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

BACKGROUND: Although in vitro fertilization has been associated with an increased risk for hypertensive disorders of pregnancy, the association of risk with in vitro fertilization treatment parameters is unclear. OBJECTIVE: To evaluate risk for hypertensive disorders of pregnancy by maternal fertility status and in vitro fertilization treatment parameters. MATERIALS AND METHODS: Women in 8 states who underwent in vitro 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 in vitro fertilization pregnancies were additionally categorized by oocyte source (autologous versus donor) and embryo state (fresh versus thawed). Both the fertile and in vitro fertilization births were limited to singletons only, and the in vitro 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 in vitro fertilization pregnancies from autologous oocytes-fresh embryos, the reference group was fertile women (subgroup analysis 1). For analyses within the in vitro fertilization group, the reference group was autologous oocytes-fresh embryos (subgroup analysis 2). RESULTS: The study population included 1,465,893 pregnancies (1,382,311 births to fertile women and 83,582 births to in vitro fertilization-treated women). Compared to fertile women, in vitro 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 in vitro 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. CONCLUSION: The risk for hypertensive disorders of pregnancy is increased for in vitro 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 in vitro 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.

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

BACKGROUND: Over the past 2 decades the characteristics of women giving birth in the United States and the nature of the births themselves have changed dramatically, with increases in older maternal age, plural births, cesarean deliveries, and conception from infertility treatment. OBJECTIVE: We sought to evaluate the risk of severe maternal morbidity by maternal fertility status, and for in vitro fertilization pregnancies, by oocyte source and embryo state combinations. STUDY DESIGN: Women in 8 states who underwent in vitro fertilization cycles resulting in a live birth during 2004 through 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, all others were categorized as fertile. In vitro fertilization pregnancies were additionally categorized by oocyte source (autologous vs donor) and embryo state (fresh vs thawed). Maternal morbidity was identified from the birth certificate, modeled using logistic regression, and reported as adjusted odds ratios [95% confidence intervals]. The reference group was fertile women. RESULTS: The study population included 1,477,522 pregnancies (1,346,118 fertile, 11,298 subfertile, 80,254 in vitro fertilization autologous-fresh, 21,964 in vitro fertilization autologous-thawed, 13,218 in vitro fertilization donor-fresh, and 4670 in vitro fertilization donor-thawed pregnancies): 1,420,529 singleton, 54,573 twin, and 2420 triplet+ pregnancies. Compared to fertile women, subfertile and the 4 groups of in vitro fertilization-treated women had increased risks for blood transfusion and third- or fourth-degree perineal laceration (subfertile, 1.58 [1.23-2.02] and 2.08 [1.79-2.43]; autologous-fresh, 1.33 [1.14-1.54] and 1.37 [1.26-1.49]; autologous-thawed, 1.94 [1.60-2.36] and 2.10 [1.84-2.40]; donor-fresh, 2.16 [1.69-2.75] and 2.11 [1.66-2.69]; and donor-thawed, 2.01 [1.38-2.92] and 1.28 [0.79-2.08]). Also compared to fertile women, the risk of unplanned hysterectomy was increased for in vitro fertilization-treated women in the autologous-thawed group (2.80 [1.96-4.00]), donor-fresh group (2.14 [1.33-3.44]), and the donor-thawed group (2.46 [1.33-4.54]). The risk of ruptured uterus was increased for in vitro fertilization-treated women in the autologous-fresh group (1.62 [1.14-2.29]). Among women with a prior birth, the risk of blood transfusion after a vaginal birth was increased for subfertile women (2.91 [1.38-6.15]), and women in all 4 in vitro fertilization groups (autologous-fresh, 1.93 [1.23-3.01]; autologous-thawed, 2.99 [1.78-5.02]; donor-fresh, 5.13 [2.39-11.02]; and donor-thawed, 5.20 [1.83-14.82]); the risk after a cesarean delivery was increased in the autologous-thawed group (1.74 [1.29-2.33]) and the donor-fresh group (1.62 [1.07-2.45]). Unplanned hysterectomy was increased in the autologous-thawed (2.31 [1.43-3.71]) and donor-thawed (2.45 [1.06-5.67]) groups. CONCLUSION: The risks of severe maternal morbidity are increased for subfertile and in vitro fertilization births, particularly in pregnancies that are not from autologous, fresh cycles.