4-step ASCOT in POI Women to Promote Follicular Rescue

Fundación IVI

Status and phase: Completed; Phase 3

Conditions: Premature Ovarian Insufficiency

Treatments: Procedure: Platelet Rich Plasma ovarian injection; Drug: G-CSF treatment for Bone marrow derived stem cell Mobilization

Study type: Interventional

Funder types: Other

Identifiers

NCT04475744

1912-FIVI-113-SH

Details and patient eligibility

About

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.

Enrollment: 42 patients

Sex: Female

Ages: 18 to 38 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects who meet the following will be considered eligible to participate in the clinical trial:

  1. Informed consent form dated and signed.

  2. Age between 18 and 38 (both inclusive)

  3. 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:

  1. Simultaneous participation in another clinical study that, at the researcher's criteria, could interfere with the results of this study.
  2. Age ≥ 39
  3. Autoimmune origin of POI
  4. Genetic risk factors for POR (e.g. Turner Syndrome, FMR1 premutation, etc);
  5. Acquired conditions associated with POR (e.g. Chemotherapy);
  6. Clinical endometriosis
  7. Previous ovarian surgery considered as a risk of POR
  8. Previous gonadotoxic treatment
  9. Known intolerance or allergic reactions to components of the study product, i.e. lactose

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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42 participants in 2 patient groups

Control arm

No Intervention group

Description:

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.

4-step ASCOT arm

Experimental group

Description:

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.

Treatment:

Procedure: Platelet Rich Plasma ovarian injection

Drug: G-CSF treatment for Bone marrow derived stem cell Mobilization