Enhanced Fertility After Diagnostic Hysterosalpingography Using Oil-Based Contrast Agents May Be Attributable to Immunomodulation

Yun, Anthony J.; Lee, Patrick Y.

doi:10.2214/ajr.183.6.01831725

Cited by 26 publications

(15 citation statements)

References 35 publications

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“…A debate about the therapeutic effects of tubal flushing started over six decades ago. Several potential mechanisms have been proposed to explain such therapeutic effects, including mechanical flushing out of the debris or mucus plugs in the Fallopian tubes, enhancement of ciliary activity and immunobiological actions on the endometrium or peritoneum.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness on fertility outcome of tubal flushing with different contrast media: systematic review and network meta‐analysis

Wang

Welie

Rijswijk

et al. 2019

Ultrasound in Obstet & Gyne

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Objectives To compare, in women with infertility, the effectiveness and safety of tubal flushing using oil-based contrast medium, water-based contrast medium or their combination, and no tubal flushing, and to evaluate the effectiveness of tubal flushing on fertility outcome over time. MethodsWe performed a systematic review and network meta-analysis, searching the electronic databases MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials, and trial registries, up to 25 September 2018. We included randomized controlled trials (RCTs) comparing the following interventions with each other or with no intervention in women with infertility: tubal flushing using water-based contrast medium, tubal flushing using oil-based contrast medium or additional tubal flushing with oil-based medium following diagnostic tubal flushing with water-based medium. The outcomes included clinical pregnancy, live birth, ongoing pregnancy, miscarriage, ectopic pregnancy and adverse events. ResultsOf the 283 studies identified through the search, 14 RCTs reporting on 3852 women with infertility were included. Network meta-analysis showed that tubal flushing using oil-based contrast medium was associated with higher odds of clinical pregnancy within 6 months after randomization and more subsequent live births compared with tubal flushing using water-based medium (odds ratio (OR), 1.67 (95% CI, 1.38-2.03), moderate certainty of evidence ; and OR, 2.18 (95% CI,, ConclusionsIn women with infertility undergoing fertility workup, tubal flushing using oil-based contrast medium probably increases clinical pregnancy rates within 6 months after randomization and may increase subsequent live-birth rates, compared with tubal flushing using water-based contrast medium and compared with no intervention. Evidence on fertility outcomes beyond 6 months is inadequate to draw firm conclusions.

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Section: Introductionmentioning

confidence: 99%

Effectiveness on fertility outcome of tubal flushing with different contrast media: systematic review and network meta‐analysis

Wang

Welie

Rijswijk

et al. 2019

Ultrasound in Obstet & Gyne

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“…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.…”

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confidence: 76%

“…Yun and Lee, the authors of "Enhanced Fertility After Diagnostic Hysterosalpingography Using OilBased 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.…”

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confidence: 99%

Enhanced Fertility After Diagnostic Hysterosalpingography May Be a Myth

Spring¹,

Barkan²

2004

American Journal of Roentgenology

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“…The underlying mechanism of the fertility-enhancing effect of flushing with oil-based contrast medium is unknown. Various studies suggest an immunobiological effect of the oil on the endometrium and the peritoneum (Izumi et al , 2017, Johnson, 2005, Johnson, 2014, Mikulska et al , 1994, Sawatari et al , 1993, Yun and Lee, 2004) or enhancement of the tubal ciliary activity (Soules and Spadoni, 1982). Another potential explanation is a mechanical effect, during tubal patency testing with oil-based contrast medium debris or mucus plugs flushes out of the fallopian tubes (Gillespie, 1965).…”

Section: Discussionmentioning

confidence: 99%

Tubal flushing with oil- or water-based contrast medium: can we identify markers that indicate treatment benefit?

Rijswijk

Welie

Dreyer

et al. 2019

Human Reproduction Open

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STUDY QUESTION Can we identify patient characteristics that distinguish which ovulatory infertile women undergoing hysterosalpingography (HSG) benefit more or less from flushing with oil-based contrast medium compared to water-based contrast medium? SUMMARY ANSWER In ovulatory infertile women, HSG with oil-based contrast medium resulted in higher 6-month ongoing pregnancy and live birth rates as compared to HSG with water-based contrast medium and this treatment effect was independent of characteristics of the couple. WHAT IS KNOWN ALREADY We recently showed that in infertile women undergoing HSG, flushing with oil-based contrast medium resulted in more ongoing pregnancies than flushing with water-based contrast medium. STUDY DESIGN, SIZE, DURATION We used data from our randomized clinical trial (RCT) in which 1,119 ovulatory infertile women undergoing HSG during fertility work-up were randomized for use of oil-based (N = 557) or water-based (N = 562) contrast medium. PARTICIPANTS/MATERIALS, SETTING, METHODS We built logistic regression models to predict ongoing pregnancy and live birth (secondary outcome) as a function of the specific contrast, the specific marker, and marker-by-contrast-interaction. Markers considered were female age, maternal ethnicity, female smoking, body mass index (BMI), duration of infertility, infertility being primary or secondary, sperm quality, and previous appendectomy. MAIN RESULTS AND THE ROLE OF CHANCE The 6-month ongoing pregnancy rates in the overall population were 39.7% after use of oil-based contrast versus 29.1% after use of water-based contrast medium [relative risk (RR), 1.37; 95% confidence interval (CI), 1.16–1.61; P < 0.001]. Among the studied baseline characteristics, BMI (P = 0.002) and semen volume (P = 0.02) were statistically significant prognosticators. The treatment effect of oil-based contrast was stronger in women with a BMI ≤30 kg/m2 [RR, 1.54; 95% CI, 1.23–1.92; P = 0.002], and in women whose partner had a semen volume >3 ml [RR, 1.77; 95% CI, 1.28–2.46; P = 0.02]. Also, in women who smoked, the treatment effect of flushing with oil was stronger, but this interaction did not reach statistical significance (P = 0.066). We found no positive effect of oil-based contrast in obese women. We found similar but weaker associations for live birth, which was probably due to lower number of events resulting in less power. LIMITATIONS, REASONS FOR CAUTION The RCT was restricted to infertile ovulatory women younger than 39 years of age without endocrinological disorders and at low risk for tubal pathology. Our results should not be generalized to infertile women who do not share these features. WIDER IMPLICATIONS OF THE FINDINGS All infertile, ovulatory women younger than 39 years with a low risk for tubal pathology will benefit from an HSG with oil-based contrast; therefore, this should be offered to them after fertility work-up. STUDY FUNDING/COMPETING INTEREST(S) The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (AMC and VUmc) of the Amsterdam UMC. The study displayed in this paper was funded by an unconditional research grant from Guerbet. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). K.D. reports consultancy for Guerbet, during the conduct of the study, and also reports research grants from Guerbet. C.B.L. reports grants from Guerbet, during the conduct of the study, and grants from Ferring, grants from Merck, and personal fees from Ferring, outside the submitted work. P.H. reports grants from Guerbet, during the conduct of the study, and grants from Ferring and Merck, outside the submitted work. V.M. reports receiving travel and speakers fee as well as research grants from Guerbet. B.W.M. reports consultancy for ObsEva, Merck, Merck KGaA, and Guerbet, and research grants from Guerbet and Merck. The other authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER NTR 3270 www.trialregister.nl TRIAL REGISTRATION DATE 1 February 2012. DATE OF FIRST PATIENT’S ENROLMENT 3 February 2012.

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Enhanced Fertility After Diagnostic Hysterosalpingography Using Oil-Based Contrast Agents May Be Attributable to Immunomodulation

Cited by 26 publications

References 35 publications

Effectiveness on fertility outcome of tubal flushing with different contrast media: systematic review and network meta‐analysis

Effectiveness on fertility outcome of tubal flushing with different contrast media: systematic review and network meta‐analysis

Enhanced Fertility After Diagnostic Hysterosalpingography May Be a Myth

Tubal flushing with oil- or water-based contrast medium: can we identify markers that indicate treatment benefit?

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