A retrospective study of ovarian tissue cryopreservation in female patients with hematological diseases for fertility preservation.

PURPOSES: To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases. METHODS: We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized. RESULTS: A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81 years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12 ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24 IU/L in examination before OTC. FSH was greater than 10.0 IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 109/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 109/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 109/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 109/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58 min, and the average blood loss was 32.1 ± 41.6 mL. The maximum blood loss was 200 mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 109/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20 days and began HSCT within 30 days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3 years after HSCT and resumed regular menstruation 6 months after OTT. CONCLUSIONS: Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.

Accuracy of transvaginal ultrasound and magnetic resonance imaging for diagnosis of deep endometriosis in bladder and ureter: a meta-analysis.

This meta-analysis aimed to determine the accuracy of transvaginal ultrasound (TVS) and pelvic magnetic resonance imaging (MRI) in diagnosing urinary tract endometriosis (UTE). A comprehensive search of the Pubmed and Embase was conducted between January 1989 and June 2020. Studies that described the accuracy of MRI or TVS for the diagnosis of UTE using surgical data as the reference standard were included. Of the 913 citations identified, 23 studies were analysed. For detection of endometriosis in bladder endometriosis (BE), the overall pooled sensitivities of TVS and MRI were 72% and 68% respectively, and their specificities were 99% and 100% respectively. For detection of endometriosis in the ureteral endometriosis (UE), the overall pooled sensitivities of TVS and MRI were 97% and 87% respectively, and their specificities were both 100%. In conclusion, both TVS and MRI provide good accuracy with specific strong points in diagnosing UTE and seem useful first-line methods from a clinical perspective. Besides, pelvic MRI and TVS are more accurate for predicting UTE localised in the ureter than bladder, especially in terms of sensitivity.IMPACT STATEMENTWhat is already known on this subject? Previous studies have confirmed high diagnostic value of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) on bladder endometriosis (BE) respectively. However, high heterogeneity was found for both sensitivity and specificity and no meta-analysis has yet been performed to test the diagnostic value of TVS and MRI for ureteral endometriosis (UE).What the results of this study add? In this meta-analysis, we firstly confirmed high diagnostic value of TVS and MRI on UE respectively. For detection of UE, the overall pooled sensitivities of TVS and MRI were 97% and 87% respectively, and their specificities were both 100%.What the implications are of these findings for clinical practice and/or further research? Early preoperative diagnosis and accurate understanding of the widespread distribution of endometriosis are prerequisites for radical surgical in UTE. In the present study, we updated the previous results on the accuracy of TVS and MRI for the diagnosis of BE and firstly confirmed high diagnostic value of TVS and MRI on UE. Both TVS and MRI provide good accuracy with specific strong points in diagnosing UTE and seem useful first-line methods from a clinical perspective.

Antral follicle count is reduced in the presence of endometriosis: a systematic review and meta-analysis.

Studies suggest that the presence of endometriosis may lead to impaired ovarian reserve, while results evaluating the changes in antral follicle count (AFC) in endometriosis remain controversial. A systematic search returned 15 studies, of which nine compared AFC between patients with and without endometriosis, five articles reported differences in AFC between affected and unaffected ovaries in patients with unilateral ovarian endometriosis and one reported both of the above two situations. Overall results showed a significant decrease in AFC and anti-Müllerian hormone (AMH) and increase in serum FSH concentrations in patients with endometriosis when compared with controls. Additionally, the AFC for the ovary with the endometrioma was also significantly lower than that of the contralateral ovary in patients with unilateral ovarian endometriosis. Moreover, it appears that the AFC in patients with endometriosis where the ovaries are not affected or in early stage were not significantly different in the control group. These findings demonstrate that endometriosis is associated with reduced AFC and AMH and elevated serum concentrations of FSH, suggesting a reduction in ovarian reserve in patients with endometriosis, especially in those with ovarian endometrioma and advanced stage.

Clinical characteristics, treatment status and complications in women with tube ovarian abscess and endometriosis: a retrospective study.

BACKGROUND: The aim of our present study was to investigate the clinical characteristics, treatment status and complications in women with endometriosis (EM) and tube ovarian abscess (TOA) to determine the possible association between TOA and EM. METHODS: Medical records were used to analyze the clinical characteristics, treatment and complications. Twenty women who were diagnosed with TOA with EM were compared with 93 women diagnosed as having TOA without EM between January, 2008 and December, 2018. RESULTS: In this study, TOA patients with EM were significantly more likely to have a lower age range (20-39 years) than the non-EM group [11/20 (55.0%) vs 27/93 (29.0%)]. In addition, TOA patients with EM were associated with a significantly lower rate of parity [11/20 (55.0%) vs 75/93 (80.6%)], higher rates of infertility [8/20(40%) vs 0/93(0%)] and a significantly lower incidence of elevated blood platelet counts [5/20 (25%) vs 43/93 (46.2%)]. Furthermore, women with EM had greater blood loss (347 ± 445.77 vs 204.67 ± 289.46) and an increased complication rate [3/20(15%) vs 0/93(0%)]. Among the 3 patients who had complications in the EM group, 2 patients had septic shock and 1 patient had intestinal obstruction. And 1 case who had septic shock followed by IVF treatment. There was no significance difference on other factors. CONCLUSIONS: The present study indicated that EM did not increase the difficulty and time of treatment in patients with TOA, but increased bleeding during surgery and serious complications. It is suggested that doctors should pay more attention to postoperative treatment and nursing in women with TOA and EM, especially those who have a history of recent infertility treatment and related procedures.

Serum and peritoneal fluid leptin levels in endometriosis: a systematic review and meta-analysis.

The role of leptin in the development of endometriosis has been investigated previously. However, researches on the change of leptin levels in endometriosis remains controversial. So, we aimed to clarify changes of leptin levels in patients with endometriosis and their association with the progression of endometriosis. We searched PubMed, Embase, Web of Science, and The Cochrane Library to identify relevant studies published before May 25, 2020. The detected levels of leptin in patients with endometriosis versus controls were evaluated in this meta-analysis. Eighteen studies met our inclusion criteria, five studies detected serum, nine detected peritoneal fluid and another four detected both serum and peritoneal fluid leptin levels. The overall results showed that peritoneal fluid leptin levels in patients with endometriosis was significantly higher than that in the control group, but the serum and corrected peritoneal fluid leptin levels were comparable in both groups. Subgroup analysis failed to eliminate the high degree of heterogeneity included in the studies and showed that peritoneal fluid leptin levels were significantly elevated in both early and advanced endometriosis. In conclusion, peritoneal fluid rather than serum leptin levels was elevated in patients with endometriosis, which did not seem to be related to the severity of endometriosis, but was related to body mass index.

Fibrinogen alpha chain promotes the migration and invasion of human endometrial stromal cells in endometriosis through focal adhesion kinase/protein kinase B/matrix metallopeptidase 2 pathway†.

Fibrinogen alpha chain (FGA), a cell adhesion molecule, contains two arginyl-glycyl-aspartic acid (RGD) cell adhesion sequences. Our previous study demonstrated that FGA, as an up-regulated protein in endometriosis (EM), was closely related to disease severity and involved in the development of EM. However, the biological functions and underlying mechanism of FGA in EM have not been fully understood. To explore the roles of FGA in EM, we analyzed the effects of FGA on the biological behaviors of human primary eutopic endometrial stromal cells (EuESC). The results indicated FGA knockdown suppressed the migration and invasion ability of EuESC, which also altered the distribution of cytoskeletal filamentous and cell morphology. Western blot analysis demonstrated that knockdown of FGA attenuated the migration-related protein levels of vimentin and matrix metallopeptidase 2 (MMP-2), but not integrin subunit alpha V (ITGAV) and integrin subunit beta 3 (ITGB3). Meanwhile, integrin-linked transduction pathways were detected. We found FGA knockdown significantly suppressed the expression of focal adhesion kinase (FAK) level and protein kinase B (AKT) phosphorylation, without extracellular-signal-regulated kinase (ERK) dependent pathways. Treatment with the AKT inhibitor MK2206 or RGD antagonist highly decreased the effects of FGA on the migration and invasion of EuESC. RGD antagonist treatment strongly inhibited FAK- and AKT-dependent pathways, but not ERK pathways. Our data indicated that FGA may enhance the migration and invasion of EuESC through RGD sequences binding integrin and activating the FAK/AKT/MMP-2 signaling pathway. This novel finding suggests that FGA may provide a novel potential approach to the treatment of EM, which provides a new way to understand the pathogenesis of EM.

[Effect of Curcumin on TGF-ß2 Regulated PPAR-γ/PDGF-ß Signaling Pathway in Lung Fibroblasts of Mice].

OBJECTIVE: To explore the effect of curcumin on TGF-ß2 regulated peroxisome proliferater activated receptor y (PPAR-γ)/platelet derived growth factor ß (PDGF-ß) signaling pathway in lung fibroblasts of mice. METHODS: C57BL/6 mouse lung fibroblasts were in vitro cultured with TGF-ß2, curcumin, or TGF-ß2 plus curcumin. The cell proliferation was detected by cell growth counting in the blank control group, low, middle, and high dose curcumin groups (5, 25, 50 µmol/L), the TGF-ß2 (10 ng/mL) group, TGF-ß2 (10 ng/mL) plus curcumin (5, 25, 50 µmol/L) groups. mRNA expressions of PPAR-γ, platelet-derived growth factor receptor ß (PDGFR-ß), fibroblast growth factor R1 (FGFR1) were detected using reverse transcription PCR. Protein levels of PPAR-γ and collagen-1 were detected using Western blot and ELISA in the blank control group, the TGF-ß2 group, the TGF-ß2 (10 ng/mL) plus curcumin 50 µmol/L group. RESULTS: Compared with the blank control group, curcumin 50 µmol/L showed the most significant inhibition on cell proliferation at 48 h and 72 h. Compared with the TGF-ß2 group, TGF-ß2 (10 ng/mL) plus curcumin 50 mol/L also showed the most significant inhibition on cell proliferation at 48 h and 72 h. Compared with the blank control group, mRNA expressions of PPAR-γ and PDGF-ß, as well as protein expression of PPAR-γ increased, the collagen-1 expression also increased in the TGF-ß2 group (P < 0.05). Compared with the TGF-ß2 group, mRNA expressions of PPAR-γ obviously increased in the TGF-ß2 (10 ng/mL) plus curcumin 25 µmol/L group and the TGF-ß2 (10 ng/mL) plus curcumin 50 µmol/L group, higher than that in the TGF-ß2 (10 ng/mL) plus curcumin 5 [µmol/L group (P < 0.05). mRNA expressions of PPAR-γ was higher in the TGF-ß2 (10 ng/mL) plus curcumin 50 µmol/L group than in the TGF-ß2 (10 ng/mL) plus curcumin 25 µmol/L group (P < 0.05). mRNA expressions of PDGF-ß was lower in TGF-ß2 (10 ng/mL) plus curcumin groups than in the TGF-ß2 group (P < 0.05). Besides, PDGF-ß mRNA expressions were lower in the TGF-ß2 (10 ng/mL) plus curcumin 50 µmol/L group than in the TGF-ß2 (10 ng/mL) plus curcumin 5 µmol/L group and the TGF-ß2 (10 ng/mL) plus curcumin 25 µmol/L group (P < 0.05). There was no statistical difference in FGFR1 mRNA expressions between the TGF-ß2 group and 3 TGF-ß2 plus curcumin groups (P > 0.05). Compared with the TGF-ß2 group, PPAR-γ protein expressions increased and collagen-1 protein expressions decreased in the TGF-ß2 (10 ng/mL) plus curcumin 50 µLmol/L group (P < 0.05, P < 0.01). CONCLUSIONS: Curcumin not only could inhibit TGF-ß2 induced proliferation of lung fibroblasts, but also could inhibit the synthesis of collagens. These might be associated with up-regulating PPAR-γ expressions and down-regulating PDGF-ß expressions. Therefore, curcumin might inhibit the occurrence and developing of lung fibrosis through blocking PPAR-γ/PDGF-ß signaling pathway.

Postmenopausal endometrial non-benign lesion risk classification through a clinical parameter-based machine learning model.

OBJECTIVE: This study aimed to develop and evaluate a machine learning model utilizing non-invasive clinical parameters for the classification of endometrial non-benign lesions, specifically atypical hyperplasia (AH) and endometrioid carcinoma (EC), in postmenopausal women. METHODS: Our study collected clinical parameters from a cohort of 999 patients with postmenopausal endometrial lesions and conducted preprocessing to identify 57 relevant characteristics from these irregular clinical data. To predict the presence of postmenopausal endometrial non-benign lesions, including atypical hyperplasia and endometrial cancer, we employed various models such as eXtreme Gradient Boosting (XGBoost), Random Forest (RF), Logistic Regression (LR), Support Vector Machine (SVM), Back Propagation Neural Network (BPNN), as well as two ensemble models. Additionally, a test set was performed on an independent dataset consisting of 152 patients. The performance evaluation of all models was based on metrics including the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, precision, and F1 score. RESULTS: The RF model demonstrated superior recognition capabilities for patients with non-benign lesions compared to other models. In the test set, it attained a sensitivity of 88.1% and an AUC of 0.93, surpassing all alternative models evaluated in this study. Furthermore, we have integrated this model into our hospital's Clinical Decision Support System (CDSS) and implemented it within the outpatient electronic medical record system to continuously validate and optimize its performance. CONCLUSIONS: We have trained a model and deployed a system with high discriminatory power that may provide a novel approach to identify patients at higher risk of postmenopausal endometrial non-benign lesions who may benefit from more tailored screening and clinical intervention.

[Prediction of chemoresistance in epithelial ovarian cancer by clinical factors].

OBJECTIVE: To compare the clinical features and prognosis among patients with different chemosensitivity and determine the specific clinical influencing factors of chemotherapeutic resistance. METHODS: In references to the 2010 NCCN clinical practice guidelines on ovarian cancer and in accordance with the length of disease-free interval, 244 patients were divided into 3 groups: platinum-resistant, partially sensitive and platinum-sensitive. The differences of clinical features, treatment and prognosis were compared among these 3 groups. RESULTS: The resistant, partially sensitive, sensitive rates to platinum-based chemotherapy were 23.4%, 13.5% and 63.1% respectively. Such factors as age, pathological type, primary tumor size. intraperitoneal chemotherapy and venous chemotherapy regimen had no effect on the responses to the combination platinum-based chemotherapy. The platinum-resistant percentage of advanced stage patients without optimal cytoreductive surgery was higher (P < 0.01). The poorly differentiated rate of partially sensitive patients was higher than that of platinum-sensitive ones (P < 0.05). The CA125 level and lymph node metastasis rate of platinum-resistant patients were higher than those of platinum-sensitive patients (P < 0.05, P < 0.01). The 5-year survival rates of resistant, partially sensitive and sensitive patients were 9.5%, 38.4% and 81.9% respectively. There were statistics differences in overall survival and progression-free survival among the 3 groups (P < 0.01). CONCLUSION: Advanced ovarian cancer, poor differentiation, lymph node-positivity, CA125 rising above 1000 × 10(3) U/L and suboptimal cytoreductive surgery would lead to the occurrences of resistance or partially sensitivity. Clinical factors have some reference values for the prediction of resistance. But it is impossible to accurately determine chemoresistance.

Effects of bariatric surgery on patients with obesity and polycystic ovary syndrome: a meta-analysis.

BACKGROUND: Bariatric surgery is effective for polycystic ovary syndrome (PCOS), while the exact mechanism remains unclear. OBJECTIVES: To assess the impact of bariatric surgery on PCOS patients and further explore the possible mechanism. SETTING: A meta-analysis. METHODS: We searched PubMed, Web of Science, The Cochrane Library, and Embase to identify relevant studies published before November 2020. RESULTS: Twenty-one studies met our inclusion criteria, and we identified 552 patients with PCOS study. Results showed that the prevalence of preoperative PCOS, menstrual irregularity, hirsutism, type 2 diabetes (T2D), hypertension, infertility, and depression significantly decreased after bariatric surgery. Levels of total testosterone, fasting insulin, and luteinizing hormone (LH) decreased and estradiol increased, while levels of follicle-stimulating hormone (FSH) and LH/FSH did not show significant changes during the 3-month follow-up. There were decreases in testosterone and fasting insulin levels when the postoperative follow-up time was 6 months or ≥12 months. Levels of fasting blood glucose and triglycerides were significantly reduced after 6 months or ≥12 months of bariatric surgery. High-density lipoprotein (HDL) and sex hormone-binding globulin (SHBG) significantly improved ≥12 months after bariatric surgery. CONCLUSION: Symptoms of PCOS and related complications are significantly alleviated after bariatric surgery. In addition, we found a significant improvement on anomalous secretion of gonadotropins, glucose metabolism, and lipid metabolism in patients with PCOS after bariatric surgery.

Current biomarkers for the detection of endometriosis.

A clinically reliable non-invasive test for endometriosis is expected to reduce the diagnostic delay. Although varieties of biomarkers have been investigated for decades, and cancer antigen-125, cancer antigen-199, interleukin-6, and urocortin were the most studied ones among hundreds of biomarkers, no clinically reliable biomarkers have been confirmed so far. Some emerging technologies including "omics" technologies, molecular imaging techniques, and microRNAs are promising in solving these challenges, but their utility to detect endometriosis has yet to be verified. New combinations of researched indicators or other non-invasive methods and further exploration of the emerging technologies may be new targets and future research hotspots for non-invasive diagnosis of endometriosis. In conclusion, researches of biomarkers for the detection of endometriosis are still ongoing and may benefit from novel molecular biology, bioinformatics methods and a combination of more diverse monitoring methods. Though it will be a daunting task, the identification of a specific set of diagnostic biomarkers will undoubtedly improve the status of endometriosis.

[Clinical value of serum CA19-9, CA125 and CP2 in mucinous ovarian tumor: a retrospective study of 273 patients].

OBJECTIVE: To evaluate the diagnostic and prognostic value of serum CA19-9, CA125 and CP2 in mucinous ovarian tumors. METHODS: In this retrospective study, the serum CA19-9, CA125 and CP2 levels of 273 hospitalized patients with ovarian tumors of either mucinous or non-mucinous type were analyzed. RESULTS: (1) CA19-9 had the biggest area under curve (AUC) in mucinous tumors followed with CA125 while CA125 and CP2 had bigger AUC in non-mucinous tumor. (2) For the diagnosis of mucinous tumors, CA19-9 and CA125 combination showed a greatly increased sensitivity compared with CA19-9 or CA125 alone (93.8% versus 75.0% and 66.7%, P<0.05) with no significant improvement of the specificity (P>0.05). For the diagnosis of non-mucinous tumors, CA125 and CP2 combination showed an increased sensitivity compared with CA125 or CP2 alone (85.0% versus 80.7%, P>0.05, 85.0% versus 70.6%, P<0.05) with no significant improvement of the specificity (P>0.05). (3) Seventy percent of tumor marker-positive patients could undergo cytoreductive surgery. Compared with those who could not undergo cytoreductive surgery, they were more likely to have normal tumor marker two months after surgery (P<0.05) and longer interval to re-elevation of tumor markers (P>0.05), with lower recurrence and death rate (P<0.05). All of the 20 tumor marker-negative patients could have cytoreductive surgery with only 10% recurrence. (4) CA19-9 increased mainly in recurrent mucinous tumor, while CA125 increased dominantly in recurrent non-mucinous tumor. (5) The survival rate of CA125 and CP2 positive patients was much lower than CA125 and CP2 negative patients (P<0.05), while the survival rate was similar between CA19-9 positive and CA19-9 negative patients. CONCLUSIONS: CA19-9 is a sensitive index for diagnosis of mucinous ovarian tumors. Combination of CA19-9 with CA125 can improve the sensitivity of diagnosis and postoperative monitoring of mucinous ovarian tumors. Combination of CA125 with CP2 is more valuable in the diagnosis of non-mucinous ovarian tumors.

[Efficacy and tolerability of the combination of oxaliplatin, ifosfamide, and epirubicin in treatment of recurrent or platinum-resistant ovarian epithelial cancer patients].

OBJECTIVE: To evaluate the efficacy and tolerability of the combination of oxaliplatin, ifosfamide and epirubicin (IAP) in treatment of recurrent or platinum-resistant ovarian cancer patients. METHODS: A total of 25 patients received the combined chemotherapy of ifosfamide (3 - 4 g/m(2)), epirubicin (50 - 60 mg/m(2)) and oxaliplatin (130 mg/m(2)). The cycles were repeated every 21 days. The efficacy and toxicity were evaluated in 21 patients who received more than 2 cycles of IAP chemotherapy. RESULTS: The overall response rate was 71%, with a complete response in 10 (48%), partial response in 5 (24%), stable disease in one (5%), and disease progression in 5 (24%). The median progression-free and overall survival time were 11 (1 to 33) months and 31 (1 to 71) months. While overall response rate was 60% in 10 patients with primary platinum resistant, and 88% in 8 patients with secondary platinum-resistant. Grade III - IV myelosuppression rate was 30%. The most common non-hematologic toxicity was perineurotoxicity (38%). CONCLUSIONS: The combination of oxaliplatin, ifosfamide and epirubicin appears to be effective for recurrent or platinum-resistant ovarian cancer patients as salvage chemotherapy and the toxicity is also tolerable. However, it needs to be evaluated by multiple clinical trials.

[Classification tree analysis in serous ovarian adenocarcinoma patients for prognostic factors associated with three-year survival probability].

OBJECTIVE: To analyze the prognostic factors associated with three-year survival outcome in patients with serous ovarian adenocarcinoma by classification tree. METHODS: Retrospectively we analyzed 81 cases with serous ovarian adenocarcinoma who had 3-year clinical outcomes and were hospitalized in People's Hospital from Jan 1991 to Dec 2003 by classification and regression trees (CART) software. Establish the classification tree. RESULTS: Among the factors that were associated with the 3-year survival rate, age was the most important factor, other factors in turn were International Federation of Gynecology and Obstetrics (FIGO) stage, lymphoid metastasis, residual size after operation, chemotherapy and pathologic grade. By substitution variable analysis, it was demonstrated that there was cross interaction between age and residual size as well as age and chemotherapy. CONCLUSION: Age, FIGO stage, lymphoid metastasis, residual size after operation, chemotherapy and pathologic grade are important prognostic factors related with three-year survival probability of serous ovarian adenocarcinoma patients.

[Outcome analysis of stage III - IV endometriosis after conservative surgery].

OBJECTIVE: To analyze the recurrence and fertility outcome of stage III - IV endometriosis after conservative surgery. METHODS: A retrospective study was performed on 90 women with stage III - IV endometriosis who had been diagnosed by pathology after conservative surgery. They were divided into three groups: 16 without endocrine therapy (Group A), 52 treated with gestrinone (Group B), 22 treated with gonadotropin releasing hormone agonist (GnRHa) (Group C). The number of infertile patients in the three groups was 10, 15 and 10, respectively. The recurrent and pregnant outcomes were compared after a median follow-up of 48.5 months (2 - 7 years). RESULTS: The recurrent rate of groups A, B, and C was 18.8% (3/16), 30.8% (16/52) and 13.6% (3/22), respectively (P = 0.247); the recurrent time in the three groups were Group A: 63.8 months, Group B: 63.3 months, and Group C: 47.6 months (P = 0.376). There were no significant differences in pregnant outcome among the three groups. The cumulative pregnant rates were 70.0% (7/10), 66.7% (10/15) and 60.0% (6/10), respectively (P = 0.890). There was also no difference in the first pregnant interval after surgery (P = 0.092) and 65.2% of the patients acquired pregnancy spontaneously in the first year after surgery. CONCLUSIONS: Neither gestrinone nor GnRHa can prolong the recurrent time or reduce the recurrent rate after conservative surgery. Surgery can improve the fertility ability of stage III and IV endometriosis patients; however, the pregnant rate cannot be improved with endocrine therapy after conservative surgery.

Effects of Previous Laparoscopic Surgical Diagnosis of Endometriosis on Pregnancy Outcomes.

BACKGROUND: The association between the previous history of endometriosis and obstetric outcomes is still ambiguous. This study aimed to evaluate the effects of previous history of operatively diagnosed endometriosis on pregnancy outcomes. METHODS: A total of 98 primiparous women who had been diagnosed with endometriosis by previous laparoscopic surgery were included in this retrospective cohort study. Pregnancy outcomes were compared between these women (study group) who had a live birth and 300 women without endometriosis (control group) who had a live birth. In the study group, the pregnancy outcomes of 74 women who conceived naturally (no assisted reproductive technology [ART] subgroup) were simultaneously compared with 24 women who conceived by ART (ART subgroup). RESULTS: Miscarriage was observed in 23 of 98 women with endometriosis (23.5%). There were 75 women who had a live birth after laparoscopic diagnosis of endometriosis in the study group eventually. On multivariate analysis, the postpartum hemorrhage rate increased significantly in the study group when compared with the control group (adjusted odds ratio: 2.265, 95% confidence interval: 1.062, 4.872; P = 0.034). There was an upward tendency of developing other pregnancy-related complications, such as preterm birth, placental abruption, placenta previa, cesarean section, fetal distress/anemia, and others in the study group than in the control group. However, the differences showed no statistical significance. Within the study group, the occurrence rate of postpartum hemorrhage and preterm birth was both higher in the ART subgroup than in the no ART subgroup. The differences both had statistical significance (44.4% vs. 17.5%, P = 0.024 and 27.8% vs. 1.8%, P = 0.010, respectively). At the same time, median (interquartile range) for gestational age at delivery in the ART subgroup was significantly shorter than that in the no ART subgroup (38 weeks [36-39 weeks] vs. 39 weeks [38-40 weeks]; P = 0.005). CONCLUSIONS: Endometriosis may affect obstetric outcomes. Women with endometriosis have a higher risk of postpartum hemorrhage. Women with endometriosis who conceived by ART may have a higher risk of postpartum hemorrhage and preterm birth than those conceived naturally.

Evaluation of Circulating Endometrial Cells as a Biomarker for Endometriosis.

BACKGROUND: Circulating endometrial cells (CECs) have been reported to be present in the peripheral blood of women with endometriosis (EM), providing clear and specific evidence of the presence of ectopic lesions. In this study, we established a method with a high detection rate of CECs, assessed the diagnostic value of CECs for EM and compared with serum CA125, and proposed a hypothesis for the pathogenesis of EM from the new perspective of CECs. METHODS: The participants were enrolled prospectively from October 2015 to July 2016. The peripheral blood samples were collected from 59 participants, and the blood cells were isolated for immunofluorescence staining via microfluidic chips. The cells that were positive for vimentin/cytokeratin and estrogen/progesterone receptor and negative for CD45 were identified as CECs. The serum CA125 level was tested with electrochemiluminescence immunoassay. RESULTS: The detection rate of CECs reached 89.5% (17/19) in the EM group, which was significantly higher than that of the control group (15.0% [6/40], P < 0.001) and was independent of menstrual cycle phases. Furthermore, a positive CEC assay detected 4/5 cases of Stage I-II EM. In contrast, a positive CA125 test had limited value in detecting EM (13/19, 68.4%) and detected only one case of Stage I-II EM. CONCLUSION: CECs are promising biomarkers for EM with great potential for a noninvasive diagnostic assay.

Humoral immune responses induced by anti-idiotypic antibody fusion protein of 6B11scFv/hGM-CSF in BALB/c mice.

BACKGROUND: We have previously developed and characterized a monoclonal anti-idiotype antibody, designated 6B11, which mimics an ovarian carcinoma associated antigen OC166 - 9 and whose corresponding monoclonal antibody is COC166 - 9 (Ab1). In this study, we evaluate the humoral immune responses induced by the fusion protein 6B11 single-chain variable fragment (scFv)/human granulocyte macrophage colony-stimulating factor (hGM-CSF) and 6B11scFv in BALB/c mice. METHODS: The fusion protein 6B11scFv/hGM-CSF was constructed by fusing a recombinant single-chain variable fragment of 6B11scFv to GM-CSF. BALB/c mice were administrated by 6B11scFv/hGM-CSF and 6B11scFv, respectively. RESULTS: The fusion protein 6B11scFv/hGM-CSF retained binding to the anti-mouse F (ab) 2' and was also biologically active as measured by proliferation of human GM-CSF dependent cell TF1 in vitro. After immunization with the 6B11scFv/hGM-CSF and 6B11ScFv, BALB/c mice showed significantly enhanced Ab3 antibody responses to 6B11scFv/hGM-CSF compared with the 6B11scFv alone. The level of Ab3 was the highest after the first week and maintained for five weeks after the last immunization. Another booster was given when the Ab3 titer descended, and it would reach to the high level in a week. CONCLUSION: The fusion protein 6B11scFv/hGM-CSF can induce humoral immunity against ovarian carcinoma in vivo. We also provide the theoretical foundation for the application of the fusion protein 6B11scFv/hGM-CSF for active immunotherapy of ovarian cancer.

[Study of immunization protocol of ovarian carcinoma associated 6B11 anti-idiotypical minibody].

OBJECTIVE: To probe better immunization dose and interval of anti-idiotypical minibody (6B11 minibody) in animals and to guide the clinical trials of ovarian epithelial cancer treatment. METHODS: Minibody was induced with isopropylthiogalactoside (IPTG) in E.coli and analyzed with direct enzyme linked immunosorbent assay (ELISA). Normal BALB/c mice were randomly divided into groups A, B, C, D, E, F, immunized with the murine monoclonal anti-idiotypic antibody 6B11 minibody 150 microg, 100 microg, 50 microg, and mice IgG 100 microg, human IgG 100 microg, phosphate buffered saline (PBS) 100 microl at d(1), d(14), d(28) respectively. Anti-anti-idiotypic antibody (Ab3) level was tested and antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) effect of mouse spleen cells to human ovarian carcinoma SKOV3 cells were measured using (51)Cr-release assay. UV absorption values were tested at 490 nm. RESULTS: 6B11 minibody was successfully expressed on E.coli and could react with a murine monoclonal antibody COC166-9. Ab3 could not be detected until one week after d(14)'s boost, its level gradually elevated and peaked one week after d(28)'s boost, and maintained at high level for about six weeks then declined dramatically seven weeks after d(28)'s boost. When boosted again at seven weeks after d(28)'s boost, the Ab3 level elevated quickly one week after, and maintained at this level at least for two weeks. The Ab3 level of group B was higher than groups A and C, mean A (absorption) value during six weeks after d(28)'s boost was 1.05 in group A, 1.06 in group B, 0.94 in group C, and there was no significant difference (P > 0.05). At four different effector cell/target cell (E/T) ratios, the ADCC was highest in group A and lowest in group C; when the E/T ratio was 1:125, (51)Cr releasing rate was 23% in group A, 17% in group B, and 12% in group C, the difference between groups A, B, C had statistical significance (P < 0.05). When serum was diluted at 1:50, the CDC effects were higher in group A and B than in group C ((51)Cr releasing rate was 47%, 39%, 26% respectively; P < 0.05), but there was no significant difference between groups A and B (P > 0.05). CONCLUSION: 6B11 anti-idiotypic minibody of ovarian carcinoma can be used as tumor vaccine, the suitable immunization protocol in animals may be: prime at d(1), d(14) and d(28) at a dose of 100 microg; prime interval is six weeks.