Lipiodol Prior to FET (LIFE)

NCT ID: NCT06563908

Last Updated: 2024-08-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

784 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-08-10

Study Completion Date

2026-12-31

Brief Summary

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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

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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

Conditions

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IVF Frozen Embryo Transfer Hysterosalpingography

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Lipiodol® uterine treatment prior to IVF/ICSI

For those who are randomized to 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®. After that the procedure to assess study participants' pain perception.

Endometrial preparation for frozen embryo transfer will perform on the subsequence cycle

Group Type EXPERIMENTAL

Lipiodol® uterine treatment prior to IVF/ICSI

Intervention Type PROCEDURE

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 the cervix. Uterine cannulation using the Cook HSG catheter will be applied to conduct Lipiodol® treatment. Prewarmed (37oC) Lipiodol® will be slowly instilled, with intermittent fluoroscopic X-ray guidance. Up to 10 ml of Lipiodol® will be slowly injected into the uterus and directly monitored by fluoroscopy. If intravasation was observed on X-ray (contrast apparent in the venous system), instillation will be stopped immediately.

No Lipiodol® uterine treatment prior to IVF/ICSI

For those who are randomized to no intervention arm (control group), there will be no HSG performed.

Endometrial preparation for frozen embryo transfer will perform on the subsequence cycle

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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 the cervix. Uterine cannulation using the Cook HSG catheter will be applied to conduct Lipiodol® treatment. Prewarmed (37oC) Lipiodol® will be slowly instilled, with intermittent fluoroscopic X-ray guidance. Up to 10 ml of Lipiodol® will be slowly injected into the uterus and directly monitored by fluoroscopy. If intravasation was observed on X-ray (contrast apparent in the venous system), instillation will be stopped immediately.

Intervention Type PROCEDURE

Other Intervention Names

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Lipiodol® flushing prior to IVF/ICSI

Eligibility Criteria

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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
Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Guerbet

INDUSTRY

Sponsor Role collaborator

Mỹ Đức Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Central Contacts

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Tuong M Ho, MD

Role: CONTACT

(+84) 903633377

Tien K Le, MD

Role: CONTACT

(+84) 962803875

References

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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.

Reference Type BACKGROUND
PMID: 23290741 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24119894 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14887769 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18133559 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8137969 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25929235 (View on PubMed)

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 BWJ. Oil-Based or Water-Based Contrast for Hysterosalpingography in Infertile Women. N Engl J Med. 2017 May 25;376(21):2043-2052. doi: 10.1056/NEJMoa1612337. Epub 2017 May 18.

Reference Type BACKGROUND
PMID: 28520519 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1325928 (View on PubMed)

Sawatari Y, Horii T, Hoshiai H. Oily contrast medium as a therapeutic agent for infertility because of mild endometriosis. Fertil Steril. 1993 Apr;59(4):907-11. doi: 10.1016/s0015-0282(16)55880-4.

Reference Type BACKGROUND
PMID: 8384577 (View on PubMed)

Mikulska D, Kurzawa R, Rozewicka L. Morphology of in vitro sperm phagocytosis by rat peritoneal macrophages under influence of oily contrast medium (Lipiodol). Acta Eur Fertil. 1994 May-Jun;25(3):203-6.

Reference Type BACKGROUND
PMID: 7900503 (View on PubMed)

Johnson NP, Farquhar CM, Hadden WE, Suckling J, Yu Y, Sadler L. The FLUSH trial--flushing with lipiodol for unexplained (and endometriosis-related) subfertility by hysterosalpingography: a randomized trial. Hum Reprod. 2004 Sep;19(9):2043-51. doi: 10.1093/humrep/deh418. Epub 2004 Jul 22.

Reference Type BACKGROUND
PMID: 15271870 (View on PubMed)

Johnson NP, Bhattu S, Wagner A, Blake DA, Chamley LW. Lipiodol alters murine uterine dendritic cell populations: a potential mechanism for the fertility-enhancing effect of lipiodol. Fertil Steril. 2005 Jun;83(6):1814-21. doi: 10.1016/j.fertnstert.2004.11.065.

Reference Type BACKGROUND
PMID: 15950655 (View on PubMed)

Reilly SJ, Glanville EJ, Dhorepatil B, Prentice LR, Mol BW, Johnson NP. The IVF-LUBE trial - a randomized trial to assess Lipiodol(R) uterine bathing effect in women with endometriosis or repeat implantation failure undergoing IVF. Reprod Biomed Online. 2019 Mar;38(3):380-386. doi: 10.1016/j.rbmo.2018.11.015. Epub 2018 Dec 7.

Reference Type BACKGROUND
PMID: 30679138 (View on PubMed)

Fatourechi V. Subclinical hypothyroidism: an update for primary care physicians. Mayo Clin Proc. 2009;84(1):65-71. doi: 10.4065/84.1.65.

Reference Type BACKGROUND
PMID: 19121255 (View on PubMed)

Other Identifiers

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1767/QD-BYT

Identifier Type: -

Identifier Source: org_study_id

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