The first experience of reproductive function restoration in patients with Asherman’s syndrome using autologous mesenchymal stem cells

Abstract

The main goal of Asherman’s syndrome treatment is to restore the volume and shape of the uterine cavity, regenerate the endometrium and reproductive function. Recently, in addition to ultrasound diagnostics of intrauterine synechiae, office hysteroscopy is widely used. The most standardized stages of Asherman’s syndrome treatment are hysteroscopic dissection of the uterine cavity synechiae and endometrium re-adhesion prevention in the postoperative period, which is achieved by the introduction of the intrauterine device, anti-adhesive drugs or balloon catheters inserted intrauterinely. The main difficulties are to find effective ways to prevent adhesion that occurs after removal of mechanical means from the uterine cavity and ways to restore the endometrium morphology in patients wishing to achieve pregnancy. The most promising technique in this area is the use of autologous endometrial stem cells. Here is a case of treatment of a reproductive age patient with infertility and Asherman’s syndrome. The clinical case was a part of a clinical trial Clinical Trials.gov Identifier: NCT04675970. On the eve of the operative stage for uterine cavity synechiae separation 20.0 ml of venous blood was taken. Mesenchymal stem cells (MSCs) were isolated from the patient’s peripheral blood using the magnetic separation method of the autoMACS Pro Separator (Miltenyi Biotec). According to the international instructions, 6th passage MSCs were clinically used. Confirmation of belonging the derived cells to the MSCs group was performed using the set Bio-Techne FMC-020 (Great Britain). In addition, MSCs were differentiated to endometrial cells, which was confirmed using endometrial cell matching markers in generations P0-P3 (passage 0 – passage 3) with the MicroBead Kit (USA). The operative stage of treatment included office hysteroscopy, mechanical synechiolysis in the endocervix and endometrium and introduction of a silver-containing intrauterine device. Subendometrial injection of autologous endometrial MSCs was performed to restore the endometrium structure at the end of hysteroscopy. High dose adjuvant estrogen therapy followed for 3 weeks. Pregnancy was achieved spontaneously 2 years after the intervention. The patient gave birth to a full-term baby girl.The results of the clinical case indicate the prospects for the use of autologous blood stem cells converted into endometrial cells in the treatment of infertility in patients with CA in the absence of effect from previous attempts to restore fertility by traditional therapies.