In vitro fertilization and risk for hypertensive disorders of pregnancy: associations with treatment parameters

Abstract

Although invitro fertilization has been associated with an increased risk for hypertensive disorders of pregnancy, the association of risk with invitro fertilization treatment parameters is unclear. To evaluate risk for hypertensive disorders of pregnancy by maternal fertility status and invitro fertilization treatment parameters. Women in 8 states who underwent invitro fertilization resulting in a live birth during 2004-2013 were linked to their infant's birth certificates. A 10:1 sample of births from non-in vitro fertilization deliveries were selected for comparison. Those with an indication of infertility treatment on the birth certificate were categorized as subfertile and omitted from the study population; all others were categorized as fertile. The invitro fertilization pregnancies were additionally categorized by oocyte source (autologous versus donor) and embryo state (fresh versus thawed). Both the fertile and invitro fertilization births were limited to singletons only, and the invitro fertilization pregnancies were limited to those using partner sperm. Hypertensive disorders of pregnancy (including gestational hypertension and preeclampsia) were identified from the birth certificate, modeled using logistic regression, and reported as adjusted odds ratios and 95% confidence intervals. For analyses of invitro fertilization pregnancies from autologous oocytes-fresh embryos, the reference group was fertile women (subgroup analysis 1). For analyses within the invitro fertilization group, the reference group was autologous oocytes-fresh embryos (subgroup analysis 2). The study population included 1,465,893 pregnancies (1,382,311 births to fertile women and 83,582 births to invitro fertilization-treated women). Compared to fertile women, invitro fertilization-treated women with autologous-fresh cycles were not at increased risk for hypertensive disorders of pregnancy (adjusted odds ratio, 1.04; 95% confidence interval, 0.99, 1.08). Among invitro fertilization births (subgroup analysis 2), the risk for hypertensive disorders of pregnancy was increased for the autologous-thawed (adjusted odds ratio, 1.30; 95% confidence interval, 1.20, 1.40); donor-fresh (adjusted oddds ratio, 1.92; 95% confidence interval, 1.71, 2.15); and donor-thawed (adjusted odds ratio, 1.70; 95% confidence interval, 1.47, 1.96) groups. Excluding women with pregestational diabetes or chronic hypertension as well as adjusting for body mass index and infertility diagnoses did not substantially change the results. When stratified by <34 weeks (early-onset hypertensive disorders of pregnancy) versus ≥34 weeks (late-onset hypertensive disorders of pregnancy), only the donor-fresh group had an increased risk of early-onset hypertensive disorders of pregnancy, but the risks for all other oocyte source-embryo state groups compared to autologous-fresh were increased for late-onset hypertensive disorders of pregnancy. The risk for hypertensive disorders of pregnancy is increased for invitro fertilization-treated women in pregnancies conceived via frozen embryo transfer (with both autologous or donor oocyte) and fresh donor oocyte embryo transfer. No increase in risk was seen with autologous oocyte-fresh embryo transfers invitro fertilization cycles. Excluding women with pregestational diabetes or chronic hypertension as well as adjusting for body mass index and infertility diagnoses did not substantially change the results.