Fertility medication in treating infertility

Fertility Drugs

Clomiphene

It is useful in those who are infertile due to anovulation or oligoovulation.

MOA – Enhanced release of pituitary gonadotropins by reduction in the negative feedback of endogenous estrogen due to prolonged depletion of hypothalamic  and pituitary estrogen receptors, resulting in follicular recruitment, selection, assertion of dominance of niphene.

Dosage – 50-150 mg/day. Will start on day 2 to day 5 of cycle for 5 days with ovulation rate of 70-92%

Side effects – Hot flushes, abdominal distension, blocking discomfort, breast discomfort, nausea and vomiting, head ache, usual symptoms and multiple pregnancy.

 

Letrozole

Prevents the aromatase from producing estrogens by competitive, reversible binding to the haeme of its cystochrome P 450 unit.

Dosage – 2.5 to 5mg /day. Will start on day 2 or 3 of cycle for 5 days

Side effects – Hot flushes, arthalgia, fatigue, nausea.

 

MRH Agonist

Control of gonadotropin reaction is exerted by hypothalamic release of GnRH.

MOA – GnRH agonist increases gonadotropin secretion (flare up effect) and usually requires 7-10 days to achieve a state of pituitary suppression. Prolonged administration leads to down regulation of GnRH receptors.

Route of administration – Parenteral, nasal spray.

Side effects – Flushes, decreased letrido, impotence, vaginal dryness, reduced breast size, emotional instability.

 

Gonadotropins

Are glycoprotein polypeptide hormones secreted by gonadotrope cells. This family  includes FSH (Folllicle Stimulating hormone) and LH (Luteinizing hormones) secreted by anterior pituitary gland which HCG (human chorionic gonadotropin) secreted by placenta in pregnant humans. The gonadotropins  act on the gonads, controlling gamete and sex hormone production.

The use of gonadotropins started as early as 1959 by purification and use of pituitary and urine gonadotropins followed later in 1985 by further purification of urinary gonadotropins producing highly purified HMG. Considerable improvements have facilitated both separation of KSH from LH and its production by recombinant technology.

The objective of the fertility treatment is optimization  of outcome with minimization is opting of risk. A flexible gonadotropin dosing during stimulation is essential for optimizing the cycle outcome. The optimum dose is based on  individual patient characteristics like age, BMI, antral follicle count, basal FSH, previous stimulation outcome, etc.,

Dosage – 37.5 IU to 450 IU (daily injections) intra muscular or subcutaneous.

Side effects – Abdominal pain, nausea, breast swelling, runny or stuffy nose, allergic reactions (rarely with urinary products, swelling of lower legs, weight gain, head ache, shortness of breath, bloating (moderate to severe) multiple pregnancy.

 

HCG

Owing to inconsistency of spontaneous LH surge in controlled ovarian stimulation the final triggering of ovulation is performed using HCG. Following HCG trigger the follicles rupture 36-40 hrs later.

MOA – Used as a surrogate LH surge because of the degree of homology between two hormones. They both have almost identical alfa subunits and bind to the LH receptor but differ in their beta sub interleading to better stability and longer half life.

Dosage – 2000, 5000 or 10000 IU – urinary HCG, rHCG – 250 mcg/500 mcg.

Side effects – Features of OHSS – abdominal pain, nausea, vomiting, diarrhoea shortness of breath, swelling of legs weight gain.

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