# The type of endometrial preparation for embryo transfer after egg donation affects obstetric outcomes and the expression of placental angiogenic biomarkers

## TL;DR

Using natural or modified natural cycles for embryo transfer in egg donation leads to better pregnancy and baby outcomes compared to artificial cycles.

## Contribution

This study shows that natural/modified natural cycles reduce pregnancy complications and improve placental angiogenic biomarker expression in oocyte donation.

## Key findings

- Natural/modified natural cycles had lower rates of preeclampsia and placental previa compared to artificial cycles.
- Babies born after natural/modified natural cycles had lower rates of low birth weight and ICU admission.
- Natural cycles showed higher pro-angiogenic gene expression, while artificial cycles had increased anti-angiogenic markers.

## Abstract

We investigated the impact of natural cycle/modified natural cycle and artificial cycle in oocyte donation pregnancies on obstetric/neonatal outcomes and placental angiogenic biomarkers.

A total number of 201 singleton live births resulted from in vitro fertilization with oocyte donation were enrolled: n = 70 after natural cycle/modified natural cycle endometrial preparation and n = 131 after artificial cycle endometrial preparation. Moreover, 35 placental biopsies were collected: n = 12 after natural cycle/modified natural cycle endometrial preparation, n = 23 after artificial cycle endometrial preparation. Finally, 24 placentae from women with a spontaneous, healthy singleton pregnancy at term, who showed no signs of maternal, placental or fetal disease were used as control.

We reported a lower incidence of both hypertensive disorders of pregnancy (7.1% Vs 18.3%, p < 0.05), including preeclampsia, and placental previa (0 Vs 6.1%, p < 0.05) in natural/modified natural cycles compared to artificial cycle. Furthermore, better neonatal outcomes, at least in terms of low birth weight (5.7% Vs 20.9%, p < 0.05) and intensive care unit admission (2.9% Vs 15.6%, p < 0.05), were observed. From a molecular point of view, a significant gene over-expression of pro-angiogenic placental growth factor and vascular endothelial growth factor were obtained in natural cycles. Conversely, anti-angiogenic Soluble Fms-Like Tyrosine Kinase- 1 levels were increased in artificial cycle group placentae compared to natural/modified natural cycle and controls.

Natural/modified cycles should be promoted as preferential approach for endometrial preparation in oocyte donation pregnancies, at least when regular (or inducible) ovulatory cycles are present.