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Peptide

Kisspeptin-54

Kisspeptin-54 (KP-54) is the major circulating isoform of kisspeptin in humans, a 54-amino-acid neuropeptide encoded by the KISS1 gene. It is a critical regulator of reproductive function, acting as the primary stimulator of gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. Kisspeptin is essential for puberty onset and fertility, and clinical trials have shown promise for its use in IVF treatment, particularly for preventing ovarian hyperstimulation syndrome.

Research notice. This page is for education and research. Peptides may not be FDA-approved for human use and may only be legally available for research. Talk to a qualified clinician before considering any peptide.

Best evidence
Grade A
Conditions studied
2
Outcomes
7
Graded outcomes
5200

Evidence by condition

  • Strong
  • Moderate
  • Limited
  • Very limited

2 conditions

Infertility

Infertility: outcomes studied for Kisspeptin-54
GradeOutcomeEffectSizeStudiesPeopleStudies list
Ovarian Hyperstimulation Syndrome Prevention

Only 7% of kisspeptin-treated women developed mild OHSS, with no moderate, severe, or critical cases - a significant improvement over standard hCG triggers in high-risk patients.

Improves (the measure goes up)Large effect16 studies

Studies that measured ovarian hyperstimulation syndrome prevention

and 6 more in the citations list

Oocyte Maturation (IVF)

Phase 2 clinical trial showed kisspeptin-54 effectively triggered oocyte maturation in 95% of women at high risk of OHSS, with embryo formation in 90%.

Improves (the measure goes up)Large effect15 studies

Studies that measured oocyte maturation (ivf)

and 5 more in the citations list

Egg Maturation Trigger

Kisspeptin-54 successfully triggers egg maturation sufficient for fertilization, embryo implantation, and live birth in IVF patients.

Improves (the measure goes up)Large effect14 studies

Studies that measured egg maturation trigger

and 4 more in the citations list

IVF Pregnancy Rate

A single injection of kisspeptin-54 resulted in mature eggs successfully fertilized and transferred, with pregnancy achieved in 23% of subfertile patients undergoing IVF.

Improves (the measure goes up)Moderate effect14 studies

Studies that measured ivf pregnancy rate

and 4 more in the citations list

Subfertility

Subfertility: outcomes studied for Kisspeptin-54
GradeOutcomeEffectSizeStudiesPeopleStudies list
LH Secretion

Kisspeptin-54 potently stimulates LH release in healthy women and those with hypothalamic amenorrhea, with effects similar to or exceeding exogenous GnRH.

Improves (the measure goes up)Large effect13 studies

Studies that measured lh secretion

and 3 more in the citations list

FSH Secretion

Acute kisspeptin administration increases FSH secretion as part of the coordinated gonadotropin response through the hypothalamic-pituitary axis.

Improves (the measure goes up)Moderate effect13 studies

Studies that measured fsh secretion

and 3 more in the citations list

Reproductive Hormone Recovery (Hypothalamic Amenorrhea)

Twice-weekly kisspeptin-54 administration for 8 weeks stimulated reproductive hormone release in women with hypothalamic amenorrhea, though chronic administration shows tachyphylaxis.

Improves (the measure goes up)Moderate effect12 studies

Studies that measured reproductive hormone recovery (hypothalamic amenorrhea)

and 2 more in the citations list

Key findings

  • Ovarian Hyperstimulation Syndrome PreventionInfertilityImproves (the measure goes up)
  • Oocyte Maturation (IVF)InfertilityImproves (the measure goes up)
  • Egg Maturation TriggerInfertilityImproves (the measure goes up)

Safety notes in the studies

  • Only 7% of kisspeptin-treated women developed mild OHSS, with no moderate, severe, or critical cases - a significant improvement over standard hCG triggers in high-risk patients.
  • Phase 2 clinical trial showed kisspeptin-54 effectively triggered oocyte maturation in 95% of women at high risk of OHSS, with embryo formation in 90%.

Studies cited

29 studies from PubMed

  1. Kisspeptins Regulating Fertility: Potential Future Therapeutic Approach in Infertility TreatmentJ Clin Med, 2025 · PMID 40429279
  2. Kisspeptin and its Current Clinical Status-A Systematic Review.Current medicinal chemistry, 2025 · PMID 38265397
  3. Advances in clinical applications of kisspeptin-GnRH pathway in female reproductionReprod Biol Endocrinol, 2022 · PMID 35606759
  4. Kisspeptin-10 in cryodiluent improves the post-thaw quality of Nili-Ravi buffalo (Bubalus bubalis) bull spermatozoa.Andrologia, 2022 · PMID 36054451
  5. Clinical Potential of Kisspeptin in Reproductive HealthTrends Mol Med, 2021 · PMID 34210598
  6. MINI REVIEW: Role of Kisspeptin-GPR54 system in regulation of reproductive functions in human and other mammals.Pakistan journal of pharmaceutical sciences, 2021 · PMID 34248018
  7. Kisspeptin receptor agonist has therapeutic potential for female reproductive disordersJ Clin Invest, 2020 · PMID 33196464
  8. Role of Kisspeptin in Regulation of Reproductive and Immune Reactions.Biochemistry. Biokhimiia, 2020 · PMID 33045946
  9. Kisspeptin Influence on Polycystic Ovary Syndrome-a Mini Review.Reproductive sciences (Thousand Oaks, Calif.), 2020 · PMID 31919796
  10. The role of kisspeptin system in cancer biology.Critical reviews in oncology/hematology, 2019 · PMID 31401420
  11. KISS1/KISS1R and Breast Cancer: Metastasis Promoter.Seminars in reproductive medicine, 2019 · PMID 31972865
  12. Kisspeptin/Kisspeptin Receptor System in the OvaryFront Endocrinol (Lausanne), 2018 · PMID 29354093
  13. The kisspeptin receptor: A key G-protein-coupled receptor in the control of the reproductive axis.Best practice & research. Clinical endocrinology & metabolism, 2018 · PMID 29678280
  14. A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial.Human reproduction (Oxford, England), 2017 · PMID 28854728
  15. Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) TherapyJ Clin Endocrinol Metab, 2015 · PMID 26192876
  16. Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilizationJ Clin Invest, 2014 · PMID 25036713
  17. The kisspeptin-GnRH pathway in human reproductive health and diseaseHum Reprod Update, 2014 · PMID 24615662
  18. Kisspeptin-54 levels are increased in patients with colorectal cancer.World journal of surgery, 2012 · PMID 22552499
  19. Plasma Kisspeptin-54 levels in gastric cancer patients.International journal of surgery (London, England), 2012 · PMID 22959969
  20. Kisspeptin and fertility.The Journal of endocrinology, 2011 · PMID 21084385
  21. The role of kisspeptin/GPR54 in the reproductive system.In vivo (Athens, Greece), 2011 · PMID 21576407
  22. Twice-weekly administration of kisspeptin-54 for 8 weeks stimulates release of reproductive hormones in women with hypothalamic amenorrheaClin Pharmacol Ther, 2010 · PMID 20668878
  23. Kisspeptin: a critical regulator of puberty and reproductive function.Current drug targets, 2010 · PMID 20426767
  24. Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxisJ Clin Endocrinol Metab, 2009 · PMID 19820030
  25. Oestrogen, kisspeptin, GPR54 and the pre-ovulatory luteinising hormone surge.Journal of neuroendocrinology, 2009 · PMID 19207812
  26. Kisspeptin: a novel role in the regulation of reproductive function.Drug news & perspectives, 2009 · PMID 20140277
  27. Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women.The Journal of clinical endocrinology and metabolism, 2007 · PMID 17635940
  28. The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humansJ Clin Endocrinol Metab, 2005 · PMID 21795450
  29. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human malesJ Clin Endocrinol Metab, 2005 · PMID 18497267