Meta-analysis ranks growth hormone, testosterone, other add-ons for low egg count

A 2025 meta-analysis combined the results of 22 studies and found no clear improvement in live birth rates from hormonal add-on for poor ovarian response, though growth hormone and testosterone ranked as the most promising options, and growth hormone increased the number of eggs retrieved.

When patients begin ovarian stimulation, doctors monitor how many follicles grow and how many eggs can be retrieved. Some ovaries don’t respond as strongly to stimulation, even with higher medication doses. This is known as a poor ovarian response (POR), typically when three or fewer eggs are collected after stimulation. It’s often linked to diminished ovarian reserve (DOR), which means fewer eggs remain in the ovaries and AMH or antral follicle counts are low.

Clinicians often use the Bologna criteria to define poor responders to diagnose a poor response. According to the Bologna criteria, women with POR are defined as having at least 2 of the 3 criteria (Ferraretti and Gianaroli 2014):

1. Advanced age (>40)
2. Previous poor ovarian response (cycles canceled or 3 or less eggs retrieved)
3. Diminished ovarian reserve (<5 antral follicle count, <0.8 ng/ml or 5.4 pmol/L AMH)

To improve their odds, many clinics try hormonal add-ons, such as testosterone, DHEA, human growth hormone, or letrozole. These are intended to boost follicle development, improve egg quality, or make the ovaries more responsive to stimulation. However, studies on these treatments have shown mixed results, and it’s still unclear which, if any, truly help.

A new network meta-analysis by Etrusco et al. (2025) compared all major hormonal add-ons side-by-side in women with a poor response to see which treatments actually improved egg yield, pregnancy, or live birth. Besides these meta-analysis results, the authors also used a ranking approach called SUCRA, which estimates how likely each treatment is to perform best overall (the higher the SUCRA %, the better chance the treatment works).

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Study details

• Study design: Systematic review and network meta-analysis of 22 randomized controlled trials (RCTs).
• Participants: 4,131 women with POR defined by Bologna criteria, aged ~35–41 years undergoing IVF/ICSI.
• Add-ons compared: human growth hormone, testosterone, DHEA, recombinant LH, estrogen priming, letrozole, and clomiphene citrate.
• Primary outcome: Live birth rate

A closer look at the hormonal add-ons in this study

The hormonal add-ons aim to improve egg yield in patients with a poor ovarian response by making the ovaries more sensitive to stimulation, for example through enhancing FSH responsiveness or by promoting more synchronized follicle growth.

• Testosterone: Used as a pretreatment before ovarian stimulation to improve follicle sensitivity to FSH.
• DHEA: Taken as a pretreatment before stimulation to increase ovarian androgen and estrogen precursors that may support follicle growth.
• Estrogen priming: As a pretreatment given in the cycle before stimulation to help synchronize follicle development and improve the response to gonadotropins.
• Growth hormone: Added during stimulation to potentially enhance follicular development and egg maturation by increasing IGF-1 activity in the ovary.
• Recombinant LH: Administered with FSH during stimulation to support estrogen production and oocyte maturation.
• Letrozole: Used early in stimulation to suppress estrogen production and raise intra-ovarian androgens, which may improve FSH response.
• Clomiphene citrate: Taken during stimulation to increase FSH and LH release by blocking estrogen feedback.

Hormonal add-ons show no difference in live birth rate

Based on 8 RCTs:

• Compared to control: No differences (very low quality of evidence).
• Compared to other hormonal add-ons: No differences (very low quality of evidence).
• Heterogeneity: Low (no major variability in studies).
• Top SUCRA rankings: Testosterone (34.0%) and growth hormone (23.9%)

Although none reached statistical significance, testosterone and GH ranked as the most promising options for potential live birth improvement.

Clinical pregnancy rates

Based on 19 RCTs:

• Compared to control: Estrogen priming showed a reduction in the odds of clinical pregnancy by about half (OR 0.49 [95% CI 0.29-0.84]; low quality of evidence).
• Compared to other add-ons: Growth hormone improved clinical pregnancy rates vs estrogen, estrogen performed worse than DHEA, and LH was less effective than growth hormone (very low to low quality of evidence).
• Heterogeneity: Low.
• Top SUCRA rankings: Growth hormone (46.3%) and testosterone (44.6%)

Number of oocytes retrieved

Based on 22 RCTs:

• Compared to control: Growth hormone increased the number of oocytes retrieved (standardized mean difference 0.93 [95% CI 0.02–1.84], very low quality of evidence).
• Compared to other add-ons: Growth hormone performed better than clomiphene (very low quality of evidence).
• Heterogeneity: Moderate, possible publication bias.
• Top SUCRA ranking: Growth hormone (53.2%) and DHEA (17.1%).

Number of mature oocytes retrieved

Based on 17 RCTs:

• Compared to control: Growth hormone increased the number of mature oocytes (standardized mean difference 1.46 [95% CI 0.26–2.66], very low quality of evidence).
• Compared to other add-ons: GH outperformed clomiphene (very low quality of evidence).
• Heterogeneity: Low.
• Top SUCRA ranking: Growth hormone (67.9%) and DHEA (15.7%).

Fertilization rate

Based on 14 RCTs:

• Compared to control: Estrogen priming reduced the odds of fertilization by about half (OR 0.49 [0.29–0.84], low quality of evidence).
• Compared to other add-ons: GH improved rates compared with estrogen (low quality of evidence).
• Heterogeneity: Low.
• Top SUCRA ranking: LH (37.3%) and clomiphene (22.3%).

Other outcomes

Here I’ll just highlight the differences to control.

• Duration of stimulation: No differences compared with control (15 studies); letrozole ranked highest for shortest duration (SUCRA = 52.0%).
• Total gonadotropin dose: Letrozole required less medication (standardized mean difference −7.02 [95% CI −12.82 to −1.22], 15 studies); letrozole ranked highest (SUCRA = 67.0%).
• Estradiol levels at trigger: Letrozole lowered estradiol compared with control (standardized mean difference −2.42 [95% CI −4.38 to −0.47], 14 studies); GH produced the highest levels (SUCRA = 46.3%).
• Cancellation rate: No differences compared with control (8 studies); GH ranked highest for lowest cancellation risk (SUCRA = 45.1%).

Conclusions

This meta-analysis found no differences in live birth rates for any of the add-ons, but SUCRA ranked growth hormone and testosterone pretreatment as having the highest chance of potentially increasing live birth rates.

For the meta-analysis, they did find differences in:

• Clinical pregnancy rates (decreased with estrogen priming vs control).
• Number of eggs retrieved (increased with growth hormone vs control).
• Number of mature eggs (increased with growth hormone vs control).
• Fertilization rates (decreased with estrogen priming vs control).
• Total gonadotropin dose (less with letrozole vs control).
• Estradiol levels at trigger (lower with letrozole vs control).

For the SUCRA analysis, growth hormone ranked among the top treatments, showing the highest probabilities for improving egg yield, maturity, and clinical pregnancy rates. Testosterone also ranked highly for pregnancy outcomes, while letrozole showed favorable rankings for shorter stimulation, lower medication use, and reduced estradiol levels.

While SUCRA rankings can indicate which treatments are most likely to perform best overall, they don’t replace direct evidence showing a significant benefit over control.

A recent meta-analysis of 38 studies in women with DOR found that DHEA, testosterone, high-dose gonadotropins, and delayed-start protocols improved egg yield, with testosterone also linked to higher live birth rates. The authors of the current study noted that this earlier analysis used a traditional rather than network meta-analysis approach, which they say is more limited. You can read more about this recent study in my post Meta-analysis combines 38 studies on treatments for diminished ovarian reserve, which also provides more details on dosage/timing of the add-ons.

The overall certainty of evidence was low to very low, underscoring the need for high-quality randomized controlled trials that use live birth as the primary outcome. Still, this meta-analysis represents one of the most comprehensive and reliable combinations of RCT data currently available.

Limitations: Most trials were small and heterogeneous, dosing regimens varied widely, and neonatal outcomes were rarely reported.

Want to read more about POR or DOR?

Related studies

These additional studies were referenced by the authors of the paper and haven’t been covered on Remembryo. They may be helpful if you’re exploring this topic further. This section is available for paid subscribers.

Reference

Etrusco A, Agrifoglio V, Castillo Farfán JC, Bernabeu Garcia A, Laganà AS, Moliner Renau B, D’Amato A, De Franciscis P, Fuentes Rozalén A, Riemma G. Effectiveness of hormone add-on strategies in ovarian stimulation for women with poor ovarian response: a systematic review and network meta-analysis of randomized controlled trials. J Assist Reprod Genet. 2025 Oct 25. doi: 10.1007/s10815-025-03633-z. Epub ahead of print. PMID: 41136866.

 

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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.

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