Successful preimplantation genetic testing for fibrodysplasia ossificans progressiva: a case report.

PURPOSE OF THE STUDY: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant condition that leads to significant disability and morbidity, characterised by the formation of heterotopic hard tissues within connective tissues. The condition has an incidence of approximately one per two million people worldwide. There is no known single effective treatment available for FOP. We report the world's first case of a healthy infant born following in vitro fertilisation (IVF) and preimplantation genetic testing for monogenic disorder (PGT-M) using Karyomapping for FOP. CASE PRESENTATION: A 30-year-old Caucasian female with FOP presented with her partner seeking IVF with PGT-M to achieve a healthy pregnancy with an embryo unaffected by FOP. METHODS: The couple underwent IVF and PGT-M using Karyomapping as the testing method. A multi-disciplinary team approach was utilised in planning this case, considering the additional risks of oocyte retrieval, pregnancy and childbirth in women with FOP. MAIN FINDINGS: The oocyte retrieval was covered with a 5-day course of prednisolone to reduce the risk of a localised inflammatory reaction, which could result in subsequent heterotopic ossification. This was subsequently weaned down with reducing doses every two days. The patient underwent uncomplicated oocyte retrieval, yielding 12 mature oocytes. Following intracytoplasmic sperm injection (ICSI), ten zygotes having two pro-nuclei were cultured, and six underwent trophoectoderm biopsy and vitrification 5-6 days after retrieval. PGT-M via Karyomapping revealed four out of six (66.7%) of blastocysts were not carriers of the maternal high-risk FOP allele. In total, the patient had three separate embryo transfers. Pregnancy was achieved following the third frozen embryo transfer, which went to 37 weeks' gestation, and delivered by Caesarean section. The baby was born in excellent condition and is unaffected by FOP. CONCLUSION: IVF/ICSI and PGT-M using Karyomapping was successfully implemented to identify embryos carrying the high-risk FOP allele resulting in a healthy livebirth.

Intrauterine instillation of human chorionic gonadotropin at the time of blastocyst transfer: Systematic review and meta-analysis.

Intrauterine instillation (IU) of Human Chorionic Gonadotropin (hCG) before embryo transfer (ET) has been proposed to enhance implantation success rates. This is the first meta-analysis to evaluate the effect at the blastocyst-stage. A systematic literature search was performed using Medline, Embase, Cochrane Library and Google. Randomized clinical trials (RCTs) were included. The primary outcome combined live birth rate (LBR) and ongoing pregnancy rate (OPR). The secondary outcomes were clinical pregnancy rate (CPR), implantation rate (IR) and miscarriage rate (MR). 93 citations were identified, of which there were seven eligible RCTs. 2499 participants were included in the meta-analysis; 1331 were assigned to an experimental group and 1168 were assigned to the control group. The overall effect of IU hCG instillation on LBR and OPR was not significant: risk ratio (RR) 1.00 (95% CI, 0.90-1.12). Analysis of secondary outcomes found the effect of IU hCG instillation was not significant. Analysis of the data suggests that the studies conducted have too much heterogeneity to identify whether a specific cohort may have a significant benefit. The findings of this meta-analysis demonstrate that there is insufficient evidence at present to support the use of IU hCG instillation prior to blastocyst-stage ET.

Social egg freezing: Motivations, treatment experiences and the impact of Covid-19 - a single-center experience.

INTRODUCTION: This study aims to assess the motivations and treatment experiences of women undergoing social egg freezing and to understand the impact of the Covid-19 pandemic. MATERIAL AND METHODS: Between January 2011 to December 2021, 191 social egg freezing patients were recruited from the Lister Fertility Clinic, London UK. Participants completed a validated questionnaire investigating patients' perspectives of social egg freezing. A response rate of 46.6% was achieved. RESULTS: In all, 93.9% of women expressed concern regarding age-related fertility decline which influenced their decision to undergo social egg freezing. The majority (89.5%) of women were not in a relationship at the time of social egg freezing and considered this a motivating factor. Also, 39.0% of participants had side effects related to treatment which affected work and social life. Participants were significantly more likely to experience side effects if they underwent multiple egg freezing cycles (χ2 , p < 0.01) or if they cryopreserved oocytes during the COVID-19 pandemic (χ2 , p < 0.05). Of the women, 64.0% wished to have cryopreserved oocytes at a younger age, a view significantly more likely if older than 37 years at first social egg freezing cycle (χ2 , p < 0.001). Also, 82.3% of women reported their decision to undergo social egg freezing was not delayed due to concerns regarding COVID-19 exposure during treatment; 44.1% considered the pandemic made them more willing to undergo social egg freezing. CONCLUSIONS: Most participants did not regret their decision to undergo social egg freezing but the majority wished they had cryopreserved oocytes at a younger age. This highlights the importance of early education to optimize outcomes and patient choice. The egg freezing process can be stressful, women may have concerns around social egg freezing and unprecedented situations such as the COVID-19 pandemic may alter treatment experience.

Fertility preservation and realignment in transgender women.

Medical care for transgender people is multi-faceted and attention to individual reproductive aspirations and planning are an essential, yet often overlooked aspect of care. Given the impact of hormonal therapy and other gender affirmation procedures on reproductive function, extensive counselling and consideration of fertility preservation is recommended prior to their commencement. This review article explores the reproductive aspirations of transgender women and considers the current disparity between stated desires regarding utilisation of fertility preservation services. Current fertility preservation options and prospective treatments currently showing promise in the research arena are explored.

Does advanced paternal age affect outcomes following assisted reproductive technology? A systematic review and meta-analysis.

Infertility affects more than 14% of couples, 30% being caused by male factor infertility. This meta-analysis includes 28 studies, selected according to PRISMA guidelines. Data were extracted from these studies to collate cycles separating paternal age at 30, 35, 40, 45 and 50 years (±1 year). Primary outcomes of interest were clinical pregnancy, live birth and miscarriage rates. Secondary outcomes were the number of fertilized eggs, cleavage-stage embryos and blastocysts, and embryo quality per cycle. Fixed-effects and random-effects models giving pooled odds ratios (OR) were used to assess the effect of paternal age. This meta-analysis included a total 32,484 cycles from 16 autologous oocyte studies and 12 donor oocyte studies. In autologous cycles, a statistically significant effect of paternal age <40 years was noted in clinical pregnancy (OR 1.65, 95% confidence interval [CI] 1.27-2.15), live birth (OR 2.10, 95% CI 1.25-3.51) and miscarriage (OR 0.74, 95% CI 0.57-0.94) rates. Paternal age <50 years significantly reduced miscarriage rate (OR 0.68, 95% CI 0.54-0.86), and increased blastocyst rate (OR 1.61, 95% CI 1.08-2.38) and number of cleavage-stage embryos (OR 1.67, 95% CI 1.02-2.75) in donor oocyte cycles, where maternal age is controlled. This is an important public and societal health message highlighting the need to also consider paternal age alongside maternal age when planning a family.

Evaluating the use of telemedicine in gynaecological practice: a systematic review.

OBJECTIVES: The aim of this systematic review is to examine the use of telemedicine in the delivery and teaching of gynaecological clinical practice. To our knowledge, no other systematic review has assessed this broad topic. DESIGN: Systematic review of all studies investigating the use of telemedicine in the provision of gynaecological care and education. The search for eligible studies followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and focused on three online databases: PubMed, Science Direct and SciFinder. ELIGIBILITY CRITERIA: Only studies within gynaecology were considered for this review. Studies covering only obstetrics and with minimal information on gynaecology, or clinical medicine in general were excluded. All English language, peer-reviewed human studies were included. Relevant studies published up to the date of final submission of this review were considered with no restrictions to the publication year. DATA EXTRACTIONS AND SYNTHESIS: Data extracted included author details, year of publication and country of the study, study aim, sample size, methodology, sample characteristics, outcome measures and a summary of findings. Data extraction and qualitative assessment were performed by the first author and crossed checked by the second author. Quality assessment for each study was assessed using the Newcastle-Ottawa scale. RESULTS: A literature search carried out in August 2020 yielded 313 records published between 1992 and 2018. Following a rigorous selection process, only 39 studies were included for this review published between 2000 and 2018. Of these, 19 assessed gynaecological clinical practice, eight assessed gynaecological education, one both, and 11 investigated the feasibility of telemedicine within gynaecological practice. 19 studies were classified as good, 12 fair and eight poor using the Newcastle-Ottawa scale. Telecolposcopy and abortion care were two areas where telemedicine was found to be effective in potentially speeding up diagnosis as well as providing patients with a wide range of management options. Studies focusing on education demonstrated that telementoring could improve teaching in a range of scenarios such as live surgery and international teleconferencing. CONCLUSIONS: The results of this review are promising and demonstrate that telemedicine has a role to play in improving clinical effectiveness and education within gynaecology. Its applications have been shown to be safe and effective in providing remote care and training. In the future, randomised controlled studies involving larger numbers of patients and operators with measurable outcomes are required in order to be able to draw reliable conclusions.

The Impact of Focality and Centricity on Vulvar Intraepithelial Neoplasia on Disease Progression in HIV+ Patients: A 10-Year Retrospective Study.

BACKGROUND: The impact of lesion focality and centricity in relation to patient outcome and disease recurrence of vulvar intraepithelial neoplasia (VIN) is an understudied area of research, especially in immunocompromised women. The prevalence and incidence of VIN have increased steadily since the 1980s because of the co-existence of human papillomavirus (HPV) and human immunodeficiency virus (HIV). In this study, we retrospectively examined the records of VIN patients to determine the effect of lesion focality and centricity with respect to the interval to disease recurrence. MATERIALS AND METHODS: All women diagnosed with VIN and managed between January 2002 and December 2011 were included (n = 90) and followed up until December 2017. Symptoms at the time of presentation, including HIV positivity (n = 75), were collated, including the influences of multifocality and multicentricity on time to disease recurrence. RESULTS: Multicentricity caused a more rapid recurrence of disease than unicentricity (p = 0.006), whereas multifocality increased the risk of recurrence more than unifocality (p < 0.0001). Viral load in the HIV+ patients was not associated with time to disease recurrence, but the reduced number of CD4+ lymphocytes present in HIV+ patients was. Treatment modalities had no effect on disease recurrence. CONCLUSION: Both focality and centricity have effects on interval to recurrence and final patient outcome, with multifocal disease having a poorer prognosis. Centricity and focality should be recorded at the time of diagnosis and act as a warning for disease recurrence. HIV+ VIN patients with multifocal disease and/or known immunosuppression (low CD4+ lymphocyte counts) should be regarded as "high-risk" patients and treated accordingly.

Does the use of calcium ionophore during artificial oocyte activation demonstrate an effect on pregnancy rate? A meta-analysis.

OBJECTIVE: To study the effect, if any, of calcium ionophore as a method of artificial oocyte activation (AOA) on pregnancy outcomes and fertilization rates. DESIGN: Meta-analysis of randomized controlled trials, prospective observational and retrospective trials, case reports, and a case-control trial. SETTING: University-affiliated teaching hospital. PATIENT(S): Infertile couples undergoing fertilization treatment. INTERVENTION(S): Use of calcium ionophore during AOA. MAIN OUTCOME MEASURE(S): Odds ratio (OR) as the summary statistic for binary variables was used. Both a fixed and random effects model were applied. Subgroup analysis using quantitative methodology (risk of bias, metaregression) and graphical comparison (funnel plot) assessed statistical heterogeneity. RESULT(S): Fourteen studies were selected. AOA with calcium ionophore increased the overall clinical pregnancy rate (per ET; OR = 3.48; 95% confidence interval [CI], 1.65-7.37) and the live birth rate (OR = 3.33; 95% CI, 1.50-7.39). This effect of adding calcium ionophore was further demonstrated with fertilization, cleavage, blastocyst, and implantation rates. Subgroup analysis further supported our findings (studies where n > 10 in both arms; random and fixed effects models). A metaregression (beta = -.145) found that as the quality of the study increases, the effect of calcium ionophore is significantly more pronounced with regards to overall pregnancy rate. CONCLUSION(S): AOA with calcium ionophore treatment after intracytoplasmic sperm injection (ICSI) results in a statistically significant improvement in fertilization, cleavage, blastulation, and implantation rates, as well as overall pregnancy and live-birth rates. The conclusion of this systematic review, demonstrating a strong effect of calcium ionophore use, is reassuring and promising, particularly for couples for whom ICSI alone yields poor fertilization rates.

Leadership and management in the undergraduate medical curriculum: a qualitative study of students' attitudes and opinions at one UK medical school.

OBJECTIVE: To explore undergraduate medical students' attitudes towards and opinions about leadership and management education. DESIGN: Between 2009 and 2012 we conducted a qualitative study comprising five focus group discussions, each devoted to one of the five domains in the Medical Leadership Competency Framework, (Personal Qualities, Working with Others, Managing Services, Improving Services and Setting Direction). Each discussion examined what should be learnt, when should learning occur, what methods should be used, how should learning be assessed, what are the barriers to such education. PARTICIPANTS: 28 students from all three clinical years (4-6) of whom 10 were women. RESULTS: 2 inter-related themes emerged: understanding the broad perspective of patients and other stakeholders involved in healthcare provision and the need to make leadership and management education relevant in the clinical context. Topics suggested by students included structure of the National Health Service (NHS), team working skills, decision-making and negotiating skills. Patient safety was seen as particularly important. Students preferred experiential learning, with placements seen as providing teaching opportunities. Structured observation, reflection, critical appraisal and analysis of mistakes at all levels were mentioned as existing opportunities for integrating leadership and management education. Students' views about assessment and timing of such education were mixed. Student feedback figured prominently as a method of delivery and a means of assessment, while attitudes of medical professionals, students and of society in general were seen as barriers. CONCLUSIONS: Medical students may be more open to leadership and management education than thought hitherto. These findings offer insights into how students view possible developments in leadership and management education and stress the importance of developing broad perspectives and clinical relevance in this context.

Cytoskeletal dynamics and supracellular organisation of cell shape fluctuations during dorsal closure.

Fluctuations in the shape of amnioserosa (AS) cells during Drosophila dorsal closure (DC) provide an ideal system with which to understand contractile epithelia, both in terms of the cellular mechanisms and how tissue behaviour emerges from the activity of individual cells. Using quantitative image analysis we show that apical shape fluctuations are driven by the medial cytoskeleton, with periodic foci of contractile myosin and actin travelling across cell apices. Shape changes were mostly anisotropic and neighbouring cells were often, but transiently, organised into strings with parallel deformations. During the early stages of DC, shape fluctuations with long cycle lengths produced no net tissue contraction. Cycle lengths shortened with the onset of net tissue contraction, followed by a damping of fluctuation amplitude. Eventually, fluctuations became undetectable as AS cells contracted rapidly. These transitions were accompanied by an increase in apical myosin, both at cell-cell junctions and medially, the latter ultimately forming a coherent, but still dynamic, sheet across cells. Mutants with increased myosin activity or actin polymerisation exhibited precocious cell contraction through changes in the subcellular localisation of myosin. thick veins mutant embryos, which exhibited defects in the actin cable at the leading edge, showed similar timings of fluctuation damping to the wild type, suggesting that damping is an autonomous property of the AS. Our results suggest that cell shape fluctuations are a property of cells with low and increasing levels of apical myosin, and that medial and junctional myosin populations combine to contract AS cell apices and drive DC.