeks. On the day of elective cesarean, the presentation of baby was found to be transverse with head on right side and back posterior. This was confirmed on USG. She underwent a cesarean section was taken up and on exploration of the uterus a septa measuring 3 inch was found arising from fundus i.e., subseptate uterus was discovered. Her postoperative period was uneventful. Patient was discharged after nine days in a satisfactory condition. However, the patient did not come for follow-up. Case 2

In the second case, a 23-year-old primigravida presented on 3/10/2010 with 39 weeks of gestational 43

CASE REPORT age (according to her LMP and 37 weeks 6 days according to USG done at the time of admission), pain in abdomen for six hours and leaking per vaginum for one hour. On examination, lie of the baby was found to be transverse, cervix was 2 cm dilated and 80% effaced and membranes were absent, which was confirmed on USG. Patient was taken for cesarean section in view of transverse lie and at the time of operation lie was found to be longitudinal with breech presentation. On exploration a septa of about 2 inches was found arising from the fundus and was incompletely dividing the uterine cavity. Her postoperative period was uneventful. She was discharged after eight days in a satisfactory condition. She was advised for follow-up at six weeks. Discussion Incidence of uterine malformation in population is 0.5%. Subseptate uterus belong to Class III B according to American Fertility Society Classification (AFS) of mullerian anomalies. Apoptosis has been proposed as a mechanism by which the septum regresses. Bcl-2, a protein involved in regulating apoptosis was found absent in septa of subseptate uterus. Absence of this protein plays a pivot role in persistence of septum.2 Patients with this anomaly often have recurrent abortions, which is due to abundant muscle tissue in the septum, abnormal endometrium overlying the septum leading to abnormal implantation. Only about 40% of pregnancy reaches term with a constantly changing fetal presentation even beyond 36 weeks of pregnancy when it should have been stabilized. This was the presentation in our case in which the lady within one week of our observation had breech, cephalic and transverse lie on different occasions, which were confirmed by USG also. In other case, lie

of the fetus changed at term in a short period of time in labor within few hours. After 22 weeks of gestation, enlargement of uterus obliterates some subtle findings suggestive of anatomic variability so the patient should be examined before this juncture with a conventional transabdominal or transvaginal approach. Power Doppler in the first trimester (4-9 weeks) using 3D studies can be performed to reach at correct diagnosis.3 Patient usually gives history of dysmenorrhea, menorrhagia in the interval period. They may be pregnant despite presence of an intrauterine contraceptive device (IUCD) because of incomplete occupancy of IUCD of whole of the uterus. Various diagnostic modalities like hysterosalpingogram, hysteroscopy, laparoscopy are helpful to detect the anomaly before the patient conceives. The recommended therapy for subseptate uterus in the past was abdominal metroplasty. During the past several years, hysteroscopic resection of uterine septum with intrauterine resectoscope, hysteroscopic resection of uterine septum using flexible or rigid scissors or Neodymium-YAG laser or transcervical septum resection using metzenbaun scissors under fluoroscopic guidance has replaced the transabdominal approach.4 Unstable lie at term or in labor should arouse suspicion for the obstetricians to be aware of any mullerian anomaly, most common culprit of which may be subseptate uterus. References 1. Williams Obstetrics. 23rd edition, pg.:968-9, 893. 2. Te Lendes Operative pg.:565, 567.

Gynaecology.

10th

edition,

3. Ian Donalds Practical Obs Problems. 6th edition, pg.:73. 4. Obs and Gynae By Mimi C Berman, Harris L. Cohen pg :60.

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Asian Journal of Obs and Gynae Practice, Vol. 3, July-September 2013

45 Answers

Lymphadenectomy is required in clinically suspicious groin lymph nodes. Vagino-urethral margin of resection is common site of failure. Prognosis is poor if lymph nodes are involved. These are resistant to radiotherapy, interferon-a2b is the first agent to show value as an adjuvant to surgery.

Staging is same as other carcinoma vulva but histological microstaging is very important.

This is a case of vulval malignant melanoma; an elevated pigmented mass is seen at vulva in picture A and picture B is showing same type of pigmentation in lymph node of left groin. It is the second most common vulval malignancy.

What is this photograph showing?

How do you stage this disease?

How does management differ?

Questions

Photo Quiz

Associate Professor Dept. of Obstetrics and Gynecology AIIMS, New Delhi

Dr Nutan Aggarwal

PHOTO QUIZ

Dr Vidushi Kulshrestha

FLOW CHART

Female Genital Tuberculosis Introduction

•• Female genital tuberculosis (GTB) affects about 12% patients with pulmonary TB and represents 15-20% cases of extrapulmonary TB.

Senior Research Associate Dept. of Obstetrics and Gynecology AIIMS, New Delhi

Prof. Alka Kriplani

MD, FRCOG, FAMS, FICOG, FICMCH, FIMSA, FCLS Professor and Head Dept. of Obstetrics and Gynecology Director in-charge WHO HRRC and Family Planning AIIMS, Ansari Nagar, New Delhi E-mail:kriplanialka@gmail.com

Cont’d (Investigations ...)

Diagnostic laparoscopy

•• It is a common cause of infertility. •• The reported prevalence of GTB in infertility clinics varies widely with an incidence of 0.69% in Australia and upto

•• Usually indicated as work-up of infertility or chronic pelvic pain. •• May detect early GTB. Fluid may be taken from POD for lab tests. Biopsy can be taken directly from the lesions.

•• Incidence is still higher (48%) in tubal factor infertility. Infertility is the commonest presentation of GTB, reported in

•• Presence of tubercles, caseation and calcification is definitive of GTB. Thick beaded tubes, straw colored fluid in POD,

Pathogenesis

In infertility: Hysterosalpingography* (HSG) may reveal tubal block, dilated tortuous tubes, beaded tubes, calcification, tobacco pouch appearance, tubal diverticulae, fluffiness of tubal outline, irregular uterine cavity, small cavity, extravasation of dye

19% in India.

upto 58% cases.

Simultaneous tubal patency can be tested.

adhesions, perihepatic adhesions (Fitz-Hugh-Curtis syndrome), hydrosalpinx, adherent mass are suggestive of GTB.

GTB almost always occurs secondary to primary focus elsewhere-lungs (commonest), lymph nodes, gastrointestinal tract, urinary tract, skeletal system, military TB.

Modes of spread •• Hematogenous in 90%. •• Descending direct spread via lymphatics and from adjacent organs. •• Ascending route is very rare. It occurs by sexual transmission from male partner with urogenital TB.

Newer diagnostic tests

Primary site of involvement

Fallopian tubes in 90%, uterus in 80%, ovary in 30%, cervix in 15%, pelvic peritoneum in 40-50% and very rarely, vulva and vagina in 1%. Fallopian tubes: Usually bilaterally affected •• Usually mucosa is first involved (endosalpingitis) in hematogenous spread, but direct spread of infection from adjacent organs may first cause exo-salpingitis. •• Sequelae are fibrosis, calcification, tortuous tubes, adhesions, hydrosalpinx, pyosalpinx, tubo-ovarian mass or abscess, salpingitis isthmica nodosa, tobacco pouch tubes and frozen pelvis in extreme cases. Uterus: Most common affected site is cornua •• GTB causes ulcerative lesions which heal by fibrosis leading to Asherman syndrome. •• Pyometra and myometrial caseation may also occur. Ovary: Surface tubercles, adhesions, capsule thickening, caseous abscess or TO mass may form. Cervix, vagina, vulva: Lesions may be nonhealing ulcers or nodules and may mimic malignancy. Histology: Typical lesion is the caseous granuloma with infiltrates of multinucleate giant cells (Langhans cells), lymphocytes, chronic inflammatory cells and epitheloid cells around a central necrotic and caseated area. Healed lesions are fibrotic.

Clinical features

Symptoms: Patients with GTB may be asymptomatic and can go unrecognized till they seek treatment for infertility. There may be positive past history of TB or history of contact. Patients may complain of: •• Menstrual disorders: ¾¾ Menorrhagia (40%), pubertal menorrhagia, postmenopausal bleeding ¾¾ Hypomenorrhea or oligomenorrhea ¾¾ Amenorrhea - both primary and secondary •• Infertility - primary or secondary •• Chronic pelvic pain, lump in abdomen •• Vaginal discharge/postcoital bleeding •• Nonhealing fistula •• Constitutional symptoms - weight loss, loss of appetite, pyrexia with evening rise

Signs •• General: Evidence of extragenital lesions. •• Abdominal examination may reveal doughy feeling, irregular mass, ascites, encysted fluid which may mimic ovarian cyst. •• Per vaginal examination may reveal vulval/vaginal lesions, pelvic mass, thickened adnexa, enlarged uterus (pyometra), and rarely, fistula.

Investigations in a suspected case of GTB General: Hemoglobin, TLC, DLC, ESR, Mantoux test, chest X-ray (Anemia, lymphocytic leukocytosis, raised ESR, positive Mantoux, evidence of pulmonary TB may be found, but not necessarily in all cases) Premenstrual* Endometrial aspiration or first day menstrual discharge should be sent: •• In formalin - for histopathology •• In saline- for acid-fast bacilli (AFB), culture and DNA-PCR for Mycobacterium tuberculosis *Tubercular granulomas are close to surface of endometrium in premenstrual phase. Sometimes, they may be absent even in presence of disease due to repeated shedding at menstruation.

Radiology: Has less role in absence of a mass •• Ultrasound pelvis: May detect tubo-ovarian mass, ascites, hydrosalpinx •• CT/MRI is indicated, if mass mimics malignancy Biopsy from lesions of cervix, vagina or vulva Hysteroscopy is indicated in hypomenorrhea/amenorrhea to diagnose uterine synechia

*HSG is contraindicated in active disease to avoid flare up of TB.

Cont’d...

Radiometric methods: Gives quick results in 5-10 days unlike 6 weeks taken by conventional Lowenstein Jensen’s media. •• BACTEC system: Uses fatty acid substances like palmitic acid or formic acid labeled with radioactive carbon. •• MGIT (Mycobacterial growth inhibitor tube): It is a radioactive detection system using fluorochromes.

Colorimetric methods

•• MB/Bact- Detects bacterial growth by colorimetric methods. It also takes 2 weeks to give the results.

RNA-PCR (Reverse transcriptase or RT-PCR) detects actively replicating bacilli; thus, can detect viable organisms, hence active disease. The use of mRNA-based PCR has been evaluated in pulmonary specimens (sputum) for detecting viability of mycobacteria and determining drug-susceptibility. But pick-up rate of GTB is less. ELISA* by using monoclonal antibody against molecular antigens like 45 kDa antigen. DOT ELISA against 55 kDa is recently being used. Utility in GTB is not backed with many studies in literature. Interferon-gamma-release assays (IGRA)*: These immunologic tests measure the production of interferon (IFN)gamma by TB-specific T. lymphocytes after encountering M. tuberculosis antigens. The available ones are: •• QuantiFERON-TB Gold in tube (QFT-IT) •• T-SPOT TB test Though these are available in the market, there is no supporting evidence in literature as of now. *If at all any marker protein or antigen is positive for tuberculosis, it is only suggestive of TB and not confirmatory.

Dilemmas and challenges in diagnosis of GTB The crux of effective management of GTB is an early diagnosis of GTB before the damage to reproductive organs has occurred. This, however, is a challenge because: •• Despite the advent of many new diagnostic tests, there is still no gold standard test for GTB •• Definitive diagnosis by demonstration of Mycobacterium requires: ¾¾ ≥10,000 bacilli/ml by microscopy for AFB in smear ¾¾ 1,000/ml by Lowenstein Jensen’s culture ¾¾ ≥100 bacilli/ml by Bactec culture Hence these conventional tests are usually negative in GTB as female GTB is a paucibacillary disease. Reported positivity in litearure is about 4% by smear, 12-20% by culture and 13-28% by histopathology.

•• Though molecular diagnosis by DNA-PCR (polymerase chain reaction) is a useful adjunct in diagnosis of GTB, because

¾¾ In can pick up <10 organisms/ml ¾¾ It is rapid and takes 1-2 days ¾¾ It can also be applied to sterile fluids like peritoneal fluid where the culture is difficult due to a low bacterial load.

(DNA-PCR targets various gene segments -65 kDa, IS6110 element, mpt 64 gene)

But DNA-PCR can be positive in presence of dead/dormant bacilli even in absence of disease (false-positive cases) or by lab-contamination •• Though laparoscopy is now being increasingly used for diagnosis of GTB in infertility as it offers dual advantage of pelvic organ visualization and sample collection for lab-diagnosis from inaccessible sites. But laparoscopy may be normal in very early disease •• Many new diagnostic tests are coming up, but they are expensive, routinely not available, done in only research setting. •• Hence, clinician has to rely on high index of suspicion on clinical grounds. Another foremost dilemma is whether to start ATT if •• Only DNA-PCR is positive •• All other laboratory tests (smear, culture, histopath) and laparoscopy are negative for TB •• Clinical features are also not suggestive of GTB as asymptomatic cases are common. To increase pick up of early cases •• High index of suspicion is required. •• Infertile patients should be subjected to whole battery of tests for GTB as only one test may be positive in one patient whereas others may be negative. •• Multiple samples for lab tests may also increase the diagnostic yield.

Treatment

Chemotherapy: Antitubercular therapy (ATT) remains the mainstay of treatment. Most female GTB cases come in Category III of RNTCP (Revised National Tuberculosis Control Program). Seriously ill patients come in Category I. ...Cont’d

Doses of first-line ATT Daily (mg/kg)

In 50 kg pt.

Intermittent (thrice/week) (mg/kg)

5 (4-6)

300 mg/day

10 (8-12)*

Rifampicin (R)

10 (8-12)

450 mg/day

10 (8-12)

Pyrazinamide (Z)

25 (20-30)

1,500 mg/day

35 (30-40)*

Treatment: Stop INH, rifampicin, pyrazinamide at once •• Continue ethambutol •• Start ofloxacin and streptomycin •• Weekly follow-up with LFT, and when they come to normal, reintroduce hepatotoxic drugs. One by one as follows: Day 1: INH 50 mg/day Day 4: INH 100 mg/day Day 7: INH 200 mg/day Day 14: INH 300 mg/day Day 21: Rifampicin Day 28: Pyrazinamide

Ethambutol (E)

15 (15-20)

600 mg/day

30 (25-35)*

Mechanism of action

Streptomycin (S)

15 (12-18)

0.75 g/day

15 (12-18)

Anti-TB drug

Isoniazid (H)

Recommended dose

Isoniazid: Bactericidal for rapidly dividing organisms, prevents emergence of resistance to other drugs Rifampicin: Bactericidal for rapidly dividing organisms, prevents emergence of resistance to other drugs Pyrazinamide: Bactericidal Ethambutol, streptomycin: Bacteriostatic or weakly bactericidal for rapidly dividing organisms, prevents emergence of resistance to other drugs Second-line drugs for TB: Thiacetazone, capreomycin, prothionamide, ethionamide, para-aminosalicylic acid (PAS), cycloserine

*Intermittent doses are higher than daily doses. All anti-TB drugs should be given as a single daily dose. Rifampicin should be taken on empty stomach. Pyridoxine 20 mg/day supplementation should be added to ATT. Direct observation is recommended in intermittent regimens. Thiacetazone is contraindicated in HIV co-infection. WHO advocates direct observation of therapy to improve cure rates and to reduce drug resistance.

Effect of ATT on pregnancy

Adverse reactions with ATT

Rifampicin, INH, ethambutol and pyrazinamide are considered safe in pregnancy. Streptomycin, fluoroquinolones and other second-line drugs are relative contraindications in pregnancy.

Isoniazid: Hepatitis, peripheral neuritis, nausea, vomiting, agranulocytosis Rifampicin: Hepatitis, ↓efficacy of oral contraceptives and other drugs-corticosteroids Pyrazinamide: Hepatitis, arthralgia Ethambutol: Optic neuritis, headache, nausea, GI disturbance Streptomycin: Ototoxic, nephrotoxic, rash, ataxia

Prognosis of GTB

Menstrual symptoms may improve with treatment except in cases of complete obliteration of uterine cavity. Prognosis for fertility is very poor in histologically proven cases, if tubes are already damaged or if uterine cavity is destroyed. However, if the disease is picked up early with PCR, better pregnancy rates have been reported. Hysteroscopic synechiolysis followed by IVF-embryo transfer has been tried, although pregnancy rate is lower (15-20%). With microsurgery, pregnancy rates are upto 22%.

Drug-induced hepatitis with ATT Mild hepatitis: When ↑ in liver enzymes is upto 3 times the normal range It occurs in 10% cases on ATT ATT is not discontinued Enzymes usually return to normal within few weeks even on ATT Severe hepatitis: When ↑ in liver enzymes is >3 times the normal range Occurs in 1% case on ATT

Indications of surgery in GTB

Cont’d...

•• Persistent/recurrent disease (e.g. pelvic masses) on treatment •• Nonhealing fistula •• Multiple drug-resistant disease

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The title page (page 1) should contain the title, names of authors (first name will be shortened to initials), degrees, affiliation of authors i.e., department, section or unit of an institution, hospital or organization and the city, state and or country where it is located, a list of 3-5 key words, and name and address of the author responsible for correspondence. Abstract

A separate page must accommodate the abstract which should not exceed 200 words. A structured abstract is required for original research articles. A standard abstract is required for review and case report articles. Structured abstract

A structured abstract limited to 200 words, should contain the following major headings, objectives(s) study design, results and conclusion(s). The objective(s) reflects the purpose of the study, that is the hypothesis that is being tested. The study design should include the setting for the study, the subjects (number and type), the treatment or intervention, and the type of statistical analysis. The results include the outcome of the study and statistical significance if appropriate. The conclusion(s) state(s) the significance of the results. Standard abstract

There are no subheadings in the standard abstract. Text

Only standard abbreviations are to be used. The full term for which an abbreviation stands should precede its first use in the text unless it is a

standard unit of measurement. Regular articles are customarily organized in the following sections: In the introduction, state concisely the purpose and rationale for the study and cite only the most pertinent references as background. In the material and methods section describe briefly the plan, the subjects, methods and procedures utilized, and the statistical methods employed. In the results section present the detailed findings. Include mention of all tables, and/or figures. Figures and tables should supplement not duplicate the text. Discussion should consider the results in relation to the hypothesis tested and should be put into context with those reported by other workers. Conclusions drawn should be completely supported by the data in the text. Review and update articles should preferably have highlights emphasizing crucial points in the text, typed on separate pages at the end of the text. Few MCQs (multiple choice questions) based on the text will also help increase readers interest in the article. References

References must be numbered in the order in which they first appear in the text. Identify references in text, tables and legends by arable numerals in parentheses. The style of reference and abbreviated title of journals must follow that of Index Medicus. For journal references, list all authors when 6 or less, when 7 or more list only first three and add et al. The title of the manuscript will be printed after the author’s names, before the abbreviated title of the journal e.g.,: De Cherney AH, Diamond MP, Lavy G and Polan ML. Endometrial ablation for intractable uterine bleeding. Obstet. Gynecol. 1987;70: 668-670. For book reference list all authors of the book, title, edition, city of publication, publisher, year of publication, chapter and page in that order. Goldrath MH and Garry R. Nd:YAG laser ablation of the endometrium In: Endoscopic Surgery for Gynaecologists 2nd Edition, Sutton C and Diamond N (Eds.), WB Saunders, London 1993:16-21. References should be limited to 20 except for the possible exception of special review articles, The editorial board of the journal has decided to adopt the Vancouver style of uniform requirements for manuscripts submitted to biomedical journals (N Engl J Med 1991;324:421-428) These notes for contributors confirm with the Vancouver style. Figures

The term figure includes all types of illustrations such as graphs, diagrams, photographs, flow charts and line drawings. Photographs should be supplied in high quality glossy paper usually 127 mm × 173 mm (5" x 7"). In case of microphotograph stains used and magnification should be mentioned. Each illustration should bear on its back the figure number, name of the forwarding author and an arrow indicating the top. All illustrations should be submitted in duplicate. Legends of figures

Legends for all figures must be typed together in numerical order double spaced on a separate sheet. All illustrations and figures must be referred to in the text and abbreviated as “Fig.” Tables

Tables should be typed on separate sheets of paper, one table to a page and included at the end of the text. They should be numbered in Arabic numerals. Titles should be brief yet indicate clearly the purpose or content of each table. Acknowledgment

Acknowledgment should be made to funding institutions and organizations and if to persons, only to those who have made substantial contribution to the study. Electronic manuscripts

Electronic manuscripts have the advantage that there is no need for the rekeying of text, thereby avoiding the possibility of introducing errors and fast processing of the article. Format your disk correctly and ensure that only the relevant file (one complete article only) is on the floppy/compact disk. Also specify the type of computer and word processing package used and label the disk with your name and the name of the file on the disk.