Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial

TLDR

Androgens synergize with FSH to enhance folliculogenesis, as shown in macaque studies. The study examined whether pretreatment with transdermal testosterone improves ovarian response in low‑responder IVF patients. In a randomized trial of 62 women, one group received transdermal testosterone before standard gonadotrophin stimulation, while the control group received high‑dose gonadotrophin with a minidose GnRH agonist, with the primary endpoint being low‑responder incidence and the secondary endpoint ovum retrieval. Transdermal testosterone pretreatment significantly reduced low‑responder incidence and increased ovum retrieval rates compared with high‑dose gonadotrophin plus minidose GnRH agonist, indicating improved ovarian sensitivity in low‑responder IVF patients.

Abstract

Studies in macaques have indicated that androgens have some synergistic effects with FSH on folliculogenesis. This study investigated the usefulness of pretreatment with transdermal testosterone in low-responder IVF patients.Randomized clinical trial including 62 infertile women who had a background of the first IVF treatment cycle cancelled because of poor follicular response. Patients were randomized in two treatment groups in their second IVF attempt. In patients in Group 1 (n = 31), transdermal application of testosterone preceding standard gonadotrophin ovarian stimulation under pituitary suppression was used. In Group 2 (n = 31 patients), ovarian stimulation was carried out with high-dose gonadotrophin in association with a minidose GnRH agonist protocol. The primary end-point was the incidence of low-responder patients. The main secondary outcome was the incidence of patients reaching ovum retrieval.The percentage of cycles with low response was significantly lower in Group 1 than in Group 2 (32.2 versus 71% 95% confidence interval for the difference, 15.7-61.6; P < 0.05). The number of patients with ovum retrieval tended to be higher in Group 1 than in Group 2 (80.6 versus 58.1% P = 0.09), the difference reaching statistical significance (81.2 versus 41.1%; P < 0.05) when only patients having normal basal FSH levels (16 and 17 patients in Groups 1 and 2, respectively) were considered.Pretreatment with transdermal testosterone may improve the ovarian sensitivity to FSH and follicular response to gonadotrophin treatment in previous low-responder IVF patients. This approach leads to an increased follicular response compared with a high-dose gonadotrophin and minidose GnRH agonist protocol.