Clinical trial NCT04379973: Live Birth After Additional Tubal Flushing With Oil-based Contrast Versus no Additional Flushing:
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Infertility, Female
Lead sponsor: University Hospital, Antwerp
Sponsor class: OTHER
First posted: 2020-05-08
Enrollment: 736
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Live birth
timeFrame: Delivery
Secondary outcomes:
measure: Type of pregnancy
timeFrame: 15 months after Hyfosy
measure: Number of miscarriages
timeFrame: 15 months after Hyfosy
measure: Amount of pregnancy complications
timeFrame: 15 months after Hyfosy
measure: Number of ectopic pregnancies
timeFrame: 15 months after Hyfosy
measure: Number of clinical pregnancies
timeFrame: 15 months after Hyfosy
measure: Complication during or after Hyfosy with intervention
timeFrame: immediately after intervention
measure: Pain score of the Hyfosy with or without intervention
timeFrame: immediately after Hyfosy
measure: Pain score of the intervention with IMP if applicable
timeFrame: immediately after intervention
measure: Thyroid function of baby
timeFrame: 3 days after delivery
measure: Birthweight
timeFrame: at delivery
measure: Gestational age at delivery
timeFrame: at delivery
measure: Neonatal care
timeFrame: at delivery
measure: Number of babies
timeFrame: at delivery
measure: Maternal thyroid function
timeFrame: 4 weeks, 26 weeks, 15 weeks after delivery
measure: General quality of life
timeFrame: 26 weeks
measure: Disease-specific quality of life
timeFrame: 26 weeks
measure: Neonatal Mortality
timeFrame: at delivery
measure: Major Congenital Anomaly
timeFrame: at delivery
measure: Gender of baby
timeFrame: at delivery
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Antwerp University Hospital
city: Antwerp
country: Belgium
facility: GZA Sint Augustinus
city: Bonheiden
country: Belgium
facility: Imelda
city: Brasschaat
country: Belgium
facility: AZ Klina
city: Brugge
country: Belgium
facility: AZ Sint Jan Brugge
city: Brussel
country: Belgium
facility: CHIREC
city: Brussel
country: Belgium
facility: UCL Saint Luc
city: Brussel
country: Belgium
facility: UZ Brussel
city: Genk
country: Belgium
facility: Ziekenhuis Oost Limburg
city: Gent
country: Belgium
facility: AZ Sint Lucas
city: Gent
country: Belgium
facility: UZ Gent
city: Lennik
country: Belgium
facility: Hôpital Erasme
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHC Mont Légia
city: Liège
country: Belgium
facility: CHR Citadelle
city: Turnhout
country: Belgium
facility: AZ Turnhout
Study officials:
References:
citation: 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.