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.

Assisted reproductive technologies in Africa: The African Network and Registry for ART, 2020.

RESEARCH QUESTION: What were the utilization, effectiveness and safety of assisted reproductive technology (ART) in Africa during 2020? DESIGN: Cross-sectional, cycle-based and retrospective summary data were collected from voluntarily participating ART centres. RESULTS: During 2020, 37,063 ART procedures were reported by 67 centres in 15 countries. Autologous fresh transfers were predominant at 65.0%, whereas autologous frozen embryo transfers (FET) represented 26.2% and oocyte donation cycles remained less than 10%. Women undergoing autologous fresh embryo transfer had a mean age of 34.9 years and received a mean number of 2.4 embryos per transfer. The clinical pregnancy rate (CPR) per embryo transfer was 37.3% after fresh embryo transfer and 37.8% after frozen embryo transfer. The cumulative CPR per aspiration was 41.9% in autologous cycles. Most ART procedures resulted in a multiple delivery rate above 20%. After autologous ART, multiples were predominantly born preterm (twin and triplet deliveries 59.5% versus singleton 21.9% born before 37 weeks), with a substantially increased perinatal mortality compared with ART singletons (59.0‰ versus 22.2‰). Cycle-based data documented that elective single embryo transfer (eSET) provides the optimal balance of effectiveness (eSET CPR per embryo transfer 36.7%) and safety. CONCLUSION: This fourth report of the African Network and Registry for ART provides real-world evidence of ART utilization, practices and outcomes in Africa, which is relevant to many stakeholders. It critically informs and represents regional ART development based on national, regional and global cooperation.

The varying estimation of infertility in Ethiopia: the need for a comprehensive definition.

BACKGROUND: Infertility is a marginalized sexual and reproductive health issue in low-resource settings. Globally, millions are affected by infertility, but the lack of a universal definition makes it difficult to estimate the prevalence of infertility at the population level. Estimating the prevalence of infertility may inform targeted and accessible intervention, especially for a resource-limited country like Ethiopia. This study aims to estimate the prevalence of female infertility in Ethiopia using the Demographic and Health Survey (DHS) through two approaches: (i) the demographic approach and (ii) the current duration approach. METHODS: Data from 15,683 women were obtained through the 2016 Ethiopian DHS. The demographic approach estimates infertility among women who had been married/in a union for at least five years, had never used contraceptives, and had a fertility desire. The current duration approach includes women at risk of pregnancy at the time of the survey and determines their current length of time-at-risk of pregnancy at 12, 24, and 36 months. Logistic regression analysis estimated the prevalence of infertility and factors associated using the demographic approach. Parametric survival analysis estimated the prevalence of infertility using the current duration approach. All estimates used sampling weights to account for the DHS sampling design. STATA 14 and R were used to perform the statistical analysis. RESULTS: Using the demographic definition, the prevalence of infertility was 7.6% (95% CI 6.6-8.8). When stratified as primary and secondary infertility, the prevalence was 1.4% (95% CI 1.0-1.9) and 8.7% (95% CI 7.5-10.1), respectively. Using the current duration approach definition, the prevalence of overall infertility was 24.1% (95% CI 18.8-34.0) at 12-months, 13.4% (95% CI 10.1-18.6) at 24-months, and 8.8% (95% CI 6.5-12.3) at 36-months. CONCLUSION: The demographic definition of infertility resulted in a lower estimate of infertility. The current duration approach definition could be more appropriate for the early detection and management of infertility in Ethiopia. The findings also highlight the need for a comprehensive definition of and emphasis on infertility. Future population-based surveys should incorporate direct questions related to infertility to facilitate epidemiological surveillance.

Assisted reproductive technologies in Africa: The African Network and Registry for ART, 2018 and 2019.

RESEARCH QUESTION: What were the utilization, practices and outcomes of assisted reproductive technology (ART) in Africa in 2018 and 2019? DESIGN: Cycle-based data (CBD) and retrospective summary data were collected cross-sectionally from voluntarily participating ART centres. RESULTS: During 2018, 43,958 ART procedures were reported by 67 centres in 16 countries, increasing to 45,185 procedures reported by 70 centres in 18 countries in 2019. Autologous fresh procedures predominated at 70%, whereas autologous frozen embryo transfers (FET) increased from 21.2% to 23.1% and oocyte donation cycles remained below 10%. In 2019, the mean age of women undergoing autologous fresh embryo transfer was 33.9 years and received a mean number of 2.4 embryos per transfer. The clinical pregnancy rate (CPR) per fresh embryo transfer was 42.8% in 2018 and 38.4% in 2019, with corresponding rates of 38.3% and 31.8% after FET. In both years, most ART procedures, excluding single embryo transfer (SET), were associated with a multiple delivery rate above 20%, reaching over 30% after elective dual embryo transfer in autologous cycles and after fresh oocyte donation. Multiples were predominantly born preterm with a substantially increased perinatal mortality rate. The CBD for both years showed that elective SET (eSET) achieved a high CPR without compromising safety. CONCLUSION: This third report of The African Network and Registry for Assisted Reproductive Technology documents the prevailing practice of multiple embryo transfers in a cohort of relatively young women while highlighting the importance of disaggregating eSET, non-eSET and double embryo transfer. The high CPR after eSET and the increase in cryopreservation cycles are encouraging trends towards decreasing the number of embryos transferred without compromising effectiveness. Improved follow-up of ART pregnancies is required.

The status of ART in the public health sector in Africa: a multi-country survey.

RESEARCH QUESTION: What is the current availability of treatment with assisted reproductive technology (ART) in the public sector in Africa, and what are the facilitators and barriers towards its provision? DESIGN: Cross-sectional quantitative and qualitative data were collected in two phases from February 2020 to October 2021. Key informants were identified from countries known to provide ART in Africa based on data from the African Network and Registry for Assisted Reproductive Technology and the 2019 Surveillance from the International Federation of Fertility Societies. Quantitative data were collected via a structured questionnaire (Phase 1); public centre-specific quantitative and qualitative data were then collected via a semi-structured questionnaire followed by a virtual interview (Phase 2). Data were analysed descriptively. RESULTS: Informants from 18 countries reported the existence of 185 ART centres in 16 countries. Twenty-four centres (13.0%) in 10 of 16 countries (62.5%) were public. The majority of public centres (20/22 [90.9%]) reporting on ART performed <500 ART cycles per annum. Although public institutions covered most of the cost for ART, copayments from patients were universally required. The number of ART cycles per annum was inversely correlated to the copayment. Lack of policy and legislation, high costs and bureaucratic obstacles were identified by participants as the leading challenges in the delivery of public service ART. CONCLUSION: Lack of public ART services leads to chronic and profound health inequities. Enablers of public service ART in the region are the same known to support ART services in general, namely policy and legislation, appropriate funding and good health service infrastructure. Addressing these requires the collated efforts of many stakeholders.

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.

Assisted reproductive technology in Africa: a 5-year trend analysis from the African Network and Registry for ART.

RESEARCH QUESTION: What were the trends in utilization, outcomes and practices in assisted reproductive technology (ART) in Africa between 2013 and 2017? DESIGN: Cycle-based data and retrospective summary data were collected cross-sectionally from voluntarily participating ART centres. RESULTS: During the 5-year period, 153,917 ART procedures were reported from 73 centres in 18 countries. ART utilization remained low in all countries and years. Autologous fresh ART was by far the most common intervention, with little change in the clinical pregnancy rate (CPR) per aspiration (34.9% in 2013; 31.7% in 2017) and a consistent preponderance of young women. Oocyte donation represented less than 10% of reported procedures. Although the transfer of multiple embryos prevailed, elective single-embryo transfer (eSET) resulted in a CPR of 43.2% per transfer in fresh autologous cycles, which was notably higher compared with non-elective SET cycles (16.6%) and all dual embryo transfers (DET; 37.3%). Compared with eSET, elective DET further increased the CPR by less than 5% while raising the multiple delivery rate by 33.4%. The majority of multiples were born preterm. Many pregnancies were, however, lost to follow-up, compromising the delivery and birth outcome data. CONCLUSION: ART monitoring has been successfully established in Africa although progress must continue. Although data are not yet representative, best evidence indicates low access to ART. Perinatal outcome supports eSET, but other social determinants responsible for multiple embryo transfers are important factors to consider. Efforts must be directed at improving pregnancy follow-up. Registry data are integral to the widening of access to high-quality ART in Africa.

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 technologies in Africa: first results from the African Network and Registry for Assisted Reproductive Technology, 2013.

RESEARCH QUESTION: What were utilization, outcomes and practices in assisted reproductive technology (ART) in Africa in 2013? DESIGN: To initiate a data registry in Africa, retrospective summary data were collected in a cross-sectional survey. RESULTS: Forty ART centres from 13 countries collectively reported 25,770 initiated cycles. Regional ART utilization could not be established due to large inter-country variations and insufficient data. The pregnancy rate per aspiration for fresh non-donor IVF and intracytoplasmic sperm injection was 28.0% and 35.8%, with a preponderance of women under 35 years (57.3%). Deliveries were reported for only 56.1% of pregnancies; the remainder were lost to follow-up. A mean of 2.41 embryos were transferred. The multiple delivery rate was 26.7% (25.5% twins and 1.2% triplets). Most twins (52.7%) and triplets (73.7%) were born pre-term. Oocyte donation represented 7% of all fresh and frozen transfers. CONCLUSION: This marks the beginning of an ART registry in Africa, Since ART utilization could not be established, the degree of access to ART remains speculative. Pregnancy rates were favourable but underpinned by a preponderance of young women and the transfer of multiple embryos. Efforts are needed to explore treatment barriers, improve pregnancy follow-up and reduce the high rate of multiples. This inaugural report from the African Network and Registry for Assisted Reproductive Technology (ANARA) indicates a willingness and ability of ART centres to voluntarily report and monitor utilization and outcomes of ART, which reflects a rising standard of ART in Africa. It is anticipated that more centres and countries will join ANARA to continue this trend.

Poor recovery of households from out-of-pocket payment for assisted reproductive technology.

STUDY QUESTION: How do households recover financially from direct out-of-pocket payment for government subsidized ART? SUMMARY ANSWER: After a mean of 3.8 years, there was poor recovery from initiated financial coping strategies with the poorest households being disproportionatley affected. WHAT IS KNOWN ALREADY: Out-of-pocket payment for health services can create financial burdens for households and inequities in access to care. A previous study conducted at a public-academic institution in South Africa documented that patient co-payment for one cycle of ART resulted in catastrophic expenditure for one in five households, and more frequently among the poorest, requiring diverse financial coping strategies to offset costs. STUDY DESIGN, SIZE, DURATION: An observational follow-up study was conducted ~4 years later to assess financial recovery among the 135 couples who had participated in this previous study. Data were collected over 12 months from 73 informants. PARTICIPANTS/MATERIALS, SETTING, METHOD: The study was conducted at a level three referral hospital in the public-academic health sector of South Africa. At this institution ART is subsidized but requires patient co-payments. A purpose-built questionnaire capturing socio-economic information and recovery from financial coping strategies which had been activated was administered to all informants. Financial recovery was defined as the resolution of strategies initiated for the specific purpose of covering the original ART cycle. Results were analysed by strategy and household with the latter including analysis by tertiles based on socio-economic status at the time of the original expenditure. In addition to descriptive statistics, the Pearson Chi squared test was used to determine differences between socioeconomic tertiles and associations between recovery and other variables. MAIN RESULTS AND THE ROLE OF CHANCE: The participation rate in this follow-up study was 54.1% with equal representation from the three socio-economic tertiles. The average duration of follow-up was 46.1 months (±9.78 SD) and respondents' mean age was 42 years (range 31-52). The recovery rate was below 50% for four of five strategies evaluated: 23.1% of households had re-purchased a sold asset; 23.5% had normalized a previous reduction in household spending, 33.8% had regained their savings, and 48.7% were no longer bolstering income through additional work. Two-thirds of households (60.0%) had repaid all loans and debts. The poorest households showed lower rates of recovery when compared to households in the richest tertile. Complete recovery from all strategies initiated was reported by only 10 households (13.7%): 1 of 19 in the lowest tertile, 3 of 30 in the middle and by 6 of 24 households in the richest tertile (P > 0.05). No association was found between the degree of financial recovery and additional cost burdens incurred, including related to babies born; or between the degree of recovery and ongoing pursuit of ART. LIMITATIONS, REASONS FOR CAUTION: The sample size was limited. The participation rate was just over 50%. Results were dependent on participants' narrative and recall. WIDER IMPLICATIONS OF THE FINDINGS: The willingness of patients to pay for ART does not necessarily imply the ability to pay. As a result, the lack of comprehensive third-party funding for ART can create immediate and long-term financial hardship which is more pronounced among poorer households. While more data on the impact of out-of-pocket payment for ART are needed to illustrate the problem in other low resource settings, the results from South Africa provide useful information for similar developing countries. The current absence of more extensive data should therefore not be a barrier to the promotion of financial risk protection for infertile couples, especially the poorest, in need of ART. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by a Masters Student Grant from the Faculty of Health Sciences, University of Cape Town. The authors had no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

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.

International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2006.

STUDY QUESTION: What are the access, effectiveness and safety of assisted reproductive technology (ART) worldwide in 2006? SUMMARY ANSWER: ART access, effectiveness and safety vary markedly among countries. Overall, there was an increase in the use of ICSI, single embryo transfer (SET) and frozen embryo transfer (FET). There was a decline in the multiple delivery rate (DR) and preterm birth rate. WHAT IS KNOWN ALREADY: ART is widely practiced worldwide and there is a need for its continuous monitoring to improve the comprehensiveness and quality of ART data and services. STUDY DESIGN, SIZE, DURATION: This is a retrospective, cross-sectional survey of ART cycles undertaken worldwide in 2006. PARTICIPANTS, SETTING, METHODS: A total of 2352 clinics in 56 countries provided data. Data were analyzed at a country and regional level. The forms for data collection were developed by the International Committee Monitoring Assisted Reproductive Technologies (ICMART) and sent to each country or regional ART register. MAIN RESULTS AND THE ROLE OF CHANCE: A total of >1,050,300 initiated cycles resulted in an estimated >256,668 babies. The overall pregnancy rates (PRs) and DRs per aspiration for IVF were 30.7 and 22.8%, respectively, and for ICSI 29.7 and 20.0%, respectively. The PRs and DRs for FETs were 26.4 and 17.8%, respectively. Multiple DR per PR were 22.2% for twins and 1.5% for triplets following fresh IVF/ICSI and 16.4% for twins and 0.8% for triplets for FETs. Ovarian hyperstimulation syndrome complicated >4585 cycles (0.6%). Access to ART varied from 11 to 3988 cycles per million population. ICSI comprised 66.0% of all initiated cycles, FET 27.4% and SET 20.7%. Perinatal mortality rate was 25.2 per 1000 births for fresh IVF/ICSI and 17.5 per 1000 for FETs. LIMITATIONS, REASONS FOR CAUTION: 44.6% of the countries provided incomplete data. Quality of data varies among individual countries and is dependant on the policy of the local regulatory authority for monitoring ART clinics. Continuous efforts are needed to improve comprehensiveness and quality of data collected. WIDER IMPLICATIONS OF THE FINDINGS: Adopting the policy of SET, FET and the cessation of transferring more than two embryos should be widely applied. ICMART will continue helping countries and regions to establish their own ART registries. STUDY FUNDING/COMPETING INTEREST(S): ICMART receives financial support from medical societies: European Society for Human Reproduction and Embryology (ESHRE), American Society for Reproduction Medicine (ASRM), Fertility Society of Australia (FSA), Japan Society for Reproductive Medicine (JSRM), Latin American Network for Reproductive Medicine (REDLARA) and Middle East Fertility Society (MEFS) and Society for Assisted Reproductive Technology (SART). All authors have no conflict of interest in relation to this work. We declare no support or financial relationship with any organizations or any activities that could appear to have influenced the submitted work.

Addressing the Rehabilitation Needs of Women Experiencing Infertility in Ethiopia: Time for Action.

The psychological, social, and financial disabilities caused by infertility are significant for women, particularly those living in low- and middle-income countries such as Ethiopia. Although rehabilitation can be an important form of support for such women, infertility is frequently overlooked as a disability or potential target of rehabilitation interventions. This study aimed to determine what rehabilitation-related services and supports are available for women experiencing infertility in Ethiopia. We used an Interpretive Description design. We purposefully selected fourteen rehabilitation, medical, and policy service providers from diverse institutions across three geographical locations. We used semi-structured questions during our in-person and telephone interviews. The data were analyzed using reflexive thematic analysis with the assistance of NVivo. We identified five main themes, including (a) policies related to infertility, (b) the concept that disabilities are physically visible fails to recognize infertility, (c) the need for rehabilitation services for women with infertility, (d) the importance of wellness services for women experiencing infertility, and (e) the role of religion in rehabilitation services. In conclusion, it is essential to strengthen the policies around infertility, incorporate rehabilitation services in fertility care, and view infertility as a disabling condition for women who experience it in Ethiopia.

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: A retrospective, cross-sectional survey of 3,103 assisted reproductive technology clinics in 74 countries in 2015 and 3,249 clinics in 79 countries in 2016 that submitted cycle and pregnancy outcome data through national and regional registries. SETTING: Seventy-nine countries and >3,000 assisted reproductive technology clinics. PATIENT(S): Patients undergoing assisted reproductive technology procedures. INTERVENTION(S): Assisted reproductive technology. MAIN OUTCOME MEASURE(S): Outcomes on country, regional, and global levels. RESULT(S): Reported for 2015: 2,358,239 cycles with 548,652 infants born; for 2016: 2,807,963 cycles with 647,188 infants born. Estimated in 2015, ≥2,683,677 cycles resulted in >675,134 infants; in 2016, ≥3,100,448 cycles resulted in ≥723,026 infants. Reported cycles represent approximately 80% of global utilization. In 2015 and 2016, 27.6% and 27.8%, respectively, of women undergoing fresh autologous treatment cycles were aged ≥40 years. Frozen-thawed embryo transfer (ET) cycles accounted for 47.0% and 51.9%, respectively, of all ETs in 2015 and 2016. Oocyte donation cycles accounted for 6.7% and 7.1% of all ETs 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 ET 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 ETs 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 ETs in frozen-thawed ET autologous treatment 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(S): Utilization of assisted reproductive technology treatment and births per cycle increased from 2015 to 2016, although multiple births were reduced. An increasing proportion of frozen-thawed ET cycles, continuing wide variation in use of intracytoplasmic sperm injection, and an increase in single ET rates are reported.

Declining global fertility rates and the implications for family planning and family building: an IFFS consensus document based on a narrative review of the literature.

BACKGROUND: Family-planning policies have focused on contraceptive approaches to avoid unintended pregnancies, postpone, or terminate pregnancies and mitigate population growth. These policies have contributed to significantly slowing world population growth. Presently, half the countries worldwide exhibit a fertility rate below replacement level. Not including the effects of migration, many countries are predicted to have a population decline of >50% from 2017 to 2100, causing demographic changes with profound societal implications. Policies that optimize chances to have a child when desired increase fertility rates and are gaining interest as a family-building method. Increasingly, countries have implemented child-friendly policies (mainly financial incentives in addition to public funding of fertility treatment in a limited number of countries) to mitigate decreasing national populations. However, the extent of public spending on child benefits varies greatly from country to country. To our knowledge, this International Federation of Fertility Societies (IFFS) consensus document represents the first attempt to describe major disparities in access to fertility care in the context of the global trend of decreasing growth in the world population, based on a narrative review of the existing literature. OBJECTIVE AND RATIONALE: The concept of family building, the process by which individuals or couples create or expand their families, has been largely ignored in family-planning paradigms. Family building encompasses various methods and options for individuals or couples who wish to have children. It can involve biological means, such as natural conception, as well as ART, surrogacy, adoption, and foster care. Family-building acknowledges the diverse ways in which individuals or couples can create their desired family and reflects the understanding that there is no one-size-fits-all approach to building a family. Developing education programs for young adults to increase family-building awareness and prevent infertility is urgently needed. Recommendations are provided and important knowledge gaps identified to provide professionals, the public, and policymakers with a comprehensive understanding of the role of child-friendly policies. SEARCH METHODS: A narrative review of the existing literature was performed by invited global leaders who themselves significantly contributed to this research field. Each section of the review was prepared by two to three experts, each of whom searched the published literature (PubMed) for peer reviewed full papers and reviews. Sections were discussed monthly by all authors and quarterly by the review board. The final document was prepared following discussions among all team members during a hybrid invitational meeting where full consensus was reached. OUTCOMES: Major advances in fertility care have dramatically improved family-building opportunities since the 1990s. Although up to 10% of all children are born as a result of fertility care in some wealthy countries, there is great variation in access to care. The high cost to patients of infertility treatment renders it unaffordable for most. Preliminary studies point to the increasing contribution of fertility care to the global population and the associated economic benefits for society. WIDER IMPLICATIONS: Fertility care has rarely been discussed in the context of a rapid decrease in world population growth. Soon, most countries will have an average number of children per woman far below the replacement level. While this may have a beneficial impact on the environment, underpopulation is of great concern in many countries. Although governments have implemented child-friendly policies, distinct discrepancies in access to fertility care remain.

Catastrophic payment for assisted reproduction techniques with conventional ovarian stimulation in the public health sector of South Africa: frequency and coping strategies.

STUDY QUESTION: How often does out-of-pocket payment (OPP) for assisted reproduction techniques (ART) with conventional ovarian stimulation result in catastrophic expenditure for households? SUMMARY ANSWER: Catastrophic cost was a frequent event affecting 51% of the poorest study participants and one in five couples in total. WHAT IS KNOWN ALREADY: There is increasing concern about catastrophic spending on health by households in low resource settings, but to date no study has evaluated OPP for ART. STUDY DESIGN, SIZE, DURATION: We conducted a prospective observational study comprising 135 couples undergoing ART between March 2009 and June 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was set at an urban, level 3 referral hospital in the public and academic health sector of South Africa. At this institution ART is subsidized but requires co-payment by patients. Couples undergoing ART with conventional ovarian stimulation using GnRH analogs were recruited. A questionnaire capturing information on socioeconomic status, monthly household expenditure, OPP for the index ART cycle and financial coping strategies was administered. Households were categorized into tertiles according to socio-economic status. In addition to descriptive statistics, annualized OPP for ART services as a percentage of annual non-food household expenditure was calculated to estimate catastrophic health care expenditure. The Pearson χ(2) test and a logistic regression were used to identify factors related to incurring catastrophic spending. MAIN RESULTS AND THE ROLE OF CHANCE: In total, one in five couples (22%) incurred catastrophic expenditure (P < 0.01), defined as an OPP of ≥ 40% of annual non-food expenditure. Households used a range of coping strategies including reduced expenditure on items such as clothing and food, use of savings, borrowing money and taking on extra work. Differences were observed between the socio-economic tertiles: in the poorest tertile, 51% of households faced catastrophic costs compared with only 2% of the richest tertile (P < 0.01). Participants in the poorest tertile were more likely to be black (P < 0.01), and less likely to have health insurance (P < 0.01) or female full-time employment (P < 0.01). Longer duration of infertility was an additional risk factor for catastrophic payment (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: No attempt was made to obtain proof of any payment or expenditure, and all information collected relied on participants' verbal account. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to document the frequency of catastrophic expenditure for ART using conventional ovarian stimulation in a low resource setting. Our results show that not all couples unable to afford treatment forfeit infertility care; instead poor couples are willing to suffer catastrophic financial hardship in order to pay. ART counselling therefore needs to include financial risk counselling in the short term. Long-term interventions comprise cost-reducing strategies as well as health systems strategies that reduce or eliminate the need for OPP for ART wherever possible. Robust evidence on mild versus conventional stimulation for ART in low resource settings is also required in the form of local RCTs which address the many clinical and health economic variables and exclude bias. Our data cannot be extrapolated to patients undergoing ART elsewhere or to patients undergoing ART with mild ovarian stimulation. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Medical Research Council of South Africa and the University of Cape Town (University Research Committee and Faculty of Health Sciences Research Committee). The authors had no competing interests. TRIAL REGISTRATION NUMBER: not applicable.

Global fertility care with assisted reproductive technology.

Assisted reproductive technology has progressed greatly since the birth of Louise Brown in 1978. The pregnancy rates have increased, care is safer with significantly reduced multiple pregnancy and complication rates, infants have good health, and millions of people have been able to have the families they desired. The major challenges facing assisted reproductive technology are to continue to increase the quality of care, increase utilization through more societal funding, and expand care to nontraditional and marginalized populations in all countries, especially lower- and middle-income countries where access is currently limited. Significant collaboration among professionals, organizations, the World Health Organization, and policymakers is occurring and will be necessary to achieve these goals.

Financial costs of assisted reproductive technology for patients in low- and middle-income countries: a systematic review.

STUDY QUESTION: What are the direct costs of assisted reproductive technology (ART), and how affordable is it for patients in low- and middle-income countries (LMICS)? SUMMARY ANSWER: Direct medical costs paid by patients for infertility treatment are significantly higher than annual average income and GDP per capita, pointing to unaffordability and the risk of catastrophic expenditure for those in need. WHAT IS KNOWN ALREADY: Infertility treatment is largely inaccessible to many people in LMICs. Our analysis shows that no study in LMICs has previously compared ART medical costs across countries in international dollar terms (US$PPP) or correlated the medical costs with economic indicators, financing mechanisms, and policy regulations. Previous systematic reviews on costs have been limited to high-income countries while those in LMICs have only focussed on descriptive analyses of these costs. STUDY DESIGN SIZE DURATION: Guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA), we searched PubMed, Web of Science, Cumulative Index of Nursing and Allied Health Literature, EconLit, PsycINFO, Latin American & Caribbean Health Sciences Literature, and grey literature for studies published in all languages from LMICs between 2001 and 2020. PARTICIPANTS/MATERIALS SETTING METHODS: The primary outcome of interest was direct medical costs paid by patients for one ART cycle. To gauge ART affordability, direct medical costs were correlated with the GDP per capita or average income of respective countries. ART regulations and public financing mechanisms were analyzed to provide information on the healthcare contexts in the countries. The quality of included studies was assessed using the Integrated Quality Criteria for Review of Multiple Study designs. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 4062 studies identified, 26 studies from 17 countries met the inclusion criteria. There were wide disparities across countries in the direct medical costs paid by patients for ART ranging from USD2109 to USD18 592. Relative ART costs and GDP per capita showed a negative correlation, with the costs in Africa and South-East Asia being on average up to 200% of the GDP per capita. Lower relative costs in the Americas and the Eastern Mediterranean regions were associated with the presence of ART regulations and government financing mechanisms. LIMITATIONS REASONS FOR CAUTION: Several included studies were not primarily designed to examine the cost of ART and thus lacked comprehensive details of the costs. However, a sensitivity analysis showed that exclusion of studies with below the minimum quality score did not change the conclusions on the outcome of interest. WIDER IMPLICATIONS OF THE FINDINGS: Governments in LMICs should devise appropriate ART regulatory policies and implement effective mechanisms for public financing of fertility care to improve equity in access. The findings of this review should inform advocacy for ART regulatory frameworks in LMICs and the integration of infertility treatment as an essential service under universal health coverage. STUDY FUNDING/COMPETING INTERESTS: This work received funding from the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by the World Health Organization (WHO). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: This review is registered with PROSPERO, CRD42020199312.