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   Table of Contents - Current issue
January-June 2021
Volume 8 | Issue 1
Page Nos. 1-102

Online since Wednesday, June 30, 2021

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Editors view point p. 1
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Coming out of deadly second wave − what next for fertility? p. 2
Abha Maheshwari
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IFS recommendations for COVID-19 Vaccination COVID-19 before ART p. 4
Sonia Malik, Kuldeep Jain, KU Kunjumoideen, AK Pandey, Charu Jandial, Sumita Aggarwal, Sudha Prasad, Neena Malhotra
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Hypogonadotropic hypogonadism and assisted reproductive techniques: a review p. 12
Garima Kapoor, Bindu Bajaj
Backgroud: Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder that manifests as absent or delayed pubertal development and infertility due to defective secretion or action of gonadotropin-releasing hormone (GnRH). The incidence is 1 in 10,000 in men and 1 in 50,000 in women. Materials and Methods: An online search was made on Google scholar and PubMed with search words hypogonadotropic hypogonadism (HHG), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), intrauterine insemination, male, and female, and the retrospective/prospective studies that met the inclusion criteria were selected. Inclusion criteria: The studies included were retrospective and researched the effect of assisted reproductive techniques (ART) on women with CHH. The studies were included if they had any one of the following primary outcomes: fertilization rate (FR), implantation rate (IR), clinical pregnancy rate (PR) per cycle/embryo transfer (ET), and live birth rate (LBR). Exclusion criteria: (1) Review articles, (2) case reports, (3) duplication of studies, and (4) studies with no available endpoints. Secondary outcomes were any of the following: abortion rate, multiple gestations, ovarian hyperstimulation syndrome, and any adverse effect. The studies were reviewed for the demographic profile of the patients, drugs, and their doses used for stimulation protocol, fresh/ frozen sample used, ART procedure, number of metaphase II (M II) oocytes retrieved, FR, IR, clinical PR, and adverse outcomes. Results: Seven studies have shown a statistically significant increased requirement of dose and duration of gonadotropins in women with CHH while reporting a comparable metaphase II (M II) oocyte recovery rate, FR, PR, IR, and LBR, when compared with controls. Five studies were selected for male HHG with ART, varying from a sample size of 4 to 31. Inj human chorionic gonadotropin (HCG) and Inj human menopausal gonadotropin (HMG)/recombinant follicle-stimulating hormone (rFSH) was used to induce spermatogenesis for a period of 6 to 24 months. In men with azoospermia/unable to conceive after gonadotropin therapy, ICSI was performed. Testicular sperm extraction (TESE) was used for the extraction of sperm in azoospermic men. FR from 41.7% to 82%, CPR from 17.6% to 51.5%, and LBR from 20% to 41.3% have been reported. Conclusion: Controlled ovarian hyperstimulation (COH) with IVF/ICSI should be offered to those patients who fail to conceive naturally or with intrauterine insemination/gonadotropin therapy. Newer regimes of COH (HCG with HMG/FSH), vitrified-thawed ET for female HHG, and pretreatment with FSH followed by HCG and follitropins for induction of spermatogenesis in male HHG look promising and need to be researched further.
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Assisted reproductive technology and its Association with autism in children p. 20
Pinkee Saxena
The use of assisted reproductive technology for conception has slowly increased over time. There has been a concern about the risk of autism spectrum disorders in children conceived. The relationship between assisted reproductive technology and autism spectrum disorders is complex and results are conflicting. More robust studies are needed to arrive at a definitive conclusion.
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IUI: Optimizing results, minimizing complications p. 25
Pikee Saxena, Archana Mishra
Intrauterine insemination is a procedure in Assisted Reproductive Techniques (ART) where processed and concentrated motile sperms are placed directly into the uterine cavity. Although NICE [2013] recommends In Vitro Fertilisation over intrauterine insemination after 2 years of unprotected intercourse, Intrauterine Insemination (IUI) appears to be a low cost and effective option before proceeding for In Vitro Fertilisation (IVF). Minimal requirement for IUI is patency of at least one fallopian tube. Adequate number of motile sperms should be present in pre wash specimen of semen. At total sperm count 3–5 million, pregnancy rate is less than 1% per cycle. In unexplained infertility there may be undetected subtle functional defects in follicular development, maturation and ovulation like luteinised unruptured follicle, luteal phase defect. Ovarian stimulation increases the number of dominant follicles and improves their quality resulting in improvement in pregnancy rate. Single IUI has benefits of fewer visits, less cost and stress. Evidence suggests no difference in clinical pregnancy rate between single versus double IUI. WHO recommends ejaculatory abstinence of 2–7 days before semen collection (WHO, 2010), for diagnostics and semen preparation. Shorter time interval between processing and insemination leads to less sperm chromatin decondensation & sperm DNA fragmentation and higher Pregnancy Rate. The luteinizing hormone surge can be detected almost 36 hours before ovulation in serum and 24 hours before ovulation in urine. The optimal time interval between human chorionic gonadotropin (hCG) injection and IUI seems to be between 12 and 36 hours; 24 hours after leutinising hormone (LH) Surge. Nature of sperms is the best guide for choice of technique. “Swim up” techniques are recommended in cases of normozoospermia and “Density Gradient” should be chosen in cases of any pathology of semen. The pregnancy rate per cycle is highest in the first three treatment cycles. Most couples show acceptable cumulative ongoing pregnancy rates after six cycles of IUI with ovulation induction. In vitro fertilization should be considered after 3–6 cycles taking all factors into consideration.
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Platelet-rich plasma in female infertility: A comprehensive review of current literature p. 30
Pandey Divya
Platelet-rich plasma (PRP) is a novel approach in regenerative medicine. Being autologous, it is free from immunogenic reaction, cross-infection, easy to prepare, and easily accessible to physicians as well as patients. It has a rich milieu of multiple growth factors and bioactive molecules with capacity of regenerating tissues. Though there exist multiple protocols for PRP preparation, the common principle remains achievement of enriched plasma with platelet concentration approximately 4 to 5 times more than the circulating blood. Autologous PRP has found its potential application in different medical specialties including reproductive medicine. This study will review the current literature on potential PRP application in female infertility.
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Oocyte recovery rates in flushing versus nonflushing during oocyte retrieval in assisted reproductive techniques p. 36
Gittika Sharma, Abha Majumdar, Shweta Mittal Gupta
Follicular aspiration under transvaginal ultrasound guidance is performed as part of assisted reproductive technology (ART) to retrieve oocytes for in vitro fertilization (IVF). However, controversy as to whether follicular flushing following aspiration yields a larger number of oocytes than aspiration only is ongoing. The aim of this study was to assess the safety and efficacy (oocyte recovery rates) of follicular flushing when compared with aspiration only performed in women undergoing ART. The study was conducted at Sir Gangaram Hospital, New Delhi. Retrospective data of 100 females undergoing ART was taken from September 2019 to September 2020. Patients were divided into two groups of 50 each. In first group, patients underwent oocyte retrieval using double lumen needle (flushing technique) and in the second group, single lumen needle (no flushing) were used. Females with age ≤37 years who were having ≤9 follicles, size ≥14 mm during oocyte retrieval when undergoing ARTs. Categorical variables were presented in number and percentage (%) and continuous variables, as mean ± standard deviation and median. Normality of data was tested by Kolmogorov–Smirnov test. If the normality was rejected, then nonparametric test was used. Quantitative variables were compared using Mann–Whitney test. Follicular flushing had significantly better oocyte recovery rates when compared with no flushing (P < 0.05). There was no significant difference (P > 0.05) in M2 rates in patients undergoing intracytoplasmic sperm injection (ICSI) when compared in both the groups. There was no significant difference (P > 0.05) in fertilization rates in patients undergoing IVF and ICSI, respectively, in both the groups. Double lumen needle with flushing technique gives better oocyte recovery rates in low responder women undergoing ARTs. Hence, follicular flushing may be considered in such patients for oocyte retrieval.
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Comparison of clinical outcomes of “single blastocyst” versus “double blastocyst” transfer in assisted reproductive technology p. 40
Kavisha Lambhate, Jayesh Amin
The transfer of multiple embryos after in vitro fertilization (IVF) increases the risk of twins and higher order births. Multiple births are associated with significant health risks and maternal and neonatal complications, as well as physical, emotional, and financial stresses that can strain families and increase the incidence of depression and anxiety disorders in parents. Elective single-embryo transfer (eSET) is among the most effective methods to reduce the risk of multiple births with IVF. Many patients and clinicians have been reluctant to adopt eSET due to studies reporting higher live-birth rates with the transfer of two or more embryos rather than eSET. The aim of the study was to determine whether elective single blastocyst transfer compromises pregnancy outcomes compared to double blastocyst transfer. The study is prospective observational study which included 25 patients with single blastocyst transfer (group 1) and 27 patients with double blastocyst transfer (group 2) as per the inclusion criteria. Controlled ovarian stimulation (COS) with gonadotropin-releasing hormone antagonist protocol was carried out. The treatment outcomes were compared between the two groups. Data described as mean ± standard deviation or percentages. The statistical analysis was performed using Student t test, the Chi-squared test, and linear regression models. A P-value of <0.05 is considered statistically significant. Statistical analysis was performed with the Statistical Package for Social Sciences (SPSS version 24.0). Statistical analysis showed that the clinical pregnancy rate in the single blastocyst group was 56%, whereas in the double blastocyst group, it was 62.0%. The proportional comparison among the two groups was not found to be statistically significant (P = 0.319), but the multiple pregnancy rate was observed to be 70% in double blastocyst group, whereas in single blastocyst group, it was 0%, which was found to be statistically significant (P = 0.0001). eSET should be encouraged to decrease incidence of multiple pregnancies and associated complications.
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Comparison of physiological-ICSI (PICSI) with ICSI in cases of moderate to severe oligoasthenoteratozoospermia (OAT) − a randomized control study p. 44
Suman Mishra, Bharti Jain, Shyam Shankar
Objective: To compare the efficiency of physiological intracytoplasmic sperm injection (PICSI) over intracytoplasmic sperm injection (ICSI) in Oligoasthenoteratozoospermic patients. Design: Randomized control study. Setting: KJIVF and laparoscopy center Delhi. Methods: From September 2019 to May 2020, 45 patients of male factor felled under our criteria of OAT were divided into two groups of PICSI and ICSI. Sperm selection was performed under high magnification in both the groups and results were compared. Outcome measure: Primary outcome: Fertilization rate, cleavage rate, blastulation, and utility rate; Secondary outcome: Clinical pregnancy rates and miscarriage rates. Results: 20 PICSI and 25 ICSI treatments were performed and observed that the rate of blastulation and embryo utility shows significant difference in PICSI group (P = 0.013). The pregnancy percentage was also better in PICSI but implantation, fertilization, cleavage; clinical pregnancy rates were clinically comparable in both the groups but not statistically significant. Conclusion: The outcomes of our study are independent of male factor and it only depends on intervention whether it was PICSI or ICSI. The blastulation rate and embryo utility shows statistically significant difference between PICSI and ICSI groups. Hence, we are slowly progressing toward the superiority of PICSI over ICSI but enough evidences are still not available.
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Assessment of oxidative stress in follicular fluid of infertile women undergoing IVF procedure p. 52
Shreya Nautiyal, Geeta Goswami, M. Gouri Devi
Oxidative stress (OS) plays an important role in biological processes of reproduction, and yet there is no accurate indicator to measure it. The objective of the study was to correlate the effect of ROS (reactive oxygen species) on embryo quality and pregnancy outcome. This was achieved by measuring levels of ROS present in granulosa cells and follicular fluid (FF) of women undergoing IVF (in vitro fertilization). ROS in FF is measured using thiobarbituric acid reactive substances assay kit (Abcam) and granulosa cells were measured with the help of flow cytometry. The results showed that high levels of FF malondialdehyde were found in nonpregnant women as compared to pregnant group and were found to be significant (P < 0.0001) and ROS in granulosa cells showed the same trend but was found to be statistically nonsignificant (P = 0.1658). It was also seen that the number of metaphase II oocytes were affected neither by ROS in granulosa cells nor in FF (P > 0.05) but had an impact on the quality of embryos (P < 0.05). Hence, we can conclude that OS is a real threat to embryos especially in vitro and it has a negative impact on IVF outcomes. Imbalance in ROS can lead to poor fertilization rate, implantation, and pregnancy outcomes and ROS levels in FF and granulosa cells can be taken as a potential marker to detect IVF treatment outcomes.
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Pregnancy outcome after endometrial scratching in intrauterine insemination: A randomized controlled trial p. 58
Priyanka Singh, Shaheen Anjum
Objective: To study the effect of local endometrial scratching on the outcomes of intrauterine insemination cycle. Design: Randomized controlled trial. Study setting: Department of Obstetrics & Gynecology, JN Medical College, Aligarh Muslim University, Aligarh. Materials and methods: A total of 77 patients were enrolled in the study. Patients undergoing controlled ovarian stimulation with intrauterine insemination were randomly allocated in two groups. In group A (n = 31), endometrial scratching was carried out on D8/D9 of same menstrual cycle in which intrauterine uterine insemination (IUI) was performed and in group B (control group; n = 31), endometrial scratching was not performed. Primary outcome was measured by pregnancy rate, while secondary outcome was measured by endometrial indices. Results: Pregnancy rate was 16.2% in group A in which endometrial scratching was carried out in IUI cycle, whereas in group B, pregnancy rate was 9.6%. Although in group A, pregnancy rate was higher when compared with group B, the results were not statistically significant (P > 0.05). The mean endometrial thickness of women in group A was 9.329 ± 0.934 which was significantly higher than endometrial thickness of group B, that is, 7.72 ± 2.0. In group A, greater number of women (41.93%, n = 13) had zone 3 endometrial flow than group B (19.35%, n = 6). However, the difference was not statistically significant (P > 0.05). Conclusion: Endometrial scratching in follicular phase in the same cycle of stimulation with IUI gives better pregnancy rate in comparison with IUI without endometrial scratching. However, the results can be of proven clinical significance only if larger group of population is studied.
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The predictive value of endometrial thickness for assessing neonatal birth weight in ART p. 64
Harpreet Kaur, Sudha Prasad
Background: Neonatal birth weight is lower after assisted reproductive technology (ART) conception compared with natural conception. The aim of this retrospective study was to evaluate the predictive potential of measuring maternal endometrial thickness (ET) in women undergoing ART for assessing neonatal birth weight. Methods: and Results</ST> The patients (n = 100) were screened for meeting inclusion criteria with primary or secondary infertility and who underwent In-vitro Fertilization/Intracytoplasmic sperm injection (IVF/ICSI) or frozen embryo transfer (FET) cycles were enrolled in the study. All women received the antagonist protocol with recombinant gonadotropins/urinary gonadotropins or human menopausal gonadotropin as a stimulation protocol. Only singleton pregnancies were used in neonatal birth weight (n = 70) measurements. Retrospective data were collected for age, body mass index (BMI), and ET done by two-dimensional ultrasound that had successful pregnancy. The antenatal details, birth weight/gender of neonates were noted. A univariate regression analysis was performed between ET and neonatal birth weight in patients with live births (n = 70) to evaluate association between these parameters. The data were adjusted for variables such as age, BMI, and gestational duration. There was significant association of ET with neonatal birth weight and ET was observed to be a significant independent predictor for neonatal birth weight (slope 0.168, P = 0.0052). Conclusion: The present study suggests that ET measurement at the time of human chorionic gonadotropin (hCG) trigger in Indian women undergoing ART cycles can be a reliable independent predictor for assessing neonatal birth weight
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Cumulative live-birth rate per ovum pickup in patients with different causes of infertility undergoing in vitro fertilization and embryo transfer: A retrospective study p. 69
Aditi Kanwatia, U.N. Jindal, Sanjeev Kumar, Anupam Gupta
Aims: To evaluate whether the various causes of infertility have an impact on cumulative clinical pregnancy rate (CCPR) and cumulative live-birth rate (CLBR) following first ovum pickup. Settings and Design: A retrospective cohort study between January, 2015 and December, 2018 at the tertiary assisted reproductive technology (ART) Centre in northern India (Jindal IVF and Sant Memorial Hospital, Chandigarh). Materials and Methods: A total of 788 patients who underwent first oocyte retrieval during the study period were included based on selection criteria. All patients were divided into various diagnostic categories. All ovum pickup along with subsequent fresh- and frozen-embryo transfer attempts (maximum three) till: a) attained a clinical pregnancy; b) attained a live birth; or c) all the embryos were transferred. The data were analyzed using SPSS-22. The descriptive and comparative analysis was performed using one-way analysis of variance. Results: The overall CCPR and CLBR were 54.82% and 50.63%, respectively. The live-birth rates were lowest in patients with the diagnosis of poor responders (25%) and those with genital tuberculosis (37.78%) and highest in those patients with endometriosis (64.10%) and male factor infertility (64.71%).
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Impact of color Doppler assessment and interventions on the outcome of frozen-embryo transfer in infertile women p. 74
Geetanjali Setia, Sonia Malik
Context: A good blood supply is essential for endometrial receptivity which in turn impacts the outcome of frozen-embryo transfers (FETs) in infertile women. With the advent of Doppler ultrasound, studying endometrial blood flow has emerged as an important means of evaluating endometrial receptivity. Aim: This study was undertaken to assess the usefulness of color Doppler as a marker of predictor of outcome in FET cycles. Settings and Design: This was a retrospective study conducted at the Southend Fertility and IVF Centre on all women who underwent FET cycle as part of the infertility management at the center. Materials and Methods: A total of 400 women were recruited in the study with 200 in case group (Group A) and 200 in control group (Group B). Statistical analysis: Statistical analysis was carried out using data analysis software system, SPSS V27 and Microsoft excel. Results: In Group A, 70 (35%) women became pregnant and 130 (65%) did not conceive. On the other hand, in Group B, 55 (28%) women became pregnant, and 145 (72%) did not conceive. Conclusion: Endometrial and subendometrial vascularity as measured by color Doppler is a useful predictor for pregnancy in FET cycles. However, there is still no larger consensus as to whether measurement of endometrial and subendometrial blood flow using color Doppler is useful and whether it plays any role in predicting of the pregnancy cycle outcome. Further large randomized trials are required to reach to definite conclusion on this topic.
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A prospective randomized comparative study between transdermal estradiol gel and oral estradiol valerate tablets for successful clinical outcome in frozen-thawed embryo transfer cycles p. 83
Jaya Kumari, Kanad D Nayar, Shweta Gupta, Sabina Sanan, Preeti Mehra
Background: The aim of this study was to evaluate the use of transdermal estradiol gel and compare it with oral estradiol valerate tablets for the preparation of endometrium in frozen-thawed embryo transfer (FET) cycles. Methods: This prospective trial included 100 women undergoing FET cycles during study period and they were randomized into one of the two groups. Group 1 (n = 50) received oral estradiol valerate tablet and group 2 (n = 50) received transdermal estradiol gel from day 2 of menstrual cycle and endometrial thickness monitored with transvaginal ultrasonography. Primary outcome of this study was to compare clinical pregnancy rate (CPR) between the two groups. Secondary outcomes were implantation rates (IRs), CPRs, miscarriage rates (MRs), endometrial thickness at the start of progesterone, cycle cancellation rates, undesirable side effects, and patient satisfaction score. Statistical testing was performed with SPSS 17.0. Results: There was no clinically significant difference in biochemical pregnancy rate, CPR, IR, and MR between the two groups. Endometrial thickness on day of progesterone start was higher in group 2 as opposed to group 1 (9.81 ± 0.861 vs. 9.46 ± 0.830; P-value = 0.043) which was clinically significant. Almost 37.5% patients (n = 18) in group 1 had mild adverse effects when compared with only 12.76% (n=6) in gel group (group 2). Conclusion: We conclude that transdermal estradiol gel is equally efficacious as oral estrogen in hormone replacement FET cycles but with added advantage of better patient comfort and lesser side effects with transdermal gel.
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Effect of age on semen parameters p. 92
Kavitha Bacchu, MIrudhubashini Govindarajan, Madhumitha Balasundaram, Ramya Jayaram, Tara Mahendran
Aim: This study was designed to evaluate the effect of age on various semen parameters. Settings: Womens Center and Hospitals Pvt. Limited, Coimbatore. Design: Observational cross-sectional study was conducted from October 2020 to March 2021. Study subjects: Male partners of 366 infertile couples attending the infertility clinic at Womens Center, Coimbatore. Materials and methods: Semen samples collected by masturbation were evaluated for parameters such as volume, sperm concentration, motility, and morphology as per the standard World Health Organization 2010 (5th edition) guidelines. Outcome measures: Comparison of volume, concentration, normal morphology, and motility in different age groups: <30, 30–35, 36–40, and >40 years. Results: No significant association of volume, concentration, and normal morphology with age was observed. However, there was a significant decline in motility with age. Conclusion: In the present study, motility was the only semen parameter that had a significant negative association, whereas all the other parameters did not exhibit any change with advancing age.
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Acute abdomen in ART pregnancy p. 98
Papa Dasari, Mongolngnbi Sairem Chanu, S. Niranjana
Acute abdomen during late pregnancy is a rare event. A 35-year-old second gravida with a history of previous early pregnancy loss, and two in vitro fertilization failures was hospitalized following the development of hypertension at 25 weeks and 6 days of pregnancy. She conceived under donar oocyte program because of low ovarian reserve due to stage IV endometriosis. She was type II diabetes mellitus and her blood sugars were controlled with Metformin and Insulin. At 32 weeks and 4 days of gestation, she had sudden onset pain abdomen and developed eclampsia. Preterm labor and placental abruption were suspected but there were no findings suggestive of abruption on ultrasonography. She had persistent diffuse pain abdomen and developed tachycardia and worsening pallor over 4 hours for which laparotomy was performed. At laparotomy, there was 1.5 L of hemoperitoneum due to ruptured endometriotic cyst which was adherent at fundus of uterus. Alive male baby 1.9 kg was delivered and partial cystectomy was undertaken. Both mother and baby were discharged after 14 days. Endometriosis though believed to regress during pregnancy, it can rupture during pregnancy and result in life-threatening situation.
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