Follitropin
Also known as: Bravelle, Follistim, follitropin alfa/beta/delta, FSH, Gonal-F, Gonal‑F, Puregon, recombinant human FSH, Rekovelle, rFSH
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Summary
Follitropin is a recombinant follicle‑stimulating hormone (FSH) used to stimulate ovarian follicle growth in assisted reproductive technologies such as in‑vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). Commercial preparations include follitropin alfa (standard dosing) and follitropin delta, which is dosed individually based on a woman's anti‑Müllerian hormone (AMH) level and body weight. The drug is administered by injection to promote the development of multiple mature oocytes for retrieval.
Mechanism of Action
Recombinant FSH binds the G‑protein‑coupled FSH receptor on granulosa cells of ovarian follicles. This activates adenylate cyclase, raises intracellular cAMP, and triggers aromatase expression, leading to estradiol synthesis and follicular proliferation. The hormone also supports the expression of LH receptors, preparing follicles for final maturation and ovulation when triggered pharmacologically.
What the Research Shows
Randomised trials in Europe (ESTHER‑1, 1,329 women) and Asia (1,009 women) compared individualized follitropin delta dosing with conventional follitropin alfa. Both studies found non‑inferior ongoing‑pregnancy rates, with delta showing fewer poor or excessive responses and a lower incidence of early ovarian hyperstimulation syndrome (OHSS). A later trial (ADAPT‑1) using conventional fixed doses of delta (15 µg/day) versus alfa (225 IU/day) reported similar oocyte yields and clinical‑pregnancy rates, confirming comparable efficacy. A review of r‑FSH versus urinary FSH suggested r‑FSH yields more oocytes and higher pregnancy rates, though trials lacked power for definitive conclusions.
Reported Benefits
Evidence indicates follitropin effectively induces multi‑follicular growth for IVF, achieving pregnancy and live‑birth rates comparable to traditional regimens. Individualised follitropin delta dosing reduces the risk of poor or excessive responses and appears to lower early OHSS incidence while using less total gonadotropin. Conventional dosing of delta provides ovarian responses similar to alfa, offering flexibility in dosing units (µg versus IU).
Limitations of the Evidence
Most data derive from short‑term, single‑cycle trials; cumulative pregnancy outcomes after subsequent frozen‑embryo transfers are not well documented. Some trials were funded by the manufacturer, and the ADAPT‑1 analysis was descriptive without formal hypothesis testing. Direct head‑to‑head comparisons with urinary FSH rely on meta‑analyses rather than large, powered RCTs, leaving cost‑effectiveness and long‑term safety less certain.
Safety Considerations
In the reported trials, follitropin was generally well tolerated. Individualised delta dosing showed a modest reduction in early OHSS (≈5 % vs ≈9 % with alfa). No new serious adverse events were identified, and the overall safety profile was comparable between delta and alfa. Monitoring for ovarian response and signs of OHSS remains standard clinical practice.
How It Is Administered
Follitropin is supplied as a sterile solution for subcutaneous or intramuscular injection. Dosing of follitropin alfa is expressed in international units (IU), typically starting at 150–225 IU daily. Follitropin delta is expressed in micrograms (µg) and can be prescribed as an individualized fixed dose (e.g., 12 µg or weight‑based 0.10–0.19 µg/kg) or as a conventional 15 µg daily start. Injections are administered once daily during the ovarian stimulation phase.
Routes of Administration
Goals & Uses
- Male infertility (hypogonadotropic hypogonadism)ReproductiveModerate
- Ovulation induction in anovulatory womenReproductive EndocrinologyHigh
- Treatment of male infertility due to hypogonadotropic hypogonadismMale Reproductive HealthHigh
- Female infertility (ovulation induction)ReproductiveHigh
- Controlled ovarian stimulation for ARTReproductive EndocrinologyHigh
- Stimulation of spermatogenesisMale Reproductive HealthModerate
Contraindications
- Hormone-sensitive tumors (ovarian, uterine, breast, pituitary)OncologyHigh
- Severe ovarian hyperstimulation syndrome (OHSS) riskReproductiveHigh
- Uncontrolled thyroid diseaseEndocrineModerate
- Known hypersensitivity to FSH or any excipientAllergyHigh
- PregnancyPopulationHighPotential fetal risk or insufficient safety data
- Hormone‑dependent tumors (e.g., estrogen‑dependent breast cancer)OncologyHigh
- Primary ovarian failure / hypergonadotropic hypogonadismEndocrineHigh
- Uncontrolled thyroid or adrenal dysfunctionEndocrinologyHigh
- Ovarian cysts or enlargement of undetermined originGynecologicHigh
- Hypersensitivity to FSH or excipientsImmunologicHigh
Adverse Effects
- Abdominal discomfortGastrointestinalUncommon
- Injection site reactionsLocalCommon
- Multiple gestationReproductiveUncommon
- HeadacheNeurologicUncommonPain in the head or upper neck
- Ovarian hyperstimulation syndromeReproductive / EndocrineCommon
- Thromboembolic eventsCardiovascularRare
- Ovarian torsionReproductiveRare
- Multiple pregnancyReproductiveUncommon
- Injection‑site reactionsLocalCommon
- Ovarian hyperstimulation syndrome (OHSS)ReproductiveUncommon
Drug Interactions
- Anticoagulants (e.g., warfarin)Low
- Oral contraceptivesModerateDelayed gastric emptying may affect absorption timing
- Human Chorionic Gonadotropin (hCG)Low
- GnRH antagonists (e.g., cetrorelix, ganirelix)Low
- GnRH agonists/antagonistsModerate
- Clomiphene citrateLow
- GnRH agonists (e.g., leuprolide)Low
Population Constraints
- Pediatric patientsAgeAbsolute
- Patients with thrombophiliaHematologicRelative
- Women of advanced reproductive age (>40 years)AgeRelative
- Pregnant womenReproductiveAbsolute
- Elderly (>65)AgeRelative
- Patients with polycystic ovary syndrome (PCOS)EndocrineRelative
- ChildrenPediatricRelative
- Renal or hepatic impairmentOrgan DysfunctionRelative
Regulatory Status
- European UnionApprovedApproved: same as USEMA‑approved biosimilars available.
- United StatesApprovedApproved: female infertility (ovulation induction, IVF), male infertility (hypogonadotropic hypogonadism)Multiple brand products (Gonal‑F, Follistim).
- United KingdomApprovedApproved: same as USRegulated by MHRA.
Approved as several biosimilar products; indications vary slightly between jurisdictions.
Evidence & Sources
- Journal ArticleModerateNyboe Andersen A, et al.2017-01-01T00:00:00.000000Z
- Journal ArticleModeratePalagiano A, Nesti E, Pace L2004-01-01T00:00:00.000000Z
- Journal ArticleModerateQiao J, et al.2021-01-01T00:00:00.000000Z
- Journal ArticleModerateBernabeu A, et al.2025-01-01T00:00:00.000000Z
Frequently Asked Questions
What is the difference between follitropin alfa and follitropin delta?
Both are recombinant FSH, but alfa is given in fixed IU doses, whereas delta is dosed in micrograms and can be individualized according to a woman's AMH level and body weight, aiming to optimise response and reduce OHSS risk.
Does follitropin improve the chance of a live birth?
Randomised trials report live‑birth rates that are comparable between follitropin delta and alfa, with one Asian study showing a statistically higher live‑birth rate for delta. Overall, the drug enables successful IVF cycles with outcomes similar to standard protocols.
Is there a higher risk of ovarian hyperstimulation syndrome with follitropin?
Individualised dosing of follitropin delta has been associated with a lower incidence of early OHSS compared with conventional alfa dosing, while overall safety profiles are similar. Monitoring remains essential for all patients.
Can follitropin be used in women who have not responded well to other fertility drugs?
Follitropin is the most commonly used agent for ovarian stimulation and is employed after pituitary down‑regulation with GnRH agonists or antagonists. Trials include women with varied responses, and individualized delta dosing aims to improve outcomes for low‑ and high‑responders.
How is the medication administered?
It is injected once daily, either subcutaneously or intramuscularly, using pre‑filled pens or syringes. The dose is determined by the prescribing clinician based on the selected preparation (IU for alfa, µg for delta) and the patient’s individual characteristics.
What is Follitropin used for?
Follitropin is educationally associated with: Male infertility (hypogonadotropic hypogonadism), Ovulation induction in anovulatory women, Treatment of male infertility due to hypogonadotropic hypogonadism, Female infertility (ovulation induction), Controlled ovarian stimulation for ART, Stimulation of spermatogenesis. Educational only — not medical advice.
How is Follitropin administered?
Recorded routes of administration: Intramuscular, Subcutaneous.
What are the potential side effects of Follitropin?
Reported adverse effects include: Abdominal discomfort, Injection site reactions, Multiple gestation, Headache, Ovarian hyperstimulation syndrome, Thromboembolic events, Ovarian torsion, Multiple pregnancy, Injection‑site reactions, Ovarian hyperstimulation syndrome (OHSS). This list is not exhaustive — consult a qualified clinician.
Who should avoid Follitropin?
Recorded contraindications: Hormone-sensitive tumors (ovarian, uterine, breast, pituitary), Severe ovarian hyperstimulation syndrome (OHSS) risk, Uncontrolled thyroid disease, Known hypersensitivity to FSH or any excipient, Pregnancy, Hormone‑dependent tumors (e.g., estrogen‑dependent breast cancer), Primary ovarian failure / hypergonadotropic hypogonadism, Uncontrolled thyroid or adrenal dysfunction, Ovarian cysts or enlargement of undetermined origin, Hypersensitivity to FSH or excipients. Consult a qualified clinician before use.