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Enhanced Fertility After Diagnostic Hysterosalpingography May Be a Myth

¹ Kaiser Permanente Oakland Medical Center, 280 W MacArthur Blvd., Oakland, CA 94611.
² Kaiser Permanente Santa Rosa Medical Offices, 3559 Round Barn Blvd., Santa Rosa, CA 95403.

Received June 8, 2004; accepted after revision June 17, 2004.

This article is a commentary on the preceding article by Yun and Lee.

Address correspondence to D. B. Spring (David.Spring{at}kp.org).

Drs. Yun and Lee, the authors of "Enhanced Fertility After Diagnostic Hysterosalpingography Using Oil-Based Contrast Agents May Be Attributable to Immunomodulation" [1], theorize about the explanation of the enhanced rates of fertility and term pregnancies related to performance of hysterosalpingography (HSG) and specifically to the use of an oil-based contrast agent in HSG. Their theory rests on the assumption that use of oil-soluble contrast agents in HSG is associated with the increased postprocedural fertility and term pregnancy rates compared with the rates after use of water-soluble contrast agents in HSG. Yun and Lee are thus proposing a mechanism by which oil-soluble contrast agents in HSG would be used to enhance the rate of postprocedural reproductive success compared with the rate found after use of water-soluble contrast agents in HSG. Several early studies with sample size and methodologic limitations and a meta-analysis of their results indicated that this interpretation is possible [2–5]. We note that the earliest of these studies, a retrospective investigation with several methodologic weaknesses, was the only cited study whose authors concluded that HSG performance per se was associated with enhanced reproductive success [3].

We conducted an adequately powered randomized trial to evaluate potential therapeutic effects of contrast media in HSG [6]. Our prospective, randomized study of 666 infertile women compared reproductive success rates after HSG with water-soluble and oil-soluble contrast agents. We designed our study to have a statistical power sufficient to detect a difference between live birth rates associated with these agents of 20% vs 10%, two thirds the size of the 30% versus 10% difference detected in the excellent study by Rasmussen et al. [4]. We did not detect such a difference. In our study, the differences among the live birth rates of 20.4% after use of a water-soluble contrast agent, 19.4% after use of oil-soluble contrast agents (Ethiodol [ethiodized poppy seed oil], Savage Laboratories), and 21.8% after sequential use of both were not statistically significant (² = 0. 97, p = 0.61). These reproductive success rates are statistically indistinguishable, indicating no differences in the fertility-promoting effects of the different HSG contrast media that we evaluated. Thus, regardless of whether Ethiodol does or does not have significant immunomodulatory effects, our findings indicate that it is not associated with increased conception or term pregnancy rates compared with water-soluble contrast agents. This finding argues strongly against the authors' interpretation [1], calling its foundation into question.

As likely an explanation for increased term pregnancy rates after HSG, if such an effect were real, is not that either oil-based or water-based agents have a causal effect but rather that couples are more intensively trying to become pregnant at the time of HSG studies. Measurement of the time and frequency of intercourse before and after HSG and analysis of the association of reproductive success with intercourse frequency might indicate the extent to which this factor has confounded analyses indicating that HSG has therapeutic effects. To our knowledge, no such randomized, prospective study has been conducted.

Whatever immunologic perturbations may result from HSG, little or no evidence supports the hypothesis that enhanced fertility and term pregnancy rates are related directly to contrast agents of any kind. No statistically significant difference in the term pregnancy rates associated with oil-versus water-soluble contrast agents has been found. The myth of the "therapeutic effect" of HSG should be put aside until it has been convincingly proven to exist.

References

1. Yun AJ, Lee PY. Enhanced fertility after diagnostic hysterosalpingography using oil-based contrast agents may be attributable to immunomodulation. AJR2004; 183:1725 –1727[Free Full Text]
2. Soules MR, Spadoni LR. Oil versus aqueous media for hysterosalpingography: a continuing debate based on many opinions and few facts. Fertil Steril1982; 38:1 –11[Medline]
3. Mackey RA, Glass RH, Olson LE, Vaidya R. Pregnancy following hysterosalpingography with oil and water soluble dye. Fertil Steril 1971;22:504 –507[Medline]
4. Rasmussen F, Lindequist S, Larsen C, Justesen P. Therapeutic effects of hysterosalpingography: oil-versus water-soluble contrast media—a randomized prospective study. Radiology1991; 179:75 –78[Abstract/Free Full Text]
5. 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? Fertil Steril 1994;61:470 –477[Medline]
6. Spring DB, Barkan HE, Pruyn SC. Potential therapeutic effects of contrast materials in hysterosalpingography: a prospective randomized clinical trial—The Kaiser Permanente Infertility Work Group.Radiology2000; 214:53 –57[Abstract/Free Full Text]

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This article has been cited by other articles:

				N. P. Johnson, W. E. Hadden, L. W. Chamley, D. B. Spring, H. E. Barkan, A. J. Yun, and P. Y. Lee Fertility Enhancement by Hysterosalpingography with Oil-Soluble Contrast Media: Reality Not Myth Am. J. Roentgenol., December 1, 2005; 185(6): 1654 - 1657. [Full Text] [PDF]

				A. J. Yun, D. B. Spring, and H. E. Barkan Enhanced Fertility After Diagnostic Hysterosalpingography: The Debate Continues Am. J. Roentgenol., January 1, 2005; 184(1): 347 - 348. [Full Text] [PDF]

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