Possibility of women treated with fertility-sparing surgery for non-epithelial ovarian tumors to safely and successfully become pregnant-a Chinese retrospective cohort study among 148 cases / 医学前沿

This study was performed to evaluate the oncological and reproductive outcomes of childbearing-age women treated with fertility-sparing surgery (FSS) for non-epithelial ovarian tumors in China. One hundred and forty eight non-epithelial ovarian tumor women treated with FSS between January 1, 2000 and August 31, 2015 from two medical centers in China were identified. Progression-free survival (PFS) was 88.5%, whereas overall survival (OS) was 93.9%. Univariate analysis suggested that delivery after treatment is related to PFS (P = 0.023), whereas histology significantly influenced OS. Cox regression analysis suggested that only histology was associated with PFS and OS (P < 0.05). Among the 129 women who completed adjuvant chemotherapy (ACT), none developed amenorrhea. Among the 44 women who desired pregnancy, 35 (79.5%) successfully had 51 gestations including 35 live births without birth defects. Non-epithelial ovarian tumors can achieve fulfilling prognosis after FSS and chemotherapy. Histology might be the only independent prognostic factor for PFS and OS. FSS followed by ACT appeared to have little or no effect on fertility. Meanwhile, postoperative pregnancy did not increase the PFS or OS. Use of gonadotropin-releasing hormone agonist was not beneficial for fertility.

Preventing Effect of Different Dosages of Progynova in Intrauterine Adhesions After TCRS Under Laparoscope / 医药导报

Objective To explore the effect of different dosages of progynova in preventing intrauterine adhesions after transcervical resection of septum ( TCRS) under laparoscope. Methods Clinical data of 213 TCRS patients under laparoscope were retrospectively analyzed, and these cases were divided into four groups according to the dosages of progynova. Except for group A (n=26), group B, C, D were given 4,6,8 mg.d-1 of progynova.Endometrial thickness, menstrual blood volume, incidence rates of residual septal and intrauterine adhesions, rate of adverse effect, pregnancy rate after operation and rate of spontaneous abortion were compared among the four groups. Results The incidence rate of residual septal in group A, B, C, D was 11.5%, 6.9%, 6.0% and 6.3%, respectively.Incidence rate of intrauterine adhesions after operation was 46.2%, 12.5%, 9.0% and 4.2%, respectively.The pregnancy rate in group A, B, C and D was 30.8%, 59.7%, 58.2% and 60.4%, respectively. There were significant differences between group A and the other groups(all P<0.05).The high dose of progynova(8 mg.d-1) significantly increased endometrial thickness ( P<0. 05 ) and menstrual blood volume ( P<0. 05 ) . But the incidence rates of gastrointestinal tract reaction, hepatic damage and vaginal spotting in the high dose group of progynova increased obviously( P<0.05) . Conclusion Progynova is a safe and effective drug in preventing intrauterine adhesions after TCRS. It can effectively prevent intrauterine adhesions, increase pregnancy rate and improve pregnant outcome.

Correlation between physical status of human papilloma virus and cervical carcinogenesis / 华中科技大学学报（医学）（英德文版）

The prevalence of human papilloma virus (HPV)-16 in patients with cervical cancer, the physical status of HPV-16 in patients with cervical lesions, and the role of HPV-16 integration in cervical carcinogenesis were investigated. HPV genotyping was performed by using PCR approach with the primer GP5+/GP6+ and type-specific primer on biopsy specimens taken operatively from 198 women. Multiple PCR was done to detect physical status of HPV-16 in a series of cervical liquid-based cytology samples and biopsy specimens obtained from different cervical lesions with HPV-16 infection, including 112 specimens with cervical cancer, 151 specimens with CIN I, 246 specimens with CIN and 120 specimens with CINIII. The results showed that there were 112 cervical cancer samples (56.57% of total cervical cancer patients) with HPV-16 infection. The frequency of HPV-16 pure integration was 65.18% (73/112), 56.57% (47/120), 23.58% (58/246) and 7.95% (12/151) in cervical cancer, CINIII, CINII and CINI patients respectively. In situ hybridization was performed on some paraffin-embedded sections of CINII, CINIII and cervical cancer to verify the physical status of HPV-16 infection. Significant difference was observed between cervical cancer and CIN I, CINII, CINIII in the frequency of HPV-16 integration (P<0.01). It is suggested that HPV-16 is the most prevalent type and is associated with cervical cancer. In the case of HPV-16 infection there are close associations between the severity of cervical lesions and the frequency of HPV-16 integration. The application of testing HPV genotyping and physical status based on detection of HC-II HPV DNA would be in favor of predicting the prognosis of cervical precancerosis and enhancing the screening accuracy of cervical cancer.

Associated factors of early abortion among singleton pregnancies after assisted reproductive technology / 中华围产医学杂志

Objective To investigate the relative risk factors for early abortion among singleton pregnancies after assisted reproductive technology (ART) treatment. Methods A retrospective analysis was performed on 1636 singleton pregnancies, including 196 early abortion cases and 1195pregnancies with live birth after exclusion of those lost cases during follow-up, or complicated with uterine deformity, or oocyte receptor, or late abortion, or incomplete medical record, following in vitro fertilization(IVF)/ intracytoplasmic sperm injection (ICSI) treatment and the risk factors of early abortion were investigated. The early abortion rate was also compared between fresh IVF/ICSI group and frozen embryo transfer (FET) group (n=386). Results Multivariate Logistic regression analysis indicated that elder women (OR= 1. 143,95%CI: 1. 096-1. 196) and patients with polycystic ovarian syndrome (OR = 4. 309,95 % CI : 2. 564-7.243) were risk factors of spontaneous early abortion,and high mean score of transferred embryos (MSTE) (OR = 0. 808, 95% CI: 0. 717-0. 912) and endometrial triple-lined pattern on the day of human chorionic gonadotropin (hCG) administration (OR=0. 431, 95% CI: 0. 243-0.764)were protective factors. Significant difference were found in the maternal age [(32.22±4. 10) yrs vs (30.28±3. 66) yrs],the duration of infertility [(5. 90±4.26) yrs vs (5.20 ± 3. 32) yrs], basal serum follicle-stimulating hormone (FSH) level [(6. 35 ±2.30) mIU/ml vs (5.95±2.12) mIU/ml], number of transferred embryos (2. 31±0. 51) vs (2. 18±0.49), serum estradiol level on the day of hCG administration [(2467. 1 ± 1588. 8) pg/ml vs (2934. 5 ±1785.2) pg/ml] and MSTE (7.03 ±1.35 vs 7.74 ± 1.25) between the abortion group and livebirth group (all P＜0. 05). The spontaneous abortion rate was higher in the FET group than in the fresh embryo transfer group [17. 36%(67/386) vs 13.02% (213/1636), χ2 =4. 296, P=0. 023].Conclusions Women at elder age, or with long duration of infertility, high basal FSH level,polycystic ovarian syndrome, low MSTE, non-triple-lined pattern of endometrium on the day of hCG administration are at risk of spontaneous early abortion in pregnancies after ART. The rate of spontaneous abortion is higher in FET group than in fresh IVF/ICSI group.

Association of controlled ovarian hyperstimulation treatment with down-regulation of key regulators involved in embryonic implantation in mice / 华中科技大学学报（医学）（英德文版）

The debate exists whether or not gonadotropin-releasing hormone (GnRH) analogs used in controlled ovarian hyperstimulation (COH) impair endometrial receptivity. Homeobox A11 (Hoxa11), Meis homeobox 1 (Meis1), cadherin 1 (Cdh1), and catenin beta 1 (Ctnnb1) are well known to be involved in successful implantation. In this study, the endometrial expression of Hoxa11, Meis1, Cdh1, and Ctnnb1 during the peri-implantation period was investigated in an in vitro fertilization (IVF) mouse model by real-time RT-PCR and Western blot to evaluate the relationship between Hoxa11, Meis1, Cdh1, and Ctnnb1 expression and the impact of the COH on endometrial receptivity. The mimic COH protocols included GnRH agonist plus human menopausal gonadotropin (HMG) (GnRH agonist group), GnRH antagonist plus HMG (GnRH antagonist group), and HMG alone (HMG group). The expression levels of Hoxa11, Meis1, Cdh1, and Ctnnb1 mRNA and protein were decreased in all of the COH groups. The expression levels of Hoxa11 and Ctnnb1 were the lowest in the GnRH agonist group, and those of Meis1 and Cdh1 were lower in the GnRH analog groups than the HMG group. There were positive correlations between the expression of Hoxa11 and Ctnnb1, as well as the expression of Meis1 and Cdh1 among all the groups. In conclusion, the COH protocols, particularly with GnRH analogs, suppressed Hoxa11, Meis1, Ctnnb1 and Cdh1 expression, in mouse endometrium during the peri-implantation period. Our data reveal a novel molecular mechanism by which the COH protocols might impair endometrial receptivity.

Polo-like kinase-1 regulates first cleavage of one-cell embryos in culture during assisted reproduction

To investigate the role of polo-like kinase -1 [PLKl] in the first cleavage of a zygote in culture. This experiment took place in the Reproductive Medicine Center of Tongji Hospital, Wuhan, China, from 1st June 2009 to 20th November 2009. First, we detected the expression of PLKl during the first zygotic division by using Western blotting, and then we reduced the expression of PLKl during the first zygotic division by ribonucleic acid [RNA] interference [including 4 groups: PLKl small interfering RNA [siRNA], siRNA control, mock transfection, and only zona pellucida [ZP] removal], finally we evaluated and compared the first cleavage rates of the 4 groups. The expression of PLKl peaked in the first M phase of zygotic cleavage [3 samples/group, 100 zygotes/sample]. The relative amount of PLKl of the mouse zygotes was reduced significantly after siRNA transfection. The first cleavage rate of the PLKl siRNA group was significantly less than that of other groups [siRNA control, mock transfection, and only ZP removal, p=0.000]. The PLKl plays a crucial role during the first cleavage of one-cell embryos, and the zygotes are unable to divide successfully without functional PLKl

In vitro study on human trophoblast cells infected with HCMV / 华中科技大学学报（医学）（英德文版）

Human trophoblast cells were isolated and cultured in vitro in order to investigate possible pathogenesis of intrauterine infection caused by HCMV. Trophoblast cells were obtained by compound enzymes digestion and discontinuous percoll gradient. Cells and purity were identified by using immunocytochemistry assay with anti-CK7, Vim and beta-hCG antibodies. HCMV AD169 strain replication in isolated trophoblast cells and cell apoptosis were detected at different time points post infection (p.i.). The results showed that highly purified trophoblast cells were obtained. Specific virus replication was increased dramatically at the 24th h p.i., and then increased slowly during 48 h and 72 h. Apoptosis rate of trophoblast cells infected with HCMV was (34.68+/-3.14)% at 24th h p.i., while that in control group was (15.32+/-2.34)% (P<0.05). It was suggested that highly purified trophoblast cells can be isolated by the simplified cell purification method. HCMV can infect human trophoblast cells, and be quickly replicated, resulting in the accelerated apoptosis of human trophoblast cells during early time.

Von Willebrand factor antigen and ADAMTS13 activity assay in pregnant women and severe preeclamptic patients / 华中科技大学学报（医学）（英德文版）

The present study examined von Willebrand factor (vWF) levels and ADAMTS13 activity in pregnant and severe preeclamptic women in order to shed light on the prothrombotic state in severe preeclampsia. Thirty healthy women of childbearing age, 22 second trimester pregnant women, 30 third trimester pregnant women and 10 severe preeclamptic patients were recruited in this study. ADAMTS13 activity was determined by the FRETS-vWF73 assay and vWF antigen (vWF:Ag) levels by an enzyme-linked immunosorbent assay. The results showed that there were statistically significant differences in plasma vWF antigen levels between the severe preeclamptic and third trimester pregnant women, between third and second trimester pregnant women (P0.05). In conclusion, plasma ADAMTS13 activity is normal in severe preeclampsia despite the increased vWF:Ag levels. Prothrombotic state is involved in the pathogenesis of severe preeclampsia, as a result of endothelial injury.

Von Willebrand factor antigen and ADAMTS13 activity assay in pregnant women and severe preeclamptic patients / 华中科技大学学报（医学）（英德文版）

The present study examined von Willebrand factor (vWF) levels and ADAMTS13 activity in pregnant and severe preeclamptic women in order to shed light on the prothrombotic state in severe preeclampsia. Thirty healthy women of childbearing age, 22 second trimester pregnant women, 30 third trimester pregnant women and 10 severe preeclamptic patients were recruited in this study. ADAMTS13 activity was determined by the FRETS-vWF73 assay and vWF antigen (vWF:Ag) levels by an enzyme-linked immunosorbent assay. The results showed that there were statistically significant differences in plasma vWF antigen levels between the severe preeclamptic and third trimester pregnant women, between third and second trimester pregnant women (P<0.05). The third trimester pregnant women had significantly lower plasma ADAMTS13 activity than second trimester pregnant women (P<0.05). Nevertheless, no significant differences in plasma ADAMTS13 activity were found between severe preeclamptic patients and the third trimester pregnant women (P>0.05). In conclusion, plasma ADAMTS13 activity is normal in severe preeclampsia despite the increased vWF:Ag levels. Prothrombotic state is involved in the pathogenesis of severe preeclampsia, as a result of endothelial injury.

The Effects of Murine Cytomegalovirus on the Maturation,Fertilization, Cleavage and Blastula Formation of Mouse Oocytes In Vitro / 华中科技大学学报（医学）（英德文版）

To study the effects of mouse cytomegalovirus (MCMV) on the in vitro maturation, fertilization, cleavage and blastula formation of mouse oocytes, the immature oocytes were infected in vitro by MCMVs of different dosages (100 TCID50, 10 TCID50 and 1 TCID50). The oocytes were then observed for in vitro maturation, fertilization, cleavage and blastula formation and the ultrastructural changes after the culture with the viruses. Our results showed that no significant differences were found in IVM, IVF, cleavage and blastula formation among the groups treated with of virus of various dosages. And ultrastructural abnormality was observed in the oocytes treated by 100 TCID50 of viruses. It is concluded that MCMV did not have any conspicuous effects on IVM, IVF, cleavage and blastula formation of murine immature oocytes.

The effects of murine cytomegalovirus on the maturation, fertilization, cleavage and blastula formation of mouse oocytes in vitro / 华中科技大学学报（医学）（英德文版）

To study the effects of mouse cytomegalovirus (MCMV) on the in vitro maturation, fertilization, cleavage and blastula formation of mouse oocytes, the immature oocytes were infected in vitro by MCMVs of different dosages (100 TCID(50), 10 TCID(50) and 1 TCID(50)). The oocytes were then observed for in vitro maturation, fertilization, cleavage and blastula formation and the ultrastructural changes after the culture with the viruses. Our results showed that no significant differences were found in IVM, IVF, cleavage and blastula formation among the groups treated with of virus of various dosages. And ultrastructural abnormality was observed in the oocytes treated by 100 TCID(50) of viruses. It is concluded that MCMV did not have any conspicuous effects on IVM, IVF, cleavage and blastula formation of murine immature oocytes.

Co-Culture of Early Embryo with Human Decidual Stromal Cells in vitro by Improvement of Early Embryo Development / 华中科技大学学报（医学）（英德文版）

An early embryo co-culture system with human decidual stromal cells was established to study its effect on early embryonic cleavage and growth in vitro. Three hundred and eight 2-cell mouse embryos were co-cultured with human decidual stromal cell monolayer in MEM+0.4%bovine serum albumin (BSA) and 163 embryos cultured in MEM+15 % FCS alone as control. Among the mouse 2-cell embryos co-cultured with human decidual stromal cells, 72.73% developed to the morula stage and 67.21% cavitated to blastocysts with 59.74 % hatching, as compared with 61.34% to morula stage, 48.47% to blastocysts and none hatching in the controls,respectively. Co-cultured embryos cleaved slightly faster than controls and showed no or less fragmentation than those in the control. These results suggested that human decidual stromal cells can support early embryonic development and yield a reasonable number of embryos with good quality up to blastocyst stage.

Co-Culture of Early Embryo with Human Decidual Stromal Cells in vitro by Improvement of Early Embryo Development / 华中科技大学学报（医学）（英德文版）

An early embryo co-culture system with human decidual stromal cells was established to study its effect on early embryonic cleavage and growth in vitro. Three hundred and eight 2-cell mouse embryos were co-cultured with human decidual stromal cell monolayer in MEM+0.4%bovine serum albumin (BSA) and 163 embryos cultured in MEM+15 % FCS alone as control. Among the mouse 2-cell embryos co-cultured with human decidual stromal cells, 72.73% developed to the morula stage and 67.21% cavitated to blastocysts with 59.74 % hatching, as compared with 61.34% to morula stage, 48.47% to blastocysts and none hatching in the controls,respectively. Co-cultured embryos cleaved slightly faster than controls and showed no or less fragmentation than those in the control. These results suggested that human decidual stromal cells can support early embryonic development and yield a reasonable number of embryos with good quality up to blastocyst stage.