Development, pharmacology and clinical experience with clomiphene citrate

This review describes the development and pharmacology of clomiphene and those specific characteristics of both drug and patients which determine its clinical efficacy. The studies reviewed describe clinical observation of patient characteristics (age, additional infertility diagnosis, semen quality), vaginal ultrasound observations of ovaries (number and size of pre-ovulatory follicles) and endometrial lining (thickness, pattern) in 2841 clomiphene cycles in patients who required intrauterine insemination (IUI) because of poor sperm quality or an unsatisfactory postcoital test. They show that (i) conception in clomiphene cycles is related to the number and size of pre-ovulatory follicles, endometrial thickness, patient age, pelvic adhesions, type of anovulatory disorder and semen quality; (ii) pregnancy rates per clomiphene-IUI cycle are constant through at least six cycles; (iii) multiple births cannot be prevented by withholding human chorionic gonadotrophin or advising against coitus when multiple pre-ovulation follicles are present unless all follicles down to 10-12 mm diameter are counted. We also reviewed pregnancy outcome (number of gestational sacs, babies, preclinical and clinical abortion, ectopic pregnancy and birth sex) in 1744 clomiphene pregnancies from our clinic. We found that (i) preclinical and clinical abortions are increased only slightly by clomiphene use, compared to spontaneous pregnancy; (ii) clinical abortions are decreased in patients with polycystic ovaries and luteal insufficiency who use clomiphene; (iii) conception and preclinical abortions are related to endometrial thickness prior to ovulation; (iv) ectopic pregnancies are not increased by clomiphene and (v) the ratio of male births is not altered by clomiphene, except possibly in timed insemination cycles. These studies repudiate many misconceptions regarding clomiphene. They also show that clinical outcome may be improved by pre-ovulation ultrasound monitoring of ovarian and endometrial response.