ATC Class: G03GA08
VA Class: HS400
CAS Number: 9002-61-3
Brands: Novarel, Pregnyl
Uses for Gonadotropin, Chorionic
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
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
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
Gonadotropin, Chorionic Dosage and Administration
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
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
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
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
Hypogonadotropic Hypogonadism in Males
Cautions for Gonadotropin, Chorionic
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
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
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
Fetal/Neonatal Morbidity and Mortality
Exclude pregnancy before initiating treatment with hCG and menotropins.gg (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.)
Testicular tumors reported occasionally in young men with secondary infertility.e
Adequate Patient Evaluation and Monitoring
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
Category X.c (See Fetal/Neonatal Morbidity and Mortality and also Contraindications under Cautions.)
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
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
Radioimmunoassays for gonadotropins
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
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
Extensively metabolized, principally in liver and kidneys, to active metabolites.d
Excreted in urine (20%) as metabolites.d
Powder for Injection
Stimulates differentiation of and early maturation of the cells lining the seminiferous tubules (spermatogenic and Sertoli cells) of the testes.e
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
Advice to Patients
Importance of discussing duration of treatment and required monitoring procedures.p
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
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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, 2004-2014, Selected Revisions June 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
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. [PubMed 16877746]
e. AHFS drug information 2007. McEvoy GK, ed. Gonadotropin, Chorionic. Bethesda, MD: American Society of Health-System Pharmacists; 2007:3116-7.
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. [PubMed 9758439]
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. [PubMed 9589647]
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. [PubMed 8671503]
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. [PubMed 6768759]
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. [PubMed 16377065]
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. [PubMed 10831560]
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. [PubMed 8325934]
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. [PubMed 17055817]
t. Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update. 2002; 8:559-77. [PubMed 12498425]
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. [IDIS 175725] [PubMed 6889041]
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. [IDIS 150868] [PubMed 6810084]
y. Gershanik J, Boecler B, Ensley H et al. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982; 307:1384-8. [IDIS 160823] [PubMed 7133084]
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. [PubMed 6440575]
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. [IDIS 181207] [PubMed 6695984]
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. [PubMed 11547110]
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. [PubMed 9988392]
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. [PubMed 9696217]
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. [PubMed 17697490]
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. [PubMed 7698849]
oo. EMD Serono. Ovidrel (choriogonadotropin alfa) prefilled syringe FAQ’s. Rockland, MA; 2007. Available at Serono website. Accessed 2007 Nov 27.
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