Human Reproduction keynote lecture
Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman’s syndrome and endometrial atrophy: a pilot cohort study
Xavier Santamari?a, Sergio Cabanillas, Irene Cervello?, Cristina Arbona, Francisco Raga, Jaime Ferro, Julio Palmero, Jose Remohi, Antonio Pellicer and Carlos Simo?n.
Study question
Could cell therapy using autologous peripheral blood CD133+ bone marrow- derived stem cells (BMDSCs) offer a safe and efficient therapeutic approach for patients with refractory Asherman’s syndrome (AS) and/or endometrial atrophy (EA) and a wish to conceive?
Summary answer
In the first 3 months, autologous cell therapy, using CD133+ BMDSCs in conjunction with hormonal replacement therapy, increased the volume and duration of menses as well as the thickness and angiogenesis processes of the endometrium while decreasing intrauterine adhesion scores.
What is known already
Asherman’s syndrome (AS) is characterized by the presence of intrauterine adhesions and endometrial atrophy (EA) prevents the endometrium from growing thicker than 5 mm, resulting in menstruation disorders and infertility. Many therapies have been attempted for these conditions, but none have proved effective.
Study design, size, duration
This was a prospective, experimental, non-controlled study. There were 18 patients aged 30–45 years with refractory AS or EA recruited, and 16 of these completed the study. Medical history, physical examination, endometrial thickness, intrauterine adhesion score and neoangiogenesis were assessed before and 3 and 6 months after cell therapy.
Participants/materials, setting, methods
After the initial hysteroscopic diagnosis, BMDSC mobilization was performed by granulocyte-CSF injection, then CD133+ cells were isolated through peripheral blood aphaeresis to obtain a mean of 124.39 million cells (range 42–236),which were immediately delivered into the spiral arterioles by catheterization. Subsequently, endometrial treatment after stem cell therapy was assessed in terms of restoration of menses, endometrial thickness (by vaginal ultrasound), adhesion score (by hysteroscopy), neoangiogenesis and ongoing pregnancy rate. The study was conducted at Hospital Clinico Universitario of Valencia and IVI Valencia (Spain).
Main results and the role of chance
All 11 AS patients exhibited an improved uterine cavity 2 months after stem cell therapy. Endometrial thickness increased from an average of 4.3 mm (range 2.7– 5) to 6.7 mm (range 3.1–12) (P=0.004). Similarly, four of the five EA patients experienced an improved endometrial cavity, and endometrial thickness increased from 4.2 mm (range 2.7–5) to 5.7 mm (range 5–12)(P=0.03). The beneficial effects of the cell therapy increased the mature vessel density and the duration and intensity of menses in the first 3 months, with a return to the initial levels 6 months after the treatment. Three patients became pregnant spontaneously,
resulting in two babies born, and a miscarriage. Furthermore, seven pregnancies were obtained after fourteen embryo transfers, resulting in three biochemical pregnancies, one miscarriage, one ectopic pregnancy, and two babies born.
Limitations, reasons for caution
Limitations of this pilot study include the small sample size and the lack of control group. It is consider as a phase I study for this advance cell therapy
Wider implications of the findings
This novel autologous cell therapy is a promising therapeutic option for patients with these incurable pathologies and a wish to conceive