A single-arm phase III study exploring the efficacy and safety of LNG-IUS 8, a low-dose levonorgestrel intrauterine contraceptive system (total content 13.5 mg), in an Asia-Pacific population.

OBJECTIVE: The objective was to evaluate the efficacy and safety of a low-dose levonorgestrel intrauterine system with total content 13.5 mg (average approximately 8 µg/24 h over the first year; LNG-IUS 8; Jaydess®) in an Asia-Pacific population. STUDY DESIGN: An open-label, single-arm phase III study conducted at 25 centers in China, Australia and Korea assessed LNG-IUS 8 use over 3 years in nulliparous and parous women (N=1114) aged 18-40 years with regular menstrual cycles (21-35 days). Primary outcome was pregnancy rate, expressed as the Pearl Index. Secondary outcomes included 3-year cumulative failure rate, treatment-emergent adverse events (TEAEs), discontinuation rate, bleeding profile and placement pain. RESULTS: The full analysis set comprised 925 women (mean age 31.6 years, 6.4% nulliparous). Overall unadjusted Pearl Index was 0.35 (95% confidence interval 0.15-0.70); the 3-year cumulative failure rate was 0.9% (95% confidence interval 0.4-1.9). TEAEs and study drug-related TEAEs were reported in 70.1% and 31.2% of women, respectively. Overall, 27.9% of women discontinued the study, 16.9% due to adverse events. Frequent or prolonged bleeding (World Health Organization criteria) decreased from the first to the twelfth 90-day reference intervals (from 5.0% to 0.7% and from 44.1% to 3.0%, respectively), and the percentage of women with amenorrhea increased over time (from 0.4% to 10.8%). Pain on placement was reported as "none" or "mild" in 91.9% of women. CONCLUSIONS: LNG-IUS 8 was an effective and well-tolerated contraceptive method, providing another option for women in the Asia-Pacific region. IMPLICATIONS: In this phase III study, LNG-IUS 8 was shown to be highly effective and well tolerated in an Asia-Pacific population and was not associated with any new or unexpected safety events. LNG-IUS 8 provides another contraceptive option for women in the Asia-Pacific region.

[Effectiveness of intravenous immunoglobulin therapy in treating unexplained recurrent spontaneous abortion and its effect on the level of serum soluble human leucocyte antigen G].

OBJECTIVE: To explore the effectiveness of intravenous immunoglobulin (IVIG) in treating patients with unexplained recurrent spontaneous abortion (URSA) and the effect of IVIG on the level of soluble human leucocyte antigen G (sHLA-G). METHODS: This prospective trial conducted at PUMC Hospital between 2004 and 2008 included 60 women with URSA. The patients were allocated into IVIG group (30 cases) and control group (30 cases). IVIG was intravenously used before conception at a dose of 0.2g/kg; once pregnancy was confirmed,IVIG was continued every 4 weeks till the 20th gestational week. Traditional Chinese medicine or/and progesterone were used in control group. The outcome of pregnancy was evaluated by live birth rate and effective rate(defined as the embryo living 4 week longer than previous pregnancy). Serum samples were collected randomly before pregnancy and in the 6th-8th gestational week from IVIG group (15 samples),control group (15 samples),and healthy women (20 samples). The levels of sHLA-G,interferon γ (IFN-γ), interleukin-2 (IL-2), and interleukin-10 (IL-10) were determined by enzyme-linked immunosorbant assay (ELISA). RESULTS: The pregnancy rate was 93.3% in IVIG group. The live birth rate and effective rate were 85.7% (24/28) and 92.9% (26/28) in IVIG group,which were significantly higher than those in control group [56.7% (17/30) (P=0.021) and 63.3% (19/30) (P=0.011)]. Emesis occurred in one woman (3.3%) in IVIG group had during IVIG infusion but was relieved by lowering the speed of infusion. The mean sHLA-G level was (61.37∓35.57) U/ml in control group and (62.70∓37.24) U/ml in IVIG group (P>0.05); both of them were significantly lower than that of healthy women (88.49∓25.37) U/ml (Pü0.05). After pregnancy was achieved, the levels of sHLA-G and IL-10 were (34.19∓14.21) U/ml and (11.71∓2.75) pg/ml, respectively in the IVIG group, which were significantly higher than those in control group [(23.71∓12.83) U/ml and (8.71∓3.01) pg/ml, respectively] (P=0.008). CONCLUSIONS: Low-dose IVIG before and after pregnancy is a safe and effective in treating URSA. IVIG improves the development of fetus by up-regulating sHLA-G and IL-10 levels.

[Fetal anomalies in second trimester in recent ten years: clinical analysis of 116 cases].

OBJECTIVE: To evaluate the prevalence of fetal anomalies in recent 10 years and explore the effective methods of early diagnosis and treatment. METHODS: The clinical and pathological data of 116 pregnant women who underwent induced abortion in the second trimester due to fetal anomalies 1998 - 2007 were analyzed retrospectively. RESULTS: The fetal anomaly rate in the period 2003 - 2997 was 8.7 per thousand, significantly higher than that in the period 1998 - 2002 (3.1 per thousand, P < 0.001). The diagnostic methods of fetal anomalies used during the period 2003 - 2007 did not show significant differences compared with those used during the period 1998 - 2002. The gestational week when the fetal anomalies were detected in 2002 - 2007 was 19.3 weeks, not significantly preceded compared with that during 1998 - 2002 (22.4 weeks, P > 0.05). The top 5 fetal anomalies with high incidence rates were Down' syndrome, anencephalus, lip/palate cleft, fatal cystic hygroma of the neck, and cardiac anomalies. There were 30 cases of advanced maternal age over 35 years, 60.0% of whose fetuses showed chromosome abnormality. CONCLUSION: The incidence of fetal anomalies increases in recent years. The risk of fetal anomalies is high in the pregnant women in elder age. Pregnancy in advanced maternal age show high risk to occur fetal anomaly. Better approaches to diagnose fetal anomaly earlier are still to be found.

[Efficacy and safety of drospirenone-ethinylestradiol on contraception in healthy Chinese women: a multicenter randomized controlled trial].

OBJECTIVE: To evaluate the contraception efficacy, mode of bleeding, side effects and other positive effects of drospirenone-ethinylestradiol (Yasmin) in healthy Chinese women. METHODS: This was a multicenter, randomized, control study of 768 healthy Chinese women who consulted about contraception. The subjects were randomized into Yasmin group (30 microg ethinylestradiol plus 3 mg drospirenone, 573 cases) or desogestrel group (30 microg ethinylestradiol plus 150 microg desogestrel, 195 cases) with the ratio of 3:1. Each individual was treated for 13 cycles. Further visits were required at cycle 4, cycle 7, cycle 10 and cycle 13 of treatment Weight, height, body mass index were evaluated at each visit. The menstrual distress questionnaire (MDQ) was given to the women at baseline, visit 3 (cycle 7) and visit 5 (after cycle 13). RESULTS: The values of basal features were similar between two groups (P > 0.05). The Pearl index (method failure) of Yasmin was 0. 208/hundred women year which was lower than that of desogestrel (0. 601/hundred women year). The mode of bleeding was similar between two groups after trial without showing any significant difference. According to MDQ subscale, the improvement of water retention and increasing appetite during inter-menstrual period and water retention and general well-being during menstrual period in the Yasmin group (-0.297, -0.057, 0.033, 0.150 respectively) was more obvious than that in the desogestrel group (-0.108, 0.023, 0.231, -0.023 respectively) with a significant difference (P < 0.05). Some other values which improved in both two groups, especially the improvement of breast tenderness and pain and skin abnormality in Yasmin group (18.0%, 89/494; 12.6%, 62/494) was more distinct than that in desogestrel group (11.3%, 19/168; 5.4%, 9/168). The mean weight increased in desogestrel group (0.57 kg) while it decreased in Yasmin group (-0.28 kg) with a significant difference (P < 0.01). CONCLUSIONS: Both Yasmin and desogestrel have good efficacy on contraception and similar modes of menstrual bleeding. Yasmin is better than desogestrel in terms of weight control and premenstrual syndrome of oral contraceptive.

[Clinical analysis of 47 cases of placenta accreta in the second and third trimesters].

OBJECTIVE: To explore the clinical characters, diagnosis and treatment methods of placenta accreta. METHODS: A retrospective analysis was made of 47 cases of placenta accreta admitted during May 1997 to May 2007 into Peking Union Medical College Hospital. They included 17 cases in the second trimester and 30 cases in the third. RESULTS: Among all the patients, the incidence of placenta accreta was 0.262% (47/17 918). Most of these cases (81%, 38/47) experienced a uterine procedure. 30% (14/47) of the cases were found with placenta previa and 11% (5/47) with myoma in the current pregnancy. 11% (5/47) of all the cases suffered postpartum hemorrhage. In the 17 cases in the second trimester, 12 were diagnosed by ultrasonography and 5 by clinical evidence. While in the 30 cases in the third trimester, 8 were diagnosed by biopsy, 2 by ultrasonography, and 20 by clinical evidence. 45 cases were cured by conservative treatment, which included dilatation and curettage, uterine artery embolization (UAE) with or without methotrexate (MTX), tamping B-lynch suture, singly with MTX, and mifepristone. Only 2 cases received cesarean hysterectomy. CONCLUSIONS: The incidence of placenta accreta seems on the rise. The incidence in the second trimester is higher than that in the third. In the second trimester, most cases can be diagnosed by ultrasonography after labor, and presently UAE is the best conservative management. While in the third trimester clinical evidence is the most frequent diagnostic approach. A majority of the cases could be cured by conservative therapies, which help them avoid a hysterectomy.

[Risk factors in the living environment of early spontaneous abortion pregnant women].

OBJECTIVE: To study the relationship between early spontaneous abortion and living environment, and explore the risk factors of spontaneous abortion. METHODS: We conducted analysis based on the interview of 200 spontaneous abortion cases and the matched control (age +/- 2 years) by using multifactor Logistic regression analysis. RESULTS: The proportions of watching TV > or =10 hours/week, operating computer > or =45 hours/week, using copycat, microwave oven and mobile phone, electromagnetism equipment near the dwell or work place, e. g. switch room < or =50 m and launching tower < or =500 m in the cases are significantly higher than those in the controls in single factor analysis (all P < 0.05). After adjusted the effect of other risk factors by multifactor analysis, using microwave oven and mobile phone, contacting abnormal smell of fitment material > or =3 months, having emotional stress during the first term of pregnancy and spontaneous abortion history were significantly associated with risk of spontaneous abortion. The odds ratios of these risk factors were 2.23 and 4.63, respectively. CONCLUSION: Using microwave oven and mobile phone, contacting abnormal smell of fitment material > or =3 months, having emotional stress during the first term of pregnancy, and spontaneous abortion history are risk factors of early spontaneous abortion.

[Clinical observation of propofol combined with misoprostol for painless induced abortion].

OBJECTIVE: To observe the effects of propofol combined with misoprostol for painless induced abortion. METHODS: Two hundred early pregnant women, nullipara or pluripara with history of cesarean section, were randomly divided into two groups: control group receiving intravenous injection of propofol 2.5 mg/kg and then underwent induced abortion after becoming unconscious, and experimental group receiving misoprostol 200 microg intravaginally two hours before undergoing induced abortion. The effects on anesthesia, cervix dilatation, uterotonic degree, bleeding and abortion syndrome were observed. RESULTS: Anesthesia was 100% effective in both groups. No induced abortion syndrome occurred. For the effect on cervical dilatation, No.6 Hegars dilator were smoothly inserted into the cervical canal in 96 cases (96%) in the experimental group and in only 8 cases (8%) in the control group (P < 0.01). For the effect on uterotonic degree, 79 cases in the experimental group (79%) and 30 cases in the control group (30%) showed 1 approximately 2 cm of uterine contraction (P < 0.01). Seventy-five cases in the experimental group (75%) and 25 cases in the control group (25%) showed blood loss of less than 15 ml (P < 0.01). CONCLUSION: Intravenous injection of propofol combined with misoprostol administered intravaginally is effective in anesthesia and cervical dilatation with less bleeding and absence of abortion syndrome.

Effects of anticoagulation protein defect in maternal plasma on spontaneous abortion.

OBJECTIVE: To investigate the mechanism of anticoagulation protein defect in the pathogenesis of unexplained recurrent miscarriage. METHODS: Fifty-seven patients with a history of unexplained abortion were enrolled as the investigation group for tests of protein C, protein S, antithrombin III (AT-III), as well as activated protein C resistance (APC-R). The control group consisted of fifty healthy women with a history of normal pregnancy and delivery. Blood samples were obtained for, measuring serum activity of protein C, protein S, AT-III, and APC-R. Patients with positive APC-R were tested for factor V (FV) Leiden gene mutation by PCR-RFLP method. RESULTS: Of the 57 patients, 12 (21.1%), 1 (1.8%), and 5 (8.8%) cases were found with protein S, protein C, and AT-III deficiency respectively, and 13 (22.8%) cases with positive results of APC-R. Of the control group, no protein C or AT-III deficiency was ever found, whereas 2 (4.0%) volunteers were presented with protein S deficiency and 3 (6.0%) with positive results of APC-R. No FV Leiden gene mutation was identified in all the patients with positive APC-R results. Late spontaneous abortion cases had higher incidence of anticoagulation protein defect than the early cases. CONCLUSION: Anticoagulation protein defect may play a role in the pathogenesis of fetal loss, especially for those occurring in late stage of pregnancy.

Lower uterine segment pregnancy with placenta increta complicating first trimester induced abortion: diagnosis and conservative management.

OBJECTIVE: To discuss the diagnosis of and conservative management for lower uterine segment pregnancy with placenta increta complicating first trimester abortion. METHODS: Four patients with previous caesarean section and severe hemorrhage in induced abortion in the first trimester were studied. Uterine artery embolization (UAE) was used to control bleeding and preserve the uterus. RESULTS: UAE controlled heavy uterine bleeding satisfactorily. One of the four patients asked for a hysterectomy after UAE, and her pathology report confirmed "lower uterine segment pregnancy with placenta increta". CONCLUSION: Previous caesarean section is a risk factor for lower uterine segment pregnancy with placenta increta. UAE is one of the best conservative management methods for heavy hemorrhage, especially for women who desire future fertility.

[Clinical analysis of lower uterine segment pregnancy with heavy hemorrhage in inducing abortion].

OBJECTIVE: To discuss the diagnosis and conservation managements for the lower uterine segment pregnancy complicating the first trimester inducing abortion cases. METHOD: Four cases of lower uterine segment pregnancy that had heavy hemorrhage and received bilateral uterine artery embolization (UAE) were analysed. RESULTS: Four patients with previous caesarean section had torrential hemorrhage when they received inducing abortion in the first trimester. Digital subtractive angiography (DSA) showed branches of uterine artery were bleeding, the site of the branches were equivalent to the lower segment of uterus. UAE could control heavy uterine bleeding satisfactory and save their uterus successfully. One of four patients asked hysterectomy after UAE, her pathological examination of the operative specimen confirmed "lower uterine segment pregnancy with placenta increta". CONCLUSION: Previous caesarean section is one risk factor of lower uterine segment pregnancy, UAE is one of the best satisfactory conservation managements; the main prevent methods are controlling caesarean section rate and paying attention to the contraception.

Unbound E2F modulates TGF-beta1-induced apoptosis in HuH-7 cells.

E2F is an important target of the retinoblastoma protein (pRb) and plays a critical role in G(1)/S progression through the cell cycle. TGF-beta1 arrests HuH-7 cells in G(1) by suppressing phosphorylation of pRb and induces apoptosis by inhibiting its expression. In this study, we examined the downstream effects of TGF-beta1-induced apoptosis and the potential roles for pRb and E2F. The results indicated that greater than 90% of the TGF-beta1-induced preapoptotic cells were arrested in G(1) phase of the cell cycle. This was associated with a significant increase in both E2F-DNA-binding activity and transcription of E2F-responsive reporter constructs. In contrast, no significant changes were observed in E2F mRNA and protein levels, and the overexpression of pRb partially inhibited E2F activation. Gel-shift assays identified more than four E2F complexes from preapoptotic and synchronized G(1) HuH-7 cells, each exhibiting different patterns of E2F-associated proteins. The increased E2F activity did not affect the association patterns with pRb, p107 and p130, but altered the formation of an E2F-DP-1 complex. In contrast, E2F-DP-2 exhibited little change in the preapoptotic cells. Moreover, TGF-beta1 induced apoptosis at G(1) and inhibited entry into S phase irrespective of the increased E2F activity. The release of preapoptotic cells from TGF-beta1 resulted in rapid S phase entry and subsequent apoptosis in 33% of cells over a 72 hour period. In conclusion, the results demonstrate that TGF-beta1-induced apoptosis in HuH-7 cells is associated with a marked increase in activity of transcription factor E2F that is partially inhibited by overexpression of pRb. Preapoptotic changes are, in part, reversible upon removal of TGF-beta1 and the majority of cells re-enter the normal cell cycle. Finally, TGF-beta1-induced apoptosis with the associated increase in E2F activity can occur in both the G(1) and S phases of the cell cycle.