Ovulation-Inducing

AgentPresented by: Zinab Al-hajari

Chemical structure:Clomiphene citrate is a

a non-steroidal selective estrogen receptor modulator (SERM) related structurally to triphenylethylene.

It is available as a racemic mixture of

cis (zuclomiphene) and trans form (enclomipene).

Cl

OCH2CH2NCH2CH3

CH2CH3

Mechanism of action:

Clomiphene is a partial agonist at oestrogen receptor.

It leads to an increase in the secretion of gonadotropins and oestrogen by inhibiting estradiol’s feedback effect on the gonadotropins.

Pituitary

hypothalamus

Ovaries

Estrogens

FSH + LH

Clomiphene Citrate

-Ve

+ Ve

+ Ve

Pharmacokinetics:Clomiphene is readily absorbed orally.Has a very large volume of distribution high bioavailability It reaches peak plasma concentration within 6h

Its half-life of an oral dose is about 5 days. Metabolized in the liver by the cytochrome P-450 pathway and there is evidence of enterohepatic recyclingExcreted principally in the feces and minimally

in the urine

Dosage:• The recommended dosage at the beginning of

therapy is 50 mg/d for 5 days, Starting on day 2–5 of the cycle .

ovulation

occurs Does not occur

The next course can be started (can be maintained for 6-12 m ) Double the dose to 100 mg/d

Patients who don’t ovulate for 3 courses

are unlikely to respond to

CC

Effects:Stimulate ovulation in women with

oligomenorrhea or amenorrhea due to ovulatory dysfunction.

The majority of patients suffer from polycystic ovary syndrome( 7% ), which is characterized by

Ovarian hyperandrogenism Olig- or anovulationInfertility

Ovulation can be documented by using any one of a number of methods: Basal body temperature (BBT)

Midcycle LH

Serial transvaginal ultrasound

Clinical uses:Used for treatment of disorders of ovulation in patients wishing to become pregnant.

It is not used in patient with pituitary or hypothalamic failure

Treatment of gynecomastia.

Treatment results:About 80% can be expected to respond by having ovulatory cycles.Approximately half of these patient become pregnantclomiphene resistant are likely to be

• obese• insuline resistant• hyperandrogenic

Adverse effects:Multiple pregnancy Ovarian enlargementAbdominal distension Hot flushesVisual symptomsNausea and VomitingHeadache

Serious medical conditions:

Ovarian hyperstimulation syndrome (OHSS):

Ovulation induction with injectable gonadotropins is a more common cause of OHSS than is clomiphene

serious medical complication characterized by: cystic enlargement of ovaries A marked increase in vascular permeability.

Overdose:As a result of the use of more than the recommended dose during clomiphene citrate therapy. Symptoms:

• Nausea, vomiting• Vasomotor flushes• visual blurring• Ovarian enlargement with pelvic or abdominal

pain. 

Contraindication and cautions:

Pregnancy Nursing motherOvarian cyst or enlargement not due to PCOSLiver diseaseAny patient who complains of abdominal symptoms should be examined carefully Special precaution must be taken in patient who have visual symptomsOrganic intracranial lesion such as pituitary tumorHypersensitivity to the drug

Drug interaction:

Danazole may reduce the response to clomiphene

Alternative and combination regimen:

1- With insuline sensitizing agent2- With HCG3- With glucocorticoid