Author:
Mashayekhi M.,Mirzadeh E.,Chekini Z.,Ahmadi F.,Eftekhari-Yazdi P.,Vesali S.,Madani T.,Aghdami N.
Abstract
Abstract
Background
Premature ovarian failure (POF) is characterized by the loss of ovarian activity before the age of 40 years. Stem cell therapy has the capability to create a regenerative microenvironment and is a proposed treatment for POF-related infertility due to the presence of renewal folliculogenesis and germ cells in the adult ovaries. In this study, we assessed the safety, feasibility, efficacy and dose adjustment of autologous adipose-derived stromal cells (ADSCs) and their ability to improve ovarian function in POF patients.
Methods
This study was a non-randomized clinical trial, phase I. Nine women with a definitive diagnosis of POF were divided into three groups (n = 3 per group) that received either 5 × 106, 10 × 106, or 15 × 106 autologous ADSCs suspension transplanted in the one ovary. Participants were followed-up at 24 h after the transplantation, and at 1 and 2 weeks, and 1, 2, 3, 6, and 12 months after the transplantation. The primary objective was to evaluate the safety of ADSCs transplantation. Secondary objectives included the effects of ADSCs transplantation on the resumption of menstruation, hormones level (Follicle-stimulating hormone (FSH) and anti-Müllerian hormone), ovarian function (Antral follicle count and ovary volume by ultrasonography evaluation) as well as dose escalation.
Results
Participants had not shown any early-onset possible side effects and secondary complications during follow-up. The menstruation resumption was observed in four patients which established for several months. In the 15 × 106 group, two POF patients had a return of menstruation second months after the intervention. Two other POF patients in 5 × 106 and 10 × 106 cell groups reported menstruation resumption at 1 month after the intervention. We observed decreased serum FSH levels of less than 25 IU/l in four patients. In two patients in 5 × 106 and 10 × 106 cell groups, serum FSH showed an inconsistent decline during a 1 year follow up after ADSCs transplantation. The ovarian volume, AMH, and AFC were variable during the follow-up and no significant differences between cell groups (p > 0.05).
Conclusions
We showed the intra-ovarian embedding of ADSCs is safe and feasible and is associated with an inconsistent decline in serum FSH. This should be further investigated with a large RCT.
Trial registration
NCT02603744, Registered 13 November 2015 - Retrospectively registered, http://www.Clinicaltrials.gov
Publisher
Springer Science and Business Media LLC
Subject
Obstetrics and Gynaecology,Oncology
Reference33 articles.
1. Beck-Peccoz P, Persani L. Premature ovarian failure. Orphanet J Rare Dis. 2006;1(1):9.
2. Shelling AN. Premature ovarian failure. Reproduction. 2010;140(5):633–41.
3. POI EGGo, Webber L, Davies M, Anderson R, Bartlett J, Braat D, et al. ESHRE guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016;31(5):926–37.
4. Ayesha VJ, Goswami D. Premature ovarian failure: an association with autoimmune diseases. J Clin Diagn Res. 2016;10(10):QC10.
5. Vegetti W, Marozzi A, Manfredini E, Testa G, Alagna F, Nicolosi A, et al. Premature ovarian failure. Mol Cell Endocrinol. 2000;161(1–2):53–7.
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