Human Chorionic Gonadotropin (hCG)
Also known as: hCG, HCG, Human Chorionic Gonadotrophin, Chorionic Gonadotropin, urinary hCG (u-hCG), recombinant hCG (r-hCG), Pregnyl, Ovitrelle, Hyperglycosylated hCG (hCG-H), hCGβ, β-core fragment hCG (bcf-hCG), β-hCG, free beta-subunit hCG
Glycoprotein hormone / Gonadotropin
What it is
hCG is a complex glycoprotein hormone composed of an α-subunit (shared with LH, FSH, TSH) and a hormone-specific β-subunit; the β-subunit contains two N-glycosylation and four O-glycosylation sites. At least five common molecular forms exist: regular hCG, sulfated hCG, hyperglycosylated hCG (hCG-H), free β-subunit, and hyperglycosylated free β-subunit. Regular hCG, produced by syncytiotrophoblast cells, acts as an agonist at the LH/hCG receptor (LHCGR), stimulating progesterone production by corpus luteum cells, supporting myometrial quiescence, and promoting uterine angiogenesis (PMID 25707740; PMID 29509368). hCG-H, produced by cytotrophoblast cells, functions as an autocrine invasion promoter, acting on TGF-β receptor 2 rather than LHCGR, and is the major hCG isoform during the first 2–3 weeks of pregnancy (PMID 25707740; PMID 26676718; PMID 30287399). hCG-H activates LHCGR with lower potency than regular hCG (EC50 7.1–14 pmol/L vs. 3.3 pmol/L for hCG reference). Immunomodulatory effects include stimulation of LIF production, inhibition of IL-6 by endometrial epithelial cells, modulation of uterine NK cells, Treg cells, and B cells to promote maternal immune tolerance. The free β-subunit and hyperglycosylated free β-subunit act as autocrines promoting growth and invasion in malignancies (PMID 22455390; PMID 20654692). β-core fragment hCG (bcf-hCG) promotes proliferation of glandular epithelial cells and influences endometrial gene expression including HOXA10 relevant to embryo implantation.
Class: Glycoprotein hormone / Gonadotropin
What it's studied for
- Ovulation trigger / assisted reproduction (IVF/ICSI) — intramuscular or subcutaneous hCG injection to trigger final oocyte maturation Human RCT
- Retrospective cohort of 2641 cycles: dual trigger with 2,000 IU hCG + GnRH agonist yielded higher implantation rates (50.0% vs. 32.0%) vs. hCG-only and comparable ongoing pregnancy rates (46.8% vs. 39.5%); OHSS rates low across all groups. PMID 41239008 Oliva et al., Journal of Assisted Reproduction and Genetics (2026)
- Meta-analysis of 17 RCTs (n=4751): intrauterine hCG ≥500 IU before cleavage-stage ET improved live birth rate (RR 1.57, 95%CI 1.32–1.87) and clinical pregnancy rate (RR 1.49, 95%CI 1.32–1.68); no benefit found for blastocyst-stage ET or doses <500 IU; no evidence of miscarriage reduction. PMID 30341915 Craciunas et al., Cochrane Database of Systematic Reviews (2018)
- Intrauterine (intracavity) hCG administration to improve endometrial receptivity and embryo implantation in subfertile women undergoing ART Human RCT
- Moderate-quality evidence for improved live birth and clinical pregnancy with IC-hCG ≥500 IU at cleavage-stage ET; insufficient evidence for blastocyst-stage ET. PMID 30341915 Craciunas et al., Cochrane Database of Systematic Reviews (2018)
- In vitro/ex vivo study: hCG loaded into uterine exosomes upregulated LIF and Trophinin, downregulated Muc-16 and IGFBP1; hCG-loaded exosomes had greater effect on endometrial receptivity markers than hCG alone. PMID 33737084 Hajipour et al., Life Sciences (2021)
- Corpus luteum support and progesterone maintenance in bovine embryo recipients Animal studies only
- In beef cows, ≥1000 IU hCG improved luteal area, progesterone concentration, and pregnancy per embryo transfer vs. control; accessory CL rate was dose-dependent; combining eCG + hCG reduced blood perfusion without further improving P/ET. PMID 40273828 Mattos et al., Animal Reproduction Science (2025)
- Prevention of recurrent miscarriage (hCG supplementation) Mixed
- Meta-analysis of Cochrane-identified trials: hCG supplementation appeared to reduce miscarriage risk (OR 0.26, 95%CI 0.14–0.52), but trials were methodologically heterogeneous and used urinary rather than recombinant hCG; authors concluded a new stratified RCT comparing r-hCG vs. u-hCG vs. placebo is needed. PMID 20653339 Carp, Gynecological Endocrinology (2010)
- Review: different teams have studied addition of hCG in patients with recurrent miscarriages or implantation failures; a sufficient dose of hCG appears necessary to maintain maternal tolerance, but definitive clinical evidence is lacking. PMID 32231662 Gridelet et al., Frontiers in Immunology (2020)
- Pregnancy confirmation and monitoring (serum/urine β-hCG measurement) Human observational
- In 4434 cleavage-stage fresh/frozen-thawed SET cycles, β-hCG cutoff values on day 14 post-ET were established: 89.6 mIU/L (pregnancy vs. none), 241.1 mIU/L (biochemical vs. clinical), 585.9 mIU/L (adverse vs. non-adverse outcome), 981.1 mIU/L (singleton vs. twin live birth). PMID 35733148 Zhang et al., Reproductive Health (2022)
- Gestational age-specific reference ranges for total serum hCG established in 8195 pregnant women; maternal smoking, BMI, parity, ethnicity, fetal sex, placental weight, and hyperemesis associated with total hCG levels. PMID 25963653 Korevaar et al., European Journal of Epidemiology (2015)
- Diagnosis and monitoring of gestational trophoblastic disease (GTD) and gestational trophoblastic neoplasia (GTN) Human observational
- Retrospective study (n=176): hCG ≥1400 IU/L at 2nd week post-molar evacuation (AUC 0.92, aOR 6.51) and ratio of 2nd-week to post-evacuation hCG ≥0.02 (AUC 0.88, aOR 12.27) independently predicted GTN. PMID 36116082 Rakprasit et al., Archives of Gynecology and Obstetrics (2023)
- Hyperglycosylated hCG proportion distinguishes quiescent GTD (no/low hCG-H, no therapy needed) from minimally invasive (chemorefractory, <40% hCG-H) and aggressive GTD (>40% hCG-H); waiting until total hCG >3000 IU/L before chemotherapy was successful in 10/10 minimally invasive cases. PMID 19822356 Cole & Muller, Gynecologic Oncology (2010)
- Proportion hyperglycosylated hCG (hCG-H/total hCG) marks persistent hydatidiform mole (100% detection at 5.1% false detection), distinguishes aggressive from minimally aggressive choriocarcinoma/GTN, and identifies quiescent GTD cases that will progress. PMID 25275660 Cole, International Journal of Gynecological Cancer (2014)
- Prenatal screening for Down syndrome (trisomy 21) and other aneuploidies Human observational
- In 21,641 maternal serum samples, hyperglycosylated-hCG (h-hCG) combined with maternal age, NT, and PAPP-A detected 78% of first-trimester Down syndrome cases at 3% FPR; h-hCG could replace free-beta measurements as early as 10 weeks. PMID 17590886 Palomaki et al., Prenatal Diagnosis (2007)
- Monitoring of medical abortion completeness via serum hCG decline Human observational
- Prospective study (n=59) of women ≤63 days gestation undergoing medical abortion with mifepristone 200 mg + misoprostol 800 mcg buccally: mean hCG decline was 70.0% by Day 3 and 91.4% by Day 5; a single Day-5 hCG may be clinically useful for early confirmation of complete abortion. PMID 27621046 Pocius et al., Contraception (2017)
- Tumor marker for nontrophoblastic malignancies (hCGβ free subunit) Human observational
- Review: ectopic hCGβ expression is widespread across cancer subtypes; free β-subunit detected in serum of cancer patients; proposed roles in angiogenesis, metastasis, and immune escape; hCG-based tumor vaccine showed protection against mammary tumors in mice. PMID 20654692 Iles et al., Molecular and Cellular Endocrinology (2010)
- Serum free β-subunit or urinary β-core fragment detected in 68% of ovarian, 51% of endometrial, and 46% of cervical malignancies; associated with poor prognosis; hyperglycosylated hCG is absolute marker of invasive mole and choriocarcinoma. PMID 19007977 Muller & Cole, Gynecologic Oncology (2009)
- Early detection of pregnancy after IVF and embryo transfer (hHCG vs. HCG+β assay comparison) Human observational
- In 155 women post-IVF ET: diagnostic performance of hyperglycosylated HCG and HCG+β on day 4 was not significantly different (AUC 0.88 vs. 0.90); superiority of hHCG over HCG+β was not demonstrated. PMID 34924288 Bosch et al., Reproductive Biomedicine Online (2022)
- Ovarian follicle stimulation in swine (veterinary use) Animal studies only
- In prepuberal gilts, supplemental hCG (100–200 IU) increased corpora lutea numbers but caused dose-dependent follicular cyst development; additional hCG did not significantly improve ovulation rates. PMID 26130853 Manjarín et al., Canadian Journal of Veterinary Research (2015)
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Not specified (clinical practice context; Ovidrel is subcutaneous) | 5,000–10,000 IU hCG (standard trigger) OR 250–500 mcg Ovidrel (recombinant hCG); OR 1,500–2,000 IU hCG (dual trigger arm) | Single injection at time of ovulation trigger | human | Research PMID 41239008 |
| Intrauterine (via embryo transfer catheter) | Variable doses; subgroup analyses at <500 IU vs. ≥500 IU intrauterine (IC-hCG) | Single intrauterine administration around time of embryo transfer | human | Research PMID 30341915 |
| Not specified (cattle study) | 500, 1000, or 2000 IU hCG (Exp. 1); 1000 IU hCG (Exp. 2) | Single injection two days after ovulation (Exp. 1); single injection on Day 14 of protocol (Exp. 2) | animal | Research PMID 40273828 |
| Not specified (swine study) | 100 IU or 200 IU additional hCG at 24 h after initial 200 IU hCG + 400 IU eCG | Single supplemental injection | animal | Research PMID 26130853 |
| Intrauterine injection (ex vivo mouse model) | Loading capacity: 710.05 ± 73.74 IU/mg (sonication) or 245.06 ± 95.66 IU/mg (freeze-thaw) for exosome loading | In vitro/ex vivo single application | animal | Research PMID 33737084 |
| Not specified | Not specified (meta-analysis of trials using urinary hCG supplementation); dose varied across included trials | Early pregnancy supplementation; duration varied across trials | human | Research PMID 20653339 |
| Serum monitoring only | 200 mg mifepristone + 800 mcg buccal misoprostol (abortion regimen monitored by serum hCG decline; hCG not administered as treatment) | Follow-up hCG measured Day 1, 3, 5, and Days 7–14 | human | Research PMID 27621046 |
| subcutaneous injection | 250 IU | every other day (EOD) | TRT/testosterone replacement therapy users seeking to maintain testicular function and fertility | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 500 IU | twice per week (e.g. Monday/Thursday) | TRT users preferring a twice-weekly injection schedule aligned with testosterone injections | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 500 IU | every other day (EOD) | anabolic steroid users running post-cycle therapy (PCT) | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 1000 IU | every other day (EOD) | anabolic steroid users with significant HPTA suppression post-cycle | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| intramuscular or subcutaneous injection | 1500 IU | three times per week | men diagnosed with hypogonadotropic hypogonadism or secondary hypogonadism seeking fertility | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 125 IU | every other day (EOD) | TRT users sensitive to estrogen or prone to side effects at higher HCG doses | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 500 IU | once per week | TRT users on once-weekly testosterone injection schedules | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| intramuscular injection | 10000 IU | single injection | anabolic steroid users or bodybuilders using HCG as a trigger shot or to acutely restore testicular volume | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 250 IU | twice per week | TRT users seeking testicular maintenance with twice-weekly injection schedule | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.
Safety signals
- Ovarian hyperstimulation syndrome (OHSS) risk with hCG ovulation triggers in IVF; dual trigger with reduced hCG dose (1,500–2,000 IU) studied to mitigate this risk PMID 41239008
- Dose-dependent follicular cyst development in gilts receiving supplemental hCG (100–200 IU additional dose); cyst frequency and number increased with dose PMID 26130853
- Commercial hCG preparations may contain EGF and TGF-β1 contaminants that activate signaling pathways independently of hCG; this is a purity/contamination concern for therapeutic and research preparations PMID 26495869
- Elevated serum hCG without pregnancy or malignancy can result from rheumatoid factor interference, heterophile antibodies, pituitary secretion, passive plasma transfer, or familial hCG syndrome — leading to unnecessary diagnostic workup or harmful therapy PMID 39661999
- Persistently elevated hCG levels without clear etiology may cause suspicion of cancer or ectopic pregnancy and lead to harmful therapy; specific assay panels are needed to characterize the source PMID 37279342
- Point-of-care urine hCG devices susceptible to false negative results at low concentrations (20–300 IU/L), potentially leading to missed early pregnancy and inappropriate clinical management PMID 25549977
- Low hyperglycosylated hCG at implantation is associated with subsequent spontaneous abortion and biochemical pregnancy failure; whether this is causative or a marker of abnormal conceptus remains unclear PMID 22386126
Contraindications
- Combining eCG and hCG in bovine embryo recipients was associated with reduced corpus luteum blood perfusion without further improvement in pregnancy rates, making this combination inadvisable in that model PMID 40273828
- Use of low-dose intrauterine hCG (<500 IU) at cleavage-stage embryo transfer showed no benefit over no treatment (and results were consistent with possible disadvantage); current evidence does not support this dose PMID 30341915
- No absolute contraindications in humans are explicitly stated in the reviewed abstracts. Clinical contraindications require verification from prescribing information and regulatory sources not covered in these abstracts. PMID 30341915
References
- [1] PMID 41239008 — Retrospective cohort of 2641 cycles: dual trigger with 2,000 IU hCG + GnRH agonist yielded higher implantation rates (50.0% vs. 32.0%) vs. hCG-only and comparab
- [2] PMID 30341915 — Meta-analysis of 17 RCTs (n=4751): intrauterine hCG ≥500 IU before cleavage-stage ET improved live birth rate (RR 1.57, 95%CI 1.32–1.87) and clinical pregnancy
- [3] PMID 33737084 — In vitro/ex vivo study: hCG loaded into uterine exosomes upregulated LIF and Trophinin, downregulated Muc-16 and IGFBP1; hCG-loaded exosomes had greater effect
- [4] PMID 40273828 — In beef cows, ≥1000 IU hCG improved luteal area, progesterone concentration, and pregnancy per embryo transfer vs. control; accessory CL rate was dose-dependent
- [5] PMID 20653339 — Meta-analysis of Cochrane-identified trials: hCG supplementation appeared to reduce miscarriage risk (OR 0.26, 95%CI 0.14–0.52), but trials were methodologicall
- [6] PMID 32231662 — Review: different teams have studied addition of hCG in patients with recurrent miscarriages or implantation failures; a sufficient dose of hCG appears necessar
- [7] PMID 35733148 — In 4434 cleavage-stage fresh/frozen-thawed SET cycles, β-hCG cutoff values on day 14 post-ET were established: 89.6 mIU/L (pregnancy vs. none), 241.1 mIU/L (bio
- [8] PMID 25963653 — Gestational age-specific reference ranges for total serum hCG established in 8195 pregnant women; maternal smoking, BMI, parity, ethnicity, fetal sex, placental
- [9] PMID 36116082 — Retrospective study (n=176): hCG ≥1400 IU/L at 2nd week post-molar evacuation (AUC 0.92, aOR 6.51) and ratio of 2nd-week to post-evacuation hCG ≥0.02 (AUC 0.88,
- [10] PMID 19822356 — Hyperglycosylated hCG proportion distinguishes quiescent GTD (no/low hCG-H, no therapy needed) from minimally invasive (chemorefractory, <40% hCG-H) and aggress
- [11] PMID 25275660 — Proportion hyperglycosylated hCG (hCG-H/total hCG) marks persistent hydatidiform mole (100% detection at 5.1% false detection), distinguishes aggressive from mi
- [12] PMID 17590886 — In 21,641 maternal serum samples, hyperglycosylated-hCG (h-hCG) combined with maternal age, NT, and PAPP-A detected 78% of first-trimester Down syndrome cases a
- [13] PMID 27621046 — Prospective study (n=59) of women ≤63 days gestation undergoing medical abortion with mifepristone 200 mg + misoprostol 800 mcg buccally: mean hCG decline was 7
- [14] PMID 20654692 — Review: ectopic hCGβ expression is widespread across cancer subtypes; free β-subunit detected in serum of cancer patients; proposed roles in angiogenesis, metas
- [15] PMID 19007977 — Serum free β-subunit or urinary β-core fragment detected in 68% of ovarian, 51% of endometrial, and 46% of cervical malignancies; associated with poor prognosis
- [16] PMID 34924288 — In 155 women post-IVF ET: diagnostic performance of hyperglycosylated HCG and HCG+β on day 4 was not significantly different (AUC 0.88 vs. 0.90); superiority of
- [17] PMID 26130853 — In prepuberal gilts, supplemental hCG (100–200 IU) increased corpora lutea numbers but caused dose-dependent follicular cyst development; additional hCG did not
- [18] PMID 26495869 — Commercial hCG preparations may contain EGF and TGF-β1 contaminants that activate signaling pathways independently of hCG; this is a purity/contamination concer
- [19] PMID 39661999 — Elevated serum hCG without pregnancy or malignancy can result from rheumatoid factor interference, heterophile antibodies, pituitary secretion, passive plasma t
- [20] PMID 37279342 — Persistently elevated hCG levels without clear etiology may cause suspicion of cancer or ectopic pregnancy and lead to harmful therapy; specific assay panels ar
- [21] PMID 25549977 — Point-of-care urine hCG devices susceptible to false negative results at low concentrations (20–300 IU/L), potentially leading to missed early pregnancy and ina
- [22] PMID 22386126 — Low hyperglycosylated hCG at implantation is associated with subsequent spontaneous abortion and biochemical pregnancy failure; whether this is causative or a m
- [23] PMID 25707740 — in-prose reference
- [24] PMID 22455390 — in-prose reference
- [25] PMID 29509368 — in-prose reference
- [26] PMID 26676718 — in-prose reference
- [27] PMID 30287399 — in-prose reference
- [28] PMID 40869294 — in-prose reference
- [29] PMID 31010310 — in-prose reference
- [30] PMID 29588177 — in-prose reference
- [31] PMID 23159297 — in-prose reference