Testosterone pretreatment of no benefit to women at risk of poor response to IVF

Treatment with transdermal testosterone prior to initiating ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) does not appear to increase the chances of becoming pregnant for women at risk of having a poor ovarian response, as shown in the T-TRANSPORT trial presented at ESHRE 2023.

Compared with placebo gel, a 2-month course of 5.5-mg testosterone gel did not improve IVF/ICSI outcomes for women with poor ovarian response according to the Bologna criteria.

Clinical pregnancy rate, the primary endpoint, was 16.42 percent with testosterone vs 17.53 percent with placebo, with a relative risk of 1.07 (95 percent confidence interval [CI], 0.64–1.79) in favour of placebo, reported lead study author Prof Nikolaos Polyzos, head of the Department of Reproductive Medicine at Dexeus University Hospital in Barcelona, Spain. [ESHRE 2023, abstract O-066]

“Analysis of the results per-age strata also failed to demonstrate significant differences,” Polyzos added.

Clinical pregnancy rates between the testosterone and placebo groups in women across the following age groups were as follows: <36 years (17.90 percent vs 24.00 percent), 36–39 years (20.40 percent vs 21.10 percent), and ≥40 years (12.30 percent vs 10.50 percent).

Likewise, testosterone had no significant effect on ovarian stimulation outcomes, including the number of oocytes retrieved (mean, 3.69 vs 3.42), the number of metaphase II oocytes (mean, 2.60 vs 2.61), the number of 2PN embryos (mean, 2.15 vs 1.78), and the number of D3 embryos (mean, 1.90 vs 1.46).

Cycle outcomes were also comparable in the testosterone and placebo groups. Cancellation rates were 24.40 percent vs 13.50 percent, the proportions of women who reached the ovum pickup stage were 63.00 percent vs 70.32 percent, and the proportions of women who had embryo transfer (49.60 percent vs 52.90 percent), respectively.

As for safety, women exposed to testosterone gel had higher frequency of acne (21.48 percent vs 15.48 percent), hirsutism (14.81 percent vs 7.10 percent), and alopecia (2.22 percent vs 1.29 percent) compared with those exposed to placebo gel. There was not much difference in the number of women who had at least one androgenic event (28.15 percent vs 20.65 percent), according to Polyzos.

“Very important, we did not have a single [participant who dropped out of] the study because of the medication,” he added. 

Not the answer

“The role of androgens in the treatment of infertile women has been extensively investigated over the last 20 years. Early animal studies and small human studies supported a potentially beneficial role of androgen pretreatment for the management of poor ovarian responders,” Polyzos said.

“Still, available evidence regarding androgen administration remains inconclusive, and clinical guidelines do not support their use in infertile women, mainly due to the lack of robust evidence regarding efficacy, the small sample sizes, the lack of data regarding safety, and the lack of uniform dose and duration of testosterone pretreatment for poor ovarian responders,” he added.

Data from the T-TRANSPORT trial indicate that testosterone does not provide an answer to the treatment of women at risk of poor response to IVF. Despite the trial’s discouraging results, Polyzos shared that they would conduct post hoc analyses to investigate whether testosterone affects ovarian reserve markers, follicular fluid biomarkers, cumulus cells gene expression, and libido in women with poor ovarian response.

T-TRANSPORT included 316 women at risk of poor response to IVF according to the Bologna criteria who were treated at 10 centres across four European countries (Spain, Belgium, Denmark, and Switzerland). These women were randomly assigned to receive either 5.5 mg of testosterone gel or placebo gel for about 60 days before the initiation of ovarian stimulation for IVF/ICSI.

A total of 290 women reached the interim stage, including 135 in the testosterone group (mean age 37.96 years) and 155 in the placebo group (mean age 38.06 years). Anti-Mullerian hormone, antral follicle count, basal follicle stimulating hormone, and body mass index were similar between the two groups.