Journal of Human Reproductive Science
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    Table of Contents - Current issue
Coverpage
July-September 2019
Volume 12 | Issue 3
Page Nos. 175-269

Online since Monday, September 16, 2019

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EDITORIAL  

From the editor's desk p. 175
Madhuri Patil
DOI:10.4103/jhrs.JHRS_124_19  
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REVIEW ARTICLE Top

Perinatal outcomes following assisted reproductive technology p. 177
Sesh Kamal Sunkara, Parimala Chinta, Mohan S Kamath
DOI:10.4103/jhrs.JHRS_83_19  
As the use of routine assisted reproductive technology (ART) becomes widespread along with the extended applications such as ART with donor gametes, surrogacy, and preimplantation genetic testing (PGT), it becomes more pertinent to evaluate risks associated with them. Perinatal outcomes and long-term safety for the women and children are paramount. In this review, we aimed to detail the perinatal outcomes in relation to the ART procedures routinely applied as the extended applications of ART with a focus on singleton pregnancies. While there seems to be a higher risk of adverse perinatal outcomes with some of the ART procedures, the absolute risk increase is generally low. It is important for clinicians to have this knowledge to better counsel and care for their patients.
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ORIGINAL ARTICLES Top

Sperm DNA integrity in leukocytospermia and its association with seminal adenosine deaminase p. 182
Harsha Pratap, Suma Yekappa Hottigoudar, Kubera Siddappa Nichanahalli, Soundaravally Rajendran, Hanuman Srinivas Bheemanathi
DOI:10.4103/jhrs.JHRS_1_19  
Background: The study aimed to examine the effect of leukocytospermia on sperm quality and the levels of seminal adenosine deaminase (ADA) enzyme in males attending an infertility clinic in a tertiary hospital and to detect the association, if any, between seminal ADA and sperm quality. Methodology: Consenting male subjects, between 21 and 45 years, attending the infertility clinic and qualifying the eligibility criteria were recruited following informed consent. The collected semen samples were analyzed for the routine parameters based on the WHO protocols and for sperm DNA fragmentation. The seminal leukocyte count was detected using the peroxidase method, and the seminal ADA was assessed using spectrophotometry. Results: Samples from 110 participants were included in the study; leukocytospermia was detected in 33% of the samples. A significant reduction in the sperm quality with respect to conventional semen parameters (sperm motility and sperm vitality) and sperm DNA fragmentation index (SDFI) was noted in the presence of leukocytospermia. Furthermore, a significant positive correlation between the levels of seminal ADA and SDFI was noted (P = 0.000, r = 0.412). Conclusion: The sperm motility and DNA integrity are significantly compromised in the presence of leukocytospermia when the leukocyte count is > 1 million/mL of semen as well as 0.5–1 million/mL of semen. The positive correlation noted between seminal ADA levels and increased sperm DNA damage paves way for the possibility of seminal ADA to be an indicator of silent male genital tract inflammation as well as low-quality semen.
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The effect of sperm DNA fragmentation index on the outcome of intrauterine insemination and intracytoplasmic sperm injection p. 189
Nagireddy Siddhartha, Nellepalli Sanjeeva Reddy, Monna Pandurangi, Tamizharasi Muthusamy, Radha Vembu, Kanimozhi Kasinathan
DOI:10.4103/jhrs.JHRS_22_19  
Context: Elevated sperm DNA fragmentation index (DFI) is found to affect normal embryonic development, implantation and fetal development after intrauterine insemination (IUI), in vitro fertilization and intracytoplasmic sperm injection (ICSI). Estimation of DFI by terminal deoxynucleotidyl transferase-mediated fluorescent deoxy uridine nucleotide nick end labeling (TUNEL) assay was found to have a high predictive value for pregnancy after fertility treatments. Aim: This study aims to find the effect of increased sperm DNA fragmentation by TUNEL assay on reproductive outcome after IUI and ICSI. Primary Objective: To find the association of DFI and pregnancy rate in IUI and ICSI. Secondary Objectives: To find the association of DFI with fertilization and implantation in ICSI. To find the association of DFI with miscarriage rate. Settings and Design: A prospective observational study performed at a tertiary care university teaching hospital. Subjects and Methods: 105 male partners of infertile couple planned for IUI and ICSI underwent estimation of sperm-DFI by TUNEL assay. The treatment outcomes were compared between the DFI-positive (≥20%) and DFI-negative (<20%) groups. Statistical Analysis Used: Statistical analysis was performed by SPSS version 17, Software. P < 0.05 was considered statistically significant. Results: The men with abnormal semen analysis were significantly higher in the DFI-positive group (77.15% vs. 22.85%). There was no significant difference in the pregnancy rate in IUI cycles (17.6% vs. 11.8%); but in the ICSI, the pregnancy rate was significantly reduced in the DFI-positive group (16.7% vs. 47.4%). Conclusions: Elevated DFI significantly affects the pregnancy rate in ICSI cycles.
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Evaluation of seminal fructose and citric acid levels in men with fertility problem p. 199
Makhadumsab M Toragall, Sanat K Satapathy, Girish G Kadadevaru, Murigendra B Hiremath
DOI:10.4103/jhrs.JHRS_155_18  
Context: Male infertility is a medical problem, attributed to 50% of infertility. Seminal plasma can be an anticipating factor as it comprises secretions of accessory sex gland, thus offering novel and precise ways to understand potential roles of these biochemical markers in male infertility. Aim: The objective of this study was to assess the correlation between biochemical markers and sperm parameters in envisaging male infertility. Subjects and Design: We enlisted 105 men with fertility issue as patients and 25 fertile men as controls to evaluate the sperm parameters and biochemical markers, namely fructose and citric acid in ascertaining male infertility. Materials and Methods: The semen samples from patients were collected properly and analyzed according to the World Health Organization-2010 manual. Later samples were centrifuged, seminal plasma was collected, and biochemical markers assessment was carried out by standard protocols. Statistics: Descriptive statistics, independent t-test, one-way ANOVA, and Pearson correlation were used for statistical analysis of different variables using SPSS 20.0. The mean sperm count and motility by all infertile conditions displayed a significant difference when compared with the controls (P < 0.05). Results: The mean fructose levels of oligozoospermia showed a nonsignificance difference when compared with controls (P < 0.05). Asthenozoospermia, asthenoteratozoospermia, and azoospermia had a significance difference (P < 0.05) for citric acid levels. Pearson correlation coefficient showed significant negative correlation of sperm count (r = −0.564) and sperm motility (r = −0.574) with fructose levels. Whereas seminal citric acid concentration had a positive correlation with sperm count (r = 0.458) and sperm motility (r = 0.446). Conclusion: Therefore, evaluation of certain biochemical markers of seminal fluid may benefit in understanding the functionality of accessory glands which subsidizes significantly to the seminal volume.
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Role of oxidative stress and antioxidants in male infertility: An interventional study p. 204
Ganeswar Barik, Latha Chaturvedula, Zachariah Bobby
DOI:10.4103/jhrs.JHRS_135_18  
Aims: The study aims, in infertile men, (i) to assess oxidative stress parameters in semen plasma and (ii) to study the effect of antioxidants in those with abnormal semen parameters. Settings and Design: This was an interventional study. Population: Ninety men attending and infertility clinic in a tertiary center were enrolled in the study. Materials and Methods: The present study was conducted in the departments of obstetrics and gynecology and biochemistry in a tertiary center. Ethical approval was obtained from the institute ethics subcommittee, and the study was conducted between July 2014 and July 2016. The study was conducted on two groups of 45 men with normal semen parameters in group 1 and 45 men with abnormal semen parameters in group 2. Results: Malondialdehyde (MDA) value was higher in men with abnormal semen parameters, which was statistically significant. The total antioxidant assay was higher in men with abnormal semen parameters, which was not statistically significant. Oxidative stress index (OSI) value was higher in men with normal semen parameters, which was not statistically significant. After 90 days of antioxidants therapy to men with abnormal semen parameters, MDA value decreased, total antioxidant assay increased, and OSI value decreased, which were statistically significant. Semen parameters such as sperm concentration, motility, and normal morphology improved after 90 days of antioxidant therapy, which were statistically significant. Conclusions: Oxidative stress is increased in men with abnormal semen parameters. Antioxidant therapy improves sperm concentration and motility and decreases oxidative stress in the semen plasma.
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Are we justified doing routine intracytoplasmic sperm injection in nonmale factor infertility? A retrospective study comparing reproductive outcomes between in vitro fertilization and intracytoplasmic sperm injection in nonmale factor infertility p. 210
Reeta Biliangady, Poornima Kinila, Rubina Pandit, Nutan Kumari Tudu, Uma Maheswari Sundhararaj, Indu S. T. Gopal, Ambika G Swamy
DOI:10.4103/jhrs.JHRS_8_19  
Introduction: Intracytoplasmic sperm insemination (ICSI) came into use in 1992 to improve fertilization in couples with male factor infertility undergoing in vitro fertilization (IVF) or in couples with fertilization failure in a prior IVF cycle. Our aim was to find out if routine ICSI has any additional benefit over conventional IVF in non male factor cases in modern Assisted Reproductive Technology (ART). Methods: This is a retrospective single centre study undertaken at a private IVF center. A total of 350 patients with normal male factor were included in the study of which 186 underwent conventional IVF and 134 were subjected to ICSI. They were then compared for various reproductive parameters with Live Birth Rate (LBR) being the primary outcome. P value < 0.05 was considered statistically significant. Results: Fertilization rates (89.99% vs 85.1%), Blastocyst formation rates (62.86% vs 50.61%) and clinical pregnancy rates (37.85% vs 32.35%) were found to be higher in the IVF group compared to the ICSI group though not statistically significant. The live birth rates in the IVF group was also higher than the ICSI group (32.71% vs 24.26%). Conclusion: IVF edged over ICSI in all aspects resulting in better clinical outcome with higher take home babies in non-male factor infertility. Our results show that routine ICSI should not be used as a blanket therapy for all cases in ART.
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Comparison of clinical, metabolic, hormonal, and ultrasound parameters among the clomiphene citrate-resistant and clomiphene citrate-sensitive polycystic ovary syndrome women p. 216
Garima Sachdeva, Shalini Gainder, Vanita Suri, Naresh Sachdeva, Seema Chopra
DOI:10.4103/jhrs.JHRS_89_18  
Objective: The objective of the study is to compare the clinical, metabolic, hormonal, and ultrasound parameters among the clomiphene citrate (CC)-sensitive and CC-resistant polycystic ovary syndrome (PCOS) women. Materials and Methods: This was a prospective observational study. Setting: The study was conducted at the infertility outpatient department in a government hospital. Sample Size: A total of 164 women with PCOS-related infertility were included. Intervention: Incremental dose of CC from 50 mg/day to 100 mg/day to 150 mg/day over three cycles was given. Response: Ovulation was the outcome. Those who failed to ovulate with 150 mg CC were CC resistant. Results: Of the total 164 PCOS women, 88 (53.7%) were CC resistant and 76 (46.3%) were CC sensitive. Of the 76 PCOS women who ovulated, maximum, i.e., 37 (22.6%) women ovulated with 100 mg CC. The most common diagnostic feature of PCOS in this study was hyperandrogenism (96.3%). CC-resistant PCOS women had significantly higher weight, waist circumference, waist-hip ratio, and body mass index (BMI). Significantly longer menstrual cycles and hyperandrogenism were significantly more common in CC-resistant group. CC-resistant group had a significantly higher ovarian reserve (ovarian volume, antral follicle count, and anti-Müllerian hormone values). Baseline luteinizing hormone (LH) values and LH-follicle stimulating hormone ratio were significantly higher in the CC-resistant group. Conclusion: Clomiphene-resistant PCOS women have significantly higher hyperandrogenism, longer cycles, more deranged metabolic profile, higher BMI, and ovarian reserve. These differences should be kept in mind while deciding the ovulation induction protocol.
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Laparoscopic ovarian drilling reduces testosterone and luteinizing hormone/follicle-stimulating hormone ratio and improves clinical outcome in women with polycystic ovary syndrome p. 224
Priyanka Sinha, Thyagaraju Chitra, Dasari Papa, Hanumanthappa Nandeesha
DOI:10.4103/jhrs.JHRS_161_18  
Background: Laparoscopic ovarian drilling (LOD) is one of the common modes of treatment for women with polycystic ovary syndrome (PCOS) who are resistant to clomiphene citrate. The data related to the effect of LOD on sex hormones are limited. Aim: The objective of the study was to investigate the effect of LOD on hormonal parameters and clinical outcomes in women with PCOS. Settings and Design: This study was conducted in a tertiary care hospital. Materials and Methods: Fifty PCOS patients who were admitted for LOD were enrolled in the study. Serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were estimated in all the patients before and after LOD. Statistical Analysis: Paired t-test was used to assess the differences in hormonal parameters before and after LOD. Results: LOD reduces testosterone (P < 0.001), LH (P < 0.001), and LH/FSH ratio (P < 0.001), increases FSH (P < 0.001) levels, and improves the rate of ovulation (38/50) and clinical pregnancy (21/50) in PCOS. When subgroup analysis was done, LOD significantly reduced testosterone and LH/FSH ratio in ovulatory and conceived groups. Furthermore, the menstrual cycle became regular, and hirsutism and acne were reduced after LOD in women with PCOS. Conclusions: LOD reduces testosterone and LH/FSH ratio and improves clinical outcome in PCOS.
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The enigma of early progesterone rise: Is it associated with the type of gonadotropin used? p. 229
Abhijit A Oka, Gauri A Oka
DOI:10.4103/jhrs.JHRS_120_18  
Background: It is debated whether the use of recombinant follicle-stimulating hormone (r-FSH) or human menopausal gonadotropin (HMG) is associated with progesterone (P) elevation in the late follicular phase. Aims: The aim is to determine whether the type of gonadotropin used for controlled ovarian stimulation (COS) in in vitro fertilization (IVF) is associated with P elevation in the late follicular phase using antagonist protocol. Setting and Design: This was a retrospective data analysis in the IVF unit. Methods: Data of women who underwent COS between January 2005 and December 2017. Statistical Analysis: Chi-square and unpaired Student's t-test in SPSS 20. Results: Data of 439 women was analyzed. Mean age was 31.45 ± 4.6 years. HMG was used in 193 (44%), r-FSH in 232 (52.8%), and a combination of both in 14 (3.2%) women. Proportion of women with elevated P was significantly higher in r-FSH group as compared to HMG group (19/232 [8.2%] vs. 6/193 [3.1%]; P= 0.027). Mean P levels were significantly higher in r-FSH group (0.75 ng/ml vs. 0.59 ng/ml; P = 0.049). Mean estradiol (E2) levels at trigger were significantly higher in women with elevated P as compared to normal P(2893.4 ± 2091.8 pg/ml vs. 1668.3 ± 1508.6 pg/ml respectively; P< 0.000). Fresh embryo transfers performed in 18/27 women with elevated P resulted in pregnancy in three (16.7%) women. Two had biochemical pregnancies and one was lost to follow-up. Conclusions: Use of r-FSH and E2 levels at trigger are associated with elevated P levels in the late follicular phase. Fresh embryo transfers performed in spite of elevated P levels were associated with low pregnancy rates and unfavorable outcomes.
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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. 234
Srinivas Sangisapu, Sandeep Karunakaran
DOI:10.4103/jhrs.JHRS_156_18  
Background: Studies have shown that premature rise of progesterone in controlled ovarian stimulation (COS) at the time of human chorionic gonadotropin (hCG) trigger is negatively associated with in vitro fertilization (IVF) outcome in fresh IVF cycles. Some authors have failed to demonstrate this. One large single centre retrospective cohort study has compared the pre and post hCG progesterone and observed that the ratio of the rise in progesterone could be a positive predictor. There is paucity of literature on this aspect. Aims and Objectives: To compare the serum progesterone at hCG trigger and ovum pick-up (OPU) with IVF outcome by estimating the respective paired hormone levels. Material and Methods: Serum progesterone levels at hCG trigger and OPU are compared retrospectively in 301 fresh IVF cycles with IVF outcome by long protocols with GnRH agonists for two years. Parametric and nonparametric testing of null hypothesis is performed. P value <0.05 is taken as significant. Results: There is no predictive association of IVF outcome with either progesterone levels. The ratio of rise in progesterone is strongly positively associated with IVF outcome (P < 0.001). However, after adjusting for confounders and modifiers the retrieved number of oocytes are positively associated with IVF outcome (P = 0.044). Conclusions: The ratio of rise in progesterone is significantly associated with number of oocytes retrieved which in turn is associated with successful IVF outcome in fresh cycles. Ratio of rise in progesterone seems to be therefore an indirect parameter for predicting successful IVF outcome in fresh cycles.
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Observational study of the social determinants of health in subfertile versus nonsubfertile women p. 240
Pedro M Tabernero-Rico, Juan A Garcia-Velasco
DOI:10.4103/jhrs.JHRS_20_19  
Context: Subfertility affects about 15% of couples worldwide. There are several factors that affect subfertility called social determinants of health (SDH): biological factors as age, ethnic origin, and body mass index; behavioral factors as alcohol intake, smoking, coffee, dietary restriction, physical activity, and psychological state; and contextual factors as education, work activity, and income level. Aims: The aim of the study is to evaluate the distribution's relevance of the SDH in subfertile women versus nonsubfertile women. Settings and Design: A prospective comparative study with two groups of women recruited over 1 year at hospital consultation: one group with subfertile women excluding women without a male partner or with a previous child and another one formed by primigravidae, excluding those receiving assisted reproduction techniques to become pregnant. Subjects and Methods: We compare the different factors between subfertile and nonsubfertile women one by one. Second, a multivariate analysis was conducted with logistic regression. In all cases, informed consent was obtained. Results: Regular physical exercise 3–4 times/week (odds ratio [OR]: 0.33, 95% confidence interval [CI]: 0.15–0.71) or healthy food products such as fish 1–2 times/week (OR: 0.40, 95% CI: 0.17–0.95) were associated with nonsubfertile women. Conclusions: The distribution of SDH in natural fertility is not altogether homogeneous. Weight control by means of restricting calorie intake, greater consumption of healthy foods such as fish, regular physical exercise, and lower age are positively associated with fertility. Population-level intervention is possible to improve women's health, as these are modifiable factors. Ethnic origin can be considered as a relevant factor, as it may condition the distribution of other determinants.
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The effect of nursing consultation based on orem's theory of self-care and Bandura's concept on infertility stress p. 247
Asmaa Zaidouni, Fatima Ouasmani, Amal Benbella, Jalal Kasouati, Rachid Bezad
DOI:10.4103/jhrs.JHRS_159_18  
Introduction: Infertility is one of the most stressful experiences in a couple's life. Several approaches have been proposed to manage infertility stress during the medically assisted technology process. Objective: The objective was to examine the effect of nursing consultation on the stress experienced by infertile couples before starting infertility treatment. Materials and Methods: This cross-sectional study was conducted from November 2017 to November 2018 among 120 infertile couples (240 patients) for whom stress was assessed. One hundred and thirteen patients of them who had a high infertility stress level were invited to participate in this randomized study (57 were assigned to the control group and 56 were included in the intervention group). The intervention group received nursing consultation based on Orem's theory and Bandura's concept in addition to the routine nursing care. Perceived Stress Scale-10 (PSS-10) and General Self-Efficacy Scale (GSES) were used before and after nursing intervention. Statistical Analysis: The Chi-square test followed by a paired t-test and independent t-test was used for data analysis by SPSS software (version 20). Results and Discussion: There were no statistically significant differences before nursing intervention between the two groups in terms of PSS-10 (t = 1.18, P = 0.23) and GSES (t = −0.40, P = 0.689) scores, but a significant difference emerged in the intervention group following the nursing intervention: a reduction of the PSS score (t = −8.91, P = 0.000) and an increase in the GSES score (t = −5.25, P = 0.000, with 95% confidence interval (CI)). Conclusion: Nursing consultation has been shown to be beneficial in decreasing perceived stress and increased self-efficacy for infertile couples undergoing assisted reproductive technologies.
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CASE REPORTS Top

The robertsonian translocation of ‘21/22’ in nonobstructive azoospermia: A rare case report from India p. 255
Paresh Singhal, Ajay Malik, Nikita Naredi, Gurmeet Pranaya, Amit Agrawal
DOI:10.4103/jhrs.JHRS_13_19  
Robertsonian translocation is a subtype of balanced translocation involving two acrocentric chromosomes. Individuals who are carrier of this abnormality are at increased risk of infertility or bad obstetric history. This case is reported with the aim to describe a male who presented with nonobstructive azoospermia at a tertiary care center. The individual was phenotypically normal but carrier of a Robertsonian translocation of two acrocentric chromosomes. With this literature, we emphasize that conventional cytogenetic is an essential diagnostic tool for screening genetic factors in infertility.
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Extensive primary male genital tuberculosis p. 258
Reddy Ravikanth, Kanagasabai Kamalasekar, Nishchil Patel
DOI:10.4103/jhrs.JHRS_3_19  
Genital tuberculosis (GTB) is uncommon, and the most common genital sites of tuberculous infection are epididymis and prostate; isolated testicular TB is extremely rare, comprising only 3% of GTB. The usual modes of genital involvement include descending infection from the kidneys, intracanalicular or direct extension from neighboring foci in the genital tract, and hematogenous dissemination. Ultrasonography (USG) and USG-guided fine-needle aspiration cytology of testicular swelling may confirm the diagnosis of GTB. Anti-TB chemotherapy is the mainstay of treatment to ensure the complete resolution of the lesion. Infertility in GTB is a result of obstruction at the terminal portion of the ejaculatory duct, resulting in dilatation of the proximal ductal system including the vas deferens preventing seminal vesicle secretions from reaching the ejaculate. Seminal vesicle secretions make up the bulk of the ejaculate, contain fructose, and alkalinize the ejaculate, and with obstruction, patients present with azoospermia or aspermia. Here, we present a rare case of extensive primary GTB in a 36-year-old male.
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India's first successful surrogate birth after percutaneous oocyte retrieval following modified radical hysterectomy and right ovarian transposition to the anterior abdominal wall p. 262
Priya Selvaraj, Kamala Selvaraj, Chitrathara Gangadharan, Vijaya Annigeri, Kalaichelvi Srinivasan, Mahalakshmi Sivakumar
DOI:10.4103/jhrs.JHRS_53_19  
A 31-year-old woman, who is a known case of polycystic ovary syndrome, underwent modified radical hysterectomy and right ovarian transposition to the anterior abdominal wall for endometrioid adenocarcinoma Grade II. She then visited our facility for in vitro fertilization (IVF) and surrogacy in the year 2016. Three cycles of IVF were performed using gonadotropin-releasing hormone (GnRH) antagonist in the first two attempts and GnRH agonist in the third attempt, with percutaneous technique of oocyte retrieval from the transpositioned right ovary. In the third attempt in July 2017, we were able to retrieve five oocytes and subsequently froze three embryos and one blastocyst. The surrogate underwent sequential transfer in June 2018 which resulted in a positive clinical singleton pregnancy. The outcome of IVF following percutaneous oocyte retrieval led to a successful pregnancy and subsequent delivery by emergency cesarean by a healthy female baby on February 16, 2019. This is the first reported case of ovarian hyperstimulation and percutaneous aspiration of oocytes from a transpositioned right ovary (subcutaneous plane) in our country. Global literature survey revealed publications only of transabdominal retrieval of ovaries moved above the pelvic brim.
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A rare case of swyer syndrome in two sisters with successful pregnancy outcome in both p. 267
Anupam Gupta, Ritika Bajaj, Umesh N Jindal
DOI:10.4103/jhrs.JHRS_14_19  
Swyer syndrome is a disorder of sex development characterized by gonadal dysgenesis in a phenotypic female with normally developed Mullerian structures but a 46XY karyotype resulting from failure of testicular development in the early embryogenesis. It can have X-linked, Y-linked, or autosomal inheritance. We had a case of two sisters who presented with primary amenorrhea and primary infertility. On investigation, both had hypergonadotropic hypogonadism, 46XY karyotype, and streak gonads. They conceived following in vitro fertilization (IVF) with ovum donation. Prophylactic gonadectomy has been done in one and advised in other due to the increased risk of gonadoblastoma which is as high as 15%–35%. Such patients should be counseled that despite hypoplastic uterus, successful pregnancy can be achieved through IVF and ovum donation.
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