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.

The long-term costs and effects of tubal flushing with oil-based versus water-based contrast during hysterosalpingography.

RESEARCH QUESTION: What are the long-term costs and effects of oil- versus water-based contrast in infertile women undergoing hysterosalpingography (HSG)? DESIGN: This economic evaluation of a long-term follow-up of a multicentre randomized controlled trial involved 1119 infertile women randomized to HSG with oil- (n = 557) or water-based contrast (n = 562) in the Netherlands. RESULTS: In the oil-based contrast group, 39.8% of women needed no other treatment, 34.6% underwent intrauterine insemination (IUI) and 25.6% had IVF/intracytoplasmic sperm injection (ICSI) in the 5 years following HSG. In the water-based contrast group, 35.0% of women had no other treatment, 34.2% had IUI and 30.8% had IVF/ICSI in the 5 years following HSG (P = 0.113). After 5 years of follow-up, HSG using oil-based contrast resulted in equivalent costs (mean cost difference -€144; 95% confidence interval [CI] -€579 to +€290; P = 0.515) for a 5% increase in the cumulative ongoing pregnancy rate compared with HSG using water-based contrast (80% compared with 75%, Relative Risk (RR) 1.07; 95% CI 1.00-1.14). Similarly, HSG with oil-based contrast resulted in equivalent costs (mean cost difference -€50; 95% CI -€576 to +€475; P = 0.850) for a 7.5% increase in the cumulative live birth rate compared with HSG with water-based contrast (74.8% compared with 67.3%, RR 1.11; 95% CI 1.03-1.20), making it the dominant strategy. Scenario analyses suggest that the oil-based contrast medium is the dominant strategy up to a price difference of €300. CONCLUSION: Over a 5-year follow-up, HSG with an oil-based contrast was associated with a 5% increase in ongoing pregnancy rate, a 7.5% increase in live birth rate and similar costs to HSG with water-based contrast.

Oil-based or water-based contrast for hysterosalpingography in infertile women: a cost-effectiveness analysis of a randomized controlled trial.

OBJECTIVE: To determine the cost effectiveness of the use of oil-based versus water-based contrast in infertile women undergoing hysterosalpingography (HSG). DESIGN: Economic evaluation alongside a multicenter randomized trial. SETTING: Hospitals. PATIENT(S): Infertile women with an ovulatory cycle, 18-39 years of age, low risk of tubal pathology. INTERVENTION(S): Use of oil-based versus water-based contrast during HSG. MAIN OUTCOME MEASURE(S): Costs per additional ongoing pregnancy and per live birth within 6 months of randomization, incremental cost-effective ratios (ICERs). RESULT(S): A total of 1,119 women were randomized to HSG (oil-based contrast, n = 557; water-based contrast, n = 562). After HSG, most women had no additional treatment; a minority had IUI or IVF. In the oil group, 39.7% women had an ongoing pregnancy within 6 months of randomization versus 29.1% women in the water group. There was a 10.7% increase in the live birth rate in the oil group. For ongoing pregnancy, the mean costs per couple were US$2,014 in the oil group and US$1,144 in the water group, with a corresponding ICER of US$8,198 per additional ongoing pregnancy. For live birth, the mean costs per couple were US$11,532 in the oil group and US$8,310 in the water group, with a corresponding ICER of US$30,112 per additional live birth. CONCLUSION(S): Hysterosalpingography with oil-based contrast results in higher 6-month ongoing pregnancy and live birth rate. If society is willing to pay US$8,198 for an additional ongoing pregnancy, HSG with oil-based contrast is a cost-effective strategy compared with HSG with water-based contrast for infertile, ovulatory women at low risk for tubal pathology. CLINICAL TRIAL REGISTRATION NUMBER: Dutch Trial Register, NTR 6577 (www.trialregister.nl).

The FOAM study: is Hysterosalpingo foam sonography (HyFoSy) a cost-effective alternative for hysterosalpingography (HSG) in assessing tubal patency in subfertile women? Study protocol for a randomized controlled trial.

BACKGROUND: Tubal pathology is a causative factor in 20% of subfertile couples. Traditionally, tubal testing during fertility work-up is performed by hysterosalpingography (HSG). Hysterosalpingo-foam sonography (HyFoSy) is a new technique that is thought to have comparable accuracy as HSG, while it is less expensive and more patient friendly. HyFoSy would be an acceptable alternative for HSG, provided it has similar effectiveness in terms of patient outcomes. METHODS/DESIGN: We aim to compare the effectiveness and costs of management guided by HyFoSy or by HSG. Consenting women will undergo tubal testing by both HyFoSy and HSG in a randomized order during fertility work-up. The study group will consist of 1163 subfertile women between 18 and 41 years old who are scheduled for tubal patency testing during their fertility work-up. Women with anovulatory cycles not responding to ovulation induction, endometriosis, severe male subfertility or a known contrast (iodine) allergy will be excluded. We anticipate that 7 % (N = 82) of the participants will have discordant test results for HyFoSy and HSG. These participants will be randomly allocated to either a management strategy based on HyFoSy or a management strategy based on HSG, resulting in either a diagnostic laparoscopy with chromopertubation or a strategy that assumes tubal patency (intrauterine insemination or expectant management). The primary outcome is ongoing pregnancy leading to live birth within 12 months after randomization. Secondary outcomes are patient pain scores, time to pregnancy, clinical pregnancy, miscarriage rate, multiple pregnancy rate, preterm birth rate and number of additional treatments. Costs will be estimated by counting resource use and calculating unit prices. DISCUSSION: This trial will compare the effectiveness and costs of HyFoSy versus HSG in assessing tubal patency in subfertile women. TRIAL REGISTRATION: Dutch Trial Register (NTR 4746, http://www.trialregister.nl ). Date of registration: 19 August 2014.

A study of the cost, accuracy, and benefits of 3-dimensional sonography compared with hysterosalpingography in women with uterine abnormalities.

OBJECTIVES: We conducted a prospective blinded study to evaluate the costs, accuracy, risks, and benefits of 3-dimensional (3D) transvaginal sonography compared to hysterosalpingography. METHODS: A total of 101 women aged 26 to 44 years with evidence of uterine anomalies were enrolled. All participants had routine hysterosalpingography as part of their infertility evaluation as well as 3D transvaginal sonography as part of the study. Surgical findings were used as the standard for final diagnosis. RESULTS: A total of 6 normal uteri and 119 uterine anomalies were classified: 30 congenital uterine anomalies (3 arcuate, 1 unicornuate, 4 bicornuate, 2 didelphys, and 20 septate uteri) and 89 acquired anomalies (38 polyps, 30 fibroids, 17 synechiae, and 4 adenomyosis). Congenital anomalies were correctly identified in 30 of 30 cases by 3D sonography but from 10 to 30 of 30 cases by hysterosalpingography. The detection rates for acquired uterine anomalies were lower for both techniques: 44 to 89 of 89 cases for 3D sonography and 22 to 74 of 89 cases for hysterosalpingography. Only 7 of the 20 septi would have been surgically corrected if patients only had hysterosalpingography. On the contrary, 30 of 30 patients with congenital uterine anomalies, 2 of 4 patients with adenomyosis, and all 6 patients with normal uteri were spared from surgery with diagnoses by 3D sonography. No adverse effects were reported after sonography, and only 6 minor ones were reported after hysterosalpingography. CONCLUSIONS: Three-dimensional transvaginal sonography provides visualization and evaluation of the uterine cavity with similar or better accuracy than standard hysterosalpingography in the office setting, with lower cost and morbidity.

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.

Cost-effectiveness of hysterosalpingography, laparoscopy, and Chlamydia antibody testing in subfertile couples.

OBJECTIVE: To evaluate the cost-effectiveness analysis of hysterosalpingography (HSG), laparoscopy, and Chlamydia antibody testing (CAT) in subfertile couples. DESIGN: Cost-effectiveness analysis. SETTING: Decision analytic framework. PATIENT(S): Data of >2,000 subfertile couples in the Canadian Infertility Treatment Evaluation Study. Results of CA-125 measurement and CAT were simulated from baseline characteristics. INTERVENTION(S): Expectant management was considered to be the reference strategy (strategy 1). In strategy 2 and 3, IVF was offered either immediately or after 2.5 years. In strategy 4, the decision to offer or delay treatment was based on the couple's chance of spontaneous conception. Nine strategies incorporated combinations of CAT, CA-125 measurement, HSG, and laparoscopy. MAIN OUTCOME MEASURE(S): Expected live birth rates, expected number of IVF cycles, and expected total costs. RESULT(S): The strategy starting with CAT was the most cost-effective in couples whose 3-year chance of conception was >14%, whereas the strategy starting with HSG was the most cost-effective in couples with worse fertility prospects. CONCLUSION(S): The diagnostic work-up to detect tubal pathology in subfertile couples should start with CAT in couples with relatively good fertility prospects and immediate HSG in couples with relatively poor fertility prospects.

Assessment of the value of preliminary films at hysterosalpingography.

The usefulness of preliminary films in the Hysterosalpingographic evaluation of infertility is studied using the Hysterosalpingogram of 200 patients, comprising 83 primary and 117 secondary infertility cases. There were overall 12 (6.0%) demonstrable lesions, 4 (4.8%) in the preliminary films of primary infertility patients and 8 (6.8%) in that of secondary infertility patients. Osseous lesions were found in 4 (2.0%) patients comprising 2 (2.4%) patients with primary infertility and 2 (1.7%) patients with secondary infertility. Non-osseous lesions were found in 8 (4.0%) patients, comprising 2 (2.4%) patients with primary infertility and 6 (5.1%) patients with secondary infertility. The overall numbers of pathological lesions, 12 (6.0%) discerned through preliminary film are too few to justify its continued practice. This and other relevant factors that would prohibit the use of preliminary films at Hysterosalpingography are discussed.

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.

Recanalization of obstructed fallopian tube by selective salpingography and transvaginal bougie dilatation: outcome and cost analysis.

OBJECTIVE: To investigate effectiveness and cost of transcervical salpingography and recanalization in the management of infertility caused by tubal occlusion. DESIGN: Retrospective analysis of patients investigated with transcervical selective salpingography and, in some instances, treated by transcervical recanalization. SETTING: Four hundred patients with hysterosalpingography diagnosis of obstructed fallopian tubes (clinical environment) are investigated. A repeat hysterosalpingogram after administration of a prostaglandin antagonist demonstrated patency of the tubes in 82 patients and selective transcervical salpingography demonstrated patency in an additional 131 patients. INTERVENTION: Transcervical tubal recanalization. Of the remaining 187 patients, recanalization by transcervical technique was successful in 145 patients. The underlying etiology for tubal obstruction was salpingitis isthmica nodosa in 62, salpingitis and perisalpingitis in 71, endometriosis in 8, failed surgical anastomosis in 43, and undeterminate cause in 3 patients. Pregnancy was attained in 24 patients, there were 10 minor and 1 major complication. OUTCOME MEASURE: Attained and maintained patency of tubes, pregnancy, attendant complications. CONCLUSION: A pregnancy rate of 12.8% was attained after transcervical recanalization of obstructed tubes. An attendant increased rate of pregnancy in patients proven patent after selective salpingography, valuable detailed information about proximal and distal tubes after recanalization of the obstructed proximal tube segment, the low rate of complications, and low cost are factors recommending the use of this technique. Moreover, tubal surgery or IVF treatment are not influenced adversely by prior transcervical tubal recanalization and remain an option for patients who failed to attain pregnancy.

Use of algorithmic pathways to develop quality, cost-effective clinical care.

STUDY OBJECTIVES: To analyze the cost of diagnosis and treatment associated with hydrosalpinges and pelvic adhesions using algorithmic pathways. DESIGN: Analysis of six pathways: (1) Chlamydia IgG antibody titer -> hysterosalpingogram -> diagnostic laparoscopy -> in vitro fertilization (IVF); (2) Chlamydia IgG antibody titer -> diagnostic laparoscopy -> therapeutic laparoscopy -> IVF; (3) hysterosalpingogram -> diagnostic laparoscopy -> therapeutic laparoscopy -> IVF; (4) diagnostic laparoscopy -> therapeutic laparoscopy -> IVF; (5) no treatment; and (6) IVF only. SETTING: A tertiary care practice at a university-associated hospital. PATIENTS: Patients were retrospectively chosen on the basis of availability of results of Chlamydia IgG titers, operative notes from laparoscopy, and hysterosalpingograms (HSGs). All patients identified with these three results available were included. INTERVENTIONS: Determination of results of laparoscopic treatment, IVF, and no therapy (observation only), based on the literature. MEASUREMENTS AND MAIN RESULTS: The theoretical cost to achieve pregnancy for each pathway was calculated by mathematical modeling. The greatest number of pregnancies for the least cost ($18, 883/pregnancy) was from the diagnosis and treatment of adhesions at laparoscopy with no previous screening. The least costly approach to pregnancy for blocked tubes ($26,614/pregnancy) was to start with an HSG. All pathways for adhesions and any screening pathway using HSG for hydrosalpinges were more cost effective than IVF. CONCLUSIONS: These pathways are limited, as they require several assumptions and are based on a tertiary care population. Although HSG and laparoscopy appeared to be the most cost-effective approaches to pregnancy, a primary care group may have a more cost-effective response to the use of Chlamydia trachomatis IgG antibody screening.