Cetrorelix (Cetrotide)
Cetrorelix Acetate (Ac-D-Nal(2)-D-Cpa-D-Pal(3)-Ser-Tyr-D-Cit-Leu-Arg-Pro-D-Ala-NH2)
FDA-approved synthetic decapeptide GnRH antagonist used to inhibit premature LH surges during controlled ovarian stimulation for IVF, with 0.25 mg daily established as the minimal effective multidose regimen (FDA label ANDA218150; PMID 9130900).
Last updated: 2026-03-10
Safety Summary
In clinical studies of 949 patients, reported adverse events (>=1%) were OHSS (3.5%, moderate-severe), nausea (1.3%), and headache (1.1%). Injection site reactions were transient, mild, and short-duration (FDA label ANDA218150). Enzyme elevations (ALT, AST, GGT, alkaline phosphatase) found in 1-2% of patients, up to 3x upper limit of normal; clinical significance not determined (FDA label ANDA218150). Post-marketing: cases of hypersensitivity reactions including anaphylactoid reactions reported. One severe anaphylactic reaction (cough, rash, hypotension) observed in a patient after 7 months of treatment at 10mg/day for a non-infertility indication (FDA label ANDA218150). Single doses up to 120mg were tolerated without overdosage signs (FDA label ANDA218150). In a 2025 retrospective cohort (n=9,424), OHSS incidence was lower with cetrorelix than ganirelix (0.4% vs 1.1%, p=0.01), though this comparison was observational (PMID 40297130). FDA FAERS data show 156 reports of OHSS, 42 drug ineffective, 40 spontaneous abortion, 40 premature ovulation, 28 each for abdominal distension, abdominal pain, and ascites (FDA FAERS data). Community reports from online communities confirm mild injection site rashes/itching resolving within an hour as the most common complaint, with occasional headaches, bloating, and fatigue.
Known Side Effects
common
common
common
common
uncommon
rare
Who Should NOT Use This
Cetrorelix is contraindicated in pregnant women. In rats, dose of 139 mcg/kg (approximately 4x human dose) resulted in 100% resorption rate. In animals maintaining pregnancy, no increase in fetal abnormalities. Fetal resorption is a logical consequence of antigonadotrophic properties. It is not known whether cetrorelix is excreted in human milk (FDA label ANDA218150).
Cases of hypersensitivity including anaphylactoid reactions reported in post-marketing surveillance (FDA label ANDA218150).
Cross-reactivity with GnRH analog class (FDA label ANDA218150).
Listed as contraindication in FDA label. Pharmacokinetic studies not performed in renal impairment (FDA label ANDA218150).
Treatment not advised in women with severe allergic conditions. Special care in women with signs/symptoms of active allergic conditions. Listed in Precautions section, not formal Contraindications (FDA label ANDA218150).
Talk to Your Doctor
Before considering Cetrorelix (Cetrotide), discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-16]
Evidence Assessment
Tier 1 -- FDA-approved since 1999 for prevention of premature LH surges in controlled ovarian stimulation. Core clinical program included 9 Phase II/III studies with 878 patients (EMA scientific discussion). FDA label reports safety data on 949 patients across 5 clinical trials (2 Phase 2 dose-finding, 3 Phase 3). Phase 3 trials demonstrated efficacy with LH surge prevention rates of 98-100% and clinical pregnancy rates of 19.8-22.6% per attempt (FDA label ANDA218150). ESHRE guidelines recommend GnRH antagonist protocol as standard for IVF/ICSI (PMC10201282). Cochrane systematic reviews confirm comparable live birth rates to GnRH agonist protocols with reduced OHSS risk. Multiple generic approvals (ANDA218150, ANDA218061) confirm continued regulatory acceptance. Evidence is strong for IVF-related ovulation control but not for experimental non-IVF uses such as oncology or intranasal delivery, which remain preclinical or otherwise limited (PMID 40593190; PMID 41458598).
1FDA Label: Cetrorelix Acetate for Injection -- Prescribing Information
FDA / Gland Pharma Limited - FDA Label (ANDA218150) (2024) - Regulatory document (pooled Phase 2/3 data) - 949 patients (safety); 732 patients across 5 clinical trials (efficacy)
In Phase 3 trials: LH surge prevention 98-100%, clinical pregnancy rate 19.8-22.6% per attempt. Adverse events: OHSS 3.5%, nausea 1.3%, headache 1.1%. Single doses up to 120mg tolerated. 184 pregnancies from 732 patients. Median treatment 5 days (range 1-15). Absolute bioavailability 85%.
Limitations: Studies excluded PCOS, low/no ovarian reserve, and stage III-IV endometriosis. Population 95.5% Caucasian.
2A single injection of a gonadotropin-releasing hormone (GnRH) antagonist (Cetrorelix) postpones the luteinizing hormone (LH) surge: further evidence for the role of GnRH during the LH surgePMID 8062939
Leroy I et al. - Fertility and Sterility (1994) - Clinical study (dose-ranging, open-label) - 10 normal ovulatory women
Single 5mg dose: LH reduced 56% +/- 19%, FSH 29.5% +/- 16%, E2 decreased 85% +/- 17%. Single 3mg dose: LH reduced 66% +/- 18%, FSH 32% +/- 6%, E2 decreased 81% +/- 12%. LH surge delayed 6-17 days. Very well tolerated; only slight transient erythema/pruritus at injection site.
Limitations: Small sample size (n=10). Normal volunteers only, not IVF patients.
3Comparison of different doses of gonadotropin-releasing hormone antagonist Cetrorelix during controlled ovarian hyperstimulationPMID 9130900
Albano C et al. - Fertility and Sterility (1997) - Dose-finding clinical study - 69 patients (32 at 0.5mg, 30 at 0.25mg, 7 at 0.1mg)
No premature LH surge at 0.5mg or 0.25mg doses. One premature LH surge (18 mIU/mL) with concomitant progesterone rise at 0.1mg (1/7 patients), leading to discontinuation of that dose. Established 0.25mg as minimal effective daily dose.
Limitations: Relatively small sample sizes per dose group. Single center.
4Prospective, randomized trial comparing cetrorelix acetate and ganirelix acetate in a programmed, flexible protocol for premature luteinizing hormone surge prevention in assisted reproductive technologiesPMID 16009165
Wilcox J et al. - Fertility and Sterility (2005) - RCT (prospective, open-label, randomized, comparative) - 185 infertile patients across 16 ART centers
No premature LH surge in either group. No significant differences in IVF/ICSI or ET outcomes including pregnancy rate. Cetrorelix (3mg single dose) required significantly fewer injections than ganirelix (0.25mg daily), increasing patient convenience. Similar safety profiles.
Limitations: Open-label design. Single-dose cetrorelix vs daily ganirelix (different dosing regimens).
5Cetrorelix in an oral contraceptive-pretreated stimulation cycle compared with buserelin in IVF/ICSI patients treated with r-hFSH: a randomized, multicentre, phase IIIb studyPMID 16537563
Huirne JA et al. - Human Reproduction (2006) - RCT (randomized, multicentre, Phase IIIb) - 182 patients (91 cetrorelix, 91 buserelin)
OC-pretreated cetrorelix regimen resulted in similar oocyte numbers, cancellation rates, r-hFSH requirements, and pregnancy rates compared to long buserelin protocol. Both well tolerated. Allowed scheduling of oocyte retrieval with few weekend/holiday retrievals.
Limitations: Non-inferiority design. Open-label. Focused on oocytes retrieved rather than live-birth endpoints.
6Comparison of pregnancy outcomes and safety between cetrorelix and ganirelix in IVF/ICSI antagonist protocols: a retrospective cohort studyPMID 40297130
Peng X et al. - Frontiers in Reproductive Health (2025) - Retrospective cohort study with propensity score matching - 9,424 patients (2,365 cetrorelix, 7,059 ganirelix, after 1:3 PSM)
Cetrorelix showed superior LH surge control: LH >=10 U/L 4.9% vs 7.6% (p<0.001), LH ratio >=2: 6.1% vs 9.2% (p<0.001). Better endometrial receptivity: Type A morphology 66.2% vs 60.1%. Lower OHSS: 0.4% vs 1.1% (p=0.01). Comparable live birth rates: 47.2% vs 49.4% (p=0.074). Notes cetrorelix available in 45 countries.
Limitations: Retrospective design. Single center in China. PSM cannot fully control for unmeasured confounders.
7Cetrorelix promotes cell apoptosis via the PI3K-AKT-FOXO1 pathway in epithelial ovarian cancerPMID 41458598
Zhang N et al. - Frontiers in Oncology (2025) - In vitro and in vivo (xenograft mouse model) + clinical IHC - Cell lines + xenograft model + EOC tissue samples (clinical correlation)
Cetrorelix facilitated EOC apoptosis both in vitro and in xenograft model via PI3K-AKT-FOXO1 pathway. FOXO1 knockdown attenuated cetrorelix-induced apoptosis. GnRHR knockdown abrogated the effect, confirming receptor specificity.
Limitations: In vivo FOXO1 activation not quantitatively assessed in xenograft tissues. Preclinical study -- no human therapeutic trial. Clinical IHC data is correlative.
8Cetrorelix suppresses the dominant follicle and synchronizes follicular waves and ovulation in cattlePMID 41395811
Farmer DR et al. - Biology of Reproduction (2025) - Animal study (cattle, 3 experiments) - n=8 per group across 3 experiments
Cetrorelix caused dominant follicle regression and earlier FSH surge. New wave emergence 3.4-3.6 days post-treatment, ovulation 12.4 days later. 13/23 heifers became pregnant. CL diameter smaller but progesterone production unaffected.
Limitations: Animal study (cattle). Small sample sizes. Not directly translatable to human use.
9Intranasal Delivery of Cetrorelix Via Lipid Liquid Crystal Nanoparticles: Characterization and Pharmacokinetic Studies in RatsPMID 40593190
Tafazzoli Mehrjardi S et al. - AAPS PharmSciTech (2025) - Preclinical (rat pharmacokinetics) - Rat model
LLC nanoparticle intranasal formulation achieved enhanced brain Cmax (238 vs 202.5 ng/mL for simple nasal, vs 218.2 ng/mL for SC injection) while drastically reducing serum exposure (Cmax 93.1 vs 4983.3 ng/mL for SC).
Limitations: Rat model only. First-time formulation concept. No human data.
10Switching from cetrorelix to dydrogesterone in an IVF cycle - a new strategy for unexpected freeze-all cyclesPMID 37850848
Antunes RdA et al. - JBRA Assisted Reproduction (2023) - Case report - 1 patient
34-year-old female: successful switch from cetrorelix to oral dydrogesterone mid-stimulation when OHSS risk detected. 24 oocytes retrieved (16 MII), no premature LH peak, no OHSS symptoms.
Limitations: Single case report. No comparator. Cannot establish efficacy or safety from one case.
11Synthesis of Diastereomerically Pure Cetrorelix Acetate by Using Fmoc Solid-Phase Peptide Synthesis (SPPS) Strategy: A Commercially Viable ApproachPMID 40386934
Aluri K et al. - Journal of Peptide Science (2025) - Chemistry/synthesis methodology - N/A (analytical chemistry)
Racemization of L-arginine and L-serine minimized to below 0.5% using HATU/HOBt/HOAt/TMP coupling. Commercially viable SPPS approach for pure cetrorelix production.
Limitations: Synthetic methodology study only. No biological or clinical data.
12Comparative Analysis of Different Puberty Inhibiting Mechanisms of Two GnRH Agonists and the GnRH Antagonist Cetrorelix Using a Female Rat Model
Roth C et al. - Pediatric Research (2000) - Animal study (female rat model) - Multiple groups of prepubertal/peripubertal female rats
All three GnRH analogs retarded puberty onset. Cetrorelix exerted only inhibitory effects on pituitary-gonadal axis, while agonists had mixed stimulatory/inhibitory effects. Cetrorelix significantly lowered GnRH receptor and LH-beta subunit gene expression.
Limitations: Animal model (rat). No human data for puberty indication. Drug provided by manufacturer as gift.
13Cetrorelix in the treatment of female infertility and endometriosis
Finas D et al. - Expert Opinion on Pharmacotherapy (2006) - Review - N/A (review)
Cetrorelix advantages in ovarian stimulation: less treatment time, reduced gonadotropin needs, fewer side effects vs GnRH agonists. Also useful for endometriosis with fewer side effects than GnRH agonists.
Limitations: Narrative review. Does not present new data.
14Role of cetrorelix in the prevention and treatment of ovarian hyperstimulation syndrome: a prospective case control study
Mishra VV et al. - International Journal of Reproduction, Contraception, Obstetrics and Gynecology (2023) - Prospective case-control study - 102 patients (51 cetrorelix, 51 control)
Cetrorelix 0.25mg x5 days from OPU: significantly lower moderate (p<0.05) and severe OHSS. No critical OHSS in either group.
Limitations: Small sample size. Non-randomized. Single center.
15Efficacy of GnRH antagonists in the treatment of uterine fibroids: a meta-analysis
Sanchez Martin MJ et al. - Archives of Gynecology and Obstetrics (2025) - Meta-analysis (11 RCTs) - 4,164 patients across 11 RCTs
GnRH antagonists vs placebo: superior bleeding control, fibroid volume reduction. Cetrorelix was one of the antagonists evaluated.
Limitations: Most included studies used oral GnRH antagonists, not cetrorelix specifically. Only 1 study included cetrorelix directly.
16Cetrorelix in reproductive medicinePMID 37223762
Findeklee S, Diedrich K - F&S Reports (PMC10201282) (2022) - Review/book chapter - N/A (review)
Comprehensive overview of cetrorelix history, dosing, effects, and safety. Half-life approximately 30 hours single injection, up to 80 hours multiple injections. Bioavailability 85%. Albumin binding approximately 85%. ESHRE recommends antagonist protocol as standard. Price approximately 56 EUR/injection vs approximately 17 EUR for GnRH agonists.
Limitations: Narrative review without systematic methodology.