P-391 Early pregnancy complications after frozen-thawed embryo transfer in different cycle regimes: Increased risks for miscarriages and bleedings in Hormone replacement cycles
Authors: Von Wolff M , Levy J , Pape J 
Published: June 2022

Study question

What are the associations between cycle regime and early pregnancy complications after frozen-thawed embryo transfers and what are the respective life birth rates per pregnancy?

Summary answer

Hormone replacement cycles are associated with doubled odd ratios of bleedings and miscarriages &lt;12 weeks leading to lowest life birth rates (LBR) per pregnancy (68.2%).

What is known already

So far, there are only few studies which analysed both, the associations between cycle regime and early pregnancy complications as well as life birth rates (LBR) per pregnancy after frozen-thawed embryo transfer (FET). In 2017, a Cochrane analysis did not find sufficient evidence to support the use of a specific cycle regimen in preference to another since there were only four direct comparisons. In 2021, a network meta-analysis including 26 RCTs and 113 cohort studies revealed lowest LBR in hormone replacement cycles compared with other endometrial preparation protocols but without stating the reasons for the lowest LBR.

Study design, size, duration

Retrospective cohort study analyzing a total of 7342 pregnancies after FET that were registered in the Swiss IVF Registry from 2014 to 2019.

Participants/materials, setting, methods

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 bleedings, miscarriages and ectopic pregnancies, deliveries (including intrauterine deaths) and LBR. Incidences were compared using Fisher exact and Chi-square tests. Multivariate mixed model analysis with pregnancy complications as outcome was performed.

Main results and the role of chance

The incidences of bleeding in first trimester (NC: 3.5%, SC: 4.3%, HRC: 8.4%; p&lt;.001) and miscarriage &lt;12 weeks (NC: 19.0%, SC: 19.7%, HRC: 29.1%; p&lt;.001) were significantly higher in HRC-FET.

Multivariate analysis revealed doubled odds ratio of bleedings in first trimester (aOR 1.92; 95% CI 1.30-2.81; p&lt;.001) and miscarriages &lt;12 weeks (aOR 1.82; 95% CI 1.51-2.19; p&lt;.001) in HRC-FET vs. NC-FET. There were comparable odds ratio in HRC-FET vs. SC-FET and no differences between NC-FET vs. SC-FET. Highest LBR per pregnancy (NC: 78.0%, SC: 77.2%, HRC: 68.2%%; p&lt;.001) was reported in NC-FET.

Limitations, reasons for caution

The data were drawn from a registry analysis with limited information on patients’ characteristics. Data such as BMI were not available. As the study is based on a register analysis, some errors in data collection cannot be excluded.

Wider implications of the findings

This is the latest large European register study evaluating early pregnancy complications and LBR per pregnancy after FET by cycle regime. Miscarriage rate was highest in HRC-FET which can be translated into lower LBR. Thus, HRC-FET should be avoided if medically possible, to achieve better pregnancy outcomes.

Trial registration number

Non required