Cetrorelix
The injection that holds back ovulation during IVF, so the eggs are still there to collect
Cetrorelix blocks the receptor for GnRH, the brain signal that triggers ovulation, so the premature LH surge that can release eggs before retrieval does not happen. Approved in 2000 as Cetrotide, it is injected once a day from about the fifth day of ovarian stimulation until the trigger shot.
What is it?
IVF stimulates the ovaries with injected FSH so that many follicles grow at once. The pituitary can respond with a premature surge of LH that releases or spoils the eggs before they are collected. The older answer is a GnRH agonist, which overstimulates the pituitary until it stops responding, a process that takes weeks. Cetrorelix blocks the receptor directly, so it can be started partway through stimulation.
The label is specific: 0.25 mg injected under the skin once a day, starting on stimulation day 5 (morning or evening) or day 6 (morning) and continuing until the day of the hCG trigger. It also tells prescribers not to give hCG if the ovaries respond excessively, to reduce the chance of ovarian hyperstimulation syndrome.
Two large registration studies tested the two ways of giving it. In 1,066 women on daily 0.25 mg and 541 on a single 3 mg dose, more than 90% reached the hCG trigger and egg retrieval, pregnancy rates per embryo transfer were 27% and 28%, and severe hyperstimulation occurred in under 1% of cycles. Among those given the single 3 mg dose, 73% needed only that one injection. In a separate randomised trial, a single 3 mg dose prevented the LH surge in all 115 patients who received it, with fewer eggs and embryos than a depot agonist but similar pregnancy rates.
The label's pharmacokinetic table explains why one dose can cover several days. After a single 3 mg injection, the elimination half-life in healthy women was about 63 hours; after daily 0.25 mg injections for 14 days it was about 21 hours, and plasma levels peaked roughly an hour after each dose. Cetrorelix is absorbed rapidly from under the skin, and the label lists no formal drug interaction studies.
The trials found a consistent trade. Compared with agonist protocols, cetrorelix produced fewer eggs but similar pregnancy rates, with shorter stimulation and less hyperstimulation. A 2016 Cochrane review of GnRH antagonists as a class, cetrorelix and ganirelix together, found no conclusive difference in live birth against long agonist protocols across 12 trials, lower hyperstimulation across 36, and more cycles cancelled for poor response.
Its largest single study outside fertility was in the prostate. In a placebo-controlled phase 2 trial of 140 men with symptomatic benign prostatic hyperplasia, every cetrorelix regimen improved the International Prostate Symptom Score quickly, peaking 5.4 to 5.9 points down against 2.8 on placebo, with the difference holding to week 20. A second dose-ranging study of a long-acting cetrorelix pamoate injection found the best result, a 4-point improvement beyond placebo, with 60 mg followed by 30 mg two weeks later, sustained for six months despite only moderate and transient testosterone suppression. Cetrorelix was never approved for this use.
A rheumatoid arthritis trial showed the same pattern of biological effect without a clear clinical result: five days of cetrorelix lowered TNF-alpha and gave more ACR20 responses, but missed its primary endpoint, and the effect faded once treatment stopped. In the US, Cetrotide's only indication remains the inhibition of premature LH surges in controlled ovarian stimulation.
Mechanism of Action
Cetrorelix blocks the GnRH receptor on the pituitary, suppressing LH and FSH within hours instead of after weeks of agonist-induced desensitisation.
Direct receptor block
Blocking the GnRH receptor stops the premature LH surge that can release or spoil eggs before collection.
Starts and stops quickly
Absorbed rapidly with a peak about an hour after injection; half-life about 21 hours with daily dosing and 63 hours after 3 mg (label).
Less hyperstimulation
Antagonist protocols caused less ovarian hyperstimulation than long agonist protocols in randomised trials.
Published Research
The studies behind cetrorelix, read from their PubMed abstracts: the IVF registration and comparison trials, and its trials in prostate enlargement and rheumatoid arthritis.
The two registration studies
Two large studies tested daily 0.25 mg (1,066 women) and a single 3 mg dose (541). In both, more than 90% reached the hCG trigger and egg retrieval, pregnancy rates per embryo transfer were 27% and 28%, severe hyperstimulation occurred in under 1% of cycles, and 73% of the single-dose group needed only one injection.
One dose against a depot agonist
In a multicentre randomised trial, a single 3 mg dose (115 patients) prevented the LH surge in every patient. Compared with depot triptorelin (39), it yielded fewer eggs and embryos with similar pregnancy rates, a shorter stimulation and less hyperstimulation.
Less hyperstimulation
Randomised against the long buserelin protocol, the daily cetrorelix protocol had less moderate or severe hyperstimulation (1.1% against 6.5%), with pregnancy rates per cycle of 22% and 26%, a difference that was not significant.
Benign prostatic hyperplasia: phase 2, 140 men
All cetrorelix regimens rapidly improved IPSS, peaking at -5.4 to -5.9 against -2.8 on placebo, with significant differences to week 20 and good tolerability.
Long-acting cetrorelix pamoate in BPH
A 60 mg then 30 mg intramuscular regimen gave a 4-point IPSS improvement beyond placebo, sustained for six months, with only moderate, transient testosterone suppression.
Outside fertility: rheumatoid arthritis
In a randomised, double-blind proof-of-concept trial in 99 people with active rheumatoid arthritis, five days of cetrorelix missed its primary endpoint, the change in disease activity score (p = 0.091), although TNF-alpha fell and more patients reached an ACR20 response (40% against 18%). The effects faded after treatment stopped.
Dosing Data
Cetrotide is injected under the skin once daily during IVF stimulation, from day 5 or 6 until the hCG trigger.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the Cetrotide prescribing information (DailyMed set aca7768e, version 18, effective September 22, 2025) and the trials.
Contraindications & Cautions
From the label.
Legal Status
Approved for fertility treatment.
Frequently Asked Questions
?When is cetrorelix injected during IVF?
Once a day from stimulation day 5 or 6 until the day of the hCG trigger, at 0.25 mg under the skin.
?Does it lower the risk of ovarian hyperstimulation?
Randomised trials and the 2016 Cochrane review found less hyperstimulation than with long agonist protocols, but it still occurred in 3.5% of women in the label's clinical studies.
?Can it be used in pregnancy?
No. The label contraindicates it in known or suspected pregnancy and in breastfeeding.
?How long does it last?
The label gives a half-life of about 63 hours after a single 3 mg dose and about 21 hours with daily 0.25 mg injections, which is why a single 3 mg dose was tested as an alternative to daily injections.
?How does it compare with an agonist protocol?
Trials found fewer eggs but similar pregnancy rates, shorter stimulation and less hyperstimulation (1.1% against 6.5% in one trial against long buserelin).
?Was it tried for prostate enlargement?
Yes, in phase 2 trials in benign prostatic hyperplasia, where it improved urinary symptom scores against placebo, but it was never approved for that use.
?Does it interact with other drugs?
The label says no formal drug interaction studies have been performed.
?Who should not use it?
The label rules it out in pregnancy, breastfeeding and severe kidney impairment, and in anyone hypersensitive to cetrorelix, other GnRH-related peptides or mannitol; pregnancy must be excluded before starting.
References
- [fda-pi] Cetrotide (cetrorelix acetate for injection) prescribing information: indications, dosage, contraindications, precautions, adverse reactions and pharmacokinetics (DailyMed SPL version 18, effective September 22, 2025; read October 1, 2026).
- [pubmed] Olivennes F, et al. "Safety and efficacy of a 3 mg dose of the GnRH antagonist cetrorelix in preventing premature LH surges: report of two large multicentre, multinational, phase IIIb clinical experiences." Reprod Biomed Online, 2003;6(4):432-8. PMID: 12831588.
- [pubmed] Olivennes F, et al. "Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a single dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin)." Fertil Steril, 2000;73(2):314-20. PMID: 10685535.
- [pubmed] Ludwig M, et al. "Significant reduction of the incidence of ovarian hyperstimulation syndrome (OHSS) by using the LHRH antagonist Cetrorelix (Cetrotide) in controlled ovarian stimulation for assisted reproduction." Arch Gynecol Obstet, 2000;264(1):29-32. PMID: 10985616.
- [pubmed] Debruyne F, et al. "Placebo-controlled dose-ranging phase 2 study of subcutaneously administered LHRH antagonist cetrorelix in patients with symptomatic benign prostatic hyperplasia." Eur Urol, 2008;54(1):170-7. PMID: 18417275.
- [pubmed] Debruyne F, et al. "Dose-ranging study of the luteinizing hormone-releasing hormone receptor antagonist cetrorelix pamoate in the treatment of patients with symptomatic benign prostatic hyperplasia." Urology, 2010;76(4):927-33. PMID: 20932411.
- [pubmed] Kåss AS, et al. "Short-term treatment with a gonadotropin-releasing hormone antagonist, cetrorelix, in rheumatoid arthritis (AGRA): a randomized, double-blind, placebo-controlled study." Scand J Rheumatol, 2014;43(1):22-7. PMID: 24182325.
- [pubmed] Al-Inany HG, et al. "Gonadotrophin-releasing hormone antagonists for assisted reproductive technology." Cochrane Database Syst Rev, 2016;4(4):CD001750. PMID: 27126581.
Sources & Citations
Studies were read from their PubMed records (October 6, 2026); the label and Drugs@FDA are listed below with their read dates.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.