Background
Male subfertility contributes to at least 50% of subfertility in couples. Around 39% of subfertile men have idiopathic subfertility (male subfertility with an unknown cause or origin). Gonadotrophins (hormones that stimulate sperm production) have been used in the treatment of men with this condition, but results have been inconsistent. We reviewed the evidence.
Study characteristics
We found six randomised controlled trials, with 456 participants.
Key results
There was a trend towards an increase in live birth and pregnancy rates during and within three months of gonadotrophin treatment. The quality of the evidence was very low. We did not find enough studies to allow final conclusions about the use of gonadotrophins in the treatment of men with idiopathic male factor subfertility. The quality of the evidence was very low. More studies on this subject are needed. The evidence is current to January 2013.
Encouraging preliminary data suggest a beneficial effect on live birth and pregnancy of gonadotrophin treatment for men with idiopathic male factor subfertility, but because the numbers of trials and participants are small, evidence is insufficient to allow final conclusions. Large multi-centre trials with adequate numbers of participants are needed.
Male factors leading to subfertility account for at least half of all cases of subfertility worldwide. Although some causes of male subfertility are treatable, treatment of idiopathic male factor subfertility remains empirical. Researchers have used gonadotrophins to improve sperm parameters in idiopathic male factor subfertility with the ultimate goal of increasing birth and pregnancy rates, but results have been conflicting.
To determine the effect of systemic follicle-stimulating hormone (FSH) on live birth and pregnancy rates when administered to men with idiopathic male factor subfertility .
We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (14 January 2013), the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 12 of 12, 2012), Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE (1946 to 14 January 2013), Ovid EMBASE (1980 to week 2 of 2013), Ovid PsycINFO (1806 to week 2 of 2013), trial registers for ongoing and registered trials at ClinicalTrials.gov (19 January 2013), the World Health Organisation International Trials Registry Platform (19 January 2013), The Cochrane Library Database of Abstracts of Reviews of Effects (19 January 2013) and OpenGrey for grey literature from Europe (19 January 2013). Searches were not limited by language. Bibliographies of included and excluded trials and abstracts of major meetings were searched for additional trials.
Randomised controlled trials (RCTs) in which gonadotrophins were compared with placebo or no treatment for participants with idiopathic male factor subfertility.
Two review authors independently selected the trials, assessed risk of bias and extracted data on live birth, pregnancy and adverse effects. We included data on pregnancies that occurred during or after gonadotrophin therapy. Study authors and pharmaceutical companies were asked to provide missing and unpublished data and/or additional information.
Six RCTs with 456 participants and variable treatment and follow-up periods were included. From the limited data, the live birth rate per couple randomly assigned (27% vs 0%; Peto odds ratio (OR) 9.31, 95% confidence interval (CI) 1.17 to 73.75, one study, 30 participants, very low-quality evidence) and the spontaneous pregnancy rate per couple randomly assigned (16% vs 7%; Peto OR 4.94, 95% CI 2.13 to 11.44, five studies, 412 participants, I2 = 0%, moderate-quality evidence) were significantly higher in men receiving gonadotrophin treatment than in men receiving placebo or no treatment. No significant difference between groups was noted when intracytoplasmic sperm injection (ICSI) or intrauterine insemination (IUI) was performed. None of the included studies reported miscarriage rates, and adverse events data were sparse.