Purpose: To report fertility treatment use and outcomes among patients who use donor sperm for intrauterine insemination (IUI), in vitro fertilization (IVF), and reciprocal IVF (co-IVF). Methods: This is a retrospective review of patients who used donor sperm at an urban, southeastern academic reproductive center between 2014 and 2020. Results: Among the 374 patients presenting for care, 88 (23.5%) were single, 188 (50.3%) were in a same-sex female partnership, and 98 (26.2%) had a male partner with a diagnosis of male factor infertility. Most patients did not have infertility (73.2%). A total of 1106 cycles were completed, of which there were 931 IUI cycles, 146 traditional IVF cycles, and 31 co-IVF cycles. Live birth rates per cycle were 11% in IUI, 42% in IVF, and 61% in co-IVF. Of all resulting pregnancies, hypertensive disorders were most commonly experienced (18.0%), followed by preterm delivery (15.3%), neonatal complications (9.5%), gestational diabetes (4.8%), and fetal growth restriction (4.8%). Of the 198 infants born, fifteen (8.3%) required admission to the neonatal intensive care unit and three (1.7%) demised. Pregnancy and neonatal complications were more likely to occur in older patients and patients with elevated body mass index. Conclusion: The use of donor sperm for fertility treatment is increasing. These data show reassuring live birth rates; however, they also highlight the risks of subsequent pregnancy complications. With the expansion of fertility treatment options for patients, these data assist provider counseling of patients regarding anticipated cycle success rates and possible pregnancy complications.

STUDY QUESTION: Is the use of donor oocytes in women <35 years of age associated with an increased risk of adverse perinatal outcomes compared to use of autologous oocytes? SUMMARY ANSWER: Among fresh assisted reproductive technology (ART) cycles performed in women under age 35, donor oocyte use is associated with a higher risk of preterm birth, low birth weight and stillbirth (when zero embryos were cryopreserved) as compared to autologous oocytes. WHAT IS KNOWN ALREADY: Previous studies demonstrated elevated risk of poor perinatal outcomes with donor versus autologous oocytes during ART, primarily among older women. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study using data reported to Centers for Disease Control and Prevention's National ART Surveillance System (NASS) during the period from 2010 to 2015 in order to best reflect advances in clinical practice. Approximately 98% of all US ART cycles are reported to NASS, and discrepancy rates were <6% for all fields evaluated in 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included all non-banking fresh and frozen ART cycles performed between 2010 and 2015 in women under age 35 using autologous or donor eggs. Cycles using cryopreserved eggs, donated embryos or a gestational carrier were excluded. Among fresh embryo transfer cycles, we calculated predicted marginal proportions to estimate the unadjusted and adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for the association between donor versus autologous oocyte use and stillbirth, spontaneous abortion, preterm delivery and low birth weight among singleton pregnancies or births. Stillbirth models were stratified by number of embryos cryopreserved. All models were adjusted for patient and treatment characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 71 720 singleton pregnancies occurring during 2010-2015, singletons resulting from donor oocytes were more likely to be preterm (15.6% versus 11.0%; aRRs 1.39: CI 1.20-1.61) and have low birth weight (11.8% versus 8.8%; aRRs 1.34; CI 1.16-1.55) than those resulting from autologous oocytes. With zero embryos cryopreserved, donor versus autologous oocyte use was associated with increased risk for stillbirth (2.1% versus 0.6%; aRRs 3.73; CI 1.96-7.11); no association with stillbirth was found when ≥1 embryo was cryopreserved (0.54% versus 0.56%; aRR 1.15; CI 0.59-2.25). LIMITATIONS, REASONS FOR CAUTION: The data come from a national surveillance system and is thus limited by the accuracy of the data entered by individual providers and clinics. There may be unmeasured differences between women using donor eggs versus their own eggs that could be contributing to the reported associations. Given the large sample size, statistically significant findings may not reflect clinically important variations. WIDER IMPLICATIONS OF THE FINDINGS: Risks of preterm birth, low birth weight and stillbirth among singleton pregnancies using donor oocytes were increased compared to those using autologous oocytes. Further study regarding the pathophysiology of the potentially increased risks among donor oocyte recipient pregnancy is warranted. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

OBJECTIVE: To assess trends of tubal factor infertility and to evaluate risk of miscarriage and delivery of preterm or low birth weight (LBW) neonates among women with tubal factor infertility using assisted reproductive technology (ART). METHODS: We assessed trends of tubal factor infertility among all fresh and frozen, donor, and nondonor ART cycles performed annually in the United States between 2000 and 2010 (N=1,418,774) using the National ART Surveillance System. The data set was then limited to fresh, nondonor in vitro fertilization cycles resulting in pregnancy to compare perinatal outcomes for cycles associated with tubal compared with male factor infertility. We performed bivariate and multivariable analyses controlling for maternal characteristics and calculated adjusted risk ratios (RRs) and 95% confidence intervals (CI). RESULTS: The percentage of ART cycles associated with tubal factor infertility diagnoses decreased from 2000 to 2010 (26.02-14.81%). Compared with male factor infertility, tubal factor portended an increased risk of miscarriage (14.0% compared with 12.7%, adjusted RR 1.08, 95% CI 1.04-1.12); risk was increased for both early and late miscarriage. Singleton neonates born to women with tubal factor infertility had an increased risk of preterm birth (15.8% compared with 11.6%, adjusted RR 1.27, 95% CI 1.20-1.34) and LBW (10.9% compared with 8.5%, adjusted RR 1.28, 95% CI 1.20-1.36). Significant increases in risk persisted for early and late preterm delivery and very low and moderately LBW delivery. A significantly elevated risk was also detected for twin, but not triplet, pregnancies. CONCLUSION: Tubal factor infertility, which is decreasing in prevalence in the United States, is associated with an increased risk of miscarriage, preterm birth, and LBW delivery as compared with couples with male factor infertility using ART.

Objective: To describe the prevalence and treatment characteristics of assisted reproductive technology (ART) cycles involving specific male factor infertility diagnoses in the United States. Design: Cross-sectional analysis of ART cycles in the National ART Surveillance System (NASS). Setting: Clinics that reported patient ART cycles performed in 2017 and 2018. Patient(s): Patients who visited an ART clinic and the cycles were reported in the NASS. The ART cycles included all autologous and donor cycles that used fresh or frozen embryos. Intervention(s): Not applicable. Main Outcome Measures: Analyses used new, detailed reporting of male factor infertility subcategories, treatment characteristics, and male partner demographics available in the NASS. Result(s): Among 399,573 cycles started with intent to transfer an embryo, 30.4% (n = 121,287) included a male factor infertility diagnosis as a reason for using ART. Of these, male factor only was reported in 16.5% of cycles, and both male and female factors were reported in 13.9% of cycles; 21.8% of male factor cycles had >1 male factor. Abnormal sperm parameters were the most commonly reported diagnoses (79.7%), followed by medical condition (5.3%) and genetic or chromosomal abnormalities (1.0%). Males aged ≤40 years comprised 59.6% of cycles with male factor infertility. Intracytoplasmic sperm injection was the primary method of fertilization (81.7%). Preimplantation genetic testing was used in 26.8%, and single embryo transfer was used in 66.8% of cycles with male factor infertility diagnosis. Conclusion(s): Male factor infertility is a substantial contributor to infertility treatments in the United States. Continued assessment of the prevalence and characteristics of ART cycles with male factor infertility may inform treatment options and improve ART outcomes. Future studies are necessary to further evaluate male factor infertility.

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.

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The COVID-19 pandemic has claimed the lives of over one million people worldwide, and has affected all aspects of healthcare worldwide, including the delivery of care to patients with fertility-related diagnoses. In the United States, the response of US fertility clinics to the COVID-19 pandemic was coordinated by the American Society for Reproductive Medicine (ASRM). ASRM acted quickly to develop guidelines for limiting fertility treatment and clinic consultations during the early days of the pandemic, and then safely restarting fertility treatment. A survey of patients with fertility-related diagnoses who presented for care during the first months of the pandemic revealed that a majority of patients who presented for care during the early months of the pandemic experienced delayed or cancelled treatment cycles. Patients with infertility subsequently reported a desire to resume fertility care, but emphasized the importance of their clinic having policies and procedures in place to limit the risk of infection.

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.

Objective: To summarize current understanding of the effects of novel and prior coronaviruses on human reproduction, specifically male and female gametes, and in pregnancy. Design: Review of English publications in PubMed and Embase to April 6, 2020. Method(s): Articles were screened for reports including coronavirus, reproduction, pathophysiology, and pregnancy. Intervention(s): None. Main Outcome Measure(s): Reproductive outcomes, effects on gametes, pregnancy outcomes, and neonatal complications. Result(s): Seventy-nine reports formed the basis of the review. Coronavirus binding to cells involves the S1 domain of the spike protein to receptors present in reproductive tissues, including angiotensin-converting enzyme-2 (ACE2), CD26, Ezrin, and cyclophilins. Severe Acute Respiratory Syndrome Coronavirus 1 (SARS–CoV-1) may cause severe orchitis leading to germ cell destruction in males. Reports indicate decreased sperm concentration and motility for 72–90 days following Coronavirus Disease 2019 (COVID-19) infection. Gonadotropin-dependent expression of ACE2 was found in human ovaries, but it is unclear whether SARS–Coronavirus 2 (CoV-2) adversely affects female gametogenesis. Evidence suggests that COVID-19 infection has a lower maternal case fatality rate than SARS or Middle East respiratory syndrome (MERS), but anecdotal reports suggest that infected, asymptomatic women may develop respiratory symptoms postpartum. Coronavirus Disease 2019 infections in pregnancy are associated with preterm delivery. Postpartum neonatal transmission from mother to child has been reported. Conclusion(s): Coronavirus Disease 2019 infection may affect adversely some pregnant women and their offspring. Additional studies are needed to assess effects of SARS–CoV-2 infection on male and female fertility.

On March 11, 2020, the World Health Organization declared the outbreak of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) a global pandemic, reporting community-scale transmission worldwide with more than 8 million cases of confirmed coronavirus disease (COVID-19). On March 17, the American Society for Reproductive Medicine provided early key recommendations, updated and affirmed on March 30, including suspending initiation of new treatment cycles aimed at achieving pregnancy. The European Society of Human Reproduction and Embryology provided similar recommendations that expanded even further to include consideration of avoidance of spontaneous conception. These recommendations were made in the infancy of the pandemic when little was known about the implications of the novel coronavirus on implantation and pregnancy. Over the past several months, new developments in molecular virology and immunobiology of SARS-CoV-2 have improved our understanding of the novel coronavirus. In light of the rapidly expanding knowledge base and the realization that care cannot be paused indefinitely, fertility clinics around the world are beginning to resume treatment.