Article

International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2008, 2009 and 2010

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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 interests: 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.

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... As ICSI is a less natural and more intrusive technique, which necessitates extra time, this limited positive effect favoring ICSI regarding TFF may not be enough to support ICSI as the first-line treatment for couples without male factor infertility. This evidence is in agreement with other reports recently published [120][121][122][123]. Table 2 depicts the broad ICSI application in male and non-male factor infertility. ...
... Since its first use almost 30 years ago, the application of ICSI as a fertilization method has raised steadily, even though the percentage of infertile couples with severe male factors has not increased [125]. Thus, it seems evident that currently, ICSI is applied broadly, even though there is no clear evidence of its benefit in couples without male factor infertility [113,114,123,125,126]. Boulet and collaborators analyzed data on ART between 1996 and 2012 and reported increased use of ICSI from 36.4% in 1996 to 76.2% in 2012, even though male-factor infertility remained unchanged at about 36% of cycles [118]. ...
... Boulet and collaborators analyzed data on ART between 1996 and 2012 and reported increased use of ICSI from 36.4% in 1996 to 76.2% in 2012, even though male-factor infertility remained unchanged at about 36% of cycles [118]. Another trial published by Dyer and colleagues analyzing the worldwide data on ART performed between 2008 and 2010 found that ICSI was used as a fertilization method in about 67% of about 4.5 million cycles completed [123]. However, there is considerable variation according to countries; in Asia, ICSI is applied in about 55% of the treatments, 65% of cases in Europe, 85% of patients in Latin America, and almost 100% of patients in the Middle East [123]. ...
Article
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Since the birth of Louise Brown in 1978 via IVF, reproductive specialists have acquired enormous knowledge and refined several procedures, which are nowadays applied in assisted reproductive technology (ART). One of the most critical steps in this practice is the fertilization process. In the early days of IVF, a remarkable concern was the unpleasant outcomes of failed fertilization, overtaken by introducing intracytoplasmic sperm injection (ICSI), delineating a real breakthrough in modern ART. ICSI became standard practice and was soon used as the most common method to fertilize oocytes. It has been used for severe male factor infertility and non-male factors, such as unexplained infertility or advanced maternal age, without robust scientific evidence. However, applying ICSI blindly is not free of potential detrimental consequences since novel studies report possible health consequences to offspring. DNA methylation and epigenetic alterations in sperm cells of infertile men might help explain some of the adverse effects reported in ICSI studies on reproductive health in future generations. Collected data concerning the health of ICSI children over the past thirty years seems to support the notion that there might be an increased risk of epigenetic disorders, congenital malformations, chromosomal alterations, and subfertility in babies born following ICSI compared to naturally conceived children. However, it is still to be elucidated to what level these data are associated with the cause of infertility or the ICSI technique. This review provides an overview of epigenetic mechanisms and possible imprinting alterations following the use of ART, in particular ICSI. It also highlights the sperm contribution to embryo epigenetic regulation and the risks of in vitro culture conditions on epigenetic dysregulation. Lastly, it summarizes the literature concerning the possible epigenetic disorders in children born after ART.
... Infertility is a condition defined by the failure to achieve pregnancy despite 12 months of regular sexual intercourse, with the average frequency of 3-4 intercourses per week, without the use of contraceptives [1]. ...
... The management options depend on the age of the woman and duration of infertility, and is diag-nosed when all standard elements of the assessment give correct results. The share of the unexplained factor in relation to the known factors of infertility increases steadily [1,2]. Infertility with an undetermined cause is probably associated with less reproductive efficiency, oocyte or sperm abnormalities, fertilization, implantation or embryonic development phase abnormalities that cannot be determined by standard treatment methods. ...
... The use of ICSI has increased considerably since 1992 [9,34,35]. A previous cross-sectional survey of ART treatment in 60 countries during 2010 by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) stated that 63.0% of all cycles performed ICSI [34]. The proportion of ICSI in the study was 26.2%, which is consistent with the data in National ART Service Provision Surveys (29.2%), but much lower than that in Europe 2014 report (71.3%) [35] and the USA in 2019 (56.4%) [9]. ...
... The use of ICSI has increased considerably since 1992 [9,34,35]. A previous cross-sectional survey of ART treatment in 60 countries during 2010 by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) stated that 63.0% of all cycles performed ICSI [34]. The proportion of ICSI in the study was 26.2%, which is consistent with the data in National ART Service Provision Surveys (29.2%), but much lower than that in Europe 2014 report (71.3%) [35] and the USA in 2019 (56.4%) [9]. ...
Article
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Purpose Assisted reproductive technology (ART) has an impact on secondary sex ratio (SSR), which is seemed to be elevated after blastocyst transfer (BT) but decreased following ICSI procedure. We aim to assess whether the higher SSR associated with BT could be influenced by fertilization method used. Methods All consecutive IVF/ICSI cycles (fresh and frozen) involving single embryo transfer (SET) resulting in a live birth between 2015 and 2019 were retrospective analyzed. Logistic regression was used to model the effect on the SSR of maternal and specific ART characteristics. Results Six thousand nine hundred twenty-two women were included with the crude SSR of 54.8%. The impact of BT on SSR is influenced by the fertilization method used. After adjustment for potential confounders, the SSR in the ICSI BT group was significantly higher when compared to ICSI cleavage-stage embryo SET (aOR 1.24; 95% CI 1.10–1.40, P < 0.001). However, this effect was not detected among SBT with IVF treatment (aOR 1.04; 95% CI 0.97–1.12, P = 0.260). Assessing blastocyst morphological parameters, high trophectoderm quality was significantly associated with elevated SSR (aOR 1.76, 95% CI 1.34–2.31 [A vs. C], and aOR 1.28, 95% CI 1.14–1.44 [B vs. C]). No significant difference was shown in expansion, inner cell mass, or days of blastocyst formation between male and female blastocysts. Conclusions The impact of BT on SSR could be influenced by the fertilization method used. The higher SSR was observed after BT with ICSI procedures but not with IVF. Interpretation of the findings is limited by the potential for selection and confounding bias.
... In most low income countries, where parent is seen as a social obligation to have babies and infertility is unacceptable and is stigmatized due to the way the society valued children [13,14]. Infertile women Asian Pacific Journal of Reproduction 2022; 11(1): [12][13][14][15][16][17][18][19] Asian Pacific Journal of Reproduction Journal homepage: www.apjr.net ...
... For most infertile couples, in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) could be their last opportunity to have children; some of the infertile couples opted out and are also denied further fertility treatment for several reasons. The International Committee Monitoring Assisted Reproductive Technology reported in 2011 that about 3 million children were delivered worldwide by IVF [18,19]. A study from Nigeria estimated that 30% to 40% of patients with infertility as a result of tubal blockage will require ART treatment [4,20]. ...
Article
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Objective: To identify factors that determine the uptake of in-vitro fertilization (IVF), and to determine the predicting effect of the identified factors on the uptake of IVF among couples attending fertility clinic at a tertiary health institution in Benin City, Nigeria. Methods: This study adopted a cross-sectional descriptive design. A self-structured questionnaire tested was validated and administered to 250 couples who attended fertility clinic. Data were collected from March 2021 to June 2021 and were analyzed using the Statistical Package for Social Science (SPSS) version 21. Data were presented and interpreted using descriptive statistics and inferential statistics such as Chi-square, univariate statistics and multivariate logistic regression analysis. Results: Among 250 couples, 154 (61.6%) were willing to adopt IVF. The multivariate logistic regression analysis showed that catholic religion [odds ratio (OR) 0.21, 95% confident interval (CI) 0.54-0.73], family income (OR 1.50, 95% CI 1.10-2.00) and age (OR 1.04, 95% CI 1.01-1.10) were the major factors that determined the uptake of IVF, with P-value of
... Assisted reproductive technology is widely practiced worldwide, and annually enables millions of subfertile couples to achieve pregnancy [1,2]. The success rate of frozen-thawed embryo transfer (FET) has steadily increased globally over the last decade due to the increased availability of viable embryos and consistent advancement in this exciting technology [1][2][3][4][5][6]. ...
... Assisted reproductive technology is widely practiced worldwide, and annually enables millions of subfertile couples to achieve pregnancy [1,2]. The success rate of frozen-thawed embryo transfer (FET) has steadily increased globally over the last decade due to the increased availability of viable embryos and consistent advancement in this exciting technology [1][2][3][4][5][6]. ...
Preprint
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Purpose The aim of this study was to elucidate the effect of hatching status on in vitro fertilization outcomes in frozen–thawed blastocyst transfer cycles. Methods Frozen–thawed embryo transfer (FET) cycles performed at a single fertility center between 2016 and 2021 were retrospectively assessed. Analyses were restricted to 6821 frozen–thawed blastocyst transfers in women aged 24–47 years. For optimal comparability, double embryo transfer cycles consisting of one hatching and one hatched blastocyst were excluded. Implantation and pregnancy rates were evaluated and compared between subgroups, based on patients’ age (≤ 38 years vs. >38 years), blastocyst grade (good vs. bad grade) and number of transferred embryos (single embryo transfer [SET] vs. double embryo transfer [DET]). Results Hatched blastocyst transfer was associated with higher implantation and clinical pregnancy rates in the SET group (15.7% and 15.6%, respectively; p < 0.05). The transfer of two hatched blastocysts had a trend of higher implantation and clinical pregnancy rates, compared to the transfer of two hatching blastocysts (19.5% and 20.4%, respectively; p < 0.05) in the DET group. In the hatched blastocyst transfer group, the clinical pregnancy and implantation rates were higher, regardless of a woman’s age and embryo quality. Conclusion The IVF treatment outcomes improved when the blastocysts were hatched during FET cycles. Hence, hatched blastocyst transfer in FET cycles shall be considered as a superior method in IVF practice.
... Introduction Non-male factor infertility conditions constitute approximately half of all infertility cases [1] and usually conventional in vitro fertilization (IVF) is recommended treatment in those conditions, particularly in tubal and idiopathic infertility. Intracytoplasmic sperm injection (ICSI) was developed to overcome male factor infertility, however, there recently has been an increasing trend in ICSI usage irrespective of the etiology, demonstrating an overuse of this insemination technique [2][3][4][5]. ...
... Metabolomic signature from SCM was assessed in a total of 131 1D proton NMR spectra. Spent media from only good quality blastocysts on day 5 of development as per Istanbul consensus [4] was used to assess the metabolomic signature. The average number of SCM used for metabolomic profiling from both IVF and ICSI groups per patient was approximately 2.5 (from a total of 47 IVF and 47 ICSI derived SCM from 19 patients). ...
Article
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Intracytoplasmic sperm injection (ICSI) was developed to overcome male factor infertility, however, there recently has been an increasing trend in ICSI usage irrespective of the etiology, demonstrating an overuse of this insemination technique. There is a limited knowledge on the behaviour of ICSI derived embryos in non-male factor infertility patients. Metabolomic assessment of preimplantation embryos in conjunction with morphological evaluation can provide better understanding of embryonic behaviour. Hence, this study was undertaken to explore if there are any metabolomic differences between IVF and ICSI derived sibling day-5 blastocysts from non-male factor infertility patients. This prospective study included nineteen couples with non-male factor infertility undergoing Assisted Reproductive Technology. The sibling oocytes retrieved from each patient were randomly assigned to two groups and inseminated either by IVF or ICSI. Spent culture media (SCM) in which embryos were cultured up to day 5 were collected and investigated using sensitivity enhanced NMR based metabolite profiling utilizing high resolution (800 MHz) NMR equipped with cryogenically cooled micro-coil (1.7 mm) probe. The metabolomic signature between IVF and ICSI derived sibling blastocysts was assessed. A significant reduction in the concentrations of pyruvate, citrate, glucose and lysine were observed in both IVF and ICSI sibling embryos compared to medium control (P< 0.05–0.001). Further, histidine and valine level was found lower in ICSI embryos compared to medium control (P<0.05) during 96 hours of in vitro culture. Notably, between IVF and ICSI SCM, no significant difference in the concentration of the metabolites was found. Our results suggest that ICSI in non-male factor does not alter the SCM metabolomic signature during 96 hours of embryonic development.
... During 2011, for instance, there were 81,378 such cycles in the United States and 169,169 in Japan. 2 A gap of this scale was also recorded for the preceding 3 years. 3 Beyond oocyte aspiration, the other major category of procedures in terms of which ART activity is typically measured is the oocyte-transfer frequency, and, in this respect as well, Japan holds the record by far. Specifically, it documented 92,719 such cycles for 2011, which is an order of magnitude larger than the corresponding figure for the United States-29,231. 4 It is precisely this striking volume of transfers that made the popular magazine, The Economist, recently publish a column Spain-another heavy-weight user of ART-enacted its first law on assisted reproduction in 1988, amending it in 2003, and then overhauling the entire legislation on assisted reproduction in 2006. ...
Article
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This article puts the spotlight on the world's largest artificial reproduction technology (ART) industry-that of Japan, seeking to explain the exceptional tardiness of the government there to install a comprehensive legal framework that regulates these practices. By relying on minutes from a conversation with an influential parliamentarian active in this area, as well as official documents, media reports, and an interview conducted with key physicians, the article reconstructs the historical trajectory leading to the enactment in December 2020 of the Assisted Reproduction Technology Act. The author contends that it is only on the background of an overview of what happened in the two decades preceding the promulgation of this Act that a sense can be made of why the latter came to be as scant and evasive as it is in terms of provisions, de facto leaving unaltered the socially and ethically undesirable situation of self-regulation in ART application by the Japanese doctors. This article adds credence to the hypothesis with regard to the issue of regulatory governance of emerging technologies more broadly that the direction of travel is toward soft, as opposed to hard, law.
... With the rationale that intracytoplasmic sperm injection (ICSI) is likely to reduce the likelihood of poor fertilization and to comfort both the patient and the physician, many clinicians tend to use ICSI as the preferred method of fertilization in couples with prolonged duration of infertility [6][7][8]. ICSI was initially developed for male factor infertility and then there has been an increase in the use of ICSI for all causes of infertility [9][10][11]. ...
Article
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Background Intracytoplasmic sperm injection (ICSI) is increasingly used among in vitro fertilization (IVF) cycles without male factor infertility. For couples with prolonged infertility duration, the preferred insemination method may vary across laboratories and clinics. We analyzed whether ICSI is effective for non-male factor infertility with long infertility duration. Methods Seventeen thousand four hundred seventy-seven IVF/ICSI cycles from women with non-male factor infertility were included, of these 4177 women with infertility duration ≥ 5 years were in the final analysis. Primary outcome was the live birth rate after first embryo transfer. Secondary outcomes were rates of clinical pregnancy and fertilization. Results A nonlinear relationship was observed between infertility duration and IVF fertilization rate, which decreased with infertility years up to the turning point (4.8 years). 4177 women with infertility ≥ 5 years were categorized by IVF (n = 3806) or ICSI (n = 371). Live birth rate after first embryo transfer was 43.02% in ICSI and 47.85% in IVF group (adjusted odds ratio (aOR), 0.91; 95% confidence interval (CI), 0.72–1.15). Fertilization rate per metaphaseII (aOR, 1.10; 95% CI, 0.86–1.40) and clinical pregnancy rate (aOR, 0.89; 95% CI, 0.71–1.13) were similar between the two groups. Sensitive analyses (women ≥ 35 years) did not show a benefit of ICSI over IVF. Conclusions Women with infertility exceeding 4.8 years had decreased incidence of IVF fertilization. The use of ICSI showed no significant improvement in fertilization and live birth rates for non-male factor couples with ≥ 5 years of infertility.
... While disclosure of donor-conceived status to children is now widely recognised as best practice (Frith et al., 2018), generations of parents of donor-conceived people were advised by clinicians not to tell their children of their donorconceived status, and not to seek out identifying information about their donors (Adams & Lorback, 2012). Since the conception of Louise Brown, the first person conceived via in vitro fertilisation in 1978, the fertility industry has accelerated rapidly, so much so that between the years 2008 and 2010, the number of babies born using ART worldwide grew at a rate of nine per cent per annum (Dyer et al., 2016). In 2018, over 19,000 babies were born using ART in Australia and New Zealand, including 406 babies through donor sperm insemination, 761 babies from oocyte or embryo donation and 86 through gestational surrogacies (Newman et al., 2018). ...
Chapter
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For qualitative researchers, reflexivity is always an important aspect of ethical practice. However, in research on donor conception, there is a particular need for greater attention to be paid to the ways in which researchers' positionality, experiences and attitudes influence the research process and findings. With the aim of 'doing reflexivity', in this chapter I explore three phases of becoming: becoming donor-conceived, becoming activist and becoming researcher. In 'becoming donor-conceived', I explore how connecting with other donor-conceived people online strongly influenced the way that I understood my own experiences and contributed to my own sense of belonging. Next, I describe how through 'becoming activist', I became more aware of the political value of donor-conceived people's voices and the need to privilege donor-conceived people's perspectives in research. Finally, I explore how I navigate my position as an 'insider' in my research including how I manage risk and reciprocity. People with lived experience bring different priorities and ways of thinking and doing research into the research process. I argue that it is vital that donor conception researchers engage with and empower donor-conceived people to influence policy and practice responses to this complex topic.
... Data from the United States show a similar pattern that ICSI use has been shown to have increased from 36.4% in 1996 to 76.2% in 2012 for all etiologic subgroups with the largest increase in non-male factor infertility cases [5]. Contemplating the global situation, the ICSI/C-IVF ratio is lowest in Asia as 1.4, this is followed by Australia, New Zealand and Saharan countries as 2 and highest in the Middle East, reaching up to more than 60 [15]. Despite ICSI having a high popularity in the field of reproductive treatments, both American Society of Reproductive Medicine (ASRM) and ESHRE guidelines inadvise routine implementation of ICSI for all oocytes and suggest to reserve it for the male factor infertility cases or for patients with a history of TFF in previous attempts [16,17]. ...
Article
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Background We aimed to analyse our clinical results for a particular subgroup of patients with poor ovarian response (POR) to clarify if lower number of oocytes is a drawback for proceeding to C-IVF. Materials and methods In this retrospective study, patient files of all couples (#1733) who underwent oocyte retrieval between January 2017 and December 2019 were reviewed and 191 cases diagnosed with non-male factor infertility in which ≤ 3 cumulus–oocyte complexes available for fertilisation were analysed. Exclusion criteria were: woman age > 42, patients with a history of previous ART trial, prenatal genetic testing cycles and couples undergoing total cryopreservation for any indication. Three groups were constructed depending on the method of fertilisation and on semen quality as follows: IVF non-male factor (Group 1, n = 77); ICSI non-male factor (Group 2, n = 65); ICSI male factor-ICSI/MF n = 49 according to WHO reference values. Main outcome parameters were: fertilisation rate, implantation rate and live birth rate. Results Fertilisation rate per collected COC was significantly higher in group 1 compared to the other two groups (85.68%, 72.58%, 73.33% respectively, p = 0.004). FR per inseminated oocyte also tended to be higher in group 1 but not reaching a statistically significant level. Both techniques yielded similar implantation rates (20.42%, 28.49%, 23.33% respectively, p = 0.407) and live birth rates (26.8%, 30.6%, 31.1%, respectively, p = 0.643). Conclusion In the presence of normal semen parameters, low egg number is not an indication to perform ICSI. The choice of fertilisation method should be based primarily on semen quality, in combination with the patient’s previous history regardless of the ovarian reserve.
... The clinical effectiveness of IVF is variable across regions with reported efficiency ranging from 20% to 40%. IVF is mainly hampered by the current limitations of embryo quality assessment methods [3]. Indeed, the main embryo quality assessment method is based on morphological evaluation, which consists of daily static observation under the microscope. ...
Preprint
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An important limitation to the development of Artificial Intelligence (AI)-based solutions for In Vitro Fertilization (IVF) is the absence of a public reference benchmark to train and evaluate deep learning (DL) models. In this work, we describe a fully annotated dataset of 756 videos of developing embryos, for a total of 337k images. We applied ResNet, LSTM, and ResNet-3D architectures to our dataset and demonstrate that they overperform algorithmic approaches to automatically annotate stage development phases. Altogether, we propose the first public benchmark that will allow the community to evaluate morphokinetic models. This is the first step towards deep learning-powered IVF. Of note, we propose highly detailed annotations with 16 different development phases, including early cell division phases, but also late cell divisions, phases after morulation, and very early phases, which have never been used before. We postulate that this original approach will help improve the overall performance of deep learning approaches on time-lapse videos of embryo development, ultimately benefiting infertile patients with improved clinical success rates (Code and data are available at https://gitlab.univ-nantes.fr/E144069X/bench_mk_pred.git).
... Simultaneously, developments and enhancements of many important laboratory technologies have transformed the field, including the introduction embryo cryopreservation in the early 1980s [1][2][3]. Globally, the frequency of frozen embryo transfers (FET) continues to increase, likely due to improvements in embryo survival with the introduction of vitrification, implementation of guidelines promoting single embryo transfer and therefore increased cryopreservation of supernumerary embryos, efforts to reduce rates of ovarian hyperstimulation syndrome (OHSS), utilization of preimplantation genetic testing, and the increase in embryo cryopreservation for fertility preservation [1,[4][5][6][7][8]. ...
Article
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The use of frozen embryo transfer in assisted reproductive technology (ART) has steadily increased since development in the early 1980’s. While there are many benefits to delayed frozen embryo transfer, certain adverse perinatal outcomes are noted to be more common in these transfers when compared to fresh transfers, specifically hypertensive disorders of pregnancy. Frozen embryo transfers require coordination between the embryo’s developmental stage and the endometrial environment and can occur in either ovulatory or programmed cycles. Though there is no consensus on the ideal method of endometrial preparation prior to frozen embryo transfer, emerging data suggests differences in maternal and neonatal outcomes, specifically increased rates of hypertensive disorders of pregnancy in programmed cycles. Other reported differences include an increased risk of cesarean delivery, placenta accreta, postpartum hemorrhage, low birthweight, preterm birth, post term delivery, macrosomia, large for gestational age, and premature rupture of membranes in programmed cycles. The mechanism by which these differences exist could reflect inherent differences in groups selected for each type of endometrial preparation, the role of super physiologic hormone environments in programmed cycles, or the unique contributions of the corpus luteum in ovulatory cycles that are not present in programmed cycles. Given that existing studies are largely retrospective and have several key limitations, further investigation is needed. Confirmation of these findings has implications for current practice patterns and could enhance understanding of the mechanisms behind important adverse perinatal outcomes in those pursuing assisted reproduction.
... Because infertility treatment has become widespread owing to technological advancement, the proportion of children conceived through infertility treatment was higher in our study than in previous studies. [24][25][26] Therefore, statistical differences might be detectable in our study. In addition, Open access frozen-thawed embryos have been used for most ARTs in Japan. ...
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Objectives This study aimed to examine the association between infertility treatment and neurodevelopment in children at 2 and 3.5 years of age. Design Prospective cohort study. Setting and participants The study population consisted of mother–child pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Miyagi and Iwate Prefectures, Japan. Pregnant women were recruited in obstetric clinics or hospitals and their children were followed up by the questionnaire. Outcome measures The children’s neurodevelopmental outcomes were assessed at 2 and 3.5 years of age using the Ages and Stages Questionnaire, third edition (ASQ-3), which consists of questions on five developmental domains. We performed a multivariate logistic regression analysis of the association between infertility treatment (including ovulation induction (OI), artificial insemination with husband’s sperm (AIH) and assisted reproductive technology (ART)) and the clinical range of ASQ-3. Results Of 9655 mother–child pairs, 273 (2.8%) and 487 (5.0%) were conceived through OI/AIH and ART, respectively. The odds of having developmental delays at 2 years of age were higher in children conceived through OI/AIH (OR, 1.36; 95% CI 1.00 to 1.85) and ART (OR, 1.36; 95% CI 1.07 to 1.72) than in those conceived naturally. Additionally, OI/AIH and ART were significantly associated with communication (OR, 1.93; 95% CI 1.25 to 2.98) and gross motor (OR, 1.50; 95% CI 1.08 to 2.09) delays, respectively. There were no statistically significant differences in the odds of having developmental delays at 3.5 years of age in children conceived through OI/AIH (OR, 1.13; 95% CI 0.79 to 1.61) and ART (OR, 1.03; 95% CI 0.78 to 1.37). Conclusion In this study, we found a significant association between infertility treatment and children’s neurodevelopment at 2 years of age, whereas no statistically significant differences were found at 3.5 years of age.
... The International Committee Monitoring Assisted Reproductive Technologies (ICMART) has reported 20.4% twin deliveries following fresh non-donor transfers and a triplet rate of 1.1% in 2010. [9] There are no large studies reporting the association between multiple gestations and ROP. [10][11][12][13] In the current study, we aimed to evaluate the role of birth order and the associated risk factors in the development of ROP in 1040 Asian Indian infants of multiple gestations. ...
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To evaluate the role of birth order in the development of retinopathy of prematurity (ROP) in Asian Indian infants of multiple gestations. A total of 1257 infants born from multiple gestations, screened for ROP between January 2011 to December 2017 under the Karnataka Internet Assisted Diagnosis of Retinopathy of Prematurity (KIDROP) program, were included. The online database of a detailed demographic and clinical record was used for the analysis. Details of postnatal interventions like use of supplemental oxygen, neonatal diseases, congenital heart diseases, phototherapy, and plurality (twins or triplets) were noted. The data was analysed to compare the distribution of ROP and risk factors across the plurality of birth. Of the 1257 infants, 1040 (82.7%) with complete data were included for the analysis. The mean BW of the study cohort was 1605 g (95% CI, 1583–1628 g) and the mean GA was 32.8 weeks (95% CI, 32.7–33.0 weeks). Of the 1040 infants, 719 infants (69.13%) had no ROP and 321 (30.87%) had any stage ROP. Any ROP was seen in 30.80% of first born, 31.00% of second born, and 30.8% of the third born, but this was not statistically significant. Type 1 ROP was seen in 6.3% of first born, 7.5% of second born, and in none of the third born. The incidence of ROP among multiple gestations seems to be dependent on birth weight, irrespective of the birth order. A normal screening protocol used for singleton infants should suffice for infants born out of plurality.
... After the first "test-tube baby," Louise Brown was born after conception by in vitro fertilization experiment (IVF) in 1978 (Steptoe and Edwards, 1978). IVF-and intracytoplasmic sperm injection (ICSI)-based Assisted Reproductive Technology (ART) development has rapidly soared (Bonduelle et al., 2005;Dyer et al., 2016;Fishel, 2018;Saito et al., 2018). Since 1978, millions of babies were born by ART, marking the technology a widespread alternative for treating human infertility in the past decades (Meldrum, 2013;Sunderam et al., 2015;Johnson, 2019). ...
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Objective: To report a rare case in which an IVF-ET twin pregnancy gave birth to a partial trisomy 21 chimera girl. Design: Case report. Setting: University hospital. Patient: A girl with partial trisomy 21 mosaicism after in vitro fertilization and embryo transfer. Interventions: In vitro fertilization (IVF) and embryo transfer (ET). Main Outcome Measure: Karyotype analysis, Copy Number Variation sequencing (CNV-seq), stLFR-WGS, and Short Tandem Repeat (STR) analysis. Results: Being assisted with IVF and EF technology, the couple successfully gave birth to twin sisters at 37 weeks of gestational age. The NonInvasive Prenatal Testing (NIPT) and Nuchal Translucency (NT) examination showed no detectable genetic abnormalities during pregnancy. However, the younger infant displayed growth retardation and feeding difficulties after birth, which was not observed in her twin sister. Further genetic counseling and diagnosis suggested that she is a Chimera with complex partial trisomy 21. The stLFR-WGS assay showed multiple CNV variations in Chr21 and STR analysis confirmed the paternal origin of the additional fragments. Conclusion: It is rare for IVF-ET-assisted twin pregnancy to give birth to a girl with a complex combination of abnormal Chr21, which might result from paternal chromosome rearrangement during meiosis and mitosis.
... Globally, it is estimated that more than eight million babies have been conceived through ART [3]. However, infertility treatment is a long-term and expensive therapy with high dropout rates [4] and nearly half of all couples who started ART are likely to remain childless even after multiple treatment cycles, with foreseeable sequelae in terms Maria Teresa Villani and Daria Morini have contributed equally to this work and share first authorship. of psychological, social, and economic health [5][6][7]. In this context, mathematical models are generated predict strong outcomes, such as pregnancy and live birth rates. ...
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Purpose Several mathematical models have been developed to estimate individualized chances of assisted reproduction techniques (ART) success, although with limited clinical application. Our study aimed to develop a decisional algorithm able to predict pregnancy and live birth rates after controlled ovarian stimulation (COS) phase, helping the physician to decide whether to perform oocytes pick-up continuing the ongoing ART path. Methods A single-center retrospective analysis of real-world data was carried out including all fresh ART cycles performed in 1998–2020. Baseline characteristics, ART parameters and biochemical/clinical pregnancies and live birth rates were collected. A seven-steps systematic approach for model development, combining linear regression analyses and decision trees (DT), was applied for biochemical, clinical pregnancy, and live birth rates. Results Of fresh ART cycles, 12,275 were included. Linear regression analyses highlighted a relationship between number of ovarian follicles > 17 mm detected at ultrasound before pick-up (OF17), embryos number and fertilization rate, and biochemical and clinical pregnancy rates (p < 0.001), but not live birth rate. DT were created for biochemical pregnancy (statistical power–SP:80.8%), clinical pregnancy (SP:85.4%), and live birth (SP:87.2%). Thresholds for OF17 entered in all DT, while sperm motility entered the biochemical pregnancy’s model, and female age entered the clinical pregnancy and live birth DT. In case of OF17 < 3, the chance of conceiving was < 6% for all DT. Conclusion A systematic approach allows to identify OF17, female age, and sperm motility as pre-retrieval predictors of ART outcome, possibly reducing the socio-economic burden of ART failure, allowing the clinician to perform or not the oocytes pick-up.
... As ICSI-based treatments, regardless of need, continue to rise as a proportion of all treatment cycles (Dyer et al., 2016) alternative methods, including HA-binding, are being developed for enriching sperm of a higher quality for use in ICSI procedures (Lepine et al., 2019). Based on our models' outputs, extending on the findings of our original report (Miller et al., 2019), we hypothesize that the reduction in miscarriage in the trial's PICSI arm was linked to the more successful avoidance of sperm with a repairable defect in their DNA. ...
Article
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Study question: What effects did treatment using hyaluronic acid (HA) binding/selection prior to ICSI have on clinical outcomes in the Hyaluronic Acid Binding sperm Selection (HABSelect) clinical trial? Summary answer: Older women randomized to the trial's experimental arm (selection of sperm bound to immobilized (solid-state) HA) had the same live birth rates as younger women, most likely a result of better avoidance of sperm with damaged DNA. What is known already: Recent randomized controlled trials (RCTs) investigating the efficacy of HA-based sperm selection prior to ICSI, including HABSelect, have consistently reported reductions in the numbers of miscarriages among couples randomized to the intervention, suggesting a pathological sperm-mediated factor mitigated by prior HA-binding/selection. The mechanism of that protection is unknown. Study design, size, duration: The original HABSelect Phase 3 RCT ran from 2014 to 2017 and included 2752 couples from whom sperm samples used in control (ICSI) and intervention (Physiological IntraCytoplasmic Sperm Injection; PICSI) arms of the trial were stored frozen for later assessment of DNA quality (DNAq). The trial overlapped with its mechanistic arm, running from 2016 to 2018. Participants/materials, setting, methods: As miscarriage reduction was a significant secondary outcome of the trial, samples (n = 1247) selected for the mechanistic analysis were deliberately enriched for miscarriage outcomes (n = 92 or 7.4%) from a total of 154 miscarriages (5.6%) among all (n = 2752) couples randomized by stratified random sampling. Values from fresh semen samples for sperm concentration (mml), percentage forward progressive motility and percentage HA-binding score (HBS) were obtained before being processed by differential density gradient centrifugation or (rarely) by swim-up on the day of treatment. Surplus sperm pellets were recovered, aliquoted and cryopreserved for later analysis of DNAq using slide-based Comet, TUNEL, acridine orange (AO) and the sperm chromatin dispersion (SCD) assays. Following their classification into normal and abnormal sample subcategories based on reference values for sperm concentration and motility, relationships with HBS and DNAq were examined by Spearman correlation, Student's t-tests, Mann Whitney U tests, and logistic regression (univariable and multivariable). Parsimonious selection enabled the development of models for exploring and explaining data trends. Potential differences in future cumulative pregnancy rates relating to embryo quality were also explored. Main results and the role of chance: Results from the 1247 sperm samples assayed for HBS and/or DNAq, generated data that were considered in relation to standard physiological measures of (sperm) vitality and to treatment outcomes. All measures of HBS and DNAq discriminated normal from abnormal sperm samples (P < 0.001). SCD correlated negatively with the Comet (r = -0.165; P < 0.001) and TUNEL assays (r = -0.200; P < 0.001). HBS correlated negatively with AO (r = -0.211; P < 0.001), Comet (r = -0.127; P < 0.001) and TUNEL (r = -0.214; P < 0.001) and positively with SCD (r = 0.255; P < 0.001). A model for predicting live birth (and miscarriage) rates included treatment allocation (odds ratio: OR 2.167, 95% CI 1.084-4.464, P = 0.031), female age (OR 0.301, 95% CI 0.133-0.761, P = 0.013, per decade) and the AO assay (OR 0.79, 95% CI 0.60-1. 02.761, P = 0.073, per 10 points rise). A model predicting the expected rate of biochemical pregnancy included male age (OR 0.464, 95% CI 0.314-0.674, P < 0.001, per decade) and the SCD assay (OR 1.04, 95% CI 1.007-1.075, P = 0.018, per 10 point rise). A model for conversion from biochemical to clinical pregnancy did not retain any significant patient or assay variables. A model for post-injection fertilization rates included treatment allocation (OR 0.83, 95% CI 0.75-0.91, P < 0.001) and the Comet assay (OR 0.950, 95% CI 0.91-1.00, P = 0.041). Limitations, reasons for caution: HABSelect was a prospective RCT and the mechanistic study group was drawn from its recruitment cohort for retrospective analysis, without the full benefit of randomization. The clinical and mechanistic aspects of the study were mutually exclusive in that measures of DNAq were obtained from residual samples and not from HA-selected versus unselected sperm. Models for fitting mechanistic with baseline and other clinical data were developed to compensate for variable DNAq data quality. HABSelect used a solid-state version of PICSI and we did not assess the efficacy of any liquid-state alternatives. PICSI reduced fertilization rates and did not improve the outlook for cumulative pregnancy rates. Wider implications of the findings: Notwithstanding the interventional effect on fertilization rates and possibly blastocyst formation (neither of which influenced pregnancy rates), poor sperm DNAq, reflected by lower HBS, probably contributed to the depression of all gestational outcomes including live births, in the HABSelect trial. The interventional avoidance of defective sperm is the best explanation for the equalization in live birth rates among older couples randomized to the trial's PICSI arm. As patients going forward for assisted conception cycles globally in future are likely to be dominated by an older demographic, HA-based selection of sperm for ICSI could be considered as part of their treatment plan. Study funding/competing interest(s): The study was supported by the National Institute for Health Research (NIHR) EME (Efficacy and Mechanism Evaluation)-11-14-34. National Research Ethics Service approval 11/06/2013: 13/YH/0162. S.L. is CEO of ExamenLab Ltd (company number NI605309). Trial registration number: ISRCTN99214271.
... Moreover, there has been a steady decline in the number of deliveries resulting in a live-born neonate in industrialized countries with high economic activity (3). This partially translates into an increase of almost 20% between 2011 and 2020 in the total number of assisted reproduction technology (ART) cycles, according to the last International Committee for Monitoring Assisted Reproductive Technologies (ICMART) world report (4)(5)(6)(7)(8)(9). In particular, it has been shown that the male factor is solely implicated in 20% to 30% of cases of infertility, but male factor infertility contributes to approximately 40% to 50% of cases among couples diagnosed with infertility (10), partly due to decline in semen quality (11)(12)(13)(14). ...
Article
Objective To investigate whether men's adherence to dietary patterns promoted for the prevention of cardiovascular disease is associated with semen parameters and couples’ assisted reproductive technology (ART) outcomes. Design Prospective cohort study. Setting Fertility center at an academic medical center. Patient(s) A total of 245 men and their female partners who underwent 438 ART cycles between 2007 and 2020. Intervention(s) Male pretreatment dietary intake was assessed with a 131-item food frequency questionnaire from which we calculated eight a priori defined scores: Trichopoulou Mediterranean, Alternate Mediterranean, Panagiotakos Mediterranean, Healthy Eating Index, Alternative Healthy Eating Index, American Heart Association, Dietary Approaches to Stop Hypertension, and Plant-based. Main Outcome Measure(s) The primary outcome was live births per treatment cycle. The secondary outcomes were fertilization, implantation, and clinical pregnancy and seminogram parameters. Result(s) There was an inverse association between greater adherence by men to the Panagiotakos Mediterranean diet and the American Heart Association dietary pattern and lower fertilization rate. However, there were no significant associations between men’s adherence to any of the analyzed dietary patterns and the probabilities of implantation, clinical pregnancy, or live birth in multivariable-adjusted models. No significant differences in any of the semen parameters were found between participants of the lowest quartile and those of the highest quartile of the eight dietary patterns. Conclusion(s) These findings suggest that men’s adherence to several a priori defined dietary scores with documented cardiovascular benefits is not related to major outcomes of infertility treatment with ART or semen quality.
... Despite the current requirements of the HFEA, ICSI itself has never been subjected to the same scrutiny before its implementation for routine use [85]. Moreover, ICSI application in cases of non-male factor infertility is continuously rising [94]. While this is "justified" by a potential reduction in the risk of fertilisation failure [95], a wealth of data have reported that ICSI provides no real benefit to non-male factor patients [96], while some report that ICSI application to normozoospermic men may reduce the rates of clinical pregnancy and live birth [81]. ...
Article
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Hyaluronic acid (HA)-binding is reported to predict the fertilising capacity of spermatozoa, while HA-bound sperm selection is reported to reduce the incidence of miscarriage. However, the clinical effectiveness of these techniques remains uncertain. This work investigated the prognostic value of sperm-HA binding (HAB) as a predictor of treatment outcomes, and whether HAB-sperm selection for Invitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) improves clinical outcomes or reduces miscarriage rates. A systematic review of the literature was carried out. A modified version of the Downs and Black Checklist was used to assess bias and study quality on eleven selected studies. No significant correlations were found between HAB score and fertilisation, clinical pregnancy, or live birth rates (low-quality evidence). Three studies reported a significant reduction in the incidence of miscarriage, including a Cochrane review (low-quality evidence). While the prognostic value of HAB scores is currently undetermined, there is evidence that HAB-sperm selection prior to insemination reduces the incidence of miscarriage following ART. Moreover, there are no reports of detrimental effects of HAB-sperm selection on treatment outcomes when compared with conventional IVF or ICSI. Therefore, it is unclear why it is assigned as a treatment “add-on” with a red light by the HFEA, and why its routine use is not recommended.
... Since then, the ART gemellary pregnancy rate in the UK has dropped from 26.6% in 2008 to 16.3% in 2013, and the overall live birth rate with ART has not been affected (Harbottle et al., 2015). Over the past decade, in order to reduce the ART gemellary pregnancy rate, European, American, Japanese, and Australian scientists have actively promoted SET, achieving a SET rate of 50%-85% (De Geyter et al., 2020;Kushnir et al., 2017;Dyer et al., 2016). ART in China has undergone a dramatic development in the past 30 years, but the gemellary pregnancy rate still remains high. ...
Article
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Objective: To investigate transfer strategies in the frozen-thawed embryo transfer (FET) cycle. Methods: The clinical data of 1,652 FET patients were divided into five groups according to the number and quality of the transferred blastocyst: high-quality single blastocyst group (group A, n = 558), high-quality plus poor-quality double blastocyst group (group B, n = 435), poor-quality double blastocyst group (group C, n = 241), high-quality double blastocyst group (group D, n = 298), and poor-quality single blastocyst group (group E, n = 120). Inter-group comparison analyses of primary conditions, pregnancy outcomes and neonatal outcomes were then performed. Results: Group A had the highest embryo implantation rate (67.38%), significantly different from the implantation rates of the other four groups. The gemellary pregnancy rate (1.60%), preterm birth rate (5.58%), neonatal birth weight (3,350g [3,000g, 3,650g]), neonatal birth age (39.57 weeks [38.71, 40.34]), and incidence of low birth weight (7.02%) in group A were different from those in groups B, C, and D, but did not significantly differ from those in group E. Moreover, the proportions of male infants born in groups A (56.86%) and D (59.41%) were significantly higher than those in the other three groups. Double blastocyst transfer (0.528, 95% CI [0.410-0.680], P < 0.001) and high-quality blastocyst transfer (0.609, 95% CI [0.453-0.820], P = 0.001) were found to be protective factors for live birth. In addition, double blastocyst transfer was also the largest risk factor for pregnancy complications (3.120, 95% CI [2.323-4.190], P < 0.001) and neonatal complications (2.230, 95% CI [1.515-3.280], P < 0.001), especially for gemellary pregnancy (59.933, 95% CI [27.298-131.58], P < 0.001) and preterm birth (3.840, 95% CI [2.272-6.489], P < 0.001). Based on the ROC curves, a double blastocyst transfer could predict gemellary pregnancy reliably with a high area under the curve (AUC = 78.53%). Additionally, a double blastocyst transfer could effectively predict a high risk of pregnancy complications (AUC = 65.90%), neonatal complications (AUC = 64.80%) and preterm birth (AUC = 66.20%). Conclusion: The live birth rate of frozen-thawed high-quality single blastocyst transfer is lower than that of double high-quality blastocyst transfer, which can significantly increase the embryo implantation rate. High-quality single blastocyst transfer also significantly lowers the risk of gemellary pregnancy, preterm birth, and low birth weight, and can significantly improve maternal and infant outcomes. After weighing the pros and cons of live birth with pregnancy and neonatal complications, the authors believe that high-quality single blastocyst transfer is the optimal FET strategy for young women and is worthy of further clinical application. Despite this recommendation, high-quality single blastocyst transfer can increase the risk of monozygotic twins, as well as significantly increase the proportion of male infants born.
... In the past few years, the percentage of pregnancies obtained from in vitro fertilization (IVF) is dramatically increasing, overall due to an implementation of new technologies and to the relevant percentage of infertile couples in reproductive-age estimated to be between 8 and 12% worldwide and of 15% in Italy [1,2]. An increase in the number of couples that resorted to ART has been registered, going from 77.509 in 2018 to 78.618 in 2019 [2]. ...
Article
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The number of pregnancies achieved using in vitro fertilization (IVF) is rapidly increasing around the world. The chance of obtaining a successful pregnancy is also significantly improved due to technological advances and improvement in infertility treatment. Despite this success, there is evidence that pregnancy conceived by IVF has an increased risk of adverse maternal and perinatal outcome mainly represented by the development of hypertensive diseases, pre-eclampsia, and fetal growth restriction. Although different cofactors may play a role in the genesis of these diseases, the development of the placenta has a pivotal function in determining pregnancy outcomes. Advances in ultrasound technology already allows for evaluation in the first trimester, the impedance to flow in the uterine artery, and the placental volume using Doppler and three-dimensional techniques. This review article aims to describe the modification occurring in placental volume and hemodynamics after IVF and to summarize the differences present according to the type of IVF (fresh vs. frozen-thawed embryos).
... As ICSI-based treatments, regardless of need, continue to rise as a proportion of all treatment cycles (Dyer et al., 2016) alternative methods, including HA-binding, are being developed for enriching sperm of a higher quality for use in ICSI procedures (Lepine et al., 2019). Based on our models' outputs, extending on the findings of our original report (Miller et al., 2019), we hypothesize that the reduction in miscarriage in the trial's PICSI arm was linked to the more successful avoidance of sperm with a repairable defect in their DNA. ...
Article
Full-text available
(Abstracted from Hum Reprod 2022;37:1106–1125) With intracytoplasmic sperm injection (ICSI), many natural barriers that would normally prevent the entry of abnormal sperm are lost, increasing the importance of sperm DNA integrity for successful in vitro fertilization. There is currently no consensus on the optimal assay for measuring sperm DNA quality (DNAq), defined as any structural aspect of sperm chromatin that can compromise function if disrupted.
... Alarming data indicate that human fertility is constantly decreasing, which leads to the performance of around 1435 assisted reproductive technology (ART) cycles per million of habitants in Europe every year [1]. Infertility is considered as a disease by the World Health Organization, with an estimated incidence of 8-12% couples at reproductive age worldwide [2]. ...
Article
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Assisted reproductive technology (ART) is an essential tool to overcome infertility, and is a worldwide disease that affects millions of couples at reproductive age. Sperm selection is a crucial step in ART treatment, as it ensures the use of the highest quality sperm for fertilization, thus increasing the chances of a positive outcome. In recent years, advanced sperm selection strategies for ART have been developed with the aim of mimicking the physiological sperm selection that occurs in the female genital tract. This systematic review sought to evaluate whether advanced sperm selection techniques could improve ART outcomes and sperm quality/functionality parameters compared to traditional sperm selection methods (swim-up or density gradients) in infertile couples. According to preferred reporting items for systematic reviews and meta-analyses (PRISMA guidelines), the inclusion and exclusion criteria were defined in a PICOS (population, intervention, comparator, outcome, study) table. A systematic search of the available literature published in MEDLINE-PubMed until December 2021 was subsequently conducted. Although 4237 articles were recorded after an initial search, only 47 studies were finally included. Most reports (30/47; 63.8%) revealed an improvement in ART outcomes after conducting advanced vs. traditional sperm selection methods. Among those that also assessed sperm quality/functionality parameters (12/47), there was a consensus (10/12; 83.3%) about the beneficial effect of advanced sperm selection methods on these variables. In conclusion, the application of advanced sperm selection methods improves ART outcomes. In spite of this, as no differences in the reproductive efficiency between advanced methods has been reported, none can be pointed out as a gold standard to be conducted routinely. Further research addressing whether the efficiency of each method relies on the etiology of infertility is warranted.
... ART encompasses all interventional measures, including in vitro handling of both human sperm and oocytes and of embryos for reproduction issues. ART includes in vitro fertilization (IVF) and embryo transfer, gamete and embryo cryopreservation, embryo biopsy, intracytoplasmic sperm injection (ICSI), and preimplantation genetic testing (Dyer et al., 2016). ...
Article
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Infertility is a prevalent worldwide health issue and is defined by the World Health Organization (WHO) as a global health problem. Considering the importance of the psychological dimensions of infertility, various measurement tools have been used to measure the variables involved in infertility, of which the most widely used are the following: the Symptom Checklist 90 (SCL90), the Brief Symptom Inventory (BSI), the State-Trait Anxiety Inventory Form (STAI), and the Depression Anxiety Stress Scale (DASS). Therefore, given the problems of infertile people in terms of psychological dimensions, the aim of this meta-analysis was to assess the psychological assessment score in infertility. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, we applied an online database with no time restriction. Data were gathered using a random-effect model to estimate the standard mean difference (SMD) for the evaluation of the strength of association analyses. Our data demonstrated a significant higher SCL90 score (CISCL90: 0.96, 0.34–1.57, heterogeneity: 94%, pheterogeneity < 0.001), and a non-significant higher DASS score (CIAnxiety: 0.82, -0.14 to 1.79; CIDepression: 0.8, -0.28 to 1.87; and CIStress: 0.82, -0.24 to 1.88). It is essential to seek for strategies to help infertile patients overcome their infertility-related psychological problems.
... For instance, the usage rates of ICSI vs. standard IVF vary from region to region, with a 55% usage in Asia, 65% in Europe, 73% in North America, and 86% in South America. The highest proportion of ICSI is utilized in the Middle East with almost all cycles using ICIS to fertilize oocytes [9,137]. Many other clinical and laboratory differences exist, such as types of COH regimes, protocols for oocyte retrieval, including sedation equipment setup; differences in treatment strategies, clinical guidelines, methodological standards, and experience; differences in disease definitions, etc. ...
Article
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Infertility, although not a life-threatening condition, affects around 15% of couples trying for a pregnancy. The increasing availability of large datasets from various sources, together with advances in machine learning (ML) and artificial intelligence (AI), are enabling a transformational change in infertility care. However, real-world applications of data-driven medicine in infertility care are still relatively limited. At present, very little can prevent infertility from arising; more work is required to learn about ways to improve natural conception and the detection and diagnosis of infertility, improve assisted reproduction treatments (ART) and ultimately develop useful clinical-decision support systems to assure the successful outcome of either fertility preservation or infertility treatment. In this opinion article, we discuss recent influential work on the application of big data and AI in the prevention, diagnosis and treatment of infertility. We evaluate the challenges of the sector and present an interpretation of the different innovation forces that are driving the emergence of a systems approach to infertility care. Efforts including the integration of multi-omics information, collection of well-curated biological samples in specialised biobanks, and stimulation of the active participation of patients are considered. In the era of Big Data and AI, there is now an exciting opportunity to leverage the progress in genomics and digital technologies and develop more sophisticated approaches to diagnose and treat infertility disorders.
... Infertility is a global public health issue, affecting 15% of all couples of reproductive age. The clinical definition of infertility used by the World Health Organization (WHO) is "a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse" [1]. ...
... In vitro fertilization and embryo transfer (IVF-ET) is now widely used in the treatment of infertility, and the number of cycles performed in IVF is increasing dramatically worldwide. The number and proportion of FET cycles is also steadily increasing [2]. Successfully predicting the probability of pregnancy in the IVF cycle is a long-standing problem [3]. ...
Article
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Background This study aimed to identify multiple endometrial receptivity related factors by applying non-invasive, repeatable multimodal ultrasound methods. Combined with basic clinical data, we further established a practical prediction model for early clinical outcomes in Freeze-thawed Embryo Transfer (FET). Methods Retrospective analysis of clinical data of infertility patients undergoing FET cycle in our Center from January 2017 to September 2019. Receiver operating characteristic (ROC) curve and decision curve analyses were performed by 500 bootstrap resamplings to assess the determination and clinical value of the nomogram, respectively. Results A total of 2457 FET cycles were included. We developed simple nomograms that predict the early clinical outcomes in FET cycles by using the parameters of age, BMI, type and number of embryos transferred, endometrial thickness, FI, RI, PI and number of endometrial and sub-endometrial blood flow. In the training cohort, the area under the ROC curve (AUC) showed statistical accuracy (AUC = 0.698), and similar results were shown in the subsequent validation cohort (AUC = 0.699). Decision curve analysis demonstrated the clinical value of this nomogram. Conclusions Our nomogram can predict clinical outcomes and it can be used as a simple, affordable and widely implementable tool to provide guidance and treatment recommendations for FET patients.
... One in six to eight couples of reproductive age suffer from infertility [1]. In vitro fertilization (IVF) is widely used globally, with millions of babies born through IVF each year [2]. With the development of cryopreservation, the freeze-all embryo transfer strategy has been increasingly used in clinical practice in the last decade [3], as it reduces late-onset ovarian hyperstimulation syndrome (OHSS) and bypasses impaired endometrial receptivity resulting from ovarian stimulation [4][5][6][7]. ...
Article
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Purpose To explore an interaction effect between serum anti-Müllerian hormone (AMH) levels and the relative treatment effect of a freeze-all versus a fresh embryo transfer strategy on live birth. Methods This was a retrospective cohort study investigating couples with infertility and eligible for both freeze-all and fresh embryo transfer between 2017 and 2019. Women with an absolute indication for a freeze-all strategy were excluded. Multivariable fractional polynomial interaction analysis within a logistic regression model was used to evaluate whether the treatment effect of a freeze-all versus a fresh transfer strategy varied at different AMH levels. Non-linear interactions were also considered. The primary outcome was the live birth after the first transfer. Results A total of 13,503 women underwent a fresh embryo transfer and 2247 women underwent a freeze-all strategy. Live birth rates were slightly higher in the freeze-all group compared to those in the fresh embryo transfer group (35% vs 33%). There was a non-linear interaction between baseline serum AMH levels and the relative treatment effect of a freeze-all strategy versus a fresh transfer strategy on live birth (P = 0.0161). The benefit on live birth from a freeze-all embryo transfer strategy was greatest in women with a high serum level (> 7 ng/ml). The interaction remained valid when different imputation methods were used. Conclusion As serum AMH level increased, there was a nonlinear increase in relative treatment effect of a freeze-only transfer versus a fresh transfer strategy on live birth, and such an effect reaches its maximum in women with high AMH levels.
Article
Introduction: The aim was to describe and compare changes in the reproductive pattern of women in their 40s observed over a decade in Scandinavia. Material and methods: Cross-sectional study using the total population of women aged 40-49 years between 2008-2018 in Denmark, Norway and Sweden (on average n = 1.5 million). Aggregated data concerning birth and induced abortion rate were collected and analyzed from national health registers. National data on redeemed prescriptions of hormonal contraceptives in the three countries were collected from prescription registers. Births after spontaneous and assisted conceptions were identified by using cross-linked data on deliveries from the Medical Birth Registers and National Registers of Assisted Reproduction in the three countries. Results: Use of hormonal contraception increased among women aged 40-44 years in Denmark from 24% to 31%, in Sweden from 27% to 30%, and in Norway from 22% to 24%. The levonorgestrel-releasing intrauterine device was the most frequently used method in all countries. Birth rates among women 40-44 years increased continuously from 9.5 to 12/1000 women in Denmark and from 11.7 to 14.3/1000 in Sweden, but remained stable in Norway at ~11/1000 women. There was a doubling of assisted conceptions in Denmark from 0.71 to 1.71/1000 women, Sweden from 0.43 to 0.81/1000 and Norway from 0.25 to 0.53/1000 women 40-49 years of age. Sweden had the highest induced abortion rate (7.7 to 8.1/1000 women) in women aged 40-49 years during the study period. Conclusions: From 2008 to 2018, birth rates continuously increased among women aged 40-49 years in Denmark and Sweden and births resulting from assisted reproductive technology doubled in all three countries.
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This paper shows the Catholic approach to the ethical dilemmas in human reproduction presented from a Confucian perspective on surrogacy, prenatal testing and preimplantation genetic diagnosis. The Confucian tradition points out the rules that enable the community to live a good life. However, these conducts are not meritorious for a future spiritual life, as it is not a theistic or revealed religion like Catholicism. Its ethics is fundamentally relational and examines the type of interaction that allows co-flourishment. Among these teachings, it provides gender roles. For example, women’s duties include caring for and submission to the family and childbearing. Confucianism considers reproduction necessary for the lineage to endure through time, fulfilling the desires of parents, families and ancestors. It is somewhat open to the use of surrogacy as one of the emergent technologies to assist reproduction. The same is true with prenatal testing and preimplantation genetic diagnosis to select healthier babies, as therapeutic and enhancement interventions are allowed in Confucianism. In contrast, Catholicism follows a reasoned faith and Magisterium, which explain and review the current problems of humanity. Catholicism considers that human beings should be procreated and not just biologically reproduced. Accordingly, the three techniques are forbidden, except when prenatal testing is aimed at treating the diseased embryo, as every human life, whether sick or healthy, is a gift from God.
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Ovarian stimulation is a key issue in assisted reproductive technology (ART) treatment. ART practice in Japan is unique with various types of ovarian stimulation protocols, which may contribute to lower pregnancy rates compared to other countries. This review aims to clarify optimal individualized ovarian stimulation for improving the pregnancy rate per one oocyte retrieval cycle in Japan. We performed a literature review to describe ovarian stimulation, classification of infertile women depending on ovarian reserve and response, and Japanese ART data and discussed optimal conventional and mild ovarian stimulation protocols in Japan. According to Japanese ART registry data, the live birth rate of 30-35-year-old women was 32%-37% per ET cycle; therefore, four to five embryos are calculatedly needed when aiming a cumulative live birth rate of ≥80%. Mild stimulation aimed at collecting 5-10 oocytes can be alternative choice as an optimal ovarian stimulation protocol in young women. In 40-year-old women, the live birth rate is 18.8%, resulting in eight or more embryos as necessary. Conventional stimulation must be required in women with advanced age. In poor responders, however, mild stimulation may be sufficient for maximumly extracting their ovarian function. In Japan, mild ovarian stimulation can be selected in patients with a good prognosis and poor responders; however, conventional ovarian stimulation is necessary for women in advanced age.
Article
Background The effects of acupuncture on in-vitro fertilization outcomes remain controversial. This study aimed to perform a meta-analysis to assess the effectiveness of acupuncture as an adjuvant therapy to embryo transfer compared to sham-controls or no adjuvant therapy controls on improving pregnancy outcomes in women undergoing in-vitro fertilization. Methods A systematic literature search up to January 2021 was performed and 29 studies included 6623 individuals undergoing in-vitro fertilization at the baseline of the study; 3091 of them were using acupuncture as an adjuvant therapy to embryo transfer, 1559 of them were using sham-controls, and 1441 of them were using no adjuvant therapy controls. They reported a comparison between the effectiveness of acupuncture as an adjuvant therapy to embryo transfer compared to sham-controls or no adjuvant therapy controls on improving pregnancy outcomes in women undergoing in-vitro fertilization. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated assessing the effectiveness of acupuncture as an adjuvant therapy to embryo transfer compared to sham-controls or no adjuvant therapy controls using the dichotomous method with a random or fixed-effect model. Results Significantly higher outcomes with acupuncture were observed in biochemical pregnancy (OR, 1.98; 95% CI, 1.55–2.53, p < 0.001); clinical pregnancy (OR, 1.70; 95% CI, 1.46–1.98, p < 0.001); ongoing pregnancy (OR, 1.78; 95% CI, 1.41–2.26, p < 0.001); and live birth (OR, 1.58; 95% CI, 1.15–2.18, p = 0.005) compared to no adjuvant therapy controls. However, no significant difference were found between acupuncture and no adjuvant therapy controls in miscarriage (OR, 0.96; 95% CI, 0.48–1.92, p = 0.91). No significant difference was observed with acupuncture in biochemical pregnancy (OR, 1.16; 95% CI, 0.65–2.08, p = 0.62); clinical pregnancy (OR, 1.13; 95% CI, 0.83–1.54, p = 0.43); ongoing pregnancy (OR, 1.04; 95% CI, 0.66–1.62, p = 0.87); live birth (OR, 1.02; 95% CI, 0.73–1.42, p = 0.90), and miscarriage (OR, 1.16; 95% CI, 0.86–1.55, p = 0.34) compared to sham-controls. Conclusions Using acupuncture as an adjuvant therapy to embryo transfer may improve the biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth outcomes compared to no adjuvant therapy controls. However, no significant difference was found between acupuncture as an adjuvant therapy to embryo transfer and sham-controls in any of the measured outcomes. This relationship forces us to recommend the use of acupuncture as adjuvant therapy in women undergoing in-vitro fertilization and inquire further studies comparing acupuncture and sham-controls to reach the best procedure.
Chapter
Obtaining good quality oocytes and preparing them for in-vitro fertilization (IVF) is a key stage in assisted reproduction. This is a complex process with many pitfalls, making good clinical preparation and laboratory technique essential for success. Illustrated throughout, this book will be valuable to clinical embryologists, laboratory personnel wishing to redefine or develop technique and improve outcomes, IVF quality managers, and gynecologists performing oocyte retrieval. Featuring descriptions of the underlying science along with practical advice on methods and trouble-shooting, this comprehensive manual will aid all those involved in this complex process of oocyte retrieval and preparation in navigating towards optimal outcomes.
Article
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Purpose To investigate whether history of comorbidities is associated with markers of ovarian reserve among subfertile women. Methods This observational study includes 645 women seeking fertility care at the Massachusetts General Hospital who enrolled in the Environment and Reproductive Health (EARTH) study (2005–2019). Women completed a comprehensive questionnaire including medical diagnosis of comorbidities. Ovarian reserve markers including antral follicle count (AFC), assessed by transvaginal ultrasound, and circulating serum levels of day 3 FSH and AMH, are assessed by immunoassays. We fit linear regression models to evaluate the association between history of comorbidities and markers of ovarian reserve while adjusting for confounders. Results Self-reported history of hypertension, cancer, and neurological disorders was negatively associated with AFC in unadjusted models and in adjusted models for age, smoking, physical activity, comorbidity count, and BMI. Adjusted mean AFC (95% CI) was lower among women with history of hypertension, compared to women with no self-reported history of hypertension (11.5 vs 15.6, p value 0.0001). In contrast, day 3 FSH levels were positively related to history of eating disorders in both unadjusted and adjusted models (10.8 vs. 7.43 IU/L, p value ≤ 0.0001). Self-reported history of other comorbidities was unrelated to AFC, day 3 FSH, and AMH levels. Conclusions History of hypertension, cancer, and neurological disorders was negatively associated with AFC, and eating disorders were positively related to day 3 FSH levels. The prevention of common comorbidities among women in reproductive age may help increase women’s fertility given the declining birth rates and increasing use of assisted reproductive technologies in the past years.
Conference Paper
Vast research has been carried out on the way Jewish women feel about their infertility and their use of assisted reproductive technologies (ART). This has been particularly researched in Israel, a distinctly pro-natalist country. Building on this scholarship, this thesis explores the infertility experiences of Orthodox Jewish Women living in London. Based on twenty-six interviews, conducted between 2017 and 2018, with Orthodox Jewish women living in North West London, this thesis presents some of the challenges these women faced when experiencing infertility, and the ways in which they found strength and support to navigate their journeys through ART. This thesis is comprised of two parts. Part I provides the background context for the thesis in three chapters. Chapter 1 introduces the reader to Judaism and British Jewry along with the development of its denominations and the meaning behind ‘community’. Chapter 2 broadly discusses Jewish meanings attributed to fertility and infertility alongside studies on the way individuals experience infertility, reproduction and pregnancy with a particular focus on Jewish scholarship. Chapter 3 outlines the methodology used, explaining how this thesis was developed from thought into fruition. Part II of the thesis concentrates on original data, with four data chapters each concentrating on a key theme emerging from the data – My destiny (Chapter 4), My Rabbi (Chapter 5), My Relationships (Chapter 6), My Identity (Chapter 7), a discussion chapter (Chapter 8), and a final chapter for conclusions, reflections and future work (Chapter 9). The key findings of this thesis illustrate that while all women believed their infertility was God given, their acceptance of these perceived ‘tests of faith’ was not smooth. The relationships that appeared to suffer the most were those the women held with their mothers. Inversely, the relationships that flourished most, as a result of infertility, were those which the women held with their Rabbis. This research gives useful insight into an under researched population. Its findings could offer guidance to medical professionals, counsellors, policy makers, and religious leaders. Additionally, this work could be encouraging for other Orthodox Jewish women when facing infertility.
Preprint
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Background: We aimed to analyse our clinical results for a particular subgroup of patients with poor ovarian response (POR) in order to clarify if lower number of oocytes is a drawback for proceeding to C-IVF Materials and methods: In this retrospective study, patient files of all couples (#1733) who underwent oocyte retrieval between January 2017 and December 2019 were reviewed and 191 cases diagnosed with non-male factor infertility in which ≤3 cumulus-oocyte-complexes available for fertilisation were analysed. Exclusion criteria were: woman age>42, patients with a history of previous ART trial, prenatal genetic testing cycles and couples undergoing total cryopreservation for any indication. Three groups were constructed depending on the method of fertilisation and on semen quality as follows: IVF non-male factor (Group 1,n=77); ICSI non-male factor (Group 2, n=65); ICSI male factor- ICSI/MF n=49 according to WHO reference values. Main outcome parameters were: fertilisation rate, implantation rate and live birth rate. Results: Fertilisation rate per collected COC was significantly higher in group 1 compared to the other two groups (85,68%, 72,58%, 73,33% respectively, p=0,004). FR per inseminated oocyte also tended to be higher in group 1 but not reaching a statistically significant level. Both techniques yielded similar implantation rates (20,42%, 28,49%, 23,33% respectively, p=0,407) and live birth rates (26,8%, 30,6%, 31,1% respectively, p=0.643). Conclusions: In the presence of normal semen parameters, low egg number is not an indication to perform ICSI. The choice of fertilisation method should be based primarily on semen quality, in combination with the patient’s previous history regardless of the ovarian reserve.
Article
Infertility is a medical condition that can be overcome thanks to advances in medically assisted reproductive (MAR) therapies. Despite the ultimate measure of MAR efficacy being the birth of a new human being, there are ethical and methodological questions as to which outcome best translates the value of MAR in cost-effectiveness analyses. Many authors favour cost per life birth outcomes instead of more traditional cost per quality-adjusted life years (QALYs), which raises generalizability issues for decision-makers. Nonetheless, infertility and infertility treatments substantially differ from other health conditions and health treatments, particularly in the way they affect quality of life of the infertile couple. Collecting quality of life measures in infertility and pregnancy are also surrounded by challenges not easily overcome. We reflect on cost-effectiveness methods applied to MAR technologies, on ethical considerations of valuing a MAR-generated life, and on its broader societal value for consideration by decision-makers.
Chapter
Approximately five million children have been born worldwide as a result of assisted reproductive technology (ART). These techniques are now practised independently in most of the world's nations. Although the vast majority of ART parents and children are healthy following the procedures involved, there is an imperative to maintain a high standard of practice and monitor outcomes carefully. Interpretation of outcome data is difficult for a variety of reasons. As ART technologies evolve and new variants are established, the need for robust assessment of outcomes increases. This book gives a thorough review of potential complications of ART, with detailed analysis of outcome data for the various conditions described. A worldwide perspective is given throughout, with an international team of chapter authors.
Article
Full-text available
Objective To date, evidence regarding the effectiveness and safety of two consecutive cycles of single embryo transfer (2SETs) compared with one cycle of double embryo transfer (DET) has been inadequate, particularly considering infertile women with different prognostic factors. This study aimed to comprehensively summarize the evidence by comparing 2SETs with DET. Methods PubMed, Embase, Cochrane Library databases, ClinicalTrails.gov, and the WHO International Clinical Trials Registry Platform were searched up to March 22, 2022. Peer-reviewed, English-language randomized controlled trials (RCTs) and observational studies (OS) comparing the outcomes of 2SETs with DET in infertile women with their own oocytes and embryos were included. Two authors independently conducted study selection, data extraction, and bias assessment. The Mantel–Haenszel random-effects model was used for pooling RCTs, and a Bayesian design-adjusted model was conducted to synthesize the results from both RCTs and OS. Main Results Twelve studies were finally included. Compared with the DET, 2SETs were associated with a similar cumulative live birth rate (LBR; 48.24% vs. 48.91%; OR, 0.97; 95% credible interval (CrI), 0.89–1.13, τ 2 = 0.1796; four RCTs and six observational studies; 197,968 women) and a notable lower cumulative multiple birth rate (MBR; 0.87% vs. 17.72%; OR, 0.05; 95% CrI, 0.02–0.10, τ 2 = 0.1036; four RCTs and five observational studies; 197,804 women). Subgroup analyses revealed a significant increase in cumulative LBR (OR, 1.33; 95% CrI, 1.29–1.38, τ 2 = 0) after two consecutive cycles of single blastocyst transfer compared with one cycle of double blastocyst transfer. Moreover, a lower risk of cesarean section, antepartum hemorrhage, preterm birth, low birth weight, and neonatal intensive care unit admission but a higher gestational age at birth and birth weight were found in the 2SETs group. Conclusion Compared to the DET strategy, 2SETs result in a similar LBR while simultaneously reducing the MBR and improving maternal and neonatal adverse outcomes. The 2SETs strategy appears to be especially beneficial for women aged ≤35 years and for blastocyst transfers.
Article
Purpose Little is known about oncofertility practice in developing countries that usually suffer from a shortage of health services, especially those related to cancer care. Materials and Methods To learn more about oncofertility practice in developing countries, we generated a survey to explore the barriers and opportunities associated with oncofertility practice in five developing countries from Africa and Latin America within our Oncofertility Consortium Global Partners Network. Responses from Egypt, Tunisia, Brazil, Peru, and Panama were collected, reviewed, and discussed. Results Common barriers were identified by each country, including financial barriers (lack of insurance coverage and high out-of-pocket costs for patients), lack of awareness among providers and patients, cultural and religious constraints, and lack of funding to help to support oncofertility programs. Conclusion Despite barriers to care, many opportunities exist to grow the field of oncofertility in these five developing countries. It is important to continue to engage stakeholders in developing countries and use powerful networks in the United States and other developed countries to aid in the acceptance of oncofertility on a global level.
Article
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Introduction It is uncertain whether Assisted Reproductive Technology (ART) is associated with an increased risk of poor breastfeeding outcomes and what could be possible mechanisms. This study aimed to examine the effect of mode of conception on breastfeeding outcomes during the first two months postpartum and identify the potential mediating pathways for this relationship. Methods A retrospective cohort study was conducted in a sample of 3,565 women with live births. Participants were classified by mode of conception as follows: fertile women who conceived naturally (fertile women; n = 2,857), women with infertility who conceived naturally (sub-fertile women; n = 483), and women with infertility who conceived through ART (women with infertility; n = 310). The infant-feeding patterns were assessed with four-time points before two months postpartum. Binary and multinomial logistic regression and causal mediation analyses were performed. Results The rates of breastfeeding initiation and discontinuation across modes of conception were similar. However, infertile and sub-fertile women had 37% (95% CI 1.02, 1.83) and 56% (95% CI 1.06, 2.27) increased risks of introducing formula before the first week postpartum, respectively, and 35% (95% CI 1.01, 1.82) and 52% (95% CI 1.04, 2.24) higher risks of exclusive breastfeeding for less than one week, respectively, compared to fertile women. The relationships were mainly mediated through multiple gestation and admission to neonatal/pediatric intensive care units (NICU/PICU; proportions of mediation were over 50%). The effects of mode of conception on breastfeeding outcomes became not significant in cases of singleton birth. Conclusions Sub-fertile women and women with infertility intended to breastfeed but experienced higher perinatal risks in the early postpartum period. Multiple gestation and admission to NICU/PICU forced them to introduce formula earlier than preferred, thus leading to a shorter duration of exclusive breastfeeding. Single embryo transfer policy and breastfeeding support in NICU/PICU could help those women achieve positive early breastfeeding outcomes.
Article
It is more than thirty years that perinatologists and healthcare personals, aim to reduce the morbidity associated with multiple pregnancy. In many cases these complications stem from pregnancies achieved via artificial reproductive technologies (ART). Although dramatic measures have been taken to control those risks by increasing the proportion of single embryo transfers, multiple pregnancy rate still remains relatively high among patient conceived via ART, carrying risks to both mothers and newborns, and are coupled with the related economic burden associated with prematurity. The aim of this review is to provide the current evidence regarding single embryo transfer, to assist decision makers and to promote patient knowledge toward an elective policy to reduce the risk of twining. Single embryo transfer may aid in further reduction of multiple pregnancy, and in most cases will maintain patient autonomy and right of choice.
Chapter
In many countries, marriage is no longer considered a prerequisite for childbearing. Cohabitation and children born outside of marriage are both on the rise. Advances in assisted reproductive technology have made it more feasible to have a child without a partner or within the context of a same-sex union, at least for women. In this chapter, I discuss the delay and decrease in marriage, the spread of cohabitation, how people find a mate, trends in same-sex unions, and how changes in partnerships have affected fertility. Although fewer people are married, marriage continues to be one of the most persistent and strongest determinants of fertility. Many individuals also appear to have problems finding a partner, although the reasons differ fundamentally for men and women.
Article
Aim: The purpose of the study was to establish a mathematical model to help rank the order of blastocysts and assist selection of which blastocysts to warm in vitrified-thawed embryo transfer cycles. Design: A total of 2862 women who underwent first vitrified-thawed single blastocyst transfer (SBT) between July 2015 and July 2019 were retrospectively recruited and randomized into a training set (n = 2289) and testing set (n = 573). Least absolute shrinkage and selection operator (LASSO) regression was used to screen the factors critical to live birth (LB). Subsequently, a nomogram model was established to convert the effect of each factor on LB into a measurable score. The efficacy of the model was then evaluated by the receiver operating characteristic and calibration curve. The performance of the model was also internally tested in the testing set. Results: Maternal age, endometrial thickness, oocyte number, day-3 embryo quality, blastocyst morphology, and blastulation day were selected as the critical predictors of LB in the vitrified-thawed SBT cycle and fitted into a nomogram model. The area under the curve (AUC) of the model was 0.67, and the AUC in the testing set was 0.64, which indicates moderate discrimination. The calibration curve showed good concordance between prediction and observation. Importantly, the score of each variable in the nomogram helped to rank the order of the blastocysts resulting in LB. Conclusions: The nomogram model can provide guidance for embryo selection in vitrified-thawed blastocyst transfer cycles, which may help to optimize the LB rate.
Article
This review appraises the evidence on the difference between single and double embryo transfer (SET and DET) in assisted reproduction technologies (ART) regarding the four health care quality dimensions most important to fertility patients and doctors. Regarding safety, DET not only creates the uncontested perinatal risks of twin pregnancies but compelling evidence added that singleton pregnancies after a vanishing twin also have poorer perinatal outcomes. SET is as effective as DET as shown by meta-analyses of RCTs, comparing 2 cycles of SET vs. DET and shown by cumulative live birth rates of entire ART trajectories of up to six cycles. Proposing SET, which is safer and as effective as DET, as golden standard is not irreconcilable with patient-centered care if patients are thoroughly informed on the reasoning behind the proposition and welcomed to challenge whether it fits their personal values. The cost-efficiency of SET is clearly higher and this even induced certain countries to start reimbursing ART on the condition of SET. In conclusion, SET should be the golden standard offered to all patients. The question is not if to apply SET but how to apply SET in terms of patient selection, patient-centered counselling and coverage of treatment. Key massage : This review highlights that single embryo transfer (SET) complies with important aspects of quality of care in reproductive medicine by encompassing safety, effectiveness, patient-centeredness and efficiency which leads to equity. SET should therefore be the standard of care in assisted reproductive technologies.
Chapter
Despite the advances of assisted reproduction technologies over the past 40 years, IVF remains relatively inefficient. The chance of a live birth per oocyte retrieved is only about 5%. The application of biotechnology enables to increase the pregnancy rate and assisted reproduction rates. In Europe, national regulations on assisted reproduction range from permissive to relatively strict; some countries do not even have targeted legislation. There are many questions in the field of assisted reproduction where biotechnologies may help—with diagnostics of causes of infertility in women and men, differentiate embryo quality and perceptivity of endometrium by using genomic, transcriptomic, metabolomic, and proteomic methods. The field of assisted reproduction throws us many questions about stem cells, nuclear transfer, mitochondrial diseases and its prevention, embryo genomics, epigenetics, cultivation media bioinformation detection. We describe biotechnology in the IVF process, in andrology, early embryo development, evaluation of embryo quality proces, as well as omics methods of culture blastocyst systems.
Article
Background Embryos with higher morphological quality may have a greater potential to achieve clinical pregnancy leading to live birth regardless of the type of cleavage-stage embryos or blastocysts. Few studies have investigated the impacts of embryo grading on the long-term health of offspring. Objective This pilot study aimed to examine the associations between embryo morphological quality and the physical, metabolic and cognitive development of singletons conceived by in vitro fertilization/intracytoplasmic sperm injection at their pre-school age. Study design This matched cohort study included singletons born to infertile couples who underwent fresh cleavage-stage embryo transfer cycles with good- or poor-quality embryos from 2014 to 2016 at the reproductive center of Women's Hospital, School of Medicine, Zhejiang University. A total of 144 4- to 6-year-old children participated in the follow-up assessment from 2020-2021, and the response rate of poor-quality embryo offspring was 39%. Singletons in the good-quality embryo group were matched to singletons in the poor-quality embryo group at a 2:1 ratio according to the fertilization method and the children’s age (±1 year). We measured offspring’s height, weight, body mass index, blood pressure, thyroid hormone levels and metabolic indicators. Neurodevelopmental assessments using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition and Adaptive Behavior Assessment System, Second Edition were performed. We also collected data from the medical records. A linear regression model was used to analyze the association between embryo morphological quality and offspring health outcomes. Results A total of 48 singletons conceived with poor-quality embryo transfer and 96 matched singletons conceived with good-quality embryo transfer were included in the final analysis. Age, sex, height, weight, body mass index, blood pressure, thyroid function and metabolic indicators were comparable in the two groups. After adjustment for potential risk factors by linear regression Model 1 and Model 2, poor-quality embryo offspring exhibited a tendency toward higher free thyroxine levels than did good-quality embryo offspring (beta: 0.22, 95% confidence interval: 0.09 to 0.90; beta: 0.22, 95% confidence interval: 0.09 to 0.91, respectively), but this difference was not clinically significant. Regarding neurodevelopmental assessment, there was no difference in the full-scale intelligence quotient of the Wechsler Preschool and Primary Scale of Intelligence (109.96 ± 12.42 versus 109.60 ± 14.46, P = 0.88) or the general adaptive index of the Adaptive Behavior Assessment System (108.26 ± 11.70 versus 108.08 ± 13.44, P = 0.94) between the two groups. The subindices of the two tests were also comparable. These findings remained after linear regression analysis. Conclusion At 4-6 years of age, singletons born from poor-quality embryo transfer have comparable metabolic and cognitive development to those born from good-quality embryo transfer using fresh cleavage-stage embryos. The results of this pilot study indicate that poor-quality embryos that can survive implantation and result in live birth are likely to have developmental potential comparable to that of good-quality embryos.
Article
Embryo quality determines the success of in vitro fertilization and embryo transfer (IVF-ET) treatment. Biomarkers for the evaluation of embryo quality have some limitations. Apoptosis in cumulus cells (CCs) is important for ovarian function. PTEN ( phosphatase and tensin homolog ) is a well known tumour suppressor gene that functions as a mediator of apoptosis and is crucial for mammalian reproduction. In the present study, we analyzed the expression level of PTEN in human CCs and aimed to investigate its association with embryo developmental competence in IVF treatment cycles. The PTEN mRNA level in CCs was measured using real-time fluorescence quantitative PCR. The association of the differential expression of PTEN with embryo quality was analyzed. Our data showed that PTEN mRNA levels were significantly decreased in CCs surrounding mature oocytes compared with immature oocytes. Similar changes were found in the analysis of fertilization and blastocyst formation. The speculation that the measurement of PTEN mRNA levels in human CCs would provide a useful tool for selecting oocytes with greater chances to implant into the uterus needs to be further verified through single-embryo transfer in the future. The proapoptotic mechanism of PTEN in human reproduction needs to be further studied.
Article
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BACKGROUND Although the possibilities for the treatment of infertility have been improved tremendously, not every couple will be treated successfully. METHODS Crude overall pregnancy rates of 50–65% per patient can be achieved nowadays, irrespective of the type of profertility treatment applied first. RESULTS IVF only accounts for about 20% of the pregnancies achieved. Dropout is an important reason for not reaching the estimated pregnancy rate. Even after failed IVF, spontaneous pregnancies do occur. Sperm and oocyte donation (OD) offer additional chances to subfertile couples. Severity of the male factor (in sperm donation) and young donor age (in OD) are important determinants of success. CONCLUSIONS Analysis of assisted reproduction technology outcomes would benefit from more universally accepted definitions and deserves better statistical analysis. Long-term cumulative live birth rates of 80% may be expected if dropout can be limited. Milder stimulation, a patient-friendlier approach and better counseling may help to keep more patients in the program.
Article
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How often does out-of-pocket payment (OPP) for assisted reproduction techniques (ART) with conventional ovarian stimulation result in catastrophic expenditure for households? Catastrophic cost was a frequent event affecting 51% of the poorest study participants and one in five couples in total. 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. We conducted a prospective observational study comprising 135 couples undergoing ART between March 2009 and June 2011. The study was set at an urban, level 3 referral hospital in the public and academic health sector of South Africa. At this institution ART is subsidized but requires co-payment by patients. Couples undergoing ART with conventional ovarian stimulation using GnRH analogs were recruited. A questionnaire capturing information on socioeconomic status, monthly household expenditure, OPP for the index ART cycle and financial coping strategies was administered. Households were categorized into tertiles according to socio-economic status. In addition to descriptive statistics, annualized OPP for ART services as a percentage of annual non-food household expenditure was calculated to estimate catastrophic health care expenditure. The Pearson χ(2) test and a logistic regression were used to identify factors related to incurring catastrophic spending. 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). No attempt was made to obtain proof of any payment or expenditure, and all information collected relied on participants' verbal account. 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. 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. not applicable.
Article
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We present the first report from the South African Register of Assisted Reproductive Techniques. All assisted reproductive technology (ART) centres in South Africa were invited to join the register. Participant centres voluntarily submitted information from 2009 on the number of ART cycles, embryo transfers, clinical pregnancies, age of female partners or egg donors, and use of fertilisation techniques. Data were anonymised, pooled and analysed. The 12 participating units conducted a total of 4 512 oocyte aspirations and 3 872 embryo transfers in 2009, resulting in 1 303 clinical pregnancies. The clinical pregnancy rate (CPR) per aspiration and per embryo transfer was 28.9% and 33.6%, respectively. Fertilisation was achieved by intracytoplasmic sperm injection in two-thirds of cycles. In most cycles, 1 - 2 embryos or blastocysts were transferred. Female age was inversely related to pregnancy rate. The register achieved a high rate of participation. The reported number of ART cycles covers approximately 6% of the estimated ART demand in South Africa. The achieved CPRs compare favourably with those reported for other countries.
Article
Full-text available
Many countries now have registers of assisted conception that were initially set up to evaluate the effectiveness of treatment, to monitor pregnancy outcomes and the health of treated women, and to assess any immediate risks for the women and their children. World reports, based on information from national registers, have enabled international comparisons of the extent to which the various techniques of assisted conception are used to treat infertile couples, as well as comparisons of pregnancy outcome. The reports also provide comparative data on pregnancy rates in populations rather than in single in-vitro fertilization (IVF) centres. To determine whether newly introduced techniques such as intracytoplasmic sperm injection are associated with any increased risks of birth defects or other adverse outcomes, information notified to registers will often need to be supplemented by clinical reports or by linkage of data in IVF registers and other health data systems. Further efforts to improve the quality of information on assisted conception within each country and internationally need to be well supported so that the effectiveness of treatment and the outcomes of treated couples and their children can be evaluated properly.
Article
Traditionally, IVF success rates have been reported in terms of live birth per fresh cycle or embryo transfer. With the increasing use of embryo freezing and thawing it is essential that we report not only outcomes following fresh but also those after frozen embryo transfer as a complete measure of success of an IVF treatment. Most people agree that an individual's chance of having a baby following fresh and frozen embryo transfer should be described as cumulative live birth rate. However, views on the most appropriate parameters required to calculate such an outcome have been inconsistent. There is an additional dimension—time for all frozen embryos to be used up by a couple, which can influence the outcome. Given that cumulative live birth rate is generally perceived to be the preferred reporting system in IVF, it is time to have an international consensus on how this statistic is calculated, reported and interpreted by stakeholders across the world.
Article
Developed countries have experienced both some population growth and unprecedented declines in fertility rates during the last half of the twentieth century. Couples now have fewer than two children on average in most European countries and they tend to postpone these births until a later age. A decline in male fertility has been suggested by some studies of semen quality, but there is contrasting evidence of shorter times to pregnancy for couples trying to conceive. An important economic factor is the income of young men relative to their parents' incomes, which determines how they rate the ability of their own earnings to support a family. Lower relative income in the 1970s was associated with a lower fertility rate. The decline in fertility in the USA may have been attenuated by the sharp rise in female income during the late 1960s and early 1970s, allowing women to take advantage of purchased child care, thus maintaining the relative family income. The level of demand for children does not appear to be set by known psychological factors, although explanations for the desire to reproduce have been sought in biological, psychoanalytical and socio-cultural research. Recent studies indicate that adults with secure attachment relationships are more interested in being parents. Possible epidemiological factors include age at first marriage, but in Eastern Europe, where age at first marriage is as low as 22 years, fecundity rates do not exceed 1.5. When mothers' age cohorts are analysed, the mean fecundity rate has been falling since the 1920s. Health factors affecting population trends include the change in contraceptive prevalence over the last 40 years. The prevalence of sub-fertility remains close to 10%, and studies from a number of countries indicate that ~50% of infertile couples make use of infertility services including IVF and intracytoplasmic sperm injection which are available in 45 countries covering 78% of the world's population. It is estimated that the level of service is sufficient for less than one-third of the need.
Article
The purpose of this committee opinion, which replaces the 2006 ASRM Practice Committee document titled Multiple Pregnancy Associated with Infertility Therapy, is to provide physicians with pertinent information that may help to avoid multiple gestations and to aid in patient counseling regarding the associated risks. (Fertil Steril (R) 2012;97:825-34. (C)2012 by American Society for Reproductive Medicine.)
Article
Is preimplantation genetic diagnosis for aneuploidy (PGD-A) with analysis of all chromosomes during assisted reproductive technology (ART) clinically and cost effective? The majority of published studies comparing a strategy of PGD-A with morphologically assessed embryos have reported a higher implantation rate per embryo using PGD-A, but insufficient data has been presented to evaluate the clinical and cost-effectiveness of PGD-A in the clinical setting. Aneuploidy is a leading cause of implantation failure, miscarriage and congenital abnormalities in humans, and a significant cause of ART failure. Preclinical evidence of PGD-A indicates that the selection and transfer of euploid embryos during ART should improve clinical outcomes. A systematic review of the literature was performed for full text English language articles using MEDLINE, EMBASE, SCOPUS, Cochrane Library databases, NHS Economic Evaluation Database and EconLit. The Downs and Black scoring checklist was used to assess the quality of studies. Clinical effectiveness was measured in terms of pregnancy, live birth and miscarriage rates. Nineteen articles meeting the inclusion criteria, comprising three RCTs in young and good prognosis patients and 16 observation studies were identified. Five of the observational studies included a control group of patients where embryos were selected based on morphological criteria (matched cohort studies). Of the five studies that included a control group and reported implantation rates, four studies (including two RCTs) demonstrated improved implantation rates in the PGD-A group. Of the eight studies that included a control group, six studies (including two RCTs) reported significantly higher pregnancy rates in the PGD-A group, and in the remaining two studies, equivalent pregnancies rates were reported despite fewer embryos being transferred in the PGD-A group. The three RCTs demonstrated benefit in young and good prognosis patients in terms of clinical pregnancy rates and the use of single embryo transfer. However, studies relating to patients of advanced maternal age, recurrent miscarriage and implantation failure were restricted to matched cohort studies, limiting the ability to draw meaningful conclusions. Relevant studies may have been missed and findings from RCTs currently being undertaken could not be included. Given the uncertain role of PGD-A techniques, high-quality experimental studies using intention-to-treat analysis and cumulative live birth rates including the comparative outcomes from remaining cryopreserved embryos are needed to evaluate the overall role of PGD-A in the clinical setting. It is only in this way that the true contribution of PGD-A to ART can be understood. No specific funding was used to undertake this study. Evelyn Lee does not report any conflict of interest. Associate Professor Illingworth is an employee of and a shareholder in Virtus Health which is a provider of clinical preimplantation genetic services to patients in Australia Dr Leeanda Wilton is an employee of and a shareholder in Virtus Health which is a provider of PGD services in Australia Dr Chambers previously received grant support to her institution from the Australian Government, Australian Research Council (ARC) Linkage Grant No. LP1002165; ARC Linkage Grant Partner Organisations were IVF Australia, Melbourne IVF and Queensland Fertility Group. TRIAL REGISTRATIONS NUMBER: NA. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Article
To analyze information on assisted reproductive technology (ART) performed worldwide and trends in outcomes over successive years. Cross-sectional survey on access, effectiveness, and safety of ART procedures performed in 53 countries during 2005. A total of 2,973 clinics from national and regional ART registries. 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, 1,052,363 ART procedures resulted in an estimated 237,315 babies born. The availability of ART varied by country from 15 to 3,982 cycles per million of population. Of all initiated fresh cycles, 62.9% were intracytoplasmic sperm injection. The overall delivery rate per fresh aspiration was 19.6% and for frozen embryo transfer 17.4%, with a cumulative delivery rate of 23.9%. With wide regional variations, single embryo transfer represented 17.5% of cycles, and the proportion of deliveries with twins and triplets from fresh transfers was 23.6% and 1.5%, respectively. Systematic collection and dissemination of international ART data allows patients, health professionals, and policy makers to examine and compare the impact of reproductive strategies or lack of them as markers of reproductive health.
Article
To systematically quantify the impact of consumer cost on assisted reproduction technology (ART) utilization and numbers of embryos transferred. Ordinary least squared (OLS) regression models were constructed to measure the independent impact of ART affordability-measured as consumer cost relative to average disposable income-on ART utilization and embryo transfer practices. Not applicable. Women undergoing ART treatment. None. OLS regression coefficient for ART affordability, which estimates the independent effect of consumer cost relative to income on utilization and number of embryos transferred. ART affordability was independently and positively associated with ART utilization with a mean OLS coefficient of 0.032. This indicates that, on average, a decrease in the cost of a cycle of 1 percentage point of disposable income predicts a 3.2% increase in utilization. ART affordability was independently and negatively associated with the number of embryos transferred, indicating that a decrease in the cost of a cycle of 10 percentage points of disposable income predicts a 5.1% increase in single-embryo transfer cycles. The relative cost that consumers pay for ART treatment predicts the level of access and number of embryos transferred. Policies that affect ART funding should be informed by these findings to ensure equitable access to treatment and clinically responsible embryo transfer practices.
Article
The Inter-American Court of Human Rights (the Court) has ruled that the Supreme Court of Costa Rica's judgment in 2000 prohibiting in vitro fertilization (IVF) violated the human right to private and family life, the human right to found and raise a family, and the human right to non-discrimination on grounds of disability, financial means, or gender. The Court's conclusions of violations contrary to the American Convention on Human Rights followed from its ruling that, under the Convention, in vitro embryos are not "persons" and do not possess a right to life. Accordingly, the prohibition of IVF to protect embryos constituted a disproportionate and unjustifiable denial of infertile individuals' human rights. The Court distinguished fertilization from conception, since conception-unlike fertilization-depends on an embryo's implantation in a woman's body. Under human rights law, legal protection of an embryo "from conception" is inapplicable between its creation by fertilization and completion of its implantation in utero.
Article
STUDY QUESTION Do births following single embryo transfers (SET) have a reduced risk of perinatal mortality compared with those following double embryo transfers (DET)? SUMMARY ANSWER SET is associated with reduced risk of perinatal mortality compared with DET. WHAT IS KNOWN ALREADY Fetal, neonatal and perinatal mortality are important indicators for monitoring pregnancy and childbirth, particularly for births following assisted reproductive technology (ART) treatments. Following the introduction of SET, there has been a decline in the perinatal mortality rate (PMR) among babies born after ART in Australia and New Zealand. STUDY DESIGN, SIZE, DURATION This population study (census) included 50 258 births of ≥20 weeks gestation and/or ≥400 g of birthweight following embryos transfer cycles in Australia and New Zealand during the period 2004–2008. PARTICIPANTS/MATERIALS, SETTING, METHODS The PMR was calculated according to the number of embryos transferred and other demographic and treatment-related factors. Perinatal deaths were defined as the number of fetal deaths (stillbirths) plus the number of neonatal deaths (deaths that occur before 28 days after birth). MAIN RESULTS AND THE ROLE OF CHANCE The PMR was 16.2 per 1000 births (n= 813). Of the 813 perinatal deaths, 630 were fetal deaths and 183 neonatal deaths. Twins had a significantly higher PMR (27.8 per 1000 births) than singletons (12.4 per 1000 births). The risk of perinatal mortality for all births following DET was 53% higher than for all births following SET (adjusted risk ratio 1.53, 95% confidence interval (95% CI): 1.29–1.80). Births following fresh DET had a 58% increased risk of perinatal mortality compared with births following fresh SET (risk ratio 1.58, 95% CI: 1.32–1.90). LIMITATIONS, REASONS FOR CAUTION Information on outcomes was missing from
Article
For the 10%-15% of American married couples who experience reproductive problems, in vitro fertilization (IVF) is the leading technologically advanced treatment procedure. IVF's expense, however, may prevent many couples from receiving treatment, and those who are treated may take an overly aggressive approach in order to reduce the probability of failure. Aggressive treatment, which occurs through an increase in the number of embryos transferred during IVF, can lead to medically dangerous multiple births. We evaluate the principle policy proposal – insurance mandates – for improving IVF access and outcomes. We use data from US markets during 1995-2003 to show that broad insurance mandates for IVF result in large increases in treatment access and also signi…cantly less aggressive treatment. More limited insurance mandates, which may apply to a subset of insurers or provide weaker guidelines for insurer behavior, generally have little e¤ect on IVF markets.
Article
Many definitions used in medically assisted reproduction (MAR) vary in different settings, making it difficult to standardize and compare procedures in different countries and regions. With the expansion of infertility interventions worldwide, including lower resource settings, the importance and value of a common nomenclature is critical. The objective is to develop an internationally accepted and continually updated set of definitions, which would be utilized to standardize and harmonize international data collection, and to assist in monitoring the availability, efficacy, and safety of assisted reproductive technology (ART) being practiced worldwide. Seventy-two clinicians, basic scientists, epidemiologists and social scientists gathered together at the World Health Organization headquarters in Geneva, Switzerland, in December 2008. Several months before, three working groups were established as responsible for terminology in three specific areas: clinical conditions and procedures, laboratory procedures, and outcome measures. Each group reviewed the existing International Committee for Monitoring Assisted Reproductive Technology glossary, made recommendations for revisions and introduced new terms to be considered for glossary expansion. A consensus was reached on 87 terms, expanding the original glossary by 34 terms, which included definitions for numerous clinical and laboratory procedures. Special emphasis was placed in describing outcome measures, such as cumulative delivery rates and other markers of safety and efficacy in ART. Standardized terminology should assist in analysis of worldwide trends in MAR interventions and in the comparison of ART outcomes across countries and regions. This glossary will contribute to a more standardized communication among professionals responsible for ART practice, as well as those responsible for national, regional, and international registries.
Article
Assisted reproductive technology (ART) is the most successful treatment for the 9% of people at reproductive age who suffer with infertility, but only a small percentage of those needing ART actually access it. Access varies greatly internationally owing to religious, cultural and political factors, probably the most important factor being each society's perspective on the moral status of the embryo. Economic factors, the nature of the healthcare system and public funding affect access both among and within countries. Regulations and guidelines are highly variable, but critical, in determining access and types of services. Cross-border travel for reproductive care is not uncommon. In the future, better public funding of ART, technological improvements, lower cost and slow international harmonization with fewer differences in ART services will probably increase access significantly.
Article
This article examines the high prevalence of primary and secondary infertility in low-resource countries. Provision of assisted reproductive technology (ART) to overcome both female and male infertility is in line with the reproductive rights agenda developed at the International Conference on Population and Development (ICPD) in Cairo 15 years ago. In addition to the right to control fertility, reproductive rights must encompass the right to facilitate fertility when fertility is threatened. Facilitation of fertility may require resort to ART, among both men and women. Egypt is highlighted as a positive example of progress in this regard.
Article
This paper is based on a Cochrane review of the same title by the same authors published in The Cochrane Library, issue 3, 2003 (see www.CochraneLibrary.net for information) with permission from the Cochrane Collaboration-John Wiley and Sons. Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the review. The objective of this review was to investigate whether ICSI improves live-birth rate in comparison with IVF in couples with non-male factor subfertility. We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 30 May 2002), the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2002), PubMed (January 1992 to September 2003) and reference lists of articles. Trials were included if they compared the effects of ICSI and IVF on live births, pregnancy and fertilization outcomes. Only randomized studies were included in this review. Two reviewers extracted data independently. There were no randomized data comparing live-birth rates. The single identified study did not find a difference in pregnancy rates (OR 1.4, 95% CI 0.95-2.2). There were no randomized data on miscarriage rates, or on other adverse events such as congenital malformations that may be of concern (415 couples randomized). Two studies used alternation to assign their couples and did have live birth as an outcome. These studies showed a significantly higher fertilization rate in the IVF group, but no difference in pregnancy, miscarriage or live-birth rate. Whether ICSI should be preferred to IVF for cases of non-male factor subfertility remains an open question. Further research should focus on live-birth rates and adverse events.
Article
The traditional reliance on the transfer of multiple embryos during in vitro fertilisation (IVF) in order to maximise the chance of pregnancy, has resulted in increasing rates of multiple pregnancies. Women undergoing IVF had a 20 - fold increased risk of twins and 400 - fold increased risk of higher order pregnancies (Martin 1998). The maternal and perinatal morbidity and mortality as well as national health service costs associated with multiple pregnancies is significantly high in comparison with singleton births (Luke 1992; Callahan 1994; Goldfarb 1996). Single embryo transfer is now being considered as an effective means of reducing this iatrogenic complication. This systematic review evaluates the effectiveness of elective two embryo transfer in comparison with single and more than two embryo transfer following IVF and ICSI (intra cytoplasmic sperm injection) treatment. The aim of this review is to determine, whether in couples who undergo IVF/ICSI: (1) the elective transfer of two embryos improves the probability of livebirth compared with: (a) Single embryo transfer, (b) Three embryo transfer or (c) Four embryo transfer.(2) the elective transfer of three embryos improves the probability of livebirth compared with: (a) Single embryo transfer, or (b) Four embryo transfer, We searched the Cochrane Menstrual Disorders and Subfertility Group's trials register (searched June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), MEDLINE (1970 to 2003), EMBASE (1985 to 2003) and reference lists of articles. We also handsearched relevant conference proceedings and contacted researchers in the field. Only randomised controlled trials were included. Two reviewers independently assessed eligibility and quality of trials. We found no studies that compared a policy of transferring multiple embryos on one cycle versus a policy of cryo- preservation and transfer of a single embryo over multiple cycles. We also found no trials comparing transfer of two versus three embryos. Three small, poorly reported trials compared transfer of two versus one embryo in a single cycle, and one small, poorly reported trial compared transfer of two versus four embryos in a single cycle. The clinical pregnancy rate per woman/couple associated with two embryo transfer was significantly higher compared to single embryo transfer (OR 2.08, 95% CI 1.24 to 3.50; test for overall effect p = 0.006). The live birth rate per woman/couple associated with two embryo transfer was also significantly higher than that associated with single embryo transfer (OR 1.90, 95% CI 1.12 to 3.22, test for overall effect p=0.02). The multiple pregnancy rate was significantly lower in women who had single embryo transfer (OR 9.97, 95% CI 2.61 to 38.19; p = 0.0008). The effectiveness of double embryo transfer versus four embryo transfer was tested in a single trial. There was no statistically significant differences in the clinical pregnancy rate (OR 0.75, 95% CI 0.26 to 2.16; p=0.6), and multiple pregnancy rates (OR 0.44. 95% CI 0.10 to 1.97; p = 0.28) between the two groups. The livebirth rate in the four embryo transfer group was higher compared to the two embryo transfer group, but the results were not statistically significant (OR 0.35, 95% CI 0.11 to 1.05; p = 0.06). The results of this systematic review suggest that live birth and pregnancy rates following single embryo transfer are lower than those following double embryo transfer as are the chances of multiple pregnancy including twins. As such, it is unlikely that the conclusions are robust enough to catalyse a change in clinical practice. The studies included are limited by their small sample size, so that even large differences might be hidden. Cumulative livebirth rates are seldom reported. The data were inadequate to draw conclusions about single embryo transfer and first frozen single embryo transfer (1FZET) or subsequent single frozen embryo transfers. Until more evidence is available single embryo transfer may not be the preferred choice for all patients undergoing IVF/ICSI. Clinicians may need to individualise protocols for couples based on their risks of multiple pregnancy. A definitive pragmatic, large multi centre randomised controlled trial comparing single embryo versus double embryo transfer in terms of clinical and cost effectiveness as well as acceptability is required. The primary outcome measured should be cumulative livebirth per woman/couple.
Assisted reproduction technology in Australia and New Zealand
  • A Macaldowie
  • E Lee
  • G M Chambers
Macaldowie A, Lee E, Chambers GM. Assisted reproduction technology in Australia and New Zealand 2013. Assisted reproduction technology series no. 18. Sydney: The University of New South Wales, 2015.
American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. 2012 Assisted Reproductive Technology Fertility Clinic Success Rates Report
Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. 2012 Assisted Reproductive Technology Fertility Clinic Success Rates Report. Atlanta, GA: US Dept of Health and Human Services, 2014.
Number of embryos for transfer following in vitro fertilisation or intra-cytoplasmic sperm injection
  • Z Pandian
  • J Marjoribanks
  • O Ozturk
  • G Serour
  • S Bhattacharya
Pandian Z, Marjoribanks J, Ozturk O, Serour G, Bhattacharya S. Number of embryos for transfer following in vitro fertilisation or intra-cytoplasmic sperm injection. Cochrane Database Syst Rev 2013;7:CD003416. doi: 10.1002/14651858.CD003416.pub4.
Practice Committee of the American Society for Reproductive Medicine. Multiple gestation associated with infertility therapy
Practice Committee of the American Society for Reproductive Medicine. Multiple gestation associated with infertility therapy. Fertil Steril 2012; 97:825-834.