Journal of Human Reproductive Science
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    Table of Contents - Current issue
April-June 2022
Volume 15 | Issue 2
Page Nos. 101-203

Online since Thursday, June 30, 2022

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Editorial commentary Highly accessed article p. 101
Padma Rekha Jirge
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The reproductive functions of the human brain regions: A systematic review Highly accessed article p. 102
Izuchukwu Azuka Okafor, Ugochukwu Damian Okpara, Kingsley Chinemerem Ibeabuchi
Reproduction remains a vital characteristic of living things necessary for survival and continuity. Specific brain regions and structures are responsible for regulating the different aspects of human reproduction. This study systematically reviewed the brain regions that play structural, hormonal and physiological roles in controlling the various aspects of human reproduction from puberty, sexual function, gametogenesis, childbirth and fertility to infertility to inform advancement in research and therapeutic interventions in human reproductive disorders. A systematic literature search of online databases (MEDLINE, Europe PMC and Google Scholar) was made using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for observational and cross-sectional studies providing evidence for the role(s) of the brain region in human reproduction from the year 2011–2021. Out of 141 articles found, 15 studies met the inclusion criteria, including six cross-sectional and nine randomised controlled trials. The study acknowledged the roles of the pituitary gland, hypothalamus and pineal gland, widely known for regulating the human reproductive system in a gender-based approach while highlighting essential gaps and opportunities for future research. This review provides a 10-year update and overview of the role of different brain regions in human reproduction and will stimulate future research in human reproduction.
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Ovarian stimulation in assisted reproductive technology cycles for varied patient profiles: An Indian perspective p. 112
Padma Rekha Jirge, Madhuri Milind Patil, Rohit Gutgutia, Jatin Shah, Mridubhashini Govindarajan, Varsha Samson Roy, Nalini Kaul-Mahajan, Faddy I Sharara
Controlled ovarian stimulation has been an integral part of in vitro fertilisation (IVF) treatment cycles. Availability of different gonadotropins for ovarian stimulation and gonadotropin releasing hormone (GnRH) analogues for prevention of premature rise of leutinising hormone during follicular phase offer an opportunity to utilise them for a successful outcome in women with different subsets of ovarian response. Further, use of GnRH agonist as an alternative for human chorionic gonadotropin improves safety of ovarian stimulation in hyper-responders. Mild ovarian stimulation protocols have emerged as an alternative to conventional protocols in the recent years. Individualisation plays an important role in improving safety of IVF in hyper-responders while efforts continue to improve efficacy in poor responders. Some of the follicular and peri-ovulatory phase interventions may be associated with negative impact on the luteal phase and segmentalisation of the treatment with frozen embryo transfer may be an effective strategy in such a clinical scenario. This narrative review looks at the available evidence on various aspects of ovarian stimulation strategies and their consequences. In addition, it provides a concise summary of the evidence that has emerged from India on various aspects of ovarian stimulation.
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Effect of Aloe vera (Barbadensis Mill) on letrozole induced polycystic ovarian syndrome in swiss albino mice p. 126
Shridhar C Ghagane, Makhadumsab M Toragall, A Aimen Akbar, Murigendra B Hiremath
Background: Polycystic ovarian syndrome (PCOS) is the predominant endocrine abnormality in premenopausal women characterised by hyperandrogenism, ovulatory dysfunction, metabolic disturbances such as, insulin resistance and obesity. Aim: The key objective of this study was to evaluate the efficacy of Aloe vera as a treatment drug to identify the factors among female Swiss albino mice (PCOS) models displaying ovarian and metabolic abnormalities and serum sex steroids that are associated with insulin sensitivity. Study Setting and Design: The laboratory breed 4 months adult virgin female Swiss albino mice showing regular estrous cycle and weighing about 20–30 g were employed in present study under CPCSEA guidelines with ethical clearance from the institutional ethical committee. These mice were categorized into two groups with 10 mice in each as control and test animals. Materials and Methods: The mice which were categorised into two groups with 10 mice in each. Carboxy methyl cellulose control and letrozole were induced for 21 days followed by 30 days treatment with distilled water for control, Diane as standard drug and Aloe vera gel formulation. Body weight, estrous cycle, biochemical estimations, hormone assay and histopathology were the parameters studied. Statistical Analysis: IBM SPSS version 20.0 was used for the mean and standard error calculations of biochemical and antioxidants estimation. Results: During the induction period, we observed a significant increase in the body weight, decrease in the number of estrous cycle, and the concomitant increase in diestrous. The biochemical estimations showed changes in the regular activity; hormonal imbalance was observed in hormone assay and cyst formation was also observed in the histopathological study. After the treatment of Aloe vera and Diane, all the parameters showed considerable good results. Conclusion: The findings of the current study provide a baseline data for designing further investigations on the therapeutic benefits of Aloe vera as an adjunct therapy in the management of PCOS.
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Effects of babydance lubricant on sperm parameters p. 133
Alemeh Rafaee, Kianoosh Kakavand, Niloofar Sodeifi, Faramarz Farrahi, Marjan Sabbaghian
Background: Semen analysis is a common test conducted for diagnosing the cause of male infertility, so using an innocuous lubricant can be beneficial to reduce the semen collection difficulties. Aims: In this study, the effects of BabyDance™ lubricant gel, a paraben-free lubricant, on sperm parameters were investigated. Study Setting and Design: It was a prospective study and a total of 45 individuals were enrolled. Materials and Methods: First, the semen samples of 20 patients referred to Royan Research Institute were incubated with different concentrations of gel, and subsequently, the sperm motility and vitality were evaluated. In the second phase, 25 individuals who had a spermogram test were asked to apply the gel in the new semen examination. Statistical Analysis: Obtained data were statistically analysed using SPSS software. Results: The results of the in vitro phase revealed that this gel does not affect the pH, sample colour, viability, total motility and progressive and non-progressive motility of spermatozoa at any concentration. The second phase results also represented no difference in spermatozoal characteristics with and without gel use. Moreover, 100% of the participants in the second phase were satisfied with the gel and recommended that to other patients. Conclusion: It was concluded that this gel can be considered a harmless product to sperm and can be a beneficial option for clients referring to infertility centres that facilitate the semen collection process.
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Retrospective analysis of the first collection versus the second collection in severe oligo-asthenoteratozoospermia cases in self-intracytoplasmic sperm injection patients p. 138
Deven V Patel, Trupti Patel, Naroda Maheshwari, Shradha Soni, RG Patel
Background: It is well established that high-quality semen can lead to an improved fertilisation rate. Ejaculatory abstinence (EA) certainly can influence sperm quality such as volume, count, motility and morphology. However, very few studies have addressed the influence of EA on intracytoplasmic sperm injection (ICSI) outcome and especially in males with severe oligo-asthenoteratozoospermia (OAT) syndrome. Aim: This study was undertaken with the purpose of evaluating the advantage of shorter abstinence period (1-h sequential ejaculation) in males with severe OAT syndrome on total usable embryo rate and thereby emphasising the potential application of consecutive ejaculate. Study Setting: This retrospective cohort study consisted of all the infertile couples undergoing ICSI cycle with the indicated seminal characteristics who had consulted the tertiary care hospital between January 2021 and July 2021. Materials & Methods: All couples in the study had idiopathic male infertility. Retrospectively, two groups were analysed, i.e., Group A with 56 subjects in which first semen sample was used for ICSI cycle and another Group B with 41 subjects in which second semen sample collected within a shorter abstinence period of 1 h was used. Statistical Analysis: The data were descriptively analysed using GraphPad Prism (vs. 9.2). Unpaired t-test and analysis of variance test were used to determine the significance. P < 0.05 was considered statistically significant. Results: The age of female subjects in Group A was 29.9 ± 3.5 years while it was 29.4 ± 3.4 years in Group B. Similarly, the age of male subjects was 32.2 ± 3.6 years and 31.9 ± 4.1 years in Group A and Group B, respectively, with no statistical differences in any gender between the groups (P > 0.05). Apart from initial progressive motility (P = 0.004), none of the parameters such as total volume, total sperm count and morphology were significantly different (P > 0.05) between Group A and samples of Group B. Similarly, parameters such as volume (P = 0.006) and post-wash motility (P < 0.001) were significantly different between Group A and samples of Group B. However, there was no significant difference in sperm count and morphology (P > 0.05). Grade 1 embryos on day 3 were 345 (62.8%) in Group A and 170 (54.3%) in Group B. Overall, the total usable embryos in Group A and Group B were 222 (40.4%) and 148 (47.3%), respectively (P > 0.05). Conclusion: With regard to compromised sperm parameters, our findings do suggest that the second ejaculate is quite relevant to 'in vitro' reproductive treatments and a simple request for a second consecutive ejaculate (shorter abstinence period of 1 h) could provide the same results in terms of fertilisation. We observed the increased chances of usable embryos in the second ejaculate group.
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Does choosing microfluidics for sperm sorting offer an advantage to improve clinical pregnancies in donor egg recipients? p. 143
Sapna Srinivas, Suhasini Donthi, Anupama Deenadayal Mettler, Aarti Deenadayal Tolani, Mamata Deenadayal
Background: Microfluidics (MF), an advanced sperm sorting technology results in the extraction of spermatozoa with higher DNA integrity and lower DNA damage compared to existing conventional sperm sorting methods. Aims: The aim of the present study is to assess the efficiency of MF and to isolate the best spermatozoa for intracytoplasmic sperm injection (ICSI) over the density gradient (DG) technique. Settings and Design: We recruited couples who choose the oocyte donation programme for this study to eliminate confounding factors associated with oocyte quality. Materials and Methods: Sperm was processed by MF (n = 180) and DG (n = 151). ICSI was performed and positive pregnancy, miscarriage and clinical pregnancy rates were compared. Statistical Analysis Used: All variables were analysed using Graph Pad Prism 5. The unpaired two-tailed t-test was used to assess the significance. A value of P < 0.05 was considered statistically significant. Results: There was no significant difference in pregnancy rates between the groups. However, a clear demarcation is seen in terms of clinical pregnancy rates, where the DG group achieved higher clinical pregnancies (91.7%) compared to the MF group (80.7%). Further, we compared miscarriage rates and biochemical pregnancies, and found a significantly higher miscarriage and biochemical pregnancy rate in the MF group (14.5% and 4%, respectively) compared to the DG group (6% and 1%, respectively). Conclusions: Based on the available literature, we anticipated a higher clinical pregnancy rate with MF compared with conventional processing. Our results show MF does not have any add-on positive effect on clinical pregnancy rate.
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Impact of COVID-19 pandemic on clinical and embryological outcomes of assisted reproductive techniques p. 150
Manish Banker, Parul Arora, Jwal Banker, Anand Shah, Reena Gupta, Sandeep Shah
Background: The emergence of the COVID pandemic unfolded a series of precautions and dilemmas and the complete suspension of health services. With the gradual emergence of data showing near minimal effects of the virus on pregnancy, Assisted Reproductive Techniques (ART) services were gradually resumed following guidelines and advisories. Aim: The purpose of this study was to detect the COVID positivity rate in women undergoing ART treatment during the COVID pandemic and compare clinical and embryological outcomes to the ART cycles performed in the pre-COVID era. Study Design and Settings: This was a retrospective cohort study of all women undergoing controlled ovarian stimulation, followed by a fresh or frozen embryo transfer (ET) between 1st October 2019 and 31st March 2020 (control group) and between 1st April 2020 and 31st September 2020 (study group) at Nova IVF Fertility Clinic, Ahmedabad. Material and Methods: The study group underwent ART during the first wave of COVID-19 pandemic in India and when gradual unlocking of facilities including ART was advised as per the national ART advisory by the ICMR in December 2020. The outcomes were compared with the control group (cycles in pre-covid time). Statistical Analysis: Statistical analysis was performed in SPSS (v25.0) and included Mann-Whitney U, Fisher's exact and Pearson Chi-square as appropriate. Values of P < 0.05 were considered statistically significant. Results: A total of 367 in vitro fertilisation (IVF) stimulations were initiated. A total of 342 retrievals and 606 ETs (171 fresh and 435 frozen) were completed during the study period with a COVID positivity rate of 6.8% (25/367) amongst fresh and 3.9% (18/453) amongst frozen ETs, respectively; the PR and IR in the study group was similar to the control group (47.6 vs. 55.1 P = 0.4 and 68.7 vs. 66.4; P = 0.52, respectively). The maternal complication rates were similar in both groups with a COVID positivity rate of 10.2% (23/225) and 1 maternal death in the study group. The live birth rates were similar. Conclusions: We did not find a noteworthy difference in the clinical and embryological outcomes in the IVF cycles conducted in the COVID era as compared to the pre-COVID time. Thus, with adequate precautions and safety measures, ART services conducted during the COVID pandemic have comparable birth outcomes and can be safely advocated.
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Selecting euploid embryos for transfer by preimplantation genetic testing with the help of next-generation sequencing in poor prognosis patients: A retrospective cohort analysis p. 157
Pooja Nadkarni Singh, Akanksha Mahajan Pathak, Prabhakar Singh, Meha Desai
Background: The current embryo selection methods rely on subjective grading of embryo morphology or a real-time monitoring of the embryonic development and assessment of multiple quantitative endpoints. Even up to 40% of morphologically normal embryos harbour aneuploidies. Preimplantation genetic testing (PGT) is a technology, which gives opportunity to identify euploid embryos before implantation. Aims: This study seeks to determine the role of PGT in poor prognosis patients, i.e., patients with advanced maternal age (AMA) (maternal age ≥35 years), recurrent pregnancy loss (RPL) (miscarriages ≥2) and recurrent implantation failures (RIFs) (in vitro fertilisation failures ≥3). Setting and Design: A retrospective case–control study was done on a group of patients who underwent intracytoplasmic sperm injection for the indications of AMA, RPL and RIF. Materials and Methods: In 33 cases who opted for PGT, day 5 blastocysts were subjected to trophectoderm biopsy with the help of next-generation sequencing. Euploid blastocyst was transferred in hormone replacement cycle at a later date. In 154 controls, blastocyst transfer was done based on morphological grading. Pregnancy outcomes are compared in terms of implantation rate, pregnancy rate, miscarriage rate and multiple pregnancy rate. Statistical Analysis Used: Chi-square test was used for comparisons between the study groups with respect to percentage. P < 0.05 was considered statistically significant. Results: The highest aneuploidy rate was found in embryos with AMA. Implantation rate was found to be statistically significantly higher in the PGT group as compared to the non-PGT group. However, take-home baby rates were not improved by PGT. There were less number of mean embryos transferred in the PGT group and lower multiple pregnancy rate. Conclusions: With the application of PGT, embryo selection rates and implantation rates improved in poor prognosis patients.
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Relationship between maternal serum thyroid-stimulating hormone and in vitro fertilisation-conceived pregnancy outcomes p. 163
Ayla Coussa, Thomas M Barber, Zakwan Khrait, Samer Cheaib, Hayder A Hasan
Background: Thyroid dysfunction impairs female fertility and pregnancy outcome. Optimal preconception and gestational TSH level is still debatable in IVF-conceived pregnancies. Aims: To explore the relationships of IVF success and pregnancy outcomes with maternal serum levels of TSH (at both preconception and 12-week IVF-conceived pregnancy). Also, to confirm or refute the recommended TSH level ≤2.5μIU/mL. Setting and Design: Retrospective cohort. Material and Methods: 158 IVF-conceived pregnant women and 117 age-matched controls non-pregnant (≤39years, BMI 18.5-38kg/m2) were recruited. Preconception and 12-week IVF-conceived pregnancy serum samples were analysed for reproductive hormones, fasting glucose, insulin and TSH levels. Data of pregnant women at 28 weeks for GDM screening (75-gram OGTT) and up until delivery were included. Statistical Analysis: Binary logistic regression used to predict association between preconception TSH levels and IVF success, and pregnancy outcomes. Association of delta change of hormones was determined with linear regression. Significance level P≤0.05 with 95% confidence interval (CI). Results: Overall, median (IQR) age was 32(6)years, BMI 25.4(6.9)kg/m2, HbA1c 5.2(0.52)% and TSH 1.82(1.4)μIU/mL. There was no significant association between preconception TSH level and IVF success rate. During the first trimester of IVF-conceived pregnancy, delta change in TSH level was associated with that of progesterone (P=0.03). 12-week gestation TSH level did not predict adverse pregnancy outcomes (i.e. onset of GDM, delivery type and premature delivery); but a higher TSH level predicted earlier delivery in weeks. There was a higher risk of delivery by caesarean section when TSH>2.5μIU/mL. Conclusion: Variation of maternal TSH within normal range (0.4-4.0μIU/mL) at preconception and 12-week gestation has no predictive effect on IVF success and pregnancy outcomes in IVF-pregnancy. Our data provide no support for a recommended preconception TSH level ≤2.5μIU/mL in IVF-conceived pregnancy, but rather promote a preconception TSH level within normal range.
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The use of integrative medical services to address psychological concerns around infertility in an Indian academic medical centre p. 171
Hita Nayak, Brigitte Gerstl, Neha Sharma, Lohith Chengappa Appaneravanda, Devika Gunasheela
Background Alternative and complementary therapies have been gaining popularity as ways to reduce anxiety in patients. Aim: This study aimed to assess whether yoga and meditation could decrease the severity of anxiety in Indian women diagnosed with infertility Study. Setting and Design: This was a retrospective data analysis of anxiety score of 354 women undergoing treatment at a tertiary infertility hospital between January 2016 and December 2018. Materials and Method: Women participated in group yoga, meditation and counselling therapy intervention during their treatment period. A self-reported questionnaire that used the Generalised Anxiety Disorder-7 criteria measured the participants' severity of anxiety at the start of and again at the end of the intervention. Statistical Analysis Used: Demographic analysis and a two-tailed paired t-test were applied between groups. Results: The results indicated that there was a statistically significant mean reduction (7.3 ± 2.7) in the anxiety scores of the participants between entry (12.94 ± 2.65) and following exposure (5.39 ± 1.99) to the intervention (P < 0.0001). The mean reduction in scores remained similar between participants who received ≤6 sessions (7.50 ± 2.68) and participants who received >6 sessions (7.10 ± 2.64) (P > 0.05). Among the participants that experienced mild anxiety at baseline (n = 43), 72.1% (n = 31) reported experiencing minimal anxiety following the intervention (P < 0.0001). Among those that experienced moderate anxiety at baseline (n = 213), 32.4% (n = 69) reported experiencing minimal anxiety post-intervention (P < 0.0001). Participants who expressed severe anxiety at baseline (n = 94, 26.6%), reported experiencing minimal anxiety (13.8% [n = 13)], mild anxiety (81.9% [n = 77]) and moderate anxiety (4.3% [n = 4]) after exposure to the intervention (P < 0.0001). None of the participants reported experiencing severe anxiety post-intervention. Conclusion: The benefits of alternative anxiety-reduction therapies for women diagnosed with infertility have been demonstrated in this study. These therapies can be used to complement the routine treatment of such patients.
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Re-examining psychometric properties of fertility problem inventory: A clinic-based study from India p. 177
Ansha Patel, Binu Valsalakumari Sreekumaran Nair, Sumit Kumar Das, Pratap Kumar, Podila Satya Venkata Narasimha Sharma
Background: The fertility problem inventory (FPI) is one of the most widely used measures that tap the diverse psychological problems faced by infertile couples. Research on translated versions of FPI has also reflected its high clinical significance. Aim: This research aimed to explore the psychometric properties and the clinical validity of the original 46-item FPI in an Indian sample. Setting and Design: This cross-sectional study was conducted in a tertiary hospital setup of a medical college. Materials and Methods: The original FPI was translated and pilot tested. The translated FPI was taken by 205 consenting infertile patients (113 women and 92 men). The psychometric properties of FPI were thus explored. Statistical Analysis Used: Exploratory factor analysis with minimum residual method of extraction followed by oblimin rotation was performed. Perceived Stress Scale was used to establish the convergent validity of the newly developed FPI-Kannada version (FPI-K). A cut-off score for the FPI-K was obtained separately for males and females using ROC analysis in which hamilton anxiety scale was used as the gold standard. Results: Only 32 items of the original FPI had factor loadings above 0.3 and overall six factors explained these items with a cumulative percentage variation of 32%. Overall Cronbach's alpha for FPI-K was 0.671 and it had a good convergent validity. Conclusions: The new FPI-K had 6 sub-domains and the clinical utility of same is discussed.
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Cytogenetic studies in primary amenorrhoea cases p. 187
Elham Ghadirkhomi, Akram Ghdirkhomi, Seyed Abdolhamid Angaji
Background: Amenorrhoea is considered a kind of menstrual disorder in a woman of reproductive age. It is a symptom with many potential causes such as an abnormality in the hypothalamic–pituitary–ovarian axis, anatomical abnormalities of the genital tract or functional causes. Aims: In this study, we aimed to investigate chromosomal abnormalities in patients presenting with primary amenorrhoea. Setting and Design: This study was conducted in the medical genetic laboratory. Materials and Methods: Chromosomal analysis was carried out in 134 cases that were referred to the human genetic laboratory from 2010 to 2017, employing (GTG) Giemsa banding. Statistical Analysis Used: Statistical analyses were carried out by Microsoft Office Excel (2019). Results: The karyotype results revealed 77.6% (n = 104) with normal chromosome composition while 22.38% (n = 30) showed chromosomal abnormalities. Among the patients with abnormal chromosome constituents, 53.54% exhibited numerical aberration and 46.66% showed structural abnormalities. Conclusion: The present study has emphasised that karyotyping is one of the fundamental investigations in the evaluation of primary amenorrhoea.
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MTR, MTRR and CBS gene polymorphisms in recurrent miscarriages: A case control study from North India p. 191
Seerat Talwar, Sweta Prasad, Lovejeet Kaur, Jyoti Mishra, Manju Puri, Mohinder Pal Sachdeva, Kallur Nava Saraswathy
Context: According to various epidemiological studies, the aetiology of recurrent miscarriages (RMs) is multifactorial. The goal of this study is to learn more about the link between genetic polymorphisms and RM. Aim: To evaluate the association of 5-Methytetrahydrofolate-Homocysteine Methyltransferase (MTR) A2756G, 5-Methytetrahydrofolate-Homocysteine Methyltransferase Reductase (MTRR) A66G and cystathionine beta-synthase (CBS) 844INS68 genetic polymorphisms with RM and also to understand the combined effect of the selected genotypes. Setting and Design: This was a hospital-based, case–control, observational study. Materials and Methods: A total of 516 participants were recruited in the present study, of which 200 RM cases and 258 controls were included in the present study. Fasting blood sample (~5ml) was drawn from all the participants and were screened for genetic polymorphisms of MTR A2756G, MTRR A66G and CBS 844INS68. Statistical Analysis Used: The frequency, odd's ratio and Hardy-Weinberg equilibrium were evaluated. SPSS (version 21.0) was used for the data analysis. Results: MTR A2756G genetic polymorphism was not associated with the risk of RM. The ancestral allele of MTRR A66G and the mutant allele of CBS 844INS68 was causing an increased risk of more than two folds for RM. CBS 844INS68 in combination with MTR A2756G was found to pose an increased risk of more than two folds for RM. Conclusion: Genetic polymorphisms particularly MTRR A66G and CBS 844INS68 seems to be elevating the risk and hence making women susceptible for RM.
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Crossing the hurdle of a low oocyte yield in an in vitro fertilization cycle to obtain mature oocytes p. 197
Pratap Kumar, Shubha Rao, Anjali Mundkur, Prashanth Adiga, Rashmi K Ullagaddi, Vidyashree G Poojari
The complex process of oocyte maturation involves a coordinated set of events to take place so that an adequate number of oocytes can be obtained during an oocyte pickup procedure following controlled ovarian stimulation. A weak link in any of the steps can yield a sparse number of oocytes which can be a setback in the process.
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Random start ovarian stimulation p. 200
Pratap Kumar, Shubha Rao, Anjali Mundkur, Prashanth Adiga, Vidyashree G Poojari, Rashmi K Ullagaddi
Fertility preservation is emerging in recent years as an important option for various indications many of which being for cancer patients and for certain benign conditions as well. In the present case report, we set out to utilise the same protocol, however, for different indications.
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