Platelet Rich Plasma Uterine Infusion

Evaluating Cytokine Concentrations in the Endometrium Before and After Autologous Platelet Rich Plasma Uterine Infusion Preceding Frozen Embryo Transfer

Platelet Rich Plasma (PRP), a rich source of important growth factors, has been shown to significantly affect the body's ability to heal and regenerate tissues. It is an affordable, accessible treatment with little risk of side effects that is being utilized in many areas of regenerative and cosmetic medicine. PRP is also relatively easy to prepare with supplies on hand in most IVF clinics. Specifically relating to reproductive function, PRP has been demonstrated to increase cellular proliferation and decrease fibrosis in damaged rat endometrium. It is hypothesized that infusing the uterus with Platelet Rich Plasma at measured intervals prior to embryo transfer will increase concentrations of implantation-promoting cytokines while reducing concentrations of inflammatory cytokines during the window of implantation.

Study Overview

• Status: Withdrawn
• Conditions: Infertility; Endometriosis
• Intervention / Treatment: Biological: PRP Experimental

Detailed Description

1. Platelet Rich Plasma (PRP), a rich source of important growth factors, has been shown to significantly affect the body's ability to heal and regenerate tissues.7 It is an affordable, accessible treatment with little risk of side effects that is being utilized in many areas of regenerative and cosmetic medicine. PRP is also relatively easy to prepare with supplies on hand in most IVF clinics. PRP has shown great promise in veterinary medicine to regenerate tissues and reduce endometrial inflammation.8 Specifically relating to reproductive function, PRP has been demonstrated to increase cellular proliferation and decrease fibrosis in damaged rat endometrium.6 Endometritis, which is characterized by an increase in inflammatory cells, erosion of the endometrial epithelial layer as well as endometrial edema has been a large cause of infertility in cattle and therefore revenue loss in the cattle industry. A recent study applying uterine infusion of PRP as the intervention demonstrated decreased markers for inflammation in cattle in vivo and as well as decreased inflammatory markers in in vitro cultured endometrial cells exposed to PRP.6 A similar in vitro study was conducted on horses; the authors noticed a decrease in clinical uterine infections in mares along with an increased embryo recovery rate.31 Chronic endometritis is hypothesized to be one of the potential factors involved in recurrent implantation failure in women.32 Using these previous studies in veterinary medicine as a model for potential benefit in human patients, it would be prudent to explore the mechanism of PRP action in humans. It is hypothesized that infusing the uterus with Platelet Rich Plasma at measured intervals prior to embryo transfer will increase concentrations of implantation-promoting cytokines while reducing concentrations of inflammatory cytokines during the window of implantation. TGF-b, IL-6 and LIF are known to be promoters of implantation, while TNF-a and IL-4 are pro-inflammatory factors and can inhibit implantation.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patient at REI clinic population
• Ages 23 to 45
• Undergo frozen embryo transfers with clinic standard medicated protocols
• Transferring one or two embryos on day 5 or 6 of development

Exclusion Criteria:

• BMI >32
• Low level or high-level mosaic
• Aneuploid embryos only will be excluded
• Desiring day 3 or fresh embryo

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRP Experimental; The treatment group will receive 1 ml of autologous PRP infused into the cervix via Rocket IUI catheter at 72+/- 5 hours and 48 +/- 5 hours prior to embryo transfer. Prior to the first PRP infusion, endometrial secretions will be aspirated as described in a previous study regarding endometrial secretions. An embryo transfer catheter will be introduced trans-cervically. A 2 mL syringe will be used to gradually add suction, aspirating secretions from the endometrium. The outer sheath of the embryo catheter will be positioned in the exterior, and the inner catheter retracted into the outer sheath, to avoid cervical fluid contamination in the collected endometrial secretions. Secretions will be deposited into screw top cryovials by snipping the end of the transfer catheter containing secretion off into the tube. These tubes will then be snap-frozen in liquid nitrogen. Process will be repeated prior to embryo transfer	Biological: PRP Experimental; All participants will have 5 2ml tubes of blood collected at 72 +/- 5 hr prior to embryo transfer and again at 48 +/- 5 hour prior to embryo transfer. This blood will be processed to create PRP for the uterine infusion per protocol.
Placebo Comparator: PRP Control; Negative control patients will have endometrial secretions aspirated at identical intervals to the test group but will not receive PRP infusions.	Biological: PRP Experimental; All participants will have 5 2ml tubes of blood collected at 72 +/- 5 hr prior to embryo transfer and again at 48 +/- 5 hour prior to embryo transfer. This blood will be processed to create PRP for the uterine infusion per protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the effect of autologous uterine PRP infusion on factors critical to the implantation process	Compare differences of the levels TGF- b, IL-6 and LIF in endometrial secretions pre- and post-treatment.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the effect of autologous uterine PRP infusions on factors that are deleterious to embryo implantation	By measuring and comparing levels of TNF-a and IL-4 post uterine infusion with PRP.	18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine if autologous uterine PRP infusion influences implantation rates after frozen embryo transfer.	Compare implantation rates after frozen embryo transfer post PRP infusion to implantation rates in the control group.	18 months

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: Eastern Virginia Medical School
• Investigators: Principal Investigator: Courtney Marsh, MD, MPH, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2023
• Primary Completion (Actual): February 16, 2023
• Study Completion (Actual): February 16, 2023

Study Registration Dates

• First Submitted: January 24, 2023
• First Submitted That Met QC Criteria: September 27, 2024
• First Posted (Actual): October 1, 2024

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: September 27, 2024
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: IVF; Embryo Transfer; implantation failure
• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Infertility; Endometriosis
• Other Study ID Numbers: STUDY00149149

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No