Review question
The main aim of this review was to assess whether application of seminal plasma to the female genital tract around the time of embryo transfer improves live birth rates in assisted reproductive technology (ART) cycles. Seminal plasma is the fluid part of the ejaculate, and the female genital tract consists of the vagina, the neck of the womb and the womb.
Background
In ART cycles, the egg and sperm are mixed outside the body to develop embryos. One or two of the embryos are replaced into the womb in a very small amount of artificial fluid. During this process, the woman's body does not come into contact with seminal plasma at all, unlike during normal intercourse where the male partner ejaculates in the vagina, exposing the latter to seminal fluid. It has been suggested that seminal plasma contains several molecules which can help the embryos to attach to the womb. The logical question is whether application of some seminal plasma to the vagina/neck of the womb or womb increases the chances of a live birth after ART.
Study characteristics
This Cochrane review included 11 randomised controlled trials, in which women were randomly allocated to receive seminal plasma or not. These trials included a total of 3215 women undergoing ART. The evidence is current to October 2017.
Key results
We found no clear evidence to suggest whether seminal plasma application influences rates of live birth or miscarriage in women undergoing ART. However, we found low-quality evidence suggesting that seminal plasma application may possibly lead to more clinical pregnancies than standard ART. There was low-quality evidence suggesting little or no difference between the groups in rates of multiple pregnancy. There was insufficient evidence to reach any conclusions about the risk of ectopic pregnancy (pregnancy in which the embryo attaches outside the womb), and no data were available on infectious complications or other adverse events.
We conclude that seminal plasma application is worth further investigation focusing on live birth and miscarriage rates.
Quality of evidence
The quality of evidence ranged from very low to low.The main limitations were risk of bias (associated with poor reporting of study methods) and lack of data for the primary outcome of live birth rate.
In women undergoing ART, there was insufficient evidence to determine whether there was a difference between the seminal plasma and the standard ART group in rates of live birth (low-quality evidence) or miscarriage (low-quality evidence). There was low-quality evidence suggesting little or no difference between the groups in rates of live birth or ongoing pregnancy (composite outcome). We found low-quality evidence that seminal plasma application may be associated with more clinical pregnancies than standard ART. There was low-quality evidence suggesting little or no difference between the groups in rates of multiple pregnancy. There was insufficient evidence to reach any conclusions about the risk of ectopic pregnancy, and no data were available on infectious complications or other adverse events.
We conclude that seminal plasma application is worth further investigation, focusing on live birth and miscarriage rates.
The female genital tract is not exposed to seminal plasma during standard assisted reproductive technology (ART) cycles. However, it is thought that the inflammatory reaction triggered by seminal plasma may be beneficial by inducing maternal tolerance to paternal antigens expressed by the products of conception, and may increase the chance of successful implantation and live birth.
To assess the effectiveness and safety of application of seminal plasma to the female genital tract prior to embryo transfer in ART cycles.
We searched the following databases from inception to October 2017: Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, Cochrane Central Register of Studies Online (CRSO), MEDLINE, Embase, CINAHL and PsycINFO. We also searched trial registers for ongoing trials, including International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. Other sources searched were; Web of Knowledge, OpenGrey, LILACS, PubMed, Google Scholar, and the reference lists of relevant articles.
We included randomised controlled trials (RCTs) conducted among women undergoing ART, comparing any procedure that would expose the female genital tract to seminal plasma during the period starting five days before embryo transfer and ending two days after it versus no seminal plasma application.
Two review authors independently selected trials, assessed risk of bias, and extracted data. We pooled data to calculate relative risks (RRs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I2 statistic. We assessed the overall quality of the evidence for the main outcomes using GRADE methods. Our primary outcomes were live birth rate and miscarriage rate. Secondary outcomes were live birth/ongoing pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, and the incidence of other adverse events.
We included 11 RCTs (3215 women). The quality of the evidence ranged from very low to low. The main limitations were risk of bias (associated with poor reporting of allocation concealment and other methods) and imprecision for the primary outcome of live birth rate.
Live birth rates: Seminal plasma application made little or no difference in live birth rates (RR 1.10, 95% CI 0.86 to 1.43; 948 participants; 3 studies; I2 = 0%). Low-quality evidence suggested that if the live birth rate following standard ART was 19%, it would be between 16% and 27% with seminal plasma application.
Miscarriage rate: Seminal plasma application made little or no difference in miscarriage rates (RR 1.01, 95% CI 0.57 to 1.79; 1209 participants; 4 studies; I2 = 0%). Low-quality evidence suggested that if the miscarriage rate following standard ART was 3.7%, the miscarriage rate following seminal plasma application would be between 2.1% and 6.6%.
Live birth or ongoing pregnancy rates: Seminal plasma application made little or no difference in live birth or ongoing pregnancy rates (RR 1.19, 95% CI 0.95 to 1.49; 1178 participants; 4 studies; I2 = 4%, low-quality evidence). The evidence suggested that if the live birth or ongoing pregnancy rate following standard ART was 19.5%, it would be between 18.5% and 29% with seminal plasma application.
Clinical pregnancy rates: We are uncertain whether seminal plasma application increases clinical pregnancy rates (RR 1.15, 95% CI 1.01 to 1.31; 2768 participants; 10 studies; I2 = 0%). Very low-quality evidence suggested that if the clinical pregnancy rate following standard ART was 22.0%, it would be between 22.2% and 28.8% with seminal plasma application. This finding should be regarded with caution, as a post hoc sensitivity analysis restricted to studies at overall low risk of bias did not find a significant difference between the groups (RR 1.06, 95% CI 0.81 to 1.39; 547 participants; 3 studies; I2 = 0%).
Multiple pregnancy rate: Seminal plasma application may make little or no difference to multiple pregnancy rates (RR 1.11, 95% CI 0.76 to 1.64; 1642 participants; 5 studies; I2 = 9%). Low-quality evidence suggested that if the multiple pregnancy rate following standard ART was 7%, the multiple pregnancy rate following seminal plasma application would be between 5% and 11.4%.
Ectopic pregnancy: There was insufficient evidence to determine whether seminal plasma application influenced the risk of ectopic pregnancy (RR 1.59, 95% CI 0.20 to 12.78, 1521 participants; 5 studies; I2 = 0%) .
Infectious complications or other adverse events: No data were available on these outcomes