Gender inequality and utilization of ART: an international cross-sectional and longitudinal analysis.

STUDY QUESTION: What is the association between a country's level of gender equality and access to ART, as measured through ART utilization? SUMMARY ANSWER: ART utilization is associated with a country's level of gender equality even after controlling for the level of development. WHAT IS KNOWN ALREADY: Although gender equality is recognized as an important determinant of population health, its association with fertility care, a highly gendered condition, has not been explored. STUDY DESIGN, SIZE, DURATION: A longitudinal cross-national analysis of ART utilization in 69 countries during 2002-2014 was carried out. PARTICPANTS/MATERIALS, SETTING, METHODS: The Gender Inequality Index (GII), Human Development Index (HDI), and their component indicators were modelled against ART utilization using univariate regression models as well as mixed-effects regression methods (adjusted for country, time, and economic/human development) with multiple imputation to account for missing data. MAIN RESULTS AND THE ROLE OF CHANCE: ART utilization is associated with the GII. In an HDI-adjusted analysis, a one standard deviation decrease in the GII (towards greater equality) is associated with a 59% increase in ART utilization. Gross national income per capita, the maternal mortality ratio, and female parliamentary representation were the index components most predictive of ART utilization. LIMITATIONS, REASONS FOR CAUTION: Only ART was used rather than all infertility treatments (including less costly and non-invasive treatments such as ovulation induction). This was a country-level analysis and the results cannot be generalized to smaller groups. Not all modelled variables were available for each country across 2002-2014. WIDER IMPLICATIONS OF THE FINDINGS: Access to fertility care is central to women's sexual and reproductive health, to women's rights, and to human rights. As gender equality improves, so does access to ART. This relation is likely to be reinforcing and bi-directional, with progress towards global, equitable access to fertility care also improving women's status and participation in societies. STUDY FUNDING/COMPETING INTEREST(S): External funding was not provided for this study. G.D.A. declares consulting fees from Labcorp and CooperSurgical. G.D.A. is the founder and CEO of Advanced Reproductive Care, Inc., as well as the Chair of the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) and the World Endometriosis Research Foundation, both of which are unpaid roles. G.M.C. is an ICMART Board Representative, which is an unpaid role, and no payments are received from ICMART to UNSW, Sydney, or to G.M.C. to undertake this study. O.F., S.D., F.Z.-H., and E.K. report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

COVID-19-related uncertainty: fertility staff experiences of its sources, processing, responses, and consequences.

STUDY QUESTION: What are fertility staff experiences of managing COVID-19-related uncertainty after fertility clinics re-opened? SUMMARY ANSWER: Staff identified many COVID-19-related uncertainty sources, the main being the COVID-19 health threat, to which most clinics and staff responded effectively by implementing safety protocols and building strong collaborative environments that facilitated the acquisition and application of information to guide organizational responses during a rapidly changing situation, but with costs for staff and patients. WHAT IS KNOWN ALREADY: COVID-19 created significant disruption in fertility care delivery, including temporary clinic closure and treatment delay. Patients experienced significant distress, including concerns regarding the impact of COVID-19 and its vaccine on fertility and pregnancy. Multiple studies show that COVID-19-related uncertainty is a major threat and burden for healthcare staff, but this has not been investigated in reproductive medicine. STUDY DESIGN, SIZE, DURATION: A cross-sectional, online mixed-method bilingual (English, Spanish) survey (active 25 January-23 May 2021) was distributed to fertility staff across the UK, Latin America, and Africa. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligibility criteria were being a healthcare worker at a fertility clinic that had re-opened since its COVID-19-related closure, 18 years of age or older and ability to respond in English or Spanish. The survey was created in English, translated to Spanish, made available using Qualtrics, and consisted of four parts: (i) background and physical and mental wellbeing, (ii) open-ended questions regarding COVID-19 uncertainty, (iii) appraisal items regarding perceptions and impact of uncertainty, and (iv) changes in the workplace. The British Fertility Society and the African Network and Registry of Assisted Reproduction circulated the survey across the UK and Africa via email hyperlinks and social media platforms. The Argentinian Society of Reproductive Medicine and the Latin American Network of Assisted Reproduction distributed the survey across Latin America in the same manner. Thematic analysis was performed on responses from open-ended question to produce basic codes. Deductive coding grouped sub-themes across questions into themes related to the theory of uncertainty management. Descriptive statistics and repeated measures analysis of variance were used on the quantitative data. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 382 staff consented to the survey, 107 did not complete (28% attrition), and 275 completed. Sixty-three percent were women, 69% were physicians, and 79% worked at private clinics. Thematic analysis produced 727 codes, organized in 92 sub-themes, and abstracted into 18 themes and one meta-theme reflecting that uncertainty is stressful but manageable. The types of uncertainties related to the threat of COVID-19 (20.6%), unpredictability of the future (19.5%), failure of communication (11.4%), and change in the workplace (8.4%). Staff appraisals of negative and positive impact of uncertainty were significantly lower (P < 0.001) than appraisals of stress, controllability, and having what it takes to cope with uncertainty. To process uncertainty, clinics focused on information dissemination (30.8%) and building a collaborative work environment (5.8%), while staff employed proactive coping (41.8%) and emotional and cognitive processing (9.6%). Main organizational responses consisted on work restructuring (41.3%, e.g. safety protocols), adapting to adversity (9.5%, e.g. supplies, preparation), and welfare support (13.8%), though staff perceived lack of support (17.5%). Negative consequences of uncertainty were worse self- and patient welfare (12.1%) and worse communication due to virtual medicine and use of mask (9.6%). Positive consequences were work improvements (8.3%), organizational adaptation (8.3%), improved relationships (5.6%), and individual adaptation (3.2%). Ninety-two percent of participants thought changes experienced in the workplace due to COVID-19 were negative, 9.1% nor negative nor positive, and 14.9% positive. Most staff thought that their physical (92.4%) and mental health (89.5%) were good to excellent. LIMITATIONS, REASONS FOR CAUTION: Participants were self-selected, and most were physicians and embryologists working at private clinics based in Latin America. The study did not account for how variability in national and regional COVID-19 policy shaped staff experiences of uncertainty. WIDER IMPLICATIONS OF THE FINDINGS: To address COVID-19 uncertainty, clinics need to promote collaborative (clinic, staff, patients) processing of uncertainty, clear team coordination and communication, organizational flexibility, and provision of support to staff and patients, with an emphasis on cognitive coping to decrease threat of and increase tolerance to uncertainty. Uncertainty management interventions bespoke to fertility care that integrate these components may increase clinics resilience to COVID-19-related and other types of uncertainty. STUDY FUNDING/COMPETING INTERESTS: Cardiff University funded this research. S.G. reports consultancy fees from Ferring Pharmaceuticals A/S, speaker fees from Access Fertility, SONA-Pharm LLC, Meridiano Congress International, and Gedeon Richter, and grants from Merck Serono Ltd. F.Z.-H. reports speaker fees from Ferring Pharmaceuticals A/S and that he is a chair of the Latin American Registry of ART, Committee of Ethic and Public Policies, and Chilean Society of Obstetrics and Gynecology and a vice chair of the International Committee for monitoring ART. K.A., N.C., G.B., and J.B. report no conflict in relation to this work. TRIAL REGISTRATION NUMBER: N/A.

ART in Latin America: the Latin American Registry, 2020.

RESEARCH QUESTION: What was the utilization, effectiveness and safety of assisted reproductive technology (ART) in Latin America during 2020? DESIGN: Retrospective collection of multinational data on ART performed by 188 institutions in 16 countries. RESULTS: Overall, 87,732 initiated cycles resulted in 12,778 deliveries and 14,582 births. The major contributors were Brazil (46.0%), Mexico (17.0%) and Argentina (16.8%). However, the highest utilization (cycles/million inhabitants) was Uruguay with 558, followed by Argentina with 490 and Panama with 425 cycles/million. Globally, women aged ≥40 years increased to 34% while women ≤34 dropped to 24.7%. After removing freeze-all cycles, the delivery rate per oocyte retrieval was 14.8% for intracytoplasmic sperm injection and 15.6% for IVF. Single-embryo transfer (SET) represented 38.3% of all fresh transfers, with delivery rate per transfer of 20.0%; this increased to 32.4% for elective SET (eSET) and 34.2% for blastocyst eSET, compared with blastocyst elective double embryo transfer (eDET) of 37.9%. However, multiple births increased from 1% in eSET to 30.5% in eDET. Perinatal mortality increased from 7.7‰ in singletons to 24.4‰ in twins and 64.0‰ in triplets. Frozen embryo transfer (FET) represented 66.6% of all transfers, with a delivery rate/transfer of 29.0%, significantly higher than 23.9% after fresh transfers at all ages (P < 0.0001). Preimplantation genetic testing, reported in 8920 cycles, significantly improved delivery rate and decreased miscarriage rates at all ages (P ≤ 0.041), including oocyte donation (P = 0.002). Endometriosis was diagnosed in 28.3% of cases. The delivery rate in 5779 women after removal of peritoneal endometriosis was significantly better than tubal and endocrine factors in women aged 35-39 (P = 0.0004) and women aged ≥40 (P = 0.0353). CONCLUSIONS: Systematic collection and analysis of big data in a south-south cooperation model allow regional growth by implementing evidence-based reproductive decisions.

Assisted reproductive technologies in Latin America: the Latin American Registry, 2019.

RESEARCH QUESTION: What was the utilization, effectiveness and safety of assisted reproductive technology (ART) in Latin America during 2019? DESIGN: This was a retrospective collection of multinational data on ART performed at 196 institutions from 15 countries. RESULTS: A total of 106,918 initiated cycles, 18,133 deliveries and 21,096 births were reported. ART utilization was 24-558 cycles per million inhabitants. Women aged ≥40 years represented 32.9% of fresh IVF and intracytoplasmic sperm injection (ICSI) cycles. After removing freeze-all cycles, the delivery rate per oocyte retrieval was 17.3% for ICSI and 19.5% for IVF. Overall, single-embryo transfer (SET) represented 36.2% of fresh transfers, with a 19.5% delivery rate per transfer, increasing to 30.7% for elective SET and 32.7% for blastocyst elective SET (eSET). The delivery rate for double-embryo transfers (DET) was 27.8%, increasing to 37.1% after elective DET. This 6.4% increment in deliveries between eSET and elective DET resulted in a 12-fold increase in twin births. Furthermore, overall perinatal mortality was more than two-fold higher for twin compared with singleton deliveries. The delivery rate for frozen-thawed SET reached 28.1%, most being blastocyst transfers. Of all births, 72.3% were singletons, 26.4% twins and 1.3% triplets and higher multiples. Preterm deliveries reached 14.3% for singletons and 58.1% for twins. Perinatal mortality was 7.4‰ in singletons, 17.2‰ for twins and 62.9‰ for triplets or higher. CONCLUSIONS: The number of initiated cycles has slowly increased in countries with laws or regulations facilitating access. FET cycles predominate and blastocyst SET are also increasing. The data show that, especially in young women and oocyte recipients, when there is more than one blastocyst for transfer, eSET should be the rule.

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.

Celebrating 30 years of ART in Latin America; and the 2018 report.

RESEARCH QUESTION: What are the trends in patient characteristics, effectiveness and safety of assisted reproductive technology (ART) performed in Latin America over the past three decades, as well as the detailed outcomes of procedures initiated in 2018? DESIGN: Retrospective collection of multinational data including epidemiology and outcomes of ART performed between 1990 and 2018. RESULTS: Over these 30 years we report 955,117 initiated cycles, 191,191 deliveries and 238,045 live births. In 1990, 66.5% of women were ≤34 years and 8.7% ≥40 years; in 2018, 26.4% of women were ≤34 years and 32.0% were ≥40 years. In 1990, 60.4% of transfers included ≥3 embryos, falling to 13.5% in 2018, and single embryo transfer (SET) increased from 13.8% to 30.4% between 1990 and 2018. Delivery rate per fresh transfer increased from approximately 17% in the 1990s to 25% in 2018, with a meaningful drop in high-order multiples, from 5-9% in the 1990s to 0.4% in 2018. This drop is associated with increasing use of frozen embryo transfer (FET) (57% in 2018) compared with 10% in 2000. In 2018, delivery rate in FET was 28.3%, reaching 31.2% in freeze-all cycles; and the cumulative live birth rate (fresh + FET) was 41.9%. Elective SET also increased, from 0.9% in 2010 to 10% in 2018. The delivery rate in elective SET (31.7%) was only 5.4% lower than elective double embryo transfer (DET) (37.1%); however, multiple births increased from 2.1% to 25.5% twins and 0.4% triplets in elective DET. CONCLUSION: The Latin American Registry of Assisted Reproduction (RLA) celebrates 30 years of voluntary reporting from a total of nearly 200 centres in 15 countries. This South-South Cooperation network has proven to be an efficient and safe system for technological transfer and regional growth.

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.

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.

Assisted reproductive technology in Latin America: the Latin American Registry, 2017.

RESEARCH QUESTION: What was the utilization, effectiveness and safety of assisted reproductive technologies (ART) carried out in Latin America during 2017. DESIGN: Retrospective collection of multinational data on ART carried out in 188 institutions from 15 Latin American countries. RESULTS: In this study, 93,600 initiated cycles, 16,976 deliveries and 20,404 births reported. Utilization of ART was 221 cycles per million inhabitants (15 to 535). Women aged 40 years and above represented 30.5% of fresh IVF and intracytoplasmic sperm injection (ICSI); however, after removing freeze-all cycles, delivery rate per oocyte retrieval was 19.9% for ICSI and 20.2% for IVF. Overall, single embryo transfer (SET) represented 26.9% of fresh transfers, with 18.2% delivery rate per transfer, increasing to 32.3% in elective SET. Delivery rate in double embryo transfers (DET) was 28.3% increasing to 37.3% with elective DET. This 5% increment in births in elective DET over elective SET resulted in a tenfold increase in twin births, gestational periods almost 3 weeks' shorter and a threefold increase in perinatal mortality. Delivery rate in frozen-thawed SET reached 25.5% increasing to 30.8% with DET, most being blastocyst transfers. Of all births, 66.9% were singletons, 31.4% twins and 1.6% triplets and higher. Overall, preterm deliveries reached 9.5% in singletons, 64.3% in twins and 97.9% in triplets; perinatal mortality was 9.4‰ in singletons, 25.3‰ in twins and 63.3‰ in high-order multiples. CONCLUSIONS: The number of initiated cycles has slowly increased. Frozen embryo transfers, blastocyst transfers and SET are also increasing. Our data show that, especially in young women and oocyte recipients, when there is more than one blastocyst for transfer, elective SET should be the rule.

Assisted reproductive techniques in Latin America: the Latin American Registry 2016.

RESEARCH QUESTION: What was the utilization, effectiveness and perinatal outcome of assisted reproductive technologies (ART) performed in Latin America during 2016? DESIGN: Retrospective collection of multinational data on ART performed in 178 institutions from 15 Latin American countries. RESULTS: This paper reports on 85,474 initiated cycles, 15,070 deliveries and 18,182 babies born in this period. Of all fresh autologous IVF/intracytoplasmic sperm injection (ICSI) cycles, 40.9% were performed in women aged 35-39 years, and 31.1% in women aged ≥40 years. After removing freeze-all cycles, delivery rate per oocyte retrieval was 20.31% for ICSI and 21.85% for IVF. Fresh single embryo transfer including all age categories represented 22.96%, with a 15.35% delivery rate per transfer. Double embryo transfer represented 61.58% of transfers, with a 27.62% delivery rate per transfer. Multiple births included 18.12% twins and 0.55% triplets and higher. In oocyte donation, delivery rate per transfer was 32.89%, with a twin and triplet rate of 23.48% and 0.73%, respectively. Overall, preterm deliveries reached 17.11% in singletons, 65.69% in twins and 95.51% in triplets. Perinatal mortality was 8.0‰ in singletons, 19.0‰ in twins, and 62.3‰ in high-order multiples. CONCLUSIONS: The number of initiated cycles continues to increase. Compared with previous years, the number of embryos transferred decreased while the proportion of single embryo transfers increased with a drop in multiple births. It is vital to motivate health care providers and consumers to continue this trend.

Assisted reproductive techniques in Latin America: the Latin American Registry, 2015.

RESEARCH QUESTION: What was the utilization, effectiveness and safety of assisted reproductive technologies (ART) performed in Latin American countries during 2015, and what were the regional trends? DESIGN: Retrospective collection of multinational data on assisted reproduction techniques (IVF and intracytoplasmic sperm injection [ICSI], frozen embryo transfer, oocyte donation, preimplantation genetic testing and fertility preservation), from 175 institutions in 15 Latin American countries. RESULTS: In total, 41.25% of IVF/ICSI cycles were performed in women aged 35-39 years, and 28.35% in women aged ≥40 years. After removing freeze-all cycles, delivery rate per oocyte retrieval was 21.39% for ICSI and 24.29% for IVF. Multiple births included 19.58% twins and 0.95% triplets and higher. In oocyte donation, delivery rate per transfer was 36.77%, with a twin and triplet rate of 27.65% and 1.06%, respectively. Overall, preterm deliveries reached 17.38% in singletons, 64.94% in twins and 98.41% in triplets. Perinatal mortality in 14,936 births and 18,391 babies born was 10.5 per 1000 in singletons, 17.9 per 1000 in twins, and 57.1 per 1000 in high-order multiples. Elective single embryo transfer represented 3.11% of fresh transfers, with a 31.78% delivery rate per transfer. Elective double embryo transfer represented 23.3% of transfers, with a 37.79% delivery rate per transfer. Out of 18,391 babies born, 63.22% were singletons, 34.4% twins, and 2.38% triplets and higher. CONCLUSIONS: Given the effect of multiple births on prematurity, morbidity and perinatal mortality, reinforcing the existing trend of reducing the number of embryos transferred remains mandatory.

Endometriosis does not affect live birth rates of patients submitted to assisted reproduction techniques: analysis of the Latin American Network Registry database from 1995 to 2011.

PURPOSE: The purpose of this study is to compare the results of ART treatment in patients with and without endometriosis in a large cohort of patients from different centers over an extented period of time. METHODS: This retrospective study is using data from patients undergoing 27,294 cycles of IVF/ICSI treatment between 1995 and 2011 that were registered in the database of the Latin American Registry maintained by the Latin America Network of Assisted Reproduction. RESULTS: The mean number of retrieved oocytes was higher in the control group, but the mean number of metaphase II oocytes was similar. Fertilization rate and transfer rate were higher in the control group. We observed higher pregnancy rates, per cycle initiated and per embryo transfer and higher live birth rate in the endometriosis group. In the group of patients with 25-35 years old, the number of oocytes, fertilization rate, and number of transferred embryos were significantly higher in the control group. However, pregnancy rate and live birth rate were higher in the endometriosis group. In the group of patients with 36-40 years old, the number of transferred embryos was higher in the control group, but the pregnancy rate and live birth rate were higher in the endometriosis group. In the group of patients with 41 to 42 years old, the number of transferred embryos and the transfer rate were higher in the control group, but the pregnancy rate was higher in the endometriosis group. CONCLUSION: Our results demonstrate that endometriosis does not affect the outcome of patients subjected to IVF/ICSI and although patients with endometriosis present lower number of oocytes and higher cancelation rate, these shortcomings do not reduce pregnancy and live birth rates.

The International Glossary on Infertility and Fertility Care, 2017.

STUDY QUESTION: Can a consensus and evidence-driven set of terms and definitions be generated to be used globally in order to ensure consistency when reporting on infertility issues and fertility care interventions, as well as to harmonize communication among the medical and scientific communities, policy-makers, and lay public including individuals and couples experiencing fertility problems? SUMMARY ANSWER: A set of 283 consensus-based and evidence-driven terminologies used in infertility and fertility care has been generated through an inclusive consensus-based process with multiple stakeholders. WHAT IS KNOWN ALREADY: In 2006 the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) published a first glossary of 53 terms and definitions. In 2009 ICMART together with WHO published a revised version expanded to 87 terms, which defined infertility as a disease of the reproductive system, and increased standardization of fertility treatment terminology. Since 2009, limitations were identified in several areas and enhancements were suggested for the glossary, especially concerning male factor, demography, epidemiology and public health issues. STUDY DESIGN, SIZE, DURATION: Twenty-five professionals, from all parts of the world and representing their expertise in a variety of sub-specialties, were organized into five working groups: clinical definitions; outcome measurements; embryology laboratory; clinical and laboratory andrology; and epidemiology and public health. Assessment for revisions, as well as expansion on topics not covered by the previous glossary, were undertaken. A larger group of independent experts and representatives from collaborating organizations further discussed and assisted in refining all terms and definitions. PARTICIPANTS/MATERIALS, SETTING, METHODS: Members of the working groups and glossary co-ordinators interacted through electronic mail and face-to-face in international/regional conferences. Two formal meetings were held in Geneva, Switzerland, with a final consensus meeting including independent experts as well as observers and representatives of international/regional scientific and patient organizations. MAIN RESULTS AND THE ROLE OF CHANCE: A consensus-based and evidence-driven set of 283 terminologies used in infertility and fertility care was generated to harmonize communication among health professionals and scientists as well as the lay public, patients and policy makers. Definitions such as 'fertility care' and 'fertility awareness' together with terminologies used in embryology and andrology have been introduced in the glossary for the first time. Furthermore, the definition of 'infertility' has been expanded in order to cover a wider spectrum of conditions affecting the capacity of individuals and couples to reproduce. The definition of infertility remains as a disease characterized by the failure to establish a clinical pregnancy; however, it also acknowledges that the failure to become pregnant does not always result from a disease, and therefore introduces the concept of an impairment of function which can lead to a disability. Additionally, subfertility is now redundant, being replaced by the term infertility so as to standardize the definition and avoid confusion. LIMITATIONS, REASONS FOR CAUTION: All stakeholders agreed to the vast majority of terminologies included in this glossary. In cases where disagreements were not resolved, the final decision was reached after a vote, defined before the meeting as consensus if passed with 75%. Over the following months, an external expert group, which included representatives from non-governmental organizations, reviewed and provided final feedback on the glossary. WIDER IMPLICATIONS OF THE FINDINGS: Some terminologies have different definitions, depending on the area of medicine, for example demographic or clinical as well as geographic differences. These differences were taken into account and this glossary represents a multinational effort to harmonize terminologies that should be used worldwide. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A.

The impact of endometriosis on the outcome of Assisted Reproductive Technology.

BACKGROUND: Endometriosis has been described to impair fertility through various mechanisms. However, studies evaluating the reproductive outcomes of women undergoing assisted reproductive technologies show controversial results. The aim of this study is to assess whether the reproductive outcome is impaired among women with endometriosis-associated infertility undergoing IVF. METHODS: A retrospective cohort study was performed, including women undergoing IVF reported by the Red Latinoamericana de Reproduccion Asistida (Redlara) registry, between January 2010 and December 2012. The study group included women with endometriosis-associated infertility, and the control group women with tubal factor, endocrine disorders or unexplained infertility. Women above 40 years, severe male factor and premature ovarian failure were excluded. The reproductive outcomes of between both groups were compared. The primary outcome was live birth. Secondary outcomes included clinical pregnancy, miscarriage, number of oocytes retrieved and number of fertilized oocytes. Outcomes were assessed after the first fresh IVF cycle, and were adjusted for age and number of embryos transferred. RESULTS: A total of 22.416 women were included (3.583 with endometriosis and 18.833 in the control group). Mean age of patients in the endometriosis group and control group was 34.86 (3.47) and 34.61 (3.91) respectively, p = 0.000. The mean number of oocytes retrieved were 8.89 (6.23) and 9.86 (7.02) respectively, p = 0.000. No significant differences were observed between groups in terms of live birth (odds ratio (OR) 1.032, p = 0.556), clinical pregnancy (OR 1.044, p = 0.428) and miscarriage rates (OR 1.049, p = 0.623). Women with endometriosis had significantly lower number of oocytes retrieved (incidence risk ratio (IRR) 0.917, 95% CI 0.895-0.940), however, the number of fertilized oocytes did not differ among the two groups when adjusting for the number of oocytes retrieved (IRR 1.003, p = 0.794). An age-stratified analysis was performed, and no differences were observed in the reproductive outcomes between groups for women aged under 35 and 35 to 40. CONCLUSIONS: Reproductive outcomes among women undergoing IVF and diagnosed with endometriosis-associated infertility do not differ significantly from women without the disease. Although women with endometriosis generate fewer oocytes, fertilization rate is not impaired and the likelihood of achieving a live birth is also not affected.

Assisted reproduction techniques in Latin America: the Latin American Registry, 2014.

Multinational data on assisted reproduction techniques (IVF and intractytoplasmic sperm injection [ICSI], frozen embryo transfer, oocyte donation, preimplantation genetic diagnosis and fertility preservation) were collected from 159 institutions in 15 Latin American countries. A total of 41.34% of IVF-ICSI cycles were conducted in women aged 35-39 years and 23.35% in women aged 40 years and older. After removing freeze-all cases, delivery rate per oocyte retrieval was 25.05% for ICSI and 27.41% for IVF. Multiple births included 20.78% twins and 0.92% triplets and over. In oocyte donation, twins reached 28.93% and triplets 1.07%. Preterm deliveries reached 16.4% in singletons, 55.02% in twins and 76% in triplets. Perinatal mortality in 18,162 births was 23 per 1000 in singletons, 35 per 1000 in twins, and 36 per 1000 in high-order multiples. Elective single embryo transfer represented 2.63% of fresh transfers, with a 32.15% delivery rate per transfer. Elective double embryo transfer represented 23.74% of transfers, with a 41.03% delivery rate per transfer; 11,373 babies (62.6%) were singletons; 6398 (35.2%) twins, and 391 (2.2%), triplets and more. Given the effect of multiple births on prematurity, morbidity and perinatal mortality, reinforcing the existing trend of reducing the number of embryos transferred is mandatory.

Assisted reproductive techniques in Latin America: the Latin American Registry, 2013.

Multinational data on assisted reproduction techniques undertaken in 2013 were collected from 158 institutions in 15 Latin American countries. Individualized cycle-based data included 57,456 initiated cycles. Treatments included autologous IVF and intracytoplasmic sperm injection (ICSI), frozen embryo transfers, oocyte donations. In autologous reproduction, 29.22% of women were younger than 35 years, 40.1% were 35-39 years and 30.6% were 40 years or older. Overall delivery rate per oocyte retrieval was 20.6% for ICSI and 25.4% for IVF. Multiple births included 20.7% for twins and 1.1% for triplets and over. In oocyte donations, twins reached 30% and triplets 1.4%. In singletons, pre-term births were 7.5%: 36.58% in twins and 65.52% in triplets. The relative risk for prematurity was 4.9 (95% CI 4.5 to 5.3) in twins and 8.7 (95% CI 7.6 to 10.0) in triplets and above. Perinatal mortality was 29.4 per 1000 in singletons, 39.9 per 1000 in twins and 71.6 per 1000 in high order multiples. Elective single embryo transfer represented only 2% of cycles, with delivery rate of 39.1% in women aged 34 years or less. Given the effect of multiple births and prematurity, it is mandatory to reduce the number of embryos transferred in the region.

Effect of embryo freezing on perinatal outcome after assisted reproduction techniques: lessons from the Latin American Registry of Assisted Reproduction.

Embryo cryopreservation is an integral part of assisted reproduction techniques; it allows the sequential transfer of all embryos, thus diminishing the risk of multiple pregnancies and associated perinatal complications. To address concerns about the safety of this procedure, neonatal outcome after 43,070 fresh embryo transfers was compared with 12,068 frozen-thawed embryo transfers (FET). After adjusting for maternal age, gestational age, embryo development at time of transfer, number of babies born and gestational order, FET was not found to be associated with an increase in perinatal mortality (odds ratio [OR] 1.72, 95% confidence interval [CI] 0.81 to 3.62); preterm birth (OR 1.05, 95% CI 0.93 to 1.18); or extreme preterm birth (OR 0.82, 95% CI 0.64 to 1.06). Furthermore, after correcting for known confounding factors, FET was found to be associated with an increase in neonatal weight of 39.7 g (95% CI 1.54 to 64.10; P < 0.0001). Embryo cryopreservation was, therefore, not associated with an increase in the risk of poor perinatal outcome.

Assisted reproductive technologies in Latin America: the Latin American Registry, 2012.

Multinational data on assisted reproduction technologies were collected from 155 institutions in 14 Latin American countries during 2012. Case-by-case data included 47,326 assisted reproduction technology cycles covering over 80% of cycles carried out in Latin America. Treatments included IVF, intracytoplasmic sperm injection (ICSI), frozen embryo transfers, oocyte donations and fertility preservation. Embryo transfer and IVF-ICSI was carried out in 39% of women aged 35-39 years and 31% of women aged 40 years or over. Delivery rate per oocyte retrieval was 20.9% for ICSI and 26.5% for IVF. Multiple births comprised 20.6% twins and 1.2% triplets and over. In oocyte donations, twins reached 27.8% and triplets and over 2.4%. Pre-term births in singletons were 14%. The relative risk of prematurity increased by 4.30 (95% CI 4.1 to 4.6) in twins and 43.8 (95% CI 28.5 to 67.4) in triplets and higher. Perinatal mortality increased from 25.2 per thousand in singletons to 44.4 in twins and 80.7 in triplets and over. Elective single embryo transfer was carried out in only 1.4%, of cycles, with a delivery rate of 30% in women 34 years or younger, and should be considered the way forward provided access is facilitated with public funding.