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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Pregnancy Complicated by Low Implantation

Intervention / Treatment
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* Drug: intralipid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent unexplained failed IVF, ICSI. Recurrent unexplained miscarriages. High level of peripheral and uterine NK. Exclusion Criteria: Age above forty years old. Antiphospholipid syndrome (lupus anticoagulant and/or anticardiolipin antibodies [IgG or IgM]); other recognised thrombophilic conditions (testing according to usual clinic practice). Intrauterine abnormalities (as assessed by ultrasound, hysterosonography, hysterosalpingogram, or hysteroscopy). Fibroids distorting uterine cavity. Abnormal parental karyotype. Other identifiable causes of recurrent miscarriages (tests initiated only if clinically indicated) e.g., diabetes, thyroid disease and systemic lupus erythematosus (SLE).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intralipids<br>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<br>* intravenous intralipid 20% is given to the patients known to be have either recurrent failed IVF, RPL<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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implantation failure, recurrent abortion, intralipid