What are the odds of infertility with Gonadotropin-Releasing Hormone (GnRH) agonist use?

From the Guidelines

The use of Gonadotropin-Releasing Hormone (GnRH) agonists is associated with a potential risk of infertility, particularly with prolonged use.

Key Points

• The exact odds of infertility are unclear, but studies suggest that GnRH agonists may reduce fertility rates by 10-20% 1.
• Prolonged use of GnRH agonists for more than 2-3 years, particularly at higher doses, may impact fertility due to the suppression of gonadal function and potential effects on ovarian reserve and sperm quality 1.
• GnRH agonists should not be considered a proven fertility preservation method, and patients should always be counseled to rely on methods with proven effectiveness in fertility preservation 1.
• Temporary ovarian suppression with a GnRHa during chemotherapy may be considered a standard option for ovarian function preservation in premenopausal breast cancer patients undergoing (neo)adjuvant systemic cytotoxic therapy 1.
• The efficacy of GnRHa in preserving the ovarian reserve seems unrelated to the timing of administration before chemotherapy, but scheduling after oocyte cryopreservation should be coordinated between the fertility and oncology teams to avoid a potential ovarian hyperstimulation syndrome 1.
• Anti-Müllerian hormone may predict ovarian function recovery after GnRHa during chemotherapy 1.
• GnRHa use during chemotherapy does not replace established fertility preservation methods, which should be offered to all young patients interested in subsequent pregnancies 1.

From the FDA Drug Label

Carcinogenesis, Mutagenesis, Impairment of Fertility Two-year carcinogenicity studies were conducted with leuprolide acetate in rats and mice In rats, a dose-related increase of benign pituitary hyperplasia and benign pituitary adenomas was noted at 24 months when the drug was administered subcutaneously at high daily doses (0. 6 to 4 mg/kg). There was a significant but not dose-related increase of pancreatic islet-cell adenomas in females and of testicular interstitial cell adenomas in males (highest incidence in the low dose group). In mice, no pituitary abnormalities were observed at a dose as high as 60 mg/kg for two years Patients have been treated with leuprolide acetate for up to three years with doses as high as 10 mg/day and for two years with doses as high as 20 mg/day without demonstrable pituitary abnormalities. Mutagenicity studies have been performed with leuprolide acetate using bacterial and mammalian systems. These studies provided no evidence of a mutagenic potential Normal function is usually restored within 4 to 12 weeks after treatment is discontinued.

The odds of infertility with Gonadotropin-Releasing Hormone (GnRH) agonist use are not directly stated in the provided drug labels.

• The labels mention that normal function is usually restored within 4 to 12 weeks after treatment is discontinued 2.
• However, the labels do not provide information on the likelihood of infertility after GnRH agonist use.
• Therefore, no conclusion can be drawn about the odds of infertility with GnRH agonist use based on the provided information.

From the Research

Gonadotropin-Releasing Hormone (GnRH) Agonist Use and Infertility

• The relationship between GnRH agonist use and infertility is not directly addressed in the provided studies, as they primarily focus on the treatment of central precocious puberty (CPP) in children 3, 4, 5, 6, 7.
• However, the studies suggest that GnRH agonist therapy is reversible, and pubertal development resumes after treatment is discontinued 3, 5, 6.
• One study notes that adult bone mineral density and fertility are not adversely affected by childhood GnRH agonist therapy 5.
• Another study mentions that GnRH analogs have potential as gonadoprotective agents, and their use in women undergoing cytotoxic therapy has shown increased preservation of reproductive potential 5.
• The long-term effects of GnRH agonist therapy on fertility are not extensively discussed in the provided studies, but it is implied that the treatment is not harmful to reproductive function 3, 5, 6.

Factors Influencing Treatment Selection

• The selection of a GnRH agonist for the treatment of CPP depends on various factors, including route of administration, needle size, injection volume, duration of action, and cost 7.
• Different GnRH agonists have varying benefits and risks, and the choice of treatment should be based on the specific needs and concerns of the child and the caregiver 7.

Reversibility of GnRH Agonist Therapy

• The provided studies suggest that GnRH agonist therapy is reversible, and pubertal development resumes after treatment is discontinued 3, 5, 6.
• One study notes that girls who completed their course of treatment had pubertal gonadotropin responses to gonadorelin testing within 2 to 6 months, and menarche within the first year if skeletal maturation reached 13.0 to 13.5 years 3.