Absent or Excessive Corpus Luteum Number Is Associated With Altered Maternal Vascular Health in Early Pregnancy

Abstract

Identifying modifiable factors that contribute to preeclampsia risk associated with assisted reproduction can improve maternal health. Vascular dysfunction predates clinical presentation of preeclampsia. Therefore, we examined if a nonphysiological hormonal milieu, a modifiable state, affects maternal vascular health in early pregnancy. Blood pressure, endothelial function, circulating endothelial progenitor cell numbers, lipid levels, and corpus luteum (CL) hormones were compared in a prospective cohort of women with infertility history based on number of CL: 0 CL (programmed frozen embryo transfer [FET], N=18); 1 CL (spontaneous conception [N=16] and natural cycle FET [N=12]); or >3 CL associated with in vitro fertilization [N=11]. Women with 0 or >3 CL lacked the drop in mean arterial blood pressure compared with those with 1 CL (both P=0.05). Reactive hyperemia index was impaired in women with 0 CL compared with 1 CL ( P=0.04) while baseline pulse wave amplitude was higher with > 3 CL compared with 1 CL ( P=0.01) or 0 CL ( P=0.01). Comparing only FET cycles, a lower reactive hyperemia index and a higher augmentation index is noted in FETs with suppressed CL compared with FETs in a natural cycle (both P=0.03). The number of angiogenic and nonangiogenic circulating endothelial progenitor cell numbers was lower in the absence of a CL in FETs ( P=0.01 and P=0.03). Vascular health in early pregnancy is altered in women with aberrant numbers of CL (0 or >3) and might represent insufficient cardiovascular adaptation contributing to an increased risk of preeclampsia.

Keywords: corpus luteum; endothelial progenitor cells; infertility; pregnancy; vascular endothelium.

Conflict of interest statement

Conflicts of Interest/Disclosures

KPC discloses use patents for relaxin. All other authors have no conflict of interest to declare.

Figures

Figure 1:

Vascular endothelial function measured as reactive hyperemia index (RHI; A, C) and baseline pulse wave amplitude (BPWA, B) in first trimester comparing different numbers of corpora lutea (0 CL [N=18], 1 CL [N=28] or > 3 CL [N=11]; A&B) and different modes of conception (programmed cycle frozen-thawed embryo transfer [FET, N=18], natural cycle FET [N=12] or spontaneous conception [N=16], C). Box plots represent median, 10th, 25th, 75th and 90th percentile.

Figure 2:

Comparison of angiogenic (A, C) and non-angiogenic (B, D) circulating progenitor cell (CPC) numbers in first trimester of women conceived with different numbers of corpora lutea (0 CL [N=17], 1 CL [N=23] or > 3 CL [N=8]; A&B) and different modes of conception (programmed cycle frozen-thawed embryo transfer [FET, N=17], natural cycle FET [N=8] or spontaneous conception [N=16], C&D). Box plots represent median, 10th, 25th, 75th and 90th percentile.

Figure 3:

Summary of the maternal endocrine milieu in first trimester of pregnancy and pregnancy adaptation and vascular health. (A) Comparison among groups by CL number. CL number within yellow ovary and CL hormonal products depicted by symbols at the top of the figure. Vascular parameters for each CL group represented below. Arteries (pink smooth muscle and orange endothelial lining) are centered on y-axis based on change in MAP at first trimester visit compared to preconception (small black circle in lumen), arrows (length) represent reactive hyperemia index (RHI), a measure of endothelial reactivity, and artery diameters represent baseline pulse wave amplitude (BPWA), a measure of arterial tone. Circulating progenitor cell number represented by cells in lumen. Relaxin, a vasodilator secreted by the corpus luteum (CL), and BPWA increased with CL number. RHI was highest in women with 1 CL. Women with aberrant numbers of CL (0 or > 3) had higher blood pressure levels and lacked the typical drop in mean arterial pressure (y-axis). (B). Comparison between FET groups compared with spontaneous conception to note differences based on absence of CL and /or natural vs IVF embryo. Suppression of CL development (CL=0) in frozen embryo transfer (FET) cycles was associated with a lower RHI compared with FETs in a natural cycle (CL=1), as well as lower numbers of angiogenic and non-angiogenic circulating progenitor cells (CPCs). MAP decline was greater if CL=1 and CPCs were most numerous in the natural cycle FET.