Lipiodol® For Enhancing Live Birth Rates In Infertile Couples Undergoing In Vitro Fertilization/ Intracytoplasmic Sperm Injection A Randomized Controlled Trial
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- IVF
- Sponsor
- Mỹ Đức Hospital
- Enrollment
- 784
- Primary Endpoint
- Live birth rate after the first transfer
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
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
Investigators
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
Outcomes
Primary Outcomes
Live birth rate after the first transfer
Time Frame: At 22 weeks of gestation
Live birth is defined as the complete expulsion or extraction from a woman of a product of fertilization, after 22 completed weeks of gestational age, which, after such separation, breathes or shows any other evidence of life, such as heartbeat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. If gestational age is unknown, a birth weight of 500 grams or more will be used instead
Secondary Outcomes
- Multiple pregnancy(At 7 weeks after embryo(s) placement)
- Positive pregnancy test(At 2 weeks after embryo(s) placement)
- Clinical pregnancy rate(At 5 weeks after embryo(s) placement)
- Ongoing pregnancy rate(At 10 weeks after embryo(s) placement)
- Cumulative live birth rate at 12 months after randomization(At 12 months after randomization)
- Ectopic pregnancy rate(At 12 weeks of gestation)
- Early miscarriage rate (Miscarriage <12 weeks)(At 12 weeks of gestation)
- Late miscarriage rate (Miscarriage <22 weeks)(At 22 weeks of gestation)
- Still birth rate(After 22 weeks of gestation)
- Adverse events(At delivery)
- Maternal thyroid function(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)
- Gestational diabetes mellitus rate(At 24-28 weeks of gestation)
- Hypertensive disorders of pregnancy rate(From date of randomization until the date of first documented progression, assessed up to 12 months after randomization)
- Preterm birth rate(At 22, 28, 32 and 37 weeks of gestation)
- Premature rupture of membranes rate(At 37 weeks of gestation)
- Chorioamnionitis rate(At delivery)
- Percentage of magnesium sulfate administration for neuroprotection(At delivery)
- Large for gestational age(At delivery)
- Small for gestational age(At delivery)
- Gestational age at birth(At delivery)
- Antenatal corticosteroids for lung maturation(At delivery)
- Administration of tocolytics agents(At delivery)
- Birth weight(At delivery)
- Mode of delivery(At delivery)
- Congenital anomalies(Within 28 days of birth)
- Neonatal mortality(Within 28 days of birth)
- 5-minute Apgar score(At 5 minute after birth)
- Low 5-minute Apgar score(At 5 minute after birth)
- Postpartum hemorrhage(At delivery)
- Maternal death(At delivery)
- neonatal intensive care unit (NICU) admission(Within 28 days of birth)
- 1-minute Apgar score(At 1 minute after birth)
- Neonatal thyroid function(At delivery)
- Mode of conception(From date of randomization until the date of pregnancy test or date of ultrasound, whichever came first, assessed up to 12 months)