PRP + tSVF for Premature Ovarian Failure

(OVAR-REJUV Trial)

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: Black Tie Medical, Inc.

Must not be taking: Anticoagulants, Hormonal treatments

Disqualifiers: Genetic ovarian failure, Cancer, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 1 day

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests injections of a healing mixture into the ovaries to help women with early menopause or ovarian failure. The mixture can be just a healing substance or combined with cells from their own fat. The goal is to improve ovarian function and hormone levels. This healing substance has been used in various medical fields to promote tissue regeneration and has shown promising results in improving ovarian function.

Will I have to stop taking my current medications?

Yes, you will need to stop taking Hormonal Replacement Therapy, Botanotherapy, and Danazol at least 3 months before the study and avoid them for 12 months after the intervention. You also cannot be on anticoagulants or certain other medications during the study.

What data supports the effectiveness of the treatment PRP + tSVF for Premature Ovarian Failure?

A case report suggests that using platelet-rich autologous plasma (PRP) may help increase the ovarian reserve in patients with ovarian insufficiency, showing promising results in managing this condition. ^{1 2 3 4 5}

Is PRP treatment generally safe for humans?

Research on platelet-rich plasma (PRP) treatment, including its use for ovarian issues, suggests it is generally safe in humans. Studies have shown that PRP, derived from a person's own blood, has been used without significant safety concerns in various fertility-related treatments. ^{6 7 8 9 10}

How is the PRP + tSVF treatment for Premature Ovarian Failure different from other treatments?

The PRP + tSVF treatment is unique because it involves injecting platelet-rich plasma (PRP) directly into the ovaries, which may help improve ovarian function and increase fertility by promoting tissue regeneration and blood vessel growth. This approach is novel compared to traditional treatments, as it uses the patient's own blood components to potentially rejuvenate ovarian tissue. ^{6 7 8 11 12}

Eligibility Criteria

Women over 35 with Premature Ovarian Failure, Perimenopause, or hormone imbalance who've had symptoms for at least 6 months. Participants must not have used Hormonal Replacement Therapy or certain other treatments for 3 months and agree to avoid them for a year post-study. They should have at least one ovary and no history of ovarian cancer, untreated endocrine disorders, BMI >30 kg/m2, systemic autoimmune diseases, or mental health issues that would affect participation.

Inclusion Criteria

I stopped taking Hormonal Replacement Therapy over 3 months ago.

I have not taken Botanotherapy or Danazol for the last 3 months.

I agree to follow the study rules and not use hormone therapy or certain herbal treatments for a year after the study.

Exclusion Criteria

I have been diagnosed with cancer or had active cancer in the last 2 years.

I have a history of endometriosis.

I have an untreated hormone-related condition like thyroid issues or diabetes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intra-ovarian injections of PRP, tSVF, or cSVF to improve ovarian function

1 day

1 visit (in-person)

Follow-up

Participants are monitored for hormonal response, ovarian morphology, bone density, and quality of life improvements

18 months

Regular visits every 3 months

Long-term Monitoring

Continued monitoring of bone density and body composition changes

18 months

Treatment Details

Interventions

• Cellular Isolation cSVF
• Endovaginal Ultrasound
• lipoaspiration harvest tSVF
• Platelet Rich Plasma

Trial Overview The trial is testing the effectiveness of Platelet Rich Plasma (PRP) alone versus PRP combined with Stromal Vascular Fraction (tSVF/cSVF) in reactivating ovarian function. Women will receive imaging-guided intra-ovarian injections to compare how well these treatments work and how long their effects last.

Participant Groups

Group I: ARM 4 Intra-ovarian guided placement Experimental Treatment 1 Intervention

Specifically designed 23 gauge modified oocyte harvester needle for ultrasound guided placement

Group II: ARM 3 emulsified tSVF and PRP, enriched with cSVF Experimental Treatment 6 Interventions

Blood draw, processing of PRP, white blood cell poor, high platelet multiple \>/= 4, e.g. Emcyte PRP tSVF preparation: Lipoaspiration utilizing closed microcannula harvesting of small volume (Tulip tumescent fluid infiltrator and Tulip Harvester). Decanting of free lipid. Emulsification of adipose tissue (Tulip Nanofat device). cSVF preparation: lipoaspiration as above. Isolation and Concentration of cellular stromal vascular fraction (cSVF) using a Healeon Medical CentriCyte 1000 centrifuge, incubator and shaker plate with sterile Liberase enzyme (Roche Medical) per manufacturer protocol. Quantification of viable nucleated cell count with flow cytometry. Addition of pellet of viable nucleated cells to tSVF. Blending of tSVF/cSVF emulsion with PRP at a 3:1 ratio. Endovaginal ultrasound guided intra-ovarian placement into ovary, preferably both if accessible. Intervention:

Group III: ARM 2 emulsified tSVF and PRP Experimental Treatment 5 Interventions

Blood draw, processing of PRP, white blood cell poor, high platelet multiple \>/= 4, e.g. Emcyte PRP Lipoaspiration utilizing closed microcannula harvesting of small volume (Tulip tumescent fluid infiltrator and Tulip Harvester). Decanting of free lipid. Emulsification of adipose tissue into tSVF (Tulip Nanofat device). Blending of Nanofat with PRP at a 3:1 ratio. Endovaginal ultrasound guided intra-ovarian placement into ovary, preferably both if accessible.

Group IV: ARM 1 Platelet Rich Plasma Experimental Treatment 3 Interventions

Blood draw, processing of PRP, white blood cell poor, high platelet multiple \>/= 4, e.g. (Emcyte II Pure PRP) Endovaginal ultrasound guided intra-ovarian placement into ovarian parenchyma, preferably both if accessible.

Who Is Running the Clinical Trial?

Black Tie Medical, Inc.

Lead Sponsor

Trials

2

Recruited

110+

Findings from Research

Intraovarian injection of platelet-rich plasma (PRP) significantly improved oocyte count and quality in women with diminished ovarian reserve, with a 300% increase in oocytes for pregnant patients and a 125% increase for nonpregnant patients after treatment.

The study, which analyzed 60 out of 120 cases over a period from 2015 to 2020, found that PRP treatment also led to a significant increase in endometrial thickness and a decrease in follicle-stimulating hormone (FSH) levels, suggesting a positive impact on ovarian function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Platelet-Rich Plasma Treatment Increase In Vitro Fertilization (IVF) Success in the Infertile Population? Safarova, S., Cevher Akdulum, MF., Guler, I., et al.[2023]

Intraovarian injection of platelet rich plasma (PRP) shows promise in improving ovarian reserve markers and increasing oocyte and embryo yields in patients with poor ovarian response (POR) and primary ovarian insufficiency (POI), as indicated by several case series and one prospective trial.

Patients who previously failed treatment have reported multiple live births after receiving PRP injections, suggesting that this novel treatment could enhance fertility outcomes for those with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of intraovarian injection of autologous platelet rich plasma (PRP) in patients with poor ovarian response and premature ovarian insufficiency. Herlihy, NS., Seli, E.[2022]

Platelet-rich plasma (PRP) therapy may improve ovarian function and increase pregnancy chances in women with very low ovarian reserve and premature ovarian insufficiency, based on a review of 25 studies and 2 abstracts.

Despite some skepticism about PRP's role in fertility treatments, its low-risk profile and potential benefits warrant further investigation through larger randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian response to intraovarian platelet-rich plasma (PRP) administration: hypotheses and potential mechanisms of action. Seckin, S., Ramadan, H., Mouanness, M., et al.[2023]

In a study involving 28 female rats, platelet-rich plasma (PRP) was found to significantly protect ovarian function and improve oocyte count against damage caused by cyclophosphamide (CYC), a drug known to adversely affect fertility.

The results showed that rats treated with CYC plus PRP had a higher number of fertilized oocytes and better quality embryos compared to those treated with CYC alone, indicating that PRP enhances the effectiveness of in vitro fertilization procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective Effects of Platelet-rich plasma for in vitro Fertilization of Rats with Ovarian Failure Induced by Cyclophosphamide. Budak, Ö., Bostancı, MS., Toprak, V., et al.[2023]

Intra-ovarian injection of platelet-rich plasma (PRP) significantly increased anti-Müllerian hormone (AMH) levels in 22 women with poor ovarian reserve, suggesting a potential improvement in fertility.

While AMH levels rose after PRP treatment, there were no significant changes in antral follicle counts (AFC), indicating that while PRP may enhance ovarian function, it does not necessarily increase the number of visible follicles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-ovarian infusion of autologous platelet-rich plasma in women with poor ovarian reserve: A before and after study. Hosseinisadat, R., Farsi Nejad, A., Mohammadi, F.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

A new approach of using platelet-rich autologous plasma to increase the ovarian reservoir in a Syrian patient with ovarian insufficiency: A case report. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Thrombopoietin production in a patient with chronic thrombocytopenia after plasma infusion. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Simultaneous administration of TPO and G-CSF after cytoreductive treatment of rhesus monkeys prevents thrombocytopenia, accelerates platelet and red cell reconstitution, alleviates neutropenia, and promotes the recovery of immature bone marrow cells. [2006]

4. United States pubmed.ncbi.nlm.nih.gov

Cryopreservation of cord blood CD34+ cells before or after thrombopoietin expansion differentially affects early platelet recovery in NOD SCID mice. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The efficacy of single-dose administration of thrombopoietin with coadministration of either granulocyte/macrophage or granulocyte colony-stimulating factor in myelosuppressed rhesus monkeys. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Does Platelet-Rich Plasma Treatment Increase In Vitro Fertilization (IVF) Success in the Infertile Population? [2023]

7. England pubmed.ncbi.nlm.nih.gov

The use of intraovarian injection of autologous platelet rich plasma (PRP) in patients with poor ovarian response and premature ovarian insufficiency. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Ovarian response to intraovarian platelet-rich plasma (PRP) administration: hypotheses and potential mechanisms of action. [2023]

9. Brazil pubmed.ncbi.nlm.nih.gov

Protective Effects of Platelet-rich plasma for in vitro Fertilization of Rats with Ovarian Failure Induced by Cyclophosphamide. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Benefit of Autologous Platelet-Rich Plasma Infusion in Ovarian Function Rejuvenation: Evidence from a Before-After Prospective Pilot Study. [2023]

11. Ireland pubmed.ncbi.nlm.nih.gov

Intra-ovarian infusion of autologous platelet-rich plasma in women with poor ovarian reserve: A before and after study. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Intra-ovarian injection of platelet-rich plasma into ovarian tissue promoted rejuvenation in the rat model of premature ovarian insufficiency and restored ovulation rate via angiogenesis modulation. [2021]