Abstract
STUDY QUESTION
What were utilization, outcomes and practices in assisted reproductive technology (ART) globally in 2008, 2009 and 2010?
SUMMARY ANSWER
Global utilization and effectiveness ...remained relatively constant despite marked variations among countries, while the rate of single and frozen embryo transfers (FETs) increased with a concomitant slight reduction in multiple birth rates.
WHAT IS KNOWN ALREADY
ART is widely practised in all regions of the world. Monitoring utilization, an approximation of availability and access, as well as effectiveness and safety is an important component of universal access to reproductive health.
STUDY DESIGN, SIZE, DURATION
This is a retrospective, cross-sectional survey on utilization, effectiveness and safety of ART procedures performed globally from 2008 to 2010.
PARTICIPANTS, SETTING, METHODS
Between 58 and 61 countries submitted data from a total of nearly 2500 ART clinics each year. Aggregate country data were processed and analyzed based on forms and methods developed by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART). Results are presented at country, regional and global level.
MAIN RESULTS AND THE ROLE OF CHANCE
For the years 2008, 2009 and 2010, >4 461 309 ART cycles were initiated, resulting in an estimated 1 144 858 babies born. The number of aspirations increased by 6.4% between 2008 and 2010, while FET cycles increased by 27.6%. Globally, ART utilization remained relatively constant at 436 cycles/million in 2008 and 474 cycles/million population in 2010, but with a wide country range of 8–4775 cycles/million population. ICSI remained constant at around 66% of non-donor aspiration cycles. The IVF/ICSI combined delivery rate (DR) per fresh aspiration was 19.8% in 2008; 19.7% in 2009 and 20.0% in 2010, with corresponding DRs for FET of 18.8, 19.7 and 20.7%. In fresh non-donor cycles, single embryo transfer increased from 25.7% in 2008 to 30.0% in 2010, while the average number of embryos transferred fell from 2.1 to 1.9, again with wide regional variation. The rates of twin deliveries following fresh non-donor transfers were, in 2008, 2009 and 2010, 21.8, 20.5 and 20.4%, respectively, with a corresponding triplet rate of 1.3, 1.0 and 1.1%. Fresh IVF and ICSI carried a perinatal mortality rate per 1000 births of 22.8 (2008), 19.2 (2009) and 21.0 (2010), compared with 15.1, 12.8 and 14.6/1000 births following FET in the same periods of observation. The proportion of women aged 40 years or older undergoing non-donor ART increased from 20.8 to 23.2% from 2008 to 2010.
LIMITATIONS, REASON FOR CAUTION
The data presented are reliant on the quality and completeness of data submitted by individual countries. This report covers approximately two-thirds of the world ART activity.
WIDER IMPLICATIONS OF 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 and embryo transfer practices warrant attention by clinicians and policy makers.
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 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; Government of Canada (Research grant), Ferring Pharmaceuticals (Grant unrelated to World Reports).
TRIAL REGISTRATION
not applicable.
Infertility is estimated to affect as many as 186 million people worldwide. Although male infertility contributes to more than half of all cases of global childlessness, infertility remains a woman's ...social burden. Unfortunately, areas of the world with the highest rates of infertility are often those with poor access to assisted reproductive techniques (ARTs). In such settings, women may be abandoned to their childless destinies. However, emerging data suggest that making ART accessible and affordable is an important gender intervention. To that end, this article presents an overview of what we know about global infertility, ART and changing gender relations, posing five key questions: (i) why is infertility an ongoing global reproductive health problem? (ii) What are the gender effects of infertility, and are they changing over time? (iii) What do we know about the globalization of ART to resource-poor settings? (iv) How are new global initiatives attempting to improve access to IVF? (v) Finally, what can be done to overcome infertility, help the infertile and enhance low-cost IVF (LCIVF) activism?
An exhaustive literature review using MEDLINE, Google Scholar and the keyword search function provided through the Yale University Library (i.e. which scans multiple databases simultaneously) identified 103 peer-reviewed journal articles and 37 monographs, chapters and reports from the years 2000-2014 in the areas of: (i) infertility demography, (ii) ART in low-resource settings, (iii) gender and infertility in low-resource settings and (iv) the rise of LCIVF initiatives. International Federation of Fertility Societies Surveillance reports were particularly helpful in identifying important global trends in IVF clinic distribution between 2002 and 2010. Additionally, a series of articles published by scholars who are tracking global cross-border reproductive care (CBRC) trends, as well as others who are involved in the growing LCIVF movement, were invaluable.
Recent global demographic surveys indicate that infertility remains an ongoing reproductive problem, with six key demographic features. Despite the massive global expansion of ART services over the past decade (2005-2015), ART remains inaccessible in many parts of the world, particularly in sub-Saharan Africa, where IVF clinics are still absent in most countries. For women living in such ART-poor settings, the gender effects of infertility may be devastating. In contrast, in ART-rich regions such as the Middle East, the negative gender effects of infertility are diminishing over time, especially with state subsidization of ART. Furthermore, men are increasingly acknowledging their male infertility and seeking ICSI. Thus, access to ART may ameliorate gender discrimination, especially in the Global South. To that end, a number of clinician-led, LCIVF initiatives are in development to provide affordable ART, particularly in Africa. Without access to LCIVF, many infertile couples must incur catastrophic expenditures to fund their IVF, or engage in CBRC to seek lower-cost IVF elsewhere.
Given the present realities, three future directions for research and intervention are suggested: (i) address the preventable causes of infertility, (ii) provide support and alternatives for the infertile and (iii) encourage new LCIVF initiatives to improve availability, affordability and acceptability of ART around the globe.
Gestational carriers have a right to be fully informed of the risks of the surrogacy process and of pregnancy, should receive psychological evaluation and counseling, and should have independent ...legal counsel.
There is a great deal of hype surrounding the concept of personalized medicine. Personalized medicine is rooted in the belief that since individuals possess nuanced and unique characteristics at the ...molecular, physiological, environmental exposure, and behavioral levels, they may need to have interventions provided to them for diseases they possess that are tailored to these nuanced and unique characteristics. This belief has been verified to some degree through the application of emerging technologies such as DNA sequencing, proteomics, imaging protocols, and wireless health monitoring devices, which have revealed great inter-individual variation in disease processes. In this review, we consider the motivation for personalized medicine, its historical precedents, the emerging technologies that are enabling it, some recent experiences including successes and setbacks, ways of vetting and deploying personalized medicines, and future directions, including potential ways of treating individuals with fertility and sterility issues. We also consider current limitations of personalized medicine. We ultimately argue that since aspects of personalized medicine are rooted in biological realities, personalized medicine practices in certain contexts are likely to be inevitable, especially as relevant assays and deployment strategies become more efficient and cost-effective.
STUDY QUESTION
The 14th European IVF—monitoring (EIM) report presents the results of medically assisted reproduction treatments including assisted reproductive technology (ART) cycles and ...intrauterine insemination (IUI) cycles initiated in Europe during 2010: are there changes in the trends compared with previous years?
SUMMARY ANSWER
Despite some fluctuations in the number of countries reporting, the overall number of ART cycles has continued to increase year by year, and while pregnancy rates in 2010 remained similar to those reported in 2009, the number of transfers with multiple embryos (three or more) further declined.
WHAT IS KNOWN ALREADY
Since 1997, ART data in Europe have been collected and reported in 13 manuscripts, published in Human Reproduction.
STUDY DESIGN, SIZE, DURATION
Retrospective collection of European ART data by the EIM Consortium for ESHRE; data were collected from cycles started between 1st January and 31st December 2010 by the National Registries of individual European countries, or on a voluntary basis by personal information for European countries without a national registry.
PARTICIPANTS/MATERIALS SETTING, METHODS
Out of 31 countries, 991 clinics reported 550 296 ART treatment cycles: IVF (125 994), ICSI (272 771), frozen embryo replacement (FER, 114 593), egg donation (ED, 25 187), in vitro maturation (493), preimplantation genetic diagnosis/preimplantation genetic screening (6399) and frozen oocyte replacements (4859). European data on IUI using husband/partner's semen (IUI-H) or donor semen (IUI-D) were reported from 22 and 19 countries, respectively. A total of 176 512 IUI-H (+8.4% compared with 2009) and 38 124 IUI-D (+30.4% compared with 2009) cycles were included.
MAIN RESULTS AND THE ROLE OF CHANCE
In 16 countries where all clinics reported to the national ART registry, a total of 267 120 ART cycles were performed in a population of 219 million inhabitants, corresponding to 1221 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer increased to 29.2 and 33.2%, respectively, and for ICSI, the corresponding rates also increased to 28.8 and 32.0%, when compared with the rates of 2009. In FER cycles, the pregnancy rate per thawing was 20.3%; in ED cycles the pregnancy rate per fresh transfer was 47.4% and per thawed transfer 33.3%. The delivery rate after IUI-H was 8.9 and 13.8% after IUI-D. In IVF and ICSI cycles, one, two, three and four or more embryos were transferred in 25.7, 56.7, 16.1 and 1.5%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 79.4, 19.6 and 1.0%, respectively, resulting in a total multiple delivery rate of 20.6% compared with 20.2% in 2009, 21.7% in 2008, 22.3% in 2007, 20.8% in 2006. In FER cycles, the multiple delivery rate was 12.8% (12.5% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 9.6/0.5 and 8.5/0.2%, following treatment with husband and donor semen, respectively.
LIMITATIONS, REASONS FOR CAUTION
The method of reporting is not standardized in Europe but varies among countries. Furthermore registries from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. Therefore, results should be interpreted with caution.
WIDER IMPLICATIONS OF THE FINDINGS
The 14th ESHRE report on ART and IUI treatments shows a continuing expansion of the number of ART treatment cycles in Europe, with more than half a million of cycles reported in 2010. The use of ICSI may have reached a plateau. When compared with 2009/2008, pregnancy and (multiple) delivery rates after IVF and ICSI remained relatively stable. The number of multiple embryo transfers (three or more embryos) has shown a decline.
STUDY FUNDING/COMPETING INTERESTS
The study has no external funding; all costs are covered by ESHRE. There are no competing interests.
The goals of a gestational surrogacy relationship are to have a healthy baby for the intended parents while maintaining the medical and psychological well-being of the gestational carrier. A ...successful gestational surrogacy relationship will result also in good psychosocial outcomes for the gestational carrier, intended parents, and child. Finding a gestational carrier who will achieve these goals would be the ideal. This article focuses on key medical, reproductive, and ethical considerations to optimize clinical outcomes in gestational carrier cycles. Recommendations from available clinical guidelines regarding gestational surrogacy are reviewed, along with updates from current literature.
How has the interface between genetics and assisted reproduction technology (ART) evolved since 2005?
The interface between ART and genetics has become more entwined as we increase our understanding ...about the genetics of infertility and we are able to perform more comprehensive genetic testing.
In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and ART and published an extended background paper, recommendations and two Editorials.
An interdisciplinary workshop was held, involving representatives of both professional societies and experts from the European Union Eurogentest2 Coordination Action Project.
In March 2012, a group of experts from the European Society of Human Genetics, the European Society of Human Reproduction and Embryology and the EuroGentest2 Coordination Action Project met to discuss developments at the interface between clinical genetics and ART.
As more genetic causes of reproductive failure are now recognized and an increasing number of patients undergo testing of their genome prior to conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and PGD may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from RCTs to substantiate that the technique is both effective and efficient. Whole genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo.
The legal landscape regarding assisted reproduction is evolving, but still remains very heterogeneous and often contradictory. The lack of legal harmonization and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe, and beyond.
This continually evolving field requires communication between the clinical genetics and IVF teams and patients to ensure that they are fully informed and can make well-considered choices.
Funding was received from ESHRE, ESHG and EuroGentest2 European Union Coordination Action project (FP7 - HEALTH-F4-2010-26146) to support attendance at this meeting.
Abstract
STUDY QUESTION
The 15th European IVF-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2011: are there ...any changes in the trends compared with previous years?
SUMMARY ANSWER
Despite some fluctuations in the number of countries reporting data, while the overall number of ART cycles has continued to increase year by year, the pregnancy rates in 2011 decreased slightly to those reported in 2010, and the number of transfers with multiple embryos (3+) and the multiple delivery rates declined.
WHAT IS KNOWN ALREADY
Since 1997, ART data in Europe have been collected and reported in 14 manuscripts, published in Human Reproduction.
STUDY DESIGN, SIZE, DURATION
Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE); cycles started between 1 January and 31 December 2011 are collected on a yearly basis. The data are collected by National Registers, when existing, or on a voluntary basis by personal information.
PARTICIPANTS/MATERIALS SETTING, METHODS
From 33 countries (+2 compared with 2010), 1064 clinics reported 609 973 treatment cycles including: IVF 138 592, ICSI 298 918, frozen embryo replacement (FER) 129 693, egg donation (ED) 30 198, in vitro maturation 511, preimplantation genetic diagnosis/screening 6824 and frozen oocyte replacements 5237. European data on intrauterine insemination (IUI) using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 861 IUI laboratories in 24 countries. A total of 174 390 IUI-H and 41 151 IUI-D cycles were included.
MAIN RESULTS AND THE ROLE OF CHANCE
In 17 countries where all clinics reported to the ART register, a total of 361 972 ART cycles were performed in a population of 285 million inhabitants, corresponding to 1269 cycles per million inhabitants. For all IVF cycles, the clinical pregnancy rates per aspiration and per transfer were stable with 29.1 and 33.2%, respectively, and for ICSI, the corresponding rates also were stable with 27.9 and 31.8%, respectively. In FER cycles, the pregnancy rate per thawing increased to 21.3% if compared with previous years. In ED cycles, the pregnancy rate per fresh transfer decreased to 45.8% (47.4% in 2010) and increased to 33.6% (33.3% in 2010) per thawed transfer. The delivery rate after IUI-H decreased to 8.3 (8.9 in 2010), and to 12.2% (13.8% in 2010) after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 27.5, 56.7, 14.5 and 1.3% of cycles, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (added together) were 80.8, 18.6 and 0.6%, respectively, resulting in a total multiple delivery rate of 19.2% compared with 20.6% in 2010, 20.2% in 2009, 21.7% in 2008, 22.3% in 2007 and 20.8% in 2006. In FER cycles, the multiple delivery rate was 13.2% (12.8% twins and 0.4% triplets). Twin and triplet delivery rates associated with IUI cycles were 9.7/0.6% and 7.3/0.3%, following IUI-H and IUI-D treatment, respectively.
LIMITATIONS, REASONS FOR CAUTION
The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution.
WIDER IMPLICATIONS OF THE FINDINGS
The 15th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than 600 000 cycles reported in 2011. Since 2006, the proportion of IVF to ICSI cycles has reached a plateau after a small decrease in 2009. Pregnancy and delivery rates after IVF remained relatively stable compared with 2010 and 2009. The pregnancy rate per aspiration in ICSI cycles declined for the first time by 0.9%. The multiple delivery rate is lower than ever before.
STUDY FUNDING/COMPETING INTERESTS
The study had no external funding; all costs are covered by ESHRE. There are no competing interests.
STUDY QUESTION
Based on the best available evidence in the literature, what is the optimal management of routine psychosocial care at infertility and medically assisted reproduction (MAR) clinics?
...SUMMARY ANSWER
Using the structured methodology of the Manual for the European Society of Human Reproduction and Embryology (ESHRE) Guideline Development, 120 recommendations were formulated that answered the 12 key questions on optimal management of routine psychosocial care by all fertility staff.
WHAT IS ALREADY KNOWN
The 2002 ESHRE Guidelines for counselling in infertility has been a reference point for best psychosocial care in infertility for years, but this guideline needed updating and did not focus on routine psychosocial care that can be delivered by all fertility staff.
STUDY, DESIGN, SIZE, DURATION
This guideline was produced by a group of experts in the field according to the 12-step process described in the ESHRE Manual for Guideline Development. After scoping the guideline and listing a set of 12 key questions in PICO (Patient, Intervention, Comparison and Outcome) format, thorough systematic searches of the literature were conducted; evidence from papers published until April 2014 was collected, evaluated for quality and analysed. A summary of evidence was written in a reply to each of the key questions and used as the basis for recommendations, which were defined by consensus within the guideline development group (GDG). Patient and additional clinical input was collected during the scoping and the review phase of the guideline development.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The guideline group, comprising psychologists, two medical doctors, a midwife, a patient representative and a methodological expert, met three times to discuss evidence and reach consensus on the recommendations.
MAIN RESULTS AND THE ROLE OF CHANCE: THE GUIDELINE PROVIDES
120 recommendations that aim at guiding fertility clinic staff in providing optimal evidence-based routine psychosocial care to patients dealing with infertility and MAR. The guideline is written in two sections. The first section describes patients' preferences regarding the psychosocial care they would like to receive at clinics and how this care is associated with their well-being. The second section of the guideline provides information about the psychosocial needs patients experience across their treatment pathway (before, during and after treatment) and how fertility clinic staff can detect and address these. Needs refer to conditions assumed necessary for patients to have a healthy experience of the fertility treatment. Needs can be behavioural (lifestyle, exercise, nutrition and compliance), relational (relationship with partner if there is one, family friends and larger network, and work), emotional (well-being, e.g. anxiety, depression and quality of life) and cognitive (treatment concerns and knowledge).
LIMITATIONS, REASONS FOR CAUTION
We identified many areas in care for which robust evidence was lacking. Gaps in evidence were addressed by formulating good practice points, based on the expert opinion of the GDG, but it is critical for such recommendations to be empirically validated.
WIDER IMPLICATIONS OF THE FINDINGS
The evidence presented in this guideline shows that providing routine psychosocial care is associated with or has potential to reduce stress and concerns about medical procedures and improve lifestyle outcomes, fertility-related knowledge, patient well-being and compliance with treatment. As only 45 (36.0%) of the 125 recommendations were based on high-quality evidence, the guideline group formulated recommendations to guide future research with the aim of increasing the body of evidence.
STUDY FUNDING/COMPETING INTEREST(S)
The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with literature searches, and with the implementation of the guideline. The GDG members did not receive payment. S.G., E.D., C.d.K., M.E., U.V.d.B., C.L.-J. and N.V. report no conflicts of interest. J.B. reports grants from Merck & Co, consulting fees from Merck Serono S.A. and Speaker's fees from Merck Serono S.A. P.T. reports consulting fees from the German government and being the Chair of the German Society for Fertility Counselling. C.V. reports consulting fees from Merck Serono S.A. C.M.V. reports being adviser in projects for Merck Serono S.A. and Ferring S.A. on patient educational material. T.W. reports speaker's fees from Repromed, DGPM, Breitbach, DAAG, fiore, LPTW, MSD, salary/position funding at TAB-beim-Bundestag, BZgA, and being the Vice-chair of the German Society for Fertility Counselling.
TRIAL REGISTRATION NUMBER
NA.
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