Uterine Transplantation in 2021: Recent Developments and the Future.

Uterine transplantation has evolved rapidly over the last decade. As the number of cases performed increases exponentially worldwide, emerging evidence continues to improve collective knowledge and understanding of the procedure, with the aim of improving both surgical and reproductive outcomes. Although currently restricted to women with absolute uterine factor infertility, increasing awareness as a method of fertility restoration has resulted in a demand for the procedure to be undertaken in transgender women. This manuscript summarizes the recent advances in uterine transplantation, and elaborates further upon the key novel avenues research within the field will focus on over the coming years.

The application of metabolomics in ovarian cancer management: a systematic review.

Metabolomics, the global analysis of metabolites in a biological specimen, could potentially provide a fast method of biomarker identification for ovarian cancer. This systematic review aims to examine findings from studies that apply metabolomics to the diagnosis, prognosis, treatment, and recurrence of ovarian cancer. A systematic search of English language publications was conducted on PubMed, Science Direct, and SciFinder. It was augmented by a snowball strategy, whereby further relevant studies are identified from reference lists of included studies. Studies in humans with ovarian cancer which focus on metabolomics of biofluids and tumor tissue were included. No restriction was placed on the time of publication. A separate review of targeted metabolomic studies was conducted for completion. Qualitative data were summarized in a comprehensive table. The studies were assessed for quality and risk of bias using the ROBINS-I tool. 32 global studies were included in the main systematic review. Most studies applied metabolomics to diagnosing ovarian cancer, within which the most frequently reported metabolite changes were a down-regulation of phospholipids and amino acids: histidine, citrulline, alanine, and methionine. Dysregulated phospholipid metabolism was also reported in the separately reviewed 18 targeted studies. Generally, combinations of more than one significant metabolite as a panel, in different studies, achieved a higher sensitivity and specificity for diagnosis than a single metabolite; for example, combinations of different phospholipids. Widespread metabolite differences were observed in studies examining prognosis, treatment, and recurrence, and limited conclusions could be drawn. Cellular processes of proliferation and invasion may be reflected in metabolic changes present in poor prognosis and recurrence. For example, lower levels of lysine, with increased cell invasion as an underlying mechanism, or glutamine dependency of rapidly proliferating cancer cells. In conclusion, this review highlights potential metabolites and biochemical pathways which may aid the clinical care of ovarian cancer if further validated.

Lamin A/C deficiency reduces circulating tumor cell resistance to fluid shear stress.

Metastasis contributes to over 90% of cancer-related deaths and is initiated when cancer cells detach from the primary tumor, invade the basement membrane, and enter the circulation as circulating tumor cells (CTCs). While metastasis is viewed as an inefficient process with most CTCs dying within the bloodstream, it is evident that some CTCs are capable of resisting hemodynamic shear forces to form secondary tumors in distant tissues. We hypothesized that nuclear lamins A and C (A/C) act as key structural components within CTCs necessary to resist destruction from elevated shear forces of the bloodstream. Herein, we show that, compared with nonmalignant epithelial cells, tumor cells are resistant to elevated fluid shear forces in vitro that mimic those within the bloodstream, as evidenced by significant decreases in cellular apoptosis and necrosis. Knockdown of lamin A/C significantly reduced tumor cell resistance to fluid shear stress, with significantly increased cell death compared with parental tumor cell and nontargeting controls. Interestingly, lamin A/C knockdown increased shear stress-induced tumor cell apoptosis, but did not significantly affect cellular necrosis. These data demonstrate that lamin A/C is an important structural component that enables tumor cell resistance to fluid shear stress-mediated death in the bloodstream, and may thus facilitate survival and hematogenous metastasis of CTCs.

Sports Obstetrics: Implications of Pregnancy in Elite Sportswomen, a Narrative Review.

Increasing numbers of females are participating in elite sports, with a record number having competed at the Tokyo Olympic Games. Importantly, the ages of peak performance and fertility are very likely to coincide; as such, it is inevitable that pregnancy will occur during training and competition. Whilst there is considerable evidence to promote regular exercise in pregnancy, with benefits including a reduction in hypertensive disorders, gestational diabetes, and reduced rates of post-natal depression, few studies have been conducted which include elite athletes. Indeed, there are concerns that high-intensity exercise may lead to increased rates of miscarriage and preterm labour, amongst other pregnancy-related complications. There is minimal guidance on the obstetric management of athletes, and consequently, healthcare professionals frequently adopt a very conservative approach to managing such people. This narrative review summarises the evidence on the antenatal, intrapartum, and postpartum outcomes in elite athletes and provides recommendations for healthcare providers, demonstrating that generally, pregnant athletes can continue their training, with a few notable exceptions. It also summarises the physiological changes that occur in pregnancy and reviews the literature base regarding how these changes may impact performance, with benefits arising from pregnancy-associated cardiovascular adaptations at earlier gestations but later changes causing an increased risk of injury and fatigue.

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.

Endometrial autotransplantation in rabbits: Potential for fertility restoration in severe Asherman's syndrome.

OBJECTIVE: Uterine transplantation is now considered a feasible treatment for women with absolute uterine factor infertility and has been successfully performed for a woman with Asherman's syndrome (AS). The endometrium is a clinically and histologically distinct entity from the surrounding myometrium. Endometrial transplantation (ETx) may offer a less invasive option, with less immunogenic impact, to restore fertility in women with severe AS. The objective of this study was to assess the feasibility of ETx by evaluating surgical and reproductive outcomes following endometrial autotransplantation in a rabbit model. STUDY DESIGN: A longitudinal study assessing surgical, biochemical, radiological, reproductive and histological outcomes following endometrial autotransplantation in ten New Zealand white rabbits. RESULTS: Ten procedures were performed, including 8 endometrial auto-transplants (ETx) and 2 endometrial resections (ER), to control against endometrial regeneration. Eight procedures were successful, whereas two rabbits from the ETx group died intra-operatively. Three rabbits were euthanised at 48, 72 and 96 h post-operatively to assess gross and histological appearances. Two rabbits, one from the ETx group and one from the ER group, died four weeks and eight weeks post-operatively. Three rabbits subsequently underwent two cycles of in-vitro fertilization. The first cycle resulted in an implantation rate of 57% in the un-operated uteri. In two rabbits who underwent ETx, an implantation rate of 28.6% was seen. In the second cycle, an implantation rate of 61.9 % (13 implantations) was observed in the control uteri. In the two ETx females, an implantation rate of 14.3 % was seen. No pregnancies were seen in either cycle in the animals who underwent ER. Despite successful implantations in both cycles in the ETx rabbits, no livebirths were achieved. Following death or euthanasia there was gross and microscopic evidence of viable endometrium following ETx, but not following ER. CONCLUSION: This study has revealed, for the first time, the feasibility of ETx with gross and microscopic evidence of viable endometrium, and the demonstration of clinical pregnancies. Whilst further studies are essential, and the achievement of successful livebirths fundamental, ETx may offer a potential fertility restoring opportunity for women with severe, treatment refractory cases of AS.

Super natural killer cells that target metastases in the tumor draining lymph nodes.

Tumor draining lymph nodes are the first site of metastasis in most types of cancer. The extent of metastasis in the lymph nodes is often used in staging cancer progression. We previously showed that nanoscale TRAIL liposomes conjugated to human natural killer cells enhance their endogenous therapeutic potential in killing cancer cells cultured in engineered lymph node microenvironments. In this work, it is shown that liposomes decorated with apoptosis-inducing ligand TRAIL and an antibody against a mouse natural killer cell marker are carried to the tumor draining inguinal lymph nodes and prevent the lymphatic spread of a subcutaneous tumor in mice. It is shown that targeting natural killer cells with TRAIL liposomes enhances their retention time within the tumor draining lymph nodes to induce apoptosis in cancer cells. It is concluded that this approach can be used to kill cancer cells within the tumor draining lymph nodes to prevent the lymphatic spread of cancer.

TRAIL-coated leukocytes that prevent the bloodborne metastasis of prostate cancer.

Prostate cancer, once it has progressed from its local to metastatic form, is a disease with poor prognosis and limited treatment options. Here we demonstrate an approach using nanoscale liposomes conjugated with E-selectin adhesion protein and Apo2L/TRAIL (TNF-related apoptosis-inducing ligand) apoptosis ligand that attach to the surface of leukocytes and rapidly clear viable cancer cells from circulating blood in the living mouse. For the first time, it is shown that such an approach can be used to prevent the spontaneous formation and growth of metastatic tumors in an orthotopic xenograft model of prostate cancer, by greatly reducing the number of circulating tumor cells. We conclude that the use of circulating leukocytes as a carrier for the anti-cancer protein TRAIL could be an effective tool to directly target circulating tumor cells for the prevention of prostate cancer metastasis, and potentially other cancers that spread through the bloodstream.