Early Autism Spectrum Disorders in Children Born to Fertile, Subfertile, and ART-Treated Women.

INTRODUCTION: We examined the prevalence of autism spectrum disorders (ASDs) in Massachusetts (MA) comparing children born via assisted reproductive technology (ART) and children born to women with indicators of subfertility but no ART (Subfertile), to children born to women with neither ART nor indicators of subfertility (Fertile). We assessed the direct, indirect, and total effects of ART and subfertility on ASD among singletons. METHODS: This study included 10,147 ART, 8072 Subfertile and 441,898 Fertile MA resident births from the MA Outcome Study of ART (MOSART) database linked with Early Intervention program participation data. ART included fresh in vitro fertilization (IVF), fresh intracytoplasmic sperm injection (ICSI), and frozen embryo transfer. We estimated the prevalence of ASD by fertility group. We used logistic regression to assess the natural direct effect (NDE), natural indirect effect (NIE) through preterm birth, and total effects of each fertility group on ASD. RESULTS: The NDE indicated that, compared to the Fertile group, the odds of ASD were not statistically higher in the ART (ORNDE 1.07; 95% CI 0.88-1.30), Subfertile (ORNDE 1.11; 95% CI 0.89-1.38), IVF (ORNDE 0.91; 95% CI 0.68-1.22), or ICSI (ORNDE 1.13; 95% CI 0.84-1.51) groups, even if the rate of preterm birth was the same across all groups. The total effect (product of NDE and NIE) was not significant for ART (ORTotal Effect 1.08; 95% CI 0.89-1.30), Subfertile (ORTotal Effect 1.11; 95% CI 0.89-1.38), IVF (ORTotal Effect 0.92; 95% CI 0.69-1.23), or ICSI (ORTotal Effect 1.13; 95% CI 0.84-1.52). CONCLUSION: Compared to children born to Fertile women, children born to ART, ICSI, or IVF, or Subfertile women are not at increased risk of receiving an ASD diagnosis.

The impact of single-step and sequential embryo culture systems on obstetric and perinatal outcomes in singleton pregnancies: the Massachusetts Outcomes Study of Assisted Reproductive Technology.

OBJECTIVE: To compare the obstetric and perinatal outcomes of deliveries conceived with embryos from single-step vs. sequential culture media systems. DESIGN: Historical cohort of Massachusetts vital records linked to assisted reproductive technology clinic data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System and laboratory embryology data from two large academic hospital fertility centers. SETTING: Not applicable. PATIENTS: Patients with singleton live birth deliveries between 2004 and 2017 conceived with autologous assisted reproductive technology cycles with fresh blastocyst transfer using either single-step (n = 1,058) or sequential (n = 474) culture media systems. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Associations of single-step vs. sequential culture with obstetric outcomes (mode of delivery, placental abnormalities, pregnancy-induced hypertension, and gestational diabetes) and perinatal outcomes (preterm birth, low birthweight, small-for-gestational-age, and large-for-gestational-age [LGA]) were assessed with multivariate logistic modeling, adjusted for maternal age, race/ethnicity, education, parity, insurance type, protein supplementation, oxygen concentration, fertilization method, and number of transferred embryos. RESULTS: Compared with sequential culture, single-step culture was associated with increased odds of LGA (adjusted odds ratio 2.1, 95% confidence interval 1.04-4.22). There were no statistically significant differences between single-step and sequential culture media systems in the odds of placental abnormalities, pregnancy-induced hypertension, gestational diabetes, prematurity, small-for-gestational-age, or low birthweight. CONCLUSIONS: Single-step culture is associated with increased odds of LGA, indicating that embryo culture media systems may affect perinatal outcomes.