A review of the use of lipiodol flushing for unexplained infertility

There has been speculation for decades regarding the role of flushing women’s fallopian tubes in improving the chance of pregnancy. More recent evidence has highlighted a possible specific role for lipiodol (ethiodized oil), an oil-soluble contrast medium, in the enhancement of fertility by these means. This systematic review was designed to assess the effectiveness of tubal flushing with various contrast media in improving the chance of pregnancy. The review was performed using Cochrane guidelines, including only data from randomized controlled trials. Results confirm the effectiveness of flushing with lipiodol in improving the chance of pregnancy and live birth. Although there was limited evidence to suggest a possible benefit of oil- over water-soluble contrast media, the answer to this question remains unclear. The specific groups who appear to benefit most from lipiodol flushing are couples with unexplained infertility, but particularly couples where the woman has endometriosis in the context of normal patent fallopian tubes. As a simple, low-cost, minimally invasive intervention that carries a low risk of complications and no increased risk of multiple pregnancy, lipiodol flushing may prove an appealing alternative to established fertility treatments for many couples. Similar content being viewed by others

Weir WC, Weir DR. Therapeutic value of salpingograms in infertility. Fertil Steril 1951; 2: 514–22 Gillespie H. The therapeutic aspect of hysterosalpingography. Br J Radiol 1965: 38: 301–2 Mackey RA, Glass RH, Olson LE, et al. Pregnancy following hysterosalpingography with oil and water soluble dye. Fertil Steril 1971; 22: 504–7 Barwin N. Hysterosalpingography in infertility. Ulster Med J 1971; 41: 61–5 DeCherney AH, Kort H, Barney JB, et al. Increased pregnancy rate with oil-soluble hysterosalpingography dye. Fertil Steril 1980; 33: 407–10 Yaegashi N, Kuramoto M, Nakayama C, et al. Pregnancy rates after hysterosalpingography: comparing water soluble contrast medium with oily contrast medium. Acta Obstet Gynaecol Jpn 1987; 39: 1812–4 Acton C, Davitt J, Ryan E. Hysterosalpingography in infertility: an experience of 3631 examinations. Aust N Z J Obstet Gynaecol 1988; 28: 127–33 Massouras HG. Presentation of an insufflator-instillator and the use of it. Fertil Steril 1970; 21: 407–10 Soules MR, Spadoni LR. Oil versus aqueous media for hysterosalpingography: a continuing debate based on many opinions and few facts. Fertil Steril 1982; 28: 1–11 Lindequist S, Justesen P, Larsen C, et al. Diagnostic quality and complications of hysterosalpingography: oil- versus water-soluble contrast media: a randomized prospective study. Radiology 1991; 179: 69–74 Nunley W, Bateman B, Kithchin J, et al. Intravasation during hysterosalpingography using oil-base contrast medium: a second look. Obstet Gynecol 1987; 70: 309–12 Johnson NP, Taylor K, Nadgir AA, et al. Can diagnostic laparoscopy be avoided in routine investigation for infertility? Br J Obstet Gynaecol 2000; 107: 174–8 Watson A, Vandekerckhove P, Lilford R, et al. A meta-analysis of the therapeutic role of oil soluble contrast media at hysterosalpingography: a surprising result? Fertil Steril 1994; 61: 470–7 Johnson N, Vandekerckhove P, Watson A, et al. Tubal flushing for subfertility (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2004 Alper MM, Garner PR, Spence JEH, et al. Pregnancy rates after hysterosalpingography with oil- and water-soluble contrast media. Obstet Gynecol 1986; 68: 6–9 De Boer AD, Vemer HM, Willemsen WNP, et al. Oil or aqueous contrast media for hysterosalpingography: a prospective, randomized, clinical study. Eur J Obstet Gynecol Reprod Biol 1998; 28: 65–8 Letterie GS, Rose GS. Pregnancy rates after the use of oil-based and water-based contrast media to evaluate tubal patency. South Med J 1990; 83: 1402–3 Rasmussen F, Lindequist S, Larsen C, et al. Therapeutic effect of hysterosalpingography: oil- versus water-soluble contrast media: a randomized prospective study. Radiology 1991; 179: 75–9 Spring DB, Barkan HE, Pruyn SC. Potential therapeutic effects of contrast materials in hysterosalpingography: a prospective randomized clinical trial. Radiology 2000; 214: 53–7 Yang KN, Yeh NG, Pan SB. The therapeutic effects of oil-soluble hysterosalpingography contrast medium following water-soluble hysterosalpingography contrast medium. Chin Med J 1989; 44: 293–7 Nugent D, Watson AJ, Killick SR, et al. A randomized controlled trial of tubal flushing with lipiodol for unexplained infertility. Fertil Steril 2002; 77: 173–5 Ogata R, Nakamura G, Uchiumi Y, et al. Therapeutic efficacy of hysterosalpingography (HSG) in infertility, a prospective, randomized, clinical study. Jap J Fertil Steril 1993; 38: 91–4 Grant A. Infertility surgery of the oviduct. Fertil Steril 1971; 22: 496–503 Kerin J, Surrey E, Williams D, et al. Falloposcopic observations of endotubal isthmic plugs as a cause of reversible obstruction and their histological characterization. J Laparoendosc Surg 1991; 1: 103–10 Sulak PJ, Letterie GS, Coddington CC, et al. Histology of proximal tubal occlusion. Fertil Steril 1987; 48: 437–40 Thurmond A, Rosch J. Nonsurgical fallopian tube recanalisation for treatment of infertility. Radiology 1990; 174: 371–4 Honore GM, Holden AE, Schenken RS. Pathophysiology and management of proximal tubal blockage. Fertil Steril 1999; 71: 785–95 Pinto AB, Hovsepian DM, Wattanakumtornkul S, et al. Pregnancy outcomes after fallopian tube recanalization: oil-based versus water-soluble contrast agents. J Vasc Interv Radiol 2003; 14: 69–74 Johnson J, Montoya I, Olive D. Ethiodol oil contrast medium inhibits macrophage phagocytosis and adherence by altering membrane electronegativity and microviscosity. Fertil Steril 1992; 58: 511–7 Sawatari Y, Hori T, Hoshiai H. Oily contrast medium as a therapeutic agent for infertility because of mild endometriosis. Fertil Steril 1993; 59: 907–11 Goodman S, Rein M, Hill J. Hysterosalpingography contrast media and chromotubation dye inhibit peritoneal lymphocyte and macrophage function in vitro: a potential mechanism for fertility enhancement. Fertil Steril 1993; 59: 1022–7 Mikulska D, Kurzawa R, Rozewicka L. Morphology of in vitro sperm phagocytosis by rat peritoneal macrophages under influence of oily contrast medium (lipiodol). Acta Eur Fertil 1994; 25: 203–6 Johnson NP, Farquhar CM, Hadden WE, et al. The FLUSH trial: flushing with lipiodol for unexplained (and endometriosis-related) subfertility by hysterosalpingography: a randomised trial. Hum Reprod 2004; 19: 2043–51 Kao LC, Germeyer A, Tulac S, et al. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology 2003; 144: 2870–81 Lindequist S, Rasmussen F, Larsen C. Use of iotrolan versus ethiodized poppy-seed oil in hysterosalpingography. Radiology 1994; 191: 513–7 Steiner AZ, Meyer W, Clark RL, et al. Oil-soluble contrast during hysterosalpingography in women with proven tubal patency. Obstet Gynecol 2003; 101: 109–13 Schwabe MG, Shapiro SS, Haning RV. Hysterosalpingography with oil contrast medium enhances fertility in patients with infertility of unknown etiology. Fertil Steril 1983; 40: 604–6 Wolf G, Fitzpal P. Hysterosalpingography with a new contrast medium. Fortschr Geb Rontgenstrahlen Nuklearmed Erganzungsbd 1989; 128: 190–4 Jansen RP. Minimal endometriosis and reduced fecundability: prospective evidence from an artificial insemination by donor program. Fertil Steril 1986; 46: 141–3 Toma SK, Stovall DW, Hammond MG. The effect of laparoscopic ablation or Danocrine® on pregnancy rates in patients with stage I or II endometriosis undergoing donor insemination. Obstet Gynecol 1992; 80: 253–6 Fukui A, Fujii S, Yamaguchi E, et al. NK cell subpopulations and cytotoxicity for infertile patients undergoing in vitro fertilisation. Am J Reprod Immunol 1999; 41: 413–22 Johnson NP, Bhattu S, Wagner A, et al. Lipiodol alters murine uterine dendritic cell populations: a potential mechanism for the fertility enhancing effect of lipiodol. Fertil Steril 2005; 83: 1814–21 Jacobson TZ, Barlow DH, Koninckx PR, et al. Laparoscopic surgery for subfertility associated with endometriosis (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2004 Hughes E, Collins J, Vandekerckhove P. Clomiphene citrate for unexplained subfertility in women (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2004 Pandian Z, Bhattacharya S, Nikolaou D, et al. In vitro fertilisation for unexplained subfertility (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2004 Acknowledgments This review and figures 1–4 are based on a Cochrane Review published in the Cochrane Library[14] (copyright Cochrane Library, reproduced with permission). The following people from the Cochrane MDSG have had an important role in the original Cochrane review and subsequent updates: Patrick Vandekerckhove, Andrew Watson, Richard Lilford, Tasuku Harada, Ed Hughes, Andy Vail, Cindy Farquhar, Michelle Proctor, Ruth Withers, and Sue Hall. I am also grateful for inspiration from the insights of my colleagues Wendy Hadden, radiologist, and Larry Chamley, reproductive biologist. No sources of funding were used to assist in the preparation of this review. The author has no conflicts of interest that are directly relevant to the content of this review. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Johnson, N.P. A Review of the Use of Lipiodol Flushing for Unexplained Infertility. Mol Diag Ther 4, 233–243 (2005). https://doi.org/10.2165/00024677-200504040-00004 Published: Issue date: DOI: https://doi.org/10.2165/00024677-200504040-00004