Follitropin Alfa

Follitropin Alfa is a recombinant form of human Follicle‑Stimulating Hormone (FSH) produced in genetically modified Chinese hamster ovary (CHO) cells. The molecule is composed of two non‑covalently linked glycoprotein subunits: an α‑subunit of 92 amino acids and a β‑subunit of 111 amino acids, mirroring the naturally occurring human FSH.

The purported benefits of Follitropin Alfa include stimulating the development of ovarian follicles in women and supporting sperm production in men who have certain types of reproductive hormone deficiencies. In assisted reproductive technology settings it is used to increase the number of mature eggs retrieved and thereby may improve the chances of achieving pregnancy.

Follitropin alfa helps stimulate the development of ovarian follicles in women undergoing assisted reproductive techniques. In a large real‑world multicenter study of 463 women receiving follitropin alfa (Ovaleap®) in a GnRH antagonist protocol, the average number of oocytes retrieved was 11.8, and the clinical pregnancy rate was 41.3%, with a live birth rate of 31.6%. Another clinical cohort compared three different follitropin alfa preparations (biosimilars and originator) in a progestin‑primed ovarian stimulation protocol and found no significant differences in cumulative live birth rates across them, suggesting reliable efficacy ^{1, 2}. Thus, one major benefit of follitropin alfa is its consistent ability to produce a substantial number of mature oocytes and support meaningful pregnancy rates.

In men with hypogonadotropic hypogonadism, follitropin alfa combined with hCG has been shown to effectively induce spermatogenesis. In a study of azoospermic men treated for 18 months, about 80% achieved a sperm concentration ≥1.5 × 10⁶/mL, and several achieved even higher counts. Another long-term trial also showed that this treatment led to sperm concentrations up to 20 × 10⁶/mL in some patients and resulted in clinical pregnancies ^{3, 4}. Therefore, another key benefit of follitropin alfa is its ability to restore sperm production in men with certain hormonal infertility.

Follitropin alfa when used in fertility treatment, commonly causes ovarian hyperstimulation syndrome (OHSS), which can lead to swollen, painful ovaries and fluid shifts that, in severe cases, result in blood clots, kidney problems, or respiratory distress. Other frequent side effects reported in clinical studies include headache, nausea, abdominal pain, and the development of ovarian cysts ^{5, 6}. In male patients with hypogonadotropic hypogonadism treated with follitropin alfa and hCG, common adverse effects included acne (in over half of patients) and gynecomastia in about 10%. Long‑term safety surveillance has documented case reports of serious risks: over more than 427,000 post‑marketing treatment cycles there were reports of OHSS, hypersensitivity, and, in very rare instances, fatal outcomes such as complications from OHSS ^{7, 8}. Overall, while Follitropin alfa is effective in stimulating fertility, its use is associated with a range of adverse effects, from common, manageable symptoms to rare but potentially serious complications.

Follitropin alfa is a recombinant form of follicle‑stimulating hormone (FSH) that binds to the FSH receptor (FSHR), a G‑protein coupled receptor primarily on granulosa cells in the ovary. Ligand binding induces a conformational change in FSHR, activating G\ₛ proteins and raising intracellular cAMP, which in turn activates protein kinase A (PKA) and other downstream effectors ^{9, 10}. This signaling network, which also involves pathways such as MAPK and Akt, promotes granulosa cell proliferation, differentiation, and upregulation of aromatase, driving follicular maturation and estradiol synthesis.

Follitropin alfa, marketed as Gonal‑F, is FDA‑approved for human use in the United States. The FDA approved it in March 2004 for use in fertility treatments to stimulate follicular development. In athletic contexts, follitropin alfa is considered a therapeutic agent for female infertility and is not included on the WADA Prohibited List.