Journal of Human Reproductive Science
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    Table of Contents - Current issue
Coverpage
October-December 2019
Volume 12 | Issue 4
Page Nos. 271-358

Online since Tuesday, December 17, 2019

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EDITORIAL  

From the editor's desk Highly accessed article p. 271
Madhuri Patil
DOI:10.4103/jhrs.JHRS_165_19  
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REVIEW ARTICLES Top

Female unexplained infertility: A disease with imbalanced adaptive immunity Highly accessed article p. 274
Motahareh Ehsani, Mousa Mohammadnia-Afrouzi, Mohammad Mirzakhani, Sedighe Esmaeilzadeh, Mehdi Shahbazi
DOI:10.4103/jhrs.JHRS_30_19  
Unexplained infertility (UI) among women consists of only 10-17% of infertile females. Unexplained or idiopathic infertility is a condition, in which couples are not able to conceive without any definite causes. The presence of the decidual immune system (innate or adaptive) is essential for a successful pregnancy and fertility that is mediated by T helper (Th) 1, Th2, Th17, T follicular helper, CD8+ CD28− T, and regulatory T cells, as well as autoantibodies such as antiphospholipid antibody, antithyroid antibody, antiovarian antibody, cytokines, and chemokines. Therefore, altered proportions or levels of the mentioned compartments of the adaptive immune system may cause pregnancy failure and infertility, especially in UI. Consequently, a deep understanding of immunological compartments in females with UI may help us to define the causes of this disease with regard to immunology. This review will discuss immunological factors, including cellular, molecular components, and transcription factors that are involved in the etiology of UI.
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T-shaped uterus in the 21st century (Post DES era) – We need to know more! p. 283
Akanksha Sood, Muhammad Akhtar
DOI:10.4103/jhrs.JHRS_101_19  
T-Shaped uterus is a rare uterine malformation, and has classically been associated with “in-utero” exposure of DES (diethylstilbestrol). Surprisingly, the prevalence of T shaped uterus is significant even today. Hysteroscopic metroplasty is a simple procedure which can potentially improve outcomes in sub-fertile women, but the data is not robust. There is a need for centralised database for registration of women with T shaped uterine anomalies, which will help in defining clear diagnostic criteria, surgical indication & technique, and follow up of reproductive outcomes after the procedure.
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ORIGINAL ARTICLES Top

Causes and prevalence of factors causing infertility in a public health facility p. 287
Priyanka Sanjay Deshpande, Alka ShantiPrakash Gupta
DOI:10.4103/jhrs.JHRS_140_18  
Background: Infertility causes change according to local demographics. There is thus the need to find the causes of infertility in context to local population to aid and direct management strategies accordingly. Aims: The aims were to study the causes of infertility and to calculate the proportion of the individual factors contributing to it in the population coming to a tertiary level public health facility. Setting and Design: This cross-sectional, observational study was done in an infertility clinic in a medical college and government hospital. Materials and Methods: The study comprised 120 couples who came for infertility evaluation and treatment. Cause of infertility in the couple was assigned on the basis of history and examination findings. The prevalence of each cause was evaluated. Statistical Analysis: Results were tabulated, and the prevalence of individual factors was calculated. Intratable analysis was done using SPSS 16.0. Results: Primary infertility (57.5%) was more prevalent than secondary infertility (42.5%). Female factor accounted for 46.6% of the cases with polycystic ovarian syndrome (PCOS) being the leading cause (46%). Infertility was seen equally in lean and obese PCOS cases. Infectious causes such as pelvic inflammatory disease and tuberculosis were significantly associated with tubal factor infertility (P = 0.001). Infertility causes changed as the age of marriage increased. In couples married for less than 5 years, PCOS was the main cause whereas later,male factor and unexplained infertility were the most common causes seen. Male factor contributed to 20% of the cases of infertility, and both tobacco and alcohol consumption were significantly associated with abnormal semen reports (P = 0.001). Conclusion: Causes of infertility vary according to the age of the couples and age of marriage. Although PCOS remains the main cause, infections are a major cause of tubal factor infertility, and tobacco and alcohol worsen the male factor. One-third of the cases still remain unexplained.
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The effect of suboptimal semen parameters on male partner's ability to conceive. Is he really subfertile because the test says so? p. 294
Rubina Izhar, Zubaida Masood, Samia Husain, Suhaima Tahir, Mataa-E- Masood
DOI:10.4103/jhrs.JHRS_29_19  
Context: In many developing countries, subfertility treatment is not covered by government-funded institutions. It is observed that healthcare providers incriminate male factor for subfertility even when only a slight deviation from presumed normal criteria is observed. Aim: This study aims to provide scientific evidence that pregnancies are possible at semen parameters that are below the generally accepted lower limits of normal. Setting and Design: This was a retrospective cohort study conducted from January 2014 to December 2018. Materials and Methods: During the study period, couples who conceived without any treatment of male partner were included. The World Health Organization (WHO) reference values for semen analysis were utilized to assess the reports. The primary outcome measure was conception despite abnormal semen parameters. Statistical Analysis Used: Data were analyzed using the SPSS software program, version 15.0 (IBM, Armonk, USA). Results: Of the 332 couples included, 233 (70.1%) couples conceived despite suboptimal semen parameters, The most common criterion not satisfied was rapid linear motility –200 (85.8%), 87 (37.3%) men were oligozoospermic, 94 (40.3%) were asthenozoospermic, and 21 (9%) were teratozoospermic. The abnormalities were more common in men having primary subfertility (71.7% vs. 28.3%, P = 0.002). The abnormalities were most common in the age group 40–44 years (n = 91, 39.1%) and those who were overweight (n = 110, 47%). Conclusions: A consensus for defining poor semen criteria is the need of the hour so that these males can be counseled satisfactorily. WHO criteria are a standard commonly employed, but they do not necessarily predict the fertility potential.
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There is no association between premature ovarian insufficiency and levels of fetuin-A/α2-Heremans-Schmid glycoprotein p. 299
A Seval Ozgu-Erdinc, Zeynep Asli Oskovi Kaplan, Yaprak Engin-Ustun, Nafiye Yilmaz, Gulcin Yildirim, Aytekin Tokmak, Kudret Erkenekli, Salim Erkaya, Dilek Uygur
DOI:10.4103/jhrs.JHRS_104_19  
Objective: Fetuin-A is a well-known negative acute-phase protein and has been used liberally to predict vascular disease. The aim of this study was to evaluate the association between serum human fetuin-A/alpha2-Heremans–Schmid glycoprotein levels and idiopathic premature ovarian insufficiency (POI). Methods: A total of 75 women were included in this case–control study between January 2013 and December 2013. Serum fetuin-A concentrations were measured in 36 women with idiopathic POI and 39 healthy women with regular cycles. Blood samples were drawn after a 12-h overnight fast and were kept at −80°C for subsequent assay. The serum levels of fetuin-A were assessed by commercial ELISA kits (BioVendor Laboratory Medicine Inc., Brno, Czech Republic) and serum concentration values were expressed as μg/ml. Results: The mean serum fetuin-A levels of idiopathic POI and control women were 229.02 ± 27.79 and 232.37 ± 65.56, respectively, with P = 0.771 (independent samples t-test). Our results showed no statistically significant difference between serum fetuin-A levels of idiopathic POI women and controls. Conclusion: The mean values of serum fetuin-A in idiopathic POI women were not significantly different from controls, which implies that there is no significant association between serum fetuin-A levels and idiopathic POI.
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A multicenter phase IV study to investigate the immunogenicity of recombinant human follicle-stimulating hormone and its impact on clinical outcomes in females undergoing controlled ovarian stimulation p. 303
Abha Majumdar, Le Hoang, Ly T Loc, Padma Srivastava, Chitra Ramamurthy, Ratnabali Chakravorty, Yogeshwar S Nandanwar, MD Rashmi, Rahul V Mayekar, Jayashree Sridhar, Ganesh H Divekar, James John
DOI:10.4103/jhrs.JHRS_33_19  
Context: Therapeutic proteins can cause immune responses, which may have clinical implications. Aims: The aim of the study was to assess the immunogenicity of recombinant human follicle-stimulating hormone (r-hFSH), when used for controlled ovarian stimulation (COS). Settings and Design: Prospective, multicenter study conducted at reproductive medicine clinics in India and Vietnam. Materials and Methods: A total of 285 women, aged 20–40 years, undergoing 354 COS cycles for either intrauterine insemination (IUI) orin vitro fertilization (IVF) were studied. The primary outcome measure was the incidence of development of anti-drug antibodies (ADA) and their neutralization potential. Other outcome measures were follicle development, dose and duration of r-hFSH, positive serum pregnancy test, clinical pregnancy, cycle cancellation, and adverse events (AEs). Statistical Analysis Used: A sample size of 250 was planned. Descriptive statistics are presented. Results: Four patients tested positive for ADA after r-hFSH administration at different time points; all of them tested negative, subsequently. None were found to have neutralization potential. The mean dose and duration of r-hFSH were 816 IU and 8.1 days in IUI and 2183 IU and 9.5 days in IVF, respectively. The serum and clinical pregnancy rates were 12.4% and 11.6% in IUI and 32.7% and 29.9% in IVF cycles, respectively. Seven AEs were reported, including two cases of ovarian hyperstimulation syndrome; two AEs were judged to be serious. Conclusions: The tested r-hFSH has very low immunogenic potential and did not lead to the development of neutralizing antibodies. The overall efficacy and safety of the drug were in-line with existing literature data, and no specific clinical impact of immunogenicity could be identified.
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Does double dose of recombinant human chorionic gonadotropin for final follicular maturation in in vitro fertilization cycles improve oocyte quality: A prospective randomized study p. 310
Neeta Singh, Bhavana Girish, Neena Malhotra, Reeta Mahey, Vanamail Perumal
DOI:10.4103/jhrs.JHRS_125_18  
Context: In in vitro fertilization (IVF) cycles, the recommended dose of recombinant human chorionic gonadotropin (r-hCG), for triggering final follicular maturation is 250 μg, although there is some disagreement. Aims: The aim of our study was to assess the effect on the number of mature oocytes retrieved after triggering ovulation in IVF cycles using 250 μg or 500 μg of r-hCG. Settings and Design: Prospective, single-center, randomized study. Subjects and Methods: 100 women undergoing IVF with embryo transfer. The primary outcome measure was the total number of oocytes retrieved per follicle, number of mature oocytes, and number of embryos generated. The secondary outcomes included clinical and biochemical pregnancy rates and incidence of ovarian hyperstimulation syndrome. Results: Mean number of oocytes retrieved (6.5 ± 4.0 vs. 6.4 ± 3.9, P = 0.3) and mean number of mature oocytes (4.0 ± 2.3 vs. 3.2 ± 2.3, P = 0.09) were similar in the two groups; however, mean number of oocytes retrieved per follicle was found to be higher with 500 μg r-hCG (67.4 ± 23.9 vs. 77.5 ± 23.3, P = 0.04). In the subgroup of poor responder women, there was a significant increase in the number of mature oocytes retrieved with double dose of r-hCG (2.2 ± 1.8 vs. 3.7 ± 1.9, P = 0.06), leading to improvement in fertilization and clinical pregnancy rates. Conclusions: Double dose of r-hCG for final follicular maturation in IVF cycles resulted in improvement in mean number of oocytes per follicle but did not result in improved pregnancy rates in the women. In the subset of poor responders, 500 μg r-hCG seems to be more advantageous than the lower dose, although larger randomized trials are needed to generalize this strategy.
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Outcomes of intracytoplasmic sperm injection in infertile men with nontense vaginal hydrocele: A prospective cohort study p. 316
Adel E Elgergawy, Ayman S Dawood, Ahmed M Abbas, Salah A. M Nagla
DOI:10.4103/jhrs.JHRS_45_19  
Objective: To evaluate the effect of nontense vaginal hydrocele in male partner with oligoasthenospermia on the success rates of the intracytoplasmic sperm injection (ICSI). Patients and Methods: Enrolled patients (n = 60) were divided into two groups: Group I who have oligoasthenospermia with nontense vaginal hydrocele (study group) and Group II who have oligoasthenospermia with no hydrocele group (control group). The primary outcomes included the fertilization and pregnancy rates whereas the secondary outcomes included any complications occurred. Results: There were no differences in demographic characteristics between both groups. Semen parameters were poorer in the hydrocele group than in the nonhydrocele group regarding count and motility (P < 0.001). The volume of testis was reduced significantly in the hydrocele group (P < 0.001). The results of ICSI regarding fertilization rate, number and quality of developed embryos, and pregnancy rates are not statistically different between both groups. Conclusion: Hydrocele affects both sperm count and motility, but it has no effects on ICSI outcomes. Clinical pregnancy rate was comparable in patients with or without hydrocele. Hence, the surgical management of hydrocele before ICSI is not recommended.
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Is it time to move toward freeze-all strategy? – A retrospective study comparing live birth rates between fresh and first frozen blastocyst transfer p. 321
Reeta Biliangady, Rubina Pandit, Nutan Kumari Tudu, Poornima Kinila, Uma Maheswari, Indu S. T Gopal, Ambika G Swamy
DOI:10.4103/jhrs.JHRS_146_18  
Background: Cryopreservation of all embryos followed by transfer in subsequent cycles has emerged as an effective alternative to fresh embryo transfer (ET) in order to overcome the negative effect of superovulation on endometrial receptivity. Aims: The aim of this study was to compare the reproductive outcomes between fresh ET and first frozen ET (FET) from “freeze-all” group of embryos. Setting: This study was conducted at a private in vitro fertilization center. Design: This was a retrospective study. Patients and Methods: A total of 503 patients fulfilling the inclusion criteria between 2012 and 2017 were included. Of 503, 386 patients underwent fresh ET and 117 patients underwent FET following cryopreservation of all embryos. The results of only first FET were considered to eliminate the confounding factor of poor-quality embryos in subsequent transfer. Results: FET resulted in statistically significant higher live birth rate (44.44% vs. 33.41%), implantation rate (45.08% vs. 30.22%), and clinical pregnancy rate (57.26% vs. 38.6%) compared to fresh ETs. No difference was observed in the abortion rate between the two groups. Conclusion: Reproductive outcomes were significantly better in the freeze-all group compared to fresh ET suggesting that the altered hormone levels during controlled ovarian stimulation could mediate an asynchrony between the endometrium and the transferred embryos, leading to implantation failure.
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What are the predictive factors for preeclampsia in oocyte recipients? p. 327
Celine Pimentel, Duros Solene, Jaffre Frédérique, Bouzille Guillaume, Leveque Jean, Le Lous Maëla
DOI:10.4103/jhrs.JHRS_43_19  
Objectives: Oocyte donation pregnancies are more frequently complicated by preeclampsia (PE), which cause significant fetal-maternal morbidity and mortality. Our objective was to determine risk factors for PE in oocyte recipients (OR). Our secondary objective was to describe the course of pregnancy and the neonatal outcome in this group. Methods: This was a historical-prospective study. One hundred and fifty OR who gave birth to children at over 22 weeks of amenorrhea between January 2010 and June 2018 were included in the study. Results: Risk factors for PE in OR found in univariate analysis were as follows: primiparity, primipaternity, body mass index (BMI), and anti-Müllerian hormone (AMH) of the OR and age and AMH of the oocyte donors (OD). In multivariate analysis, the BMI of the OR (odds ratio [OR]: 1.2, 95% confidence interval [CI]: [1.1–1.4], P = 0.0474) and the AMH of the OD (OR: 1.2, 95% CI: [1.2–1.4], P = 0.0481) were found to be statistically significant risk factors for PE. In addition, we observed an increase in the rate of prematurity in the OR that were not associated with fetal growth retardation, despite the occurrence of PE. Conclusion: In OR, the allogeneic nature of pregnancy induces an increased risk of PE, the pathophysiology of which seems different from that in other methods of conception. Thus, risk factors for PE should be reconsidered to take into account the impact of certain characteristics of OD such as age and AMH.
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Predictors of metabolic syndrome among polycystic ovary syndrome sisters p. 334
Bindu Kulshreshtha, Neera Sharma, Shubhi Pant, Akhila Prasad, Anubhuti Chitkara, Bhawna Pahuja, Isha Pahuja
DOI:10.4103/jhrs.JHRS_172_18  
Aims: Metabolic syndrome among PCOS sisters may vary depending on the phenotype. The aim of the present study was to analyze the prevalence of metabolic syndrome among different phenotypes of PCOS sisters. Design: Case control study. Materials and Methods: Two hundred sisters of PCOS patients and 99 age matched healthy controls underwent history, clinical examination, biochemical parameters for metabolic syndrome and hormonal assessment. Results: Of 200 sisters, 85 were unaffected (UA group), 21 sisters had hyperandrogenemia (HA group), and 94 sisters had irregular periods or hyperandrogenemia. We observed that the frequency of metabolic syndrome among PCOS sisters was comparable to age and weight matched controls (30% vs 27%). The prevalence of metabolic syndrome was higher in HA and AFFECTED sisters (around 30% in both) compared to UA sisters (20%). The presence of metabolic syndrome was significantly associated with age, BMI, HOMA-IR and free testosterone. After correction for age and BMI, metabolic syndrome was significantly associated with HOMA-IR (P - 0.05) and free testosterone (P - 0.03). Conclusion: Based on above findings, we conclude that affected sisters and those with higher age, BMI and hyperandrogenemia have a high risk of metabolic syndrome compared to unaffected sisters.
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CASE REPORTS Top

India's first child using PGT-M, PGT-A and HLA matching for helping a sibling having β-thalassemia major p. 341
Jwal M Banker, Parul Arora, Rajni Khajuria, Manish Banker
DOI:10.4103/jhrs.JHRS_50_19  
β-thalassemia is a common single-gene disorder in India, with hematopoietic stem cell transplantation (HSCT) being the only cure. HSCT with matched unrelated donor is less successful, whereas finding a human leukocyte antigen (HLA)-matched related donor is difficult. Preimplantation genetic testing for monogenic diseases (PGT-M) with HLA matching is a novel option to have a matched sibling for HSCT for couples having an affected child. We present the first such case report in India. A couple, both carriers of β-thalassemia and having an affected son, underwent PGT-M with HLA matching combined with preimplantation genetic testing for aneuploidies of embryos to have a β - thalassemia-free child. This resulted in birth of a 10/10 HLA-matched sibling.
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Swyer syndrome with heterotopic adrenal cortical tissue in streak gonads: A rare case and review of literature p. 345
Manu Goyal, Shuchita Batra, Pratibha Singh, Shashank Shekhar, Poonam Elhence
DOI:10.4103/jhrs.JHRS_44_19  
Swyer syndrome is a 46 XY pure gonadal dysgenesis. Affected individuals are phenotypically female with external female genitalia, hypoplastic Mullerian structures, and the presence of streak gonads. Gonadectomy is indicated due to increased risk of development of malignancy in streak gonads. We hereby report a case of 15-year-old patient with Swyer syndrome who underwent laparoscopic gonadectomy. Histopathological examination showed streak gonads with the presence of accessory adrenal cortical tissue. The patient was put on hormonal replacement therapy postsurgery. Heterotopic adrenal rest may be an incidental finding in normal ovary and testis. Its presence in streak gonads has never been reported, and we propose a theory of increased risk of gonadal and adrenal tumors, possibly because of mutations in disorders of sex differentiation.
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Complete androgen insensitivity syndrome: Dilemmas for further management after gonadectomy p. 348
Pratibha Singh, Meenakshi Gothwal, Garima Yadav, Kuldeep Singh
DOI:10.4103/jhrs.JHRS_151_18  
Complete androgen insensitivity syndrome is a rare condition, wherein a genetic male is phenotypically female and is raised as a female. Treatement requires timely gonadectomy, need for long term hormonal replaceent therapy, psycological and genetic counseling. The type, dose, duration of hrt is not well studied. Reproductive issues also need to be addressed in these young woman. We report here a case of complete androgen insensitivity which posed a quandary for management of long term bone health. Review of literature for management is discussed. These cases are best managed by a multi-disciplenary team comprising of gynecologist, geneticist, endocrinologist and clinical psycologist or psychiatrist.
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Sildenafil Citrate: Novel Therapy in the Management of Ovarian Torsion p. 351
Kedar N Ganla, Rana A Choudhary, Priyanka H Vora, Umesh V Athavale
DOI:10.4103/jhrs.JHRS_52_19  
Ovarian torsion is defined as partial or complete rotation of ovarian vascular pedicle, leading to the obstruction of venous outflow and arterial inflow. It is an emergency condition with an incidence of 2%–15% in patients with adnexal masses. The main risk in ovarian torsion is an ovarian mass or an enlarged ovary with a long pedicle. Due to the rotation of ovarian tissue axis on its vascular pedicle, there is compression of vessels followed by stromal edema, hemorrhagic infarction, and necrosis of adnexa. Expedient diagnosis poses a difficult challenge because clinical presentation is a variable and often misleading. We report a case of right ovarian torsion after oocyte retrieval for in vitro fertilization, where vaginal sildenafil citrate was successfully used to reduce ovarian edema by improving venous drainage. It also helped in maintaining ovarian tissue perfusion and preventing reperfusion injury and spontaneous detorsion of the ovary without any surgical intervention.
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Heterotopic cervical pregnancy: A rare case treated by transvaginal aspiration p. 355
Sindhu Bhairavi, Soumyaroop Dash, Sebanti Dash
DOI:10.4103/jhrs.JHRS_147_18  
Cervical pregnancy is a rare form of ectopic pregnancy. Heterotopic cervical pregnancy is much more rare scenario. This is a case of Heterotopic cervical pregnancy treated successfully by transvaginal ultrasound guided aspiration.
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ERRATUM Top

Comparative Study of Serum Progesterone Levels at the Time of Human Chorionic Gonadotropin Trigger and Ovum Pickup in Predicting Outcome in Fresh in vitro Fertilization Cycles p. 358

DOI:10.4103/0974-1208.273123  
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