| Postpartum hemorrhage(PPH)remains an important cause of maternal mortality worldwide,accounting for more than 25%of maternal mortality.In 1997,B-Lynch et al.introduced B-Lynch uterus compression suture and many postpartum hemorrhage women were treated and avoided hysterectomy.Since then,various modified uterine compression sutures have been reported.However,in recent years,complications related to uterine compression suture(UCS)have also been reported successively,such as myometrial damage,necrosis;catastrophic uterine rupture in the middle and late pregnancy;intrauterine adhesions(IUA),secondary infertility,etc.In fact,this is just the tip of the iceberg.Many complications associated with it have not been reported.A small number of foreign experts and scholars have noticed and paid more attention to the occurrence of complications,especially IUA and secondary infertility and made further reminders.But the feasible solution has yet to be reported.The current study suggests that long-term ischemia and hypoxia result in endometrial cell degeneration and necrosis,and the lose of normal regeneration and fibrous connective tissue hyperplasia are important causes of IUA.The uterine cavity on outside of the suture line is relatively closed,the blood drainage is not smooth,and it is easy to cause local endometritis.The local inflammation and the absorption time of suture all play an important role in the occurrence of IUA.Poujade et al.reported that the rate of IUA after UCS was 26.7%(4/15).The impact on normal pregnancy of IUA after UCS has been a matter of general concern.Previous studies has proved that IUA can reduce female fertility and cause infertility and has become the second cause of female secondary infertility.So,there is an urgent need to design a surgical approach which can treat PPH effectively and meanwhile reduce the IUA and infertility rate.Therefore,detachable uterine compression suture(RUCS)was designed.After hemostasis,the suture should be removed in time to reduce the complications related to compression suture.In the first part,through clinical case-control studies,this topic is to investigate the safety and effectiveness of RUCS for the treatment of uterine atony-induced PPH and to clarify the feasibility of reducing the complications associated with uterine compression suture by RUCS.Embryonic migration and implantation require good interaction and receptivity between the embryonic trophoblast and endometrium.Endometrial receptivity is characterized by the specific state in which the endometrium allows embryo adhesion and implantation,which is one of the key factors in the establishment of pregnancy.it is important to identify markers of endometrial receptivity for the evaluation of endometrial state.Many studies suggest that HOXA10?LIF?integrin ?V?3 are the iconic molecule for endometrial receptivity.HOXA10 have a pleiotropic effect on adult endometrial,including interstitial decidualization,cell infiltration,and pinopode growth.Its pleiotropic effects may be achieved by regulating downstream target genes,including the genes EMX2?IGFBP-1 and integrin ?V?3.The genes EMX2 and IGFBP-1 are downregulated,while integrin ?V?3 is upregulated.Integrin ?V?3,the first target gene of HOXA10 found in the endometrium,acts as a bridge molecule between the endometrium and trophoblast.LIF is regulated by HOXA11 and is essential for early embryo implantation and growth.LIF can induce endometrial cells to express genes ITGAV,ITGB3 and ITGB5.In the second part,UCS rat model was established to observe the pathological changes of endometrium under lightmicroscope,implantation embryos and the expression of endometrial receptive makers HOXA10,LIF and ?V?3,to explore the molecular mechanism of UCS-related infertility.These results will provide a theoretical basis for the feasibility of RUCS to reduce UCS-related complications and increasing the conception rate,explore the effect of different uterine compression time on endometrial injury in rats,and provide theoretical basis for clinical screening for the best time to remove stitches.Part I Clinical analysis of RUCS to reduce postpartum hemorrhage compression suture related complicationsObjectiveTo explore the safety and efficacy of RUCS for the treatment of uterine atony-induced PPH and to clarify the feasibility of RUCS to reduce uterine compression suture related complications.MethodsIn this study,a retrospective analysis method was adopted.Forty women with intractable PPH due to uterine atony during cesarean section in the obstetric department of Qianfoshan Hospital of Shandong Province from June 2013 to May 2017 were divided into study group and control group,twenty each group.RUCS was applied in study group and traditional compression suture was used in control group.All subjects gave birth by cesarean section again after compression suture.Hemostatic effect,blood loss during cesarean section and 2 hours,24 hours,48 hours after operation,recent postoperative complications(postoperative fever,recovery time of infection index,antibiotic application time,duration of lochia,ultrasound of uterine at 42 days postpartum),long-term postoperative complications(IUA,placental adhesion,uterine necrosis,uterine rupture etc.)were compared between the two groups.Results1.By comparing the hemostatic effect between the two groups,it was found that the success rate in study group was 95%and that in control group was 100%.There was no significant difference between the two groups(P>0.05).2.By comparing the blood loss during and 2,24,and 48 hours after operation between the two groups,it was found that the bleeding volume of the study group was 750±102ml in operation,51.8±10.1ml at 2 hours,164.5±17.3ml at 24 hours after operation.And the compression suture was removed 24 hours after surgery to observe the bleeding amount.The bleeding volume was 201.2±16.3ml at 48 hours after operation;The corresponding values of the control group were 720±90ml in operation,55.0±9.9ml,158.6±16.8ml,and 211.3±15.7ml at 2,24 and 48 hours after operation,respectively.There was no significant difference between the two groups(P>0.05).3.By comparing the incidence of recent postoperative complications between the two groups,it was found that in study group 2 patients had a fever with the temperature higher than 38?,antibiotic application time was 2.6±0.9 days,and white blood cells were 12.4±2.2×109 at 72 hours after operation.,the duration of lochia was 32.4±3.9 days,the uterine involution rate was 100%at 42 days postpartum;in control group,8 patients had a fever with the temperature higher than 38?,the antibiotic application time was 3.8±1.2 days,and the white blood cell was 14.5±3.4×109 at 72 hours after operation,the duration of lochia was 38.6±3.2 days,and the uterine involution rate was 70%at 42 days postpartum.The indexes of the study group were significantly better than those of the control group(P<0.05).No uterine necrosis occurred in either group.4.By comparing the hysteroscopy results performed half a year after cesarean between the two groups,it was found no uterine adhesion occurred in study group.However,the light,medium and severe adhesions in control group were 4,1,and 1 cases,respectively.The different totality between the two groups was statistically significant(P<0.05).5.By comparing the incidence of long-term postoperative complications between the two groups,it was found that there were significant differences in the incidence of IUA,placental adhesion,pelvic adhesion,local myometrial necrosis between the two groups(P<0.05).The secondly infertility rate was lower in the study group,but the difference was not statistically significant(P>0.05).There was no significant difference in the incidence of uterine rupture(P>0.05).The blood loss during the second cesarean was 769±99ml in study group and 899±106m in control group,the difference was statistically significant(P<0.05).Conclusion1.RUCS has the same effectiveness in treating PPH compared with traditional UCS.2.RUCS can reduce the occurrence of complications related to UCS and make higher safety.RUCS have protective function on PPH happened in repeated cesarean section.3.By reducing endometrial compression time,RUCS can lessen endometrial damage,cut down the incidence of IUA and potentially improve embryonic implantation rate.Part ?:Molecular biological mechanism of RUCS to reduce endometrial receptive damage in ratsObjectiveUCS rat model was established to observe the pathological changes of endometrium under light microscope,implantation embryos and the expression changes of endometrial receptive makers HOXA10,LIF and ?V?3,to explore the mechanism of UCS-related infertility and the feasibility of RUCS to reduce UCS-related infertility and improve conception rate.To explore the effect of different uterine compression time on endometrial injury in rats,and provide theoretical basis for clinical screening for the best time to remove stitches.MethodsForty SPF healthy female Sprague-Dawley rats,aged 12 weeks,were randomly divided into two groups:group A and group B,20 rats each.In group A,UCS was performed on the left uterus of each rat as the UCS group,UCS was not performed on the right uterus,and it was used as the control group;In group B,UCS was performed on the left uterus of each rat as the UCS group,and RUCS was performed on the right uterus,and the compression suture was removed at 24 hours after surgery as the RUCS group.At the same time,In group C,30 SD rats were randomly divided into three groups,0-hour-RUCS group,24-hour-RUCS group,48-hour-RUCS group.The uterine compression suture was removed at 0,24 and 48 hours after surgery respectively.The endometrium was taken out on the 4th day of pregnancy after three estrous cycles.The embryo number and histopathological changes of the endometrium under light microscope were observed.The endometrial HOXA10,LIF,and ?V?3 mRNA and protein expression levels were detected by qRT-PCR,western blot and immunohistochemistry.Results1.The pathological changes of endometrium under light microscope:the number of endometrial glands per unit area decreased,fibrous tissue between glands proliferated in the USC group.The difference is statistically significant(P<0.05)2.The expression levels of HOXA10,LIF and ?V?3 mRNA and protein in UCS group in group A were significantly lower than that in control group(P<0.05).Immunohistochemical staining analysis confirmed this result.The difference of embryonic implantation rate between the two groups is statistically significant(2,3±0.9 vs 5.2±1.2,P<0.05).3.The expression levels of HOXA10,LIF and ?V?3 mRNA and protein in RUCS group in group B were significantly higher than that in UCS group in group B(P<0.05),but lower than that in control group in group A(P<0.05).The difference of embryonic implantation rate between the two groups is statistically significant(4.5±1.2 vs 2.6±1.0,P<0.05).4.Compared with the 0-hour-RUCS group,the expression levels of HOXA10,LIF and?V?3 mRNA and protein in 24,48-hour-RUCS group were significantly decreased,and the difference was statistically significant(P<0.05).Conclusion1.UCS impairs endometrium in rats,reduces endometrial receptivity by inhibiting the expression of endometrial HOXA10,LIF and ?V?3,and leads to UCS-related infertility.2.RUCS reduces endometrial receptivity injury and increases embryonic implantation rate in rats by improving the expression of endometrial HOXA10,LIF and ?V?3.3.The endometrial receptivity in rats is affected by the time of compression suture.For a certain period of time,the longer the compression is,the worse the endometrial receptivity is.It can provide theoretical support for screening the best time for suture removal(both for the purpose of treating PPH and minimizing endometrial damage)after uterine compression suture in treating human PPH. |
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