The Epidemiology of Perinatal/Neonatal Outcomes among Twins Stratified by Mode of Conception and the Ef-fect of Advanced Maternal Age in The United States

Background: To compare neonatal outcomes among twin preg-nancies conceived as a result of fertility treatments, including Assisted Reproductive Technology (ART), ovulation induction (OI), intrauterine insemination (IUI) and twin pregnancies con-ceived spontaneously A retrospective population-based study Materials and Methods: This is a population-based analysis of neonatal outcomes in twin pregnancies in the United States based on their mode of conception: 1) Fertility enhancing drugs for OI/IUI, 2) ART (including in vitro fertilization (IVF) and in-tracytoplasmic sperm injection (ICSI), and 3) spontaneous con-ception (SC). We used Natality files from the National Center for Health Statistics from 2014-2016. All twin gestations with reported variable for mode of conception were included. The primary outcome was the rate of composite neonatal morbid-ity (CNM) and was defined by presence of at least one of the followings: gestational age (GA) at delivery < 28 weeks, 5 min Apgar score < 7, assisted ventilation > 6 hours, neonatal inten-sive care unit (NICU) admission, antibiotics administration or seizure. Statistical analysis was performed using R-3.4.1.Results: Included in this study were 388,045 twin deliveries of which 334,677 (86.2%) resulted from SC, 36,883 (9.5%) from ART and 16,485 (4.2%) were conceived by OI/IUI. CNM was positive in 134108/334677 (40.1%; 95%CI 39.9-40.2) of SCs, 16283/36883 (44.1%; 95%CI 43.6-44.7) of ART and 7108/16485 (43.1%; 95%CI 42.4-43.9) of OI/IUI fertility treat-ments. The differences between these 3 groups were statistically significant before and after adjustment for potential covariates. Conclusions: In this retrospective study, we observed that the rate of neonatal morbidity was slightly higher in twins con-ceived by IVF/ICSI and OI/IUI compared to SC. This slightly increased rate however, is not clinically significant and overall reassurance can therefore be provided regarding neonatal out-comes to the patients undergoing fertility treatments.P value is calculated based on Multinomial Logistic Regression with Mode of Conception as dependent variable and the fol-lowing covariates: maternal age, body mass index (BMI), race/ ethnicity, marital status, gestational hypertension and diabetes. Part B- Title: Perinatal Mortality among Twins Stratified By Mode Of Conception In The United States (2014-2015)Objective: To perform an epidemiological study of perinatal mortality rate among twins based on their mode of conception: Assisted Reproductive Technology (ART), less invasive fertil-ity treatments including ovulation induction (OI) and intrauter-ine insemination (IUI), and spontaneous conception (SC).Design: A retrospective population-based studyMaterials and Methods: We performed a population-based retrospective analysis of twin perinatal mortality in the United States (2014-2015) among newborn twins without congenital malformations and/or chromosomal abnormalities. We utilized ‘Period Linked Birth – Infant death’ and ‘Fetal Death’ data files from the National Center for Health Statistics for years 2014 – 2015. Perinatal mortality was defined as stillbirth at ≥22 weeks gestation or neonatal death up to 28 days after birth. Perina-tal mortality was calculated for different categories of mode of conception: 1) ART (including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), 2) fertility enhancing drugs for OI/IUI, and 3) SC. Statistical analysis was performed using R-3.4.1.Results: Included in this study were 388,045 twin deliveries of which 334,677 (86.2%) were from SC, and 36,883 (9.5%) and 16,485 (4.2%) were results of ART and OI/IUI treatments, respectively. Rate for perinatal mortality was 3792/334677 (11 per 1000; 95%CI 10-12) in SCs, 464/36883 (13 per 1000; 95%CI 12-14) in ART fertility treatments and 215/16485 (13 per 1000; 95%CI 11-15) for twin deliveries conceived from OI/ IUI. (Chi2 = 8.05, P=0.01).Conclusions: We observed that perinatal mortality rate is high-er among twins conceived following fertility treatments, in-cluding ART and OI/IUI, compared to twins conceived without these treatments. Although this slightly increased risk is clini-cally insignificant, counselling patients before undergoing any form of fertility treatment should include discussion of the risks of perinatal death.