Mouse Model of Transgender Men Finds Active Testosterone Worsens IVF Outcomes

A study presented at ENDO 2022 in Atlanta this past summer suggests that active testosterone therapy for transgender men may negatively impact IVF outcomes.

Research presented by Amanda Schwartz, MD, a reproductive endocrinology and infertility fellow at the University of Michigan, found that female mice currently receiving testosterone had fewer and less developed eggs retrieved. In contrast, discontinuing testosterone therapy in mice led to similar egg retrieval rates compared to the control group.

The authors write that the impact of testosterone (T) on reproductive potential is poorly understood and that masculinizing hormones have demonstrated mixed effects on ovarian histology and data on assisted reproductive outcomes are limited to small case series. “There is consensus among major medical societies to encourage fertility preservation counseling prior to initiation of gender-affirming hormone care,” they write, “however, it is uncertain whether a break in T treatment prior to undergoing oocyte cryopreservation is beneficial. We hypothesized that T treatment would not have an impact on IVF outcomes.”

For this study, the researchers implanted 38 female mice with silastic tubing with either 10 mg T enthanate in ethanol (n=20) or ethanol alone (n=18) at 10 weeks of age. The mice were divided into four groups: current T implant, current sham implant, T cessation, and control cessation.

The team monitored T levels and reproductive cycles. Mice with the testosterone and sham implants underwent ovarian stimulation 12 weeks post-implantation. Implants were removed after 12 weeks for the testosterone cessation and control cessation groups, and mice underwent ovarian stimulation two weeks later.

Mice with current T treatment had fewer oocytes retrieved (17 vs. 36), compared with the current sham implant group. The mice undergoing active testosterone therapy also had fewer mature oocytes (13 vs. 28.1), and two-cell embryos (12.78 vs. 26.9) retrieved than the current sham implant group. There was no significant difference in maturity or fertilization rate. Females who had 2-cell embryos transferred from current T implant mice were less likely to have a live birth than those with transfers from current sham implant mice (25% vs. 80%). Conversely, the T cessation group and control showed no significant difference between total oocytes, mature oocytes or 2-cell embryos retrieved.

“In a mouse model of gender-affirming testosterone, active T treatment negatively impacted IVF outcomes,” the authors conclude. “Improved outcomes following cessation of T treatment support reversibility of T impact on reproductive potential.”