The Therapeutic Potential of Multipotent Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Endometrial Regeneration.

Disruption of endometrial regeneration, fibrosis formation, and intrauterine adhesions underlie the development of "thin" endometrium and/or Asherman's syndrome (AS) and are a common cause of infertility and a high risk for adverse obstetric outcomes. The methods used (surgical adhesiolysis, anti-adhesive agents, and hormonal therapy) do not allow restoration of the regenerative properties of the endometrium. The experience gained today with cell therapy using multipotent mesenchymal stromal cells (MMSCs) proves their high regenerative and proliferative properties in tissue damage. Their contribution to regenerative processes is still poorly understood. One of these mechanisms is based on the paracrine effects of MMSCs associated with the stimulation of cells of the microenvironment by secreting extracellular vesicles (EVs) into the extracellular space. EVs, whose source is MMSCs, are able to stimulate progenitor cells and stem cells in damaged tissues and exert cytoprotective, antiapoptotic, and angiogenic effects. This review described the regulatory mechanisms of endometrial regeneration, pathological conditions associated with a decrease in endometrial regeneration, and it presented the available data from studies on the effect of MMSCs and their EVs on endometrial repair processes, and the involvement of EVs in human reproductive processes at the level of implantation and embryogenesis.

Feasibility of in vitro maturation of oocytes collected from patients with malignant ovarian tumors undergoing fertility preservation.

OBJECTIVE: In vitro maturation of oocytes collected from oophorectomy samples might be a promising approach in the field of oncofertility. In this study, we evaluate the feasibility of in vitro maturation of oocytes collected from oophorectomy samples in patients with ovarian tumors. METHODS: This prospective observational study included 27 patients with malignant ovarian tumors. Patients underwent oophorectomy and ovarian tissue was examined for the presence of immature cumulus-oocyte complexes. These were matured in vitro for 48 hours. Mature oocytes were vitrified or used for fertilization. Serum anti-müllerian hormone (AMH) levels were analyzed in 11 patients and cancer antigen 125 (CA125) levels in 16 patients. RESULTS: In this study, 99 cumulus-oocyte complexes were obtained from 17 patients (63%). The mean (SE) age of the patients was 33.47±1.86 years (range 16-44). A total of 14 patients had ovarian cancer (IA-IVB), one patient had ovarian cancer IC and endometrial cancer IA, one patient had endometrial cancer stage IA with metastasis into the ovary, and one patient had cervical cancer stage IIB with metastasis in the ovary. Oocytes were not obtained in 10 patients who had diminished ovarian reserve due to age (>38 years), chemotherapy, or previous surgical treatment. On average, 5.8 cumulus-oocyte complexes were obtained per patient. The maturation rate was 40.4% with an average of 2.8 metaphase II oocytes per patient. As a result of the study, 3 blastocysts in 3 patients and 22 oocytes in 9 patients were vitrified. CONCLUSIONS: In vitro maturation of oocytes collected from oophorectomy samples in patients with malignant ovarian tumors may result in oocyte and blastocyst vitrification. However, it should be offered to patients before surgery and chemotherapy. This method might be most beneficial in patients younger than 38 years, with AMH serum levels >1 ng/mL and without a large tumor burden.