Lipiodol Prior to FET (LIFE)

Официальное название

Lipiodol® For Enhancing Live Birth Rates In Infertile Couples Undergoing In Vitro Fertilization/ Intracytoplasmic Sperm Injection A Randomized Controlled Trial

Обзор

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.

Подробное описание

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

Вмешательства

• Процедура Lipiodol® uterine treatment prior to IVF/ICSI
  Lipiodol®, treatment will be performed by a HSG technique with X-ray screening on day 3 or day 5 after oocyte retrieval. The contrast medium will be Lipiodol Ultra Fluide® (Guerbet, France), an iodized poppy seed oil obtained by substitution of ethyl esters for the glyceryl esters of Lipiodol®. One millilitre of Lipiodol Ultra Fluide® contains 0.48g iodine. Women will lie in the left lateral or supine position. Radiologists will use a 'no touch' technique after applying antiseptic solution to th

Первичные конечные точки

• Live birth rate after the first transfer [Срок оценки: At 22 weeks of gestation]

Вторичные конечные точки (12)

• Positive pregnancy test [Срок оценки: At 2 weeks after embryo(s) placement]
• Clinical pregnancy rate [Срок оценки: At 5 weeks after embryo(s) placement]
• Ongoing pregnancy rate [Срок оценки: At 10 weeks after embryo(s) placement]
• Multiple pregnancy [Срок оценки: At 7 weeks after embryo(s) placement]
• Cumulative live birth rate at 12 months after randomization [Срок оценки: At 12 months after randomization]
• Ectopic pregnancy rate [Срок оценки: At 12 weeks of gestation]
• Early miscarriage rate (Miscarriage <12 weeks) [Срок оценки: At 12 weeks of gestation]
• Late miscarriage rate (Miscarriage <22 weeks) [Срок оценки: At 22 weeks of gestation]
• Still birth rate [Срок оценки: After 22 weeks of gestation]
• Adverse events [Срок оценки: At delivery]
• Maternal thyroid function [Срок оценки: 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 [Срок оценки: At 24-28 weeks of gestation]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Thoma ME, McLain AC, Louis JF, King RB, Trumble AC, Sundaram R, Buck Louis GM. Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach. Fertil Steril. 2013 Apr;99(5):1324-1331.e1. doi: 10.1016/j.fertnstert.2012.11.037. Epub 2013 Jan 3. PMID 23290741
• Abrao MS, Muzii L, Marana R. Anatomical causes of female infertility and their management. Int J Gynaecol Obstet. 2013 Dec;123 Suppl 2:S18-24. doi: 10.1016/j.ijgo.2013.09.008. Epub 2013 Sep 11. PMID 24119894
• WEIR WC, WEIR DR. Therapeutic value of salpingograms in infertility. Fertil Steril. 1951 Nov-Dec;2(6):514-22. doi: 10.1016/s0015-0282(16)30725-7. No abstract available. PMID 14887769
• KING EL, HERRING JS. Sterility studies in private practice. Am J Obstet Gynecol. 1949 Aug;58(2):258-66. doi: 10.1016/0002-9378(49)90378-6. No abstract available. PMID 18133559
• Watson A, Vandekerckhove P, Lilford R, Vail A, Brosens I, Hughes E. A meta-analysis of the therapeutic role of oil soluble contrast media at hysterosalpingography: a surprising result? Fertil Steril. 1994 Mar;61(3):470-7. doi: 10.1016/s0015-0282(16)56578-9. PMID 8137969
• Mohiyiddeen L, Hardiman A, Fitzgerald C, Hughes E, Mol BW, Johnson N, Watson A. Tubal flushing for subfertility. Cochrane Database Syst Rev. 2015 May 1;2015(5):CD003718. doi: 10.1002/14651858.CD003718.pub4. PMID 25929235
• Dreyer K, van Rijswijk J, Mijatovic V, Goddijn M, Verhoeve HR, van Rooij IAJ, Hoek A, Bourdrez P, Nap AW, Rijnsaardt-Lukassen HGM, Timmerman CCM, Kaplan M, Hooker AB, Gijsen AP, van Golde R, van Heteren CF, Sluijmer AV, de Bruin JP, Smeenk JMJ, de Boer JAM, Scheenjes E, Duijn AEJ, Mozes A, Pelinck MJ, Traas MAF, van Hooff MHA, van Unnik GA, de Koning CH, van Geloven N, Twisk JWR, Hompes PGA, Mol B PMID 28520519
• Johnson JV, Montoya IA, Olive DL. Ethiodol oil contrast medium inhibits macrophage phagocytosis and adherence by altering membrane electronegativity and microviscosity. Fertil Steril. 1992 Sep;58(3):511-7. doi: 10.1016/s0015-0282(16)55254-6. PMID 1325928

Идентификаторы

NCT: NCT06563908 · 1767/QD-BYT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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