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To compare the incidence of multiple sclerosis (MS) among women who had undergone assisted reproductive technology (ART) treatment with the women who had conceived a child without previous ART treatment.A register-based nationwide cohort study.Women with a first ovarian stimulation cycle before in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (i.e., ART treatment) recorded in the Danish IVF register between 1996 and 2018; and women recorded in the Danish Medical Birth Register with the birth of their first child where date of conception is between 1996 and 2018. The cohort was observed until March 10, 2021.Mainly included IVF, ICSI, and fresh embryo transfer with hormone stimulation.A diagnosis of MS recorded in the Danish Multiple Sclerosis Registry. Crude and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were calculated.A total of 585,716 women were included in the cohort of which 63,791 (11%) were exposed to at least one initiated IVF or ICSI cycle during the study period. Cycles with oocyte donation were excluded. The median follow-up time for the entire cohort was 12.4 years (Q1-Q3= 6.6-18.1). Compared with women conceiving without previous ART, ART treated women were older (31.8 years vs. 27.5 years), more often had a university degree (45% vs. 36%), and more often had received other fertility treatments than IVF or ICSI before cohort entry (26% vs. 3%). We found no association between incident MS and exposure to ART compared with non-ART pregnancy (aHR=1.08; 95 % CI, 0.93-1.25). An analysis following intention-to-treat principle on a propensity score matched sub cohort confirmed our results. In subgroup analysis including all ART cycles among the ART treated women, we found no increased risk of MS within 2 years of ART cycle start for successful ART cycles (pregnancy) compared with failed ART cycles (no pregnancy) (aHR=1.01; 95% CI, 0.58-1.76). We found a non-significant trend toward increased risk of MS with increasing numbers of ART cycles although based on small numbers.Women treated with ART do not seem to be at increased risk of developing MS compared with the women not exposed to ART.

Objective: To assess the risk of neurodevelopmental disorders in singletons born after the use of assisted reproductive technology (ART) compared with singletons born without the use of ART. Design: Nordic register-based study. Setting: Cross-linked data from Medical Birth Registers and National ART and Patient Registers; liveborn singletons in 1995-2014 in Denmark and Finland, 2005-2015 in Norway, and 1995-2015 in Sweden with follow-up to 2014 (Denmark and Finland) or 2015 (Norway and Sweden). Patients: A total of 5,076,444 singletons: 116,909 (2.3%) born with and 4,959,535 (97.7%) born without the use of ART (non-ART). Interventions: In vitro fertilization, intracytoplasmic sperm injection, and fresh and frozen embryo transfer. Main Outcome Measures: The primary outcomes (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes) were learning and motor functioning disorders (F80-F83), autism spectrum disorder (F84), attention-deficit/hyperactivity disorder and conduct disorders (F90-F92), and tic disorders (F95). Crude hazard ratios (HRs) and adjusted hazard ratios (aHRs) with 95% confidence intervals were calculated. Results: Singletons in the ART cohort had a higher adjusted risk of learning and motor functioning disorders (HR, 1.01 [0.96-1.07]; aHR, 1.17 [1.11-1.24]) and a tendency toward a higher risk of autism spectrum disorder (HR, 1.12 [1.04-1.21]; aHR, 1.07 [0.98-1.16]) and attention-deficit/hyperactivity disorder and conduct disorders (HR, 0.82 [0.77-0.86]; aHR, 1.17 [0.99-1.12]) but not of tic disorders (HR, 1.21 [1.06-1.38]; aHR, 1.17 [0.96-1.27]). No differences in risk were found between children born after in vitro fertilization and intracytoplasmic sperm injection or after fresh and frozen embryo transfer. Conclusions: Our findings of only small differences in neurodevelopment between ART and non-ART singletons are reassuring and in line with previous studies. (C) 2022 by American Society for Reproductive Medicine.

Objective To compare self-reported quality of life, psychosocial well-being, and physical well-being during assisted reproductive technology (ART) treatment in 1,023 women allocated to either a short GnRH antagonist or long GnRH agonist protocol. Design Secondary outcome of a prospective phase 4, open-label, randomized controlled trial. Four times during treatment a questionnaire on self-reported physical well-being was completed. Further, a questionnaire on self-reported quality of life and psychosocial well-being was completed at the day of hCG testing. Setting Fertility clinics at university hospitals. Patient(s) Women referred for their first ART treatment were randomized in a 1:1 ratio and started standardized ART protocols. Intervention(s) Gonadotropin-releasing hormone analogue; 528 women allocated to a short GnRH antagonist protocol and 495 women allocated to a long GnRH agonist protocol. Main Outcome Measure(s) Self-reported quality of life, psychosocial well-being, and physical well-being based on questionnaires developed for women receiving ART treatment. Result(s) Baseline characteristics were similar, and response rates were 79.4% and 74.3% in the GnRH antagonist and GnRH agonist groups, respectively. Self-reported quality of life during ART treatment was rated similar and slightly below normal in both groups. However, women in the GnRH antagonist group felt less emotional (adjusted odds ratio [AOR] 0.69), less limited in their everyday life (AOR 0.74), experienced less unexpected crying (AOR 0.71), and rated quality of sleep better (AOR 1.55). Further, women receiving GnRH agonist treatment felt worse physically. Conclusion(s) Women in a short GnRH antagonist protocol rated psychosocial and physical well-being during first ART treatment better than did women in a long GnRH agonist protocol. However, the one item on self-reported general quality of life was rated similarly. Clinical Trial Registration Number NCT00756028.

Objective: To compare the effect of maternal age on assisted reproductive technology (ART) and spontaneous conception (SC) pregnancies regarding maternal and neonatal complications. Design: Nordic retrospective population-based cohort study. Data from national ART registries were cross-linked with national medical birth registries. Setting: Not applicable. Patient(s): A total of 300,085 singleton deliveries: 39,919 after ART and 260,166 after SC. Intervention(s): None. Main Outcome Measure(s): Hypertensive disorders in pregnancy (HDP), placenta previa, cesarean delivery, preterm birth (PTB; = 28 weeks). Adjusted odds ratios (AORs) were calculated. Associations between maternal age and outcomes were analyzed. Result(s): The risk of placenta previa (AOR 4.11-6.05), cesarean delivery (AOR 1.18-1.50), PTB (AOR 1.23-2.19), and LBW (AOR 1.44-2.35) was significantly higher in ART than in SC pregnancies for most maternal ages. In both ART and SC pregnancies, the risk of HDP, placenta previa, cesarean delivery, PTB, LBW, and SGA changed significantly with age. The AORs for adverse neonatal outcomes at advanced maternal age (>35 years) showed a greater increase in SC than in ART. The change in risk with age did not differ between ART and SC for maternal outcomes at advanced maternal age. Conclusion(s): Having singleton conceptions after ART results in higher maternal and neonatal outcome risks overall, but the impact of age seems to be more pronounced in couples conceiving spontaneously. (C) 2016 by American Society for Reproductive Medicine.

Objective To study perinatal outcomes in singletons born after intrauterine insemination (IUI) compared with children born after in vitro fertilization (IVF), intracytoplasmic sperm injection, and spontaneous conception (SC), and to assess predictors of poor outcome in singletons born after IUI, exploring the effect of ovarian stimulation. Design National cohort study, 2007–2012. Setting Danish national registries. Patient(s) Four thousand two hundred twenty-eight singletons born after insemination with partner semen (IUI-H) and 1,881 singletons born after insemination with donor semen. Intervention(s) None. Main Outcome Measure(s) Preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA). Result(s) Children born after IUI-H had higher risks of PTB, LBW, and SGA vs. SC singletons (adjusted odds ratios [aOR] 1.3; 95% confidence interval (CI), 1.1–1.5; 1.4; 95% CI, 1.2–1.7; and 1.4; 95% CI, 1.2–1.6), respectively. Compared with IVF, risk of SGA was similar, but risks of PTB and LBW were lower (aOR 0.6; 95% CI, 0.5–0.8; and 0.8; 95% CI, 0.6–0.9). Compared with intracytoplasmic sperm injection, no differences were found. For children born after IUI with donor semen, results were similar to those for IUI-H. Risks of LBW and SGA were higher in IUI singletons born after ovarian stimulation with clomiphene citrate, compared with natural-cycle IUI (aOR 1.5; 95% CI, 1.1–2.1 and 1.6; 95% CI, 1.1–2.4). Treatment with follicle-stimulating hormone vs. natural-cycle IUI did not seem to affect perinatal outcomes. Conclusion(s) Singletons born after IUI had higher risk of adverse perinatal outcomes compared with SC children, similar to ICSI, but favorable outcomes compared with IVF. Stimulation with clomiphene citrate was associated with higher risk of SGA compared with natural-cycle IUI, but follicle-stimulating hormone treatment did not seem to be associated with adverse outcomes.

To examine infant outcome of singletons born after cryopreservation of embryos (Cryo).National population-based controlled follow-up study.Denmark, 1995-2007.The study population was 957 Cryo singletons (Cryo-IVF, n=660; Cryo-ICSI, n=244; Cryo-IVF/-ICSI, n=53). The first control group was all singletons born after fresh IVF or intracytoplasmic sperm injection (ICSI) during the same period (IVF, n=6904; ICSI, n=3425). The second control group comprised a random sample of non-assisted reproductive technology (ART) singletons (n=4800).All observations were obtained from national registers.Low birth weight (LBW;2500 g), preterm birth (PTB;37 weeks), congenital malformations, mortality, and morbidity.Birth weight was higher in Cryo (mean=3578 g, SD=625) versus fresh (mean=3373 g, SD=648) and in Cryo versus non-ART (mean=3537 g, SD=572), and this was also the case for first birth only. Lower adjusted risk of LBW (odds ratio [OR]=0.63; 95% confidence interval [CI], 0.45-0.87) and PTB (OR=0.70; 95% CI, 0.53-0.92) was observed in Cryo versus fresh. Similar LBW and PTB rates were observed when comparing Cryo with non-ART, but the perinatal mortality rate was doubled in Cryo (1.6%) compared with non-ART (0.8%) singletons, and the adjusted risks of very preterm birth (34 weeks) and neonatal admittance were also significantly increased. No significant differences in the prevalence rates of birth defects, neurological sequelae, malignancies, and imprinting-related diseases were observed between the Cryo and the two control groups. However higher malformation and cerebral palsy rates were observed in the total Fresh vs. non-ART group.Cryo singletons have better neonatal outcome than offspring after fresh ET but poorer compared with non-ART singletons.