Endometriosis, Infertility
Conditions
Keywords
implantation failure, IVF, Embryo Transfer
Brief summary
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.
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.
Interventions
BIOLOGICALPRP 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.
Sponsors
Eastern Virginia Medical School
University of Kansas Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
2\. It is not possible to blind clinical staff for the procedure. It is not necessary for the integrity of the study to blind participants as we are assessing their pregnancy outcomes. Regardless of which group they are assigned, participants will partake in routine prenatal care, as well as two additional study visits. They will know which group they have been assigned at the time of the procedure based on if they receive the treatment prior to implantation or not.
Intervention model description
40 patients will be enrolled in each of the control and test groups, using a confidence interval of 95% and a 5% margin of error Total participants expected = 80.
Eligibility
Sex/Gender
FEMALE
Age
23 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the effect of autologous uterine PRP infusion on factors critical to the implantation process | 18 months | Compare differences of the levels TGF- b, IL-6 and LIF in endometrial secretions pre- and post-treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine the effect of autologous uterine PRP infusions on factors that are deleterious to embryo implantation | 18 months | By measuring and comparing levels of TNF-a and IL-4 post uterine infusion with PRP. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Determine if autologous uterine PRP infusion influences implantation rates after frozen embryo transfer. | 18 months | Compare implantation rates after frozen embryo transfer post PRP infusion to implantation rates in the control group. |
Countries
United States
Outcome results
None listed