Gonadotrophins and Ovulation Stimulants (Efficacy)

In in vitro fertilization (IVF) protocols, women are given different gonadotrophins or ovulation-stimulating hormones to stimulate the development of ovarian follicles and the production of a greater number of eggs. There is a high percentage of women who do not respond adequately to treatment with these drugs, and this may be due to different factors, including genetic factors.

Gonadotropins, such as follitropin-alpha, follitropin-beta, menotropin, and urofollitropin are hormones that stimulate ovulation. These hormones are prescribed during clinical fertilization treatments.

ACTION MECHANISM

In women, these hormones stimulate follicular growth and maturation, favoring the secretion of estrogens and other gonadal steroids.

CONTRAINDICATIONS

Gonadotropin treatment is contraindicated when the patient has hypersensitivity to gonadotropins, hypothalamic or pituitary tumors; ovarian enlargement or cysts not due to polycystic ovarian disease, gynecological bleeding of unknown origin; ovarian, uterine, or breast carcinoma.

It should not be used when an effective response is not obtained in: primary ovarian failure, malformations of sexual organs or fibroid tumors of the uterus incompatible with pregnancy.

CAUTIONS

Cautions should be taken when prescribing gonadotropin treatment in cases of hepatic and renal failure, porphyria, or in a patient with family history of porphyria.

Treatment with gonadotropins may increase the risk of ovarian hyperstimulation syndrome, especially in women with polycystic ovary, those who have suffered multiple or ectopic pregnancies or abortions, in women who suffer or have suffered from neoplasms of the reproductive system (benign or malignant) and thromboembolic disorders.

Before prescribing gonadotropins, the presence of hypothyroidism, adrenal insufficiency or hyperprolactinemia should be ruled out.

Monitor ovarian response using ultrasound and estradiol determination to early identify risk factors for ovarian hyperstimulation.

SIDE EFFECTS

Pain, redness, bruising, swelling and/or irritation at the injection site. Headache; abdominal pain, nausea, vomiting, diarrhea; ovarian cysts; mild or moderate ovarian hyperstimulation syndrome.

PHARMACOLOGIC INTERACTIONS

Gonadotrophins enhance the follicular response when prescribed concomitantly with other ovulation-stimulating medications (such as hCG or clomiphene citrate)

BRAND NAMES

Follitropin α: Gonal F®
Follitropin β: Puregon®
Menotropin: Menopur®
Urofollitropin: Fostipur®

Genes analyzed

FSHR

Bibliography

Baldini GM, Catino A, Palini S, et al. The Polymorphism Asn680Ser on the FSH Receptor and Abnormal Ovarian Response in Patients with Normal Values of AMH and AFC. Int J Mol Sci. 2023 Jan 5;24(2):1080.

Mahey R, Rajput M, Dada R, et al . Prevalence of FSH-R Asn680Ser and Ala307Thr receptor polymorphism and their correlation with ART outcomes among infertile Indian-Asian women-a prospective cohort study. J Hum Genet. 2024 Apr 25.

Morón FJ, Ruiz A. Pharmacogenetics of controlled ovarian hyperstimulation: time to corroborate the clinical utility of FSH receptor genetic markers. Pharmacogenomics. 2010 Nov;11(11):1613-8.

Nenonen HA, Lindgren IA, Prahl AS, et al . The N680S variant in the follicle-stimulating hormone receptor gene identifies hyperresponders to controlled ovarian stimulation. Pharmacogenet Genomics. 2019 Jul;29(5):114-120.