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Objectives To present a flexible protocol of vaginal pessaries for older women with significant pelvic organ prolapse (POP). Design A prospective cohort study of 140 consecutive older women (aged ≥65 years) with significant POP treated with individually fitted vaginal pessaries. After initial insertion, each patient was invited for a first evaluation after 1 month and subsequent follow-ups at increasing intervals of 1 month. During each examination, the pessary was removed and the vagina was inspected for infection, bleeding, or erosions. All patients were advised to use a vaginal estrogen cream twice a week. Setting The study was conducted during 2020 in the urogynecology clinic of a tertiary medical center. Participants The study cohort included 140 consecutive older women with significant and symptomatic POP treated with vaginal pessaries. Main outcome Primary outcomes included time intervals between follow-up visits, pessary-associated complications, need to change the pessary, need to remove the pessary temporarily, and whether the patients eventually underwent POP surgery. Results The mean age of the patients at the time of pessary fitting was 76.7 ± 9.2 years (range 65-100 years). Mean interval between follow-up examinations was 3.3 ± 1.1 months (range 1-6 months). Most patients (83.6%) used a ring pessary with support, but only a small number of patients were able to maintain the pessary by themselves. Of the 140 patients, five (3.6%) patients only eventually underwent POP surgery, and in 11 (7.9%) patients, the vaginal pessary had to be removed for 2-4 weeks because of significant vaginal discharge or superficial erosions. Additionally, 12 (8.6%) patients developed stress urinary incontinence following pessary insertion. Conclusions Customized management with vaginal pessary for symptomatic POP in older women is effective and safe, and is a suitable therapeutic alternative for older women who are unable or unwilling to undergo reconstructive pelvic surgery.

The present study aimed to determine the semen quality and cryopreservation outcomes among adolescent transgender females at the time of fertility preservation (FP) before initiating gender-affirming hormone (GAH) treatment. This retrospective cohort study included 26 adolescent transgender females who underwent FP in our Fertility Institute between 06/2013 and 10/2020. Pre-freezing semen parameters were compared to WHO 2010 reference values. Post-thaw semen parameters were used to determine the adequate assisted reproductive technology (ART). A multivariate linear regression analysis was performed to assess the impact of medical and lifestyle factors on semen quality. The mean age at which adolescent transgender females underwent FP was 16.2 ± 1.38 years. The median values of all semen parameters in our study group were significantly lower compared to the WHO data, including volume (1.46 mL vs 3.2 mL, respectively, P = 0.001 ), sperm concentration (28 × 106/mL vs 64 × 106/mL, P < 0.001), total sperm number (28.2 × 106 vs 196 × 106, P < 0.001), total motility (51.6% vs 62%, P < 0.001), and normal morphology (2% vs 14%, P < 0.001). The frequency of semen abnormalities was teratozoospermia 72%, hypospermia 52%, oligozoospermia 28%, and azoospermia 4%. The median post-thaw total motile count was 0.17 × 106/vial, and the quality was adequate only for ICSI in 87.7% of the thawed semen samples. No correlation was found between selected medical and lifestyle factors and poor semen parameters. Semen quality is strongly reduced among adolescent transgender females before hormone therapy and their stored sperm samples are suitable for intracytoplasmic sperm injection (ICSI) rather than conventional IVF/intrauterine insemination (IUI).

To investigate the possible associations of muscle and visceral fat mass with the prognosis of patients hospitalized with acute pancreatitis. Body composition analysis (Sliceomatic, TomoVision, Montreal, Canada) was performed on CT images at the L3 level in patients admitted with acute pancreatitis during 2008–2014. Regression analysis was used to examine associations of body composition with 1-year mortality and 1-year readmission rates. A total of 158 patients were included (mean age 63.7 ± 17.4 years, 91 (57.6%) were male). Fat was the most abundant tissue (408 ± 180 cm2 surface area). None of the prognostic factors examined were associated with 1-year mortality. Values below compared to above the medians for muscle mass and visceral fat were associated with higher mean 1-year readmissions: 1.7 versus 1.0, p = 0.02 and 1.6 versus 1.1, p = 0.09, respectively. Logistic regression analysis showed an association of high visceral fat with reduced 1-year readmission (OR 0.995, 95% CI 0.991–1.000, p = 0.03). Linear regression analysis showed an inverse correlation of visceral fat mass with the number of 1-year readmissions (HR −0.004, 95% CI −0.008–000, p = 0.070). Higher amounts of visceral fat and muscle mass were positively associated with lower recurrent hospitalizations in patients admitted with acute pancreatitis. These results support the importance of nutritional rehabilitation in patients after admission due to acute pancreatitis.

PURPOSE: To compare assisted reproductive technology (ART) outcomes among transgender men with those of fertile cisgender women. METHODS: This retrospective cohort study included 12 transgender men, six with no testosterone exposure and six after testosterone treatment, and 12 cisgender women (oocyte donors) who underwent ART in our institution between June 2017 and December 2019. Statistical analyses compared ART data and outcomes between three groups: cisgender women, transgender men without testosterone exposure, and transgender men after testosterone exposure. Comparisons were also made between transgender men with and without testosterone exposure. RESULTS: The transgender men with no testosterone exposure (23.3 ± 4 years) were significantly younger than the transgender men who had undergone testosterone treatment (30.3 ± 3.8 years; P = 0.012) and the cisgender women (29.1 ± 3.1 years; P = 0.004). The amount of FSH used for ovulation induction (1999 ± 683 mIU/mL) was significantly lower among transgender men without prior testosterone exposure compared with that among cisgender women (3150 ± 487 mIU/mL; P = 0.007). There were no differences in the peak estradiol levels, the number of oocytes retrieved, the number of MII oocytes, and the oocyte maturity rates between the three groups. Five out of six testosterone-treated transgender men underwent embryo cryopreservation, and they all achieved good-quality embryos. CONCLUSIONS: Transgender men have an excellent response to ovulation stimulation even after long-term exposure to testosterone. Oocyte/embryo cryopreservation is, therefore, a feasible and effective way for them to preserve their fertility for future biological parenting.

The researchers' aim was to assess provider gender preference among women attending the urogynecology clinic. Two hundred women with pelvic floor disorders completed a detailed questionnaire regarding possible gender preferences in choosing their urogynecologist. One-third of women preferred a female doctor while two-thirds had no preference. We found that embarrassment during the pelvic examination was the main reason for same-gender preference. This preference was significantly associated with educational level and being religious. In conclusion, although one-third of female patients prefer female urogynecologists, professional skills are considered to be more important factors when it comes to actually make a choice.

The disposition decision is a frequently unresolved issue for many IVF users with surplus frozen embryos (SFEs), and this study draws attention to their experiences and moral work, locating it in the Jewish-Israeli context that legally enables the donation of SFEs to research but prohibits donation to other infertile people. To explore the (mis)understandings and (mis)communication underlying IVF users’ decisions concerning the fate of their SFEs, the records of 674 IVF users with SFEs stored for more than 5 years during 1996–2011 were analyzed, and 89 IVF users with different disposition decisions were recruited for semi-structured interviews. With an average of 5.1 SFEs, after an average of 8 years of storage, no response to a written request for a disposition decision came from 60% (n = 404) of IVF users with SFEs. Payment for storage and defrosting were the two most frequent choices (13%, n = 89 and 89, respectively) followed by donation to research and transfer (7%, n = 47 and 45, respectively). Three themes emerged from the interviews: misunderstanding the consequences of not returning the disposition form, communication gaps regarding donation to research, and the unmet wish to donate embryos to infertile people. We conclude by discussing the experiences and views of IVF users as reflecting the implications of the liminality and boundary-work surrounding the frozen embryo as a moral work object, and their consequences for policy recommendations.

Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti- Tumor necrosis factors (TNFs), however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included, 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A), the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16–22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9), 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52, 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9), 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.

Background The coronavirus disease 2019 (COVID-19) pandemic has forced health-care providers to find creative ways to allow continuity of care in times of lockdown. Telemedicine enables provision of care when in-person visits are not possible. Sheba Medical Center made a rapid transition of outpatient clinics to video consultations (VC) during the first wave of COVID-19 in Israel. Objective Results of a survey of patient and clinician user experience with VC are reported. Methods Satisfaction surveys were sent by text messages to patients, clinicians who practice VC (users) and clinicians who do not practice VC (non-users). Questions referred to general satisfaction, ease of use, technical issues and medical and communication quality. Questions and scales were based on surveys used regularly in outpatient clinics of Sheba Medical Center. Results More than 1200 clinicians (physicians, psychologists, nurses, social workers, dietitians, speech therapists, genetic consultants and others) provided VC during the study period. Five hundred and forty patients, 162 clinicians who were users and 50 clinicians who were non-users completed the survey. High level of satisfaction was reported by 89.8% of patients and 37.7% of clinician users. Technical problems were experienced by 21% of patients and 80% of clinician users. Almost 70% of patients but only 23.5% of clinicians found the platform very simple to use. Over 90% of patients were very satisfied with clinician’s courtesy, expressed a high sense of trust, thought that clinician’s explanations and recommendations were clear and estimated that the clinician understood their problems and 86.5% of them would recommend VC to family and friends. Eighty-seven percent of clinician users recognize the benefit of VC for patients during the COVID-19 pandemic but only 68% supported continuation of the service after the pandemic. Conclusion Our study reports high levels of patient satisfaction from outpatient clinics VC during the COVID-19 pandemic. Lower levels of clinician satisfaction can mostly be attributed to technical and administrative challenges related to the newly implemented telemedicine platform. Our findings support the continued future use of VC as a means of providing patient-centered care. Future steps need to be taken to continuously improve the clinical and administrative application of telemedicine services.

Summary Isolating human MEK/ERK signaling-independent pluripotent stem cells (PSCs) with naive pluripotency characteristics while maintaining differentiation competence and (epi)genetic integrity remains challenging. Here, we engineer reporter systems that allow the screening for defined conditions that induce molecular and functional features of human naive pluripotency. Synergistic inhibition of WNT/β-CATENIN, protein kinase C (PKC), and SRC signaling consolidates the induction of teratoma-competent naive human PSCs, with the capacity to differentiate into trophoblast stem cells (TSCs) and extraembryonic naive endodermal (nEND) cells in vitro. Divergent signaling and transcriptional requirements for boosting naive pluripotency were found between mouse and human. P53 depletion in naive hPSCs increased their contribution to mouse-human cross-species chimeric embryos upon priming and differentiation. Finally, MEK/ERK inhibition can be substituted with the inhibition of NOTCH/RBPj, which induces alternative naive-like hPSCs with a diminished risk for deleterious global DNA hypomethylation. Our findings set a framework for defining the signaling foundations of human naive pluripotency., Graphical abstract, Highlights • Inhibition of SRC, PKC, and WNT consolidates human naive pluripotency induction • Competitiveness of p53 depleted human PSCs in cross-species chimeric embryos • Opposing net effect for ACTIVIN and WNT on mouse versus human naive pluripotency • 2i and ERKi independent alternative human naive-like PSC conditions, Engineered systems were used to screen for conditions that enable robust induction of human naive PSCs without the obligation for exogenous transgenes or feeder cells. The latter allowed defining the signaling and transcriptional foundations of human naive PSCs with enhanced (epi)genetic stability and competence for differentiation into all lineages.

PURPOSE: To compare fertility preservation (FP) outcomes among adolescent transgender males with those of cisgender females. METHODS: This retrospective cohort study included nine adolescent transgender males and 39 adolescent cisgender females who underwent FP between January 2017–April 2019 and September 2013–April 2019, respectively. The transgender males were referred before initiating testosterone, and the cisgender females were referred due to cancer diagnosis before starting anticancer treatment. Statistical analyses compared assisted reproductive technology (ART) data and FP outcomes between two groups. RESULTS: Basal FSH levels (5.4 ± 1.7 mIU/mL) and AFC (19.8 ± 5.6) of all transgender males were normal compared with standard references. The mean age of transgender males and cisgender females was similar (16.4 ± 1.1 vs 15.5 ± 1.3 years, respectively, P = 0.064). The amount of FSH used for stimulation was significantly lower among the former compared with the latter (2416 ± 1041 IU vs 4372 ± 1877 IU, P < 0.001), but the duration of stimulation was similar (12.6 ± 4.0 and 10.1 ± 2.8 days, P = 0.086). Peak estradiol level was significantly higher among transgender males compared with cisgender females (3073 ± 2637 pg/mL vs 1269 ± 975 pg/mL, respectively, P = 0.018), but there were no significant differences in number of retrieved oocytes between the two groups (30.6 ± 12.8 vs 22 ± 13.2, P = 0.091), number of MII oocytes (25.6 ± 12.9 vs 18.8 ± 11.2, P = 0.134), or maturity rates (81.5 ± 10.0% vs 85.4 ± 14.6%, P = 0.261). CONCLUSIONS: Adolescent transgender males have an excellent response to ovulation stimulation before initiating testosterone treatment. Oocyte cryopreservation is, therefore, a feasible and effective way for them to preserve their fertility for future biological parenting.

Objective: To describe patient characteristics at presentation, management, and fertility preservation rates among a cohort of Israeli children and adolescents with gender dysphoria (GD). Methods: We performed a retrospective chart review of 106 consecutive children and adolescents with GD (

Objective To assess the effect of a sharp increase in estrogen levels on overactive bladder (OAB) symptoms among women undergoing ovulation induction. Methods 100 consecutive women (mean age 36.9 ± 5.2 years) who underwent IVF treatments, were prospectively enrolled. Three validated questionnaires on urinary urgency, urinary incontinence, and lower urinary tract symptoms were used to evaluate patient's OAB symptoms before ovulation induction (low estradiol level) and prior to ovum pickup (peak estradiol level). Results Of the 100 women, 49 reported OAB symptoms prior to ovulation induction (mean USIQ severity score 33) and 51 women were asymptomatic. Of the 49 symptomatic women, 44 (90%) remained symptomatic (mean USIQ severity score 34) and 5 women became asymptomatic through ovulation induction. Of the 51 asymptomatic women, 24 (47%) developed de novo OAB symptoms, while 27 women (53%) remained asymptomatic through ovulation induction. The mean peak estradiol level was significantly higher among women who remained asymptomatic in comparison to women with de novo OAB symptoms (2069 versus 1372 pg/ml; respectively). Moreover, in most (63%) women who remained asymptomatic, peak estradiol levels were higher than 1500 pg/ml, whereas in most (67%) women who became symptomatic, peak estradiol levels were lower than 1500 pg/ml. Conclusion A higher estradiol level appears to have a protective effect against the development of OAB symptoms during ovulation induction. Further, in most (63%) women who remained asymptomatic, peak estradiol levels were higher than 1500 pg/ml. This finding may suggest a threshold for estradiol activity in the lower urinary tract.

What is the fertility preservation rate among transgender women who have received professional fertility counselling compared with transgender men?This retrospective cohort study included 56 transgender women and 56 transgender men referred for comprehensive fertility counselling at the Gender Clinic of the Tel Aviv Sourasky Medical Center's Fertility Institute between January 2017 and April 2019. Statistical analyses were performed to compare transgender men with transgender women who preserved fertility and transgender people who preserved fertility and those that did not.The fertility preservation rate of transgender women was significantly higher than that of transgender men (85.7% versus 35.7%, respectively, P 0.001). The fertility preservation rate among transgender women was associated with being older and not having undergone gender-affirming hormone (GAH) treatment. The fertility preservation rate was higher among adolescent transgender boys compared with adolescent transgender girls (35% versus 6.25%, respectively, P = 0.005). The duration of GAH treatment among the transgender men who preserved fertility was 70 months compared with 18.6 months for transgender women (P = 0.05). All transgender boys opted for oocyte cryopreservation, while half of the transgender men who had not started GAH opted for oocyte cryopreservation, and half of those who had already started on GAH opted for embryo cryopreservation.High fertility preservation rates among transgender individuals were found after comprehensive fertility counselling. Fertility preservation rates among adults were higher among transgender women compared with transgender men, while the opposite was found in transgender adolescents.

OBJECTIVE To investigate the developmental potential of oocytes and embryos derived from extremely small follicles (

Background Patient preferences regarding the gender of their physicians is a highly sensitive issue, which can be particularly salient in intimate medical situations. Previously published studies found that women tend to prefer female physicians, especially in the case of obstetricians and gynecologists. Data regarding other intimate specialties, such as breast surgery, are scarce. The present study was undertaken to assess gender preferences of women regarding their choice of a breast surgeon. Methods Five hundred and fifteen consecutive women who attended breast clinics in two university-affiliated tertiary hospitals were prospectively enrolled. A 25-item anonymous questionnaire was completed by women independently and used to assess their preferences in selecting their breast surgeon. Of the 515 women, 500 (97 % response rate; mean age 50.6 ± 15.4 years) completed the anonymous questionnaire. Results Overall, 160 (32 %) women preferred to undergo breast examination by a female breast surgeon, 296 (59 %) had no preference, and only 44 (9 %) preferred a male surgeon. A same-gender preference was significantly and independently associated with younger age of the patients (Odds Ratio = 0.978, 95 % Confidence Interval 0.962–0.994, P = 0.007) and being married (Odds Ratio = 0.563, 95 % Confidence Interval 0.347–0.916, P = 0.021). However, only small and equal numbers of patients preferred to undergo breast surgery by a female (14 %) or a male (13 %) surgeon, and most patients (73 %) had no gender preferences. Furthermore, the three most important factors, which affected in general the actual selection, were surgical ability (93 %), experience (91.2 %) and knowledge (78.6 %), rather than physician gender per se. Conclusions Overall, about a third of women prefer a female breast surgeon for their breast examination. Embarrassment during the examination was the major reason for same-gender preference. In contrast, when it comes to breast operations, preference for a female surgeon is less pronounced, with the professional skills of the surgeons becoming the predominant consideration. The fact that almost a third of the potential patients prefer female surgeons with regard to their breast examinations emphasizes the need to increase the number of female surgeons. Such an increase can be achieved through academic and economic changes that will enable more women to specialize in general surgery. Trial registration Trial registration is not required for this type of research.

Patients' preferences in choosing obstetricians/gynecologists are widely investigated, but studies among traditional populations are lacking. Bedouins comprise a traditional Arab Muslim society in the Arabian Peninsula (Saudi Arabia), The Levant (Syria, Jordan and Israel) and North Africa (Egypt). Most of the Bedouins in Israel populate several villages, mostly in the southern part of the country. This cross-sectional study compared 200 Bedouin and 200 Jewish women who responded to an anonymous questionnaire. Queried on gender alone, more Bedouin responders preferred female obstetricians/gynecologists (59.5 vs. 33% Jewish responders, p value

The purpose of the study was to explore the effect of blastomere biopsy for preimplantation genetic diagnosis (PGD) on the embryos’ dynamics, further cleavage, development, and implantation. The study group included 366 embryos from all PGD treatments (September 2012 to June 2014) cultured in the EmbryoScope™ time-lapse monitoring system. The control group included all intracytoplasmic sperm injection (ICSI) embryos cultured in EmbryoScope™ until day 5 during the same time period (385 embryos). Time points of key embryonic events were analyzed with an EmbryoViewer™. Most (88 %) of the embryos were biopsied at ≥8 cells. These results summarize the further dynamic development of the largest cohort of biopsied embryos and demonstrate that blastomere biopsy of cleavage-stage embryos significantly delayed compaction and blastulation compared to the control non-biopsied embryos. This delay in preimplanation developmental events also affected postimplantation development as observed when the dynamics of non-implanted embryos (known implantation data (KID) negative) were compared to those of implanted embryos (KID positive). Analysis of morphokinetic parameters enabled us to explore how blastomere biopsy interferes with the dynamic sequence of developmental events. Our results show that biopsy delays the compaction and the blastulation of the embryos, leading to a decrease in implantation.

Aim To investigate the effect of bariatric surgery on male lower urinary tract symptoms (LUTS) and sexual function. Methods Fifty-five consecutive obese men who underwent a laparoscopic sleeve gastrectomy were prospectively enrolled. Two validated questionnaires, the International Prostate Symptoms Score (IPSS) and the International Index of Erectile Function (IIEF) were used to assess LUTS and sexual function, before and 3 months after surgery. Fifty-three men (mean age 39 ± 12.5 years) completed all pre and postoperative questionnaires. Mean body mass index (BMI) before and 3 months after surgery was 42.8 ± 5.3 and 31.3 ± 5.4 kg/m2; respectively. Results Preoperatively, 41 (77%) men (mean age 40 ± 12.9, mean BMI 42.2 ± 5 kg/m2) had some degree of LUTS and 39 (74%) men (mean age 40.7 ± 12.4, mean BMI 42.8 ± 5.6 kg/m2) were sexually active. Postoperatively, the total IPSS score decreased significantly (5.5 ± 4.4 vs. 2.7 ± 2.6; P

The aim of this study was to evaluate the effect over time of bariatric surgery on female pelvic floor symptoms.In total, 160 consecutive adult women were requested to complete four anonymous questionnaires [International Consultation on Incontinence Questionnaire (ICIQ), Bristol Female Lower Urinary Tract Symptoms (BFLUTS), Pelvic Floor Distress Inventory (PFDI-20) and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12)] before bariatric surgery and at 3-6 months and 12-24 months postoperatively. Strict criteria were used to define clinically significant urinary incontinence (UI), pelvic organ prolapse (POP) and colorectal-anal (CRA) symptoms. Statistical analyses were performed using paired, two-sided, Student's t test for continuous data, and Fisher's exact test for categorical data.Altogether, 101 women (67%, mean age 41.6 ± 11.8 years, mean preoperative body mass index 41.6 ± 4.6 kg/m²) completed all questionnaires. In women who had preoperative UI (42.6%), mean ICIQ score decreased from 9.5 ± 4.0 at baseline to 3.0 ± 3.6 (p .001) and 2.9 ± 3.9 (p .001) at 3-6 and 12-24 months postoperatively, respectively. In women who had preoperative POP symptoms (17.8%), mean PFDI-20/POP score decreased from 23.8 ± 10.9 at baseline to 12.7 ± 12.9 (p = .010) and 13.7 ± 17.1 (p = .025) at 3-6 and 12-24 months postoperatively. In women who had preoperative CRA symptoms (35.6%), mean PFDI-20/CRA score decreased from 26.0 ± 14.9 at baseline to 15.4 ± 15.1 (p = .001) and 18.8 ± 15.4 (p = .045) at 3-6 and 12-24 months postoperatively. De novo postoperative POP and CRA symptoms were reported by up to 16% of patients.Surgically induced weight loss is associated with significant improvements in UI, POP and CRA symptoms. The maximal clinical effect was achieved within 3-6 months, and remained constant throughout the second postoperative year. Nevertheless, de novo POP and CRA symptoms are expected in up to 16% of patients.

Pre-implantation genetic diagnosis (PGD) is required in order to screen and diagnose embryos of patients at risk of having a genetically affected offspring. A biopsy to diagnose the genetic profile of the embryo may be performed either before or after cryopreservation. The aim of this study was to determine which biopsy timing yields higher embryo survival rates.Retrospective cohort study of all PGD patients in a public IVF unit between 2010 and 2013. Inclusion criteria were patients with good-quality embryos available for cryopreservation by the slow freezing method. Embryos were divided into two groups: biopsy before and biopsy after cryopreservation. The primary outcome was embryo survival rates post thawing.Sixty-five patients met inclusion criteria. 145 embryos were biopsied before cryopreservation and 228 embryos were cryopreserved and biopsied after thawing. Embryo survival was significantly greater in the latter group (77% vs. 68%, p 0.0001).Cryopreservation preceding biopsy results in better embryo survival compared to biopsy before cryopreservation.

Pulsed electromagnetic fields (PEMFs) have been considered a potential treatment modality for fracture healing, however, the mechanism of their action remains unclear. Mammalian target of rapamycin (mTOR) signaling may affect osteoblast proliferation and differentiation. This study aimed to assess the osteogenic differentiation of mesenchymal stem cells (MSCs) under PEMF stimulation and the potential involvement of mTOR signaling pathway in this process. PEMFs were generated by a novel miniaturized electromagnetic device. Potential changes in the expression of mTOR pathway components, including receptors, ligands and nuclear target genes, and their correlation with osteogenic markers and transcription factors were analyzed. Involvement of the mTOR pathway in osteogenesis was also studied in the presence of proinflammatory mediators. PEMF exposure increased cell proliferation and adhesion and the osteogenic commitment of MSCs even in inflammatory conditions. Osteogenic-related genes were over-expressed following PEMF treatment. Our results confirm that PEMFs contribute to activation of the mTOR pathway via upregulation of the proteins AKT, MAPP kinase, and RRAGA, suggesting that activation of the mTOR pathway is required for PEMF-stimulated osteogenic differentiation. Our findings provide insights into how PEMFs influence osteogenic differentiation in normal and inflammatory environments.

Preimplantation genetic diagnosis (PGD) may pose risks to pregnancy outcome owing to the invasiveness of the biopsy procedure. This study compares outcome of singleton and twin clinical pregnancies conceived after fresh embryo transfers of PGD (n = 89) and matched intracytoplasmic sperm injection (ICSI) pregnancies (n = 166). The study was carried out in a single university affiliated centre. Because of the paucity of available data, a literature-based meta-analysis of studies comparing neonatal outcome of PGD and ICSI pregnancies was also conducted. In the retrospective cohort study, obstetric and neonatal outcome were available in 67 PGD and 118 ICSI pregnancies. Perinatal outcomes were comparable between PGD and ICSI pregnancies. Meta-analysis revealed similar outcomes, except for higher rate of low birth weight (

Study question What is the optimal timing for blastomere biopsy during the 8-cell stage, at which embryos will have the best implantation potential? Summary answer Fast-cleaving embryos that are biopsied during the last quarter (Q4) of the 8-cell stage and are less affected by the biopsy procedure, and their implantation potential is better than that of embryos biopsied earlier during the 8-cell stage (Q1-Q3). What is known already Blastomer biopsy from cleavage-stage embryos is usually performed on the morning of Day 3 when the embryos are at the 6- to 8-cell stage and is still the preferred biopsy method for preimplantation genetic diagnosis (PGD) for monogentic disorders or chromosomal translocations. Human embryos usually remain at the 8-cell stage for a relatively long 'arrest phase' in which cells grow, duplicate their DNA and synthesize various proteins in preparation for the subsequent division. Study design, size, duration This is a retrospective cohort study. The study group (195 embryos) included all 8-cell stage embryos that underwent blastomere biopsy for PGD for monogenetic disorders and chromosomal translocations in our unit between 2012-2014 and cultured in the EmbryoScope until transfer. The control group (115 embryos) included all embryos that underwent intracytoplasmic sperm injection without a biopsy during the same period. Participants/materials, setting, methods The 8-cell stage was divided into four quarters: the first 5 h post-t8 (Q1), 5-10 h post-t8 (Q2), 10-15 h post-t8 (Q3) and at 15-20 h post-t8 (Q4). Non-biopsied control embryos were divided into four equivalent quarters. Embryos were evaluated for timing of developmental events following biopsy including timing of first cleavge after biopsy, timing of comapction (tM) and start of blastulation (tSB). Timing of these events were compared between PGD and control embryos, as well as with 56 PGD implanted embryos with Known Implantation Data (PGD-KID-positive embryos). Main results and the role of chance Embryos that were biopsied during Q3 (10-15 h from entry into 8-cell stage) were delayed in all three subsequent developmental events, including first cleavage after biopsy, compaction and start of blastulation. In contrast, these events occurred exactly at the same time as in the control group, in embryos that were biopsied during Q1, Q2 or Q4 of the 8-cell stage. The results show also that embryos that were biopsied during Q1, Q2 or Q3 of the 8-cell stage demonstrated a significant delay from the biopsied implanted embryos already in t8 as well as in tM and tSB. However, embryos that were biopsied during Q4 demonstrated dynamics similar to those of the biopsied implanted embryos in t8 and tM, and a delay was noticed only in the last stage of tSB. Limitations, reasons for caution This is a retrospective study that is limited to the timing of biopsy that is routinely performed in the IVF lab. A prospective study in which biopsy will be performed at a desired timing is needed in order to differ between the effect of biopsy itself and the cleavage rate of the embryo. Wider implications of the findings Our findings showed that blastomere biopsy can be less harmful to further development if it is carried out during a critical period of embryonic growth, i.e during Q4 of the 8-cell stage. They also demonstrated the added value of time-lapse microscopy for determining the optimal timing for blastomere biopsy. Study funding/competing interest(s) The study was funded by the routine budget of our IVF unit. Trial registration number N/A.

Genomic aberrations have been identified in many human pluripotent stem cell (hPSC) cultures. Commonly observed duplications in portions of chromosomes 12p and 17q have been associated with increases in genetic instability and resistance to apoptosis, respectively. However, the phenotypic consequences related to sporadic mutations have not been evaluated to date. Here, we report on the effects of a single-copy deletion of the chr17p13.1 region, a sporadic mutation that spontaneously arose independently in several subclones of a human embryonic stem cell culture. Compared to cells with two normal copies of chr17p13.1 (“wild-type”), the cells with a single-copy deletion of this region (“mutant”) displayed a selective advantage when exposed to stressful conditions, and retained a higher percentage of cells expressing the pluripotency marker POU5F1/OCT4 after 2 weeks of in vitro differentiation. Knockdown of TP53, which is a gene encompassed by the deleted region, in wild-type cells mimicked the chr17p13.1 deletion phenotype. Thus, sporadic mutations in hPSCs can have phenotypic effects that may impact their utility for clinical applications.

There are several studies on patients’ preference for same-gender physicians, especially female preference for same-gender gynecologists. Data regarding the preferences of urology patients, of whom the majority are males, are scarce. The objective of this study is to assess provider gender preference among urology patients. One hundred and nineteen consecutive men (mean age 57.6 years) who attended a urology clinic in one university-affiliated medical center were prospectively enrolled. A self-accomplished 26-item anonymous questionnaire was used to assess patients’ preferences in selecting their urologist. Of the 119 patients, 51 (42.8%) preferred a male urologist. Patients exhibited more same-gender preference for physical examination (38.3%), or urological surgery (35.3%), than for consultation (24.4%). Most patients (97%) preferred a same-gender urologist because they felt less embarrassed. Four patient characteristics were identified to be significantly associated with preference for a male urologist: religious status, country of origin, marital status, and a prior management by a male urologist. Of these, religious status was the most predictive parameter for choosing a male urologist. The three most important factors that affected actual selection, however, were professional skills (84.6%), clinical experience (72.4%), and medical knowledge (61%), rather than physician gender per se. Many male patients express gender bias regarding their preference for urologist. However, professional skills of the clinician are considered to be more important factors when it comes to actually making a choice.

The self-renewal and differentiation capacities of human pluripotent stem cells (hPSCs) make them a promising source of material for cell transplantation therapy, drug development, and studies of cellular differentiation and development. However, the large numbers of cells necessary for many of these applications require extensive expansion of hPSC cultures, a process that has been associated with genetic and epigenetic alterations. We have performed a combinatorial study on both hESCs and hiPSCs to compare the effects of enzymatic vs. mechanical passaging, and feeder-free vs. mouse embryonic fibroblast feeder substrate, on the genetic and epigenetic stability and the phenotypic characteristics of hPSCs. In extensive experiments involving over 100 continuous passages, we observed that both enzymatic passaging and feeder-free culture were associated with genetic instability, higher rates of cell proliferation, and persistence of OCT4/POU5F1-positive cells in teratomas, with enzymatic passaging having the stronger effect. In all combinations of culture conditions except for mechanical passaging on feeder layers, we noted recurrent deletions in the genomic region containing the tumor suppressor gene TP53, which was associated with decreased mRNA expression of TP53, as well as alterations in the expression of several downstream genes consistent with a decrease in the activity of the TP53 pathway. Among the hESC cultures, we also observed culture-associated variations in global gene expression and DNA methylation. The effects of enzymatic passaging and feeder-free conditions were also observed in hiPSC cultures. Our results highlight the need for careful assessment of the effects of culture conditions on cells intended for clinical therapies.

PURPOSE: The purpose of the study was to compare the morphokinetic parameters of embryos carrying balanced chromosomal translocations with those carrying unbalanced chromosomal translocations using time-lapse microscopy. METHODS: The study group included 270 embryos that underwent biopsies on day 3 for preimplantation genetic diagnosis (PGD) for chromosomal translocations in our unit between 2013 and 2015. All embryos were incubated under time-lapse microscopy and evaluated for timing of developmental events up to day 5. The timing of these events was compared between balanced and unbalanced embryos, potentially viable and nonviable variants, and maternal versus paternal inheritance of the translocation. RESULTS: The PGD analysis found that 209 (77%) of the 270 biopsied embryos carried an unbalanced translocation. Embryos carrying unbalanced translocations, which are expected to lead to implantation failure or miscarriage, cleaved less synchronously and were delayed in time of cleavage to the 4-cell stage (t4) and in time of start of blastulation (tSB) compared with balanced embryos (P

Summary Given the association between mutational load and cancer, the observation that genetic aberrations are frequently found in human pluripotent stem cells (hPSCs) is of concern. Prior studies in human induced pluripotent stem cells (hiPSCs) have shown that deletions and regions of loss of heterozygosity (LOH) tend to arise during reprogramming and early culture, whereas duplications more frequently occur during long-term culture. For the corresponding experiments in human embryonic stem cells (hESCs), we studied two sets of hESC lines: one including the corresponding parental DNA and the other generated from single blastomeres from four sibling embryos. Here, we show that genetic aberrations observed in hESCs can originate during preimplantation embryo development and/or early derivation. These early aberrations are mainly deletions and LOH, whereas aberrations arising during long-term culture of hESCs are more frequently duplications. Our results highlight the importance of close monitoring of genomic integrity and the development of improved methods for derivation and culture of hPSCs.

The high number of IVF procedures performed in Israel has had an unforeseen consequence: accumulation of large amounts of surplus frozen embryos. After five years that the frozen embryos are kept for free, patients need to make an embryo disposition decision. One option is donation for research. The donation rate in Israel is very low. Our aim was to understand the attitudes, values and perceptions of female IVF patients that decided to donate their surplus frozen embryos to research. The study setting was a tertiary IVF unit which during the 2000–2009 period treated 241 patients who had their frozen pre-embryos stored for more than five years. The study population consists of the 12 patients (from among the 241) who had decided to donate their excess frozen pre-embryos to research. In-depth interviews were carried out with 8 of those 12 patients. IVF patients who donated their surplus frozen pre-embryos to research viewed the frozen embryo as a valuable resource that does not have human identity yet. The majority expressed a gradualist approach to the human status of the embryo as requiring successful implantation and development in the uterus. All the respondents chose donation to research not because it was their first choice but because they did not want or were unable to use the pre-embryos in the future, in addition to not willing to thaw them. For many of the respondents, donation to research was accompanied by a sense of uncertainty. All would have preferred to donate their pre-embryos to infertile women or couples, an option which is currently prohibited in Israel. The moral reasoning behind decisions that patients make regarding excess pre-embryos is important for health care practitioners to consider when offering decision-making alternatives and counseling. For our respondents, the scarcity of donating excess frozen pre-embryos to research may reflect patients' preference for embryo donation to infertile couples. Recommended ways to increase donation to research may include public education and awareness, as well as targeted communication with IVF patients by multi-professional IVF unit teams comprised of a medical doctor and a professional trained in bioethics.