O-182 Higher risk of preeclampsia and pregnancy-induced hypertension with artificial cycle for Frozen-thawed Embryo Transfer compared to ovulatory cycle or fresh transfer following In Vitro Fertilization
Authors: Epelboin S , Labrosse J , Fauque P , Levy R , Mouzon J. De , Boyer M , Vienne C. De , Bergere M , Valentin M , Devaux A , Hester L , Sermondade N , Jonveaux P , Pessione1 F 
Published: August 2021

Abstract

Study question
Is there an increased risk of preeclampsia after Frozen-thawed Embryo Transfer(FET) compared to In Vitro Fertilization-fresh transfer(IVF-fresh-ET) according to endometrial type of preparation for FET?

Summary answer
The frequency of preeclampsia and hypertension were significantly higher in the group of artificial cycle (AC-FET) compared to ovulatory cycle (OC-FET) and fresh-ET (P &lt; 0.0001).

What is known already
Risks of maternal morbidity are known to be reduced in pregnancies resulting from FET compared to fresh-ET except for the risk of preeclampsia, that was reported to be significantly higher in pregnancies resulting from FET compared to fresh-ET or spontaneous conception. Most recent studies demonstrate an equal live birth rate with either OC-FET or AC-FET preparation. Few studies compared the maternal vascular morbidities with the two hormonal environments that preside over the early stages of embryonic development: OC (major role of the corpus luteum) and AC (prolonged hormone replacement with high doses of estrogen and progesterone).

Study design, size, duration
We conducted a 2013-2018 French nationwide cohort study comparing maternal vascular morbidities in 3 groups of single pregnancies&gt; 22 weeks of gestation (WG): FET with AC or OC preparation, and IVF (conventional or ICSI)-fresh-ET.Data were extracted from the French National Health System database (&gt;99% of national deliveries) in which all hospitalizations are registered, containing information on patient characteristics, diagnoses and treatments. Records were merged anonymously. Access to the database was legally approved.

Participants/materials, setting, methods
68 025 deliveries were included: fresh-ET(n = 48 152), OC-FET(n = 9 500), AC-FET(n = 10 373). In OC-FET, a luteal phase support with progesterone was administered for maximum 6 WG if pregnancy. In AC-FET, progesterone was co-administered with estrogen until 12 WG. Embryos were transferred at cleavage or blastocyst stage.
Vascular disorders were recorded if hospitalization for preeclampsia/eclampsia or hypertension (history of hypertension excluded). Maternal characteristics were included in multivariate analysis. Adjusted odds ratios(aOR) and 95% confidence intervals(CI) were estimated.

Main results and the role of chance
Maternal characteristics: In multivariate analysis, patients in the FET groups were older (33.4 years (std=4.3) vs. 33.2 years (std=4.4) for fresh-ET, respectively, P &lt; 0.0001), less often primiparous (aOR=0.68[0.66-0.71], P &lt; 0.0001) or smokers (aOR=0.84[0.75-0.95]) or with premature ovarian insufficiency (POI) (aOR=0.68 [0.58-0.79]), more frequently with polycystic ovaries (PCOS) (aOR=1.25[1.12-1.39]) and comparable for obesity or diabetes.
In FET groups, 52.2% were AC-FET. There was no difference for maternal age, parity, obesity, smoking, history of diabetes between AC and OC-FET. Endometriosis (aOR=1.26[1.16-1.38]), PCOS (aOR=1.79[1.50-2.15]) and POI (aOR=2.0[1.48-2.72]) were more frequent in AC-FET.

Risks of vascular disorders
The rate of preeclampsia (5.3% vs. 2.3% vs. 2.4%, respectively, P &lt; 0.0001) and hypertension (4.7% vs. 3.4% vs. 3.3%, respectively, P = 0.0002) was significantly higher in AC-FET versus OC-FET and fresh-ET.
In multivariate analysis, the risk of preeclampsia increased with age, primiparity, obesity, diabetes and POI. The risk was higher in AC-FET versus OC-FET (aOR=2.42 [2.06-2.85]) and fresh-ET (aOR=2.43[2.2-2.7]), P &lt; 0.00001. No difference was found between OC-FET and fresh-ET (P = 0.91). The risk of pregnancy-induced hypertension increased with age &gt;40, primiparity, smoking, obesity and diabetes and was higher in AC-FET versus OC-FET (aOR=1.50[1.29-1.74], P &lt; 0.0001) and fresh-ET (aOR=1.50[1.35-1.67], P &lt; 0.0001) and not different between OC-FET and fresh-ET (P = 0.86).

Limitations, reasons for caution
While the strength of this study relies in the number and exhaustiveness of subjects analysed, its limitations are its retrospective and register-based nature that did not enable to refine the risk according to details of techniques and treatments in each group.

Wider implications of the findings
This large nationwide cohort study highlights 2 important information for physicians : i) the possible deleterious role of high supra-physiological and prolonged doses of estrogen-progesterone supplementation on vascular pathologies ii) the protective role of the corpus luteum present in stimulated or spontaneous OC for their prevention.

Trial registration number
Not applicable