Does the type of ovarian stimulation matter for intrauterine insemination?

This study evaluated pregnancy rates and the chances of having twins with different types of ovarian stimulation. This study found that using gonadotrophins had the highest pregnancy rates, but also the highest chance of twins.

Intrauterine stimulation (IUI) is an infertility treatment where sperm are directly injected into the uterus. Stimulating the ovaries before the procedure can increase the number of eggs. However, ovarian stimulation may increase the chances of multiple pregnancies (twins or triplets). Multiple pregnancies are at greater risk of complications. If no ovulation stimulation is used, it is called natural cycle IUI.

There are several drugs that can be used for ovarian stimulation. Gonadotrophins are hormones that stimulate eggs to mature. Clomiphene citrate (Clomid) and letrozole (Femara) are drugs that help the body produce more hormones. These drugs are gentler than direct hormone exposure but tend to result in fewer eggs. How these methods affect the safety and effectiveness of IUI are unclear.

This study analyzed the results of 26 studies of IUI. These studies included 5316 couples across 9 countries. Women had IUI with or without ovarian stimulation (natural cycle IUI). Stimulation included the use of letrazole, clomiphene citrate (CC), or gonadotrophin hormones.

Compared to natural cycle, pregnancy/birth was 46% more likely with Gn. With letrazole, it was 15% higher. With CC, it was 5% higher. Letrazole had a 9% higher pregnancy/birth likelihood compared to CC.

Patients undergoing Gn IUI had a 67% higher risk of multiple births compared to CC. In some studies, doctors cancelled the IUI if more than three follicles developed from Gn. In these studies, the risk of multiple births was 20% lower for Gn than for CC. Looking only at studies without a cancellation policy, the risk was 2.75 times higher for Gn than for CC.

This meta-analysis found that Gn IUI had higher pregnancy rates but also higher risk of multiples compared to other forms of IUI. Strict rules about canceling IUI in cycles with multiple follicles lowered this risk.

This paper was not able to do a meta-analysis of multiple pregnancy risk due to differences between studies. For the pregnancy/birth analysis, the certainty of evidence was low to moderate.

Discuss your options for IUI with your doctor, including the risk of multiple pregnancies.