Study of PRP in Women With Evidence of Diminished Ovarian Reserve (PRP4AGE)

Study of Ovarian Function Following Intraovarian Injection of Platelet Rich Plasma (PRP) In Women With Evidence of Diminished Ovarian Function

The hypothesis of the study is that ovaries of women with a history of poor response to ovulation induction may benefit from exposure to growth factors known to be present in Platelet Rich Plasma (PRP). Since even ovaries from women with poor response still contain primordial follicles (which, however, no longer undergo recruitment), it is hoped that PRP injections into ovaries will activate follicular recruitment pathways and, subsequently, result in follicle growth. Should such growth be observed, follicles will be supported with routine daily gonadotropin stimulation until hCG trigger.

Study Overview

• Status: Recruiting
• Conditions: Diminished Ovarian Reserve; Ovarian Failure
• Intervention / Treatment: Procedure: A-PRP

Detailed Description

The hypothesis of the study is that ovaries of women with a history of poor response to ovulation induction may benefit from exposure to growth factors known to be present in PRP.

Autologous Platelet Rich Plasma (A-PRP) is plasma with a concentration of platelets above the blood baseline. A-PRP is developed from autologous blood. Within A-PRP, the concentration of platelets delivers an increased number of growth factors. In this study A-PRP will be prepared using Regen Lab PRP Kit which is approved by US-FDA for preparation of PRP.

PRP is becoming widely used in a variety of medical procedures seeking tissue remodeling and/or healing as an intervention. To date, applications in orthopedics, wound healing, dermatology and plastic surgery have gained general acceptance, primarily as the role of platelets and their activation in tissue repair and recovery has become better understood at a cellular and molecular level. This knowledge base provides a foundation for the present study because of the ready availability of FDA-approved kits for autologous PRP preparations and the recognition that the aging ovary acquires tissue pathologies in the form of wound healing and fibrosis as a result of repeat ovulations over the reproductive lifespan of women. Since PRP is an autologous blood product, and is widely used via injection into various organs and tissues, safety concerns are minimal.

This study will involve only adult women with a diagnosis of diminished ovarian reserve. All consenting participants will receive injections of autologous Platelet RIch Plasma (A-PRP) in both ovaries under ultrasound guidance performed after induction of IV sedation.

Assumption of this study is that in women with previous poor response to ovulation induction will show limited follicle growth. The study will try to estimate effect of PRP on this condition by comparing post-PRP response to the previous response. The investigators recognize that there will be a possibility of apparent response based on regression to the mean. The investigators expect that study of fifty patients should be enough to determine if there is a potential clinical effect and to allow estimation of that effect for power calculations for future studies.

• Study Type: Interventional
• Enrollment (Anticipated): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: David Barad, MD; Phone Number: 212 944-4400; Email: dbarad@theCHR.com
• Study Contact Backup: Name: Jolanta Tapper; Phone Number: 212 994-4400; Email: jtapper@theCHR.com

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • Center For Human Reproduction
      • Principal Investigator: David H Barad, MD MS
      • Principal Investigator: Norbert Gleicher, MD
      • Contact: Jolanta Tapper; Phone Number: 212-994-4400; Email: jtapper@theCHR.com
      • Contact: Alexandra Braileanu-Rata; Phone Number: 212 994-4400; Email: arata@thechr.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Women with failure to respond well to ovulation induction by having fewer than 1 cleavage stage embryo in response to past ovulation induction who do not qualify for the PRP4POI study
• Age 54 years and under.
• FSH > 12
• AMH < 1.1
• -No Aspirin or Motrin for one week before treatment

Exclusion Criteria:

• Age > 54 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.

Relative contraindications for PRP

• Chronic liver diseases in the exacerbation phase
• Chronic intoxication against the background of long-term use of alcohol, addictive drugs, an administration of potent medications
• Use of steroidal anti-inflammatory drugs in less than 2 days before drawing the blood, an injection of corticosteroids in little less than 2 weeks before the procedure
• Pregnancy
• Inflammatory skin diseases, chronic dermatosis in the exacerbation phase, for example, psoriasis, atopic eczema, etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A-PRP; The cortex of each ovary will be injected with autologous platelet rich plasma.	Procedure: A-PRP; The cortex of each ovary will be injected with autologous platelet rich plasma. Up to seven different sites will be injected under ultrasound guidance. The patient will be under IV sedation.; Other Names: Autologous Platelet Rich Plasma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Emergence of new ovarian follicles with evidence of estradiol production	Emergence of new ovarian follicles greater than 4 mm in average diameter as measured using pelvic sonography with evidence of change estradiol serum estradiol levels as measured using a immuno assay.	Change from baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum AMH	Increase in serum AMH from baseline level as measured using an immuno assay	Change from baseline to 12 weeks
Number of participants with retrieval of oocytes in an IVF cycle	Number of participants with retrieval of oocytes in an IVF cycle	6 months
Number of participants that establish a Clinical Pregnancy	Number of participants that establish a Clinical Pregnancy	12 months

Collaborators and Investigators

• Sponsor: Center for Human Reproduction
• Investigators: Study Chair: Norbert Gleicher, MD, Medical Director

Publications and helpful links

General Publications

• Barad DH, Albertini DF, Molinari E, Gleicher N. Preliminary report of intraovarian injections of autologous platelet-rich plasma (PRP) in extremely poor prognosis patients with only oocyte donation as alternative: a prospective cohort study. Hum Reprod Open. 2022 Jun 28;2022(3):hoac027. doi: 10.1093/hropen/hoac027. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: February 17, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): May 19, 2023
• Last Update Submitted That Met QC Criteria: May 18, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Platelet Rich Plasma
• Other Study ID Numbers: 09182018-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We do not plan to share individual patient data.

Drug and device information, study documents

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