Abstract
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.
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?
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.
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.
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.
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.
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.
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.
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.
None.
N/A.
Abstract
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.
To analyze information on assisted reproductive technology (ART) performed worldwide, and trends in outcomes over successive years.
Cross-sectional survey on access, efficiency, and safety of ART ...procedures performed in 55 countries during 2007.
Not applicable.
Infertile women and men undergoing ART globally.
Collection and analysis of international ART data.
Number of cycles performed, by country and region, including pregnancies, single and multiple birth rates, and perinatal mortality.
Overall, >1,251,881 procedures with ART were reported, and resulted in 229,442 reported babies born. The availability of ART varied by country, from 12 to 4,140 treatments per million population. Of all aspiration cycles, 65.2% (400,617 of 614,540) were intracytoplasmic sperm injection. The overall delivery rate per fresh aspiration was 20.3%, and for frozen-embryo transfer (FET), 18.4%, with a cumulative delivery rate of 25.8%. With wide regional variations, single-embryo transfer represented 23.4% of fresh transfers, and the proportion of deliveries with twins and triplets from fresh transfers was 22.3% and 1.2%, respectively. The perinatal mortality rate was 19.9 per 1,000 births for fresh in vitro fertilization using intracytoplasmic sperm injection, and 9.6 per 1,000 for FET. The proportion of women aged ≥40 years increased to 19.8% from 15.5% in 2006.
The international trend toward <3 transferred embryos continued, as did the wider uptake of FET. This was achieved without compromising delivery rates. The application of ART for women aged >40 years was a major component of ART services in some regions and countries.
How do households recover financially from direct out-of-pocket payment for government subsidized ART?
After a mean of 3.8 years, there was poor recovery from initiated financial coping strategies ...with the poorest households being disproportionatley affected.
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.
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.
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.
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.
The sample size was limited. The participation rate was just over 50%. Results were dependent on participants' narrative and recall.
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.
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.
Not applicable.
A number of studies have explored motives for parenthood in the Western industrialized world. These studies have documented that children are mostly desired for reasons relating to happiness and ...personal well-being. To date, limited data pertaining to parenthood motives in African countries exist. Insight into the value of children can, however, be derived from studies on infertility, as the negative repercussions of involuntary childlessness reflect the value of children to parents and the community. According to these studies children secure conjugal ties, offer social security, assist with labour, confer social status, secure rights of property and inheritance, provide continuity through re-incarnation and maintaining the family lineage, and satisfy emotional needs. Parenthood therefore appears to have more and, arguably, deeper roots in African communities when compared to industrialized countries.
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 χ2 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.
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.
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.
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.
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.
PDF
