Journal of Human Reproductive Science
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    Table of Contents - Current issue
July-September 2018
Volume 11 | Issue 3
Page Nos. 209-302

Online since Tuesday, November 20, 2018

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From the editor's desk Highly accessed article p. 209
Madhuri Patil
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Insight into different aspects of surrogacy practices p. 212
Nayana Hitesh Patel, Yuvraj Digvijaysingh Jadeja, Harsha Karsan Bhadarka, Molina Niket Patel, Niket Hitesh Patel, Nilofar Rahematkhan Sodagar
Surrogacy is an important method of assisted reproductive technology wherein a woman carries pregnancy for another couple. Number of couples around the world require surrogacy services for various reasons. Although this arrangement seems to be beneficial for all parties concerned, there are complex social, ethical, moral, and legal issues associated with it. It is these complexities that have made this practice unpopular in many parts of the world. Surrogacy in India has had its own journey from India becoming popular as a surrogacy center since 2002 to the Surrogacy (Regulation) Bill, 2016, which would restrict the option of surrogacy for many. Surrogacy is an important medical service for all those couples who would otherwise not have been able to produce a child. Surrogacy would be practiced harmoniously if delicate issues associated with surrogacy will be addressed properly through appropriately framed laws which would protect the rights of surrogate mothers, intended parents, and child born through surrogacy.
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Role of mental health practitioner in infertility clinics: A review on past, present and future directions p. 219
Ansha Patel, P S. V. N. Sharma, Pratap Kumar
A large body of literature has emerged over the past four decades which highlights the need to address emotional needs in infertility and integrates psychological services within routine fertility care. Evidenced-based guidelines in most countries propagate that the mental health expert (MHP) plays a vital role as a team member in reducing the impact of infertility on the lives of patients, across all stages of treatment. In accordance with these global developments, inclusion of psychosocial care in fertility treatments is an upcoming trend in our nation. This review article brings forth the traditional role of MHP in infertility, compares patient-centered care with counseling, and elaborates on the guidelines on determinants of patient needs and suitability for structured psychological interventions. It also highlights the evidence-based studies on the application of psychotherapy in infertility.
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Difficult embryo transfer: A systematic review p. 229
Puneet Arora, Vandana Mishra
We performed a systematic review on the clinical epidemiology and outcome of difficult embryo transfers (ETs) in infertility patients who present with difficult ET. We searched PubMed, ScienceDirect, and Elsevier journals from 1980 to June 2017. We aimed to determine the most successful method resulting in highest pregnancy rates (PRs) in patients with difficult ET. We identified 50 articles, in which 36 were reviewed and 15 were included. Analysis of the data collected showed that the majority of the difficult ETs were caused by cervical stenosis and the most common treatment was cervical dilation. We concluded that cervical dilation was effective at managing difficult ET. Hegar dilators used a minimum of 3 weeks before ET showed to have higher PR.
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Role of saline infusion sonohysterography in infertility evaluation p. 236
Vinita Singh, Byasdev Mishra, Snehil Sinha, Sarita Agrawal, Pushpawati Thakur
Introduction: Etiology of infertility is multifactorial, and fallopian tube abnormality being one of the most important causes accounts for up to 40% of female subfertility if not less and is further increasing. Saline infusion sonohysterography (SIS) procedure is gaining popularity and is being widely practiced and accepted as a screening tool in assessing tubal patency in infertile patients attending infertility clinic and has become popular as a routine test for the evaluation of the uterine cavity in the investigation of infertility and abnormal uterine bleeding. Objective: To compare the results of SIS with that of hysterosalpingography in infertility evaluation and to observe the role of SIS to find out endometrial pathology and tubal patency in infertility patients. Materials and Methods: A retrospective, observational study was done on the basis of record maintained in the ultrasound register and case record sheets of all infertile women who underwent infertility treatment and fulfilled the inclusion criteria from June 2015 to August 2016. Results: SIS had sensitivity of 91%, specificity of 76% positive predictive value (PPV) of 95%, negative predictive value (NPV) of 66%, and accuracy of 89% of SIS in evaluating tubal patency. Further, SIS showed sensitivity of 83.3%, specificity of 60%, PPV of 75%, NPV of 75%, and accuracy of 72% in detecting pelvic pathology. Conclusion: In a low-resource country like India where patients are also less educated, SIS can prove to be a useful tool in initial workup of infertility patients with better compliance, low cost, and better results in a single visit.
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Perifollicular vascularity in poor ovarian responders in In vitro fertilization cycles p. 242
Asifa Majeed, PS Divyashree, Kamini A Rao
Context: Poor response is reported in 9%–24% of stimulated cycles. Color Doppler indices of follicular blood flow are correlated with oocyte recovery, fertilization rate, developmental potential of oocyte, and pregnancy rate in in vitro fertilization (IVF) treatment. Aim: The aim of this study is to find out the correlation between perifollicular vascularity with clinical outcomes in poor ovarian responders during IVF cycles. Settings and Design: A total of 49 poor ovarian responder women undergoing conventional IVF-embryo transfer procedure at a tertiary care hospital between September 2014 and 2015 were included in the study. It was a prospective observational study. Subjects and Methods: Patients were recruited on the day of trigger following a transvaginal ultrasound if they developed ≤4 dominant follicles of ≥16 mm diameter. After ovarian stimulation patients who had all follicles with low-grade vascularity were classified as Group A, those with follicles with high-grade vascularity were Group C, and Group B included patients with follicles of both good and poor vascularity. Statistical Analysis Used: Analysis of variance and Chi-square/Fisher's exact test and software, namely SAS 9.2 and SPSS 15, has been used. Results: A total 49 patients were recruited for the study.10 patients were allocated in Group A, 26 patients in Group B and 13 in Group C. Both groups were comparable in terms of age, period of infertility, follicle-stimulating hormone, luteinizing hormone, and gonadotrophin requirement. The number of metaphase II oocytes and good quality oocytes was significantly higher in Group C. Implantation rate, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, and live birth rate were comparable among all groups. Conclusions: Perifollicular vascularity has an important role to play in clinical outcomes in poor ovarian responders in IVF cycles.
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Chromosomal aberrations in couples with pregnancy loss: A retrospective study p. 247
Asoke K Pal, Prafulla S Ambulkar, Jwalant E Waghmare, Vandana Wankhede, Moreshwar R Shende, Aaditya M Tarnekar
Background: Recurrent pregnancy loss is a challenging reproductive problem, and chromosomal anomalies approximately affect 2%–8% of couples with recurrent pregnancy loss. The chromosomal abnormality, especially balanced translocation rearrangement in either parent, is the important cause of recurrent spontaneous abortion. Aims: The aim of this study was to investigate the role and prevalence of chromosomal anomalies in recurrent miscarriages. The results will be helpful for counseling and make the decision for alternative options and precaution for the affected couples and also support to make a national database. Settings and Design: The present retrospective study was carried out in 172 couples (344 individuals) having the history of three or more recurrent spontaneous abortion. The cytogenetic analysis was done in all 344 individuals using G-banding and karyotyping. Results: Out of 172 couples, 17 couples (9.88%) had different types of structural or numerical chromosomal abnormalities. The structural aberrations were observed in 15 (8.72%) couples, and numerical aberrations were seen in 2 (1.16%) couples. Out of 17 couples, 8 (47.05%) had balanced translocations, 2 (11.76%) had the Robertsonian translocation, 5 (29.41%) had the pericentric inversion of chromosome 8, 9, and Y, and only 2 (11.76%) women showed sex chromosome numerical aberrations. Conclusions: Cytogenetic analysis should be an important routine investigation in couples with repeated miscarriages. Cytogenetic analysis is essential and helpful for genetic counseling to take precaution and implementing proper reproductive alternatives. Studies on the genetic basis of pregnancy loss should be taken up to generate data on these issues from different regions.
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Effect of intrauterine perfusion of granulocyte colony-stimulating factor on endometrial parameters and In Vitro fertilization outcome in women undergoing In Vitro fertilization/intracytoplasmic sperm injection cycles: A randomized controlled trial p. 254
Shivani Jain, Reeta Mahey, Neena Malhotra, Mani Kalaivani, Pant Sangeeta, Ashok Bhatt, Neeta Singh, Alka Kriplani
Context: Studies have found intrauterine perfusion of granulocyte colony-stimulating factor (G-CSF) to improve endometrial thickness and implantation rates in women undergoing in vitro fertilization (IVF). Aims: To study the effect of intrauterine perfusion of G-CSF on endometrial parameters and IVF outcomes in patients undergoing fresh embryo transfers. Settings and Design: This was a randomized double-blinded placebo-controlled trial conducted at assisted reproduction unit of a tertiary care center. Subjects and Methods: One hundred and fifty patients undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment and fresh embryo transfers were randomized to intervention and placebo groups. Patients in the intervention group received intrauterine perfusion of 300 μg (0.5 ml) of G-CSF on the day of ovulation trigger. Patients in placebo group received intrauterine perfusion of 0.5 ml normal saline on the day of ovulation trigger. The primary outcome measure was clinical pregnancy rate. The secondary outcome measures were change in endometrial thickness, volume, and vascularity on the day of embryo transfer; biochemical pregnancy rate, implantation rate, ongoing pregnancy rate, and live birth rate. Statistical analysis was carried out using STATA 12.0 (StataCorp LP, College Station, Texas, USA). Results: Endometrial vascularity in the intervention group was significantly higher on the day of embryo transfer compared to the placebo group. Clinical pregnancy rate was 27.6% in the intervention group compared to 18.9% in the placebo group and the difference was not statistically significant (P = 0.207). There was no statistically significant difference between biochemical pregnancy rate, implantation rate, ongoing pregnancy rate, live birth rate and endometrial parameters between the two groups. Conclusions: Routine use of G-CSF in unselected IVF cycles may not lead to increase in positive IVF outcomes. More trials with larger sample sizes are required before approving or refuting the role of routine G-CSF in increasing IVF success rates. (CTRI/2017/10/010310).
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Evaluating the utility of intralipid infusion to improve live birth rates in patients with recurrent pregnancy loss or recurrent implantation failure p. 261
Anne E Martini, Sue Jasulaitis, Louis F Fogg, Meike L Uhler, Jennifer E Hirshfeld-Cytron
Context: Intralipid is used to improve clinical outcomes in patients with recurrent pregnancy loss (RPL) or recurrent implantation failure (RIF) with elevated natural killer (NK) cells. Data supporting this practice is conflicting but suggestive of minimal benefit. Aims: The aims of this study are to determine if intralipid infusion improves live birth rates and if is a cost-effective therapy in the RPL/RIF population. Settings and Design: This was a large REI private practice, retrospective cohort study. Subjects and Methods: Charts of 127 patients who received intralipid from 2012 to 2015 were reviewed and compared to historical control data. T-tests and Chi-square analyses evaluated demographics and cycle statistics. Chi-square analyses assessed impact on clinical pregnancy and live birth rates. Cost analysis was performed from societal perspective with a one-way sensitivity analysis. Results: Patients with live births were noted to have a higher average number of previous live births and were more likely to have had a frozen embryo transfer in the intralipid cycle in comparison to those with unsuccessful pregnancy outcomes. Neither clinical pregnancy nor live birth rates were significantly improved from baseline rates quoted in the literature (P = 0.12 and 0.80, respectively). Intralipid increased costs by $681 per live birth. If live birth rates were >40% using intralipid and <51% without intervention, neither strategy was favored. Conclusions: Intralipid does not improve live birth rates and is not cost-effective for patients with RIF or RPL and elevated NK cells. This study supports the growing literature demonstrating the minimal benefit of screening for and treating elevated peripheral NK cells.
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Towards a common etiopathogenesis: Periodontal disease and endometriosis p. 269
Vidya Thomas, Ashita S Uppoor, Swati Pralhad, Dilip G Naik, Pralhad Kushtagi
Context: Periodontal disease and endometriosis are seen to share a common pathogenesis. There is only one report suggesting the possible association between the two conditions. Aims: To study the association between endometriosis and periodontal disease. Settings and Design: This was a case–control study. Subjects and Methods: Periodontal screening was carried out in 25 women with endometriosis and 25 women without endometriosis. Severity of periodontal disease was classified based on the extent of loss of attachment. Statistical Analysis Used: Student's t-test, Mann–Whitney U test, and Karl Pearson correlation coefficient tests were used for statistical analysis. Results: The proportion of women with severe periodontitis was seen to be higher among women with endometriosis (70%). Conclusions: The results of the present study indicate the existence of a relationship between endometriosis and periodontal disease. However, further studies among larger cohorts of endometriosis may provide evidence about the association.
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Empty follicle syndrome: A challenge to physician p. 274
Neeta Singh, Venus Dalal, Alka Kriplani, Neena Malhotra, Reeta Mahey, Vanamail Perumal
Background: Empty follicle syndrome (EFS) is a condition in which no oocytes are retrieved from normally growing ovarian follicles after ovarian stimulation. It is a rare and frustrating condition of obscure etiology. Objective: The objective of this study was to estimate the incidence of EFS and study factors related to it. Design: This was a retrospective study. Setting: This study was conducted in hospital-based research center. Methods: In 1968 in vitro fertilization cycles from January 2010 to August 2016 were studied. Agonist, antagonist, and miniflare protocols were used for the stimulation. Results: The incidence of EFS is 2.38% (47/1968 cycles). Antagonist protocol group (76.59%, n = 36) had highest incidence of EFS (6.69%). Literature on EFS depicts decreased ovarian reserve (DOR) as the main cause, but only 4.25% of patients had DOR in our study. Interestingly, polycystic ovary syndrome and unexplained infertility were found in 31.9% of the cases. Serum anti-Müllerian hormone (AMH) levels (mean ± standard deviation [SD]) were 4.47 ± 3.54 ng/ml, and antral follicle count (AFC) was 15.30 ± 8.07 (mean ± SD) emphasizing that diminished ovarian reserve is not the main factor for EFS. All patients (n = 95) who underwent ovum pickup on day when any patient had EFS were taken as control. Patients with EFS were compared with controls. A statistically significant difference was not observed in serum AMH (P = 0.38) and AFC (P = 0.52). Conclusion: EFS is an uncommon event. Antagonist cycles have higher chances of empty follicle at ovum pickup. Looking at the profile of patients in this study, we conclude that EFS is not a manifestation of DOR.
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An intrauterine insemination audit at tertiary care hospital: A 4½ years' retrospective analysis of 800 intrauterine insemination cycles p. 279
Leena Wadhwa, Ashish Fauzdar, Sanjana Narula Wadhwa
Background: There are many variables that may influence the success rates of intrauterine insemination (IUI) treatment. Therefore, a regular audit program is needed for planning effective infertility treatment and improving pregnancy outcomes. Aims and Objectives: The main objective of this study was to identify the crucial predicting factors that can influence the IUI success. Materials and Methods: A retrospective analysis of 800 IUI cycles done from January, 2013 to August, 2017 in 651 couples with various etiologies of infertility. The common etiologies included female factor of ovulatory dysfunction, tubal, endocrinal, male factor, male and female factors combined, and unexplained factors. Ovulation induction was done either by clomiphene citrate (CC) alone or in combination of CC with gonadotropins or pure gonadotropins only. Human chorionic gonadotropin trigger was given when at least one dominant follicle measuring ≥18 mm with an endometrial thickness of >7 mm was obtained. IUI was done post 36 h of trigger. The double-density gradient method was the preferred method of sperm preparation. Results: In 800 cycles in corresponding 651 couples, the total outcome was 113 pregnancies (14.1%) per cycle with overall pregnancy rate (PR) per couple of 17.3%. The highest PR was observed in the patient with ovulatory dysfunction (21.2%), followed by patients with combined factor (15.1%) and male factor (14.7%). In the study, a higher PR was achieved in the female ≤25 years (18.9%) P < 0.04 with significant findings with duration of infertility ≤5 years (15.1%) having primary infertility (14.5%) with low body mass index <25 (14.1%). IUI success rate was highest in the first cycle (14.6%) followed by second cycle (14.0%) and third cycle (3.5%). Conclusion: IUI audit enables the characterization of prognostic factors to achieve improved PR. This study identifies the factors that can predict improved pregnancy outcome in women age ≤25 years and endometrium thickness between 9 and 11 mm. We also recommend IUI as a first line of infertility treatment for couples in low-income setting provided the women age and duration of infertility are acceptably low.
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Retained intrauterine bony fragments as a cause of secondary infertility in a tertiary level Indian hospital p. 286
Shalini Gainder, Parul Arora, Lakhbir Kaur Dhaliwal
Background: Midtrimester surgical abortions often result in retained intrauterine fetal bones and consequent secondary infertility. Aim: To study the incidence of women presenting with retained intrauterine bones as a cause of secondary infertility in a tertiary level Indian hospital and pregnancy rates following retrieval of these fragments. Setting and Design: Retrospective data analysis in the infertility clinic of PGIMER (Post Graduate Institute of Medical Education and Research), a tertiary level hospital of Northern India. Materials and Methods: Women diagnosed with retained intrauterine bony fragments were subjected to hysteroscopic removal of these fragments. Incidentally diagnosed retained bones on hysteroscopy were also removed. Such women were followed for spontaneous resumption of fertility or were subjected to ovulation induction, and pregnancy rates were noted. Results: Retained fetal bones accounted for 0.28% of all women with infertility and 12% (22/144) of all the uterine causes of infertility requiring an operative hysteroscopic procedure for treatment. Only 5 (27.7%) of 18 women conceived after the hysteroscopic retrieval of bony fragments: three had full-term vaginal deliveries, one had a midtrimester abortion, and one woman is in her third trimester. Conclusion: Despite surgical retrieval, fertility rates may be lower due to inflammatory damage to the endometrium.
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Steroidogenesis and VEGF production doesn't alter in leydig cells within the homeostatic range of testicular temperature p. 291
Atul Kumar Goyal, Jyoti Saini
Context: Physiologically defined homeostatic temperature range for human testis falls within 32°C–37°C and any deviation outside that range can result in impaired steroidogenesis. However, whether temperature deviation within the homeostatic range can affect the steroidogenesis, is still a question of the investigation. Aim: In the present study, we investigated the production of progesterone, testosterone, and vascular endothelial growth factor (VEGF) within the homeostatic temperature range of testis, i.e., 32°C–37°C. Setting and Design: We used mouse Leydig tumor cells-1 (MLTC-1) cell line as a model in the present study. Materials and Methods: Progesterone and testosterone production by MLTC-1 cells was measured by radioimmunoassay and VEGF production was measured using ELISA. Statistical Analysis Used: Data were analyzed using GraphPad Prism software version 7.04. Student's t-test and ANOVA were used to calculate the P value. P < 0.05 was considered statistically significant. Results and Conclusions: Results of our study indicate that there is no significant difference in production of progesterone, testosterone, and VEGF within the homeostatic range of the testicular temperature. Thus, we concluded that testicular cells are able to regulate the steroidogenesis and VEGF production under the homeostatic range of the testicular temperature.
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Different endometrial receptivity in each hemiuterus of a woman with uterus didelphys and previous failed embryo transfers p. 297
Francisco Carranza, Ana González-Ravina, Víctor Blasco, Manuel Fernández-Sánchez
The aim of this report is to describe the clinical case of a 31-year-old patient with uterus didelphys (double uterus) and primary infertility, who had been through several embryo transfers in the context of an in vitro fertilization (IVF) treatment with no success. In the case described, the patient is subjected to a new IVF treatment after an endometrial receptivity array (ERA) test performed in both hemiuteri, to assess endometrial receptivity. As a result, the test showed that the right-sided hemiuterus was receptive in 5 days since the beginning of progesterone administration while the left-sided hemiuterus was not receptive in that day. The IVF treatment is performed with vitrified oocytes and a single embryo in day-3 stage is transferred to the right hemiuterus. We concluded that the ERA analysis is a useful tool for IVF patients with uterus didelphys to choose the most appropriate hemiuterus and day to perform embryo transfer.
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Persistent mullerian duct syndrome with testicular seminoma in transverse testicular ectopia p. 300
Sharada R Rane, Deepak Pandurang Dangmali, Sharvari D Vishwasrao, Shaila C Puranik
Persistent Mullerian Duct Syndrome (PMDS) is a disorder of male pseudohermaphroditism characterized by the persistence of Mullerian duct derivatives (uterus, fallopian tubes, and upper two-third of vagina) in a phenotypically and genotypically male. Transverse testicular ectopia (TTE) is a rare congenital anomaly in which both gonads migrate toward same hemiscrotum. About 150 cases of PMDS and 100 cases of TTE have been reported in previous studies. Testicular tumor in patients with PMDS with TTE is very rare. We report a case of testicular seminoma in a 35-year-old male patient with PMDS and TTE. Preoperative diagnosis was not possible in most of the reported cases.
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