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

Abstract

Background: Births to subfertile women, with and without infertility treatment, have been reported to have lower birthweights and shorter gestations, even when limited to singletons. It is unknown whether these decrements are due to parental characteristics or aspects of infertility treatment.

Objective: The objective of the study was to evaluate the effect of maternal fertility status on the risk of pregnancy, birth, and infant complications.

Study design: All singleton live births of ≥22 weeks' gestation and ≥350 g birthweight to Massachusetts resident women in 2004-2010 were linked to hospital discharge and vital records. Women were categorized by their fertility status as in vitro fertilization, subfertile, or fertile. Women whose births linked to in vitro fertilization cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System were classified as in vitro fertilization. Women with indicators of subfertility but not treated with in vitro fertilization were classified as subfertile. Women without indicators of subfertility or in vitro fertilization treatment were classified as fertile. Risks of 15 adverse outcomes (gestational diabetes, pregnancy hypertension, antenatal bleeding, placental complications [placenta abruptio and placenta previa], prenatal hospitalizations, primary cesarean delivery, very low birthweight [<1500 g], low birthweight [<2500 g], small-for-gestation birthweight [z-score ≤-1.28], large-for-gestation birthweight [z-score ≥1.28], very preterm [<32 weeks], preterm [<37 weeks], birth defects, neonatal death [0-27 days], and infant death [0-364 days of life]) were modeled by fertility status with the fertile group as reference and the subfertile group as reference, using multivariate log binomial regression and reported as adjusted risk ratios and 95% confidence intervals.

Results: The study population included 459,623 women (441,420 fertile, 8054 subfertile, and 10,149 in vitro fertilization). Women in the subfertile and in vitro fertilization groups were older than their fertile counterparts. Risks for 6 of 6 pregnancy outcomes and 6 of 9 infant outcomes were increased for the subfertile group, and 5 of 6 pregnancy outcomes and 7 of 9 infant outcomes were increased for the in vitro fertilization group. For 4 of the 6 pregnancy outcomes (uterine bleeding, placental complications, prenatal hospitalizations, and primary cesarean) and 2 of the infant outcomes (low birthweight and preterm) the risk was greater in the in vitro fertilization group, with nonoverlapping confidence intervals to the subfertile group, indicating a substantially higher risk among in vitro fertilization-treated women. The highest risks for the in vitro fertilization women were uterine bleeding (adjusted risk ratio, 3.80; 95% confidence interval, 3.31-4.36) and placental complications (adjusted risk ratio, 2.81; 95% confidence interval, 2.57-3.08), and for in vitro fertilization infants, very preterm birth (adjusted risk ratio, 2.13; 95% confidence interval, 1.80-2.52), and very low birthweight (adjusted risk ratio, 2.15; 95% confidence interval, 1.80-2.56). With subfertile women as reference, risks for the in vitro fertilization group were significantly increased for uterine bleeding, placental complications, prenatal hospitalizations, primary cesarean delivery, low and very low birthweight, and preterm and very preterm birth.

Conclusion: These analyses indicate that, compared with fertile women, subfertile and in vitro fertilization-treated women tend to be older, have more preexisting chronic conditions, and are at higher risk for adverse pregnancy outcomes, particularly uterine bleeding and placental complications. The greater risk in in vitro fertilization-treated women may reflect more severe infertility, more extensive underlying pathology, or other unfavorable factors not measured in this study.

Keywords: adverse pregnancy outcomes; assisted reproductive technology; infertility; subfertility.