Lutropin alfa
The only recombinant luteinising hormone ever sold, made to answer a question about LH that the trials never settled
Lutropin alfa is recombinant human LH, approved as Luveris to be given alongside FSH. Two decades of trials have mostly answered that whether adding LH helps depends on who is asked. Its US approval was withdrawn in 2016.
What is it?
Recombinant FSH contains no LH activity, and LH matters for follicle development: it drives the androgen supply that granulosa cells convert to oestrogen. Lutropin alfa was made to put the missing half back, and was approved in the US on October 8, 2004 for use with FSH.
Its clearest result is a negative one. In a phase 3 trial of 939 women with poor ovarian response, a fixed-ratio FSH-plus-LH combination was compared with FSH alone; the primary and secondary efficacy endpoints came out comparable, and both regimens were safe. It is the largest randomised test of the drug's reason to exist.
Smaller trials have found narrower effects. In 244 women with poor ovarian reserve, adding recombinant LH raised the proportion of top-quality embryos from 11% to 17%. In 146 down-regulated women, a week of LH before FSH increased small antral follicles and normally fertilised embryos. Adding LH late in stimulation did nothing: oestradiol rose but oocyte maturation, pregnancy and live birth did not.
Large observational datasets point to the same niche. Across 9,787 stimulations, adding recombinant LH was associated with more live births only in moderate and severe poor responders, and a meta-analysis of women aged 35 to 40 found higher pregnancy and implantation rates without a difference in live birth. In normal responders and in overweight women it changed little, and 150 IU a day did no better than 75 IU.
The trade-off is consistent: fewer oocytes, a slightly thicker endometrium, and sometimes faster early embryo development. Beyond IVF, recombinant LH and FSH given to infant boys with gonadotropin deficiency raised testosterone and testicular volume. What that leaves is a drug with a real mechanism, a plausible niche in poor responders, and no decisive trial. FDA withdrew its US approval at EMD Serono's request in April 2016.
Mechanism of Action
Lutropin alfa is recombinant human luteinizing hormone, given with FSH to supply the LH activity that recombinant FSH lacks.
Androgen supply for follicles
LH drives the androgen supply that granulosa cells convert to oestrogen, which recombinant FSH alone does not provide.
Fewer but possibly better oocytes
Adding it usually retrieves slightly fewer oocytes, with benefit seen mainly in poor responders and older women.
Male gonadotropin deficiency
With FSH in infant boys lacking gonadotropins, it raised testosterone and testicular volume.
Published Research
These are the trials that describe lutropin alfa, read from their PubMed abstracts: four randomised studies asking when, and whether, added LH helps.
Phase 3 in poor responders
939 women classified as poor ovarian responders were randomised to a fixed-ratio recombinant FSH plus LH combination or FSH alone, after long agonist down-regulation. The primary and secondary efficacy endpoints were comparable, and both regimens had a favourable safety profile.
Embryo quality in poor ovarian reserve
244 expected poor responders were randomised to FSH with LH (2:1) or FSH alone. Top-quality embryos per woman were 17% with LH against 11% without; the trial was powered on embryo quality, not births.
Adding LH late in stimulation
114 normally ovulating women received FSH until the lead follicle reached 14 mm, then 75 IU of lutropin alfa or placebo daily. Oestradiol at trigger was higher with LH, but mature oocytes, fertilisation, pregnancy and live birth rates were unchanged.
LH before FSH
146 profoundly down-regulated women were randomised to seven days of 300 IU recombinant LH before standard FSH, or to FSH alone. The LH pretreatment increased small antral follicles before stimulation and the yield of normally fertilised embryos.
Poor responders, real-world
Across 9,787 stimulations, adding recombinant LH to FSH alfa was associated with higher cumulative live birth in moderate (14.3% against 11.3%) and severe (9.8% against 4.4%) poor responders, but not mild.
Antagonist protocol, multicentre
In a propensity-matched multicentre study, adding recombinant LH in the GnRH antagonist protocol was associated with higher cumulative live birth (66.95% against 61.16%) without more hyperstimulation.
Overweight and obese women
In matched overweight or obese women, FSH plus recombinant LH used more gonadotrophin and retrieved slightly fewer oocytes, with no significant difference in cumulative live birth.
Normal responders
In normal responders, adding recombinant LH sped up early embryo development on time-lapse imaging but did not change oocyte yield, blastocysts, pregnancy or live birth.
Priming in low ovarian reserve
In low-prognosis women, recombinant LH priming before a high-dose antagonist protocol was associated with fewer cancelled retrievals and a higher ongoing pregnancy rate (29.7% against 17.0%) in a retrospective comparison.
150 versus 75 IU
In women aged 35 to 39 on 300 IU FSH, 150 IU of recombinant LH gave no better results than 75 IU: oocytes, clinical pregnancy (32.8% against 32.5%) and live birth were similar.
Infant boys with gonadotropin deficiency
Eleven boys given continuous subcutaneous recombinant LH and FSH in infancy had rises in testosterone, inhibin B and testicular volume, and at early adolescence their testes remained larger than in untreated boys.
Hypo-responders pooled
In women who responded poorly to FSH alone, adding recombinant LH was associated with higher clinical pregnancy (odds ratio 2.03) and implantation rates and about two more eggs retrieved, without a difference in mature eggs or miscarriage.
Women of advanced age
Pooling 12 studies, women aged 35 to 40 on FSH plus recombinant LH had higher clinical pregnancy (OR 1.45) and implantation rates, fewer oocytes, and no difference in live birth.
Endometrium and embryos
A meta-analysis found adding recombinant LH thickened the endometrium slightly but reduced oocyte numbers and high-quality embryos; 75 IU a day was associated with higher clinical pregnancy.
Dosing Data
Luveris is no longer approved in the US. Studies have given 75 to 300 IU a day by injection alongside FSH.
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 trials above; the US label is no longer current.
Contraindications & Cautions
A prescription fertility injection, given only with FSH and under monitoring.
Legal Status
Approved in the US as Luveris; withdrawn in 2016.
Frequently Asked Questions
?What is lutropin alfa?
Recombinant human luteinising hormone, sold as Luveris and given with recombinant FSH.
?Does adding LH to FSH help?
In the largest trial, 939 poor responders did no better with LH added; smaller trials found better embryo quality in some poor responders.
?Can I still get it?
Not in the US: FDA withdrew Luveris's approval at the sponsor's request in 2016. Fixed-ratio FSH-plus-LH products exist elsewhere.
?Why does LH matter at all?
Recombinant FSH has no LH activity, and LH drives the androgen supply that becomes oestrogen. Whether adding it helps is unsettled.
?Who benefits most from adding LH?
The data point to poor responders and women aged 35 to 40. In a real-world analysis of 9,787 stimulations, benefit on cumulative live birth appeared in moderate and severe poor responders, but not mild ones.
?Is a higher LH dose better?
Not in the one comparison found: in women aged 35 to 39, 150 IU a day gave the same pregnancy and live birth rates as 75 IU.
References
- [pubmed] Humaidan P, et al. "Efficacy and safety of follitropin alfa/lutropin alfa in ART: a randomized controlled trial in poor ovarian responders." Hum Reprod, 2017;32(3):544-555. PMID: 28137754.
- [pubmed] Musters AM, et al. "The effect of recombinant LH on embryo quality: a randomized controlled trial in women with poor ovarian reserve." Hum Reprod, 2012;27(1):244-50. PMID: 22095792.
- [pubmed] Tarlatzis B, et al. "The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study." Hum Reprod, 2006;21(1):90-4. PMID: 16172149.
- [pubmed] Durnerin CI, et al. "Effects of recombinant LH treatment on folliculogenesis and responsiveness to FSH stimulation." Hum Reprod, 2008;23(2):421-6. PMID: 18084048.
- [pubmed] le Cotonnec JY, et al. "Clinical pharmacology of recombinant human luteinizing hormone: Part I. Pharmacokinetics after intravenous administration to healthy female volunteers and comparison with urinary human luteinizing hormone." Fertil Steril, 1998;69(2):189-94. PMID: 9496327.
- [other] US FDA, Drugs@FDA (openFDA): no application for lutropin alfa or Luveris. Read September 30, 2026.
- [other] US Federal Register 2016-08336, April 12, 2016: FDA withdraws approval of NDA 21-322 for Luveris at EMD Serono's voluntary request, effective that day. Read September 30, 2026.
- [other] US Federal Register E6-9139, June 13, 2006: regulatory review period for Luveris; NDA 21-322 approved October 8, 2004. Read September 30, 2026.
- [pubmed] Conforti A, et al. "The role of recombinant LH in women with hypo-response to controlled ovarian stimulation: a systematic review and meta-analysis." Reprod Biol Endocrinol, 2019;17(1):18. PMID: 30728019.
- [pubmed] Arvis P, et al. "Effect of recombinant LH supplementation on cumulative live birth rate compared with FSH alone in poor ovarian responders: a large, real-world study." Reprod Biomed Online, 2021;42(3):546-554. PMID: 33431337.
- [pubmed] Conforti A, et al. "Recombinant human luteinizing hormone co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age: a systematic review and meta-analysis of randomized controlled trials." Reprod Biol Endocrinol, 2021;19(1):91. PMID: 34154604.
- [pubmed] Mao R, et al. "Recombinant human luteinizing hormone increases endometrial thickness in women undergoing assisted fertility treatments: a systematic review and meta-analysis." Front Pharmacol, 2024;15:1434625. PMID: 39135787.
- [pubmed] Wang M, et al. "Recombinant LH supplementation improves cumulative live birth rates in the GnRH antagonist protocol: a multicenter retrospective study using a propensity score-matching analysis." Reprod Biol Endocrinol, 2022;20(1):114. PMID: 35941630.
- [pubmed] Zhou X, et al. "Recombinant LH supplementation and cumulative live birth rate in overweight/obese women: a retrospective cohort study." Reprod Biomed Online, 2025;51(6):105076. PMID: 41138397.
- [pubmed] Stefano C, et al. "Recombinant LH supplementation during ovarian stimulation modulates early embryo morphokinetics without affecting IVF outcomes in normal responders: a retrospective time-lapse study." J Assist Reprod Genet, 2026;43(8):2457-2467. PMID: 42399463.
- [pubmed] Guglielmi D, et al. "Recombinant LH priming improves follicular efficiency and pregnancy outcomes in women with diminished ovarian reserve undergoing antagonist IVF stimulation." Front Endocrinol (Lausanne), 2026;17:1877719. PMID: 42568412.
- [pubmed] Matorras R, et al. "Comparison of the Administration of 150 or 75 IU of Recombinant LH in Agonist ICSI Cycles Stimulated with Recombinant FSH in Women Aged 35-39: A Comparative Study." J Reprod Infertil, 2023;24(4):269-278. PMID: 38164428.
- [pubmed] Lambert AS, et al. "Early adolescence assessment of eleven boys treated with continuous subcutaneous infusion (CSGI) of recombinant LH and FSH during infancy." Endocr Connect, 2025;14(4). PMID: 40042209.
Sources & Citations
Studies were read from their PubMed abstracts; Luveris approval history from FDA and the Federal Register. Read October 7, 2026.
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.