Investigators will examine safety and efficiency of the cell product of autologous bone marrow-derived mesenchymal stem cells (MSC) for patients with repeated IVF failures and hypoplastic or/and fibrosis process of endometrium

Sixty patients eligible for the study will be divided to two groups (experimental and control) according to randomization (envelope) procedure in 1:1 ratio.

For patients of the main group bone marrow stem cells will be extracted from the crest of the ilium using standard methodology. After extraction and cultivation final product of autologous bone marrow-derived mesenchymal stem cells will be transplanted to endometrial cavity on menstrual cycle day 5-6. Meanwhile patients will receive three cycles of hormonal replacement therapy (4 mg Progynova (Bayer Pharma, Germany) daily on menstrual cycle day 5-25 in combination with 20 mg Duphaston (Abbott Healthcare Products, B.V., Netherlands) daily from day 15 to day 25. On day 20 of hormonal replacement therapy (HRT) of the last (third) cycle Pipelle-biopsy of endometrium will be performed. Obtained material will be analyzed by immunohistochemistry with the assessment of estrogen and progesterone receptors, VEGFa, GM-CSF, CD133+, CD34 and CD56. Ultrasound characteristics of endometrial quality will be registered on day 9-10 and day 19-21 of every cycle. When morphological and echographic parameters of endometrium are found satisfactory for embryo transfer, the HRT for endometrial preparation for frozen/thawed embryo transfer cycle will be initiated. If acceptable endometrial characteristics are not achieved, patients could be offered to undergo repeated (not more than 3) transplantation of MSC procedures.

Control group will receive three standard cycles of HRT following hysteroscopy before frozen/thawed embryo transfer. If endometrial characteristics are found unsatisfactory, gestational surrogacy might be offered.

Inclusion Criteria:

• Repeated IVF attempts with high and good quality embryo transfer in fresh and frozen IVF cycles;
• Age 20-44 years;
• Endometrial thickness less than 6 mm in 2 or more of HRT cycles for endometrial preparation for embryo transfer
• Hysteroscopic evidence of fibrosis processes of uterine cavity with the absence of positive dynamics of HRT in 3 months following operation;
• Signed informed consent.

Exclusion Criteria:

• Contraindication for pregnancy;
• Absence of cryopreserved embryos, stored at clinic's cryobank;
• BMI > 30 kg/m2;
• Impaired carbohydrate metabolism according to glucose tolerance test;
• Thrombosis in anamnesis;
• Oncological diseases in anamnesis;
• Diagnosed inherited thrombophilia;
• Uterine fibroids of more than 4 cm or more than 2 fibroids of 2.5 cm diameter;
• Nodal form of adenomiosis;
• Ovarian cysts more than 4 cm in diameter.