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

Infertility, Female Clinical Trial

— HYFOIL  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04379973
• Other study ID #: HYOIL
• Status: Recruiting
• Phase: Phase 4
• Start date: May 25, 2021
• Est. completion date: December 1, 2025

Study information

• Verified date: May 2024
• Source: University Hospital, Antwerp
• Contact: Diane De Neubourg
• Phone: +32 3 821 45 98
• Email: diane.deneubourg[@]uza.be
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 736
• Est. completion date: December 1, 2025
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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)

Related Conditions & MeSH terms

• Flushing
• Infertility
• Infertility, Female

Intervention

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

Locations

Country	Name	City	State
Belgium	Antwerp University Hospital	Antwerp
Belgium	GZA Sint Augustinus	Antwerp
Belgium	Imelda	Bonheiden
Belgium	AZ Klina	Brasschaat
Belgium	AZ Sint Jan Brugge	Brugge
Belgium	CHIREC	Brussel
Belgium	UCL Saint Luc	Brussel
Belgium	UZ Brussel	Brussel
Belgium	Ziekenhuis Oost Limburg	Genk
Belgium	AZ Sint Lucas	Gent
Belgium	UZ Gent	Gent
Belgium	Hôpital Erasme	Lennik
Belgium	UZ Leuven	Leuven
Belgium	CHC Mont Légia	Liège
Belgium	CHR Citadelle	Liège
Belgium	AZ Turnhout	Turnhout

Sponsors (1)

Lead Sponsor	Collaborator
Dafne Balemans

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Delivery
Secondary	Type of pregnancy	single or multiple pregnancy	15 months after Hyfosy
Secondary	Number of miscarriages	presence of miscarriages	15 months after Hyfosy
Secondary	Amount of pregnancy complications	gestational diabetes, hypertensive disease, placenta praevia, intrauterin growth restriction, premature birth	15 months after Hyfosy
Secondary	Number of ectopic pregnancies	the presence of ectopic pregnancy	15 months after Hyfosy
Secondary	Number of clinical pregnancies	the presence of clinical pregnancy	15 months after Hyfosy
Secondary	Complication during or after Hyfosy with intervention	embolism, anaphylactic shock, pelvic inflammatory disease, intravasation, infection and hemorrhage	immediately after intervention
Secondary	Pain score of the Hyfosy with or without intervention	VAS (0 = no pain; 10 = worst possible pain)	immediately after Hyfosy
Secondary	Pain score of the intervention with IMP if applicable	VAS (0 = no pain; 10 = worst possible pain)	immediately after intervention
Secondary	Thyroid function of baby	heel prick test (TSH, FT4)	3 days after delivery
Secondary	Birthweight	Birthweight of baby	at delivery
Secondary	Gestational age at delivery	Live birth after how many weeks pregnancy	at delivery
Secondary	Neonatal care	Neonatal care (Yes/No)	at delivery
Secondary	Number of babies	Number of babies after live birth	at delivery
Secondary	Maternal thyroid function	TSH, FT4 determination	4 weeks, 26 weeks, 15 weeks after delivery
Secondary	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	26 weeks
Secondary	Disease-specific quality of life	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	26 weeks
Secondary	Neonatal Mortality	Neonatal death after delivery	at delivery
Secondary	Major Congenital Anomaly	Neonatal major anomaly	at delivery
Secondary	Gender of baby	Gender of baby (M/F)	at delivery