Aggressive Cervical Dilation Exploits Potential Weakness in the Septum of Duplicated Cervix during Hysteroscopic Cervix-preserving Metroplasty of Complete Septate Uterus: A Cohort Study.

STUDY OBJECTIVE: To evaluate whether aggressive cervical dilation is effective for creating the initial perforation between noncommunicating cavities of the complete septate uterus (CSU), which serves as the first step of hysteroscopic cervix-preserving metroplasty (CPM). DESIGN: A retrospective cohort. SETTING: A tertiary referral center. PATIENTS: Fifty-three patients with CSU were diagnosed using vaginal examinations, combined two- and three-dimensional vaginal ultrasounds, and office-based hysteroscopies. INTERVENTIONS: Patients who had received hysteroscopic CPM with the initial perforation created by aggressive cervical dilation or by the traditional method of bougie-guided incisions were compared. MEASUREMENTS AND MAIN RESULTS: Of the 53 patients with CSU, 44 patients received hysteroscopic CPM that required the creation of a perforation. Patients who received aggressive cervical dilation for creation of the perforation had nonsignificantly shorter surgical times (33.5 minutes, 95% confidence interval [CI], 28.4-38.6 vs 48.7 minutes, 95% CI, 28.2-71.3, p = .099), used significantly lower volumes of distending media (3.6 liters, 95% CI, 3.1-4.1 vs 6.8 liters, 95% CI, 4.2-9.3, p <.001), and had higher success rates (84.4%, 95% CI, 67.2-94.7 vs 50.0%, 95% CI, 21.1-78.9, p = .019). The sites of perforation all occurred on the endocervical septum and were generally fibrous and avascular. CONCLUSION: We present a novel, effective method for creating the initial perforation in hysteroscopic CPM. The success may be because of the existence of a potential weakness in the septum of the duplicated cervix, which spontaneously tears upon aggressive mechanical dilation. The method forgoes the risks associated with sharp incisions based on potentially unreliable cues and may greatly simplify the procedure.

Clinical use of aqueous subcutaneous progesterone compared with vaginal progesterone as luteal support in in vitro fertilization: A randomized controlled study in Taiwan.

OBJECTIVE: This study aims to compare the efficacy, tolerability and patient satisfaction between aqueous subcutaneous progesterone (Prolutex, 25 mg/vial; IBSA) and vaginal progesterone (Crinone, 90 mg/tube; Merck) as luteal support for fresh embryo transfers in in-vitro fertilization (IVF). MATERIALS & METHODS: In this prospective randomized study, 65 patients who underwent IVF were recruited and randomly assigned to either the Prolutex (25 mg daily, n = 33) or Crinone (90 mg daily, n = 32) group. The luteal support regimens were given daily, starting from two days after oocyte pickup. If the serum pregnancy test was positive, luteal support was continued until 7 weeks of gestation. Primary outcomes were clinical pregnancy rate and serum progesterone level at the mid-luteal phase and at 4 weeks of gestation. Secondary outcomes were drug tolerability and patient satisfaction assessed by questionnaire. RESULTS: There were no significant differences in clinical pregnancy rates (Prolutex 25.0% versus Crinone 33.3%, p = 0.699), serum progesterone levels and patient satisfaction between Prolutex and Crinone group. Although the patients that had received Prolutex complained of more local pain at the injection sites, they also had less annoying vaginal discharges and vulvar discomforts. CONCLUSION: Prolutex is of comparable efficacy and patient satisfaction to Crinone, and its availability means patients have more options in regards to the routes of progesterone administration as luteal phase support during IVF.

First report of a successful pregnancy by preimplantation genetic testing for Beckwith-Wiedemann syndrome.

OBJECTIVE: Beckwith-Wiedemann syndrome (BWS) is a rare imprinting gene disorder. Maternal CDKN1C mutation comprises 5% of etiologies of BWS. There is no successful report of preventing BWS by preimplantation genetic testing for monogenic disease (PGT-M) in the literature. Is PGT-M applicable for preventing BWS ? CASE REPORT: This 39-year-old woman conceived naturally and delivered a boy who was diagnosed of BWS. The genetic testing of her son revealed CDKN1C gene mutation, and of the mother showed a carrier of the same mutation. She underwent controlled ovarian stimulation, oocyte pickup, and intracytoplasmic sperm injection. Trophectoderm biopsies were performed and samples were checked for PGT. Two wild-type and euploid embryos were thawed and transferred. One intrauterine pregnancy was achieved. The patient delivered a healthy female baby at 37 weeks of gestation. CONCLUSION: In this case, we first report a successful pregnancy with a wild-type CDKN1C gene baby achieved by PGT-M.

Intentional endometrial injury enhances angiogenesis through increased production and activation of MMP-9 by TNF-α and MMP-3 in a mouse model.

There have been reports of improved pregnancy rates after performing intentional endometrial injuries, also known as endometrial scratching, in patients with recurrent implantation failure. In our previous study on intentional endometrial injury, we found an increased expression of matrix metalloproteinase (MMP)-3 following induced injuries to the mice endometrium. In the current study, we further examine whether the rise in MMP-3 could contribute to increased angiogenesis. Female C57B1/6 mice were obtained at 12 weeks of age, and intentional endometrial injuries were induced mechanically in the left uterine horns. Using the appropriate media, uterine-washes were performed on the injured and uninjured (control) horns of the harvested uteri. The uterine tissues were further processed for tissue lysates, histopathology and immunohistochemistry. The results show that intentional endometrial injuries caused an increase in secreted LPA in the injured horns, which were detected in the uterine-washes. In addition, LPA induced increased production of TNF-α in human endometrial epithelial cells (hEEpCs). Furthermore, TNF-α appeared to induce differential and cell-specific upregulation of the MMPs: MMP-3 was upregulated in the epithelial (hEEpCs), while MMP-9 was upregulated in the endothelial cells (human endometrial endothelial cells; hEEnCs). The upregulation of MMP-3 appeared to be necessary for the activation of MMP-9, whose active form stimulated the formation of vessel-like structure by the hEEnCs. The results of this study suggest that there may be enhanced angiogenesis following intentional endometrial injuries, which is mediated in part by TNF-α-induced and MMP-3-activated MMP-9 production.

Optimal time interval between hysteroscopic polypectomy and frozen-thawed blastocyst transfer: A retrospective study.

The optimal timing of frozen-thawed blastocyst transfer following hysteroscopic polypectomy is an important and unanswered clinical question. In this study, we conducted a retrospective survey of cases from an infertility center at an academic hospital. We reviewed the charts of all patients who received in-vitro fertilization and frozen-thawed blastocyst transfers (FBT) at the center from January 2009 to November 2019. One hundred and two patients with prior diagnosis of endometrial polyp that were treated with hysteroscopic polypectomy before received their first FBT at the center were identified as cases. Patients without prior diagnosis of endometrial polyp, and who received their first FBT at the center were defined as controls. Controls were enrolled at a 1-to-1 ratio to the cases. The cases and controls did not show differences in baseline characteristics, endometrial thickness, or the number of good blastocysts transferred. The clinical pregnancy rates and live birth rates were similar. Regarding the optimal interval between polypectomy and FBT, a cut-off of 120 days was identified from the ROC curve. A stratified analysis showed that when FBT was performed within an interval of 120 days after polypectomy, there were higher biochemical pregnancy rates (73.2%, 45.2%; OR 3.3; P = .007) and clinical pregnancy rates (64.8%, 41.9%; OR 2.54; P = .032), when compared with intervals greater than 120 days. There were no significant differences in implantation and live birth rates. In conclusion, pregnancy rates following FBT in patients who had received prior endometrial polypectomy were comparable to pregnancy rates after FBT in patients without endometrial polyp. Subgroup analysis showed that an interval greater than 120 days between hysteroscopic polypectomy and FBT was associated with decreased pregnancy rates. Patients who wish to receive embryo transfer after polypectomy should wait no longer than 120 days.

A novel GnRH-antagonist protocol by switching to medroxyprogesterone when patients being at risk of ovarian hyperstimulation syndrome during ovarian stimulation.

BACKGROUND/PURPOSE: To investigate whether switching GnRH antagonist (GnRHant) to medroxyprogesterone acetate (MPA) sequentially in the middle of controlled ovarian stimulation could effectively prevent premature LH surge in a GnRHant protocol in patients turn out to be at a high risk of ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. METHODS: This is a retrospective cohort study. RESULTS: Premature LH surge did not occur in both groups of patients. The switch protocol group had a significantly fewer days of GnRHant treatment (3.1 ± 1.0 vs. 6.5 ± 1.2) compared with GnRHant protocol group. The mean duration of MPA treatment was 3.6 ± 1.1 days. There were no statistically significant differences in terms of live birth, implantation, and clinical pregnancy rates. CONCLUSION: This study showed that MPA could sequentially replace GnRHant and effectively prevent premature LH surge after several days of GnRHant administration in patients being at high risk of OHSS during controlled ovarian stimulation. Switch protocol could individualize freeze-all policy and reduce the injection burden of GnRHant.

Mitochondrial Dysfunction Induced by High Estradiol Concentrations in Endometrial Epithelial Cells.

CONTEXT: A supraphysiological estradiol (E2) concentration after ovarian stimulation is known to result in lower embryo implantation rates in in vitro fertilization. Endometrial epithelial cell (EEC) apoptosis occurs after the stimulation with high E2 concentrations, and mitochondria play important roles in cell apoptosis. OBJECTIVE: To investigate the mitochondrial function in EECs after the stimulation with high E2 concentrations. MATERIALS AND METHODS: Human EECs were purified and cultured with different E2 concentrations (10-10, 10-9, 10-8, 10-7 M) in vitro, in which 10-7 M is supraphysiologically high. Eight-week-old female mouse endometrium was obtained 5.5 days after the injection of 1.25 IU or 20 IU equine chorionic gonadotropin, roughly during the embryo implantation window, to examine the in vivo effects of high E2 concentrations on mouse EECs. RESULTS: In vivo and in vitro experiments demonstrated decreased mitochondrial DNA contents and ATP formation after EECs were stimulated with supraphysiologically high E2 concentrations than those stimulated with a physiologic E2 concentration. Less prominent immunofluorescence mitochondrial staining, fewer mitochondria numbers under electron microscopy, lower 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide aggregate/monomer ratio, and greater reactive oxygen species (ROS) production were found after EECs were stimulated with supraphysiologically high E2 concentrations. The high E2-induced ROS production was reduced when EECs were pretreated with N-acetyl-cysteine in vitro, but remained unchanged after the pretreatment with coenzyme Q10. CONCLUSION: High E2 concentrations increase extramitochondrial ROS production in EECs and subsequently result in mitochondrial dysfunction.

HSD3B1 gene polymorphism and female pattern hair loss in women with polycystic ovary syndrome.

BACKGROUND/PURPOSE: Genetic variant of HSD3B1 1245 is known to augment androgen production at peripheral tissue as skin. This study aimed to investigate whether women with polycystic ovary syndrome inheriting this variant exhibit specific androgenic phenotypes. METHODS: A cross-sectional study of Taiwanese women with polycystic ovary syndrome, defined by Rotterdam criteria, at the reproductive endocrinology outpatient clinic in a university affiliated hospital. RESULTS: The presence of female pattern hair loss in women with polycystic ovary syndrome was significantly associated with an increased body mass index, decreased sex hormone binding globulin and high density lipoprotein cholesterol levels, elevated triglyceride levels, and increased prevalence of hypertension. Using stepwise multivariate logistic regression analysis, body mass index, triglyceride and HSD3B1 1245 AC or CC genotype were significantly related to female pattern hair loss in women with polycystic ovary syndrome after considering other variables. Overweight women with polycystic ovary syndrome had significantly higher risk of female pattern hair loss than normal-weight women with polycystic ovary syndrome. The presence of female pattern hair loss was higher in overweight women with polycystic ovary syndrome who comprised HSD3B1 AC or CC genotype compared with wild type. CONCLUSION: Carrying the HSD3B1 1245C allele and overweight are associated with the presence of female pattern hair loss in women with polycystic ovary syndrome.

Improved hemostasis with plasma kinetic bipolar sealing device in the vaginal steps of laparoscopic-assisted vaginal hysterectomy.

OBJECTIVE: During the vaginal steps of laparoscopic-assisted vaginal hysterectomy (LAVH), excessive bleeding occurs if the vascular pedicles are not securely clamped. Accordingly, this study investigates if an advanced bipolar sealing device (PlasmaKinetics [PK] Sealer), compared to conventional sutures, could improve the efficacy and safety in the vaginal steps of LAVH. MATERIAL AND METHODS: The medical records of 101 women who underwent LAVH for a non-malignant condition between June 2014 and August 2017 were retrospectively reviewed. Among the women, 60 received LAVH using conventional sutures (control group), while 41 using the PK Sealer during vaginal steps (PK group). RESULTS: A 35% reduction (76.1 vs. 117.3 mL) in the blood loss was observed in the PK group. The natural logarithm (ln) of the blood loss was significantly lower in the PK group than in the control group (P = .045). The percentage of cases which achieved the minimal blood loss goal (<50 mL) was significantly higher in the PK group than in the control group (61 vs. 48%, P = .044). After adjusting for confounding factors, the PK group still exhibited a significantly lower ln intraoperative blood loss (OR -0.477, P = .002) than the control group. CONCLUSION: The PK bipolar sealing device provides a safe and effective alternative in reducing blood loss in the vaginal steps of LAVH.

New ultrasound grading system for cesarean scar pregnancy and its implications for management strategies: An observational cohort study.

A cesarean section pregnancy (CSP) indicated the gestational sac (GS) implanted in the previous cesarean scar. The clinical manifestations of CSP present a wide range of variations, and the optimal management is yet to be defined. We retrospectively enrolled 109 patients with the diagnosis of CSP from our department and categorized them into four grades based on the ultrasound presentation. Grade I CSP indicated the GS embedded in less than one-half thickness of the lower anterior corpus; and grade II CSP represented the GS extended to more than one-half thickness of overlying myometrium. Grade III CSP implied the GS bulged out of the cesarean scar; and grade IV CSP denoted that GS became an amorphous tumor with rich vascularity at the cesarean scar. Seventy-eight women received surgery, and the complication rate was 14.1% (11/78). Linear regression analysis demonstrated a significant association between the invasiveness of the surgery and their ultrasound gradings. The mainstream operation for grade I CSP was transcervical resection, while the majority of grade III and IV patients required hysterotomy or hysterectomy. Another 31 women received chemotherapy with methotrexate as their initial treatment. The success rate for chemotherapy was 61.3%; the remaining patients required further surgery due to persistent CSP or heavy bleeding during or after chemotherapy. Fifteen patients (48.3%) receiving chemotherapy suffered from complications (mostly bleeding). Among them, 7 (22.6%) patients experienced bleeding of more than 1,000 mL, and 9 (29.0%) of these 31 patients required blood transfusions. Our novel ultrasound grading system for CSP may help to communicate between physicians, and determine the optimal surgical strategy. Chemotherapy with methotrexate for CSP is not satisfactory and is associated with a higher rate of complications.

Large cell neuroendocrine carcinoma of the endometrium: A case report and literature review.

OBJECTIVE: To report a case and review published cases of large cell neuroendocrine carcinoma (LCNEC) of the endometrium. CASE REPORT: A 51-year-old female presented with postmenopausal bleeding and a palpable pelvic mass. An endometrial biopsy showed a malignant mixed Mullerian tumor (MMMT). Suboptimal debulking surgery was performed. The final pathology revealed stage IVB endometrial LCNEC. Post-operative adjuvant chemotherapy with cisplatin and etoposide was administered. Two months after discontinuing adjuvant chemotherapy, salvage chemotherapy with cisplatin and ifosfamide was administered due to tumor progression; however, obstructive ileus was noted 2 months later. A segmental small bowel resection and palliative colostomy were performed. She died secondary to a post-operative infection 8 days after the operation. CONCLUSION: Endometrial LCNEC is a rare but aggressive disease. If diagnosed, combined therapies, including staging surgery, following by adjuvant radiotherapy and chemotherapy, should be performed.

Transcervical double-balloon catheter as an alternative and salvage method for medical termination of pregnancy in midtrimester.

OBJECTIVE: Termination of pregnancy in midtrimester can be performed surgically or medically. The aim of this study was to evaluate the medical methods, and the additional efficacy of using a transcervical double-balloon catheter in midtrimester termination. MATERIALS AND METHODS: In this retrospective study, we included 167 pregnant women admitted during the period from January 1, 2011, to June 31, 2015, who were between 14 weeks and 28 weeks of gestation, and underwent intended termination of pregnancy at our center. Each of the 167 patients was allocated to either the cervical ripening balloon (CRB) group (with double-balloon catheter) or the non-CRB (without double-balloon catheter) group, by the choice or preference of the patient and her attending physician. Termination of pregnancy in the CRB group (72 patients) was conducted by placing a transcervical double-balloon catheter (COOK CRB), with both the uterine and vaginal balloons inflated with 30-80 mL of normal saline, and held in place for 12 hours, whereas in the non-CRB group (95 patients) vaginal and oral misoprostol alone were administered. RESULTS: There were no significant differences between the CRB and non-CRB groups with regard to induction-to-delivery time (23.1 hours vs. 21.1 hours) and successful abortion rate within 30 hours (80.0% vs. 83.7%). There were no severe complications in both groups. CONCLUSION: There was no significant additional benefit of using a double-balloon catheter in midtrimester termination of pregnancy, although the technique was considered simple and generally well-tolerated. Placing a transcervical double-balloon catheter could be the primary method, or one of the alternative medical methods if the patient and/or obstetrician prefers no operation.

Risk factors associated with failure of treatment for cesarean scar pregnancy.

OBJECTIVE: To identify risk factors associated with treatment failure among women with cesarean scar pregnancy (CSP). METHODS: In a retrospective study, the medical records of patients with CSP treated at National Taiwan University Hospital, Taipei, Taiwan, from 1994 to 2015 were reviewed. The women were managed primarily with hysterotomy, evacuation, or methotrexate. Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to evaluate the factors associated with treatment failure. RESULTS: Among 90 patients, 44 underwent hysterotomy, 18 underwent evacuation, and 28 received methotrexate. The success rates were 100% (44/44) for hysterotomy, 83% (15/18) for evacuation, and 57% (16/28) for methotrexate (P<0.001). ROC curve analysis indicated that a pregnancy length of 8 weeks and a mean sac diameter (MSD) of 4 cm were both predictive of failure of treatment by primary evacuation and methotrexate. In multivariate logistic regression analysis, an MSD of 4 cm or more was the only independent risk factor for treatment failure (odds ratio 68.99, 95% confidence interval 6.27-759.60; P=0.001). CONCLUSION: Primary hysterotomy was suitable for treatment of CSP of any size. Failure of primary evacuation or methotrexate usually occurred when the MSD was larger than 4 cm.

Geriatric Suicide Attempt and Risk of Subsequent Dementia: A Nationwide Longitudinal Follow-up Study in Taiwan.

OBJECTIVE: It was unclear whether older people without dementia who attempted suicide were at increased risk of subsequently developing dementia. METHODS: Using the Taiwan National Health Insurance Research Database, 1,189 patients aged ≥ 65 years who attempted suicide and 4,756 age- and sex-matched control subjects were enrolled in our study and followed to the end of 2011. Those who developed dementia during the follow-up were identified. RESULTS: Cox regression analysis, after adjusting for demographic data and medical comorbidities, found that geriatric suicide attempt was associated with an increased risk of subsequent dementia (HR: 7.40; 95% CI: 6.11-8.97; Wald χ2 = 414.87, df = 1, p < 0.001). Both patients aged between 65 and 79 years (HR: 7.74; 95% CI: 6.17-9.71; Wald χ2 = 312.62, df = 1, p < 0.001) and patients aged ≥ 80 years (HR: 6.94; 95% CI: 4.73-10.17; Wald χ2 = 97.78, df = 1, p < 0.001) who attempted suicide had an increased risk of developing dementia in later life. CONCLUSION: The elderly who attempted suicide were prone to developing dementia in later life, independent of depression and medical comorbidities. Further studies are necessary to clarify the underlying mechanisms between geriatric suicide and dementia and whether the prompt intervention for geriatric suicide may reduce this risk.

Neither cortisol nor brain-derived neurotrophic factor is associated with serotonin transporter in bipolar disorder.

Converging evidence indicates the hypothalamus-pituitary-adrenal axis and serotonergic neurons exert reciprocal modulatory actions. Likewise, brain-derived neurotrophic factor (BDNF) has been implicated as a growth and differentiation factor in the development of serotonergic neurons. The aim of this study was to examine the interaction of cortisol and BDNF on serotonin transporter (SERT) in bipolar disorder (BD). Twenty-eight BD and 28 age- and gender-matched healthy controls (HCs) were recruited. (123)I-ADAM with single-photon emission computed tomography (SPECT) was applied for measurement of SERT availability in the brain, which included the midbrain, thalamus, putamen and caudate. Ten milliliters of venous blood was withdrawn, when the subject underwent SPECT, for the measurement of the plasma concentration of cortisol and BDNF. SERT availability was significantly decreased in the midbrain and caudate of BD compared with HCs, whereas plasma concentration of cortisol and BDNF did not show a significant difference. The linear mixed-effect model revealed that there was a significant interaction of group and cortisol on SERT availability of the midbrain, but not BDNF. Linear regression analyses by groups revealed that cortisol was associated with SERT availability in the midbrain in the HCs, but not in BD. Considering previous studies, which showed a significant association of cortisol with SERT availability in the HCs and major depressive disorder (MDD), our result replicated a similar finding in HCs. However, the negative finding of the association of cortisol and SERT availability in BD, which was different from MDD, suggests a different role for cortisol in the pathophysiology of mood disorder.

Prenatal diagnosis of true diphallia and associated anomalies.

BACKGROUND: Diphallia poses several surgical, psychological, and esthetic issues. Currently, diphallia is only diagnosed after birth. CASE: We present a true diphallia in one fetus of dichorionic twins noted at 23 weeks of gestation. In this fetus, two phallus-like protrusions and a bifid scrotum, as well as a duplicated collecting system of both kidneys, were found on ultrasonogram. Unfortunately, the fetus died near term. CONCLUSION: Diphallia, although exceedingly rare, can be precisely diagnosed antenatally. Careful ultrasound examination of the origins of the fetal phallus and of other adjacent organs is essential to establish the diagnosis of diphallia and to detect any associated anomalies.