Aggressive sperm immobilization improves reproductive outcomes in patients with suboptimal semen parameters and previous ICSI fertilization failure.

Intracytoplasmic sperm injection (ICSI) is the most effective procedure to resolve male infertility, enhancing overall fertilization and pregnancy outcomes. However, it is important to note that fertilization failure (FF) can still occur in a few cases after ICSI. This study aims to introduce a specialized technique of aggressive sperm immobilization for ICSI and evaluate its impact on reproductive outcomes in cases involving prior fertilization failure. All infertile couples with male partners having suboptimal semen samples and previous ICSI fertilization failure were evaluated using retrospective data from National Taiwan tertiary university hospital (NTUH) between January 2016 and February 2022. Fertilization failure in our study was defined as less than 30% fertilization rate (FR, the number of normally fertilized oocytes divided by the total number of injected mature oocytes). Data involving both standard (routine procedure) and aggressive sperm immobilization (SI) techniques during different ICSI cycles were included in this study. Standard and aggressive SI methods were performed by compressing the distal half tail of the spermatozoa ≦ 5 and 15 times prior to ICSI respectively. Generalized estimating equations analysis were applied to compare the clinical outcomes between two procedures. Overall, data from 23 infertile couples who had undergone 65 ICSI cycles (31 standard SI with low fertilization rate and 34 aggressive SI) were included in the study. The average FR in the ICSI cycles with standard SI and aggressive SI were 23.6 ± 23.1% and 49.5 ± 31.8 respectively (P = 0.0002). The majority of embryos were transferred at the day 3 stage, with an average number transferred of 2.6 ± 0.9 in the aggressive SI group and 1.9 ± 0.9 in the standard group. The number of embryos transferred per transfer cycle was higher in the aggressive SI (P = 0.015), whereas the number of good-quality embryos was similar between the two procedures (P = 0.44). There were one and seven live births from the standard SI cycles and aggressive SI cycles respectively. In conclusion, aggressive SI was associated with a significantly higher FR, resulting in more available embryos for transfer without compromising embryo quality. Therefore, this specialized technique improved pregnancy outcome among infertile couples with a previous ICSI-FF. It can be a safe, economic, and effective method to improve the assisted reproductive technologies outcomes for infertile patients affected by previous ICSI-FF.

CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative, promotes apoptosis and inhibits vasculogenic mimicry via targeting TRAP1.

CVM-1118 (foslinanib) is a phosphoric ester compound selected from 2-phenyl-4-quinolone derivatives. The NCI 60 cancer panel screening showed CVM-1125, the major active metabolite of CVM-1118, to exhibit growth inhibitory and cytotoxic effects at nanomolar range. CVM-1118 possesses multiple bioactivities, including inducing cellular apoptosis, cell cycle arrest at G2/M, as well as inhibiting vasculogenic mimicry (VM) formation. The TNF receptor associated protein 1 (TRAP1) was identified as the binding target of CVM-1125 using nematic protein organization technique (NPOT) interactome analysis. Further studies demonstrated CVM-1125 reduced the protein level of TRAP1 and impeded its downstream signaling by reduction of cellular succinate levels and destabilization of HIF-1α. The pharmacogenomic biomarkers associated with CVM-1118 were also examined by Whole Genome CRISPR Knock-Out Screening. Two hits (STK11 and NF2) were confirmed with higher sensitivity to the drug in cell knock-down experiments. Biological assays indicate that the mechanism of action of CVM-1118 is via targeting TRAP1 to induce mitochondrial apoptosis, suppress tumor cell growth, and inhibit vasculogenic mimicry formation. Most importantly, the loss-of-function mutations of STK11 and NF2 are potential biomarkers of CVM-1118 which can be applied in the selection of cancer patients for CVM-1118 treatment. CVM-1118 is currently in its Phase 2a clinical development.

Primary spontaneous inguinal endometriosis: Two cases with emphasis on the diagnostic approach.

OBJECTIVE: While endometriosis is common, inguinal endometriosis with hernia is rarely observed, making its preoperative diagnosis challenging. CASE REPORT: We report two cases of inguinal endometriosis with different presentations and focus on tailored surgical treatment. The two patients in our series presented with painful swelling in the right groin area. Surgery and pathological examination confirmed the diagnosis of endometriosis in both cases. Herniorrhaphy and excision of the extraperitoneal round ligament were performed in one patient with concomitant inguinal endometriosis and indirect inguinal hernia. CONCLUSION: We highlight the importance of the preoperative evaluation of concomitant pelvic endometriosis, round ligament involvement, and endometriosis within the inguinal hernia sac. Inguinal endometriosis with or without hernia should be considered even in reproductive-aged women without a previous medical and surgical history. Postoperative hormonal therapy, including dienogest, can be considered to prevent disease recurrence.

Adding a nonpainful end to reduce pain recollection of Pap smear screening: a randomized controlled trial.

ABSTRACT: The pain experienced during Pap tests is a crucial gap in reducing cervical cancer burden. This study sought to investigate whether adding a nonpainful step at the end of Pap tests helps women recall less pain. We conducted a randomized controlled trial on women aged 30 to 70 years at a cervical cancer screening center. A nonpainful step was added at the end of Pap test in the modified Pap group. The outcomes included recalled pain after Pap smear screening, real-time pain, and 1-year willingness to receive further Pap tests. Among 266 subjects in the intention-to-treat analysis, the modified Pap group (n = 133) experienced lower 5-minute recalled pain than the traditional Pap group on a 1 to 5 numeric scale (mean [SD], 1.50 [0.77] vs 2.02 [1.12]; P < 0.001) and a 0 to 10 visual analog scale (2.12 [1.79] vs 3.12 [2.23]; P < 0.001). In exploratory subgroup analyses, the association between the modified Pap test and reduced 5-minute recalled pain was not affected by predicted pain, demographic, or socioeconomic characteristics, but it was more apparent in postmenopausal women. Consistently, the modified Pap test attenuated 1-year recalled pain on both pain scales. Furthermore, the modified Pap test increased 1-year willingness grade to receive further Pap tests (adjusted ß [SE], 2.11 [0.27]; P < 0.001). In conclusion, adding a nonpainful step at the end of Pap smear screening reduces on-site and long-term recalled pain and strengthens willingness to undergo subsequent Pap tests regularly. The modified Pap test contributes to cervical cancer screening participation.

The role of circulating miRNAs in mechanism of action and prediction of therapeutic responses of metformin in polycystic ovarian syndrome.

OBJECTIVE: To study the involvement of microribonucleic acids (miRNAs) in the pathogenesis of chronic anovulation and mechanism of metformin treatment in polycystic ovary syndrome (PCOS). DESIGN: Case-control and prospective validation cohort study. SETTING: Tertiary university hospital. PATIENT(S): A total of 146 patients with PCOS and chronic anovulation and 20 non-PCOS controls were enrolled. Patients who resumed ovulation after metformin treatment (MET-OV) and remained anovulatory after metformin treatment (MET-AO) were assigned to MET-OV and MET-AO groups, respectively. INTERVENTION(S): All patients with PCOS received metformin treatment for 6 months. MAIN OUTCOME MEASURE(S): Baseline and chronological changes in the plasma levels of 14 miRNAs (miR-21, 93, 132, 193b, 221, 222, 223, 27a, 125b, 200b, 212, 320a, 429, and 483) selected by literature review, anthropometric data, and hormonal as well as metabolic profiles were measured. Predictive modeling based on baseline circulatory miRNA levels and clinical parameters was performed to predict ovulation recovery after metformin treatment. RESULT(S): No significant differences were observed in the baseline hormonal and metabolic profiles between the MET-OV and MET-AO groups. However, the expression of miR-27a, miR-93, and miR-222 was significantly higher in the MET-OV group than that for the MET-AO and control groups. After 6 months of metformin treatment, the levels of insulin, luteinizing hormone, and 6 circulating miRNAs (miR-21, 27a, 93, 221, 222, and 223) and homeostatic model assessment for insulin resistance decreased significantly in the MET-OV group, but remained unchanged in the MET-AO group. The area under curve, sensitivity, and specificity of the adjusted prediction model, based on miRNA levels and clinical parameters using logistic regression analysis for predicting ovulatory response after metformin treatment, were 0.807, 0.892, and 0.632, respectively. CONCLUSION(S): The present study demonstrated a distinct pattern of baseline expression and chronological changes in the levels of several circulatory miRNAs between the MET-OV and MET-AO groups, suggesting that aberrantly overexpressed diabetogenic miRNAs are involved in the pathophysiology of chronic anovulation in PCOS, and their down-regulation might contribute toward the therapeutic effects of metformin. This could provide new insights into the mechanism of action and applicability of individualized metformin therapy in women with PCOS.

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.

Impacts of Saharan Mineral Dust on Air-Sea Interaction over North Atlantic Ocean Using a Fully Coupled Regional Model.

This study examines the modifications of air-sea coupling processes by dust-radiation-cloud interactions over the North Atlantic Ocean using a high-resolution coupled atmosphere-wave-ocean-dust (AWOD) regional model. The dust-induced mechanisms that are responsible for changes of sea surface temperature (SST) and latent and sensible heat fluxes (LHF/SHF) are also examined. Two 3-month numerical experiments are conducted, and they differ only in the activation and deactivation of dust-radiation-cloud interactions. Model results show that the dust significantly reduces surface downward radiation fluxes (SDRF) over the ocean with the maximum change of 20-30 W m-2. Over the dust plume region, the dust effect creates a low-pressure anomaly and a cyclonic circulation anomaly, which drives a positive wind stress curl anomaly, thereby reducing sea surface height and mixed layer depth. However, the SST change by dust, ranging from -0.5 to 0.5 K, has a great spatial variation which differs from the dust plume shape. Dust cools SST around the West African coast, except under the maximum dust plume ridge, and extends westward asymmetrically along the northern and southern edges of the dust plume. Dust unexpectedly warms SST over a large area of the western tropical North Atlantic and north of the dust plume. These SST changes are controlled by different mechanisms. Unlike the SST change pattern, the LHF and SHF changes are mostly reduced underneath the dust plume region, though they are different in detail due to different dominant factors, and increased south of the dust plume over the tropic.

Obesity alters ovarian folliculogenesis through disrupted angiogenesis from increased IL-10 production.

OBJECTIVE: Obesity has been reported to have a modulatory effect on the ovulatory functions of patients with polycystic ovary syndrome. The role of adipokines in this obesity-associated ovulatory disturbance has not been extensively explored. In this study, the relationships between obesity, adipokine production from visceral fat, and ovarian folliculogenesis were explored in a mice model of induced obesity. METHODS: Obesity was induced in female C57BL/6 mice fed ad libitum with high-fat feed and fructose water for 4 weeks. Follicular developments in the ovaries were assessed by histopathology in these diet-induced obese mice. Changes in adipokine expression in the peri-ovarian adipose tissues were screened with an adipokine array. The adipokine with the most significant increase over time was identified. The functions of the adipokine in angiogenic processes were evaluated in a cell model of endothelial proliferation. The in vivo effects of neutralizing this adipokine using specific antibodies were assessed in the same obesity model. RESULTS: A high-fat and fructose diet induced an accumulation of early ovarian follicles and a reduction in mature follicles and corpus lutea. The number of microvessels in the early follicles also decreased. The adipokine protein array of the peri-ovarian adipose tissues identified a progressive increase in IL-10 expression with the duration of the obesogenic diet. In vitro experiments in the endothelial cell model confirmed IL-10 as a disrupter of VEGF-induced angiogenesis. Administration of anti-IL-10 antibodies prevented the histopathological changes induced by the obesogenic diet and further highlighted the role of IL-10 in disrupting folliculogenesis. CONCLUSIONS: Obesity may disrupt normal folliculogenesis through increased production of IL-10 in visceral fats. This relationship may help clarify the reported association between obesity and ovulatory dysfunction, which has been found in patients with polycystic ovary syndrome. However, the duration of this study was short, which limited conclusions on the long-term reproductive outcomes.

Metformin: a novel promising option for fertility preservation during cyclophosphamide-based chemotherapy.

Cyclophosphamide (CP) could cause severe gonadotoxicity via imbalanced activation of primordial follicles through PI3K/AKT/mTOR activation. Whether metformin, a widely prescribed anti-diabetes agent with mTOR inhibitory effect, could preserve ovarian function against CP toxicity is unknown. Female C57BL/6 mice were randomized into seven groups (n = 11), including control, CP-alone, CP + metformin, CP + sirolimus or everolimus, metformin-alone and sirolimus-alone groups. The duration of pharmaceutical treatment was 4 weeks. CP treatment significantly impaired ovarian function and fertility in mice. CP + metformin treatment significantly attenuated the gonadotoxicity comparing to CP-alone treatment (primordial follicle count: 17.6 ± 4.2 versus 10.3 ± 2.7 follicles/high-power field; P = 0.027). CP + metformin treatment also tended to increase antral follicular count (5.4 ± 1.1 versus 2.5 ± 1.6 follicles/section), serum AMH levels (4.6 ± 1.2 versus 2.0 ± 0.8 ng/ml) and the litter size (4.2 ± 1.3 versus 1.5 ± 1.0 mice per pregnancy), compared with CP-alone group. Expression of phospho-mTOR and the number of TUNEL-positive granulosa cells increased after CP treatment and decreased in the CP + metformin groups, suggesting the mTOR inhibitory and anti-apoptotic effects of metformin. In in-vitro granulosa cell experiments, the anti-apoptotic effect of metformin was blocked after inhibiting p53 or p21 function, and the expression of p53 mRNA was blocked with AMPK inhibitor, suggesting that the anti-apoptotic effect was AMPK/p53/p21-mediated. In conclusion, concurrent metformin treatment during CP therapy could significantly preserve ovarian function and fertility and could be a promising novel fertility preserving agent during chemotherapy. The relatively acceptable cost and well-established long-term safety profiles of this old drug might prompt its further clinical application at a faster pace.

Role of human papillomavirus status after conization for high-grade cervical intraepithelial neoplasia.

Human papillomavirus (HPV) is the well-established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high-grade cervical intraepithelial neoplasia (HG-CIN). We conducted an observational study for long-term outcomes and HPV genotype changes after conization for HG-CIN. Between 2008 and 2014, patients with newly diagnosed HG-CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG-CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non-surveillance (non-S) group. For the S group (n = 493), the median follow-up period was 74.3 months. Eighty-four cases had recurrent CIN Grade 2 or worse (CIN2+) (5-year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type-specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9-valent vaccine types. Among the 7397 non-S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non-S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type-specific HPV infections, effective therapeutic vaccines are an unmet medical need.

Evaluating the Impact of Assimilating Aerosol Optical Depth Observations on Dust Forecasts Over North Africa and the East Atlantic Using Different Data Assimilation Methods.

This study evaluates the impact of assimilating moderate resolution imaging spectroradiometer (MODIS) aerosol optical depth (AOD) data using different data assimilation (DA) methods on dust analyses and forecasts over North Africa and tropical North Atlantic. To do so, seven experiments are conducted using the Weather Research and Forecasting dust model and the Gridpoint Statistical Interpolation analysis system. Six of these experiments differ in whether or not AOD observations are assimilated and the DA method used, the latter of which includes the three-dimensional variational (3D-Var), ensemble square root filter (EnSRF), and hybrid methods. The seventh experiment, which allows us to assess the impact of assimilating deep blue AOD data, assimilates only dark target AOD data using the hybrid method. The assimilation of MODIS AOD data clearly improves AOD analyses and forecasts up to 48 hr in length. Results also show that assimilating deep blue data has a primarily positive effect on AOD analyses and forecasts over and downstream of the major North African source regions. Without assimilating deep blue data (assimilating dark target only), AOD assimilation only improves AOD forecasts for up to 30 hr. Of the three DA methods examined, the hybrid and EnSRF methods produce better AOD analyses and forecasts than the 3D-Var method does. Despite the clear benefit of AOD assimilation for AOD analyses and forecasts, the lack of information regarding the vertical distribution of aerosols in AOD data means that AOD assimilation has very little positive effect on analyzed or forecasted vertical profiles of backscatter.

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.

Hyperactive CREB signaling pathway involved in the pathogenesis of polycystic ovarian syndrome revealed by patient-specific induced pluripotent stem cell modeling.

OBJECTIVE: To study whether and how the pathogenesis of polycystic ovarian syndrome (PCOS) is related to epigenetic aberrations. DESIGN: A case-control experimental study. SETTING: Tertiary university hospital. PATIENT(S): Eighteen patients with PCOS and ten non-PCOS control subjects. INTERVENTIONS(S): Patient-specific induced pluripotent stem cells (iPSCs) were obtained from skin fibroblasts through the application of nonviral episomal reprogramming and were differentiated into ovarian granulosa cells (GCs) with the use of a cocktail of growth factors. Primary ovarian GCs were collected during transvaginal oocyte retrieval surgery. MAIN OUTCOME MEASURE(S): Characterization and functional validation of iPSC-derived GCs were conducted. Whole-genomic DNA methylation profiles in women with and without PCOS in both iPSC-derived GCs and primary adult GCs were analyzed with the use of the Illumina 850K MethylationEPIC Beadchip. RESULT(S): The iPSC-derived GCs successfully expressed GC-associated genes and aromatase activity after differentiation. Whole-genomic DNA methylation analysis of the iPSC-derived GCs and adult GCs both revealed a hyperactive CREB signaling pathway in the PCOS group compared with the control group. The expression of CREB-binding protein (CBP) mRNA was significantly higher in the iPSC-derived GCs in the PCOS group, and the expression of CBP protein was also significantly higher in the primary GCs from women with PCOS. CONCLUSION(S): The combination of DNA methylomic analysis in primary adult GCs and iPSC-derived GCs showed that a preserved persistent hyperactivation of the CREB signaling pathway might be involved in the pathogenesis of PCOS. These results could have implications on the early developmental origin, inheritance nature, and environmental interaction effects of this disease.

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.

Increased platelet factor 4 and aberrant permeability of follicular fluid in PCOS.

BACKGROUND/PURPOSE: Abnormal folliculogenesis is one of the cardinal presentations of polycystic ovarian syndrome (PCOS) and permeability of follicular wall has been proposed to be involved in the normal follicular growth. However, whether or not there is a change in intrafollicular permeability underlies PCOS is unknown. METHODS: This was a tertiary center-based case-control study. From 2014 to 2015, thirteen patients with PCOS who underwent in vitro fertilization-embryo transfer (IVF-ET) were enrolled. Eleven normo-ovulatory patients who underwent IVF-ET due to male factor and/or tubal factor infertility were enrolled as the control group. The influence of ovarian follicular fluid (FF) on endothelial cell permeability was evaluated using a human umbilical vein endothelial cell monolayer permeability assay. The intrafollicular expression profiles of angiogenesis-related proteins were analyzed using a Human Angiogenesis Protein Array Kit. RESULTS: The FF from PCOS patients caused significantly poorer endothelial cell permeability comparing with the effect of FF from the control group (46% ± 12% vs. 58% ± 9%, P = 0.023). Among the 55 angiogenesis-related proteins tested, there was a significantly higher level of intrafollicular platelet factor 4 (PF4) and PF4/IL-8 complex in the PCOS group (p = 0.004). The anti-permeability effect of PF4 was related to the decrease in the intercellular gaps and antagonistic binding with IL-8. CONCLUSION: Our study provides the first evidence of the pathophysiologic contribution of the well-known angiostatic protein, PF4, on human reproductive biology. The increase of the intrafollicular PF4 and its anti-permeability effect might affect the formation of FF and folliculogenesis in PCOS.

Early stop of progesterone supplementation after confirmation of pregnancy in IVF/ICSI fresh embryo transfer cycles of poor responders does not affect pregnancy outcome.

Previous studies indicated that progesterone can be withdrawn at the time of the first positive ß-hCG test without compromising the clinical pregnancy outcome in normal ovarian responder. However, the effect of early stop of progesterone supplementation for patients with poor ovarian response (POR) has not been investigated. This study retrospectively collected data from patients with POR in 156 IVF/ICSI fresh embryo transfer (ET) cycles in single tertiary center from January 2010 to June 2016. All the patients met ESHRE consensus, the Bologna criteria, of POR and had hCG injection for luteal phase support (LPS) on day 2, 5 and 8 after ovum pick-up. The pregnant patients were divided into two groups: early stop group represented those who stopped LPS from day of positive pregnancy test; control group represented those who kept progesterone supplementation till gestational age of 9 weeks. There were no significant differences in age, BMI, parity, hormone data, number of follicles>10(mm), endometrial thickness and number of embryos transferred between the two groups. After adjustment for possible confounders with multivariate logistic regression analysis, the clinical pregnancy rates (55.0% vs. 57.1%, P = 0.35), ongoing pregnancy rates (47.0% vs. 46.4%, P = 0.66), miscarriage rates (34.0% vs. 26.7%, P = 0.66) and live-birth rates (44.0% vs. 46.4%, P = 0.41) were not statistically different between early stop group and the control group. Our study indicates that early stop of progesterone supplementation on the day of positive pregnancy test for patients of POR using hCG as LPS in fresh ET cycles does not affect pregnancy outcome.

Advantages of cumulative pregnancy outcomes in freeze-all strategy in high responders - A case-control matching analysis of a large cohort.

BACKGROUND/PURPOSE: The freeze-all strategy in high responders is considered to be a safe and effective strategy for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment; however, the cumulative pregnancy outcomes have not been established. METHODS: A retrospective, single-center cohort study was conducted and 1311 high-responder patients (>20 oocytes retrieved and/or a serum estradiol level > 3000 pg/ml on the triggering day) were recruited from 2006 to 2015. The study group (n = 351) underwent the freeze-all strategy with subsequent thawed embryo transfer (ET), and the control group (n = 960) received fresh-cycle ET and subsequent thawed ET if needed. A case-control matching analysis was performed to match the two groups for the number of retrieved oocytes. The primary outcomes were the ongoing pregnancy rate (OPR) of the first ET cycle and the cumulative OPR. RESULTS: After matching, there was a significantly higher OPR in the first ET cycle (49.5% vs. 32.2%, p < 0.0001; n = 301 in each group) and the cumulative OPR (69.4% vs. 55.1%, p < 0.0001) in the study group, with significantly fewer total transferred embryos and cycles. The advantages of the freeze-all strategy for the OPR in the first ET cycle (OR: 1.97, p < 0.0001) and the cumulative OPR (OR: 1.49, p = 0.032) remained statistically significant after adjusting for other possible confounding factors in multivariate logistic regression analysis. CONCLUSION: For high responders, the freeze-all strategy with thawed ET achieved a significantly higher OPR in the first ET cycle and a higher cumulative OPR than the fresh ET strategy.

Embedding fistulojejunostomy: An easy and secure technique for refractory external pancreatic fistula.

BACKGROUND: Refractory external pancreatic fistula (REPF) is a rare but troublesome event. Fistulojejunostomy with direct suture of the fistula wall to jejunal wall has been demonstrated as a solution. However, it is sometimes technically difficult and some cases of failure were reported. METHODS: An embedding fistulojejunostomy (EFJ) was designed. The fistula tract was detached from the abdominal wall and impactedly inserted into a Roux-en-Y jejunal lumen without direct suture of the fistula wall to the jejunal wall. Five patients with REPF for > 3 months underwent this procedure in the past 10 years. The preoperatively-placed drainage tubes temporarily exteriorized the pancreatic fluid for 30 days. RESULTS: All fistulojejunostomy procedures were accomplished within 15 minutes. Four patients had uneventful recovery with a postoperative hospital stay ≤ 10 days. One patient had wound infection and needed hospitalization for 23 days. Except for one patient who required pancreatic enzyme supplements for 8 months, no other patient had pancreatic exocrine insufficiency. After follow up for 12-124 months, no patient required pancreatic enzyme supplements, and no patient had recurrent fistula or diabetes mellitus. CONCLUSION: EFJ makes fistulojejunostomy easier and more secure with a satisfactory early and long-term outcome. It may be a desirable technique for REPF.

Liver resection for hepatocellular carcinoma in patients with hematological malignancies.

BACKGROUND: Improvements in antimetabolite drugs have prolonged the survival of patient with hematological malignancies. However, these drugs may have hepatotoxic side effects and may induce acute liver failure, chronic liver fibrosis, cirrhosis, or even hepatocellular carcinoma (HCC). Although liver resection remains a curative option for HCC, its role in HCC with hematological malignancies has never been fully explored. METHODS: A retrospective review of 1725 patients who underwent curative liver resection for newly diagnosed HCC between 1994 and 2016 was conducted. Among these patients, 16 had a history of hematological malignancies (HM group). Their hematological malignancies were well-controlled at the time of liver resection. The clinicopathological characteristics of the HM group, along with their short- and long-term outcomes after liver resection, were compared with those of the other 1709 patients without hematological malignancy (non-HM group). RESULTS: All HM group patients were seropositive for hepatitis marker surface for hepatitis B and C. No significant differences were observed in any background characteristics between the two groups. The postoperative complication rate and 90-day mortality in the HM and non-HM groups were 25 and 20.4%, P = 0.754, and 0 and 0.6%, P = 1.000, respectively. The 5-year disease-free and overall survival rates for the HM and non-HM groups were 42.3 and 35.1%, P = 0.552, and 69.5 and 56.9%, P = 0.192, respectively. CONCLUSIONS: Hepatitis markers should be examined during chemotherapy for hematological malignancies. Regular liver imaging studies are recommended for seropositive cases. When HCC occurs secondary to a well-controlled hematological malignancy, liver resection is suggested in selected patients.

Murray secretion scale and fiberoptic endoscopic evaluation of swallowing in predicting aspiration in dysphagic patients.

The objective of this retrospective review is to evaluate the ability of the Murray secretion scale to predict aspiration as determined by fiberoptic endoscopic evaluation of swallowing. Patients with dysphagia undergoing a fiberoptic endoscopic evaluation of swallowing study between January 2013 and November 2015 from a single, tertiary care institution were retrospectively reviewed. The Murray secretion scale and penetration aspiration scale on fiberoptic endoscopic evaluation of swallowing examination were determined. Spearman's correlation analysis, sensitivity, specificity, predictive values, and relative risk evaluating the relationship between the Murray secretion scale and aspiration on fiberoptic endoscopic evaluation of swallowing were calculated. Subgroups of head and neck cancer patients, penetration group, and aspiration group were also analyzed. The mean age of the cases (N = 212) was 62.4 years. Eighty percent were male. There was a strong correlation between Murray secretion scale grade and penetration aspiration scale score (r = 0.785, p < 0.001). The sensitivity and specificity of a Murray secretion scale grade 2 or higher in predicting aspiration were 74 and 90%, respectively. Individuals with a Murray secretion scale grade of 2 or higher were 13.6 times more likely to aspirate than patients with a lower Murray secretion scale grade. All subgroups showed similar trend. Determination of a Murray secretion scale grade, determined by flexible nasopharyngoscopy, may predict patients at high risk for aspiration. In clinical scenarios where more complete assessments of aspiration risk are immediately impossible or impractical, the Murray secretion scale grade may add valuable information to assist in clinical decision-making in patients with dysphagia.