Adverse pregnancy, birth, and infant outcomes in twins: effects of maternal fertility status and infant gender combinations; the Massachusetts Outcomes Study of Assisted Reproductive Technology

Abstract

Background It is unknown whether the risk of adverse outcomes in twin pregnancies among subfertile women, conceived with and without in vitro fertilization (IVF), differ from those conceived spontaneously. Objective To evaluate the effects of fertility status on adverse perinatal outcomes in twin pregnancies on a population basis. Study Design All twin live births of ≥22 weeks’ gestation and ≥350 grams birthweight to Massachusetts resident women in 2004–10 were linked to hospital discharge records, vital records, and IVF cycles. Women were categorized by their fertility status as in vitro fertilization (IVF), subfertile, or fertile, and by twin pair genders (all, like, unlike). Women whose births linked to IVF cycles were classified as IVF; those with indicators of subfertility but without IVF treatment were classified as subfertile; all others were classified as fertile. Risks of six adverse pregnancy outcomes (gestational diabetes, pregnancy hypertension, uterine bleeding, placental complications (placenta abruptio, placenta previa, and vasa previa), prenatal hospitalizations, primary cesarean), and nine adverse infant outcomes (very low birthweight, low birthweight, small-for-gestation birthweight, large-for-gestation birthweight, very preterm (<32 weeks), preterm, birth defects, neonatal death, and infant death) were modeled by fertility status with the fertile group as reference, using multivariate log binomial regression and reported as adjusted relative risk ratios (ARRs) and 95% confidence intervals (CI). Results The study population included 10,352 women with twin pregnancies (6,090 fertile, 724 subfertile, and 3,538 IVF). Among all twins, the risks for all six adverse pregnancy outcomes were significantly increased for the subfertile and IVF groups, with highest risks for uterine bleeding (ARR 1.92, 2.58, respectively), and placental complications (ARR 2.07and 1.83, respectively). Among all twins, the risks for those born to subfertile women were significantly increased for very preterm birth, and neonatal and infant death (ARR 1.36, 1.89, and 1.87, respectively); risks were significantly increased among IVF twins for very preterm birth, preterm birth, and birth defects (ARR 1.28, 1.07, and 1.26, respectively). Conclusions Risks of all maternal and most infant adverse outcomes are increased for subfertile and IVF twins. Among all twins, the highest risks were for uterine bleeding and placental complications for the subfertile and IVF groups, and neonatal and infant death in the subfertile group. These findings provide further evidence supporting single embryo transfer and more cautious use of ovulation induction.

Risk of severe maternal morbidity by maternal fertility status: a US study in 8 states

“…Our prior analyses of twin pregnancies (which were additionally linked to hospital discharge data, as well as birth certificates) have reported a 2-fold increased risk of uterine bleeding and placental complications (abruptio placenta, placenta previa, vasa previa) in subfertile and IVF pregnancies. 34 Nationally in the United States, cesarean rates parallel advancing maternal age: in 2015, women aged 40 years were more than twice as likely to deliver by cesarean as women age <20 years (48.4% vs 20.4%). 1 In 2015, the overall low-risk cesarean delivery rate (cesarean delivery among nulliparous women with full-term singletons in a vertex presentation) was 25.8%, ranging from 16.7% for women ages <20 years to 52.0% for women ages 40 years.…”

Pregnancy, birth, and infant outcomes by maternal fertility status: the Massachusetts Outcomes Study of Assisted Reproductive Technology

“…The first analysis of perinatal outcomes from the MOSART study was based on singleton and twin births in 2004–08, and examined four adverse outcomes: preterm birth, low birthweight, small for gestational age, and perinatal death (30). In this analysis, based on births in 2004–10, we have increased the sample size by nearly 50% (singleton births from 320,135 to 459,623), expanded the number of adverse outcomes from four to 15 (six maternal and nine infant), and separated the analysis by plurality, with the results in singletons presented in this paper, and the results for twins (further divided by like gender and unlike gender pairs) in a subsequent paper (40). This analysis was repeated and expanded to clarify associations, and to further identify factors that may be in the pathway between fertility status, treatment, and perinatal outcomes.…”

Risk factors and high-risk subgroups of severe acute maternal morbidity in twin pregnancy: A population-based study

“…CART analysis found that at the beginning of pregnancy oocyte donation is the most discriminating factor for severe acute maternal morbidity. This increased maternal risk in women with twin pregnancies after IVF contradicts some previous studies exploring this association [9,[18][19][20]. The latter, however, were limited by their inability to differentiate between spontaneous pregnancy and ovulation-inducing drugs alone and between in vitro fertilization with autologous and donated oocytes.…”