Endometrial Rejuvenation Study

Study Overview
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Brief Summary
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To evaluate the response of the endometrial lining after subcutaneous administration of the medication AMD3100. This medication mobilizes stem cells and will be used in a population of infertile women with a thin endometrium who are undergoing frozen-thawed embryo transfer. The investigators will assess associations between response to stem cell mobilization and pregnancy outcomes.

Detailed Description
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This study seeks to help each participant build a better endometrial lining which is suitable to implantation and maintenance of a healthy pregnancy. While animal models demonstrating the effectiveness of stem cell recruitment on improved endometrial thickness and pregnancy outcomes are plentiful, human studies are lacking. The use of stem cells from the peripheral circulation in humans could potentially allow for enhanced endometrial proliferation. The objective of this study is to perform a prospective randomized, controlled trial to evaluate the response of the endometrial lining after subcutaneous administration of AMD3100 (plerixafor). AMD3100 is an immunostimulant used to mobilize hematopoietic stem cells in the bloodstream. This intervention will be studied in a population of infertile women with a thin endometrium who have failed previous embryo transfer cycles and are undergoing a frozen-thawed embryo transfer. This study seeks to evaluate both the endometrial response to stem cell mobilization via AMD3100 as well as pregnancy outcomes.

Official Title
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Endometrial Response Following Use of the Stem Cell Mobilizing Agent AMD3100 in a Population of Infertile Women With a Thin Endometrial Lining

Conditions
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Infertility of Uterine Origin

Intervention / Treatment
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* Drug: AMD3100
* Drug: Normal saline
* Procedure: dilation and curettage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients planning to undergo a frozen-thawed embryo transfer cycle using a single euploid blastocyst. Patients who have previously undergone at least 2 unsuccessful frozen-thawed embryo transfer cycles, defined as failure to achieve a clinical pregnancy (visualization of intrauterine gestational sac on ultrasound) or a cancelled embryo transfer cycle due to inadequate endometrial thickness. Patients with a diagnosis of thin endometrial lining (less than 6 mm maximum thickness) during at least one prior unsuccessful embryo transfer cycle. Initiation of the most recent unsuccessful frozen-thawed embryo transfer cycle with a thin endometrial lining must have occurred after January 1, 2017. Exclusion Criteria: Fewer than 2 prior unsuccessful frozen-thawed embryo transfer cycles. Most recent unsuccessful frozen-thawed embryo transfer prior to January 1, 2017. No euploid embryos available for transfer. Mullerian anomalies, excluding arcuate uterus Submucosal fibroids History of uterine surgery, excluding polypectomy, D&C, and Cesarean section Communicating hydrosalpinx without plans for surgical correction prior to study enrollment. Failure of patient to agree to enrollment in study with written consent. History of drug sensitivity or adverse reaction to AMD3100 (plerixafor). Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>Patients in this arm will not receive the study drug. A placebo of normal saline will be injected subcutaneously and the D&C procedure will be completed. | Drug: Normal saline<br>* Subjects in this arm will have a placebo of normal saline administered subcutaneously x1 dose<br>Procedure: dilation and curettage<br>* all participants will undergo routine D&C procedure<br>* Other names: D&C;|
| Experimental: Intervention<br>Patients in this arm will receive a dose of the study drug, AMD3100, injected subcutaneously and the D&C procedure will be completed. | Drug: AMD3100<br>* Subjects in this arm will have AMD3100 administered per the standard dosing regimen of 0.24 mg/kg actual body weight subcutaneous x1 dose<br>Procedure: dilation and curettage<br>* all participants will undergo routine D&C procedure<br>* Other names: D&C;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrial thickness | measurement of endometrial thickness | measured on day prior to progesterone initiation during frozen embryo transfer cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of participants with a chemical pregnancy | defined by a positive bHCG | 9-11 days post embryo transfer | 
| number of participants with a clinical pregnancy | defined as the presence of an intrauterine gestational sac | seen as early as 18 days post embryo transfer | 
| number of participants with a live births | number of deliveries resulting from embryo transfer | typically 9 months from embryo transfer | 
| endometrial volume | measurement of uterine endometrium based on 3D ultrasound | measured at baseline visit during cycle 1 (one month) and after progesterone initiation during cycle 4 (one month) |