Clomiphene Test

INDICATION

Demonstration of the capacity for ovulation to be induced in a woman with infertility and anovulation, using clomiphene, a selective oestrogen receptor modulator.

CONTRAINDICATIONS

Pregnancy.

PREPARATION

Timing of cycle needs to be explained (first day of period = day 0).
Women without cycles have to start test at an arbitrary time.

SIDE EFFECTS

Rarely causes abdominal bloating. Small risk of multiple pregnancy.
Rarely, ovarian hyperstimulation with cardiovascular collapse, ascites and pleural effusions.

METHOD

This can be arranged from home by the patient's GP (discuss with endocrinology lab ext 33381).

1. Give clomiphene for 5 days at dose of 50 mg/day starting at day 5.
2. Blood is taken for baseline measurements on day 6 and at 2 day intervals between days 18 and 24, measuring LH, FSH, progesterone and oestradiol.
3. Keep a temperature chart.
4. If the test is unsuccessful over 2 cycles, repeat using higher doses of clomiphene (100 and 200 mg/day), cautiously.

INTERPRETATION

A rise in LH and FSH occurs, probably as a consequence of an anti-oestrogen effect giving a rise in GnRH. This in turn leads to follicular maturation, oestrogen production, LH release, and ovulation.
Thus a positive result is a:
rise in LH (to >20 U/l).
rise in FSH (to >10 U/l).
rise in progesterone to >30 nmol/l.
rise in temperature by >0.5ºC to help confirm ovulation.

SENSITIVITY AND SPECIFICITY

The sensitivity and specificity is poorly defined. The difficulties with this test are:
a variable response to a given dose
the mechanism of clomiphene action is not known
therefore no clear-cut guidelines for a negative result
The potential value is that a positive result confirms relatively minor hypothalamo-pituitary dysfunction causing anovulation that should resolve spontaneously or be easily treated.

REFERENCE

Sverdloff R.S. et al., Endo. Metab. Clin N. Amer. 17, 301-332 (1988).