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

Abstract

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.

The use of oil‐soluble contrast media for tubal flushing in infertility: A consensus statement from ACCEPT (Australasian CREI Consensus Expert Panel on Trial evidence)

“…The trial included women aged 18‐39 who had been trying to conceive for at least one year with low risk of tubal pathology and in whom tubal patency testing was indicated. A secondary analysis aimed to determine which subgroups would most benefit and found that all women <39 years were likely to benefit but postulated additional value for lean women, smokers and those with male partners who have ejaculate volume >3 mL 9 . Weak data also raise the possibility that women with endometriosis may particularly benefit and further studies in this group were recommended 3 …”

Hysterosalpingo-Foam Sonography to Replace HSG in Evaluating Tubal Patency in Indonesian Subfertile Patients

“…Therefore the higher VAS score in the HSG procedure as compared to the subsequent HyFoSy procedure in this study was not biased by psychological factor of expecting pain in the subsequent procedure [17]. In regard to possible therapeutic effect of conventional HSG that may have altered the findings on HyFoSy, the studies on the effect of tubal flushing with HSG to increase live birth rate had a low quality of evidence [18]. Therefore, conventional HSG was not likely to have altered the findings on HyFoSy in our study.…”

An individualized decision between physical therapy or surgery for patients with degenerative meniscal tears cannot be based on continuous treatment selection markers: a marker-by-treatment analysis of the ESCAPE study

“…However, to select the best treatment for an individual patient it is important to quantify the benefit of one treatment over the other [ 8 ]. Previous marker-by-treatment analysis provided clinicians an evidence based method to select the best treatment for ovulatory infertile women [ 30 ]. In middle aged and older patients with a meniscal tear, the results from RCTs show that meniscal surgery has no clinical advantage over non-surgical treatment (such as physical therapy) or placebo surgery.…”