Journal of Human Reproductive Science
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    Table of Contents - Current issue
Coverpage
October-December 2020
Volume 13 | Issue 4
Page Nos. 249-355

Online since Monday, December 28, 2020

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EDITORIAL  

Editorial Commentary Highly accessed article p. 249
Padma Rekha Jirge
DOI:10.4103/jhrs.JHRS_236_20  
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REVIEW ARTICLES Top

Future of Health Services: The Role of Physicians in the Disruptive Era p. 250
Budi Wiweko, Sarah Chairani Zakirah
DOI:10.4103/jhrs.JHRS_172_19  
This article aimed to address the role of physicians in future health in the disruptive era. Physicians in this disruptive era must increase their capability and knowledge to compensate for this development. Advances in technology increase the impact on health care and the significance of disruption. Disruptive innovation encompasses several fields, such as physics, digital, and biology. Big data as one of the most important parts in clinical aspects encompass high-throughput cellular and protein-binding assays toward chemoinformatic-driven databases. Health status can be modified by changing epigenetic factor, such as lifestyle and environment. As a result, they affect human genetics and provide the insight of pathophysiology of disease, clinical treatment, and early preventive action. Disruptive innovations in health-care align with the development of artificial intelligence, machine learning, robotics, Internet of things, digitalization, and genomics. New paradigm shifting in physician–patient relationships is relevant to consumer health informatics.
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Anti-Müllerian Hormone: A Personal View of the Empowering Analyte p. 257
Richard Fleming
DOI:10.4103/jhrs.JHRS_231_20  
Circulating Anti Mullerian hormone (AMH) represents the total number of granulosa cells in the ovaries and is therefore a direct measure of the number of growing follicles within the ovaries. The close agreement of the main commercial assays for circulating AMH is allowing improved validation of the test in numerous circumstances. Consequently, it can be explored in all circumstances where ovarian activity may be relevant, and thereby bring improved guidance to the choices doctors and patients need to make in their reproductive lives. Apart from numerous aspects of ovarian stimulation, the main areas of impact are in endometriosis and the menopause. The best advice approach requires use of this evidence in many circumstances, and the future will see its measurement on a widespread basis.
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The Prevalence of Polycystic Ovary Syndrome: A Brief Systematic Review p. 261
Ritu Deswal, Vinay Narwal, Amita Dang, Chandra S Pundir
DOI:10.4103/jhrs.JHRS_95_18  
Background: Polycystic ovary syndrome (PCOS), the major endocrinopathy among reproductive-aged women, is not yet perceived as an important health problem in the world. It affects 4%–20% of women of reproductive age worldwide. The prevalence, diagnosis, etiology, management, clinical practices, psychological issues, and prevention are some of the most confusing aspects associated with PCOS. Aim: The exact prevalence figures regarding PCOS are limited and unclear. The aim of this review is to summarize comprehensively the current knowledge on the prevalence of PCOS. Materials and Methods: Literature search was performed through PubMed, ScienceDirect, Cochrane Library, and Google Scholar (up to December 2019). All relevant articles published in English language were identified following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Our analysis yielded 27 surveys with a pooled mean prevalence of 21.27% using different diagnostic criteria. The proportion of women with PCOS also increased in the last decade. Conclusion: The current review summarizes and interprets the results of all published prevalence studies and highlights the burden of the syndrome, thereby supporting early identification and prevention of PCOS in order to reverse the persistent upward trend of prevalence.
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ORIGINAL ARTICLES Top

Evaluation of Reproductive Outcome in Infertile Hypothyroid Women on Thyroxine Therapy p. 272
Leena Wadhwa, K Monica Marghret, Sarika Arora
DOI:10.4103/jhrs.JHRS_14_20  
Introduction: Thyroid dysfunction is associated with increased risk of infertility. Serum thyroid stimulating hormone (TSH) screening in all women seeking infertility care is recommended and hypothyroid infertile women should be treated with thyroxine until the preconception serum TSH level is <2.5 mU/l.[1] However, insufficient evidence exist to determine if thyroxine therapy improves fertility in subclinical hypothyroid women who are trying to conceive naturally. Objectives: The objective is to study the effect of thyroxine therapy on reproductive outcome in infertile women with clinical and subclinical hypothyroidism (SCH). Materials and Methods: The study is a descriptive cohort study with 72 subjects. Women between 20 and 40 years of age with primary or secondary infertility with hypothyroidism were studied and thyroid profile including free T3, T4, TSH, and thyroid antibodies were done. Thyroxine was given to clinical, subclinical hypothyroid subjects depending on TSH levels such that serum TSH levels are maintained < 2.5 mU/L. Serial thyroid function test was done every 6 weeks until the optimal levels were reached. Once normal TSH levels were reached subjects were followed up for 6 months. Reproductive outcome was analyzed in two groups. Group A included hypothyroid infertile women who conceived and Group B included those who did not conceive following thyroxine therapy. Results: Thirty-eight out of 72 subjects (54%) conceived during thyroxine treatment (Group A) of which 4 cases had miscarriage. Maximum infertile women in Group A (20/38) conceived between 6 and 12 months (52.6%) of thyroxine therapy. Significant decrease was observed in mean TSH levels over a period of 6 months (P < 0.001). The infertility period until pregnancy in Group A reduced significantly from 5.2 ± 1.8 years to 0.5 ± 0.8 years after thyroxine treatment (P = 0.001). Conclusion: Thyroxine therapy enhances fertility in infertile women with clinical and SCH.
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Divergences in Clinical, Anthropometric, Metabolic, and Hormonal Parameters among Different Phenotypes of Polycystic Ovary Syndrome Presenting at Endocrinology Outpatient Departments: A Multicenter Study from Bangladesh p. 277
A B. M. Kamrul-Hasan, Fatema Tuz Zahura Aalpona, Marufa Mustari, Farhana Akter, Mohammad Motiur Rahman, Shahjada Selim
DOI:10.4103/jhrs.JHRS_34_20  
Background: Polycystic ovary syndrome (PCOS) is a heterogeneous androgen-excess disorder. Data comparing the PCOS phenotypes in Bangladesh are scarce. Objectives: The objective of this study was to find out the distribution of Rotterdam classified PCOS phenotypes and to compare the phenotypes concerning clinical, anthropometric, metabolic, and hormonal parameters. Subjects and Methods: In this cross-sectional study, 370 PCOS cases in the age group of 20–45 years diagnosed by the Rotterdam consensus criteria were recruited from the endocrinology outpatient departments of several tertiary hospitals of Bangladesh. Metabolic syndrome (MetS) was diagnosed using the International Diabetes Federation criteria. Results: The prevalence of phenotypes A, B, C, and D were 59.2%, 14.1%, 11.9%, and 14.9%, respectively. More than one-third (34.6%) of the women had pre-hypertension (pre-HTN)/hypertension (HTN), 34.1% had abnormal glucose intolerance (AGT), 93.0% had dyslipidemia, and 57.0% had MetS. The hyperandrogenic phenotypes (A, B, and C) had higher prevalence of pre-HTN/HTN, AGT, dyslipidemia, and MetS compared to the normoandrogenic phenotype D, though the differences were statistically insignificant. The clinical and biochemical markers of hyperandrogenism (Ferriman-Gallwey score, hirsutism, acne, and serum testosterone levels) did not differ among the hyperandrogenic phenotypes. The serum prolactin level was highest in phenotype C. No differences were observed in most other clinical, anthropometric, metabolic, and hormonal parameters among the four phenotypes. Conclusion: Phenotype A is the most prevalent phenotype of PCOS in our setting. The prevalence of MetS was considerably high. Most of the clinical, anthropometric, and metabolic parameters were similar across the four PCOS phenotypes in this study.
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Role of Gene Xpert in the Detection of Genital Tuberculosis in Endometrial Tissue among Women with Infertility p. 285
Kriti Tiwari, Sudha Prasad, Renu Tanwar
DOI:10.4103/jhrs.JHRS_52_20  
Objective: The objective of the study is to evaluate the clinical utility of Gene Xpert compared with other available diagnostic modalities in prompt diagnosis of female genital tuberculosis (TB) causing infertility. Material and Methods: This was a prospective, cross-sectional analytical study. Premenstrual endometrial biopsy specimens were collected from 176 infertile women of reproductive age group suspected of having genital TB. Samples were processed for acid-fast bacilli, culture, histopathology, polymerase chain reaction (PCR), and Gene Xpert. Patients detected positive on Gene Xpert and PCR were subjected to laparoscopy to look for affirmative findings of genital TB. The results were analyzed using composite gold standard consisting of patients positive with culture, histopathology, and laparoscopy. Results: A total of 18 patients were found positive using composite gold standard. Laparoscopy was positive in 15 patients, whereas culture and histopathology were positive in three and two patients, respectively. Gene Xpert was positive in two patients. None of them was detected with rifampicin resistance. The sensitivity of Gene Xpert was 11.11% whereas the specificity was 100%. Conclusion: Since genital TB is a paucibacillary disease, multiple diagnostic modalities are needed for diagnosis. Gene Xpert appears to be a useful modality in diagnosis of genital TB, owing to its high specificity, and can be recommended in conditions where microscopy, culture, and histopathology are negative; however, further randomized studies are required to support our hypothesis.
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A Study on Diagnostic Evaluation of Two Different Rapid DNA Polymerase Chain Reaction Techniques Namely Gene Xpert Mycobacterium Tuberculosis/Rifampin (MTB/RIF) and Mycoreal Polymerase Chain Reaction in the Diagnosis of Endometrial Tuberculosis Considering Culture as Gold Standard p. 290
M Ashwini, N Ashwini, N Arunkumar, Devika Gunasheela
DOI:10.4103/jhrs.JHRS_16_20  
Context: The study involves the evaluation of two polymerase chain reaction (PCR) techniques one of which has been endorsed by the WHO for their diagnostic capabilities. Aims: The aim of this study is to evaluate the diagnostic accuracy of GeneXpert mycobacterium tuberculosis/Rifampin (MTB/RIF) and mycoreal PCR techniques in the diagnosis of endometrial tuberculosis (TB) considering culture as the gold standard. Settings and Design: A retrospective study conducted at Gunasheela surgical and maternity hospital. Patients who attended the outpatient department between January 2013 and August 2016, satisfying the eligibility criteria, were included in the study. Methodology: Women included in the study underwent endometrial pipelle sampling premenstrually after ruling out pregnancy in that cycle. Endometrial samples were tested for TB by Mycoreal PCR, Gene Xpert and BACTEC culture. Statistical Analysis Used: Statistical analysis was done using the R software version 3.6.1. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of test were calculated. Results: A total of 3229 samples were analyzed, of which 1754 were evaluated by Mycoreal TB PCR and 1475 were evaluated by Gene Xpert MTB/RIF assay. The sensitivity of mycoreal TB PCR technique was 34.78%, specificity was 99.08%, PPV was 33.33%, NPV was 99.13%, and accuracy was 98.23%. The sensitivity of GeneXpert MTB/RIF technique was 6.90%, specificity was 99.79%, PPV was 40.00%, NPV was 98.16%, and accuracy was 97.97%. Conclusions: MYCOREAL seemed to be more sensitive than Gene Xpert (MTB/RIF) considering culture as the gold standard in the diagnosis of endometrial TB.
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Three-Dimensional Automated Volume Calculation (Sonography-Based Automated Volume Count) versus Two-Dimensional Manual Ultrasonography for Follicular Tracking and Oocyte Retrieval in Women Undergoing in vitro Fertilization-Embryo Transfer: A Randomized Controlled Trial p. 296
Nilofar Noor, Chithira Pulimoottil Vignarajan, Neena Malhotra, Perumal Vanamail
DOI:10.4103/jhrs.JHRS_91_20  
Aim: To compare the oocyte yield using three-dimensional (3D) automated and two-dimensional (2D) ultrasound-based follicle tracking in women undergoing in vitro fertilization-embryo transfer (IVF-ET). Settings and Design: A randomized controlled trial was conducted in the Reproductive Medicine Unit of a teaching medical institute from January 2017 to December 2018. Materials and Methods: A total of 130 patients undergoing IVF-ET were enrolled and randomized into two groups (65 patients in each group). In Group A, follicular tracking during controlled ovarian stimulation (COS) was done using 3D Sonography- based Automated Volume Count (SonoAVC), whereas in Group B, follicular tracking was done by manual ultrasonography (2D USG). The primary outcome measures were the number of oocytes retrieved (the total number and the number of mature oocytes). Secondary outcomes were fertilization rate, cleavage rate, total number of embryos and time taken to perform scans. Other outcome measures were clinical pregnancy rate, miscarriage rate and live birth rate (LBR). Statistical Analysis Used: Chi-square test, Student's t-test, Z-test, Wilcoxon rank-sum test, Bland–Altman's plot. Results: The two groups were comparable with regard to assisted reproductive technology (ART) outcomes. Group B required more time for performing the scan (P < 0.01). Conclusion: Automated SonoAVC ultrasound can be used interchangeably with manual 2D USG for follicle tracking during COS giving comparable ART outcomes with the added advantage of saving time. Our study implies the promising results of applying artificial intelligence in follicular tracking during COS.
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Novel Technique of Vaginoplasty Developing Normal Vagina, Role of Stemness Markers and Translational Genes p. 303
Pravin Mhatre, Vikas Dighe, Dhanjit Kumar Das, Amol Pawar
DOI:10.4103/jhrs.JHRS_68_20  
Aims and Objectives: To study development of neo-vagina by metaplastic conversion of peritoneum, To identify translational Stemness markers using NANOG/OCT4/SOX2 from serial neo-vaginal mRNA, cDNA and to study role of WNT and HOXA genes in patients undergoing vaginoplasty. Material and Methods: 75 MRKH Syndrome women underwent laparoscopic peritoneal vaginoplasty (LPV). Two patients underwent serial neo-vaginal biopsies on day 0, 7-9, 12-14, 21 and 33. Fifteen MRKHS and twelve controls were subjected for neo-vaginal biopsy to detect genes upregulation. Remaining patients were evaluated anatomically and functionally. Results: The translational stemness markers NANOG, OCT4 and SOX2 responsible for neo-vaginal formation were identified. Their appearance, concentration at different stages of conversion were demonstrated. The neo-vagina has shown up-regulation of these translational stemness markers. The study demonstrates expression of the specific genes (WNT4, WNT5A and WNT7A) and their role in formation of the neo-vagina. In the subjects stemness markers (NANOG, OCT4 and SOX2) appeared from day 9 to 14 of the neo-vaginal biopsies and after achieving the peak declined later. Genetic analysis showed low values in HOXA 9,10,11,13 and up-regulation of WNT 4A,5A,7 genes in neo-vagina. Conclusions: Study shows peritoneal metaplastic conversion to normal vagina, identified the translational stemness markers and genes responsible. The neo-vagina has shown up-regulation of these genes. The study demonstrates expression of the specific genes (WNT4, WNT5A and WNT7A) and their role in formation of the neo-vagina. Furthering this research, activating these genes may lead to treatment of developmental defects of Mullerian duct, obviating the need of transplant.
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Safe Gynecological Laparoscopic Surgery during COVID Times p. 310
Prakash Harikant Trivedi, Soumil Prakash Trivedi, Nilesh Maruti Ghadge, Dinesh Popatlal Bajani, Aditi Soumil Trivedi
DOI:10.4103/jhrs.JHRS_185_20  
Background: SARS-CoV-2 virus is largely transmitted via respiratory droplets and the highest transmission risks arise when undertaking aerosol generating procedures like laparoscopy. Most national societies had advised the urgent suspension of elective surgery with the focus shifting to emergency and cancer surgery only during this pandemic. However very little is known regarding the risks to the health care professionals undertaking emergency laparoscopic procedures. Aims and Objective: To demonstrate safety at laparoscopy by modifying the technique for safe management of patients during the COVID-19 pandemic. Design and Setting: This is an observational cohort study. This study was done at a tertiary care reference hospital for minimal access gynaecological surgery. Safety of 42 semi-urgent and emergency laparoscopic surgeries in patients was evaluated for a period of 5 months after taking informed written consent of patients to participate in the study. Materials and Methods: Use of double closed circuit laparoscopic suction evacuation and filtration systems with closed circuit anaesthesia with specialized Heat and Moisture Exchangers (HME) bacterial & viral (BV) filters to make laparoscopic surgery safe. Results: 57.14% of the patients were 41 years or more. 47.6% presented either with menorrhagia, irregular vaginal bleeding or post-menopausal vaginal bleeding and 26.19 % patients were keen to conceive. In 50% patients, surgery was done in 60 minutes or less. Post-operatively, none of the patients had any complications and all were followed up for 14 days for COVID-19 infection. No staff, doctors or anaesthetist were detected COVID-19 positive during the follow up period. The limitation of the study was, that it was an observational study done in COVID-19 negative patients only. Conclusions: Safety at laparoscopy can be maintained when it is performed by an experienced surgeon who has full knowledge of safe laparoscopic techniques and performs it in the shortest time possible and with all due precautions.
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Emotional Impact of Delay in Fertility Treatment due to COVID-19 Pandemic p. 317
Harpreet Kaur, Gautham T Pranesh, Kamini A Rao
DOI:10.4103/jhrs.JHRS_144_20  
Background: COVID-19 pandemic is an unprecedented public health emergency. When the pandemic started in our country fertility treatment was suspended for sometimes following national and international guidelines. This has led to delay in fertility treatment for some couples which was emotionally upsetting. Methodology and Design: This study was done on the patients enrolled at our various fertility units across India. The survey questionnaire was sent to patients during the month of first May to June 15, 2020, when COVID-19 pandemic was active across the country, and fertility units were just resuming the services back. The questionnaire was distributed to 100 patients who were currently under treatment and their response was recorded. Ethical committee approval was not taken as surveys are exempted from IRB. Results: This survey was undertaken to understand the emotional impact of delay/cancelation in the fertility treatment during the COVID-19 pandemic. The survey revealed that majority (95%) of couples felt cancelation of cycles as upsetting and 16% reporting it to be extremely upsetting. The impact was seen in the form of mood disturbances, anxiety, sleep disturbances, and depressive ideas. Almost half of the couples (49.4%) were desirous to start the fertility treatment immediately. Their knowledge regarding COVID-19 and pregnancy and future child was limited. Conclusion: COVID-19 has had impact on every sphere of life. Delay in treatment and cancelation of cycles were emotionally upsetting to majority of couples and they were keen to restart the treatment sooner than later.
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Resuming Assisted Reproduction Services during COVID-19 Pandemic: An Initial Indian Experience p. 323
Padma Rekha Jirge, Sadhana Patwardhan, Shishir Narendra Jirge, Deepali A Bhomkar, Shruti M Chougule, Anita Salpekar, Deepak Modi
DOI:10.4103/jhrs.JHRS_211_20  
Background: The pandemic of COVID-19 has affected many countries and medical services including assisted reproductive treatment (ART) have been hampered. Aim: The study was conducted to assess the preparedness of ART clinics and staff to resume services; patients' reasons to initiate treatment; and key performance indicators (KPIs) of ART laboratories during the pandemic. Setting and Design: This was a semidescriptive, prospective study in two private in vitro fertilization (IVF) clinics in Maharashtra, India, when COVID-19 testing for asymptomatic people was unavailable. Materials and Methods: Time required for replenishing consumables and clinic preparedness to function under “new norms” of pandemic was documented. Infection mitigation measures and triaging strategy were evaluated. KPIs following resumption were analyzed. The Student's t-test was performed for comparing parameters. Results: Thirty percent of the patients consulted through telemedicine accepted or were eligible to initiate treatment on clinic resumption. Lack of safe transport and financial constraints prevented majority from undergoing IVF, and 9% delayed treatment due to fear of pandemic. With adequate training, staff compliance to meet new demands was achieved within a week, but procuring consumables and injections was time-consuming. Fifty-two cycles of IVF were performed including fresh and frozen embryo transfers with satisfactory KPIs even during pandemic. Conscious sedation and analgesia during oocyte retrieval were associated with reduced procedure time and no intervention for airway maintenance compared to general anesthesia. Self-reported pain scores by patients ranged from nil to mild on a graphic rating scale. Conclusions: This study provides practical insight for the resumption of IVF services during the COVID-19 pandemic.
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A Preliminary Experience of Integration of an Electronic Witness System, its Validation, Efficacy on Lab Performance, and Staff Satisfaction Assessment in a Busy Indian in vitro Fertilization Laboratory p. 333
Sweta Gupta, Ashish Fauzdar, Vikram Jeet Singh, Ajay Srivastava, Kamlesh Sharma, Sabina Singh
DOI:10.4103/jhrs.JHRS_66_20  
Background: Electronic witness system (EWS) is one of the recent advancements in the field of in vitro fertilization (IVF) that uses radiofrequency identification (RFID) technology to monitor all critical work carried out in each stage of IVF procedures cycle. Objective: The main objective of the study was validation and integration of electronic witnessing system, assessment of its efficacy on lab performance, and staff satisfaction in a busy tertiary IVF center. Materials and Methods: The study data included analysis of 187 consecutive cycles for installation and validation of EWS. The laboratory outcomes were analyzed for development of good-quality embryos followed up for the pregnancy outcome. Results: A total of 751 RFIG tags were involved with 77 patient-assigned barcodes for the all the analyzed cycles. During validation of EWS, a total of 02 (0.46%) red flags were highlighted by EWS from pre-allocated tags within the frequency range of the reader. The maturation rate (83.1%), fertilization rate (74.3%), cleavage rate (93.5%), day 3 grade-A embryo development rate (64.6%), good grade blastocyst development rate (26.4%) were observed in EWS group that was comparable to other groups with no significant difference (P > 0.005). Frozen embryo transfer of EWS cases observed a clinical pregnancy rate (50.0%) that was higher than other groups though statistically not significant as sample size was small. Conclusions: Our preliminary study suggests that EWS does not affect the gametes, embryos, and pregnancy rate, however a larger randomized clinical trials should be undertaken to evaluate the safety and efficacy of EWS.
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Chromosomal Aberrations in 224 Couples with Recurrent Pregnancy Loss p. 340
Ghada Mohamed Elhady, Soha Kholeif, Nahla Nazmy
DOI:10.4103/jhrs.JHRS_11_20  
Background: Recurrent pregnancy loss (RPL) is a major reproductive health issue, affecting 2%–5% of couples. Genetic factors, mainly chromosomal abnormalities, are the most common cause of early miscarriage accounting for 50%–60% of first trimester abortion. Aim: To estimate the prevalence and nature of chromosomal anomalies in couples with recurrent miscarriage. Patients and Methods: This study included 224 couples with a history of 2 or more abortions. Both partners were karyotyped as part of the primary investigation. Cytogenetic analysis was carried out using the standard method. Results: A total of 224 couples with a history of two or more recurrent abortions were enrolled in this study. Chromosomal abnormalities were detected in 26 couples (11.6%) and 28 individuals (6.25%). We found a structural chromosome abnormality in 17/28 patients (60.7%); 12 patients had a reciprocal translocation (42.9%) including one patient with an additional inversion of the Y chromosome, 4 (14.3%) had a Robertsonian translocation, and one patient (3.6%) carried a paracentric inversion of chromosome 2. Numerical chromosome aberrations were detected in 5 patients; three patients (10.7%) with sex chromosome abnormalities and two (7.1%) with a marker chromosome. Six patients (21.4%) showed a heteromorphic variant involving chromosome 9. Conclusion: The prevalence of chromosomal abnormalities in couples with RPL is within the range reported worldwide. Cytogenetic analysis should become an integral part of the investigations of couples with at least two pregnancy losses of undetermined etiology.
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CASE REPORTS Top

Management of a Multiple Endocrine Neoplasia 1 Patient in Pregnancy p. 349
Deepanshu Dhiman, Summit Dev Bloria, Pranshuta Sabharwal, Rashi Sarna, Rajeev Chauhan
DOI:10.4103/jhrs.JHRS_164_19  
Multiple endocrine neoplasia (MEN) syndrome has rarely been reported during pregnancy. The multiple manifestations of the syndrome along with the normal body changes associated with pregnancy can prove to be difficult to manage. We describe our experience of the diagnosis and management of MEN1 syndrome in a pregnant female.
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Complete Uterine Septum with Cervical Duplication and Longitudinal Vaginal Septum: An Anomaly Supporting Alternative Embryological Development p. 352
Arpita De, Abhinav Jain, Reva Tripathi, Aruna Nigam
DOI:10.4103/jhrs.JHRS_4_20  
The diagnosis and management of Mullerian abnormalities have revolutionized with the advent of magnetic resonance imaging, three-dimensional ultrasound, and endoscopic techniques. All the earlier unclassified abnormalities can now be classified as per the new European Society of Human Reproduction and Embryology 2013 nomenclature. The presence of complete uterine septum with cervical duplication and longitudinal vaginal septum reinforces the alternative theory of Mullerian development. The presence of this complex anomaly is discussed in the light of embryonic development along with management issues.
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