What is the Best Moment for Performing an HSG in Women With a Unfulfilled Childwish

Study Overview
=================
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.

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.

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

Conditions
-----------------
Female Infertility

Intervention / Treatment
-----------------
* Drug: Lipiodol UltraFluid


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Direct HSG during fertility work-up<br>Tubal flushing at HSG with Lipiodol® (oil-based contrast medium) (max. 15mL) incorporated in the fertility work-up | Drug: Lipiodol UltraFluid<br>* 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.<br>* Other names: Oil-based contrast;|
| Active Comparator: Delayed HSG 6 months after completing fertility work-up<br>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<br>* 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.<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hysterosalpingography, Infertility, Fallopian tubes, Tubal flushing, Pregnancy, Live birth, Cost-effectiveness, Randomized controlled trial