MedPath

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

Phase 4
Recruiting
Conditions
Infertility, Female
Interventions
Registration Number
NCT04379973
Lead Sponsor
Dafne Balemans
Brief 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. 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
736
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Tubal flush with Lipiodol Ultra Fluide® after HyfosyLipiodol Ultra Fluide®-
Primary Outcome Measures
NameTimeMethod
Live birthDelivery

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 Outcome Measures
NameTimeMethod
Birthweightat delivery

Birthweight of baby

Amount of pregnancy complications15 months after Hyfosy

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

Number of babiesat delivery

Number of babies after live birth

Maternal thyroid function4 weeks, 26 weeks, 15 weeks after delivery

TSH, FT4 determination

Thyroid function of baby3 days after delivery

heel prick test (TSH, FT4)

Disease-specific quality of life26 weeks

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

Number of miscarriages15 months after Hyfosy

presence of miscarriages

Number of ectopic pregnancies15 months after Hyfosy

the presence of ectopic pregnancy

Number of clinical pregnancies15 months after Hyfosy

the presence of clinical pregnancy

Pain score of the Hyfosy with or without interventionimmediately after Hyfosy

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

Neonatal careat delivery

Neonatal care (Yes/No)

Major Congenital Anomalyat delivery

Neonatal major anomaly

Type of pregnancy15 months after Hyfosy

single or multiple pregnancy

Complication during or after Hyfosy with interventionimmediately after intervention

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

Pain score of the intervention with IMP if applicableimmediately after intervention

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

Gestational age at deliveryat delivery

Live birth after how many weeks pregnancy

General quality of life26 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

Neonatal Mortalityat delivery

Neonatal death after delivery

Gender of babyat delivery

Gender of baby (M/F)

Trial Locations

Locations (16)

Hôpital Erasme

🇧🇪

Lennik, Belgium

CHC Mont Légia

🇧🇪

Liège, Belgium

Ziekenhuis Oost Limburg

🇧🇪

Genk, Belgium

CHR Citadelle

🇧🇪

Liège, Belgium

GZA Sint Augustinus

🇧🇪

Antwerp, Belgium

AZ Sint Lucas

🇧🇪

Gent, Belgium

AZ Turnhout

🇧🇪

Turnhout, Belgium

Antwerp University Hospital

🇧🇪

Antwerp, Belgium

Imelda

🇧🇪

Bonheiden, Belgium

AZ Sint Jan Brugge

🇧🇪

Brugge, Belgium

UZ Brussel

🇧🇪

Brussel, Belgium

CHIREC

🇧🇪

Brussel, Belgium

UCL Saint Luc

🇧🇪

Brussel, Belgium

UZ Gent

🇧🇪

Gent, Belgium

UZ Leuven

🇧🇪

Leuven, Belgium

AZ Klina

🇧🇪

Brasschaat, Belgium

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