Intralipid Therapy for Recurrent Implantation Failure and Recurrent Miscarriages: Is it a Hope or Myth?A Randomized Clinical Trial (ILRIFRM)

Phase 4 Study of the Efficacy of Intralipid Treatment in Patients With Recurrent Implantation Failure and Miscarriages With High Peripheral and Uterine Natural Killer Cells

Both organ-specific and systemic autoimmunity are associated with an increased prevalence of recurrent miscarriage and reproductive failure, rendering the role of the maternal immunological system in fertility a key concept. It is believed by some that central to this theme is the maternal cytokine profile, with particularly T-helper (Th) cells. Immune modulating therapies have therefore been mooted as potential therapeutic strategies. Recent reports of high pregnancy rates achievable in women with RIF have added fuel to the debate regarding the effectiveness of intralipids in modulating the immune system.

Study Overview

• Status: Withdrawn
• Conditions: Pregnancy Complicated by Low Implantation
• Intervention / Treatment: Drug: intralipid

Detailed Description

The investigators would like to assess if that intralipids therapy is an effective treatment for women undergoing repeated failed assisted reproduction cycles and recurrent miscarriages against traditional methods in randomised clinical trial (RCT).

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt
    • Women's Health Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Recurrent unexplained failed IVF, ICSI.
2. Recurrent unexplained miscarriages.
3. High level of peripheral and uterine NK.

Exclusion Criteria:

1. Age above forty years old.
2. Antiphospholipid syndrome (lupus anticoagulant and/or anticardiolipin antibodies [IgG or IgM]); other recognised thrombophilic conditions (testing according to usual clinic practice).
3. Intrauterine abnormalities (as assessed by ultrasound, hysterosonography, hysterosalpingogram, or hysteroscopy).
4. Fibroids distorting uterine cavity.
5. Abnormal parental karyotype.
6. Other identifiable causes of recurrent miscarriages (tests initiated only if clinically indicated) e.g., diabetes, thyroid disease and systemic lupus erythematosus (SLE).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: intralipids; Two hundreds patients (group1) with abnormal NK activity results (NKa)will receive intralipids 20% i.v. (9 mg/mL total blood volume -corresponds to 2 mL of intralipids 20% diluted in 250 mL saline; or 18 mg/mL - corresponds to 4 mL of intralipids 20% diluted in 250 mL saline) infusions and their NKa will be tested periodically. The determination of NK cell function will be performed by flow cytometry using K562 cells as targets,then follow up of the patients by the Doppler of endometrial blood follow at the time of luteal phase,and the clinical pregnancy rate.Group(2)of 180 patients will receive placebo.

Drug: intralipid; intravenous intralipid 20% is given to the patients known to be have either recurrent failed IVF, RPL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effectiveness of intralipid on normalization of nk level and rate of clinical pregnancy .	Two hundreds patients (group1) with abnormal NK activity results (NKa)will receive intralipids 20% i.v. (9 mg/mL total blood volume -corresponds to 2 mL of intralipids 20% diluted in 250 mL saline; or 18 mg/mL - corresponds to 4 mL of intralipid 20% diluted in 250 mL saline) infusions and their NKa will be tested periodically. The determination of NK cell function will be performed by flow cytometry using K562 cells as targets,then follow up of the patients by the Doppler of endometrial blood follow at the time of luteal phase,and the clinical pregnancy rate.Group(2)of 200 patients will receive other routine measures.	2 ys

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the rate of continuation of pregnancy beyond 12 weeks of pregnancy,the adverse effects related to the drug.	Two hundreds patients (group1) with abnormal NK activity results (NKa) will receive intralipids 20% i.v. (9 mg/mL total blood volume -corresponds to 2 mL of intralipid 20% diluted in 250 mL saline; or 18 mg/mL - corresponds to 4 mL of intralipid 20% diluted in 250 mL saline) infusions and their NKa were tested periodically. The determination of NK cell function will be performed by flow cytometry using K562 cells as targets,then follow up of the patients by the Doppler of endometrial blood follow at the time of luteal phase,and the clinical pregnancy rate.Group(2)of 200 patients will receive routine measures.	2 ys

Collaborators and Investigators

• Sponsor: Woman's Health University Hospital, Egypt
• Investigators: Principal Investigator: Alaa M Ismail, M D, Faculty of Medicine,Assiut university,Egypt

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): August 1, 2012
• Study Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: August 20, 2012
• First Submitted That Met QC Criteria: August 31, 2012
• First Posted (Estimate): September 6, 2012

Study Record Updates

• Last Update Posted (Actual): January 8, 2021
• Last Update Submitted That Met QC Criteria: January 6, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: intralipid; implantation failure; recurrent abortion
• Additional Relevant MeSH Terms: Pregnancy Complications; Abortion, Spontaneous; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; Soybean oil, phospholipid emulsion
• Other Study ID Numbers: ILRIFRM