Age-related fertility decline: is there a role for elective ovarian tissue cryopreservation?

Age-related fertility decline (ARFD) is a prevalent concern amongst western cultures due to the increasing age of first-time motherhood. Elective oocyte and embryo cryopreservation remain the most established methods of fertility preservation, providing women the opportunity of reproductive autonomy to preserve their fertility and extend their childbearing years to prevent involuntary childlessness. Whilst ovarian cortex cryopreservation has been used to preserve reproductive potential in women for medical reasons, such as in pre- or peripubertal girls undergoing gonadotoxic chemotherapy, it has not yet been considered in the context of ARFD. As artificial reproductive technology (ART) and surgical methods of fertility preservation continue to evolve, it is a judicious time to review current evidence and consider alternative options for women wishing to delay their fertility. This article critically appraises elective oocyte cryopreservation as an option for women who use it to mitigate the risk of ARFD and introduces the prospect of elective ovarian cortex cryopreservation as an alternative.

Uterus Transplantation: A 50-Year Journey.

This paper provides an analysis of the last 50 years of uterus transplantation (UTx). Animal research on UTx began in the 1960s, aiming to solve tubal factor infertility. The success of in vitro fertilization shifted the focus onto uterine factor infertility. Early research in small and large animals improved following the advent of immunosuppression and established the uterus' ability to tolerate cold ischemia and to function following vessel reanastamosis. Upon the achievement of the first live birth following UTx in 2014, human research has started to focus on reducing donor morbidity, optimal immunosuppression regimes, and the development of deceased donor UTx programmes.

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.

Evaluation of the Tramline Sign in the Prediction of Placenta Accreta Spectrum and Perioperative Outcomes in Anterior Placenta Previa.

PURPOSE: To evaluate perioperative outcomes and the prognostic role of the tramline sign in a cohort of women with anterior placenta previa. MATERIALS AND METHODS: Retrospective analysis of 3D ultrasound volumes from women with anterior placenta previa who underwent ultrasound examination beyond 32 weeks. 3D and 3D color volumes were obtained from a sagittal section of the uterus bisecting a partially full bladder and processed using Crystal Vue and Crystal Vue Flow rendering to look for the "tramline sign". "Partial obliteration" was defined as a loss of some or part of the uterine-serosal interface and "full obliteration" as when both interfaces were interrupted. Postnatal ascertainment of placenta accreta spectrum (PAS) was confirmed by findings recorded intraoperatively or on a pathology report. RESULTS: 65 cases were included. The tramline sign was "partially" (17) or "fully" (19) obliterated in 36 cases (55.4 %), and present in 29 (44.6 %). Obliteration was associated with earlier gestational age at delivery (35 + 1 (26 + 3-38 + 3) vs. 36 + 4 (25 + 3-38 + 0) weeks, p = 0.005), greater estimated blood loss (800 (400-11 000) vs. 600 (300-2100) mls, p = 0.003), longer operative time (155 (60-240) vs. 54 (25-80) minutes, p < 0.001), higher rate of hysterectomy (97.2 % vs. 0.0 %, p < 0.001), longer postoperative admission (7 (3-19) vs. 3 (1-5) days, p < 0.001) and a 100 % rate of postnatal diagnosis of PAS. The finding of an "obliterated" tramline sign identified all women that required hysterectomy and all cases of PAS. CONCLUSION: A "partially or fully obliterated" tramline sign is strongly associated with indicators of operative complexity, the postnatal confirmation of PAS, and the need for peripartum hysterectomy.

Fertility treatment and cancers-the eternal conundrum: a systematic review and meta-analysis.

STUDY QUESTION: Does fertility treatment (FT) significantly increase the incidence of breast, ovarian, endometrial or cervical cancer? SUMMARY ANSWER: Overall, FT does not significantly increase the incidence of breast, ovarian or endometrial cancer and may even reduce the incidence of cervical cancer. WHAT IS KNOWN ALREADY: Infertility affects more than 14% of couples. Infertility and nulliparity are established risk factors for endometrial, ovarian and breast cancer, yet the association with FT is more contentious. STUDY DESIGN, SIZE, DURATION: A literature search was carried out using Cochrane Library, EMBASE, Medline and Google Scholar up to December 2019. Peer-reviewed studies stating cancer incidence (breast, ovarian, endometrial or cervical) in FT and no-FT groups were identified. Out of 128 studies identified, 29 retrospective studies fulfilled the criteria and were included (n = 21 070 337). PARTICIPANTS/MATERIALS, SETTING, METHODS: In the final meta-analysis, 29 studies were included: breast (n = 19), ovarian (n = 19), endometrial (n = 15) and cervical (n = 13), 17 studies involved multiple cancer types and so were included in each individual cancer meta-analysis. Primary outcome of interest was cancer incidence (breast, ovarian, endometrial and cervical) in FT and no-FT groups. Secondary outcome was cancer incidence according to specific fertility drug exposure. Odds ratio (OR) and random effects model were used to demonstrate treatment effect and calculate pooled treatment effect, respectively. A meta-regression and eight sub-group analyses were performed to assess the impact of the following variables, maternal age, infertility, study size, outliers and specific FT sub-types, on cancer incidence. MAIN RESULTS AND THE ROLE OF CHANCE: Cervical cancer incidence was significantly lower in the FT group compared with the no-FT group: OR 0.68 (95% CI 0.46-0.99). The incidences of breast (OR 0.86; 95% CI 0.73-1.01) and endometrial (OR 1.28; 95% CI 0.92-1.79) cancers were not found to be significantly different between the FT and no-FT groups. Whilst overall ovarian cancer incidence was not significantly different between the FT and no-FT groups (OR 1.19; 95% CI 0.98-1.46), separate analysis of borderline ovarian tumours (BOT) revealed a significant association (OR 1.69; 95% CI 1.27-2.25). In further sub-group analyses, ovarian cancer incidence was shown to be significantly higher in the IVF (OR 1.32; 95% CI 1.03-1.69) and clomiphene citrate (CC) treatment group (OR 1.40; 95% CI 1.10-1.77), respectively when compared with the no-FT group. Conversely, the incidences of breast (OR 0.75; 95% CI 0.61-0.92) and cervical cancer (OR 0.58; 95% CI 0.38-0.89) were significantly lower in the IVF treatment sub-group compared to the no-FT group. LIMITATIONS, REASONS FOR CAUTION: The large, varied dataset spanning a wide study period introduced significant clinical heterogeneity. Thus, results have to be interpreted with an element of caution. Exclusion of non-English citations, unpublished work and abstracts, in order to ensure data accuracy and reliability was maintained, may have introduced a degree of selection bias. WIDER IMPLICATIONS OF THE FINDINGS: The results for breast, ovarian, endometrial and cervical cancer are reassuring, in line with previously published meta-analyses for individual cancers but the association between IVF and CC treatment and an increase in ovarian cancer incidence requires additional work to understand the potential mechanism driving this association. In particular, focusing on (i) discriminating specific treatments effects from an inherent risk of malignancy; (ii) differential risk profiles among specific patient sub-groups (refractory treatment and obesity); and (iii) understanding the impact of FT outcomes on cancer incidence. STUDY FUNDING/COMPETING INTEREST(S): This study did not receive any funding. The authors have no financial, personal, intellectual and professional conflicts of interest to declare. PROSPERO REGISTRATION NUMBER: CRD42019153404.

Anxiety and stress in women with suspected endometrial cancer: Survey and paired observational study.

OBJECTIVE: To determine the anxiety and stress levels of women with suspected endometrial cancer and factors affecting this. METHODS: Prospective survey and paired observational study of consecutive women with suspected endometrial cancer in a rapid access gynaecology clinic. Structured questionnaire including a GAD-7 anxiety test and a modified stress thermometer were used. Patients ranked their perception of a cancer diagnosis on 0-5 Likert scale (0 = confident not cancer and 5 = cancer). Patients requiring an endometrial tissue biopsy were asked to rank their pain on a visual analogue scale (VAS), this was paired with the survey results. RESULTS: 250 patients completed the study and 23 of which underwent an endometrial tissue biopsy. The median age was 50-59 years old and 59% of women spoke English as their first language. 32% of patients had significant levels of anxiety with GAD-7 score ≥10. The median stress score was three out of five on Likert scale. GAD-7 anxiety scores were higher in women who perceived that they received insufficient information prior to clinic (sufficient information 5 vs. insufficient information 9.5, P = 0.00036) or had a disability (disability 9 vs. no disability 5.5, P = 0.00374). The median VAS score from the biopsies was seven out of 10 (range 1-10). Patients with higher anxiety levels (GAD-7 scores) were more likely to believe they had cancer P <0.00001. CONCLUSIONS: These findings confirm high levels of anxiety and stress in women with suspected endometrial cancer. Adequate pre-clinic information is essential, particularly for minority groups.

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.

Intraoperative Ultrasound during Fertility-Sparing Surgery: A Systematic Review and Practical Applications.

Fertility-sparing surgery (FSS) is an established concept within operative gynaecology. Intraoperative ultrasound (IOUS) has the potential of assessing lesion margins, allowing complete resection with minimal damage to the surrounding healthy tissue and could potentially play a major role in FSS for benign or malignant gynaecological pathologies. In this paper, we review the current literature on the use of IOUS in gynaecological FSS. We also propose technical guidance on the IOUS during FSS. The findings of this review demonstrate that IOUS can assist in the safe resection of disease with high rates of completion, low rates of recurrence and without damage to the nearby healthy reproductive organs. Improved training in transvaginal ultrasonography and minimal access surgery are likely to facilitate the application of IOUS in FSS.

Conservative management of uterine adenosarcoma: lessons learned from 20 years of follow-up.

PURPOSE: Uterine adenosarcomas (UAs) account for 5-8% of cases of uterine sarcomas. Treatment includes total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Fertility preservation is an emerging concept in gynaecology oncology and is particularly relevant in UA, where cases are diagnosed as young as 15-year-old. This manuscript demonstrates a case of UA which was treated conservatively, achieved successful livebirths and underwent completion hysterectomy after two decades of follow-up. METHOD: This was a retrospective case note review. RESULTS: An 18-year-old nulliparous woman presented with abnormal vaginal bleeding. Ultrasound identified an endometrial polyp, which was histologically diagnosed as low-grade adenosarcoma. She was advised to undergo TAH and BSO, but instead decided to preserve her fertility and opted for conservative management. She was monitored with pelvic ultrasound, hysteroscopy and endometrial biopsy bi-annually, with annual pelvic magnetic resonance imaging for 10 years which was uneventful. 11 years post-operatively she conceived following in-vitro fertilization (IVF) but suffered a miscarriage at 16 weeks likely due to cervical incompetence. She subsequently conceived with twins. She delivered spontaneously preterm at 28 weeks. Both children are alive and well. After 20 years of follow-up, she underwent a laparoscopic hysterectomy with no evidence of recurrence. She remains disease free. CONCLUSION: Whilst radical completion surgery should be advised in UA, this case, in addition to all published conservatively managed cases of UA, demonstrates that conservative management is possible in appropriately selected women. Intensive monitoring post-operatively is essential owing to the risk of recurrence; however, this may pose deleterious side effects which require consideration.

3D ultrashort echo time MRI of the lung using stack-of-spirals and spherical k-Space coverages: Evaluation in healthy volunteers and parenchymal diseases.

BACKGROUND: Ultrashort echo time (UTE) has been shown to improve lung MRI quality in three dimensions. The evaluation of 3D-UTE stack-of-spirals VIBE (3D-USV) sequence for parenchymal diseases and a comparison of performance with that of a spherical mode of acquisition is needed. PURPOSE: To assess MRI quality using a prototypical 3D-USV sequence and to compare performance with that of a spherical acquisition using Pointwise Encoding Time Reduction with Radial Acquisition (PETRA). STUDY TYPE: Monocenter, prospective. POPULATION: Twelve healthy volunteers and 32 adult patients with either cystic fibrosis (CF; n = 16) or interstitial lung disease (ILD; n = 16). FIELD STRENGTH/SEQUENCE: Both free-breathing 3D-USV and PETRA were completed at 1.5T. ASSESSMENT: In healthy volunteers, visual analysis of imaging quality was scored using a Likert scale. Quantitative evaluation of apparent signal ratio (Sr) and contrast ratio (Cr) was measured. Patients with CF and ILD completed both computed tomography (CT) and MRI. Depiction of structural alterations was assessed using dedicated clinical scores. All evaluations were done in consensus by two readers. STATISTICAL TESTS: Comparison of means was assessed using the Wilcoxon signed rank test. Concordance and agreement between CT and MRI were assessed using the intraclass correlation coefficient (ICC) and kappa test. RESULTS: In controls, 3D-USV yielded lower artifacts owing to better automatic respiratory synchronization than PETRA (P < 0.001). However, Sr and Cr of 3D-USV were found significantly lower by 2.25- and 2.36-fold, respectively (P < 0.001). In patients, 3D-USV and PETRA showed comparable performances to assess airway severity in CF (Bhalla score, ICC = 0.89 and ICC = 0.92, respectively) and presence of structural alterations in ILD such as honeycombing (kappa = 0.68 and kappa = 0.69, respectively). DATA CONCLUSION: 3D-USV enables high-resolution morphological imaging of the lung without need of an external device to compensate respiratory motions. Automation and robustness of the method may facilitate clinical application for both airway and interstitial lung investigations. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;48:1489-1497.

Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multicentre study.

BACKGROUND: Survival benefit from surgical debulking of ovarian cancer (OC) is well established, but some women, despite total macroscopic clearance of disease, still have poor prognosis. We aimed to identify biomarkers to predict benefit from conventional surgery. METHODS: Clinical data from women debulked for high-stage OC were analysed (Hammersmith Hospital, London, UK; 2001-2014). Infinium's HumanMethylation27 array interrogated tumour DNA for differentially methylated CpG sites, correlated to survival, in patients with the least residual disease (RD; Hammersmith Array). Validation was performed using bisulphite pyrosequencing (Charité Hospital, Berlin, Germany cohort) and The Cancer Genome Atlas' (TCGA) methylation data set. Kaplan-Meier curves and Cox models tested survival. RESULTS: Altogether 803 women with serous OC were studied. No RD was associated with significantly improved overall survival (OS; hazard ratio (HR) 1.25, 95% CI 1.06-1.47; P=0.0076) and progression-free survival (PFS; HR 1.23, 95% CI 1.05-1.43; P=0.012; Hammersmith database n=430). Differentially methylated loci within FGF4, FGF21, MYLK2, MYLK3, MYL7, and ITGAE associated with survival. Patients with the least RD had significantly better OS with higher methylation of MYLK3 (Hammersmith (HR 0.51, 95% CI 0.31-0.84; P=0.01), Charité (HR 0.46, 95% CI 0.21-1.01; P=0.05), and TCGA (HR 0.64, 95% CI 0.44-0.93; P=0.02)). CONCLUSIONS: MYLK3 methylation is associated with improved OS in patients with the least RD, which could potentially be used to determine response to surgery.

Ultrasound-Guided Laparoscopic Ovarian Wedge Resection in Recurrent Serous Borderline Ovarian Tumours.

OBJECTIVE: The aim of this study was to demonstrate the use of intraoperative ultrasound-guided ovarian wedge resection in the treatment of recurrent serous borderline ovarian tumors (sBOTs) that are too small to be visualized laparoscopically. METHODS: This was a prospective analysis of all women with recurrent sBOTs that were not visible laparoscopically, who underwent intraoperative ultrasound-guided ovarian wedge resection between January 2015 and December 2016 at the West London Gynaecological Cancer Centre, Imperial College NHS Trust, London, United Kingdom. RESULTS: We evaluated 7 patients, with a median age of 35 years (range, 28-39 years). Six women were nulliparous, whereas 1 woman had a single child. Previous surgical intervention left 5 women with a single ovary, whereas the remaining 2 had previous ovarian-sparing surgery. The median size of recurrence was 18 mm (range, 12-37 mm). All women underwent uncomplicated intraoperative guided ovarian wedge resections. Histological assessment confirmed sBOT in all 7 cases. Six of the women remain disease-free. One woman recurred postoperatively with her third recurrence, who previously had bilateral disease and noninvasive implants with microinvasive disease and micropapillary pattern. No cases progressed to invasive disease. The median follow-up time was 12 months (range, 1-20 months). One pregnancy has been achieved postoperatively but resulted in miscarriage. CONCLUSIONS: Continuous intraoperative ultrasound can be used to facilitate complete tumor excision in recurrent sBOT while minimizing the removal of ovarian tissue in women with recurrent sBOT. It is essential that surgical techniques evolve simultaneously with diagnostic imaging modalities to enable surgeons to treat such pathology.

Surgery for Recurrent Uterine Cancer: Surgical Outcomes and Implications for Survival-A Case Series.

OBJECTIVE: The purpose of this study was to describe the patterns of relapse in uterine cancer (UC) and the role of surgery in the recurrent setting. METHODS: We describe surgical and clinical outcomes of all patients who underwent surgery for recurrent UC in a gynecological oncology tertiary referral center between May 1, 2013, and April 30, 2016. Progression-free survival and overall survival were estimated using Kaplan-Meier methods with the surgery at relapse being the starting point. RESULTS: We evaluated 15 patients with a median age of 66 years. The predominant histology was the endometrioid variant (n = 11; 73.3%). The median interval between the end of previous treatment and relapse surgery was 24 months (range, 8-164). Locoregional pelvic recurrences were the most common type of recurrence (n = 13; 86.7%) with the para-aortic lymph node space being the most commonly affected extrapelvic site (13%). Patients predominantly presented with a multifocal pattern of relapse (n = 10; 66.7%) requiring multivisceral resections such as bowel (n = 7; 46.6%) and/or bladder/ureteric resections (n = 8; 53.3%) to achieve complete tumor clearance. All patients were operated tumor free with a 30-day major morbidity and mortality rate of 6.7% and 0%, respectively. Five patients (33.3%) received postoperative chemotherapy or radiotherapy. Five patients (33.3%) relapsed, and 3 died within a mean follow-up of 12.4 months (95% confidence interval [CI], 6.5-18.2). Two of those patients had a sarcoma.Mean progression-free survival and overall survival for the entire cohort postrelapse surgery was 21.7 months (95%CI, 13.9-29.5) and 26.0 months (95%CI, 18.4-33.7), respectively. Survival was significantly worse in patients with nonendometrioid histology (P < 0.0001). CONCLUSIONS: Surgery for UC relapse seems feasible with acceptable morbidity and high complete resection rates despite the multifocal patterns of relapse in a selected group of patients in a reference center for gynecological cancers. Larger scale studies are warranted to establish the value of surgery at relapse for UC.

Psychological Issues Associated With Absolute Uterine Factor Infertility and Attitudes of Patients Toward Uterine Transplantation.

CONTEXT: Uterine transplantation (UTx). OBJECTIVE: To explore patients' knowledge of and attitudes toward UTx before and after a short educational intervention via a video and question and answer (Q&A) session. DESIGN: Large, in-depth survey investigating patients' motivations, aims, and beliefs on UTx. SETTING: Imperial College London. PARTICIPANTS: Women diagnosed with absolute uterine factor infertility (AUFI) who were seeking information on UTx and had already volunteered to participate in the study. INTERVENTION: A semistructured interview involving a brief baseline questionnaire before a Q&A session and a 20-minute video exploring the main risks and benefits for UTx. MAIN OUTCOME MEASURES: Attitudes of self-referred patients with AUFI toward UTx before and after education focusing on UTx. Rank order of importance of key UTx-related issues. RESULTS: Forty women were interviewed. Following the video presentation and Q&A session, 97.5% (n = 39) would undergo UTx ahead of surrogacy and adoption in full knowledge that the latter 2 options would be ultimately safer for their own well-being and the fact that the graft could fail even prior to conception. All felt that UTx should take place, and 92.5% saw UTx as achievable. CONCLUSION: The study demonstrates a keen interest in UTx, partly because other options seem difficult to access. It is worth noting that people appear to be distancing themselves from the risk. This requires careful assessment in any clinical program. This study is the first to demonstrate a qualitative relationship between patients with AUFI and their curiosity and desire for UTx. It paves the way for forming the introduction into the psychological assessment of a potential patient.

Machine learning and radiomics for segmentation and classification of adnexal masses on ultrasound.

Ultrasound-based models exist to support the classification of adnexal masses but are subjective and rely upon ultrasound expertise. We aimed to develop an end-to-end machine learning (ML) model capable of automating the classification of adnexal masses. In this retrospective study, transvaginal ultrasound scan images with linked diagnoses (ultrasound subjective assessment or histology) were extracted and segmented from Imperial College Healthcare, UK (ICH development dataset; n = 577 masses; 1444 images) and Morgagni-Pierantoni Hospital, Italy (MPH external dataset; n = 184 masses; 476 images). A segmentation and classification model was developed using convolutional neural networks and traditional radiomics features. Dice surface coefficient (DICE) was used to measure segmentation performance and area under the ROC curve (AUC), F1-score and recall for classification performance. The ICH and MPH datasets had a median age of 45 (IQR 35-60) and 48 (IQR 38-57) years old and consisted of 23.1% and 31.5% malignant cases, respectively. The best segmentation model achieved a DICE score of 0.85 ± 0.01, 0.88 ± 0.01 and 0.85 ± 0.01 in the ICH training, ICH validation and MPH test sets. The best classification model achieved a recall of 1.00 and F1-score of 0.88 (AUC:0.93), 0.94 (AUC:0.89) and 0.83 (AUC:0.90) in the ICH training, ICH validation and MPH test sets, respectively. We have developed an end-to-end radiomics-based model capable of adnexal mass segmentation and classification, with a comparable predictive performance (AUC 0.90) to the published performance of expert subjective assessment (gold standard), and current risk models. Further prospective evaluation of the classification performance of this ML model against existing methods is required.

INvestigational Study Into Transplantation of the Uterus (INSITU): a cross-sectional survey among women with uterine factor infertility in the UK assessing background, motivations and suitability.

IMPORTANCE: The study summarises the selection prescreen criteria currently used in the UK for a uterus transplant and highlights the number of women who are suitable to proceed. OBJECTIVES: To assess the demographics, motivations, reasons and suitability among women with absolute uterine factor infertility (AUFI) to undergo uterine transplantation (UTx). DESIGN: A cross-sectional survey. SETTING: An electronic questionnaire was sent via email to women with AUFI who had previously been referred to the UTx research team or approached the Womb Transplant UK Charity. The questions assessed suitability to undergo UTx based on demographic information, perceptions to adoption and surrogacy and reasons why UTx was preferable. Responses were assessed against the study selection criteria. PARTICIPANTS: Women with AUFI. RESULTS: 210 women completed the questionnaire. The most common aetiology of AUFI in our cohort was Mayer-Rokitansky-Küster-Hauser (68%; n=143) whereas 29% (n=62) had previously undergone hysterectomy. 63% (n=132) of the cohort had previously considered adoption, 5% (n=11) had attempted it and 2 (1%) had successfully adopted. The most common reason cited to undergo UTx over adoption was to experience gestation (n=63; 53%), while 37% (n=44) wanted a biologically related child. 76% (n=160) of participants had previously considered surrogacy, 22 (10%) had attempted it and 2 (1%) had successfully become mothers using a surrogate. The most common reason to undergo UTx over surrogacy was to experience gestation (n=77; 54%). 15% (n=21) were concerned about the legal implications, 14% (n=20) identified the financial cost as a barrier and 8% (n=12) could not consider it due to religious reasons. On adhering to the selection criteria, 65 (31%) women were suitable to proceed with the trial. CONCLUSION: The study demonstrates that implementing commonly used selection criteria for a UTx led to an attrition rate of more than two-thirds of women who requested to initially undergo the process. As more studies present outcomes following UTx, critical assessment of the selection criteria currently used is warranted to ensure potential recipients are not being unnecessarily excluded. TRIAL REGISTRATION NUMBER: NCT02388802.

Study protocol for a randomised controlled trial on the use of intraoperative ultrasound-guided laparoscopic ovarian cystectomy (UGLOC) as a method of fertility preservation in the management of benign ovarian cysts.

INTRODUCTION: The lifetime risk of women undergoing surgery for the presence of benign ovarian pathology in the UK is 5%-10%. Despite minimally invasive surgical techniques, evidence suggests a number of healthy ovarian follicles and tissues are resected intraoperatively, resulting in subsequent decline of ovarian reserve. As such, there is an increasing demand for the implementation of fertility preservation surgery (FPS). This study will evaluate the effect on ovarian reserve following two different surgical interventions for the management of benign ovarian cysts. METHODS AND ANALYSIS: We will conduct a two-armed randomised controlled trial comparing laparoscopic ovarian cystectomy, considered gold standard treatment as per the Royal College of Obstetricians and Gynaecologists (RCOG) Green Top guidelines for the management of benign ovarian cysts, with ultrasound-guided laparoscopic ovarian cystectomy (UGLOC), a novel method of FPS. The study commencement date was October 2021, with a completion date aimed for October 2024. The primary outcome will be the difference in anti-Müllerian hormone (AMH) (pmol/L) and antral follicle count (AFC) measured 3 and 6 months postoperatively from the preoperative baseline. Secondary outcomes include assessment of various surgical and histopathological findings, including duration of hospital stay (days), duration of surgery (minutes), presence of intraoperative cyst rupture (yes/no), presence of ovarian tissue within the resected specimen (yes/no) and the grade of follicles excised within the specimen (grade 0-4). We aim to randomise 94 patients over 3 years to achieve power of 80% at an alpha level of 0.05. ETHICS AND DISSEMINATION: Findings will be published in peer-reviewed journals and presented at national and international conferences and scientific meetings. The Chelsea NHS Research and Ethics Committee have awarded ethical approval of the study (21/LO/036). TRIAL REGISTRATION NUMBER: NCT05032846.

Fertility Sparing Surgery and Borderline Ovarian Tumours.

To determine the oncological outcomes following fertility-sparing surgery (FSS) for the management of Borderline Ovarian Tumours (BOTs). A retrospective analysis of participants diagnosed with BOTs between January 2004 and December 2020 at the West London Gynaecological Oncology Centre was conducted. A total of 172 women were diagnosed; 52.3% (90/172) underwent FSS and 47.7% (82/172) non-FSS. The overall recurrence rate of disease was 16.9% (29/172), of which 79.3% (23/29) presented as the recurrence of serous or sero-mucinous BOTs and 20.7% (6/29) as low-grade serous carcinoma (LGSC). In the FSS group, the recurrence rate of BOTs was 25.6% (23/90) presenting a median 44.0 (interquartile range (IQR) 41.5) months, of which there were no episodes of recurrence presenting as LGSC reported. In the non-FSS group, all recurrences of disease presented as LGSC, with a rate of 7.7% (6/78), following a median of 47.5 months (IQR 47.8). A significant difference between the type of surgery performed (FSS v Non-FSS) and the association with recurrence of BOT was observed (Pearson Chi-Square: p = 0.000; x = 20.613). Twelve women underwent ultrasound-guided ovarian wedge resection (UGOWR) as a novel method of FSS. Recurrence of BOT was not significantly associated with the type of FSS performed (Pearson Chi- Square: x = 3.166, p = 0.379). Non-FSS is associated with negative oncological outcomes compared to FSS, as evidenced by the higher rate of recurrence of LGSC. This may be attributed to the indefinite long-term follow up with ultrasound surveillance all FSS women undergo, enabling earlier detection and treatment of recurrences.