Assessment of the feasibility of human amniotic membrane stem cell-derived cardiomyocytes in vitro.

Myocardial infarction (MI) is a leading cause of death worldwide, resulting in extensive loss of cardiomyocytes and subsequent heart failure. Inducing cardiac differentiation of stem cells is a potential approach for myocardial regeneration therapy to improve post-MI prognosis. Mesenchymal stem cells (MSCs) have several advantages, including immune privilege and multipotent differentiation potential. This study aimed to explore the feasibility of chemically inducing human amniotic membrane MSCs (hAMSCs) to differentiate into cardiomyocytes in vitro. Human amniotic membrane (AM) samples were obtained from routine cesarean sections at Far Eastern Memorial Hospital. The isolated cells exhibited spindle-shaped morphology and expressed surface antigens CD73, CD90, CD105, and CD44, while lacking expression of CD19, CD11b, CD19, CD45, and HLA-DR. The SSEA-1, SSEA-3, and SSEA-4 markers were also positive, and the cells displayed the ability for tri-lineage differentiation into adipocytes, chondrocytes, and osteoblasts. The expression levels of MLC2v, Nkx2.5, and MyoD were analyzed using qPCR after applying various protocols for chemical induction, including BMP4, ActivinA, 5-azacytidine, CHIR99021, and IWP2 on hAMSCs. The group treated with 5 ng/ml BMP4, 10 ng/ml Activin A, 10 µM 5-azacytidine, 7.5 µM CHIR99021, and 5 µM IWP 2 expressed the highest levels of these genes. Furthermore, immunofluorescence staining demonstrated the expression of α-actinin and Troponin T in this group. In conclusion, this study demonstrated that hAMSCs can be chemically induced to differentiate into cardiomyocyte-like cells in vitro. However, to improve the functionality of the differentiated cells, further investigation of inductive protocols and regimens is needed.

Monitoring Phthalates in Maternal and Cord Blood: Implications for Prenatal Exposure and Birth Outcomes.

Although many phthalates are endocrine-disrupting chemicals that are associated with adverse birth outcomes, the relationship between maternal phthalate exposure and birth outcomes is not yet conclusive. The objective of the present study was to investigate the association between prenatal exposure to phthalates in human maternal and cord blood and birth outcomes of the infants. Sixty-five mother-infant pairs were recruited in Taipei City and New Taipei City, and birth outcomes of the infants were recorded. Twelve phthalate metabolites were measured in maternal and cord blood samples. The mean of mono-ethyl phthalate, mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP) was relatively higher than that of the other metabolites in both maternal and infant blood. There was a significant difference (p < 0.05) for mono-methyl phthalate (MMP) and MnBP between the maternal blood and cord blood of male infants. Mono-benzyl phthalate (MBzP), MMP, MiBP, and ∑di-2-ethylhexyl phthalate (∑DEHP) in maternal blood were inversely correlated with the anogenital index (AGI) of male infants, with a p value between 0.011 and 0.033. Mono-n-octyl phthalate, MMP, MiBP, MnBP, and MBzP were positively correlated with the AGI of female infants, with a p value between 0.001 and 0.034. Cord blood levels of MnBP, mono-(2-ethyl-5-oxohexyl)-phthalate, MEHP, and ∑DEHP were found to be inversely associated with head circumference in all the infants, adjusted for gestational age. Phthalate monoesters are potentially estrogenic and antiandrogenic chemicals. Longitudinal follow-up of the present study population could help clarify the long-term impact of phthalates on growth and the health effects of background exposure levels. Environ Toxicol Chem 2022;41:715-725. © 2022 SETAC.

S100A8/A9 Enhances Immunomodulatory and Tissue-Repairing Properties of Human Amniotic Mesenchymal Stem Cells in Myocardial Ischemia-Reperfusion Injury.

Paracrine factors of human mesenchymal stem cells (hMSCs) have the potential of preventing adverse cardiac remodeling after myocardial infarction (MI). S100A8 and S100A9 are calcium-binding proteins playing essential roles in the regulation of inflammation and fibrous tissue formation, and they might modulate the paracrine effect of hMSCs. We isolated human amniotic mesenchymal stem cells (hAMSCs) and examined the changes in the expression level of regulatory genes of inflammation and fibrosis after hAMSCs were treated with S100A8/A9. The anti-inflammatory and anti-fibrotic effects of hAMSCs pretreated with S100A8/A9 were shown to be superior to those of hAMSCs without S100A8/A9 pretreatment in the cardiomyocyte hypoxia/reoxygenation experiment. We established a murine myocardial ischemia/reperfusion model to compare the therapeutic effects of the conditioned medium of hAMSCs with or without S100A8/A9 pretreatment. We found the hearts administered with a conditioned medium of hAMSCs with S100A8/A9 pretreatment had better left ventricular systolic function on day 7, 14, and 28 after MI. These results suggest S100A8/A9 enhances the paracrine therapeutic effects of hAMSCs in aspects of anti-inflammation, anti-fibrosis, and cardiac function preservation after MI.

Responsive Feeding, Infant Growth, and Postpartum Depressive Symptoms During 3 Months Postpartum.

Responsive feeding is crucial to the formation of life-long healthy eating behavior. Few studies have examined maternal responsive feeding in early infancy among a Chinese population. This prospective study describes maternal responsive feeding and factors associated with maternal responsive feeding, with emphasis on infant growth and maternal depressive symptoms, during the first 3 months postpartum in Taiwan. From 2015 to 2017, 438 pregnant women were recruited and followed at 1 and 3 months postpartum. Maternal responsive feeding at 3 months was measured on a 10-item 5-point Likert-type scale. Maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale with a cutoff score of 10. Infant growth was categorized into four groups based on weight-for-length Z scores from birth to 3 months: no change, increase but in the normal range, increase to overweight, and decrease to underweight. Multiple regression revealed that postpartum depressive symptoms, primipara, and decreased infant weight-for-length Z score were negatively associated with maternal responsive feeding, while exclusive breastfeeding and maternal age younger than 29 years were positively associated with maternal responsive feeding. Heath professionals should educate mothers on responsive feeding, with emphases on first-time and non-exclusive breastfeeding mothers, as well as those with depressive symptoms, advanced maternal age, and infants who are becoming underweight.

The impact of situation-background-assessment-recommendation (SBAR) on safety attitudes in the obstetrics department.

OBJECTIVE: Previous studies evaluating the situation-background-assessment-recommendation (SBAR) have been shown to increase effective nurse-physician communication and collaboration. The purpose of this study is to evaluate the impact of the SBAR technique on safety attitudes in the obstetrics department. MATERIALS AND METHODS: This study implemented the SBAR Collaborative Communication Education course and was conducted in a medical center from February 2012 to March 2015, which included an educational session on fetal heart rate monitoring, a case-based discussion, and a video demonstration on traditional and SBAR communication. The nurses in the obstetrics department were requested to report their clinical findings and recommendations using a novel SBAR list when abnormal fetal heart beat tracings occurred. All obstetric nurses were requested to complete the Chinese-version of the Safety Attitudes Questionnaire before and after the SBAR educational course. The primary outcome was to evaluate the effect of the SBAR technique on the safety attitudes of the obstetrics department. The secondary outcome was to evaluate the effect of the SBAR technique on the 5-minute Apgar score for neonates. RESULTS: Most values, including teamwork climate, safety climate, job satisfaction, and working conditions, significantly improved at both postintervention surveys compared with the preintervention survey. There were no significant differences in the number of the neonates with less than seven 5-minute Apgar scores between the pre- and postintervention periods. CONCLUSION: The SBAR technique, which uses a novel structured handover list, is a feasible tool for nurse-obstetrician communication, and it may improve most dimensions of safety attitudes in the obstetrics department.

Impact of clinical audits on cesarean section rate.

OBJECTIVE: Many countries have noted a substantial increase in the cesarean section rate (CSR). Several methods for lowering the CSR have been described. Understanding the impact of clinical audits on the CSR may aid in lowering CSR. Thus, our aim is to elucidate the effect of clinical audits on the CSR. MATERIALS AND METHODS: We retrospectively analyzed 3781 pregnant women who gave birth in a medical center between January 2008 and January 2011. Pregnant women who delivered between January 2008 and July 2009 were enrolled as the pre-audit group (n = 1592). After August 2009, all cesarean section cases that were audited were enrolled in the audit group (n = 2189). The CSR was compared between groups. RESULTS: The overall CSR (34.5% vs. 31.1%, adjusted odds ratio [OR] = 0.83, p = 0.008) and the cesarean section rate due to dystocia (9.6% vs. 6.2%, p < 0.001) were significantly lower in the audit group than the pre-audit group. However, there was no significant difference in the rate of operative vaginal delivery between groups. Consensus on the unnecessity for cesarean section was achieved in 16 (8.2%) of 195 audit cases in the monthly audit conference. In nulliparous pregnant women (n = 2148), multivariate analysis revealed that clinical audit (OR = 0.78), maternal age (OR = 1.10), gestational age at delivery (OR = 0.80), and fetal body weight at birth (OR = 1.0005) were independent predictors of cesarean section (all p < 0.05). Most variables of maternal and perinatal morbidity and mortality did not differ before and after audits were implemented. CONCLUSION: Clinical audits appear to be an effective strategy for reducing the CSR. Therefore, we recommend strict monitoring of the indications in dystocia for cesarean section to reduce the CSR.

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.

Safety and efficacy of manual syringe infusion of distending media for hysteroscopic procedures: a case-control study.

OBJECTIVES: Adverse events associated with large volumes of distending media in hysteroscopic procedures can be life-threatening. The aim of this study was to evaluate the safety and efficacy of manual syringe infusion (MI) of distending media for hysteroscopic procedures. STUDY DESIGN: Between January 2011 and December 2013, the medical records of all women who underwent hysteroscopic procedures using MI or the conventional pump-infusion method (PI, the control group) were reviewed. The Wilcoxon rank-sum test, the Chi-square test and the multivariate logistic regression analysis were employed for statistical analysis. RESULTS: The MI group (n=82) had a significantly lower average volume of infused fluid (1117 ± 712 mL vs. 2216 ± 1502 mL, respectively; p<0.001), less operative time (22.2 ± 9.7 vs. 30.4 ± 9.8 min, respectively; p<0.001) and lower postoperative abdominal pain scores (0.6 ± 0.7 vs. 0.8 ± 0.7, respectively; p=0.04) than the PI group (n=58). Subgroup analysis of women who underwent hysteroscopic myomectomy revealed a significantly lower amount of infused fluid for the MI group than for the PI group (1737 ± 905 mL vs. 3441 ± 1952 mL, respectively; p=0.001). Infused fluid amount (coefficient=0.08, p<0.001) was the only significant independent factor affecting fluid deficit, with a constant of 76.1. CONCLUSION: The MI method appears to be a safe and feasible method for delivering distending media during hysteroscopic procedures.

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.

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.

Luteal support for IVF/ICSI cycles with Crinone 8% (90 mg) twice daily results in higher pregnancy rates than with intramuscular progesterone.

BACKGROUND: The use of progesterone for luteal support has been demonstrated to be beneficial in assisted reproductive cycles, yet the optimal route of progesterone administration has still not been established. This article is a retrospective study in a tertiary reproductive medical unit to compare luteal progesterone supplementation with vaginal gel or intramuscular progesterone. METHODS: A total of 144 in vitro fertilization or intracytoplasmic sperm injection cycles were analyzed, 67 cycles using vaginal gel 90 mg twice daily and 77 cycles using intramuscular progesterone 50 mg daily as luteal support. RESULTS: Both groups had similar mean age, cause of infertility, baseline hormone levels, dosage of recombinant follicle-stimulating hormone, number of retrieved and fertilized oocytes, and number of transferred embryos. The vaginal gel group had significantly lower mid-luteal serum progesterone levels but higher implantation rate (32.5% vs. 18.5%, p = 0.001) and ongoing pregnancy rate (55.2% vs. 32.5%, p = 0.006). Within each group, mid-luteal serum progesterone levels between pregnant or non-pregnant patients were comparable. For patients with serum estradiol levels on day of human chorionic gonadotropin greater than 5,000 pg/mL, vaginal gel still resulted in better ongoing pregnancy and implantation rates. CONCLUSION: The use of vaginal progesterone gel twice daily for luteal support results in better pregnancy outcomes than intramuscular progesterone. A high local progesterone effect from vaginal gel might improve endometrial receptivity under extraordinarily high serum estradiol levels.

Prospective comparison of short and long GnRH agonist protocols using recombinant gonadotrophins for IVF/ICSI treatments.

This is a prospective comparative study investigating cost and effectiveness of IVF/ intracytoplasmic sperm injection (ICSI) treatments after stimulation with recombinant gonadotrophins following either the short or long gonadotrophin-releasing hormone (GnRH) agonist protocol. Patients in the short protocol (n = 120) were administered buserelin nasal sprays from day 2 of the menstrual cycle and recombinant FSH from day 5. Patients in the long protocol (n = 120) were administered buserelin from the previous mid-luteal phase and recombinant FSH after achieving down-regulation. The average age and basal FSH concentrations of both groups were similar. The serum LH concentrations during ovarian stimulation were significantly higher with the short protocol. The total cost of recombinant gonadotrophins (US$527 +/- 184 versus US$795 +/- 244, P < 0.001) was significantly lower in the short protocol, but there was no significant difference in delivery rates (47.5 versus 36.7%) between the short and long protocols. LH flare-up during the short protocol does not seem to impair the treatment outcome. Using recombinant gonadotrophins, the short GnRH agonist protocol is an effective and cheaper choice for IVF/ICSI treatments.