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Objective: To report utilization, effectiveness, and safety of assisted reproductive technologies in 2015 and 2016., Design: A retrospective, cross-sectional survey of 3,103 assisted reproductive technology clinics in 74 countries in 2015 and 3,249 clinics in 79 countries in 2016 that submitted cycle and pregnancy outcome data through national and regional registries., Setting: Seventy-nine countries and >3,000 assisted reproductive technology clinics., Patient(s): Patients undergoing assisted reproductive technology procedures., Intervention(s): Assisted reproductive technology., Main Outcome Measure(s): Outcomes on country, regional, and global levels., Result(s): Reported for 2015: 2,358,239 cycles with 548,652 infants born; for 2016: 2,807,963 cycles with 647,188 infants born. Estimated in 2015, ≥2,683,677 cycles resulted in >675,134 infants; in 2016, ≥3,100,448 cycles resulted in ≥723,026 infants. Reported cycles represent approximately 80% of global utilization. In 2015 and 2016, 27.6% and 27.8%, respectively, of women undergoing fresh autologous treatment cycles were aged ≥40 years. Frozen-thawed embryo transfer (ET) cycles accounted for 47.0% and 51.9%, respectively, of all ETs in 2015 and 2016. Oocyte donation cycles accounted for 6.7% and 7.1% of all ETs in 2015 and 2016. Intracytoplasmic sperm injection was performed in 57.7% and 56.4% of autologous aspiration cycles in 2015 and 2016, respectively. The cumulative delivery rate per aspiration cycle for fresh and frozen-thawed ET was 32.4% in 2015 and 33.1% in 2016, respectively. The average number of transferred embryos was 1.70 in 2015 and 1.69 in 2016. The proportion of single ETs in fresh autologous cycles increased from 42.1% in 2015 to 44.0% in 2016. The twin delivery rate decreased from 16.0% in 2015 to 14.7% in 2016, and the triplet rate decreased from 0.6% in 2015 to 0.4% in 2016. The proportion of single ETs in frozen-thawed ET autologous treatment cycles was 62.2% in 2015 and 64.2% in 2016, with twin and triplet rates of 10.1% and 0.3% in 2015 and 10.0% and 0.2% in 2016, respectively., Conclusion(s): Utilization of assisted reproductive technology treatment and births per cycle increased from 2015 to 2016, although multiple births were reduced. An increasing proportion of frozen-thawed ET cycles, continuing wide variation in use of intracytoplasmic sperm injection, and an increase in single ET rates are reported., Competing Interests: Declaration of Interests M.S.K. reports travel support from Ferring, IBSA, and Merck, outside the submitted work. G.M.C. reports funding from the International Committee for Monitoring Assisted Reproductive Technologies (ICMART). The National Perinatal Epidemiology and Statistics Unit (NPESU) of the University of New South Wales, Sydney (UNSW) received funding. S.D. has nothing to disclose. F.Z.H. reports travel expenses to give a scientific lecture from Ferring Pharma, Director, responsible for the Latin American Registry of ART, Chair Committee of Ethics and Public Policies; Chilean Society of Obstetrics and Gynecology, Vice Chair ICMART, outside the submitted work. J.D.M. is Chair of Société de Médecine de la Reproduction, France, unpaid, outside the submitted work. O.I. has nothing to disclose. M.B. reports consulting fees from ABBOTT INIDA; honoraria from BAZEL PHARMA and MERCK SPEC; Board of Director, Pacific Rim Society of Reproductive Medicine; Board of Director, POSEIDON Group; Regional Director, IFFS Triennial Report, outside the submitted work. S.C.J. reports travel fee for lectures supported by Ferring; travel support from the Japan Society for Reproductive Medicine for attending meetings, outside the submitted work. B.F. has nothing to disclose. E.E. has nothing to disclose. V.B. reports consulting fees from Organon, Society for Assisted Reproductive Technology Executive Council, not paid, outside the submitted work. G.D.A. reports honoraria from Organon; travel support from ESHRE; Chair, International Committee for Monitoring ART. unpaid; President, World Endometriosis Research Foundation, unpaid; ICMART NGO Liaison Observer, Board of the International Federation of Fertility Societies, unpaid; ASRM: Member, Global Health Committee, American Society for Reproductive Medicine, unpaid; founder and CEO of Advanced Reproductive Care, Inc. (d/b/a ARC®Fertility), outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether the use of assisted reproductive technology (ART) therapy for conception is associated with imprinting disorders in children and the impact of parental factors related to infertility., Design: A nationwide register-based cohort study., Setting: Swedish national registers and nationwide quality IVF register., Patient(s): All liveborn singletons in Sweden (N = 2,084,127) between 1997 and 2017 with follow-up to December 31, 2018., Intervention(s): The use of specific methods implemented in ART., Main Outcome Measure(s): The International Classification of Diseases version 10 was used to identify three distinct imprinting disorder groups: Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS), and Silver-Russell syndrome (SRS), as well as central precocious puberty. The Cox model combined with inverse probability treatment weights was used to estimate the weighted hazard ratio (wHR) with a 95% confidence interval (CI), accounting for multiple confounders., Result(s): A total of 1,044 children were diagnosed with the disorders of interest, and 52 of them were conceived using ART therapy. The overall risk of being diagnosed with any of the studied imprinting disorders was elevated in children conceived using ART therapy compared with all other children (HR, 1.84; 95% CI, 1.38-2.45). After adjusting for parental background factors, the association was partially attenuated (wHR, 1.50; 95% CI, 0.97-2.32), but remained in the weighted comparison restricted to children of couples with known infertility (wHR, 1.52; 95% CI, 1.05-2.21). For the specific diagnoses of PWS/SRS, and BWS compared with children of couples with known infertility, children conceived with ART therapy showed a small excess risk, which could not be distinguished from the null (wHR, 1.56; 95% CI, 0.93-2.62 and 1.80; 95% CI, 0.99-3.28, respectively). Further subgroup analysis showed that the combined use of intracytoplasmic sperm injection and cryopreserved embryos was associated with a higher risk of both PWS/SRS (wHR, 4.60; 95% CI, 1.72-12.28) and BWS (wHR, 6.69; 95% CI, 2.09-21.45). The number of central precocious puberty cases in children conceived using ART therapy was too small (N = 3) to make any meaningful inference., Conclusion(s): The combined use of intracytoplasmic sperm injection and cryopreserved embryos was associated with small elevated risks of PWS/SRS, and BWS in children, independent of parental factors related to infertility., Competing Interests: Declaration of Interests M.Y. reports funding from the Chinese Scholarship Council for the submitted work. A.R.P. has nothing to disclose. E.I. reports funding from grants from Stockholm County Council (FoUI-961392) and Karolinska Institutet; Merck; honoraria for lectures; Illumina; payment for lectures; and travel costs to the conference outside the submitted work. A.S.O. reported grants from the National Institutes of Health and the Swedish Council for Working Life and Social Welfare during the conduct of the study and personal fees from Abbott (the Scientific and Medical Advisory Council) outside the submitted work. K.A.R.W. reports funding from the Swedish Research Council, the Swedish Cancer Society grants, the Swedish Childhood Cancer Fund, Radiumhemmets Forskningsfonder, Stockholm County Council Research and Development FoU grants, Karolinska Institutet, IngaBritt och Arne Lundbergs Forskningsstiftelse, and Stockholm County Council for the submitted work; funding from Foundation Stiftelse Bert Lundins minne grant 2022 and Research grants from NovoNordisk, Merck, Gedeon Richter and Ferrring Pharmaceuticals; royalties from YES Student Litteratur, Sweden, author of chapter in medical text book; consulting fees from The Swedish Ministry of Health and Welfare as expert in assisted reproduction and fertility preservation for transgender people; honoraria from Roche for chairmanship and lectures for education of oncologists, honoraria from Pfizer for chairmanship and lectures for education of oncologists, honoraria from Organon for lectures for obstetricians or gynecologists and reproductive medicine specialists, honoraria from IBSA for Advisory Board for educational event; support from Organon for participation in Journées Fertilité 2023, Paris, France; support from Regionstockholm for participation as chair of the Swedish Interest Group in Reproductive Medicine Fert-ARG, for the Swedish Society of Obstetrics and Gynecology (SFOG); participation at the advisory board for Merck, Nordic countries, and participation at the advisory board for Ferring, National Coordinator of Study; time-lapse equipment for preclinical research from Merck Pharmaceuticals, unrestricted grant; grant for experimental in vitro research from Ferring Pharmaceuticals, an unrestricted grant outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether parental infertility is associated with differences in cardiometabolic trajectories in offspring., Design: Pooled observational analysis in three prospective cohorts., Setting: Three nationwide pregnancy cohorts., Patients: A total of 14,609 singletons from the UK Avon Longitudinal Study of Parents and Children, the Portuguese Geraçao 21, and the Amsterdam Born Children and Their Development study. Each cohort contributed data up to ages 26, 12, and 13 years, respectively., Intervention: Parental infertility is defined as time-to-pregnancy of ≥12 months (n = 1,392, 9.5%)., Main Outcome Measures: Trajectories of body mass index (BMI), waist circumference, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C) level, high-density lipoprotein cholesterol (HDL-C) level, triglycerides level, and glucose level were compared in the offspring of couples with and without infertility. Trajectories were modeled using mixed-effects models with natural cubic splines adjusting for cohort, sex of the offspring, and maternal factors (age, BMI, smoking, educational level, parity, and ethnicity). Predicted levels of cardiometabolic traits up to 25 years of age were compared with parental infertility., Results: Offspring of couples with infertility had increasingly higher BMI (difference in mean predicted levels by age 25 years: 1.09 kg/m2, 95% confidence interval [0.68-1.50]) and suggestively higher diastolic blood pressure at age 25 years (1.21 mmHg [-0.003 to 2.43]). Their LDL-C tended to be higher, and their HDL-C values tended to be lower over time (age: 25 years, LDL-C: 4.07% [-0.79 to 8.93]; HDL-C: -2.78% [-6.99 to 1.43]). At age 17 years, offspring of couples with infertility had higher waist circumference (1.05 cm [0.11-1.99]) and systolic blood pressure (age: 17 years; 0.93 mmHg [0.044-1.81]), but these differences attenuated at later ages. No intergroup differences in triglyceride and glucose level trajectories were observed. Further adjustment for paternal age, BMI, smoking, and educational level, and both parents' histories of diabetes and hypertension in the cohort with this information available (Avon Longitudinal Study of Parents and Children) did not attenuate intergroup differences., Conclusion: Offspring of couples with infertility relative to those of fertile couples have increasingly higher BMI over the years, suggestively higher blood pressure levels, and tend to have greater values of LDL-C and lower values of HDL-C with age., Competing Interests: Declaration of interests A.H. has nothing to disclose. A.E. has nothing to disclose. H.B. has nothing to disclose. T.G.M.V. has received grants from the Amsterdam Academic Medical Centre, Amsterdam Public Health Services, and the Dutch Organization for Health Research and Development during the study. A.F. has received support from the British Heart Foundation, the UKMedical Research Council, the European Research Council, Wellcome Trust, and the Templeton Foundation during the study. D.A.L. has received support from the UKMedical Research Council, the National Institute of Health Research, the European Research Council, and the UKBritish Heart Foundation during the study. M.C.M. has received grants from the European Research Council during the study., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We aimed to review the global literature in the past 10 years regarding the impact of infertility on depression, anxiety, stress, and quality of life while exploring the potential clinical utility of psychosocial fertility questionnaires. PubMed, Scopus, and CINAHL were searched for English-published articles since 2013 on key search terms related to infertility, assisted reproductive technologies, and psychological terms such as depression, anxiety, mood disorders, and quality of life. The search yielded 7,947 articles, of which 366 articles were independently deemed relevant by the 3 reviewers. Anxiety, depression, and diminished quality of life are prevalent in the infertility experience of both men and women. Studies from around the world show similar experiences independent of culture., Competing Interests: Declaration of interests A.M.B. has nothing to disclose. T.D. has nothing to disclose. I.K.L. has nothing to disclose. A.B. has nothing to disclose. S.W. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Cultivating awareness for reproduction as a window to future health presents an opportunity for early identification and modification of risk factors that can affect both individual and population-level morbidity and mortality. Infertility could serve as both a window into future health as well as a pathway to future pathology. The underlying mechanisms of infertility may share common pathways with long-term risk for health and well-being. Making this identification early in the disease process may improve opportunities for intervention, and deepen our understanding of long-term risk. Additionally, fertility treatments may increase individual risk. Only by making these associations and designing studies to understand how disease and treatment risk impact health can we truly fulfill our goal of building healthy families. The aim of this review is to discuss the short-term impact of fertility challenges and treatment, long-term associations of infertility with morbidity and mortality, and the role of parity in modifying these risk associations., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the association of interpregnancy interval on perinatal outcomes and whether this was influenced by mode of conception., Design: Retrospective cohort., Setting: Centers for Disease Control and Prevention's natality national database., Patient(s): Patients who had an index singleton live birth with a preceding live birth. Index pregnancies from 2016 to 2019 were conceived with in vitro fertilization (IVF) (n = 32,829) or ovulation induction/intrauterine insemination (OI/IUI) (n = 23,016) or without assistance (n = 7,564,042)., Intervention(s): None., Main Outcome Measure(s): The primary outcomes evaluated were preterm birth (<37 weeks) and low birth weight (<2,500 g). Multivariable logistic regression was performed to evaluate the association of interpregnancy intervals with perinatal outcomes stratified by mode of conception. Adjusted odds ratios and 95% confidence intervals (CIs) were presented., Result(s): Compared with the interpregnancy interval reference group of 12 to <18 months, a <12 month interpregnancy interval was associated with an increase in preterm birth (<37 weeks) for pregnancies conceived with OI/IUI or without assistance (aOR, 1.42; 95% CI, 1.16-1.74, and aOR, 1.14; 95% CI, 1.13-1.15, respectively), whereas IVF was not associated with an increase (aOR, 0.90; 95% CI, 0.77-1.04). A <12 month interpregnancy interval was associated with an increase in low birth weight for pregnancies conceived with IVF or OI/IUI or without assistance (aOR, 1.34; 95% CI, 1.09-1.64; aOR, 1.33; 95% CI, 1.01-1.76; and aOR, 1.26; 95% CI, 1.24-1.27, respectively)., Conclusion(s): An interpregnancy interval of at least 12 months reduces adverse perinatal outcomes for pregnancies conceived with and without infertility treatment., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate the changes in infertility from 1995-2019 and determine the association of individual-level characteristics with fertility in the United States., Design: Cross-sectional study., Setting: Periodic data from 1995, 2002, 2006-2010, 2011-2013, 2013-2015, 2015-2017, and 2017-2019 cycles of the National Survey for Family Growth were used for this analysis. The National Survey for Family Growth comprises samples of the household-level population of women aged 15-44 years in the United States., Patient(s): Surveyed married and cohabiting women aged 15-44 years., Intervention(s): None., Main Outcome Measure(s): The primary outcomes were the rates of infertility across subgroups of married or cohabiting women. For secondary outcomes, we performed bivariable and multivariable logistic regression models using the pooled sample (N = 53,764) to determine the association of individual-level characteristics, including age, parity, pelvic inflammatory disease treatment, education, income, race or ethnicity, and receipt of sexual and reproductive health services, with the odds of 12-month infertility among married or cohabiting women., Result(s): The fluctuations in infertility over this period, with a low of 5.8% in 2006-2010 and a high of 8.1% in 2017-2019, were not found to be statistically significant. This trend was present across nearly all subgroups. The multivariable model showed that women who were older and nulliparous, had fewer years of education, had lower income, were non-Hispanic black, or were not receiving sexual and reproductive health services were more likely to be infertile., Conclusion(s): This study confirms that parity, age, race, and education level continue to have an association with infertility. Further, the results demonstrate that access to sexual and reproductive health services plays an important role in infertility. In contrast to previous studies, infertility in the United States is no longer on the decline, and Hispanic ethnicity did not have a significant relationship with infertility. Given the rise of sexually transmitted infections and the persistent lack of access to sexual and reproductive health services, particularly among already vulnerable groups, the connection between access to care and infertility is ripe for further investigation., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the association between subfertility and risk of cardiovascular disease (CVD) outcomes., Design: Prospective study., Setting: Population-based cohort., Patient(s): We studied 31,629 women and 17,630 men participating in the Trøndelag Health Study., Intervention(s): Self-reported subfertility. As men were not directly asked about fertility, male partners of female participants were identified through linkage to the Medical Birth Registry of Norway and assigned the fertility information obtained from their partners., Main Outcome Measure(s): The primary outcomes were stroke and coronary heart disease in women and men with and without a history of subfertility. The secondary outcomes were myocardial infarction and angina (subgroups of coronary heart disease) and any CVD (stroke or coronary heart disease). Information on CVD was available by linkage to hospital records. We used Cox proportional hazards models adjusted for age at participation in the Trøndelag Health Study (linear + squared), birth year, smoking history, cohabitation, and education. Cardiometabolic factors were assessed in separate models., Result(s): A total of 17% of women and 15% of men reported subfertility. In women, subfertility was modestly associated with an increased risk of stroke (age-adjusted hazard ratio [aaHR], 1.19; 95% confidence interval [CI], 1.02-1.39; adjusted hazard ratio [aHR]; 1.18; 95% CI, 1.01-1.37) and coronary heart disease (aaHR, 1.19; 95% CI, 1.06-1.33; aHR, 1.16; 95% CI, 1.03-1.30) compared with fertile women. In men, we observed a weak positive association for stroke (aaHR, 1.11; 95% CI, 0.91-1.34; aHR, 1.10; 95% CI, 0.91-1.33) and a weak inverse association for coronary heart disease (aaHR, 0.92; 95% CI, 0.81-1.05; aHR, 0.93; 95% CI, 0.81-1.06)., Conclusion(s): We observed modestly increased risks of CVD outcomes in women and some weak associations in men, although with no strong statistical evidence on sex differences. We acknowledge that we were only able to include men linked to pregnancies ending at 12 completed gestational weeks or later, potentially resulting in selection bias and misclassification of history of subfertility in analyses of male partners. Despite the large sample size, our results indicate the need for larger studies to obtain precise results in both sexes and determine whether there are true sex differences., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether assisted reproductive technology (ART) treatment adds obstetric and neonatal risks over and above that of underlying infertility-related diagnoses., Design: Retrospective study of linked ART, birth certificate, hospital discharge data, and outpatient insurance claims data in Massachusetts (2013-2017)., Setting: Database., Patient(s): Singleton deliveries in women with and without diagnoses of tubal disease, polycystic ovarian syndrome (PCOS), other ovulatory conditions, or endometriosis, identified from the insurance claims and ART data., Intervention(s): None., Main Outcome Measure(s): ART and non-ART pregnancy and delivery outcomes were compared with each other and with women with no history of infertility or usage of fertility treatment (fertile group). Generalizing estimating equations with Poisson distribution and exchangeable correlation structure were used to obtain adjusted relative risk ratios (aRRs) and 95% confidence intervals (CIs)., Result(s): Infertility-related diagnoses significantly increased the risks of pregnancy hypertension (PCOS: aRR, 1.13, 95% CI 1.00-1.27), preeclampsia/eclampsia (tubal: aRR 1.28, 95% CI 1.02-1.61; PCOS: aRR 1.23, 95% CI 1.06-1.43; other ovulatory: aRR 1.11, 95% CI 1.02-1.20), gestational diabetes (tubal: aRR 1.28, 95% CI 1.08-1.50; PCOS: aRR 1.58, 95% CI 1.42-1.75; other ovulatory: aRR 1.19, 95% CI 1.12-1.26), and placental problems (tubal aRR 1.47, 95% CI 1.11-1.94), as well as low birthweight and prematurity, compared with deliveries from the fertile group. Within each diagnosis, the use of ART consistently increased the risk of placental problems (aRR 1.49-2.86) but varied for other conditions., Conclusion(s): Our study demonstrated that compared with the fertile group, risk was elevated in pregnancies and deliveries from women with tubal, PCOS, other ovulatory, and endometriosis diagnoses who did/did not undergo ART treatment. Placental abnormalities were particularly elevated in ART compared to non-ART deliveries having the same diagnosis., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the proportion of pregnancies resulting in birth that were conceived with the use of clomiphene citrate (CC) and the frequency of multiple pregnancy., Design: Whole-of-population cohort study, constructed through data linkage. Comprehensive Australian Government records of dispensed medications were linked to state Perinatal Registry records for all births of at least 20 weeks' gestation., Setting: The state of South Australia., Patient(s): Women who maintained pregnancy for at least 20 weeks and gave birth between July 2003 and December 2015, a total of 150,713 women with 241,561 pregnancies., Intervention(s): Not applicable., Main Outcome Measure(s): Ongoing pregnancy occurring in proximity to CC, defined as dispensing from 90 days before to the end of a conception window derived from newborn date of birth and gestational age., Result(s): Linkage to dispensed prescription records was achieved for 97.9% of women. Women who conceived with CC tended to be older and socioeconomically advantaged and more likely than other women to have a history of miscarriage. Ongoing pregnancies associated with CC comprised 1.6% of the total; 5.7% were multiple births (mostly twins, 94.6%) compared with 1.5% in the remainder (98.5% twins)., Conclusion(s): In South Australia, 1.6% of pregnancies (1 in 60) of at least 20 weeks' gestation were conceived proximal to CC dispensing. Of these, 5.7% were multiple pregnancies. This takes the proportion of women who achieved an ongoing pregnancy with medical assistance from 4.4%, based on reports from assisted reproductive technology clinics, to 6% in total., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate long-term reproductive outcomes in couples who were enrolled in a large randomized controlled trial that studied optimal treatment for unexplained infertility., Design: Telephone survey, administered between March 2019 and February 2020., Setting: Large urban university-affiliated fertility center., Patient(s): Couples who enrolled in the Fast Track and Standard Treatment Trial (FASTT)., Intervention(s): None., Main Outcomes Measure(s): Number of live births, methods of conception, adoption, and satisfaction regarding family size., Result(s): Of the 503 couples enrolled in FASTT, 311 (61.8%) were contacted and 286 (56.9%) consented to participate. The mean age and follicle-stimulating hormone level at the time of enrollment in FASTT were 33.1 ± 3.2 years and 6.8 ± 2.2 mIU/mL, respectively, for those who participated in this study. The mean age at follow-up was 49.5 ± 3.4 years. Of the 286 women, 194 (67.8%) had a live birth during the trial and 225 (78.7%) continued to try to conceive after FASTT. Of those who tried to conceive without treatment, 101 of 157 (64.3%) had a successful live birth, whereas 12 (5.3%) women had a live birth via intrauterine insemination and 82 (36.4%) via autologous oocyte in vitro fertilization. Overall, 182 (80.9%) women achieved a live birth after FASTT., Conclusion(s): The majority of couples were able to achieve a live birth after FASTT. Only 19 (6.6%) never achieved a live birth during their reproductive years. Moving to treatment sooner allows the opportunity to achieve >1 live birth, which is associated with increased satisfaction regarding family size. This further supports access to care and insurance coverage for infertility treatment., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate similarities and differences in clinical and laboratory practices among high-performing fertility clinics., Design: Cross-sectional questionnaire study of selected programs., Setting: Academic and private fertility practices performing in vitro fertilization (IVF)., Patient(s): Not applicable., Intervention(s): A comprehensive survey was conducted of 13 IVF programs performing at least 100 cycles a year and having high cumulative singleton delivery rates for 2 years., Main Outcome Measure(s): Clinical and laboratory IVF practices., Result(s): Although many areas of clinical practice varied among top programs, some commonalities were observed. All programs used a combination of follicle-stimulating hormone and luteinizing hormone for IVF stimulation, intramuscular progesterone in frozen embryo transfer cycles, ultrasound-guided embryo transfers, and a required semen analysis before starting the IVF cycle. Common laboratory practices included vitrification of embryos at the blastocyst stage, air quality control with positive air pressure and high-efficiency particulate air filtration, use of incubator gas filters, working on heated microscope stages, and incubating embryos in a low-oxygen environment, most often in benchtop incubators., Conclusion(s): Some areas of consistency in clinical and laboratory practices were noted among high-performing IVF programs that are likely contributing to their success. High-performing programs focused on singleton deliveries. As the field of IVF is rapidly evolving, it is imperative that we share best practices in an effort to improve outcomes from all clinics for the good of our patients., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the clinical pregnancy rate (CPR) and live birth rate (LBR) of embryo transfer episodes (ETEs) performed by Reproductive Endocrinology and Infertility fellows vs. those of ETEs performed by faculty physicians., Design: Retrospective cohort analysis., Setting: Academic reproductive endocrinology and infertility practice., Patient(s): In total, 3,073 ETEs for 1,488 unique patients were performed by fellows or faculty physicians between January 2009 and January 2020., Intervention(s): None., Main Outcome Measure(s): Clinical pregnancy rate and LBR., Result(s): Fifteen fellows performed 1,225 (39.9%) of 3,073 ETEs after completing 30 mock transfers. On comparing outcomes among fellowship years (FY1, FY2, and FY3), CPR (44.1% vs. 43.2% vs. 45.7%, respectively, P = .83) and LBR (39.1% vs. 38.1% vs. 38.4%, respectively, P = .97) were not significantly different. Fellowship year 1 fellows' initial 30 ETEs vs. all the remaining FY1 ETEs had a significantly higher CPR (48.1% vs. 40.5%, respectively, P = .030) and LBR (45.4% vs. 34.3%, respectively, P = .001). There were no significant differences between faculty versus fellow ETEs in terms of CPR (43.0% vs. 45.0%, respectively, P = .30) or LBR (37.3% vs. 39.8%, respectively, P = .16), even after adjusting for patient age, body mass index, primary infertility diagnosis, autologous vs. donor oocyte, fresh vs. frozen embryo, number of embryos transferred, type of transfer catheter, and year of transfer (P = .32 for CPR, P = .22 for LBR)., Conclusion(s): Appropriately trained FY1 fellows had success rates maintained throughout all FYs. There were no significant differences in clinical outcomes between fellow- and faculty-performed transfers. These data demonstrated that allowing fellows to perform live embryo transfers is not detrimental to clinical outcomes., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To identify, besides maternal age and the number of previous pregnancy losses, additional characteristics of couples with unexplained recurrent pregnancy loss (RPL) that improve the prediction of an ongoing pregnancy., Design: Hospital-based cohort study in couples who visited specialized RPL units of two academic centers between 2012 and 2020., Setting: Two academic centers in the Netherlands., Patients: Clinical data from 526 couples with unexplained RPL were used in this study., Intervention(s): None., Main Outcome Measures: The final model to estimate the chance of a subsequent ongoing pregnancy was determined using a backward selection process and internally validated using bootstrapping. Model performance was assessed in terms of calibration and discrimination (area under the receiver operating characteristic curve)., Results: Subsequent ongoing pregnancy was achieved in 345 of 526 couples (66%). The number of previous pregnancy losses, maternal age, paternal age, maternal body mass index, paternal body mass index, maternal smoking status, and previous in vitro fertilization/intracytoplasmic sperm injection treatment were predictive of the outcome. The optimism-corrected area under the receiver operating characteristic curve was 0.63 compared with 0.57 when using only the number of previous pregnancy losses and maternal age., Conclusions: The identification of additional predictors of a subsequent ongoing pregnancy after RPL, including male characteristics, is significant for both clinicians and couples with RPL. At the same time, we showed that the predictive ability of the current model is still limited and more research is warranted to develop a model that can be used in clinical practice., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To develop and validate a preconception risk prediction index for severe maternal morbidity (SMM), defined by the Centers for Disease Control and Prevention as indicators of a life-threatening complication, among infertile patients., Design: Retrospective analysis of live births and stillbirths from 2007 to 2017 among infertile women., Setting: National commercial claims database., Patient(s): Infertile women identified on the basis of diagnosis, testing, or treatment codes., Intervention(s): None., Main Outcome Measure(s): The primary outcome was SMM, identified as any indicator from the Centers for Disease Control and Prevention Index except blood transfusion alone, which was found to overestimate cases. Twenty preconception comorbidities associated with a risk of SMM were selected from prior literature. Targeted ensemble learning methods were used to rank the importance of comorbidities as potential risk factors for SMM. The independent strength of the association between each comorbidity and SMM was then used to define each comorbidity's risk score., Result(s): Among 94,097 infertile women with a delivery, 2.3% (n = 2,181) experienced an SMM event. The highest risk of SMM was conferred by pulmonary hypertension, hematologic disorders, renal disease, and cardiac disease. Associated significant risks were lowest for substance abuse disorders, prior cesarean section, age ≥40 years, gastrointestinal disease, anemia, mental health disorders, and asthma. The receiver operating characteristic area under the curve for the developed comorbidity score was 0.66. Calibration plots showed good concordance between the predicted and actual risk of SMM., Conclusion(s): We developed and validated an index to predict the probability of SMM on the basis of preconception comorbidities in patients with infertility. This tool may inform preconception counseling of infertile women and support maternal health research initiatives., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study how the attributes of mosaicism identified during preimplantation genetic testing for aneuploidy relate to clinical outcomes, in order to formulate a ranking system of mosaic embryos for intrauterine transfer., Design: Compiled analysis., Setting: Multi-center., Patient(s): A total of 5,561 euploid blastocysts and 1,000 mosaic blastocysts used in clinical transfers in patients undergoing fertility treatment., Intervention(s): None., Main Outcome Measure(s): Implantation (gestational sac), ongoing pregnancy, birth, and spontaneous abortion (miscarriage before 20 weeks of gestation)., Result(s): The euploid group had significantly more favorable rates of implantation and ongoing pregnancy/birth (OP/B) compared with the combined mosaic group or the mosaic group affecting only whole chromosomes (implantation: 57.2% vs. 46.5% vs. 41.8%; OP/B: 52.3% vs. 37.0% vs. 31.3%), as well as lower likelihood of spontaneous abortion (8.6% vs. 20.4% vs. 25%). Whole-chromosome mosaic embryos with level (percent aneuploid cells) <50% had significantly more favorable outcomes than the ≥50% group (implantation: 44.5% vs. 30.4%; OP/B: 36.1% vs. 19.3%). Mosaic type (nature of the aneuploidy implicated in mosaicism) affected outcomes, with a significant correlation between number of affected chromosomes and unfavorable outcomes. This ranged from mosaicism involving segmental abnormalities to complex aneuploidies affecting three or more chromosomes (implantation: 51.6% vs. 30.4%; OP/B: 43.1% vs. 20.8%). Combining mosaic level, type, and embryo morphology revealed the order of subcategories regarding likelihood of positive outcome., Conclusion(s): This compiled analysis revealed traits of mosaicism identified with preimplantation genetic testing for aneuploidy that affected outcomes in a statistically significant manner, enabling the formulation of an evidence-based prioritization scheme for mosaic embryos in the clinic., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Human Immunodeficiency Virus is a serious but manageable chronic disease that affects persons of reproductive age, many of whom express a desire for biological parenthood. This document is a revision of the original document of the same name, last published in 2015 (Fertil Steril 2015;104:e1-8)., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the association of sleep parameters on female and male reproductive functions., Design: Systematic review., Setting: Not applicable., Patient(s): Female and male individuals, either healthy or infertile., Intervention(s): Relevant articles were identified according to the The Preferred Reporting Items for Systematic Reviews and Meta-analyses recommendations in the PubMed and EMBASE databases from January 1, 2000 to June 8, 2020., Main Outcome Measure(s): The association between sleep and ovary function, spermatic function, natural fertility, and in vitro fertilization (IVF) outcomes was assessed., Result(s): A total of 33 studies that looked at the association between sleep and either ovary function (n = 10), spermatic function (n = 12), natural fertility (n = 5), or IVF outcomes (n = 6) were included. Overall, female and male fertility, as well as IVF outcomes may be affected by short sleep duration, evening chronotype, or shift/night work schedules. However, the results were hardly comparable due to the heterogeneous study methodologies used., Conclusion(s): Sleep may be an original and innovative parameter to consider in the reproduction field. Further investigation is needed to elucidate how sleep and fertility are interrelated and how sleep might constitute a useful modifiable target in infertility management., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To test the hypothesis that telomere shortening and/or loss are risk factors for infertility., Design: Retrospective analysis of the telomere status in patients with infertility using conventional cytogenetic data collected prospectively., Setting: Academic centers., Patient(s): Cytogenetic slides with cultured peripheral lymphocytes from 50 patients undergoing fertility treatment and 150 healthy donors, including 100 donors matched for age., Intervention(s): Cytogenetic slides were used to detect chromosomal and telomere aberrations., Main Outcome Measure(s): Telomere length and telomere aberrations were analyzed after telomere and centromere staining., Result(s): The mean telomere length of patients consulting for infertility was significantly less than that of healthy donors of similar age. Moreover, patients with infertility showed significantly more extreme telomere loss and telomere doublet formation than healthy controls. Telomere shortening and/or telomere aberrations were more pronounced in patients with structural chromosomal aberrations. Dicentric chromosomes were identified in 6/13 patients, with constitutional chromosomal aberrations leading to chromosomal instability that correlated with chromosomal end-to-end fusions., Conclusion(s): Our findings demonstrate the feasibility of analyzing telomere aberrations in addition to chromosomal aberrations, using cytogenetic slides. Telomere attrition and/or dysfunction represent the main common cytogenetic characteristic of patients with infertility, leading to potential implications for fertility assessment. Pending further studies, these techniques that correlate the outcome of assisted reproduction and telomere integrity status may represent a novel and useful diagnostic and/or prognostic tool for medical care in this field., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether body mass index (BMI) affects intrauterine insemination treatment success., Design: Retrospective cohort study., Setting: Academic medical center., Patient(s): A total of 3,217 intrauterine insemination treatment cycles in 1,306 patients., Intervention(s): None., Main Outcome Measure(s): Primary outcome was live birth rate stratified by BMI. Secondary outcomes included rates of clinical pregnancy (defined as an intrauterine pregnancy with a heartbeat present on ultrasound), multiple gestation, biochemical pregnancy, missed abortion, ectopic, and spontaneous abortion., Result(s): Women with BMI 25 to 29.99 kg/m 2 or ≥30 kg/m 2 were equally likely to have a live birth as women of normal BMI. Women with BMI ≥30 kg/m 2 did have a higher likelihood of biochemical pregnancy than women with normal BMI., Conclusion(s): A BMI between 25 and 29.99 kg/m 2 or ≥30 kg/m 2 does not appear to have a negative effect on live birth after intrauterine insemination. Obesity may be associated with a higher risk of biochemical pregnancy after intrauterine insemination., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study the true prevalence of recurrent implantation failure., Design: Retrospective cohort study., Setting: A private assisted reproductive technology center., Patient(s): Women (n = 4,429) with anatomically normal uterus who underwent up to three consecutive frozen euploid single embryo transfers (FE-SETs) were included in the study. Cycles with donor eggs or gestational carriers were excluded., Intervention(s): None., Main Outcome Measure(s): Cumulative outcomes from these cycles were analyzed. A logistic regression model was used to assess the differences of outcomes between first, second, and third FE-SET and a Kaplan-Meier curve as used to analyze cumulative implantation rate., Result(s): The mean age of the patients included in the study was of 35.4 years. The sustained implantation rates of the first, second, and third FE-SET were 69.9%, 59.8%, and 60.3% per transfer, respectively. The cumulative sustained implantation rate after up to three consecutive FE-SET was 95.2%. The live birth rates after the first, second, and third FE-SET were 64.8%, 54.4%, and 54.1% per transfer, respectively. The cumulative live birth rate after up to three consecutive FE-SET was 92.6%. The miscarriage rate after observing a positive heartbeat was not different between the first (7.2%), second (8.8%), and third (12.7%) FE-SET., Conclusion(s): Our findings suggest that true recurrent implantation failure is rare. For those patients with the ability to make euploid blastocysts, <5% would fail to achieve a clinical pregnancy with three embryos transferred. It remains to be further investigated whether this threshold identifies a truly recalcitrant group or simply a statistical certainty based on random variation., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study compliance and effectiveness of the mHealth nutrition and lifestyle coaching program Smarter Pregnancy in couples undergoing in vitro fertilization (IVF) treatment with or without intracytoplasmic sperm injection (ICSI)., Design: Multicenter, single-blinded, randomized controlled trial, conducted from July 2014 to March 2017., Setting: IVF clinics., Patient(s): A total of 626 women undergoing IVF treatment with or without ICSI and 222 male partners., Interventions(s): Couples were randomly assigned to the light (control group) or regular (intervention group) Smarter Pregnancy program. Both groups filled out a baseline screening questionnaire on nutrition and lifestyle behaviors, and the intervention group received coaching tailored to inadequate behaviors during the 24-week period., Main Outcome Measure(s): Difference in improvement of a composite dietary and lifestyle risk score for the intake of vegetables, fruits, folic acid supplements, smoking, and alcohol use after 24 weeks of the program., Result(s): Compared with control subjects, women and men in the intervention group showed a significantly larger improvement of inadequate nutrition behaviors after 24 weeks of coaching. At the same time, the women also showed a significantly larger improvement of inadequate lifestyle behaviors., Conclusion(s): The mHealth coaching program Smarter Pregnancy is effective and improves the most important nutritional and lifestyle behaviors among couples undergoing IVF/ICSI treatment. International multicenter randomized trials are recommended to study the effect of using Smarter Pregnancy on pregnancy, live birth, and neonatal outcome., Netherlands Trial Register Number: NTR4150., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the maternal demographic, health, and fertility variables underlying prematurity., Design: Retrospective: Society for Assisted Reproductive Technology Clinic Outcome Reporting System data linked to Massachusetts birth certificates and hospital stays., Setting: Not applicable., Patients: We included 166,963 privately insured, singleton, first births to women ≥18 years of age between 2004 and 2013. Deliveries were as follows: assisted reproductive technology (ART) when linked to Society for Assisted Reproductive Technology Clinic Outcome Reporting System, medically assisted reproduction (MAR) when fertility treatment was indicated on the birth certificate, unassisted subfertile (USF) when there were indications of subfertility but no treatment, and fertile if none of the above., Intervention: None., Main Outcome Measures: Late preterm birth (LPTB; 34-36 weeks) and early preterm birth (EPTB; <34 weeks) were compared with term deliveries (≥37 weeks). Covariates that statistically significantly influenced prematurity in binary analysis were modeled by using multinomial logistic regression. Backward elimination and mediation analysis were used to determine the influence of single parameters on outcomes of others., Results: LPTB was increased in the USF (adjusted odds ratio [AOR] 1.32, 95% confidence interval [CI] 1.06-1.65) and ART (AOR 1.42, 95% CI 1.30-1.56) but not MAR (AOR 1.16, 95% CI 0.98-1.37). ETPB was increased in all (USF: AOR 1.67, 95% CI 1.21-2.31; MAR: AOR 1.67, 95% CI 1.31-2.12; ART: AOR 1.40, 95% CI 1.21-1.61). The strongest effectors of prematurity were placental problems (LPTB: AOR 4.02; EPTB: AOR 10.28), pregnancy hypertension (LPTB: AOR 2.14; EPTB: AOR 2.88), and chronic hypertension (LPTB: AOR 1.85; EPTB: AOR 2.79). Mediation analysis demonstrated a statistically significant indirect effect of placental problems for ART and subfertility., Conclusion: The greatest effectors of prematurity were placental problems and hypertensive disorders. ART and, to a lesser extent, subfertility were both associated with preterm birth directly and indirectly mediated by placenta problems., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess trends, predictors, and perinatal outcomes of ovarian hyperstimulation syndrome (OHSS) associated with in vitro fertilization (IVF) cycles in the United States., Design: Retrospective cohort study using National Assisted Reproductive Technology Surveillance System (NASS) data., Setting: Not applicable., Patient(s): Fresh autologous and embryo-banking cycles performed from 2000 to 2015., Interventions(s): None., Main Outcome Measure(s): OHSS, first-trimester loss, second-trimester loss, stillbirth, low birth weight, and preterm delivery., Result(s): The proportion of IVF cycles complicated by OHSS increased from 10.0 to 14.3 cases per 1,000 from 2000 to 2006, and decreased to 5.3 per 1,000 from 2006 to 2015. The risk of OHSS was highest for cycles with more than 30 oocytes retrieved (adjusted risk ratio [aRR] 3.85). OHSS was associated with a diagnosis of ovulatory disorder (aRR 2.61), tubal factor (aRR 1.14), uterine factor (aRR 1.17) and cycles resulting in pregnancy (aRR 3.12). In singleton pregnancies, OHSS was associated with increased risk of low birth weight (aRR 1.29) and preterm delivery (aRR 1.32). In twin pregnancies, OHSS was associated with an increased risk of second-trimester loss (aRR 1.81), low birth weight (aRR 1.06), and preterm delivery (aRR 1.16)., Conclusion(s): Modifiable predictive factors for OHSS include number of oocytes retrieved, pregnancy following fresh embryo transfer, and the type of medication used for pituitary suppression during controlled ovarian hyperstimulation. Patients affected by OHSS had a higher risk of preterm delivery and low birth weight. Clinicians should take measures to reduce the risk of OHSS whenever possible., (Copyright © 2020 American Society for Reproductive Medicine. All rights reserved.)

Like all industries, fertility clinics should identify and follow reference markers of its activity-key performance indicators (KPI)-to allow assisted reproductive technology outcomes to be monitored and compared. Clinical KPIs revolve around following set parameters of the patient population, procedures, and outcome data. Moreover, KPIs should also include identified protocols and standard operating procedures followed in daily practice and should keep track of multiple pregnancy rates, a ruthless confounder of assisted reproductive technology outcomes., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effectiveness of growth hormone (GH) supplementation in improving the in vitro fertilization (IVF) outcomes of poor responders., Design: Systematic review and meta-analysis., Setting: Not applicable., Patient(s): Poor ovarian responders undergoing conventional IVF or intracytoplasmic sperm injection (ICSI)., Intervention(s): Randomized controlled trials (RCTs) of poor ovarian responders undergoing a single IVF/ICSI cycle with GH supplementation versus conventional controlled ovarian stimulation. This review was registered in the PROSPERO database before starting data extraction (CRD42020151681)., Main Outcome Measure(s): Primary outcome was live birth rate. Clinical pregnancy rate, miscarriage rate, ongoing pregnancy rate, number of oocytes, number of mature (metaphase II [MII]) oocytes and the number of embryos available to transfer were considered as secondary outcomes., Result(s): Twelve RCTs were included; 586 women were assigned to the intervention group and 553 to the control group. The analysis revealed that patients receiving GH supplementation did not show an increased live birth rate, miscarriage rate, or ongoing pregnancy rate. However, GH supplementation in poor responders increased clinical pregnancy rate, number of oocytes retrieved (mean difference 1.62), number of MII oocytes (mean difference 2.06), and number of embryos available to transfer (mean difference 0.76). Sensitivity and subgroup analyses did not provide statistical changes to pooled results., Conclusion(s): The present meta-analysis provides evidence that GH supplementation may improve some reproductive outcomes in poor responders, but not live birth rates., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether academic achievement among children conceived following fertility treatment is different from that of children born to fertile women while also considering the underlying infertility., Design: Population-based cohort study., Setting: Denmark., Patient(s): The study population consisted of all 154,536 firstborn, live-born, singleton children in Denmark between 1995 and 2000 who completed their ninth grade with an examination., Intervention(s): The Danish Infertility Cohort was used to identify children conceived after fertility treatment (n = 10,099), and information on mean school marks was obtained from Statistics Denmark., Main Outcome Measure(s): Linear regression models were used to estimate mean differences (MDs) and 95% confidence intervals (CIs). Multiple logistic regression models were used to estimate odds ratios (OR) and 95% CI of not passing the ninth-grade examination., Results: The crude overall mean marks for children conceived after the various fertility treatment procedures were in general higher than in children born to fertile women. However, after adjustment for potential confounders, the overall mean marks were statistically significantly lower for children conceived after the various fertility treatment procedures (e.g., any fertility treatment: MD -0.13; 95% CI -0.18, -0.08) compared with children born to fertile women. Further, children conceived after any fertility treatment had a statistically significant lower crude likelihood of not passing the ninth-grade examination (OR 0.66; 95% CI 0.53, 0.81) compared with children born to fertile women, whereas no difference was observed in the confounder adjusted analyses (OR 1.15; 95% CI 0.89, 1.49). When children born to women requiring fertility assistance but without fertility treatment in the index pregnancy were used as a reference group, no differences in the adjusted overall mean marks and the likelihood of not passing the ninth grade with an examination were observed., Conclusion: Our findings indicate that fertility treatment per se is not associated with lower school marks and the likelihood of not passing the ninth grade with an examination. Hence, we suggest that factors related to both fertility problems and cognitive development may more likely explain the slightly lower academic performance (i.e., modest lower mean marks) among children conceived after fertility treatment., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study the association between prepregnancy subnormal body weight and obstetrical outcomes after autologous in vitro fertilization (IVF) cycles., Design: Systematic review and meta-analysis., Setting: Not applicable., Patient(s): Women with prepregnancy subnormal body weight (body mass index <18.5 kg/m 2 ) and normal body weight (body mass index 18.5-25 kg/m 2 ) after assisted reproductive treatment., Interventions(s): None., Main Outcome Measure(s): Clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate. CPR and LBR were calculated at per-woman and per-cycle levels., Result(s): A total of 38 cohort studies with low risk of bias were included. Meta-analyses showed that, compared with normal-weight women, those underweight before pregnancy had a lower CPR at per-woman and per-cycle levels. Compared with normal weight, underweight before pregnancy had little impact on LBR at both per-woman and per-cycle levels, nor on miscarriage rate., Conclusion(s): Compared with women of normal weight, women who were underweight before pregnancy had modest association with a lower CPR, but underweight did not seem to affect LBR or miscarriage after IVF., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of elevated maternal prepregnancy body mass index (BMI) on intelligence and growth of singletons after in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI)., Design: Cohort study., Setting: University hospital., Patient(s): Singletons born to infertile couples who underwent an autologous IVF/ICSI cycle from 2002 to 2012 and were followed up with at the age of 3-6 years from 2009 to 2017., Interventions(s): We compared the health of offspring born to overweight/obese women and normal weight women through assisted reproductive technology (ART)., Main Outcome Measure(s): Age- and sex-specific BMI z-scores, verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and full intelligence quotient (FIQ)., Result(s): After adjusting for confounders, obese women were more likely than normal-BMI women to have obese children (20.0% vs. 5.1%), and overweight women had increased risks of having overweight children (13.6% vs. 8.2%) or obese children (10.1% vs. 5.1%) compared with normal-BMI women. Maternal prepregnancy BMI had a weakly negative effect on estimated IQ of children, but after adjusting for parental educational level, the IQ scores of offspring were similar between groups. However, after adjusting for confounders, offspring of obese women showed increased prevalence of intellectual disability (IQ <80) in VIQ (16.9% vs. 8.5%) and FIQ (10.8% vs. 3.9%) compared with normal-BMI women., Conclusion(s): Maternal prepregnancy obesity is associated with increased risks for obesity and overweight at early ages in offspring conceived through IVF/ICSI and may also affect the risk of intellectual disability of offspring. Overall, we suggest that weight management is essential for women before entering an IVF/ICSI cycle for ensuring long-term child health., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the extent to which assisted oocyte activation (AOA) improves clinical outcomes in patients diagnosed with oocyte activation deficiencies (OADs)., Design: Retrospective cohort study comparing AOA cycles and previous intracytoplasmic sperm injection (ICSI) cycles in couples experiencing low or total failed fertilization after ICSI. Importantly, the sperm-related oocyte-activating capacity was examined in all patients before AOA with the use of the mouse oocyte activation test (MOAT)., Setting: Infertility center at a university hospital., Patient(s): A total of 122 couples with a history of low or total failed fertilization after ICSI., Intervention(s): ICSI, MOAT, AOA, and embryo transfer., Main Outcome Measure(s): Fertilization, pregnancy, and live birth rates., Result(s): MOAT revealed 19 patients with a sperm-related OAD (MOAT group 1), 56 patients with a diminished sperm-related oocyte-activating capacity (MOAT group 2), and 47 patients with a suspected oocyte-related OAD (MOAT group 3). AOA (191 cycles) significantly improved fertilization, pregnancy, and live birth rates in all MOAT groups compared with previous ICSI attempts (243 cycles). Fertilization rates after AOA were significantly different among MOAT groups 1 (70.1%), 2 (63.0%), and 3 (57.3%). Between MOAT group 1 and 3, significant differences in pregnancy (49.0% vs. 29.4%) and live birth (41.2% vs. 22.1%) rates were observed. In total, 225 embryo transfers resulted in 60 healthy live births following AOA., Conclusion(s): Patients undergoing diagnostic testing before AOA show a significant improvement in clinical outcomes compared with previous cycles. Our findings highlight that AOA should be reserved for patients with clear OADs., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To characterize the available support for infertility treatment and populations served by private foundations across the United States., Design: Web-based cross-sectional survey., Setting: Not applicable., Patient(s): Not applicable., Intervention(s): None., Main Outcome Measure(s): Geographies and populations served, dollar-amount and scope of financial assistance provided by private foundations for individuals seeking financial assistance for infertility treatment., Result(s): Thirty-seven private foundations were identified, 25 responded (68% response rate). More than one-half of the foundations had awarded grants to lesbian, gay, and transgender individuals, as well as single men and women. Forty percent of the foundations serve only a single state or geographic region. Foundations have provided 9,996 grants for infertility treatment, 1,740 in 2016 alone, with an average value of $8,191 per grant. The Livestrong foundation has provide more than 90% of these grants, and only to patients with a history of cancer. Twelve percent of foundations provide assistance for fertility preservation in patients with cancer, and 20% provide assistance for elective oocyte cryopreservation., Conclusion(s): Private foundations significantly increase access to infertility care for individuals and couples affected by cancer who could otherwise not afford treatment. Significant heterogeneity exists regarding the populations served and the services available for grant support by these foundations, and the landscape of options for patients unaffected by cancer is severely limited., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the association of fresh and frozen embryo transfer with the development of ischemic placental disease (IPD), hypothesizing that differences in implantation environment affect placentation and thus pregnancy outcomes., Design: We performed a secondary analysis of a retrospective cohort study of deliveries linked to IVF cycles., Setting: Tertiary hospital and infertility treatment center., Patient(s): We included all women who underwent an autologous IVF cycle and had a live-born infant or an intrauterine fetal demise (IUFD). We excluded women less than 18 years of age., Intervention(s): We compared pregnancies resulting from frozen embryo transfer (frozen) cycles with those resulting from fresh embryo transfer (fresh) cycles., Main Outcome Measure(s): The primary outcome was a composite outcome of IPD or IUFD due to placental insufficiency. Ischemic placental disease included pre-eclampsia, placental abruption, and small for gestational age (SGA). We calculated risk ratios (RRs) and 95% confidence intervals (CIs)., Result(s): Compared with fresh cycles, frozen cycles had a lower risk of IPD or IUFD from placental insufficiency (RR 0.75, 95% CI 0.59-0.97). Frozen cycles also conferred a lower risk of SGA than fresh cycles (RR 0.58, 95% CI 0.41-0.81). Risks of pre-eclampsia (RR 1.3, 95% CI 0.84-1.9) and abruption (RR 1.2, 95% CI 0.56-2.4) were similar., Conclusion(s): There was a lower risk of IPD among frozen cycles compared with fresh cycles. This association was largely driven by lower risk of SGA among frozen cycles., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the efficacy and safety of blastocyst transfer derived from small follicles (SF; ≤10 mm) and large follicles (LF; ≥11 mm)., Design: Retrospective cohort study., Setting: Private clinic., Patient(s): Patients (n = 1,072) 30-40 years old who underwent blastocyst transfer (BT; n = 1,247) between January 2012 and December 2014., Intervention(s): Oocytes retrieved during a modified natural cycle from both LF and SF were fertilized by a conventional method or intracytoplasmic sperm injection. The blastocysts were frozen, thawed, and transferred one by one in the following spontaneous ovulatory cycles or hormone replacement cycles., Main Outcome Measure(s): BT resulted in live births and major congenital anomalies., Result(s): SF-derived BTs (n = 597) yielded 55 chemical abortions (9.2%), 73 clinical abortions (12.2%), and 261 live births (43.8%), whereas LF-derived BTs (n = 650) yielded 71 chemical abortions (10.9%), 73 clinical abortions (11.2%), and 311 live births (47.9%). These incidences were not statistically different between SF- and LF-derived BTs. The incidence of abnormal karyotypes was also not statistically different between SF- and LF-derived spontaneous abortions (71% [39/55] vs. 72% [40/55], respectively). The incidence of major congenital anomalies in neonates did not differ between SF- and LF-derived pregnancies (1.5% and 1.3%, respectively; relative risk = 1.10, 95% confidence interval [0.55-3.21])., Conclusion(s): SF-derived BT is as efficacious and safe as LF-derived BT., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To summarize and assess the impact of key research generated through the Society of Assisted Reproductive Technology (SART)-initiated United States IVF registry and annual reporting system., Design: Review., Setting: Eligible studies included those that analyzed data generated by the National IVF data collection program (through SART or Centers for Disease Control and Prevention)., Patient(s): Not applicable., Intervention(s): Not applicable., Main Outcome Measure(s): Summarize and report outcomes of research using National IVF registry data., Result(s): The Society of Assisted Reproductive Technology was founded in 1985 and published the first annual US IVF data report 30 years ago in 1988 in Fertility and Sterility. In 1995, the Centers for Disease Control and Prevention subsequently began collecting data from IVF programs and published their first report in 1997. This annual National IVF data collection and reporting is a significant responsibility and effort for IVF programs. Using these data sources, 199 articles have been published by clinicians and researchers from across the country. This research has guided the development of evidence-based assisted reproductive technology (ART) practice guidelines during the past 30 years, which have ultimately led to improved quality and patient care., Conclusion(s): Since the first SART National IVF data report publication 30 years ago, SART has achieved its original goals of creating a national IVF registry that successfully assesses clinical effectiveness, quality of care, and safety., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether post-warming culture duration (1 hour vs. 18 hours) influences implantation rates (IRs) of good-quality blastocysts (GQB) in a good-prognosis population., Design: Prospective interventional randomized study., Setting: University hospital., Patient(s): One hundred sixty-two GQB transfers., Intervention(s): Patients' vitrified blastocysts were randomly allocated to group A, warming on the day before transfer (n = 81), or B, warming on the day of transfer (n = 81)., Main Outcome Measure(s): IR, live birth rate, reexpansion degree, and quality after warming and immediately before transfer., Result(s): Quality of the warmed and transferred blastocysts was similar (respectively, 39.1% and 32.7% top quality [≥B4AA/AB/BA] in group A vs. 41.7 and 42.2% in group B). In group A, 14 of 102 blastocysts (12.2%) appeared to be unsuitable for transfer, versus only 1 of 103 (0.9%) in group B, thus leading to an additional warming. As expected, reexpansion degree just before transfer was higher in group A (0.90 vs. 0.70). Likewise, the proportion of hatched blastocysts before transfer was higher after a longer culture period (38.6% in group A vs. 12.7% in group B). IRs were similar (38.0% in group A vs. 36% in group B), as were live birth rates (35.8% in group A vs. 34.6% in group B)., Conclusion(s): IRs were not different, whatever the duration of post-warming culture of GQB. Both warming strategies could be applied to good-prognosis patients to optimize the laboratory workflow without any detrimental effect., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the impact of using donor sperm in assisted reproductive technology (ART) cycles on perinatal outcomes., Design: Historical cohort study., Setting: US national database from the Society of Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 2012 to 2013., Patient(s): Patients undergoing the first fresh autologous ART cycle using either donor or partner sperm., Intervention(s): None., Main Outcome Measure(s): Miscarriage, preterm birth, low birthweight rates., Results: A total of 134,710 fresh autologous ART cycles were evaluated from the SART CORS database. Following exclusion criteria and after restricting to the first cycle, 2,123 donor sperm and 42,799 partner sperm ART cycles were included in the final analyses. After adjusting for all confounding variables (including maternal age, race, body mass index, smoking status, gravidity, history of preterm birth, highest follicle stimulating hormone count, blastocyst transfer percentage, total embryo transferred, and etiology of infertility), no statistically significant differences in miscarriage rates, preterm births, very preterm births, low birthweight, and very low birthweight were observed. Birthweight was significantly lower in the partner sperm group than in the donor sperm group (3,292 ± 601 and 3,233 ± 592 g in donor and partner sperm groups, respectively, adjusted P value 0.003); however, this small absolute difference (adjusted effect estimate 42 g, 95% CI 14.7-70.9) does not carry clinical significance., Conclusions: The use of donor sperm in fresh autologous ART cycles was not associated with increased miscarriage, preterm births, or low birthweights, as compared to cycles using partner sperm. This information can be used in patient counseling to reassure patients using donor sperm in ART cycles., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study if parental subfertility is related to the occurrence of the male genital anomalies, cryptorchidism and hypospadias., Design: Population-based cohort study., Setting: Not applicable., Patient(s): A total of 80,220 singleton boys and their mothers from the Danish National Birth Cohort and the Aarhus Birth Cohort., Intervention(s): None., Main Outcome Measure(s): The two congenital anomalies; cryptorchidism and hypospadias, registered within the Danish National Patient Register up until December 31, 2012., Result(s): By means of Cox regression analyses, we found no associations between waiting time-to-pregnancy (TTP) and cryptorchidism or hypospadias among those who conceived spontaneously. The highest hazard ratio for cryptorchidism was seen among boys of couples with a TTP>12 months who conceived after fertility treatment (adjusted hazard ratio [aHR] 1.19, 95% confidence interval 0.92-1.55). For hypospadias, we found that boys of couples with a TTP>12 months who conceived after fertility treatment, had a 71% higher risk of hypospadias (aHR 1.71, [95% confidence interval 1.24-3.36]) as compared with boys of couples with a TTP<5 months., Conclusion(s): The findings from this study showed that boys of couples with TTP>12 months who conceived after fertility treatment, had a higher occurrence of hypospadias than boys conceived spontaneously of couples with a short TTP. Among those who conceived spontaneously, TTP was not associated with hypospadias or cryptorchidism. These findings indicate that fertility treatment or severity of subfertility is related to hypospadias., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Approximately 21% of women of reproductive age and 22% of men of reproductive age in the United States smoke cigarettes. Substantial harmful effects of cigarette smoke on fecundity and reproduction have become apparent but are not generally appreciated. This committee opinion reviews the potential deleterious effects of smoking on conception, ovarian follicular dynamics, sperm parameters, gamete mutations, early pregnancy, and assisted reproductive technology (ART) outcomes. It also reviews the current status of smoking cessation strategies. This document replaces the 2012 ASRM Practice Committee document of the same name (Fertil Steril 2012;98:1400-6)., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Preimplantation genetic testing for monogenic diseases for adult-onset conditions is ethically permissible for a range of conditions including when the condition is serious and no safe, effective interventions are available. The Committee strongly recommends that a genetic counselor experienced with PGT-M counsel patients considering such procedures. This document replaces the document titled "Use of preimplantation genetic diagnosis for serious adult-onset conditions: a committee opinion," last published in Fertil Steril 2013;100;54-7., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study the reason(s) why insured patients discontinue in vitro fertilization (IVF) before achieving a live birth., Design: Cross-sectional study., Setting: Private academically affiliated infertility center., Patient(s): A total of 893 insured women who had completed one IVF cycle but did not return for treatment for at least 1 year and who had not achieved a live birth were identified; 312 eligible women completed the survey., Intervention(s): None., Main Outcome Measure(s): Reasons for treatment termination., Result(s): Two-thirds of the participants (65.2%) did not seek care elsewhere and discontinued treatment. When asked why they discontinued treatment, these women indicated that further treatment was too stressful (40.2%), they could not afford out-of-pocket costs (25.1%), they had lost insurance coverage (24.6%), or they had conceived spontaneously (24.1%). Among those citing stress as a reason for discontinuing treatment (n = 80), the top sources of stress included already having given IVF their best chance (65.0%), feeling too stressed to continue (47.5%), and infertility taking too much of a toll on their relationship (36.3%). When participants were asked what could have made their experience better, the most common suggestions were evening/weekend office hours (47.4%) and easy access to a mental health professional (39.4%). Of the 34.8% of women who sought care elsewhere, the most common reason given was wanting a second opinion (55.7%)., Conclusion(s): Psychologic burden was the most common reason why insured patients reported discontinuing IVF treatment. Stress reduction strategies are desired by patients and could affect the decision to terminate treatment., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To understand the barriers that serodiscordant couples with human immunodeficiency virus (HIV) face in accessing services for risk reduction and infertility using assisted reproductive technology (ART)., Design: Two-arm cross-sectional telephone "secret shopper" study., Setting: Infertility clinics designated by the Society for Assisted Reproductive Technology (SART), 140 from 15 American states with the highest prevalence of heterosexual HIV-infected men., Patient(s): Clinical and nonclinical staff at SART-registered clinics., Intervention(s): Standardized telephone calls to SART-registered clinics by investigators in the roles of physician and patient callers., Main Outcome Measure(s): Availability and difference in services offered to callers and the rate of referral if the clinic did not provide these services., Result(s): Of the 140 sampled SART clinics across 15 states, callers in both patient and physician roles spoke to a staff member at greater than 90% of targeted clinics (127 clinics total). Of the physician callers 63% were told that the clinic could offer services, as compared to 40% of patient callers. Of the 55 clinics that were unable to provide services to the patient caller, 51% referred to other clinics with confidence that they could offer these services; 67% of clinics would provide services for both prevention and infertility purposes., Conclusion(s): Risk reduction services for HIV were more available at the sampled fertility clinics than previously reported in the literature. However, the responses depended on the person calling. The clinics demonstrated low rates of concordance with the American Society for Reproductive Medicine's guidelines, which endorse referral of patients to other facilities from sites unable to offer services., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To report on outcomes from a university-based low-cost and low-complexity IVF program using mild stimulation approaches and simplified protocols to provide basic access to ART to a socioculturally diverse low-income urban population., Design: Retrospective cohort study., Setting: Academic infertility center., Patient(s): Sixty-five infertile couples were enrolled from a county hospital serving a low-resource largely immigrant population., Interventions(s): Patients were nonrandomly allocated to one of four mild stimulation protocols: clomiphene/letrozole alone, two clomiphene/letrozole-based protocols involving sequential or flare addition of low-dose gonadotropins, and low-dose gonadotropins alone. Clinical fellows managed all aspects of cycle preparation, monitoring, oocyte retrieval, and embryo transfer under an attending preceptor. Retrieval was undertaken without administration of deep anesthesia, and laboratory interventions were minimized. All embryo transfers were performed at the cleavage stage., Main Outcome Measure(s): Sociomedical demographics, treatment response, and pregnancy outcomes were recorded., Result(s): From August 2010 to June 2016, 65 patients initiated 161 stimulation IVF cycles, which resulted in 107 retrievals, 91 fresh embryo transfers, and 40 frozen embryo transfer cycles. The mean age of patients was 33.3 years, and mean reported duration of infertility was 5.3 years; 33.5% (54/161) of cycles were cancelled before oocyte retrieval, with 13% due to premature ovulation. Overall, cumulative live birth rates per retrieval including subsequent use of frozen embryos was 29.0%; 44.6% (29/65) of patients enrolled in the program achieved pregnancy., Conclusion(s): Use of mild stimulation protocols, simplified monitoring, and minimized laboratory handling procedures enabled access to care in a low-resource socioculturally diverse infertile population., (Copyright © 2017. Published by Elsevier Inc.)