Pharmacology of medications used for ovarian stimulation

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madman

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Practice Points

The mechanisms of action of medications used to stimulate the ovaries are based on the physiology of the hypothalamic-pituitary-ovarian axis

Common ovulatory disorders include hypothalamic anovulation, polycystic ovary syndrome and ovarian insufficiency/hypergonadotropic anovulation

Whenever possible attempts should be made to treat the underlying ovarian disorder, such as hypothyroidism or a prolactin-secreting lactotroph adenoma

The ideal treatment for WHO I anovulation (hypothalamic amenorrhea) is pulsatile GnRH, administered via a subcutaneous pump (available in Europe but not the United States)

The aromatase inhibitor Letrozole is superior to Clomiphene for ovulation induction in polycystic ovary syndrome, and now considered the first line therapy

The gonadotropins LH and FSH, derived from menopausal urine or recombinant, are used for ovulation induction or as part of controlled ovarian hyperstimulation (COH) as part of assisted reproductive technology (ART) cycles

FSH alone can produce follicular maturation, but patients with hypothalamic dysfunction require LH, and outcomes of COH in ART may be superior with mixed preparations

Glucocorticoids, androgens and Coenzyme Q10 may be used as adjuvants for ovarian stimulation but lack proven efficacy.






Research Agenda

The hypothalamic KISS1 system has emerged as a major target for future research into ovarian stimulation and the treatment of reproductive disorders

The role of androgens in ovarian stimulation for poor responders requires further investigation

Co-Enzyme Q10 is a mitochondrial nutrient that may improve outcomes of ovarian stimulation; clinical trials are ongoing

Long-acting FSH preparations may replace daily FSH injections as part of COH in the future

The search for orally active gonadotropin agonists is ongoing, but has thus far been unsuccessful

Oral GnRH antagonists such as Elagolix are being investigated in the treatment of endometriosis-associated pain and leiomyomyas, and may become part of stimulation protocols in ART in the future

Pharmacogenomics research may assist in the choice of ovarian stimulation in ART in the future.
 

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