P-776 Maternal and neonatal outcomes of singletons and twins after frozen-thawed embryo transfer in different cycle regimes: Increased risks of hypertensive disorders in Hormone replacement cycles
Authors: Pape J , Lévy J , Von Wolff M 
Published: June 2022

Abstract

Study question
What are the associations between cycle regime and maternal and neonatal outcomes after frozen-thawed embryo transfer leading to singleton or twin life birth?

Summary answer
Hormone replacement cycles are associated with higher and natural or low-dose stimulation with lower risks for bleeding, hypertension and preeclampsia in singleton and twin pregnancies.

What is known already
So far, there is no consensus on optimal cycle regimen for endometrial preparation: Frozen-thawed embryo transfers can be either performed in Natural Cycles (NC-FET), low-dose Stimulation Cycles (SC-FET) or Hormone Replacement Cycles (HRC-FET). In previous studies, HRC-FET was shown to be associated with an increase of serious maternal and neonatal complications, i.e. preeclampsia (doubled to tripled risk), postpartum hemorrhage (doubled risk), placenta accrete (sixfold risk), post-term birth (sixfold risk) and Caesarean section (doubled risk) compared to NC-FET or SC-FET. These results indicate that risks are increased in cycles in which the development of follicles and luteal bodies is medically inhibited.

Study design, size, duration
Retrospective cohort study analyzing a total of 4636 singletons and also 544 twins born 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 cycle regimes: NC-FET (n = 776), SC-FET (n = 758) and HRC-FET (n = 3646) leading to life birth. Maternal outcomes included pregnancy complications such as bleedings, isolated hypertension (&gt;140/90 mmHg) and preeclampsia. Neonatal outcomes comprised gestational age and weight, mode of delivery and neonatal status.
Incidences were compared using Fisher exact or Chi-square tests. Multivariate mixed model analysis was performed for singleton and twin pregnancies.

Main results and the role of chance
In singleton pregnancies, the incidences of bleeding in first trimester (NC: 2.8%, SC: 2.6%, HRC: 7.0%; p&lt;.001), isolated hypertension (NC: 0.9%, SC: 0.2%, HRC: 1.8%; p = &lt;.001) and preeclampsia (NC: 1.7%, SC: 0.3%, HRC: 2.8%, p&lt;.001) were significantly higher in HRC-FET. Gestational diabetes occurred most (NC: 4.6%, SC: 7.0%, HRC: 4.5%; p = 0.032) and intrauterine growth restriction least frequently (NC: 1.9%, SC: 0.2%, HRC: 1.3%; p = 0.004) in SC-FET. Highest spontaneous birth rates were reported in NC-FET (NC: 51.2%, SC: 45.0%, HRC: 33.8%; p&lt;.001). Multivariate analysis revealed doubled odds ratio of bleeding in first trimester (aOR 2.01; 95% CI 1.20-3.37; p = 0.008%) and preeclampsia (aOR 2.13; 95% CI 1.12-4.05; p = 0.021) in HRC-FET vs. NC-FET and sixfold odds ratio of preeclampsia in HRC-FET vs. SC-FET (aOR 6.37; 95% CI 1.48-27.54; p = 0.013). Outcomes of SC-FET and NC-FET were comparable.
In twin pregnancies, the incidences of preeclampsia were significantly higher in HRC-FET (NC: 2.7%, SC: 1.0%, HRC: 7.2%, p = 0.026). There were no differences in delivery mode between cycle regime. Multivariate analysis revealed numerically higher odds ratio of preeclampsia in HRC-FET vs. NC-FET (aOR 2.57; 95% CI 0.55 - 12.07; p = 0.232) and in HRC-FET vs. SC-FET (aOR 4.07; 95% CI 0.47 - 34.91; p = 0.2) but without reaching significance.

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 first large register study to demonstrate a clear association between the three different cycle regimes and pregnancy complications both in singleton and twin pregnancies. HRC-FET showed the highest maternal risks of hypertensive disorders, therefore, it should be avoided and replaced by SC-FET or NC-FET if medically possible.

Trial registration number
Not applicable.