Effect of intrauterine ozone therapy on Asherman syndrome, an experimental rat model.

BACKGROUND/AIMS: Evaluate the effect of ozone therapy alone or in combination with estradiol in management of Asherman syndrome in a rat model. MATERIALS AND METHODS: 48 rats were used and divided into eight groups. In all the groups right uterine horn was used for the experiment while the left horns received no action. Groups A underwent two operations, and groups B three times each. Group 1A and 1B were determined as the sham group. Ozone gas was given to Group 2 alone; estradiol orally was given to Group 3 alone; estradiol and ozone gas together was given to Group 4. RESULTS: In ozone therapy group; the diameter of the uterus, the uterine lumen and the uterine glands were increased, the endometrial epithelium was thicker in the group that received double ozone application, and the number and diameter of the endometrial gland increased in the combined use of ozone and estradiol. In the rats who underwent two surgeries, the maximum number of pregnancies and advanced pregnancies were observed in the left uterine horn. The minimum number of pregnancies were achieved in estradiol alone group. In the group receiving combined treatment with ozone and estradiol, pregnancies were observed at a higher gestational age. CONCLUSION: Ozone had a positive effect on the treatment of Asherman syndrome and has a significant impact on achieving pregnancy.

Cell-based therapy in thin endometrium and Asherman syndrome.

Numerous treatment strategies have so far been proposed for treating refractory thin endometrium either without or with the Asherman syndrome. Inconsistency in the improvement of endometrial thickness is a common limitation of such therapies including tamoxifen citrate as an ovulation induction agent, acupuncture, long-term pentoxifylline and tocopherol or tocopherol only, low-dose human chorionic gonadotropin during endometrial preparation, aspirin, luteal gonadotropin-releasing hormone agonist supplementation, and extended estrogen therapy. Recently, cell therapy has been proposed as an ideal alternative for endometrium regeneration, including the employment of stem cells, platelet-rich plasma, and growth factors as therapeutic agents. The mechanisms of action of cell therapy include the cytokine induction, growth factor production, natural killer cell activity reduction, Th17 and Th1 decrease, and Treg cell and Th2 increase. Since cell therapy is personalized, dynamic, interactive, and specific and could be an effective strategy. Despite its promising nature, further research is required for improving the procedure and the safety of this strategy. These methods and their results are discussed in this article.

Medicina natural y tradicional en el tratamiento de 3 mujeres con síndrome de Asherman / Natural and traditional medicine in the treatment of 3 women with Asherman syndrome

Se presentan 3 casos clínicos de féminas con síndrome de Asherman, procedentes del Policlínico Docente Ramón López Peña, tratadas con medicina natural y tradicional. Se aplicaron técnicas bioenergéticas (acupuntura y microsistema de oreja, hidroterapia, dietas hipotóxicas, reflexoterapia podal) y de respiración. Todas las pacientes mejoraron su cuadro clínico, pues se le restableció el flujo menstrual y la gestación, lo cual demostró la eficacia del tratamiento empleado(AU)

Three case reports of females with Asherman syndrome, belonging to Ramón López Peña Teaching Polyclinic, treated with natural and traditional medicine are presented. Bioenergetic techniques (acupuncture and ear microsystem, hydrotherapy, hipotoxic diets, foot reflex therapy) and breathing techniques were applied. All the patients improved their clinical pattern, because the menstrual flow and pregnancy were reestablished, which demonstrated the effectiveness of the treatment(A)

Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman's syndrome and endometrial atrophy: a pilot cohort study.

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: AS is characterized by the presence of intrauterine adhesions and 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 were 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 Clínico 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) ( ITALIC! 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) ( ITALIC! 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 one baby boy born, one ongoing pregnancy and a miscarriage. Furthermore, seven pregnancies were obtained after fourteen embryo transfers, resulting in three biochemical pregnancies, one miscarriage, one ectopic pregnancy, one baby born and one ongoing pregnancy. LIMITATIONS, REASONS FOR CAUTION: Limitations of this pilot study include the small sample size and the lack of control group. 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. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Spanish Ministry of Science and Innovation (SAF 2012-31017, Principal Investigator C.S.), Spanish Ministry of Health (EC11-299, Principal Investigator C.S.) and Regional Valencian Ministry of Education (PROMETEOII/2013/018, Principal Investigator C.S.). Four authors (X.S., I.C., A.P. and C.S.) are co-inventors of the patent resulting from this work (Application number: 62/013,121). S.C., C.A., F.R., J.F., J.P. and J.R. have no conflict of interest in relation to this work. TRIAL REGISTRATION NUMBER: This study was registered with ClinicalTrials.gov (NCT02144987).