rFSH75 IU/vial

rFSH is a purified preparation of recombinant human follicle-stimulating hormone (r-hFSH) produced by recombinant DNA technology, used in the treatment of infertility.

Established / FDA-approved uses

• Ovulation induction in women with anovulatory infertility (e.g., WHO Group I/II anovulation) who have not responded to other measures such as clomiphene citrate.
• Controlled ovarian stimulation (COS) for the development of multiple follicles in women undergoing assisted reproductive technology (ART) procedures such as in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI).
• Induction of spermatogenesis in men with hypogonadotropic hypogonadism who have a documented deficiency of FSH; used in combination with human chorionic gonadotropin (hCG).

Adjunct / combination-therapy uses

• Often used together with a GnRH agonist or GnRH antagonist to prevent a premature LH surge during COS cycles.
• May be combined with low-dose hCG or luteinizing hormone (LH) activity in women with profound LH deficiency.

rFSH is not indicated for use outside specialist-supervised fertility treatment protocols.

Each vial, ampoule, or pre-filled pen of Recombinant Follicle Stimulating Hormone contains purified recombinant human follicle-stimulating hormone (r-hFSH) manufactured using recombinant DNA technology in a mammalian cell line, commonly available in strengths of 75 IU, 150 IU, 225 IU, 300 IU, 450 IU, and 900 IU, supplied either as a lyophilised powder with diluent for reconstitution or as a ready-to-use injectable solution.

rFSH is a biotechnology-derived gonadotropin that is structurally and biologically similar to endogenoushuman follicle-stimulating hormone (FSH). It is manufactured using recombinant DNA technology rather thanbeing purified from human urine, giving a highly consistent, high-purity product with minimal batch-to-batchvariability.

In women, rFSH stimulates the growth and maturation of ovarian follicles; in men, it stimulatesSertoli cell function and spermatogenesis. It is administered exclusively by injection under close medicalsupervision as part of a fertility treatment protocol.

Gonadotropin; Fertility hormone – Follicle-Stimulating Hormone (FSH) analogue (rFSH)

Mechanism

Recombinant Follicle Stimulating Hormone binds to FSH receptors located on granulosa cells of ovarian follicles in women and on Sertolicells within the seminiferous tubules of the testis in men.

• In women: stimulates recruitment and growth of a cohort of ovarian follicles, promotesgranulosa cell proliferation, and increases aromatase-mediated conversion of androgens to estradiol.
• In men: stimulates Sertoli cell activity and supports spermatogenesis, typically togetherwith hCG-driven testosterone production.

Pharmacokinetics

After subcutaneous injection, Recombinant Follicle Stimulating Hormone is absorbed slowly, reaching peak serum concentrations withinapproximately 12–24 hours, with an elimination half-life of roughly 24–40 hours, allowing once-daily dosing.

rFSH is given by subcutaneous injection, usually self-administered (after training) or given by a caregiver/nurse, using a pre-filled pen, cartridge, or reconstituted vial with the accompanying syringe. Injection sites should be rotated (e.g., abdomen, thigh) to reduce local irritation.

No formal drug-drug interaction studies have been conducted for rFSH, as it is a protein hormone thatis not metabolized by hepatic cytochrome P450 enzymes. Clinically relevant considerations include:

• Clomiphene citrate: commonly used together with or before rFSH in ovulation inductionprotocols; concurrent use may increase the follicular response, requiring closer monitoring.
• Human chorionic gonadotropin (hCG): used together with rFSH to trigger final oocyteor sperm maturation; combined use increases the risk of ovarian hyperstimulation syndrome (OHSS) if follicularresponse is excessive.
• GnRH agonists/antagonists: used concurrently in ART cycles to prevent a premature LH surge;may require higher doses of rFSH due to pituitary down-regulation.

Common

• Injection-site reactions (pain, redness, bruising, swelling)
• Headache
• Abdominal pain, bloating, or discomfort
• Nausea
• Ovarian cyst formation

Serious (require prompt medical attention)

• Ovarian hyperstimulation syndrome (OHSS) – potentially life-threatening; see Precautions and Warnings.
• Multiple pregnancy
• Ovarian torsion
• Thromboembolic events (venous or arterial)
• Hypersensitivity/allergic reactions

Patients on rFSH should report severe abdominal pain, rapid weight gain, breathlessness, or reduced urination immediately.

Pregnancy: rFSH is contraindicated once pregnancy has been confirmed, as there is noindication for its continued use during pregnancy and no benefit to the fetus. It should be discontinued assoon as pregnancy is diagnosed. As with all gonadotropins used for ovulation induction/COS, treatment carriesan increased risk of multiple gestation, which itself carries added maternal and fetal risk.

Lactation: There are no adequate data on the excretion of rFSH into human milk. Becauseits use is specific to achieving pregnancy, it is not indicated during breastfeeding; a physician should beconsulted regarding fertility treatment timing in relation to lactation.

Ovarian hyperstimulation syndrome (OHSS)

rFSH can cause OHSS, a potentially life-threatening condition characterized by rapid ovarian enlargement,ascites, pleural effusion, hemoconcentration, and thromboembolic events. Risk is minimized through careful,individualized dosing and close monitoring (serial ultrasound and estradiol levels); treatment should bewithheld or the dose reduced if ovarian response is excessive.

Multiple pregnancy

Use of rFSH for ovulation induction or COS is associated with a significantly increased risk of multiplepregnancy (twins or higher-order), which carries additional maternal and perinatal risk.

Specialist monitoring required

rFSH must only be used under the supervision of a physician experienced in the management of fertilitydisorders, with access to ultrasound and hormone (estradiol) monitoring. It should never be self-titrated bypatients without close clinical supervision.

Other precautions

• Increased risk of ectopic pregnancy in women with a history of tubal disease.
• Risk of thromboembolic events, particularly in women with additional risk factors or established OHSS.
• Ovarian torsion has been reported following gonadotropin therapy.
• Congenital malformation rates in ART pregnancies may be slightly higher than in spontaneous conceptions, possibly related to parental characteristics rather than the treatment itself.

The effects of overdose with rFSH are not fully characterized, but excessive dosing is expected toincrease the risk of ovarian hyperstimulation syndrome (OHSS) in women. There is no specific antidote.Any suspected overdose or signs of severe OHSS (severe abdominal pain, marked abdominal distension, nausea,vomiting, rapid weight gain, breathlessness, or reduced urine output) require immediate medical attention;contact a physician or emergency services, or a poison control center, without delay.

Store in a refrigerator (2°C–8°C), protected from light, and do not freeze, unless the specific product labeling permits room-temperature storage for a limited period after first use (follow the manufacturer's instructions on the pack). Keep out of reach of children.

Renal/hepatic impairment

The safety and pharmacokinetics of rFSH have not been specifically established in patients with renal orhepatic impairment; use with caution and under specialist supervision if prescribed in such patients.

Elderly

rFSH is indicated only for use in the reproductive age group; it has no established use in elderly patients.

Pediatric

See Pediatric Uses.

Duration of rFSH therapy is individualized and specialist-supervised: controlled ovarian stimulation cycles for ART typically last about 8–14 days until hCG trigger; ovulation induction courses are individualized per cycle; induction of spermatogenesis in men with hypogonadotropic hypogonadism generally requires a minimum of 3–4 months, and sometimes up to 12–24 months, of combined therapy before a response is assessed.

For lyophilised powder presentations of rFSH, reconstitute using only the diluent (sterile water for injection) supplied in the same pack, immediately before administration. Gently swirl the vial to dissolve the powder — do not shake, as vigorous agitation may denature the protein. Use the reconstituted solution immediately; discard any unused portion. Pre-filled pen or cartridge presentations do not require reconstitution.

Gonadotropins; Fertility / ovulation-inducing agents; Follicle-stimulating hormone (FSH) analogues

Recombinant Follicle Stimulating Hormone acts as an FSH receptor agonist, binding FSH receptors on ovarian granulosa cells to stimulate follicular growth and estradiol production in women, and on testicular Sertoli cells to stimulate spermatogenesis in men.

X

Safety and efficacy of rFSH have not been established in prepubertal children, and it is not indicated for use in this population. In adolescent males with confirmed hypogonadotropic hypogonadism, use may be considered only under the direct supervision of a pediatric or reproductive endocrinologist, following an individualized specialist protocol.