Autologous Platelet-Rich Plasma Intra-ovarian Infusion in Poor Responders

Study Overview
=================
Brief Summary
-----------------
Autologous PRP intra ovarian infusion may improve ovarian response, patients' hormonal profile as well as fresh embryo transfer (ET)-ICSI cycles' outcome in patients presenting with Poor Ovarian Response (POR).

Detailed Description
-----------------
This triple-blind Randomized Controlled Trial (RCT) aims to investigate the effectiveness of autologous PRP intra ovarian infusion on improving ovarian tissue functionality and fresh ET-ICSI cycles' performance in regard to patients presenting with POR. PRP is blood plasma prepared from fresh whole blood that has been enriched with platelets. It is collected from peripheral veins and contains several growth factors such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), platelet derived growth factor (PDGF), transforming growth factor (TGF) and other cytokines all of which stimulate tissue proliferation and growth. PRP has been employed in several medical conditions in Orthopedics, Dermatology, and Ophthalmology for wound healing. It's efficacy in ovarian rejuvenation and reactivation and endometrial regeneration has not been fully elucidated. This study aims to investigate the effect of autologous PRP intra ovarian infusion on improving ovarian tissue functionality in POR patients.

Official Title
-----------------
Investigating Improvement of Ovarian Function Following Autologous PRP Intra-ovarian Infusion in Poor Responders

Conditions
-----------------
Ovary; Anomaly, Infertility, Female

Intervention / Treatment
-----------------
* Biological: PRP
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Poor Ovarian Response according to Bologna Criteria (fulfilling 2 out of 3 of the following) Age ≥ 40 years AMH < 1.1 ng/ml OR AFC < 7 ≤ 3 oocytes with a conventional stimulation protocol) Discontinuation of any complementary/adjuvant treatment including hormone replacement, acupuncture, and botanotherapy, for at least three months prior to recruitment. Willing to comply with study requirements Exclusion Criteria: Any pathological disorder related to reproductive system anatomy Cycle irregularities Amenorrhea Endometriosis Adenomyosis Fibroids and adhesions Infections in reproductive system Current or previous diagnosis of cancer in reproductive system History of familiar cancer in reproductive system Severe male factor infertility Prior referral for PGT Ovarian inaccessibility -Endocrinological disorders (Hypothalamus- Pituitary disorders, thyroid dysfunction, diabetes mellitus, metabolic syndrome) BMI>30 kg/m2 or BMI<18.5 kg/m2 Systematic autoimmune disorders

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 47 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group of participants receiving PRP treatment<br>Women presenting with POR, treated with autologous PRP intra ovarian infusion and undergoing a subsequent fresh ET-ICSI cycle on the third month of the follow-up period. | Biological: PRP<br>* Autologous PRP intra ovarian infusion<br>|
| Placebo Comparator: Control Group: participants receiving Platelet Free Plasma<br>Women presenting with POR, treated with autologous PFP intra ovarian infusion and undergoing a subsequent fresh ET-ICSI cycle on the third month of the follow-up period | Biological: Placebo<br>* Autologous PFP intra ovarian infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of oocytes retrieved | Number of oocytes retrieved following COS in the first fresh ICSI-ET cycle following intervation performed on the third month of the follow-up period | 34-36 hours following hCG administration | 
| AMH levels | Serum AMH levels evaluated monthly for three consecutive months | Follow-up period of three months entailing monthly evaluation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | Clinical pregnancy rate, following the first fresh ET-ICSI cycle performed on the third month of the follow-up period | 6-7 weeks following last menstruation | 
| Antral Follicle Count | AFC evaluated monthly, on day 2 of the menstrual cycle, for three consecutive months | Follow-up period of three months entailing monthly evaluation |