Expression of tissue factor and tissue factor pathway inhibitors during ovulation in rats: a relevance to the ovarian hyperstimulation syndrome.

BACKGROUND: Blood coagulation has been associated with ovulation and female infertility. In this study, the expression of the tissue factor system was examined during ovulation in immature rats; the correlation between tissue factor and ovarian hyperstimulation syndrome (OHSS) was evaluated both in rats and human follicular fluids. METHODS: Ovaries were obtained at various times after human chorionic gonadotropin (hCG) injection to investigate the expression of tissue factor system. Expression levels of ovarian tissue factor, tissue factor pathway inhibitor (Tfpi)-1 and Tfpi-2 genes and proteins were determined by real-time quantitative polymerase chain reaction (qPCR), and Western blot and immunofluorescence analyses, respectively. Expression levels of tissue factor system were also investigated in ovaries of OHSS-induced rats and in follicular fluid of infertile women. RESULTS: The expression of tissue factor in the preovulatory follicles was stimulated by hCG, reaching a maximum at 6 h. Tissue factor was expressed in the oocytes and the preovulatory follicles. Tfpi-2 mRNA levels were mainly increased by hCG in the granulosa cells whereas the mRNA levels of Tfpi-1 were decreased by hCG. Human CG-stimulated tissue factor expression was inhibited by the progesterone receptor antagonist. The increase in Tfpi-2 expression by hCG was decreased by the proliferator-activated receptor γ (PPARγ) antagonist. Decreased expression of the tissue factor was detected in OHSS-induced rats. Interestingly, the tissue factor concentrations in the follicular fluids of women undergoing in vitro fertilization were correlated with pregnancy but not with OHSS. CONCLUSIONS: Collectively, the results indicate that tissue factor and Tfpi-2 expression is stimulated during the ovulatory process in rats; moreover, a correlation exists between the levels of tissue factor and OHSS in rats but not in humans.

Use of Combined Oral Contraceptives in Perimenopausal Women.

While perimenopausal women have low fecundity, they are still capable of becoming pregnant and the majority of pregnancies occurring during perimenopause are unintended pregnancies. Therefore, even during perimenopause, contraception must be used if unintended pregnancies are to be avoided. However, many perimenopausal women and healthcare providers believe that older people should not take combined oral contraceptives (COC) because doing so may be dangerous. However, to date, there is no evidence that taking COC presents an increased risk of cardiovascular events or breast cancer for middle-aged women as compared to other age groups, and in their recommendations, the Centers for Disease Control and Prevention (CDC) also do not list age itself as a contraindication for COC. Perimenopausal women often experience menstrual irregularity, heavy menstrual bleeding, and vasomotor symptoms. Taking COCs can help control these symptoms and significantly reduce the risk of ovarian cancer, endometrial cancer, and colorectal cancer. The objective of the present review is to examine the usage methods of COC among perimenopausal women and the health issues that may arise from taking COC in perimenopausal women.

Non-absorbable and partially-absorbable mesh during pelvic organ prolapse repair: A comparison of clinical outcomes.

INTRODUCTION: The aim of this study was to compare the clinical outcomes of non-absorbable and partially-absorbable mesh intervention in pelvic organ prolapse. METHODS: This was a retrospective cohort study of patients who underwent transvaginal mesh operation for anterior and apical vaginal prolapse at a single tertiary center from January 2007 to December 2013. RESULTS: The group treated with partially-absorbable mesh showed better objective surgical outcomes than those treated with non-absorbable mesh in 1- and 2-year follow-ups. Recurrence rate was higher in the group with partially-absorbable mesh than in the non-absorbable mesh group, without any statistically significant difference. Mesh exposure were similar in both groups. Vaginal erosion, dyspareunia and de novo stress urinary incontinence were more common in the non-absorbable group without statistical significance. Buttock pain was more common but not significant in the partially-absorbable group. There were no significant differences in quality-of-life scores after mesh operation between both groups. CONCLUSION: Patients treated with partially-absorbable mesh showed better objective surgical outcomes with similar postoperative complications than those treated with non-absorbable mesh.

Factors associated with recurrence after colpocleisis for pelvic organ prolapse in elderly women.

INTRODUCTION: The aim of this study was to evaluate the factors associated with recurrence after colpocleisis for pelvic organ prolapse in elderly women. METHODS: This was a retrospective cohort study of patients who underwent colpocleisis for stage 3 or 4 pelvic organ prolapse at a single tertiary center from January 2007 to December 2015. RESULTS: A total of 107 patients who underwent colpocleisis were reviewed. Duration from prolapse occurrence to surgery was significantly longer (24.6 ± 22.8 years vs 8.0 ± 12.9 years, p = 0.021) in patients who had recurrence after colpocleisis than in those without recurrence. CONCLUSION: Duration of prolapse was longer in patients with recurrence than in those who had a successful outcome.

Regulation of interleukin-11 expression in ovulatory follicles of the rat ovary.

The aim of the present study was to examine the regulation of interleukin (IL)-11 expression, as well as the role of IL-11, during ovulation in gonadotropin-primed immature rats. Injection of equine chorionic gonadotropin (eCG), followed by human CG (hCG) to induce superovulation stimulated expression of the Il11 gene in theca cells within 6h, as revealed by northern blot and in situ hybridisation analyses. Real-time reverse transcription-polymerase chain reaction analysis showed that the IL-11 receptor, α subunit gene was expressed in granulosa and theca cells and that injection of hCG had no effect on its expression. IL-11 protein expression was stimulated in theca cells by hCG. LH-stimulated increases in Il11 mRNA levels in cultured preovulatory follicles were inhibited by protein kinase A and mitogen-activated protein kinase kinase inhibitors. Toll-like receptor (TLR) 2 and TLR4 were detected in preovulatory follicles, and the TLR4 ligand lipopolysaccharide, but not the TLR2 ligand Pam3Cys, increased Il11 mRNA levels in theca cells, but not in granulosa cells. Treatment of preovulatory follicles with IL-11 stimulated progesterone production and steroidogenic acute regulatory protein (Star) gene expression. Together, these results indicate that IL-11 in theca cells is stimulated by mitogen-activated protein kinase signalling and TLR4 activation, and increases progesterone production during ovulation.

Placenta Percreta-Induced Uterine Rupture at 7th Week of Pregnancy After In Vitro Fertilization in a Primigravida Woman: Case Report.

BACKGROUND: Placenta percreta is the most severe form of abnormal placental attachment. Spontaneous uterine rupture due to placenta percreta is extremely rare and difficult to diagnose in the first trimester. Most prior cases were associated with some risk factor for placenta percreta. We report a case of placenta percreta-induced spontaneous uterine rupture at the 7th week of pregnancy after in vitro fertilization in a primigravida woman who was not otherwise at risk of placenta percreta. CASE REPORT: A 34-year-old, primigravida woman at the 7th week of pregnancy presented with sudden severe abdominal pain. The patient was impregnated by frozen embryo transfer. The patient's antenatal course was unremarkable and she had no risk factor for placenta percreta. An emergency laparotomy was performed to diagnose the cause of hemoperitoneum and the operative findings included a hemoperitoneum of 2000 mL and a fundal uterine defect of 3 × 2 cm with placental tissue penetrating through the uterine serosa. Histopathologic examination confirmed the diagnosis of placenta percreta. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Placenta percreta is associated with serious morbidity and mortality during pregnancy, but it is quite rare and difficult to diagnosis in the first trimester. Emergency physicians should suspect uterine rupture due to placenta percreta in pregnant women with abdominal pain even in their first trimester of pregnancy and without risk factors of placenta percreta, especially in in vitro fertilization pregnancies.

Accuracy and precision of a new portable ultrasound scanner, the Biocon-700, in residual urine volume measurement.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to examine the accuracy of a new portable abdominal ultrasound (US) machine (Biocon-700, Mcube Technology, Seoul, Korea) for measuring postvoid residual (PVR) urine. METHOD: One-hundred and twenty-five patients with voiding problems underwent PVR measurements, which were compared with the postvoid bladder volume measurements obtained by catheterization within 5 min in the same patients. Accuracy was assessed by comparing the two methods, and correlation coefficients were obtained. RESULT: The Pearson's correlation coefficient between PVR volume as measured by US and by catheterization was 0.872 (R 2 = 0.76). The mean difference was 23.59 ± 37.32 ml (95% confidence interval, 17.5-30.65 ml), and the absolute scan error tended to increase with a greater amount of catheterized residual urine volume (R 2 = 0.49). CONCLUSIONS: Accuracy of the Biocon-700 scanner is as good as catheter assessments of residual volume and is therefore a sufficient alternative to catheterization for determining residual urine volume.

Cumulus cell-expressed type I interferons induce cumulus expansion in mice.

Ovulation resembles the inflammatory response. The purpose of the present study was to examine the expression and role of type I interferons (IFNs) Ifnalpha and Ifnbeta in mouse ovaries during the process of ovulation. An in vivo injection of equine chorionic gonadotropin (CG)-human CG (hCG) stimulated Ifnalpha and Ifnbeta mRNA in cumulus-oocyte complexes (COCs) within 6 h. Type I IFN receptor (Ifnar1 and Ifnar2) genes were also expressed in preovulatory follicles without a change by hCG. Immunofluorescent study revealed the expression of protein signals of Ifnalpha, Ifnbeta, and Ifnar1 in cumulus cells. Treatment of COCs with Ifnalpha or Ifnbeta in vitro induced cumulus expansion that was comparable to that mediated by epiregulin. In cultured COCs, the levels of Ifnalpha and Ifnbeta mRNA increased by epiregulin and follicle-stimulating hormone, but not by prostaglandin E2. Ifnalpha and Ifnbeta activated multiple signaling events (signal transducer and activator of transcription-1/3, Akt, and mitogen-activated protein kinase 1/2) and stimulated the expression of genes known to impact COC expansion (Has2, Ptx3, Tnfaip6, and Ptgs2). Interestingly, treatment of COCs with Toll-like receptor (TLR) 2 and TLR4 ligands (lipopolysaccharides, Pam3Cys, and hyaluronan fragments) increased Ifnalpha and Ifnbeta mRNA, while coculture with anti-TLR2/4 neutralizing antibody abolished these effects. Taken together, these results demonstrate that the type I IFN system is operating in mouse cumulus cells and plays a role in the induction of cumulus expansion during the ovulatory process in mice.

Thyroid dysfunction and subfertility.

The thyroid hormones act on nearly every cell in the body. Moreover, the thyroid gland continuously interacts with the ovaries, and the thyroid hormones are involved in almost all phases of reproduction. Thyroid dysfunctions are relatively common among women of reproductive age, and can affect fertility in various ways, resulting in anovulatory cycles, high prolactin levels, and sex hormone imbalances. Undiagnosed and untreated thyroid disease can be a cause of subfertility. Subclinical hypothyroidism (SCH), also known as mild thyroid failure, is diagnosed when peripheral thyroid hormone levels are within the normal reference laboratory range, but serum thyroid-stimulating hormone levels are mildly elevated. Thyroid autoimmunity (TAI) is characterized by the presence of anti-thyroid antibodies, which include anti-thyroperoxidase and anti-thyroglobulin antibodies. SCH and TAI may remain latent, asymptomatic, or even undiagnosed for an extended period. It has also been demonstrated that controlled ovarian hyperstimulation has a significant impact on thyroid function, particularly in women with TAI. In the current review, we describe the interactions between thyroid dysfunctions and subfertility, as well as the proper work-up and management of thyroid dysfunctions in subfertile women.

Uterine artery pseudoaneurysm manifesting as delayed postpartum hemorrhage after precipitous delivery: three case reports.

Precipitous delivery may lead to serious maternal and neonatal complications. Uterine artery pseudoaneurysm (UAP) is one of the causes of delayed postpartum hemorrhage. Here we describe 3 cases of UAP manifesting as delayed postpartum hemorrhage after precipitous delivery. The duration of the second stage of labor in cases 1, 2, and 3 was 15, 15, and 60 min, respectively. Excessive vaginal bleeding occurred 10, 9, and 31 days after delivery, respectively. Ultrasonogram and pelvic angiography revealed the UAP in each case and uterine artery embolization was performed. UAP may be a complication of precipitous delivery.

Comparison of oxidative stress markers in umbilical cord blood after vaginal and cesarean delivery.

OBJECTIVE: The purpose of our study was to investigate the effect of the mode of delivery on the oxidant and antioxidant system in umbilical cord blood. METHODS: We performed gas analysis of umbilical venous blood and umbilical arterial blood immediately after delivery in 38 women; eighteen women had a vaginal delivery while 20 women delivered via cesarean section at over 37 weeks gestation. We examined lipid peroxide concentration by thiobarbituric acid reaction, protein carbonyl content by 2,4-dinitrophenylhydrazine reaction, and total antioxidant capacity by oxygen radical absorbance capacity assay. RESULTS: Lipid peroxide levels in umbilical venous blood were significantly higher in patients delivering by planned cesarean section (1.81 ± 0.06 nmol/mg protein) than those with vaginal delivery (1.24 ± 0.05 nmol/mg protein) (P < 0.05). Antioxidant capacity in umbilical venous blood was significantly higher in patients delivering by planned cesarean section (119.70 ± 0.13 µM/µL) than those with a vaginal delivery (118.70 ± 0.29 µM/µL) (P < 0.05). There was no significant difference in the carbonyl content of umbilical venous blood or in the lipid peroxide, carbonyl content, and total antioxidant capacity of umbilical arterial blood. CONCLUSION: Lipid peroxidation levels and antioxidant capacity in umbilical venous blood were higher in patients delivering by planned cesarean section than those with a vaginal delivery. Therefore, we propose that both the mother and neonate are exposed to higher oxidative stress during cesarean section delivery.

Anatomic and functional outcomes with the prolift procedure in elderly women with advanced pelvic organ prolapse who desire uterine preservation.

STUDY OBJECTIVE: To assess the clinical outcomes of total mesh repair with the Prolift technique as treatment of advanced pelvic organ prolapse in elderly patients who desire uterine preservation. DESIGN: Case control series study (Canadian Task Force classification II-2). SETTING: Medical school-affiliated hospital. PATIENTS: Sixty-eight patients over the age of 70 years with advanced pelvic organ prolapse, Pelvic Organ Prolapse Quantification stage III (n = 59) or IV (n = 9), underwent a total Prolift procedure and were followed up for a minimum of 2 years. INTERVENTIONS: Transvaginal pelvic floor repairs were performed with a total Prolift system. The concurrent pelvic surgery included midurethral sling operation with a TVT-O, if indicated. The assessment included intraoperative and postoperative complications, Urogenital Distress Inventory scores, and Incontinence Impact Questionnaire scores. MEASUREMENTS AND MAIN RESULTS: Objective and subjective data were available for 68 patients. The anatomic success rate was 97.1% after 2 years. Complications included bladder perforation in 1 patient (1.5%), de novo stress urinary incontinence in 20 patients (29.4%), dyspareunia in 4 patients (22.2%), and vaginal erosion in 1 patient (1.5%). The Pelvic Organ Prolapse Quantification stages, Urogenital Distress Inventory scores, and Incontinence Impact Questionnaire scores all improved significantly after surgery. CONCLUSIONS: The total Prolift procedure is an alternative surgical option that uses a minimally invasive transvaginal approach to surgically treat elderly patients with advanced pelvic organ prolapse.

Primary invasive carcinoma of the vagina after Le Fort partial colpocleisis for stage IV pelvic organ prolapse: a case report.

We present here the case report of a postmenopausal woman who complained of recurrent pus-like vaginal discharge and perianal pain 1 year after Le Fort colpocleisis, which was subsequently identified as a primary invasive carcinoma of the vagina. Biopsy confirmed a squamous cell carcinoma in the vagina, and the disease was classified as stage III according to FIGO staging. The patient received pelvic radiotherapy. This case emphasizes that differential diagnosis of recurrent vaginal discharge that presents remote from obliterative procedure for pelvic organ prolapse should consider not only pyometra, but also other causes.

HPV-18 is a poor prognostic factor, unlike the HPV viral load, in patients with stage IB-IIA cervical cancer undergoing radical hysterectomy.

OBJECTIVES: This study was conducted to determine the prognostic significance of the human papillomavirus (HPV) genotype using the HPV DNA chip (HDC) test and the HPV viral load by the hybrid capture II assay (HC2) in FIGO stage IB-IIA cervical cancer undergoing radical hysterectomy. METHODS: Between January 2001 and December 2005, 204 consecutive patients who underwent radical hysterectomy with pelvic lymphadenectomy for International Federation of Gynecology and Obstetrics (FIGO) stage IB1-IIA cervical cancer were retrospectively reviewed. The Cox proportional hazard models adjusted for covariates were used for analyses and a receiver operating characteristic (ROC) curve was used to determine the HPV viral load in predicting disease progression. RESULTS: Of the 204 cases, the HDC was positive in 195 (95.6%) and the HC2 was positive in 192 (94.1%). The 5-year progression-free survival (PFS) was 78.4%. On multivariate analysis, HPV-18 positivity was an independent prognostic factor predictive for disease progression. The risk of recurrence was higher for HPV-18 positivity (hazard ratio=2.664; 95% confidence interval [CI], 1.437-4.938; P=0.003). The 5-year PFS rate for patients who were HPV-18-negative was 83.8%, which was higher than the 5-year PFS for patients who were HPV-18-positive (54.1%; P<0.001). The area under the ROC curve for the HPV viral load was 0.550 (P=0.314; 95% CI, 0.455-0.644). CONCLUSIONS: The HPV-18 genotype is a reliable prognostic factor of early-stage cervical cancer; however, the HPV viral load may not be helpful in predicting disease prognosis.

Expression of peroxiredoxin I regulated by gonadotropins in the rat ovary.

OBJECTIVE: Peroxiredoxins (Prxs) play an important role in regulating cellular differentiation and proliferation in several types of mammalian cells. This report examined the expression of Prx isotype I in the rat ovary after hormone treatment. METHODS: Immature rats were injected with 10 IU of pregnant mare's serum gonadotropin (PMSG) to induce the growth of multiple preovulatory follicles and 10 IU of human chorionic gonadotropin (hCG) to induce ovulation. Immature rats were also treated with diethylstilbestrol (DES), an estrogen analogue, to induce the growth of multiple immature follicles. Northern blot analysis was performed to detect gene expression. Cell-type specific localization of Prx I mRNA were detected by in situ hybridization analysis. RESULTS: During follicle development, ovarian Prx I gene expression was detected in 3-day-old rats and had increased in 21-day-old rats. The levels of Prx I mRNA slightly declined one to two days following treatment with DES. A gradual increase in Prx I gene expression was observed in ovaries obtained from PMSG-treated immature rats. Furthermore, hCG treatment of PMSG-primed rats resulted in a gradual stimulation of Prx I mRNA levels by 24 hours (2.1-fold increase) following treatment, which remained high until 72 hours following treatment. In situ hybridization analysis revealed the expression of the Prx I gene in the granulosa cells of PMSG-primed ovaries and in the corpora lutea of ovaries stimulated with hCG for 72 hours. CONCLUSION: These results demonstrate the gonadotropin and granulosa cell-specific stimulation of Prx I gene expression, suggesting its role as a local regulator of follicle development.

Complications Following Outside-in and Inside-out Transobturator-Tape Procedures with Concomitant Gynecologic Operations.

This study was undertaken to compare the complications of outside-in transobturator tape procedures (TOT) and inside-out transobturator tape procedures (TVT-O) with concomitant gynecologic surgery for the treatment of female stress urinary incontinence (SUI). A retrospective review of 206 consecutive patients who underwent either TOT or TVT-O with concomitant gynecologic operations between March 2008 and February 2011 was conducted. The incidence of perioperative complications was compared. For statistical analysis, chi-squared tests were used. There were no reports of intraoperative complications such as vaginal injury or bladder perforation. Postoperative complications were noted in 23 procedures (11.2%). These included 6 cases of urinary retention (2.9%), 2 cases of vulva hematoma (1.0%), 7 cases of urinary tract infection (3.4%), 4 cases of de novo urgency (2.9%), and 4 cases of vaginal erosion (2.9%). There were no significant differences in complication rates between the two groups. Our results suggest that inside-out and outside-in procedures are simple and safe techniques that may have a low rate of complications when used with a concomitant gynecologic operation.