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

Background: 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. Methods: 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. Results: 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. Conclusions: 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.