Live Delivery Research Articles

Lactic Acid Bacteria as a Live Delivery System for the in situ Production of Nanobodies in the Human Gastrointestinal Tract

Lactic acid bacteria (LAB) are among the most widely used microorganisms in food fermentation. However, some LAB species can also be used as live vehicles for the in situ delivery of therapeutic molecules to the mucosa of the human gastrointestinal tract (GIT). Many LAB species have 'qualified presumption of safety' status, and survive passage through the GIT. Indeed, some are part of the usual GIT microbiota. These are appropriate candidates for the in situ production of recombinant prophylactic and therapeutic proteins. Live recombinant LAB that produce microbial antigens have been shown to elicit an immune response that confers protection against the corresponding pathogens; these LAB could therefore be used as oral vaccines. In addition, some LAB have been genetically engineered to produce therapeutic, neutralizing antibodies. The variable domain of heavy-chain-only antibodies from camelids - known as VHH antibodies or nanobodies - have peculiar properties (nanoscale size, robust structure, acid resistance, high affinity and specificity, easily produced in bacteria, etc.) that make them ideal choices as LAB-produced immunotherapeutic agents. The present review examines the advantages offered by LAB for the in situ production of therapeutic proteins in the human GIT, discusses the use of in situ-produced VHH antibody fragments, and assesses the usefulness of this strategy in the treatment of infectious and non-infectious gastrointestinal diseases.

Regenerative therapy by endometrial mesenchymal stem cells in thin endometrium with repeated implantation failure. A novel strategy.

ObjectiveOur primary objective was to evaluate the endometrial changes before and after the transfer of endometrial mesenchymal stem cells (enMSCs) in a population of thinned endometrium women, with absence or hypo-responsiveness to estrogen and repeated implantation failure (RIF). The secondary objective was to evaluate the clinical outcomes of the intervention in terms of clinical pregnancy (CP), early abortions, ongoing pregnancy and live birth delivery rate (LBDR) per in vitro fertilization (IVF) cycle.MethodsA longitudinal and experimental study. The intervention was defined as "subendometrial inoculation of enMSCs," and the post-intervention changes were evaluated by the following variables: endometrial thickness (Eth), endometrial flow cytometry (enFC), endometrial histopathology (enHP) and endometrial immunohistochemistry (enIHQ). The variables were analyzed after the intervention (Post-treatment) regarding previous values (Pretreatment).ResultsEth values before and after treatment with enMSCs were 5.24±1.24 mm vs. 9.93±0.77 (p=0.000), respectively. Endometrial Flow Cytometry showed significant differences in favor of Normalized variables in the post-treatment assessment, associated with the pretreatment, LT/Li, LB/Li, NK/Li, CD8/CD3+ and CD4/CD8 (p≤0.015), respectively. Only two variables Li/PC and CD4/CD3 had NS (p=0.167 and 0.118). A similar analysis was performed on enHP with an HP increase post-treatment (p=0.007). The CP rate was 79.31% (23/29), a live birth delivery rate per embryo transfer was 45.45% (10/22) and ongoing pregnancy 7/29 (24.14%).ConclusionSubendometrial enMSCs inoculation produces a significant increase in endometrial thickness; normalize the enHP, enIHQ and enFC. As a result, IVF after treatment with enMSCs yields a higher rate of CP and LBDR.

Efficacy of salivary and diastase extracts of Piper betle in modulating the cellular stress in placental trophoblast during preeclampsia

Background: Betle leaf (BL) is an ancient herb with a potential nontoxic natural antioxidant efficacy. Oral intake and chewing betel leaves have an effort on the moving parts of salivary gland and induce salivation and detoxification; hence plays a vital role in oral hygiene. BL produces and activates various salivary enzymes which include α-amylase, lipase, lysozyme, and lactoperoxidase. BL possess antibacterial, antioxidant, anti-diabetic, immunomodulatory, and antihypertensive properties. Hence, it can be effective in the treatment of hypertensive disorder of pregnancy like preeclampsia (PE). Objective: In this context, two extracts of BL (Salivary BL extract [SBLE] and diastase BL extract [DBLE]), proved to impart efficient radical scavenging activity in our previous research work were utilized to analyze their efficacy on the level of 4-hydroxy nonenal (4-HNE), heme oxygenase-1 (HO-1), asymmetric dimethylarginine (ADMA), adiponectin/leptin in the trophoblast isolated from placental tissue of both normotensive and preeclamptic patients. Materials and Methods: Trophoblasts were isolated from both subjects and incubated with different extracts of Piper betle (saliva and diastase) to assess the cellular stress in placental trophoblast during PE. Results: Results demonstrate that extracts of BL exhibit a significant role in regulating 4-HNE, ADMA, leptin, HO-1, and adiponectin in preeclamptic trophoblasts. Still, SBLE showed relatively higher efficiency in defining the level of 4-HNE, ADMA, leptin, HO-1, and adiponectin in preeclamptic trophoblasts than DBLE, suggesting that it may be attributed to the interaction of the phytochemicals present in BL with the components of saliva. Conclusion: Hence, BL may be recommended as the effective natural remedy in the management of pathological complications of PE; which may preclude low birthweight babies and ensure live fetal delivery. Abbreviations Used: 4-HNE: 4-hydroxy-nonenal, ADMA: Asymmetric dimethylarginine, BL: Betel leaf, BLE: Betel leaf extract, CO: Carbon monoxide, DB: Diastase with betel leaf, DBLE: Diastase betel leaf extract, ELISA: Enzyme-linked immunosorbent assay, eNOS: Endothelial nitric oxide synthase, FBS: Fetal bovine serum, GSH: Reduced glutathione, HBSS: Hank's balanced salt solution, HO-1: Heme oxygenase-1, iNOS: Inducible nitric oxide synthase, NO: Nitric oxide, NOS: Nitric oxide synthase, PE: Preeclampsia, ROS: Reactive oxygen species, SB: Saliva with betel leaf, SBLE: Salivary betel leaf extract.

Are Fetuses Affected by Gastroschisis Benefited from Prenatal Maternal Corticosteroid Use and Early Parturition?

Introduction: Gastroschisis (G) is a congenital defect of the abdominal walls through which intestinal herniation and permanent exposure to amniotic liquid (AL) and its components are developed at the end of gestation. G affects mostly fetuses from young mothers under 25 - 29 years old, but it occurs more often in fetuses of mothers’ ages between 12 - 15 years old. Some authors assert that it is not the low weight, nor the low gestational age that influences mortality. In addition to morphological alterations, histological alterations are characterized by disorganization, distribution and the degree of ganglia maturity and myenteric plexuses. The literature describes parturition anticipation of G disease carriers to minimize damages to intestinal loops. There are studies suggesting corticosteroids at the end of gestation in order to avoid morphological and histological damages to the intestinal loop. Objective: Identify if live newborn infants delivery anticipation, that is, gestational date less than 37 weeks and prenatal maternal use of corticosteroid were benefited from early enteral diet, namely, less than 10 post-surgery days. Material and Method: From 33 newborns researched in the period from 2010 to 2014; 28 newborns full records were included in the study with 15.2% mortality rate. These newborns were divided in 3 groups according to maternal age: 6 newborns from mothers’ age between 16 - 20 years old (Group 1); 14 newborns from mothers’ age between 21 - 25 years old (Group 2) and 8 newborns from mothers’ age between 26 - 29 years old (Group 3). Gestational age at birth and prenatal maternal usage of corticosteroid and beginning oral feeding were assessed. Results: From 28 newborns, 19 mothers ingested prenatal corticosteroid and 16 newborns received the first enteric diet 10 days before and 3 days later. The mothers of the other 9 newborns were not treated with corticosteroid; only 3 newborns were fed before 10 days and 6 were fed later (p = 0.0016). Regarding gestational age, 17 newborns were born before 37 weeks and their 1st enteral diet was offered before 10 days. From the 11 newborns born after 37 weeks, only 4 received the 1st enteral diet before 10 days (p = 0.015). Conclusion: Newborn infants born with gestational age below 37 weeks, whose mothers received prenatal corticosteroid, were benefited with the first enteral diet before 10 postoperative days.

Can we predict the IVF/ICSI live birth rate?

Objectives:To find a pretreatment predictor for achieving a live birth. Assisted reproduction technology with IVF/ICSI is the ultimate chance for some couples to conceive a child. The expectations are high and it is important to give them a realistic perspective about the chances of achieving a live birth.Methods:A retrospective cohort study of all IVF/ICSI cycles performed in our center between 2012 and 2016. We considered only those cycles with a live birth delivery after 24 weeks, or cycles with no surplus embryos left. The following data was evaluated: AMH; AFC; age; BMI; previous diagnosis; type of treatment; number of previous deliveries; ethnicity, smoking status. Univariate and multivariate analysis were used to examine the association of live birth with baseline patient characteristics. We determined the odds-ratio for all the statistically significant variables (p<0.05), in a multivariate model. The results are presented according to the predictors founded.Results:739 cycles were evaluated: 9.1% were canceled; 10.2% did not have oocytes; 15.6% did not have D2 embryos; 31.4% achieved a live birth. The univariate analysis revealed statistically significant differences regarding AMH, AFC and women’s age between couples with and without a live birth (p<0.001), and the cause of infertility. We found no association with live births in other variables. These variables were categorized and used in a multivariate analysis.Conclusion:Age, AMH, AFC and cause, when sub-classified, are independently associated with the results of an IVF/ICSI treatment. These results enable couples to face real expectations in their particular scenario.

Bactofection of SW620 cell by Lactococcus lactis M4

In this study, a local dairy isolate, L. lactis M4 was investigated for its ability to be developed as a live delivery vector to deliver plasmid DNA into human colon cancer cell line, SW620. L. lactis M4 strain was found to adhere to and internalize SW620 cells optimally after 2 hours of infection period at a multiplicity of infection 250:1, bacteria per cancer cell. Bacteria also managed to survive intracellularly for 7 hours. Entry into SW620 cells was inhibited by Cytochalasin D and Vinblastine, indicating that cell uptake was dependent on microfilament and microtubule stability. Bactofection of SW620 cells by L. lactis M4 was demonstrated through the expression of fluorescent proteins from a novel dual-expression plasmid, pHSR. L. lactis M4 was able to express red fluorescent protein intracellularly of SW620 cells, which were subsequently observed to express green fluorescent protein at 3 hours post-invasion. The expression of fluorescent proteins from pHSR resulted from the bactofection of SW620 cells by L. lactis M4 has proven that this strain can be developed as a vector to deliver plasmid DNA into the cancer cell.

The Relationship between Total Cholesterol and Postpartum Impaired Glucose Tolerance in Women with Gestational Diabetes Mellitus

Background: To investigate the association between concentrations of total cholesterol (TC), at the time of gestational diabetes mellitus (GDM) diagnosis, and risk of postpartum impaired glucose tolerance. Methods: This is a retrospective cohort study. Women who were diagnosed GDM with a live singleton delivery between January 1 2013 and December 31 2017 were included in this study (n=2, 839). Women were grouped based on the TC quartiles at the time of GDM diagnosis, and relationship between TC and risk of postpartum glucose intolerance was assessed by COX regression. Findings: A total of 855 women were in the final analysis. Higher TC quartile at diagnosis of GDM was associated with a decreased risk of postpartum impaired glucose tolerance. Women in the highest TC quartile (>7·0 mmol L-1) had approximately only half-risk of any postpartum glucose intolerance, compared with women in the lowest TC quartile (<5·5 mmol L-1). Interpretation: The increased concentration of TC, at the time of GDM diagnosis, was related to a reduced risk of postpartum disorders of glucose metabolism in GDM women. We speculated that the increase of cholesterol may be a compensatory and adaptive response to pregnancy, and failure or deficiency to compensation may cause the occurrence of glucose metabolism disorders. Funding Statement: The study was supported by National Natural Science Foundation of China (Grant No: 81571452), Natural Science Foundation of Guangdong Province (Grant No: 2017A030310191), and Clinical Medical Project 5010 of Sun Yat-sen University, China (Grant No: 2012004). Declaration of Interests: No potential conflicts of interest relevant to this article were reported. Ethics Approval Statement: This study was approved by the Institutional Review Board of The First Affiliated Hospital of Sun Yat-sen University. All procedures were conducted in accordance with the Declaration of Helsinki.

Ideal embryo transfer position and endometrial thickness in IVF embryo transfer treatment.

To establish an ideal transfer strategy by investigating the relationships among embryo transfer (ET) depth, endometrial thickness, and subsequent in vitro fertilization treatment clinical pregnancy outcomes. In the present retrospective analysis, data from in vitro fertilization-ET treatment cycles conducted at a fertility center in Shanghai, China, between October 2014 and March 2015 were analyzed. Women were divided into groups 1-4 according to transfer depth (<10; 10-15, 15-20, and >20mm, respectively), as measured by air bubbles. Additionally, 391 women were divided into groups A-C according to endometrial thickness (<7, 1-12, and >12mm, respectively). Clinical pregnancy outcomes were assessed by group. Data from 501 cycles were included. Clinical pregnancy and live delivery rates were significantly higher in group 2 (P=0.009 and P=0.002, respectively) and group 3 (P=0.008 and P=0.001, respectively) than in group 4. Among the 394 patients with endometrial thickness data available, clinical pregnancy and live delivery rates were higher in group B (P=0.028 and P=0.015, respectively) and group (P=0.013 and P=0.013, respectively) than in group A. Correct transfer depth and endometrial thickness can increase the rates of clinical pregnancy, implantation, and live delivery. Placing the embryos at 10-20mm from the fundus and at an endometrial thickness of more than 7mm is recommended for optimal clinical pregnancy outcomes.

Effective mucosal live attenuated Salmonella vaccine by deleting phosphotransferase system component genes ptsI and crr.

Salmonella enterica is a major human pathogen that causes invasive non-typhoidal Salmonellosis (iNTS), resulting in significant morbidity and mortality. Although a number of pre-clinical and clinical studies have reported on the feasibility of developing a safe and effective vaccine against iNTS, there have been no licensed Salmonella vaccines available to protect against NTS strains. Vaccine formulations of highest priority for NTS are live attenuated vaccines, which can elicit effective induction of intestinal mucosal and intracellular bacteria-specific cell mediated immune responses. Since glucose is crucial for intracellular survival and replication in host cells, we constructed strains with mutations in components of the glucose uptake system, called the phosphotransferase system (PTS), and compared the relative virulence and immune responses in mice. In this study, we found that the strain with mutations in both ptsI and crr (KST0556) was the most attenuated strain among the tested strains, and proved to be highly effective in inducing a mucosal immune response that can protect against NTS infections in mice. Thus, we suggest here that KST0556 (ΔptsIΔcrr) is a potential live vaccine candidate for NTS, and may also be a candidate for a live delivery vector for heterologous antigens. Moreover, since PTS is a well-conserved glucose transporter system in both Gramnegative and Gram-positive bacteria, the ptsI and crr genes may be potential targets for creating live bacterial vectors or vaccine strains.

Basal Serum Anti-Müllerian Hormone Level as a Predictor of Clinical Outcomes in Freezing-all Embryo Transfer Program.

As a novel biomarker, there is inconsistent evidence regarding the association between anti-Müllerian hormone (AMH) and live birth rate in freezing-all embryo transfer cycles. We aim to assess the prognostic effect of baseline AMH on clinical outcomes, especially live birth rate in freezing-all embryo transfer cycles. A total of 828 non-polycystic ovary patients that underwent their first frozen-thawed embryo transfers in our center between January 2010 and January 2015 were recruited in this retrospective analysis. Patients were stratified into three groups based on their baseline AMH concentration: low AMH group (<1.4 ng/mL), middle AMH group (1.4-5.8 ng/mL) and high AMH group (>5.8 ng/mL). The results showed that low AMH level was associated with adverse clinical outcomes. The differences in implantation rate (21.9% vs. 43.2% vs. 58.8%, P<0.001), clinical pregnancy rate (32.0% vs. 55.2% vs. 65.7%, P<0.001), live birth delivery rate (21.8% vs. 43.6% vs. 52.7%, P<0.001) and miscarriage rate (31.8% vs. 17.5% vs. 15.4%, P=0.014) among the three groups were statistically significant. After adjusting confounders (i.e. age, baseline FSH level, AFC, endometrium thickness, endometrium preparation protocols, number of embryos transferred, etiologies of infertility), differences in live birth rate, clinical pregnancy rate and implantation rate between groups remained significant. The further age subgroup analysis demonstrated that low AMH concentration was significantly associated with poor outcomes both in young and advanced patients. The area under the curve for serum AMH, age, AFC and FSH were 0.635, 0.634, 0.615 and 0.543 respectively, for predicting live birth. In conclusion, baseline AMH was an independent prognostic factor of live birth rate of freezing-all embryo transfers, but its predictive value on live birth rate was of limited clinical value.

Adenomyosis

The usual treatment for severe adenomyosis has been hysterectomy, because its removal is complicated by infiltrative tissue destruction of normal uterine myometrium.. Yet many women wish to retain their uterus to preserve their ability to become pregnant and carry babies. Our objective was to see if it is possible to remove very large, symptomatic adenoymas with a technique that allows safe future childbearing. Complete excision of adenomyotic tissue and reconstruction of the uterine wall by a triple-flap method to prevent uterine rupture in subsequent pregnancies. From June 1998 to August 2017, 113 women with very severe adenomyosis who desired pregnancy, and all of whom had severe and debilitating symptoms were enrolled and followed for relief of symptoms and successful pregnancy and live birth. A dramatic reduction of menstrual symptoms occurred immediately and 69.5% of women delivered a healthy baby at term without any incidence of uterine rupture. Adenomyosis is a disabling disease in women that until recently had been treated by hysterectomy. However, many patients wish to preserve their uterus for childbearing, necessitating the need for a more effective conservative approach in treating this disease. The “triple-flap method” described here has not only significantly decreased the symptoms of adenomyosis but has also increased fertility in these patients with no incidence of uterine rupture. A successful live baby delivery rate of 69.5% has been achieved in these women who otherwise would have undergone hysterectomy.

Development and evaluation of an intelligent traceability system for waterless live fish transportation

Chinese consumers prefer to purchase fish that have only recently been killed. The supplying of live fish is routinely delivered by water. However, the traditional transportation of live fish with water results in small volume of transportation and may cost prohibitive. Therefore, cold anesthetized waterless live fish transport is considered an alternative and promising strategy, since this is likely to demand less energy with large freight volume. This paper aims to develop an intelligent traceability platform based on HACCP system that integrates wireless monitoring and quality control models to improve the quality control and safety transparency in waterless fish transportation. In this research Chinese sturgeon is taken as experiment subjects for long-distance transportation. Oxygen change model is established as a life-sustained key factor by hybrid prediction method can optimize fish survivability. Survival prediction model is also designed for improvement of live delivery quality with minimum stress accumulation under precise temperature condition. For tracing function evaluation, the QR Code combined with existing EPC traceability technology enables users to expediently query and quickly trace the safety transport information from aquaculture to markets. To demonstrate the automatic monitoring and intelligent traceable management in this platform, sturgeon delivery experiments have been evaluated and analyzed. The results illustrate this system can reduce the potential risks, implement quality control with high survival results, and improve the live fish transport volume at low-costly. In brief, application of this smart platform will provide an effective, suitable technical reference for aquatic enterprises to follow, and help them to adjust the waterless transport techniques for the other types of aquatic products.

Reproductive outcomes following women with previous cesarean scar pregnancy

Objective: To investigate the reproductive outcomes after the previous cesarean scar pregnancy (CSP). Methods: The clinical data of 138 patients with CSP in Tianjin Medical University General Hospital from January 2011 to March 2016 were collected and analyzed.Fifty-four cases underwent uterine artery embolization+ dilation & curettage (UAE+ D&C) surgery, 41 cases underwent D&C surgery, and 43 cases underwent laparoscopic surgery.Reproductive outcomes were followed up and analyzed. Results: All women were followed up for (46±17) months.It was encouraging that 37 women got 42 spontaneous pregnancies among 50 women with fertility plan, and the subsequent spontaneous pregnancy rate was 74.0%(37/50). Unfortunately, 6 women experienced recurrence of CSP (RCSP) in the subsequent pregnancies, and the RCSP rate was 14.3%(6/42). There were no significant differences with regard to spontaneous pregnancy rate and RCSP rate among the 3 groups (P>0.05). Nineteen women had led to a live delivery indeed without the presence of placenta previa, placenta accrete, uterine rupture and postpartum hemorrhage in the perinatal period. Conclusion: The reproductive outcomes following the previous CSP include the intrauterine pregnancy, spontaneous abortion and RCSP.The individualized treatments on CSP had no significant differences to the subsequent spontaneous pregnancy rate which was favorable in the future fertility plan.The incidence of RCSP was not significantly reduced by laparoscopic uterine scar repair.The risk of RCSP appeared to be increased in the subsequent pregnancies, and early diagnosis and treatment were needed to exclude the abnormal CSP.The overall perinatal outcomes were favorable.

Application of testicular spermatozoa cryopreservation in assisted reproduction.

To evaluate the efficiency of spermatozoa cryopreservation and to compare the clinical pregnancy outcomes in intracytoplasmic sperm injection (ICSI) using fresh versus cryopreserved spermatozoa collected by testicular sperm aspiration (TESA). A retrospective study was performed to compare the outcomes of men who accepted frozen-spermatozoa-based TESA-ICSI with those of men who underwent TESA-ICSI using fresh spermatozoa between January 1, 2015, and December 30, 2016. The groups were matched for age. The rates of fertilization, good-quality embryos, blastocyst formation, and clinical pregnancy outcomes were obtained from clinical records and were compared between the groups. There were no significant differences between the frozen TESA group (n=79) and the fresh TESA group (n=194) in the rates of fertilization (71.4% vs 73.4%), good-quality embryos (55.3% vs 54.5%), blastocyst formation (60.9% vs 60.1%), clinical pregnancy (61.7% vs 55.1%), and live delivery (51.1% vs 45.7%) (P>0.05 for allcomparisons). Freezing low-count sperm collected by TESA with a cryoprotectant was an efficient method in the treatment of male factor infertility.

Functional cargo delivery into mouse and human fibroblasts using a versatile microfluidic device

Efficient intracellular cargo delivery is a key hurdle for the translation of many emerging stem cell and cellular reprogramming therapies. Recently, a microfluidic-based device constructed from silicon was shown to transduce macromolecules into cells via shear-induced formation of plasma membrane pores. However, the scalability and widespread application of the current platform is limited since physical deformation-mediated delivery must be optimized for each therapeutic application. Therefore, we sought to create a low-cost, versatile device that could facilitate rapid prototyping and application-specific optimization in most academic research labs. Here we describe the design and implementation of a microfluidic device constructed from Polydimethylsiloxane (PDMS) that we call Cyto-PDMS (Cytoplasmic PDMS-based Delivery and Modification System). Using a systematic Cyto-PDMS workflow, we demonstrate intracellular cargo delivery with minimal effects on cellular viability. We identify specific flow rates at which a wide range of cargo sizes (1-70kDa) can be delivered to the cell interior. As a proof-of-principle for the biological utility of Cyto-PDMS, we show (i) F-actin labeling in live human fibroblasts and (ii) intracellular delivery of recombinant Cre protein with appropriate genomic recombination in recipient fibroblasts. Taken together, our results demonstrate that Cyto-PDMS can deliver small-molecules to the cytoplasm and biologically active cargo to the nucleus without major effects on viability. We anticipate that the cost and versatility of PDMS can be leveraged to optimize delivery to a broad array of possible cell types and thus expand the potential impact of cellular therapies.

Perinatal and Peripartum Outcomes in Vanishing Twin Pregnancies Achieved by In Vitro Fertilization.

To compare perinatal and peripartum outcomes of vanishing twin gestations with singleton and dichorionic twin gestations in pregnancies conceived by in vitro fertilization. We conducted a retrospective cohort study of vanishing twin pregnancies after fresh and cryopreserved autologous in vitro fertilization cycles performed at our institution from 2007 to 2015. Singleton, dichorionic twin, and dichorionic twin pregnancies with spontaneous reduction to one by 14 weeks of gestation (vanishing twins) were included. Analysis was restricted to patients with a live birth delivery at our institution at or beyond 24 weeks of gestation. The primary outcomes were gestational age and birth weight at delivery; secondary outcomes included peripartum morbidities. A subanalysis further differentiated the vanishing twin pregnancies between those in which demise of the twin occurred before compared with after identification of fetal cardiac activity. Logistic regression models were used to estimate the adjusted odds ratio (OR) with a 95% CI of outcomes. There were 1,189 pregnancies that met inclusion criteria (798 singleton, 291 twin, and 100 vanishing twin). The mean gestational age at birth and birth weights were 38.6±2.3 weeks of gestation and 3,207±644 g in singleton pregnancies, 35.5±2.7 weeks of gestation and 2,539±610 g in twin pregnancies, and 38.5±1.8 weeks of gestation and 3,175±599 g in vanishing twin pregnancies. When compared with twins, those with a vanishing twin had lower odds of preterm delivery (OR 0.13, 95% CI 0.07-0.23; adjusted OR 0.12, 95% CI 0.07-0.22) and small-for-gestational-age birth weight (OR 0.24, 95% CI 0.13-0.45; adjusted OR 0.14, 95% CI 0.07-0.28). In pregnancies conceived by in vitro fertilization that progress to at least 24 weeks of gestation, vanishing twin and singleton pregnancies had similar perinatal and peripartum outcomes. Both were significantly better than twin pregnancies.

Effects of body mass index on the outcomes of in vitro fertilization in Chinese patients with polycystic ovary syndrome: a retrospective cohort study

To investigate the effects of body mass index (BMI) on the outcomes of in vitro fertilization (IVF) in Chinese patients with polycystic ovary syndrome (PCOS). In the retrospective cohort study, a total of 1074 patients with PCOS undergoing IVF between April 2010 and May 2017 in two reproductive medicine centers, respectively in eastern China (Women’s Hospital, School of Medicine, Zhejiang University, Zhejiang Province) and in southern China (Maternal and Child Health Care Hospital of Liuzhou, Guangxi Province), were included. The patients were divided into four groups according to the recommended Chinese BMI cut-off points: underweight (BMI< 18.5 kg/m2), normal weight (18.5 kg/m2≤BMI<24.0 kg/m2), overweight (24.0 kg/m2≤BMI<28.0 kg/m2), and obese (BMI≥ 28.0 kg/m2). The basic characteristics of the PCOS patients, the details of IVF treatment, and the pregnancy outcomes were collected. There were no significant differences among the normal weight, overweight, and obese PCOS patients undergoing IVF on the biochemical pregnancy rate, clinical pregnancy rate, miscarriage rate, live birth rate, or term delivery rate (P>0.05), although the overweight and obese PCOS patients required more gonadotropin (Gn) (P<0.001) as well as longer stimulation period (P<0.001), and got less retrieved oocytes (P<0.05) and fertilized oocytes (P<0.05). The underweight PCOS patients required less Gn (P<0.05) and achieved higher live birth rate and term delivery rate (P<0.05), compared with the normal weight PCOS patients. High BMI had no negative effects on the outcomes of IVF in Chinese patients with PCOS; however, the conclusion may seem a little limited due to the retrospective design and the potential bias.

Impact of a History of Hypertension in Pregnancy on Later Diagnosis of Atrial Fibrillation.

BackgroundAtrial fibrillation/flutter (AF) produces significant morbidity in women and is typically attributed to cardiac remodeling from multiple causes, particularly hypertension. Hypertensive pregnancy disorders (HPDs) are associated with future hypertension and adverse cardiac remodeling. We evaluated whether women with AF were more likely to have experienced a HPD compared with those without.Methods and ResultsA nested case–control study was conducted within a cohort of 7566 women who had a live or stillbirth delivery in Olmsted County, Minnesota between 1976 and 1982. AF cases were matched (1:1) to controls based on date of birth, age at first pregnancy, and parity. AF and pregnancy history were confirmed by chart review. We identified 105 AF cases: mean age 57±8 (mean±SD) years, (controls 56±8 years), 32±8 years (controls 31±8 years) after the first pregnancy. Cases were more likely to have obesity during childbearing years, and hypertension, diabetes mellitus, dyslipidemia, coronary disease, valvular disease, and heart failure at the time of AF diagnosis. Cases were more likely to have a history of HPDs, compared with controls: 28/105 (26.7%) cases versus 12/105 (11.4%) controls, odds ratio: 2.60 (95% confidence interval, 1.21–6.04). After adjustment for hypertension and obesity, the association was attenuated and no longer statistically significant; odds ratio (95% confidence interval, 2.12 (0.92–5.23).ConclusionsWomen with AF are more likely to have had a HPD, a relationship at least partially mediated by associated obesity and hypertension. Given the high morbidity of AF, studies evaluating the benefit of screening for and management of cardiovascular risk factors in women with a history of HPD should be performed.

Reporting on longitudinal live birth rates and cumulative delivery rates are more realistic outcome measures than sperm retrieval rates in couples undergoing mTESE–ICSI

The live birth rates (LBRs) in men with non-obstructive azoospermia (NOA) undergoing microdissection TESE (mTESE) are under reported, with surgical sperm retrieval rate often used as the primary outcome measure. We analysed longitudinal and cumulative delivery rates following mTESE– intracytoplasmic sperm injection (ICSI) in NOA. Sperm was retrieved in 45% of patients undergoing mTESE. Median male and female age were 42 years (IQR 37–47) and 35 years (IQR 31–38) respectively. A total of 141 ICSI cycles and 23 frozen embryo transfers resulted in 62 pregnancies and 37 LBRs. The longitudinal LBR, crude and expected cumulative delivery rates after five cycles were 15.5%, 48.7% and 71.1%, respectively. Reassuringly, there was no significant difference in pregnancy rate (PR) (p = 0.37) or LBR (p = 0.68) using fresh or frozen sperm or embryo (p = 0.74). Sperm retrieval was significantly correlated with Johnsen score (JS) (p = 0.006) and hypospermatogenesis (HS) (p = 0.04), whilst LBR only significantly correlated with female age (p = 0.04). The longitudinal LBR for a couple embarking on mTESE for azoospermia is only 15.5%, although the cumulative delivery rates are promising. Reassuringly, the outcomes using fresh versus frozen embryos or sperm are comparable. Reporting on delivery rates from a single mTESE procedure are more objective and realistic measures of treatment success in men with NOA.

22‐1: Distinquished Paper and Invited Paper: Live Delivery of Neurosurgical Operating Theatre Experience in Virtual Reality

A system for assisting in microneurosurgical training and for delivering a live surgical experience was developed and experimented in hospital premises. An interactive neurosurgery experience from the operation theatre was presented together with associated medical content on virtual reality eyewear of remote users. Details of the 360‐degree capture, signal delivery, and display systems are presented, and the presence experience and the visual quality questionnaire results are discussed.