Menotropins

How Menotropins works

Menotropins supply FSH activity that drives recruitment and growth of ovarian follicles, together with LH activity that stimulates thecal androgen production as substrate for follicular estradiol synthesis. The ovary is stimulated directly, bypassing the pituitary; a separate hCG dose is then used to trigger final maturation.

What research has looked at

• FDA-approved for development of multiple follicles and pregnancy in ovulatory women as part of an assisted reproductive technology cycle.
• In the single pivotal randomised, open-label, multicentre trial (373 women in the menotropins arm), the primary efficacy endpoint of continuing pregnancy — an ultrasound-visualised gestational sac with fetal heartbeat at 10 or more weeks after embryo transfer — was met in 87 women (23 percent), non-inferior to recombinant human FSH on a two-sided 95 percent confidence interval, intent-to-treat analysis.
• Clinical pregnancy was reported in 98 women (26 percent), but this was a secondary efficacy parameter and the study was not powered to demonstrate differences in it.
• Supplies both FSH and LH activity in a single preparation, unlike recombinant FSH products which supply FSH alone. The label establishes no efficacy advantage over recombinant FSH — the pivotal trial demonstrated non-inferiority only.

Evidence level: Approved labeling. Official prescribing information exists, based on clinical trials in people. These are areas studied or reported, not promised effects.

Reported side effects and risks

• Contraindicated in pregnancy (may cause fetal harm), in high FSH levels indicating primary ovarian failure, in uncontrolled non-gonadal endocrinopathies (for example thyroid, adrenal, or pituitary disorders), in sex hormone-dependent tumours of the reproductive tract and accessory organs, in tumours of the pituitary gland or hypothalamus, in abnormal uterine bleeding of undetermined origin, in ovarian cyst or enlargement of undetermined origin not due to polycystic ovary syndrome, and in prior hypersensitivity to menotropins products or their excipients.
• Should only be used by physicians experienced in infertility treatment, requires access to appropriate monitoring facilities, and the lowest effective dose should be used.
• Abnormal ovarian enlargement: hCG must be withheld if the ovaries are abnormally enlarged on the last day of therapy, to reduce the chance of ovarian hyperstimulation syndrome. Intercourse must be prohibited when there is significant ovarian enlargement because cyst rupture can cause hemoperitoneum, which may require surgical intervention.
• Ovarian hyperstimulation syndrome, reported in 7.2 percent of the 373 treated women in the pivotal IVF trial and in 6.2 percent (27 of 434 women) in the pooled two-trial adverse-reaction dataset. It is distinct from uncomplicated ovarian enlargement and can progress rapidly, with fluid accumulating in the peritoneal cavity, thorax and potentially the pericardium. It peaks about seven to ten days after treatment and is more common, more severe and more protracted if pregnancy occurs, so women should be assessed for at least two weeks after hCG administration.
• Pulmonary and vascular complications: atelectasis, acute respiratory distress syndrome and exacerbation of asthma; thromboembolic events both in association with and separate from ovarian hyperstimulation syndrome, with sequelae including venous thrombophlebitis, pulmonary embolism, pulmonary infarction, stroke, arterial occlusion resulting in loss of limb, and rarely myocardial infarction. In rare cases these have resulted in death.
• Ovarian torsion, which may be related to ovarian hyperstimulation syndrome, pregnancy, previous abdominal surgery, past torsion, previous or current ovarian cyst, or polycystic ovaries.
• Multi-fetal gestation and birth: multiple pregnancy diagnosed by ultrasound occurred in 35.3 percent of the 85 pregnancies in the pivotal IVF trial, with associated maternal and fetal risk.
• Congenital malformations: incidence after IVF or ICSI may be slightly higher than after spontaneous conception, thought to relate to parental characteristics and to the higher rate of multi-fetal gestation. The label states there is no indication that gonadotropin use during IVF or ICSI is associated with increased malformation risk.
• Ectopic pregnancy: incidence may be increased because women undergoing assisted reproduction often have tubal abnormalities. Intrauterine pregnancy should be confirmed early by beta-hCG testing and transvaginal ultrasound.
• Spontaneous abortion: risk is increased with gonadotropin products, although causality has not been established and the increase may reflect the underlying infertility.
• Ovarian neoplasms, both benign and malignant, have been infrequently reported in women who have had multiple drug therapy for controlled ovarian stimulation; a causal relationship has not been established.
• Required laboratory and imaging monitoring: ultrasound assessment of follicular development, alone or combined with serum estradiol measurement, is needed to time the ovulatory trigger, detect ovarian enlargement, and minimise the risk of ovarian hyperstimulation syndrome and multiple gestation.
• Common adverse reactions at 2 percent or greater in IVF/ICSI trials: abdominal pain 6.7 percent, headache 6.2 percent, injection site pain and reaction 3.9 percent, abdominal cramps 3.0 percent, abdomen enlarged 2.3 percent, injection site inflammation 2.3 percent. Thrombophlebitis was reported in less than 1 percent.
• There is no US labeled use in men; off-label use of human menopausal gonadotropin in male fertility protocols is outside this label. No boxed warning is present on the US label.

Sources

1. PubMed research on Menotropins · NIH · National Library of Medicine
2. DrugBank record for Menotropins · DrugBank
3. Active clinical trials for Menotropins · U.S. National Library of Medicine

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Menotropins FAQ