Ovarian stimulation protocols (anti-oestrogens, gonadotrophins with and without GnRH agonists/antagonists) for intrauterine insemination (IUI) in women with subfertility.

BACKGROUND: Intrauterine insemination (IUI) combined with ovarian hyperstimulation (OH) has been demonstrated to be an effective form of treatment for subfertile couples. Several ovarian stimulation protocols combined with IUI have been proposed, but it is still not clear which stimulation protocol and which dose is the most cost-effective.
OBJECTIVES: To evaluate ovarian stimulation protocols for intrauterine insemination for all indications. SEARCH STRATEGY: We searched for all publications which described randomised controlled trials comparing different ovarian stimulation protocols followed by IUI. We searched the Menstrual Disorders and Subfertility Group's Central register of Controlled Trials (CENTRAL). We searched the electronic databases of MEDLINE (January 1966 to present) and EMBASE (1980 to present). SELECTION CRITERIA: Randomised controlled trials only were considered for inclusion in this review. Trials comparing different ovarian stimulation protocols combined with IUI were selected and reviewed in detail. DATA COLLECTION AND ANALYSIS: Two independent review authors independently assess trial quality and extracted data. MAIN
RESULTS: Forty three trials involving 3957 women were included. There were 11 comparisons in this review. Pregnancy rates are reported here since results of live birth rates were lacking. Seven studies (n = 556) were pooled comparing gonadotrophins with anti-oestrogens showing significant higher pregnancy rates with gonadotrophins (OR 1.8, 95% CI 1.2 to 2.7). Five studies (n = 313) compared anti-oestrogens with aromatase inhibitors reporting no significant difference (OR 1.2 95% CI 0.64 to 2.1). The same could be concluded comparing different types of gonadotrophins (9 studies included, n = 576). Four studies (n = 391) reported the effect of adding a GnRH agonist which did not improve pregnancy rates (OR 0.98 95% CI 0.6 to 1.6), although it resulted in significant higher multiple pregnancy rates (OR 2.9 95% CI 1.0 to 8). Data of three studies (n = 299) showed no convincing evidence of adding a GnRH antagonist to gonadotrophins (OR 1.5 95% CI 0.83 to 2.8). The results of two studies (n = 297) reported no evidence of benefit in doubling the dose of gonadotrophins (OR 1.2 95% 0.67 to 1.9) although the multiple pregnancy rates and OHSS rates were increased. For the remaining five comparisons only one or none studies were included. AUTHORS'
CONCLUSIONS: Robust evidence is lacking but based on the available results gonadotrophins might be the most effective drugs when IUI is combined with ovarian hyperstimulation. When gonadotrophins are applied it might be done on a daily basis. When gonadotrophins are used for ovarian stimulation low dose protocols are advised since pregnancy rates do not differ from pregnancy rates which result from high dose regimen, whereas the chances to encounter negative effects from ovarian stimulation such as multiples and OHSS are limited with low dose gonadotrophins. Further research is needed for each comparison made.