Abstract: We included 17 RCTs with a total of 1496 participants. Apart from two trials, the trial participants were women identified as 'poor responders' to standard IVF protocols. The included trials compared either testosterone or DHEA treatment with placebo or no treatment. When DHEA was compared with placebo or no treatment, pre-treatment with DHEA was associated with higher rates of live birth or ongoing pregnancy (OR 1.88, 95% CI 1.30 to 2.71; eight RCTs, N = 878, I² statistic = 27%, moderate quality evidence). This suggests that in women with a 12% chance of live birth/ongoing pregnancy with placebo or no treatment, the live birth/ongoing pregnancy rate in women using DHEA will be between 15% and 26%. However, in a sensitivity analysis removing trials at high risk of performance bias, the effect size was reduced and no longer reached significance (OR 1.50, 95% CI 0.88 to 2.56; five RCTs, N = 306, I² statistic = 43%). There was no evidence of a difference in miscarriage rates (OR 0.58, 95% CI 0.29 to 1.17; eight RCTs, N = 950, I² statistic = 0%, moderate quality evidence). Multiple pregnancy data were available for five trials, with one multiple pregnancy in the DHEA group of one trial (OR 3.23, 95% CI 0.13 to 81.01; five RCTs, N = 267, very low quality evidence). When testosterone was compared with placebo or no treatment we found that pre-treatment with testosterone was associated with higher live birth rates (OR 2.60, 95% CI 1.30 to 5.20; four RCTs, N = 345, I² statistic = 0%, moderate evidence). This suggests that in women with an 8% chance of live birth with placebo or no treatment, the live birth rate in women using testosterone will be between 10% and 32%. On removal of studies at high risk of performance bias in a sensitivity analysis, the remaining study showed no evidence of a difference between the groups (OR 2.00, 95% CI 0.17 to 23.49; one RCT, N = 53). There was no evidence of a difference in miscarriage rates (OR 2.04, 95% CI 0.58 to 7.13; four RCTs, N = 345, I² = 0%, low quality evidence). Multiple pregnancy data were available for three trials, with four events in the testosterone group and one in the placebo/no treatment group (OR 3.09, 95% CI 0.48 to 19.98; three RCTs, N = 292, very low quality evidence). One study compared testosterone with estradiol and reported no evidence of a difference in live birth rates (OR 2.06, 95% CI 0.43 to 9.87; one RCT, N = 46, very low quality evidence) or miscarriage rates (OR 0.70, 95% CI 0.11 to 4.64; one RCT, N = 46, very low quality evidence). The quality of the evidence was moderate, the main limitations being lack of blinding in the included trials, inadequate reporting of study methods, and low event and sample sizes in some trials. In women identified as poor responders undergoing ART, pre-treatment with DHEA or testosterone may be associated with improved live birth rates. The overall quality of the evidence is moderate. There is insufficient evidence to draw any conclusions about the safety of either androgen. Definitive conclusions regarding the clinical role of either androgen awaits evidence from further well-designed studies.

Plain-language summary: This Cochrane review included 17 randomised controlled trials which compared treatment with the androgens DHEA or T with placebo or no treatment in a total of 1496 women, almost all of whom had been identified as 'poor responders' to standard assisted reproduction protocols. The main outcomes were live birth (defined as delivery of a live baby after 20 weeks gestation) or ongoing pregnancy rates, miscarriage, clinical pregnancy rates (fetal heartbeat confirmed on ultrasound) and multiple pregnancy rates. We examined the evidence published up to 12 March 2015. DHEA and T use may be associated with increased live birth rates. The evidence for the use of DHEA suggested that in women with a 12% chance of live birth with placebo or no treatment, the live birth rate in women using DHEA will be between 15% and 26%. The evidence for the use of T suggested that in women with an 8% chance of live birth with placebo or no treatment, the live birth rate in women using T will be between 10% and 32%. When we removed from the analyses the studies at high risk of bias, this increase was no longer present for DHEA or T. There is insufficient evidence to draw any conclusions about the safety of either androgen. The quality of the trials was moderate, and the main limitations were lack of blinding, inadequate reporting of study methods and small sample sizes in some included trials.