Ovarian PRP for Diminished Ovarian Reserve (oPRP)

Ovarian Platelet-Rich Plasma Injections for Diminished Ovarian Reserve Patients: A Double-Blinded Placebo-Control Trial

This prospective double-blinded randomized placebo control study aims to determine if In Vitro Fertilization (IVF) outcomes are improved by ovarian platelet-rich plasma injections (oPRP) for women diagnosed with diminished ovarian reserve (DOR). Women with DOR notoriously have the lowest chance of pregnancy and live birth compared to age-matched peers with a normal or robust ovarian reserve.

Study Overview

• Status: Not yet recruiting
• Conditions: Diminished Ovarian Reserve
• Intervention / Treatment: Other: oPRP

Detailed Description

A randomized, double-blind, placebo-controlled trial comparing ovarian injection of platelet-rich plasma vs. placebo in women diagnosed with diminished ovarian reserve at risk for a poor ovarian response (POR) between 35 to 42 years of age. Participants for this study include patients who are planning to undergo IVF with preimplantation genetic testing for aneuploidy (PGT-A) followed by a frozen embryo transfer (FET) cycle. Only patients with either a euploid embryo or eligible mosaic embryo (following consultation with a geneticist), as determined by PGT-A, will be allowed to proceed with a single blastocyst FET cycle

All patients will have a baseline ultrasound and blood work at the time of menses, approximately one month prior to starting their initial IVF cycle. Routine monitoring will be required to determine the day of ovulation. Once an LH surge is detected or if a lead follicle on pelvic ultrasound is deemed large enough to induce ovulation, a "trigger" shot with 250 mcg/0.5 mL of Ovidrel® will be self-administered subcutaneously (SQ). Based upon the patient's randomization, either oPRP or ovarian Serum (oS) injections will be performed under anesthesia and within 72 hours from the day of ovulation. Following their ovarian injections, all patients will return for monitoring with the onset of menses approximately 14 to 16 days from the date of ovulation.

A medication protocol will be determined at the start of each IVF cycle. Either a natural (nIVF), mild (mIVF) or conventional (cIVF) IVF protocol will be chosen by the treating physician. This determination will be based on findings from the repeat pelvic ultrasound with AFC and blood work for anti-mullerian hormone (AMH), follicle stimulating hormone (FSH), lutenizing hormone (LH), estradiol (E2), progesterone (P4), and beta-human chorionic gonadotrophin (B-hCG). Natural IVF will be considered for patients with only 1-2 antral follicles, mIVF for patients with 2-4 antral follicles observed, and cIVF for patients with four or more antral follicles visualized at the time stimulation started.

Patients will begin their designated protocol and return four to five days following medication start. A repeat pelvic ultrasound will be performed to measure the growth and size of all follicles visualized along with the endometrial thickness. Also, blood work for E2, FSH, LH, and P4 will be obtained. Monitoring for follicular and endometrial development will continue routinely and as needed, until the majority of all follicles observed have a mean diameter between 15 to 22 mm. Induction of ovulation will commence 35 and a half hours prior to oocyte retrieval, by self-administration of 10,000 IU hCG SQ.

The patient will receive deep IV sedation anesthesia by a board-certified anesthesiologist for her oocyte retrieval and placement of either her second oPRP or oS injections. Using transvaginal ultrasound guidance, all follicles visualized under ultrasound will be aspirated using standard practices by patients undergoing IVF at GNF. Aspirates will be collected in 10 ml test tubes. All oocytes will be assessed at the time of retrieval for maturity. All oocytes that are deemed mature (MII) will undergo intracytoplasmic sperm injection (ICSI), to maximize fertilization rates, 2-4 hours after identification of the first polar body. All immature (non MII) oocytes will be isolated under a stereomicroscope and transferred into maturation media and incubated further in a triple gas mixture (90% N2, 5% CO2, and 5% O2) for up to 24 hours to allow maturation prior to ICSI. Following the oocyte retrieval, either oPRP or oS will be performed as described previously.

Monitoring will recommence two weeks following the first oocyte retrieval to identify if any residual follicles or ovarian cysts are present. If the ovaries are deemed resting and no active ovarian cysts persist, then the patient will begin her second IVF cycle. Again, the medication protocol will be determined by findings observed on pelvic ultrasound including AFC and ovarian hormone testing. If the patient is deemed ineligible to start another IVF cycle, then she will return with the following menstrual period to begin her second IVF cycle. The process of monitoring patients, inducing ovulation and collecting oocytes will be identical to the first oocyte retrieval. However, no additional oPRP or oS injections will be performed.

• Study Type: Interventional
• Enrollment (Anticipated): 230
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alicia Broussard, PhD; Phone Number: 3174456958; Email: a.broussard@generationnextfertility.com
• Study Contact Backup: Name: Jesse Hade, MD; Phone Number: 2126410906; Email: j.hade@generationnextfertility.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 42 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Clinical diagnosis of diminished ovarian reserve
• Clinical diagnosis of poor ovarian response
• Women age 35-42

Exclusion Criteria:

• Clinical diagnosis of premature ovarian failure
• Clinical diagnosis of menopause.
• Under 35 years of age
• Over 42 years of age

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oPRP injections; Patients own prepared PRP will be injected into each ovary	Other: oPRP; Prepared sample from patient's own blood collected and processed
Placebo Comparator: Placebo; Patient's serum will be injected into the ovary (not rich with platelets)	Other: oPRP; Prepared sample from patient's own blood collected and processed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
oPRP changes Ovarian Response and the total Number of oocytes retrieved	Total oocyte yield	12 months
oPRP impacts the Number or Euploid Embryos available for frozen embryo transfers	Available embryos for frozen embryo transfers	12 months

Collaborators and Investigators

• Sponsor: Generation Next Fertility
• Collaborators: Igenomix
• Investigators: Principal Investigator: Jesse Hade, MD, Generation Next Fertility

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2023
• Primary Completion (Anticipated): March 1, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: March 6, 2023
• First Submitted That Met QC Criteria: March 16, 2023
• First Posted (Actual): March 30, 2023

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 16, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: DOR; Ovarian Platelet Rich Plasma; Ovarian PRP
• Other Study ID Numbers: IORG0010499_202301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Collaboration to share protocol may be requested with PI
• IPD Sharing Time Frame: April 2023 to April 2024
• IPD Sharing Access Criteria: Protocol may be shared with other research bodies upon request for collaboration
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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