Clomiphene treatment for women with unexplained infertility: placebo-controlled study of hormonal responses and conception rates

Abstract

One hundred and eighteen patients with unexplained infertility were treated with clomiphene (Clomid, Merrell) in a randomized placebo-controlled cross-over study lasting up to 3 months with each preparation. Compared with placebo, clomiphene led overall to a 66% increase in mid-luteal serum progesterone levels (from mean 43 nmol/l to 71 nmol/l, p less than 0.001) and a 53% rise in the 3-month cumulative conception rate (from 14.6% to 22.33%, p less than 0.05). The greatest relative increase in conception rates with clomiphene was in women with infertility lasting more than 3 years (3-month rates from 2.9% to 14.4%, p less than 0.05). Differences in conception rates were not related to the rises in progesterone, and there was no carryover effect of clomiphene into the following placebo cycles in terms of progesterone levels or conceptions. The findings suggest that couples with unexplained infertility of less than 3 years duration are essentially normal, but with more than 3 years duration there is often a subtle disorder of ovulation that is corrected by clomiphene therapy.

Use of clomiphene citrate in women

“…In couples whose infertility remains unexplained after careful and thorough evaluation, empiric treatment with CC may be justified, particularly in young couples with a short duration of infertility and in those unwilling or unable to pursue more aggressive therapies involving greater costs, risks, and logistical demands (15,16). The efficacy of empiric CC treatment may be attributed to correction of subtle and unrecognized ovulatory dysfunction and/or "superovulation" of more than a single ovum (16).…”

The effect of administering vaginal estrogen to clomiphene citrate stimulated cycles on endometrial thickness and pregnancy rates in unexplained infertility

“…This is the first study aiming to minimize the adverse effects of CC on end organs where LE was added to CC. A rest period of one month was used when changing from one treatment method to the other due to the cumulative effect of CC (22). There may be various reasons for the lack of a difference in pregnancy rates in this study.…”

Clomiphene Citrate for Women with Unexplained Infertility

“…Several studies have shown that luteal phase deficiency, whether characterized by low peak progesterone levels, short luteal phase, or delayed endometrial development is corrected by CC [28][29][30][31]. In one randomized placebo controlled study, CC increased mid-luteal progesterone levels 66 % (from 43 to 71 nmol/l) and 3-month cumulative pregnancy rates 53 % (from 14.6 to 22.3 %) [7]. The definition of normal progesterone in the luteal phase is a subject of controversy since progesterone is secreted in a pulsatile fashion in relation to pituitary LH release.…”

“…The advantages of CC over gonadotropins for ovulation induction (OI) include: a low incidence of multiple pregnancies and ovarian hyperstimulation syndrome (OHSS), low cost, oral administration, and less need for cycle monitoring. Numerous reports exist of an improvement in pregnancy rates for women with unexplained infertility treated with CC in randomized studies [5][6][7][8] although some studies did not find an improvement in pregnancy rates with CC or CC-IUI [9][10][11].…”