The role of seminal plasma for improved outcomes during in vitro fertilization treatment: review of the literature and meta-analysis

Background: There is a growing body of evidence surrounding the role played by seminal plasma in human implantation. Seminal fluid contains several proteins that interact with cervical and uterine epithelial cells inducing active immune tolerance. We sought to answer the study question: Does exposure to seminal plasma improve pregnancy outcomes in women undergoing IVF? Methods: Randomized controlled trials (RCTs) were searched for via MEDLINE, EMBASE, the Cochrane Library, National Research Register, ISI conference proceedings, ISRCTN register and Meta-register, from 1966 to December 2013. Search terms included: 'seminal plasma', 'seminal fluid', 'sexual intercourse', 'IVF', 'ICSI', 'ART', 'pregnancy rate', 'implantation', 'embryo transfer' and 'live birth'. This analysis included all RCTs comparing the outcome of IVF treatments in patients exposed to seminal plasma near the time of oocyte pickup (OPU) or embryo transfer (ET) with that of placebo controls or controls with no exposure to seminal plasma. The main intervention was exposure to seminal plasma around the time of OPU or embryo transfer during an IVF cycle. The main outcomes were clinical pregnancy and live birth/ongoing pregnancy rates. Data were collected by two independent authors and statistically pooled via meta-analysis following intention to treat and per protocol principles using RevMan (v5.2.10). I-2 statistic, forest plots and chi-squared heterogeneity tests were used. Results: In total 2204 patients were included in seven RCTs. Meta-analysis revealed a statistically significant improvement in clinical pregnancy rate (RR 1.23, 95% CI 1.06-1.42, P = 0.006) by intention to treat. Per protocol analysis also revealed a statistically significant improvement in clinical pregnancy rate (RR 1.24, 95% CI 1.07-1.43, P = 0.003). There was no statistically significant improvement seen for the outcome of ongoing pregnancy/live birth rate, but the available data were very limited. The methodology and quality of the studies were variable. Conclusions: There are significantly improved outcomes when women are exposed to seminal plasma around the time of ovum pick-up or embryo transfer, with statistical significance for clinical pregnancy but not for ongoing pregnancy/live birth rates being achieved. This meta-analysis is limited by the small number of studies of variable methodology. Further research is required to determine the effect on live birth rate; however, this meta-analysis indicates a significantly improved clinical pregnancy rate and a potential method for improving IVF outcomes.