Intrauterine Insemination: An Ineffective Treatment

  • Erica B. Johnstone
  • Jessie Dorais


The IUI procedure is commonly utilized as a treatment for unexplained infertility, mild male factor infertility, and minimal-to-mild endometriosis despite limited to absent evidence of efficacy for any indication. The IUI procedure is typically performed in conjunction with ovulation induction or controlled ovarian stimulation, and this combined treatment approach is associated with a significant inherent and unacceptable risk of producing a multifetal gestation. In contrast to IVF, where success rates continue to improve and multifetal gestation rates continue to decline, the success rates associated with the IUI procedure have remained stagnant and multifetal gestation rates have remained constant. Further, despite the chance that an individual may experience a cost saving if a pregnancy were achieved after COH/IUI, population studies fail to support the utilization of unstimulated or stimulated IUI as cost-effective treatments. Thus, based on a lack of data demonstrating efficacy, cost considerations, and the adverse effects associated with the procedure as it is typically performed, IUI should no longer be offered as part of routine treatment in modern day infertility practices.


Ovarian Stimulation Clomiphene Citrate Ovulation Induction Expectant Management Control Ovarian Hyperstimulation 
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  1. 1.
    Cohen MR. Intrauterine insemination. Int J Fertil. 1962;7:235–40.PubMedGoogle Scholar
  2. 2.
    Dodson WC, Whitesides DB, Hughes CL, Jr., Easley HA, 3rd, Haney AF. Superovulation with intrauterine insemination in the treatment of infertility: a possible alternative to gamete intrafallopian transfer and in vitro fertilization. Fertil Steril. 1987;48(3):441–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Yen SSC, Strauss JF, Barbieri RL. Yen and Jaffe’s reproductive endocrinology: physiology, pathophysiology, and clinical management. 5th ed. Philadelphia, PA: Elsevier/Saunders; 2004.Google Scholar
  4. 4.
    ESHRE Capri Workshop Group. Intrauterine insemination. Hum Reprod update. 2009;15(3):265–77.Google Scholar
  5. 5.
    Wilcox AJ, Weinberg CR, Baird DD. Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med. 1995;333(23):1517–21.PubMedCrossRefGoogle Scholar
  6. 6.
    Nulsen J, Wheeler C, Ausmanas M, et al. Cervical mucus changes in relationship to urinary luteinizing hormone. Fertil Steril. 1987;48(5):783–6.PubMedGoogle Scholar
  7. 7.
    Steures P, van der Steeg JW, Hompes PG, et al. Effectiveness of intrauterine insemination in subfertile couples with an isolated cervical factor: a randomized clinical trial. Fertil Steril. 2007;88(6):1692–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Helmerhorst FM, van Vliet HA, Gornas T, et al. Intrauterine insemination versus timed intercourse for cervical hostility in subfertile couples. Obstet Gynecol Surv. 2006;61(6):402–14; quiz 23.Google Scholar
  9. 9.
    Robinson JN, Forman RG, Nicholson SC, et al. A comparison of intrauterine insemination in superovulated cycles to intercourse in couples where the male is receiving steroids for the treatment of autoimmune infertility. Fertil Steril. 1995;63(6):1260–6.PubMedGoogle Scholar
  10. 10.
    Horvath PM, Beck M, Bohrer MK, et al. A prospective study on the lack of development of antisperm antibodies in women undergoing intrauterine insemination. Am J Obstet Gynecol. 1989;160(3):631–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Hughes EG. The effectiveness of ovulation induction and intrauterine insemination in the treatment of persistent infertility: a meta-analysis. Hum Reprod. 1997;12(9):1865–72.PubMedCrossRefGoogle Scholar
  12. 12.
    Bensdorp AJ, Cohlen BJ, Heineman MJ, et al. Intra-uterine insemination for male subfertility. Cochrane Database Syst Rev. 2007;(3):CD000360.Google Scholar
  13. 13.
    Francavilla F, Sciarretta F, Sorgentone S, et al. Intrauterine insemination with or without mild ovarian stimulation in couples with male subfertility due to oligo/astheno- and/or teratozoospermia or antisperm antibodies: a prospective cross-over trial. Fertil Steril. 2009;92(3):1009–11.PubMedCrossRefGoogle Scholar
  14. 14.
    Bhattacharya S, Harrild K, Mollison J, et al. Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial. Br Med J. 2008;337:a716.CrossRefGoogle Scholar
  15. 15.
    Gregoriou O, Vitoratos N, Papadias C, et al. Pregnancy rates in gonadotrophin stimulated cycles with timed intercourse or intrauterine insemination for the treatment of male subfertility. Eur J Obstet Gynecol Reprod Biol. 1996;64(2):213–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Karlstrom PO, Bergh T, Lundkvist O. A prospective randomized trial of artificial insemination versus intercourse in cycles stimulated with human menopausal gonadotropin or clomiphene citrate. Fertil Steril. 1993;59(3):554–9.PubMedGoogle Scholar
  17. 17.
    Zikopoulos K, West CP, Thong PW, et al. Homologous intra-uterine insemination has no advantage over timed natural intercourse when used in combination with ovulation induction for the treatment of unexplained infertility. Hum Reprod. 1993;8(4):563–7.PubMedGoogle Scholar
  18. 18.
    Gregoriou O, Vitoratos N, Papadias C, et al. Controlled ovarian hyperstimulation with or without intrauterine insemination for the treatment of unexplained infertility. Int J Gynaecol Obstet. 1995;48(1):55–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Arcaini L, Bianchi S, Baglioni A, et al. Superovulation and intrauterine insemination vs. superovulation alone in the treatment of unexplained infertility. A randomized study. J Reprod Med. 1996;41(8):614–8.PubMedGoogle Scholar
  20. 20.
    Melis GB, Paoletti AM, Ajossa S, et al. Ovulation induction with gonadotropins as sole treatment in infertile couples with open tubes: a randomized prospective comparison between intrauterine insemination and timed vaginal intercourse. Fertil Steril. 1995;64(6):1088–93.PubMedGoogle Scholar
  21. 21.
    Zeyneloglu HB, Arici A, Olive DL, et al. Comparison of intrauterine insemination with timed intercourse in superovulated cycles with gonadotropins: a meta-analysis. Fertil Steril. 1998;69(3):486–91.PubMedCrossRefGoogle Scholar
  22. 22.
    Aribarg A, Sukcharoen N. Intrauterine insemination of washed spermatozoa for treatment of oligozoospermia. Int J Androl. 1995;18 Suppl 1:62–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Ford WC, Mathur RS, Hull MG. Intrauterine insemination: is it an effective treatment for male factor infertility? Baillieres Clin Obstet Gynaecol. 1997;11(4):691–710.PubMedCrossRefGoogle Scholar
  24. 24.
    Agarwal S, Mittal S. A randomised prospective trial of intrauterine insemination versus timed intercourse in superovulated cycles with clomiphene. Indian J Med Res. 2004;120(6):519–22.PubMedGoogle Scholar
  25. 25.
    Steures P, van der Steeg JW, Hompes PG, et al. Intrauterine insemination with controlled ovarian hyperstimulation versus expectant management for couples with unexplained subfertility and an intermediate prognosis: a randomised clinical trial. Lancet. 2006;368(9531):216–21.PubMedCrossRefGoogle Scholar
  26. 26.
    Abu Hashim H, Ombar O, Abd Elaal I. Intrauterine insemination versus timed intercourse with clomiphene citrate in polycystic ovary syndrome: a randomized controlled trial. Acta Obstet Gynecol Scand. 2011;90(4):344–50.PubMedCrossRefGoogle Scholar
  27. 27.
    Wordsworth S, Buchanan J, Mollison J, et al. Clomifene citrate and intrauterine insemination as first-line treatments for unexplained infertility: are they cost-effective? Hum Reprod. 2011;26(2):369–75.PubMedCrossRefGoogle Scholar
  28. 28.
    Custers IM, van Rumste MM, van der Steeg JW, et al. Long-term outcome in couples with unexplained ­subfertility and an intermediate prognosis initially randomized between expectant management and immediate treatment. Hum Reprod. 2012;27(2):444–50.PubMedCrossRefGoogle Scholar
  29. 29.
    Sacks PC, Simon JA. Infectious complications of intrauterine insemination: a case report and literature review. Int J Fertil. 1991;36(6):331–9.PubMedGoogle Scholar
  30. 30.
    Fauser BC, Devroey P, Macklon NS. Multiple birth resulting from ovarian stimulation for subfertility treatment. Lancet. 2005;365(9473):1807–16.PubMedCrossRefGoogle Scholar
  31. 31.
    Tarlatzis BC, Grimbizis G. Future use of clomiphene in ovarian stimulation. Will clomiphene persist in the 21st century? Hum Reprod. 1998;13(9):2356–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Schieve LA, Devine O, Boyle CA, et al. Estimation of the contribution of non-assisted reproductive technology ovulation stimulation fertility treatments to US singleton and multiple births. Am J Epidemiol. 2009;170(11):1396–407.PubMedCrossRefGoogle Scholar
  33. 33.
    Bedaiwy MA, Mousa NA, Esfandiari N, Forman R, Casper RF. Follicular phase dynamics with combined aromatase inhibitor and follicle stimulating hormone treatment. J Clin Endocrinol Metab. 2007;92(3):825–33.PubMedCrossRefGoogle Scholar
  34. 34.
    Ragni G, Caliari I, Nicolosi AE, Arnoldi M, Somigliana E, Crosignani PG. Preventing high-order multiple pregnancies during controlled ovarian hyperstimulation and intrauterine insemination: 3 years’ experience using low-dose recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonists. Fertil Steril. 2006;85(3):619–24.PubMedCrossRefGoogle Scholar
  35. 35.
    Matorras R, Ramon O, Exposito A, Corcostegui B, Ocerin I, Gonzalez-Lopera S, et al. Gn-Rh antagonists in intrauterine insemination: the weekend-free protocol. J Assist Reprod Genet. 2006;23(2):51–4.PubMedCrossRefGoogle Scholar
  36. 36.
    Gorry A, White DM, Franks S. Infertility in polycystic ovary syndrome: focus on low-dose gonadotropin treatment. Endocrine. 2006;30(1):27–33.PubMedCrossRefGoogle Scholar
  37. 37.
    Tur R, Barri PN, Coroleu B, Buxaderas R, Parera N, Balasch J. Use of a prediction model for high-order multiple implantation after ovarian stimulation with gonadotropins. Fertil Steril. 2005;83(1):116–21.PubMedCrossRefGoogle Scholar
  38. 38.
    Mitwally MF, Biljan MM, Casper RF. Pregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation. Am J Obstet Gynecol. 2005;192(2):381–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Dickey RP, Taylor SN, Lu PY, Sartor BM, Rye PH, Pyrzak R. Risk factors for high-order multiple pregnancy and multiple birth after controlled ovarian hyperstimulation: results of 4,062 intrauterine insemination cycles. Fertil Steril. 2005;83(3):671–83.PubMedCrossRefGoogle Scholar
  40. 40.
    Iberico G, Vioque J, Ariza N, Lozano JM, Roca M, Llacer J, et al. Analysis of factors influencing pregnancy rates in homologous intrauterine insemination. Fertil Steril. 2001;81(5):1308–13.PubMedCrossRefGoogle Scholar
  41. 41.
    Calaf Alsina J, Ruiz Balda JA, Romeu Sarrio A, Caballero Fernandez V, Cano Trigo I, Gomez Parga JL, et al. Ovulation induction with a starting dose of 50 IU of recombinant follicle stimulating hormone in WHO group II anovulatory women: the IO-50 study, a prospective, observational, multicentre, open Trial. BJOG. 2003;110(12):1072–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Tur R, Barri PN, Coroleu B, Buxaderas R, Martinez F, Balasch J. Risk factors for high-order multiple implantation after ovarian stimulation with gonadotrophins: evidence from a large series of 1878 consecutive pregnancies in a single centre. Hum Reprod. 2001;16(10):2124–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Schachter M, Raziel A, Friedler S, Strassburger D, Bern O, Ron-El R. Monozygotic twinning after assisted reproductive techniques: a phenomenon independent of micromanipulation. Hum Reprod. 2001;16(6):1264–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Gleicher N, Oleske DM, Tur-Kaspa I, Vidali A, Karande V. Reducing the risk of high-order multiple pregnancy after ovarian stimulation with gonadotropins. N Engl J Med. 2000;343(1):2–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Nuojua-Huttunen S, Tomas C, Bloigu R, Tuomivaara L, Martikainen H. Intrauterine insemination treatment in subfertility: an analysis of factors affecting outcome. Hum Reprod. 1999;14(3):698–703.PubMedCrossRefGoogle Scholar
  46. 46.
    Ragni 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(4):619–22.PubMedCrossRefGoogle Scholar
  47. 47.
    De Geyter C, De Geyter M, Nieschlag E. Low multiple pregnancy rates and reduced frequency of cancellation after ovulation induction with gonadotropins, if eventual supernumerary follicles are aspirated to ­prevent polyovulation. J Assist Reprod Genet. 1998;15(3):111–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Tadokoro N, Vollenhoven B, Clark S, Baker G, Kovacs G, Burger H, et al. Cumulative pregnancy rates in couples with anovulatory infertility compared with unexplained infertility in an ovulation induction programme. Hum Reprod. 1997;12(9):1939–44.PubMedCrossRefGoogle Scholar
  49. 49.
    Goverde AJ, McDonnell J, Vermeiden JP, et al. Intrauterine insemination or in-vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost-effectiveness analysis. Lancet. 2000;355(9197):13–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Reindollar RH, Regan MM, Neumann PJ, et al. A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial. Fertil Steril. 2010;94(3):888–99.PubMedCrossRefGoogle Scholar
  51. 51.
    Reindollar RH, Thornton KL, Ryley D. A randomized clinical trial to determine optimal infertility therapy in couples when the female partner is 38-42 years: preliminary results from the forty and over infertility treatment trial (FORT-T). Fertil Steril. 2011;96(3)Suppl:S1.Google Scholar
  52. 52.
    Gardner DK, Surrey E, Minjarez D, et al. Single blastocyst transfer: a prospective randomized trial. Fertil Steril. 2004;81(3):551–5.PubMedCrossRefGoogle Scholar
  53. 53.
    Custers IM, Konig TE, Broekmans FJ, et al. Couples with unexplained subfertility and unfavorable prognosis: a randomized pilot trial comparing the effectiveness of in vitro fertilization with elective single embryo transfer versus intrauterine insemination with controlled ovarian stimulation. Fertil Steril. 2011;96(5):1107–11.e1.PubMedCrossRefGoogle Scholar
  54. 54.
    Practice committee of society for assisted reproductive technology; practice committee of american ­society for reproductive medicine. Elective single-embryo transfer. Fertil Steril. 2012;97(4):835–42.Google Scholar
  55. 55.
    Pashayan N, Lyratzopoulos G, Mathur R. Cost-effectiveness of primary offer of IVF vs. primary offer of IUI followed by IVF (for IUI failures) in couples with unexplained or mild male factor subfertility. BMC Health Serv Res. 2006;6:80.PubMedCrossRefGoogle Scholar
  56. 56.
    Van Voorhis BJ, Barnett M, Sparks AE, et al. Effect of the total motile sperm count on the efficacy and cost-effectiveness of intrauterine insemination and in vitro fertilization. Fertil Steril. 2001;75(4):661–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Khalil MR, Rasmussen PE, Erb K, et al. Homologous intrauterine insemination. An evaluation of prognostic factors based on a review of 2473 cycles. Acta Obstet Gynecol Scand. 2001;80(1):74–81.PubMedCrossRefGoogle Scholar
  58. 58.
    Dickey RP, Pyrzak R, Lu PY, et al. Comparison of the sperm quality necessary for successful intrauterine insemination with World Health Organization threshold values for normal sperm. Fertil Steril. 1999;71(4):684–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Reproductive Endocrinology and Infertility, Utah Center for Reproductive MedicineUniversity of UtahSalt Lake CityUSA

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