Use of Autologous Exosomes vs Platelet Growth Factors to Regenerate the Ovary in Women With Infertility (Exosomas2024-1)

NCT06773572 | Completed

• 2 other identifiers: Exosom2024-1Eficacia en el uso de exosomas
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Ovarian stromal fibrosis resulting from each ovulation and due to aging is characterized by a decrease in hyaluronic acid concentrations, loss of synthesis and migration proteins CD63 and CD81, decreased miRNA125, miRNA21, miRNA132 and miRNA199. Also, enzymatic alterations affecting kinases and mitochondrial sirtuins SIRT3-5 with increased oxygen free radicals preventing the normal maintenance and development of folliculogenesis, leading to the inability to reproduce at advanced ages and accelerating the onset of pathologies secondary to the decrease of ovarian estrogens. Methodology: An observational, prospective, randomized, comparative, double-blind, analytical pilot study in 30 women between 38 and 46 years of age, with diminished ovarian reserve and who refused the egg donation procedure. Three groups were designated: one for autologous exosomes, one for PRP and one with physiological solution.

Conditions

Infertility, Female; Reproductive Techniques, Assisted

Keywords

reproductive function; exosomes; follicular function; fertility; pregnancies

Outcome Measures

Primary Outcomes (1)

• Primary Phase

  This study was carried out on a total of 30 patients, with an average age of 41.20 ± 2.86 years, for a minimum age of 38 and a maximum of 46 years (53.3% with ages ≤ 40 years and 46.7% aged \> 40 years), with a desire to become mothers, with a previous diagnosis of resistance or ovarian failure and who also refuse egg donation.

  Follow-up for 12 weeks for each patient.

Secondary Outcomes (1)

• Follow-ups at birth

  From the procedure to birth

Other Outcomes (1)

• Evaluation of the parameters of the second control that included

  Monitoring during pregnancy until birth

Study Arms (3)

Autologous Exososomes procedure obtained from the patients' own platelets.

ACTIVE COMPARATOR

Intraovarian injection (into the ovarian cortex) was performed over four cycles, once a month in each ovary on days 7, 8, or 9 of the menstrual cycle. Blood was drawn using the selected PRP kit; in this case, all the PRP was placed into two 20 cc syringes and filtered for exosomes using the EXOSMAT kit for autologous platelet exosomes. As a result, 5 to 6 cc of liquid composed exclusively of platelet-derived exosomes was obtained, with a concentration of 5 to 6 trillion exosomes per milliliter. Finally, 2 to 3 cc were administered to each ovary via the transvaginal route.

Procedure: Autologous Exososomes procedure obtained from the patients' own platelets.

Patient group for activated platelet growth factors

ACTIVE COMPARATOR

Intraovarian injection (into the ovarian cortex) was performed over four cycles, once a month in each ovary on days 7, 8, or 9 of the menstrual cycle. The plasma was prepared in two 5 cc syringes to administer 2 to 3 cc into each ovary (into the ovarian cortex) with the patient under sedation. The PRP was applied via the transvaginal route using a follicular aspiration needle for the PRP group.

Procedure: Patient group for activated platelet growth factors

3. Group of patients for physiological solution.

PLACEBO COMPARATOR

A total of 2 to 3 cc of saline solution was administered into each ovarian cortex over four cycles, following the same protocol as the previous two groups.

Procedure: the control group

Interventions

Autologous Exososomes procedure obtained from the patients' own platelets. PROCEDURE

Intraovarian injection (into the ovarian cortex) was performed over four cycles, once a month in each ovary on days 7, 8, or 9 of the menstrual cycle. Blood was drawn using the selected PRP kit; in this case, all the PRP was placed into two 20 cc syringes, and the exosomes were filtered using the EXOSMAT kit for autologous platelet exosomes. A total of 5 to 6 cc of liquid composed exclusively of platelet-derived exosomes was obtained, with a concentration of 5 to 6 trillion exosomes per milliliter. Finally, 2 to 3 cc were administered to each ovary via the transvaginal route.

Autologous Exososomes procedure obtained from the patients' own platelets.

Patient group for activated platelet growth factors PROCEDURE

the plasma was placed in two 5 cc injectors to place 2 to 3 cc in each ovary (in the ovarian cortex) with the patient sedated. The PRP was placed transvaginally and using a follicular aspiration needle for the PRP group. All biostimulations were performed in early follicular phase (day 7, 8 or 9) in all groups according to their assigned technique.

Patient group for activated platelet growth factors

the control group PROCEDURE

Finally, the control group received 2 to 3 cc of physiological solution in each ovarian cortex for 4 cycles as the two previous groups. All these procedures were performed transvaginally under controlled surgical sedation with follicular aspiration needle in the ovarian cortex and guided by transvaginal echosonogram

3. Group of patients for physiological solution.

Eligibility Criteria

• Age: 38 Years - 48 Years
• Gender Eligibility Details: Women aged 38 to 46 years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female patients between 38 and 46 years of age.
• Patients with a desire to become a mother
• Patients with Body Mass Index (BMI) between 23 and 30.
• Patients with proven ovarian insufficiency, according to the parameters mentioned above.
• Patients who refuse egg donation.
• Patients with full willingness to participate in the study and who have understood and signed the informed consent.
• Patients with both ovaries without oncological pathologies, active endometriomas or suspicious ovarian or other tumors.
• Patients with platelet count over 250 thousand.
• Patients with no history of hematological diseases.
• Patients without treatment with anticoagulants.
• Patients with no active infection at the time.

You may not qualify if:

• Female patients outside the age range of 38 to 46 years old.
• Patients who are not willing to become mothers.
• Patients with a BMI outside the range of 23 to 30
• Patients without ovarian insufficiency
• Patients who do not wish to participate in the procedure and have not signed the informed consent form.
• Patients with suspected or diagnosed oncological diseases.
• Patients with platelet count of less than 250 thousand
• Patients with a history of hematological diseases.
• Patients with anticoagulant treatment.
• Patients with any type of active infection.

Sponsors & Collaborators

• Biotech Fertility C.A.: lead

Study Sites (1)

Biotech Fertility C.A

Caracas, 1080, Venezuela

Location

Related Publications (3)

• Bhatta M, Majumdar A, Ghosh U, Ghosh P, Banerji P, Aridoss S, Royal A, Biswas S, Venkatesh BT, Adhikary R, Dutta S. Sexually transmitted infections among key populations in India: A protocol for systematic review. PLoS One. 2023 Mar 13;18(3):e0279048. doi: 10.1371/journal.pone.0279048. eCollection 2023.

  PMID: 36913427 BACKGROUND

• Melo P, Navarro C, Jones C, Coward K, Coleman L. The use of autologous platelet-rich plasma (PRP) versus no intervention in women with low ovarian reserve undergoing fertility treatment: a non-randomized interventional study. J Assist Reprod Genet. 2020 Apr;37(4):855-863. doi: 10.1007/s10815-020-01710-z. Epub 2020 Feb 7.

  PMID: 32030554 RESULT

• Navarro C, Torrecillas Cabrera P, Teppa Garran A. Comparative analysis of the use of autologous exosomes and platelet-derived growth factors in women with premature ovarian insufficiency and infertility: A prospective, randomized, observational, analytical study. Regen Ther. 2025 Jun 30;30:309-320. doi: 10.1016/j.reth.2025.06.007. eCollection 2025 Dec.

  PMID: 40678344 DERIVED

MeSH Terms

Conditions

Infertility, Female; Helping Behavior

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility; Social Behavior; Behavior

Study Officials

• Carmen T Navarro Arrieta, Odontology

  Biotech Fertility C.A.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Human Reproduction Specialist

Model Details: An observational, prospective, randomized, comparative, double blind and analytic pilot study conducted in a fertility clinic in Caracas, Venezuela from January 2024 to September 2024, where a total of 30 patients between 38 and 46 years of age willing to become mothers underwent ovarian biostimulation procedures. Interventional Study Model: This is a quantitative correlational, inter and intra group study that aims to measure the response of the aged or resistant ovary to the contribution of platelet growth factors in activated PRP, Autologous Exosomes and their different components such as Micro-mRNA, Proteins, Sirtuins and extracellular matrix stimulants, in addition to the response to the action of the physiological solution and the trauma of ovarian puncture to reactivate the ovary, favoring the formation of new oocytes contained in the so-called Oogonia Nests.

Study Record Dates

• First Submitted: December 22, 2024
• First Posted: January 14, 2025
• Study Start: January 3, 2024
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: January 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, CSR
• Time Frame: Once the study is published in the definitive journal, you will be able to obtain all the data for a period of two years after its publication.
• Access Criteria: Medical specialists in Human Reproduction will be able to access the original tables and graphs of the study and inquire about the methodology and type of materials and supplies used.

Locations

VE (1)