Human menopausal gonadotropin (hMG)

hMG is extracted from the urine of postmenopausal women, whose pituitaries release large amounts of FSH and LH. It contains both activities in equal amounts [1]. In highly purified products, most of the LH activity comes from hCG [5].

IVF. Whether the LH activity helps has been argued for decades. In the MERiT trial of 731 women having IVF, highly purified hMG yielded fewer eggs than recombinant FSH (10.0 vs 11.8) but a higher share of top-quality embryos, and ongoing pregnancy rates were 27% vs 22%: non-inferior, but superiority was not shown [5]. In the MEGASET trial of 749 women with single-blastocyst transfer, ongoing pregnancy was 30% vs 27% and cumulative live birth 40% vs 38% [6]. In 620 women expected to over-respond, hMG gave a similar ongoing pregnancy rate (35.5% vs 30.7%) with less than half the ovarian hyperstimulation (9.7% vs 21.4%) and fewer early pregnancy losses [7]; at the same number of eggs retrieved, the odds of hyperstimulation were halved [8]. Pooling 59 trials, the 2026 Cochrane review rated live birth as probably lower (OR 0.83) and hyperstimulation as probably higher (OR 1.42) with recombinant FSH than with hMG [2]. An earlier meta-analysis reached the same direction of effect [9], and a pooled analysis of five trials of highly purified hMG against follitropin alfa found no advantage for the recombinant product [10].

Ovulation induction in PCOS. For women with polycystic ovary syndrome who do not ovulate on clomiphene or letrozole, a 2025 Cochrane review could not say whether hMG is better or worse than urinary FSH (very-low certainty), but found gonadotropins as a class gave more live births than continuing clomiphene [11].

Men with gonadotropin deficiency. In men whose hypogonadism began before puberty, hCG alone rarely brings sperm counts to normal; adding hMG normalised counts in 5 of 7 men without a history of undescended testes [3]. In 17 Chinese men, 11 needed hMG added after at least 6 months of hCG, and 12 of the 17 went on to father a pregnancy [12]. A German series of 42 men found sperm in 54 of 57 treatment courses and pregnancies in 26 of 36, with no difference between hCG/hMG and pulsatile GnRH [4]. Even men left untreated until their forties produced sperm in 3 of 6 cases after two years [13].

Other male uses. A Cochrane review of FSH preparations for unexplained male subfertility found more spontaneous pregnancies (16% vs 7%) across five small trials, but judged the evidence insufficient [14]. A single case report describes a bodybuilder whose steroid-induced azoospermia persisted a year after stopping, and recovered after 3 months of hCG with hMG [15].

FSH acts on the granulosa cells around each egg, recruiting and growing follicles and driving them to make oestradiol; in a multiple-dose study, FSH exposure raised oestradiol and follicle growth in step with the dose [1]. In the testis, FSH acts on the Sertoli cells that nurse developing sperm, which is why men who lack it often need hMG on top of hCG [3].

The LH activity, mostly hCG in modern products, changes the hormonal environment of stimulation: women given hMG had higher oestradiol and lower progesterone at the end of stimulation than women given recombinant FSH, even after adjusting for follicle numbers, and a rise in progesterone was linked to lower pregnancy rates in the recombinant FSH group [5].

The main risk in women is ovarian hyperstimulation syndrome (OHSS). In MERiT, moderate or severe early OHSS occurred in 1.4% on hMG and 1.6% on recombinant FSH [5]; in women expected to over-respond, rates were 9.7% on hMG and 21.4% on recombinant FSH [7]. A UK guideline sets out how to identify and prevent it [19]. Two triplet pregnancies occurred in the hMG arm of MERiT after two-embryo transfers [5]. In women with PCOS, gonadotropins may raise the miscarriage rate compared with continuing clomiphene [11].

In healthy women given single doses, headache was the only adverse effect above 10% (14% after 300 IU), and 39–44% had mild pain at the injection that lasted only while it was given [1]. In MERiT the most common adverse events besides menstrual bleeding were miscarriage, pelvic pain, headache and hyperstimulation, at similar rates on both products [5]. Adverse event data from trials in men are sparse [14].

In men, hMG is given together with Human chorionic gonadotropin (hCG), which supplies the LH activity needed for testosterone [3][4]. In IVF it is used with a GnRH agonist or antagonist to prevent a premature LH surge and an hCG or GnRH agonist trigger at the end [5][8].