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Journal: Zhonghua fu chan ke za zhi

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Objective: To determine the levels of coagulation and inflammatory factors in women with moderate and severe ovarian endometriosis so as to investigate the possible role of coagulation and inflammatory factors in the pathogenesis, diagnosis and treatment of this disease.Methods:From June 2015 and June 2017, clinical data of 366 patients with pathologically diagnosed moderate and severe ovarian endometriosis (case group) and 244 patients with pathologically diagnosed benign ovarian cysts (control group) in Women’s Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The levels of coagulation indicators, inflammatory factors and serum tumor markers were measured. Then, the values of these indicators in diagnosis of endometriosis were analyzed.Results:(1) The levels of plasma prothrombin time (PT) and thrombin time (TT) in patients with ovarian endometriosis [median: 12.8 s (range: 12.4-13.2 s) and 15.5 s (range: 15.1-15.9 s), respectively] were significantly shorter than those with benign ovarian cysts [median: 13.0 s (range: 12.5-13.4 s) and 15.7 s (range: 15.3-16.1 s), respectively; allP<0.01]. The levels of plasma fibrinogen (FIB) and D-dimer [D-D; median: 3.1 g/L (range: 2.8-3.5 g/L) and 0.9 mg/L (range: 0.6-2.1 mg/L) , respectively] in patients with ovarian endometriosis were significantly higher than those with benign ovarian cysts [median: 2.8 g/L (range: 2.6-3.2 g/L) and 0.6 mg/L (range: 0.4-1.2 mg/L), respectively;P=0.000]. Moreover, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio [PLR; median: 2.3 (range: 1.8-3.1) and 144 (range: 113-179), respectively] in patients with ovarian endometriosis were significantly higher than those with benign ovarian cysts [median: 2.1 (range: 1.6-2.8) and 128 (range: 104-165), respectively;P<0.01]. Furthermore, in patients with ovarian endometriosis, the levels of PT were significantly shorter in stage Ⅳ endometriosis than that in stage Ⅲ endometriosis (P<0.05). The levels of FIB and PLR in patients with stage Ⅳ endometriosis were significantly higher than those in patients with stage Ⅲ endometriosis (P<0.01) . (2) The cut-off value of CA(125) was 27.2 kU/L with a sensitivity of 83.6%, the cut-off value of FIB was 3.1 g/L with a sensitivity of 53.2%, while the sensitivity of combination index (FIB×CA(125)) was 84.9%.Conclusion:The abnormality of coagulation and inflammatory factors may be involved in the pathogenesis of moderate and severe ovarian endometriosis, and the detection of coagulation and inflammatory factors may be have important clinical significance for the diagnosis and treatment of moderate and severe ovarian endometriosis.

Concepts: Oncology, Pathology, Coagulation, Ovarian cyst, Ovarian cancer, Prothrombin time, Endometriosis, Zhejiang University

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Objective: To investigate and analyze disease status and risk factors of venous thromboembolism (VTE) during pregnancy and puerperium in our country. Methods: Clinical datas were collected from 575 patients diagnosed with VTE during pregnancy and puerperium and hospitalized in nine medical institutions in our country from January 1, 2015 to November 30, 2019, and retrospectively analyzed it’s disease status and risk factors. Results: (1) The proportion of VTE in pregnancy and puerperium was 50.6% (291/575) and 49.4% (284/575), respectively. Four patients died, the mortality rate was 0.7% (4/575). The cause of death was pulmonary embolism. (2) The location of VTE during pregnancy and puerperium was mainly in the lower limb vascular (76.2%, 438/575), followed by pulmonary vessels (7.1%, 41/575). (3) In the risk factors of VTE, cesarean section accounted for 32.3% (186/575), maternal advance age accounted for 27.7% (159/575), braking or hospitalization during pregnancy accounted for 13.6% (78/575), other risk factors accounted for more than 5% were previous VTE, obesity, preterm birth, assistant reproductive technology conception and so on, pre-eclampsia and multiple pregnancy accounted for 4.9% (28/575) respectively. In addition, some patients with VTE did not have any of the above risk factors, and the incidence rate was as high as 23.1% (133/575). Conclusions: The occurrence of VTE during pregnancy and puerperium is related to multiple risk factors, and could lead to matemal death, It is very necessary to screen VTE risk factors for all pregnant women, to make corresponding prevention and control measures.

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Objective: To investigate the clinical characteristics and early identification of spontaneous rupture of uterus caused by placenta percreta. Methods: The clinical data of 12 patients with spontaneous uterine rupture caused by placenta percreta and admitted to the First Affiliated Hospital of Zhengzhou University from June 2014 to December 2019 were collected. The age, gestational age, gestational history, clinical manifestations, diagnostic methods, uterine operation history, rupture location, surgical method, treatment and outcome were analyzed. Results: (1) General condition: the median age of pregnant women was 37 years (range: 30-43 years), and the median gestational week of uterine rupture was 29+6 weeks (range: 18+3-36+3 weeks). (2) Clinical manifestation: among the 12 pregnant women, 9 showed different degrees of abdominal pain; chest distress accompanied by waist soreness, abdominal distension in 2 cases; one asymptomatic pregnant women was found with uterine rupture during elective cesarean section. Preoperative color Doppler ultrasonography indicated that 9 of the 12 pregnant women had peritoneal effusion, and 6 of them underwent diagnostic peritoneal puncture or posterior vault puncture for non-clotting blood extraction. (3) Uterine operation history and rupture location: among the 12 cases of spontaneous rupture of uterus caused by placenta percreta pregnant women, 10 had placenta previa after cesarean section, including 4 cases of rupture at the incision of the original cesarean section, 3 cases of rupture at the penetrating placental implantation of the lower segment of the anterior wall of the uterus, and 1 case of placenta percreta occurred at the myomectomy site of the right angle of the uterus. Among the 2 pregnant women with spontaneous uterine rupture caused by penetrating placental implantation without a history of cesarean section, 1 case with history of multiple abortions, and uterine rupture occurred at the bottom of the palace, 1 had rupture of placental penetrating implantation after hysteroscopic electroresection of endometrial polyps, and the uterine rupture occurred at the anterior wall of the lower segment of the uterus. (4) Maternal and fetal outcomes: 11 pregnant women were injected with suspension RBC and 1 pregnant woman was not injected with blood products. Nine cases underwent hysteroplasty and 3 cases underwent subtotal hysterectomy. There were 11 maternal survivors and 1 maternal death; 7 neonates survived and 6 stillbirths. Conclusions: Uterine rupture caused by placenta percreta is of great harm to mother and infant, due to its heterogeneity in clinical manifestations, which increases the possibility of misdiagnosis. For pregnant women with risk factors of placenta percreta, early diagnosis should be made during pregnancy. For those who have been diagnosed with placenta percreta, when there is typical or atypical uterine rupture, doctors should be alert to the occurrence of uterine rupture.

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Objective: To analyze the effect of pregnancy with adenomyosis on perinatal outcome. Methods: From April 2014 to April 2019, singleton pregnant women complicated with adenomyosis in Peking University Third Hospital was selected and the perinatal outcomes were analyzed retrospectively. Results: The age of patients in the pregnancy with adenomyosis group (study group) was not different from that of the control group (median: 35 vs 34 years old, P>0.05); the body mass index was higher than that of the control group (median: 23.9 vs 21.8 kg/m2, P<0.01); the rate of assisted reproductive technology was significantly higher than that of the control group [25.3% (64/253) vs 3.1% (8/257), P<0.01]. Compared with the control group, the gestational age at delivery was significantly lower in the study group (median: 38.0 vs 39.2 weeks, P<0.01); the rates of preterm birth [17.1% (44/257) vs 4.7% (12/257), P<0.01] and preeclampsia [13.7% (35/255) vs 5.8% (15/257), P=0.003] were significantly higher in the study group. The incidence of severe postpartum hemorrhage in the study group was significantly higher than that in the control group [5.8% (14/241) vs 1.2% (3/257), P=0.004]. The incidence of cesarean section was higher in the study group [(57.0% (146/256) vs 31.5% (81/257), P<0.01]. Neonatal weight was lower in the study group than that in the control group (median: 3 140 vs 3 440 g, P<0.01); the incidence of small for gestational age (SGA) was higher in the study group [21.5% (55/256) vs 4.7% (12/257), P<0.01]. There were no significant differences in umbilical artery pH and 1-minute Apgar score between the study group and the control group (all P>0.05). Conclusions: Pregnant women complicated with adenomyosis has low fertility, and most of them need assisted reproductive technology to conceive. The pregnant women with adenomyosis has the poor perinatal outcome, including an increased incedence of preterm birth, preeclampsia, postpartum hemorrhage, cesarean section and SGA, and low newborn weight.

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Objective: To measure the coagulation function of patients with adenomyosis so as to explore its relationship with increased menstrual amount and its clinical significance. Methods: From January 2014 to May 2019, clinical data of patients with hysterectomy in which 111 pathologically diagnosed adenomyosis (case group) and 115 with uterine myoma (control group) in Peking University First Hospital were retrospectively analyzed. The changes in coagulation function of the two groups were compared, and the correlation between coagulation and uterine volume in the adenomyosis group was analyzed. Results: (1) The activated partial thromboplastin time (APTT) was longer in the adenomyosis group than that in the uterine myoma group [(30.4±3.1), (29.6±2.5) s, respectively; P<0.05], while the thrombin time (TT) was shorter than that in the control group [(14.2±1.2), (14.6±1.0) s, respectively; P<0.05]. (2) According to the results of the Pearson correlation test, there was a positive correlation between prothrombin time (PT; r=0.135, P=0.042) and fibrinogen (FIB-C; r=0.139, P=0.036). (3) Platelet counts were higher in the anemia group of adenomyosis than that in the non-anemia group [(323±79)×109/L, (274±56)×109/L, respectively; P<0.05]. (4) FIB-C in non-anemia group of adenomyosis was lower than non-anemia group of uterine myoma [(2.8±0.5), (3.0±0.6) g/L, respectively; P<0.05], the anemia group of adenomyosis shortened TT compared with the anemia group of uterine myoma [(14.4±1.2), (15.2±0.9) s, respectively; P<0.05]. Conclusion: Patients with adenomyosis have abnormal coagulation function, which may be related to the increase amount of menstruation, and anemia may also be involved in coagulation disorders.

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Objective: To observe the expression, correlation and significance of chemokine (C-X-C motif) ligand 12 (CXCL12) and chemokine (C-X-C motif) receptor 4 (CXCR4) in endometrium and myometrium of adenomyosis. Methods: Totally 38 patients were selected in this study, who underwent hysterectomy for adenomyosis at Beijing Obstetrics and Gynecology Hospital from October 2017 to December 2018 as the adenomyosis group, and, in the same period, selected 31 patients with cervical intraepithelial neoplasia Ⅲ or cervical cancer undergoing hysterectomy served as control group. The expression levels of mRNA and protein for CXCL12, CXCR4 in the endometrium and myometrium of the two groups were detected by immunohistochemistry and real-time PCR. Results: (1) The protein levels of CXCL12 and CXCR4 in endometrium in uterus with adenomyosis (0.229±0.025 and 0.226±0.016) were significantly higher than those in endometrium in uterus without adenomyosis (0.153±0.018 and 0.178±0.026); compared with each other, the differences were statistically significant (all P<0.05). And the expressions of CXCL12 and CXCR4 proteins in uterine myometrium of adenomyosis were 0.222±0.045 and 0.126±0.058, respectively, which were higher than those in the control group (0.091±0.029 and 0.099±0.020); compared with each other, the differences were statistically significant (all P<0.05). (2) The expression levels of CXCL12 and CXCR4 mRNA in endometrium of patients with adenomyosis were 6.31±0.12 and 8.49±0.21, respectively, which were higher than those in the control group (1.23±0.10 and 1.36±0.13); compared with each other, the differences were statistically significant (all P<0.05). Moreover, the expression levels of CXCL12 and CXCR4 mRNA in myometrium of patients with adenomyosis were 9.11±0.12 and 8.45±0.16, respectively, which were higher than those in the control group (1.18±0.08 and 1.46±0.13); compared with each other, the differences were statistically significant (all P<0.05). (3) In endometrium and myometrium of uterus with adenomyosis, CXCL12 and CXCR4 mRNA expression levels were positively associated (r=0.478, 0.542, all P<0.05). Conclusions: The levels of CXCL12 and CXCR4 in the endometrium and myometrium of adenomyosis are increased and positively correlated. The two chemokine may be involved in the development of adenomyosis.

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Objective: To analyze the perinatal outcomes in different methods of multifetal pregnancy reduction in dichorionic triamniotic (DCTA) triplet pregnancy. Methods: A retrospective analysis was performed on 57 cases of DCTA triplets in Peking University Third Hospital from January 1, 2010 to January 1, 2020, including 27 cases in expectant pregnancy group and 30 cases in selective fetal reduction (FR) group. The selective FR group was further divided into 3 subgroups according to different FR methods:retaining monochorionic dichorionic (MCDA) group, retaining dichorionic dichorionic (DCDA) group, and retaining singleton group. The perinatal outcomes of expectant pregnancy group and 3 subgroups of selective FR group were compared. Results: The gestational weeks in selective FR group was (34.5±5.7) weeks, and full-term delivery rate was 53% (16/30), respectively higher than those of the expectant pregnancy group (29.9±6.0) weeks and 7% (2/27). The miscarriage rate of the selective FR group was 10% (3/30), lower than that of the expectant pregnancy group (33%, 9/27). The differences between the two groups were statistically significant (all P<0.05). The ratios of pregnancy complications and newborn admission to neonatal ICU (NICU) in the selective FR group were lower than those of the expectant pregnancy group (all P<0.05). In the selective FR group, the gestational weeks in retaining MCDA group (6 cases), retaining DCDA group (13 cases), and retaining singleton group (11 cases) were (32.2±4.3), (33.0±6.3), and (37.4±4.7) weeks; the miscarriage rates were 1/6, 1/13, and 1/11; the premature delivery rates were 4/6, 7/13, and 0/11; the full-term delivery rates were 1/6, 5/13, and 10/11; pregnancies with at least 1 survivor rates were 5/6, 12/13, and 10/11; NICU occupancy rates were 6/8, 9/18 and 0/10, respectively. The retaining singleton group had the highest rate of full-term delivery and the lowest rate of NICU occupancy. Compared with other groups, the differences were statistically significant (all P<0.05). The full-term delivery rate was significantly higher in the retaining DCDA group than that of the expectant pregnancy group (P<0.05). Conclusions: The risk of DCTA triplet pregnancy is high. Reduction of the MCDA pair to singleton has the highest rate of full-term delivery and the lowest rate of NICU occupancy. For pregnant women who wish to retain twin pregnancy, the risk should be fully informed, and consider reduction of one fetus of the MCDA and retaining DCDA twins to continue pregnancy.

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Objective: To investigate the clinical features, etiology, and prognosis of sepsis during pregnancy and the postpartum period. Methods: Sixty-eight pregnant women with maternal sepsis treated in Peking Union Medical College Hospital from January 1997 to December 2019 were collected, and divided into obstetric infection group (30 cases) and non-obstetric infection group (38 cases) according to different infection sources. Clinical manifestations, types of infection sources, microbiological characteristics, treatment and outcomes were studied and analyzed. Results: (1) General conditions and clinical features: sepsis occurrence rate was 57% (39/68) and 43% (29/68) in prenatal and postpartum period, repectively. Statistical analysis showed that incidence of respiratory, renal, liver and coagulation dysfunction in non-obstetric infection group were significantly higher than those in obstetric infection group, and multiple organ dysfunction, cardiac arrest and blood lactate≥4 mmol/L were more common (all P<0.05). Sequential organ failure score in non-obstetric infection group was also significantly higher than that in obstetric infection group (P<0.05). (2) Types of infection sources and microbiological characteristics: the most common maternal sepsis was genital tract sepsis (37%, 25/68). Chorioamnionitis was the most common cause in obstetric sepsis (40%, 12/30), while intra-abdominal infection was the most common cause in non-obstetric sepsis (34%, 13/38). Thirty-seven patients (54%, 37/68) were diagnosed as bloodstream infection (BSI). Gram-negative bacteremia accounted for 70% (26/37), the most common pathogen of which was Escherichia coli. BSI was most commonly secondary to a genital tract infection (65%, 17/26). (3) Treatment: the ICU hospitalization rates and the utilization rate of mechanical ventilation and vasoactive agents in non-obstetric group were higher than those in obstetric group with significant differences (all P<0.05). Thirty-two patients (47%, 32/68) underwent surgery to remove the infection sources, including 5 cases of hysterectomy. (4) Prognosis: the case fatality rate of maternal sepsis was 19% (13/68), which was significantly higher in the non-obstetric infection group (29%,11/38) compared with the obstetric infection group (7%,2/30; P=0.020). The time from diagnosis of sepsis to termination of pregnancy was (5.5±8.6) days in prenatal women, and time in obstetric infection group [(1.9±2.2) days] was significantly less than that of non-obstetric infection group [(7.7±10.3) days, P=0.029]. Adverse pregnancy outcomes were higher in the first and second trimester (72%, 18/25) than in the third trimester (21%, 3/14), and the difference was statistically significant (P=0.002). Conclusions: Sepsis during pregnancy and the postpartum period is a potentially life-threatening disease. Pregnant women with non-obstetric sepsis have more complications, more serious condition and worse prognosis than those with obstetric infection. Timely detection of risk factors, early identification and active treatment are helpful to improve maternal and fetal prognosis.

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Objective: To compare the clinical outcomes of one and two blastocysts in the freeze-thaw transplantation cycle. Methods: Totally 3 675 cycles of frozen thawed blastocyst transplantation in Reproductive Medical Center of the Second Nanning People’s Hospital from January 2012 to December 2016 were analyzed retrospectively. According to the quantity and quality of transferred blastocysts, all the patient were divided into two groups: (1) one embryo group, including the single excellent group (one high quality blastocyst) and the single non excellent group (one non high quality blastocyst); (2) two embryo groups, including the double excellent group (two high quality blastocysts), the one excellent and one non excellent group (one high quality blastocyst+one non high quality blastocyst), and the two non excellent group (two non high quality blastocysts were transplanted). Then the patients were divided into subgroups according to their ages: less than 35 years old, 35-40 years old and over 40 years old. On this basis, the implantation rate, clinical pregnancy rate, multiple birth rate and live birth rate were compared. Results: (1) The implantation rate, clinical pregnancy rate, multiple birth rate, preterm birth rate and live birth rate were all significantly increased, while the abortion rate was significantly reduced in the double blastocyst group (all P<0.05). (2) In the group of<35 years old, the rates of multiple birth and preterm birth in the double blastocyst group were significantly higher than those in the single optimal group (P<0.01). (3) In the 35-40 years old group, the clinical pregnancy rate, multiple birth rate and live birth rate of the double excellent group were significantly higher than those of the single excellent group (P<0.01); while the clinical pregnancy rate and live birth rate of the one excellent and one non excellent group and the double non excellent group were not significantly different from those of the single excellent group (P>0.05), but the multiple birth rate and preterm birth rate were significantly increased (P<0.01). The clinical pregnancy rate, live birth rate and multiple birth rate of double non optimal group were significantly higher than those of single non optimal group (P<0.01). (4) In the group>40 years old, there were no significant differences in clinical pregnancy rate and live birth rate between the two groups (P>0.05). There were no significant differences in implantation rate, clinical pregnancy rate and live birth rate between double non optimal group and single non optimal group (P>0.05). Conclusion: No matter the age of the patients, if the couple have high quality blastocysts, we should give priority to single high quality blastocyst transplantation; even if they have no high quality blastocysts, we should also consider single blastocyst transplantation, in order to reduce the risk of multiple pregnancy and improve the cumulative live birth rate, so as to improve the pregnancy outcome.

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Objective: To evaluate the value of p16INK4a detected by p16INK4a immunostaining as a new generation of cervical cytology for primary screening and secondary screening in population-based cervical cancer screening, and in improving cytological diagnosis. Methods: Between 2016 and 2018, 5 747 non-pregnant women aged 25-65 years with sexual history were recruited and underwent cervical cancer screening via high-risk (HR)-HPV/liquid-based cytological test (LCT) test in Shenzhen and surrounding areas. All slides were immuno-stained using p16INK4a technology, among them, 902 cases were offered p16INK4a detection during primary screening, and the remaining 4 845 cases were called-back by the virtue of abnormal HR-HPV and LCT results for p16INK4a staining. Participants with complete LCT examination, HR-HPV test, p16INK4a staining and histopathological examination results were included in this study. The performance of p16INK4a in primary and secondary screening, and in assisting cytology to detect high grade squamous intraepithelial lesion [HSIL, including cervical intraepithelial neoplasia (CIN) Ⅱ or Ⅲ] or worse [HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+] were analyzed. Results: (1) One-thousand and ninety-seven cases with complete data of p16INK4a and histology were included. Pathological diagnosis: 995 cases of normal cervix, 37 cases of low grade squamous intraepithelial lesion (LSIL), 64 cases of HSIL and one case of cervical cancer were found. Among them, 65 cases of HSIL (CIN Ⅱ)+ and 34 cases of HSIL (CIN Ⅲ)+ were detected. The positive rate of p16INK4a in HSIL (CIN Ⅱ)+ was higher than that in CINⅠ or normal pathology (89.2% vs 10.2%; P<0.01). (2) p16INK4a as primary screening for HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+ was equally sensitive to primary HR-HPV screening (89.2% vs 95.4%, 94.1% vs 94.1%; P>0.05), but more specific than HR-HPV screening (89.8% vs 82.5%, 87.7% vs 80.2%; P<0.05). p16INK4a was equally sensitive and similarly specific to cytology (≥LSIL; P>0.05). (3) The specificity of LCT adjunctive p16INK4a for detecting HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+ were higher than that of LCT alone or adjunctive HR-HPV (P<0.01), while the sensitivity were similar (P>0.05). (4) p16INK4a staining as secondary screening: p16INK4a was significantly more specific (94.1% vs 89.7%, 91.9% vs 87.4%; P<0.01) and comparably sensitive (84.6% vs 90.8%, 88.2% vs 91.2%; P>0.05) to cytology for triaging primary HR-HPV screening. HPV 16/18 to colposcopy and triage other HR-HPV with p16INK4a was equally sensitive (88.2% vs 94.1%; P=0.500) and more specific (88.3% vs 83.0%; P<0.01) than HPV 16/18 to colposcopy and triage other HR-HPV with LCT≥ atypical squamous cells of undetermined significance (ASCUS), and the referral rate decreased (14.0% vs 19.4%; P=0.005). Conclusions: For primary screening, p16INK4a is equally specific to cytology and equally sensitive to HR-HPV screening. p16INK4a alone could be an efficient triage after primary HR-HPV screening. In addition, p16INK4a immunostaining could be used as an ancillary tool to cervical cytological diagnosis, and improves its accuracy in cervical cancer screening.