In vitro fertilization (IVF) outcomes vary depending on the type of gonadotropin used for ovarian stimulation, with evidence suggesting differences in live birth rates and the risk of ovarian hyperstimulation syndrome (OHSS). According to a March 2025 Cochrane systematic review, recombinant follicle-stimulating hormone (rFSH) generally shows distinct efficacy and safety profiles compared to human menopausal gonadotropin (HMG) and biosimilar alternatives, though clinical choice often depends on individual patient factors and risk profiles.
Comparative Efficacy of Gonadotropins in IVF
Choosing the right hormone protocol is a fundamental step in the IVF process. Gonadotropins are used to stimulate the ovaries to produce multiple eggs for retrieval. Research indicates that the choice of medication impacts both the likelihood of a successful pregnancy and the risk of complications.
Data from 59 studies involving 18,119 women suggest that live birth rates are typically lower with rFSH compared to purified or highly purified human menopausal gonadotropin (HMG/HP-HMG). When comparing rFSH to biosimilar versions, however, rFSH is associated with higher rates of both live births and clinical pregnancies.
When evaluating rFSH against purified follicle-stimulating hormone (FSH-HP) or follitropin delta, researchers found little to no significant difference in live birth outcomes. Clinical pregnancy rates—confirmed via ultrasound—followed a similar trend, showing consistency across these specific treatment comparisons.
Managing Ovarian Hyperstimulation Syndrome (OHSS)
OHSS remains a primary concern in fertility treatment, characterized by swollen ovaries and fluid leakage into the abdomen. Clinical data indicates that the risk of developing OHSS is influenced by the specific gonadotropin administered.
According to the review, the risk of OHSS is higher when using rFSH compared to HMG/HP-HMG or follitropin delta. Conversely, when comparing rFSH to FSH-HP, there is little to no observed difference in OHSS occurrence. Comparisons between rFSH and biosimilars also show little to no significant variation in the risk of this condition. Clinicians often balance these risks against the desired ovarian response when designing a stimulation cycle.
Limitations and Future Research Directions
While these findings provide a framework for understanding hormone performance, the evidence base faces certain limitations. Most existing studies focus on fresh embryo transfers, meaning these results may not fully translate to cycles involving frozen embryos.
Furthermore, many studies in the field are sponsored by the pharmaceutical companies that manufacture these specific hormones, which may influence reported outcomes. Future research is expected to prioritize cumulative success rates across multiple frozen embryo transfer cycles to provide a more comprehensive view of treatment effectiveness. Experts continue to stress that developing standardized strategies for the prevention and management of OHSS remains a priority for fertility clinics worldwide.
Summary of Treatment Comparisons
| Comparison | Live Birth Outcome | OHSS Risk |
|---|---|---|
| rFSH vs. HMG/HP-HMG | Probably decreased with rFSH | Probably higher with rFSH |
| rFSH vs. FSH-HP | Little to no difference | Little to no difference |
| rFSH vs. Follitropin Delta | Little to no difference | Probably higher with rFSH |
| rFSH vs. Biosimilars | Probably higher with rFSH | Little to no difference |
Note: This summary is based on the findings of the March 2025 Cochrane systematic review. Patients undergoing fertility treatment should consult with their reproductive endocrinologist to discuss which stimulation protocol is most appropriate for their specific medical history and reproductive goals.
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