Levels And Significance Of Serum PGE₂?IL-1??IL-18 Of Infertile Patients With Endometriosis

Objective:Endometriosis?EMs?,as a common disease in gynecology and reproductive diseases,has certainly adverse effects on women's reproductive health.Its occurrence and development are closely related to various cytokines,but there is no specific theory.The aims of the article are 1)to study the differences of clinical outcomes after assisted reproductive therapy for infertility patients with tubal dysfunction or EMs.2)To explore the possible correlation between Prostaglandin E₂?Prostaglandin E₂,PGE₂?,Interleukin-1??IL-1??,and Interleukin-18?IL-18?cytokines in the development of EMs,and to study the effects of serum PGE₂,IL-1?and IL-18 levels on IVF treatment process and outcome.We expect to provide suitable ideas for treatments on EMs-related infertility patients who have IVF-assisted reproductive therapy in the future.3)By in vitro cell experiments,we decide to verify whether the PGE₂ has the effect of promoting proliferation and migration of endometrial cells or not,the correlation between PGE₂and promoting the secretion of inflammatory factors by endometrial cells,and further understand the molecular mechanism between the pathogenesis of PGE₂ and EMs.Methods:1)We retrospectively analyze patients who underwent IVF in the First Hospital of Lanzhou University's Reproductive Medicine Specialist Hospital from 2016 to 2017,and divided them into EMs infertility group and control group,collect statistical data and analyze their treatment process and clinical outcomes.2)Women aged 20-40 years old who were treated with IVF in the First Affiliated Hospital of Lanzhou University on November 2018 to February 2019were enrolled.According to the inclusion criteria,they were Classified into EMs group?30 cases?and simple patients with tubal infertility?29cases?,serum PGE₂,IL-1?and IL-18 levels were measured by enzyme-linked immunosorbent assay.3)Ishikawa cells were used to replace primary endometrial cells.CCK8 and Transwell experiments were used to study the effect of PGE₂ on the proliferation rate and migration of Ishikawa cells.1×10^-6mol/L PGE₂ was added for culture and qRT-PCR was performed.The expression level of IL-1?mRNA was detected,the secretion level of IL-1?was detected by enzyme-linked immunosorbent assay,and the expression of P65 protein in NF-kB pathway was detected by Western-Blot assay.Analyze data using SPSS 2.0 software.Results:1)Compared with the control group,the EMs group had higher ovulation induction days and Gn usage,but there was no significant difference?P>0.05?.However,the quality of embryos and clinical pregnancy rate were significantly lower than those of simple tubal infertility?P<0.05?.There was no significant difference in the number of eggs obtained and the number of2PN between the two groups.2)Serum CA125 was significantly higher in the EMs group than in the control group?55.73±120.53 vs.17.41±9.42,P=0.04?,serum IL-1?was significantly increased?32.16±23.59 vs.21.97±32.16,P=0.030?,and PGE₂ levels were also significantly elevated?58.42±35.13 vs.39.85±13.59,P=0.008?;there was a significant positive correlation between serum PGE₂ and IL-1?,IL-18.However,serum PGE₂,IL-1?,and IL-18 levels were not correlated with the number of eggs obtained,the number of 2PN,the number of high-quality embryos,and the total amount of Gn.PGE₂ can significantly promoted the proliferation and migration of Ishikawa cells in a concentration-dependent manner.When 1×10^-6mol/L PGE₂ was applied to Ishikawa cells,IL-1?mRNA level was significantly increased?2???Ct=2.95±1.08,P<0.01?,and IL-1?was secreted?9.62±0.79 vs.11.06±1.34,P<0.01?.The level of p65 protein in the NF-?B pathway was increased,but there was no significant difference?13.53±3.66 vs.19.83±2.92,P=0.08?.Conclusions:The high-grade embryo rate and clinical pregnancy rate decreased significantly.And the serum levels of PGE₂ and IL-1?in the EMs-related infertility group were significantly higher than those in the simple tubal infertility group.There was no difference on IL-18 levels.This study showed that serum PGE₂,IL-1?,IL-18 were not associated with the number of eggs obtained,2PN number,number of high-quality embryos,and total amount of Gn.By the way,PGE₂ can significantly promote the proliferation and migration of endometrial cells,and directly promote the secretion of IL-1?on endometrial cells,resulting in local inflammation microenvironmental disorders.