Research & Bioactivity
Human Menopausal Gonadotrophin (HMG) is a gonadotrophin preparation containing both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity, and researchers have studied it extensively in the context of ovarian stimulation and reproductive biology. Much of the published research has examined HMG in clinical and retrospective cohort studies involving women undergoing assisted reproductive technology (ART) procedures, including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Studies have compared highly purified HMG (HP-HMG) against recombinant FSH formulations and other gonadotrophin types, investigating metrics such as follicular output rate, oocyte yield, and overall ovarian response efficiency across thousands of stimulation cycles. Research has also investigated HMG within the broader context of luteal-phase stimulation protocols and its relationship to complications such as ovarian hyperstimulation syndrome (OHSS), a condition that has been documented in case reports and observational studies. Additionally, researchers have examined how different gonadotrophin protocols — including those incorporating HMG — interact with agents used to prevent premature LH surges, such as GnRH antagonists and progestins, in controlled ovarian stimulation settings.
Published Research
Ovarian hyperstimulation syndrome with pleural effusion after unassisted pregnancy during a luteal-phase stimulation cycle.
Emole A, Sinha N, Aboukhalil D, Gupta S, Eyvazzadeh A — 2026
OBJECTIVE: To describe a rare case of ovarian hyperstimulation syndrome (OHSS) presenting as an isolated right-sided pleural effusion because of endogenous human chorionic gonadotropin (hCG) production from a naturally conceived pregnancy during a luteal-phase ovarian stimulation cycle. DESIGN: Single-patient case report with longitudinal follow up. SUBJECT: A healthy 36-year-old woman with a 15-month history of primary infertility who was undergoing her second luteal-phase ovarian stimulation cycle. EXPOSURE: Controlled ovarian stimulation with menotropins, recombinant follicle-stimulating hormone, letrozole and somatropin, followed by endogenous hCG production from an unexpected naturally conceived pregnancy; no exogenous hCG trigger was administered. MAIN OUTCOME MEASURES: Onset and clinical course of OHSS; volume and recurrence of pleural effusion; need for thoracentesis or an indwelling pleural catheter; maternal and neonatal outcome. RESULTS: A total of 17 ovarian follicles developed by stimulation day 11 with a modest peak estradiol concentration of 279 pg/mL, underscoring the unexpected nature of the subsequent severe presentation. Serum hCG measured 53 mIU/mL on day 11 and rose to 231 mIU/mL 2 days later, confirming conception and prompting cancelation of the stimulation cycle. After 6 days, the patient developed worsening dyspnea; imaging revealed a large right pleural effusion. Three thoracenteses over 10 days removed 4,700 mL of fluid before placement of a 12-French indwelling pleural catheter, which promptly relieved symptoms. Bilateral ovarian enlargement was present with no evidence of ascites. The pregnancy then progressed uneventfully until preterm delivery of a healthy infant at 32 weeks of gestation; both mother and child were discharged in good condition. CONCLUSION: Ovarian hyperstimulation syndrome can occur despite low estradiol concentrations and the absence of an exogenous hCG trigger. Endogenous hCG from an unrecognized early pregnancy can independently provoke severe vascular hyperpermeability even in canceled cycles with low estradiol and no trigger shot. Clinicians should maintain vigilance for respiratory complications and perform routine pregnancy testing during luteal-phase stimulation to avert delayed diagnosis and morbidity.
Gonadotrophin type and antral follicle count-adjusted follicular recruitment and oocyte yield in 4525 antagonist cycles.
Dhaenens L, Rottiers AS, Vandierendonck F, Hellebaut S, Heindryckx B, et al. — 2026
RESEARCH QUESTION: Do FSH types (recombinant FSH [rFSH] versus highly purified human menopausal gonadotrophin (HP-HMG) versus corifollitropin alfa (CFA) differ in the efficiency of ovarian response, as assessed by follicular output rate (FORT) and follicle-to oocyte index (FOI)? DESIGN: Retrospective cohort study analysing 4525 antagonist IVF and intracytoplasmic sperm injection cycles using CFA (n = 728), rFSH (n = 1848) or HP-HMG (n = 1949). The FORT and FOI indices were calculated as ratios of follicle or oocyte yield to antral follicle count (AFC). Generalized estimating equations were used to account for clustering by patient with covariates for age, anti-Müllerian hormone (AMH), weight, stimulation duration, gonadotrophin dose and elective freeze. RESULTS: The CFA yielded the highest ovarian response indices (FORT 16-22 [61.6%], FOI-COC [106.4%], FOI-MII [81.1%]), compared with rFSH (49.3%, 98.0%, 74.6%) and HP-HMG (39.6%, 71.5%, 46.5%). Stratified analyses confirmed this ranking across AMH strata. In low AMH (<1.1 ng/ml), FOI-MII was 81.4% with CFA, 64.5% with rFSH and 49.2% with HP-HMG. In normal/high AMH (1.1-3 ng/ml) FOI-MII was 86.3%, 64.5% and 53.1%. Generalized additive model analyses demonstrated a modest non-linear AMH effect only for CFA, peaking at about 1.5-2.0 ng/ml before declining, whereas rFSH rose gradually and HP-HMG remained quite flat. Age-stratified analyses showed a uniform decline across FSH types. The risk of OHSS (>18 follicles ≥11 mm) was lowest with CFA (6.5%), compared with 19.8% for HP-HMG and 39.2% for rFSH. CONCLUSION: After adjusting for AFC, CFA achieved the highest FORT and FOI across most AMH strata, consistently outperforming HP-HMG and matching or exceeding rFSH, while maintaining the lowest follicle-count-based OHSS risk.
Medroxyprogesterone acetate vs. GnRH antagonist for preventing premature LH surge during ovarian stimulation in assisted reproductive technology: a retrospective cohort study.
Jimenez MM, Jesam C, Sequeira K, Alcantar K — 2026
OBJECTIVE: To compare the effectiveness of medroxyprogesterone acetate (MPA) vs. cetrorelix (GnRH antagonist) in preventing premature LH surge during ovarian stimulation in assisted reproductive technology (ART) cycles, including cycles for intracytoplasmic sperm injection (ICSI) and fertility preservation. DESIGN: Single-center, retrospective observational cohort study. SETTING: Private fertility clinic in Santiago, Chile. PATIENTS: A total of 2,964 ART cycles conducted between January 2018 and December 2022 were included after excluding 425 cycles that were cancelled. Among these, 1,793 were ICSI cycles (1,529 antagonist, 264 MPA) and 1,171 were fertility preservation cycles (862 antagonist, 309 MPA). INTERVENTIONS: Ovarian stimulation using recombinant FSH and/or menotropins with ovulatory suppression by either oral MPA (10 mg/day) or daily cetrorelix (0.25 mg). MAIN OUTCOME: Follicular response, oocyte yield, embryo development, euploidy and mosaicism rates, implantation, clinical pregnancy, miscarriage, and live birth outcomes. RESULTS: In fertility preservation cycles, MPA produced higher numbers of follicles ≥17 mm (8.7 vs. 6.7), oocytes retrieved (12.2 vs. 10.7), and mature oocytes (9.1 vs. 7.9; < 0.01 for all). In ICSI PGT-A cycles, MPA was associated with a higher number of biopsied blastocysts and frozen embryos per patient, while euploid, implantation, and live birth rates were comparable to the antagonist group. Cancellation, fertilization, and miscarriage rates did not differ significantly. CONCLUSIONS: MPA is a safe and effective oral alternative to GnRH antagonists for LH suppression during ovarian stimulation in ART, providing comparable reproductive outcomes while reducing treatment burden.
Effectiveness of minimal stimulation versus conventional GnRH antagonist protocols in controlled ovarian hyperstimulation: a retrospective analysis of 10769 IVF/ICSI cycles.
Sanagoudar SV, Chandra V, Murdia K, Murdia N, Nigam S, et al. — 2026
BACKGROUND: The aim of this study was to find the efficacy of minimal stimulation protocol over antagonist protocol in infertile couples. METHODS: A total of 10769 patients who visited between January 2018 and January 2022 were included in this retrospective study. To reduce potential bias and baseline heterogeneity between the two groups, Propensity Score Matching was employed, so the data after propensity matching was N.=978. Group 1 - minimal stimulation group (N.=347) - received clomiphene citrate 100 mg along with gonadotropin (≤150 IU), either recombinant follicle-stimulating hormone (r-FSH) or human menopausal gonadotropin (hMG). Group 2, the conventional dose antagonist group (N.=631), received a conventional dosage of r-FSH (≥225 IU) as per institutional practice. RESULTS: The minimal stimulation group had a considerably higher live birth rate (58.20%) than the antagonist group (51.20%), with a P value of 0.035, demonstrating a statistically significant benefit for the minimal stimulation procedure. For live birth rate, endometrial thickness (odds ratio [OR] = 1.22, 95% confidence interval [CI]: 1.09-1.36, P<0.001), number of embryos transferred (OR=1.95, 95% CI: 1.37-2.78, P<0.001), and sperm count (OR=1.01, 95% CI: 1.00-1.05, P=0.044) were significant predictors. In the subgroup anti-Müllerian hormone (AMH; 1.5-2.5 ng/mL), the antagonist protocol yielded a significantly higher number of oocytes retrieved and mature oocytes; however, the minimal protocol demonstrated superior blastulation rates, good blastocyst quality, and a notably higher live birth rate. CONCLUSIONS: Compared to the standard treatment, the minimal stimulation group's live birth rate was much higher, indicating that some patient populations might benefit from fewer drugs and less stimulation.
Optimizing mature oocyte yield in IVF: clinical comparison of r-hFSH+r-hLH and HMG in women with a stimulation dosage of at least 300 IU of gonadotropins.
Fatemi H, Steinmacher S, Melado L, ElKhatib I, Marqueta L, et al. — 2026
OBJECTIVE: To study the impact of luteinizing hormone (LH) in stimulation medication on the mature oocyte yield obtained in in women receiving ovarian stimulation (OS) with a dosage of at least 300 IU gonadotropins. DESIGN: Retrospective cohort study (01/2016-05/2024). SETTING: Tertiary assisted reproductive technology center. PATIENTS: Women undergoing OS stimulation of at least 300 IU gonadotropins. INTERVENTION: OS using r-hFSH+r-hLH or HMG as stimulation medication. MAIN OUTCOME MEASURE: Retrieved mature oocyte number. RESULTS: A total of 1,286 patients (696 in the HMG group and 590 in the r-hFSH+r-hLH group) were included in the unmatched cohort. Before matching, the r-hFSH+r-hLH versus HMG-groups showed significant differences in AMH (0.8 vs 1.2ng/mL,p<0.001), starting doses (85.1% vs 70.1% on 450IU,p<0.001), and categorized BMI distribution (p=0.003). After propensity score matching (age, BMI, AMH, basal FSH, starting dose), 1052 cycles were analyzed with a 1:1 match ratio. In the matched cohort after further adjusting for confounders, r-hFSH+r-hLH use was associated with significantly higher collected oocyte count (IRR 1.10, 95% CI 1.03-1.17, p=0.004) and mature oocyte count (IRR 1.12, 95% CI 1.04-1.21, p=0.003) compared to HMG. The sensitivity analysis looking at the interaction of AMH with gonadotropin type showed the effect is mostly significant for those with normal ovarian reserve (AMH between 1.0-3.5ng/mL, IRR: 1.19, 95% CI: 1.07 to 1.33, P = 0.001) but not for those with low (≤1ng/mL, P = 0.180) or high ovarian reserve (>3.5ng/mL, P = 0.932). Analysis of maturation rates showed no significant effect of medication type (p=0.143). The euploid blastocyst count after stimulation in the matched cohort and HMG use was associated with a 22% lower yield compared to r-hFSH+r-hLH (IRR 0.78, 95% CI 0.66-0.93, p=0.006) after adjusting for AMH, basal FSH, female age, dose, body mass index. CONCLUSION: The use of r-hFSH+r-hLH is associated with a significantly higher mature oocyte and euploid blastocyst count compared to HMG and the effect was most pronounced in women with normal ovarian reserve.