Artificial cycle frozen-thawed embryo transfer may up preeclampsia, hypertension risk

Women who undergo artificial cycle frozen-thawed embryo transfer (AC-FET) may have an elevated risk of preeclampsia and pregnancy-induced hypertension (PIH) compared with women who undergo ovulatory cycle frozen-thawed embryo transfer (OC-FET) or in vitro fertilization-fresh transfer (fresh-ET), according to a nationwide cohort study from France presented at ESHRE 2021.

The cohort comprised 68,025 singleton births after >22 weeks gestation between 2013–2017 included in the French National Health System database. Of these, 48,152 births were following conventional fresh-ET, 9,500 following natural OC-FET, and 10,373 following AC-FET (with hormone replacement therapy). Hospitalization for preeclampsia, eclampsia, or hypertension was compared across the three groups. Women with a history of hypertension were excluded.

Women in the FET groups were older than those in the fresh-ET group (mean 33.4 vs 33.2 years; p<0.0001) and were less likely to be primiparous (adjusted odds ratio [adjOR], 0.68, 95 percent confidence interval [CI], 0.66–0.71; p<0.0001). They were also less likely to be smokers (adjOR, 0.84, 95 percent CI, 0.75–0.95; p=0.005) or have premature ovarian insufficiency (POI; adjOR, 0.68, 95 percent CI, 0.58–0.79; p<0.0001), and more likely to have polycystic ovary syndrome (PCOS; adjOR, 1.25, 95 percent CI, 1.12–1.39; p<0.0001). Rates of diabetes and obesity were comparable between groups (p=0.81 and p=0.63, respectively). [ESHRE 2021, abstract O-182]

Among the FET groups, 52.2 percent of women had undergone AC-FET. Maternal age, parity, smoking status, history of diabetes, and obesity rates did not differ between women who underwent OC- and AC-FET. Compared with women who underwent OC-FET, those who underwent AC-FET were more likely to have POI (adjOR, 2.01, 95 percent CI, 1.48–2.72), PCOS (adjOR, 1.79, 95 percent CI, 1.50–2.15), or endometriosis (adjOR, 1.26, 95 percent CI, 1.16–1.38; p<0.0001 for all).

Preeclampsia rates were highest among women who underwent AC-FET compared with OC-FET and fresh-ET (5.3, 2.3, and 2.4 percent, respectively; p<0.0001), as were the rates of PIH (4.7, 3.4, and 3.3 percent, respectively; p=0.0002).

The risk of preeclampsia was significantly increased in women who underwent AC-FET compared with OC-FET (adjOR, 2.42, 95 percent CI, 2.06–2.85) or fresh-ET (adjOR, 2.43, 95 percent CI, 2.2–2.7; p<0.00001). Age, primiparity, obesity, diabetes, and POI were associated with an increased risk of preeclampsia.

The risk of PIH was also elevated among women who underwent AC-FET compared with OC-FET (adjOR, 1.50, 95 percent CI, 1.29–1.74) or fresh-ET (adjOR, 1.50, 95 percent CI, 1.35–1.67; p<0.0001). Factors tied to an increased risk of PIH were age >40 years, primiparity, smoking, diabetes, and obesity.

The risk of preeclampsia or PIH did not significantly differ between women who underwent OC-FET and fresh-ET (p=0.91 and p=0.86, respectively).

According to study author Dr Sylvie Epelboin from the Hôpital Bichat-Claude Bernard, Paris, France, the risk of maternal morbidity is known to be reduced in pregnancies resulting from FET compared with fresh-ET, with the exception of preeclampsia which is reportedly higher after FET vs fresh-ET or spontaneous conception.

“This study demonstrates that FET preparation by AC was significantly associated with an increased risk of vascular disorders compared with OC-FET and fresh-ET,” she said. “Since results obtained by OC do not strain the chances of pregnancy, OC preparation could be advocated as first-line endometrial preparation in FET as often as the choice in possible in ovulatory women,” she added.

The findings also raise two important questions, she continued. “[The results highlight] the possible deleterious role of high supra-physiological and prolonged doses of oestrogen-progesterone supplementation on vascular pathologies [and] the protective role of the corpus luteum present in stimulated or spontaneous OC for the prevention of vascular disorders,” she concluded.