Embryonic Aneuploidy after Preimplantation Genetic Screening: Age- and Indication-Matched Comparative Study between Indian and Spanish Population.

BACKGROUND: Recent studies show that there are differences in female fertility in different ethnic groups with ovarian aging and IVF treatment outcomes. Advanced maternal age is a known risk factor for miscarriage, accounting largely due to genetically abnormal fetus. AIMS AND OBJECTIVES: This study investigates if there are any differences in rates of embryo aneuploidy based on age and indications for preimplantation genetic screening (PGS) between Indian and Spanish women. MATERIALS AND METHODS: This multicenter study was carried out at fertility centers in India and Spain. Data from autologous IVF cycles of women <45 years age (Spanish: 39.4 ± 3.8 years; Indian: 35.3 ± 4.6 years) were included. A total of 37,962 embryos from 7009 IVF cycles from Spain and 1894 embryos from 308 IVF cycles from India, having similar clinical indications, underwent similar IVF treatment protocol. The embryos were analyzed by PGS using either a day-3 or day-5/6 embryo biopsy. RESULTS: Both Indian and Spanish ethnic population showed a reduction in aneuploidy rate in day-5/6 biopsy compared with day-3 biopsy (Spanish: 53.3% vs. 81.1%, P < 0.01; Indian: 50% vs. 75%, P < 0.02). There was a significant decrease in highly abnormal or chaotic embryos in trophectoderm biopsies compared with day-3 biopsies (Spanish: 2% vs. 16.1%, P < 0.01; Indian: 2.5% vs. 17.7%, P < 0.01). Both the populations showed similar trend in aneuploidy rate with maternal age. The results showed no significance between aneuploidy rate compared within different age groups and indications. However, there was a significant reduction in the miscarriage rate in Spanish population in day-3 biopsy compared with Indian population (10.7% vs. 19.8%; P < 0.05; 95% confidence interval [0.0044-0.0712]). There were no differences in the clinical outcomes compared between the two populations. CONCLUSION: This study shows that the aneuploidy rates between Indian and Spanish women of the same age group undergoing IVF treatment do not differ. An in-depth analysis to compare the types of anomalies reported with PGS in both the population will be of much interest.

A Multicenter, Randomized, Equivalence Trial of a New Recombinant Human Chorionic Gonadotropin Preparation versus Ovitrelle® for Ovulation in Women Undergoing Intrauterine Insemination Following Ovarian Stimulation.

CONTEXT: A new indigenous recombinant human chorionic gonadotropin (r-hCG) has been developed in India with a comparable pharmacological profile to that of Ovitrelle® (Merck Serono). AIMS: This study aims to compare the efficacy and safety of the new r-hCG with that of Ovitrelle for induction of ovulation in women undergoing intrauterine insemination (IUI). SETTINGS AND DESIGN: Randomized (2:1), multicenter, open-label, equivalence clinical trial conducted in India. SUBJECTS AND METHODS: A total of 217 women, aged 20-37 years, undergoing IUI were administered the new r-hCG (test) 250 mcg or Ovitrelle 250 mcg (comparator) after ovarian stimulation with gonadotropins. The ovulation rate was compared as the primary outcome. In addition, pregnancy rates, incidence of adverse events (AEs), and development of immunogenicity were assessed. Statistical Analysis Used: The ovulation and pregnancy rates were compared using Chi-squared test with statistical significance at P < 0.05. RESULTS: With 144 women in the test group and 73 in the comparator group, the ovulation rate (85.4% vs. 78.1%; P = 0.17) and pregnancy rate (serum ß hCG test) (11.8% vs. 12.3%; P = 0.91) were similar in both groups. A total of 15 AEs were reported (11 in the test r-hCG group and 4 in the comparator group) in 11 women; none of these were serious, and all were judged to be unrelated to the study drug. No subject developed immunogenic reaction to the test drug. CONCLUSIONS: The new preparation of r-hCG was equivalent to the conventional preparation of r-HCG in the induction of ovulation in patients undergoing IUI.

Personalized Embryo Transfer Helps in Improving In vitro Fertilization/ICSI Outcomes in Patients with Recurrent Implantation Failure.

AIMS: This study aims to compare clinical outcomes in patients of recurrent implantation failure (RIF), who had embryo transfer (ET) following a receptive (R) endometrial receptivity array (ERA) and a personalized embryo transfer (pET) after a nonreceptive (NR) ERA. SETTINGS AND DESIGN: This was a retrospective observational study. STUDY PERIOD: July 2013-September 2017. SUBJECTS AND METHODS: Two hundred and forty-eight patients having unexplained RIF who underwent ERA test were included in the study. Clinical outcomes were compared between patients having a receptive (R) ERA and those having a NR ERA who underwent a pET-based on ERA. STATISTICAL ANALYSIS USED: Chi-square and t-test. RESULTS: ERA predicted receptive (R) endometrium at P + 5 in 82.3% (204/248) patients and NR in 17.7% (44/248) patients. Average failed previous in vitro fertilization cycles were 3.67 ± 1.67 among receptive ERA patients and 4.09 ± 1.68 among NR ERA patients. Pregnancy rate (PR), clinical PR, implantation rate (IR), abortion rate (AR), ongoing pregnancy rate (OPR), and cumulative PR were comparable between patients having receptive ERA who had a routine Embryo Transfer (ET) and those with an NR ERA who underwent a pET. CONCLUSIONS: ERA is helpful in identifying the window of implantation (WOI) through genetic expressions of the endometrium to pinpoint embryo transfer timing. pET guided by ERA in patients of RIF with displaced WOI improves IRs and OPRs.

One Plus One Is Better Than Two: Cumulative Reproductive Outcomes Are Better after Two Elective Single Blastocyst Embryo Transfers Compared to One Double Blastocyst Embryo Transfer.

AIMS: The aim of this study is to compare cumulative in vitro fertilization-intracytoplasmic sperm injection outcomes following two elective single embryo transfer (eSET) versus one double embryo transfer (DET) using blastocyst(s). SETTINGS AND DESIGN: This was retrospective observational study. STUDY PERIOD: The study was conducted during January 2015-December 2015. SUBJECTS AND METHODS: Forty-one fresh + 25 frozen eSET versus 123 DET using self-oocytes and 68 fresh + 35 frozen eSET versus 184 DET using donor-oocytes were included in the study. All failing to achieve live birth after first eSET underwent frozen embryo transfer cycle with second blastocyst. Cumulative outcome after two eSET were compared with one DET. STATISTICAL ANALYSIS USED: The analysis was performed by Chi-square and t-test. RESULTS: In self-oocytes group, higher but statistically nonsignificant cumulative clinical pregnancy rate (CPR) (58.5% vs. 57.7%, P = 0.92) and live birth rate (LBR) (48.7% vs. 44.7%, P = 0.65) with significantly lower multiple pregnancy rate (MPR) (4.2% vs. 45%, P = 0.0002) were obtained; whereas in donor-oocytes group, comparable cumulative CPR (73.5% vs. 65.7%, P = 0.24), significantly higher LBR (64.7% vs. 48.9%, P = 0.02) and significantly lower MPR (4% vs. 51.2%, P = 0.00005) were obtained after two eSET vs. one DET. In self-oocytes group, the incidence of prematurity (10% vs. 21.4%, P > 0.05) and low birth weight (25% vs. 45.6%, P > 0.05) were lower but statistically nonsignificant, whereas in donor-oocytes group, incidence of prematurity was lower but statistically nonsignificant (26.7% vs. 38.8%, P > 0.05) while of low birth weight was significantly lower (32.7% vs. 51.2%, P = 0.0038) after two eSET versus one DET. CONCLUSION: Cumulative LBR was higher with lower incidence of multiple births, prematurity and low birth weight after two eSET versus one DET using self- or donor-oocytes. Higher use of eSET improves reproductive outcomes in patients with good prognosis.

Morphokinetic behavior of euploid and aneuploid embryos analyzed by time-lapse in embryoscope.

BACKGROUND: Embryonic aneuploidy may result in miscarriage, implantation failure, or birth defects. Thus, it is clinically necessary to avoid the selection of aneuploid embryos during in vitro fertilization treatment. AIM: The aim of this study was to identify the morphokinetic differences by analyzing the development of euploid and aneuploid embryos using a time-lapse technology. We also checked the accuracy of a previously described model for selection of euploid embryos based on morphokinetics in our study population. MATERIALS AND METHODS: It is a retrospective study of 29 cycles undergoing preimplantation genetic screening from October 2013 to April 2015 at our center. Of 253 embryos, 167 suitable for biopsy embryos were analyzed for their chromosomal status using array-comparative genome hybridization (CGH). The morphokinetic behavior of these embryos was further analyzed in embryoscope using time-lapse technology. RESULTS: Among the analyzed embryos, 41 had normal and 126 had abnormal chromosome content. No significant difference in morphokinetics was found between euploid and aneuploid embryos. The percentage of embryos with blastulation was similar in the euploid (65.85%, 27/41) and aneuploid (60.31%, 76/126) embryos (P = 0.76). Although hard to define, majority of the chromosomal defects might be due to meiotic errors. On applying embryo selection model from Basile et al., embryos falling within optimal ranges for time to division to 5 cells (t5), time period of the third cell cycle (CC3), and time from 2 cell division to 5 cell division (t5-t2) exhibited greater proportion of normal embryos than those falling outside the optimal ranges (28.6%, 25.9%, and 26.7% vs. 17.5%, 20.8%, and 14.3%). CONCLUSION: Keeping a track of time interval between two stages can help us recognize aneuploid embryos at an earlier stage and prevent their selection of transfer. However, it cannot be used as a substitute for array CGH to select euploid embryos for transfer.

Ethnicity is an independent predictor of IVF-ICSI outcome: a study of 5,549 cycles in Spain and India.

AIM: To determine the role of ethnicity on IVF/ICSI outcomes between Indian and white Caucasian women. SETTINGS AND DESIGN: Retrospective cohort study. MATERIALS AND METHODS: White Caucasian and Indian women undergoing IVF/ICSI treatment cycles. Total 5549 self, non-donor, fresh IVF cycles conducted from January 2014 to March 2015, out of which, 4227 were white Caucasian and 1322 were Indian. Data were collected on baseline characteristics, IVF cycle parameters and outcomes. Ongoing pregnancy rate (OPR) was measured as main outcome. RESULTS: Indian women differed significantly from white Caucasian women in baseline characteristics like age (30.6 ± 0.2 versus 37.6 ± 0.1 years; p < 0.001), BMI (22.3 ± 0.2 versus 26.6 ± 1.0 kg/m2; p < 0.05), duration of infertility (6.9 ± 3.0 versus 2.5 ± 0.1 years; p < 0.001) and antral follicle count (AFC) (8.9 ± 0.4 versus 7.5 ± 0.2; p < 0.001). Indian women had lower implantation rate (30.1% versus 39.6%: p < 0.001) and OPR (35.1% versus 41.7%: p < 0.001) compared with white Caucasian women. Regression analysis proved independent effect of ethnicity on OPR (OR 0.944; 95% CI 0.928-0.961: p < 0.001) Conclusions: OPR was significantly lower among Indian ethnic group following IVF/ICSI suggest that ethnicity, like age, is a major and an independent predictor of IVF outcome.

Quality management systems for your in vitro fertilization clinic's laboratory: Why bother?

Several countries have in recent years introduced prescribed requirements for treatment and monitoring of outcomes, as well as a licensing or accreditation requirement for in vitro fertilization (IVF) clinics and their laboratories. It is commonplace for Assisted Reproductive Technology (ART) laboratories to be required to have a quality control system. However, more effective Total Quality Management systems are now being implemented by an increasing number of ART clinics. In India, it is now a requirement to have a quality management system in order to be accredited and to help meet customer demand for improved delivery of ART services. This review contains the proceedings a quality management session at the Indian Fertility Experts Meet (IFEM) 2010 and focuses on the creation of a patient-oriented best-in-class IVF laboratory.

Transfer of human frozen-thawed embryos with further cleavage during culture increases pregnancy rates.

AIM: To compare the pregnancy rate following transfer of frozen-thawed embryos with or without overnight culture after thawing. SETTINGS AND DESIGN: This is a retrospective analysis of frozen-thawed embryo transfer (FET) cycles performed between January 2006 and December 2008. MATERIALS AND METHODS: Out of 518 thaw cycles, 504 resulted in embryo transfers (ETs). Of the total FET cycles, 415 were performed after an overnight culture of embryos (group A); and in 89 cycles, ET was performed within 2 hours of embryo thawing (group B). STATISTICAL ANALYSIS: The data were statistically analyzed using chi-square test. RESULTS: We observed that with FET, women ≤30 years of age had a significantly higher (P=0.003) pregnancy rate (PR=28.9%) as compared to women >30 years of age (17.5%). A significantly higher (P<0.001**) pregnancy rate was also observed in women receiving 3 frozen-thawed embryos (29%) as compared to those who received less than 3 embryos (10.7%). The difference in PR between group A (PR=24.3%) and group B (PR=20.3%) was not statistically significant. However, within group A, ET with cleaved embryos showed significantly (P≤0.01) higher pregnancy rate compared to the uncleaved embryos, depending on the number of cleaved embryos transferred. CONCLUSION: No significant difference was noticed between FETs made with transfer of embryos with overnight culture and those without culture. However, within the cultured group, transfer of embryos cleaved during overnight culture gave significantly higher PR than transfers without any cleavage.

Successful pregnancies and a live birth after intracytoplasmic sperm injection in globozoospermia.

Globozoospermia is a severe form of teratozoospermia characterized by round-headed acrosomeless spermatozoa. Here we present two successful pregnancies and a live birth after intracytoplasmic sperm injection.