In Vitro Oocyte Maturation With Autologous Exosomes in Women

NCT07249411 | Completed

• 1 other identifier: Exosom2025-1
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a preliminary, prospective, randomized, controlled clinical trial designed to evaluate the safety and feasibility of supplementing in vitro maturation (IVM) media with autologous exosomes in women with diminished ovarian reserve undergoing assisted reproductive technology. The purpose of the study is to determine whether autologous exosomes can support the meiotic progression of immature metaphase I oocytes during a 24-36 hour culture period and to establish whether the intervention is safe, biologically feasible, and suitable for further clinical evaluation. Mature oocytes obtained after culture are fertilized using intracytoplasmic sperm injection, and resulting embryos are cryopreserved for future transfer in a subsequent phase of the research. No embryo transfer is performed during this preliminary phase.

Conditions

Diminished Ovarian Reserve

Keywords

Oocyte maturation; Meiotic arrest; In vitro maturation; Autologous exosomes; Diminished ovarian reserve; Assisted reproductive technology

Outcome Measures

Primary Outcomes (2)

• Proportion of Metaphase I Oocytes Reaching Metaphase II After In Vitro Cultureautologous exosomes obtained using the ExoSMarT® exosome filtration system

  This measure evaluates the number and proportion of metaphase I oocytes that progress to the metaphase II stage after 24-36 hours of in vitro culture in either conventional IVM medium or IVM medium supplemented with autologous exosomes. Maturation will be identified by the presence of the first polar body. Data will be summarized as a proportion of total metaphase I oocytes cultured.

  24-36 hours

• Number of Mature Oocytes Fertilized After Intracytoplasmic Sperm Injection (ICSI)

  This measure records the number and proportion of in vitro-matured metaphase II oocytes that demonstrate normal fertilization after ICSI, defined by the presence of two pronuclei under standard embryology laboratory criteria.

  Approximately 18 hours after ICSI

Study Arms (2)

MI oocytes were cultured in conventional IVM medium supplemented with 10 µg of autologous exosomes o

ACTIVE COMPARATOR

* Group I (Control): MI oocytes were cultured exclusively in conventional IVM medium (VITROLIFE®). * Group II (Experimental): MI oocytes were cultured in conventional IVM medium supplemented with 10 µg of autologous exosomes obtained using the ExoSMarT® exosome filtration system

Other: MI oocytes were cultured in conventional IVM medium supplemented with 10 µg of autologous exosomes obtained using the ExoSMarT® exosome filtration system

MI oocytes were cultured exclusively in conventional IVM medium (VITROLIFE®).

ACTIVE COMPARATOR

MI oocytes were cultured exclusively in conventional IVM medium (VITROLIFE®).

Other: MI oocytes were cultured in conventional IVM medium supplemented with 10 µg of autologous exosomes obtained using the ExoSMarT® exosome filtration system

Interventions

MI oocytes were cultured in conventional IVM medium supplemented with 10 µg of autologous exosomes obtained using the ExoSMarT® exosome filtration system OTHER

MI oocytes were cultured in conventional IVM medium supplemented with 10 µg of autologous exosomes obtained using the ExoSMarT® exosome filtration system

MI oocytes were cultured exclusively in conventional IVM medium (VITROLIFE®).; MI oocytes were cultured in conventional IVM medium supplemented with 10 µg of autologous exosomes o

Eligibility Criteria

• Age: 38 Years - 48 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women with primary or secondary infertility associated with diminished ovarian reserve, defined by ultrasound findings and laboratory parameters (FSH \> 10 mIU/mL and estradiol \< 60 pg/mL).
• Serum anti-Müllerian hormone (AMH) concentration \< 1 ng/mL.
• Antral follicle count \< 3-6 follicles per ovary.
• Anatomical preservation of both ovaries.
• Body mass index (BMI) between 24.5 and 30 kg/m².
• Absence of active oncological pathologies or connective tissue diseases (collagenopathies).
• No history of clinically relevant hematological disorders.
• Adequate serum levels of vitamins essential for reproductive function, including vitamin D, B-complex, and vitamin C.
• Last live birth within ≤ 10 years prior to study initiation.
• Normal thyroid function (TSH and free thyroid hormones within range).
• Absence of antiphospholipid antibody syndrome.
• Male partner with semen parameters within normal limits, according to the World Health Organization (WHO) criteria, 2010 (5th edition) and 2021 (6th edition).
• Signed informed consent for participation in the study.

You may not qualify if:

• Patients without a diagnosis of infertility.
• Women without documented diminished ovarian reserve.
• Serum anti-Müllerian hormone (AMH) concentration \> 1 ng/mL.
• Antral follicle count \> 3-6 follicles per ovary.
• Absence of one or both ovaries.
• Body mass index (BMI) \> 30 kg/m².
• Presence of active oncological pathologies or connective tissue diseases (collagenopathies).
• History of clinically relevant hematological disorders.
• Deficient or altered serum levels of vitamins essential for reproductive function (vitamin D, B-complex, and vitamin C).
• Last live birth \> 10 years prior to study initiation.
• Altered thyroid function (TSH or free thyroid hormones out of range).
• History of antiphospholipid antibody syndrome.
• Male partner with abnormal semen parameters according to the World Health Organization (WHO) criteria, 2010 (5th edition) and 2021 (6th edition).
• Refusal to sign informed consent for study participation.

Sponsors & Collaborators

• Biotech Fertility C.A.: lead

Study Sites (1)

Biotech Fertility C.A

Caracas, 1080, Venezuela

Location

Related Publications (16)

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• Chand AL, Legge M. Amino acid transport system L activity in developing mouse ovarian follicles. Hum Reprod. 2011 Nov;26(11):3102-8. doi: 10.1093/humrep/der298. Epub 2011 Sep 13.

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• Kiyama R, Wada-Kiyama Y. Estrogenic endocrine disruptors: Molecular mechanisms of action. Environ Int. 2015 Oct;83:11-40. doi: 10.1016/j.envint.2015.05.012. Epub 2015 Jun 11.

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• Coticchio G, Dal Canto M, Mignini Renzini M, Guglielmo MC, Brambillasca F, Turchi D, Novara PV, Fadini R. Oocyte maturation: gamete-somatic cells interactions, meiotic resumption, cytoskeletal dynamics and cytoplasmic reorganization. Hum Reprod Update. 2015 Jul-Aug;21(4):427-54. doi: 10.1093/humupd/dmv011. Epub 2015 Mar 4.

  PMID: 25744083 BACKGROUND

• Esbert M, Reig A, Ballestros A, Seli E. Oocyte maturation defect in women undergoing IVF: contributing factors and effects on mature sibling oocyte outcomes. J Assist Reprod Genet. 2025 Mar;42(3):773-780. doi: 10.1007/s10815-024-03353-w. Epub 2025 Jan 9.

  PMID: 39786528 BACKGROUND

• Coticchio G, Cimadomo D, Rienzi L. The daunting goal to rescue oocytes collected immature in conventional ovarian stimulation cycles. Fertil Steril. 2025 May;123(5):747-748. doi: 10.1016/j.fertnstert.2025.02.026. Epub 2025 Feb 22.

  PMID: 39993495 BACKGROUND

• 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 BACKGROUND

• Tornell J, Billig H, Hillensjo T. Resumption of rat oocyte meiosis is paralleled by a decrease in guanosine 3',5'-cyclic monophosphate (cGMP) and is inhibited by microinjection of cGMP. Acta Physiol Scand. 1990 Jul;139(3):511-7. doi: 10.1111/j.1748-1716.1990.tb08953.x.

  PMID: 2173353 BACKGROUND

• Cho WK, Stern S, Biggers JD. Inhibitory effect of dibutyryl cAMP on mouse oocyte maturation in vitro. J Exp Zool. 1974 Mar;187(3):383-6. doi: 10.1002/jez.1401870307. No abstract available.

  PMID: 4362350 BACKGROUND

• Dekel N, Beers WH. Development of the rat oocyte in vitro: inhibition and induction of maturation in the presence or absence of the cumulus oophorus. Dev Biol. 1980 Mar 15;75(2):247-54. doi: 10.1016/0012-1606(80)90160-8. No abstract available.

  PMID: 6154623 BACKGROUND

• Schultz RM, Montgomery RR, Belanoff JR. Regulation of mouse oocyte meiotic maturation: implication of a decrease in oocyte cAMP and protein dephosphorylation in commitment to resume meiosis. Dev Biol. 1983 Jun;97(2):264-73. doi: 10.1016/0012-1606(83)90085-4.

  PMID: 6189752 BACKGROUND

• Horner K, Livera G, Hinckley M, Trinh K, Storm D, Conti M. Rodent oocytes express an active adenylyl cyclase required for meiotic arrest. Dev Biol. 2003 Jun 15;258(2):385-96. doi: 10.1016/s0012-1606(03)00134-9.

  PMID: 12798295 BACKGROUND

• Hinckley M, Vaccari S, Horner K, Chen R, Conti M. The G-protein-coupled receptors GPR3 and GPR12 are involved in cAMP signaling and maintenance of meiotic arrest in rodent oocytes. Dev Biol. 2005 Nov 15;287(2):249-61. doi: 10.1016/j.ydbio.2005.08.019. Epub 2005 Oct 17.

  PMID: 16229830 BACKGROUND

• Kovanci E, Rohozinski J, Simpson JL, Heard MJ, Bishop CE, Carson SA. Growth differentiating factor-9 mutations may be associated with premature ovarian failure. Fertil Steril. 2007 Jan;87(1):143-6. doi: 10.1016/j.fertnstert.2006.05.079. Epub 2006 Dec 6.

  PMID: 17156781 BACKGROUND

• Vaccari S, Horner K, Mehlmann LM, Conti M. Generation of mouse oocytes defective in cAMP synthesis and degradation: endogenous cyclic AMP is essential for meiotic arrest. Dev Biol. 2008 Apr 1;316(1):124-34. doi: 10.1016/j.ydbio.2008.01.018. Epub 2008 Jan 26.

  PMID: 18280465 BACKGROUND

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Reproductive Endocrinologist Consultant of Reproductive Medicine and Laparoscopic Surgery

Model Details: prospective, randomized, controlled clinical trial designed to evaluate the safety and efficacy of the intervention in women diagnosed with infertility.

Study Record Dates

• First Submitted: November 13, 2025
• First Posted: November 25, 2025
• Study Start: January 2, 2023
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

VE (1)