Also Known As: HCG, hCG, β-hCG, choriogonadotropin alfa, chorionic gonadotropin, Pregnyl, Novarel, Profasi, Ovidrel, Ovitrelle
HCG is a heterodimeric glycoprotein hormone of the cystine-knot growth-factor superfamily and is chemically a protein, NOT a synthetic peptide. It consists of a 92-amino-acid α-subunit (shared with LH, FSH and TSH) and a 145-amino-acid β-subunit (β-hCG, HCG-specific) that associate non-covalently and bear extensive N-linked and O-linked glycosylation; the assembled glycoprotein has a molecular weight of approximately 36–37 kDa, with glycans accounting for roughly 25–30% of the mass. Pharmaceutical HCG is produced either by purification from the urine of pregnant women (urinary hCG, e.g. Pregnyl, Novarel, Profasi) or by recombinant DNA technology in Chinese-hamster-ovary cells (choriogonadotropin alfa, marketed as Ovidrel in the US and Ovitrelle in the EU). Acting through the LHCGR, HCG reproduces an LH-like signal with a markedly longer plasma half-life (~29 h subcutaneous Ovidrel vs ~30 min for LH), which enables single-dose triggering of final follicular maturation in ART and substitution of LH in male hypogonadotropic hypogonadism.
HCG is a placental glycoprotein hormone that signals predominantly through the luteinizing hormone / choriogonadotropin receptor (LHCGR) — a Class A G-protein-coupled receptor — driving Gαs → adenylyl cyclase → cAMP → PKA-mediated steroidogenesis in gonadal target cells; the four O-linked glycans on the β-subunit C-terminal peptide produce an LH-like signal with a markedly longer plasma half-life than endogenous LH.
In a normal menstrual cycle, the pituitary LH surge triggers final follicular maturation, oocyte meiotic resumption and ovulation; in pregnancy, HCG produced by the syncytiotrophoblast of the implanting blastocyst takes over corpus-luteum support to sustain progesterone secretion until placental steroidogenesis is established. Because HCG and LH share the LHCGR (Pierce & Parsons 1981), exogenous pharmaceutical HCG — whether purified from pregnancy urine or produced recombinantly in CHO cells — is used clinically and in research to mimic the LH surge in controlled-ovarian-stimulation cycles and to substitute for LH in men with hypogonadotropic hypogonadism. The C-terminal peptide of β-hCG carries four O-linked glycans (Ser121, Ser127, Ser132, Ser138 of the mature β-chain) that protect the molecule from rapid renal clearance (Cole 2010), giving it a substantially longer half-life than LH and enabling once-per-cycle dosing as an ovulation trigger. Recombinant choriogonadotropin alfa is produced in genetically engineered CHO cells, secreted into the medium and purified by chromatography; urinary hCG is purified from large pools of pregnancy urine and standardised by bioassay in International Units.
The regulatory evidence base rests on two Phase III head-to-head trials of recombinant vs urinary hCG as ovulation trigger (Driscoll 2000; Chang 2001), an RCT of intratesticular testosterone maintenance under exogenous-testosterone-induced gonadotropin suppression (Coviello 2005), comprehensive reviews of HCG isoforms as tumour markers (Stenman 2006) and biological functions (Cole 2010), and a criteria-based meta-analysis refuting the Simeons "HCG diet" claim (Lijesen 1995).
Studies report that subcutaneous Ovidrel 250 µg vs intramuscular Profasi 5,000 IU produced equivalent primary endpoints (oocytes retrieved, mature oocytes, fertilisation rate), with higher serum progesterone 6–7 days after trigger in the rhCG arm and fewer local-injection-site reactions.
— Driscoll et al., Hum Reprod 2000;15(6):1377–1381
Studies report a mean oocyte yield of 13.6 (Ovidrel 250 µg) vs 14.6 (Ovidrel 500 µg) vs 13.7 (Profasi 10,000 IU) in an open randomised three-arm study — non-inferiority of the 250 µg recombinant subcutaneous dose with fewer local injection-site reactions, providing the clinical basis for the FDA (2000) and EMA (2001) Ovidrel/Ovitrelle approvals.
— Chang et al., Fertil Steril 2001;76(1):67–74
Studies report that hCG co-administration (125, 250 or 500 IU every other day) in healthy men under exogenous testosterone preserved intratesticular testosterone in a dose-dependent manner, while testosterone alone produced a ~94% drop from baseline — the mechanistic rationale for adding hCG to testosterone regimens to preserve the spermatogenic axis.
— Coviello et al., J Clin Endocrinol Metab 2005;90(5):2595–2602
Studies describe the differential diagnostic utility of intact hCG, free β-subunit, hyperglycosylated hCG and the urinary β-cf fragment in gestational trophoblastic disease, testicular germ-cell tumours and selected non-trophoblastic malignancies — and emphasise that assays detecting only intact hCG can miss free-β-subunit-secreting tumours.
— Stenman et al., Hum Reprod Update 2006;12(6):769–784
Studies classify four hCG-related molecules with distinct biology: pregnancy hCG (syncytiotrophoblast, endocrine function), hyperglycosylated hCG (cytotrophoblast, invasion), free β-subunit (multiple non-trophoblastic malignancies) and pituitary hCG (low levels in postmenopausal women) — a stratification that shapes tumour-marker interpretation and research logic.
— Cole, Reprod Biol Endocrinol 2010;8:102
Studies document, in a meta-analysis of 24 trials (8 controlled, 16 uncontrolled), that HCG as an adjunct to a very-low-calorie diet produces no weight loss, no fat redistribution, no reduction in hunger and no improvement in well-being beyond the calorie restriction itself; the FDA has separately issued public warnings against unapproved "homeopathic" HCG weight-loss products.
— Lijesen et al., Br J Clin Pharmacol 1995;40(3):237–243
Observed in research settings
In Phase III ART trials and decades of clinical experience, HCG has been generally well-tolerated, with adverse events that overlap substantially between recombinant and urinary preparations. The clinically most important risks observed in research settings are ovarian hyperstimulation syndrome (OHSS) in women undergoing controlled ovarian stimulation, gynecomastia and acne in men receiving hCG, and injection-site reactions and hypersensitivity across populations.
Pierce JG, Parsons TF Glycoprotein hormones: structure and function Annu Rev Biochem 1981;50:465–495. 1981 .
Wu H, Lustbader JW, Liu Y, Canfield RE, Hendrickson WA Structure of human chorionic gonadotropin at 2.6 Å resolution from MAD analysis of the selenomethionyl protein (PDB 1HCN) Structure 1994;2(6):545–558. 1994 .
Lijesen GKS, Theeuwen I, Assendelft WJJ, Van Der Wal G The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis Br J Clin Pharmacol 1995;40(3):237–243. 1995 .
Driscoll GL, Tyler JPP, Hangan JT, Fisher PR, Birdsall MA, Knight DC 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(6):1377–1381. 2000 .
Chang P, Kenley S, Burns T, Denton G, Currie K, DeVane G, O'Dea L 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 IVF–ET Fertil Steril 2001;76(1):67–74. 2001 .
Coviello AD, Matsumoto AM, Bremner WJ, Herbst KL, Amory JK, Anawalt BD, Sutton PR, Wright WW, Brown TR, Yan X, Zirkin BR, Jarow JP Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression J Clin Endocrinol Metab 2005;90(5):2595–2602. 2005 .
Stenman UH, Tiitinen A, Alfthan H, Valmu L The classification, functions and clinical use of different isoforms of HCG Hum Reprod Update 2006;12(6):769–784. 2006 .
Cole LA Biological functions of hCG and hCG-related molecules Reprod Biol Endocrinol 2010;8:102. 2010 .
U.S. Food and Drug Administration / EMD Serono Ovidrel® (choriogonadotropin alfa) — Highlights of Prescribing Information; NDA 21-149 approved 20 September 2000 FDA Drugs@FDA, 2010 label revision. 2000 .
European Medicines Agency Ovitrelle (choriogonadotropin alfa) — EPAR product information; centralised marketing authorisation 2 February 2001 EMA, EMEA/H/C/000320. 2001 .
GnRH Agonist (natural human decapeptide; pulsatile stimulation of the pituitary–gonadal axis)
Natural human GnRH/LHRH decapeptide (pyroEHWSYGLRPG-NH₂); full GnRHR agonist that, when delivered pulsatilely, stimulates pituitary LH/FSH secretion — historically FDA-approved as Factrel (diagnostic) and Lutrepulse (pulsatile pump), now discontinued in the US but available in EU/Canada as Lutrelef.
View DetailsThymic peptide hormone analogue / immune modulator (slug: immune-other; pleiotropic TLR2/TLR9-mediated effect rather than a classical single-receptor agonist)
Synthetic 28-amino-acid N-acetylated thymic peptide (thymalfasin / Zadaxin); pleiotropic TLR2/TLR9-mediated immune modulator — approved as Zadaxin in 35+ countries (Italy, China, Vietnam, Mexico and others) for chronic hepatitis B and as a vaccine adjuvant in immunocompromised populations, but NOT FDA-approved in the United States — only orphan-drug designations exist there.
View DetailsGHRH(1-29) Receptor Agonist (Growth-Hormone Secretagogue, GRF Class)
Synthetic GHRH(1-29) amide (Geref); the shortest fragment of human growth-hormone-releasing hormone that retains full biological activity — historically FDA-approved for pediatric GH deficiency and voluntarily withdrawn from the US market in 2008 for commercial reasons.
View Details