Premature Ovarian Insufficiency
Conditions
Brief summary
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.
Interventions
DRUGG-CSF treatment for Bone marrow derived stem cell Mobilization
Mobilization treatment. On the fifth day, collection will be started.
PROCEDUREPlatelet 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.
Sponsors
Instituto Valenciano de Infertilidad, IVI VALENCIA
IVI Madrid
Hospital Universitario La Fe
Fundación IVI
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 38 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AFC | 6-month | Follicular development assessed by antral follicular count between controls and treated patients after the 4-step ASCOT technique during the follow up period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FSH, AMH and E2 levels | 6-month | hormone levels in plasma |
| Number of COS and IVF cycle parameters for each patient, initiated before and after treatment. | 6-month | COS and IVF cycle variables will be recorded if COS initiated |
| Menses recovery (YES/NO) | 6-12 months | If menses recovery is noted by patients should be informed and recorded |
| Ovarian function (YES/NO) | 6-12 months | Antral follicles detected by untrasound, menses recover and decrease in FSH levels will be considered as positive ovarian function |
Countries
Spain
Outcome results
None listed