Benefits of Empiric Nutritional and Medical Therapy for Semen Parameters and Pregnancy and Live Birth Rates in Couples with Idiopathic Infertility: A Systematic Review and Meta-analysis

Context: The empiric use of medical and nutritional supplements to improve semen parameters and pregnancy rates in couples with idiopathic infertility has reached global proportions, although the evidence base for their use in this setting is controversial.
Objective: We systematically reviewed the evidence comparing the benefits of nutritional and medical therapy on pregnancy rate and semen parameters in men with idiopathic infertility.
Evidence acquisition: Literature search was performed using MEDLINE, EMBASE, LILACS and the Cochrane Library (searched from January 1st 1990 to September 19th 2017). We adopted the methods as detailed in the Cochrane Handbook. GRADE was adopted in order to assess certainty of evidence.
Evidence synthesis: Literature search identified 5663 citations, and after abstract and full-text screening 61 studies (59 RCTs and 2 non-randomised comparative studies) were included. Pooled results demonstrated that pentoxyfylline, co-enzyme Q10, L-carnitine, FSH, Tamoxifen and kallikrein all resulted in improvements in semen parameters. Individual studies identified several other medical and nutritional therapies that improved semen parameters, but data were limited to individual studies with inherent methodological flaws. There were limited data available on live birth and pregnancy rates for all interventions. GRADE certainty of evidence for all the outcomes was very low mainly due methodological flaws and inconsistencies with study design, and inconsistency. Some outcomes were also downgraded due to imprecision of results.
Conclusions: There is some evidence that empiric medical and nutritional supplements may improve semen parameters. There is very limited evidence that empiric therapy leads to improved live birth rates, spontaneous pregnancy or pregnancy following assisted-reproductive techniques. However, the findings should be interpreted with caution as there were some methodological flaws, as a number of studies were judged to be either at high or unclear risk of bias for many domains.
Patient summary: This review has identified several medical and nutritional treatments such as pentoxyfylline, co-enzyme Q10, L-carnitine, FSH, Tamoxifen and kallikrein, appear to improve semen parameters. In spite of this, there are limited data suggesting pregnancy and live birth rates are increased, and is attributable to methodological flaws in studies and the low number of reported pregnancies.