Absolute Risk of Adverse Obstetric Outcomes Among Twin Pregnancies After In Vitro Fertilization by Maternal Age | Neonatology | JAMA Network Open | JAMA Network
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    Original Investigation
    Obstetrics and Gynecology
    September 10, 2021

    Absolute Risk of Adverse Obstetric Outcomes Among Twin Pregnancies After In Vitro Fertilization by Maternal Age

    Author Affiliations
    • 1Center for Reproductive Medicine, Peking University Third Hospital, Beijing, China
    • 2Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
    • 3National Clinical Research Center for Obstetrical and Gynecology, Peking University Third Hospital, Beijing, China
    • 4Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, China
    • 5National Center for Healthcare Quality Management in Obstetrics, Beijing, China
    • 6Department of Biostatistics, Peking University School of Public Health, Beijing, China
    • 7Clinical Trial Unit, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
    • 8Centre for Data Science in Health and Medicine, Peking University, Beijing, China
    • 9China Standard Medical Information Research Center, Shenzhen, China
    JAMA Netw Open. 2021;4(9):e2123634. doi:10.1001/jamanetworkopen.2021.23634
    Key Points

    Question  What is the absolute risk of adverse obstetric outcomes stratified by in vitro fertilization (IVF), twin or singleton pregnancy, and maternal age?

    Findings  In this cohort study of 16 879 728 pregnant women, the twin pregnancy rate was 32.1% among those who conceived via IVF. Twin pregnancies conceived via IVF had higher absolute obstetric risks in each maternal age compared with IVF-conceived singleton pregnancies or non–IVF-conceived twin pregnancies.

    Meaning  These findings suggest that twin pregnancy, IVF, and advanced maternal age are independently associated with adverse obstetric outcomes, and their coexistence may lead to the aggravation of obstetric risk.


    Importance  Twin pregnancy is a common occurrence in pregnancies conceived with in vitro fertilization (IVF), but the absolute risk of adverse obstetric outcomes stratified by IVF, twin or singleton pregnancy, and maternal age are unknown.

    Objective  To estimate the absolute risk of adverse obstetric outcomes at each maternal age among twin pregnancies conceived with IVF.

    Design, Setting, and Participants  This retrospective cohort study included pregnant women with infants born from January 1, 2013, to December 31, 2018, based on the Hospital Quality Monitoring System in China. Data were analyzed from September 1, 2020, to June 30, 2021.

    Exposures  Twin pregnancy with IVF (IVF-T), singleton pregnancy with IVF (IVF-S), twin pregnancy with non-IVF (nIVF-T), and singleton pregnancy with non-IVF (nIVF-S).

    Main Outcomes and Measures  Sixteen obstetric outcomes, including 10 maternal complications (gestational hypertension, eclampsia and preeclampsia, gestational diabetes, placenta previa, placental abruption, placenta accreta, preterm birth, dystocia, cesarean delivery, and postpartum hemorrhage) and 6 neonatal complications (fetal growth restriction, low birth weight, very low birth weight, macrosomia, malformation, and stillbirth).

    Results  Among 16 879 728 pregnant women aged 20 to 49 years (mean [SD] age, 29.2 [4.7] years), the twin-pregnancy rates were 32.1% in the IVF group and 1.5% in the non-IVF group (relative risk, 20.8; 95% CI, 20.6-20.9). The most common adverse obstetric outcomes after pregnancy conceived with IVF were cesarean delivery (88.8%), low birth weight (43.8%), preterm birth (39.6%), gestational diabetes (20.5%), gestational hypertension and preeclampsia and eclampsia (17.5%), dystocia (16.8%), and postpartum hemorrhage (11.9%). The absolute risk of most adverse obstetric outcomes in each subgroup presented in 2 dominant patterns: Pattern A indicated the absolute risk ranging from IVF-T to nIVF-T to IVF-S to nIVF-S, and pattern B indicated the absolute risk ranging from IVF-T to IVF-S to nIVF-T to nIVF-S. Both patterns showed an elevated obstetric risk with increasing maternal age in each subgroup.

    Conclusions and Relevance  In this cohort study, twin pregnancy, IVF, and advanced maternal age were independently associated with adverse obstetric outcomes. Given these findings, promotion of the elective single embryo transfer strategy is needed to reduce multiple pregnancies following IVF technologies. Unnecessary cesarean delivery shouldh be avoided in all pregnant women.