4-step ASCOT in POI Women to Promote Follicular Rescue

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.

Study Overview

• Status: Completed
• Conditions: Premature Ovarian Insufficiency
• Intervention / Treatment: Drug: G-CSF treatment for Bone marrow derived stem cell Mobilization; Procedure: Platelet Rich Plasma ovarian injection

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain
    • IVI Madrid
  • Valencia, Spain
    • IVI Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control arm; 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; 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; Mobilization treatment. On the fifth day, collection will be started.; Procedure: Platelet Rich Plasma ovarian injection; Mobilized peripheral blood will be obtained to prepare the PRP for injection. Both ovaries will be injected when proper anatomical access can be assessed.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fundación IVI
• Collaborators: Instituto Valenciano de Infertilidad, IVI VALENCIA; Hospital Universitario La Fe; IVI Madrid

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Actual): October 30, 2023
• Study Completion (Actual): October 30, 2023

Study Registration Dates

• First Submitted: July 10, 2020
• First Submitted That Met QC Criteria: July 14, 2020
• First Posted (Actual): July 17, 2020

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Primary Ovarian Insufficiency; Menopause, Premature
• Other Study ID Numbers: 1912-FIVI-113-SH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No