Higher risk of pre-eclampsia and other vascular disorders with artificial cycle for frozen-thawed embryo transfer compared to ovulatory cycle or to fresh embryo transfer following in vitro fertilization

Abstract

BackgroundRisks of maternal morbidity are known to be reduced in pregnancies resulting from frozen embryo transfer (FET) compared to fresh-embryo transfer (fresh-ET), except for the risk of pre-eclampsia, reported to be higher in FET pregnancies compared to fresh-ET or natural conception. Few studies have compared the risk of maternal vascular morbidities according to endometrial preparation for FET, either with ovulatory cycle (OC-FET) or artificial cycle (AC-FET). Furthermore, maternal pre-eclampsia could be associated with subsequent vascular disorders in the offspring.MethodsA 2013-2018 French nationwide cohort study comparing maternal vascular morbidities in 3 groups of single pregnancies was conducted: FET with either OC or AC preparation, and fresh-ET. Data were extracted from the French National Health System database. Results were adjusted for maternal characteristics and infertility (age, parity, smoking, obesity, history of diabetes or hypertension, endometriosis, polycystic ovary syndrome and premature ovarian insufficiency).ResultsA total of 68025 single deliveries were included: fresh-ET (n=48152), OC-FET (n=9500), AC-FET (n=10373). The risk of pre-eclampsia was higher in AC-FET compared to OC-FET and fresh-ET groups in univariate analysis (5.3% vs. 2.3% and 2.4%, respectively, P<0.0001). In multivariate analysis the risk was significantly higher in AC-FET compared to fresh-ET: aOR=2.43 [2.18-2.70], P<0.0001). Similar results were observed for the risk of other vascular disorders in univariate analysis (4.7% vs. 3.4% and 3.3%, respectively, P=0.0002) and in multivariate analysis (AC-FET compared to fresh-ET: aOR=1.50 [1.36-1.67], P<0.0001). In multivariate analysis, the risk of pre-eclampsia and other vascular disorders were comparable in OC-FET and fresh-ET: aOR=1.01 [0.87-1.17, P= 0.91 and aOR=1.00 [0.89-1.13], P=0.97, respectively).Within the group of FET, the risks of pre-eclampsia and other vascular disorders in multivariate analysis were higher in AC-FET compared to OC-FET (aOR=2.43 [2.18-2.70], P<0.0001 and aOR=1.5 [1.36-1.67], P<0.0001, respectively).ConclusionThis nationwide register-based cohort study highlights the possibly deleterious role of prolonged doses of exogenous estrogen-progesterone supplementation on gestational vascular pathologies and the protective role of the corpus luteum present in OC-FET for their prevention. Since OC-FET has been demonstrated not to strain the chances of pregnancy, OC preparation should be advocated as first-line preparation in FET as often as possible in ovulatory women.

Ovulation induction and subfertile untreated conception groups offer improved options for interpreting risks associated with ART

“…Previous studies report that fresh embryo transfer and controlled ovarian hyperstimulation are associated with small for gestational age, placenta praevia, preterm birth and low birth weight [ 6 ]. In contrast, FET is associated with large for gestational age and preeclampsia with particular risks related to the use of hormone preparation cycles to prepare the endometrium for frozen embryo replacement [ 37 , 38 ].…”

Low-dose aspirin prophylaxis to prevent hypertensive disorders of pregnancy after in vitro fertilisation: a scoping review protocol

“… 14 A potential mechanism is the absence of corpus luteum which secretes vasoactive substances (such as vascular endothelial growth factor and relaxin), after FET with HRT. 15 Altered angiogenic balance is the precursor to the molecular basis of PE. 16 Relaxin is involved in the creation of a low-resistance vascular system, reducing arterial stiffness and peripheral vascular resistance.…”