Project UB-OVF
Long Term Follow up Patients With Premature Ovarian Failure ex Vivo Gene Therapy,
ClinicalTrials.gov Identifier: NCT04675970.
This is a multi-centers of long term safety and efficacy follow up study for patients with premature ovarian failure (the women aged younger than 40 years, who present with amenorrhoea, hypergonadotropic hypogonadism, and infertility) who have been treated with ex vivo gene therapy drug product in Institute of Bio-Stem Cell Rehabilitation UAB – sponsored clinical studies. After completing the parent clinical study (approximately 6 month), eligible subject will be followed for additional 2 years for total of 2 years and 6 month post drug product infusion. No investigation drug product will be administered in the study.
The main difficulties during the severe Asherman’s syndrome treatment are to find effective ways to prevent adhesions that occurs after removal of intrauterine synechia and to restore the endometrium morphology in patients wishing to achieve pregnancy. The most promising technology in this area is the use of autologous endometrial stem cells.
New method of Asherman’s syndrome treatment included hysteroscopic synechiolysis, subendometrial injection of autologous MSCs with an office hysteroscope; introduction of silver-IUD into the uterine cavity for 1 month, adjuvant estrogen therapy for 3 weeks. The 6th passage MSCs were clinically used. MSCs were differentiated to endometrial cells, which was confirmed by cell matching markers in generations P0-P3 with the MicroBead Kit (USA).The operative stage of treatment included outpatient hysteroscopy, mechanical synechiolysis, introduction of a silver-containing intrauterine device. Subendometrialinjection of 4 million autologous endometrial MSCs was performed at the end of hysteroscopy. High dose adjuvant estrogen therapy followed for 3 weeks. In a month the patients underwent IUD removal, second-look office hysteroscopy, additional synechiolysis, subendometrial injection of 2 millions of autologous endometrial cells.
16-20 months after last procedure, as a result of spontaneous conception, patients gave birth to a live full-term babies, postpartum period without complications.
The results of the clinical cases indicate the prospects for the use of autologous blood stem cells converted into endometrial cells in the treatment of infertility in patients with Asherman’s syndrome in the absence of effect from previous attempts to restore fertility by traditional therapy.