Pregnyl

Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced by the placenta, with actions nearly identical to luteinizing hormone. FDA-approved urinary-derived products are Pregnyl and Novarel (chorionic gonadotropin for injection, USP, for intramuscular use) and generic chorionic gonadotropin; recombinant choriogonadotropin alfa (Ovidrel) is approved for subcutaneous use in assisted reproduction.

• Prepubertal cryptorchidism not due to anatomical obstruction.
• Selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to pituitary deficiency) in males.
• Induction of ovulation and pregnancy in anovulatory infertile women whose anovulation is secondary and not due to primary ovarian failure, and who have been appropriately pretreated with human gonadotropins.
• Choriogonadotropin alfa: final follicular maturation and early luteinization in assisted reproductive technology, and ovulation induction.

hCG binds the luteinizing hormone/chorionic gonadotropin receptor. In males it stimulates Leydig cells to produce testosterone and other androgens, supporting spermatogenesis and testicular descent. In females it triggers final follicular maturation and ovulation, and supports the corpus luteum and progesterone production.

hCG is not active orally and is given by intramuscular or subcutaneous injection. After IM injection, peak serum levels occur within about 6 hours. Elimination is biphasic, with a terminal half-life of roughly one day; a portion is excreted unchanged in urine. Testosterone rises within days of dosing in males.

Current Pregnyl labeling (Rev 03/2025):

• Prior hypersensitivity to human gonadotropins, including hCG, or any excipient.
• High serum FSH indicating primary gonadal failure in women.
• Uncontrolled non-gonadal endocrinopathies (thyroid, adrenal or pituitary).
• Tumors of the hypothalamus or pituitary; tumors of the ovary, breast or uterus in females, or of the breast or prostate in males.
• Malformations of the reproductive organs incompatible with pregnancy, or uterine fibroids incompatible with pregnancy.
• Abnormal vaginal bleeding of undetermined origin.

Novarel labeling (older format) lists precocious puberty, prostatic carcinoma or other androgen-dependent neoplasm, and prior allergic reaction to hCG. Current Pregnyl labeling treats precocious puberty as a precaution.

• Use by prescribers experienced in managing infertility or the labeled endocrine disorders.
• Anaphylaxis and other hypersensitivity reactions have been reported.
• Ovarian hyperstimulation syndrome (OHSS), ovarian enlargement and cyst rupture can follow ovulation induction; OHSS can progress rapidly and cause fluid shifts, thromboembolism and organ dysfunction.
• Multiple pregnancy occurs more often with ovulation induction.
• Arterial thromboembolism has been reported with hCG used with menotropins.
• hCG can induce precocious puberty in boys treated for cryptorchidism; stop if signs occur.
• Androgen-induced fluid retention: use with caution in cardiac or renal disease, hypertension, epilepsy, migraine or asthma.
• With ovulation induction, ovarian torsion, ectopic pregnancy and spontaneous abortion are also described in labeling.

No formal drug interaction studies are described in labeling. Use with menotropins, follitropins or clomiphene adds to the risk of OHSS and multiple pregnancy. hCG produces positive serum and urine pregnancy tests and can interfere with hCG-based tumor markers for some time after dosing.

Headache, irritability, restlessness, depression, fatigue, edema, precocious puberty, gynecomastia, injection-site pain and hypersensitivity reactions. In women undergoing ovulation induction: OHSS, ovarian cysts, multiple gestation and thromboembolic events.

Current Pregnyl labeling (Rev 03/2025) states that hCG is not indicated in pregnancy; it may be used for luteal-phase support and is discontinued once pregnancy is confirmed. Older-format Novarel labeling also cautions that hCG may cause fetal harm when given to a pregnant woman. Follow current product labeling on use in pregnancy. It is not known whether exogenous hCG passes into breast milk; use during lactation only if the prescriber judges it necessary.

Males: serum testosterone, signs of virilization or precocious puberty in boys, semen analysis when fertility is the goal, and breast changes. Females undergoing ovulation induction: ultrasound follicle monitoring, serum estradiol, and signs of OHSS such as abdominal pain, distension and rapid weight gain.

• Pregnyl (chorionic gonadotropin for injection, USP) Prescribing Information.
• Novarel (chorionic gonadotropin for injection, USP) Prescribing Information, Ferring Pharmaceuticals.
• Ovidrel (choriogonadotropin alfa injection) Prescribing Information, EMD Serono.