Follitropin alfa
Human follicle-stimulating hormone made in hamster ovary cells rather than purified from urine. It grows ovarian follicles for IVF and ovulation induction and, with hCG, restarts sperm production in men whose pituitary has stopped making FSH.
Follitropin alfa (Gonal-f) is recombinant human FSH, approved in the US on September 29, 1997, the same day as follitropin beta. It is dosed daily in international units under fertility-specialist monitoring; ovarian hyperstimulation syndrome and multiple pregnancy are the risks that set its rules.
What is it?
Follicle-stimulating hormone is the pituitary signal that grows ovarian follicles in women and supports sperm production in men. It is a glycoprotein of two subunits: an alpha subunit it shares with LH, hCG and TSH, and a beta subunit that gives it its identity. Follitropin alfa is that hormone made by recombinant DNA technology in Chinese hamster ovary cells. The Gonal-f label describes subunits of 92 and 111 amino acids whose primary and tertiary structures are indistinguishable from those of human FSH, and a molecular weight of about 31 kDa. Before it, FSH for treatment was purified from urine. A 1995 study of routine IVF use noted that the recombinant preparation does not come from a human source and can be self-injected under the skin, and a 1999 study in men judged it comparable with urinary FSH at restoring fertility.
In the US, FDA approved Gonal-f on September 29, 1997 (BLA 020378), the same day it approved Organon's follitropin beta, Follistim (BLA 020582), according to Drugs@FDA. A prefilled multi-dose pen, Gonal-f RFF Redi-ject, followed on May 25, 2004 (BLA 021684). The multi-dose vial label covers three uses: inducing ovulation and pregnancy in oligo-anovulatory women whose infertility is functional rather than due to primary ovarian failure; developing multiple follicles in ovulatory women during assisted reproduction; and inducing sperm production in men with primary or secondary hypogonadotropic hypogonadism, the condition in which the pituitary does not drive the testes. The pen's label covers the two uses in women only.
The labelled doses are specific. For ovulation induction the first cycle starts at 75 IU a day for 14 days, individualised afterwards, never above 300 IU a day. For assisted reproduction it starts at 150 IU a day, adjusted after three to five days in steps of 75 to 150 IU, never above 450 IU a day. Only physicians experienced in infertility treatment should prescribe it, and monitoring facilities must be available, because it can cause ovarian hyperstimulation syndrome and multiple births. Trials show why dose matters: in a randomised trial of 124 women, 225 IU a day retrieved more oocytes than 150 IU in women aged 32 or younger (11.8 against 7.0), made no difference in older women, and all four cases of ovarian hyperstimulation occurred on the higher dose.
In men, it works only alongside hCG. The label says to give hCG alone first, two to three times a week, until testosterone is normal, which may take three to six months, then add follitropin alfa 150 IU three times a week. In a US phase III study of 36 men with severe hypogonadotropic hypogonadism, 22 of 29 who received it (75.9%) reached a sperm concentration of at least 1.5 million per mL, 8 (27.5%) reached more than 20 million, and five pregnancies followed; acne affected 52% and breast enlargement 10%. An Australian study of eight men found sperm in seven at a median six months, and three partners became pregnant.
Much of its modern evidence is as the reference other gonadotropins are measured against. A Korean recombinant FSH (DA-3801) was non-inferior to it for oocytes retrieved in 97 women. A European biosimilar, Bemfola, matched its pharmacokinetics in 23 healthy women, with half-lives of 43.6 and 42.6 hours. In ADAPT-1, follitropin delta 15 µg a day produced ovarian responses similar to follitropin alfa 225 IU a day. In 939 poor responders, adding lutropin alfa in a fixed-ratio product retrieved the same number of oocytes as follitropin alfa alone, with post-hoc signals that need confirming.
Its risks come from what it does. The label warns of hypersensitivity and anaphylaxis; ovarian hyperstimulation syndrome, which can require hospital care; thromboembolic and pulmonary complications; ovarian torsion; abnormal ovarian enlargement, in which case hCG should be withheld; multi-fetal gestation, whose rate depends on the number of embryos transferred; and a possibly higher incidence of congenital malformations after assisted reproduction. Absorption slows as body-mass index rises (label). Follitropin alfa is not on WADA's Prohibited List; its sport row is in the Legal table below.
Mechanism of Action
Follitropin alfa does what the pituitary's own FSH does: it binds the FSH receptor on the cells that support eggs and sperm. Given in larger, steadier doses than the pituitary would release, it grows several follicles at once, which is both the point of IVF stimulation and the source of its main risk.
Follicle growth
On granulosa cells, FSH drives the recruitment and growth of ovarian follicles and their estradiol production; in IVF the goal is several mature follicles, counted by ultrasound before the hCG trigger.
Over-response
Too many follicles can cause ovarian hyperstimulation syndrome; in one trial all four cases occurred on 225 IU a day, none on 150 IU.
Sperm production
On Sertoli cells, FSH supports spermatogenesis; in men with hypogonadotropic hypogonadism it works after hCG has first restored testosterone.
A daily hormone
Its half-life after one injection was 42.6 hours in healthy women, and absorption slows as body-mass index rises (label), so it is injected daily and adjusted by response.
Published Research
PubMed returns about 2,000 records for follitropin alfa or Gonal-f. Our evidence set holds 14 papers; 9 name it in their titles and have an abstract, and all 9 are carded below, all studies in people. Most modern trials use it as the comparator for newer gonadotropins, so the cards include those comparisons.
Routine IVF without GnRH analogues, 71 women
In a multicentre study, 58 women reached hCG over 171 cycles on three or four ampoules a day; about 6 oocytes were collected per cycle and the clinical pregnancy rate was 23.8% per transfer. Mild injection-site pain affected fewer than 20% and two cases of ovarian hyperstimulation occurred. The authors note it can be self-injected and does not come from a human source.
Men with gonadotrophin deficiency, Australia
Ten men received hCG for 3 to 6 months, then self-injected recombinant FSH with hCG for 18 months. Of the eight who started FSH, seven produced sperm at a median of 6 months and five reached 1.5 million per mL at a median of 9 months; testes grew by 4.2 mL on average, and three partners became pregnant.
150 IU against 225 IU for IVF, 124 women
At a fixed 225 IU a day, women aged 32 or younger yielded more oocytes than at 150 IU (11.8 against 7.0); in older women the numbers were similar, and fertilisation, embryos and pregnancy rates did not differ. Cancellations for poor response were 15.0% against 3.3%, and all four cases of ovarian hyperstimulation occurred at 225 IU.
A Korean recombinant FSH against it, 97 women
In a phase III non-inferiority trial, DA-3801 retrieved 13.0 oocytes against 10.6 with Gonal-f, meeting non-inferiority, with a lower total FSH dose and a shorter stimulation; pregnancy, implantation and adverse-event rates were comparable.
Phase III in men with hypogonadotropic hypogonadism, 36 men
After hCG alone for 3 to 6 months, follitropin alfa 150 IU with hCG on alternate days for 18 months brought 22 of 29 treated men (75.9%) to at least 1.5 million sperm per mL; median concentration at 18 months was 5.2 million, testes grew and five pregnancies followed. Acne (52%) and gynecomastia (10%) were the commonest side effects.
A biosimilar's pharmacokinetics, 23 women
After single injections in healthy women whose own FSH was suppressed with leuprolide, Bemfola and Gonal-f had near-identical exposure (AUC 424.9 and 432.8 IU·h/L), peak at 24 hours and half-lives of 43.6 and 42.6 hours. No immune reaction to the hormone was seen.
Adding LH in poor responders, 939 women
In women with poor ovarian response, a fixed-ratio product of follitropin alfa and lutropin alfa retrieved the same number of oocytes as follitropin alfa alone, the primary endpoint. Post-hoc analyses suggested fewer failed pregnancy outcomes and more live births with the combination in moderate and severe poor responders, findings the authors say need further study.
DNA damage in granulosa cells, 18 women
In a small randomised study, granulosa cells collected after stimulation with four recombinant FSH products showed different comet-assay DNA damage, with Gonal-f and Puregon higher than Corneumon and Pergoveris. Whether this affects outcomes was not studied.
ADAPT-1: follitropin delta against it
In an assessor-blind trial at clinics in Austria, France, Italy, Spain and the UK, conventional dosing with follitropin delta 15 µg a day produced ovarian responses similar to follitropin alfa 225 IU a day in women aged 18 to 40 undergoing IVF or ICSI.
Dosing Data
Follitropin alfa is dosed by label in international units, one injection under the skin a day for women, and adjusted by a fertility specialist from ultrasound and hormone monitoring.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the label and the studies above.
Contraindications & Cautions
From the label; a clinician decides.
Legal Status
Follitropin alfa is an approved prescription medicine. The sport row below comes from the dataset.
Frequently Asked Questions
?What is follitropin alfa used for?
In the US, Gonal-f is approved to induce ovulation in women whose infertility is functional rather than due to primary ovarian failure, to develop multiple follicles during assisted reproduction, and, with hCG, to induce sperm production in men with hypogonadotropic hypogonadism. The Redi-ject pen is labelled for the two uses in women.
?Was Gonal-f the first recombinant FSH?
Not in the US by itself: Drugs@FDA shows Gonal-f and Organon's follitropin beta (Follistim) were both approved on September 29, 1997.
?What dose is used for IVF?
The label starts assisted reproduction at 150 IU a day, adjusted after three to five days in steps of 75 to 150 IU, never above 450 IU a day. In one trial 225 IU retrieved more oocytes than 150 IU only in women aged 32 or younger, and all ovarian hyperstimulation cases occurred on the higher dose.
?Can it help men with low sperm counts?
Only men whose pituitary does not drive the testes (hypogonadotropic hypogonadism), and only with hCG. In a phase III study 75.9% of treated men reached at least 1.5 million sperm per mL after up to 18 months. It cannot help primary testicular failure.
?Is follitropin alfa banned in sport?
No. It is not on WADA's 2026 or 2027 Prohibited Lists; the Legal table below gives the dataset's entry.
References
- [fda-pi] Gonal-f (follitropin alfa) for injection and Gonal-f RFF Redi-ject (follitropin alfa) injection Prescribing Information. EMD Serono (DailyMed versions published 2025-09-05 and 2025-04-07, read 2026-09-28).
- [fda-pi] US FDA, Drugs@FDA: Gonal-f, BLA 020378, approved 1997-09-29; Gonal-f RFF Redi-ject, BLA 021684, approved 2004-05-25 (EMD Serono); Follistim (follitropin beta), BLA 020582, approved 1997-09-29 (Organon) (read 2026-09-28).
- [pubmed] Strowitzki T, et al. "Ovarian stimulation in women undergoing in-vitro fertilization and embryo transfer using recombinant human follicle stimulating hormone (Gonal-F) in non-down-regulated cycles." Hum Reprod, 1995;10(12):3097-101. PMID: 8822421.
- [pubmed] Liu PY, et al. "Efficacy and safety of recombinant human follicle stimulating hormone (Gonal-F) with urinary human chorionic gonadotrophin for induction of spermatogenesis and fertility in gonadotrophin-deficient men." Hum Reprod, 1999;14(6):1540-5. PMID: 10357972.
- [pubmed] Yong PY, et al. "A prospective randomized clinical trial comparing 150 IU and 225 IU of recombinant follicle-stimulating hormone (Gonal-F*) in a fixed-dose regimen for controlled ovarian stimulation in in vitro fertilization treatment." Fertil Steril, 2003;79(2):308-15. PMID: 12568839.
- [pubmed] Moon SY, et al. "Comparison of the efficacy and safety of a new recombinant human follicle-stimulating hormone (DA-3801) with follitropin-alpha (Gonal-F) in women undergoing controlled ovarian hyperstimulation for assisted reproductive technology." J Obstet Gynaecol Res, 2007;33(3):305-15. PMID: 17578360.
- [pubmed] Matsumoto AM, et al. "Stimulation of spermatogenesis with recombinant human follicle-stimulating hormone (follitropin alfa; GONAL-f): long-term treatment in azoospermic men with hypogonadotropic hypogonadism." Fertil Steril, 2009;92(3):979-990. PMID: 18930190.
- [pubmed] Wolzt M, et al. "Comparison of pharmacokinetic and safety profiles between Bemfola(®) and Gonal-f(®) after subcutaneous application." Eur J Drug Metab Pharmacokinet, 2016;41(3):259-65. PMID: 25633239.
- [pubmed] Humaidan P, et al. "Efficacy and safety of follitropin alfa/lutropin alfa in ART: a randomized controlled trial in poor ovarian responders." Hum Reprod, 2017;32(3):544-555. PMID: 28137754.
- [pubmed] Alcalá-Sánchez X, et al. "Comparison of DNA damage in granulosa cells of women undergoing controlled ovarian stimulation in in vitro fertilization protocols with the recombinant human follicle-stimulating hormones Corneumon(®), Gonal-F(®), Pergoveris(®) and Puregon(®): a randomized trial." Arch Gynecol Obstet, 2024;309(5):2107-2114. PMID: 38441601.
- [pubmed] Bernabeu A, et al. "Ovarian stimulation with follitropin delta for in vitro fertilization: a multicentre, randomized, assessor-blind comparison with follitropin alfa using conventional dosing regimens (ADAPT-1 trial)." Hum Reprod, 2025;40(9):1660-1670. PMID: 40633120.
Sources & Citations
Every PubMed citation on this page has been checked against its record. The Gonal-f and Gonal-f RFF Redi-ject labels (DailyMed, published September 5 and April 7, 2025) and Drugs@FDA were read on September 28, 2026. Grey Peptides sells nothing and links to no vendor.
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