Exploring the knowledge and attitudes of women of reproductive age from the general public towards egg donation and egg sharing: a UK-based study.

STUDY QUESTION: What are the knowledge and views of UK-based women towards egg donation (ED) and egg sharing (ES)? SUMMARY ANSWER: Lacking knowledge of the practices of ED and ES could be an influential factor in donor egg shortages, rather than negative perceptions or lack of donor anonymity and financial incentives. WHAT IS KNOWN ALREADY: The increasing age of women trying to conceive has led to donor egg shortages, with ED and ES failing to meet demand. Indeed, in recent years in the UK, ES numbers have fallen. This results in long waiting lists, forcing patients abroad for fertility treatment to take up cross border reproductive care. Previous research suggests a lack of knowledge of ED among members of the general public; however, no study has yet assessed knowledge or views of ES in the general public. STUDY DESIGN, SIZE, DURATION: Six hundred and thirty-five UK-based women over 18 years were voluntarily recruited from social media community groups by convenience sampling. The recruitment period was from February to April 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants completed a previously validated questionnaire regarding female fertility, ED and ES, including knowledge, perceptions and approval of the practices and relevant legislation. This included ranking key benefits and issues regarding egg sharing. The questionnaire was completed using the online Qualtrics survey software. Statistical analysis was conducted using SPSS. MAIN RESULTS AND THE ROLE OF CHANCE: Regarding knowledge of ED and ES, 56.3% and 79.8%, respectively had little or no prior knowledge. Upon explanation, most approved of ED (85.8%) and ES (70.4%). A greater proportion of respondents would donate to a family member/friend (49.75%) than to an anonymous recipient (35.80%). Overall, ES was viewed less favourably than ED, with ethical and practical concerns highlighted. Women aged 18-30 years were significantly more likely to approve of egg donation practice compared to those aged >30 years (P < 0.0001). Those against ES found fears of financial coercion or negative psychological wellbeing the most concerning. About 35.8% and 49.7% would personally consider anonymous and known ED, respectively, whilst 56.7% would consider ES. Those answering in favour of egg sharing were significantly more likely to give higher benefit ratings compared to those against the practice (P < 0.001). Most agreed (55.8%) with and were not deterred to donate (60.1%) by the 'Disclosure of Donor Identity' legislation. Only 31.6% agreed with the compensatory cap; however, 52.7% would not be more motivated to donate by an increased cap. LIMITATIONS, REASONS FOR CAUTION: There were several limitations of the study, including the use of convenience sampling and the voluntary nature of participation opening the study up to sampling and participation bias. Finally, closed questions were predominantly used to allow the generation of quantitative data and statistical analysis. However, this approach prevented opinion justification and qualitative analysis, limiting the depth of conclusions drawn. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the first study to survey the general public's knowledge and views of ED/ES using a previously validated questionnaire. The conclusion that lack of knowledge could be contributing to the current donor shortfall in the UK demonstrates that campaigns to inform women of the practices are necessary to alleviate donor oocyte shortages. STUDY FUNDING/COMPETING INTEREST(S): No external funds were used for this study. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: NA.

A systematic review exploring the patient decision-making factors and attitudes towards pre-implantation genetic testing for aneuploidy and gender selection.

INTRODUCTION: Pre-implantation genetic testing for aneuploidy (PGT-A) is in high demand worldwide, with ongoing debate among medical societies as to which patient groups it should be offered. The psychological aspects for patients regarding its use, lag behind the genomic technological advances, leaving couples with limited decision-making support. The development of this technology also leads to the possibility for its utilization in gender selection. Despite the controversy surrounding these issues, very few studies have investigated the psychological aspects of patients using PGT-A. MATERIAL AND METHODS: This systematic review provides an up-to-date analysis of the psychosocial aspects surrounding PGT for aneuploidy and sex selection, as well as decision-making factors. A systematic search of English peer-reviewed journals of three computerized databases were undertaken following PRISMA guidelines. The qualitative data were extracted using thematic analysis. PROSPERO Registration number: CRD42019126439. RESULTS: The main outcome measures were patients' motivations, decision-making factors, attitudes and experiences surrounding the use of PGT for aneuploidy and sex selection. Ten studies were included, four for PGT-A and six for sex selection. Attitudes towards PGT-A were positive, with the main motivating factors being decreasing miscarriage rate, reducing the risk of termination of pregnancy and reducing the time to pregnancy. Consistently raised concerns regarding PGT-A were the financial burden and moral beliefs. The vast majority of patients felt sufficiently knowledgeable to make the decision; however, studies did reveal that a minority mis-interpreted certain potential benefits of PGT-A. Studies investigating PGT for sex selection predominantly reported the main motivation was to achieve gender balance within the family dynamic, with most studies finding no difference between couples using PGT for gender selection to have male or female offspring. CONCLUSIONS: Although this systematic review was limited by the small number of studies investigating this topic, a significant minority of patients appeared to misunderstand certain benefits and limitations of PGT-A. Fertility clinics must ensure they provide adequate counseling to all patients using PGT-A. With the use of PGT-A on the rise globally, there is a need to develop decision support tools for couples who have an increasing number of genetic testing options becoming available to them.

Exploring women's attitudes, knowledge, and intentions to use oocyte freezing for non-medical reasons: A systematic review.

INTRODUCTION: Women are postponing childbearing and preventing age-related fertility decline with oocyte freezing for non-medical reasons (OFNMR). The objective of this systematic evaluation was to gain an understanding of women's attitudes and knowledge of, and intentions to use OFNMR among users of OFNMR and the general public. MATERIAL AND METHODS: A systematic search of MEDLINE, EMBASE, and PyschINFO databases was undertaken, for studies that examined the psychosocial attitudes among women toward OFNMR. The search was limited to English language and no time restriction was set for publications. Extracted data were analyzed using thematic analysis and the study was performed according to PRISMA guidelines with prospective PROSPERO registration (CRD4201912578). RESULTS: Overall, 35 studies met the inclusion criteria. Studies were broadly categorized into studies investigating users or potential users of OFNMR, and studies examining the views of members of the general public. Users of OFNMR have good knowledge of age-related fertility decline and awareness of the OFNMR procedure. Lack of partner was identified as the most common motivating factor to undertake OFNMR, with cost as a predominant concern. Knowledge among the general public of OFNMR is highly variable. Underestimation of age-related fertility decline is common among the general public. Intentions of women to use OFNMR also varied drastically between studies. CONCLUSIONS: Women are predominantly motivated to freeze eggs by the lack of a suitable partner, but cost is a significant barrier. Increasing the number of women pursuing OFNMR at an earlier stage may positively impact upon the risk of future involuntary childlessness. Better information should be made available to both women and men about their fertility and options to inform their reproductive decision-making.

Managing subfertility in patients with heart disease: What are the choices?

More women with heart disease are reaching reproductive age and will want to embark upon pregnancy. Furthermore, many of these women are delaying pregnancy until later in life when they may be exposed to a greater number of complications from their heart disease. A relatively high proportion of these women will pursue fertility treatment to achieve a pregnancy; consequently, the management of subfertile couples where the woman (or man) has heart disease is of growing importance. In this review, we discuss how fertility investigations and treatment can impact a women with heart disease and how some of the potential complications can be minimized or avoided. We also consider surrogacy, which is an important option when pregnancy is contraindicated.

Uterine NK cells underexpress KIR2DL1/S1 and LILRB1 in reproductive failure.

A significant proportion of recurrent miscarriage, recurrent implantation failure and infertility are unexplained, and these conditions have been proposed to have an etiology of immunological dysfunction at the maternal-fetal interface. Uterine Natural Killer cells (uNK) comprise three subsets and are the most numerous immune cells found in the uterine mucosa at the time of implantation. They are thought to play an important role in successful pregnancy by regulation of extravillous trophoblast (EVT) invasion and spiral artery remodelling. Here, we examine the frequency, phenotype and function of uNK1-3 from the uterine mucosa of 16 women with unexplained reproductive failure compared to 11 controls with no reproductive problems, during the window of implantation. We report that KIR2DL1/S1 and LILRB1 expression is lower in the reproductive failure group for both uNK (total uNK, uNK 2 and 3) and pNK. We also show that degranulation activity is significantly reduced in total uNK, and that TNF-α production is lower in all uNK subsets in the reproductive failure group. Taken together, our findings suggest that reproductive failure is associated with global reduction in expression of uNK receptors important for interaction with HLA-C and HLA-G on EVT during early pregnancy, leading to reduced uNK activation. This is the first study to examine uNK subsets during the window of implantation in women with reproductive failure and will serve as a platform to focus on particular aspects of phenotype and function of uNK subsets in future studies. Further understanding of uNK dysregulation is important to establish potential diagnostic and therapeutic targets in the population of women with unexplained reproductive failure.

A review on the motivations, decision-making factors, attitudes and experiences of couples using pre-implantation genetic testing for inherited conditions.

BACKGROUND: In pre-implantation genetic testing (PGT), fertile couples undergo IVF with genetic testing of embryos to avoid conceptions with a genetic condition. There is an exponentially increasing uptake with over 600 applications listed by the Human Fertilisation and Embryology Authority in the UK. The psychological aspects of the decision-making process and the experience of PGT, however, are relatively underevaluated, with the potential to leave patients unsupported in their journeys. OBJECTIVE AND RATIONALE: In this review, we aim to comprehensively report on every aspect of couples' experiences of PGT. We consider what motivates users, the practical and ethical decisions involved and how couples navigate the decision-making process. Additionally, we report on the social and psychological impact on couples who are actively undergoing or have completed the PGT process. SEARCH METHODS: A systematic search of English peer-reviewed journals of three computerized databases was undertaken following PRISMA guidelines. Studies that examined the motivations, attitudes, decision-making factors and experiences of patients who have been actively engaged in the PGT process were included. No restrictions were placed on study design or date of publication. Studies examining patients using PGT in a hypothetical context or solely using PGT for aneuploidy were excluded. Qualitative data were extracted using thematic analysis. OUTCOMES: The main outcomes were patient motivations, deciding factors and attitudes, as well as the patient experience of coming to a decision and going through PGT.Patients were primarily motivated by the desire to have a healthy child and to avoid termination of pregnancy. Those with a sick child or previous experience of termination were more likely to use PGT. Patients also felt compelled to make use of the technology available, either from a moral responsibility to do so or to avoid feelings of guilt if not. The main factors considered when deciding to use PGT were the need for IVF and the acceptability of the technology, the financial cost of the procedure and one's ethical standpoint on the creation and manipulation of embryos. There was a general consensus that PGT should be applied to lethal or severe childhood disease but less agreement on use for adult onset or variable expression conditions. There was an agreement that it should not be used to select for aesthetic traits and a frustration with the views of PGT in society. We report that couples find it difficult to consider all of the benefits and costs of PGT, resulting in ambivalence and prolonged indecision. After deciding on PGT use, we found that patients find the process extremely impractical and psychologically demanding. WIDER IMPLICATIONS: This review aimed to summarize the current knowledge on how patients decide to use and experience PGT and to make suggestions to incorporate the findings into clinical practice. We cannot stress enough the importance of holistic evaluation of patients and thorough counselling prior to and during PGT use from a multidisciplinary team that includes geneticists, IVF clinicians, psychologists and also patient support groups. Large prospective studies using a validated psychological tool at various stages of the PGT process would provide an invaluable database for professionals to better aid patients in their decision-making and to improve the patient experience.

Insights into the hyperglycosylation of human chorionic gonadotropin revealed by glycomics analysis.

Human chorionic gonadotropin (hCG) is a glycoprotein hormone that is essential for the maintenance of pregnancy. Glycosylation of hCG is known to be essential for its biological activity. "Hyperglycosylated" variants secreted during early pregnancy have been proposed to be involved in initial implantation of the embryo and as a potential diagnostic marker for gestational diseases. However, what constitutes "hyperglycosylation" is not yet fully understood. In this study, we perform comparative N-glycomic analysis of hCG expressed in the same individuals during early and late pregnancy to help provide new insights into hCG function, reveal new targets for diagnostics and clarify the identity of hyperglycosylated hCG. hCG was isolated in urine collected from women at 7 weeks and 20 weeks' gestation. hCG was also isolated in urine from women diagnosed with gestational trophoblastic disease (GTD). We used glycomics methodologies including matrix assisted laser desorption/ionisation-time of flight (MALDI-TOF) mass spectrometry (MS) and MS/MS methods to characterise the N-glycans associated with hCG purified from the individual samples. The structures identified on the early pregnancy (EP-hCG) and late pregnancy (LP-hCG) samples corresponded to mono-, bi-, tri-, and tetra-antennary N-glycans. A novel finding was the presence of substantial amounts of bisected type N-glycans in pregnancy hCG samples, which were present at much lower levels in GTD samples. A second novel observation was the presence of abundant LewisX antigens on the bisected N-glycans. GTD-hCG had fewer glycoforms which constituted a subset of those found in normal pregnancy. When compared to EP-hCG, GTD-hCG samples had decreased signals for tri- and tetra-antennary N-glycans. In terms of terminal epitopes, GTD-hCG had increased signals for sialylated structures, while LewisX antigens were of very minor abundance. hCG carries the same N-glycans throughout pregnancy but in different proportions. The N-glycan repertoire is more diverse than previously reported. Bisected and LewisX structures are potential targets for diagnostics. hCG isolated from pregnancy urine inhibits NK cell cytotoxicity in vitro at nanomolar levels and bisected type glycans have previously been implicated in the suppression of NK cell cytotoxicity, suggesting that hCG-related bisected type N-glycans may directly suppress NK cell cytotoxicity.

Sperm DNA fragmentation in subfertile men: the effect on the outcome of intracytoplasmic sperm injection and correlation with sperm variables.

OBJECTIVE: To present the first UK data on sperm DNA fragmentation levels in subfertile men and fertile controls, the correlation with semen variables, and to assess the effect on the outcome of intracytoplasmic sperm injection (ICSI). PATIENTS, SUBJECTS AND METHODS: In all, 56 subfertile men undergoing ICSI (28 with positive and 28 with a negative outcome for paternity) and 10 control fertile semen donors were recruited. The sperm DNA fragmentation index (DFI) was assessed on raw pre-preparation samples using the sperm chromatin structure assay. A mean of 5212 sperm were analysed per sample and DFI data are presented by fertility status, ICSI outcome and correlated with semen variables (assessed using World Health Organisation criteria). RESULTS: Total DFI was significantly higher in subfertile men than in fertile controls (mean and median of 22.8% and 17.0% vs 8.4% and 5.0%; P < 0.001), as was the proportion of both moderate DFI (16.4% and 13.0% vs 6.4% and 4.0%; P = 0.001) and high DFI (6.2% and 6.1 vs 2.0% and 1.0%; P = 0.01). This difference remained significant when the control men were compared only with the subfertile men with successful paternity. There was no significant difference in DFI in the subfertile men when analysed by ICSI outcome (mean and median of 24.5% and 17.0% vs 22.3% and 21.0% for successful and unsuccessful cycles, respectively; P = 0.94). There was a positive statistically significant correlation (r = 0.37; P = 0.02) between the DFI and sperm morphology. CONCLUSIONS: This study confirms a relationship between male subfertility and sperm DFI; we discuss the correct role for genetic testing of sperm in the evaluation of subfertile men. Although DNA fragmentation data might help to decide a suitable treatment, once it is decided to proceed with ICSI, DFI levels have no effect on the outcome.

Investigating the effect of an abnormal cervico-vaginal and endometrial microbiome on assisted reproductive technologies: A systematic review.

The female reproductive tract has an active microbiome, and it is suggested that these microbes could influence the outcome of assisted reproductive technologies (ART). This systematic review aimed to assess the vaginal/uterine microbiome, specifically with regard to improving the outcome of ART. English peer-reviewed journals were searched for studies investigating the vaginal/uterine micriobiome and female reproductive tract, using PRISMA guidelines. Twenty-six studies were included, 19 studying the vaginal and seven investigating the uterine microbiome. Studies using culture-based technologies found an abnormal vaginal microbiome AVM was not associated with ART outcome. However, studies using sequence-based technologies found an abnormal vaginal microbiome had a negative effect on ART. An abnormal uterine microbiome impacted ART outcome in all of the studies which used culture-based methods and the most extensive of the two studies using metagenomic sequencing. This review has revealed a lack of translational data relating an abnormal vaginal/uterine microbiome to ART outcomes, with inconsistencies between the results of the different studies. Therefore the nature of the relationship between the vaginal/uterine microbiome and fertility remains unknown. As we better characterize this relationship using modern metagenomic techniques, the potential to manipulate the female reproductive tract microbiome to improve ART could be a reality.

Metabolomics as a tool to identify biomarkers to predict and improve outcomes in reproductive medicine: a systematic review.

BACKGROUND: Infertility is a complex disorder with significant medical, psychological and financial consequences for patients. With live-birth rates per cycle below 30% and a drive from the Human Fertilisation and Embryology Authority (HFEA) to encourage single embryo transfer, there is significant research in different areas aiming to improve success rates of fertility treatments. One such area is investigating the causes of infertility at a molecular level, and metabolomics techniques provide a platform for studying relevant biofluids in the reproductive tract. OBJECTIVE AND RATIONALE: The aim of this systematic review is to examine the recent findings for the potential application of metabolomics to female reproduction, specifically to the metabolomics of follicular fluid (FF), embryo culture medium (ECM) and endometrial fluid. To our knowledge no other systematic review has investigated this topic. SEARCH METHODS: English peer-reviewed journals on PubMed, Science Direct, SciFinder, were systematically searched for studies investigating metabolomics and the female reproductive tract with no time restriction set for publications. Studies were assessed for quality using the risk of bias assessment and ROBIN-I. OUTCOMES: There were 21 studies that met the inclusion criteria and were included in the systematic review. Metabolomic studies have been employed for the compositional analysis of various biofluids in the female reproductive tract, including FF, ECM, blastocoele fluid and endometrial fluid. There is some weak evidence that metabolomics technologies studying ECM might be able to predict the viability of individual embryos and implantation rate better than standard embryo morphology, However these data were not supported by randomized the controlled trials (RCTs) which showed no evidence that using metabolomics is able to improve the most important reproductive outcomes, such as clinical pregnancy and live-birth rates. This systematic review provides guidance for future metabolomic studies on biofluids of the female reproductive tract, with a summary of the current findings, promise and pitfalls in metabolomic techniques. The approaches discussed can be adapted by other metabolomic studies. WIDER IMPLICATIONS: A range of sophisticated modern metabolomic techniques are now more widely available and have been applied to the analysis of the female reproductive tract. However, this review has revealed the paucity of metabolomic studies in the field of fertility and the inconsistencies of findings between different studies, as well as a lack of research examining the metabolic effects of various gynecological diseases. By incorporating metabolomic technology into an increased number of well designed studies, a much greater understanding of infertility at a molecular level could be achieved. However, there is currently no evidence for the use of metabolomics in clinical practice to improve fertility outcomes.

Use of surgical sperm retrieval in azoospermic men: a meta-analysis.

OBJECTIVE: To compare the outcome of intracytoplasmic sperm injection (ICSI) cycles [1] using epididymal and testicular sperm in patients with obstructive azoospermia (OA); [2] using surgically retrieved sperm in patients with OA and nonobstructive azoospermia (NOA); and [3] using fresh and frozen-thawed sperm. DESIGN: Meta-analysis of published data. SETTING: Assisted conception unit. PATIENT(S): Ten reports (734 cycles: 677 transfers) were identified as suitable to assess source of sperm; 9 reports (1,103 cycles: 998 transfers) to assess etiology; and 17 reports (1,476 cycles: 1,377 transfers) to assess the effect of cryopreservation. INTERVENTION(S): Surgical sperm retrieval/ICSI. MAIN OUTCOME MEASURE(S): Fertilization rate (FR), implantation rate (IR), clinical pregnancy rate (CPR), and ongoing pregnancy rate (OPR) per embryo transfer. RESULT(S): Meta-analysis demonstrated no significant difference in any outcome measure between the use of epididymal or testicular sperm in men with OA. Meta-analysis showed a significantly improved FR (relative risk [RR] 1.18; 95% confidence interval [CI]: 1.13-1.23) and CPR (RR 1.36; 95% CI: 1.10-1.69) in men with OA as compared to NOA with a nonsignificant increase in OPR. There was no difference in either IR or miscarriage rate between the two groups. Comparing fresh with frozen-thawed epididymal sperm there was no difference in FR or IR, a significantly higher CPR (RR 1.20; 95% CI: 1.0-1.42), and no difference in OPR. No difference in fertilization or pregnancy outcome was noted when the testicular cycles were analyzed separately, but IR was significantly impaired using frozen-thawed sperm (RR 1.75; 95% CI: 1.10-2.80). CONCLUSION(S): Meta-analysis of published data confirms that etiology of azoospermia and cryopreservation of surgically retrieved sperm impacts on ICSI outcome, and allows us to make several recommendations for clinical practice. Origin of sperm, in men with similar etiology, does not affect outcome.