The Cost-effectiveness of Hysterosalpingography Versus Hysterosalpingo-foam Sonography During Fertility Work-up (FOil)

Is, in Infertile Women Undergoing a Basic Fertility Work-up, Tubal Flushing With Oil-based Contrast Medium During Hysterosalpingography (HSG) Cost-effective Compared to Tubal Flushing by Hysterosalpingo-foam Sonography (HyFoSy)?

Hysterosalpingography (HSG) and hysterosalpingo-foam sonography are two methods to assess tubal patency during fertility work-up. This study aims to investigate the effectiveness of tubal flushing with oil-based contrast during HSG compared to tubal flushing during HyFoSy in women undergoing fertility work-up. The hypothesis is that tubal flushing with oil-based contrast during HSG leads to more live births than tubal flushing during HyFoSy.

Study Overview

• Status: Recruiting
• Conditions: Infertility
• Intervention / Treatment: Procedure: Oil-based contrast; Procedure: ExEm Foam

Detailed Description

Background: The diagnostic work-up for infertility generally includes estimating the risk for tubal pathology and if indicated assessing tubal patency. Traditionally, tubal patency testing during the fertility work-up is performed with hysterosalpingography (HSG). In previous studies it has been demonstrated that tubal flushing with oil-based contrast during HSG resulted in more ongoing pregnancies than when HSG is performed with water-based contrast. HyFoSy is a more patient friendly alternative for HSG. Up till now, the fertility enhancing effect of tubal flushing with ExEm Foam during HyFoSy has only been studied in relatively small and observational studies.

Objectives:The main objective of this study is to determine whether tubal flushing with oil-based contrast during HSG results into more pregnancies leading to live births when compared to tubal flushing with ExEm Foam during HyFoSy, and whether this approach is cost-effective. In this study the safety of both strategies will also be compared.

Rationale: The hypothesis is that tubal flushing with oil-based contrast during HSG leads to more live births compared to tubal flushing with ExEm Foam during HyFoSy in women with an indication for tubal patency testing. If more live births are achieved, expensive fertility treatments will be less needed, which makes tubal flushing with oil-based contrast during HSG a cost-effective strategy.

Study design: This study is a multicenter randomized controlled trial with an economic analysis alongside it. Women with indication for tubal patency testing will be randomized to tubal flushing with oil-based contrast during HSG and tubal flushing with ExEm Foam during HyFoSy.

• Study Type: Interventional
• Enrollment (Estimated): 1102
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Danah Kamphuis, Msc; Phone Number: +312044444567; Email: FOil@amsterdamumc.nl
• Study Contact Backup: Name: Velja Mijatovic, Prof; Phone Number: +312044444567; Email: mijatovic@amsterdamumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • AmsterdamUMC
    • Contact: Danah Kamphuis; Email: FOil@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infertile women or women with oligo-or anovulation
• Indication for tubal patency testing during the fertility work-up
• Sufficient understanding of the Dutch or English language
• Signed informed consent

Exclusion Criteria:

• Severe male factor with a total motile sperm count <3x106ml (pre-washed)
• Known contrast (iodine) allergy
• Women who have had a gynecologic procedure within the last 30 days
• Women with known or suspected reproductive tract neoplasia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tubal flushing during HSG with oil-based contrast; Tubal flushing during HSG HSG will be performed by a gynaecologist, fertility doctor or nurse according to local protocols. HSG will be performed in the follicular phase of the cycle. Preferably, HSG is performed in the next cycle after randomization, but if this is not feasible the procedure may be postponed up till one month after randomization. After cleaning the vagina and cervix, a vacuum cervix adapter will be applied to the cervix or a Lipiodol resistant balloon catheter or hysterophore will be placed through the cervix. Up to 15ml of Lipiodol Ultra Fluid will be injected into the uterine cavity and its spread directly monitored by fluoroscopy. Six to eight radiographs will be taken and assessed by a gynaecologist or radiologist. The maximum amount of oil-based contrast medium is set at 15ml.	Procedure: Oil-based contrast; oil-based contrast fluid, Lipiodol Ultra Fluid. Lipiodol is a solution of iodinated ethyl esters of fatty acids of poppyseed oil. Equivalent to 480 mg iodine per ml. The maximum dosage is 15ml. Lipiodol is produced by Guerbet, France. Lipiodol is FDA approved and registered as contrast agent for HSG.
Active Comparator: Tubal flushing HyFoSy; Tubal flushing during HyFoSy will be performed by a gynaecologist, fertility doctor, sonographer or nurse according to local protocols. HyFoSy will be performed in the follicular phase of the cycle. Preferably, HyFosy is performed in the next cycle after randomization, but if this is not feasible the procedure may be postponed up till one month after randomization. During HyFoSy approximately 5-10cc of foam will be introduced through a little cervical balloon-less applicator into the uterine cavity. During infusion of the foam into the uterine cavity, a transvaginal ultrasound will be performed which shows whether the Fallopian tubes are patent. The assessment of the procedure will be done by the one who performed the procedure.	Procedure: ExEm Foam; ExEm Foam which is created by mixing 5ml ExEm-gel and 5ml of purified water. ExEm-gel contains hydroxyethylcellulose and glycerol. The ExEm Foam is distributed by IQ Medical Ventures, the Netherlands. ExEm Foam is FDA approved, CE marked and registered as contrast agent for HyFoSy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of pregnancies leading to live birth.	Pregnancy is defined as a positive pregnancy test, increase in human chorionic gonadotropin (HCG) level or a pregnancy shown on ultrasonographic examination. Live birth is defined as the birth of live baby born beyond 24 weeks of pregnancy.	within six months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to pregnancy leading to live birth	Calculated from the day of randomization till the first day of the last menstrual bleeding before a positive pregnancy test.	within six months after randomization
Number of clinical pregnancies	Clinical pregnancy is defined as gestational sac with or without heartbeat visible on ultrasound.	within six months after randomization
Number of miscarriages	Miscarriage is defined as presence of non-vitality on ultrasound or spontaneous loss off pregnancy	within six months after randomization
Number of multiple pregnancies	Multiple pregnancy is defined as two or more vital intrauterine pregnancies at 12 weeks gestation.	within six months after randomization
Number of adverse events	e.g. infection, intravasation, thyroid dysfunction	within one months after tubal patency testing
Procedural pain scores	measured by Visual Analogue Scale (VAS) on a scale from 0.0 to 10.0 centimeter immediately after tubal patency testing.	Within 15 minutes after tubal patency testing
Number of fertility treatment cycles	e.g. intra uterine insemination, in vitro fertilization, intracytoplasmatic sperm injection	within six months after randomization
Number of pregnancy complications	e.g. pregnancy induced hypertension, fetal growth restriction, still birth.	within six months after randomization
Number of ectopic pregnancies	Ectopic pregnancy is defined as no intrauterine gestational sac with: an ectopic gestational sac OR HCG concentration >1500 international units per liter (IU/L) with free fluid/ectopic mass on ultrasound or serum HCG >2000IU/L without free fluid/ectopic mass on ultrasound	within six months after randomization
Cost-effectiveness	Comparing the costs (including costs for tubal patency testing and additional fertility treatments) and the effects (chance of live birth)	within six months after randomization

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: May 5, 2023
• First Submitted That Met QC Criteria: May 30, 2023
• First Posted (Actual): May 31, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Cost-effectiveness; Live birth; Hysterosalpingography; Hysterosalpingo Foam Sonography; Infertility work-up
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility
• Other Study ID Numbers: NL83352.018.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No