Objectives To compare progestin ovarian stimulation protocols with gonadotropin-releasing hormone analogue (agonists and antagonists) protocols on newborn outcomes. Methods The PubMed, Embase, Cochrane Central Register of Controlled Trials, and BioMed Central databases were searched for studies comparing progestin prime ovarian stimulation (PPOS) protocols with gonadotropin-releasing hormone analogues. Data were pooled by meta-analysis using a random effects model. Main outcome measures Primary endpoint was the risk of newborn congenital malformations. Results A total of 4 studies involving 9274 live-born infants were included. No important harm was observed with PPOS in terms of congenital malformations (OR 0.92; 95% CI 0.63-1.34; p = 0.65) (very low quality of evidence (QOE)) and low birth weight (OR 1.06; 95% CI 0.95-1.18; p = 0.29) (very low QOE) as compared with GnRH-a short protocols. In addition, a trend to a lower risk of preterm birth (OR 0.90; 95% CI 0.80-1.02; p = 0.10) (very low QOE) was found among patients treated with a PPOS protocol.Conclusions PPOS protocols, compared with GnRH-a protocols, are associated with a similar congenital malformation risk profile. Therefore, PPOS might represent a safe and appealing treatment option for infertile patients.
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