Corpus luteum number and maternal circulatory adaptation from early pregnancy onwards: the Rotterdam Periconception Cohort (Predict Study).

study questionIs the number of corpora lutea (CL) associated with maternal circulatory adaptation to pregnancy, as assessed by blood pressure and uterine artery Doppler pulsatility and resistance indices? SUMMARY ANSWER: Pregnancies without a corpus luteum have a higher mean arterial pressure throughout pregnancy and lower uterine artery pulsatility and resistance indices in the first and second trimesters, compared to pregnancies where one or more than one corpus luteum is present. WHAT IS KNOWN ALREADY: Different modes of conception result in varying numbers of corpus luteum in early pregnancy. Previous research has demonstrated significant differences in hypertensive disorders of pregnancy and birthweight in women with 0, 1, and multiple CL, as well as altered maternal cardiovascular adaptation. Although direct causal evidence is limited, these differences are thought to reflect the presence or absence of corpus luteum-derived hormones, suboptimal decidualization in programmed cycles, or both. STUDY DESIGN, SIZE, DURATION: This prospective study used data from the ongoing Rotterdam Periconception Cohort, including women with singleton pregnancies enrolled from 2010 to 2022 at the Erasmus MC, University Medical Center, a tertiary care facility. PARTICIPANTS/MATERIALS, SETTING,

methodsThe study population for this research involved pregnancies in 1986 women: 1456 with one corpus luteum (1292 due to natural conception or insemination and 164 due to natural cycle frozen embryo transfer), 457 with more than one corpus luteum (due to fresh embryo transfer), and 73 with no corpus luteum (due to artificial cycle (AC)-FET). Linear mixed models were adjusted for maternal age, body mass index, nulliparity, smoking, pre-existing hypertension, and uterine artery Doppler outcomes, including mean arterial pressure. MAIN RESULTS AND THE ROLE OF CHANCE: Adjusted mean arterial pressure during pregnancy was significantly higher in women with 0 vs 1 CL (β + 2.19 mmHg, 95% CI [0.43-3.95], P = 0.015), but was not different between those with >1 and 1 CL (β -0.35 mmHg [-1.22 to 0.53], P = 0.438). This was also true for diastolic but not for systolic blood pressure. Uterine artery Doppler indices were available for 624 women. Adjusted uterine artery pulsatility index (PI) and resistance index (RI) were significantly lower in women with 0 CL compared to 1 CL, both at 11 weeks (PI: 1.53, 95% CI [1.38-1.69] vs 1.72 [1.65-1.79], P = 0.026; RI: 0.69, [0.66-0.73] vs 0.73 [0.72-0.75], P = 0.034) and at 22 weeks gestational age (PI: 0.64 [0.57-0.72] vs 0.81 [0.78-0.85], P < 0.001; RI: 0.44 [0.41-0.46] vs 0.51 [0.50-0.53], P < 0.001). In pregnancies with >1 CL, uterine artery indices were comparable to the 1 CL group, except for a slightly higher RI at 22 weeks (0.54 [0.52-0.55], P = 0.011). Restricting the analyses to only pregnancies conceived using ARTs did not change the observed directions of the effects. LIMITATIONS, REASONS FOR CAUTION: This study was conducted in a tertiary hospital setting, which may limit generalizability to other populations. Details on luteal support were incomplete, and the corpus luteum number was inferred based on the mode of conception, which could introduce confounding by indication. WIDER IMPLICATIONS OF THE

findingsThese results align with previous literature and provide robust evidence from a large cohort, adjusting for confounders. Notably, uterine artery models were additionally adjusted for the observed differences in mean arterial pressure. However, despite this adjustment, the differences in uterine artery indices between CL groups persisted, indicating that these cannot be explained by the higher mean arterial pressure and suggesting the involvement of distinct vascular mechanisms. The observed differences in circulatory adaptation to pregnancy between conceptions with corpus luteum numbers may underlie the higher incidence of hypertensive disorders of pregnancy after conception without a corpus luteum. Additionally, these insights further support the preference for certain ARTs, where feasible, to optimize maternal and neonatal outcomes. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Departments of Obstetrics and Gynaecology and Internal Medicine of the Erasmus MC, University Medical Center, Rotterdam, the Netherlands. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: This study is registered at the Dutch Trial Register (NTR6854).