Can Double Intrauterine Insemination (IUI) improve Pregnancy Outcomes?

Intrauterine insemination (IUI) is typically performed the day after a positive leutinizing hormone (LH) surge or 24-36 hours after an injection of human Chorionic Gonadotropin (hCG), which is also called a “trigger injection” which serves the function of an LH surge.  The timing of the IUI is critical in order to maximize the pregnancy rate.  In the past, there had been limited data as to whether or not two consecutive IUI procedures in the peri-ovulatory timeframe increased pregnancy rates over a single IUI.  However, studies in recent years have provided more data in order to answer the question:  Does double IUI improved outcomes when compared to a single IUI in the same treatment cycle?

A prospective study of 450 patients, conducted by by Tonguc et al and published in the journal Fertility & Sterility in 2009, compared pregnancy rates if a single IUI was performed 24 hours after an hCG trigger injection, if a single IUI was performed 36 hours after an hCG trigger injection, or if two successive IUIs were performed 12 and 36 hours after hCG injection.  This study showed no difference in pregnancy rates among the compared groups; therefore, the study showed that there was no advantage to double IUI in the same treatment cycle.

A randomized controlled trial, by Rahman et al published in Fertility and Sterility in 2010, of 160 patients with unexplained subfertility found similar pregnancy rates between double IUI and a single IUI, suggesting that double IUI offers no advantage over single IUI.  Furthermore, a meta-analysis of 6 randomized trials that examined the subject of double IUI versus a single IUI among 829 women with unexplained subfertility, conducted by Polyzos et al and also published in Fertility & Sterility in 2010, led to the conclusion that there is no clear benefit to double IUI in terms of clinical pregnancy rate when compared with a single IUI.

A systematic review and meta-analysis by Zavos et al, published in the Asian Journal of Andrology, found that the available evidence for the use of double IUI is “fragmentary and weak” in cases of male factor subfertility.  Another systematic Cochrane review published in 2003 found no difference in pregnancy rate per couple with double IUI compared to a single IUI.

In a large retrospective cohort study of women who used donor sperm for IUI, conducted by Zarek et al and published inFertility & Sterility in 2014, in which 2,486 double IUI and 673 single IUI cycles were included, there was no benefit of double IUI over single IUI as the clinical pregnancy rates were similar.

Although some small studies can be found that support double IUI, the overwhelming majority of the existing medical literature on this topic shows no benefit of double IUI compared with a single IUI, and double IUI certainly increases treatment costs for the patient.  The European Society for Human Reproduction and Embryology (ESHRE) Workshop Group publication “Intrauterine Insemination”, published in the journal Human Reproduction Update in 2009, also noted that there seems to be no benefit to double IUI over a single IUI.