With the ongoing debate on the right timing for intrauterine insemination (IUI), the use of double IUI is hypothesized to overcome this problem since it is performed at different time intervals in the same cycle. The strategy thus holds a potential advantage in increasing the chances of in vivo fertilization. However, studies comparing the efficacy of double versus single IUI have reported contradictory findings with respect to the clinical pregnancy rates. A recent meta-analysis of randomized controlled trials reports the lack of statistically significant variation in the clinical pregnancy rates with double and single IUI in couples with unexplained infertility. The findings of the study are published in the online edition of the journal, Fertility and Sterility.
Nikolaos P Polyzos from the Panhellenic Association for Continual Medical Research, Athens, Greece, and coworkers, selected 6 randomized trials comprising of 829 women, to compare the pregnancy outcomes between double and single IUI in women with unexplained infertility. The researchers obtained the data from various databases such as Cochrane and Medline (through March 2009) and also from abstract books on the annual meetings (2001–2008) of the European Society of Human Reproduction and Embryology (ESHRE) and American Society for Reproductive Medicine (ASRM).
The clinical pregnancy rates reported with double and single IUI were13.6% and 14.4%, respectively. On statistical analysis, both the groups showed no substantial variation in the chances of clinical pregnancy (odds ratio=0.92; P=0.715). Based on the findings, it was concluded that double IUI does not confer significant benefits in improving the overall clinical pregnancy rate in couples with unexplained infertility.
Similarly, an earlier prospective randomized study by Alborzi et al (Fertility and Sterility, 2003) demonstrated the lack of difference in effectiveness between the two IUI regimens (along with controlled ovarian hyperstimulation) in patients with male factor, cervical factor, and unexplained infertility. Another randomized and prospective trial by Osuna and colleagues, (Fertility and Sterility, 2004) also reported comparable findings with regard to the pregnancy rate when one or two inseminations were performed per cycle. However, the investigators found improved pregnancy rate in double IUI procedure, on administration of clomiphene citrate with or without 5,000 IU of human chorionic gonadotropin (hCG) and gonadotropins.
In stark contrast, in a more recent study, Cantineau et al (Cochrane Database of Systematic Reviews, 2008) reported a significantly enhanced pregnancy rate with double, compared to single, IUI in subfertile couples (odds ratio=1.8). The researchers analyzed the data from different databases like Cochrane, Medline, EMBASE, etc., and short-listed 6 randomized controlled, parallel trials comprising of 1,785 women undergoing IUI in stimulated cycles. Despite the positive outcome observed with double IUI, the systemic review suggested the need for further research before recommending it as the standard clinical practice.
A report by the Practice Committee of the ASRM (Fertility and Sterility, 2006) supports the short-term use of IUI for unexplained infertility, based on level 1 evidence. In a recent review study, Quaas and Dokras (Reviews in Obstetrics and Gynecology, 2008) evaluated the efficacy of the existing treatment modalities for unexplained infertility. The study suggests that the treatment is empiric, since a specific defect or functional impairment is not associated with unexplained infertility. Some of the treatment options include:
• Lifestyle changes and expectant management
• IUI and clomiphene citrate
• IUI in controlled ovarian hyperstimulation (COH) cycles
• IVF/ICSI
The researchers further observed that although numerous studies have assessed the efficacy of double over single IUI, exclusive data on unexplained infertility is not available since most of the trials include patients with different types of infertility, including male factor and cervical factor infertility.
References
1. Polyzos NP, Tzioras S, Mauri D, Tatsioni A. Double versus single intrauterine insemination for unexplained infertility: a meta-analysis of randomized trials. Fertil Steril. 2009 Aug 7. [Epub ahead of print]
2. Alborzi S, Motazedian S, Parsanezhad ME, Jannati S. Comparison of the effectiveness of single intrauterine insemination (IUI) versus double IUI per cycle in infertile patients. Fertil Steril. 2003 Sep;80(3):595-9.
3. Osuna C, Matorras R, Pijoan JI, Rodríguez-Escudero FJ. One versus two inseminations per cycle in intrauterine insemination with sperm from patients’ husbands: a systematic review of the literature. Fertil Steril. 2004 Jul;82(1):17-24.
4. Cantineau AEP, Heineman MJ, Cohlen BJ. Single versus double intrauterine insemination (IUI) in stimulated cycles for subfertile couples. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD003854. DOI: 10.1002/14651858.CD003854
5. Practice Committee of the American Society for Reproductive Medicine. Effectiveness and treatment for unexplained infertility. Fertil Steril. 2006 Nov;86(5 Suppl 1):S111-4.
6. Quaas A, Dokras A. Diagnosis and treatment of unexplained infertility. Rev Obstet Gynecol. 2008 Spring;1(2):69-76.
