Journal of Human Reproductive Science
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   2015| July-September  | Volume 8 | Issue 3  
    Online since September 11, 2015

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Endometrial receptivity array: Clinical application
Nalini Mahajan
July-September 2015, 8(3):121-129
DOI:10.4103/0974-1208.165153  PMID:26538853
Human implantation is a complex process requiring synchrony between a healthy embryo and a functionally competent or receptive endometrium. Diagnosis of endometrial receptivity (ER) has posed a challenge and so far most available tests have been subjective and lack accuracy and a predictive value. Microarray technology has allowed identification of the transcriptomic signature of the window of receptivity window of implantation (WOI). This technology has led to the development of a molecular diagnostic tool, the ER array (ERA) for diagnosis of ER. Use of this test in patients with recurrent implantation failure (RIF) has shown that the WOI is displaced in a quarter of these patients and use of a personalized embryo transfer (pET) on the day designated by ERA improves reproductive performance. Our results in the Indian population revealed an endometrial factor in 27.5% RIF patients, which was significantly greater than the non-RIF group 15% (P = 0.04). After pET, the overall ongoing pregnancy rate was 42.4% and implantation rate was 33%, which was at par with our in-vitrofertilization results over 1-year. We also performed ERA in patients with persistently thin endometrium, and it was reassuring to find that the endometrium in 75% of these patients was receptive despite being 6 mm or less. A pregnancy rate of 66.7% was achieved in this group. Though larger studies are required to validate these results ERA has become a useful tool in our diagnostic armamentarium for ER.
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Dhat syndrome: Evolution of concept, current understanding, and need of an integrated approach
Sujita Kumar Kar, Siddharth Sarkar
July-September 2015, 8(3):130-134
DOI:10.4103/0974-1208.165143  PMID:26538854
Dhat syndrome has often been construed as a culture-bound sexual neurosis of the Indian subcontinent. Symptoms similar to that of Dhat syndrome has been described in other cultures across different time periods. The present paper looks at the evolution of the concept of Dhat syndrome in India. The review also takes an overview of the current understanding of this syndrome in terms of nosological status as a distinct entity and its "culture-bound" status. The narrative finally attempts to discuss the integrated approach for the treatment of this disorder.
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Successful fertilization and embryo development after spermatid injection: A hope for nonobstructive azoospermic patients
Geeta Goswami, Sarabjeet Singh, M Gouri Devi
July-September 2015, 8(3):175-177
DOI:10.4103/0974-1208.165147  PMID:26538862
Spermatids are the earliest male germ cells with haploid set of chromosomes. Spermatid injection was introduced in human assisted reproduction for the treatment of men with non-obstructive azoospermia. Spermatozoa can be recovered in half of patients with nonobstructive azoospermia. The use of spermatids for intracytoplasmic injection (ICSI) has been proposed for cases in which no spermatozoa can be retrieved. However, there are low pregnancy rates following ICSI using round spermatids from men with no elongated spermatids or spermatozoa in their testes. The in vitroculture of immature germ cells has been proposed as a means to improve this poor outcome. Oocyte activation rarely occurs when injected with a spermatid. Therefore, spermatid injection requires use of calcium ionophores for oocyte activation which is otherwise carried out by PLC zeta from mature sperms. This is the only option available for the nonobstructive azoospermic patients to have their own biological child.
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Microdeletion of Y chromosome as a cause of recurrent pregnancy loss
Shubhra Agarwal, Arjit Agarwal, Anuradha Khanna, Kiran Singh
July-September 2015, 8(3):159-164
DOI:10.4103/0974-1208.165145  PMID:26538859
CONTEXT: In majority of couples experiencing recurrent pregnancy loss (RPL), etiology is still unknown. Two genetic factors have been suggested to underlie miscarriage in a subset of patients, namely skewed X chromosome inactivation in females and Y chromosome microdeletions in their partners. In males, microdeletions of the Y chromosome are known to cause spermatogenetic failure and male infertility. AIMS: The aim of the study was to find out the role of Y chromosome microdeletion in male partners of couples experiencing RPL. SETTINGS AND DESIGN: University hospital and genetic laboratory. Prospective case–control study. SUBJECTS AND METHODS: 59 couples with a history of RPL and 20 fertile controls (FC) with no miscarriage were included in the study. The study subjects were divided into male partners of RPL couples with abnormal semen parameters (AS) (n = 8), and couples with normal semen parameters (NS) (n = 51). Fertile controls with normal semen parameters were (FC) (n = 20). Y chromosome microdeletion was performed on 40 male partners of RPL and 20 FC. STATISTICAL ANALYSIS USED: Chi-square test. P <0.05 were considered statistically significant. RESULTS: 13 of the 40 RPL cases showed deletion in three azoospermia factor loci on the long arm of Y chromosome. The P value was significant with Y chromosome microdeletion in RPL cases as compared to 20 FC where no Y chromosome microdeletion was present. CONCLUSIONS: Y chromosome microdeletion may be an important hidden cause of recurrent pregnancy miscarriage and can be offered to couples with the undiagnosed cause of miscarriage.
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Effect of endometrial biopsy on intrauterine insemination outcome in controlled ovarian stimulation cycle
Leena Wadhwa, Amrita Pritam, Taru Gupta, Sangeeta Gupta, Sarika Arora, Rajkumar Chandoke
July-September 2015, 8(3):151-158
DOI:10.4103/0974-1208.165144  PMID:26538858
OBJECTIVE: The objective was to evaluate the effect of endometrial biopsy (EB) on intrauterine insemination (IUI) outcome in controlled ovarian stimulation (COS) cycle. DESIGN: Prospective randomized control study. SETTING: Tertiary care center. MATERIALS AND METHODS: A total of 251 subjects were enrolled in the study. Subjects undergoing COS with IUI were randomly allocated into three groups. Group A: EB was taken between D19 and 24 of the spontaneous menstrual cycles that precedes the fertility treatment and IUI, which was done in next cycle (n = 86). Group B: EB was taken before D6 of the menstrual cycle, and fertility treatment and IUI was done in the same cycle (n = 90). Group C: (control group) no EB in previous 3 cycle (n = 75). MAIN OUTCOME MEASURE: Clinical pregnancy rate (CPR). RESULTS: Clinical pregnancy rate was 19.77%, 31.11%, and 9.3% for Group A, Group B, and Group C, respectively. The results show a highly significant value for the paired t-test of intervention Group B and control Group C of the cases (P = 0.000957). CPR was maximum afterfirst cycle of ovulation induction and IUI following EB scratch in both Groups A and in Group B (P < 0.001). CONCLUSIONS: Endometrial biopsy done in early follicular phase in the same cycle of stimulation with IUI gives better CPR as compared with EB done in the luteal phase of the previous cycle.
  5 3,327 167
Sample size estimation and power analysis for clinical research studies: Retraction

July-September 2015, 8(3):186-186
DOI:10.4103/0974-1208.165154  PMID:26538865
  5 5,047 288
Empty follicle syndrome: Successful pregnancy following dual trigger
K Deepika, Suvarna Rathore, Nupur Garg, Kamini Rao
July-September 2015, 8(3):170-174
DOI:10.4103/0974-1208.165152  PMID:26538861
Empty follicle syndrome (EFS) is an uncommon, but the frustrating complication of assisted reproductive technology with failure to obtain oocytes after an adequate ovarian response to stimulation. Most of the reported cases of EFS are drug-related problems which are actually avoidable and do not represent any potential pathology and that the risk of genuine EFS (GEFS) is much smaller than was once thought. Our case is thefirst report of a pregnancy obtained after management of GEFS with dual trigger in a gonadotropin-releasing hormone (GnRH) antagonist cycle. In this report, we present a patient who underwent two oocyte retrievals, in which no oocytes were obtained. In the third in-vitrofertilization cycle, a dual trigger with the combination of GnRH agonist and human chorionic gonadotropin yielded 11 oocytes, which led to the transfer of 2 blastocysts resulting in a live birth. Changing the treatment protocol with dual trigger brought about a successful outcome.
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Pregnancy outcome of assisted reproductive technology cycle in patients with hypogonadotropic hypogonadism
Monna Pandurangi, M Tamizharasi, N Sanjeeva Reddy
July-September 2015, 8(3):146-150
DOI:10.4103/0974-1208.165141  PMID:26538857
CONTEXT: Ovulation induction in patients with hypogonadotropic hypogonadism (HH) is a challenge to the treating physician. The threshold for ovarian response in HH may differ substantially from that of normal patients. To reach that threshold levels of follicle stimulating hormone, in a step-up protocol longer duration of stimulation is required in some cases so as to prevent multiple pregnancy and to eliminate the risk of ovarian hyperstimulation syndrome. AIM: To evaluate the duration of stimulation, quality of oocytes, and embryo, and the pregnancy outcome in the assisted reproductive technology (ART) cycles in patients with HH. MATERIALS AND METHODS: Over the period of 4 years, we had 14 patients with HH in whom 21 cycles of ovulation induction were done. Of these 7 patients underwent oocyte retrieval and intracytoplasmic sperm injection (ICSI). We present a retrospective study of these 7 patients who underwent ART to evaluate the duration of stimulation, quality of oocytes and embryo, and the pregnancy outcome. RESULTS: In the study group on ovulation induction with gonadotropins, only one patient had the duration of stimulation of the standard 12 days, the remaining 6 patients took ≥12 days to respond to stimulation (maxium being 54 days). Mean ET in these patients was 8.9 mm. Six patients had >70% good quality MII oocytes. One patient responded poorly and had only 2 good quality MII oocytes (50%). After ICSI procedure, resultant embryos were of grade 1 and 2 in all the patients irrespective of the duration of stimulation. Fertilization rate in these patients was 85% (except in one 50% fertilization rate), and the cumulative pregnancy rate was 68.6%. CONCLUSION: In the patients with HH the quality of oocytes and embryos, and the pregnancy rate is not affected even if the duration of stimulation is prolonged.
  4 3,096 177
Relevance of semen polymerase chain reaction positive for tuberculosis in asymptomatic men undergoing infertility evaluation
Subodh Kumar Regmi, Urvashi B Singh, Jai Bhagwan Sharma, Rajeev Kumar
July-September 2015, 8(3):165-169
DOI:10.4103/0974-1208.165148  PMID:26538860
OBJECTIVE: Male partners of infertile women with genital tuberculosis (TB) are often screened for genital TB. We aimed to evaluate the clinical significance of a positive screening semen polymerase chain reaction (PCR) for Mycobacterium tuberculosis test (TB-PCR) in asymptomatic men undergoing infertility evaluation and determine the need for a detailed investigation and treatment for TB. MATERIALS AND METHODS: Between March 2012 and January 2013, male partners of 15 infertile women with a diagnosis of genitourinary TB (GUTB) as the cause of infertility, tested positive either on semen PCR for TB (13 cases), or Mycobacterium Growth Indicator Tube-960 test (2 cases). These asymptomatic men underwent infertility evaluation along with evaluation for GUTB. Diagnosis of GUTB was based on standard clinical criteria, which included a high index of suspicion along with clinical, laboratory, and/or radiological evidence of GUTB. Men who had no clinical evidence of GUTB were followed up with clinical evaluation, semen analysis, and repeat semen PCR for TB after 6 months. RESULTS: Fourteen subjects consented for inclusion in the study. One had a history of pulmonary TB 20 years earlier. Another patient was found to have mediastinal lymphadenopathy (tubercular). All except one had a normal semen analysis. None of the patients met the standard clinical criteria for GUTB diagnosis. 8 patients followed up at 6 months with repeat semen analysis, which was similar to the baseline values and no clinical evidence of TB. INTERPRETATION AND CONCLUSIONS: Asymptomatic men with positive screening semen PCR for TB do not have clinical evidence of TB. Male partners of women with infertility and GUTB should not be screened if they have no symptoms.
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Dehydroepiandrosterone as an adjunct to gonadotropins in infertile Indian women with premature ovarian aging: A pilot study
Nisha Malik, Alka Kriplani, Nutan Agarwal, Neerja Bhatla, Garima Kachhawa, Raj Kumar Yadav
July-September 2015, 8(3):135-141
DOI:10.4103/0974-1208.165142  PMID:26538855
BACKGROUND: Dehydroepiandrosterone (DHEA) supplementation is a relatively recent development that augments ovarian responsiveness in patients with poor ovarian reserve and premature ovarian aging (POA). AIMS: To evaluate the efficacy of DHEA supplementation prior to gonadotropins for ovulation induction in women with POA. DESIGN: Prospective randomized controlled study. METHODS: Fifty infertile women with POA were randomized into two groups of 25 each. Group 1 received tablet DHEA 25 mg while group 2 received placebo thrice daily for 6 months. After 3 months, gonadotropin induction with intrauterine insemination was done. STATISTICAL ANALYSIS: Groups were compared using t-test and Mann–Whitney U-test as appropriate. Pre- and post-parameters were compared using t-test -paired and Wilcoxon signed-rank tests as appropriate. RESULTS: Of 50 patients, 62% (31/50) presented with primary and 38% (19/50) with secondary infertility. The mean age was 32.1 ± 4.7 years. Serum antimullerian hormone levels (1.5 ± 0.6–1.9 ± 0.4 ng/ml vs. 1.4 ± 0.5–1.5 ± 0.6 ng/ml) and antral follicle count (3.2 ± 1.0–9.3 ± 3.1 vs. 3.3 ± 1.1–3.4 ± 1.4) improved significantly in DHEA group after 3 months. Serum follicular stimulating hormone and estradiol levels though showed significant intra-group improvement (16.9 ± 5.5 mIU/ml to 14.7 ± 6.2 mIU/ml and 86.6 ± 57.5 pg/ml to 105.6 ± 54.3 pg/ml, respectively) with DHEA, the inter group difference was not significant. Ovulation increased from 48% to 86.3% in DHEA group versus 44–66% in placebo group. Six women (24%) conceived after DHEA in comparison to none in the placebo group. CONCLUSIONS: DHEA supplementation may have a beneficial role as an adjunct to gonadotropins in the treatment of infertility with POA, but further evidence is required.
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Pregnancy outcome with coexisting mole after intracytoplasmic sperm injection: A case series
Asha R Rao, Karishma Dafle, G Padmashri, Damodar R Rao, NC Sivakumar
July-September 2015, 8(3):178-181
DOI:10.4103/0974-1208.165149  PMID:26538863
Partial/complete hydatidiform mole with coexisting fetus is a rare condition. Optimal management is a challenge that remains a dilemma since these pregnancies are associated with maternal as well as fetal complications including hemorrhage, preeclampsia, thromboembolic disease, intra uterine demise and increased risk of persistent trophoblastic disease. Here we report 2 cases of partial mole with live fetus after ICSI and a case of complete mole with coexisting fetus after ICSI in a turner mosaic that resulted in a live birth.
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Deep venous thrombosis in a patient undergoing In-vitrofertilization with oocyte donation
Nalini Mahajan, Padmaja Naidu, Shalu Gupta, Kumkum Rani
July-September 2015, 8(3):182-185
DOI:10.4103/0974-1208.165150  PMID:26538864
Deep venous thrombosis (DVT) has been reported extensively following ovarian hyperstimulation syndrome during in-vitrofertilization (IVF). Pregnancy per seincreases the risk of DVT due to a hypercoagulable state. The long-term use of hormone replacement therapy (HRT) is another critical factor associated with DVT in women. However, an association between the short-term use of HRT in oocyte donation (OD) cycles and DVT has not yet been reported. We present a case of 43-year-old woman who developed DVT after IVF-OD. DVT was diagnosed at 7 weeks of pregnancy and was managed with low-molecular-weight heparin. We suggest that even a short-term use of HRT should be considered a risk factor for DVT especially in the presence of additional risk factors such as obesity. The patient had an uneventful recovery and delivered three healthy though preterm babies.
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From the Editor's desk
Madhuri Patil
July-September 2015, 8(3):119-120
DOI:10.4103/0974-1208.165146  PMID:26538852
  - 2,316 108
Clomiphene based ovarian stimulation in a commercial donor program
Shruti Gupta, Ruma Satwik, Abha Majumdar, Shweta Mittal, Neeti Tiwari
July-September 2015, 8(3):142-145
DOI:10.4103/0974-1208.165151  PMID:26538856
OBJECTIVE: This study was conducted to compare an extended clomiphene-based ovarian stimulation regimen with the conventional antagonist protocol in donor-recipient cycles. MATERIALS AND METHODS: A total of 170 (N) donors were stimulated between January 2013 and December 2013. Conventional antagonist protocol (group I) was employed in (n1 = 31) cycles, and clomiphene was used in (n2 = 139) donor cycles (group II). 50 mg clomiphene was given simultaneously with gonadotropins from day 2 of the cycle until the day of trigger. The analysis was performed retrospectively for oocytes retrieved, fertilization rates, cycle cancelation, blastocyst formation, and pregnancy rates. The dosages, cost, and terminal E2 (estradiol) were also compared between the two groups. RESULTS: The donor age groups were comparable in both the groups. There were no unsuccessful egg retrievals with clomiphene. The pregnancy rate (positive beta human chorionic gonadotropin) was significantly higher in the clomiphene group (odds ratio: 2.453; P = 0.02). Similarly, fertilization rate was significantly higher in the clomiphene group (59.5/50.5, P = 0.04). Eggs retrieved were similar in both groups, but the terminal E2 was significantly higher in the clomiphene group (P = 0.001). Average gonadotropin used was also significantly lower in clomiphene group (P < 0.001). CONCLUSION: Clomiphene can effectively prevent luteinizing hormone surge and limit the dose of gonadotropins thus bringing down the costs and its negative impact on the endometrium and oocyte quality.
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Understanding implantation window, a crucial phenomenon: Retraction

July-September 2015, 8(3):187-187
DOI:10.4103/0974-1208.165155  PMID:26538866
  - 2,121 113
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