Miscarriage word seems to signify that only women are involved. However miscarriage may be the result of a faulty gamete −male or female. Karyotyping should be carried out if there are two or more miscarriages. In vitro fertilization and preimplantation genetic screening may be carried out in these cases. Prenatal diagnosis has a place in recurrent pregnancy losses (RPL) and should be performed when a translocation or other abnormalities are detected. Men should be given therapy in the form of antioxidants and lifestyle changes that improve overall health and sperm function. In case of obese, men they should loose weight. Regular exercise is important. Diet should be rich in fresh fruits and vegetables. They should limit alcohol and quit smoking. Regular vitamins should be taken. Male factor could be an important cause of embryonic mortality and RPL and should be addressed in all these cases. Hence, more in depth knowledge of epigenetics and genetics is required. As sperm aneuploidy and DNA fragmentation have been shown to be responsible in some cases, it is imperative to have reliable tests for diagnosis of sperm aneuploidy and DNA fragmentation.

Infertility, defined as inability of a couple to conceive after a year of unprotected regular intercourse, with third of cases due to suboptimal sperm quality. There are modifiable and nonmodifiable risk factors that can affect the quality and quantity of sperm and hence fertility. Several separate systematic reviews exist on this topic and clinicians are often faced with a plethora of reviews with variable quality giving conflicting advice. Therefore, we summarized the current available data by conducting a systematic review of systematic reviews on risk factors such as coffee/caffeine, body mass index (BMI)/obesity, cigarette smoking, and paternal age, on sperm parameters of count, motility, and morphology so that all evidences are present together, at one place. Embase, OVID MEDLINE(R), and Cochrane central database of systematic review were searched for relevant publications between 2010 and present. Search terms were: smoking, obesity, obese, BMI, caffeine, paternal age, advanced paternal age, male infertility, male fertility, sperm motility, sperm quality, and sperm analysis. Systematic reviews that met the criteria were retrieved and the relative reference lists were searched. All included studies were quality assessed using the AMSTAR checklist tool. Electronic and manual hand search yielded a total of 318 studies, of which 11 were excluded after removing duplicates and a further 286 excluded based on titles and abstract. Full-text screening of 21 articles, excluded 10 further studies. Eleven publications were finally included. Obesity and smoking were associated with decline in sperm count and morphology, age with decline in motility and morphology. Caffeine consumption was not associated with changes in any of the three parameters. Obesity and smoking are modifiable risk factors impacting on the semen parameters; caffeine consumption may not have any adverse effects on sperm parameters. This overview was limited by the quality of included reviews which in turn were limited by observational nature of the included studies, small numbers, and heterogeneity of the population. Further prospective data collection is needed to have good quality evidence. In conclusion, high BMI, smoking, and advanced paternal age were found to be associated with decline in one or more parameters of semen quality in males, albeit the evidence is of varying strength. Caffeine was not associated with any deterioration.

To improve the clinical pregnancy rate, the in vitro fertilization clinics worldwide have ignored the “ethical and cardinal” restrain by offering scientifically unproven safe treatments for their patients and possibly compromising the unborn child’s health. Human fertilization and embryology authority requires all their licensed clinics to take into account the welfare of the unborn child and guides clinics and patients. They have instituted a traffic light monitoring system for various intermediary steps currently offered by the clinics. This review discusses the value of the scientific evidence available against the safety of the patients and the unborn child against the extra cost implications for utilizing these intermediary steps. Those in the red category should not be used as there is insufficient good-quality evidence for these steps. Those in the yellow, while having good quality evidence, require additional evidence before they are considered safe. The steps in the green category only have proven their safety by establishing good quality evidence. The intermediary steps discussed include: oocyte activation, use of time-lapse systems, need for hatching, use of hyaluronic acid, routine assessment of sperm DNA fragmentation, and use of advanced sperm selection techniques. The author offers his interpretation of the evidence and concludes by questioning the acceptability of using these intermediary steps routinely.

Objective: The present study compared the reproductive outcomes (implantation rate, pregnancy rate) between day 3 and day 5 transfers in two different age groups of patients (aged <36 years vs. aged ≥36 years). Materials and methods: The present study was conducted in the RIDGE IVF Centre, Gouri Hospital, New Delhi (India), after obtaining institutional ethical committee clearance. For frozen embryo transfers (FETs), day 3 embryos were thawed using Origio vitrification warming kit. The outcome parameters [anti mullerian hormone (AMH), antral follicle count (AFC), follicle-stimulating hormone, E2, mean number of oocytes retrieved, embryo grades A, B, and C, beta human chorionic gonadotropin (HCG), number of sacs, miscarriages, and live birth rate] were compared between age <36 versus >36 years, day 3 versus day 5 embryo, and fresh versus frozen embryo. The unpaired t test was used for comparing quantitative variables and Chi-squared test was used for comparing qualitative variables. Results: The mean age of the study population was 31.84 ± 3.74 years. The mean AMH, AFC, and oocytes retrieved were significantly more among <36 years compared to ≥36 years age group. Beta HCG and number of sacs did not differ between <36 years and ≥36 years age groups. The number of sacs formed and live birth were significantly more among frozen embryo. Day 5 embryo had significantly more positive rate of beta HCG, more number of sac formations, and live birth. Conclusion: The present study dictates that in vitro fertilization rate showed better success with women <36 years of age than >36 years old. Day 5 blastocysts had good implantation rates along with higher resulting pregnancy rates. The FET had better live birth rate.

The objective of the study was to evaluate the impact of modified intracytoplasmic sperm injection (ICSI) technique on in vitro fertilization outcomes. The study was conducted in a tertiary infertility center, New Delhi. In this retrospective cohort study, we retrospectively analyzed 247 ICSI cycles. Different inclusion and exclusion criteria were applied to remove the biasness of study. The 247 ICSI cycles were divided into two groups. Group A (n = 152) in which the patient underwent through modified ICSI technique), Group B (n = 95) in which patient underwent conventional ICSI). Modified technique involves repeated in and out movements of the injection pipette to break the oolemma without applying negative pressure to reduce the detrimental effect on oocyte. Fertilization rate was found to be higher in modified ICSI group when compared with conventional ICSI (70% vs. 63%; P = 0.0006). The embryo utilization rate was found to be similar in both the groups (38.4% vs. 40.2%). The overall blastocyst utilization rate was also comparable between both the groups. The mechanical modification of not applying negative pressure during ICSI resulted in a significant increase in fertilization rate. A larger study is required to validate the technique in terms of other embryologic parameters.

Background: Vitrification is an ultra-rapid cryopreservation method in which cells are directly exposed to liquid nitrogen (LN₂). The warming protocol for vitrification is equally important as the freezing protocol because sperm damage can occur during the warming of sample as well. The warming rate is influenced by the warming medium (air, water) and temperature. A fast warming rate causes unbalanced glycerol efflux and water influx; however, a slow warming rate causes recrystallization of intracellular water microcrystals and leads to subcellular organelles damage. Aim: To determine the optimum devitrification temperature for vitrified human sperm by comparing prefreeze and postwarm motility parameters at different temperatures. Setting and Design: The prospective study was conducted on 100 patient semen samples. Materials and Methods: The semen sample was direct plunged into LN₂ and warmed at different temperatures, that is, at room temperature (RT), 37°C and 42°C for 5 minutes. Sperm parameters were evaluated by the computer-assisted semen analyzer system. Statistical analysis was carried out by applying one-way analysis of variance was carried out using SPSS-22. The level of significance was taken as P ≤ 0.05. Results: The statistical significant difference was found in the case of recovery of all semen parameters, that is, motility (P < 0.0001), progressive motility (P < 0.0001), cryosurvival factor (P < 0.0001), curvilinear velocity (P = 0.049), straight-line velocity (P = 0.033), average path velocity (P = 0.0001), and except count (P = 0.083) between the RT, 37°C, and at 42°C. The cryosurvival factor of vitrified semen sample at RT, 37°C, and at 42°C was found to be 25.63 ± 13.885, 29.97 ± 13.212, and 41.99 ± 12.630, respectively. Hence, at 42°C, it was found to be maximum. Conclusion: The cryopreservation of the semen leads to a detrimental effect on spermatozoa. The basal semen parameters such as sperm motility, progressive motility, cryosurvival factor, and velocity parameters were affected by devitrification temperature. There was significantly high-sperm cryosurvival after warming of semen samples at 42°C when compared with warming at 37°C and RT. But velocity parameters were found to be better at 37°C.

Aims and Objectives: To determine whether raised estradiol (E2) levels administered before progesterone supplementation in frozen-embryo transfer cycles have an impact on the rates of pregnancy. Materials and Methods: A retrospective study of 242 patients who had their frozen embryo replacement cycles conducted at Southend Fertility and IVF Centre between September 2014 and April 2017. In all these patients, a baseline pelvic scan was carried out and endometrial preparation was carried out as per six different protocols. After desired endometrial lining was observed, E2 levels were measured prior to progesterone supplementation, and the impact of raised E2 levels on pregnancy outcomes was evaluated in six different protocols. Pregnancy outcome was evaluated by measuring serum beta human chorionic gonadotropin levels 16 days after the embryo transfer. Statistical analysis was performed by using standard methods and receiver operating characteristic curves plotted to compare the outcomes. Results: Mean age of the patients in the study group was 34.35 ± 6.12 years, most of the patients were less than 40 years of age and mean parity was 0.49 ± 0.55. E2 level was measured on day 2 or 3 of cycle, and mean E2 level was 11.83 ± 5.50 pg/ml. Endometrial preparation was performed with injectable or oral hormonal preparations using six different protocols. Mean peak E2 level was 1263.65 pg/ml in 149 patients with no pregnancy and 1445.01 pg/ml in 93 patients with pregnancy in all protocols. Conclusion: Elevated E2 levels had no statistically significant impact on pregnancy rates in six different study protocols (oral and injectable) used for endometrial preparation.

Aim: To find out the difference in ovarian stromal blood flow in polycystic ovary syndrome (PCOS) and non-PCOS infertile patient and role of ovarian stromal blood flow as predictor of follicular response. Design: Prospective study. Setting: KJIVF and Laparoscopy Centre, Delhi. Materials and methods: Total 120 patients were recruited and divided into two equal groups. PCOS and non-PCOS infertile women of less than 35 years of age undergoing intrauterine insemination and in vitro fertilization (IVF) were included. Baseline and poststimulation two-dimensional transvaginal ultrasound with color and power Doppler was performed. Blood flow velocity waveforms with optimal flow were selected for measurement of systolic/diastolic ratio, peak systolic velocity (PSV), pulsatility index, and resistive index. Intervention: Color Doppler for ovarian stromal blood flow. Statistical analysis: Statistical testing was performed with the statistical package for the social science system version SPSS 17.0. Results: (a) Day 2/3 ovarian stromal PSV was significantly higher in PCOS women when compared with non-PCOS. (b) Positive correlation between ovarian stromal PSV and follicular response in patients with both PCOS and non-PCOS. Conclusion: Stromal vascularity in PCOS can be used as an additional criterion for the diagnosis of PCOS and ovarian stromal blood flow can be used as predictor of follicular response in IVF cycles especially in patients with PCOS.

Objectives: To measure the efficacy of combined clomiphene citrate (CC) and letrozole versus letrozole alone in the induction of ovulation in CC-resistant polycystic ovary syndrome (PCOS) cases. Design: Outcome assessor-blinded randomized controlled trial. Setting: Infertility Centre, Kathmandu, Nepal. Participants: One hundred and ninety-eight CC-resistant PCOS cases (99 in each group). Intervention: Treatment group received CC 100 mg once a day starting day 3 or 5 of menstrual cycle alternately for 3 days and letrozole 5 mg once a day starting day 4 or 6 of menstrual cycle alternately for 3 days. The comparison group received letrozole 5 mg once a day starting day 3 or 5 of menstrual cycle for 5 days. Main outcome measures: Number of mature follicles (18–22 mm), and increase in endometrial thickness. Results: Among total participants, 159 (81 in treatment and 78 in comparison group) were analyzed. Number of matured follicles was higher in the treatment group (1.59 ± 0.16) when compared with the comparison group (1.21 ± 0.56) which was statistically significant (P = 0.03) at 95% confidence interval. There was significant difference in the mean endometrial thickness (P = 0.01) in the treatment group (9.04 ± 0.15) when compared with the comparison group (8.51 ± 0.12). The conception rate was 35.80% in treatment group and 32.05% in the comparison group which was not significant in the Chi-squared test (P = 0.62). Conclusion: The combined CC and letrozole treatment is better than letrozole alone for ovulation induction in CC-resistant PCOS cases. Trial registration: Clinical Trials Registry-India CTRI/2019/01/017311

Background: To compare the addition of fixed dose additives namely recombinant luteinizing hormone (rLH), human menopausal gonadotropin (hMG), and letrozole to conventional doses of recombinant follicle-stimulating hormone (rFSH) on ovarian response and treatment outcome among women with poor ovarian reserve (POR) undergoing controlled ovarian stimulation for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Materials and methods: In this prospective quasirandomized study, participants (N = 120) were randomized into three equal groups. rFSH with one additive (rLH, hMG, letrozole) was administered to patients from day 2/3 of cycle. Clinical, ongoing, and early pregnancy rates were primary outcome measures. Total number of oocytes retrieved, number of transferable embryos, cycle cancellation, and fertilization rates were secondary outcome measures. Results: Group A patients had higher clinical pregnancy rate (42.5%) than group B (20%) and group C (25%) with significant differences (P = 0.030) between groups A and B. Ongoing pregnancy rates were higher in group A (35%) compared to group B (12.5%) and group C (22.5%) with significant difference between groups A and B (P = 0.010). Number of patients with early pregnancy loss was numerically equivalent in all three groups. Group C showed significantly decreased levels of estradiol compared with other groups. No significant differences in secondary outcomes were observed among the groups. Conclusion: The current study demonstrates benefits of rLH in early stages of stimulation in patients with POR in terms of improvement in IVF/ICSI-associated outcomes. Further larger randomized studies are required to confirm this effect, given a modest sample size in this study.

Objectives: To assess the effect of booster dose of human chorionic gonadotropin (HCG) on the unruptured follicles in non-in vitro fertilization/intracytoplasmic sperm injection cycles. Setting and design: This randomized controlled multicenter study was conducted at Tanta and Zagazig University hospitals in the period from August 1, 2018 to January 1, 2021. Patients and methods: Enrolled patients (n = 160) who had unruptured mature Graafian follicle 48 hours after intramuscular (IM) 10,000 IU HCG dose. Patients were allocated randomly into intervention group and control group. In the intervention group, another booster dose (10,000 IU of HCG) was given IM, whereas in the control group, 1 mL normal saline was given IM. Study outcomes: Ovulation and pregnancy rates. Results: The number of cases who had follicular rupture was similar to those in the control group. The incidence of luteinized unruptured follicle (LUF) was nearly similar in both groups. No significant differences were noticed regarding pregnancy rates in both groups. Conclusion: Booster dose of HCG for unruptured follicles has no benefit in ovulation triggering nor in the prevention of LUF syndrome. There was no significant difference in pregnancy rates in both groups.

Introduction: The endometrial receptivity array (ERA), a customized microarray, is an objective test to assess the endometrial receptivity status of infertile patients. It provides an opportunity to do personalized embryo transfer (pET) by synchronizing with each patient’s window of implantation (WOI) thereby increasing the success of treatment particularly in couples with recurrent implantation failure (RIF). Aim: To find out whether pET after ERA testing in couples with RIF improves implantation and pregnancy rates. Materials and methods: This is a retrospective analysis of women with a history of RIF undergoing further infertility treatment at our center. In this study, records of 34 women with history of RIF who consented to undergo ERA from July 2016 to July 2020 were analyzed. Results: Thirty-four women with RIF who underwent ERA testing showed receptive endometrium in 21 patients (61.8%) and nonreceptive endometrium in 13 (38.2%) patients. Of these, 27 patients were included for analysis and they underwent total of 31 embryo transfer cycles. ERA showed receptive endometrium in 17 patients and nonreceptive in 10 patients. Among eight women who had nonreceptive ERA result which means displaced WOI pET resulted in an implantation rate of 45.5% and pregnancy rate of 50% which was comparable to the 55.4% background pregnancy rate of the general in vitro fertilization population during the same time period. Conclusion: Hence, there is a subset of patients with RIF who can achieve a pregnancy rate as good as general population with pET based on ERA results and ERA can be recommended to such patients.

Treatment of impaired spermatogenesis with recombinant follicle-stimulating hormone (r-FSH) has heterogenous response among patients. FSH receptor (FSHR) gene polymorphisms are known to be associated with male infertility with varied phenotype presentation. The presence of Serine 680 Asparagine (Ser680Asn) polymorphism is also linked to response to r-FSH when treating impaired spermatogenesis. We present a case of an Indian male with severe oligoasthenoteratozoospermia carrying homozygous Asn680Asn FSHR genotype, who responded favorably to r-FSH treatment, demonstrating significant improvement in seminal parameters and reduction of sperm DNA fragmentation index. Ser680Asn polymorphism of FSHR gene may serve as a clinically useful pharmacogenomic marker in identification of good responders to r-FSH treatment.