Hysterosalpingo-foam sonography versus hysterosalpingography during fertility work-up: an economic evaluation alongside a randomized controlled trial.

STUDY QUESTION: What are the costs and effects of tubal patency testing by hysterosalpingo-foam sonography (HyFoSy) compared to hysterosalpingography (HSG) in infertile women during the fertility work-up? SUMMARY ANSWER: During the fertility work-up, clinical management based on the test results of HyFoSy leads to slightly lower, though not statistically significant, live birth rates, at lower costs, compared to management based on HSG results. WHAT IS KNOWN ALREADY: Traditionally, tubal patency testing during the fertility work-up is performed by HSG. The FOAM trial, formally a non-inferiority study, showed that management decisions based on the results of HyFoSy resulted in a comparable live birth rate at 12 months compared to HSG (46% versus 47%; difference -1.2%, 95% CI: -3.4% to 1.5%; P = 0.27). Compared to HSG, HyFoSy is associated with significantly less pain, it lacks ionizing radiation and exposure to iodinated contrast medium. Moreover, HyFoSy can be performed by a gynaecologist during a one-stop fertility work-up. To our knowledge, the costs of both strategies have never been compared. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation alongside the FOAM trial, a randomized multicenter study conducted in the Netherlands. Participating infertile women underwent, both HyFoSy and HSG, in a randomized order. The results of both tests were compared and women with discordant test results were randomly allocated to management based on the results of one of the tests. The follow-up period was twelve months. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 1160 infertile women (18-41 years) scheduled for tubal patency testing. The primary outcome was ongoing pregnancy leading to live birth. The economic evaluation compared costs and effects of management based on either test within 12 months. We calculated incremental cost-effectiveness ratios (ICERs): the difference in total costs and chance of live birth. Data were analyzed using the intention to treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, 1026 of the 1160 women underwent both tubal tests and had data available: 747 women with concordant results (48% live births), 136 with inconclusive results (40% live births), and 143 with discordant results (41% had a live birth after management based on HyFoSy results versus 49% with live birth after management based on HSG results). When comparing the two strategies-management based on HyfoSy results versus HSG results-the estimated chance of live birth was 46% after HyFoSy versus 47% after HSG (difference -1.2%; 95% CI: -3.4% to 1.5%). For the procedures itself, HyFoSy cost €136 and HSG €280. When costs of additional fertility treatments were incorporated, the mean total costs per couple were €3307 for the HyFoSy strategy and €3427 for the HSG strategy (mean difference €-119; 95% CI: €-125 to €-114). So, while HyFoSy led to lower costs per couple, live birth rates were also slightly lower. The ICER was €10 042, meaning that by using HyFoSy instead of HSG we would save €10 042 per each additional live birth lost. LIMITATIONS, REASONS FOR CAUTION: When interpreting the results of this study, it needs to be considered that there was a considerable uncertainty around the ICER, and that the direct fertility enhancing effect of both tubal patency tests was not incorporated as women underwent both tubal patency tests in this study. WIDER IMPLICATION OF THE FINDINGS: Compared to clinical management based on HSG results, management guided by HyFoSy leads to slightly lower live birth rates (though not statistically significant) at lower costs, less pain, without ionizing radiation and iodinated contrast exposure. Further research on the comparison of the direct fertility-enhancing effect of both tubal patency tests is needed. STUDY FUNDING/COMPETING INTEREST(S): FOAM trial was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEm®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, and interpretation of the data. K.D. reports travel-and speakers fees from Guerbet and her department received research grants from Guerbet outside the submitted work. H.R.V. received consulting-and travel fee from Ferring. A.M.v.P. reports received consulting fee from DEKRA and fee for an expert meeting from Ferring, both outside the submitted work. C.H.d.K. received travel fee from Merck. F.J.M.B. received a grant from Merck and speakers fee from Besins Healthcare. F.J.M.B. is a member of the advisory board of Merck and Ferring. J.v.D. reported speakers fee from Ferring. J.S. reports a research agreement with Takeda and consultancy for Sanofi on MR of motility outside the submitted work. M.v.W. received a travel grant from Oxford Press in the role of deputy editor for Human Reproduction and participates in a DSMB as independent methodologist in obstetrics studies in which she has no other role. B.W.M. received an investigator grant from NHMRC GNT1176437. B.W.M. reports consultancy for ObsEva, Merck, Guerbet, iGenomix, and Merck KGaA and travel support from Merck KGaA. V.M. received research grants from Guerbet, Merck, and Ferring and travel and speakers fees from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: International Clinical Trials Registry Platform No. NTR4746.

Cost-effectiveness of tubal patency tests.

OBJECTIVE: Guidelines are not in agreement on the most effective diagnostic scenario for tubal patency testing; therefore, we evaluated the cost-effectiveness of invasive tubal testing in subfertile couples compared with no testing and treatment. DESIGN: Cost-effectiveness analysis. SETTING: Decision analytic framework. POPULATION: Computer-simulated cohort of subfertile women. METHODS: We evaluated six scenarios: (1) no tests and no treatment; (2) immediate treatment without tubal testing; (3) delayed treatment without tubal testing; (4) hysterosalpingogram (HSG), followed by immediate or delayed treatment, according to diagnosis (tailored treatment); (5) HSG and a diagnostic laparoscopy (DL) in case HSG does not prove tubal patency, followed by tailored treatment; and (6) DL followed by tailored treatment. MAIN OUTCOME MEASURES: Expected cumulative live births after 3 years. Secondary outcomes were cost per couple and the incremental cost-effectiveness ratio. RESULTS: For a 30-year-old woman with otherwise unexplained subfertility for 12 months, 3-year cumulative live birth rates were 51.8, 78.1, 78.4, 78.4, 78.6 and 78.4%, and costs per couple were €0, €6968, €5063, €5410, €5405 and €6163 for scenarios 1, 2, 3, 4, 5 and 6, respectively. The incremental cost-effectiveness ratios compared with scenario 1 (reference strategy), were €26,541, €19,046, €20,372, €20,150 and €23,184 for scenarios 2, 3, 4, 5 and 6, respectively. Sensitivity analysis showed the model to be robust over a wide range of values for the variables. CONCLUSIONS: The most cost-effective scenario is to perform no diagnostic tubal tests and to delay in vitro fertilisation (IVF) treatment for at least 12 months for women younger than 38 years old, and to perform no tubal tests and start immediate IVF treatment from the age of 39 years. If an invasive diagnostic test is planned, HSG followed by tailored treatment, or a DL if HSG shows no tubal patency, is more cost-effective than DL.

Diagnosing infertility in a district general hospital: a case-note and cost analysis.

This study aimed to observe diagnostic work-up and cost evaluation of infertile couples to identify opportunities for improvement. One hundred and seventy-four new referrals to the gynaecology clinic in a District General Hospital during 1996 and 1997 provided the cohort for analysis. Data from case notes were transferred on to data collection sheets. Data were inputted into SPSS for analysis. Primary infertility accounted for 62% of couples. One hundred and forty-two couples (81.6%) had a definitive diagnosis, and the analyses relate to these couples only. There was no single investigation performed on the whole cohort studied. Semen analysis was undertaken in 80.3% of the couples; couples with suspected male infertility were over four times more likely to have had more than two semen tests (P = 0.0005); 77.5% of couples had FSH and LH tests; and midluteal progesterone was tested in 76.1%. An increased intensity of FSH-LH hormone testing was associated with couples with anovulation (chi(2) = 6.79, P = 0.03). Serial repeat progesterone tended to be given to women with irregular or prolonged cycles (35 days or more), although this tendency was not statistically significant. The most common test for tubal patency was hysterosalpingography. Higher costs are generally associated with diagnosing endometriosis and tubal factor because of the relatively high cost of laparoscopy. The average cost of diagnosis for each patient was pound 365 and ranged from pound 64 to pound 851. In conclusion, a standard protocol of basic investigative procedures should be offered in secondary centres to all couples. Avoiding duplication and unnecessary investigations (for example, serial progesterone) may reduce costs, although offering all couples a standard protocol of tests would probably offset this observation.

HyCoSy--as good as claimed?

Hysterosalpingo contrast sonography (HyCoSy) has been compared favourably in the literature with hysterosalpingography (HSG). It does not require ionizing radiation and demonstrates the uterus and ovaries. HyCoSy is reported as being a safe, well tolerated, quick and easy investigation of Fallopian tube patency. Over a 1-year period HyCoSy was performed by two operators on 118 consecutive women who were thought likely to have patent Fallopian tubes. The examinations were graded using a local scale to assess discomfort and were correlated with tubal patency. HSG was performed on 116 patients by the same operators and discomfort recorded. 15 patients underwent both examinations. The degree of pain or reaction was graded 0 (no pain) to 4 (maximum) according to a locally devised scale. Costs of the two examinations were estimated. 89 patients examined by HyCoSy were graded 0-2. However, 23 had severe protracted pain and/or vasovagal reactions with bradycardia and hypotension. Of these, seven required resuscitation owing to prolonged symptoms, requiring treatment with atropine. 19 of the 23 had bilaterally patent Fallopian tubes. Where subsequent HSG was performed, tubal occlusion was confirmed in 8 of 15 women. Other pathologies were noted in 29 of the HyCoSy patients and there were six technical failures. During the same period no severe adverse reactions occurred in 116 patients having HSG performed by the same operators. Three of the HSG examinations were technically unsuccessful. Discomfort following HyCoSy was much greater than that reported previously. Possible mechanisms are discussed but it does not appear to be related to tubal occlusion. Diagnostic accuracy, costs and discomfort compare unfavourably with HSG.

[Cost effective media in vaginal ultrasound uterus and fallopian tube diagnosis]. / Kontrastgebende Medien in der vaginosonographischen Uterus- und Tubendiagnostik.

AIM: The recent development of hysterocontrastsonography (HyCoSy) for assessing tubal patency may provide an alternative to current methods, which are either invasive (laparoscopy and dye) or involve exposure to radiation and require a radiology department (hysterosalpingography). METHOD: Following the introduction of an intrauterine balloon catheter, the contrast agent (Echovist) is slowly injected into the cavity and tracked using ultrasound as it passes through the tubes. The technique is well tolerated as an outpatient method, and takes about 15 to 20 minutes to perform. RESULTS: In a clinical trial with infertile women we compared the results of HyCoSy to laparoscopy and dye. In 90 out of 108 tubes investigated the results agreed-equivalent to a sensitivity of 88% and a specificity of 82%. Three false negative findings on the one hand and 15 false positive findings on the other represent a negative predictive value of 96% and a positive predictive value of 58%. In approximately 50% of patients, this outpatient procedure caused little or no pain, and in 40%, moderate pain. Only a small part of the investigated group (8%) complained about serious discomfort; in two cases (3%) the procedure was discontinued because of pain. CONCLUSION: HyCoSy is a reliable and simple method to provide preliminary information about tubal patency. It may be carried out at an early stage of the algorithm to investigate the infertile couple, and may so lead to more rapid and efficient treatment.