International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology, 2014†.

STUDY QUESTION: What were the utilization, effectiveness and safety of practices in assisted reproductive technologies (ART) globally in 2014 and what global trends could be observed? SUMMARY ANSWER: The estimated total number of ART cycles conducted in 76 participating countries in 2014 was 1.93 million representing ∼66% of global activity, with 5-year trends including an increase in success rates and proportion of frozen embryo transfer (FET) cycles, improvement in cumulative live birth rates per aspiration, a continued increase in single embryo transfer (SET) and thus a reduction in multiple birth rates, an increase in preimplantation genetic testing and stabilization in the use of intracytoplasmic sperm injection (ICSI). WHAT IS KNOWN ALREADY: ART is widely practiced throughout the world but continues to be characterized by significant disparities in utilization, practice, effectiveness and safety. The International Committee for Monitoring Assisted Reproductive Technologies (ICMART) annual world report series provides an important instrument for tracking trends in ART treatment and for providing clinical and public health data to ART professionals, health authorities, patients and the general public. STUDY DESIGN, SIZE, DURATION: A retrospective, cross-sectional survey on ART procedures performed globally during 2014 was carried out. A new method for calculating ART utilization rates and number of babies born was introduced in this latest ICMART world report. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 76 countries and 2 746 ART centres submitted data through national and regional ART registries on ART cycles performed during 2014 and their treatment and pregnancy outcomes. ART cycles and outcomes are described at a country level, regionally and globally. Aggregate country data are processed and analyzed based on methods developed by ICMART. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1 629 179 ART cycles were reported for the treatment year 2014. After imputing data for missing values and non-reporting centres in reporting countries, an estimated 1 929 905 cycles resulted in >439 039 babies in reporting countries. From 2010 to 2014, the number of reported non-donor aspirations and FET cycles increased by 37.3% and 67.5%, respectively. The proportion of women aged ≥40 years undergoing non-donor ART increased from 23.2% in 2010 to 27.0% in 2014. ICSI, as a percentage of non-donor aspiration cycles, remained relatively stable at 64.8%. The IVF/ICSI combined delivery rates per fresh aspiration and FET cycle were 19.9% and 24.3%, respectively. In fresh non-donor cycles, SET increased from 30.0% in 2010 to 40.0% in 2014, while the average number of transferred embryos decreased from 1.95 to 1.73-but with wide country variation. The rate of twin deliveries following fresh non-donor transfers continued to decrease, from 20.4% in 2010 to 16.2% in 2014, and the triplet rate decreased from 1.1% to 0.5%. In FET non-donor cycles in 2014, the SET rate was 61.6%, with an average of 1.43 embryos transferred, resulting in twin and triplet rates of 10.1% and 0.2%, respectively. The cumulative delivery rate per aspiration increased from 27.1% in 2010 to 32.1% in 2014. The overall perinatal mortality rate per 1 000 births was 19.4 following fresh IVF/ICSI cycles and 9.5 following FET cycles. Among reporting countries, oocyte donation cycles represented 7.3% of all embryo transfers (89 751 transfer cycles) and resulted in 39 278 babies. LIMITATIONS, REASONS FOR CAUTION: The data presented are dependent on the quality and completeness of data submitted by individual countries to ICMART directly or through regional registries. This report covers approximately two-thirds of world ART activity. China is a major contributor of global cycles missing from this report. Continued efforts to improve the quality and consistency of ART data reported by registries are still needed, including the use of internationally agreed standard definitions (The International Glossary of Infertility and Fertility Care). A new method was introduced in this report to calculate ART utilization and number of babies born following ART; therefore, these results are not directly comparable with previous reports. WIDER IMPLICATIONS OF THE FINDINGS: The ICMART world reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment effectiveness and safety continue to increase globally, the wide disparities in access to treatment, procedures performed and embryo transfer practices warrant attention by clinicians and policymakers. The new method for estimating ART utilization and number of babies born provided more conservative estimates compared to the previuos method. STUDY FUNDING/COMPETING INTEREST(S): ICMART receives unrestricted grants from Abbott and Ferring Pharmaceuticals. ICMART also acknowledges financial support from the following organizations: American Society for Reproductive Medicine; Asia Pacific Initiative on Reproduction; European Society of Human Reproduction and Embryology; Fertility Society of Australia and New Zealand; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproducción Asistida; and the Society for Assisted Reproductive Technology. S.D. reports industry sponsorship for attendance of conference from Ferring, and research grants to support African Network and Registry of ART from Ferring and Merck outside the submitted work. F.Z.-H. reports lectures at organized webinars for Ferring and Merck. O.I. reports honoraria for consulting from Ferring, Merck and ObsEva, as well as honoraria for lectures from Ferring and Merck. G.M.C., J.d.M., M.B., M.S.K. and G.D.A. have nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology 2012†.

STUDY QUESTION: What was the utilization, effectiveness and safety of practices in ART globally in 2012 and what global trends could be observed? SUMMARY ANSWER: The total number of ART cycles increased by almost 20% since 2011 and the main trends were an increase in frozen embryo transfers (FET), oocyte donation, preimplantation genetic testing and single embryo transfers (SET), whereas pregnancy and delivery rates (PR, DR) remained stable, and multiple deliveries decreased. WHAT IS KNOWN ALREADY: ART is widely practiced throughout the world, but continues to be characterized by significant disparities in utilization, availability, practice, effectiveness and safety. The International Committee for Monitoring Assisted Reproductive Technologies (ICMART) annual world report provides a major tool for tracking trends in ART treatment for over 25 years and gives important data to ART professionals, public health authorities, patients and the general public. STUDY DESIGN, SIZE, DURATION: A retrospective, cross-sectional survey on the utilization, effectiveness and safety of ART procedures performed globally during 2012 was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixty-nine countries and 2600 ART clinics submitted data on ART cycles performed during the year 2012, and their pregnancy outcome, through national and regional ART registries. ART cycles and outcomes are described at country, regional and global levels. Aggregate country data were processed and analyzed based on methods developed by ICMART. MAIN RESULTS AND ROLE OF CHANCE: A total of 1 149 817 ART cycles were reported for the treatment year 2012. After imputing data for missing values and non-reporting clinics in reporting countries, 1 948 898 cycles (an increase of 18.6% from 2011) resulted in >465 286 babies (+17.9%) in reporting countries. China did not report and is not included in this estimate. The best estimate of global utilization including China is ∼2.8 million cycles and 0.9 million babies. From 2011 to 2012, the number of reported aspirations and FET cycles increased by 6.9% and 16.0%, respectively. The proportion of women aged 40 years or older undergoing non-donor ART increased from 24.0% in 2011 to 25.2% in 2012. ICSI, as a percentage of non-donor aspiration cycles, increased from 66.5% in 2011 to 68.9% in 2012. The IVF/ICSI combined delivery rates per fresh aspiration and FET cycles were 19.8% and 22.1%, respectively. In fresh non-donor cycles, SET increased from 31.4% in 2011 to 33.7% in 2012, while the average number of transferred embryos decreased from 1.91 to 1.88, respectively-but with wide country variation. The rates of twin deliveries following fresh non-donor transfers decreased from 19.6% in 2011 to 18.0% in 2012, and the triplet rate decreased from 0.9% to 0.8%. In FET non-donor cycles, SET was 54.8%, with an average of 1.54 embryos transferred and twin and triplet rates of 11.1% and 0.4%, respectively. The cumulative DR per aspiration increased from 28.0% in 2011 to 28.9% in 2012. The overall perinatal mortality rate per 1000 births was 21.4 following fresh IVF/ICSI and 15.9 per 1000 following FET. LIMITATIONS, REASONS FOR CAUTION: The data presented depend on the quality and completeness of data submitted by individual countries to ICMART directly or through regional registries. This report covers approximately two-thirds of` world ART activity, with a major missing country, China. Continued efforts to improve the quality and consistency of reporting ART data by registries are still needed, including the use of internationally agreed standard definitions (International Glossary of Infertility and Fertility Care). WIDER IMPLICATIONS OF THE FINDINGS: The ICMART world reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment continues to increase globally, the wide disparities in access to treatment, procedures performed and embryo transfer practices warrant attention by clinicians and policy makers. With the increasing practice of SET and of freeze all and resulting increased proportion of FET cycles, it is clear that PR and DR per aspiration in fresh cycles do not give an overall accurate estimation of ART efficiency. It is time to use cumulative live birth rate per aspiration, combining the outcomes of FET cycles with the associated fresh cycle from which the embryos were obtained, and to obtain global consensus on this approach. STUDY FUNDING/COMPETING INTEREST(S): The authors declare no conflict of interest and no specific support from any organizations in relation to this manuscript. ICMART gratefully acknowledges financial support from the following organizations: American Society for Reproductive Medicine; European Society for Human Reproduction and Embryology; Fertility Society of Australia; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproduccion Asistida; Society for Assisted Reproductive Technology; Ferring Pharmaceuticals and Abbott (both providing ICMART unrestricted grants unrelated to world reports). TRIAL REGISTRATION NUMBER: NA.

COVID-19 and assisted reproductive technology services: repercussions for patients and proposal for individualized clinical management.

The prolonged lockdown of health services providing high-complexity fertility treatments -as currently recommended by many reproductive medicine entities- is detrimental for society as a whole, and infertility patients in particular. Globally, approximately 0.3% of all infants born every year are conceived using assisted reproductive technology (ART) treatments. By contrast, the total number of COVID-19 deaths reported so far represents approximately 1.0% of the total deaths expected to occur worldwide over the first three months of the current year. It seems, therefore, that the number of infants expected to be conceived and born -but who will not be so due to the lockdown of infertility services- might be as significant as the total number of deaths attributed to the COVID-19 pandemic. We herein propose remedies that include a prognostic-stratification of more vulnerable infertility cases in order to plan a progressive restart of worldwide fertility treatments. At a time when preventing complications and limiting burdens for national health systems represent relevant issues, our viewpoint might help competent authorities and health care providers to identify patients who should be prioritized for the continuation of fertility care in a safe environment.

ART utilization: an indicator of access to infertility care.

This commentary outlines the importance of utilizing assisted reproductive technology (ART) as an indicator of access to infertility care and provides a standard way of reporting utilization to facilitate international comparisons. Factors that influence ART utilization as well as underlying inequalities and inequities in access to care are discussed. The relevance of a marker that can inform and evaluate policy initiatives, monitor progress and document change is emphasized.

Prevalence of structural birth defects in IVF-ICSI pregnancies resulting from autologous and donor oocytes in Indian sub-continent: Results from 2444 births.

INTRODUCTION: This study was conducted to evaluate and compare the incidence of birth defects in In-Vitro Fertilization-Intra Cytoplasmic Sperm Injection (IVF-ICSI) pregnancies with autologous and donor oocytes. As a secondary outcome, the prevalence of birth defects in IVF-ICSI pregnancies was compared with those from spontaneous conceptions in India. MATERIAL AND METHODS: This retrospective study included 2444 births resulting from IVF-ICSI cycles from autologous (n = 1743) and donor oocytes (n = 701) during a 3-year period in an Indian infertility center. Birth defects, if any, were noted antenatally and followed till the neonatal period, in case of live birth. RESULTS: The overall prevalence of birth defects in IVF-ICSI pregnancies in this study was 29/2444 (118.6/10 000 births) and the most common congenital anomaly was cardiac malformation (32.7/10 000 births) followed by genitourinary (28.6/10 000 births). The risks of birth defects resulting from autologous and donor oocytes did not differ (114.7/10 000 vs 128.38/10 000; P > 0.05). However, pregnancies resulting from autologous oocytes had a higher trend of gastrointestinal birth defects (20.5/10 000 births vs 0), though not statistically significant. The risk of cardiovascular birth defects resulting from IVF-ICSI pregnancies was much higher compared with the natural conceptions in India (32.7/10 000 vs 12.7/10 000 births; P = 0.03), whereas the risk of central nervous system malformations was much lower (8.1/10 000 vs 60.18/10 000 births; P = 0.005). CONCLUSIONS: Overall, there was no significant difference in birth defects resulting from IVF-ICSI with autologous or donor oocytes. The births resulting from IVF-ICSI pregnancies did not tend to have a higher rate of birth defects a compared with natural conceptions. The differences in the prevalence of certain birth defects (cardiovascular or central nervous system) reported in IVF-ICSI pregnancies may be due to improved surveillance modalities and early detection in pregnancies following IVF-ICSI. A study with larger number of sample size will give us better understanding of the prevalence of reported incidence in this study.

Dual effect of insulin resistance and cadmium on human granulosa cells - In vitro study.

Combined exposure of cadmium (Cd) and insulin resistance (IR) might be responsible for subfertility. In the present study, we investigated the effects of Cd in vitro in IR human granulosa cells. Isolated human granulosa cells from control and polycystic ovary syndrome (PCOS) follicular fluid samples were confirmed for IR by decrease in protein expression of insulin receptor-ß. Control and IR human granulosa cells were then incubated with or without 32µM Cd. The combined effect of IR with 32µM Cd in granulosa cells demonstrated significant decrease in expression of StAR, CYP11A1, CYP19A1, 17ß-HSD, 3ß-HSD, FSH-R and LH-R. Decrease was also observed in progesterone and estradiol concentrations as compared to control. Additionally, increase in protein expression of cleaved PARP-F2, active caspase-3 and a positive staining for Annexin V and PI indicated apoptosis as the mode of increased cell death ultimately leading to decreased steroidogenesis, as observed through the combined exposure. Taken together the results suggest decrease in steroidogenesis ultimately leading to abnormal development of the follicle thus compromising fertility at the level of preconception.

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.

Absence of luteal phase defect and spontaneous pregnancy in IVF patients despite GnRH-agonist trigger and "freeze all policy" without luteal phase support: a report of four cases.

Human chorionic gonadotropin (hCG) is commonly used for final oocyte maturation in "in vitro fertilization" (IVF)-treatment cycles, however, the main important risk is development of severe ovarian hyperstimulation syndrome (OHSS). OHSS can almost be avoided by using gonadotrophin-releasing-hormone agonist for final oocyte maturation in an antagonist protocol. However, primarily this approach lead to a very poor reproductive outcome, despite the use of a standard luteal phase support. The reason seems to be severe luteolysis. Obviously, luteolysis post-gonadotropin-releasing-hormone-agonist (post-GnRH-a) trigger is individual specific, and not all patients will develop a complete luteolysis, as expected previously. Luteolysis can been reverted by the administration of hCG. Unprotected intercourse around the time of ovulation induction and oocyte retrieval can lead to a spontaneous conception in IVF treatment and, endogenous hCG, produced by the trophoblast, will rescue the corpora lutea. Therefore, one should not rely on complete luteolysis after GnRH-a triggering and, especially patients for egg donation and pre-implantation-genetic diagnosis for single gene disorder, have to be counselled to avoid unprotected intercourse.

Investigating the potential role of swertiamarin on insulin resistant and non-insulin resistant granulosa cells of poly cystic ovarian syndrome patients.

BACKGROUND AND AIM: Conventional drugs have limitations due to prevalence of contraindications in PCOS patients. To explore the potential effects of swertiamarin, on abrupted insulin and steroidogenic signaling in human luteinized granulosa cells from PCOS patients with or without insulin resistance. EXPERIMENTAL PROCEDURE: hLGCs from 8 controls and 16 PCOS patients were classified for insulin resistance based on down regulation of protein expression of insulin receptor-ß (INSR- ß) as shown in our previous paper. Cells were grouped as control, PCOS-IR and PCOS-NIR, treated with swertiamarin (66 µM) and metformin (1 mM). Expression of key molecules involved in insulin signaling, fat metabolism, IGF system and steroidogenesis were compared between groups. RESULTS: Swertiamarin significantly (P < 0.05) reversed the expression of INSR-ß, PI(3)K, p-Akt, PKC-ζ, PPARγ, (P < 0.01) IRS (Ser 307) and IGF system in PCOS-IR group and was equally potent to metformin. In the same group, candidate genes viz SREBP1c, FAS, ACC-1 and CPT-1 were down regulated by swertiamarin (P < 0.001) and metformin (P < 0.001). Significant upregulation was demonstrated in expression of StAR, CYP19A1, 17ß-HSD and 3ß-HSD when treated with swertiamarin (P < 0.01) and metformin (P < 0.01) in PCOS-IR followed by increase in 17ß-HSD and 3ß-HSD enzyme activity along with estradiol and progesterone secretions. However, swertiamarin did not reveal any effect on PCOS-NIR group as compared to metformin that significantly (P < 0.01) reversed all the parameters related to steroidogenesis and down regulated basal expression of insulin signaling genes. CONCLUSION: Swertiamarin, presents itself as a potential fertility drug in hLGCs from PCOS-IR patients.

Follicular phase cycle programming using estradiol in oocyte donors-a convenient and effective approach.

Objective: To study the efficacy of estradiol for cycle programming in oocyte donors when administered in the follicular phase only. Design: Prospective interventional study. Setting: Single fertility center. Patients: Ninety-three oocyte donors underwent programmed stimulation using estradiol in the follicular phase. Their previous unprogrammed cycles were used as historical controls. Interventions: Donors received 8 mg of estradiol hemihydrate from day 2 till 1 day before the start of stimulation. Main Outcome Measures: The primary outcome measures studied were the number of oocytes retrieved, duration of stimulation, and total gonadotropin dose. The number of mature oocytes, oocyte maturation rate, fertilization rate, blastulation rate, implantation rate, and pregnancy rate were the secondary outcomes. Results: The average number of oocytes retrieved was higher in the study group (36.4 vs. 32.5). The duration of stimulation (9.22 vs. 9.21 days) and the total gonadotropin dose were similar (3,085.5 vs. 3,026 IU) between both groups. The mean number of mature oocytes retrieved was higher in the study group (30.1 vs. 26.3), but the maturation rate was similar (84.6% vs. 81.2%). The fertilization rate (77.8% vs. 78.7%), number of blastocysts, blastulation rate (32.7% vs. 33.2%), implantation rate (59.3% vs. 66.3%), and pregnancy rate (77.3% vs. 77.1%) showed no statistically significant difference. Conclusions: Estradiol usage in the follicular phase alone is an effective and convenient option for cycle programming in oocyte donors. It can yield similar mature oocytes and does not affect the clinical outcomes. Further larger sample-sized studies may be needed to validate its use which can also be extended to routine in vitro fertilization cycles. Clinical Trials Registration Number: CTRI/2020/09/027815.

Impact of COVID-19 Pandemic on Clinical and Embryological Outcomes of Assisted Reproductive Techniques.

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 Setting and Design: 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.

A Comparative Study to Assess the Efficacy of Two Different Estradiol Formulations during In Vitro Fertilization.

Improvements in stimulation protocols, introduction of vitrification, and changes in clinical practices have contributed to improved efficacy and safety of assisted reproductive technology (ART) procedures. This has also led to a concomitant increase in number of cycles requiring hormone replacement therapy (HRT) protocol for performing an embryo transfer. Successful implantation is dependent on endometrial thickness which in turn is regulated by temporal regulation of hormones. Careful control of estrogen levels determines uterine receptivity. One of the most used drugs for achieving appropriate endometrial lining of >7 mm in HRT is estradiol valerate. Although different estrogen formulations with varying physicochemical properties exist, there is not enough literature to support if the differences translate into a discernible clinical outcome in an in vitro fertilization (IVF) setting. Objective and Method. In this study, retrospective in nature, we compare the efficacy of oral estradiol hemihydrate with estradiol valerate in HRT cycles in 2,529 Indian women, undergoing treatment at a center in India between Jan 2017 and May 2019. Results. Our results primarily indicate that between the estradiol valerate and estradiol hemihydrate treatment groups, the implantation rate (IR) was 47.42% and 49.07%, respectively (P value 0.284), and the endometrial thickness (mean ± SEM in mm) that was achieved was 9.25 ± 0.038 mm and 9.57 ± 0.058 mm (P value < 0.001), respectively. There were no significant differences observed in the secondary outcome measures including clinical pregnancy rate, abortion rate, ectopic pregnancy, and live birth rate. Conclusions. Hence, this study concludes that oral estradiol hemihydrate and estradiol valerate are therapeutically equivalent and provide similar clinical outcomes in an IVF setting.

Chemotherapy Can Interfere in Implantation in In-vitro Fertilization.

Improvement in cancer treatments has allowed more women to plan a pregnancy once the disease is cured. The effects of chemotherapy on ovaries are well proven but those on the uterus, especially the endometrium and embryo implantation are still unknown. Usage of newer tyrosine kinase inhibitors such as nilotinib has revolutionized the management of leukemias. Although nilotinib has been reported to be safe in pregnancy, further studies are needed to evaluate its effect on the process of embryo implantation, especially in women undergoing in-vitro fertilization. We report a case where successful pregnancy outcome was achieved after stoppage of nilotinib before embryo transfer in a woman who had previous four failed attempts while on nilotinib and no other obvious cause of implantation failure. Despite optimal endometrial thickness and receptivity, the pale appearance of endometrium on hysteroscopy was attributed to be a possible effect of nilotinib and prompted us to withhold it.

Effect of Endometrial Thickness and duration of Estrogen Supplementation on In Vitro Fertilization-Intracytoplasmic Sperm Injection Outcomes in Fresh Ovum/Embryo Donation Cycles.

BACKGROUND: There is no consensus regarding optimal endometrial thickness and duration of estrogen supplementation in embryo transfer cycles, at present. AIMS: To observe the effect of endometrial thickness and/or duration of estrogen supplementation on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes in fresh ovum/embryo donation cycles. SETTINGS AND DESIGN: This was a retrospective observational study. The study was conducted from January 2015 to November 2017. SUBJECTS AND METHODS: Nine hundred and fifty seven fresh blastocyst transfer cycles in the recipients of oocyte/embryo donation regardless of reproductive history and diagnosis conducted at Nova IVF Fertility, Ahmedabad, Gujarat, India. Of these, 315 women had single embryo transfer (SET), while 642 had double embryo transfer (DET). Only fresh blastocysts derived from oocytes of young donors (≤30 years) and transferred in a uniform hormone replacement therapy (HRT) cycle were included. The effect of endometrial thickness and duration of estrogen on live birth rate (LBR) and other IVF/ICSI outcomes were analyzed. STATISTICAL ANALYSIS: Univariate logistic regression. RESULTS: A significant improvement in LBR was noted in the recipients with each millimeter increase in endometrial thickness starting from 6 mm after transfer of either single (odds ratio [OR] = 1.3, P = 0.003) or double (OR = 1.14, P = 0.0218) blastocysts. Lower LBR was observed in recipients having SET and who received estrogen supplementation of <10 days (OR = 0.72; P = 0.02). Implantation rate and clinical pregnancy rate also improved significantly with endometrial thickness, but there was no change in clinical abortion rate and ectopic pregnancy rate. CONCLUSIONS: After minimizing the possible oocyte factor by including only donor oocytes and that of COH using a uniform HRT protocol, LBR improved with each millimeter increase in endometrial thickness starting from 6 mm. Shorter duration of estrogen supplementation (<10 days) reduced the chances of live birth in recipients after transfer of a single blastocyst.

International Committee for Monitoring Assisted Reproductive Technologies (ICMART): world report on assisted reproductive technologies, 2013.

OBJECTIVE: To report the utilization, effectiveness, and safety of practices in assisted reproductive technology (ART) globally in 2013 and assess global trends over time. DESIGN: Retrospective, cross-sectional survey on the utilization, effectiveness, and safety of ART procedures performed globally during 2013. SETTING: Seventy-five countries and 2,639 ART clinics. PATIENT(S): Women and men undergoing ART procedures. INTERVENTION(S): All ART. MAIN OUTCOME MEASURE(S): The ART cycles and outcomes on country-by-country, regional, and global levels. Aggregate country data were processed and analyzed based on methods developed by the International Committee for Monitoring Assisted Reproductive Technology (ICMART). RESULT(S): A total of 1,858,500 ART cycles were conducted for the treatment year 2013 across 2,639 clinics in 75 participating countries with a global participation rate of 73.6%. Reported and estimated data suggest 1,160,474 embryo transfers (ETs) were performed resulting in >344,317 babies. From 2012 to 2013, the number of reported aspiration and frozen ET cycles increased by 3% and 16.4%, respectively. The proportion of women aged >40 years undergoing nondonor ART increased from 25.2% in 2012 to 26.3% in 2013. As a percentage of nondonor aspiration cycles, intracytoplasmic sperm injection (ICSI) was similar to results for 2012. The in vitro fertilization (IVF)/ICSI combined delivery rates per fresh aspiration and frozen ET cycles were 24.2% and 22.8%, respectively. In fresh nondonor cycles, single ET increased from 33.7% in 2012 to 36.5% in 2013, whereas the average number of transferred embryos was 1.81-again with wide country variation. The rate of twin deliveries after fresh nondonor transfers was 17.9%; the triplet rate was 0.7%. In frozen ET cycles performed in 2013, single ET was used in 57.6%, with an average of 1.49 embryos transferred and twin and triplet rates of 10.8% and 0.4%, respectively. The cumulative delivery rate per aspiration was 30.4%, similar to that in 2012. Perinatal mortality rate per 1,000 births was 22.2% after fresh IVF/ICSI and 16.8% after frozen ET. The data presented depended on the quality and completeness of the data submitted by individual countries. This report covers approximately two-thirds of world ART activity. Continued efforts to improve the quality and consistency of reporting ART data by registries are still needed. CONCLUSION(S): Reported ART cycles, effectiveness, and safety increased between 2012 and 2013 with adoption of a better method for estimating unreported cycles.

The Influence of Delayed Blastocyst Development on the Outcome of Frozen-Thawed Transfer of Euploid and Untested Embryos.

OBJECTIVE: The primary objective is to compare live birth rates (LBRs) following frozen embryo transfer (FET) of euploid day 5 with day 6 blastocysts. We also compared LBRs following FET of untested blastocysts vitrified on day 5 and day 6 in self-oocyte and ovum donation (OD) cycles. DESIGN: This was a retrospective observational study. SETTING: Nova IVF Fertility, Ahmedabad. MATERIALS AND METHODS: Ninety-seven FET using self-oocytes following preimplantation genetic testing A (PGT-A), 464 FET following OD, and 907 FET using self-oocytes without PGT-A testing between January 2016 and December 2017 were included in this study. MAIN OUTCOME MEASURES: LBR following FET in day 5 versus day 6 blastocysts in euploid embryos using self-oocytes and in untested embryos using both self and donor oocytes. RESULTS: In PGT-A cycles, no statistically significant difference was observed in LBRs following transfer of euploid blastocysts developed on day 5 or day 6 (D5: 53%; D6:40%, P = 0.83). However, the LBRs with day 5 blastocysts were higher compared with day 6 group in untested group using both self and donor oocytes (self D5: 52.7%; D6: 38.2%; P = 0.001 and OD D5: 44.7%; D6: 29.8%; P = 0.001). Miscarriage rates were comparable in both the groups. CONCLUSIONS: The present study demonstrated comparable pregnancy outcomes following FET of euploid embryos vitrified on day 5 and day 6. However, higher LBRs were reported in day 5 group in untested embryos.

Maternal and Neonatal Complications in Twin Deliveries as Compared to Singleton Deliveries following In vitro Fertilization.

BACKGROUND: Twin pregnancy is an iatrogenic complication following in vitro fertilization (IVF) that can be decreased using elective single-embryo transfer. However, the risks associated with twin pregnancy following IVF as compared to singleton IVF pregnancy need to be further evaluated. AIM: This study aims to compare the maternal, perinatal, and neonatal complications in singleton and twin pregnancies following IVF-intracytoplasmic sperm injection (ICSI). Settings and Design: Retrospective observational cohort study using previously collected routine patient data. MATERIALS AND METHODS: Singleton and twin deliveries following IVF/ICSI from January 2014 to August 2015 were included. Data were collected from patient records and the obstetricians of the patients. STATISTICAL ANALYSIS USED: SPSS was used for analysis. Student's t-test and Fisher's exact test were used for continuous and categorical data, respectively. Significance was kept at 0.05. RESULTS: There were 897 singleton and 382 twin deliveries (total of 1661 babies). The mean gestational age at delivery was lower in twin deliveries (34.9 ± 3.1 weeks) as compared to singleton deliveries (36.8 ± 3.2 weeks, P < 0.001). The overall incidence of maternal complications was higher in twin pregnancies (29.3% vs. 21.3%, odds ratio = 1.53, 95% confidence interval = 1.17-2.01; P = 0.003). The mean birth weight of babies was significantly lower (2.02 ± 0.58 kg vs. 2.71 ± 0.68 kg; P < 0.001) and the incidence of stillbirth plus neonatal death was higher (7.5% vs. 4.6%, P = 0.01) in the twin group as compared to the singleton group. CONCLUSION: Twin deliveries, following IVF/ICSI deliver at lower gestational age, have lower birth weight and have higher odds of stillbirth plus neonatal death as compared to singleton deliveries following IVF/ICSI.

India's First Child using PGT-M, PGT-A and HLA Matching for Helping a Sibling having ß-Thalassemia Major.

ß-thalassemia is a common single-gene disorder in India, with hematopoietic stem cell transplantation (HSCT) being the only cure. HSCT with matched unrelated donor is less successful, whereas finding a human leukocyte antigen (HLA)-matched related donor is difficult. Preimplantation genetic testing for monogenic diseases (PGT-M) with HLA matching is a novel option to have a matched sibling for HSCT for couples having an affected child. We present the first such case report in India. A couple, both carriers of ß-thalassemia and having an affected son, underwent PGT-M with HLA matching combined with preimplantation genetic testing for aneuploidies of embryos to have a ß - thalassemia-free child. This resulted in birth of a 10/10 HLA-matched sibling.