Table 2 Overview of major clinical trials comparing HP-hMG versus rFSH and rFSH/rLH- versus rFSH-containing products in ART protocols

EISG (EISG, Fertil Steril 2002 [10])

N = 781

Menopur® versus Gonal-F®

225 IU fixed dose for 5 days of either HP-hMG or rFSH alfa

Non-inferiority

Efficacy:

OPR: 25% HP-hMG versus 22% rFSH alfa, P = 0.17

Safety:

Adverse events probably and possibly related to the medication; 14.2% HP-hMG vs 13.0% rFSH alfa

OHSS: 1.9% HP-hMG vs 1.2% rFSH alfa

Miscarriage: 25.4% HP-hMG vs 27.6% rFSH alfa

MERiT (Andersen AN, et al. Hum Reprod 2006 [11])

N = 731

Menopur® versus Gonal-F®

225 IU fixed dose for 5 days of either HP-hMG or rFSH alfa, followed by individual adjustments according to the patient’s follicular response

Non-inferiority

Efficacy:

OPR per started cycle: 27% HP-hMG vs 22% rFSH alfa (95% CI: 0.89 to 1.75, P = 0.204)

Safety:

Incidence of adverse events: 51% HP-hMG vs 49% rFSH alfa

OHSS: 4% HP-hMG vs 3% rFSH alfa

Early pregnancy loss: 26% HP-hMG vs 32% rFSH alfa

Bosch E, et al. (Hum Reprod 2008 [78])

N = 280

Menopur® versus Gonal-F®

225 IU fixed starting dose for 2 days of either

HP-hMG or rFSH alfa, followed by individual adjustments according to serum oestradiol levels

Non- inferiority

Efficacy:

OPR per randomised patient: 35.0% HP-hMG (95% CI: 27.1 to 43.5) vs 32.1% rFSH alfa (95% CI: 24.5 to 40.6)

Safety:

Cycles cancelled due to risk of OHSS: 6.4% HP-hMG vs 3.6% rFSH alfa, P = 0.27

Clinical OHSS: 1.64% HP-hMG vs 1.59% rFSH alfa

Pregnancy loss: 0.82% HP-hMG vs 0.79% rFSH alfa

MEGASET (Devroey P, et al. Fertil Steril 2012 [12])

N = 749

Menopur® versus Puregon®

150 IU fixed dose for 5 days of either HP-hMG or rFSH beta, followed by dose adjustments if required of 75 IU increments, not more than every 4 days

Non-inferiority

Efficacy:

OPR in the PP population: 30% HP-hMG versus 27% rFSH beta, 95% CI: 3.0%

(− 3.8 to 9.8)

Safety:

Incidence of adverse events: 39% HP-hMG vs 37% rFSH beta

OHSS: 3% in each treatment group

Interventions associated with excessive response or to prevent early OHSS were higher in rFSH beta group (P = 0.025)

MEGASET-HR (Witz C, et al. Fertil Steril 2020 [79])

N = 620

Patients with serum AMH ≥5 ng/mL

Menopur® versus Gonal-F®

150 IU fixed start dose of either HP-hMG or rFSH alfa

Non-inferiority

Efficacy:

OPR: 35.5% HP-hMG vs 30.7% rFSH alfa, 95% CI: 4.7% (−2.7 to 12.1)

Safety:

OHSS: 9.7% HP-hMG versus 21.4% rFSH alfa, 95% CI: − 11.7% (− 17.3 to − 6.1),

P < 0.05

Incidence of treatment emergent adverse events: 57.7% HP-hMG vs 70.6% rFSH alfa

Cumulative early pregnancy loss (fresh/frozen ET): 14.5% HP-hMG vs 25.5% rFSH alfa

Taronger R, et al. (Eur J Obstet Gynecol Reprod Biol 2018 [80])

N = 234

Poor ovarian responders

Menopur® versus Elonva®

150 μg single dose of CFA followed by 300 IU HP-hMG after Day 8 until criteria for triggering ovulation were met, versus 300 IU continuous daily dose of HP-hMG

Non-inferiority

Efficacy:

OPR per started cycle: 20.2% HP-hMG vs 15.2 CFA, 95% CI: −5 (− 15.1 to 5.0),

P = 0.33

Safety:

Cancellation rate: 5.5% HP-hMG vs 3.6% CFA, P = 0.49

Errázuriz J, et al. (Front Endocrinol 2019 [81])

N = 917

Poor ovarian responders

Menopur® versus Elonva®

150 μg single dose of CFA followed by ≥300 IU HP-hMG after Day 8 until criteria for triggering ovulation were met, versus 7 x fixed daily doses of 300–450 IU HP-hMG

Non-inferiority

Efficacy:

Cumulative LBR: 16.9% HP-hMG vs 11.8% CFA + HP-hMG; P = 0.03

PERSIST (Behre, et al. RBM Online 2015 [82])

N = 202

Women aged 36–40 years

Pergoveris® versus Gonal-F®

300 IU fixed starting dose of rhFSH/rhLH from stimulation on Day 1 or rhFSH on stimulation on Days 1–5 followed by rhFSH + rhLH from stimulation Day 6.

Dose adjustments were permitted from Day 6

Non-inferiority

Efficacy:

Number of oocytes retrieved: 9.7 rhFSH/rhLH vs 10.9 rFSH alfa, 95% CI:

–3.15 to 0.59

Safety:

Adverse events reported: 31.1% rhFSH/rhLH vs 32.3% rFSH alfa

Serious AEs: 2% rhFSH/rhLH vs 0% rFSH alfa

OHSS: 3.9% rhFSH/rhLH vs 5.1% rFSH alfa

ESPART (Humaidan, et al. Hum Reprod 2017 [83])

N = 939

Poor ovarian responders

Pergoveris® versus Gonal-F®

Fixed starting dose of 300 IU rhFSH + 150 IU rhLH (Pergoveris®) or 300 IU rFSH alfa (Gonal-F®). Dose adjustments were permitted from Day 4, at increments of 75 IU of rhFSH with a maximum daily dose of 450 IU (concomitant automatic adjustments of rhLH were made with a maximum daily dose of 325 IU)

Superiority

Efficacy:

Number of oocytes retrieved: 3.3 rhFSH/rhLH vs 3.6 rFSH alfa, 95% CI:

–0.24 (−0.74 to 0.27); P = 0.182

Safety:

TEAEs: 19.9% rhFSH/rhLH vs 26.8% rFSH alfa

Serious TEAEs: 1.7% rhFSH/rhLH vs 3.6% rFSH alfa, 95% CI: 0.46 (0.19 to 1.09)

One incidence of OHSS in the rhFSH/rhLH group