RESUMO
Background and Aim: The Th17/Treg balance in peripheral blood and reproductive tissues may have a role in the etiology of unexplained recurrent pregnancy loss (URPL). In this study, we evaluated the major cytokine of Treg cells transforming growth factor-beta (TGF-ß), and their specific transcription factor Forkhead box P3 (FOXP3), as well as the most highlighted cytokine of Th17 cells (interleukin [IL]-17A) in both URPL patients and healthy women. Methods: Samples were extracted from the peripheral blood, endocervix, endometrium, and vagina of 14 patients with URPL and 12 normal non-pregnant women as a control (normal) group. Quantitative reverse transcription polymerase chain reaction was used to determine gene expression. Enzyme-linked immunosorbent assay was used to determine the levels of cytokines in the serum and cervicovaginal fluid. Results: We found that in the URPL group, FOXP3 gene expression was considerably higher in peripheral blood than in the normal group (P=0.043). TGF-ß levels in the cervicovaginal fluid were different in the URPL and normal groups (P=0.015). In comparison to the control group, women with URPL had significantly greater IL-17 gene expression in the peripheral blood (P=0.01). Conclusion: Lower TGF-ß levels in the cervicovaginal fluid of patients compared to controls may be related with increased IL-17 and FOXP3 mRNA levels in patients with URPL. Dysregulation of local immune responses in reproductive tissues may represent dysregulation of systemic regulatory immunological responses in the pathogenesis of URPL. Relevance for Patients: Dysregulation of immune responses may play a role in the pathogenesis of URPL at least in some patients with URPL. We conclude that the breakdown of tolerance in the local immune responses is more critical than the breakdown of tolerance in systemic tolerance in the pathogenesis of URPL. Therefore, modulating immune responses in the endometrium and decidua may be the focus of future therapeutic approaches in URPL. The impact of seminal plasma on the expansion of Tregs may provide a novel therapeutic intervention that has already been used in assisted reproductive technologies. Therefore, we suggest that transvaginal TGF-ß in women with URPL may induce maternal tolerance which leads to the successful pregnancy.
RESUMO
BACKGROUND: For infertile women aged over 35 years, failure of the ZP (zona pellucida) to rupture is believed to be associated with a decreased implantation rate in in vitro fertilization (IVF) or intra cytoplasmic sperm injection (ICSI). OBJECTIVE: In this research, laser assisted hatching (LAH) was offered to patients with advanced maternal age to evaluate a possible benefit. MATERIALS AND METHODS: Nine hundred thirty two cycles of IVF/ICSI in females were analyzed. Women included in this study were allocated in 4 groups. In group I and II, embryos were cultured and transferred with and without LAH in women aged ≤35, whereas embryos of group III and IV were examined with and without LAH in women aged ≥ 35. Laser manipulations were performed using a suturn-Tm3 system using 2-3 pulses of 0.8 millisecond with 400 voltage duration. The size of the hole made in the zona was measured to be 5-10 µm, depending on the zona thickness of each individual embryo. RESULTS: The performance of LAH significantly increased clinical pregnancy rates in all patients. In group I and II, the chemical (50.99% and 31.61% respectively), clinical (50% and 30.69% respectively) and multiple pregnancies (22.27% and 5.94% respectively) significantly differ between these groups. In the patients with advanced female age ≥35 the performance of LAH significantly increased chemical (30.12%) and clinical pregnancy (27.71%) rates compared to whom without LAH (18.96% and 16.37% respectively). CONCLUSION: Our data demonstrate in the patients who were less than 35 years old, multiple pregnancy rates were significantly increased compared to other groups who aged over 35 years old. In addition benefit of LAH in improving pregnancy rates after IVF or ICSI in women of advanced age (≥35) was shown.