Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2015 May 1;2015(5):CD003718.
doi: 10.1002/14651858.CD003718.pub4.

Tubal flushing for subfertility

Lamiya Mohiyiddeen  1 , Anne Hardiman, Cheryl Fitzgerald, Edward Hughes, Ben Willem J Mol, Neil Johnson, Andrew Watson
Affiliations
Meta-Analysis

Tubal flushing for subfertility

Lamiya Mohiyiddeen et al. Cochrane Database Syst Rev. .

Update in

  • Tubal flushing for subfertility.
    Wang R, Watson A, Johnson N, Cheung K, Fitzgerald C, Mol BWJ, Mohiyiddeen L. Wang R, et al. Cochrane Database Syst Rev. 2020 Oct 15;10(10):CD003718. doi: 10.1002/14651858.CD003718.pub5. Cochrane Database Syst Rev. 2020. PMID: 33053612 Free PMC article.

Abstract

Background: Establishing the patency of the fallopian tubes is a commonly undertaken diagnostic investigation for women with subfertility. This is usually achieved by flushing contrast medium through the tubes and taking radiographs. However, it has been noted that many women conceive in the first three to six months after the tubal flushing, which has raised the possibility that tubal flushing could also be a treatment for infertility. There has been debate about which contrast medium should be used (water-soluble or oil-soluble media) as this may influence pregnancy rates.

Objectives: To evaluate the effect of flushing fallopian tubes with oil- or water-soluble contrast media on live birth and pregnancy rates in women with subfertility.

Search methods: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials, MEDLINE, EMBASE, Biological Abstracts, trial registers and reference lists of identified articles. The most recent search was conducted in June 2014.

Selection criteria: Randomised controlled trials (RCTs) comparing tubal flushing with oil-soluble or water-soluble contrast media, or with no treatment, in women with subfertility.

Data collection and analysis: Two authors independently selected the trials, assessed risk of bias and extracted data. We contacted study authors for additional information. The overall quality of the evidence was assessed using GRADE methods.

Main results: Thirteen trials involving 2914 women were included, of whom 2494 were included in the analysis. Oil-soluble contrast media (OSCM) versus no interventionThe OSCM group had a higher rate of live birth (odds ratio (OR) 3.09, 95% CI 1.39 to 6.91, 1 RCT, 158 women, low quality evidence) and ongoing pregnancy (OR 3.59, 95% CI 2.06 to 6.26, 3 RCTs, 382 women, I(2) = 0%, low quality evidence) than women who had no intervention. Our findings suggest that among subfertile women with a 17% chance of an ongoing pregnancy if they have no intervention, the rate will increase to between 29% and 55% if they have tubal flushing with OSCM. Water-soluble contrast media (WSCM) versus no interventionThere was no evidence of a difference between the groups in rates of live birth (OR 1.13, 95% CI 0.67 to 1.91, 1 RCT, 334 women, very low quality evidence) or ongoing pregnancy (OR 1.14, 95% CI 0.71 to 1.84, 1 RCT, 334 women, very low quality evidence). OSCM versus WSCMTwo RCTs reported live birth: one found a higher live birth rate in the oil-soluble group and the other found no evidence of a difference between the groups. These studies were not pooled due to very high heterogeneity (I(2) = 93%). There was no evidence of a difference between the groups in rates of ongoing pregnancy, however there was high heterogeneity (OR 1.44, 95% CI 0.84 to 2.47, 5 RCTs, 1454 women, I(2) = 76%, random-effects model, very low quality evidence). OSCM plus WSCM versus WSCM aloneThere was no evidence of a difference between the groups in rates of live birth (OR 1.06, 95% CI 0.64 to 1.77, 1 RCT, 393 women, very low quality evidence) or ongoing pregnancy (OR 1.23, 95% CI 0.87 to 1.72, 4 RCTs, 633 women, I(2) = 0%, low quality evidence).There was no evidence of a difference between any of the interventions in rates of adverse events, but such events were poorly reported in most studies.

Authors' conclusions: The evidence suggests that tubal flushing with oil-soluble contrast media may increase the chance of pregnancy and live birth compared to no intervention. Findings for other comparisons were inconclusive due to inconsistency and lack of statistical power. There was insufficient evidence on adverse events to reach firm conclusions. Further robust randomised controlled trials are needed.

PubMed Disclaimer

Conflict of interest statement

Neil Johnson and Andrew Watson were investigators in separate RCTs included in this review. Ben Mol is an investigator on ongoing trial Dreyer 2014 investigating oil‐based versus water‐based contrast media.

Figures

1
1
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
Study flow diagram.
4
4
Forest plot of comparison: 1 OSCM versus no intervention, outcome: 1.1 Live birth.
5
5
Forest plot of comparison: 2 WSCM versus no intervention, outcome: 2.1 Live birth.
6
6
Forest plot of comparison: 3 OSCM versus WSCM, outcome: 3.1 Live birth.
7
7
Forest plot of comparison: 4 OSCM + WSCM versus WSCM, outcome: 4.1 Live birth.
1.1
1.1. Analysis
Comparison 1 OSCM versus no intervention, Outcome 1 Live birth.
1.2
1.2. Analysis
Comparison 1 OSCM versus no intervention, Outcome 2 Ongoing Pregnancy.
1.3
1.3. Analysis
Comparison 1 OSCM versus no intervention, Outcome 3 Miscarriage per pregnancy.
1.5
1.5. Analysis
Comparison 1 OSCM versus no intervention, Outcome 5 Ectopic pregnancy per pregnancy.
2.1
2.1. Analysis
Comparison 2 WSCM versus no intervention, Outcome 1 Live birth.
2.2
2.2. Analysis
Comparison 2 WSCM versus no intervention, Outcome 2 Ongoing Pregnancy.
2.3
2.3. Analysis
Comparison 2 WSCM versus no intervention, Outcome 3 Miscarriage per pregnancy.
2.4
2.4. Analysis
Comparison 2 WSCM versus no intervention, Outcome 4 Ectopic pregnancy.
3.1
3.1. Analysis
Comparison 3 OSCM versus WSCM, Outcome 1 Live birth.
3.2
3.2. Analysis
Comparison 3 OSCM versus WSCM, Outcome 2 Ongoing pregnancy.
3.3
3.3. Analysis
Comparison 3 OSCM versus WSCM, Outcome 3 Miscarriage per pregnancy.
3.4
3.4. Analysis
Comparison 3 OSCM versus WSCM, Outcome 4 Ectopic pregnancy.
3.5
3.5. Analysis
Comparison 3 OSCM versus WSCM, Outcome 5 Any postprocedural pain (dichotomous variable).
3.6
3.6. Analysis
Comparison 3 OSCM versus WSCM, Outcome 6 Procedural pain (continuous variable).
3.7
3.7. Analysis
Comparison 3 OSCM versus WSCM, Outcome 7 Intravasation.
3.8
3.8. Analysis
Comparison 3 OSCM versus WSCM, Outcome 8 Infection.
3.9
3.9. Analysis
Comparison 3 OSCM versus WSCM, Outcome 9 Haemorrhage.
4.1
4.1. Analysis
Comparison 4 OSCM + WSCM versus WSCM, Outcome 1 Live birth.
4.2
4.2. Analysis
Comparison 4 OSCM + WSCM versus WSCM, Outcome 2 Ongoing Pregnancy.
4.3
4.3. Analysis
Comparison 4 OSCM + WSCM versus WSCM, Outcome 3 Miscarriage per pregnancy.
4.4
4.4. Analysis
Comparison 4 OSCM + WSCM versus WSCM, Outcome 4 Ectopic pregnancy.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Al‐Fadhli 2006 {published data only}
    1. Al‐Fadhli R, Sylvestre C, Buckett W, Tulandi T. A randomized study of laparoscopic chromopertubation with lipiodol versus saline in infertile woman. Fertility and Sterility 2006;85(2):505‐7. - PubMed
Alper 1986 {published data only}
    1. Alper MM, Garner PR, Spence JEH, Quarrington AM. Pregnancy rates after hysterosalpingography with oil‐ and water‐soluble contrast media. Obstetrics and Gynecology 1986;68:6‐9. - PubMed
De Boer 1988 {published data only}
    1. Boer AD, Vemer HM, Willemsen WNP, Saunders FBM. Oil or aqueous contrast media for hysterosalpingography: a prospective, randomized, clinical study. European Journal of Obstetrics Gynecology and Reproductive Biology 1998;28:65‐8. - PubMed
Johnson 2004 {published data only}
    1. Johnson N, Farquhar C, Suckling J, Yu Y, Sadler L, Hadden W. The FLUSH Trial ‐ a randomised trial of lipiodol flushing for unexplained subfertility by hysterosalpingography. Australian and New Zealand Journal of Obstetrics and Gynaecology (refereed abstracts of original oral presentations at the Royal Australian and New Zealand College of Obstetricians and Gynaecologists 5th Scientific Meeting, Auckland). 2003; Vol. 43:406.
    1. Johnson NP, Farquhar CM, Hadden WE, Suckling J, Yu Y, Sadler L. The FLUSH Trial ‐ Flushing with lipiodol for unexplained (and endometriosis‐related) subfertility by hysterosalpingography: a randomised trial. Human Reproduction 2004;19:2043‐51. - PubMed
    1. Johnson NP, Kwok R, Stewart AW, Saththianathan M, Hadden WE, Chamley LW. Lipiodol fertility enhancement: two‐year follow‐up of a randomized trial suggests a transient benefit in endometriosis, but a sustained benefit in unexplained infertility. Human Reproduction 2007;22(11):2857‐62. - PubMed
Letterie 1990 {published data only}
    1. Letterie GS, Rose GS. Pregnancy rates after the use of oil‐based and water‐based contrast media to evaluate tubal patency. Southern Medical Journal 1990;83:1402‐3. - PubMed
Lindborg 2009 {published data only}
    1. Lindborg L, Thorburn J, Bergh C, Strandell A. Influence of HyCoSy on spontaneous pregnancy: a randomized controlled trial. Human Reproduction 2009;24:1075‐9. - PubMed
Lindequist 1994 {published data only}
    1. Lindequist S, Rasmussen F, Larsen C. Use of iotrolan versus ethiodized poppy‐seed oil in hysterosalpingography. Radiology 1994;191:513‐7. - PubMed
Nugent 2002 {published data only}
    1. Nugent D, Watson AJ, Killick SR, Balen AH, Rutherford AJ. A randomized controlled trial of tubal flushing with lipiodol for unexplained infertility. Fertility and Sterility 2002;77:173‐5. - PubMed
Ogata 1993 {published data only}
    1. Ogata R, Nakamura G, Uchiumi Y, Yokoyamay M, Watanabe Y, Nozaki M, et al. Therapeutic efficacy of hysterosalpingography (HSG) in infertility, a prospective, randomized, clinical study. Japanese Journal of Fertility and Sterility 1993;38:91‐4.
Rasmussen 1991 {published data only}
    1. Lindequist S, Justesen P, Larsen C, Rasmussen F. Diagnostic quality and complications of hysterosalpingography: oil‐ versus water‐soluble contrast media ‐ a randomized prospective study. Radiology 1991;179:69‐74. - PubMed
    1. Rasmussen F, Lindequist S, Larsen C, Justesen P. Therapeutic effect of hysterosalpingography: oil‐ versus water‐soluble contrast media ‐ a randomized prospective study. Radiology 1991;179:75‐9. - PubMed
Spring 2000 {published data only}
    1. Spring DB, Barkan HE, Pruyn SC. Potential therapeutic effects of contrast materials in hysterosalpingography: a prospective randomized clinical trial. Radiology 2000;214:53‐7. - PubMed
Steiner 2003 {published data only}
    1. Steiner AZ, Meyer WR, Clark RL, Hartmann KE. Oil‐soluble contrast during hysterosalpingography in women with proven tubal patency. Obstetrics and Gynecology 2003;101:109‐13. - PubMed
Yang 1989 {published data only}
    1. Yang KN, Yeh NG, Pan SB. The therapeutic effects of oil‐soluble hysterosalpingography contrast medium following water‐soluble hysterosalpingography contrast medium. Chinese Medical Journal 1989;44:293‐7. - PubMed

References to studies excluded from this review

Acton 1988 {published data only}
    1. Acton C, Davitt J, Ryan E. Hysterosalpingography in infertility ‐ an experience of 3631 examinations. Australian and New Zealand Journal of Obstetrics and Gynaecology 1988;28:127‐33. - PubMed
Barwin 1971 {published data only}
    1. Barwin N. Hysterosalpingography in infertility. Ulster Medical Journal 1971;41:61‐5. - PMC - PubMed
Court 2014 {published data only}
    1. Court KA, Dare AJ, Weston‐Webb M, Hadden WE, Sim RG, Johnson NP. Establishment of lipoidal as a fertility treatment ‐ Prospective study of the complete innovative treatment data set. Australian and New Zealand Journal of Obstetrics and Gynaecology 2014;54:13‐9. - PubMed
DeCherney 1980 {published data only}
    1. DeCherney AH, Kort H, Barney JB, DeVore GR. Increased pregnancy rate with oil‐soluble hysterosalpingography dye. Fertility and Sterility 1980;33:407‐10. - PubMed
Gillespie 1965 {published data only}
    1. Gillespie H. The therapeutic aspect of hysterosalpingography. British Journal of Radiology 1965;38:301‐2. - PubMed
Mackey 1971 {published data only}
    1. Mackey RA, Glass RH, Olson LE, Vaidya R. Pregnancy following hysterosalpingography with oil and water soluble dye. Fertility and Sterility 1971;22:504‐7. - PubMed
Perquin 2006 {published data only}
    1. Perquin DAM, Dorr PJ, Craen AJM, Helmerhorst FM. Routine use of hysterosalpingography prior to laparoscopy in the fertility workup: a multicentre randomized controlled trial. Human Reproduction 2006;21(5):1227‐31. - PubMed
Schwabe 1983 {published data only}
    1. Schwabe MG, Shapiro SS, Haning RV. Hysterosalpingography with oil contrast medium enhances fertility in patients with infertility of unknown etiology. Fertility and Sterility 1983;40:604‐6. - PubMed
Wolf 1989 {published data only}
    1. Wolf G, Fitzpal P. Hysterosalpingography with a new contrast medium. Fortschritte auf dem Gebiete der Rontgenstrahlem und der Nuklearmedizin ‐ Erganzungsband 1989;128:190‐4. - PubMed
Yaegashi 1987 {published data only}
    1. Yaegashi N, Kuramoto M, Nakayama C, Nakano M. Pregnancy rates after hysterosalpingography ‐ comparing water soluble contrast medium with oily contrast medium. Acta Obstetrica et Gynaecologica Japonica 1987;39:1812‐4. - PubMed

References to ongoing studies

Dreyer 2014 {published data only}
    1. Dreyer K. Oil‐based contrast versus water based contrast media in the diagnosis of tubal patency at Hysterosalpingography. A Randomized Controlled Trial. ‐ H2Olie studie. WHO ICTRP http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3270. Accessed 25 November 2014.

Additional references

Bateman 1987
    1. Bateman BG, Nunley WC, Kitchin JD, Kaizer DL. Utility of the 24‐hour delay hysterosalpingogram. Fertility and Sterility 1987;47:613‐7. - PubMed
Brent 2006
    1. Brent K, Hadden WE, Weston‐Webb M, Johnson NP. After the FLUSH trial: A prospective observational study of lipiodol flushing as an innovative treatment for unexplained and endometriosis‐related infertility. Australian and New Zealand Journal of Obstetrics and Gynaecology 2006;46:293‐7. - PubMed
Capitanio 1991
    1. Capitanio GL, Ferraiolo A, Croce S, Gazzo R, Anserini P, Cecco L. Transcervical selective salpingography: a diagnostic and therapeutic approach to cases of proximal tubal injection failure. Fertility and Sterility 1991;55:1045‐50. - PubMed
Fukui 1999
    1. Fukui A, Fujii S, Yamaguchi E, Kimura H, Sato S, Saito Y. NK cell subpopulations and cytotoxicity for infertile patients undergoing in vitro fertilisation. American Journal of Reproductive Immunology 1999;41:413‐22. - PubMed
Grant 1971
    1. Grant A. Infertility surgery of the oviduct. Fertility and Sterility 1971;22:495‐503. - PubMed
Johnson 1992
    1. Johnson J, Montoya I, Olive D. Ethiodol oil contrast medium inhibits macrophage phagocytosis and adherence by altering membrane electronegativity and microviscosity. Fertility and Sterility 1992;58:511‐7. - PubMed
Johnson 2005 (c)
    1. Johnson NP, Bhattu S, Wagner A, Blake DA, Chamley LW. Lipiodol alters murine uterine dendritic cell populations: a potential mechanism for the fertility enhancing effect of lipiodol. Fertility and Sterility 2005;83:1814‐21. - PubMed
Kerin 1991
    1. Kerin J, Surrey E, Williams D, Daykhovsky L, Grundfest W. Falloposcopic observations of endotubal isthmic plugs as a cause of reversible obstruction and their histologic characterisation. Journal of Laparoendoscopic Surgery 1991;1:103‐10. - PubMed
Lindequist 1991
    1. Lindequist S, Justesen P, Larsen C, Rasmussen F. Diagnostic quality and complications of hysterosalpingography: oil‐ versus water‐soluble contrast media ‐ a randomized prospective study. Radiology 1991;179:69‐74. - PubMed
Mikulska 1994
    1. Mikulska D, Kurzawa R, Rozewicka L. Morphology of in vitro sperm phagocytosis by rat peritoneal macrophages under influence of oily contrast medium (lipiodol). Acta Europaea Fertilitatis 1994;25:203‐6. - PubMed
Novy 1988
    1. Novy MJ, Thurmond AS, Patton P, Uchida BT, Rosch J. Diagnosis of cornual obstruction by transcervical fallopian tube cannulation. Fertility and Sterility 1988;50:434‐40. - PubMed
Nunley 1987
    1. Nunley W, Bateman B, Kithchin J, Pope T. Intravasation during hysterosalpingography using oil‐base contrast medium ‐ a second look. Obstetrics and Gynecology 1987;70:309‐12. - PubMed
Sawatari 1993
    1. Sawatari Y, Hori T, Hoshiai H. Oily contrast medium as a therapeutic agent for infertility because of mild endometriosis. Fertility and Sterility 1993;59:907‐11. - PubMed
Soules 1982
    1. Soules MR, Spadoni LR. Oil versus aqueous media for hysterosalpingography: a continuing debate based on many opinions and few facts. Fertility and Sterility 1982;28:1‐11. - PubMed
Sulak 1987
    1. Sulak PJ, Letterie GS, Coddington CC, Hayslip CC, Woodward JE, Klein TA. Histology of proximal tubal occlusion. Fertility and Sterility 1987;48:437‐40. - PubMed
Thurmond 1990
    1. Thurmond A, Rosch J. Nonsurgical fallopian tube recanalisation for treatment of infertility. Radiology 1990;174:371‐4. - PubMed
Vandekerckhove 1993
    1. Vandekerckhove P, O'Donovan P, Lilford R, Vail A, Brosens I, Hughes E. Infertility treatment: from cookery to science. The epidemiology of randomised controlled trials. British Journal of Obstetrics and Gynaecology 1993;100:1005‐36. [DOI: 10.1016/S0950-3552(96)80005-8] - DOI - PubMed
Watson 1994
    1. Watson A, Vandekerckhove P, Lilford R, Vail A, Brosens I, Hughes E. A meta‐analysis of the therapeutic role of oil soluble contrast media at hysterosalpingography: a surprising result?. Fertility and Sterility 1994;61:470‐7. - PubMed
Weir 1951
    1. Weir WC, Weir DR. Therapeutic value of salpingograms in infertility. Fertility and Sterility 1951;2:514‐22. - PubMed

References to other published versions of this review

Johnson 2002
    1. Johnson N, Venderkerckhove P, Watson A, Lilford R, Harada T, Hughes E. Tubal flushing for subfertility. Cochrane Database of Systematic Reviews 2002, Issue 3. [CENTRAL: CD003718] - PubMed
Johnson 2005 (a)
    1. Johnson N, Vanderkerckhove P, Watson A, Lilford R, Harada T, Hughes E. Tubal flushing for subfertility. Cochrane Database of Systematic Reviews 2005;Art. No.: CD003718.(DOI: 10.1002/14651858.):CD003718.pub2.. - PubMed
Johnson 2007
    1. Johnson N, Vanderkerchove P, Lilford R, Harada T, Hughes E, Luttjeboer F. Tubal flushing for subfertility. Cochrane Database of Systematic Reviews 2007, Issue 3. [DOI: 10.1002/14651858.CD003718.pub3] - DOI - PubMed
Vandekerckhove 1996
    1. Vandekerckhove P, Watson A, Lilford R, Harada T, Hughes E. Oil‐soluble versus water‐soluble media for assessing tubal patency with hysterosalpingography or laparoscopy in subfertile women. Cochrane Database of Systematic Reviews 1996, Issue 2. - PubMed