Does increasing the number of inseminations per cycle increase the probability of conception? a randomized trial comparing single versus double intrauterine insemination

Yasaswi Khandavalli, Seema Rai, Rama Singodiya Lodha


Background: Intrauterine insemination (IUI) remains an inexpensive, non-invasive, and effective first-line artificial insemination technique. The technique of IUI has evolved through various innovations since the time Cohen published the first report of IUI in 1962, and the success rate increased from 5% to >20%. The success of IUI depends upon several factors; two such prognostic factors are the timing and frequency of insemination.  The objective of this study was to compare the effectiveness of single versus double intrauterine insemination.

Methods: This prospective randomized study was carried out in 130 patients with male factor infertility, PCOS and unexplained infertility. Patients were randomly assigned into two groups. In the first group of 65 patients, single IUI was applied at 36 to 40 hours after HCG administration, to the other 65 patients in the second group, double IUIs were applied at 12 to 16 hours and 36 to 40 hours after HCG administration. The primary end-point of the study was to compare the clinical pregnancy rate between the two groups.

Results: The overall pregnancy rate was 18.46% (12/65) for single IUI group and 30.76% (20/65) for double IUI group. There was a no statistically significant difference between single and double IUI groups (p=0.16).

Conclusions: This study did find a higher pregnancy rate following double IUI; however, the difference was not statistically significant. Further, larger sample size studies are required to determine if double IUI increases the pregnancy rate.


Controlled ovarian hyper stimulation, Double, Insemination, Intrauterine insemination, Pregnancy rate, Single

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Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. International committee for monitoring assisted reproductive technology; World Health Organization. The international committee for monitoring assisted reproductive technology (ICMART) and the World Health Organization (WHO) revised glossary on ART terminology. Hum Reprod. 2009;24(11):2683-7.

Guzick DS, Carson SA, Coutifaris C, Overstreet JW, Factor-Litvak P, Steinkampf MP, et al. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. N Engl J Med. 1999;340(3):177-83.

Duran HE, Morshedi M, Kruger T, Oehninger S. Intrauterine insemination a systematic review on determinants of success. Hum Reprod Update. 2002;8(4):373-84.

Testart J, Frydman R. Minimum time lapse between luteinizing hormone surge or human chorionic gonadotropin administration and follicular rupture. Fertil Steril. 1982;37:50-3.

Abbasi R, Keingsberg D, Dnforth D, Falk RJ, Hodgen GD. Cumulative ovulation rate in human menopausal/human chorionic gonadotropin-treated monkeys: “step-up” versus “step-down” dose regimens. Fertil Steril. 1987;47:1019-24.

Alborzi S, Montazedian S, Parsanezhad ME, Jannati S. Comparison of the effectiveness of single and intrauterine insemination (IUI) double IUI per cycle in infertile patients. Fertil Steril. 2003;80:595-9.

Bagis T, Haydardedeoglu B, Kilicdag EB, Cok T, Simsek E, Parlakgumus AH. Single versus double intrauterine insemination in multi-follicular ovarian hyperstimulation cycles: a randomized trial. Hum Reprod. 2010;25(7):1684-90.

Liu 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 Assit Reprod Genet. 2006;23:75-9.

Randall GW, Gantt PA. Double versus single intrauterine insemination per cycle: use in gonadotropin cycles and in diagnostic categories of ovulatory dysfunction and male factor infertility. J Reprod Med. 2008;53(3):196-202.

Tonguc E, Var T, Onalan G, Altinbas S, Tokmak A, Karakas N, et al. Comparison of the effectiveness of single versus double intrauterine insemination with three different timing regimens. Fertil Steril. 2010;94(4):1267-70.

Ragini G, Maggioni P, Guermandi E, Testa A, Baroni E, Colombo M, et al. Efficacy of double intrauterine in controlled ovarian hyperstimulation cycles. Fertil Steril. 1999;72(4):619-22.

Cantineau AE, Heineman MJ, Cohlen BJ. Single versus double intrauterine insemination in stimulated cycles for subfertile couples: a systematic review based on a Cochrane review. Hum Reprod. 2003;18:941-6.

Osuna C, Matorras R, Pijoan JI, Rodrigues-Escuredo FJ. One versus two insemination per cycle in intrauterine insemination with sperm from patients’ husband: a systematic review of the literature. Fertil Steril. 2004;82(1):17-24.

World Health Organization, Department of Reproductive Health and Research. WHO laboratory manual for the examination and processing of human semen. Switzerland: WHO Press; 2010.

Ragini G, Somigliana E, Vegetti W. Timing of intrauterine insemination: where are we? Fertil Steril. 2004;82(1):25-6.

ESHRE TR, Group A-SPCW. Revised 2003 consesus on diagnostic criteria and long-term health risks related to polycystic ovarian syndrome. Fertil Steril. 2004; 81(1):19-25.

Allahbadia GN. Intrauterine insemination: fundamentals revisited. The J Obstet Gynecol India. 2017;67(6):385-92.

Ransom M, Blotner M, Bohrer M, Corsan G, Kermmann E. Does increasing infrequency of intrauterine insemination improve pregnancy rates significantly during superovulation cycles? Fertil Steril. 1994;61(2):303-7.

Zeyneloglu HB, Arici A, Olive DL, Duleba AJ. Comparison of intrauterine insemination with timed inter-course in superovulated cycles with gonadotropin: a meta-analysis. Fertil Steril. 1998:69:486-91.

Society for assisted reproductive technology and the American Society for Reproductive Medicine. Assisted reproductive technology in the United States: 1998 American Society for reproductive Medicine/Society for Assisted Reproductive technology registry. Fertil Steril. 2002;77:18-31.

Kang BM, Wu TC. Effect of age on intrauterine insemination with frozen donor sperm. Obstet Gynecol. 1996;88(1):93-8.

Navot D, Goldstein N, MorJoset S, Simon A, Relou A, Birkenfeld A. Multiple pregnancies: risk factors and prognostic variables during induction of ovulation with human menopausal gonadotropins. Hum Reprod. 1995;6:1152-5.

Mathieu C, Ecochard R, Bied V, Lornage J, Czyba JC. Cumulative conception rate following intrauterine artificial insemination with husband’s spermatozoa; influence of husband’s age. Hum Reprod. 1995;10:1090-7.

Collins JA, Rowe TC. Age of the female partner is a prognostic factor in prolonged unexplained infertility: a multicenter study. Fertil Steril. 1989;52:15-20.

Tomlimson MJ, Arthur AJB, Thompson KA, Kasraie JL, Bentick B. Prognostic indicators for intrauterine insemination (IUI): Statistical model for IUI success. Hum Reprod. 1996;11(9):1892-6.

Jameel T. Sperm swim-up: a simple and effective technique of semen processing for IUI. J Pak Med Assoc. 2008;58(2):71.

Pathak B. Comparison of single versus and double intrauterine insemination. Int J Reprod Contracept Obstet Gynecol. 2017;6(12):5277-81.

Yavuz A, Demirci O, Sozen H, Uludogan M, Predictive factors influencing pregnancy rates after intrauterine insemination (IUI). Iran J Reprod Med. 2013;11(3):227-34.

Sorouri ZZ, Shomali RR, Pourmarzi D. Single versus double intrauterine insemination in controlled ovarian hyperstimulation cycles: a randomized trial. Arch Iran Med. 2016;19(7):465-9.

Van Rumste MM, Custers IM, van der Veen F, van Wely M, Evers JL, Mol BW. The influence of the number of follicles on the pregnancy rates in intrauterine insemination (IUI): a meta-analysis. Human Reprod Update. 2008;14:563-70.

ESHRE Capri Workshop Group. Intrauterine insemination. Hum Reprod Update; 2009;15:265-77.

Silverberg KM, Johnson JV, Olive DL, Burns WN, Schenken RS. A prospective, randomized trail comparing two different intrauterine insemination regimens in controlled ovarian hyperstimulation cycles. Fertil Steril. 1992;57:357-61.

Ali AS, Essayed AA, Mabdelhady MA, Noreldin K, Allaha B. Comparative study between single and double intrauterine insemination in controlled ovarian hyper stimulation cycles. AAMJ. 2006;4(2):1.

Casadei L, Zamaro V, Calcagni M, Ticconi C, Dorucci M, Piccione E. Homologous intrauterine insemination in controlled ovarian hyperstimulation cycles: a comparison among three different regimens. Eur J Obstet Gynecol Reprod Biol. 2006;129:155-61.

Matilsky M, Geslevich Y, Ben-Ami M, Ben-Shlomo I, WeinerMegnagi T, Shalev E. Two-day IUI treatment cycles are more successful than one-day IUI cycles when using frozen-thawed donor sperm. J Androl. 1998;19:603-7.

Gezginç K, Görkemli H, Çelik Ç, Karatayli R, Çiçek MN, Çolakoglu MC. Comparison of single versus double intrauterine insemination. Taiwan J Obstet Gynecol. 2008;47(1):57-61.

Polyzos NP, Tzioras S, Mauri D, Tatsioni A. Double versus single intrauterine insemination for unexplained infertility: a meta-analysis of randomized trials. Fertil Steril. 2010;94:1261-6.

Zavos A, Daponte A, Garas A, Verykouki C, Papanikolaou E, Anifandis G, et al. Double versus single homologous intrauterine insemination for male factor infertility: a systematic review and meta-analysis. Asian J Androl. 2013;15(4):533-8.