Open Randomized Trial of Clinical Efficiency and Safety of Cell Product of Autologous Bone Marrow-derived Mesenchymal Stem Cells for Reparative Treatment of Destructively Changed Endometrium in Patients With Repeated IVF Failures
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Assessment of endometrial receptivity
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 44 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Assessment of endometrial receptivity
时间窗: 3-6 month after randomization
combination of endometrial thickness on ultrasound and immunohistochemistry of endometrium assessed at the biopsy day of the third cycle of HRT
次要结局
- Clinical pregnancy rate(3-4 weeks after embryo transfer)
- Treatment-Emergent Adverse Events(3-6 month after randomization)
研究者
Valeria Muller
PhD, Medical Doctor of Assisted Reproduction Technologies department
D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology