Follitropin Alfa + Lutropin Alfa

Follitropin Alfa + Lutropin Alfa is a combination recombinant gonadotropin therapy used to stimulate ovarian follicular development in women with fertility disorders.

Approved Indications:

• Female infertility due to hypogonadotropic hypogonadism: For women with low or absent endogenous FSH and LH who require controlled ovarian stimulation.
• Assisted reproductive technology (ART): Stimulation of follicular development in women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).
• Ovulation induction: In women with anovulation due to insufficient gonadotropin secretion.

Off-label / Clinically Accepted Uses:

• Mild ovarian stimulation protocols in ART cycles where combined FSH and LH support may improve follicular response.
• Use in poor ovarian responders with low LH levels to optimize follicular growth.

Adults (Females):

• Hypogonadotropic hypogonadism: Typical starting dose is 150 IU Follitropin Alfa + 75 IU Lutropin Alfa per day, administered subcutaneously.
• ART cycles (IVF/ICSI): Dosing individualized based on ovarian reserve and prior response; Follitropin Alfa 150–225 IU + Lutropin Alfa 75 IU daily is common.
• Duration: Continue until adequate follicular development is achieved (usually 8–12 days).

Special Populations:

• Elderly: Not indicated in postmenopausal women.
• Renal or hepatic impairment: No specific adjustments recommended; clinical monitoring advised.

Administration Route:

• Subcutaneous injection is preferred; intramuscular injection is an alternative.
• Administer at the same time each day to maintain consistent serum levels.

Follitropin Alfa is recombinant human FSH, and Lutropin Alfa is recombinant human LH. FSH binds to FSH receptors on ovarian granulosa cells, stimulating follicular growth and estradiol production. LH binds to LH receptors on theca cells, supporting androgen synthesis, which is a substrate for estrogen production. The combination promotes coordinated follicular maturation, oocyte development, and preparation for ovulation, mimicking the physiological FSH-LH interplay in natural menstrual cycles.

• Absorption: Rapid absorption after subcutaneous injection; peak serum levels achieved within 12–24 hours.
• Bioavailability: Approximately 70–80% for Follitropin Alfa; Lutropin Alfa is similar.
• Distribution: Primarily targets ovarian tissue; limited systemic tissue distribution.
• Metabolism: Proteolytic degradation into inactive peptides; cleared mainly by kidneys.
• Half-life: Follitropin Alfa: 24–36 hours; Lutropin Alfa: 10–12 hours.
• Excretion: Renal elimination of metabolites; minimal unchanged hormone in urine.

• Pregnancy: Not indicated during pregnancy; discontinue once pregnancy is confirmed. Use before conception only.
• Lactation: Limited data; caution advised. Excretion into breast milk is expected to be minimal, but breastfeeding during treatment is generally not recommended.

• Primary Class: Gonadotropins
• Subclass: Recombinant human FSH and LH combination therapy

• Hypersensitivity to Follitropin Alfa, Lutropin Alfa, or any excipients.
• Primary ovarian failure or ovarian cysts not due to hypogonadotropic hypogonadism.
• Uncontrolled thyroid or adrenal dysfunction.
• Pituitary or hypothalamic tumors.
• Pregnancy or active lactation (unless clinically indicated).

• Ovarian Hyperstimulation Syndrome (OHSS): High-risk in women with PCOS, multiple follicle development, or prior OHSS episodes; careful monitoring required.
• Multiple pregnancy: Risk increases with exogenous gonadotropins; adjust dosing accordingly.
• Fluid retention and thromboembolic events: Rare; monitor patients with cardiovascular or coagulation risk factors.
• Injection-site reactions: Mild pain, redness, or swelling may occur.
• Early discontinuation: Indicated if excessive ovarian response or OHSS develops.

Common:

• Headache, fatigue, abdominal discomfort, breast tenderness.
• Injection-site reactions: redness, pain, or swelling.

Serious / Rare:

• Ovarian Hyperstimulation Syndrome (OHSS): abdominal pain, ascites, rapid weight gain.
• Multiple gestations.
• Rare thromboembolic events.

Timing & Severity:

• Usually occurs during stimulation phase; severity may be dose-dependent.

• hCG therapy: Required for final oocyte maturation; dosing and timing must be coordinated.
• Estrogen/progestin therapy: May modify ovarian response; dose adjustments may be necessary.
• CYP450-metabolized drugs: No significant interactions, as both drugs are protein hormones.
• Alcohol: No significant interaction observed.

• Emphasis on individualized dosing in ART cycles based on ovarian reserve markers (AMH, AFC).
• Recombinant FSH + LH is recommended for patients with low endogenous LH or poor ovarian response.
• Monitoring protocols updated to minimize risk of OHSS and multiple pregnancies.
• Use in male infertility remains limited to hypogonadotropic hypogonadism cases requiring spermatogenesis induction.

• Store refrigerated at 2°C to 8°C; do not freeze.
• Protect from light and heat; keep in original packaging until use.
• Reconstituted solution should be used immediately; if required, store up to 24 hours at 2°C–8°C.
• Avoid vigorous shaking; gently invert vials to dissolve powder.