International Committee for Monitoring Assisted Reproductive Technology world report: assisted reproductive technology, 2015 and 2016.

OBJECTIVE: To report utilization, effectiveness, and safety of assisted reproductive technologies in 2015 and 2016. DESIGN: Retrospective, cross-sectional survey of 3103 assisted reproductive technology clinics in 74 countries in 2015 and 3249 clinics in 79 countries in 2016 that submitted cycle and pregnancy outcome data through national and regional registries. SUBJECTS: Patients undergoing assisted reproductive technology procedures. EXPOSURE: Assisted reproductive technology. MAIN OUTCOME MEASURES: Outcomes on country, regional, and global levels. RESULTS: Reported for 2015: 2,358,239 cycles with 548,652 babies born; for 2016: 2,807,963 cycles with 647,188 babies born. Estimated in 2015, ≥2,683,677 cycles resulted in >675,134 babies; in 2016, ≥3,100,448 cycles resulted in ≥723,026 babies. Reported cycles represent approximately 80% of global utilization. In 2015 and 2016, 27.6% and 27.8%, respectively, of women undergoing fresh autologous cycles were age ≥40 years. Frozen-thawed embryo transfer cycles accounted for 47.0% and 51.9%, respectively, of all embryo transfers in 2015 and 2016. Oocyte donation cycles accounted for 6.7% and 7.1% of all embryo transfers in 2015 and 2016. Intracytoplasmic sperm injection was performed in 57.7% and 56.4% of autologous aspiration cycles in 2015 and 2016, respectively. The cumulative delivery rate per aspiration cycle for fresh and frozen-thawed embryo transfer was 32.4% in 2015 and 33.1% in 2016, respectively. The average number of transferred embryos was 1.70 in 2015 and 1.69 in 2016. The proportion of single embryo transfers in fresh autologous cycles increased from 42.1% in 2015 to 44.0% in 2016. The twin delivery rate decreased from 16.0% in 2015 to 14.7% in 2016, and the triplet rate decreased from 0.6% in 2015 to 0.4% in 2016. The proportion of single embryo transfers in frozen-thawed embryo transfer autologous cycles was 62.2% in 2015 and 64.2% in 2016, with twin and triplet rates of 10.1% and 0.3% in 2015 and 10.0% and 0.2% in 2016, respectively. CONCLUSION: Utilization of assisted reproductive technology and births per cycle increased from 2015 to 2016 while multiple births were reduced . Increasing proportion of frozen-thawed embryo transfer cycles, continuing wide variation in use of intracytoplasmic sperm injection, and increase in single embryo transfer rates are reported.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The POSEIDON Criteria and Its Measure of Success Through the Eyes of Clinicians and Embryologists.

This article represents a viewpoint on the POSEIDON criteria by a group of clinicians and embryologists. Its primary objective is to contextualize the Poseidon criteria and their metric of success for the relevant Frontiers Research Topic "POSEIDON's Stratification of Low Prognosis Patients in ART: The WHY, the WHAT, and the HOW". "Low prognosis" relates with reduced oocyte number, which can be associated with low or sometimes a normal ovarian reserve and is aggravated by advanced female age. These aspects will ultimately affect the number of embryos generated and consequently, the cumulative live birth rate. The novel system relies on female age, ovarian reserve markers, ovarian sensitivity to exogenous gonadotropin, and the number of oocytes retrieved, which will both identify the patients with low prognosis and stratify such patients into one of four groups of women with "expected" or "unexpected" impaired ovarian response to exogenous gonadotropin stimulation. Furthermore, the POSEIDON group introduced a new measure of clinical success in ART, namely, the ability to retrieve the number of oocytes needed to obtain at least one euploid blastocyst for transfer in each patient. Using the POSEIDON criteria, the clinician can firstly identify and classify patients who have low prognosis in ART, and secondly, aim at designing an individualized treatment plan to maximize the chances of achieving the POSEIDON measure of success in each of the four low prognosis groups. The novel POSEIDON classification system is anticipated to improve counseling and management of low prognosis patients undergoing ART, with an expected positive effect on reproductive success and a reduction in the time to live birth.

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.

Anxiety and Stress at Different Stages of Treatment in Women Undergoing In vitro Fertilization-Intracytoplasmic Sperm Injection.

AIM: The aim of the present study is to evaluate the state anxiety (the present state of mind), trait anxiety (general anxiety), as well as perceived stress in women undergoing in vitro fertilization (IVF) treatment at three stages: T1 (on the day of start of stimulation), T2 (on the day of embryo transfer), and T3 (10 days after embryo transfer). The data at T3 level were collected telephonically. METHODOLOGY: The present study was carried out on 137 women undergoing IVF intracytoplasmic sperm injection cycle at four different clinics of four cities from October to April 2016. State-trait anxiety inventory (Spielberger) and perceived stress scale (Okun, et al.) were used as the tools. STATISTICAL ANALYSIS: The analysis was done at two levels; descriptive and inferential (analysis of variance [ANOVA], Student's t-test, Levene's test) using SPSS v16. RESULTS: The state anxiety was higher at all the three levels than trait anxiety. The overt anxiety was highest at T3 level (mean = 45.77) followed by T1 level (mean = 44.23) and T2 level (mean = 43.04). Perceived stress was elevated at T1 level (mean = 17.93) followed by T3 level (mean = 17.28) and T2 level (mean = 16.72). The results of ANOVA showed a significant difference in anxiety among all the three levels (P = 0.036), but no significant difference was found for perceived stress (P = 0.169). t-test revealed that there was a significant difference between state and trait anxiety at T1, T2, and T3 levels (P = 0.01, P = 0.21, P = 0.00, respectively). A significant difference was only seen between the T1 and T2 levels in perceived stress (P = 0.052). In state anxiety, a significant difference was observed only between T2 and T3 levels (P = 0.23). CONCLUSION: It was observed that anxiety and stress are present in women throughout the treatment. The waiting period (T3) is the most anxious for them and their level of state anxiety is higher compared to their trait anxiety. Perceived stress is observed to be more on the day of start of stimulation followed by the waiting period.

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.