Comparison of cesarean section rates between obstetricians preferring labor induction at early versus late gestational age.

OBJECTIVE: To compare the cesarean section (CS) rates of obstetricians with a preference of labor induction at early versus late gestational age. MATERIAL AND METHODS: Medical records of women who were low risk, nulliparous, singleton pregnancy, and >37 weeks and delivered their babies, were reviewed. Obstetricians, who preferred labor induction at<41 weeks, were allocated to the early induction group; and the other obstetricians were allocated to the late induction group. RESULTS: The late induction group had a higher percentage of labor induction at ≥41 weeks, compared with the early induction group (21% vs. 8%, p = 0.007). The late induction group had a lower CS rate (11.0% vs. 19.1%, p < 0.001). Multivariable Cox proportional hazard model revealed that the early induction group (hazard ratio [HR] = 2.14, p < 0.001), maternal age (HR = 1.04, p = 0.001), premature rupture of membranes (HR = 1.59, p = 0.006), and birth body weight (kg, HR = 2.13, p < 0.001) were independent predictors of CS. In women receiving labor induction (n = 312), birth body weight (kg, HR = 1.72, p = 0.04) was the sole predictor of CS; and there is a trend that the early induction group (HR = 1.54, p = 0.051) has a higher CS rate, compared with the late induction group. However, gestational age at labor induction was not a predictor of CS. CONCLUSION: In low-risk pregnancies, obstetricians preferring labor induction at early gestational age seem to be associated with a higher CS rate, compared with obstetricians preferring labor induction at late gestational age. Nonetheless, the above finding seems to be associated with physician's factor, instead of gestational age at labor induction.

Robotic or laparoscopic treatment of cesarean scar defects or cesarean scar pregnancies with a uterine sound guidance.

OBJECTIVE: To evaluate the feasibility and effectiveness of robotic/laparoscopic repair of cesarean scar defects or cesarean scar pregnancies with a uterine sound. MATERIALS AND METHODS: All consecutive women with cesarean scar defects or cesarean scar pregnancies who underwent robotic/laparoscopic repair with a bent uterine sound guidance were reviewed. Subjective changes in symptoms and objective changes in the depth and width of cesarean scar defects after surgery were reviewed. RESULTS: A total of 20 women underwent robotic (n = 3) or conventional laparoscopic (n = 17) repair of cesarean scar defects, which included postmenstrual vaginal bleeding associated with cesarean scar defects (n = 15), cesarean scar pregnancies (n = 3), accumulated pus in the cesarean scar defect (n = 1) and an incomplete abortion incarcerated in the cesarean scar defect (n = 1). Bladder perforation occurred in one woman during robotic adhesiolysis. All women with cesarean scar defects (n = 15) reported an improvement in postmenstrual vaginal bleeding after surgery. Follow-up sonography showed a decrease in the depth and width of the cesarean scar defect and an increase in the residual myometrial thickness. CONCLUSION: Robotic or laparoscopic repair with a uterine sound guidance seems to be a feasible and effective method in the treatment of cesarean scar defect or cesarean scar pregnancy.

A Preliminary Report of A Low-Dose Step-Up Regimen of Recombinant Human FSH for Young Women Undergoing Ovulation Induction with IUI.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of a recombinant human follicle stimulating hormone (r-FSH) low-dose step-up regimen for controlled ovarian hyperstimulation in patients undergoing ovulation induction (OI) with intrauterine insemination (IUI). MATERIALS AND METHODS: The study was conducted in the Department of Obstetrics and Gynecology, Far Eastern Memorial Hospital, New Taipei, Taiwan. In this prospective, observational study, consecutive infertile women (20-35 years) with regular menstrual cycles and a normal baseline FSH level were prospectively enrolled between January 2010 and September 2010. A starting dose of 112.5 IU/day r-FSH was administered on day 3 and increased by 37.5 IU/day every 2 days until a follicle ≥11 mm in diameter was present. Recombinant human chorionic gonadotropin (r-hCG) was administered when a follicle ≥18 mm was noted. Monifollicular development was defined as only one follicle with a diameter ≥16 mm. Clinical pregnancy was defined as a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs. RESULTS: A total of 29 women and 30 cycles were included. The mean daily dose of r-FSH to achieve a follicle of ≥11 mm in diameter was 131.3 ± 23.6 IU and the mean total dose was 1030.0 ± 383.2 IU. Approximately 41% of the cycles were monofollicular. Clinical pregnancy was observed in 9 (30.0%) cycles, and a fetal heart beat was observed in 7 (23.3%). There were no multiple pregnancies. Mild ovarian hyperstimulation syndrome, which was resolved with conservative management, was observed in 3 (10.0%) cycles. CONCLUSION: This r-FSH low-dose step-up regimen seems to be a feasible and practical method for OI in younger infertile women undergoing IUI.

Factors influencing the abortion interval of second trimester pregnancy termination using misoprostol.

OBJECTIVES: To determine the factors influencing the abortion interval (AI) for medical termination of second-trimester pregnancy using misoprostol. MATERIALS AND METHODS: All patients who were admitted for second-trimester pregnancy termination between January 2008 and August 2013 were reviewed. Those who received either 200 µg or 400 µg of priming vaginal misoprostol, followed by 200 µg of misoprostol orally at 6-hour intervals were enrolled. RESULTS: In a total of 101 patients, delivery occurred within 24 hours of commencement in 62 patients (61%) and within 48 hours in 84 patients (83%), and the median AI was 16.5 hours. One patient (1%) failed to deliver. The remaining 100 fetuses were delivered successfully, and the median AI was 16.3 hours. Higher parity [hazard ratio (HR) = 1.28, p = 0.04], the presence of intrauterine fetal demise (HR = 2.66, p = 0.003), and the presence of premature preterm rupture of membranes (HR = 4.51, p = 0.003) were associated with shorter AI. Additionally, all women with premature preterm rupture of membranes delivered successfully within 12 hours; higher parity (odds ratio = 2.12, p = 0.01) and lower fetal birth body weight (odds ratio = 0.992, p = 0.01) were associated with successful delivery within 12 hours. There was no significant difference in AI in the groups that received different doses of priming vaginal misoprostol (200 µg vs. 400 µg). CONCLUSION: Higher parity, intrauterine fetal demise, and preterm premature rupture of membranes were associated with shorter AI. The regimen of 200 µg oral misoprostol at 6-hour intervals following a 200 µg or 400 µg priming vaginal dose is feasible and efficacious for second trimester pregnancy termination.

The outcomes of intracytoplasmic sperm injection and laser assisted hatching in women undergoing in vitro fertilization are affected by the cause of infertility.

BACKGROUND: We sought to determine the association between factors that affected clini- cal pregnancy and live birth rates in patients who underwent in vitro fertilization (IVF) and received intracytoplasmic sperm injection (ICSI) and/or laser assisted hatching (LAH), or neither. MATERIALS AND METHODS: In this retrospective cohort study, the records of women who underwent IVF with or without ICSI and/or LAH at the Far Eastern Memorial Hospital, Taipei, Taiwan between January 2007 and December 2010 were reviewed. We divided patients into four groups: 1. those that did not receive ICSI or LAH, 2. those that received ICSI only, 3. those that received LAH only and 4. those that received both ICSI and LAH. Univariate and multivariate analyses were performed to determine factors associated with clinical pregnancy rate and live birth rate in each group. RESULTS: A total of 375 women were included in the analysis. Oocyte number (OR=1.07) affected the live birth rate in patients that did not receive either ICSI or LAH. Mater- nal age (OR=0.89) and embryo transfer (ET) number (OR=1.59) affected the rate in those that received ICSI only. Female infertility factors other than tubal affected the rate (OR=5.92) in patients that received both ICSI and LAH. No factors were found to affect the live birth rate in patients that received LAH only. CONCLUSION: Oocyte number, maternal age and ET number and female infertility fac- tors other than tubal affected the live birth rate in patients that did not receive ICSI or LAH, those that received ICSI only, and those that received both ICSI and LAH, respectively. No factors affected the live birth rate in patients that received LAH only. These data might assist in advising patients on the appropriateness of ICSI and LAH after failed IVF.

Modified novel technique for improving the success rate of applying seprafilm by using laparoscopy.

STUDY OBJECTIVE: To describe a modified surgical procedure for applying the adhesion barrier Seprafilm laparoscopically. DESIGN: Retrospective analysis with videos and illustrations showing laparoscopic application of Seprafilm. SETTING: University hospital. PATIENTS: Women undergoing fertility-sparing laparoscopic surgery (myomectomy, endometriotic ovarian cyst or dermoid cyst enucleation, and tuboplasty) via a modified technique. INTERVENTION: Two layers of Seprafilm with plastic covering were rolled together and delivered through a 10-mm trocar, and an irrigation tube was used to moisten the Seprafilm and cover the irregular postoperative rough surface of the organ. After application of Seprafilm, the patient was placed in a reverse Trendelenburg position to check whether the Seprafilm remained in situ on the target surgical surface to act as a physical barrier to adhesion development. MEASUREMENTS AND MAIN RESULTS: After changing the patient's position, illustrations and videos showed that the Seprafilm remained on the postoperative surgical surface, creating a site-specific physical barrier. On day 4 after myomectomy, second-look laparoscopy in 2 patients showed that the Seprafilm had become gel-like and remained between the intestine and posterior rough surface of the uterus. There were no systemic second-look laparoscopic data. CONCLUSION: It is feasible and easier to apply Seprafilm adhesion barrier laparoscopically using the modified technique. Further studies are warranted to prove its efficacy after such use.

Human chorionic gonadotropin up-regulates expression of myeloid cell leukemia-1 protein in human granulosa-lutein cells: implication of corpus luteum rescue and ovarian hyperstimulation syndrome.

CONTEXT: The corpus luteum is a dynamic endocrine structure with periodic development and regression during menstrual cycles. Its lifespan can be prolonged by human chorionic gonadotropin (hCG). However, the signal mechanisms of this phenomenon remain unclear. OBJECTIVE: Our objective was to investigate the molecular mechanisms of hCG in the maintenance of the viability of granulosa-lutein cells. DESIGN: Granulosa-lutein cells were obtained from women undergoing in vitro fertilization. We examined the effects of hCG on the survival of cultured granulosa-lutein cells. The signal pathway inducing antiapoptotic protein was investigated. RESULTS: hCG enhanced viability of granulosa-lutein cells through antiapoptosis but not proliferation, because the apoptotic marker of annexin V was decreased, but the proliferative markers of Ki67 and proliferating cell nuclear antigen were not increased. Myeloid cell leukemia-1 (Mcl-1) protein, but not B-cell lymphoma protein-2 or B-cell lymphoma protein-xL, was significantly induced by hCG and LH. The granulosa-lutein cells secreted vascular endothelial growth factor that induced endothelial permeability. Mcl-1 small interfering RNA increased DNA fragmentation and diminished the antiapoptotic effect of hCG. hCG induced Mcl-1 expression through the LH/hCG receptor, adenylate cyclase, protein kinase A, and cAMP response element-binding protein signal pathway. Flavopiridol inhibited Mcl-1 production, released cytochrome c, and induced apoptosis of granulosa-lutein cells. CONCLUSIONS: We first demonstrate that hCG prevents apoptosis of granulosa-lutein cells through the induction of Mcl-1 protein via the LH/hCG receptor and a cAMP response element-binding protein-dependent pathway. We may have found the molecular mechanism for luteal rescue during early pregnancy. Mcl-1 prevents apoptosis and increases cell viability but not proliferation as mechanisms for luteal rescue. Mcl-1 is a key molecule of hCG signaling.

Factors associated with failure to achieve birth emphasizing a successful singleton at term following in vitro fertilization.

OBJECTIVE: To evaluate the factors that might affect birth emphasizing a successful singleton at term (BESST) outcomes in women undergoing in vitro fertilization. METHODS: A retrospective review of assisted reproduction cases from January 1, 2001, to July 31, 2005, at the Far Eastern Memorial Hospital, Taipei, Taiwan. Variables that were potentially associated with failure to achieve BESST were evaluated using univariate and multivariate logistic regression analysis. RESULTS: Successful embryo transfer occurred in 297 of the 323 cases of assisted reproduction. In total, 123 women became pregnant and were enrolled for analysis, of whom 94 had live births and 55 achieved BESST. Multivariate analysis indicated that the number of embryos transferred, the presence of ovarian hyperstimulation syndrome, female infertility factors (other than tubal factors), and embryo quality were associated with increased relative risk of BESST failure, with odds ratios of 1.02 (95% confidence interval [CI], 1.01-1.02), 1.21 (95% CI, 1.08-1.36), 1.41 (95% CI, 1.22-1.62), and 0.79 (95% CI, 0.68-0.91), respectively. CONCLUSION: The number of embryos transferred, the presence of ovarian hyperstimulation syndrome, female infertility factors other than tubal factors, and embryo quality correlate with the risk of failure to achieve BESST.

Lysophosphatidic acid up-regulates expression of growth-regulated oncogene-alpha, interleukin-8, and monocyte chemoattractant protein-1 in human first-trimester trophoblasts: possible roles in angiogenesis and immune regulation.

The serum lysophospholipase D activity and production of lysophosphatidic acid (LPA) increase in women with pregnancy. The effects of LPA on human placenta tissue remained unclear. We investigate the expression of LPA receptors and function of LPA in human first-trimester trophoblasts. Normal villous trophoblasts were obtained from termination of first-trimester gestation. We examined the expression of LPA receptors in primary culture of trophoblasts and the tissue. The effects of LPA on the expressions of chemokines of trophoblasts were examined using RT-PCR and enzyme immunoassay. We delineate signal pathways of LPA-inducing relevant chemokines in trophoblasts. The secretory chemokines were tested for angiogenic function using human endometrial microvascular endothelial cells and for immunological chemotaxis using decidual natural killer cells and THP-1 monocytes. The results revealed the expression of LPA1 receptors in trophoblast cells. LPA enhanced growth-regulated oncogene (GRO)-alpha, IL-8 and monocyte chemoattractant protein (MCP)-1 expressions in a time- and dose-dependent manner. Mechanistic dissection disclosed that LPA functioned mainly via the LPA1 receptor, Gi protein, various signal mediators of ERK, protein kinase C, p38, Akt, and c-Jun N-terminal kinase, and nuclear factor-kappaB pathways to secrete these chemokines. LPA-induced IL-8 protein secretion of trophoblasts enhanced permeability, migration, proliferation, and capillary tube formation of human endometrial microvascular endothelial cells. LPA-induced GRO-alpha and MCP-1 incited chemotaxis of natural killer cells and monocytes. We demonstrate that LPA mediates trophoblast cells to produce GRO-alpha, IL-8, and MCP-1 via LPA1 receptors and nuclear factor-kappaB-dependent signal pathways. Through LPA-induced chemokine production, human first-trimester trophoblast cells may regulate angiogenesis and innate immune system in early pregnancy.

Signal mechanisms of vascular endothelial growth factor and interleukin-8 in ovarian hyperstimulation syndrome: dopamine targets their common pathways.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a serious complication of ovarian stimulation with massive ascites, pleural effusion and hemoconcentration. The pathophysiological signal mechanisms of OHSS are still unclear and merit further investigation. METHODS: Various angiogenic cytokines of follicular fluid and ascites of patients with risk of OHSS were measured, and examined for inducing endothelial permeability. These include vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, basic fibroblast growth factor, tumor necrosis factor-alpha, IL-1alpha, IL-1beta and platelet-derived growth factor. We explore the molecular signal pathways of major contributing cytokines in granulosa-lutein cells and endothelial cells possibly involved in OHSS. RESULTS: Neutralizing antibodies of VEGF or IL-8 significantly decreased follicular fluid- and ascites-induced endothelial permeability. Human chorionic gonadotrophin induced VEGF secretion of granulosa-lutein cells through the Sp1 and CREB dependent pathways. IL-8 activated CXCR1/2 of endothelial cells leading to VEGF receptor (VEGFR)-2 transactivation. Both VEGF and IL-8 of follicular fluid enhanced endothelial permeability via VEGFR-2-mediated Rho/Rock activation, actin polymerization and phosphorylations of VE-cadherin and occludin, resulting in opening of adherens junctions and tight junctions. Dopamine (2 microM) inhibited follicular fluid-induced VEGFR-2 signals and endothelial permeability, without diminishing migration and tube formation. CONCLUSIONS: Our results suggest that VEGF and IL-8 secreted from corpora luteae may play major roles in OHSS. Delineation of signal pathways would be helpful for treatment. Dopamine may block VEGF- and IL-8-induced endothelial permeability by inhibiting common VEGFR-2 dependent signals.