Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum

Abstract

In vitro fertilization involving frozen embryo transfer and donor oocytes increases preeclampsia risk. These in vitro fertilization protocols typically yield pregnancies without a corpus luteum (CL), which secretes vasoactive hormones. We investigated whether in vitro fertilization pregnancies without a CL disrupt maternal circulatory adaptations and increase preeclampsia risk. Women with 0 (n=26), 1 (n=23), or >1 (n=22) CL were serially evaluated before, during, and after pregnancy. Because increasing arterial compliance is a major physiological adaptation in pregnancy, we assessed carotid-femoral pulse wave velocity and transit time. In a parallel prospective cohort study, obstetric outcomes for singleton livebirths achieved with autologous oocytes were compared between groups by CL number (n=683). The expected decline in carotid-femoral pulse wave velocity and rise in carotid-femoral transit time during the first trimester were attenuated in the 0-CL compared with combined single/multiple-CL cohorts, which were similar (group-time interaction: P=0.06 and 0.03, respectively). The blunted changes of carotid-femoral pulse wave velocity and carotid-femoral transit time from prepregnancy in the 0-CL cohort were most striking at 10 to 12 weeks of gestation ( P=0.01 and 0.006, respectively, versus 1 and >1 CL). Zero CL was predictive of preeclampsia (adjusted odds ratio, 2.73; 95% CI, 1.14-6.49) and preeclampsia with severe features (6.45; 95% CI, 1.94-25.09) compared with 1 CL. Programmed frozen embryo transfer cycles (0 CL) were associated with higher rates of preeclampsia (12.8% versus 3.9%; P=0.02) and preeclampsia with severe features (9.6% versus 0.8%; P=0.002) compared with modified natural frozen embryo transfer cycles (1 CL). In common in vitro fertilization protocols, absence of the CL perturbed the maternal circulation in early pregnancy and increased the incidence of preeclampsia.

Keywords: hormones; humans; pregnancy; pulse wave analysis; relaxin.

Figure 1.

Prospective cohort study of obstetric outcomes: enrollment, inclusions, and exclusions.

Figure 2.

Changes in carotid-femoral (A) pulse wave velocity (cfPWV) and (B) pulse wave transit time (PWTT) during pregnancy in women conceiving with and without IVF. Mean ± 1.96SE (95% CI). BP, before pregnancy; PP, postpartum; m/s, meters/second; ms, milliseconds. Wilcoxon signed-rank test with Bonferroni correction was used to compare the three timepoints in the first trimester for each of the three cohorts, separately, with the pre-pregnancy baseline (BP). *p<0.017 for >1 CL, ⁺p<0.017 for 1 CL. 0 CL was not significantly different from BP at any timepoint in the first trimester. For further statistical analysis, see Results.