Early pregnancy complications after frozen-thawed embryo transfer in different cycle regimens: A retrospective cohort study

Objective: Frozen-thawed embryo transfers (FET) are a key component of assisted reproductive technologies (ART) and various cycle regimens are used worldwide because of insufficient evidence to favour particular transfer schedules. In this study, we investigated the associations between different cycle regimens and early pregnancy complications as well as live birth rates (LBR) per pregnancy after FET.Study design: We conducted a retrospective cohort study analysing a total of 7342 pregnancies after FET registered in the Swiss IVF Registry from 2014 to 2019. Women were divided into three groups according to the different cycle regimens: Natural Cycles (NC-FET, n = 998), low-dose Stimulation Cycles (SC-FET, n = 984) and Hormone Replacement Cycles (HRC-FET, n = 5360) leading to pregnancy. Outcomes included early pregnancy complications such as bleeding, miscarriages and ectopic pregnancies. Additionally, we evaluated LBR per pregnancy. Incidences were compared using Fisher's exact or Chi-square tests. Mean values were compared using t-tests. Multivariate mixed model analysis was performed with early pregnancy complications as outcome.Results: The incidence of bleeding in the first trimester (NC: 3.5 %, SC: 4.3 %, HRC: 8.4 %; p < 0.001) and miscarriage < 12 weeks (NC: 19.0 %, SC: 19.7 %, HRC: 29.1 %; p < 0.001) was highest in HRC-FET. Multivariate analysis revealed almost doubled adjusted odds ratios of bleeding in the first trimester (aOR 1.92; 95 % CI 1.30-2.81) and miscarriage < 12 weeks (aOR 1.82; 95 % CI 1.51-2.19) in HRC-FET vs NC-FET. There were comparable odds ratios in HRC-FET vs SC-FET. No differences were observed in the outcomes between SCFET and NC-FET. Highest proportion of LBR per pregnancy (NC: 78.0 %, SC: 77.2 %, HRC: 68.2 %%; p < 0.001) was reported in NC-FET. Conclusions: This is the latest large European register study evaluating early pregnancy complications and LBR per pregnancy after FET between all three different cycle regimens. Miscarriage rate was highest in HRC-FET which can be translated into lower LBR. Therefore, HRC-FET should be avoided and replaced by SC-FET or NC-FET to achieve better pregnancy outcomes.