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.

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.

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.

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.

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.

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.

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.

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.

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 (ICMART): world report on assisted reproductive technologies, 2013.

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

Economic costs of infertility care for patients in low-income and middle-income countries: a systematic review protocol.

INTRODUCTION: Infertility, a condition of the reproductive system, affects millions of individuals and couples worldwide. Despite infertility treatment's existence, it is largely unavailable and inaccessible in low/middle-income countries (LMICs) due to the prohibitive costs compounded by an absence of financing. Previous systematic reviews have shown that there is scanty information in LMICs on out-of-pocket (OOP) payments for infertility treatment. This protocol outlines the methodological approach and analytical process to appraise the extent of economic burden due to payments for infertility care services in LMICs. METHOD AND ANALYSIS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach, we will primarily search for articles indexed in PubMed, Web of Science, Cumulative Index of Nursing and Allied Health Literature, EconLit and PsycINFO databases. Grey literature from relevant organisations' virtual libraries shall also be searched. Backward and forward searches on the articles selected will also be done. Quantitative studies on infertility treatment costs from LMICs across the world regions within the last 20 years will be considered. The primary outcome of interest shall include OOP payments, catastrophic health expenditure and direct costs for infertility services. Conversely, informal payments and indirect costs related to infertility treatments shall be considered as secondary outcomes. Integrated quality Criteria for Review Of Multiple Study designs will be used to assess the quality of the studies included in the review. Meta-analysis shall be considered if sufficient studies identified are homogenous in characteristics. Also, the review shall analyse the average cost of infertility treatment against the respective countries' economic indicators like gross domestic product per capita if data permit. ETHICS AND DISSEMINATION: Research and ethics approval will not be required given this will be a review of published articles on the subject. The findings shall be disseminated through publication in a peer-reviewed journal and presentation to the WHO and its partners. PROSPERO REGISTRATION NUMBER: CRD42020199312.

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.

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.

Coordination and planning of clinical research on a national and global level.

In reproductive medicine, the needs and desires of infertility patients drive future research, with the most important outcome being live birth of a baby. Large, multicenter, randomized clinical trials are considered the best research tool to evaluate the effectiveness of medical interventions, but they can often take a long time to find definitive answers. Advances in individual participant data (IPD) and network meta-analysis have enabled research questions to be answered more quickly, but better planning could streamline this process further. To harmonize research findings that are taking place globally in this way, it is crucial that the same outcomes are collected in clinical trials conducted in reproductive medicine. Furthermore, the conduct of clinical trials often requires collaboration on an international scale; however, individual countries have their own processes for research prioritization and delivery. We describe the perspective of high- and low-resourced settings and industry as well as the mechanisms of prioritization and coordination that are in place in different settings. In addition, we discuss the importance of the patient perspective, which can help shape the research question, clinical trial design, and the logistical operations of trial delivery. The need for increased global collaboration and coalitions within and between stakeholders is evident for the research community to accelerate advances and maximize benefits in reproductive medicine.

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.

International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology, 2011.

OBJECTIVE: To report the utilization, effectiveness, and safety of practices in assisted reproductive technology (ART) globally in 2011 and assess global trends over time. DESIGN: Retrospective, cross-sectional survey on the utilization, effectiveness, and safety of ART procedures performed globally during 2011. SETTING: Sixty-five countries and 2,560 ART clinics. PATIENT(S): Women and men undergoing ART procedures. INTERVENTION(S): All ART. MAIN OUTCOME MEASURE(S): The ART cycles and outcomes on country-by-country, regional, and global levels. Aggregate country data were processed and analyzed based on methods developed by the International Committee for Monitoring Assisted Reproductive Technology (ICMART). RESULT(S): A total of 1,115,272 ART cycles were reported for the treatment year 2011. Imputing data for nonreporting clinics, 1,643,912 cycles resulted in >394,662 babies, excluding People's Republic of China. The best estimate of global utilization including People's Republic of China is approximately 2.0 million cycles and 0.5 million babies. From 2010 to 2011, the number of reported aspiration and frozen ET cycles increased 13.1% and 13.8%, respectively. The proportion of women aged ≥40 years undergoing nondonor ART increased from 23.2% in 2010 to 24.0% in 2011. As a percentage of nondonor aspiration cycles, intracytoplasmic sperm injection (ICSI) decreased slightly from 67.4% in 2010 to 66.5% in 2011. The IVF/ICSI combined delivery rates per fresh aspiration and frozen ET cycles were 19.8% and 21.4%, respectively. In fresh nondonor cycles, single ET increased from 30.0% in 2010 to 31.4% in 2011, whereas the average number of transferred embryos decreased from 1.95 in 2010 to 1.91 in 2011-again with wide country variation. The rates of twin deliveries after fresh nondonor transfers decreased from 20.4% in 2010 to 19.6% in 2011; the triplet rate decreased from 1.1%-0.9%. In frozen ET cycles performed in 2011, single ET was 51.6%, with an average of 1.59 embryos transferred and twin and triplet rates were 11.1% and 0.4%, respectively. The cumulative delivery rate per aspiration increased from 27.1% in 2010 to 28.0% in 2011. Fresh IVF/ICSI carried a perinatal mortality rate per 1,000 births of 21.0 in 2010 and 16.3 in 2011. This compared with a perinatal mortality rate after frozen ET of 14.6 per 1,000 births in 2010 and 8.6 in 2011. The data presented depend on the quality and completeness of data submitted by individual countries. This report covers approximately two-thirds of'world ART activity. CONCLUSION(S): Global ART utilization, effectiveness, and safety increased between 2010 and 2011.

Availability, effectiveness and safety of ART in sub-Saharan Africa: a systematic review.

STUDY QUESTION: What is the evidence pertaining to availability, effectiveness and safety of ART in sub-Saharan Africa? SUMMARY ANSWER: According to overall limited and heterogeneous evidence, availability and utilization of ART are very low, clinical pregnancy rates largely compare to other regions but are accompanied by high multiple pregnancy rates, and in the near absence of data on deliveries and live births the true degree of effectiveness and safety remains to be established. WHAT IS KNOWN ALREADY: In most world regions, availability, utilization and outcomes of ART are monitored and reported by national and regional ART registries. In sub-Saharan Africa there is only one national and no regional registry to date, raising the question what other evidence exists documenting the status of ART in this region. STUDY DESIGN SIZE DURATION: A systematic review was conducted searching Pubmed, Scopus, Africawide, Web Of Science and CINAHL databases from January 2000 to June 2017. A total of 29 studies were included in the review. The extracted data were not suitable for meta-analysis. PARTICIPANTS/MATERIALS SETTING METHODS: The review was conducted according to Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. All peer-reviewed manuscripts irrespective of language or study design that presented original data pertaining to availability, effectiveness and safety of ART in sub-Saharan Africa were eligible for inclusion. Selection criteria were specified prior to the search. Two authors independently reviewed studies for possible inclusion and critically appraised selected manuscripts. Data were analysed descriptively, being unsuitable for statistical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The search yielded 810 references of which 29 were included based on the predefined selection and eligibility criteria. Extracted data came from 23 single centre observational studies, two global ART reports, two reviews, one national data registry and one community-based study. ART services were available in 10 countries and delivered by 80 centres in six of these. Data pertaining to number of procedures existed from three countries totalling 4619 fresh non-donor aspirations in 2010. The most prominent barrier to access was cost. Clinical pregnancy rates ranged between 21.2% and 43.9% per embryo transfer but information on deliveries and live births were lacking, seriously limiting evaluation of ART effectiveness. When documented, the rate of multiple pregnancy was high with information on outcomes similarly lacking. LIMITATIONS REASONS FOR CAUTION: The findings in this review are based on limited data from a limited number of countries, and are derived from heterogeneous studies, both in terms of study design and quality, many of which include small sample sizes. Although representing best available evidence, this requires careful interpretation regarding the degree of representativeness of the current status of ART in sub-Saharan Africa. WIDER IMPLICATIONS OF THE FINDINGS: The true extent and outcome of ART in sub-Saharan Africa could not be reliably documented as the relevant information was not available. Current efforts are underway to establish a regional ART data registry in order to report and monitor availability, effectiveness and safety of ART thus contributing to evidence-based practice and possible development strategies. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study. The authors had no competing interests. TRIAL REGISTRATION NUMBER: PROSPERO CRD42016032336.