Clinical trial NCT06563908: Lipiodol Prior to FET (LIFE)
Official title: Lipiodol® For Enhancing Live Birth Rates In Infertile Couples Undergoing In Vitro Fertilization/ Intracytoplasmic Sperm Injection A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: IVF
Frozen Embryo Transfer
Hysterosalpingography
Keywords: Lipiodol
Hysterosalpingography
Lead sponsor: Mỹ Đức Hospital
Sponsor class: OTHER
Collaborators: name: Guerbet
First posted: 2024-08-21
Enrollment: 784
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Lipiodol® flushing is an effective fertility treatment for women with unexplained infertility. It is speculated that the treatment effect could work through a direct effect of Lipiodol® on the endometrium. Given this direct effect on the endometrium, it is further hypothesized that Lipiodol® uterine treatment prior to In Vitro Fertilization (IVF)/ Intracytoplasmic Sperm Injection (ICSI) may also improve pregnancy rates. However, the effectiveness of Lipiodol® as an adjunct to IVF/ICSI treatment has not previously been examined in a well-powered and properly conducted randomised clinical trial.

Detailed description: Study procedures:

Recruitment:

Potentially eligible patients will be given information about the study and a copy of the informed consent documents on day 2 - 3 of their menstrual cycle, when the ovarian stimulation starts. On the day of freeze-all (3 days or 5 days after oocyte retrieval), screening for eligibility will be performed by treating physicians. Eligible couples will have about an hour to decide if they will participate in the study or not. If they choose to participate in the study, investigators will ask them to sign the consent form.

Once a participant signs an informed consent she is enrolled in the study. An individual record of all non-recruited patients and reasons for exclusion (at any stage) will be obtained and stored

Randomization:

Assignment to treatment allocation will be done via a web portal hosted by Hope Research Center, Viet Nam. The randomisation schedule will be computer-generated at Hope Research Center by using HRC (Hope Research Center) Epi software, in a 1:1 ratio, with a permuted random block size of 4 or 6.

Other standard assisted reproductive treatments are similar and parallel between the two groups, except for the use of Lipiodol® flushing in the intervention group. Due to the type of interventions, this study will only be blinded to clinicians who performed the embryo transfer and embryologists in the IVF clinics.

In the subsequent cycle, all patients in both groups will undergo frozen embryo transfer by using exogenous steroids regimen, starting from day 2 to day 4 of the menstrual cycle. Oral estradiol valerate (Progynova, Bayer Schering Pharma, Germany) 8 mg/day is given for 10-12 days. Ultrasound monitoring will be performed from day tenth onward. When endometrial thickness reaches greater than or equal to 8 mm, along with a triple-line pattern, micronized progesterone 800 mg will be administrated. Frozen embryo transfer (FET) will be performed 3-5 days after progesterone administration, depending on embryo staging. After FET, estradiol and progesterone supplementation are continued for all patients until the day of the pregnancy test. Patients with a positive pregnancy test will continue to receive luteal phase support regimen until 7 weeks of gestation.

All participants will be followed up per local protocol until outcomes are achieved

Eligibility criteria: Inclusion Criteria:

* Women undergoing IVF/ICSI
* Having indications for freeze-all (day-3 or day-5)
* Agree to have ≤ 2 frozen embryos transferred
* TSH \< 2.5 mIU/mL
* Permanent resident in Viet Nam
* Agree to participate in the study by signing the inform consent

Exclusion Criteria:

* Iodine allergy
* History of salpingectomy or tubal ligation
* History of using Lipiodol® within 6 months prior, starting from the screening time
* At high risk of having Fallopian tube disorders (history of Chlamydia infection, history of pelvic inflammatory diseases, current endometriosis)
* Having evidence of Fallopian tube disorders on Hysterosalpingo - Foam Sonography (HyFoSy), hysterosalpingography (HSG), ultrasonography or laparoscopy
* Having untreated intrauterine lesions such as endometrial polyps, submucosal fibroids, etc which affect the outcome of IVF treatment
* Have a history of thyroid disease or being treated for thyroid disease
* Undergoing curettage within 30 days before performing HSG technique
* Patients having embryos from oocyte donation or in vitro maturation (IVM) cycles
* Unable or unwilling to attend Lipiodol® procedure
* Participating in another interventional study at the same time

Primary outcomes:
measure: Live birth rate after the first transfer
timeFrame: At 22 weeks of gestation
Secondary outcomes:
measure: Positive pregnancy test
timeFrame: At 2 weeks after embryo(s) placement
measure: Clinical pregnancy rate
timeFrame: At 5 weeks after embryo(s) placement
measure: Ongoing pregnancy rate
timeFrame: At 10 weeks after embryo(s) placement
measure: Multiple pregnancy
timeFrame: At 7 weeks after embryo(s) placement
measure: Cumulative live birth rate at 12 months after randomization
timeFrame: At 12 months after randomization
measure: Ectopic pregnancy rate
timeFrame: At 12 weeks of gestation
measure: Early miscarriage rate (Miscarriage <12 weeks)
timeFrame: At 12 weeks of gestation
measure: Late miscarriage rate (Miscarriage <22 weeks)
timeFrame: At 22 weeks of gestation
measure: Still birth rate
timeFrame: After 22 weeks of gestation
measure: Adverse events
timeFrame: At delivery
measure: Maternal thyroid function
timeFrame: At the day of pregnancy test, 3 months (at 7 weeks of pregnancy if the patient is pregnant) and 6 months (at 22 weeks of pregnancy if the patient is pregnant) after randomization
measure: Gestational diabetes mellitus rate
timeFrame: At 24-28 weeks of gestation
measure: Hypertensive disorders of pregnancy rate
timeFrame: From date of randomization until the date of first documented progression, assessed up to 12 months after randomization
measure: Preterm birth rate
timeFrame: At 22, 28, 32 and 37 weeks of gestation
measure: Premature rupture of membranes rate
timeFrame: At 37 weeks of gestation
measure: Chorioamnionitis rate
timeFrame: At delivery
measure: Percentage of magnesium sulfate administration for neuroprotection
timeFrame: At delivery
measure: Antenatal corticosteroids for lung maturation
timeFrame: At delivery
measure: Administration of tocolytics agents
timeFrame: At delivery
measure: Birth weight
timeFrame: At delivery
measure: Large for gestational age
timeFrame: At delivery
measure: Small for gestational age
timeFrame: At delivery
measure: Gestational age at birth
timeFrame: At delivery
measure: Mode of delivery
timeFrame: At delivery
measure: Postpartum hemorrhage
timeFrame: At delivery
measure: Maternal death
timeFrame: At delivery
measure: Congenital anomalies
timeFrame: Within 28 days of birth
measure: Neonatal mortality
timeFrame: Within 28 days of birth
measure: neonatal intensive care unit (NICU) admission
timeFrame: Within 28 days of birth
measure: 1-minute Apgar score
timeFrame: At 1 minute after birth
measure: 5-minute Apgar score
timeFrame: At 5 minute after birth
measure: Low 5-minute Apgar score
timeFrame: At 5 minute after birth
measure: Neonatal thyroid function
timeFrame: At delivery
measure: Mode of conception
timeFrame: From date of randomization until the date of pregnancy test or date of ultrasound, whichever came first, assessed up to 12 months
Other outcomes:
Locations:
Study officials:
References:
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