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Gonadotropin, Chorionic

Class: Gonadotropins and Antigonadotropins
ATC Class: G03GA08
VA Class: HS400
CAS Number: 9002-61-3
Brands: Novarel, Pregnyl

Medically reviewed on June 1, 2018


Gonad-stimulating hormone; urinary-derived, naturally occurring human chorionic gonadotropin (u-hCG).a e

Uses for Gonadotropin, Chorionic

Prepubertal Cryptorchidism

Management of prepubertal cryptorchidism not caused by anatomical obstruction.a b c e mm

Induction of testicular descent usually only temporary; response may be permanent in some patients.a b c e

Differential diagnosis (hCG stimulatory test) of cryptorchidism in prepubertal boys to predict whether subsequent orchidopexy will be required.a b c e bb In general, hCG is thought to induce testicular descent in patients in whom descent would have occurred at puberty.a b c e

Start corrective therapy for cryptorchidism before pubescence to prevent irreparable testicular damage; opinions differ regarding optimum age for treatment.e f mm Manufacturers recommend instituting u-hCG therapy for prepubertal cryptorchidism in boys 4–9 years of age.a b c e

Hypogonadotropic Hypogonadism in Males

Management of hypogonadotropic hypogonadism resulting from pituitary deficiency.a b c e f ee ff

Stimulation of spermatogenesis in males with hypogonadotropic hypogonadism secondary to pituitary deficiency.e f ee ff jj Full response may require concurrent FSH or menotropins therapy.f ee ff jj nn

Female Infertility

Used in conjunction with follicle-stimulating agent(s) (e.g., menotropins as fixed-combination preparations or separate components, FSH) to induce ovulation in anovulatory, infertile women in whom anovulation is secondary (e.g., pituitary insufficiency).a b c e g n q

Should not be used in infertile women in whom anovulation is due to primary ovarian failure.a b c e g n q

Has been used for the treatment of infertility resulting from deficiency of corpus luteum during luteal phase of menstrual cycle.e g h k n

Other Uses

Manufacturer states that u-hCG has not been shown to be effective as adjunctive therapy for the treatment of obesity.a b c e

Gonadotropin, Chorionic Dosage and Administration


Female Infertility

  • Should be prescribed only by clinicians experienced in infertility treatment and who are familiar with criteria for patient selection and cautions, precautions, and contraindications associated with hCG/follicle-stimulating therapy.a b c e r hh

  • Administer follicle-stimulating agent(s) until sufficient follicular maturation (as determined by serum estradiol concentrations and ovary ultrasound examinations) occurs.g n q t gg hh

  • When ultrasound assessment and serum estradiol concentrations show sufficient follicular maturation, discontinue follicle-stimulating therapy and administer hCG to complete final follicular maturation and induce ovulation.g n q gg hh

  • Withhold further follicle-stimulating therapy and delay or withhold hCG if ovaries show an excessive response to treatment with gonadotropins because of increased risk of ovarian hyperstimulation syndrome (OHSS).g n p q r t gg hh (See Ovarian Hyperstimulation Syndrome under Cautions.)

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

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


IM Administration

Administer only by IM injection.a b c


Reconstitute vial containing 10,000 units of chorionic gonadotropin lyophilized powder with 10 mL of bacteriostatic water for injection or water for injection (provided by manufacturer).a b

Gently agitate until powder is completely dissolved.a b


Dosage is expressed in terms of USP units (units).a b c e Each mg of u-hCG is approximately equivalent to ≥1500 USP units.e o One USP unit is equivalent to 1 WHO international unit.e

Dosage regimens vary widely; individualize dosage carefully based on condition being treated, patient age and weight, and clinician’s judgment.a b c e Following treatment regimens suggested by various experts:a b c

Pediatric Patients

Prepubertal Cryptorchidism

Boys ≥4 years of age: 4000 units 3 times weekly for 3 weeks or 5000 units every other day for 4 doses or 15 doses of 500–1000 units given over 6 weeks suggested.a b c e

Alternatively, 500 units may be given 3 times weekly for 4–6 weeks for boys ≥4 years of age.a b c e If this course of therapy is not successful, may administer a subsequent course of therapy 1 month later and increase dosage to 1000 units 3 times weekly for 4–6 weeks.a b c e

Hypogonadotropic Hypogonadism in Males

500–1000 units 3 times weekly for 3 weeks suggested, followed by same dosage twice weekly for 3 weeks.a b c e

Alternatively, 4000 units 3 times weekly for 6–9 months, followed by 2000 units 3 times weekly for 3 months.a b c e


Hypogonadotropic Hypogonadism in Males

500–1000 units 3 times weekly for 3 weeks suggested, followed by same dosage 2 times weekly for 3 weeks.a b c e

Alternatively, 4000 units 3 times weekly for 6–9 months, followed by 2000 units 3 times weekly for 3 months.a b c e

Female Infertility
Ovulation Induction

5000–10,000 units given 1 day following last dose of follicle-stimulating therapy suggested.a b c e g n q gg hh

Cautions for Gonadotropin, Chorionic


  • Precocious puberty.a b c e

  • Carcinoma of prostate or other androgen-dependent neoplasms.a b c e

  • Pregnancy.e p q gg hh

  • Known hypersensitivity to hCG or any ingredient in formulation.a b c e



Ovarian Enlargement

Risk of mild to moderate uncomplicated ovarian enlargement when used in conjunction with follicle-stimulating agent(s); may be accompanied by abdominal distention and/or pain but generally regresses without treatment within 2–3 weeks.p q gg hh Careful monitoring of ovarian response recommended.p q r gg

If ovaries are abnormally enlarged, withhold hCG administration during current course of therapy to minimize risk of OHSS.q t gg hh (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.e p q r gg hh

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

Transient liver function test abnormalities, which may be accompanied by morphologic changes (as detected by liver biopsy), reported.p q r t gg hh

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

If severe OHSS occurs, discontinue therapy, hospitalize patient, and consult clinician experienced in management of OHSS or fluid and electrolyte imbalances.p q r gg hh

Multiple Births

Multiple ovulations resulting in multiple gestations reported in approximately 20% of women during ovulation induction.a e n q

Ovarian Cysts

Enlargement of preexisting ovarian cysts or rupture of ovarian cysts with resultant hemoperitoneum reported.a b c e


Arterial thromboembolism reported.a b c e

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity demonstrated in mice.a c e

Exclude pregnancy before initiating treatment with hCG and (See Contraindications under Cautions.)

Benzyl Alcohol in Neonates

Bacteriostatic water for injection or water for injection diluent contains benzyl alcohol as a preservative, which has been associated with toxicity (fatalities) in neonates.a b c v w x y z aa (See Pediatric Use under Cautions.)

General Precautions

Androgenic Effects

May cause fluid retention; use caution in patients with asthma, seizure disorders, migraine, or cardiac or renal disease.a c e

Induction of precocious puberty may occur in prepubertal males with cryptorchidism.a b c e (See Pediatric Use under Cautions.)

Tumorigenic Effects

Testicular tumors reported occasionally in young men with secondary infertility.e

Adequate Patient Evaluation and Monitoring

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

Monitor follicular development (e.g., using ovarian ultrasound, serum estradiol concentrations) to correctly identify follicular maturation, determine timing of hCG administration, detect ovarian enlargement, and minimize risks of OHSS and multiple gestation.q r t gg hh

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

Specific Populations


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


Not known whether u-hCG is distributed into milk.a c e Use caution.a c e

Pediatric Use

Safety and efficacy not established in children <4 years of age.a b c e

Carefully monitor prepubertal males with cryptorchidism during u-hCG therapy since induction of precocious puberty may occur.a b c e If signs of precocious puberty (phallic enlargement, testicular enlargement and redness, development of pubic hair, aggressive behavior) occur, discontinue therapy;a b c e these signs are reversible ≤4 weeks after cessation of therapy.e (See Contraindications under Cautions.)

Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity (fatal “gasping syndrome”) in neonates; each multiple-dose vial of reconstituted drug contains 0.9% benzyl alcohol.a b c v w x y z aa

Geriatric Use

Safety and efficacy not established.b

Common Adverse Effects

Headache,a b c e g irritability,a b c e restlessness,a b c e depression,a b c e fatigue or tiredness,a b c e edema,a b c e precocious puberty,a b c gynecomastia,a b e ee ff pain at injection site.a b c e

Interactions for Gonadotropin, Chorionic

Laboratory Tests

Laboratory Test



Radioimmunoassays for gonadotropins

Possible cross reaction with radioimmunoassays for gonadotropins, particularly LHa c e

Individual laboratories should establish degree of cross reactivity with their gonadotropin assayc e

When requesting gonadotropin concentrations, inform laboratory of u-hCG therapyc e

Gonadotropin, Chorionic Pharmacokinetics



Following single injection in hypogonadotropic men, onset and peak stimulation of testosterone production (as indicated by plasma testosterone concentrations) occur at 24 and 80 hours, respectively.j

Following single injection in prepubertal and early pubertal boys with cryptorchidism, peak stimulation of testosterone production occurs at 2–5 days.kk


Following midcycle administration, stimulation of luteal-phase progesterone production (as indicated by serum progesterone concentrations) persists for approximately 1 week.n (See Actions.)

Following single injection in prepubertal boys with cryptorchidism, stimulation of testosterone production persists for ≥6 days.kk

Special Populations

Bioavailability is less in obese infertile women than in nonobese women.u



Distributed mainly into testes and ovaries; smaller amounts may be distributed into proximal tubules of renal cortex.e

Not known if distributed into milk.a c e



Extensively metabolized, principally in liver and kidneys, to active metabolites.d

Elimination Route

Excreted in urine (20%) as metabolites.d


Biphasic; terminal half-life is about 23–33 hours.d e u




Powder for Injection

Pregnyl or Novarel: 15–30°C.b c After reconstitution, refrigerateb at 2–8°C;c use Novarel within 30c days and Pregnyl within 60 days.b

Generic preparation: 20–25°C.a After reconstitution, refrigerate at 2–8°C;a use within 60 days.a


  • Principal pharmacologic effects of u-hCG are virtually identical to those of LH; exhibits minimal FSH activity.a b c e bb nn

  • Stimulates differentiation of, and androgen production by, interstitial cells (Leydig cells) of the testes.a b c e j bb

  • Stimulates differentiation of and early maturation of the cells lining the seminiferous tubules (spermatogenic and Sertoli cells) of the testes.e

  • Stimulates spermatogenesis and increases testes volume.f ee ff jj nn

  • Stimulates development of secondary sex characteristics in prepubertal males.a b c e ee ff

  • Induces aromatization of testosterone to estradiol in testes and peripherally; gynecomastia may ff

  • Substitutes for the endogenous LH surge responsible for ovulation;e k l stimulates late maturation of ovarian follicle,m t u resumption of oocytic meiosis,l m and initiation of rupture of preovulatory ovarian follicle.l m

  • Induces and maintains corpus luteum (as evidenced by increased serum progesterone concentrations).g h k l m n u

  • No known effect on appetite or sense of hunger, or on mobilization or distribution of body fat.a b c e

Advice to Patients

  • Importance of discussing duration of treatment and required monitoring procedures.p

  • Importance of informing patient of potential adverse effects (e.g., OHSS, multiple gestation).p hh oo

  • Importance of patients informing a clinician if severe pain or bloating in stomach or pelvic area, severe upset stomach, vomiting, or weight gain occurs.oo

  • Importance of patient informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.a b c

  • Importance of women informing their clinician if they plan to breast-feed.a b c

  • Importance of informing patient of other important precautionary information.a b c (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Chorionic Gonadotropin


Dosage Forms


Brand Names



For injection, for IM use only

10,000 USP units*

Chorionic Gonadotropin (with bacteriostatic water for injection diluent with benzyl alcohol)




Pregnyl (with water for injection diluent with benzyl alcohol)


AHFS DI Essentials. © Copyright 2018, Selected Revisions June 1, 2008. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


a. Abraxis Pharmaceutical Products. Chorionic gonadotropin prescribing information. Schaumburg, IL; 2006 May.

b. Food and Drug Administration. Pregnyl (chorionic gonadotropin) injection [2006: Organon]. Rockville, MD; FDA action date 2007 Feb 2. From Drugs@FDA website. Accessed 2007 Nov 29.

c. Ferring Pharmaceuticals. Novarel (chorionic gonadotropin) injection prescribing information. Suffern, NY; 2004 Feb.

d. Stenman U, Tiitinen A, Alfthan H et al. The classification, functions and clinical use of different isoforms of HCG. Hum Reprod Update. 2006; 12:769-84.

e. AHFS Drug Information. McEvoy GK, ed. Gonadotropin, Chorionic. Bethesda, MD: American Society of Health-System Pharmacists.

f. Buchter D, Behre HM, Kliesch S et al. Pulsatile GNRH or human chorionic gonadotropin/human menopasual gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol. 1998; 139:298-303.

g. European Recombinant Human LH Study Group. Recombinant human luteinizing hormone (LH) to support recombinant human follicle stimulating hormone (FSH)-induced follicular development in LH- and FSH-deficient anovulatory women: a dose-finding study. J Clin Endocrinol Metab. 1998; 83:1507-14.

h. Herman A, Raziel A, Strassburger D et al. The benefits of mid-luteal addition of human chorionic gonadotropin in in-vitro fertilization using a down-regulation protocol and luteal support with progesterone. Hum Reprod. 1996; 11:1552-7.

j. Smals AGH, Pieters GF, Kloppenborg PWC et al. Lack of a biphasic steroid response to single human chorionic gonadotropin administration in patients with isolated gonadotropin deficiency. J Clin Endocrinol Metab. 1980; 50:879-81.

k. Krause BT, Ohlinger R. Safety and efficacy of low dose hCG for luteal support after triggering ovulation with a GNRH agonist in cases of polyfollicular development. Eur J Obstet Gynecol Reprod Biol. 2006; 126:87-92.

l. Chang P, Kenly S, Burns T et al. Recombinant human chorionic gonadotropin (rhCG) in assisted reproductive technology: results of a clinical trial comparing two doses of rhCG (Ovidrel) to urinary hCG (Profasi) for induction of final follicular maturation in in vitro fertilization-embryo transfer. Feril Steril. 2001; 76:67-74.

m. Driscoll GL, Tyler JP, Hanagan JT et al. A prospective, randomized, controlled, double-blind, double-dummy comparison of recombinant and urinary HCG for inducing oocyte maturation and follicular luteinization in ovarian stimulation. Hum Reprod. 2000; 15:1305-10.

n. Martin KA, Hall JE, Adams JM et al. Comparison of exogenous gonadotropins and pulsatile gonadotropin-releasing hormone for induction of ovulation in hypogonadotropic amenorrhea. J Clin Endocrinol Metab. 1993; 77:125-9.

o. The United States pharmacopeia, 31st rev, and The national formulary, 26th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 2008:2294-5.

p. Serono Inc. Ovidrel (choriogonadotropin alfa) injection prescribing information. Rockland MA; 2006 Jul.

q. EMD Serono Inc. Gonal-F RFF (follitropin alfa) pen for injection prescribing information. Rockland, MA; 2005 Aug.

r. Practice Committee, American Society of Reproductive Medicine. Ovarian hyperstimulation syndrome. An educational bulletin. Fertil Steril. 2006; 86:S178-83.

t. Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update. 2002; 8:559-77.

u. Chan CCW, Ng EHY, Chan MMY et al. Biovailability of intramuscular or subcutaneous injection in obese and non-obese women. Hum Reprod. 2003;

v. American Academy of Pediatrics, Committee on Fetus and Newborn and Committee on Drugs. Benzyl alcohol: toxic agent in neonatal units. Pediatrics. 1983; 72:356-8.

w. Anon. Benzyl alcohol may be toxic to newborns. FDA Drug Bull. 1982; 12:10-11.

x. Centers for Disease Control. Neonatal deaths associated with use of benzyl alcohol. MMWR. 1982; 31:290-1.

y. Gershanik J, Boecler B, Ensley H et al. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982; 307:1384-8.

z. Menon PA, Thach BT, Smith CH et al. Benzyl alcohol toxicity in a neonatal intensive care unit: incidence, symptomatology, and mortality. Am J Perinatol. 1984; 1:288-92.

aa. Anderson CW, Ng KJ, Andresen B et al. Benzyl alcohol poisoning in a premature newborn infant. Am J Obstet Gynecol. 1984; 148:344-6.

bb. Kolon TF, Miller OF. Comparison of single versus multiple dose regimens for the human chorionic gonadotropin stimulatory test. J Urol. 2001; 166:1451-4.

ee. Barrio R de Luis D, Alonso M et al. Induction of puberty with human chorionic gonadotropin and follicle-stimulating hormone in adolescent males with hypogonadotropic hypogonadism. Fertil Steril. 1999; 71:244-8.

ff. European Metrodin HP Study Group. Efficacy and safety of highly purified urinary follicle-stimulating hormone with human chorionic gonadotropin for treating men with isolated hypogonadotropic hypogonadism. Fertil Steril. 1998; 70:256-62.

gg. Ferring Pharmaceuticals. Repronex (menotropins) injection prescribing information. Suffern, NY; 2005.

hh. EMD Serono. Luveris (lutropin alfa) injection prescribing information. Rockland, MA; 2005 May.

ii. Serono Inc: Personal communication on choriogonadotropin alfa.

jj. Bakircioglu ME, Erden HF, Ciray HN et al. Gonadotropin therapy in combination with ICSI in men with hypogonadotrophic hypogonadism. Reprod Biomed Online. 2007; 15:156-60.

kk. Tapanainen J, Martikainen H, Dunkel L et al. Steroidogenic response to a single injection of hCG in pre- and early pubertal cryptorchid boys. Clin Endocrinol. 1983; 18:355-62.

mm. Henna MR, Del Nero RGM, Sampaio CZS et al. Hormonal cryptorchidism therapy: systematic review with metanalysis of randomized clinical trials. Ped Surg Int. 2004; 20:357-9.

nn. Kung AWC, Zhong YY, Lam KSL et al. Induction of spermatogenesis with gonadotrophins in Chinese men with hypogonadotropic hypogonadism. Int J Androl. 1994; 17:241-7.

oo. EMD Serono. Ovidrel (choriogonadotropin alfa) prefilled syringe FAQ’s. Rockland, MA; 2007. Available at Serono website. Accessed 2007 Nov 27.