4-step ASCOT in POI Women to Promote Follicular Rescue

Study Overview
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Brief Summary
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To promote follicular development in POI women, G-CSF mobilized activated platelet rich plasma will be directly injected into the ovarian medulla. This is a prospective, observational, multicentric, open, pilot-controlled randomized trial which seeks to evaluate the impact of the 4-step ASCOT technique on the ovarian reserve and reproductive outcomes of POI patients. The study will be developed in two phases. In a first step, POI women will randomized to control or undergo the 4-step ASCOT technique based on the direct ovarian injection of G-CSF mobilized and activated PRP. Follow up (AFC, AMH, FSH and E2 determinations) will be developed for 3 month in the controls and for 6 months in the treated and COS initiated if growing antral follicles detected. In the second phase, POI women allocated to control group after completed the follow up period will undergo the 4-step ASCOT technique, as described in the previous phase but only one ovary will be injected, then they will undergo a 6-month follow up period as described above.

Official Title
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4-step ASCOT in POI Women to Promote Follicular Rescue

Conditions
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Premature Ovarian Insufficiency

Intervention / Treatment
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* Drug: G-CSF treatment for Bone marrow derived stem cell Mobilization
* Procedure: Platelet Rich Plasma ovarian injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who meet the following will be considered eligible to participate in the clinical trial: Informed consent form dated and signed. Age between 18 and 38 (both inclusive) Women who meet the ESHRE criteria for POI [41] presence of menstrual disturbance defined as oligo/amenorrhea for at least 4 months biochemical confirmation as evidenced by an elevated FSH level >25IU/L on two occasions > 4 weeks apart Or fluctuating POI when one of the above criteria is missing. Exclusion Criteria: Subjects who meet one or more of the following will not be considered eligible to participate in the clinical trial: Simultaneous participation in another clinical study that, at the researcher's criteria, could interfere with the results of this study. Age ≥ 39 Autoimmune origin of POI Genetic risk factors for POR (e.g. Turner Syndrome, FMR1 premutation, etc); Acquired conditions associated with POR (e.g. Chemotherapy); Clinical endometriosis Previous ovarian surgery considered as a risk of POR Previous gonadotoxic treatment Known intolerance or allergic reactions to components of the study product, i.e. lactose

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 38 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control arm<br>POI women radomized to control arm will undergo a 3-month follow up for: AFC, AMH, FSH and E2 determinations.COS will be initiated if growing antral follicles detected. In the second phase, POI women allocated to control group after completed the follow up period will undergo the 4-step ASCOT technique, as described in the previous phase but only one ovary will be injected, then they will undergo a 6-month follow up period as described above. | |
| Experimental: 4-step ASCOT arm<br>POI women randomized to the 4-step ASCOT technique will receive a direct ovarian injection of G-CSF mobilized and activated PRP. For each patient, both ovaries will be directly injected with the G-CFS activated PRP (4-step ASCOT). Follow up (AFC, AMH, FSH and E2 determinations) will be developed for 6 months and COS initiated if growing antral follicles detected. | Drug: G-CSF treatment for Bone marrow derived stem cell Mobilization<br>* Mobilization treatment. On the fifth day, collection will be started.<br>Procedure: Platelet Rich Plasma ovarian injection<br>* Mobilized peripheral blood will be obtained to prepare the PRP for injection. Both ovaries will be injected when proper anatomical access can be assessed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AFC | Follicular development assessed by antral follicular count between controls and treated patients after the 4-step ASCOT technique during the follow up period. | 6-month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FSH, AMH and E2 levels | hormone levels in plasma | 6-month | 
| Number of COS and IVF cycle parameters for each patient, initiated before and after treatment. | COS and IVF cycle variables will be recorded if COS initiated | 6-month | 
| Menses recovery (YES/NO) | If menses recovery is noted by patients should be informed and recorded | 6-12 months | 
| Ovarian function (YES/NO) | Antral follicles detected by untrasound, menses recover and decrease in FSH levels will be considered as positive ovarian function | 6-12 months |