Prognostic significance of ferroptosis pathway gene signature and correlation with macrophage infiltration in cervical squamous cell carcinoma.

BACKGROUND: Nuclear factor erythroid 2-related factor 2 (NFE2L2) plays a critical role in ferroptosis and biogenesis, however, its role in cervical squamous cell carcinoma (CESC) remains unknown. Therefore, in this study, we aimed to determine the role of NFE2L2 in CESC using multiomic analysis. METHODS: All raw data were downloaded from The Cancer Genome Atlas (TCGA) and further validated in our dataset. NFE2L2 mRNA expression and methylation data on CESC were examined using the Tumor Immune Estimation Resource (TIMER) and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) database resources. NFE2L2 expression was examined in paraffin-embedded tissues from our cohort of 240 samples each of cancerous and non-cancerous tissues. Further, cervical cancer biopsies were genetically validated. TIMER and Tumor-Immune System Interactions Database (TISIDB) were used to analyze the correlation between NFE2L2 and cluster of differentiation 163 (CD163) with co-expressed genes in tumor-infiltrating immune cells. RESULTS: The mRNA and protein levels of NFE2L2 were lower in CESC tissues than they were in adjacent tissues. Importantly, a low NFE2L2 level correlated with poor prognosis in CESC patients. NFE2L2 was specifically expressed in tumor macrophages and correlated with the tumor immune landscape and poor prognosis in the cohort data. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analysis showed that co-expressed genes are mainly associated with multiple immune-related pathways. Furthermore, our data analysis revealed that NFE2L2 and macrophage CD163 expression levels were negatively correlated. Interestingly, we discovered multiple NFE2L2 binding sites in promoters of CD163. CONCLUSION: This study confirmed the novel pyroptosis landscape in CESC, provided a role for NFE2L2 in the tumor microenvironment, and identified prognostic biomarkers for CESC and related immune infiltration.

Expression status and prognostic significance of mitochondrial dynamics OPA3 in human ovarian cancer.

Early diagnosis of ovarian cancer and the discovery of prognostic markers can significantly improve survival and reduce mortality. OPA3 protein exists in a structure called mitochondria, which is the energy production center of cells, but its molecular and biological functions in ovarian cancer are still unclear. Here, the expression of OPA3 mRNA in ovarian cancer was estimated using TCGA, Oncomine, TIMER databases. We found that functional OPA3 activation caused by mutations and profound deletions predicted poor prognosis in OV patients. OPA3 was highly expressed in both OV tissues and cells compared to normal ovarian tissues/cells. High OPA3 expression is associated with poorer overall survival (OS). The association between OPA3 and immune infiltration of ovarian cancer was assessed by TIMER and CIBERSORT algorithms. OPA3 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of OV cell lines revealed that OPA3 inactivation was associated with increased sensitivity to PFI-1, and WZ4003. Therefore, we investigated the clinical application of OPA3 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of ovarian cancer.

DHEA restores mitochondrial dynamics of cumulus cells by regulating PGAM5 expression in poor ovarian responders.

OBJECTIVE: Poor ovarian responder (POR) poses a significant challenge for in vitro fertilization (IVF). Previous studies have suggested that dehydroepiandrosterone (DHEA) may improve IVF outcomes in POR. The current study attempts to investigate the clinical benefits of DHEA in POR and the possible mechanism of DHEA on cumulus cells (CCs). MATERIALS AND METHODS: A total of 60 women who underwent IVF treatment participated, including 22 normal ovarian responders (NORs) and 38 PORs. PORs were assigned to receive DHEA supplementation (n = 18) or not (n = 20) before IVF cycles. For all patients, CCs were obtained after oocyte retrieval. In the CCs, mRNA expression of mitochondrial dynamics relataed genes were measured. RESULTS: Supplementation of DHEA in POR reduced mitochondrial fission in CCs and decreased the expression of PGAM5 in CCs. CONCLUSION: The benefit of DHEA supplementation on IVF outcomes in POR is significant, and this effect may be mediated in part through improved mitochondrial dynamics in CC.

Concomitant Benefits of an Auricular Acupressure Intervention for Women With Cancer on Family Caregiver Sleep Quality.

BACKGROUND: Sleep disturbance is a frequent and significant problem challenge for family caregivers of patients with cancer. A previously tested 6-week auricular acupressure intervention was found to reduce symptom burden in women with cancer. It is possible that such an intervention has a concomitant benefit for family caregivers. OBJECTIVES: The aim of this study was to explore if the effects of an auricular acupressure intervention on major symptoms experienced by women with ovarian cancer improves the sleep quality of family caregivers. METHODS: A quasi-randomized controlled trial with a repeated-measures design was used. Family caregivers (n = 68) of cancer patients were recruited and completed the Pittsburgh Sleep Quality Index on 4 occasions. Demographic information included age, sex, duration of caring role, and relationship to the patient. RESULTS: Family members with a longer duration of caregiving reported more sleep disturbance at baseline. As the symptom burden of treated women decreased, their family caregivers reported improved Pittsburgh Sleep Quality Index scores at 4 weeks (time 2; Cohen d = 1.075) and 6 weeks (time 3; Cohen d = 1.022). CONCLUSIONS: Reducing the symptom burden of patients with cancer can improve the sleep quality of family caregivers. IMPLICATIONS FOR PRACTICE: Auricular acupressure is a noninvasive and easy-to-apply intervention that can be applied by caregivers to assist their family member. Nursing staff can implement and test the acupressure intervention into their clinical practice and better support family-based strategies and interventions. Further studies with larger samples are needed to confirm our findings.

Combining Bioinformatics and Experiments to Identify CREB1 as a Key Regulator in Senescent Granulosa Cells.

Aging of functional ovaries occurs many years before aging of other organs in the female body. In recent years, a greater number of women continue to postpone their pregnancies to later stages in their lives, raising concerns of the effect of ovarian aging. Mitochondria play an important role in the connection between the aging granulosa cells and oocytes. However, the underlying mechanisms of mitochondrial dysfunction in these cells remain poorly understood. Therefore, we evaluated the molecular mechanism of the aging granulosa cells, including aspects such as accumulation of mitochondrial reactive oxygen species, reduction of mtDNA, imbalance of mitochondrial dynamics, and diminished cell proliferation. Here, we applied bioinformatics approaches, and integrated publicly available resources, to investigate the role of CREB1 gene expression in reproduction. Senescence hallmark enrichment and pathway analysis suggested that the downregulation of bioenergetic-related genes in CREB1. Gene expression analyses showed alterations in genes related to energy metabolism and ROS production in ovary tissue. We also demonstrate that the biogenesis of aging granulosa cells is subject to CREB1 binding to the PRKAA1 and PRKAA2 upstream promoters. In addition, cofactors that regulate biogenesis significantly increase the levels of SIRT1 and PPARGC1A mRNA in the aging granulosa cells. These findings demonstrate that CREB1 elevates an oxidative stress-induced senescence in granulosa cells by reducing the mitochondrial function.

Laser irradiation pretreatment improves endometrial preparation of frozen-thawed embryo transfer in recurrent implantation failure patients.

Recurrent implantation failure (RIF) remains a clinical dilemma. Helium-Neon (He-Ne) laser irradiation has recently become more popular under certain clinical conditions. Given the unique therapeutic effects, we were interested in determining whether pretreatment with He-Ne laser irradiation prior to frozen-thawed embryo transfer (FET) would improve the microcirculation and cause the release of growth factors and cytokines, thus improving endometrial receptivity and the clinical pregnancy rates. Patients chose for themselves whether to proceed with (n = 29) or without (n = 31) pretreatment with He-Ne laser irradiation prior to FET. The clinical pregnancy rate (37.9%) and implantation rate (20.3%) were higher in the laser-treatment group than in the control group (35.5% and 15.9%, respectively, p = .844 and .518, respectively). The live birth rate was higher in the laser-treatment group (27.6% vs. 25.8%, respectively, p = .876) and the miscarriage rate was lower in the laser-treatment group (18.2% and 27.3%, respectively, p = .611). No side effects or complications from laser irradiation were encountered in patients who received the laser treatment. We concluded that pretreatment with He-Ne laser prior to FET may be an alternative choice for RIF-affected women; however, additional well-designed prospective studies are necessary to determine the precise clinical value of this treatment.

Dehydroepiandrosterone Supplementation Improves the Outcomes of in vitro Fertilization Cycles in Older Patients With Diminished Ovarian Reserve.

Background: Dehydroepiandrosterone (DHEA) supplementation has been reported to have beneficial effects on the in vitro fertilization (IVF) outcomes of patients with poor ovarian response or diminished ovarian reserve. The Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) stratification is a set of newly established criteria for low prognosis patients. The aim of this study was to examine the potential effects of DHEA supplementation on the IVF outcomes of patients who fulfill the POSEIDON group 4 criteria. Methods: This retrospective cohort study investigated 297 cycles that fulfilled the POSEIDON group 4 criteria and underwent IVF treatment using the gonadotropin-releasing hormone antagonist protocol. The study group contained 159 cycles that received DHEA (30 mg three times per day) daily for 12 weeks before their IVF cycles. The control group included 138 cycles that underwent IVF cycles but did not receive DHEA. The baseline characteristics and cycle parameters as well as the IVF outcomes of both groups were compared. Results: In terms of baseline characteristics, more previous IVF attempts and lower AMH levels were found in the study group than in the control group. Regarding IVF outcomes, patients in the study group had significantly higher follicular oocyte index and higher numbers of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day 3 embryos and top-quality day 3 embryos than those in the control group. Besides, a higher cumulative pregnancy rate and lower cancellation rate were observed in the study group than in the control group although clinical pregnancy rate, live birth rate, and cumulative live birth rate did not differ between the two groups. Whether patients are aged ≤ 40 years or aged > 40, higher numbers of oocytes and embryos were observed in the study group than in the control group. In patients aged > 40, cumulative pregnancy rate was significantly higher in the study group than in the control group. Conclusions: Our data suggest that DHEA supplementation might increase both oocyte and embryo yields, as well as cumulative pregnancy rates, in patients fulfilling the POSEIDON group 4 criteria.

Pregnancy-induced hypertension is an independent risk factor for meconium aspiration syndrome: A retrospective population based cohort study.

OBJECTIVE: Meconium aspiration syndrome (MAS), possibly resulting from fetal hypoxia, is a respiratory distress disorder in the infant. Pregnancy-induced hypertension (PIH) can cause placental dysfunction and lead to fetal hypoxia, which may induce the development of MAS. Therefore, the aim of this study was to determine the association between PIH and MAS and to identify the predictive risk factors. MATERIALS AND METHODS: This was a retrospective cohort study. We selected patients with newly diagnosed PIH and a matched cohort group from the Taiwan National Health Insurance Research Database (NHIRD), from January 1, 2000 till December 31, 2013. For each patient in the PIH cohort, 4 subjects without PIH, matched for age and year of delivery, were randomly selected as the comparison cohort. The incidence of meconium aspiration syndrome was assessed in both groups. RESULTS: Among the 23.3 million individuals registered in the NHIRD, 29,013 patients with PIH and 116,052 matched controls were identified. Patients who experienced PIH had a higher incidence of MAS than did those without PIH. According to a multivariate analysis, PIH (odds ratio [OR] = 1.70, 95% confidence interval [CI] = 1.49-1.93, p < 0.0001) was independently associated with increased risk of MAS. Additionally, age ≥30 years (OR = 1.26, 95% CI = 1.12-1.42, p = 0.0001), nulliparity (OR = 1.13, 95% CI = 1.01-1.27, p = 0.0367) and patients with diabetes mellitus (OR = 3.09, 95% CI = 1.35-7.09, p = 0.0078) were also independent risk factors of MAS. CONCLUSION: Patients with PIH obtained higher subsequent risk for the development of MAS than those without PIH. Besides, age ≥30 years, nulliparity and patients with diabetes mellitus are the independent risk factors of developing MAS.

MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities.

Ovarian cancer comprises one of the three major malignant tumor types in the female reproductive system. The mortality rate of this cancer is the highest among all gynecological tumors, with ovarian cancer metastasis constituting an important cause of death. Therefore, markers for disease prediction and prognosis are highly desirable for early diagnosis as well as for helping optimize and personalize treatment. Recently, microRNAs (miRNAs), which consist of short-sequence RNAs that do not encode a protein, have emerged as new biomarkers in the clinical diagnosis and treatment of ovarian cancer. By pairing with bases specific to the target messenger RNA (mRNA), miRNAs cause degradation of the target mRNA or inhibit its translation, thereby regulating various cellular processes including cell proliferation and adhesion. Increasing numbers of studies have shown that miRNA expression abnormality plays an important role in the development of ovarian cancer. In this review, we discuss the mechanisms of miRNA action, current research regarding their role in the suppression or promotion of ovarian cancer, and their use as markers for diagnosis of prognosis or as therapeutic targets for this disease. Finally, we present future perspectives regarding the clinical management of ovarian cancer and the role for miRNAs therein.

Maternal pregnancy-induced hypertension increases the subsequent risk of neonatal candidiasis: A nationwide population-based cohort study.

OBJECTIVE: Neonatal candidiasis is a leading infectious cause of significant morbidity and mortality in premature birth mainly due to impaired physical barriers and immature immune system of fetus. Maternal pregnancy-induced hypertension (PIH) has been reported to be able to disturb the neonatal immune system, which could cause the increased possibility of neonatal infection. Therefore, we hypothesized that maternal PIH may increase the risk of neonatal candidiasis. The aim of this study was to evaluate whether PIH increased the risk of neonatal candidiasis and identify the predictive risk factors. MATERIALS AND METHODS: Patients with newly diagnosed PIH between January 1, 2000, and December 31, 2013 were selected from the Taiwan National Health Insurance Research Database (NHIRD). For each patient in the PIH cohort, 4 subjects without PIH, matched for age and year of delivery, were randomly selected as the comparison cohort. A Cox proportional regression model was used to estimate the risks of neonatal candidiasis in both cohorts. RESULTS: Among the 23.3 million individuals registered in the NHIRD, 29,013 patients with PIH and 116,052 matched controls were identified. Patients with PIH had a higher incidence of neonatal candidiasis than did those without PIH. According to the multivariate analysis, PIH (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.11-3.19, p < 0.0228), single parity (OR = 1.91, 95% CI = 1.00-3.65, p < 0.0499), and preterm birth (OR = 3.57, 95% CI = 1.84-6.93, p = 0.0002) were independent risk factors for the development of neonatal candidiasis. CONCLUSION: Patients who had a history of PIH was associated with an increased risk of having infants who develop neonatal candidiasis compared with those without PIH. Additionally, preterm birth was an independent risk factor for the development of neonatal candidiasis.

Dehydroepiandrosterone Ameliorates Abnormal Mitochondrial Dynamics and Mitophagy of Cumulus Cells in Poor Ovarian Responders.

Mitochondrial dysfunction is related to reproductive decline in humans, with consequences for in vitro fertilization (IVF). We assessed whether dehydroepiandrosterone (DHEA) could regulate mitochondrial homeostasis and mitophagy of cumulus cells (CCs) in poor ovarian responders (PORs). A total of 66 women who underwent IVF treatment at the Reproductive Medicine Center of Kaohsiung Veterans General Hospital were included in this study. Twenty-eight normal ovarian responders (NOR) and 38 PORs were enrolled. PORs were assigned to receive DHEA supplementation (n = 19) or not (n = 19) before IVF cycles. DHEA prevents mitochondrial dysfunction by decreasing the activation of DNM1L and MFF, and increasing MFN1 expression. Downregulation of PINK1 and PRKN occurred after DHEA treatment, along with increased lysosome formation. DHEA not only promoted mitochondrial mass but also improved mitochondrial homeostasis and dynamics in the CCs of POR. We also observed effects of alterations in mRNAs known to regulate mitochondrial dynamics and mitophagy in the CCs of POR. DHEA may prevent mitochondrial dysfunction through regulating mitochondrial homeostasis and mitophagy.

Dehydroepiandrosterone (DHEA) supplementation improves in vitro fertilization outcomes of poor ovarian responders, especially in women with low serum concentration of DHEA-S: a retrospective cohort study.

BACKGROUND: Dehydroepiandrosterone (DHEA) is now widely used as an adjuvant for in vitro fertilization (IVF) cycles in poor ovarian responders (PORs). Several studies showed that DHEA supplementation could improve IVF outcomes of PORs. However, most of the PORs do not respond to DHEA clinically. Therefore, the aim of this study is to confirm the beneficial effects of DHEA on IVF outcomes of PORs and to investigate which subgroups of PORs can best benefit from DHEA supplementation. METHODS: This retrospective cohort study was performed between January 2015 and December 2017. A total of 151 PORs who fulfilled the Bologna criteria and underwent IVF cycles with the gonadotropin-releasing hormone antagonist protocol were identified. The study group (n = 67) received 90 mg of DHEA daily for an average of 3 months before the IVF cycles. The control group (n = 84) underwent the IVF cycles without DHEA pretreatment. The basic and cycle characteristics and IVF outcomes between the two groups were compared using independent t-tests, Chi-Square tests and binary logistic regression. RESULTS: The study and control groups did not show significant differences in terms of basic characteristics. The study group demonstrated a significantly greater number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day 3 embryos and top-quality embryos at day 3 and a higher clinical pregnancy rate, ongoing pregnancy rate and live birth rate than those measures in the control group. The multivariate analysis revealed that DHEA supplementation was positively associated with clinical pregnancy rate (OR = 4.93, 95% CI 1.68-14.43, p = 0.004). Additionally, in the study group, the multivariate analysis showed that serum dehydroepiandrosterone-sulfate (DHEA-S) levels < 180 µg/dl were significantly associated with a rate of retrieved oocytes > 3 (OR = 5.92, 95% CI 1.48-23.26, p = 0.012). CONCLUSIONS: DHEA supplementation improves IVF outcomes of PORs. In PORs with DHEA pretreatment, women with lower DHEA-S level may have greater possibility of attaining more than 3 oocytes.

Hypertensive disorders of pregnancy and future heart failure risk: A nationwide population-based retrospective cohort study.

OBJECTIVE: To assess whether hypertensive disorders of pregnancy (HDP) increased the risk of subsequent heart failure (HF) and identify possible risk factors. STUDY DESIGN: A nationwide population-based retrospective cohort study. MAIN OUTCOME MEASURES: Incidence of heart failure. RESULTS: Among the 23.3 million individuals registered in the National Health Insurance Research Database in Taiwan, 29,186 patients with HDP and 116,744 matched controls were identified. The overall incidence of HF was greater in the HDP group than it was in the control group (9.83 vs. 1.67 per 10,000 person-years), with a significant incidence rate ratio (IRR = 5.88, 95% confidence interval [CI] 5.84-5.92, p < 0.0001). When stratified by age, parity, gestational age, gestational number, and follow-up years, the IRR for subsequent HF remained significantly higher in the HDP group in all stratifications. Additionally, the Kaplan-Meier analysis indicated that the cumulative incidence rate of HF was higher in the HDP group than it was in the control group. The Cox proportional-hazard model analysis showed that in addition to HDP, single parity, preterm and hypertension were independent risk factors for developing HF. Moreover, HF was more likely to develop within 5 years post-partum. Among patients with a history of HDP, the Cox proportional-hazard model showed that severe forms of HDP and increased HDP occurrences were independently associated with the subsequent development of HF. CONCLUSIONS: Patients who have experienced HDP presented an increased risk for developing HF later in life. Moreover, among individuals with a history of HDP, those with severe forms of HDP or recurrent HDP displayed an increased subsequent risk of HF.

Luteal Phase Ovarian Stimulation May Improve Oocyte Retrieval and Oocyte Quality in Poor Ovarian Responders Undergoing In Vitro Fertilization: Preliminary Results from a Single-Center Prospective Pilot Study.

INTRODUCTION: Luteal phase ovarian stimulation (LPOS) has been proven a feasible protocol for infertile patients. High progesterone level in the luteal phase could physiologically inhibit premature luteinizing hormone surge, from which poor ovarian responders (PORs) could obtain benefits. Therefore, we aimed to compare clinical outcomes between LPOS and follicular phase ovarian stimulation (FPOS) protocol in PORs undergoing in vitro fertilization (IVF). METHODS: This prospective pilot study was performed at one tertiary center from January 2016 to October 2017. A total of 60 PORs who met Bologna criteria and undergoing IVF were enrolled. Thirty PORs were allocated to the LPOS group and 30 PORs were allocated to the FPOS group. Basic characteristics, cycle characteristics, and pregnancy outcomes were compared between the two groups. RESULTS: The length of stimulation was significantly longer in the LPOS group than in the FPOS group. The numbers of retrieved oocytes, metaphase II oocytes, fertilized oocytes, and day-3 embryos were significantly higher in the LPOS group than in the FPOS group. Conversely, we could not find any significant difference for clinical pregnancy rate, ongoing pregnancy rate, abortion rate, and cancellation rate. The multivariate analysis showed that only LPOS (p = 0.007) was significantly associated the possibility to retrieve three or more oocytes, whereas basal follicle-stimulating hormone (FSH) < 8 IU/l (p = 0.103) and antral follicle count (AFC) ≥ 3 (p = 0.143) did not significantly affect this event. CONCLUSION: LPOS allows improved oocyte retrieval and oocyte quality in PORs with respect to FPOS, despite comparable pregnancy outcomes. LPOS may be considered a feasible option for oocytes accumulation in PORs. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03238833.

The Application of Dehydroepiandrosterone on Improving Mitochondrial Function and Reducing Apoptosis of Cumulus Cells in Poor Ovarian Responders.

Poor ovarian responders (PORs) pose a great challenge for in vitro fertilization (IVF). Previous studies have suggested that dehydroepiandrosterone (DHEA) may improve IVF outcomes in PORs. The current study attempted to investigate the clinical benefits of DHEA in PORs and the possible mechanisms of DHEA on cumulus cells (CCs). This was a prospective study performed at one tertiary center from January 2015 to March 2016. A total of 131 women who underwent IVF treatment participated, including 59 normal ovarian responders (NORs) and 72 PORs. PORs were assigned to receive DHEA supplementation or not before the IVF cycle. For all patients, CCs were obtained after oocyte retrieval. In the CCs, mRNA expression of apoptosis-related genes and mitochondrial transcription factor A (TFAM) gene, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, mitochondrial dehydrogenase activity and mitochondrial mass were measured. The results indicated that PORs with DHEA supplementation produces a great number of top-quality embryos at day 3 and increased the number of transferred embryos and fertilization rate compared with those without DHEA supplementation. Additionally, supplementation with DHEA in PORs decreased DNA damage and apoptosis in CCs while enhancing the mitochondrial mass, mitochondrial dehydrogenase activity and TFAM expression in CCs. In conclusion, our results showed that the benefits of DHEA supplementation on IVF outcomes in PORs were significant, and the effects may be partially mediated by improving mitochondrial function and reducing apoptosis in CCs.

Using gonadotropin-releasing hormone agonist before frozen embryo transfer may improve ongoing pregnancy rates in hyperandrogenic polycystic ovary syndrome women.

Polycystic ovary syndrome (PCOS), affecting more than 5-10% of woman at reproductive childbearing age, is characterized by anovulation and hyperandrogenism. Frozen-thawed embryo transfer (ET) has been widely used for PCOS women to minimize the risk of ovarian hyperstimulation syndrome. However, the hyperandrogenic status of PCOS women deteriorates endometrial function, which has subsequently increased miscarriage rates in PCOS women. Therefore, we conducted this retrospective study to compare the pregnancy outcomes of hyperandrogenic PCOS women with (n = 29) and without (n = 31, controls) pretreatment of gonadotropin-releasing hormone (GnRH) agonist before frozen-thawed ET. We found that pretreatment with GnRH agonist before frozen-thawed ETs could not significantly improve the clinical pregnancy rate in these hyperandrogenic PCOS women. However, the ongoing pregnancy rate was significantly increased in women with GnRH agonist pretreatment (odds ratio: 3.98, 95% confidence interval: 1.12-14.20, p = 0.033). We concluded that androgen deprivation status due to pretreatment with GnRH agonist might improve the ongoing pregnancy rate in hyperandrogenic PCOS women. Additional large, well-designed prospective studies are worthwhile and necessary.

Protection of cumulus cells following dehydroepiandrosterone supplementation.

BACKGROUND: Growing studies have demonstrated that dehydroepiandrosterone (DHEA) may improve fertility outcomes in poor ovarian responders (PORs). The aim of this study was to compare clinical outcomes and cumulus cell (CC) expression before and after DHEA treatment in PORs undergoing in vitro fertilization (IVF) cycles. METHODS: Six patients with poor ovarian response were enrolled in the study according to Bologna criteria. DHEA was supplied at least 2 months before patients entered into the next IVF cycle. Expression of apoptosis-related genes in CCs was determined by quantitative real-time PCR. Mitochondrial dehydrogenase activity of CCs was assessed by cell counting kit-8 assay. RESULTS: Metaphase II oocytes, maturation rate, embryos at Day 3, and fertilization rate significantly increased following DHEA treatment. Expression of cytochrome c, caspase 9, and caspase 3 genes in CCs were significantly reduced after DHEA therapy. Additionally, increased mitochondrial activity of CCs was observed following DHEA supplementation. CONCLUSIONS: DHEA supplementation may protect CCs via improved mitochondrial activity and decreased apoptosis, leading to better clinical outcomes in PORs.

Diagnosis and management of a rare case with placental site trophoblastic tumor.

OBJECTIVE: Placental site trophoblastic tumor (PSTT) is rare and is characterized by a slow growth. The objective of this report is to present a case of PSTT associated with irregular vaginal spotting that occurred 1 year after normal vaginal delivery. CASE REPORT: This report provides interesting ultrasound, hysteroscopy, and histology findings of PSTT. It is difficult to make a clinical diagnosis of PSTT at an early stage. Without the use of immunohistochemical analysis, PSTT may evade histological detection. An operative hysteroscopy using electrocauterization reduces active bleeding during the removal of PSTT with markedly engorged tumor vessels. CONCLUSION: Transvaginal sonography using color Doppler imaging plays a vital role in identifying residual PSTT with microscopic infiltration to the myometrium and a negative serum ß-human chorionic gonadotropin level.