LAUSR

Preeclampsia is recognized as a major cause of maternal morbidity and mortality worldwide. Despite considerable disease heterogeneity, it is universally acknowledged that the disorder originates in the placenta, but emerging data demonstrate that predisposing factors, pathophysiology, presenting signs, and postpartum legacy are predominantly cardiovascular in nature. In this issue of Hypertension, Conrad et al set out to investigate early cardiovascular effects in pregnancies conceived by in-vitro fertilization (IVF). IVF conception is a known predisposing factor for preeclampsia, especially with ovum donation—when conception occurs in the absence of a corpus luteum (CL). The authors compared changes in early pregnancy cardiovascular function between 3 groups—spontaneous conceptions with a single CL, ovum donation IVF pregnancies without a CL and IVF pregnancies with multiple CLs. Maternal cardiovascular adaptation was systematically and longitudinally evaluated in each of the 3 groups 6× in pregnancy starting with the prepregnancy follicular phase through to 18 months post-partum. Early pregnancy changes in cardiac output, left atrial dimension, E wave velocity, and augmentation index were significantly attenuated in women who conceived through ovum donation (no CL) when compared with the conceptions with one or more CLs. Thereafter, most cardiovascular indices in the ovum donation group recovered to match those in the 1 and >1 CL cohorts. The authors contend that these observations provided strong support for a critical role of CL factor(s) in the transformation of the maternal cardiovascular system in early gestation. From these important experimental results, the authors also go on to suggest that the development of a CL or replacement of missing CL factor(s) may be indicated to improve cardiovascular function and reduce preeclampsia risk in IVF pregnancies. This thorough, comprehensive, and well-conducted research in an important area of overlap between cardiovascular and pregnancy health deserves greater attention. The association between IVF pregnancy and preeclampsia was originally presumed to be related to uterine decidual-placental immune interactions and the immunology of pregnancy. However, more recent epidemiological studies have demonstrated that the increase in risk of preeclampsia with IVF pregnancies is restricted to ovum donation (no CL) pregnancies and explained by the confounding effect of advanced maternal age in nonovum donation (≥1 CL) IVF pregnancy. In this regard, the authors designed a robust experimental design to compare cardiovascular responses in various IVF groups. Their important findings support the assertion that the higher risk of preeclampsia is related to poorer early pregnancy cardiovascular adaptation. Although it is entirely plausible that CL factors may directly influence early pregnancy maternal cardiovascular adaptation, it is important to ascertain whether the cardiovascular derangement may also have predated the development of the CL (or failure to do so). Another seminal study published earlier this year in Hypertension longitudinally assessed maternal hemodynamic indices in 356 spontaneously conceived pregnancies, from prepregnancy. Preconception women who subsequently developed preeclampsia/fetal growth restriction had lower cardiac output/cardiac index and higher mean arterial pressure and total peripheral resistance compared with those with normal outcome. Closer evaluation of the cohort in the present study shows that preconception left atrial dimension were higher (Figure 2, in the study by Conrad et al) and cardiac output and peripheral/central pulse pressure lower (Figures 1 and 4, in the study by Conrad et al) compared with 1 Cl and >1 CL pregnancies. These changes are consistent with the finding that the majority of women requiring ovum donation usually suffer from premature ovarian insufficiency; a disorder where systematic review evidence demonstrates increased cardiovascular morbidity (Figure). The observations of Conrad et al corroborate the evidence that maternal prepregnancy maternal cardiovascular status contributes to preeclampsia risk status in pregnancy.