Testosterone pretreatment before IVF in DOR patients: A randomized trial

Researchers in a 2026 randomized trial found that ~9 weeks of transdermal testosterone before IVF didn’t improve pregnancy rates or egg numbers in women with diminished ovarian reserve.

Testosterone is sometimes used as an add-on before IVF in women with diminished ovarian reserve (DOR), in the hope of improving ovarian response and increasing the number of eggs retrieved. It’s often given as a transdermal gel that’s applied daily for several weeks before stimulation.

Some smaller studies and meta-analyses have suggested that testosterone may slightly increase the number of eggs retrieved and possibly improve pregnancy rates, although the evidence has been inconsistent.

In a randomized controlled trial, Polyzos et al. (2026) tested whether ~9 weeks of transdermal testosterone gel before ovarian stimulation improves IVF outcomes in women with DOR.

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Study Details

  • Study type: Multicenter, triple-blind, randomized controlled trial conducted across 10 fertility clinics in Europe between 2015 and 2022.
  • Participants: 288 women with diminished ovarian reserve undergoing IVF (average AMH ~0.45 ng/mL):
    • Testosterone group (n= 134; age breakdown: <36: 28, 36–39: 48, ≥40: 58) who received 5.5 mg transdermal testosterone gel daily for ~9 weeks before ovarian stimulation.
    • Placebo group (n= 154; age breakdown: <36: 25, 36–39: 70, ≥40: 59).
    • 288 patients were included in the intention to treat analysis, with 255 completing the study per protocol (134 placebo, 121 testosterone).
  • Baseline characteristics: Similar between groups.
  • Embryos transferred: 1-2 day 3 embryos (mostly single embryo transfer; no differences between groups).
  • Primary outcome: Clinical pregnancy rate.
  • Power calculation: Designed to detect an increase in clinical pregnancy from 14.5% to 26%.
  • Trial registration: NCT02418572.

No difference in clinical pregnancy rates with testosterone pretreatment

There was no difference in clinical pregnancy for DOR patients with testosterone pretreatment vs placebo (15.7% vs 14.9%, relative risk [95% CI]: 1.05 [0.61–1.81], p = 0.86, intention to treat).

There were no differences between age groups (<36, 36–39, ≥40), although there were smaller numbers in these subgroups.

This study included 288 patients, but was originally designed to include about 400 patients, and was stopped early because the “likelihood of the study demonstrating a significant difference in the primary outcome [clinical pregnancy] between groups if continued was extremely low.”

No meaningful change in oocyte or embryo outcomes with testosterone pretreatment

They also looked at other pregnancy and IVF outcomes for testosterone vs placebo:

  • Live birth: 10.4% vs 13.0% (no statistical difference)
  • Miscarriage and stillbirth: 28.6% vs 13.0% (no difference)
  • Oocytes retrieved: 3.8 vs 3.4 (no difference)
  • Mature oocytes (MII): 3.1 vs 2.8 (no difference)
  • Top-quality day 3 embryos: 1.0 vs 0.7 (no difference)

There was a slightly higher cancellation rate with testosterone (26.1% vs 16.7%), but this wasn’t statistically significant (p= 0.07)

For safety events:

  • Overall adverse events: similar between groups
  • Increased hair growth: higher with testosterone (14.7% vs 7.1%, p= 0.03)
  • No serious adverse events in the testosterone group

Conclusion

In this RCT, using transdermal testosterone for ~9 weeks before IVF didn’t improve clinical pregnancy rates, live birth rates, the number of eggs retrieved, or the number of high quality embryos in DOR patients.

While the study was designed to detect a large improvement (~11.5% absolute increase in clinical pregnancy), which may be unrealistic in an older, low-AMH population using day 3 embryo transfers, there was no sign of benefit. The researchers originally planned to enroll about 400 patients but stopped early because it was considered extremely unlikely to change the outcome.

One point to consider is the testosterone dose. This study used 5.5 mg/day, lower than the ~10–25 mg/day used in some studies, but it was chosen to prevent side effects. Prior data show that 10 mg/day can raise serum levels to 4.3 nmol/L, while in this study, testosterone levels reached 3.11 nmol/L (compared to 0.61 nmol/L in the placebo group). This confirms that testosterone was absorbed and levels increased, but there was no effect on egg numbers or pregnancy outcomes. Studies using higher doses have shown mixed results, and are generally small with shorter treatment periods, and no consistent improvement in outcomes.

Overall, the evidence is mixed, but this higher-quality study doesn’t support a meaningful benefit of testosterone pretreatment for DOR patients.

Limitations include the use of day 3 embryo transfers in an older, low-AMH population, where pregnancy rates are already low and small differences may be harder to detect, early stopping of the study, and a mostly older group that may not reflect younger patients.

Want to read more about DOR?

Reference

Polyzos NP, Leathersich SJ, Martínez F, Blockeel C, Gosálvez A, de la Fuente L, Pinborg A, Fàbregues F, Stoop D, Rodriguez I, de Geyter C, Davis SR, Humaidan P. Transdermal testosterone gel vs placebo in women with diminished ovarian reserve prior to in vitro fertilization: a randomized, clinical trial. Nat Commun. 2026 Feb 12;17(1):2713. doi: 10.1038/s41467-026-69557-z. PMID: 41680203; PMCID: PMC13013832.

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About Embryoman

Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.