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Infertility, FemalePhase 4HYFOILNCT04379973

Live Birth After Additional Tubal Flushing With Oil-based Contrast Versus no Additional Flushing:

A Phase 4 study testing Lipiodol Ultra Fluide® in people with Infertility, Female, run by Dafne Balemans at 16 sites in Belgium.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Ten to 15 percent of couples in their reproductive lifetime face fertility problems which is defined by WHO as the absence of pregnancy after minimal 12 months of unprotected sexual intercourse. The three most frequent causes of subfertility are: sperm defects, ovulation disorders and tubal pathology. Read more about this study

Who is it for?
Ages 18 to 40 years, women only
Conditions the study is for
Infertility, Female
What is being tested?
Lipiodol Ultra Fluide®
Could I receive a placebo?
No, everyone receives an active treatment
How many people
736 participants
Where
16 sitesBelgium
Study dates
25 May 2021to 1 Jun 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 40 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Infertile women undergoing Hyfosy as part of the fertility workup. Women will be eligible if they
  • are ≥ 18 years and < 40 years
  • have infertility defined as
  • lack of conception despite 12 months of unprotected intercourse OR;
  • if they are taking part in a donor sperm insemination programme: three cycles of donor insemination without pregnancy OR;
  • in case of treated ovulation disorder: three ovulatory ovulation induction cycles without pregnancy
  • have tubal patency of at least one Fallopian tube on Hyfosy

Who cannot join

  • Women with
  • known iodine allergy
  • allergy to poppy seed oil
  • ovulation disorders defined as less than eight menstrual cycles per year who did not have three ovulatory cycles after ovulation induction
  • contra-indication to have tubal patency testing according to the site's indication
  • active thyroid disorders
Show all 14Show fewer
  • untreated subclinical hypothyroidism (TSH>2.5mIU/L) in case of auto-immune thyroid disease
  • uterine surgery in the past two months before Hyfosy
  • a male partner (if applicable)
  • with a post-wash Total Motile Sperm Count (TMC) < 1x106 and/or TMC < 3x106 in the native sperm analysis [TMC is defined as volume X concentration X (A* (progressive) + B* (non progressive) motility in %) divided by 100] OR
  • with a history suspect of severe male factor infertility if no sperm sample is available at time of randomisation
  • an indication for IVF defined as patients who are advised to go to IVF immediately because of bilateral tubal block, severe male factor infertility, unsolved anovulatory problems, endometriosis with residual functional problems"
  • no Belgian national number (RRN/INS)
  • A+B when A,B,C is used (WHO 2010) A+B+C when A,B,C, D is used (WHO 2021)

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

Belgium16 sites

  • Antwerp University Hospital

    Antwerp

  • GZA Sint Augustinus

    Antwerp

  • Imelda

    Bonheiden

  • AZ Klina

    Brasschaat

  • AZ Sint Jan Brugge

    Bruges

  • CHIREC

    Brussels

  • UCL Saint Luc

    Brussels

  • UZ Brussel

    Brussels

  • Ziekenhuis Oost Limburg

    Genk

  • AZ Sint Lucas

    Ghent

  • UZ Gent

    Ghent

  • Hôpital Erasme

    Lennik

  • UZ Leuven

    Leuven

  • CHC Mont Légia

    Liège

  • CHR Citadelle

    Liège

  • AZ Turnhout

    Turnhout

Other trials in Belgium

About this study

Official title: Live Birth After Additional Tubal Flushing With Oil-based Contrast Versus no Additional Flushing: a Randomised, Multicentre, Parallel Group Pragmatic Trial in Infertile Women With at Least One Patent Tube at Hysterosalpingo-foam Sonography

Ten to 15 percent of couples in their reproductive lifetime face fertility problems which is defined by WHO as the absence of pregnancy after minimal 12 months of unprotected sexual intercourse. The three most frequent causes of subfertility are: sperm defects, ovulation disorders and tubal pathology. In order to exclude tubal pathology, tubal patency tests are performed under ultrasound guidance with foam (hysterosalpingo-foam sonography (Hyfosy)) or with contrast/water (hysterosalpingo-contrast sonography (Hycosy)).

This trial will investigate whether tubal flushing with an oil-soluble contrast medium (OSCM) can increase the likelihood of a spontaneous conception after tubal patency testing with Hyfosy under ultrasound guidance compared to no additional flushing in a population of infertile women between 18 and 40 years of age with absence of pregnancy after 12 months of unprotected sexual intercourse or who have three cycles of donor insemination without pregnancy or three ovulatory ovulation induction cycles without pregnancy. The use of Lipiodol Ultra Fluide® is off-label in Hyfosy.

Read more

This multicenter, randomised, open-label, comparative and pragmatic trial compares 2 arms which will be randomised 1:1:

  • Intervention group: Tubal flush with 5-10mL oil-soluble contrast medium (Lipiodol Ultra Fluide®, Guerbet, France) immediately after Hyfosy
  • Control group: No additional intervention after Hyfosy The study comprises a screening period of maximum 8 weeks (w-8 to d1), randomisation (w-8 to d1), a start study visit at which the Hyfosy is performed (d1) and a fertility treatment period of 6 months (d1-w26). If the woman is not pregnant at 6 months after Hyfosy, the follow-up will last till 12 months (w52). If the participant is pregnant at 6 months after Hyfosy, the follow-up will last till maximal 4 months after live birth or miscarriage.

The primary endpoint is the occurrence of live birth, with the first day of the last menstrual cycle in which the patient conceives within 6 months after Hyfosy. Secondary endpoints consist of reproductive outcomes, gestational age at delivery, birth weight, neonatal mortality, major congenital anomaly, neonatal outcomes and thyroid function, pregnancy complications, number of complications during or immediately after the intervention, pain score of the Hyfosy and additional flush, thyroid function of the mother, general and disease-specific quality of life.

Being tested
Lipiodol Ultra Fluide®
Medical subject headings
Infertility, Female

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lipiodol Ultra Fluide®Drug

    Tubal flush with 5-10mL oil-soluble contrast medium (OSCM) (Lipiodol Ultra Fluide®, Guerbet, France) immediately after Hyfosy. The use will be off-label.

Study groups in NCT04379973
Study groupRoleWhat they receive
Tubal flush with Lipiodol Ultra Fluide® after HyfosyExperimentalNot described
Receives: Drug: Lipiodol Ultra Fluide®
No tubal flush after HyfosyNo interventionNot described

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Live birth

    the occurrence of live birth, counting from the first day of the last menstrual cycle in which the patient conceives within 6 months after Hyfosy.

    Measured: Delivery

Secondary outcomes (19)

  1. Type of pregnancy

    single or multiple pregnancy

    Measured: 15 months after Hyfosy

  2. Number of miscarriages

    presence of miscarriages

    Measured: 15 months after Hyfosy

  3. Amount of pregnancy complications

    gestational diabetes, hypertensive disease, placenta praevia, intrauterin growth restriction, premature birth

    Measured: 15 months after Hyfosy

  4. Number of ectopic pregnancies

    the presence of ectopic pregnancy

    Measured: 15 months after Hyfosy

  5. Number of clinical pregnancies

    the presence of clinical pregnancy

    Measured: 15 months after Hyfosy

  6. Complication during or after Hyfosy with intervention

    embolism, anaphylactic shock, pelvic inflammatory disease, intravasation, infection and hemorrhage

    Measured: immediately after intervention

  7. Pain score of the Hyfosy with or without intervention

    VAS (0 = no pain; 10 = worst possible pain)

    Measured: immediately after Hyfosy

  8. Pain score of the intervention with IMP if applicable

    VAS (0 = no pain; 10 = worst possible pain)

    Measured: immediately after intervention

  9. Thyroid function of baby

    heel prick test (TSH, FT4)

    Measured: 3 days after delivery

  10. Birthweight

    Birthweight of baby

    Measured: at delivery

  11. Gestational age at delivery

    Live birth after how many weeks pregnancy

    Measured: at delivery

  12. Neonatal care

    Neonatal care (Yes/No)

    Measured: at delivery

  13. Number of babies

    Number of babies after live birth

    Measured: at delivery

  14. Maternal thyroid function

    TSH, FT4 determination

    Measured: 4 weeks, 26 weeks, 15 weeks after delivery

  15. General quality of life

    EuroQol-5D-5Levels (EQ-5D-5L):

    Level 1: indicating no problem Level 2: indicating slightproblems Level 3: indicating moderateproblems Level 4: indicating severe problems Level 5:indicating extreme problems; VAS (score 0 = worst health status; score 100 = best health status) How higher the score, how better the quality of life

    Measured: 26 weeks

  16. Disease-specific quality of life

    Fertility Quality Of Life tool (FertiQol):

    1. Very poor (0), poor (1), neither poor nor good (2), very good (4)
    2. Very dissatisfied (0), dissatisfied (1), neither satisfied nor dissatisfied (2), satisfied (3), very satisfied (4)
    3. Always (0), very often (1), quite often (2), Seldom (3), never (4)
    4. An extreme amount (0), very much (1), a moderate amount (2), a little (3), not at all (4)
    5. Completely (0), a great deal (1), moderately (2), not much (3), not at all (4)

    Scores on the response scales are reversed, summed and scaled to range from 0 to 100. Higher scores on the subscales and total scores indicate better quality of life

    Measured: 26 weeks

  17. Neonatal Mortality

    Neonatal death after delivery

    Measured: at delivery

  18. Major Congenital Anomaly

    Neonatal major anomaly

    Measured: at delivery

  19. Gender of baby

    Gender of baby (M/F)

    Measured: at delivery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 May 2020
  2. Study start25 May 2021
  3. Primary completion1 Jun 2027 (estimated)
  4. Study completion1 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
736 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04379973
Sponsor's protocol ID
HYOIL
Acronym
HYFOIL
Status last verified
Nov 2025
First submitted
23 Apr 2020
Last updated
20 Nov 2025
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • De Neubourg D, Janssens L, Verhaegen I, Smits E, Mol BW, Roelant E. Live birth after additional tubal flushing with oil-based contrast versus no additional flushing: a randomised, multicentre, parallel-group pragmatic trial in infertile women with at least one patent tube at hysterosalpingo-foam sonography (HYFOIL study). BMJ Open. 2021 Nov 29;11(11):e054845. doi: 10.1136/bmjopen-2021-054845.

    PubMed 34845077

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Lipiodol Ultra Fluide® in people with Infertility, Female, run by Dafne Balemans at 16 sites in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Live birth (time frame: Delivery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04379973, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2025.

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