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NCT Number: NCT04379973

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

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.

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Infertility, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Infertility Urogenital Diseases

Age range

18 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

Antwerp University Hospital, Antwerp, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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
  • 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)

Treatment and study plan

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.

Primary outcomes

  1. Live birth

    Time frame: Delivery

    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.

Secondary outcomes

  1. Type of pregnancy

    Time frame: 15 months after Hyfosy

    single or multiple pregnancy

  2. Number of miscarriages

    Time frame: 15 months after Hyfosy

    presence of miscarriages

  3. Amount of pregnancy complications

    Time frame: 15 months after Hyfosy

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

  4. Number of ectopic pregnancies

    Time frame: 15 months after Hyfosy

    the presence of ectopic pregnancy

  5. Number of clinical pregnancies

    Time frame: 15 months after Hyfosy

    the presence of clinical pregnancy

  6. Complication during or after Hyfosy with intervention

    Time frame: immediately after intervention

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

  7. Pain score of the Hyfosy with or without intervention

    Time frame: immediately after Hyfosy

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

  8. Pain score of the intervention with IMP if applicable

    Time frame: immediately after intervention

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

  9. Thyroid function of baby

    Time frame: 3 days after delivery

    heel prick test (TSH, FT4)

  10. Birthweight

    Time frame: at delivery

    Birthweight of baby

  11. Gestational age at delivery

    Time frame: at delivery

    Live birth after how many weeks pregnancy

  12. Neonatal care

    Time frame: at delivery

    Neonatal care (Yes/No)

  13. Number of babies

    Time frame: at delivery

    Number of babies after live birth

  14. Maternal thyroid function

    Time frame: 4 weeks, 26 weeks, 15 weeks after delivery

    TSH, FT4 determination

  15. General quality of life

    Time frame: 26 weeks

    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

  16. Disease-specific quality of life

    Time frame: 26 weeks

    Fertility Quality Of Life tool (FertiQol):

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

  17. Neonatal Mortality

    Time frame: at delivery

    Neonatal death after delivery

  18. Major Congenital Anomaly

    Time frame: at delivery

    Neonatal major anomaly

  19. Gender of baby

    Time frame: at delivery

    Gender of baby (M/F)

Sponsors and collaborators

Lead sponsor

Dafne Balemans

Other

Registry information

Official study 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

Acronym: HYFOIL

Important dates

Study start
2021
Primary completion
2027
Study completion
2027
First posted
May 8, 2020
Registry last updated
Nov 20, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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