Assisted Reproduction · Safety and Risks

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

von Versen-Höynck F, Schaub AM, Chi YY, Chiu KH, Liu J, Lingis M, Stan Williams R, Rhoton-Vlasak A, Nichols WW, Fleischmann RR, Zhang W, Winn VD, Segal MS, Conrad KP, Baker VL

Published March 2019 Hypertension (Dallas, Tex. : 1979), 73(3), 640-649
DOI 10.1161/HYPERTENSIONAHA.118.12043 PMID 30636552 PMC PMC6434532

RRM Academy Synopsis

Frozen embryo transfer without a corpus luteum tied to preeclampsia

About 13 out of 100 artificial-cycle frozen embryo transfer births involved preeclampsia. Among modified natural frozen transfers, which form a corpus luteum, about 4 out of 100 did. The finding comes from a prospective cohort of 683 singleton live births from the women's own eggs.

Key Findings

  • Artificial-cycle frozen embryo transfers, with no corpus luteum, had more preeclampsia than modified natural frozen transfers: 12.8% versus 3.9% (P=0.02).
  • Preeclampsia with severe features occurred in 9.6% of artificial-cycle frozen transfers versus 0.8% of modified natural frozen transfers.
  • With no corpus luteum compared with 1, the adjusted odds ratio was 2.73 (95% CI 1.14-6.49) for preeclampsia and 6.45 (95% CI 1.94-25.09) for preeclampsia with severe features.
  • Women with 0 corpus lutea (n=26) showed a blunted early-pregnancy drop in carotid-femoral pulse wave velocity, clearest at 10 to 12 weeks (P=0.01), versus 1 (n=23) or more than 1 (n=22).

Interpretation

The obstetric study is a prospective observational cohort, so the design shows association and cannot show cause. The cohort held 683 singleton live births from the women's own eggs at Stanford, with 41 preeclampsia cases. The authors name possible unmeasured confounders and note the vessel study was underpowered for many analyses. They found no rate difference between modified natural frozen transfer and spontaneous conception. No protocol change was tested. The authors say the data support a randomized trial.

RRM Context

A corpus luteum forms after ovulation. Artificial cycles suppress the brain signals that drive the ovary, and no corpus luteum forms. The authors note that estradiol and progesterone are replaced, but other corpus luteum products, such as relaxin, are not. Restorative reproductive medicine works with the body's own ovulatory cycle. In this cohort, pregnancies missing a product of that cycle had more preeclampsia.

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.

Topics

By this author

Related research

Assisted Reproduction › Safety and Risks › Maternal Complications · Reproductive Endocrinology › Luteal Phase › Corpus Luteum Function · Pregnancy › Pregnancy Complications › Hypertensive Disorders
Frauke von Versen-Höynck, Amelia M Schaub, Yueh-Yun Chi, Kuei-Hsun Chiu, Jing Liu, Melissa Lingis, R Stan Williams, Alice Rhoton-Vlasak, Wilmer W Nichols, Raquel R Fleischmann, Wendy Zhang, Virginia D Winn, Mark S Segal, Kirk P Conrad, Valerie L Baker
F Versen-Höynck, A Schaub, Y Chi, K Chiu, J Liu, M Lingis, A Rhoton-Vlasak, W Nichols, R Fleischmann, W Zhang, V Winn, M Segal, K Conrad, V Baker
PMID 30636552 30636552 DOI 10.1161/HYPERTENSIONAHA.118.12043 10.1161/HYPERTENSIONAHA.118.12043 von Versen-Höynck et al. 2019, von Versen-Höynck 2019