HMG
Published research and evidence base
Human menopausal gonadotropin (menotropins) is a urinary-derived gonadotropin preparation containing both follicle-stimulating hormone and luteinizing hormone activity, the latter contributed substantially by chorionic gonadotropin retained during purification. Highly purified formulations (hp-hMG) have been evaluated against recombinant FSH and against rFSH plus recombinant LH in a large randomised-controlled-trial literature covering ovarian stimulation for IVF/ICSI, ovulation induction, and combined gonadotropin therapy for spermatogenesis induction in male hypogonadotropic hypogonadism. A 2026 Cochrane update reported probable advantages for hMG/hp-hMG over rFSH in live birth and ovarian hyperstimulation syndrome, while other recent systematic reviews found comparable live birth with differing oocyte yields, and the field remains characterised by heterogeneity in dosing, protocol and endpoint definition.
- Studies cited
- 15
- Published 2023+
- 11
- Newest paper
- 2026
- Last reviewed
- Aug 2026
Recurring themes in the literature
- ovarian stimulation for IVF/ICSI
- combined FSH and LH activity
- highly purified hMG versus recombinant FSH
- live birth and cumulative live birth rate
- ovarian hyperstimulation syndrome risk
- GnRH antagonist protocols and predicted high responders
- poor ovarian response and LH supplementation
- follicular steroidogenesis and premature progesterone elevation
- ovulation induction in polycystic ovary syndrome
- spermatogenesis induction in male hypogonadotropic hypogonadism
Compound identifiers
15 published studies.
Ordered by strength of study design, then by recency. Every entry links to its source record so the finding can be checked against the paper rather than taken on our word.
- 01Clinical guideline2023
Use of gonadotropins in ovarian stimulation in Spain: Delphi consensus
Barrenetxea G, et al. · Journal of Obstetrics and Gynaecology · modified Delphi consensus among Spanish reproductive medicine specialists
Consensus statements supported FSH monotherapy for younger normal and hyper-responder patients, with LH-containing preparations such as hMG considered in defined subgroups including advanced age and hypo-response.
- 02Systematic review2026
Recombinant follicle-stimulating hormone (rFSH) versus other recombinant or urinary gonadotropins for ovarian stimulation in assisted reproductive technology cycles
Berkhout RP, et al. · Cochrane Database of Systematic Reviews · Cochrane systematic review and meta-analysis of randomised trials comparing rFSH with urinary and other recombinant gonadotropins
Live birth and clinical pregnancy were probably lower with rFSH than with hMG/hp-hMG, and ovarian hyperstimulation syndrome was probably higher with rFSH; certainty of evidence was rated moderate for the principal comparisons.
- 03Systematic review2026
Luteinizing hormone activity in ovarian stimulation: comparative efficacy and safety of gonadotropins versus recombinant follicle-stimulating hormone-a systematic review and meta-analysis
Espinós JJ, et al. · Frontiers in Endocrinology · systematic review and meta-analysis of randomised trials of LH-activity-containing gonadotropins versus rFSH alone
Gonadotropins carrying LH activity probably produced little to no difference in live birth or ongoing pregnancy compared with rFSH alone, but were associated with a more favourable ovarian hyperstimulation syndrome profile.
- 04Systematic review2026
Comparative Effectiveness of Recombinant Human Follicle-Stimulating Hormone:Recombinant Human Luteinizing Hormone in a 2:1 Ratio versus Highly Purified Human Menopausal Gonadotropin Alone in Ovarian Stimulation for Medically Assisted Reproduction Treatment Using in vitro Fertilization/Intracytoplasmic Sperm Injection: A Systematic Review and Meta-Analysis
Dahan MH, et al. · Gynecologic and Obstetric Investigation · systematic review and meta-analysis of six studies, 5,287 stimulation cycles
Oocyte yield was significantly higher with r-hFSH:r-hLH in a 2:1 ratio than with hp-hMG alone and clinical pregnancy rate favoured the recombinant combination, but data were insufficient to draw firm conclusions on live birth.
- 05Systematic review2025
Controlled ovarian stimulation protocols for assisted reproduction: a network meta-analysis
Melo P, et al. · Cochrane Database of Systematic Reviews · Cochrane network meta-analysis of randomised trials of controlled ovarian stimulation protocols
Short GnRH antagonist protocols may have reduced ovarian hyperstimulation syndrome in women with predicted normal response without an evident reduction in live birth or ongoing pregnancy; comparisons between individual gonadotropin preparations were limited by network sparsity.
- 06Systematic review2025
Evaluating Sperm Recovery Time and Efficacy of Monotherapy vs. Combination Therapies in Men with Congenital Hypogonadotropic Hypogonadism: A Systematic Review and Meta-Analysis
Pozzi E, et al. · The World Journal of Men's Health · systematic review and meta-analysis of studies in men with congenital hypogonadotropic hypogonadism treated with hCG alone or hCG combined with FSH/hMG
Combination gonadotropin therapy was associated with shorter time to sperm appearance and higher sperm recovery rates than hCG monotherapy.
- 07Systematic review2024
Gonadotropins for pubertal induction in males with hypogonadotropic hypogonadism: systematic review and meta-analysis
Alexander EC, et al. · European Journal of Endocrinology · systematic review and meta-analysis of gonadotropin regimens, including hCG plus hMG or FSH, for pubertal induction in male hypogonadotropic hypogonadism
Gonadotropin regimens increased testicular volume and induced pubertal development, but protocols were highly heterogeneous and randomised comparisons were largely absent.
- 08Systematic review2019
Required amount of rFSH, HP-hMG and HP-FSH to reach a live birth: a systematic review and meta-analysis
Bordewijk EM, et al. · Human Reproduction Open · systematic review and meta-analysis of 28 studies including 7,553 women
Differences between rFSH, hp-hMG and hp-FSH in total gonadotropin required per live birth were small, leading the authors to conclude that selection could reasonably rest on availability, cost and patient preference.
- 09Systematic review2008
Urinary hMG versus recombinant FSH for controlled ovarian hyperstimulation following an agonist long down-regulation protocol in IVF or ICSI treatment: a systematic review and meta-analysis
Coomarasamy A, et al. · Human Reproduction · meta-analysis of seven randomised trials, 2,159 women, GnRH agonist long protocol
hMG was associated with a pooled increase of approximately 4 percentage points in live birth rate relative to rFSH in agonist long-protocol IVF/ICSI cycles.
- 10Human clinical2026
Human menopausal gonadotrophin in a pre-filled injection pen is non-inferior to the US-approved powder formulation
Witz C, et al. (CLARA trial group) · Reproductive BioMedicine Online · randomised non-inferiority trial of hp-hMG solution in a pre-filled pen versus the approved lyophilised powder formulation
The pre-filled pen solution met non-inferiority criteria against the powder formulation on the primary stimulation endpoint, with comparable safety observations reported between arms.
- 11Human clinical2025
Impact of gonadotropin selection on risk of ovarian hyperstimulation syndrome in predicted high responders: a Menopur in Gonadotropin-releasing hormone Antagonist Single Embryo Transfer-High Responder trial analysis
Foulk R, et al. · F&S Reports · secondary analysis of the MEGASET-HR randomised trial, 620 women with AMH >=5 ng/mL
After adjustment for oocyte yield, hp-hMG was associated with significantly lower rates of ovarian hyperstimulation syndrome than rFSH in predicted high responders under a GnRH antagonist protocol.
- 12Human clinical2024
Serum progesterone is lower in ovarian stimulation with highly purified HMG compared to recombinant FSH owing to a different regulation of follicular steroidogenesis: a randomized controlled trial
Bosch E, et al. · Human Reproduction · randomised controlled trial in 112 oocyte donors (56 per arm), hp-hMG versus rFSH
Late-follicular serum progesterone was lower with hp-hMG than rFSH, attributed to a shift toward the delta-4 steroidogenic pathway rather than to differences in follicular recruitment.
- 13Human clinical2020
Randomized, assessor-blinded trial comparing highly purified human menotropin and recombinant follicle-stimulating hormone in high responders undergoing intracytoplasmic sperm injection
Witz CA, et al. · Fertility and Sterility · MEGASET-HR randomised assessor-blinded equivalence trial, 620 predicted high responders (AMH >=5 ng/mL), GnRH antagonist protocol with single blastocyst transfer
hp-hMG achieved ongoing pregnancy rates equivalent to rFSH despite lower oocyte yield, with fewer adverse events including ovarian hyperstimulation syndrome and early pregnancy loss.
- 14Human clinical2002
Efficacy and safety of highly purified menotropin versus recombinant follicle-stimulating hormone in in vitro fertilization/intracytoplasmic sperm injection cycles: a randomized, comparative trial
European and Israeli Study Group on Highly Purified Menotropin versus Recombinant Follicle-Stimulating Hormone · Fertility and Sterility · multicentre randomised comparative phase III trial, 781 women enrolled (373 hp-hMG, 354 rFSH)
Ongoing pregnancy rates were equivalent between hp-hMG and rFSH, with similar safety and tolerability profiles, establishing the reference comparison for later trials.
- 15Review2025
Does HCG and LH supplementation during ovarian stimulation improve clinical outcome? An evaluation of 30 years of clinical research
Mannaerts B, Yding Andersen C, Howles CM · Reproductive BioMedicine Online · narrative review of three decades of clinical research on hCG and LH supplementation, including hMG preparations
The authors concluded that a beneficial effect of hCG or LH supplementation on clinical outcome had never been definitively demonstrated for any combined gonadotropin product.
What this evidence does not establish.
Head-to-head randomised data remain insufficient to establish whether hMG or hp-hMG changes cumulative live birth rate across fresh and subsequent frozen transfers, and the magnitude of any live birth advantage over recombinant FSH varies by protocol, responder phenotype and trial era. Evidence in poor responders under POSEIDON criteria, in freeze-all strategies, and in male hypogonadotropic hypogonadism is dominated by small, heterogeneous and largely non-randomised studies, and no consensus exists on optimal LH-activity dosing.
Common questions about the research.
- What is HMG?
HMG (human menopausal gonadotropin, also called menotropin) is a urine-derived biologic preparation containing both follicle-stimulating hormone and luteinising hormone activity, conventionally in an approximately 1:1 ratio by international unit.
- How does it differ from recombinant FSH?
Recombinant FSH supplies FSH activity only, produced in cell culture. HMG is extracted from urine and supplies both FSH and LH activity, with part of the LH activity contributed by chorionic gonadotropin present in the preparation. The Cochrane comparison of the two classes across 42 trials found no statistically significant difference in live birth rate.
- What does the research report about ovarian hyperstimulation syndrome risk?
A 2026 Cochrane systematic review reported that ovarian hyperstimulation syndrome was probably higher with recombinant FSH than with hMG or highly purified hMG, at moderate certainty of evidence. A secondary analysis of the MEGASET-HR randomised trial in 620 women with AMH of 5 ng/mL or above found significantly lower rates of the syndrome with highly purified hMG than with recombinant FSH under a GnRH antagonist protocol, after adjustment for oocyte yield. No consensus exists in this literature on optimal LH-activity dosing.
Available from our catalog
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no study summarised here should be read as a recommendation.