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What are the advantages of using gonadotropins over clomiphene in assisted reproduction?

By Mónica Aura Masip M.D., M.Sc. (gynecologist).
Last Update: 01/31/2022

Clomiphene Citrate is an antiestrogenic treatment used orally to induce ovulation. Mainly, its use is aimed at those patients with absent or irregular ovulation (mostly caused by polycystic ovary syndrome), since it restores ovulation in 70% of cases. In addition, the administration of clomiphene citrate is comfortable since it is carried out orally. This drug also has a low cost and good profitability.

Its mode of action is indirect; induces the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by blocking estrogen receptors in the brain. FSH and LH are the hormones that will act on the ovary, producing an increase in follicles and ovulation.

The main problems with Clomiphene are:

  • Antiestrogenic effects on cervical mucus and the endometrium, achieving a lower pregnancy rate than gonadotropins.
  • Patients with pituitary insufficiency will not benefit from its use since these patients are not able to produce FSH and LH correctly.
  • It is not recommended to carry out more than 6 treatment cycles.
  • High rate of multiple pregnancies (7-10%) due to the development of multiple follicles.
  • Its main side effects are nausea, vomiting, flushing and dizziness. Although visual and skin effects have also been described. These are rare and dose-dependent.
  • Formation of ovarian cysts and/or enlargement of pre-existing ones (including endometriomas).

On the other hand, we have human menopausal gonadotropins (hMG) and recombinant gonadotropins (rFSH and rLH), which are subcutaneously administered and more expensive medications. These produce a direct action on the ovaries, and although their administration may be more uncomfortable for some patients, they have clear advantages. Among them is a much more precise dose adjustment than clomiphene and a higher pregnancy rate due to the absence of antiestrogenic effect on the endometrium.

In addition, gonadotropins are effective in patients with pituitary insufficiency and there is no limit to the number of cycles/treatments to be performed. Side effects of gonadotropins are also minimal.

 Mónica  Aura Masip
Mónica Aura Masip
M.D., M.Sc.
Gynecologist
Dr. Mónica Aura has a degree in Medicine and General Surgery from the Autonomous University of Barcelona (UAB). She is also a specialist in Gynecology and Obstetrics from the Hospital de Santa Creu y Sant Pau and has a Master's degree in Human Assisted Reproduction from the University Juan Carlos I of Madrid and another in Health Center Management from the UB.
Licence number: 31588
Gynecologist. Dr. Mónica Aura has a degree in Medicine and General Surgery from the Autonomous University of Barcelona (UAB). She is also a specialist in Gynecology and Obstetrics from the Hospital de Santa Creu y Sant Pau and has a Master's degree in Human Assisted Reproduction from the University Juan Carlos I of Madrid and another in Health Center Management from the UB. Licence number: 31588.