FSH Shows Modest Gains in Male Fertility but Falls Short on Pregnancy Outcomes
A systematic review of 9 studies finds FSH improves sperm count and motility in normogonadotropic men, but pregnancy benefits remain unproven.
Summary
Many fertility guidelines recommend hormonal treatments for men with poor sperm quality, but the evidence has been murky. This systematic review pooled data from nine controlled studies involving 735 men with normal gonadotropin levels but abnormal semen. FSH treatment produced modest improvements in sperm count, concentration, and motility, though morphology did not improve significantly. Combined gonadotropin therapy and tamoxifen showed no benefit. Critically, only two small studies examined pregnancy rates, and neither found a statistically significant increase. No studies on aromatase inhibitors or clomiphene met inclusion criteria. The authors conclude that FSH may have a selective role, but expected gains are modest and short-lived, and whether they translate into actual pregnancies or live births remains unknown.
Detailed Summary
Male factor infertility affects roughly half of all infertile couples, yet hormonal treatments for men with normal gonadotropin levels and poor semen quality remain controversial. Despite this uncertainty, international guidelines increasingly recommend these therapies — a disconnect that this systematic review set out to address.
Researchers from the University of Aberdeen and Imperial College London conducted two linked systematic reviews, searching major databases through February 2025. Review 1 examined changes in semen parameters; Review 2 focused on pregnancy outcomes in men undergoing assisted reproduction. Nine studies encompassing 735 normogonadotropic men with abnormal semen met inclusion criteria. Risk of bias was assessed using validated tools, and random-effects meta-analyses were performed.
FSH emerged as the only treatment showing statistically significant improvements. Sperm count rose by a mean difference of 11.0 million, concentration by 5.6 million/mL, and motility by 3.4 percentage points. Morphology did not improve significantly. Combined human chorionic gonadotropin and menopausal gonadotropin therapy, as well as tamoxifen, showed no measurable benefit. Notably, no eligible studies evaluated aromatase inhibitors or clomiphene citrate — two commonly used agents — leaving a substantial evidence gap.
On the pregnancy front, only two small studies reported data, and neither demonstrated a statistically significant increase in conception rates. This is the most clinically important gap: improved semen parameters are a surrogate endpoint, and their translation to live births — the outcome that matters most to patients — remains unestablished.
The authors cautiously support selective FSH use in this population but emphasize that benefits are modest and short-term. For clinicians, this review underscores the need for larger, well-designed randomized trials with live birth as the primary endpoint before hormonal treatment becomes standard of care for normogonadotropic male infertility.
Key Findings
- FSH significantly improved sperm count (+11M), concentration (+5.6M/mL), and motility (+3.4%) in normogonadotropic men.
- FSH did not significantly improve sperm morphology, a key fertility parameter.
- Combined gonadotropin therapy and tamoxifen showed no benefit on semen quality.
- Only two small studies assessed pregnancy rates; neither showed a statistically significant improvement.
- No eligible studies evaluated aromatase inhibitors or clomiphene, leaving major evidence gaps.
Methodology
Two linked systematic reviews searched MEDLINE, Embase, Cochrane Database, and CENTRAL through February 2025. Nine randomized and non-randomized controlled studies (n=735) were included, with risk of bias assessed via Cochrane tool and ROBUST-RCT. Random-effects meta-analyses were performed for semen parameter outcomes.
Study Limitations
The review is based on only nine small studies (735 men total), limiting statistical power and generalizability. Summary is based on the abstract only, as the full text is not open access. No eligible studies evaluated commonly used agents like aromatase inhibitors or clomiphene, and pregnancy data came from only two underpowered studies.
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