Objective To explore whether serotonin-related gene polymorphisms influence clinical outcomes of IVF treatment in recipients using donated oocytes. Design Nested case-control study. Setting University-affiliated infertility clinic. Patient(s) Two hundred forty-five women undergoing IVF treatment with donated oocytes. Intervention(s) None. Main Outcome Measure(s) Genotype and haplotype analysis of the serotonin transporter-linked polymorphic region (5-HTTLPR), rs1800532, rs6295, rs6313, and rs3813929, between recipients grouped according to the results of the oocyte donation for IVF treatment. Result(s) No differences were found between genotype distribution of the tryptophan hydroxylase 1, serotonin receptor 2A, and serotonin receptor 2C polymorphisms. Recipients carrying the LL genotype for 5-HTTLPR had lower clinical pregnancy rates (PR) and higher biochemical pregnancy loss (BPL) events. Lower implantation rates were found in CC carriers for 5-HT1A.rs6295 who also presented higher BPL rates. A lower incidence of clinical pregnancy was observed for LC haplotypes, corresponding to an increase in BPL rates. Conclusion(s) A strong association was found between early pregnancy loss and recipients carrying the 5-HTTLPR and rs6295 genetic variants. Identifying biological processes involving serotonin and embryo implantation may help to understand the dynamics of the maternal–embryo dialogue.