Ajog april june 2014 by IJCP

Volume 1, Number 1

Asian Journal of

Online Submission

Volume 1, Number 1

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

CONTENTS FROM THE ISSUE EDITOR Dr Alka Kriplani

FROM THE DESK OF GROUP EDITOR-IN-CHIEF

What is New in Obstetrics and Gynecology?

Dr 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)

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

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

ENT Dr Jasveer Singh

Cardiology Dr Praveen Chandra Dr SK Parashar

Gastroenterology Dr Ajay Kumar

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

Dentistry Dr KMK Masthan Dr Rajesh Chandna

Dermatology Dr Hasmukh J Shroff Neurology Dr V Nagarajan Journal of Applied Medicine and Surgery Dr SM Rajendran Dr Jayakar Thomas

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

REVIEW ARTICLE

Hyperprolactinemia 7 Kusum Lata, Alka Kriplani

CLINICAL STUDY

Evaluation of Perinatal Outcome by Antenatal CTG and Umbilical Artery Doppler in Pre-eclamptic Mothers

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

A Study on Correlation of Menstrual Pattern and Histopathology of Uterine Endometrium in Reproductive Age Groups of Women with Hypothyroidism

Amitava Pal, Arindam Rakshit, Rupali Modak, Ganesh Chandra Hati

A Comparative Study to Analyze the Association of Metabolic Syndrome in Females with Diagnosed Polycystic Ovarian Syndrome 23 Richa Singh, Saroj Singh, Poonam Yadav, Harpreet Kaur

Comparison of Laparoscopic-Assisted Vaginal Hysterectomy and Nondescent Vaginal Hysterectomy: A Retrospective Study 27 G Jain, SK Jha, U Palaria, G Joshi, PK Verma, N Pangti

Asian Journal of Volume 1, Number 1

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

Mullerian Agenesis: An Unusual Presentation as Hematometra and Bilateral Hematosalpinx

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Sudhir Gupta, Ankita Kumari

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Posterior Reversible Encephalopathy Syndrome in Postpartum Normotensive Woman: A Rare Presentation 33 M Siva Sundari, KS Rajeswari, Nandhini Elumalai

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Research Review

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FROM THE ISSUE EDITOR

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

Dear Reader This first issue of the journal wishes you a bright year ahead. It also reminds us to renew our pledge to bring to you every new development that is born of this field, obstetrics and gynecology. Smoking tobacco or marijuana, taking prescription painkillers, or using illegal drugs during pregnancy is associated with double or even triple the risk of stillbirth, according to research funded by the National Institutes of Health.

for evidence of several types of drugs. They looked for evidence of the stimulants cocaine and amphetamine; prescription painkillers, such as morphine and codeine, and marijuana. These tests reflect exposure late in pregnancy. Among the women who had experienced a stillbirth, more than 80% showed no traces of cotinine and 93% tested negative for the other drugs. In comparison, about 90% of women who gave birth to a live infant tested tobacco-free and 96% tested negative for other drugs.

Researchers based their findings on measurements of the chemical byproducts of nicotine in maternal blood samples; and cannabis, prescription painkillers and other drugs in umbilical cords. Taking direct measurements provided more precise information than did previous studies of stillbirth and substance use that relied only on women’s self-reporting. The study findings appear in the journal Obstetrics and Gynecology.

Based on the blood test results and women’s own responses, the researchers calculated the increased risk of stillbirth for each of the substances they examined: • Tobacco use: 1.8 - 2.8 times greater risk of stillbirth, with the highest risk found among the heaviest smokers.

“Smoking is a known risk factor for stillbirth, but this analysis gives us a much clearer picture of the risks than before,” said senior author Uma M Reddy, MD, MPH, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH institute that supported the study. “Additionally, results from the latest findings also showed that likely exposure to secondhand smoke can elevate the risk of stillbirth.” Stillbirth occurs when a fetus dies at or after 20 weeks of gestation.

• Passive exposure to tobacco: 2.1 times greater risk of stillbirth.

• Marijuana use: 2.3 times greater risk of stillbirth. • Evidence of any stimulant, marijuana or prescription painkiller use: 2.2 times greater risk of stillbirth.

The researchers noted that they could not entirely separate the effects of smoking tobacco from those of smoking marijuana. Only a small number of women tested positive for prescription painkiller use, but there was a trend towards an association of these drugs with an elevated stillbirth risk.

The researchers tested the women’s blood for cotinine, a derivative of nicotine and tested fetal umbilical cords Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

What Is New in Obstetrics and Gynecology Dr KK Aggarwal

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

In 2013, the American College of Obstetricians and Gynecologists removed proteinuria as an essential diagnostic criterion for pre-eclampsia. Pre-eclampsia can now be diagnosed based on new onset of hypertension with either proteinuria or end-organ dysfunction after 20 weeks of gestation.Massive proteinuria and fetal growth restriction have also been removed as characteristics of severe disease. In a randomized trial of over 800 women with twin gestations, use of a cervical pessary inserted between 16 and 20 weeks gestation compared to no pessary, did not reduce preterm birth or a composite of poor perinatal outcomes. The Twin Birth Study showed that planned cesarean delivery does not significantly improve neonatal outcome as compared with planned vaginal delivery when the first twin is in vertex presentation. In 2013, the World Health Organization (WHO) updated its guidelines on the prevention and treatment of human immunodeticiency cirus (HIV) in resource-limited settings to recommend initiation of antiretroviral therapy (ART) for HIVinfected patients with CD4 cell counts â&#x2030;¤500 cells/L. These guidelines also recommend initiation of a combination antiretroviral regimen for all pregnant women with HIV infection, regardless of CD4 cell count, to continue at least throughout the period of mother-to-child transmission risk, which includes the breastfeeding period. For all HIV-infected individuals in resource-limited settings, efavirenz/ tenofovir/emtricitabine is the WHO preferred firstline regimen. In a change from previous guidelines, a practice bulletin by the American College of Obstetricians

and Gynecologists endorsed the use of oral antihyperglycemic agent (glyburide) as an alternative to insulin for treatment of gestational diabetes mellitus (GDM). zz

In a largest study, first-trimester use of fluconazole (most commonly a single dose of 150 mg) in 7,352 pregnancies was not associated with an increased risk of birth defects overall.

A population-based cohort study from Sweden including over 1.5 million singleton deliveries confirmed that overweight and obese women were not only at increased risk for medically indicated preterm deliveries at all gestational ages but also observed a significant dose-response relationship between severity of obesity and risk of spontaneous extremely preterm birth (22-27 weeks).

In a 2013 systematic review and meta-analysis of randomized trials for the US Preventive Services Task Force, appropriate management of gestational diabetes mellitus (nutritional therapy, self blood glucose monitoring and administration of insulin if target blood glucose concentrations are not met with diet alone) resulted in reductions in preeclampsia, birthweight >4,000 g and shoulder dystocia.

A United States Preventive Services Task Force (USPSTF) systematic review of cohort studies of screening tests for GDM concluded that the glucose challenge test performed well at both the 130 mg/ dL (7.2 mmol/L) and 140 mg/dL (7.8 mmol/L) thresholds and performed better than fasting plasma glucose level at a threshold of 85 mg/dL (4.7 mmol/L) for identifying women who were ultimately diagnosed with GDM. Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

REVIEW ARTICLE

Hyperprolactinemia Kusum Lata*, Alka Kriplaniâ&#x20AC;

ABSTRACT Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis. It presents as an ovulatory disorder and is often associated with secondary amenorrhea or oligomenorrhea, galactorrhea and osteopenia. When hyperprolactinemia is confirmed, a cause for the disorder needs to be sought. This involves a careful history and examination, followed by laboratory tests and diagnostic imaging of the sella turcica. Dopamine agonists are the treatment of choice for the majority of patients. Cabergoline has been shown to be more effective and better tolerated than bromocriptine. Transsphenoidal surgery is usually reserved for patients who are intolerant or resistant to dopamine agonists or when hyperprolactinemia is caused by nonprolactin-secreting tumors compressing the pituitary stalk. Key words: Hyperprolactinemia, hypothalamic-pituitary axis, ovulatory disorder, sella turcica, dopamine agonists

rolactin is a pituitary-derived hormone that plays a pivotal role in a variety of reproductive functions. It negatively modulates the secretion of pituitary hormones responsible for gonadal function, including luteinizing hormone (LH) and folliclestimulating hormone (FSH). Hyperprolactinemia is a condition of elevated prolactin levels in blood which could be physiological, pathological, pharmacological or idiopathic in origin. Management depends on the cause and on the effects it has on the patient. In this review, we summarize advances in our understanding of the clinical significance of hyperprolactinemia and its management. Regulation of Prolactin Secretion Prolactin is a 198-amino acid protein (23-kd) produced in the lactotroph cells of the anterior pituitary gland. Its primary function is to enhance breast development during pregnancy and to induce lactation. Prolactin is under dual regulation by hypothalamic hormones delivered through the hypothalamic-pituitary portal circulation. Under most conditions the predominant *Senior Resident â&#x20AC; Professor and Head Dept. of Obstetrics and Gynecology AIIMS, New Delhi Address for correspondence Dr Alka Kriplani Professor and Head, Unit II, Dept. of Obstetrics and Gynecology AIIMS, Ansari Nagar New Delhi - 110 029 E-mail: kriplanialka@gmail.com

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

signal is inhibitory, preventing prolactin release and is mediated by the neurotransmitter dopamine. The stimulatory signal is mediated by the hypothalamic hormone thyrotropin-releasing hormone. The balance between the two signals determines the amount of prolactin released from the anterior pituitary gland and the amount cleared by the kidneys influences the concentration of prolactin in the blood.1,2 Epidemiology The occurrence of clinically apparent hyperprolactinemia depends on the study population and occurs in less than 1% of the general population.3 The rate is higher among patients with specific symptoms that may be attributable to hyperprolactinemia: It is estimated at 9% among women with amenorrhea, 25% among women with galactorrhea and as high as 70% among women with amenorrhea and galactorrhea3 and 17% polycystic ovarian syndrome (PCOS) patients present with hyperprolactinemia. Of these patients, approximately 30% have prolactinsecreting tumors. The prevalence is about 5% among men who present with impotence or infertility.4 Etiology The diagnosis of hyperprolactinemia should be suspected in female patients presenting with oligomenorrhea, amenorrhea, galactorrhea or infertility. Hyperprolactinemia can be physiological or pathological. Some of the common causes are listed in Table 1.5

REVIEW ARTICLE Prolactinomas account for 25-30% of functioning pituitary tumors and are the most frequent cause of chronic hyperprolactinemia.6 Prolactinomas are divided into two groups: i) Microadenomas (<10 mm), which are more common in premenopausal women and ii) macroadenomas â&#x2030;Ľ10 mm), which are more common in men and postmenopausal women.

Prolonged hypoestrogenism secondary to hyperprolactinemia causes steopenia. Bone loss occurs secondary to hyperprolactinemia-mediated sex steroid attenuation. Spinal bone density is decreased by approximately 25% in women with hyperprolactinemia10 and is not necessarily restored with normalization of prolactin levels.

Clinical Presentation

The patients can also present with neurological symptoms caused by mass effects of the pituitary tumor. Symptoms include headaches and visual loss such as bitemporal hemianopsia, hypopituitarism, seizures and cerebrospinal fluid rhinorrhea.11

Clinical presentation in women is more obvious and occurs earlier than in men. They typically present with oligomenorrhea, amenorrhea, galactorrhea or infertility.7-9 Galactorrhea is less common in postmenopausal women due to lack of estrogen.

Table 1. Physiological

Pathological

Coitus

Hypothalamic-pituitary stalk damage Granulomas Infiltrations/Irradiation

Exercise Lactation Pregnancy Sleep Stress

Normal serum prolactin levels vary between 5 and 25 ng/mL in females although physiological and diurnal variations occur.12 Serum prolactin levels are higher in the afternoon than in the morning, and hence should preferably be measured in the morning.

Pituitary

According to Endocrine Society Guidelines for diagnosis and treatment of hyperprolactinemia (The Endocrine Society, 2011), a single measurement of serum prolactin is recommended to establish the diagnosis of hyperprolactinemia; a level above the upper limit of normal confirms the diagnosis as long as the serum sample was obtained without excessive venipuncture stress.13,14

Acromegaly Macroadenoma (compressive) Macroprolactinemia Surgery Trauma Pharmacological

Systemic disorders

Anesthetics

Hypothyroidism

Anticonvulsant

Polycystic ovarian disease

Antidepressants

Chest neurogenic chest wall trauma, surgery Chronic renal failure Cirrhosis

Antihypertensives Dopamine receptor blockers Estrogens: Oral contraceptives; Neuroleptics/ antipsychotics Opiates and opiate antagonists

The evaluation is aimed at excluding physiologic, pharmacologic or other secondary causes of hyperprolactinemia. A detailed drug history should be obtained because many medications cause hyperprolactinemia, with prolactin levels of <100 ng/ mL.

Trauma: Pituitary stalk section, suprasellar surgery Tumors: Craniopharyngioma hypothalamic metastases, meningioma, suprasellar pituitary mass extension Prolactinoma

Antihistamines (H2)

Diagnostic Evaluation

Epileptic seizures

Pitfalls in Lab Diagnosis

Macroprolactinemia: The big prolactin or macroprolactin is a less bioactive form consisting of dimers, trimers or polymers of prolactin, or prolactin-immunoglobulin immune complexes and it should be suspected when a patientâ&#x20AC;&#x2122;s clinical history and/or radiological data are incompatible with the prolactin value.15,16 It is detected by polyethylene glycol precipitation method, although gel filtration chromatography remains the gold standard.17 Hook effect: When there is a discrepancy between a very large pituitary tumor and a mildly elevated prolactin Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

REVIEW ARTICLE level, serial dilution of serum samples to eliminate an artifact that can occur with some immunoradiometric assays due to saturation of the capture antibodies is recommended.18 Other Laboratory Studies

Serum thyroid-stimulating hormone (TSH), blood urea nitrogen and creatinine should be done as hypothyroidism and renal failure are the two common causes of increased prolactin. Pregnancy should always be excluded unless the patient is postmenopausal or has had a hysterectomy. In addition, hyperprolactinemia is a normal finding in the postpartum period. Role of Imaging

Any patient who has hyperprolactinemia without an identified cause requires imaging of the hypothalamicpituitary area. A mildly elevated serum prolactin level may be due to a nonfunctioning pituitary adenoma or craniopharyngioma compressing the pituitary stalk, although prolactin levels that are very high (>250 ng/mL) are almost always associated with a prolactinoma.3 Magnetic resonance imaging (MRI) with gadolinium enhancement provides the best visualization of the sellar area. Management The treatment of hyperprolactinemia depends on the underlying causes, natural course of the disease and the aim of treatment. The goals of treatment for are: • Normalization of prolactin level • Restoration of gonadal function and fertility • Avoidance of the adverse effects of chronic hyperprolactinemia like osteoporosis. An additional goal of treatment in macroprolactinoma patients is tumor shrinkage with relief of mass symptoms. Current therapeutic options include medical therapy, surgery and radiotherapy. Management of Drug-induced Hyperprolactinemia Although hyperprolactinemia commonly occurs with psychotropic medication use, only a minority of patients-typically those with hypogonadism need to Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

be considered for treatment. After a work-up to rule out alternative causes of hyperprolactinemia and bone density measurement, gonadal steroid replacement should be considered to preserve skeletal health and maintain compliance with a successful psychiatric medication regimen. The treating psychiatrist should be consulted for any change in psychotropic regimen. Whether to treat a patient who has antipsychoticinduced hyperprolactinemia with a dopamine agonist remains controversial. Some studies suggest that dopamine agonist therapy will normalize prolactin levels in only up to 75% of such patients but may lead to exacerbation of the underlying psychosis.19-22 Medical Therapy Dopamine agonists like bromocriptine and cabergoline have become the treatment of choice for the majority of patients with hyperprolactinemia. Bromocriptine was the first dopamine agonist to be introduced into clinical practice. It is a semisynthetic ergot derivative of ergoline, a D2 receptor agonist with antagonist properties at D1 receptors. Its half-life is relatively short and has to be taken 2 or 3 times daily.23 It is effective in normalizing serum prolactin levels and restoring gonadal function in 80-90% of patients, with varying degrees of tumor size reduction.24 The most common adverse effects are nausea, vomiting and headache (up to 60% of patients). Postural hypotension is common especially when initiating therapy and can result in dizziness (25%). Other side effects include a Raynaud-type syndrome of painless digital vasospasm, drowsiness, fatigue, leg cramps, insomnia, blurred vision and paresthesia.23,25 Side effects can usually be minimized by introducing the drug at a very low dosage (0.625 or 1.25 mg/d), taking the tablets with food and by very gradual dose escalation. Therapeutic dosages are generally in the range of 2.5-15 mg/day in hyperprolactinemic patients, but 5-17%26 of patients are found to be resistant, requiring dose up to 30 mg/day.23 Another alternative to oral treatment is vaginal usage of the same drug, which is well-tolerated. Vaginal absorption is nearly complete and first pass metabolism in liver is avoided allowing lower therapeutic dosing.27 It is also available in a longacting form (depot‑bromocriptine) for intramuscular injection and a slow-release oral form.28,29 9

REVIEW ARTICLE Cabergoline is an ergoline derivative with high affinity and selectivity for the D2 receptor. It has an extremely long plasma half-life of about 65 hours allowing onceor twice-weekly administration. It has been shown to achieve normal serum prolactin levels in 85-86% and restoration of normal gonadal function in 90-91%.30,31

undertaken after 2 years in patients who have achieved normoprolactinemia and significant tumor volume reduction. The risk of recurrence after withdrawal ranges from 26% to 69% and all studies have shown that recurrence is predicted by prolactin levels at diagnosis and by tumor size.

Cabergoline and bromocriptine have been compared in a multicenter collaborative study involving 459 women with hyperprolactinemic amenorrhea.25 Stable normoprolactinemia was achieved in 186 of the 223 (83%) women in the cabergoline group compared with 138 of 236 (59%) women in the bromocriptine group (p < 0.001), and resumption of ovulatory cycles or pregnancy occurred in 72 and 52%, respectively (p < 0.001).

For patients who after 2 years of therapy have achieved normal prolactin levels and no visible tumor remnant and for whom dopamine agonists have been tapered or discontinued, follow-up includes: 1) Measurement of serum prolactin levels every 3 months for the first year and then annually thereafter and 2) MRI if prolactin increases above normal levels.34 In women with microprolactinomas, it may be possible to discontinue dopaminergic therapy when menopause occurs.

Cabergoline, is more effective and causes fewer adverse effects than bromocriptine. However, it is much more expensive and is often used in patients who cannot tolerate the adverse effects of bromocriptine or in those who do not respond to bromocriptine. Therapy should be continued for approximately 12-24 months (depending on the degree of symptoms or tumor size) and then withdrawn if prolactin levels have returned to the normal range. After withdrawal, approximately one-sixth of patients maintain normal prolactin levels. Response to therapy should be monitored by checking fasting serum prolactin levels and checking tumor size with MRI. Most women (approximately 90%) regain cyclic menstruation and achieve resolution of galactorrhea. Management of Prolactinoma

Cabergoline is considered to have higher efficacy in normalizing prolactin levels and pituitary tumor shrinkage. In a placebo-controlled study, cabergoline treatment (0.125-1.0 mg twice-weekly) for 12-24 months in patients harboring prolactinsecreting microadenomas resulted in normalization of prolactin levels in 95% of patients. Cabergoline restored menses in 82% of women with amenorrhea.32 In a retrospective study of 455 patients, cabergoline normalized prolactin levels in 92% of patients with idiopathic hyperprolactinemia or a microprolactinoma and in 77% of 181 patients with macroadenomas.31 When to Discontinue Therapy Four recent studies33-36 suggest that in a subset of patients, dopamine agonist withdrawal may be safely 10

Surgery General indications for pituitary surgery include patient drug intolerance, tumors resistant to medical therapy, persistent visual-field defects in spite of medical treatment and patients with large cystic or hemorrhagic tumors. Transnasal transsphenoidal microsurgical excision of prolactinoma is the procedure of choice. Hyperprolactinemia recurred within 5 years after surgery in about 50% of patients with microprolactinomas who were initially thought to be cured.37 Re-evaluation of long-term results indicates a success rate of about 75% for surgical removal of microprolactinoma. However, the results of surgery for macroprolactinoma are poor, with a long-term success rate of only 26%.38 Radiotherapy should be reserved for resistant or malignant prolactinomas. Normalization of hyperprolactinemia occurs in approximately one-third of patients treated with radiation. Radiation therapy is associated with side effects including hypopituitarism and rarely, cranial nerve damage or second tumor formation.39 Conclusion Once diagnosis of hyperprolactinemia is confirmed the underlying cause of the disorder needs to be determined and common causes like hypothyroidism and drug intake should be ruled out. Medical therapy is the mainstay of treatment in most of the women with surgery being reserved for patients who are ...Cont'd on page no. 22

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

CLINICAL STUDY

Evaluation of Perinatal Outcome by Antenatal CTG and Umbilical Artery 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. 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 myriad of other signs and symptoms such as edema, *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, Gobinda Nagar Bankura, West Bengal - 722 102 E-mail: asmp80@rediffmail.com

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

visual disturbances, headache and epigastric pain.3 The increased incidence of perinatal morbidity and mortality seen in pregnancies complicated by preeclampsia 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 rate (FHR) tracing and fetal death. It would be ideal that this sequence of pathological changes elicited 11

CLINICAL STUDY 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 (â&#x2030;Ľ5 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:

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 â&#x20AC;&#x2DC;Reactive.â&#x20AC;&#x2122;

Absence of deceleration.

zz zz

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. The change in behavior of ultrasound waveform reflecting from a moving object - the Doppler effect was introduced in the assessment of umbilical artery 12

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 6 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 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 Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

CLINICAL STUDY 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 6 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. 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 2 weeks. Control group, in similar situation had another routine USG for FPP after 2 weeks. The neonatal outcomes of both groups were recorded in predesigned proforma and compared using Chi-square

Table 1. No. of Patients 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

Mode of delivery

Apgar score at 1 min

Normal

LSCS

Forceps

≥7

Normal (n = 10)

8 (80%)

1 (10%)

9 (90%)

1 (10%)

Raised (n = 25)

19 (76%)

6 (24%)

12 (48%)

13 (52%)

27 (77.14%)

7 (20%)

21 (60%)

14 (40%)

Total (n = 35)

P = 0.2004

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

P = 0.01

CLINICAL STUDY 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 p = 0.792

Gestational age at birth (weeks) Mean, SD 34-37

>37

Labor events 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

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

Mode of delivery

Apgar score

Birth weight (g) Mean, SD

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.

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. Observations 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 14

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 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% Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

CLINICAL STUDY almost similar findings in their study in 2010.14

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.

(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 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 Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

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 1 minute and 5 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 withou 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). 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 15

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 decelerations

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 Obstetrics and Gynecology Practice, Vol. 1, No. 1

CLINICAL STUDY 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 6 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;25:105-7. 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 Obstetrics and Gynecology Practice, Vol. 1, No. 1

CLINICAL STUDY

A Study on Correlation of Menstrual Pattern and Histopathology of Uterine Endometrium in Reproductive Age Groups of Women with Hypothyroidism Amitava Pal*, Arindam Rakshit†, Rupali Modak‡, Ganesh Chandra Hati#

ABSTRACT Objectives: To determine the correlation between histopathological findings of endometrium with the menstrual patterns of hypothyroid women and to compare with the euthyroid women. Material and methods: The hospital-based crosssectional study was conducted in the Dept. of Obstetrics and Gynecology, Burdwan Medical College, Bardhaman over 1 year from February 2010 to January 2011. Forty-six patients with abnormal uterine bleeding in the reproductive age groups (15-45 years) were evaluated for thyroid profile and subsequently dilation and curettage (D&C) operation was undertaken in OT. All the women were without organic lesion detectable either clinically or by imaging studies. Among this study population, 24 cases having low free thyroxine (FT4) and increased thyroid-stimulating hormone (TSH) level above the normal reference range (serum TSH is 0.8-5 µIU/mL and FT4 is 0.8-2 ng/dL) were designated as study group and the remaining 22 with normal thyroid profile were taken as control. Statistical analysis was performed by Student’s t-test and Chi-square test. A p value <0.05 was considered statistically significant. Results: Metrorrhagia (33.33%) and oligomenorrhea (33.33%) were two frequent symptoms in hypothyroid patients, but menorrhagia (54.54%) was the leading presentation in euthyroid women (p < 0.040). Normal cycle was noted only in three (12.50%) hypothyroid women and remaining 21 (87.50%) had functional disturbances. Functional disturbances were more common finding in hypothyroid groups of women. Metrorrhagic patient had more functional problem (81.82%; 9/11), which signify more chances of endometrial disturbances. Women with oligomenorrhea had no ovulatory disturbances. No specific difference between menstrual pattern and endometrial morphology was noted between case and control groups. Conclusion: Metrorrhagia and oligomenorrhea were the common menstrual abnormalities in hypothyroid women and functional disturbances in the form of anovulation were the most frequent histopathological feature. Key words: Menorrhagia, metrorrhagia, oligomenorrhea, FT4, TSH, anovulation

ypothyroidism signifies decreased production of thyroid hormone from the thyroid gland. The prevalence of hypothyroidism in women in the childbearing age group of 15-45 years varies from 2% to 4%.1 These women frequently presents with oligomenorrhea, menorrhagia and amenorrhea.2 To evaluate the different menstrual problems endometrial sampling is required. Apart from anovulatory cycle hypothyroidism is associated with luteal phase defect and *Associate Professor Dept. of Obstetrics and Gynecology † Postgraduate Student Dept. of Pathology Burdwan Medical College, Bardhaman, West Bengal ‡ Assistant Professor Dept. of Obstetrics and Gynecology RG Kar Medical College, Kolkata # Professor Dept. of Pathology Burdwan Medical College, Bardhaman, West Bengal Address for correspondence Dr Amitava Pal 12/3J, Northern Avenue Kolkata - 700 037, West Bengal E-mail: amitava.628@rediffmail.com

irregular shedding of the endometrium.3 Irregular shedding of endometrium is a clinicopathological entity characterized by prolonged and profuse menstrual flow coupled with pathological findings of a mixture of secretory, regressing, dissociating and regenerative endometrium. The disordered proliferative endometrium observed as a consequence of anovulatory cycle is a histological abnormal endometrium for unopposed estrogen action. In contrast to normal proliferative form it is nonuniform and often merges with hyperplasia. Endometrial hyperplasia is a heterogeneous group of lesions characterized by abnormal proliferation of glands and stroma, with predominating glandular component. It may be simple nonatypical, complex nonatypical, simple atypical and complex atypical. Some of these hyperplastic lesions are reversible and some may progress to neoplasia or may be truly neoplastic. Objectives The objective of this study was to evaluate the endometrial histopathological pattern in hypothyroid patients in childbearing age groups and also to ascertain Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

CLINICAL STUDY the correlation between histopathological findings and different menstrual irregularities in both euthyroid and hypothyroid women. Material and Methods The present hospital-based cross-sectional study was undertaken in the Dept. of Obstetrics and Gynecology, Burdwan Medical College, Bardhman in collaboration with the Dept. of Pathology and Biochemistry of the same institution from February 2010 to January 2011. The study was approved by Institutional Review Board and Ethics Committee. Forty-six women with abnormal uterine bleeding during the study period of 1 year were evaluated. All of them were without any obvious organic lesion detectable either clinically or imaging studies. Among the study population, 24 had decreased free thyroxine (FT4) or increased thyroid-stimulating hormone (TSH) level above the normal reference range and were designated as hypothyroid women (cases). Remaining 22 had normal thyroid profile and they were considered as control. Patients with the history of contraceptive use, wearing intrauterine contraceptive device (IUCD) and taking progesterone for their bleeding just prior to dilation and curettage (D&C), clinically detectable or ultrasonography (USG) proved organic lesion and amenorrhea or amenorrhea followed by bleeding per vagina with positive pregnancy test were excluded from our study. In the study group, three patients had primary infertility along with menstrual irregularity and one case had hypothyroidism. Demographic variables, such as maternal age, parity, complaints at admission, clinical findings were evaluated. Relevant investigations included Hb%, platelet count, other coagulation profile and pregnancy test. Imaging study was undertaken to evaluate organic pathology in abnormal uterine bleeding. Biochemical evaluation of thyroid hormone profile like FT4 and TSH was done in all cases by commercially available kit. Normal reference range of serum TSH is 0.8-5 µIU/mL and FT4 is 0.8-2 ng/dL. Following D&C, the endometrial tissue material was sent for processing, sectioning and staining for histopathological examination. The tissue material was categorized histopathologically under microscope by low- and high-power magnification as normal endometrium and functional disturbance of endometrium, which included ovulatory disturbances (irregular shedding) and anovulatory disturbances Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

(disordered proliferative endometrium and hyperplastic proliferative endometrium). Statistical Analysis

Statistical analysis was performed by Student’s t-test and Chi-square test. All analysis was performed by SPSS software Version 16. The p value <0.05 was considered statistically significant. Results Table 1 summarizes the patient profile. Between the two groups of variables, age and parity did not show any statistical significance but FT4 and TSH level of hypothyroid female showed statistically significant difference (p < 0.0001) when compared to euthyroid women. Table 2 shows the menstrual pattern in both the groups. Metrorrhagia (33.33%) and oligomenorrhea (33.33%) were two frequent symptoms in hypothyroid patients but Table 1. Patient Profile Parameters

Case (hypothyroid)

Control (euthyroid)

P value

(n = 24)

(n = 22)

Age (years)

30.917 ± 6.34

30.591 ± 5.84

0.856

Parity

2.04 ± 0.806

2.00 ± 0.971

0.851

TSH (µIU/mL)

7.271 ± 0.964

2.034 ± 0.822

< 0.0001*

FT4 (ng/dL)

0.563 ± 0.061

1.407 ± 0.234

< 0.0001*

Thyroid profile

Mean ± SD, *Significant (p < 0.05)

Table 2. Menstrual Pattern in Study and Control Groups Pattern of bleeding

Case (hypothyroid)

Control (euthyroid)

P value

(n = 24)

(n = 22)

Menorrhagia

6 (25)

12 (54.54)

0.040‡

Metrorrhagia

8 (33.33)

3 (13.63)

0.118

Oligomenorrhea

8 (33.33)

4 (18.18)

0.242

Hypoamenorrhea followed by heavy bleeding

1 (4.55)

0.291

Menometrrorhagia

1 (4.17)

1(4.55)

0.950

Polymenorrhea

1 (4.17)

1(4.55)

0.950

n (%), †Significant (p < 0.05)

CLINICAL STUDY Table 3. Menstrual Pattern and Endometrial Morphology in Case (Hypothyroid) and Control (Euthyroid) Groups Menstrual pattern

Proliferative

Secretory

Disordered proliferative

Hyperplastic proliferative

Irregular shedding

Hypothyroid (6)

Euthyroid (12)

Menorrhagia (18)

Chi-square = 5.625

df = 4

p = 0.229

Metrorrhagia (11) Hypothyroid (8)

Euthyroid (3)

Chi-square = 7.219

df = 3

p = 0.065

Oligomenorrhea (12) Hypothyroid (8)

Euthyroid (4)

Chi-square = 0.375

df = 2

p = 0.829

Hypoamenorrhea followed by heavy bleeding (1) Hypothyroid (0)

Euthyroid (1)

Chi-square = 0

df = 0

p = 0.0000

Menometrorrhagia (2) Hypothyroid (1)

Euthyroid (1)

Chi-square = 2

df = 1

p = 0.157

Polymenorrhea (2) Hypothyroid (1)

Euthyroid (1)

Chi-square = 0

df = 0

menorrhagia (54.54%) was the leading presentation in euthyroid women (p < 0.040). Polymenorrhea, menometrorrhagia and hypoamenorrhea followed by heavy bleeding were noted only in two cases in this group. Normal cycle was noted only in three (12.50%) of hypothyroid patients and remaining 21 (87.50%) had functional disturbances, but in euthyroid women normal cycle and functional disturbances were observed in 45.46% and 54.54% of cases, respectively. Functional disturbances were more common finding in hypothyroid groups and it was statistically significant (Chi-square = 6.148; p < 0.013) as compared to euthyroid women (Fig. 1). 20

p = 0.0000

Table 3 depicts menstrual pattern and endometrial morphology in case and control groups. No specific difference in endometrial morphology was noted between case and control groups (p value was insignificant). Menorrhagia was the most common type of bleeding in euthyroid patients. On histological examination of menorrhagia, proliferative endometrium was noted in four cases, secretory in five cases, disordered proliferative in five cases, hyperplastic proliferative two cases and irregular shedding in two cases, respectively. Among 11 patients of metrorrhagia nine cases had functional disturbances in endometrial morphology, but all metrorrhagic patients (8 cases) in hypothyroid group had functional disturbances. Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

CLINICAL STUDY 10

Hypothyroid

Euthyroid

Number of patients

2 1

1 0

4 3

Proliferative

Secretory

Normal cyclic endometrium

Disordered proliferative

Hyperplastic proliferative

Irregular shedding

Anovulatory Ovulatory endometrium endometrium

Figure 1. Histopathological features of endometrium in patients with uterine bleeding.

Out of 12 patients of oligomenorrhea, 10 had functional disturbances chiefly in the form of anovulatory endometrium. Six of them had disordered proliferative endometrium and four had hyperplastic proliferative type of endometrium and no ovulatory disturbance was noted. Both the cases of polymenorrhea had hyperplastic proliferative endometrium. Discussion A total of 46 women (study group - 24; control group - 22) were included. Apart from meticulous history and clinical examination, relevant investigations especially histopathological features of endometrium were categorized along with the level of thyroid hormone status followed by correlation in both the groups. The mean age of hypothyroid and euthyroid women were 30.917 years and 30.591 years, respectively and the mean parity were of 2.04 and 2.00. Joshi and Despande4 reported that 62.9% of clinically suspected dysfunctional uterine bleeding (DUB) cases were in the age groups of 15-44 years and majority of them were multipara, but Rosario reported a relatively higher incidence (97%) in multipara.5 The present study included only the women in the reproductive age groups. Metrorrhagia and oligomenorrhea were two frequent symptoms in the hypothyroid women in our series, but most of the studies found correlation between menorrhagia and oligomenorrhea in the same group of women.6-8 Moragianni et al demonstrated the importance of thyroid profile evaluation in patients who presented with menorrhagia9 and it would Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

not be surprising if in a proportion of women with menorrhagia, hypothyroidism clinical or subclinical often coexists.8 The incidence of polymenorrhea and menometrorrhagia were very low (4.2% each) in our study. Polymenorrhea (2.7%) was also designated as the least common type of menstrual disorder described in many reports.10,11 Hypothyroid women usually are associated with abnormal menstrual cycle due to anovulation and our study found anovulatory cycle in 66.66% of cases. Krassas7 in his study also noted that hypothyroidism is commonly associated with the failure of ovulation. So, in anovulatory cycle due to estrogen dominance there will be prolonged proliferation or disordered proliferation or hyperplasia. Mansfield et al12 reported the same histopathological finding in the anovulatory cycle. Specific mention should be made about disordered proliferation of endometrium, which some would include within hyperplasia as it lacks increased ratio of glands to stroma, which otherwise characterizes hyperplasia. In the present study, no correlation was noted between menorrhagia and subsequent histopathologic category. Pilli et al, also did not find any correlations.11 Metrorrhagic patients had more functional problems (81.82%; 9/11), which signify more chances of endometrial disturbances. Ovular oligomenorrhea was rare in the present series and our finding was inconsistent with the observations of Dutta et al.13 No significant endometrial histopathological correlation could be made in cases of polymenorrhea, menometrorrhagia and hypoamenorrhea followed by heavy bleeding because of small sample size. Conclusion In hypothyroid women, the common menstrual abnormalities were metrorrhagia and oligomenorrhea. Functional disturbance in the form of anovulation was the most frequent histopathological finding. No definite correlation was noted between menorrhagia and histology of endometrial sample in hypothyroid women. In metrorrhagic bleeding pattern incidence of abnormal endometrial histopathology was very high, but ovular oligomenorrhea was a rare finding. References 1. Bjoro T, Holmen J, KrĂźger O, Midthjell K, Hunstad K, Schreiner T, et al. Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trondelag (HUNT). Eur J Endocrinol 2000;143(5):639-47.

CLINICAL STUDY 2. Anderson BG. Free thyroxine in serum in relation to thyroid function. JAMA 1968;203(8):577-82.

8. Prentice A. Fortnightly review. Medical management of menorrhagia. BMJ 1999;319(7221):1343-5.

3. Attia AH, Youssef D, Hassan N, El-Meligui M, Kamal M, Al-Inany H. Subclinical hyperthyroidism as a potential factor for dysfunctional uterine bleeding. Gynecol Endocrinol 2007;23(2):65-8.

9. Moragianni VA, Somkuti SG. Profound hypothyroidisminduced acute menorrhagia resulting in life-threatening anemia. Obstet Gynecol 2007;110(2 Pt 2):515-7.

4. Joshi SK, Despande DH. Dysfunctional uterine bleeding. Ind J Obstet Gynecol 1964;14:360.

10. Yusuf NW, Nadeem R, Yusuf AW, Rahman R. Dysfunctional uterine bleeding. A Retrospective clinicopathological study over 2 years. Pak J. Obstet Gynaecol 1996;9:27-30.

5. Rosario YP. Dysfunctional uterine bleeding. Ind J Obstet Gynecol 1980;19:606.

11. Pilli GS, Sethi B, Mathur PR. Dysfunctional uterine bleeding. Ind J Obstet Gynecol 2002;52:87-9.

6. Krassas GE, Pontikides N, Kaltsas T, Papadopoulou P, Paunkovic J, Paunkovic N, et al. Disturbances of menstruation in hypothyroidism. Clin Endocrinol (Oxf ) 1999;50(5):655-9.

12. Mansfield MJ, Emans SJ. Adolescent menstrual irregularity. J Reprod Med 1984;29(6):399-410.

7. Krassas GE. Thyroid disease and female reproduction. Fertil Steril 2000;74(6):1063-70.

13. Dutta DC. Abnormal menstrual bleeding.Text book of Gynaecology. 2nd edition, New Central Book Agency Pvt Ltd.: Calcutta 1994:p.177.

 ...Cont'd from page no. 10

unresponsive to medical therapy. Cabergoline, which has a long half-life allowing once-or twice-weekly dosing, and a better tolerability profile, has become the dopamine agonist of choice and for management of pituitary adenomas multidisciplinary approach is needed. References 1. Asa SL, Ezzat S. The pathogenesis of pituitary tumours. Nat Rev Cancer 2002;2(11):836-49. 2. Vallette-Kasic S, Morange-Ramos I, Selim A, Gunz G, Morange S, Enjalbert A, et al. Macroprolactinemia revisited: a study on 106 patients. J Clin Endocrinol Metab 2002;87(2):581-8. 3. Biller BM, Luciano A, Crosignani PG, Molitch M, Olive D, Rebar R, et al. Guidelines for the diagnosis and treatment of hyperprolactinemia. J Reprod Med 1999;44(12 Suppl):1075-84. 4. Josimovich JB, Lavenhar MA, Devanesan MM, Sesta HJ, Wilchins SA, Smith AC. Heterogeneous distribution of serum prolactin values in apparently healthy young women, and the effects of oral contraceptive medication. Fertil Steril 1987;47(5):785-91. 5. Melmed S, Kleinberg D, Kronenberg HM, Melmed S, Polonsky KS, Larsen PR. (Eds.). Williams Textbook of Endocrinology. 11th edition, Saunders Elsevier: Philadelphia 2008:p.185-226. 6. Webster J, Scanlon MF. Prolactinomas. In: Clinical Endocrine Oncology. Sheaves R, Jenkins PJ, Wass JA (Eds.), Blackwell Science: Oxford 1997:p.189‑94.

7. Gillam MP, Molitch ME, Lombardi G, Colao A. Advances in the treatment of prolactinomas. Endocr Rev 2006;27(5):485-534. 8. Klibanski A. Clinical practice. Prolactinomas. N Engl J Med 2010;362(13):1219-26. 9. Schlechte JA. Clinical practice. Prolactinoma. N Engl J Med 2003;349(21):2035-41. 10. Schlechte J, el-Khoury G, Kathol M, Walkner L Forearm and vertebral bone mineral in treated and untreated hyperprolactinemic amenorrhea. J Clin Endocrinol Metab 1987;64(5):1021-6. 11. Biller BM. Hyperprolactinemia. Int J Fertil Womens Med 1999;44(2):74-7. 12. Melmed S, Jameson JL. Disorders of the anterior pituitary and hypothalamus. In: Harrison’s Principles of Internal Medicine. 16th edition, Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL (Eds.), McGrawHill: New Delhi 2008:p.2076‑97. 13. Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf ) 2006;65(2):265-73. 14. Mancini T, Casanueva FF, Giustina A. Hyperprolactinemia and prolactinomas. Endocrinol Metab Clin North Am 2008;37(1):67-99, viii. 15. Chahal J, Schlechte J. Hyperprolactinemia. Pituitary 2008;11(2):141-6. 16. Glezer A, Soares CR, Vieira JG, Giannella-Neto D, Ribela MT, Goffin V, et al. Human macroprolactin displays ...cont'd on page no. 26

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

CLINICAL STUDY

A Comparative Study to Analyze the Association of Metabolic Syndrome in Females with Diagnosed Polycystic Ovarian Syndrome Richa Singh*, Saroj Singh*, Poonam Yadav†, Harpreet Kaur‡

ABSTRACT Objectives: Polycystic ovarian syndrome (PCOS) is a common female endocrinopathy affecting 5-6% of women within the age group 12-45 years. This study was contemplated with the aim to study the prevalence of metabolic syndrome in patients of PCOS and to study the spectrum of clinical features of metabolic syndrome in patients of PCOS. Material and methods: This case-controlled study was conducted on 50 cases of diagnosed PCOS females and compared with 50 healthy age and body mass index (BMI) matched controls. Results: The prevalence of metabolic syndrome in PCOS patients was found to be 24% and in control group it was 6%. Among patients with metabolic syndrome 14% of patients had high blood pressure, 12% had impaired fasting glucose, 38% have high waist-hip ratio, 14% have raised serum triglycerides and 44% had decreased high-density lipoprotien (HDL). Conclusion: It is observed that metabolic syndrome manifests at an early age in women with PCOS. In order to prevent metabolic syndrome one should maintain BMI <25 and waist circumference <35 inches. Key words: Metabolic syndrome, polycystic ovarian syndrome, hyperinsulinemia

olycystic ovarian syndrome (PCOS) is one of the most common female endocrinopathy affecting 5-6% of women within the age group 12-45 years. These patients are at high-risk of developing infertility, dysfunctional uterine bleeding, endometrial carcinoma and a number of metabolic disorders including insulin resistance, hyperinsulinemia, type 2 diabetes mellitus, hypertension, dyslipidemia and cardiovascular disease. Due to these facts, early diagnosis of the syndrome should be emphasized. This background knowledge demands the necessity to work out the prevalence of metabolic syndrome in women with PCOS in our society and to measure the strength of their association in the Indian scenario.

Material and Methods This study was conducted on 50 cases of diagnosed PCOS coming to our hospital and was compared with 50 healthy age and body mass index (BMI) matched women (control group) over a period of 1 year. Inclusion Criteria

Around 50 cases diagnosed to have PCOS by the Rotterdam European Society of Human Reproduction Embryology/The American Society of Reproductive Medicine (ESHRE/ASRM) PCOS group’s revised 2003 criteria, with presence of any two of the three criteria, were recruited for the study. These criteria are:

Aims and Objectives • To study the prevalence of metabolic syndrome in patients of PCOS.

• Oligo and/or anovulation

• To study the spectrum of clinical features of metabolic syndrome in patients of PCOS.

• Polycystic ovaries (as confirmed by USG)

*Professor † Lecturer ‡ Jr - III Dept. of Obstetrics and Gynecology SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Richa Singh Professor Chauhan Nursing Home, 1/120-G, Delhi Gate Agra - 282 002, Uttar Pradesh E-mail: chauhan.richavishal@gmail.com

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

• Clinical and/or biochemical signs of hyperandrogenism

The criteria for metabolic syndrome in women with PCOS. According to National Cholesterol Education Program (NCEP), Adult Treatment Panel III (ATP III) 2001. Three out of these five will qualify for the syndrome: • Abdominal obesity (waist circumference ≥88 cm or 35 inches) and ≥80 cm for Asian females. • Triglycerides ≥150 mg/dL 23

CLINICAL STUDY • High-density lipoprotein (HDL) cholesterol ≤50 mg/dL

in Table 5. THat the prevalence of metabolic syndrome in various studies is shown in Table 6.

• Blood pressure ≥130/85 mmHg

Discussion

• Fasting plasma glucose ≥100 mg/dL or previously diagnosed type 2 diabetes. After taking careful history from the patient and conducting examination, following investigations were carried out - hemogram, fasting blood sugar, oral glucose tolerance test (OGTT), fasting insulin, fasting lipid profile, hormonal estimations for leuteinizing hormone, follicle-stimulating hormone, testosterone, estrogen, progesterone and ultrasound abdomen. In these women fasting blood was drawn for glucose, insulin and lipid profile, which included triglycerides, total cholesterol, HDL and low-density lipoprotein (LDL) cholesterol. A 2-hour 75 g glucose tolerance test was done in all PCOS patients. Two markers for obesity, such as BMI and waist-hip ratio, which depicts central obesity were used to study relationship of obesity to lipid parameters. Height (m) and weight (kg) measurements can be used to calculate the BMI (BMI = Weight in kg/height in m2). Waist-hip ratio can be calculated after measuring waist circumference between pelvic brim and costal margin, while hip circumference is taken at the level of the greater trochanter. Waist-hip ratio >0.85 is considered abnormal, while <0.85 normal. The results were subjected to statistical analysis wherever applicable. Results The profile of patients include in the study is shown in Table 1. The distribution of cases and controls according to BMI (kg/m2) is shown in Table 2.

This was a cross-sectional case-control study of 100 females attending our OPD over a period of 1 year. If we compare BMI matched cases and controls, then also lipid profile derangement is associated more with PCOS obese than non-PCOS obese (p < 0.04). This is in accordance with the study of Macut et al5 who found that overweight and normal weight women with PCOS have higher incidence of lipid profile derangement than their controls. Wild et al6 found that dyslipidemia is more common in PCOS. In our study among patients with lipid profile derangement, 44% had decreased HDL as compared Table 1. Patient Profile Age group 15-25

26-35

No.

No. %

Socioeconomic status Total

Low

High

100

Cases

Controls

P value <0.04.

Table 2. Distribution of Cases and Controls According to BMI (kg/m2) Category according to BMI (kg/m2)

Cases

Controls

No.

Underweight (≤19.9)

Normal (20-24.9)

It is seen that 67% of patients included in the study were overweight or obese. Table 3 shows distribution of cases according to fasting insulin levels. Fasting insulin levels were raised in 24% of cases and 10% of controls.

Overweight (25-29.9)

Obese (≥30)

Total

100

Distribution of cases according to components of metabolic syndrome in patients of PCOS is shown in Table 4. It was seen that ↓HDL-C levels were seen in 44% of cases and 12% of controls. Waist-hip ratio >0.85 cm was seen in 38 of cases and 14% of controls. Comparative evaluation of clinical spectrum of metabolic syndrome in cases and control is depicted

Table 3. Distribution of Cases According to Fasting Insulin Levels Category

Cases

Controls

No.

Normal

Increased

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

CLINICAL STUDY Table 4. Distribution of Cases according to Components of Metabolic Syndrome in Patients of PCOS Clinical components

Cases

Controls

Positive

BP >130/85 mmHg

Impaired fasting blood glucose (>100 mg/dL)

Waist-hip ratio >0.85 cm

↑STG (>150 mg/dL)

↓HDL-C (<50 mg/dL)

PCOS = Polycystic ovarian syndrome; BP = Blood pressure; HDL-C = High-density lipoprotein cholesterol; S. = Serum; TG = Triglyceride

Table 5. Comparative Evaluation of Clinical Spectrum of metabolic syndrome in Cases and Control Clinical parameters

Controls (50)

Cases (50)

P value

0.52

23.75

24.25

0.78

SBP (mmHg)

110

120

0.06

DBP (mmHg)

0.06

S. cholesterol (mg/dL)

175.2

201.2

0.02

S. TG (mg/dL)

110.7

133.3

0.03

HDL (mg/dL)

35.2

25.4

0.04

LDL (mg/dL)

105.2

130.8

0.04

VLDL (mg/dL)

12.2

18.12

0.02

Insulin (µIU/mL)

5.1

6.5

0.04

Fasting glucose (mg/dL)

0.04

Age (years) BMI

ANOVA test is used for calculating p value.

Table 6. Prevalence of Metabolic Syndrome in Various Studies Study Our study Glu ceck et al (USA) Dey (India)

Ehrmann et al Dokras et al4

Year

Prevalence of metabolic syndrome (%)

2012-13

2003

43-46

2011

2006

33.4

2005

47.3%

to 12% of control (p < 0.05). Low HDL is having more detrimental effect on lipid profile derangement predictions among cases, which is in accordance with a study in Teharian women by Moini et al,7 where

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

low HDL was found in 96.9% of cases of metabolic syndrome in PCOS. Study by Dey et al2 showed decreased HDL in 50% cases. In our study, waist circumference, which depicts central obesity ≥80 cm was found in 38% of cases and 14% of controls (p < 0.05). It is different from the study done by Ehrmann et al,3 which supports high value of waist circumference by citing 80% of subjects above 88 cm. In our study, fasting insulin level showed increase in 24% of cases and 10% of control (p < 0.05) it shows a significant difference among women with metabolic syndrome in comparison to those without metabolic syndrome as supported by Dokras et al4 study in 2005. We observed that, while USA women and Indian women have similar androgen levels, similar blood pressure, similar total cholesterol and LDL, USA women have higher body weight, higher fasting insulin, higher fasting glucose level, lower HDL and raised triglycerides. Most of these difference occurred as a result of higher prevalence of obesity in USA group, but other factors including characteristics of diet may also be responsible. Thus, in our study prevalence of metabolic syndrome is 24% among cases and 6% among age and BMI matched controls, which shows a statistically significant difference (p < 0.05) and thus PCOS per se is responsible for prevalence of metabolic syndrome. Conclusion It is observed that metabolic syndrome manifests at an early age in women PCOS. Hyperinsulinemia, a central factor in the pathogenesis of PCOS, also appears to be a critical link between PCOS and metabolic syndrome (MBS). Thus, there is an urgent necessity to assess the rising trend of metabolic syndrome among the women with PCOS and to take early measures for primary prevention of its long-term-sequel. In order to prevent metabolic syndrome maintain BMI <25 and waist circumference <35 inches to prevent the development of metabolic syndrome or candiovascular disease. An independent panel convened by the National Institutes of Health has recommended that well-designed, multicentric studies be conducted to determine factors such as obesity, that exacerbate a genetic predisposition.

CLINICAL STUDY The panel also determined the need for additional research to identify risks and treatments for complications and how to manage the common symptoms. References 1. 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. 2. Dey R, Mukherjee S, Roybiswas R, Mukhopadhyay A, Biswas SC. Association of metabolic syndrome in polycystic ovarian syndrome: an observational study. J Obstet Gynaecol India 2011;61(2):176-81. 3. Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN; PCOS/Troglitazone Study Group. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab

2006;91(1):48-53. 4. Dokras A, Bochner M, Hollinrake E, Markham S, Vanvoorhis B, Jagasia DH. Screening women with polycystic ovary syndrome for metabolic syndrome. Obstet Gynecol 2005;106(1):131-7. 5. Macut D, Damjanovic S, Panidis D, Spanos N, Glisic B, Petakov M, et al. Oxidised low-density lipoprotein concentration - early marker of an altered lipid metabolism in young women with PCOS. Eur J Endocrinol 2006;155(1):131-6. 6. Wild RA, Rizzo M, Clifton S, Carmina E. Lipid levels in polycystic ovary syndrome: systematic review and metaanalysis. Fertil Steril 2011;95(3):1073-9.e1-11. 7. Moini A, Javanmard F, Eslami B, Aletaha N. Prevalence of metabolic syndrome in polycystic ovarian syndrome women in a hospital of Tehran. Human Reprod Med 2012;10(2):127-30.



...Cont'd from page no. 22

low biological activity via its homologous receptor in a new sensitive bioassay. J Clin Endocrinol Metab 2006;91(3):1048-55. 17. Gibney J, Smith TP, McKenna TJ. The impact on clinical practice of routine screening for macroprolactin. J Clin Endocrinol Metab 2005;90(7):3927-32. 18. Petakov MS, Damjanović SS, Nikolić-Durović MM, Dragojlović ZL, Obradović S, Gligorović MS, et al. Pituitary adenomas secreting large amounts of prolactin may give false low values in immunoradiometric assays. The hook effect. J Endocrinol Invest 1998;21(3):184-8. 19. Cavallaro R, Cocchi F, Angelone SM, Lattuada E, Smeraldi E. Cabergoline treatment of risperidone-induced hyperprolactinemia: a pilot study. J Clin Psychiatry 2004;65(2):187-90. 20. Cohen LG, Biederman J. Treatment of risperidone-induced hyperprolactinemia with a dopamine agonist in children. J Child Adolesc Psychopharmacol 2001;11(4):435-40. 21. Smith S. Neuroleptic-associated hyperprolactinemia. Can it be treated with bromocriptine? J Reprod Med 1992;37(8):737-40. 22. Tollin SR. Use of the dopamine agonists bromocriptine and cabergoline in the management of risperidone-induced hyperprolactinemia in patients with psychotic disorders. J Endocrinol Invest 2000;23(11):765-70. 23. Webster J. A comparative review of the tolerability profiles of dopamine agonists in the treatment of hyperprolactinaemia and inhibition of lactation. Drug Saf 1996;14(4):228-38.

Erratum in: Drug Saf 1996;14(5):342. 24. Molitch ME. Disorders of prolactin secretion. Endocrinol Metab Clin North Am 2001;30(3):585-610. 25. Webster J, Piscitelli G, Polli A, Ferrari CI, Ismail I, Scanlon MF. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group. N Engl J Med 1994;331(14):904-9. 26. Morange I, Barlier A, Pellegrini I, Brue T, Enjalbert A, Jaquet P. Prolactinomas resistant to bromocriptine: longterm efficacy of quinagolide and outcome of pregnancy. Eur J Endocrinol 1996;135(4):413-20. 27. Vance ML, Evans WS, Thorner MO. Drugs five years later. Bromocriptine. Ann Intern Med 1984;100(1):78-91. 28. Merola B, Colao A, Caruso E, Sarnacchiaro F, Briganti F, Lancranjan I, et al. Oral and injectable long-lasting bromocriptine preparations in hyperprolactinemia: comparison of their prolactin lowering activity, tolerability and safety. Gynecol Endocrinol 1991;5(4):267-76. 29. Brue T, Lancranjan I, Louvet JP, Dewailly D, Roger P, Jaquet P. A long-acting repeatable form of bromocriptine as long-term treatment of prolactin-secreting macroadenomas: a multicenter study. Fertil Steril 1992;57(1):74-80. 30. Webster J, Piscitelli G, Polli A, D'Alberton A, Falsetti L, Ferrari C, et al. The efficacy and tolerability of long-term cabergoline therapy in hyperprolactinaemic disorders: an open, uncontrolled, multicentre study. European Multicentre Cabergoline Study Group. Clin Endocrinol ...cont'd on page no. 36

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

CLINICAL STUDY

Comparison of Laparoscopic-Assisted Vaginal Hysterectomy and Nondescent Vaginal Hysterectomy: A Retrospective Study Geeta Jain*, SK Jha†, U Palaria‡, G Joshi#, PK Verma¶, N Pangti§

ABSTRACT Objective: To compare the two techniques of hysterectomy, laparoscopic-assisted vaginal hysterectomy (LAVH) and nondescent vaginal hysterectomy (NDVH), in a retrospective nonrandomized analysis. Material and methods: Eighteen patients in the LAVH group were compared with 22 patients in the NDVH group by the same surgeon, after identifying them from operation theater records and computerized medical records over a period of 15 months. The two groups were compared with respect to intraoperative and postoperative parameters. Results: The mean age, parity, size of uterus and indications of surgery were similar in both the groups. However, LAVH was more expensive and more time consuming compared to NDVH. Otherwise, there was no significant difference between adverse events, recovery time and hospital stay in the two groups. Conclusion: Except for longer operating time and higher cost of surgery in the LAVH group, there was no difference between the two techniques. Key words: Laparoscopic-assisted vaginal hysterectomy, nondescent vaginal hysterectomy

ysterectomy is by far the most frequently performed major surgery in Obstetrics and Gynecology, second only to cesarean section. Traditionally, it was done by two routes, abdominal or vaginal, but now with the advent of endoscopy a third route (i.e., laparoscopic route is gaining popularity). Though, the vaginal route is the preferred route because of lower morbidity, less operative time and faster recovery, but the Vaginal Abdominal or Laparoscopic Uterine Excision (VALUE) study suggested that 67% of surgeons still use the abdominal approach as the operation of choice, particularly when dealing with pelvic pathology or carrying out oophorectomy.1

*Professor Dept. of Obstetrics and Gynecology † Assistant Professor Dept. of PSM ‡ Associate Professor Dept. of Anesthesia #Associate Professor Dept. of Obstetrics and Gynecology ¶ Assistant Professor Dept. of Surgery § Assistant Professor Dept. of Obstetrics and Gynecology Government Medical College, Haldwani, Uttarakhand Address for correspondence Dr Geeta Jain Professor, Dept. of Obstetrics and Gynecology Government Medical College Rampur Road, Haldwani - 263 139, Uttarakhand E-mail: ikneiv@hotmail.com

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

Laparoscopic hysterectomy was first done by Reich et al in 1989,2 and since then it has gained widespread acceptance. In laparoscopic-assisted vaginal hysterectomy (LAVH), laparoscopic dissection of parauterine tissues is done to the level of uterine arteries. It also allows removal of adnexae or adhesiolysis under direct vision more easily than vaginal hysterectomy. Although, LAVH is becoming increasingly popular, it is more expensive, more time consuming and above all needs special training. On the other hand, vaginal hysterectomy is cheaper, cosmetic (stitchless surgery) and associated with decreased morbidity.3 It can be accomplished even in large sized uterus by bisection, myomectomy, bisection debulking and clampless approach.4 Sheth,5 with his experience of 5,655 vaginal hysterectomies has brought a new dimension to nondescent vaginal hysterectomy (NDVH) in our country. However, there is ample evidence in favor and against LAVH.6 Summit et al,7 in his randomized trial found the outcomes of NDVH and LAVH similar, but with reduced cost. A surgeon's reluctance to perform vaginal hysterectomy in nonprolapsed enlarged uteri either because of lack of training or experience or fear of increased blood loss because access to uterine arteries sometimes becomes difficult or even impossible especially when dealing with large uterus; may contribute to the preference for LAVH. According to American College of Obstetricians and Gynecologists, 27

CLINICAL STUDY vaginal hysterectomies are preferred in women with a uterus no larger than 12 weeks of gestation size (approximately 280-300 g).8 Recently, the eVALuate study9 concluded that LAVH was associated with a significantly higher rate of major complications than abdominal hysterectomy. LAVH took longer to perform, but was associated with less pain, quicker recovery and better short-term qualityof-life measures. The aim of the present study was to compare LAVH with NDVH in a retrospective nonrandomized analysis, and to evaluate intraoperative and postoperative complications, operating time, hospital stay and cost of surgery. Material and Methods This was a retrospective observational study carried out in the Dept. of Obstetrics and Gynecology, Government Medical College, Haldwani (a tertiary teaching hospital) comparing LAVH and NDVH from October 2010 to December 2011. A total of 40 patients were identified from operation theater records and hospital-based computerized medical records undergoing hysterectomy for nonmalignant conditions by the same surgeon. Eighteen patients in LAVH group were compared with 22 in the NDVH group. The medical records of the patients were reviewed in terms of demographic characteristics, (i.e., age, socioeconomic status and parity, indication for hysterectomy, size of uterus). The intraoperative details like type of anesthesia, necessity of blood transfusion, injury to bladder/bowel or any other complication were studied. Postoperative complications were compared in both the groups. NDVH was done under spinal anesthesia. Circular incision was made around the cervix. After cutting the pubovesicocervical ligament urinary bladder was pushed upwards. Then anterior and posterior pouches were opened. The uterosacral and Mackenrodt ligaments were clamped, cut and ligated bilaterally. Then the uterine vessels were secured. Next step in bigger sized uteri was uterine bisection, myomectomy or a combination. In case of fundal fibroids myomectomy was done only if the fibroid was interfering with the delivery of fundus. In total hysterectomy last clamp was placed on fundal structures (i.e., round ligament, 28

medial part of fallopian tube, ovarian ligament). In case of salpingo-oophorectomy, after clamping the fundal structures, the ovary was pulled and the clamp was placed on infundibulopelvic ligament. After removing the uterus the vault was closed. LAVH was done under general anesthesia. Bipolar cautery was used. The uterus was manipulated with the help of myoma screw. The round ligaments were cauterized and cut bilaterally. If adnexa had to be preserved,fallopian tubes and ovarian ligaments were cauterized and cut and in patients requiring salpingooophorectomy, infundibulopelvic ligaments were cauterized and cut. The uterovesical fold of peritoneum was cut. The vaginal procedure began with opening the anterior and posterior pouches. The Mackenrodt's and uterosacral ligaments were clamped, cut and ligated bilaterally. After ligating the uterine arteries, the uterus was brought out and vault closed. Results The commonest indication for surgery in both the groups was dysfunctional uterine bleeding (DUB), followed by fibroid and cervical dysplasia as shown in Table 1. The age-wise distribution of cases, was almost similar in the two groups. Approximately 55.5% patients in LAVH group and 50% in NDVH group had parity 4-5, a favorable factor for vaginal surgery. Majority of the patients (72.2% in LAVH group and 63.6% in NDVH group) had uterine size â&#x2030;¤8 weeks. The size was similar in both the groups. LAVH took significantly longer time than NDVH. The operation could be completed in <90 minutes in 81.8% patients in the NDVH group, while the rest required 90-120 minutes. On the other hand, majority (94.4%) patients of LAVH group required >120 minutes; p value was 0.001 (Table 2). One patient of LAVH group had urinary bladder injury and the surgery had to be converted to abdominal hysterectomy, along with urinary bladder repair. In the NDVH group, one case had to be converted to abdominal hysterectomy because of minimal descent of cervix. Minor postoperative complications like fever, urinary tract infection were noted in both the groups. Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

CLINICAL STUDY Table 1. Comparison of Two Groups by Indications Indications

LAVH (n = 18)

NDVH (n = 22)

No. (%)

DUB

07 (38.9)

11 (50.0)

Fibroid

05 (27.8)

06 (27.3)

Cervical dysplasia

04 (22.2)

Others

02 (11.1)

Statistical tests χ = 1.5, df = 3, p = 0.7

Requiring blood transfusion

1 (5.6%)

02 (09.1)

Urinary bladder injury

1 (5.6%)

03 (13.6)

Laparotomy/Laparoscopy

Bowel injury

Age (in years) 08 (44.4)

08 (36.4)

41-45

06 (33.3)

07 (31.8)

> 45

04 (22.2)

07 (31.8)

Mean ± SD

42.7 ± 5.6

42.6 ± 4.8

χ2 = 0.5, df = 2, p = 0.8

t (38) = 0.05, p = 0.9

Parity-wise distribution of cases in the groups Parity 2-3 05 (27.8) 07 (31.8) χ2 = 0.1, df = 2, 4-5 10 (55.6) 11 (50.0) p = 0.9 6-7 03 (16.6) 04 (18.2) Comparison of size of uterus between the groups Size of uterus < 8 weeks

13 (72.2%)

14 (63.6%)

≥ 8-12 weeks

04 (22.2%)

07 (31.8%)

>12 weeks

01 (05.6%)

01 (04.6%)

χ2 = 0.5, df = 2, p = 0.8

Table 2. Comparison of Operating Time Between the Groups LAVH (n = 18)

NDVH (n = 22)

No. (%)

0 (0.0)

18 (81.8)

χ2 = 38.7, df = 2,

90-120 minutes

01 (5.6%)

04 (18.2)

p = 0.001

>120 minutes

17 (94.4%)

0 (0.0)

140.6 ± 8

73.2 ± 14.7

Mean ± SD

NDVH (n = 22)

Statistical tests

t (33.7) = 18.5, p = 0.001

However, one patient in the LAVH group had prolonged hospital stay (15 days) because of typhoid. Two patients in the NDVH group also had prolonged hospital stay, because of secondary hemorrhage, which was managed conservatively. One patient in LAVH group required readmission because of urinary tract Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

2 (9.1%)

1 (5.6%)

1 (4.6%)

2 (9.1%)

Pyrexia ≥ 38 C

2 (11.1%)

3 (13.6%)

Urinary tract infection

3 (16.7%)

4 (18.2%)

1 (5.6%)

1 (4.6%)

Postoperative complications Secondary hemorrhage 0

≤ 40

60-90 minutes

LAVH (n = 18) Intraoperative complications

Age-wise distribution of cases between the two groups

Operating time

Table 3. Comparison of Complications Between the Groups

Vault hematoma Readmission

infection on account of ureteric stone. One patient in the NDVH group required readmission, because of secondary hemorrhage, which responded to conservative treatment (vaginal packing, systemic and local antibiotics)(Table 3). In the NDVH group, majority patients (59.1%) required three suture materials, while in the LAVH group 83.3% required only two suture materials. One major difference in both the groups was the cost of surgery. Ours being a Government Medical College, the cost of NDVH in our hospital is only ` 800 ± 300, while that of LAVH is ` 4,300 ± 500 (p = 0.001). The cost of medicines used during and after surgery was excluded from this. Discussion In our study, the mean age of the patients was same for both the groups. The major indication of surgery was DUB in both the groups, and majority of patients had uterine size ≤8 weeks. Since, the advent of LAVH by Reich in 1989, the uptake of this procedure has been slow and subject to considerable geographic variation. The reasons could be many folds. One is the cost of equipment, as laparoscope is an expensive instrument and may not be available in many hospitals, second is the training for laparoscopic surgery. Laparoscopic surgery needs more training and the learning curve is slow. A third factor is 29

CLINICAL STUDY the time, LAVH takes compared to NDVH. This has been shown in a number of studies,6,10,11 including this one. NDVH took <90 minutes in 81.8% patients, while 94.4% patients of LAVH group required >120 minutes (p = 0.001). Therefore, given the pressure on operating time, there is often a reluctance to spend longer performing a surgery than is required.

2. Reich H, De Caprio J. McGlynn F. Laparoscopic hysterectomy. J Gynaecol Surg 1989;5:213-6.

A fourth important factor is the cost of surgery. The cost of NDVH was approximately ` 800 ± 300, while that of LAVH is ` 4,300 ± 500. The reasons are two folds, one is the higher cost of laparoscopic surgery and second is the charge of general anesthesia. The charges in our hospital are very low, being a Government Medical College, where the beds are free and majority of medicines are provided free by the government.

5. Sheth SS. The scope of vaginal hysterectomy. Eur J Obstet Gynecol Reprod Biol 2004;115(2):224-30.

However, there was no significant difference in the adverse events, postoperative recovery phase, which were almost similar in both the groups. Like Richardson12 and Roy et al11, we also did not find any difference in terms of blood loss, intra- and postoperative complications, requirement of analgesics, recuperation time and hospital stay. Conclusion The aim of the present study was to compare NDVH with LAVH. The main findings which came out from this study was the increased operating time and higher cost of surgery in the LAVH group. In comparison NDVH was cheaper and less time consuming. Otherwise, other outcome variables like intra- and postoperative complications, blood loss, postoperative pain and hospital stay were similar in both the groups. References 1. McPherson K, Metcalfe MA, Herbert A, Maresh M, Casbard A, Hargreaves J, et al. Severe complications of hysterectomy: the VALUE study. BJOG 2004;111 (7):688-94.

3. Clinch J. Length of hospital stay after vaginal hysterectomy. Br J Obstet Gynaecol 1994;101(3):253-4. 4. Unger JB. Vaginal hysterectomy for the woman with a moderately enlarged uterus weighing 200 to 700 grams. Am J Obstet Gynecol 1999;180(6 Pt 1):1337-44.

6. McCracken G, Hunter D, Morgan D, Price JH. Comparison of laparoscopic-assisted vaginal hysterectomy, total abdominal hysterectomy and vaginal hysterectomy. Ulster Med J 2006;75(1):54-8. 7. Summitt RL Jr, Stovall TG, Steege JF, Lipscomb GH. A multicenter randomized comparison of laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy in abdominal hysterectomy candidates. Obstet Gynecol 1998;92(3):321-6. 8. Precis I. An update in obstetrics and gynaecology. CD-ROM. Washington. DC. American College of Obstetricians and Gynecologists; 1989. 9. Garry R, Fountain J, Mason S, Hawe J, Napp V, Abbott J, et al. The eVALuate study: two parallel randomised trials, one comparing laparoscopic with abdominal hysterectomy, the other comparing laparoscopic with vaginal hysterectomy. BMJ 2004;328(7432):129. 10. Khanam NN, Chakma B, Chowdhary SB, Nahar K, Rahman N, Homaira R. Non-descended vaginal hysterectomy – Is a reasonable alternative to LAVH? South Asian Federation Obstet Gynecol 2009;1(1):47-52. 11. Roy KK, Goyal M, Singla S, Sharma JB, Malhotra N, Kumar S. A prospective randomised study of total laparoscopic hysterectomy, laparoscopically assisted vaginal hysterectomy and non-descent vaginal hysterectomy for the treatment of benign diseases of the uterus. Arch Gynecol Obstet 2011;284(4):907-12. 12. Richardson RE, Bournas N, Magos AL. Is laparoscopic hysterectomy a waste of time? Lancet 1995;345 (8941):36-41.

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CASE REPORT

Mullerian Agenesis: An Unusual Presentation as Hematometra and Bilateral Hematosalpinx Sudhir Gupta*, Ankita Kumari†

ABSTRACT A case of hematometra with bicornuate uterus and bilateral hematosalpinx in a 15-year-old girl complicated by vaginal agenesis and absent cervix is presented. She was managed by abdominal hysterectomy and bilateral salpingectomy. Bilateral ovaries were conserved. Key words: Mullerian agenesis, hematometra, hematosalpinx

ullerian agenesis occurs in one out of every 4,000-10,000 females.1 The independent occurrence of congenital hematometra without hematocolpos is a rare mullerian duct anomaly that results from a noncommunicating rudimentary horn with functioning endometrium or primary cervical atresia and absent upper vagina.2-4 Women affected by this disorder often have accompanying renal, skeletal and other anomalies.5 We report a case of bicornuate uterus with hematometra and bilateral hematosalpinx in a 15-year-old girl who presented with acute abdominal pain and 6 × 4 cm pelvi-abdominal mass (Fig. 1).

Case Report A 15-year-old unmarried female presented with complaint of primary amenorrhea with cyclical abdominal pain for past 12 months. Pain was relieved by oral analgesics. There were no bladder or bowel complains. Her general and systemic examinations were within normal limits. Examination per abdomen revealed a firm, well-defined, nontender, noncompressible and nonreducible mass measuring 6 × 4 cm in left iliac fossa. Per rectal examination

*Antenatal Medical Officer and Lecturer † Senior Resident Dept. of Obstetrics and Gynecology BRD Medical College, Gorakhpur, Uttar Pradesh Address of correspondence Dr Ankita Kumari H. No. 727, Anand Vihar Colony Rapti Nagar, Arogya Mandir Gorakhpur, Uttar Pradesh - 273 003 E-mail: drankita09@gmail.com

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was noncontributory. Per vaginal examination was not carried as she was unmarried. All routine examinations revealed no obvious abnormality. An ultrasound scan of pelvis and abdomen revealed hematometra with bilateral hematosalpinx. Computed tomography scan showed thick-walled cystic lesion in left lumbar region continuous with hematometra. Examination under anesthesia revealed a blind lower vagina of 2 cm. On rectal examination, tense and firm mass was felt. A diagnostic laparoscopy was performed that revealed a bicornuate uterus with hematometra; bilateral fallopian tubes were distended and bluish in color suggestive of hematosalpinx. Both ovaries were normal. Stick-like band was seen between lower half of both mullerian ducts.

Figure 1. Intraoperative pho*tograph showing bicornuate uterus with hematometra and bilateral hematosalpinx.

CASE REPORT On laparotomy, bilateral hematosalpinx with bilateral normal ovaries and distended bicornuate uterus was found. The lower part of uterus, cervix and upper three-fourth of vagina were not formed. Routine hysterectomy along with removal of both fallopian tubes was done. Both ovaries were conserved. The patient had an uneventful postoperative recovery. Her stitches were removed on the eight postoperative day and she was allowed to go home the same day. Discussion Complete cervicovaginal agenesis with a functioning endometrium in a bicornuate uterus is an extremely rare mullerian duct malformation.6 Only few cases of such abnormality have been reported along with their surgical procedures. This 15-year-old girl had cyclical abdominal pain for last 12 months. As she was in perimenarchal age and presented with an abdominal mass, it was suspected to be due to cryptomenorrhea resulting from entrapped menstrual blood in the uterine cavity causing pain. A pelvi-abdominal ultrasound showed hematometra. Diagnostic laparoscopy confirmed bicornuate uterus with bilateral hematosalpinx with absent cervix and upper vagina. Our case emphasizes that mullerian anomalies should be considered among the differential diagnosis of cyclical abdominal pain that responds poorly to analgesics. As developmental anomalies of urinary and mullerian tracts are commonly associated, the former anomalies should be specifically investigated before elective surgery is carried out. The general consensus of treatment of these patients has been to remove the mullerian structures during initial operation so as to avoid postoperative complications. The same principle of treatment was applied in the case described.

Conclusion When one encounters blocked uterus, it should be thoroughly evaluated especially in adolescents with relevant investigations keeping in mind the rare possibility of mullerian anomaly. Early diagnosis and prompt treatment is recommended in these patients to avoid future gynecological and obstetrical complications. Although technical advances favor reconstructive surgery for cervicovaginal agenesis, it must be emphasized that these complex procedures are not without complications resulting in recurrence of hematometra ultimately requiring hysterectomy. In this patient, the decision for hysterectomy was considered most appropriate to suit her social circumstances. References 1. Envans TN, Poland ML, Boving RL. Vaginal malformations. Am J Obstet Gynaecol 1981;141:910-20. 2. Rana A, Gurung G, Begum SH, Adhikari S, Neupane BB. Hysterectomy for hematometra in a 15 years-old mentally handicapped girl with congenital cervicovaginal agenesis and concomitant ovarian adenoma. J Obstet Gynaecol Res 2008;34(1):105-7. 3. Garat JM, Martinez E, Aragona F, Gosalbez R. Cervical urinary atresia with hematometra: a rare case of urinary retention in a girl. J Urol 1984;132(4):772-3. 4. Khunda SS, Al-omari S. A new approach in the management of lower mullerian atresia. J Obstet Gynaecol 1998;18(6):566-8. 5. Miller PB, Forstein DA. Creation of a neovagina by the Vecchietti procedure in a patient with corrected high imperforate anus. JSLS 2009;13(2):221-3. 6. Gurbuz A, Karateke A, Haliloglu B. Abdominal surgical approach to a case of complete cervical and partial vaginal agenesis. Fertility Sterility 2005;84(1):217.

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Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

CASE REPORT

Posterior Reversible Encephalopathy Syndrome in Postpartum Normotensive Woman: A Rare Presentation M Siva Sundari*, KS Rajeswari†, Nandhini Elumalai‡

ABSTRACT Posterior reversible encephalopathy syndrome (PRES) is a rare acute neurologic condition characterized by headache followed by deterioration, including confusion seizures or cortical visual disturbances. Our case is a rare presentation of PRES in a postpartum normotensive woman after an uneventful cesarean delivery under spinal anesthesia. Key words: Posterior reversible encephalopathy syndrome, spinal anesthesia

osterior reversible encephalopathy syndrome (PRES) has occurred in patients with hypertensive encephalopathy, renal failure, immunosuppresion and postpartum eclampsia.1,2 We report a case of PRES, which occurred in the postpartum period with normal blood pressure (BP) and managed successfully. Case Report A 26-year-old primigravida, booked, normotensive was induced at 37 weeks of gestation in view of obstetric cholestasis of pregnancy. She underwent emergency lower-segment cesarean section under spinal anesthesia in view of fetal distress. Postoperatively her BP was normal. On second postoperative day, patient developed bifrontal headache, particularly when in an erect position, it was relieved by being recumbent. Headache improved (Visual Analog Scale (VAS), 1/10) after supportive therapy including oral analgesics (paracetamol, 2 g/day), intravenous hydration and bed rest. Her BP was 120/70 mmHg. On third postoperative day, patient complained of severe throbbing headache (VAS 10/10) over the occipital area, which was no longer postural. *Associate Professor † Professor ‡ III Year MS Postgraduate Dept. of Obstetrics and Gynecology Sri Ramachandra University Porur, Chennai, Tamil Nadu Address of correspondence Dr M Siva Sundari L-170, Marvel Apoorva Apartments 4/12, Kalasathamman Koil Street Ramapuram, Chennai 600 089, Tamil Nadu E-mail: sivasundaridr@yahoo.com

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

BP was 130/70 mmHg, treated conservatively with analgesics and intravenous hydration. After 2 hours, she developed blurring of vision followed by one episode of generalized tonic and clonic convulsions. During postictal period, she had total loss of vision. Neurologist opinion was obtained. Patient was treated in intensive care unit with magnesium sulfate (Zuspan’s regime) for 24 hours, injection levetiracetam 1 g intravenous b.i.d. for 48 hours and injection mannitol 100 mL infusion t.d.s. for 24 hours. Magnetic resonance imaging (MRI) brain FLAIR T 2-weighted axial image showed bilateral symmetric hyperintense areas involving the bilateral frontal, parietal subcortical white matter, bilateral basal ganglia, occipital and cerebellar hemispheres suggestive of PRES (Figs. 1 and 2). MR venogram

Figure 1. MRI showing bilateral hyperintense areas in basal ganglia.

CASE REPORT symptom resolution without neurological deficit. Acute treatment for cerebral vasospasm is essential.6 Nimodipine, a calcium antagonist has been shown to be associated with a reduced rate of infarction because of cerebral vasospasm, but the efficacy of magnesium, a drug with calcium antagonist properties in treating cerebral vasospasm is comparable to that of nimodipine.6 Several clinical studies have shown that intravascular magnesium sulfate safely relieved maternal cerebral vasospasm.7-9 Conclusion We report this case due to rare presentation of PRES in a postpartum normotensive woman after spinal headache and successful appropriate management. References Figure 2. MRI showing bilateral hyperintense areas in occipital region.

was normal, fundus also normal. Throughout her BP was 130/70 mmHg. There was no proteinuria, renal function test, liver function test, serum electrolytes and serum calcium were normal. She completely regained her vision after 24 hours. Her neurological symptoms completely resolved by 48 hours. She was discharged on 8th postoperative day with anticonvulsant medications for 1 month. She was followed up for almost 5 months and she is free of neurological symptoms. Discussion PRES is a rare acute neurologic condition characterized by headache followed by deterioration, including confusion, seizures or cortical visual disturbances. PRES has been reported to be reversible.1 PRES refers to a clinicoradiological entity with characteristic features on neuroimaging and nonspecific symptoms comprising headache, confusion, visual disturbances and seizures.3 The lesions in PRES are thought to be due to vasogenic edema, predominantly in the posterior cerebral hemispheres and reversible with appropriate management.3 The typical MRI findings of PRES are most apparent as hyperintensity of FLAIR images in the parieto-occipital and posterior-frontal cortical and subcortical white matters. Less commonly brainstem, basal ganglia and cerebellum are involved.3 However, irreversible brain damage can sometimes occur due to late-recognition or incorrect treatment.4,5 Importantly, treating the underlying problem usually leads to 34

1. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334(8):494-500. 2. Lamy C, Oppenheim C, MĂŠder JF, Mas JL. Neuroimaging in posterior reversible encephalopathy syndrome. J Neuroimaging 2004;14(2):89-96. 3. Naqi R, Ahsan H, Azeemuddin M. Posterior reversible encephalopathy syndrome: a case series in patients with eclampsia. J Pak Med Assoc 2010;60(5):394-7. 4. Stott VL, Hurrell MA, Anderson TJ. Reversible posterior leukoencephalopathy syndrome: a misnomer reviewed. Intern Med J 2005;35(2):83-90. 5. Antunes NL, Small TN, George D, Boulad F, Lis E. Posterior leukoencephalopathy syndrome may not be reversible. Pediatr Neurol 1999;20(3):241-3. 6. Ho CM, Chan KH. Posterior reversible encephalopathy syndrome with vasospasm in a postpartum woman after postdural puncture headache following spinal anesthesia. Anesth Analg 2007;105(3):770-2. 7. Belfort MA, Moise KJ Jr. Effect of magnesium sulfate on maternal brain blood flow in preeclampsia: a randomized, placebo-controlled study. Am J Obstet Gynecol 1992;167(3):661-6. 8. Belfort MA, Saade GR, Moise KJ Jr. The effect of magnesium sulfate on maternal and fetal blood flow in pregnancy-induced hypertension. Acta Obstet Gynecol Scand 1993;72(7):526-30. 9. Naidu S, Payne AJ, Moodley J, Hoffmann M, Gouws E. Randomised study assessing the effect of phenytoin and magnesium sulphate on maternal cerebral circulation in eclampsia using transcranial Doppler ultrasound. Br J Obstet Gynaecol 1996;103(2):111-6.

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JOURNAL SCAN

Research Review

Effect of Zinc Supplementation on Pregnancy and Infant Outcomes: A Systematic Review Poor maternal zinc status has been associated with fetal loss, congenital malformations, intrauterine growth retardation, reduced birth weight, prolonged labor and pre-term or post-term deliveries. During the past 30 years, numerous randomized controlled trials of zinc supplementation have been performed. In 2007, a systematic review and meta-analysis of these trials revealed that maternal zinc supplementation resulted in a small but significant reduction in pre-term birth. A meta-analysis was undertaken with the aim to update previous review and expand the scope of assessment to include maternal, infant and child health outcomes. Electronic searches were carried out to identify peer-reviewed, randomized controlled trials where daily zinc supplementation was given for at least one trimester of pregnancy. The investigators applied the study selection criteria, assessed trial quality and abstracted data. A total of 20 independent intervention trials which took place across five continents between 1977 and 2008 were identified. These trials involved more than 11,000 births and most studies assessed the zinc effect against a background of other micronutrient supplements, but five were placebo-controlled trials of zinc alone. Zinc was supplemented in doses which ranged from 5 to 50Â mg/day. It was seen that only the risk of pre-term birth reached statistical significance (summary relative risk 0.86 [95% confidence interval 0.75, 0.99]). There was no evidence that supplemental zinc affected any parameter of fetal growth (risk of low birth weight, birth weight, length at birth or head circumference at birth). Six of the 20 trials were graded as high-quality. The evidence that maternal zinc supplementation lowers the risk of pre-term birth was graded low; evidence for a positive effect on other fetal outcomes was graded as very low. The effect of zinc supplementation on pre-term birth, if causal, might reflect a reduction in maternal infection, a primary cause of prematurity. It was concluded that results published to date suggested no harm but uncertain benefits with maternal zinc supplementation in pregnancy. The fact that maternal zinc supplementation might reduce the occurrence of preterm birth, or the frequency of diarrhea in childhood, is indeed encouraging, as even small reductions in these events would be significant public health achievements. Source: Chaffee BW, King JC. Paediatr Perinat Epidemiol 2012;26 Suppl 1:118-37.

Zinc Critical for Pregnancy BAlthough it is folic acid that usually gets much attention because it helps prevent birth defects, zinc should also be considered since it also plays a key role in pregnancy. The fact is that a womanâ&#x20AC;&#x2122;s requirement for zinc increases during pregnancy since it is needed during development of the embryo and fetus. As a result many pregnant women tend to have mild-to-moderate zinc deficiency. It has been established that zinc is crucial for the functioning of more than 300 different enzymes, which means it plays a role in a great number of bodily activities. Some of those activities are critical during pregnancy, because they involve embryo and fetal development as well as infant growth. Studies done in the recent past have shown that babies born to mothers who take zinc during pregnancy experience several important health- and growthrelated benefits. Women thus need to consider zinc supplementation both before and during pregnancy, because zinc deficiency is common among women of childbearing age. A study was conducted on nearly 1,300 pregnant women to evaluate the effect of selected nutrients during pregnancy and for 1 month after delivery. The women were divided into two groups: One group took 15 mg of

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 1

JOURNAL SCAN zinc along with a supplement that contained 60 mg of iron and 250 mg of folic acid; the other group took the supplement without the zinc. It was seen that compared with those who took the supplement only, those who took the zinc had infants with significantly larger average growth measures that began in the 4th month and continued until 1 year of age. This finding suggests that zinc supplementation helps with the accumulation of lean tissue mass, which is beneficial to a child’s health. It also supports the fact that zinc deficiency, even a mild one, can hinder growth in young children. A deficiency of zinc may also lead to an increase in preterm births. A review of 17 trials that involved more than 9,000 women and their babies, came to the conclusion that zinc supplementation helps reduce preterm births. Moreover, zinc supplementation during pregnancy has been shown to prevent specific types of memory impairments that are caused by excess alcohol use during early pregnancy. The recommended daily intake for zinc during pregnancy is 15 mg, but a higher dose may be needed because high intake of folic acid can interfere with absorption of zinc and thus create a deficiency of zinc. It is thus best to limit intake of folic acid to no more than 800 mg/day. However, women should consult their physician before taking zinc or any other supplement during pregnancy. Sources: Cole CR, Lifshitz F. Pediatr Endocrinol Rev 2008;5(4):889-96. Hess SY, King JC. Food Nutr Bull 2009; 30(1 Suppl):S60-78. Iannotti LL, Zavaleta N, Leon Z, et al. Am J Clin Nutr 2008;88(1):154-60. Mahomed K, et al. Cochrane Database Syst Revi 2006;(4):CD000230. Summers BL, et al. Behav Brain Res 2008;186(2):230-8.

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(Oxf ) 1993;39(3):323-9. 31. Verhelst J, Abs R, Maiter D, van den Bruel A, Vandeweghe M, Velkeniers B, et al Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab 1999;84(7):2518-22. 32. Webster J, Piscitelli G, Polli A, D'Alberton A, Falsetti L, Ferrari C, et al. Dose-dependent suppression of serum prolactin by cabergoline in hyperprolactinaemia: a placebo controlled, double blind, multicentre study. European Multicentre Cabergoline Dose-finding Study Group. Clin Endocrinol (Oxf ) 1992;37(6):534-41. 33. Biswas M, Smith J, Jadon D, McEwan P, Rees DA, Evans LM, et al. Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas. Clin Endocrinol (Oxf ) 2005;63(1):26-31. 34. Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi G. Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia.

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N Engl J Med 2003;349(21):2023-33. 35. Dekkers OM, Lagro J, Burman P, Jørgensen JO, Romijn JA, Pereira AM. Recurrence of hyperprolactinemia after withdrawal of dopamine agonists: systematic review and meta-analysis. J Clin Endocrinol Metab 2010;95(1):43-51. 36. Kharlip J, Salvatori R, Yenokyan G, Wand GS. Recurrence of hyperprolactinemia after withdrawal of long-term cabergoline therapy. J Clin Endocrinol Metab 2009;94(7):2428-36. 37. Serri O, Rasio E, Beauregard H, Hardy J, Somma M. Recurrence of hyperprolactinemia after selective transsphenoidal adenomectomy in women with prolactinoma. N Engl J Med 1983;309(5):280-3. 38. Serri O, Hardy J, Massoud F. Relapse of hyperprolactinemia revisited. N Engl J Med 1993;329(18):1357. 39. Brada M, Jankowska P. Radiotherapy for pituitary adenomas. Endocrinol Metab Clin North Am 2008;37(1):263-75, xi.

CASE REPORT

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