In vitro fertilization outcomes in transgender individuals with prior testosterone therapy

Do transgender and gender diverse patients with prior testosterone gender affirming hormone therapy (T-GAHT) have oocyte cryopreservation and IVF outcomes that differ from those without prior T-GAHT?

Prior T-GAHT was associated with a decrease in the total number of blastocysts after adjusting for age, but not with a difference in the number of mature oocytes.

Many TGD people pursue oocyte cryopreservation or IVF after previously initiating T-GAHT for fertility preservation and/or a partner-carried pregnancy; however, data regarding embryo outcomes are scarce. Retrospective cohort studies suggest high mature oocyte yields in oocyte cryopreservation following T-GAHT, but it is unknown whether embryos from patients with prior T-GAHT have a normal capacity to fertilize, cleave, and form blastocysts.

This was a retrospective observational cohort study of 46 ovarian stimulation cycles initiated for TGD patients assigned female at birth with and without prior T-GAHT from January 2013 to March 2024.

This study included 36 TGD patients assigned female at birth, 25 undergoing IVF and 11 undergoing oocyte cryopreservation. Prior T-GAHT timing, duration, and discontinuation, as well as stimulation cycle characteristics and outcomes collected from the electronic health record retrospectively. Cycles outcomes of TGD people with prior T-GAHT were compared to those without prior T-GAHT. The first completed cycle was used for statistical analysis, with the first initiated cycle (intention to treat) and all cycles as sensitivity analyses. The primary outcome was the number of mature oocytes retrieved for all patients and the total number of blastocysts for patients undergoing IVF. Our secondary outcomes were maturity rate, number of top-quality blastocysts (AB or better), and cumulative live birth rate. A sub-analysis of subjects with prior T-GAHT was performed assessing discontinuation timing and IVF outcomes.

Of the 36 TGD patients included, 14 subjects (20 cycles) had prior T-GAHT, 22 patients (26 cycles) had no prior T-GAHT. Accounting for multiple cycles in 10 subjects, a total of 17 IVF and 3 oocyte cryopreservation cycles were initiated in the prior T-GAHT cohort, and 18 IVF and 8 oocyte cryopreservation cycles in the no T-GAHT cohort. After adjusting for age, in the first cycle, prior T-GAHT was associated with a decrease in the total number of blastocysts (coefficient -0.62, 95% CI: -0.95, -0.30) and number of top-quality blastocysts (coefficient -1.09, 95% CI: -1.68, -0.51) but was not associated with a difference in the number of mature oocytes or maturity. Modeling using the first initiated cycle and including all 46 cycles demonstrated the same results. The first cycle cumulative live birth rate was 60% in the prior T-GAHT cohort and 87.5% in those without T-GAHT (P = 0.20). In patients with prior T-GAHT pursuing IVF for transfer, 80% were ultimately able to achieve a live birth. In the first completed IVF cycle for patients with prior T-GAHT, T-GAHT cessation of <6 months was associated with fewer top-quality blastocysts (P = 0.01) and fewer BB or better quality blastocysts (P = 0.049).

This study is primarily limited by its small sample size and retrospective study design, introducing risk of selection bias and sampling error and limiting our ability to adjust for multiple factors. Limited specificity and reliance on recall in T-GAHT initiation and discontinuation timing is a limitation in this study as it is a recurrent limitation in retrospective studies of TGD patients.

Prior T-GAHT was not associated with differences in mature oocyte number, consistent with prior literature. However, we found that prior T-GAHT and shorter discontinuation were associated with poorer embryo outcomes. This may suggest that patients undergoing oocyte cryopreservation after only brief T-GAHT discontinuation may need to cryopreserve a greater number of oocytes to yield high-quality embryos. Overall, these results add to the growing body of reassuring fertility outcomes for TGD patients with prior T-GAHT, as the majority of these patients pursuing IVF for transfer were able to achieve a live birth.

Dr Rubin's time is partially supported through the Reproductive Scientist Development Program, with full funds supplied by the American Society for Reproductive Medicine. The authors have no competing interest to disclose.

N/A.