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

Intrauterine insemination (IUI) is an assisted reproduction procedure that places sperm directly into the uterus. Additionally, medication (hormones) are given to hyper stimulate the ovaries, which results most of the time in the release of more eggs which can be fertilized and this in turn, results in higher pregnancy rates, but also in a higher number of multiple pregnancies.
Forty three trials involving 3957 women were included. The review compared different drugs for ovarian hyperstimulation showing that injections result in higher pregnancy rates compared with oral medication. However, the evidence for this result is not very strong. Furthermore, it showed that if stimulation is used it might be done with low dose injections, since multiple pregnancy rates were increased with high dose injections, without resulting in more pregnancies. This review does not show which injection should be used, since there is no convincing evidence of a difference. Finally, this review does not answer the question whether the addition of GnRH agonist or antagonist is useful.

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.

Read the full abstract...

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.


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 = 415) reported that gonadotrophins alone are more effective than with the addition of a GnRH agonist (OR 1.8 95% CI 1.1 to 3.0). 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.