A Cross-Sectional Survey of Healthcare Professionals' Knowledge, Attitude and Current Behaviours towards Female Fertility Preservation Services within the UK.

(1) Background: This study aims to establish the knowledge, attitudes and current behaviours towards female fertility preservation (FP) services amongst healthcare professionals (HCPs) in the UK. (2) Methods: An online survey was advertised publicly on the social media platform Instagram between 25 February 2021 and 11 March 2021. (3) Results: In total, 415 participants fulfilled the inclusion criteria and completed the survey. The majority of HCPs discussed FP techniques either never 39.5% (n = 164), once a year 20.7% (n = 86) or once a month 17.8% (n = 74). The majority rated their knowledge of each type of FP method as 'very poor' or 'poor' and strongly disagreed 14.2% (n = 59) or disagreed 42.2% (n = 175) with the statement they 'felt confident to counsel a patient on FP'. The majority either agreed 37.8% (n = 157) or strongly agreed 22.2% (n = 92) that it was their responsibility to discuss FP and 38.1% (n = 158) agreed or strongly agreed 19.5% (n = 81) they considered the desire for future fertility when planning treatment. The majority 87.2% (n = 362) had not experienced formal training on FP. (4) Conclusions: Discrepancies in knowledge remain regarding techniques of FP, referral pathways, awareness of facilities offering services and existing educational resources. Many HCPs recognise the importance of FP and their responsibility to initiate discussions. The knowledge that FP may not delay the treatment of cancer has also improved; however, training in FP is scarce.

Predictors of successful expectant and medical management of miscarriage: A systematic review.

INTRODUCTION: 15.3% of pregnancies result in miscarriage, management options include expectant, medical, or surgical. However, each patient has a range of variables, which makes navigating the available literature challenging when supporting individual patient decision-making. This systematic review aims to investigate whether there are any specific predictors for miscarriage management outcome. MATERIAL AND METHODS: The following databases were searched, from the start of each database up to April 2023: PubMed, Medline, and Google Scholar. Inclusion criteria were studies interrogating defined predictors for expectant or medical management of miscarriage success. Exclusion criteria were poor quality, review articles, trial protocols, and congress abstracts. Data collection was carried as per PRISMA guidelines. Quality assessment for each study was assessed using the QUIPS proforma. RESULTS: Relevant predictors include demographics, ultrasound features, presenting symptoms, and biochemical markers. Across the 24 studies there is heterogeneity in miscarriage definition, predictors reported, and management outcomes used. Associations with certain variables and miscarriage management outcomes are described. Ten studies assessed the impact of miscarriage type on expectant and/or medical management. The majority found that a diagnosis of incomplete miscarriage had a higher success rate following expectant or medical management compared to missed miscarriage or anembryonic pregnancy. CONCLUSIONS: We conclude that there is evidence supporting the possibility to offer personalized miscarriage management advice with case specific predictors. Further larger studies with consistent definitions of predictors, management, and outcomes are needed in order to better support women through the decision-making of miscarriage management.

Using online search activity for earlier detection of gynaecological malignancy.

BACKGROUND: Ovarian cancer is the most lethal and endometrial cancer the most common gynaecological cancer in the UK, yet neither have a screening program in place to facilitate early disease detection. The aim is to evaluate whether online search data can be used to differentiate between individuals with malignant and benign gynaecological diagnoses. METHODS: This is a prospective cohort study evaluating online search data in symptomatic individuals (Google user) referred from primary care (GP) with a suspected cancer to a London Hospital (UK) between December 2020 and June 2022. Informed written consent was obtained and online search data was extracted via Google takeout and anonymised. A health filter was applied to extract health-related terms for 24 months prior to GP referral. A predictive model (outcome: malignancy) was developed using (1) search queries (terms model) and (2) categorised search queries (categories model). Area under the ROC curve (AUC) was used to evaluate model performance. 844 women were approached, 652 were eligible to participate and 392 were recruited. Of those recruited, 108 did not complete enrollment, 12 withdrew and 37 were excluded as they did not track Google searches or had an empty search history, leaving a cohort of 235. RESULTS: The cohort had a median age of 53 years old (range 20-81) and a malignancy rate of 26.0%. There was a difference in online search data between those with a benign and malignant diagnosis, noted as early as 360 days in advance of GP referral, when search queries were used directly, but only 60 days in advance, when queries were divided into health categories. A model using online search data from patients (n = 153) who performed health-related search and corrected for sample size, achieved its highest sample-corrected AUC of 0.82, 60 days prior to GP referral. CONCLUSIONS: Online search data appears to be different between individuals with malignant and benign gynaecological conditions, with a signal observed in advance of GP referral date. Online search data needs to be evaluated in a larger dataset to determine its value as an early disease detection tool and whether its use leads to improved clinical outcomes.

Menstrual cycles and the impact upon performance in elite British track and field athletes: a longitudinal study.

Objective: To assess the prevalence of menstrual disorders and the perceived effect of menstrual cycles upon performance in elite athletes. Methodology: A longitudinal survey in the form of a questionnaire was sent to female track and field athletes at British Athletics every 6 months, over a five-year period between 1st October 2014 and 1st October 2019 in the United Kingdom (UK). Results: 128 athletes completed an average of 4.2 ± 2.9 questionnaires across the study period. The mean age of menarche was 14.2 ± 1.4 years, 13.4 ± 1.3 years and 12.8 ± 1.4 years in endurance, power, and thrower athletes respectively (p < 0.05). Two-thirds (66%; n = 82) reported consistently regular cycles, 30% (n = 37) irregular at some point during the period of observation and 4% (n = 5) were amenorrhoeic. 87 athletes (68%) reported dysmenorrhoea and 40 (31%) menorrhagia. More than three quarters (76.8%; n = 96) described their cycle negatively affected performance. Amongst those who reported when the negative impact occurred (n = 91), 40% (n = 36) reported this in the late luteal phase and 35% (n = 32) during the early follicular phase. 79% (n = 100) of athletes reported at least one cyclical symptom, of which bloating, lower back and pelvic pain were most frequently experienced. Conclusion: This data highlights the complex interrelationship between women's health and elite athletic performance. Athletes perceive a negative impact from their menstrual cycles upon performance with a desire to manage these more effectively, particularly during competition. Female reproductive health expertise in the multi-disciplinary management of elite athletes is required.

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.

Using simple clinical and ultrasound variables to develop a model to predict first trimester pregnancy viability.

INTRODUCTION: Early prediction of pregnancies destined to miscarry will allow couples to prepare for this common but often unexpected eventuality, and clinicians to allocate finite resources. We aimed to develop a prediction model combining clinical, demographic, and sonographic data as a clinical tool to aid counselling about first trimester pregnancy outcome. MATERIAL AND METHODS: This is a prospective, observational cohort study conducted at Queen Charlotte's and Chelsea Hospital, UK from March 2014 to May 2019. Women with confirmed intrauterine pregnancies between 5 weeks and their dating scan (11-14 weeks) were recruited. Participants attended serial ultrasound scans in the first trimester and at each visit recorded symptoms of vaginal bleeding, pelvic pain, nausea and vomiting using validated scoring tools. Pregnancies were followed up until the dating scan (11-14 weeks). Univariate and multivariate analyses were performed to predict first trimester viability. A model was developed with multivariable logistic regression, variables limited by feature selection, and bootstrapping with multiple imputation was used for internal validation. RESULTS: 1403 women were recruited and after exclusions, data were available for 1105. 160 women (14.5 %) experienced first trimester miscarriage and 945 women (85.5 %) had viable pregnancies at 11-14 weeks' gestation. The average gestational age at the initial visit (calculated from the menstrual dates) was 7 + 1 weeks (+/-12.2 days). A multivariable logistic regression model was developed to predict first trimester viability and included the variables: mean gestational sac diameter, presence of fetal heart pulsations, difference in gestational age from last menstrual period and from mean sac diameter on ultrasonography, current folic acid usage and maternal age. The model demonstrated good performance (optimism-corrected area under curve (AUC) 0.84, 95 % CI 0.81-0.87; optimism-corrected calibration slope 0.969). CONCLUSION: We have developed and internally validated a model to predict first trimester viability with good accuracy prior to the 11-14 week dating scan, which now needs to be externally validated prior to clinical use.

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.

The Clinical Application of Platelet-Rich Plasma in the Female Reproductive System: A Narrative Review.

Platelet-rich plasma is an autologous plasma containing platelets prepared from fresh whole blood drawn from a peripheral vein. Through processing, it can be prepared to contain supraphysiologic levels of platelets at three to five times greater than the level of normal plasma. PRP has been explored both in vivo and ex vivo in the human endometrium model in its ability to harness the intrinsic regenerative capacity of the endometrium. Intrauterine autologous PRP infusions have been shown to increase endometrial thickness and reduce the rate of intrauterine adhesions. In the setting of recurrent implantation failure, intrauterine infusion of PRP has been shown to increase clinical pregnancy rate. PRP also appears to hold a potential role in select patients with premature ovarian insufficiency, poor ovarian responders and in improving outcomes following frozen-thawed transplantation of autologous ovarian tissue. Further studies are required to explore the potential role of PRP in reproductive medicine further, to help standardise PRP protocols and evaluate which routes of administration are most effective.

Fertility outcomes following surgery and multiagent chemotherapy in malignant ovarian germ cell tumor survivors: a survey study.

OBJECTIVE: To assess fertility outcomes in long-term survivors of malignant ovarian germ cell tumors treated with fertility-sparing surgery with or without additional chemotherapy. METHODS: Women diagnosed and treated for malignant ovarian germ cell tumors at Charing Cross Hospital or Mount Vernon Cancer Centre between 1977 and 2015 were included. Questionnaires assessing fertility issues were sent to patients treated with fertility-sparing surgery. Fertility outcomes were evaluated according to the treatment received. The effect of the mean total dose of cyclophosphamide and cisplatin was assessed. RESULTS: A total of 146 patients were sent the questionnaire; 77 (56.5%) patients were included in the analysis. A total of 49 (64%) patients received platinum-based chemotherapy after surgery, 39 (79.6%) of these with cisplatin, vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide, and etoposide, while 10 (20.4%) with bleomycin, etoposide, and cisplatin. After any treatment, 39/46 patients (85%) became pregnant: the conception rate was not different between those receiving surgery only and those receiving also chemotherapy (85.7% vs 84.4%, p=1.0). Live birth rate was 80.4% (37/46), with no statistically significant difference between the treatment groups (p=0.42). Median age of women achieving conception was 29 years (IQR 26-33). The probability of live birth at 5 years was 48% and 40% for patients in the surgery only and chemotherapy group, respectively (p=0.55). Infertility and miscarriage rates did not differ significantly between the two treatment groups (p=0.30 and p=0.32). The mean doses of cisplatin and cyclophosphamide received by patients failing and achieving conception were not different (p=0.10, p=0.47). CONCLUSIONS: Our results suggest that fertility may not be hampered in patients with malignant ovarian germ cell tumor treated with fertility-sparing surgery or receiving additional chemotherapy.

The menstrual cycle and the COVID-19 pandemic.

BACKGROUND: The impact of COVID-19 virus on menstrual cycles in unvaccinated women is limited. OBJECTIVE: To investigate the prevalence of changes to menstrual cycle characteristics, hormonal symptoms and lifestyle changes prior to and during the COVID-19 pandemic. METHODS: A retrospective online cross-sectional survey completed by social media users between July 2020 to October 2020. Participants were living in the United Kingdom (UK), premenopausal status and, or over 18 years of age. MAIN OUTCOME(S) AND MEASURES(S): The primary outcome was to assess changes to menstrual cycle characteristics during the pandemic following the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Secondary outcomes included assessment of hormonal and lifestyle changes. RESULTS: 15,611 social media users completed the survey. Of which, 75% of participants experienced a change in their menstrual cycle, with significantly greater proportions reporting irregular menstrual cycles (P<0·001), bleeding duration more than seven days (P<0·001), longer mean cycle length (P<0·001) and overall bleeding duration (P<0·001). Over half the participants reported worsening of premenstrual symptoms including low mood/depression, anxiety and irritability. When stratified according to COVID-19 infection, there was no significant difference in menstrual cycle changes. CONCLUSION: The COVID-19 pandemic resulted in considerable variation in menstrual cycle characteristics and hormonal symptoms. This appears to be related to societal and lifestyle changes resulting from the pandemic, rather than to the virus itself. We believe this may have an impact on the individual, as well as national economy, healthcare, and population levels, and therefore suggest this should be taken into consideration by governments, healthcare providers and employers when developing pandemic recovery plans.

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.

Attitudes, knowledge, and perceptions among women toward uterus transplantation and donation in the United Kingdom.

Objective: To assess the motivations and perceptions of the general public in the United Kingdom toward donating their uterus for Uterus Transplantation after death (UTx). Design: A cross sectional study. Setting: A 32-item electronic questionnaire. Population: One hundred fifty nine females over the age of 16 living in the United Kingdom, consented and took part in the study. Main outcome measures: The motivations and perceptions toward UTx among the general public including the willingness to donate and barriers preventing donation. Results: One hundred fifty nine women completed the questionnaire. The majority had never heard of UTx (n = 107, 71%) and most were not aware the uterus could be donated after death (n = 130, 92%). 43% of the cohort were willing to donate their uterus after death (n = 57). 8% stated they wished to donate their organs but not their uterus (n = 10). 30% of women (n = 42) believed the child born following UTx would have genetic links to the donor. Over half of the respondents (n = 65, 51%) strongly agreed or agreed they would feel joy in the knowledge that donation would lead to bringing a new life into the world. A quarter of respondents strongly agreed or agreed (n = 45, 25%) that the use of their uterus by another woman would feel like an extension of life. Conclusion: The findings indicate a favorable opinion toward UTx and a positive attitude toward donation of the uterus after death among the general public in the United Kingdom. The findings also highlight the need for education around UTx now this therapeutic option is available.

Systematic review and meta-analysis: does pre-implantation genetic testing for aneuploidy at the blastocyst stage improve live birth rate?

PURPOSE: To establish if preimplantation genetic testing for aneuploidy (PGT-A) at the blastocyst stage improves the composite outcome of live birth rate and ongoing pregnancy rate per embryo transfer compared to conventional morphological assessment. METHODS: A systematic literature search was conducted using PubMed, EMBASE and Cochrane database from 1st March 2000 until 1st March 2022. Studies comparing reproductive outcomes following in vitro fertilisation using comprehensive chromosome screening (CCS) at the blastocyst stage with traditional morphological methods were evaluated. RESULTS: Of the 1307 citations identified, six randomised control trials (RCTs) and ten cohort studies fulfilled the inclusion criteria. The pooled data identified a benefit between PGT-A and control groups in the composite outcome of live birth rate and ongoing pregnancy per embryo transfer in both the RCT (RR 1.09, 95% CI 1.02-1.16) and cohort studies (RR 1.50, 95% CI 1.28-1.76). Euploid embryos identified by CCS were more likely to be successfully implanted amongst the RCT (RR 1.20, 95% CI 1.10-1.31) and cohort (RR 1.69, 95% CI 1.29-2.21) studies. The rate of miscarriage per clinical pregnancy is also significantly lower when CCS is implemented (RCT: RR 0.73, 95% CI 0.56-0.96 and cohort: RR 0.48, 95% CI 0.32-0.72). CONCLUSIONS: CCS-based PGT-A at the blastocyst biopsy stage increases the composite outcome of live births and ongoing pregnancies per embryo transfer and reduces the rate of miscarriage compared to morphological assessment alone. In view of the limited number of studies included and the variation in methodology between studies, future reviews and analyses are required to confirm these findings.

The impact of COVID-19 on the motivations of women seeking a uterus transplant.

Aim: The aim of this study was to investigate the change if any, in the motivations of women seeking a UTx and determine the impact of the COVID-19 pandemic. Methods: A cross-sectional survey. Results: 59% of women answered they were more motivated in achieving a pregnancy following the COVID-19 pandemic. 80% strongly agreed or agreed the pandemic had no impact on their motivation for a UTx, and 75% strongly agreed or agreed their desire for a baby strongly outweighs the risks of undergoing a UTx during a pandemic. Conclusion: Women continue to express a high level of motivation and desire for a UTx despite the risks imposed by the COVID-19 pandemic.

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.

Impact of polyunsaturated fatty acid supplementation on assisted reproductive technology outcomes: a systematic review.

This review explores the impact of polyunsaturated fatty acid (PUFA) supplementation in women undergoing assisted reproductive technology (ART) on reproductive outcomes. A systematic search of English peer-reviewed journals was carried out using MEDLINE, EMBASE, and the Cochrane Library to identify articles published from January 1978 to 2021. The primary outcomes assessed included pregnancy and live birth rates. Secondary outcome measures included: (i) implantation rate; (ii) fertilisation rate; (iii) number of oocytes retrieved; (iv) number of metaphase II (MII) oocytes; (v) blastocyst conversion; and (vi) embryo quality. A total of 4 randomised control trials (RCTs) met the inclusion criteria. There is a lack of high-quality research to support widespread dietary supplementation with PUFAs in women undergoing ART. Prior to its clinical recommendation, there is a need for well-designed RCTs to facilitate an in-depth understanding of PUFA supplementation in women undergoing ART.