What is the Best Moment for Performing an HSG in Women With a Unfulfilled Childwish (H2Oil-timing)

Tubal Flushing With Oil-based Contrast During HSG in Subfertile Women: Is Early Flushing Effective and Cost-effective as Compared to Delayed Flushing? - H2Oil-timing Study

The aim of this study is to determine whether direct tubal flushing with oil-based contrast at HSG incorporated in the fertility work-up results in 10% more ongoing pregnancies and a shorter time to pregnancy, which will therefore be effective and cost-effective compared to delayed tubal flushing 6 months after fertility work-up is completed in women at low risk for tubal pathology.

Study Overview

• Status: Recruiting
• Conditions: Female Infertility
• Intervention / Treatment: Drug: Lipiodol UltraFluid

Detailed Description

Rationale: The investigators hypothesize that direct tubal flushing with oil-based contrast at HSG incorporated in the fertility work-up results in 10% more ongoing pregnancies and a shorter time to pregnancy compared to delayed tubal flushing 6 months after fertility work-up is completed in women at low risk for tubal pathology, which will lead to a reduction in the need for expensive fertility treatments like IVF and/or ICSI, and will therefore be an effective and cost effective strategy.

Objective: The aim of this study is to determine whether direct tubal flushing with oil-based contrast at HSG incorporated in the fertility work-up results in 10% more ongoing pregnancies and a shorter time to pregnancy, which will therefore be effective and cost-effective compared to delayed tubal flushing 6 months after fertility work-up is completed in women at low risk for tubal pathology.

Study design: The investigators plan a multicentre randomized controlled trial with an economic analysis alongside it. Infertile women at low risk for tubal pathology will be randomized to direct tubal flushing with oil-based contrast incorporated in the fertility work-up or delayed tubal flushing 6 months after fertility work-up is completed.

Study population: Infertile women 18-38 years of age, who have a spontaneous menstrual cycle and at low risk for tubal pathology, undergoing fertility work-up.

Intervention (if applicable): Direct tubal flushing with oil-based contrast at HSG as part of the fertility work-up compared to delayed tubal flushing 6 months after the fertility work-up is completed.

Main study parameters/endpoints: The primary outcome is time to live birth, calculated from positive pregnancy test and within 12 months after randomization.

Our hypothesis is that tubal flushing at HSG with oil-based contrast incorporated in the fertility work-up will result in 10% more ongoing pregnancies and a shorter time to pregnancy, and thus reducing the need for ART and reducing costs.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: As two strategies are compared (tubal flushing with oil-based contrast at HSG incorporated in the fertility work-up versus 6 months after completion of fertility work-up) that are already applied in current practice, no additional risks or burdens are expected from the study.

• Study Type: Interventional
• Enrollment (Anticipated): 554
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: V Mijatovic; Phone Number: +312044444567; Email: mijatovic@amsterdamumc.nl
• Study Contact Backup: Name: Danah Kamphuis; Phone Number: +312044444567; Email: d.kamphuis@amsterdamumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1081HV
    • Recruiting
    • Amsterdam AMC
    • Contact: Velja Mijatovic; Email: mijatovic@amsterdamumc.nl
    • Contact: Danah Kamphuis; Email: d.kamphuis@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women between 18-39 years of age
• Spontaneous menstrual cycle
• Perceived low risk for tubal pathology
• Undergoing fertility work-up

Exclusion Criteria:

• Women with known endocrine disorders (e.g. the polycystic ovary syndrome, diabetes, hyperthyroidism and hyperprolactinemia. Except for well managed hypothyroidism with TSH between 0.3 and 2.5mIU/l)
• Ovulation disorders defined as less than eight menstrual cycles per year
• Iodine allergy
• Male subfertility defined as a post-wash total motile sperm count < 1 x10^6 spermatozoa/ml
• Not willing or able to sign the consent form

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: Direct HSG during fertility work-up; Tubal flushing at HSG with Lipiodol® (oil-based contrast medium) (max. 15mL) incorporated in the fertility work-up	Drug: Lipiodol UltraFluid; The investigational product is an oil-based contrast medium, Lipiodol® (Guerbet). Lipiodol® is a solution of ethyl esters of iodized fatty acids of poppy seed oil equivalent to 480mg I /ml and is a licensed contrast agent in the Netherlands (RVG 02806, see SmPC D2). The maximum amount of Lipiodol® per HSG procedure is 15 ml.; Other Names: Oil-based contrast
Active Comparator: Delayed HSG 6 months after completing fertility work-up; Tubal flushing at HSG with Lipiodol® (oil-based contrast medium) (max. 15mL) after a 6 months waiting period after completion of fertility work-up	Drug: Lipiodol UltraFluid; The investigational product is an oil-based contrast medium, Lipiodol® (Guerbet). Lipiodol® is a solution of ethyl esters of iodized fatty acids of poppy seed oil equivalent to 480mg I /ml and is a licensed contrast agent in the Netherlands (RVG 02806, see SmPC D2). The maximum amount of Lipiodol® per HSG procedure is 15 ml.; Other Names: Oil-based contrast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to live birth	Calculated from the last menstrual bleeding within 6 months after randomization	6 months
Time to live birth	Calculated from the last menstrual bleeding within 12 months after randomization	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of live births	Defined as the birth of a live born baby, after 24 weeks gestation	6 months
Number of live births	Defined as the birth of a live born baby, after 24 weeks gestation	12 months
Number of ongoing pregnancies	Defined as the presence of a heart beat at 10 to 12 weeks gestation	6 and 12 months
Number of ongoing pregnancies	Defined as the presence of a heart beat at 10 to 12 weeks gestation	6 months
Number of clinical pregnancies	Defined as gestational sac detected on ultrasonography	12 months
Number of miscarriages	Presence of non-vitality on ultrasound or spontaneous loss of pregnancy	6 months
Number of miscarriages	Presence of non-vitality on ultrasound or spontaneous loss of pregnancy	12 months
Number of ectopic pregnancies	Embryo implanted outside the uterine cavity	6 months
Number of ectopic pregnancies	Embryo implanted outside the uterine cavity	12 months
Number of multiple pregnancies	Pregnancy of two or more foetuses	6 months
Number of multiple pregnancies	Pregnancy of two or more foetuses	12 months
Number of complication after HSG	e.g. intravasation or infection	One month after HSG
Number of pregnancy complications	e.g. pre-term birth, hypertension	6 months
Number of pregnancy complications	e.g. pre-term birth, hypertension	12 months
Number of still births	Death or loss of the baby before or during	12 months
Number of still births	Death or loss of the baby before or during	6 months
Incidence of thyroid dysfunction after HSG	TSH and fT4 measurement (blood test)	One month after HSG
Number of cycles of artificial reproductive techniques	Number of cycles of IUI and IVF/ICSI	6 and 12 months
Number of cycles of artificial reproductive techniques	Number of cycles of IUI and IVF/ICSI	6 months
Number of cycles of artificial reproductive techniques	Number of cycles of IUI and IVF/ICSI	12 months
Neonatal thyroid dysfunction	Screening on congenital thyroid dysfunction postpartum	Within one week after birth

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): August 22, 2019
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): January 1, 2026

Study Registration Dates

• First Submitted: July 18, 2022
• First Submitted That Met QC Criteria: October 31, 2022
• First Posted (Actual): November 8, 2022

Study Record Updates

• Last Update Posted (Estimate): May 8, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Infertility; Pregnancy; Randomized controlled trial; Cost-effectiveness; Live birth; Hysterosalpingography; Fallopian tubes; Tubal flushing
• Additional Relevant MeSH Terms: Skin Manifestations; Infertility; Flushing; Infertility, Female; Antineoplastic Agents; Ethiodized Oil
• Other Study ID Numbers: NL62838.029.18; 2018.004153.24 (EudraCT Number); NL7926 (Other Identifier: NTR)

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
• product manufactured in and exported from the U.S.: No