Ajog july sept 2016

ISSN 0971-8788

Volume 2, Number 3, 2016

Asian Journal of

Obstetrics &

Gynaecology Practice In this Issue Incidence of Cervical Lesions in a Tertiary Care Hospital in South India: A 5-year Analysis Assessment of Parents' and Child's Attitude as Barrier to Dietary Compliance in Celiac Disease Laparoscopic Evaluation of Endometriosis in Infertility and Chronic Pelvic Pain in a Tertiary Care Center Evaluation of Risk Factors and Prevalence of Gestational Diabetes Mellitus in a Tertiary Care Center Endometriosis and the Role of Resveratrol Cervical Molar Pregnancy and Its Future Fertility Discoloration in the Hands

With Best Compliments from

Asian Journal of

Online Submission

Volume 2, Number 3, 2016

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 Dr KK Aggarwal Group Editor-in-Chief IJCP Group, eMedinewS and eMediNexus Dr Veena Aggarwal MD, Group Executive Editor AJOG Specialty Panel Dr Alka Kriplani Editor Consultant Editor Dr Urmil Sharma Assistant Editors Dr Nutan Agarwal (Delhi) Dr Neera Aggarwal (Delhi) Dr A Biswas (Singapore) Dr CS Dawn (Kolkata) Dr Gauri (Delhi) Dr Suneeta Mittal (Delhi) Dr S Mehra (Delhi) Dr Prashant Mangeshikar (Mumbai) Dr Prakash Trivedi (Mumbai) Dr Gita Ganguly

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

Contents from the issue editor

Heart Disease: The Most Common Cause of Death and in Urban Women 5 Alka Kriplani

FROM THE DESK OF the GROUP EDITOR-IN-CHIEF

Government Releases Draft National Policy for Women 2016

6

KK Aggarwal

Clinical Study

Incidence of Cervical Lesions in a Tertiary Care Hospital in South India: A 5-year Analysis

7

Sana Aboosalih, Leena Dennis Joseph, Sai Shalini CN, Monica Kumbhat, Rajendiran S

Editorial Board

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

Cardiology Dr Praveen Chandra Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses Dr Sidhartha Das Dr A Ramachandran Dr Samith A Shetty Dr Vijay Viswanathan Dr V Mohan Dr V Seshiah Dr Vijayakumar ENT Dr Jasveer Singh Dr Chanchal Pal

Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dr Rajiv Khosla Dr JS Rajkumar Dermatology Dr Hasmukh J Shroff Dr Pasricha Dr Koushik Lahiri Dr Jayakar Thomas Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan Dr Vineet Suri Dr AV Srinivasan Oncology Dr V Shanta Orthopedics Dr J Maheshwari

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

Assessment of Parents' and Child's Attitude as Barrier to Dietary Compliance in Celiac Disease 12 Dhan Raj Bagri, RK Gupta, Priyanshu Mathur

Laparoscopic Evaluation of Endometriosis in Infertility and Chronic Pelvic Pain in a Tertiary Care Center

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Paramjit Kaur, Ruby Bhatia, Rajwinder Kaur, Aman Dev, Surinder Kumari

Evaluation of Risk Factors and Prevalence of Gestational Diabetes Mellitus in a Tertiary Care Center Paramjit Kaur, Ruby Bhatia, Nidhi Kailey, Himani Kundoo, Aman Dev

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Asian Journal of Volume 2, Number 3, 2016

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

Review Article

Endometriosis and the Role of Resveratrol

26

Anita Kant

Printed at Bon Graphics, Chennai Copyright 2016 IJCP Publications Ltd. All rights reserved.

The copyright for all the editorial material contained in journal, in the form of layout, content including images and design, is held by IJCP Publications Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.

Case Report

Cervical Molar Pregnancy and Its Future Fertility 31 Babita Ramani, Rajat Mohanty, Sudipta Patnaik

Editorial Policies The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article.

Photo Quiz

Discoloration in the Hands

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Antonio L. Aguilar Shea, Cristina Gallardo-Mayo

Note: Asian Journal of Obs and Gynae Practice does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature in this issue.

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from the issue editor

Heart Disease: The Most Common Cause of Death and in Urban Women

Dr Alka Kriplani

Professor and Head of Unit II Dept. of Obstetrics and Gynecology AIIMS, New Delhi

I

n India, urban women are more at risk of heart disease today than they were 3 years ago. The reasons for this include an unhealthy lifestyle characterized by a predominantly high trans fat, sugar and salt diet, inadequate physical exercise, increased stress levels, dependence on addictive and extremely harmful substances like alcohol and cigarettes amongst others.

The largest group of women at risk of cardiovascular disease (CVD) are those aged 35-44. CVD risk is as high amongst housewives as it is amongst working professionals. As far as risk factors for CVD are concerned, low HDL and high BMI are the two most common contributors to CVD risk setting in as early as 35 years for women.

“The established risk factors of heart disease in women include the presence of history of heart blockages; age over 55 years; high LDL (bad cholesterol) or low HDL (good cholesterol), diabetes, smoking, high blood pressure, peripheral artery disease or family history of heart disease. Risk factors, which are more potent in women than in men include regular consumption of

tobacco which causes 50% of all coronary events in women, obesity and diabetes”.

Women can Prevent Future Heart Disease v Moderate intensity physical activity for at least 30 minutes and for 60-90 minutes for weight management on most days of the week. v Avoidance and cessation of cigarette smoking and passive smoking. v Keep waist circumference less than 35 inches. v Consume a heart-friendly diet. v Presence of high triglyceride levels. One should add omega-3 fatty acids to diet. v Control cholesterol level, high blood pressure and diabetes. v Women who smoke should avoid oral contraceptive pills. v Aspirin 80 mg in more than 65 years of age should be added. v Treat underlying depression.

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Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

5

FROM THE DESK OF the GROUP EDITOR-IN-CHIEF

Government Releases Draft National Policy for Women 2016

Dr KK Aggarwal

Group Editor-in-Chief IJCP Group, eMedinewS and eMediNexus

T

he government has released draft National Policy for Women 2016 for stakeholder comments and consultations, almost a decade and half since the National Policy for Empowerment of Women, 2001 was formulated. The document is available on the website of the Ministry of Women and Child Development. The policy was released at a press conference in the capital by Smt. Maneka Gandhi, Union Minister for Women and Child Development.

The broad objective of the policy is to create a conducive sociocultural, economic and political environment to enable women enjoy de jure and de facto fundamental rights and realize their full potential. The priority areas as defined in the draft National Policy for Women are: v Health including food security and nutrition: Focus on recognizing women’s reproductive rights, shift of family planning focus also to males, addressing health issues in a life cycle continuum such as psychological and general well-being, healthcare challenges related to nutrition/hygiene of adolescents, geriatric healthcare, expansion of health insurance schemes and undernutrition. v Education: Improve access to pre-primary education, enrolment and retention of adolescent girls, implement innovative transportation models for better schooling outcomes, advocate gender champions and address disparities with regard to ICTs. v Economy: Raising visibility, engendering macroeconomic policies and trade agreements, generate gender-disaggregated land ownership database, skill development and training for women, entrepreneurial development, review of labor laws and policies, equal employment opportunities with appropriate benefits related to maternity and child care services, address technological needs of women.

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v Governance and decision making: Increasing women’s participation in the political arena, administration, civil services and corporate boardrooms. v Violence against women: Address all forms of violence against women through a life cycle approach, legislations affecting/relating to women will be reviewed/harmonized to enhance effectiveness, improve child sex ratio (CSR), strict implementation of advisories, guidelines, standard operating procedures (SoPs) and protocols, prevention of trafficking at source, transit and destination areas for effective monitoring of the networks. v Enabling environment: Gender perspective in housing and infrastructure, ensuring safe drinking water and sanitation, gender parity in the mass media and sports, concerted efforts towards strengthening social security and support services for all women especially the vulnerable, marginalized, migrant and single women. v Environment and climate change: Addressing gender concerns during distress migration and displacement in times of natural calamities due to climate change and environmental degradation.

Promotion of environmental friendly, renewable, nonconventional energy, green energy sources for women in rural households. Other emerging issues such as making cyber spaces safe place for women, redistribution of gender roles, for reducing unpaid care work, review of personal and customary laws in accordance with the constitutional provisions, review of criminalization of marital rape within the framework women’s human rights etc. are also covered in the policy… (Press Information Bureau, May 17, 2016).

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

Clinical Study

Incidence of Cervical Lesions in a Tertiary Care Hospital in South India: A 5-year Analysis Sana Aboosalih*, Leena Dennis Joseph†, Sai Shalini CN‡, Monica Kumbhat#, Rajendiran S†

Abstract In gynecological practice, there are several lesions localized to the uterine cervix, which include several inflammatory, benign, premalignant and malignant lesions. While lesions of the cervix are a major cause of morbidity in all age groups, cervical premalignant and malignant lesions are picked up on pap smear. With proper screening and treatment, mortality from carcinoma of the cervix can be greatly reduced, which has been seen in the developed countries. The exact incidence of cervical lesions is not available in this part of India where an active pap screening is lacking. Poverty, literacy levels and urbanization are all significantly related to cervical cancer incidence and mortality. With the wide range of pathologies in the uterine cervix, some lesions may appear exuberant and can be misdiagnosed as malignant.

Hence this study was taken up, with the objective to analyze the spectrum of cervical lesions, with an emphasis on the histological and morphological aspects. A retrospective analysis over a period of 5 years was done, studying all the cervical biopsies that were received in the Dept. of Pathology, SRMC, Chennai. A total of 882 cases of cervical lesions over this period of 5 years were studied. There were 107 cases (12.13%) of malignancies, 62 cases (7.03%) were premalignant, 233 cases of benign endocervical polyps (26.42%) and inflammatory pathology was observed in 480 cases (54.42%). Malignant lesions were seen in an age group of 28-80 years, Majority of non-neoplastic lesions were seen in women of the reproductive age group.

Keywords: Cervical lesions, polyps, CIN, carcinoma cervix

T

he uterine cervix is the lower portion of the uterus, which is connected to the vaginal canal.

The cervix carries out many functions, which aid to the overall reproductive health and well being of women.1 In the gynecological practice it is known that the uterine cervix can host a spectrum of lesions.

These lesions may be neoplastic or non-neoplastic in nature. Lesions of the cervix are a major cause of morbidity in all age groups. Cervices from biopsy and hysterectomy specimens constitute majority of the gynecological specimens received in the Dept. of Pathology. While inflammatory conditions like chronic cervicitis, microglandular adenosis, etc. form majority of lesions in the reproductive age group,

*Graduate † Professor ‡ Associate Professor # Postgraduate Dept. of Pathology Sri Ramachandra University, Chennai Address for correspondence Dr Leena Dennis Joseph Professor Sri Ramachandra University, Chennai E-mail: leenadj@gmail.com

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

they resolve with proper treatment. Poverty, illiteracy, low socioeconomic status and inadequate sanitation and hygiene practices are implied in the cause of increased inflammatory pathology. However, primary malignant disease of the cervix is also common and unless picked up at an earlier stage, is a major cause of mortality among women, especially those pertaining to the lower socioeconomic group who present at later stages of this disease. Carcinoma of the cervix is on the declining trend in India according to the populationbased registries; yet it continues to be a major concern for women health in India.2 The exact incidence of various cervical lesions is not available in this part of India where an active pap screening is not in place.

The cervix with its various pathologies can sometimes appear exuberant and be misdiagnosed as malignant.

Hence a detailed histological and morphological study of the spectrum of lesions of the cervix was taken up over a period of 5 years, with the aim to analyze the various types of premalignant and malignant lesions of the cervix in our patients, which will help us to understand the prevalence of different cervical lesions and help to plan and implement screening as well as awareness programs to prevent and treat the same.

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clinical study

a

b

a

b

c

d

c

d

Figure 1. Malignant lesions of the cervix: Well differentiated squamous cell carcinoma of cervix (H&E x40) (a); Moderately differentiated squamous cell carcinoma (H&E x40) (b); Adenocarcinoma of the cervix (H&E x100) (c); and Adenocarcinoma of the cervix (H&E x40) (d).

Figure 2. Benign and Inflammatory pathology of the cervix: Chronic cervicitis (H&E x100) (a); Squamous metaplasia (H&E x40) (b); Nabothian cysts (H&E x40) (c); and Benign endocervical polyp.

(H&E x40) (d).

Material and Methods

intraepithelial neoplasia, [CIN]). Of these 15 cases presented as CIN 1, 14 cases presented as CIN 2 and 33 cases were that of CIN 3.

This is a retrospective analysis over a period of 5 years. All the cervical biopsies received in the Dept. of Pathology, Sri Ramachandra Medical College and Research Institute, Chennai, were specimens for the study. The data were obtained from the archival material of the histopathology division in our hospital. The data were analyzed and the incidence and age distribution of the various lesions were studied.

Results A total of 882 cases of cervical lesions seen in the biopsy and hysterectomy specimens over this period of 5 years were studied. There were 107 cases (12.13%) of malignancies which included 96 cases of squamous cell carcinoma and 11 cases of adenocarcinoma. The squamous cell carcinoma cases were divided into keratinising and nonkeratinising types (Fig. 1). They were also graded on the basis of differentiation.

Sixty two cases (7.03%) were premalignant (cervical Cervical lesions Malignant cases 55%

7% 12%

81% 26%

Premalignant conditions Inflammatory pathology Benign endocervical polyps

Figure 3. The pie diagram shows the distribution of the various cervical lesions.

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Inflammatory pathology was observed in 480 cases (54.42%). This included chronic cervicitis, nabothian cysts, regenerative hyperplasia, ulceration and microglandular adenosis (Fig. 2). Benign endocervical polyps were recorded in 233 cases (26.42%) (Fig. 3).

As for the age distribution, malignant lesions were seen in an age group of 28-80 years, benign polyps were seen in an age group of 20-68 years, and inflammatory conditions were seen in those between 22-78 years.

Discussion The cervix is a host to a spectrum of conditions which may be inflammatory, benign, premalignant or malignant. The exact incidence of various cervical lesions is not available in this part of India where an active pap screening is not in place.

According to a latest study by Freddie Bray et al, the worldwide cancer burden is on a projected surge from 14 million new cases in 2012 to 24 million by 2035, with the greatest increases happening in developing countries. India is one of the most populous countries in the world and has a rapidly rising cancer incidence and mortality rate.3 Amongst women, cervical cancer is one of the major cancers in India. Cervical cancer is also one of the most preventable cancers through early detection and treatment. In India, studies are showing that cervical cancer rates are uniformly decreasing in Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

clinical study all urban and rural registries.4 Despite the decreasing trend, cervical cancer is still a major cancer and analysis of the various conditions affecting the cervix would help in planning and organization of programs for its control. If treatment is administered during the earliest stages of cervical cancer, 5-year survival rates can be increased to more than 90%. Unfortunately, despite the availability of methods for prevention, more than 95% of women in India have never been screened for cervical cancer. Moreover, women in India are most often diagnosed during later stages of cervical cancer, significantly reducing survival prognosis.5 Every year in India, 122,844 women are diagnosed with cervical cancer and 67,477 die from the disease.

India has a population of 432.2 million women aged 15 years and older who are at risk of developing cancer.

It is the second most common cancer in women aged 15-44 years. India also has the highest age standardized incidence of cervical cancer in South Asia at 22, compared to 19.2 in Bangladesh, 13 in Sri Lanka, and 2.8 in Iran. Therefore, it is vital to understand the epidemiology of cervical cancer in India.2 Our study is also consistent with this finding, in this region of India where the malignant lesions were seen in an age group of 28-80 years. Most common type of carcinoma was squamous cell carcinoma, 95 cases and only 11 cases of adenocarcinoma was reported in the study.

In this study of the spectrum of cervical lesions, the most commonly encountered pathology is of the inflammatory type at 81%, which is consistent with various studies from India and around the world which say that inflammatory lesions are more commonly seen than neoplastic conditions of the cervix. The age range of inflammatory lesions in our region was 22-78 years.

Studies from other parts of the country show both chronic nonspecific cervicitis and polypoidal endocervicitis commonly found in the sexually active period of women i.e. 30-60 years, with a peak incidence in the age group 41-50 years. Chronic nonspecific cervicitis was associated with other histological changes like squamous metaplasia, koilocytosis, epidermalization and nabothian cyst. Worldwide cervical inflammatory lesions are extremely common in sexually active females, at least at the microscopic level.6 In our study, majority of cervical lesions were in the 4th-5th decade of life. Chronic nonspecific cervicitis was the most common histological diagnosis Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

made (50%). No case was seen before menarche. This is similar to other reports from India.7 It is a common phenomenon in postmenopausal women. Certain lesions of chronic nonspecific cervicitis had coexisting squamous metaplasia, nabothian cysts, dysplasia and ulceration. Chlamydia trachomatis and other pathogens are associated with upper genital tract infections, pregnancy complications or sexually transmitted infections (STI). Neglected asymptomatic patients can serve as a reservoir of STI which underscores the importance of combined culture and pap smear examination. Staphylococcus aureus (42%) is found to be the most common organism causing cervicitis besides E. coli (2%), Chlamydia (6%) and Klebsiella (2%). The findings of this study should make women aware of the importance of periodic screening for STDs and also help health professionals design control measures for chronic cervicitis.8 CIN included all cases of CIN 1, CIN 2 and CIN 3. Out of 882 cases only 7.03% cases of CIN (including CIN 1, 2 and 3) were diagnosed based on the typical histological findings. Highest incidence of CIN was in the 5th-6th decade. This study also highlights that the highest incidence of squamous cell carcinoma is in the 5th decade and this finding is consistent with the study done by Dhakal et al.9 The majority of all grades of CIN can be attributed to human papilloma virus (HPV) infection especially with the cancer associated types of HPV.10 Cervical carcinogenesis must involve the presence of additional promoting factors, since only a minority of patients harbouring HPV develop cervical dysplasia. Bacterial vaginosis has been suggested as an intriguing possible cofactor in cervical carcinogenesis. A meta-analysis study with over 10,000 women and in addition a database of more than one million cervical smears, confirmed a positive association between bacterial vaginosis and cervical precancerous lesions.11 Low education and socioeconomic status, young age at marriage or first sexual intercourse, high parity and multiple male partners sexual behavior are established risk factors for carcinoma of the cervix.12 With the advent of HPV vaccination, there is a global declining trend of cervical carcinoma and CIN.13 Full use of this vaccination is not present in India and more awareness needs to be generated to achieve better levels of prevention of this disease.

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clinical study Premalignant and malignant glandular lesions of the cervix are known to often cause diagnostic problems as various benign and malignant lesions appear exuberant and may be a challenge for the practicing pathologist, considering the different morphologies these tumors may have and the overlapping features with other benign and malignant glandular lesions from and outside the cervix. In this review, the spectrum of histopathologic appearances of cervical lesions, emphasizing morphologic key features and knowing the general trend of cervical lesions is useful.14 Cervical cytology is frequently being used to screen for cervical diseases, histopathological examination of the biopsies of cervical lesions is the single best gold standard for the diagnosis of the non-neoplastic lesions of the cervix. Studies show that there is good correlation between cervical cytology and histopathology. The regular screening of women by Pap smear is a costeffective method for early detection of premalignant and malignant cervical lesions and secondary prevention of carcinoma cervix.15,16 In our 5 year retrospective study, 882 cases of cervical lesions were reported, of these 12.13% cases were malignant, 7.03% cases were premalignant, 80.84% cases were nonmalignant. Nonmalignant lesions included 54.45% of inflammatory pathology and 26.42% cases were benign endocervical polyps. This data clearly show that nonmalignant cervical pathologies are much common than malignant and premalignant lesions of the cervix in our region. This finding is in keeping with previous reports from developing countries where benign lesions are more common than malignant lesions. Various reports from other parts of the world however show malignant lesions to be more than benign cervical lesions and the reason for this can be attributed to the fact that an active “Pap screening” programs is not in place in our country.

Many benign hyperplastic or reactive processes that occur in the female genital tract may be mistaken for neoplasms both clinically and pathologically.

Awareness of the features of such lesions will aid in their correct diagnosis and prevent overtreatment of benign processes.17 The relationship between education and cancer incidence in this rural population has shown that the risk of cervical cancer is inversely associated with increasing educational levels. Also HPV positivity in 10

the rural population of Dindigul district was found to be inversely associated with education level.18 Therefore, the role of education in the determinants of cervical cancer is evident. Education is the fundamental factor among the sociodemographic and reproductive determinants of cervical cancer in low socioeconomic categories. Public awareness through education and improvements in living standards can play an important role in reducing the high incidence of cervical cancer in India. These findings further stress the importance of formulating public health policies aimed at increasing awareness and implementation of cervical cancer screening programs.19 Targeted interventions can lead to a decrease in the projected increases in cancer burden through effective primary prevention strategies, alongside the implementation of vaccination, early detection and effective treatment programs.20 Conclusion This analysis highlighted the spectrum of cervical premalignant, malignant and inflammatory lesions in women of varying age groups in our hospital.

The incidence of CIN is 7.03% and that of cancer is 12.13% and 54.42% is representative of an inflammatory pathology. The incidence of premalignant and malignant cervical lesions are very less in developed countries where pap smear is actively used for screening. Its effectiveness has to be used in this part of India by increasing its awareness among physicians and patients.

References 1. Domblae V, Gundalli S, Sonali. Histopathological analysis of uterine lesions in hysterectomy specimens. Int J Science and Research. 2015;4(5):2171-74.

2. Sreedevi A, Javed R, Dinesh A. Epidemiology of cervical cancer with special focus on India. Int J Women's Health.

2015;7:405-14.

3. Stewart BW, Bray F, Forman D, Ohgaki H, Straif K, Ullrich A, et al. Cancer prevention as part of precision medicine: ‘plenty to be done’. Carcinogenesis. 2016;37(1):2-9.

4. Badwe RA, Dikshit R, Laversanne M, Bray F. Cancer incidence trends in India. Jpn J Clin Oncol. 2014;44(5): 401-7.

5. Beining RM. Screening for cervical cancer: an exploratory study of urban women in Tamil Nadu, India. PhD (Doctor of Philosophy) thesis, University of Iowa, 2012.

Available at: http://ir.uiowa.edu/etd/2820.

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clinical study 6. Poste P, Patil A, Andola SK. Incidence of Non-neoplastic cervical pathologies recorded at a medical college. IJAS. 2015;2(2)039-050.

7. Saravanan S, Arnold J, Arul P. Histomorphological spectrum of lesions of the cervix, a retrospective study in a tertiary care hospital. J Evol Med and Dental Sciences.

2015;4(59):10326-329.

8. Ragavi PS. Magnitude of chronic cervicitis and its related factors among women attending gynaecology OPD in a tertiary health centre - Tamilnadu. Australasian Medical Journal . 2013;6(4):258.

9. Dhakal HP, Pradhan M. Histological pattern of gynecological cancers. JNMA J Nepal Med Assoc. 2009;48(176):301-5.

10. Schiffman MH, Bauer HM, Hoover RN, Glass AG, Cadell DM, Rush BB, et al. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst.

1993;85(12):958-64.

11. Gillet E, Meys JF, Verstraelen H, Verhelst R, De Sutter P, Temmerman M, et al. Association between bacterial vaginosis and cervical intraepithelial neoplasia: Systematic review and meta-analysis. PLoS ONE. 2012;7(10):e45201.

12. Suma RK, Keerthi SY, Prasanna KS, Jayaram S. A community based study of the socio demographic and behavioural risk factors for cervical cancer among urban women in coastal Karnataka. Annals of Community Health. 2014;2(2): 35-38.

13. Baldur-Felskov B, Munk C, Nielsen TS, Dehlendorff C, Kirschner B, Junge J, et al. Trends in the incidence of cervical cancer and severe precancerous lesions in Denmark, 1997-2012. Cancer Causes Control. 2015;26(8):1105-16.

14. Loureiro J, Oliva E. The spectrum of cervical glandular neoplasia and issues in differential diagnosis. Arch Pathol Lab Med. 2014;138(4):453-83.

15. Tamboli GD , Khatod LV. Accuracy of cytological findings in abnormal cervical smear by cyto-histological comparison.

J Med Educ Res. 2013;3(2):19-24.

16. Nwachokor FN, Forae GC. Morphological spectrum of non-neoplastic lesions of the uterine cervix in Warri, SouthSouth, Nigeria. Niger J Clin Pract. 2013;16(4):429-32.

17. Medeiros F, Bell DA. Pseudoneoplastic lesions of the female genital tract. Arch Pathol Lab Med. 2010;134(3):393-403.

18. Franceschi S1, Rajkumar T, Vaccarella S, Gajalakshmi V, Sharmila A, Snijders PJ, et al. Human papillomavirus and risk factors for cervical cancer in Chennai, India: A casecontrol study. Int J Cancer. 2003;107(1):127-33.

19. Thulaseedharan JV, Malila N, Hakama M, Esmy PO, Cheriyan M, Swaminathan R, et al. Socio demographic and reproductive risk factors for cervical cancer - a large prospective cohort study from rural India. Asian Pac J Cancer Prev. 2012;13(6):2991-5.

20. Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008-2030): A population-based study. Lancet Oncol.

2012;13(8):790-801.

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Obstetrics: Atypical Antipsychotics have a Modest Risk of Fetal Malformations The use of atypical antipsychotics during pregnancy is associated with a modest level of risk for fetal malformations, according to an analysis of information contained in a large and ever-expanding registry.

The absolute risk for major malformations was 1.3% for infants exposed to an atypical antipsychotic during the first trimester, and 0.9% for unexposed infants. The findings were presented at the American Society of Clinical Psychopharmacology (ASCP) 2016 Annual Meeting: Abstract 3000502 on June 2, 2016.

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

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Clinical Study

Assessment of Parents' and Child's Attitude as Barrier to Dietary Compliance in Celiac Disease Dhan Raj Bagri*, RK Gupta†, Priyanshu Mathur‡

Abstract Celiac disease (CD) is an immune-mediated systemic disorder elicited by gluten and related prolamins in genetically susceptible individuals. Lifelong adherence to a gluten-free diet (GFD) is the cornerstone treatment of CD. It is strongly recommended that gluten elimination from diet must be strict and lifelong not only to control symptoms but also to improve quality-of-life and decrease the risk of complications. Noncompliance is a major problem and the greatest challenge which the physicians face is in predicting the compliance to the GFD in children. A study was conducted by Dept. of Pediatrics, SMS Medical College and Attached Hospitals, Jaipur, to evaluate the impact of CD and the GFD on the lifestyle and well-being of children with CD and their families, with the aim to identify factors affecting compliance to GFD and to assess parents’ and child’s attitude as barrier to dietary compliance in children with CD. Keywords: Celiac disease, gluten-free diet, compliance, quality-of-life

C

eliac disease (CD) is an immune-mediated systemic disorder elicited by gluten and related prolamins in genetically susceptible individuals and characterized by the presence of a variable combination of gluten-dependent clinical manifestations, CD-specific antibodies, HLA-DQ2 or HLA-DQ8 haplotypes, and enteropathy.1 Recently, the prevalence of CD across the European countries was shown to be 1.5% based on people who had positive biopsy and tTG results.2 In the United States, the overall prevalence of CD in children up to 5 years of age is 1 in 104.3 This disease is quite prevalent in India also with rates of 1 in 96 in North India.4 Lifelong adherence to a glutenfree diet (GFD) is the cornerstone treatment of CD.5 A GFD entails strict avoidance of all products containing the proteins from wheat, barley and rye.6 It is strongly recommended that gluten elimination from diet must be strict and lifelong not only to control symptoms but

*Ex-Senior Registrar † Professor ‡ Assistant Professor Dept. of Pediatric Medicine Sir Padampat Mother and Child Health Institute, JK Lon Hospital, SMS Medical College, Jaipur, Rajasthan Address for correspondence Dr Dhan Raj Bagri C/o Sri MP Meena 181, Deep Vihar Colony, Panchyawala Sirsi Road, Jaipur, Rajasthan E-mail: meena.drdhanraj6@gmail.com

12

also to improve quality-of-life and decrease the risk of complications.7 Although a well-planned GFD may provide adequate nutrition, it may be restrictive. Strict adherence to GFD may be more challenging in children and adolescents than in adults. Compliance to GFD varies from 45% to 81% in children as reported by the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition.8 Noncompliance is a major problem and the greatest challenge which the physicians face is in predicting the compliance to the GFD in children. Noncompliance may occur due to factors like temptation and not liking the taste of gluten-free food and alternative food grains.9 In adolescents, peer pressure, unclear labelling on ready-to-eat food, and nonavailability of gluten-free food at party, marriages, and so forth have contributed to noncompliance.10 An increasingly hectic lifestyle of teenagers has contributed to a greater reliance on packaged foods which often contain gluten and thus make it inconvenient for them to adhere to restrictive diet.10 Since parents are usually responsible for food preparation for children, low level of knowledge about the diet by the parents, nonavailability of gluten-free foods and unclear labelling lead to noncompliance in children.11 Many children experience psychological reactions to being placed on a restrictive diet (e.g., feeling deprived, depressed, angry and anxious) which have been found to further decrease compliance.12 This study evaluates the impact of CD and the GFD on the lifestyle Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

clinical study and well-being of children with CD and their families, with the aim to identify factors affecting compliance to GFD and to assess parents’ and child’s attitude as barrier to dietary compliance in children with CD. This study is significant and will contribute to the current body of research by providing healthcare practitioners with information as to what predicts the compliance to GFD, which may be used to better understand education techniques for dietary instruction so that the children living with CD have less of morbidity and achieve their normal growth potential. Participants will contribute to the understanding of CD and the challenges individuals face with the GFD. Material and Methods The present study was conducted by Dept. of Pediatrics, SMS Medical College and Attached Hospitals, Jaipur, Rajasthan, India. A total of 134 CD children and parents visiting the gastroenterology super specialty clinic were studied. These children visited the clinic for growth monitoring and compliance assessment. 100 consecutive children aged between 2 years and 15 years, diagnosed with CD as per revised European Society of Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) criteria for diagnosis of CD 1990,13 on GFD for >6 months were enrolled in the study after getting the requisite clearance from the Institute Research Review Board. Children

<2 years and >15 years of age, those who did not have a documented positive serology and/or biopsy suggestive of CD as per revised ESPGHAN criteria 1990, those on GFD for <6 months, and those children whose parents did not consent to be included in the study were excluded.

All children enrolled in the study after signing of the written informed consent form were evaluated for dietary compliance based on a 5-day dietary recall form. A child who had taken even one food article containing gluten in last 5 days was considered noncompliant and those who had strictly taken no gluten in their diet in that period were considered compliant. Diet recall was done by parents for children in preschool age up to 5 years since parents were the only one giving the eatables to these children. Children, above 5 years of age, going to school and interacting with peers, were actively involved in the dietary recall along with the parents. Parents and children in the study group were assessed for dietary compliance followed by a questionnaire based interview.

Psychosocial parameters were assessed by standard Pediatric Symptom Checklist (PSC). Dietary compliant and noncompliant groups were compared and assessed for factors affecting the dietary compliance. Predictability of all of these factors was assessed using binary logistic regression analysis with backward elimination to find out the best predictors of compliance.

Table 1. Barriers Related to Child's Attitude Question Finds keeping diet difficult

Child shares responsibility Finds taste of GFD

Finds difficult to maintain diet at school Finds difficult to maintain diet at party/marriage Finds difficult to maintain diet while travelling Finds difficult to maintain diet with friends

Response

Complaint (%)

Noncompliant (%)

P value

Difficult

4 (6.15)

8 (22.86)

<0.001

Fairly difficult

20 (30.77)

20 (57.14)

Easy

41 (63.08)

7 (20.00)

Y

43 (66.15)

10 (28.57)

N

22 (33.85)

25 (71.43)

Bad

2 (3.08)

15 (42.86)

Satisfactory

20 (30.77)

16 (45.71)

Good

39 (60.00)

3 (8.57)

Very good

4 (6.15)

1 (2.86)

Y

27 (41.54)

26 (74.29)

N

38 (58.46)

9 (25.71)

Y

24 (36.92)

28 (80.00)

N

41 (63.08)

7 (20.00)

Y

45 (69.23)

30 (85.71)

N

20 (30.77)

5 (14.29)

Y

24 (36.92)

22 (62.86)

N

41 (63.08)

13 (37.14)

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

<0.001 <0.001

<0.001 <0.001 0.814 <0.001

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clinical study Results and Discussion

Barriers Related to Parental Attitude

Three types of barriers to compliance were noted. Barriers derived from parent's attitude, those derived from child's attitude and those caused by effect of CD on feelings of children suffering from CD.

Table 2 shows 24.62% of parents of children in compliant group hardly felt a burden on their budget.

94.28% of parents with children in noncompliant group felt a fairly heavy or heavy burden on their budget while 75.38% of parents with children in compliant group felt a fairly heavy or heavy burden on their budget. It was observed that 87.69% of parents of children in compliant group cooked more than once for their children as compared to 71.43% of parents of children in noncompliant group. In compliant group 72.31% of parents believed that special diet was hardly a burden to the family, whereas in noncompliant group 57.14% parents felt it as a burden. It was noted that 36.92% of parents of children in compliant group were not hesitant to discuss the child's condition and were interacting with other parents of CD in Gastroenterology clinics; these parameters were significantly lower in noncompliant group i.e. 14.29%.

Also, 64.62% parents of compliant children and 71.73% parents of noncompliant children believed that the disease will interfere with their child's marriage; 93.28% of parents of children in noncompliant group and 75.38% of parents of children in compliant group also felt a financial burden by GFD; 71.43% parents with children in noncompliant group cooked more than once for their children as compared to 87.69% of parents with children in compliant group. All these parameters had a significant correlation (p = <0.001) with compliance and show that noncompliance was most common in parents who consider special diet a burden to budget and family and hence they avoided cooking fresh meals for the children. Hence cheap and easy to cook food will help this disease bearing families. Study by Lee et al in 200717 also shows that financial burden of gluten free food may affect compliance. Anson et al in 199011 also showed that 50% of noncompliant group parents considered diet a burden on family's budget. However this did not significantly affect compliance in their study. In his study, 56% of compliant parents considered special diet a burden, however, compliant and noncompliant parents did not differ significantly with regard to this parameter.

In study by Chauhan JC in 2010,9 60.7% of compliant parents believed that special diet was hardly a burden; 84.6% in noncompliant felt it as a burden. Olsson et al in 200815 and Lee et al in 2007,17 both have shown that

Table 1 shows results of assessment of child's attitude as a barrier to compliance to GFD, 63.08% of children in compliant group found it easy to keep compliance to GFD; 57.14% of children in noncompliant group found it fairly difficult to maintain GFD. In noncompliant group 74.29% children found it difficult to maintain GFD at school; 80% found it difficult to maintain GFD at2 family parties and marriages; 62.86% found difficult to comply to diet when with friends. It was seen that 69.23 % in compliant group and 85.79% in noncompliant group found difficulty in complying to diet while travelling.

When they were assessed regarding sharing of responsibility in maintaining GFD, 66.15% of compliant children were found to be sharing responsibility of keeping the diet, as compared to 28.57% of noncompliant children who shared responsibility of keeping the diet. It was observed that 42.86% of noncompliant children reported the taste of gluten free food as bad while 66.15% of children in compliant group found it very good or good and only 3.08% of compliant children reported food as bad. A statistically significant difference was observed when most of these results were compared. In the present study, the questionnaire included questions related to child's attitude in response to the disease and GFD. While 63.08% of children in compliant group found keeping GFD easy; only 20 % of noncompliant children found it easy to maintain a GFD. 57.14% of noncompliant children found it fairly difficult and 22.86 % children found it difficult to maintain the diet. Our study also found that 66.15% of compliant patients were fairly responsible in maintenance of GFD as compared to 28.57 % in noncompliant group. These results show that compliant patients are more involved in maintenance of their diet.

Active involvement of child is significantly related (p = <0.001) in our study to compliance as in study

by Chauhan JC, et al in 2010.9 In study by Anson et al (1990), 71% of compliant children's mothers and 44% of noncompliant children's mothers thought that the children shared responsibility in keeping diet.11 14

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

clinical study Table 2. Barriers Related to Parentsâ&#x20AC;&#x2122; Attitude Question Finds burden on budget

Response

Complaint (%)

Noncompliant (%)

P value

Heavily

12 (18.46)

16 (45.71)

<0.001

Fairly

37 (56.92)

17 (48.57)

Hardly

16 (24.62)

2 (5.71)

Y

18 (27.69)

20 (57.14)

N

47 (72.31)

15 (42.86)

>Once

57 (87.69)

25 (71.43)

Once

8 (12.31)

10 (28.57)

Y

24 (36.92)

5 (14.29)

N

41 (63.08)

30 (85.71)

Y

42 (64.62)

25 (71.43)

N

23 (35.38)

10 (28.57)

Feels burden on self

Cooks food once or more than once

In contact with other parents of children with CD Believe that disease will interfere with child's marriage

availability of cheap gluten free food was a significant factor affecting compliance. Increased availability of cheap food items is needed for celiac patients.

It was seen that 36.92% of parents of children in compliant group were not hesitant to discuss the condition with others and were able to interact with other parents in the clinic. These rates were 14.29% in noncompliant group, which were significantly lower.

This shows that efforts are required on part of healthcare providers to break the stigma among the parents and increase their interaction mutually and with medical faculty to ensure compliance. Rashid M et al (2005) reported compliance rates of 95% in those children whose families were a part of celiac support group, Canadian Celiac Association (CCA). These families regarded CCA as the best source for the information provided to them about their child's disease. Hence this significant association of compliance with the knowledge imparted about CD with the help of celiac support groups and involvement of dieticians and regular follow-up will definitely improve compliance to the GFD. Barriers Related to Child's Feelings (Table 3)

In present study, 47.69% of the compliant children never felt left out of the activities at school while only 22.86% of noncompliant children never felt left out of the activities at school. Also, 14.28% of noncompliant children and 7.69% of compliant children believed that their teacher and friends didn't understand the disease all or most of the time; 45.72% of noncompliant Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

<0.001

<0.001

0.012

0.225

children and 3.08% of complaint children felt different from other kids because of disease; 72.31% of compliant children were not having any problem in bringing GFD to school, parties while in noncompliant group this was true for 28.57% only; 62.86% felt embarrassed to bring GFD at parties. When they were inquired about their social life and asked to grade it, 9.23% children in compliant group believed that they were left out of activities at school or friends' home due to their disease all or most of the time while 48.57% children in noncompliant group believed that they were left out of activities at school or at friends' home all or most of the time. In noncompliant group; 2.86% felt different from others all the time while 42.86% felt different most of the times as compared to 0% and 3.08% respectively in the compliant group.

Feeling of embarrassment of bringing GFD to parties due to their disease; was higher in noncompliant group as compared to compliant group i.e. 80% and 27.69% respectively.

Feeling of anger for following special diet was also higher in noncompliant group as compared to compliant group i.e 91.43% and 78.46% respectively; 21.54% never felt angry to follow GFD in compliant group while this count was 8.57% in noncompliant group.

In compliant group, 66.15% of children understood the importance of following a GFD and never felt that they can be healthy without following a special diet while in noncompliant group only 20% understood this. As regards identifying the gluten free food stuff 15

clinical study 74.28% children in noncompliant group had problems all or most of the times as compared to 38.46% in compliant group who had this problem all or most of the time. Also, 72.31% in compliant group believed that their teachers and friends understood the nature of their disease compared to 51.43% in noncompliant group; 10.77% in compliant group always or most of the time felt that they were not invited for meals outside because of the disease, while 14.29% in noncompliant group believed so all or most of the time. Most of these questions showing the perception of the child about the disease and GFD significantly affected compliance (p = <0.001).

School environment While only 41.54% of compliant patients mentioned that it was difficult for them to maintain compliance at school, 74.29% of noncompliant patients found it difficult to maintain diet at school. Rashid et al (2005), also reported >50% of children felt left out of activities at school and had problems related to compliance.14 Olsson et al, in 2008 showed that for adolescents, school was the most difficult place to

comply with GFD.15 Other children bringing mainly gluten containing foods and peer pressure about taking packed food items containing gluten were responsible for difficulty in maintaining compliance at school.

Family party and marriages Noncompliant children also found it difficult to maintain GFD at family party/marriages (80%), compared to 36.92 % in the compliant group. Gluten containing food as the main dietary item served at above places was a problem for both compliant and noncompliant groups who had problems in maintaining diet at such places. Anson et al (1990) have also reported nonavailability of food at party/ marriages as barriers to compliance to GFD.11 Travelling While travelling, majority number of children in both compliant group (69.23%) and noncompliant group (85.71%) face problems with maintaining special diet.

This shows the need of easily available packed GFD and properly labelled as being gluten free for on-the-go consumption.

Table 3. Barriers Related to Child's Feelings Compliant group (%) A

B

Feel left out of activities at school or friends home

0 (0.00)

6 (9.23)

Felt different from other kids

0 (0.00)

Felt embarrassed to bring gluten free foods to parties

A

27 31 (41.54) (47.69)

1 (1.54)

1 (2.86)

16 10 8 (45.71) (28.57) (22.86)

0 (0.00)

<0.001

2 (3.08)

24 39 (36.92) (60.00)

0 (0.00)

1 (2.86)

15 10 9 (42.86) (28.57) (25.71)

0 (0.00)

<0.001

1 (1.54)

6 (9.23)

11 47 (16.92) (72.31)

0 (0.00)

3 (8.57)

15 4 10 (42.86) (11.43) (28.57)

3 (8.57)

<0.001

Felt angry about following a special diet

0 (0.00)

12 39 14 (18.46) (60.00) (21.54)

0 (0.00)

14 8 10 (40.00) (22.86) (28.57)

3 (8.57)

0 (0.00)

<0.001

Felt their teacher and friends didn't understand the disease

0 (0.00)

5 (7.69)

13 42 (20.00) (64.62)

5 (7.69)

2 (5.71)

12 15 (34.29) (42.86)

3 (8.57)

<0.001

Felt that they can be healthy without following a special diet

1 (1.54)

1 (1.54)

20 43 (30.77) (66.15)

0 (0.00)

6 8 14 7 (17.14) (22.86) (40.00) (20.00)

0 (0.00)

<0.001

Avoid restaurants

33 17 (50.77) (26.15)

6 (9.23)

6 (9.23)

3 (4.62)

18 8 (51.43) (22.86)

2 (5.71)

2 (5.71)

5 (14.29)

0.171

Avoid travelling

23 33 8 (35.38) (50.77) (12.31)

1 (1.54)

0 (0.00)

20 5 (57.14) (14.29)

3 (8.57)

7 (20.00)

0 (0.00)

<0.001

Found difficult to determine which food is gluten free

8 17 32 8 (12.31) (26.15) (49.23) (12.31)

0 (0.00)

16 10 6 (45.71) (28.57) (17.14)

2 (5.71)

1 (2.86)

<0.001

Felt they were no invited out

1 (1.54)

18 9 (51.43) (25.71)

0.002

A. All the time

16

B. Most of the time

D

B

9 40 9 4 (13.85) (61.54) (13.85) (11.43) C. Some of the time

3 (8.57)

1 (2.86)

D. Never

C

3 (8.57)

D

P value

E

6 (9.23)

C

Noncompliant group (%) E

E. Not answered

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

clinical study Taste of GFD

Psychosocial problem related to noncompliance

In response to question related taste of gluten free food, 66.15% of compliant patients graded taste of GFD to be very good or good, while only 11.43% in noncompliant group graded it to be good or very good. Child's liking taste of GFD is significantly associated with compliance (p = <0.001). Butterworth et al (2004), have also reported better compliance in patients who were frequently explained and educated by dieticians regarding selection and preparation of gluten free meals to improve the taste of the meals.16 These results highlight importance of counselling and education of parents and children in selecting and preparing gluten free foods. Parents should be taught about preparing palatable, easily available gluten free food for their children.

In our study, the mean score is increasing as the age increases in the children suffering from CD in both compliant and noncompliant patients. Hence, an older child is at more risk of noncompliance.

In our study, 18.46% of complaint and 62.86% of noncompliant children felt angry about having to follow a special diet all or most of the time. 66.15% of compliant and only 20% of noncompliant children never believed that they can be healthy without following a special diet. We also found that majority of both, compliant children (86.15%) and noncompliant children (71.43%) avoided travelling because of the fact that GFD is not easily available. Rashid M et al (2005), also studied the effect of child's feeling on compliance to GFD. In their study, 13% of compliant children felt left out of school activities due to their disease and 11% of compliant children felt that their teacher did not understand their disease. While 18% children felt themselves different from other kids, 23% were embarrassed to bring gluten free food to parties. In his study, 23% children felt angry about having to follow a special diet.14 These results indicate that these dietary restrictions have significant impact on child's social activities including school and extracurricular events. It affects their participation in school, parties and enjoyable social activities such as birthday parties. Nonavailability of gluten free items in restaurants and during travel made them avoid it. The acceptance of diet was better in children in the study by Rashid M et al as compared to that in our study which may be because of support provided by the CCA, the celiac support group which makes the children more comfortable with their condition and made them accept the diet better and hence the role of support groups re-emphasized.

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

Conclusion These results will contribute to the current body of research by providing healthcare practitioners with a framework for better dietary instruction to ensure maximum adherence to GFD. References 1. Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, Shamir R, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136-60.

2. Celiac UK, Professional eXG, newsletters/january-2011professional-exg, January 2011.

3. Hoffenberg EJ, MacKenzie T, Barriga KJ, Eisenbarth GS, Bao F, Haas JE, et al. A prospective study of the incidence of childhood celiac disease. J Pediatr. 2003;143(3):308-14.

4. Makharia GK, Verma AK, Amarchand R, Bhatnagar S, Das P, Goswami A, et al. Prevalence of celiac disease in the northern part of India: a community based study.

J Gastroenterol Hepatol. 2011;26(5):894-900.

5. Bhatnagar S, Gupta SD, Mathur M, Phillips AD, Kumar R, Knutton S, et al. Celiac disease with mild to moderate histologic changes is a common cause of chronic diarrhea in Indian children. J Pediatr Gastroenterol Nutr.

2005;41(2):204-9.

6. Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA; American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108(5):656-76.

7. Haines ML, Anderson RP, Gibson PR. Systematic review: The evidence base for long-term management of coeliac disease. Aliment Pharmacol Ther. 2008;28(9):1042-66.

8. Hill ID, Dirks MH, Liptak GS, Colletti RB, Fasano A, Guandalini S, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr.

2005;40(1):1-19.

9. Chauhan JC, Kumar P, Dutta AK, Basu S, Kumar A. Assessment of dietary compliance to gluten free diet and psychosocial problems in Indian children with celiac disease. Indian J Pediatr. 2010;77(6):649-54.

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Clinical Study

Laparoscopic Evaluation of Endometriosis in Infertility and Chronic Pelvic Pain in a Tertiary Care Center Paramjit Kaur*, Ruby Bhatia†, Rajwinder Kaur‡, Aman Dev#, Surinder Kumari$

Abstract Objective: To find out prevalence of endometriosis and to evaluate effectiveness of laparoscopy in diagnosis and staging of endometriosis in infertility and chronic pelvic pain. Material and methods: An observational study carried out on 100 patients of infertility and chronic pelvic pain in Dept. of Obstetrics and Gynecology, Rajindra Hospital, Patiala with effect from January 2011 to June 2012. Patients were subjected to laparoscopy under anesthesia. Diagnosis, staging and management of endometriosis was done as required. Results: Prevalence of endometriosis was found to be 23%. Majority of cases (34.78%) had severe endometriosis followed by stage I and II (26.09%) each. Endometriosis was detected in 24.07% and 16.12% in relation to primary and secondary infertility, respectively, while 33.3% cases with chronic pelvic pain had endometriosis. Majority of cases had minimal endometriosis, stage I (46.38%) followed by stage IV (30.77%) in primary infertility compared to 60% in stage II followed by 20% each in stage III and IV in secondary infertility. Sixty percent patients with chronic pelvic pain had severe endometriosis. Conclusion: Laparoscopy remains gold standard for diagnosis and management of endometriosis in evaluation of infertility and chronic pelvic pain.

Keywords: Endometriosis, infertility, chronic pelvic pain, laparoscopy

E

ndometriosis is presence and growth of functioning endometrial tissue containing glandular and stromal elements in places other than uterus that often results in severe pain and infertility.1 It is 7 to 10 times more common in infertile women and encountered in 70% of women with chronic pelvic pain. Seventeen percent of women with primary infertility are diagnosed with endometriosis.2 Endometriosis affects 6-10% of women of reproductive age. It was seen that 69.6% teenagers who underwent diagnostic laparoscopy for chronic pelvic pain had endometriotic implants. A genetic component has been suggested with 6.9% occurrence rate in firstdegree relatives.3 Alcohol usage, smoking and low body mass index are other risk factors. Dysmenorrhea, *Professor † Associate Professor ‡ Senior Resident Dept. of Obstetrics and Gynecology # Postgraduate Student Dept. of Preventive and Social Medicine $ Ex-Professor Dept. of Obstetrics and Gynecology Govt. Medical College and Rajindra Hospital, Patiala, Punjab Address for correspondence Dr Paramjit Kaur 40, Mohindra Complex, Kheri Gujran Road Opp. Khokhar Complex, Patiala, Punjab - 147 001 E-mail: dr.parmjit.obg@gmail.com

18

dyspareunia, infertility and chronic pelvic pain remain characteristics of endometriosis. Premenstrual spotting, dysuria, dyschezia, sciatica are associated symptoms.

The most common sites of endometriosis in decreasing order are the ovaries, anterior and posterior cul-desac, broad ligament and uterosacral ligaments, uterus, fallopian tubes, sigmoid colon and appendix. The growth of implants is dependent on steroids produced in the ovarian tissue. It varies in appearance from a few minimal lesions in an otherwise intact pelvic organs to a massive ovarian endometriotic cyst with deep infilterating endometriosis.

Clinical history along with gynecological examination, laboratory tests and transvaginal ultrasound may suggest the diagnosis.4 The greatest difficulty lies in diagnosing minimal and mild lesions. In these cases, the ideal access for confirmation is always laparoscopic.

Assessment of the accuracy of laparoscopy for diagnosing endometriosis has demonstrated that it is highly precise in ruling out the disease.5 Material and Methods The present study was carried out on 100 patients with chief complaints of infertility/chronic pelvic pain admitted in the Dept. of Obstetrics and Gynecology, Govt. Medical College, Rajindra Hospital, Patiala to evaluate effectiveness of laparoscopy in diagnosis and Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

clinical study staging of endometriosis and to find out prevalence of endometriosis in infertility and chronic pelvic pain. It was an observational study with effect from January 2011 to June 2012.

A detailed history with special reference to dysmenorrhea, dyspareunia, dysuria, menorrhagia, premenstrual spotting and dyschezia was taken.

Patients were selected for single/double puncture laparoscopic evaluation under general/regional anesthesia in postmenstrual phase after routine investigations including transvaginal sonography. An informed consent was taken for the procedure.

Hemodynamically unstable, cardiorespiratory disease, uterine height ≥16 weeks size of the pregnant uterus, acute reproductive tract infections were excluded from the study. Presence of powder burn lesions, adhesions to

No. of cases

40 30 20

21

17

13

10 0

2 20-25

25-30

30-35

35-40

Results and Observations A total of 100 patients were subjected to single or double puncture laparoscopy; 54% patients presented with primary infertility, 31% with secondary infertility and 15% with chronic pelvic pain. The mean age in the study group was 30.17 ± 4.77 years (Fig. 1).

Majority of patients were nulliparous (54%) from urban background (57%) and were of low or middle socioeconomic status (86%) (Table 1).

Congestive dysmenorrhea (35%) was the most common associated complaint followed by premenstrual spotting in 18%, menorrhagia in 12%, dyspareunia in 6% (Table 2). Prevalence of endometriosis was found to be 23% on laparoscopy followed by pelvic inflammatory disease (16%), adhesions, fibroid uterus and genital tuberculosis, while 15% cases had normal study (Fig. 2).

Majority of endometriosis patients in our study were stage IV, while 6 cases each were stage I and stage II (26.09%) (Fig. 3).

47

50

pelvic wall, to the posterior broad ligament or to both, superficial endometriosis with adjacent puckering, endometriomas <12 cm, tarry chocolate-colored fluid content were taken as visual diagnostic parameters to confirm endometriosis. Staging of endometriosis was done as per the American Society for Reproductive Medicine (ASRM) revised classifications of endometriosis.6

40-45

Age (in years) Figure 1. Age-wise distribution (total 100).

Table 2. Presenting Complaints (Total 100) Presenting complaints

Table 1. Sociodemographic Profile (Total 100) Number

Percentage (%)

Unmarried

1

1

Nulliparous

54

54

Para 1

13

13

Paar 2 and above

32

32

Parity

Residence

Number

Percentage (%)

Infertility

85

85

Primary infertility

54

54

Secondary infertility

31

31

Chronic pelvic pain

15

15

Congestive dysmenorrhoea

35

35

Menstrual irregularity

30

30

Associated Complaints

Urban

57

57

Premenstrual spotting

18

18

Rural

43

43

Menorrhagia

12

12

Dyspareunia

6

6

Socioeconomic status Low

49

49

Dysuria

3

3

Middle

37

37

Dyschezia

1

1

High

14

14

No complaints

21

21

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

19

clinical study

16

15

15

13 7 2

2

2 Mullerian agenesis

4

Chronic ectopic pregnancy

Pelvic tuberculosis

Fibroids

Adhesions

Pelvic inflammatory disease

Endometriosis

0

4

Hydrosalpinx

4

5

Ovarian enlargement

8

Polycystic ovarian disease

10

Normal study

No. of cases

20

No. of cases

23

Tubal blockade

25

8 7 6 5 4 3 2 1 0

8 6

6

3

Stage I (Minimal)

Stage II (Mild)

Stage III (Moderate)

Stage IV (Severe)

Figure 3. Staging of endometriosis (total 23) (Asrm revised classification 1994).

based on presenting symptoms as pelvic pain, age 15-24 years; infertility, age 25-34 years and dysfunctional uterine bleeding, age 35-44 years.6 Endometriosis is traditionally diagnosed after 2nd or 3rd decade; approximately one-third of patient with confirmed endomteriosis experience their first symptom before 15 years of age.7 Salehpour et al reported 36% prevalence of endometriosis in infertility and chronic pelvic pain.8

Figure 2. Clinical diagnosis in laparoscopic evaluation (total 100).

Out of 54 patients with primary infertility 24.07% (13 cases) were diagnosed as endometriosis of these 46.16% had minimal disease, while 4 cases (30.77%) were stage IV endometriosis (endometriomas and deep infiltrating endometriosis). A total of 16.12% patients with secondary infertility had endomteriosis, 80% of them with mild-to-moderate (Stage II and III) endometriosis. 33.3% patients with chronic pelvic pain were diagnosed endometriosis, 60% (3 cases) of them in stage IV disease (Table 3).

In our study, dysmenorrhea was the major associated complaint in 35% of cases of infertility and chronic pelvic pain followed by premenstrual spotting in 18%, menorrhagia in 12% and dyspareunia in 6%.

The clinical features of endometriosis are varied and the presentation depends on site of growth and severity of disease. The classic triad of dysmenorrhea, dyspareunia and infertility has been described as characteristic of the disease.1 In a study conducted by Khawaja et al among infertile women with laparoscopy is staging of endometriosis, 36.8% cases had dysmenorrhea.9 Prevalence of endometriosis in infertility and chronic pelvic pain in our study was 23%. Naseer-ud-din, 200010

Discussion The prevalence of endometriosis in our study was 23% out of a total of 100 cases with infertility and chronic pelvic pain on laparoscopic evaluation. The mean age in our study was 30.17 Âą 4.77 years with a range of 20-45 years. The age of peak diagnosis of endometriosis

Table 3. Prevalence and Staging of Endometriosis in Relation to Infertility/chronic Pelvic Pain (Total 23) Diagnosis

Endometriosis

Staging of endometriosis Stage I

20

Stage II

Stage III

Stage IV

N

%

N

%

N

%

N

%

N

%

N

%

Primary infertility

54

100

13

24.07

6

46.16

2

15.38

1

7.69

4

30.77

Secondary infertility

31

100

5

16.12

0

0

3

60

1

20

1

20

Chronic pelvic pain

15

100

5

33.33

0

0

1

20

1

20

3

60

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

clinical study and Salehpour et al8 reported 24.88% and 36% prevalence of endometriosis, respectively.

Majority of cases (34.78%) in our study were stage IV with severe disease followed by 26.09% in stage I with minimal disease. Tsuji et al 200911 found majority of the cases in stage I. Almeida Filho et al, 200812 reported 51.01% and 32.46% cases of infertility in stage II and III, respectively. The difference could be because ours is a referral tertiary care center catering to poor people who usually report late as is the case in developing countries. Endometriosis was diagnosed in 24.07% (13 cases) in relation to primary infertility and 16.12% in secondary infertility in our study.

Majority of these cases (46.16) were in stage I followed by 30.77% cases in stage IV with severe endometriosis.

Haider et al 201013 reported endometriosis 55% in primary infertility and 20% in secondary infertility, while Aziz 201014 reported endometriosis in 12.5% and 11.11%, respectively. Prevalence of endometriosis varied from 9% to 50% in infertility in various studies.1 In our study, 33.3% patients with chronic pelvic pain were diagnosed with endometriosis, with 60% of these in stage IV severe disease. Incidence of endometriosis was reported to be 17.47% in chronic pelvic pain by Almida Filho et al.12 Among women with pelvic pain, the prevalence range approximately from 30-80%.1 Conclusion Laparoscopy remains gold standard for diagnosis of endometriosis. It is an excellent tool in evaluation of patients with infertility and chronic pelvic pain as diagnosis and treatment can be accomplished in one sitting. Early diagnosis and management of endometriosis is need of the hour to prevent catastrophic sequelae. It will go a long way to prevent progression of the disease to severe form hence reducing the morbidity significantly.

References 1. John HW, Rock JA (Eds.). Endometriosis (Chap. 22). Te Linde’s Operative Gynaecology. 11th Edition, Philadelphia, USA: Wolters Kluwer; 2015. pp. 402-38.

2. Cramer DW, Missmer SA. The epidemiology of endometriosis.

Ann N Y Acad Sci. 2002;955:11-22; discussion 34-6, 396-406.

3. Simpson JL, Elias S, Malinak LR, Buttram VC Jr. Heritable aspects of endometriosis. I. Genetic studies. Am J Obstet Gynecol. 1980;137(3):327-31.

4. Abrão MS, Neme RM, Averbach M. Rectovaginal septum endometriosis: a disease with specific diagnosis and treatment. Arq Gastroenterol. 2003;40(3):192-7.

5. Wykes CB, Clark TJ, Khan KS. Accuracy of laparoscopy in the diagnosis of endometriosis: a systematic quantitative review. BJOG. 2004;111(11):1204-12.

6. Leibson CL, Good AE, Hass SL, Ransom J, Yawn BP, O'Fallon WM, et al. Incidence and characterization of diagnosed endometriosis in a geographically defined population. Fertil Steril. 2004;82(2):314-21.

7. Ballweg ML. Impact of endometriosis on women's health: comparative historical data show that the earlier the onset, the more severe the disease. Best Pract Res Clin Obstet Gynaecol. 2004;18(2):201-18.

8. Salehpour S, Zhaam H, Hakimifard M, Khalili L, Gashb YZ. Evaluation of diagnostic visual findings at laparoscopy in endometriosis. Iranian J Fertil Steril. 2007;1(3):123-6.

9. Khawaja UB, Khawaja AA, Gowani SA, Shoukat S, Ejaz S, Ali FN, et al. Frequency of endometriosis among infertile women and association of clinical signs and symptoms with the laparoscopic staging of endometriosis. J Pak Med Assoc.

2009;59(1):30-4.

10. Naseer-ud-Din, Khan A, Illahi N. Prevalence and presentation of endometriosis in patients admitted in Nishtar Hospital, Multan. JAMC. 2000;12(3):22-5.

11. Tsuji I, Ami K, Miyazaki A, Hujinami N, Hoshiai H. Benefit of diagnostic laparoscopy for patients with unexplained infertility and normal hysterosalpingography findings.

Tohoku J Exp Med. 2009;219(1):39-42.

12. Almeida Filho DP, Oliveira LJ, Amaral VF. Accuracy of laparoscopy for assessing patients with endometriosis. Sao Paulo Med J. 2008;126(6):305-8.

13. Haider G, Rani S, Talpur S, Zehra N, Munir A. Laparoscopic evaluation of female infertility. J Ayub Med Coll Abbottabad. 2010;22(1):136-8.

14. Aziz N. Laparoscopic evaluation of female factors in infertility. J Coll Physicians Surg Pak. 2010;20(10):649-52.

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Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

21

Clinical Study

Evaluation of Risk Factors and Prevalence of Gestational Diabetes Mellitus in a Tertiary Care Center Paramjit Kaur*, Ruby Bhatia†, Nidhi Kailey,‡ Himani Kundoo,# Aman Dev$

Abstract Objective: To evaluate the prevalence and associated risk factors of gestational diabetes mellitus (GDM) in pregnant women by performing one step glucose challenge test (GCT) with 75 g anhydrous glucose at 24-28 weeks or more of pregnancy.

Material and methods: The present study was done in the Dept. of Obstetrics and Gynecology, Government Medical College, Patiala, Punjab, over a period of 6 months (1 January 2015 to 30 June 2015) on 184 antenatal women with 24 weeks or more of pregnancy. GDM was diagnosed if post 2 hours glucose was ≥140 mg%. Risk factors, if any, were evaluated.

Results: Prevalence of GDM was observed to be 8.15% in our study. Majority of the patients (60%) were from rural areas; 60% of patients with GDM were 31 years of age or above; 73.33% women with GDM were obese; 53.33% patients had associated preeclampsia while 26.67% had history of previous adverse pregnancy outcome; 13.33% had family history of diabetes mellitus. Conclusion: The prevalence of GDM was observed to be 8.15%. Advanced maternal age and obesity are independent risk factors for GDM. There is increased incidence of preeclampsia in women with GDM. Keywords: Gestational diabetes mellitus, glucose challenge test, risk factors, obesity, advanced maternal age, preeclampsia

G

estational diabetes mellitus (GDM) is one of the most common complications of pregnancy.1 GDM, a carbohydrate intolerance of variable severity with onset or first diagnosed during pregnancy, is an important public health problem in South East Asian countries. African-American, Asian and Hispanic women are at a higher risk for gestational diabetes compared to white women.2 The prevalence of GDM in India varies from 9.9% in rural population to 17.8% in urban areas.3 GDM is associated with adverse maternal and fetal outcome including preeclampsia, increased cesarean section rates, perinatal mortality (2 fold increased), birth defects, macrosomia (3 fold increased), shoulder dystocia, metabolic complications *Professor † Associate Professor Dept. of Obstetrics and Gynecology, Govt. Medical College and Rajindra Hospital, Patiala, Punjab ‡ Assistant Professor Dept. of Medicine, HIHT, Jolly Grant, Dehradun # Postgraduate Student Dept. of Obstetrics and Gynecology, Govt. Medical College and Rajindra Hospital, Patiala, Punjab $ Postgraduate Student Dept. of Preventive and Social Medicine, Govt. Medical College and Rajindra Hospital, Patiala, Punjab Address for correspondence Dr Paramjit Kaur 40, Mohindra Complex, Kheri Gujran Road Opp Khokhar Complex, Patiala, Punjab -147 001 E-mail: dr.parmjit.obg@gmail.com

22

in neonates and morbidity associated with subsequent childhood obesity. The recurrence risk with future pregnancies is as high as 68%4 and there is 26% risk of developing type 2 diabetes at 15 years of followup.5 The diagnosis of GDM is an excellent window of opportunity to prevent the development of type 2 diabetes. The National Family Health Survey (NFHS) III 2005-06 reported 14.8% increase in prevalence of overweight women aged 15-49 years (ranging from 28.9% in urban areas to 8.6% in rural areas) compared to 10.6% in 1998-99.3 The increasing incidence of gestational diabetes during the past 15 years is reminiscent of similar statistics for obesity.

Maternal obesity is an important confounding factor in the diagnosis of gestational diabetes.6 The increasing incidence of GDM apart from other risk factors is because of rise in maternal age and maternal body mass index (BMI).7 Material and Methods The present study was done in the Dept. of Obstetrics and Gynecology, Government Medical College, Patiala, Punjab, over a period of 6 months from 1 January 2015 to 30 June 2015. A total of 184 pregnant women at 24-28 weeks of pregnancy or more, not previously known to have diabetes were subjected to one step glucose challenge test (GCT) with 75 g anhydrous glucose irrespective of fasting status and time of day.

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

clinical study GDM was diagnosed if post 2 hours venous glucose was ≥140 mg%. GCT was repeated 12 weeks postpartum in all cases to rule out pregestational diabetes mellitus.

Risk factors such as advanced maternal age, obesity, preeclampsia, previous adverse fetal outcome, GDM in previous pregnancy, family history of diabetes and others, if any, were evaluated.

Table 1. Distribution of Patients in Relation to GCT with 75 g Glucose (Total 84) Venous blood glucose levels at 2 hrs

No. of patients

Percentage (%)

<100 mg%

75

40.76

100-139 mg%

94

51.086

>= 140 mg%

15

8.152

Table 2. Demographic Profile of Pregnant Women with GDM (Total-15)

Observations A total of 184 pregnant women at 24-28 weeks of pregnancy or more were taken up for study. They were subjected to single step testing using 75 g oral glucose irrespective of fasting status and measuring plasma glucose 2 hour after ingestion as recommended by national guidelines for diagnosis and management of GDM.8 A venous blood glucose level of 140 mg% or more is suggestive of GDM. A total of 15 patients (8.152%) were found to have venous blood glucose level of ≥140 mg% on performing one step GCT with 75 g glucose after 2 hours (Table 1). The prevalence of GDM was 8.15% in our study group. Table 2 depicts demographic profile of GDM patients. Out Table 3. Distribution of Patients with GDM as per BMI (WHO Criteria for Asian Population) (Total -15) BMI (kg/m2)

No. of patients

Percentage (%)

-

-

No. of patients

Percentage (%)

<18.5 (underweight)

16-20

-

-

-

-

≥23.0 (overweight)

15

100

21-25

-

-

23.0-27.4 (preobese)

4

26.67

26-30

6

40

27.5-32.4 (obese class I)

4

26.67

31-35

7

46.67

32.5-37.4 (obese class II)

5

33.33

36-40

2

13.33

≥37.5 (obese class III)

2

13.33

>40

-

-

Booked

9

60

Unbooked

6

40

G1

6

40

G2

6

40

G3 and above

3

20

Rural

9

60

Urban

6

40

Educated

12

80

Uneducated

3

20

Lower

-

-

Upper lower

3

20

Lower middle

8

53.33

Previous LSCS

3

Upper middle

4

26.67

Family history of diabetes mellitus

2

13.33

Upper

-

-

Previous H/O GDM

-

-

Age in years

18.5 to 22.9 (normal)

Table 4. Association of GDM with Risk Factors (Total-15) Risk factors

Gravida

Residence

Literacy

Socioeconomic status

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

No. of patients

Percentage (%)

Advanced maternal age

9

60

Obesity

11

73.33

HT in pregnancy Gestational hypertension

-

-

Nonsevere preeclampsia

6

40

Severe preeclampsia

2

13.33

Thyroid dysfunction

2

13.33

Previous adverse pregnancy outcome

4

26.67

Ist trimester loss

3

Macrosomia

2

Still birth

2

23

clinical study of 15 cases with GDM, 60% were booked. A similar number of patients were from rural background. Nine patients (60%) with GDM were in age group of 31 years and above (Table 2). All the patients with GDM were overweight 11(73.33%) patients were obese as per WHO classification of BMI for Asian populations (Table 3). It was observed that 53.33% patients had association with preeclampsia; 26.67% had history of previous adverse outcome as abortion, macrosomia, stillbirth, previous lower segment cesarean section (LSCS) (Table 4). More than one adverse outcome was observed in same pregnancy. Two patients (13.33%) were on treatment for hypothyroidism. There was family history of diabetes in two patients. Majority (60%) of patients with GDM achieved glycemic control by diet modification and insulin (Table 5). It was observed that 53.33% of patients had LSCS for different indications (Table 6), with no adverse fetal outcome.

Table 5. Management of GDM (Total-15) Glycemic control

No. of patients Percentage (%)

Diet + lifestyle modification

3

20

Diet + insulin

9

60

Diet + oral hypoglycemics

3

20

Table 6. Mode of Delivery (Total-15) Mode of delivery

No. of patients

Percentage (%)

Vaginal delivery

7

46.67

Cesarean section

8

53.33

CPD

2

13.33

Prev LSCS

3

20

Breech presentation

1

6.67

Major degree placenta previa

1

6.67

Severe preeclampsia

1

6.67

Discussion GDM is one of the most common medical complications of pregnancy.1 The prevalence rate of 8.15% in our study is comparable to the one estimated

by Ministry of Health and Family Welfare, Govt. of India (10-14.3%) in India (13.8% in urban and 9.9% in rural population). The incidence is expected to increase to 20% i.e. one in every 5 pregnant women is likely to have GDM.8 The prevalence of GDM in the United States is 6-7% with a range of 1-25% depending on patient’s demographic profile and diagnostic thresholds.7 It was observed that 60% of patients in our study were 31 years of age and above indicating advanced maternal age to be an independent risk factor for GDM. All patients with GDM were overweight with 73.33% being obese. Several factors increase a woman’s risk for developing GDM including obesity, increased maternal age, history of GDM, family history of diabetes and belonging to ethnic group that has increased risk of developing type 2 diabetes mellitus.7 Four patients in our study group had previous adverse fetal outcome while two patients had family history of diabetes mellitus. Factors associated with low risk of developing GDM include age younger than 25-30 years, white race, BMI ≤ 25 kg/m2, no family history of diabetes and no history of glucose intolerance or adverse pregnancy outcomes related to GDM.7 None of the patients was diagnosed with GDM in previous pregnancy may be due to smaller number of patients para 1 and above in our study. Women with GDM are also at increased risk of developing type 2 diabetes mellitus, approximately 15-60% of women develop type 2 diabetes mellitus within 5-15 years of delivery.7 Majority of risk factors listed by Australian Diabetes in Pregnancy Society9 and American Diabetes Association (ADA)10 are comparable with our study

Table 7. Comparative Evaluation of Risk Factors for GDM

24

Risk factor

Australian diabetes in pregnancy society

American diabetes association

Our study

Age

Yes (> 30 years)

Yes (>25 years)

Yes (>30 years)

Obesity

Yes (not defined)

Yes (BMI >27 kg/m )

Yes

Family history of diabetes mellitus

Yes

Yes (first degree relative)

Yes (first degree relative)

Previous GDM

Yes

Not mentioned

-

High risk ethnic group

Yes

Yes

Yes

Previous adverse pregnancy outcome

Yes

Not mentioned

Yes

2

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

clinical study (Table 7). It was observed that 53.33% GDM patients had associated preeclampsia (nonsevere 40% severe 13.33%) in our study. Screening for and treatment of GDM can significantly reduce risk for preeclampsia, fetal macrosomia and shoulder dystocia.7 ADA, International Association of the Diabetes and Pregnancy Study Groups (IADPSG) and other international associations recommend universal screening at 24-30 weeks of gestation in pregnant women not previously known to have diabetes using 75 g 2 hour oral glucose tolerance test (OGTT). Only one positive result of OGTT is an adequate GDM diagnostic criteria.10,11 The 2013 National Institutes of Health Consensus conference did not recommend adoption of IADP study group recommendation.12 Therefore, ACOG (2013) continues to recommend screening all pregnant women with a patient history or the 50 g OGCT. Majority of our GDM patients (60%) were managed with diet, lifestyle modifications alongwith split dose insulin with no adverse fetal outcome.

Conclusion Universal screening at ≥ 24-28 weeks of pregnancy, not previously known to have diabetes with one step 75 g 2 hour GCT (DIPSI Guidelines) is recommended for diagnosing GDM. Advanced maternal age and obesity are independent risk factors for GDM. Preeclampsia, previous adverse pregnancy outcome and family history of diabetes are associated risk factors. Whether GDM is overdiagnosed or underdiagnosed, the point of screening and diagnosis is to decrease perinatal and obstetric morbidity.2 References 1. Committee on Practice Bulletins - Obstetrics. Practice Bulletin No. 137: Gestational diabetes mellitus. Obstet Gynecol. 2013;122(2 Pt 1):406-16.

2. Ferrara A. Increasing prevalence of gestational diabetes mellitus: a public health perspective. Diabetes Care. 2007;30 Suppl 2:S141-6.

3. Subburaj VK. Secretary to Government of India with reference to Health and Family Welfare (P) Department Letter (D) no. 356; 2007.

4. Spong CY, Guillermo L, Kuboshige J, Cabalum T. Recurrence of gestational diabetes mellitus: identification of risk factors. Am J Perinatol. 1998;15(1):29-33.

5. Lee AJ, Hiscock RJ, Wein P, Walker SP, Permezel M. Gestational diabetes mellitus: clinical predictors and longterm risk of developing type 2 diabetes: a retrospective cohort study using survival analysis. Diabetes Care.

2007;30(4):878-83.

6. Cunningham FG, Leveno KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, et al. Diabetes mellitus. In: Cunningham FG, Leveno KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, et al (Eds.). William Obstetrics. 24th Edition, New York: McGraw-Hill; 2014. pp.1125-46.

7. USPSTF Jan 2014 8. National Guidelines for Diagnosis and Management of Gestational Diabetes Mellitus, Maternal Health Division, Ministry of Health and Family Welfare, Government of India; December, 2014. Available at: http://nhm.gov.in/ nrhm-components/rmnch-a/maternal-health/guidelines. html. [Accessed on 13th Aug., 2015].

9. Hoffman L, Nolan C, Wilson JD, Oats JJ, Simmons D. Gestational diabetes mellitus-management guidelines. The Australasian Diabetes in Pregnancy Society. Med J Aust.

1998;169(2):93-7.

10. American Diabetes Association. Standards of medical care in diabetes-2007. Diabetes Care. 2007;30(Supp):S4-S41.

11. International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, Damm P, et al. International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010;33(3):676-82.

12. Vandorsten JP, Dodson WC, Espeland MA, Grobman WA, Guise JM, Mercer BM, et al. NIH consensus development conference: diagnosing gestational diabetes mellitus. NIH Consens State Sci Statements. 2013;29(1):1-31.

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Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

25

Review Article

Endometriosis and the Role of Resveratrol Anita Kant

Abstract Endometriosis is a very common yet very challenging disease that affects women in their reproductive age. Endometriosis causes severe pain and infertility in women. Endometriosis brings a huge economic burden and reduces quality-of-life. Role of estrogen has been established as a causative factor of endometriosis. Pharmacotherapy of endometriosis revolves around lowering levels of estrogen in the body. Hormone therapy for endometriosis has its limitations.

Keywords: Endometriosis, dysmenorrhea, resveratrol

E

ndometriosis is a very common yet very challenging disease that affects women in their reproductive age. Endometriosis causes severe pain and infertility in women. Endometriosis brings a huge economic burden and reduces quality-of-life. An estrogen-dependent condition, the exact molecular and cellular basis of endometriosis pathogenesis remains unclear. Existing pharmacotherapy of the condition remains inadequate. In this light, we shall discuss evidence in support of resveratrol as an option to manage endometriosis in women.1-4

Endometriosis manifests itself in the form of pelvic pain related to menstruation and infertility. Symptoms of endometriosis are progressive and may include dysmenorrhea, heavy or irregular bleeding, lower abdominal pain, pelvic pain, dyspareunia (pain during sexual intercourse), dyschezia (pain on defecation), pain during micturition, inguinal pain, pain during exercise, nausea, vomiting and bloating.1,4,5 Pain is the principal reason for seeking medical help.

Epidemiology: Exact number of subjects with endometriosis is difficult to tell. Endometriosis can only be diagnosed by laparoscopy. It is believed that endometriosis affects nearly 176 million women globally. Close to 26 million women in India suffer from endometriosis.6,7 In general population, prevalence of endometriosis may range from 4% to 10%.

Many subjects remain without any apparent symptom.

Incidence of endometriosis can high in teenagers (50%) Consultant Gynecologist Asian Institute of Medical Sciences, Faridabad, Haryana

26

with intractable dysmenorrhea, in infertile women (20-50%) and in women with pelvic pain (80%).

Approximately 4 per 1,000 women are hospitalized for endometriosis.4,5,8,9 Economic burden: In 2009, total annual healthcare cost to endometriosis was estimated to be USD 69.4 billion.10 Per person cost to healthcare for endometriosis was approximately USD 12,419. One-third of this is attributed to direct healthcare cost and remaining two-third relates to loss of productivity.3 In Indian subcontinent, where most medical expense comes out of pocket, endometriosis brings economic burden to patients due to high cost of diagnosis and cost of managing problem of infertility.5 Risk factors: Several risk factors have been identified for endometriosis.

Heredity: Heredity is an important risk factor. Risk increases if first-degree relatives, e.g., mother/sister, suffer from endometriosis.2,4,8,11 Heritable traits like height (tall women) and weight (thin women) may have impact on occurrence of endometriosia.12 Age: Rate of endometriosis tends to increase with age.

In females in the age group 20-21 years, incidence of endometriosis was 45% compared to prepubertal girls.4 Lifestyle: Personal lifestyle choices like delayed marriage, postponement of first conception, adoption of small family norm, consumption of alcohol and caffeine, may increase risk.4,9,12 Altered menstrual cycle: Subjects with shorter cycle length, longer duration of flow or reduced parity are more likely to suffer from endometriosis.4,7 Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

Review article Structural defect: Defective fallopian tubes and uterus as well as iron deficiency and hypoxia may contribute towards endometriosis.4

and pro-survival genes. Cytokines and chemokines released due to aberrant activation of immune system may also contribute towards inflammatory response.

Pathophysiology: Uterus plays a very important role in female reproductive system. Inner lining of uterus is endometrium. Endometrium is rich in glands and blood supply. For initiation and propagation of pregnancy, fertilized ovum gets implanted on endometrium.

In endometriosis, inner endometrial lining of uterus grows in places outside uterus. Such ectopic growth can happen in ovaries, fallopian tubes, vagina, cervix, uterosacral ligaments, pelvic peritoneum. In rare cases, endometrial growth has been seen in kidney, bladder, lung and brain as well.1-3

At the molecular level, role of steroid hormones play a central role in the pathophysiology of endometriosis.

Estrogen acts as promitogenic agent and promotes endometrial lesion. Synthesis of estrogen is increased due to enhanced activity of aromatase enzyme in endometrial tissue. Inactivation of active estradiol to less active estrone is reduced due to reduced expression of the metabolizing enzyme, 17β-hydroxysteroid dehydrogenase.

Etiology of endometriosis is poorly understood.

Endometriosis may be the clinical manifestation of an underlying disorder that affects the tubal motility or immune system and contribute towards progression of endometriosis. Several theories have been proposed.

None clearly explains occurrence of endometriosis. v Retrograde menstruation theory deals with flow of endometrial contents into peritoneal cavity. This is believed to result in implantation of endometrial lesion. Studies have shown that retrograde menstruation is a quite common yet most women do not have endometriosis. v Metaplasia hypothesis proposes transformation of specialized cells present in the mesothelial lining of visceral and abdominal peritoneum. It has been suggested that endogenous factors induce resident undifferentiated cells into endometrial tissue. However, appearance of endometriosis in prepubertal girls lacking estrogen cannot be explained by metaplasia hypothesis. v Immune dysfunction theory proposes defective removal of menstrual debris and promotes implantation of endometrial lesions. Women with this disorder appear to exhibit increased humoral immune responsiveness and macrophage activation.

At the cellular level, involvement of stem cells, activated macrophages and progrowth and antiapoptotic endometrial cells has been suggested. It is proposed that stem cells get settled in peritoneum and undergo transdifferentiation into endometrial tissue.

Endometrial cells exhibit upregulation of antiapoptosis Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

Prostaglandins play a role in endometriosis. Estrogen increases the synthesis of certain prostaglandins that may contribute towards pain and inflammation. Dioxin group of compounds, acting through aryl hydrocarbon receptor, may mimic activity of estrogen. Role of dioxins in human endometriosis remain inconclusive.

Free radicals and lipid peroxidation products generated due to lifestyle and diet-induced enhanced oxidative stress, may contribute towards endometriosis.2-4,10 Management: Endometriosis can be managed medically using drugs. Alternatively, ectopic growth can be removed surgically. Ideally, a combination of both approaches is employed. Medical management aims to create (1) a hypoestrogenic environment in the body using hormones and (2) manage pain.

1. Hypoestrogenic environment: Different approaches used to reduce estrogen levels in the body, include use of a (i) estrogen progesterone combination, (ii) progesterone only preparation, (iii) gonadotropic hormone release agonist, (iv) danocrine and (v) aromatase inhibitor. Hormone therapy is effective in managing endometriosis.1-3 Hormone therapy has side effects. Combinational birth control pills (contain both estrogen and progesterone) may cause nausea, decrease sex drive and break through bleeding. Gonadotropin release hormone agonist may cause bone loss, mood alteration and possibly mental fog. Danazol is a synthetic hormone that is a cross between progesterone and testosterone.

Significant drawbacks include acne, oily skin, extra hair growth and deepening voice.

2. Pain management: Pain medications do not actually treat endometriosis. Nonsteroidal anti27

review article inflammatory drugs (NSAIDs) are commonly used to relieve dysmenorrhea by minimizing inflammation. A combination of NSAIDs with oral contraceptives can be used for treating endometriosis.

Surgical treatment: In surgical therapy, reports of recurrence are as high as 30% in patients followed 3 years postlaparoscopic surgery and 40-50% in patients 5 years after surgery. Repeated surgeries are associated with increased morbidity and healthcare costs and damage to the ovarian reserve.2,3 Pharmacotherapy of endometriosis has a lot of adverse effects. Drug therapy must be continued to maintain hypoestrogenic environment. Discontinuation of hormone therapy results in return of endometriosis.

This makes it important to find a new option to treat endometriosis, that is effective and safe.13 Resveratrol in Endometriosis Sedentary lifestyle, stressful life, exposure to pollutants and consumption of refined foods create an oxidative environment with circulating free radicals. Studies have shown that consumption of diet rich in fruits and vegetables lowers risk of endometriosis.14 Health benefits of natural products like green tea, red wine, garlic, fresh fruits have been studied in the prevention of different diseases including endometriosis.13,15,16 Resveratrol (trans-3,5,4'-trihydroxystilbene) is a phytochemical compound of grapes, red wine, nuts and different berries. Resveratrol has previously been shown to exert beneficial effects in a variety of pathological conditions, such as cardiovascular diseases and cancer.15,17 Studies have shown that resveratrol exhibits antiproliferative, anti-inflammatory, antioxidant and antiangiogenic effects.

Studies have shown that resveratrol inhibited proliferation, promoted apoptosis13 and reduced invasiveness of human endometrial stromal cells, in vitro.18 Studies in mouse model of endometriosis, in vivo, have shown that resveratrol reduces growth rate of lesions, size of lesions, cell proliferation and inhibits angiogenesis; resveratrol also promoted apoptosis within lesions.13,18,19 Similar results were also obtained in rat model of endometriosis. Resveratrol reduced implant volume, increased superoxide dismutase and glutathione peroxidase levels in serum and tissue 28

samples. Catalase and malondialdehyde levels were also elevated in serum and tissues.20 A reduction of vascular endothelial growth factor (VEGF) levels and monocyte chemotactic protein-1 (MCP-1) levels in plasma and peritoneal fluid was also observed in resveratrol treated rats.21,22 Exact mechanism of action of resveratrol is not known clearly. It is suggested that resveratrol may work through the following mechanisms: v Resveratrol has been shown to activate SIRT-1 enzyme in endometrial stromal cells. Through activation of SIRT-1 resveratrol exhibits antiinflammatory effect.23 v Inhibition of expression of hydroxymethylglutarylcoenzyme A (HMG-CoA) reductase mRNA and reduction of HMG-CoA reductase enzyme activity both in vitro24 and in in vivo.25 Since statin group of drugs have shown beneficial effect in treating endometriosis, inhibition of HMG-CoA reductase may contribute towards effect of resveratrol in endometriosis. v Additional pathways may be targeted by resveratrol.

For example, AKT, p38 MAP kinase, ERK and PPAR-g may all be modulated by resveratrol to a varying degree.18 Effect on multiple pathways may explain broad-spectrum of activities of resveratrol.

Based on promising efficacy in experimental animal models, resveratrol has been tested in humans. In one small study involving 12 patients, resveratrol was administered with an estrogen progesterone combination for 2 months. Results indicated reduction of pelvic pain and dysmenorrhea.26 In a separate study, expression of aromatase and cyclooxygenase enzyme was assessed. It was observed that when resveratrol was administered along with estrogenprogesterone combination, expression of aromatase and cyclooxygenase was inhibited to a great extent. This study, however, has faced criticism.27 More controlled clinical studies must be undertaken to establish efficacy of resveratrol in the management of endometriosis.

Conclusions In summary, endometriosis is a common disorder in premenopausal women. Endometriosis results in infertility, affects quality-of-life and brings financial stress on women. Exact molecular and cellular basis Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

Review article of endometriosis is not known. Role of estrogen has been established as a causative factor of endometriosis. Pharmacotherapy of endometriosis revolves around lowering levels of estrogen in the body. Hormone therapy for endometriosis has its limitations. There is a need for a safer and more efficacious alternative. Resveratrol can be explored as a therapeutic option for endometriosis. More studies must be done under controlled conditions to establish efficacy of resveratrol.

12. Hediger ML, Hartnett HJ, Louis GM. Association of endometriosis with body size and figure. Fertil Steril. 2005; 84(5):1366-74.

References

15. Cucciolla V, Borriello A, Oliva A, Galletti P, Zappia V, Della Ragione F. Resveratrol: from basic science to the clinic. Cell Cycle. 2007;6(20):2495-510.

1. Brosens I, Benagiano G. Endometriosis, a modern syndrome. Indian J Med Res. 2011;133:581-93.

2. Suresh PS, Venkatesh T, Rajan T, Tsutsumi R. Molecular pathology and therapy of endometriosis: revisited. Androl Gynecol. Curr Res. 2013;1(3):1-7.

3. Sourial S, Tempest N, Hapangama DK. Theories on the pathogenesis of endometriosis. Int J Reprod Med. 2014;2014:179515.

4. Davila GW. Endometriosis, Practice Essentials, Pathophysiology Etiology. Workshop 2016. Available at: http://emedicine.medscape.com/article/271899-workshop 5. Khawaja UB, Khawaja AA, Gowani SA, Shoukat S, Ejaz S, Ali FN, et al. Frequency of endometriosis among infertile women and association of clinical signs and symptoms with the laparoscopic staging of endometriosis. J Pak Med Assoc.

2009;59(1):30-4.

6. Bendigeri T, Warty N, Sawant R, Dasmahapatra P, Padte K, Humane A, et al. Endometriosis: Clinical experience of 500 patients from India. The Indian Practitioner.

2015;68(7):34-40.

7. Eskenazi B, Warner ML. Epidemiology of endometriosis.

Obstet Gynecol Clin North Am. 1997;24(2):235-58.

8. Cramer DW, Missmer SA. The epidemiology of endometriosis.

Ann N Y Acad Sci. 2002;955:11-22; discussion 34-6, 396-406.

9. Thaim SA, Jha RK, Saheta A, Santra D, SamaThaim S. Comparison of effectiveness profile of danazol and gestrinone in pelvic endometriosis: a community based observational study in Wardha District-Eastern Maharashtra. IOSR Journal of Pharmacy. 2015;5(1):8-15.

10. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98(3):511-9.

11. Abbas S, Ihle P, Köster I, Schubert I. Prevalence and incidence of diagnosed endometriosis and risk of endometriosis in patients with endometriosis-related symptoms: findings from a statutory health insurance-based cohort in Germany. Eur J Obstet Gynecol Reprod Biol. 2012;160(1):79-83.

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13. Ricci AG, Olivares CN, Bilotas MA, Bastón JI, Singla JJ, Meresman GF, et al. Natural therapies assessment for the treatment of endometriosis. Hum Reprod. 2013;28(1): 178-88.

14. Halpern G, Schor E, Kopelman A. Nutritional aspects related to endometriosis. Rev Assoc Med Bras. 2015;61(6): 519-23.

16. Khan N, Mukhtar H. Multitargeted therapy of cancer by green tea polyphenols. Cancer Lett. 2008;269(2):269-80.

17. Baur JA, Sinclair, DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5(6): 493-506.

18. Bruner-Tran K, Sokalska A, Osteen K, Taylor HS, Duleba AJ. Resveratrol inhibits development of experimental endometriosis and induces apoptosis of endometrial stroma.

Fertil Steril. 2009;92(3):S64-65.

19. Rudzitis-Auth J, Menger MD, Laschke MW. Resveratrol is a potent inhibitor of vascularization and cell proliferation in experimental endometriosis. Hum Reprod. 2013;28(5): 1339-47.

20. Yavuz S, Aydin NE, Celik O, Yilmaz E, Ozerol E, Tanbek K. Resveratrol successfully treats experimental endometriosis through modulation of oxidative stress and lipid peroxidation.

J Cancer Res Ther. 2014;10(2):324-9.

21. Ergenoğlu AM, Yeniel AÖ, Erbaş O, Aktuğ H, Yildirim N, Ulukuş M, Taskiran D, et al. Regression of endometrial implants by resveratrol in an experimentally induced endometriosis model in rats. Reprod Sci. 2013;20(10): 1230-6.2 22. Cenksoy PO, Oktem M, Erdem O, Karakaya C, Cenksoy C, Erdem A, et al. A potential novel treatment strategy: inhibition of angiogenesis and inflammation by resveratrol for regression of endometriosis in an experimental rat model.

Gynecol Endocrinol. 2015;31(3):219-24.

23. Taguchi A, Wada-Hiraike O, Kawana K, Koga K, Yamashita A, Shirane A, et al. Resveratrol suppresses inflammatory responses in endometrial stromal cells derived from endometriosis: a possible role of the sirtuin 1 pathway. J Obstet Gynaecol Res. 2014;40(3):770-8.

24. Villanueva JA, Sokalska A, Cress AB, Ortega I, Bruner-Tran KL, Osteen KG, et al. Resveratrol potentiates effects of simvastatin on inhibition of mevalonate pathway

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review article in human endometrial stromal cells. J Clin Endocrinol Metab. 2013;98(3):E455-62.

25. Cho IJ, Ahn JY, Kim S, Choi MS, Ha TY. Resveratrol attenuates the expression of HMG-CoA reductase mRNA in hamsters. Biochem Biophys Res Commun. 2008;367(1): 190-4.

26. Maia H Jr, Haddad C, Pinheiro N, Casoy J. Advantages of the association of resveratrol with oral contraceptives for management of endometriosis-related pain. Int J Womens Health. 2015;4:543-9.

27. Rosser M. Endometriosis update: That’s an awful lot of red wine 2012. Available at: www.endo-update.blogspot.in/

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Three Different Gonadotropin Doses With or Without Letrozole During Ovulation Stimulation A randomized controlled trial compared the IVF outcomes between patients with poor ovarian reserve (POR) who received three different gonadotropin doses with or without the addition of letrozole during ovulation stimulation. Differences in doses of hMG and rFSH in patients with POR yielded a similar number of retrieved MII and fertilized oocytes, similar fertilization rates, number of transferred embryos, implantation, cancelation, chemical, clinical and ongoing pregnancy rates. Increasing the dose may not necessarily improve the reproductive outcome, reported the trial published online in the European Journal of Obstetrics and Gynecology and Reproductive Biology. Mild stimulation with addition of letrozole was as effective as stimulation with higher doses of gonadotropins alone.

...Cont'd from page 17 10. Errichiello S, Esposito O, Di Mase R, Camarca ME, Natale C, Limongelli MG, et al. Celiac disease: predictors of compliance with a gluten-free diet in adolescents and young adults. J Pediatr Gastroenterol Nutr. 2010;50(1):54-60.

14. Rashid M, Cranney A, Zarkadas M, Graham ID, Switzer C, Case S, et al. Celiac disease: evaluation of the diagnosis and dietary compliance in Canadian children.

Pediatrics. 2005;116(6):e754-9.

11. Anson O, Weizman Z, Zeevi N. Celiac disease: parental knowledge and attitudes of dietary compliance. Pediatrics.

1990;85(1):98-103.

15. Olsson C, Hornell A, Ivarsson A, Sydner YM. The everyday life of adolescent coeliacs: issues of importance for compliance with the gluten-free diet. J Hum Nutr Diet.

2008;21(4):359-67.

12. Mazzone L, Reale L, Spina M, Guarnera M, Lionetti E, Martorana S, et al. Compliant gluten-free children with celiac disease: an evaluation of psychological distress. BMC Pediatr. 2011;11:46.

13. Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child. 1990;65 (8):909-11.

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16. Butterworth JR, Banfield LM, Iqbal TH, Cooper BT. Factors relating to compliance with a gluten-free diet in patients with coeliac disease: comparison of white Caucasian and South Asian patients. Clin Nutr. 2004;23(5):1127-34.

17. Lee A, Newman JM. Celiac diet: its impact on quality of life. J Am Diet Assoc. 2003;103(11):1533-5.

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

Case Report

Cervical Molar Pregnancy and Its Future Fertility Babita Ramani*, Rajat Mohanty†, Sudipta Patnaik‡

Abstract Background: Cervical complete molar pregnancy is very rare and fatal and surgical intervention makes it lethal. Case report: A 37 years G2P1L1 with previous cesarean section 4 years back, had presented with brisk vaginal bleeding after evacuation at private hospital 2 days back. She was admitted in labor room,VSS Medical College, Burla at 9 pm on 22.04.2012 as an emergency case. USG report which was done at our institute, showed cervical invasive mole with right ovarian cyst. She was managed with methotrexate and no other intervention was required, as her serum b-hCG was declining. Now, she is having a normal pregnancy. Conclusion: Surgical intervention in such situations is very fatal. We propose her to go for a fertility sparing medical management.

Keywords: Cervical molar pregnancy, vaginal bleeding, injection methotrexate, serum b-hCG

C

ervical pregnancy is a rare variety of ectopic pregnancy. Incidence of cervical pregnancy is <1% of all ectopic pregnancies.1 Molar changes in the cervical pregnancy are very rare occurrence.

To preserve uterus and cervix in such a situation is really a challenge to the obstetrician.

Case Report A 37-year-old lady G2P1L1 came to the labor room, VSS Medical College, Burla, at 9 pm on 22.04.2012 in emergency with complaint of bleeding per vaginum for 2 days at 6 weeks of pregnancy for which suction and evacuation was tried at a local hospital, but she landed up with brisk hemorrhage and was referred to higher center, where sonography revealed an enlarged uterus and distended cervix with multiple tiny anechoic structures filling the dilated cervical canal (Fig. 1). Internal os was closed and there was a cervical

*Senior Resident Dept. of Obstetrics and Gynecology VSS Medical College, Burla, Sambalpur, Odisha † Senior Specialist and Consultant Dept. of Obstetrics and Gynecology ‡ Assistant Professor Dept. of Physiology SCB Medical College, Cuttack, Odisha Address for correspondence Dr Babita Ramani Qtr No: 3R/10, Doctor’s Colony VSS Medical College Campus, Burla - 768 017, Sambalpur, Odisha E-mail: babitaramani@gmail.com

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

pregnancy, so she was referred to a tertiary center.

On examination, her pulse rate was 90/min and blood pressure (BP) 110/70 mmHg with moderate degree of pallor. Abdomen was soft with normal findings. No bleeding was present on inspection of vulva.

On per speculum examination, external os was open, no bleeding through os was seen. On bimanual examination cervix was distended, os was 2 cm dilated and soft structure felt through os. Uterus was bulky, anteverted, soft, mobile, fornices were free and nontender.

Her hemoglobin was 9.8 g/dL and serum b-hCG (human chorionic gonadotropin) was 19,714.74 mIU/mL. Her liver function tests, renal function tests and thyroid-stimulating hormone were within normal limits. USG, revealed an enlarged uterus (115 × 65 × 49 mm) with complex lesion adherent to the anterior cervical wall of size 43 × 40 × 32 mm, volume 21.6 cc, mostly cystic with peripheral hypervascularity,

Figure 1. Enlarged uterus and distended cervix with multiple tiny anechoic structures filling the dilated cervical canal.

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Case Report

Figure 2. Multiple cystic lesions in the cervix.

Figure 3. Right ovarian cyst (theca lutein).

a right ovarian cyst of size 43 × 29 × 30 mm; no identifiable gestational sac was seen (Figs. 2 and 3). Left ovary was normal. Endometrial thickness was 12 mm, with signs of invasive cervical mole. Histopathology report revealed hydropic villi with irregular scalloped outline (Fig. 4).

As she was not bleeding was managed her conservatively with 1 unit of blood transfusion and injection methotrexate 1 mg/kg on D 1, 3, 5, 7 alternating with folinic acid 0.1 mg/kg. Injectable broad-spectrum antibiotic was also given, which was continued till 29.04.12 and was discharged on 01.05.12 with advice for barrier contraception.

Serial serum b-hCG gradually decreased to undetectable levels within a span of 6 weeks. She used calender method, instead of barrier contraception and conceived after 14 months in June 2013 and this time it was an intrauterine pregnancy. During this pregnancy at 6 weeks, she terminated the same by medical method.

Discussion Four cases of cervical molar pregnancy have reported in literature till now, two of them were partial cervical moles and two were complete cervical mole. Beless et al2 have given cervical cerclage like stay sutures to control the bleeding after surgical procedure. Schorge and associates3 evaluated that fertility was not impaired and pregnancy outcomes were usually normal following successful treatment of cervical molar pregnancy.

Schwentner et al4 revealed the cause of cervical molar pregnancy, which was traumatic holding of the cervix during evacuation of a missed abortion. It has also been suggested that a previous cesarean section may play a role in the etiology of cervical pregnancy and

Figure 4. Hydropic villi with irregular scalloped outline.

molar changes are related to the older age group i.e., >35 years.5 These two factors may be the main cause of the present case. Aytan et al6 terminated the partial cervical molar pregnancy by suction and evacuation followed by serial serum b-hCG evaluation. The present case was managed successfully by injection methotrexate in multiple doses alternating with folinic acid. She was also counseled about the future risk of choriocarcinoma.

Conclusion Surgical intervention in such a situation is very fatal.

We propose to go for a fertility sparing medical management.

References 1. Ushakov FB, Elchalal U, Aceman PJ, Schenker JG. Cervical pregnancy: past and future. Obstet Gynecol Surv.

1997;52(1):45-59.

2. Beless DJ. Cervical hydatidiform mole causing severe vaginal hemorrhage: a case report. J Reprod Med. 1995;40(12): 855-8.

3. Schorge JO, Goldstein DP, Bernstein MR, Berkowitz RS. Recent advances in gestational trophoblastic disease.

J Reprod Med. 2000;45(9):692-700.

4. Schwentner L, Schmitt W, Bartusek G, Kreienberg R, Herr D. Cervical hydatidiform mole pregnancy after missed abortion presenting with severe vaginal bleeding: case report and review of the literature.

Eur J Obstet Gynecol Reprod Biol. 2011;156(1):9-11.

5. Parazzini F, La Vecchia C, Pampallona S. Parental age and risk of complete and partial hydatidiform mole.

Br J Obstet Gynaecol. 1986;93(6):582-5.

6. Aytan H, Caliskan AC, Demirturk F, Koseoglu RD, Acu B. Cervical partial hydatidiform molar pregnancy. Gynecol Obstet Invest. 2008;66(2):142-4.

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Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

Photo Quiz

Discoloration in the Hands Antonio L. Aguilar Shea, Cristina Gallardo-Mayo

A

42-year-old woman had pain in her hands and discoloration on the tips of her fingers and toes when exposed to cold (Figure 1). She had chronic systemic lupus erythematosus that was diagnosed seven years earlier.

Her urinalysis findings were abnormal, including the presence of proteinuria and hematuria. Her creatinine level was normal, and her antinuclear antibody titer was 1:2,560. Renal biopsy, which was performed because of the proteinuria, revealed stage V membranous lupus nephritis.

Question Based on the patientâ&#x20AC;&#x2122;s history and physical examination findings, which one of the following is the most likely diagnosis?

A. Acrocyanosis.

Figure 1.

B. Acute peripheral arterial occlusion.

C. Frostbite.

D. Raynaud phenomenon.

See the following page for discussion.

Source: Adapted from Am Fam Physician. 2015;92(4):295-296.

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016

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Photo Quiz Summary Table Condition

Characteristics

Examination findings

Acrocyanosis

Benign condition caused by mild vasospasm

Symmetric, persistent, blue or cyanotic discoloration of the hands, feet, or face

Acute peripheral arterial occlusion

Caused by an acute stoppage of blood flow as Acute pain, skin turns pale and cold, no pulse, possible paralysis a result of an embolism of the affected area

Frostbite

Caused by freezing of the skin and underlying Skin becomes very cold and red; if the exposure persists, tissues the skin becomes numb, hard, and pale, and blisters and ulcers appear

Raynaud phenomenon

Occurs with exposure to cold or emotional stress; Skin turns white or pale because of vasoconstriction, then caused by an exaggerated vasoconstriction blue when the oxygen supply is depleted and red as the blood flow returns

Discussion The correct answer is D: Raynaud phenomenon.

Raynaud phenomenon is a discoloration of the fingertips and toes after exposure to cold or emotional stress. First, the skin turns white or pale because of exaggerated vasoconstriction, then blue when the oxygen supply is depleted and red as the blood flow returns. Raynaud phenomenon may be primary or idiopathic (not associated with other conditions) or secondary (associated with other conditions). If secondary, Raynaud phenomenon can present before the diagnosis or during the natural history of the associated condition.1,2 In this patient, Raynaud phenomenon presented with a decline in kidney function. Secondary Raynaud phenomenon is often associated with autoimmune rheumatic diseases such as systemic lupus erythematosus, scleroderma, mixed connective tissue disease, Sjögren syndrome, dermatomyositis, and polymyositis. Nail fold capillaroscopy can be used to distinguish between primary and secondary Raynaud phenomenon. An abnormal result can suggest an underlying autoimmune rheumatic disease.3,4 Treatment of Raynaud phenomenon is based on lifestyle changes (e.g., keeping the hands warm, quitting smoking, exercising regularly to avoid further attacks) and on medical treatments (e.g., calcium channel blockers, topical nitroglycerin, phosphodiesterase-5 inhibitors). Local injections of onabotulinumtoxinA or parenteral prostaglandins can also be used.2,5 Acrocyanosis is a condition characterized by a symmetric, persistent, blue or cyanotic discoloration

of the hands, feet, or face. It is caused by vasospasm of the small vessels of the skin and often occurs in newborns. It is painless and considered benign.

Acute peripheral arterial occlusion because of an embolism causes an acute stoppage of blood flow. It is often associated with cardiac conditions, such as atrial fibrillation. The patient presents with acute pain, the skin turns pale and cold, and there can be paralysis of the affected area. There is no pulse to the extremity. If blood flow is not restored promptly, tissue in the area will die.

Frostbite is caused by exposure of the skin to freezing temperatures, which damages the skin and underlying tissues. Initially, the skin becomes very cold and red.

If the exposure persists, the skin becomes numb, hard, and pale, then blisters and ulcers appear.

References 1. Maverakis E, Patel F, Kronenberg DG, et al. International consensus criteria for the diagnosis of Raynaud phenomenon.

J Autoimmun. 2014;48-49:60-65.

2. Pope JE. Raynaud’s phenomenon (primary). BMJ Clin Evid. 2013. http://clinicalevidence.bmj.com/x/systematicreview/1119/overview.html. Accessed May 18, 2015.

3. Jung P, Trautinger F. Capillaroscopy. J Dtsch Dermatol Ges. 2013;11(8):731-736.

4. Herrick AL, Cutolo M. Clinical implications from capillaroscopic analysis in patients with Raynaud’s phenomenon and systemic sclerosis. Arthritis Rheum.

2010;62(9):2595-2604.

5. Levien TL. Advances in the treatment of Raynaud’s phenomenon. Vasc Health Risk Manag. 2010;6:167-177.

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Online Submission Also e-issue @ www.ijcpgroup.com For Editorial Correspondence

Dr KK Aggarwal

Group Editor-in-Chief Asian Journal of Obstetrics and Gynaecology Practice E - 219, Greater Kailash, Part - 1, New Delhi - 110 048. Phone: 011-40587513 E-mail: editorial@ijcp.com, Website: www.ijcpgroup.com

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 2, No. 3, 2016