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

Sponsor

Amsterdam UMC, location VUmc (Other)

Overall Status

Recruiting

CT.gov ID

NCT05608590

Collaborator

ZonMw: The Netherlands Organisation for Health Research and Development (Other)

554

Enrollment

Location

Arms

64.4

Anticipated Duration (Months)

8.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Female Infertility	Drug: Lipiodol UltraFluid	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

554 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 22, 2019

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

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

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

Other Names:

Oil-based contrast

Outcome Measures

Primary Outcome Measures

Time to live birth [6 months]
Calculated from the last menstrual bleeding within 6 months after randomization
Time to live birth [12 months]
Calculated from the last menstrual bleeding within 12 months after randomization

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 39 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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