Lipiodol Prior to FET (LIFE)

NCT06563908 | Not Yet Recruiting DMC

• 1 other identifier: 1767/QD-BYT
• Study Type: interventional
• Target: 784
• Locations: 0 countries
• Sites: N/A

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.

Conditions

IVF; Frozen Embryo Transfer; Hysterosalpingography

Keywords

Lipiodol; Hysterosalpingography

Outcome Measures

Primary Outcomes (1)

• Live birth rate after the first transfer

  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

  At 22 weeks of gestation

Secondary Outcomes (34)

• 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

• Multiple pregnancy

  At 7 weeks after embryo(s) placement

• Cumulative live birth rate at 12 months after randomization

  At 12 months after randomization

Study Arms (2)

Lipiodol® uterine treatment prior to IVF/ICSI

EXPERIMENTAL

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

Procedure: Lipiodol® uterine treatment prior to IVF/ICSI

No Lipiodol® uterine treatment prior to IVF/ICSI

NO INTERVENTION

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

Interventions

Lipiodol® uterine treatment prior to IVF/ICSI 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.

Also known as: Lipiodol® flushing prior to IVF/ICSI

Lipiodol® uterine treatment prior to IVF/ICSI

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mỹ Đức Hospital: lead
• Guerbet: collaborator

Related Publications (14)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 28520519 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 8384577 BACKGROUND

• 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.

  PMID: 7900503 BACKGROUND

• 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.

  PMID: 15271870 BACKGROUND

• 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.

  PMID: 15950655 BACKGROUND

• 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.

  PMID: 30679138 BACKGROUND

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

  PMID: 19121255 BACKGROUND

Central Study Contacts

Tuong M Ho, MD

CONTACT

(+84) 903633377; tuongho.ivfmd@gmail.com

Tien K Le, MD

CONTACT

(+84) 962803875; bstien.lk@myduchospita.vn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2024
• First Posted: August 21, 2024
• Study Start: August 10, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 21, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share