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

Dafne Balemans

Status and phase

Enrolling

Phase 4

Conditions

Infertility, Female

Treatments

Drug: Lipiodol Ultra Fluide®

Study type

Interventional

Funder types

Other

Identifiers

NCT04379973

HYOIL

Details and patient eligibility

About

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.

Enrollment

736 estimated patients

Sex

Female

Ages

18 to 40 years old

Volunteers

No Healthy Volunteers

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)