Reply of the Authors

Abstract

Our study tries to explore whether double intrauterine insemination (IUI) confers any benefit in couples with unexplained infertility. The proposed sample size of 80 per group was designed to provide 80% power for the primary comparison if the pregnancy rates for single and double IUI in the unexplained infertility population being studied are 14.4% and 30.4% per patient (1Ragni G. Maggioni P. Guermandi E. Testa A. Baroni E. Colombo M. et al.Efficacy of double intrauterine insemination in controlled ovarian hyperstimulation cycles.Fertil Steril. 1999; 72: 619-622Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar), respectively. The power calculation was performed using SAS 9.1.3 (Cary, NC). The difference in these rates in the reference study is substantial, but each rate is within a range of what may be considered reasonable possibilities in the absence of data. The absence of published studies of single and double IUI in cases of unexplained infertility alone lends to our current uncertainty and necessitates studies such as this to provide preliminary estimates of their efficacy. One of the largest studies on this debate includes patients with both male factor and unexplained infertility (1Ragni G. Maggioni P. Guermandi E. Testa A. Baroni E. Colombo M. et al.Efficacy of double intrauterine insemination in controlled ovarian hyperstimulation cycles.Fertil Steril. 1999; 72: 619-622Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar). There is no consensus in the literature on this aspect and these studies have been limited by heterogeneity of various parameters (2Silverberg K.M. Johnson J.V. Olive D.L. Burns W.N. Schenken R.S. A prospective randomized trial comparing two different intrauterine insemination regimens in controlled ovarian hyperstimulation cycles.Fertil Steril. 1992; 57: 357-361Abstract Full Text PDF PubMed Google Scholar, 3Alborzi S. Motazedian S. Parsanezhad M.E. Jannati S. Comparison of the effectiveness of single intrauterine insemination (IUI) versus double IUI per cycle ininfertile patients.Fertil Steril. 2003; 80: 595-599Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 4Liu W. Gong F. Luo K. Lu G. Comparing the pregnancy rates of one versus two intrauterine inseminations (IUIs) in male factor and idiopathic infertility.J Assist Reprod Genet. 2006; 23: 75-79Crossref PubMed Scopus (35) Google Scholar). In our study, we tried to evaluate the utility of double IUI in a fairly homogeneous group of infertile patients with unexplained infertility. The dearth of data on this specific area has also made calculation of sample size difficult to determine. Further, for the OR of 0.90 (CI 95% 0.44-1.67) 6,348 patients will be needed for a sound statistical analysis in each arm, considering the prevalence of unexplained infertility in India to be around five million couple. (CEBM Statistics Calculator, KT Clearinghouse, Ottawa, Ontario, Canada). However, we get this odds ratio only after performing this study. So the present study, in light of its findings can be used as a pilot study to plan large multicenter trials in the future comprising 6,348 patients in each arm. Also, the experimental event rate (EER) for double insemination is 0.296 (considering per couple) and not 0.361 as mentioned by the Page et al. in their letter. In our published data, if “no pregnancy” is listed as an adverse outcome, the number needed to treat/harm (NNT/NNH) is 30 (Table 1). From an NNT analysis, this sample size fulfils the requirements of an intention-to-treat pilot study, although this has probably led to type II error in our study. The study is a stimulus for future trials with larger numbers, as mentioned above, and is not intended to denounce double IUI.Table 1NNT analysis for the study.Good outcomeBad outcomeControl (single IUI)2653Experimental (double IUI)2457Note: IUI = intrauterine insemination. Open table in a new tab Note: IUI = intrauterine insemination. Is there really no improvement in pregnancy rate with double intrauterine insemination in unexplained infertility?Fertility and SterilityVol. 95Issue 5PreviewTo the Editor: Full-Text PDF