Ovarian Function Following Intraovarian Injection of PRP

Study Overview
=================
Brief Summary
-----------------
Consenting women with evidence of poor ovarian reserve will be randomly assigned to treatment with either Platelet Rich Plasma (PRP) or Platelet Poor Plasma (PPP).

Detailed Description
-----------------
As women age oocytes are gradually depleted with a consequent progressive loss of ovarian function and fertility. When a woman's follicle cohort falls below a critical level, she enters a transitional time of diminished ovarian reserve known as ovarian aging. Recently the use of autologous platelet-rich plasma (A-PRP) has been proposed as an additional strategy for improving ovarian function. A-PRP is prepared from autologous blood using an FDA approved device. The rationale for the use of PRP is that it contains growth factors which stimulate cellular anabolism, inflammatory modulators that create an anti-inflammatory effect and fibrinogen which acts as a scaffold for regenerating tissue. The investigators hypothesize that the growth factors present in PRP may have a beneficial effect promoting growth and recruitment of antral follicles. The investigators will recruit a prospective cohort of 90 patients with evidence of Premature Ovarian Aging/DOR. Women invited to participate in this RCT will have FSH above 12 and AMH below 1.0 ng/mL respectively and will have had fewer than 6 oocytes retrieved in a previous ovulation attempt. Consenting participants in this trial will be randomized in a doubly blind fashion to two groups. One will receive Platelet Rich Plasma (PRP) and the other will receive Platelet Poor Plasma (PPP). Women assigned to PPP will be offerred PRP in a future cycle if they so desire.

Official Title
-----------------
Randomized Controlled Trial of Ovarian Function Following Intraovarian Injection of Platelet Rich Plasma for Women With Ovarian Aging

Conditions
-----------------
Diminished Ovarian Reserve, Diminished Ovarian Reserve Due to Advanced Maternal Age

Intervention / Treatment
-----------------
* Procedure: PRP - Platelet Rich Plasma
* Procedure: PPP - Platelet Poor Plasma


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: fewer than 6 oocytes in response to past ovulation induction desire to establish a pregnancy using IVF Age 44 years and under. FSH > 12 AMH < 1.0 No Aspirin or Motrin for one week before treatment Exclusion Criteria: Age > 45 years Marked thrombocytopenia Blood diseases Hypofibrinogenemia Hemodynamic instability Anticoagulant or antiaggregant treatment Oncological diseases (specially, skeletal system and blood) Sepsis Acute and chronic infectious diseases Autoimmune diseases, for example, lupus erythematosus, etc.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 44 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: Factorial Assignment
Interventional Model Description: Participants will be randomly assigned to treatment with either Platelet Rich Plasma (PRP) or Platelet Poor Plasma (PPP)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRP group<br>Platelet RICH Plasma prepared using RegenLab FDA approved device. | Procedure: PRP - Platelet Rich Plasma<br>* Using a sterile vacutainer technique two 8 ml samples of whole blood is drawn into two Regen Lab A-PRP vacutainers with gel separator and citrate. Invert the tube to mix with citrate. The whole blood undergoes two centrifugations, once for 3 minutes and again for 5 minutes. Using a 20-gauge 6-inch spinal needle 2 ml of Platelet POOR Plasma will be drawn off the supernatant from each tube to leave 2.5 ml of Platelet Rich Plasma in the tube. The tube is inverted several times to suspend the platelet pellet. The prepared plasma labeled with the participants name and randomization code will be transported to the procedure room.<br>|
| Placebo Comparator: PPP group<br>Platelet POOR Plasma prepared using RegenLab FDA approved device. | Procedure: PPP - Platelet Poor Plasma<br>* Using a sterile vacutainer technique two 8 ml samples of whole blood is drawn into two Regen Lab A-PRP vacutainers with gel separator and citrate. Invert the tube to mix with citrate. The whole blood undergoes two centrifugations, once for 3 minutes and again for 5 minutes. Using a 20-gauge 6-inch spinal needle 2 ml of Platelet POOR Plasma will be drawn off the supernatant from each tube. The prepared plasma will be transported to the procedure room. The prepared plasma labeled with the participants name and randomization code will be transported to the procedure room.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Embryo Transfer | Number of participants with at least one day-3 embryo 8-cell with less than 5% fragmentation in an IVF cycle | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Embryos Produced | Mean number of day-3 embryo 8-cell with less than 5% fragmentation produced | 6 weeks | 
| AMH | Serum concentration of Anti Mullerian Hormone | 4 weeks | 
| Antral Follicle Count | Number of Antral Follicles determined by pelvic sonogram on day 2 or 3 of menses | 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Infertility - Ovarian dysfunuction, Diminished Ovarian Reserve, Premature Ovarian Aging (POA)