Introduction

Gonad-stimulating hormone; biosynthetic (recombinant DNA-derived) form of human chorionic gonadotropin (hCG).

Uses for Choriogonadotropin Alfa

Female Infertility

Used in conjunction with other infertility agents (e.g., gonadotropin-releasing hormone agonist, FSH) for induction of final follicular maturation and early luteinization in ovulatory, infertile women during assisted reproductive technology (ART) programs.

Use in patients with tubal obstruction only if participating in ART programs.

Choriogonadotropin alfa (r-hCG) is equivalent to urinary-derived hCG with regard to number of oocytes recovered, fertilized oocytes or embryos, and live births.

Used in conjunction with follicle-stimulating agent to induce ovulation in anovulatory, infertile women in whom anovulation is functional and not due to primary ovarian failure.

Choriogonadotropin alfa (r-hCG) is similar to urinary-derived hCG with regard to ovulation rates.

Choriogonadotropin Alfa Dosage and Administration

General

• Should be prescribed only by clinicians experienced in infertility treatment and who are familiar with cautions, precautions, and contraindications associated with such therapy.

• Prior to treatment initiation with choriogonadotropin alfa, perform a thorough gynecologic and endocrinologic evaluation; assess pelvic anatomy and rule out early pregnancy, primary ovarian failure (as indicated by increased serum concentrations of FSH and LH and low serum estrogen concentrations), and neoplasms. (See Contraindications under Cautions.) Perform a thorough diagnostic evaluation in patients who demonstrate abnormal uterine bleeding and other signs of endometrial abnormalities. (See Contraindications under Cautions.) Evaluate partner’s infertility.

• When ultrasound assessment and serum estradiol concentrations show sufficient follicular maturation, administer choriogonadotropin alfa 1 day after last dose of follicle-stimulating agent to complete final follicular maturation and induce ovulation.

• Withhold further follicle-stimulating therapy and delay or withhold choriogonadotropin alfa if ovaries show an excessive response to treatment with gonadotropins because of increased risk of ovarian hyperstimulation syndrome (OHSS). (See Ovarian Hyperstimulation Syndrome under Cautions.)

• Encourage daily sexual intercourse beginning 1 day prior to administration of choriogonadotropin alfa until ovulation occurs (as determined by rise in basal body temperature, increase in serum progesterone concentrations, and menstruation following shift in basal body temperature). (See Adequate Patient Evaluation and Monitoring under Cautions.)

• Examine ovaries by ultrasound for persistent cysts, particularly when attempts at stimulation of ovulation follow immediately after unsuccessful stimulated cycle.

Administration

Sub-Q Administration

Administer by sub-Q injection, generally into abdomen using commercially available prefilled syringe; may be self-administered by patient.

Dosage

Adults

Female Infertility

ART

250 mcg, given 1 day following last dose of follicle-stimulating agent. (See General under Dosage and Administration.)

Ovulation Induction

250 mcg, given 1 day following last dose of follicle-stimulating agent. (See General under Dosage and Administration.)

If stimulation of ovulation is unsuccessful, adjust dosage of follicle-stimulating agent administered in subsequent cycles based on woman’s response in preceding cycle.

Prescribing Limits

Adults

Female Infertility

Sub-Q

Maximum 500-mcg single dose studied in clinical trials.

Contraindications

• Known hypersensitivity to human chorionic gonadotropin preparations (including urinary-derived hCG) or any ingredient in formulation.

• Primary ovarian failure.

• Uncontrolled thyroid or adrenal dysfunction.

• Uncontrolled organic intracranial lesions (e.g., pituitary neoplasms).

• Abnormal intrauterine or vaginal bleeding of undetermined origin.

• Ovarian cysts or enlargement of undetermined origin.

• Sex-hormone-dependent neoplasms of reproductive tract and accessory organs.

• Pregnancy.

Warnings/Precautions

Warnings

Ovarian Enlargement

Risk of mild to moderate uncomplicated ovarian enlargement; may be accompanied by abdominal distention and/or pain, but generally regresses without treatment within 2–3 weeks. Careful monitoring of ovarian response recommended.

If ovaries are abnormally enlarged during controlled ovarian stimulation, withhold choriogonadotropin alfa during current course of therapy to minimize risk of OHSS. (See Ovarian Hyperstimulation Syndrome under Cautions.)

Ovarian Hyperstimulation Syndrome

Risk of potentially severe OHSS, characterized by apparent dramatic increase in vascular permeability that may result in rapid accumulation of fluid in peritoneal cavity, thorax, and potentially, pericardium.

May progress rapidly (within 24 hours to several days). Initial manifestations include severe pelvic pain, nausea, vomiting, and weight gain. Other symptoms include abdominal pain/distention, diarrhea, severe ovarian enlargement, dyspnea, and oliguria. Hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events may occur.

Transient liver function test abnormalities, which may be accompanied by morphologic changes (as detected by liver biopsy), reported.

Occurs most often after completion of gonadotropin therapy, reaching maximum severity after 7–10 days; usually resolves spontaneously with onset of menses. Monitor patients for ≥2 weeks after hCG administration. OHSS may be more severe and protracted if pregnancy occurs.

If severe OHSS develops, discontinue therapy, hospitalize patient, and consult clinician experienced in management of OHSS or fluid and electrolyte imbalances.

Multiple Births

Multiple ovulations resulting in multiple gestations reported in 30.9 or 13.3% of women during ART programs or ovulation induction, respectively.

Risk of multiple births correlates with number of embryos transferred.

Thromboembolism

Potential for arterial thromboembolism exists.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; exclude pregnancy before initiating treatment.

Animal studies indicate adverse effects on pregnancy outcomes and/or labor. (See Contraindications under Cautions.)

General Precautions

Adequate Patient Evaluation and Monitoring

Administer only under supervision of qualified clinicians experienced in fertility disorders and interpretation of indices of ovulation.

Monitor follicular development (e.g., using transvaginal ultrasound, serum estradiol concentrations) to correctly identify follicular maturation, determine timing of choriogonadotropin alfa administration, detect ovarian enlargement, and minimize risks of OHSS and multiple gestation.

Obtain clinical confirmation of ovulation from direct and indirect indices of progesterone production, including rise in basal body temperature, an increase in serum progesterone concentrations, and menstruation following shift in basal body temperature. Sonographic evidence of ovulation includes findings of fluid in cul-de-sac, ovarian stigmata, collapsed follicle, and secretory endometrium.

Specific Populations

Pregnancy

Category X. (See Fetal/Neonatal Morbidity and Mortality and also Contraindications under Cautions.)

Lactation

Not known whether choriogonadotropin alfa is distributed into milk. Use caution.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Safety and efficacy not established.

Hepatic Impairment

Safety and efficacy not established.

Renal Impairment

Safety and efficacy not established.

Common Adverse Effects

ART: Injection site reactions (i.e., pain, bruising), abdominal pain, nausea, vomiting, postoperative pain.

Ovulation induction: Injection site reactions (i.e., pain, inflammation, bruising, other injection site reaction), ovarian cysts, ovarian hyperstimulation, abdominal pain.

General

• Should be prescribed only by clinicians experienced in infertility treatment and who are familiar with cautions, precautions, and contraindications associated with such therapy.

• Prior to treatment initiation with choriogonadotropin alfa, perform a thorough gynecologic and endocrinologic evaluation; assess pelvic anatomy and rule out early pregnancy, primary ovarian failure (as indicated by increased serum concentrations of FSH and LH and low serum estrogen concentrations), and neoplasms. (See Contraindications under Cautions.) Perform a thorough diagnostic evaluation in patients who demonstrate abnormal uterine bleeding and other signs of endometrial abnormalities. (See Contraindications under Cautions.) Evaluate partner’s infertility.

• When ultrasound assessment and serum estradiol concentrations show sufficient follicular maturation, administer choriogonadotropin alfa 1 day after last dose of follicle-stimulating agent to complete final follicular maturation and induce ovulation.

• Withhold further follicle-stimulating therapy and delay or withhold choriogonadotropin alfa if ovaries show an excessive response to treatment with gonadotropins because of increased risk of ovarian hyperstimulation syndrome (OHSS). (See Ovarian Hyperstimulation Syndrome under Cautions.)

• Encourage daily sexual intercourse beginning 1 day prior to administration of choriogonadotropin alfa until ovulation occurs (as determined by rise in basal body temperature, increase in serum progesterone concentrations, and menstruation following shift in basal body temperature). (See Adequate Patient Evaluation and Monitoring under Cautions.)

• Examine ovaries by ultrasound for persistent cysts, particularly when attempts at stimulation of ovulation follow immediately after unsuccessful stimulated cycle.

Administration

Sub-Q Administration

Administer by sub-Q injection, generally into abdomen using commercially available prefilled syringe; may be self-administered by patient.

Dosage

Adults

Female Infertility

ART

250 mcg, given 1 day following last dose of follicle-stimulating agent. (See General under Dosage and Administration.)

Ovulation Induction

250 mcg, given 1 day following last dose of follicle-stimulating agent. (See General under Dosage and Administration.)

If stimulation of ovulation is unsuccessful, adjust dosage of follicle-stimulating agent administered in subsequent cycles based on woman’s response in preceding cycle.

Prescribing Limits

Adults

Female Infertility

Sub-Q

Maximum 500-mcg single dose studied in clinical trials.

No formal drug interaction studies to date.

Laboratory Tests