Human Fertilisation And Embryology Research Articles

Live Birth After Oocyte Donation In Vitro Fertilization Cycles in Women With Endometriosis

Although multiple mechanisms have been proposed to explain the infertility related to endometriosis, there are no conclusive data on the association of endometriosis with endometrial receptivity. The oocyte donation model in assisted reproduction technology (ART) cycles can clarify this issue. To explore the association of a history of endometriosis with ART outcomes in recipients of oocyte donation. In this systematic review and meta-analysis, electronic databases were searched from inception until August 31, 2023, using combinations of relevant keywords. Moreover, we retrieved data from the databases of the Society for Assisted Reproductive Technology (SART) in the US and the Human Fertilization and Embryology Authority (HFEA) in the United Kingdom. Observational studies were included if they investigated the impact of endometriosis on ART outcomes with donor oocytes. Publicly available data related to ART from various sources were gathered, and a retrospective aggregate and nonaggregate analysis using registries of in vitro fertilization cycles with oocyte or embryo donation was conducted. The primary outcome was live birth rate (LBR) following oocyte donor cycles. The effect measures of comparisons between groups are presented as odds ratios (ORs) with a 95% CI. This study analyzed 7212 oocyte donation cycles from 4 studies for the meta-analysis, along with 162 082 cycles from 2 registries (137 182 from SART and 24 900 from HFEA). No significant differences between the groups were observed in the meta-analysis of published data after adjusting for confounding factors (OR, 0.54; 95% CI, 0.19-1.57). A statistically significant lower LBR was identified in women with endometriosis when analyzing the aggregate data from SART and HFEA databases (OR, 0.89; 95% CI, 0.81-0.97). This study found a modest decrease in LBR among women with a history of endometriosis, although only results from the pooled analysis of registry data and not those from the meta-analysis reached statistical significance. These findings suggest that a marginal impairment of uterine receptivity may contribute to infertility mechanisms in women affected by endometriosis.

Mitochondrial Donation: The UK Experience

Mutations in mitochondrial DNA (mtDNA) are inherited exclusively from our mothers and can cause a broad range of debilitating and fatal diseases. Reproductive technologies designed to uncouple the inheritance of the mitochondrial genome from the nuclear DNA genome may enable affected women to have a genetically related child with a greatly reduced risk of mtDNA disease. Such technologies involve transplantation of the nuclear DNA from the egg of an affected woman to an enucleated egg from an unaffected donor. Nuclear genome transplantation can be performed either before or after fertilisation. The latter involves transfer of pronuclei, which separately contain the maternal and paternal genomes. In parallel with legal and regulatory reform to permit therapeutic application of so called “mitochondrial donation” techniques in the UK, we have conducted preclinical studies to test the safety and efficacy of pronuclear transplantation (PNT). In 2017 Human Fertilisation and Embryology Authority (HFEA) approved the cautious use of PNT in the UK and granted the first licence for its therapeutic application in 2018. I will discuss the scientific, legal, and regulatory hurdles in the path from proof of concept to translation of mitochondrial donation to clinical treatment.

Long-term healthcare utilization and costs of babies born after assisted reproductive technologies (ART): a record linkage study with 10-years' follow-up in England.

Is the long-term health care utilization of children born after ARTmore costly to the healthcare system in England than children born to mothers with no fertility problems? Children born after ART had significantly more general practitioner (GP) consultations and higher primary care costs up to 10 years after birth, and significantly higher hospital admission costs in the first year after birth, compared to children born to mothers with no fertility problems. There is evidence that children born after ART are at an increased risk of adverse birth outcomes and a small increased risk of rare adverse outcomes in childhood. We conducted a longitudinal study of 368088 mother and baby pairs in England using a bespoke linked dataset. Singleton babies born 1997-2018, and their mothers, who were registered at GP practices in England contributing data to the Clinical Practice Research Datalink (CPRD), were identified through the CPRD GOLD mother-baby dataset; this data was augmented with further linkage to the mothers' Human Fertilisation and Embryology Authority (HFEA) Register data. Four groups of babies were identified through the mothers' records: a 'fertile' comparison group, an 'untreated sub-fertile' group, an 'ovulation induction' group, and an ART group. Babies were followed-up from birth to 28 February 2021, unless censored due to loss to follow-up (e.g. leaving GP practice, emigration) or death. The CPRD collects anonymized coded patient electronic health records from a network of GPs in the UK. We estimated primary care costs and hospital admission costs for babies in the four fertility groups using the CPRD GOLD data and the linked Hospital Episode Statistics (HES) Admitted Patient Care (APC) data. Linear regression was used to compare the care costs in the different groups. Inverse probability weights were generated and applied to adjust for potential bias caused by attrition due to loss to follow-up. Children born to mothers with no fertility problems had significantly fewer consultations and lower primary care costs compared to the other groups throughout the 10-years' follow up. Regarding hospital costs, children born after ART had significantly higher hospital admission costs in the first year after birth compared to those born to mothers with no fertility problems (difference = £307 (95% CI: 153, 477)). The same pattern was observed in children born after untreated subfertility and ovulation induction. HFEA linkage uses non-donor data cycles only, and the introduction of consent for data use reduced the availability of HFEA records after 2009. The fertility groups were derived by augmenting HFEA data with evidence from primary care records; however, there remains some potential misclassification of exposure groups. The cost of neonatal critical care is not captured in the HES APC data, which may cause underestimation of the cost differences between the comparison group and the infertility groups. The findings can help anticipate the financial impact on the healthcare system associated with subfertility and ART, particularly as the demand for these treatments grows. C.C. and this work were funded by a UK Medical Research Council Career Development Award [MR/L019671/1] and a UK MRC Transition Support Award [MR/W029286/1]. X.H. is an Australia National Health and Medical Research Council (NHMRC) Emerging Leadership Fellow [grant number 2009253]. The authors declare no competing interest. N/A.

Low E-visibility of embryologists on fertility clinic websites: a web-based cross-sectional study.

This study assessed the visibility of embryologists on fertility clinic websites among Society for Assisted Reproductive Technology (SART) and the Human Fertilisation and Embryology Authority (HFEA) member clinics. During a 1-month interval (March 2022), all Society for Assisted Reproductive Technology (SART) and the Human Fertilisation and Embryology Authority (HFEA) member fertility clinic websites were evaluated. The professional representation of the primary care team was examined including specialties, the presence of headshots, and biographies. A total of 446 fertility clinic websites were scanned in the search. The embryology team has the least common professional identification by their names (53.58%) compared to gynecology clinicians (96.21%, p < 0.001) and nurses (55.58%, p < 0.001). This trend also applies to other types of professional identifiers, such as headshots and biographies. Professional headshots of embryologists (50.34%) were less prominent than those of gynecology clinicians (93.51%, p < 0.001). A similar trend was observed in the biographies of the embryology team (47.20%) compared to gynecology clinicians (95.08%, p < 0.001). The present study revealed that embryologists have low professional visibility on fertility clinic websites. Fertility clinics may prioritize enhancing the online visibility of their embryology laboratory team. This approach could potentially enhance the recognition of their team, foster transparency, and provide accessible information about the skills and expertise of healthcare professionals involved in the treatment process.

P-681 Embryo utilisation rate and blastocyst formation rate correlate negatively with the oocyte yield and positively with live birth rate: an analysis from HFEA’s national database

Abstract Study question Do embryo utilisation rate (EUR) and blastocyst formation rate (BFR) correlate with oocyte yield and livebirth rate (LBR) in fresh IVF/ ICSI cycles? Summary answer EUR and BFR correlate positively with livebirth rate (LBR) but decline with increasing number of oocytes to a nadir when the fresh cycle LBRs plateaus. What is known already LBR in fresh IVF cycles plateaus once a certain number of oocytes are retrieved. While impaired endometrial receptivity with high ovarian response appears to be an underlying cause, other factors, such as decreasing competency of oocytes or embryos cannot be ruled out. Cytoplasmic dysmorphism of oocytes and chromosomal disorders have been shown to rise with increasing number of oocytes. Consequently, cumulative livebirth rate per oocytes has been reported to decline with increasing oocyte yield. When obvious male factor is excluded, the competency of oocytes can be reflected in the embryo grading. Study design, size, duration Retrospective analysis of 8015 fresh IVF/ ICSI cycles that met the inclusion criteria from the national database published by Human Fertilisation and Embryology Authority (HFEA) in the United Kingdom. We analysed 2 years of published data between January 2015 and December 2016. Participants/materials, setting, methods Population included couples at their first IVF treatment with single fresh blastocyst transfer, due to tubal or unexplained infertility among women aged &amp;lt;40 years. Only cycles that produced at least 1 transferable blastocyst were included to determine the blastocyst formation rate. Inclusion criteria were designed to minimise other co-factors that may influence embryo quality. Linear regression analysis was done to find the correlation between EUR/ BFR and oocyte yield; multiple regression to predict livebirth Main results and the role of chance EUR (correlation coefficient = -0.156605, p &amp;lt; 0.0001) and transferable BFR correlation coefficient = -0.156605, p &amp;lt; 0.0001) declined with increasing number of oocytes. The findings were no different whether IVF or ICSI was performed. Both EUR (OR 1.002, CI 1.001- 1,004) and (transferable) BFR (OR 1.005, CI 1.003-1.006) correlated positively with LBR (p &amp;lt; 0.0001, for both), after adjusting for other confounders including age and method of insemination. Both (transferable) BFR and EUR declined with the increasing number of oocytes falling to a nadir when around 8 oocytes were retrieved then remained static with higher oocyte yield. LBR in fresh cycles also reaches its peak at around 8 oocytes then plateaus. Limitations, reasons for caution Information on patient’s BMI or stimulation dose is not available in the HFEA database. However, it might have little impact in our findings given large sample size. Cycles with no blastocyst formation through extended culture were not included, as this intention to treat information was not available Wider implications of the findings Declining proportion of competent embryos may result in flattening of LBR graph in fresh cycles after certain number of oocytes retrieved. Increasing absolute number of competent embryos fails to boost fresh cycle LBR after a saturation point, We have to improve embryo selection than increasing ovarian stimulationto improve fresh LBR Trial registration number NA

P-572 The occupational challenges reported by UK embryologists: stress, fatigue, and burnout

Abstract Study question To determine the prevalence of occupational stress, fatigue, and burnout reported by UK embryologists and their perceived impact of work conditions on wellbeing. Summary answer The surveyed UK embryologists reported low somatic symptom severity and moderate perceived stress, but high levels of burnout and overall stressful working conditions. What is known already High levels of occupational stress, fatigue, burnout, and occupational health issues have been reported among embryologists in the Spanish, US, and international surveys. These issues were associated with embryologist’s occupational challenges and work conditions. Most (58.3%) of the previous UK survey participants reported work-related health issues, including stress/mental health problems (27.8%). However, that study did not evaluate stress and burnout utilizing the same standardized measures as recent US and international surveys, both of which identified considerably higher burnout than the Spanish survey. The present study will address this gap and identify issues that concern UK embryologists using our survey toolkit. Study design, size, duration A cross-sectional, mixed methods web-based survey was sent via email to 253 of an estimated ∼400 UK embryologists working in Human Fertilisation and Embryology Authority (HFEA)-licensed UK ART/IVF clinics and private practices in January 2023. Participants self-reported their stress levels, fatigue, burnout, and work conditions (cryopreservation, technology, overtime work, doing double-work, employer understanding, etc.). Participants/materials, setting, methods Proportions across the Maslach Burnout Inventory-General Survey (MBI-GS), Perceived Stress Scale (PSS), Patient Health Questionnaire (PHQ-15), and a single-item work unit grade (A–F), and customized occupational and sociodemographic questionnaires were calculated using descriptive statistics. Welch’s t-test and ANOVA to compare PSS and PHQ-15 scores between the groups categorized by occupational questions, and Pearson’s correlation coefficients and multivariate analysis to cross-correlate statistically significant and biologically important parameters will be utilized once the survey is closed. Main results and the role of chance To date, of 253 embryologists, 104 (41%) completed the survey (mean age 34.3 years, 88% female); 77% worked in private/for-profit, 17% government, 5% corporate, and 1% academic settings. A total of 60% of the respondents reported symptoms of burnout on the MBI exhaustion dimension and 42% on MBI cynicism, and 68% of them reported being unable to cope with their workload. The PSS showed moderate perceived stress, and the PHQ-15 showed low somatic symptom severity, with 38% reporting fatigue. Additionally, 2% experienced constant, 13% high, 33% moderate, 37% mild, and 15% no anxiety. Moreover, 53% reported the current cryopreservation processes caused anxiety, 63% reported technology would ease the burden on the lab staff, and 74% reported technology would lessen their stress as an embryologist. Regarding their workplace environment and culture, 80% reported working overtime, 57% found themselves doing double work due to a lack of technology integrations and analog record, and 80% felt their employers did not understand their occupational challenges. When asked to rate their work unit safety, 38% of embryologists gave their laboratories grade of A (excellent), 50% B (very good), 10% C (acceptable), 3% D (poor), and 0% F (failing). Limitations, reasons for caution This study is limited by the self-reporting nature of the data collection via on-line surveys, which precluded interviewing or follow-up questions of embryologists. Wider implications of the findings Overall, work-related health issues and occupational challenges reported by UK embryologists align with results from recent surveys and could be addressed by organizational enhancements and technology improvements. Lower levels of job-specific stress and burnout among them compared to their colleagues might be due to HFEA-provided structure/certainty to their professional responsibilities. Trial registration number NCT05708963

P-283 Is it time to abandon the practice of double embryo transfer?

Abstract Study question Can single embryo transfer (SET) with euploid embryos be an effective strategy for improving livebirth rate (LBR) and reducing multiple pregnancy rate (MPR)? Summary answer SET of euploid embryos leads to higher LBR and lower MPR per embryo transfer cycle compared to DET of untested embryos in all age groups. What is known already Multiple pregnancy, IVF, and advanced maternal age are independently associated with adverse obstetric outcomes and their coexistence is likely to lead to aggravation of obstetric risks. DET is often recommended in women aged over 37 with the aim of improving LBR but at the cost of significantly higher MPR. Preimplantation genetic testing for aneuploidy (PGT-A) was pioneered to select euploid embryos for transfer. We evaluate whether utilization of PGTa with a subsequent transfer of a single euploid embryo can be an effective strategy for reducing MPR and achieving higher LBR compared to DET of untested embryos. Study design, size, duration This is retrospective national cohort study using data from the UK Human Fertilisation and Embryology Authority (HFEA). We analysed 137, 186 IVF treatment cycles performed between 2017-2018 in the UK. Other than grouping by maternal age, no further confounders were controlled for. Both fresh and frozen transfers were included. Participants/materials, setting, methods We included all IVF treatment cycles. Cycles undertaken for donation or embryo storage were excluded. Cycle parameters including age, ethnicity, the number of previous cycles, previous infertility history, previous pregnancy outcomes, gestational age at delivery, birthweight and early pregnancy outcomes were evaluated. We compared the LBR and MPR per embryo transfer cycle following a SET of a euploid embryo (PGTa SET) vs. a DET of untested embryos. Main results and the role of chance PGTa was utilised in 1990 IVF treatment cycles, of which 1521 had a SET of a euploid embryo (76%, 95% CI 75-78%). Of 135, 195 IVF cycles in which PGTa was not utilised, there 37, 281 had DET of untested embryos (28%, 95% CI 27-28%). There were 319 IVF treatment cycles in which there were no euploid embryos to transfer following PGTa (16%, 95% CI 14-18%). In the untested group, there were 16, 680 IVF treatment cycles in which there were no embryos to transfer (12%, 95% CI 12-13%). Per embryo transfer cycle, the LBR was significantly higher and the MPR was significantly lower in all age groups in PGTa SET group vs. DET of untested embryos group (including those aged under 35) (43.7% vs. 31.4%, p &amp;lt; 0.001 and 0.3% vs. 8.4%, p &amp;lt; 0.0001, respectively). Limitations, reasons for caution It is unclear whether the HFEA dataset includes all intended collections when assessing outcomes, thus we were unable to report on outcomes per cycle started. Wider implications of the findings Advanced maternal age is associated with increased perinatal risk and maternal morbidity. This population are particularly vulnerable to multiple pregnancy. PGTa followed by SET of a euploid embryo is an effective strategy for reducing MPR and improving LBR in all age groups. Trial registration number not applicable

P-463 Data from 143,251 women indicates that black women access at-home fertility testing services later in life compared to white women in the United Kingdom

Abstract Study question Does ethnicity play a role in fertility assessment-seeking behaviour of Black women in the United Kingdom (UK)? Summary answer Black women approach an at-home reproductive health and fertility assessment service later in their fertility journey than White women. What is known already Evidence from the Human Fertilisation and Embryology Authority (HFEA) shows that Black patients access fertility care two years later than the national average in the United Kingdom (UK) (36.4 vs 34.6 years). Additionally, previous research has shown different prevalences of reproductive health conditions associated with infertility amongst Black women, such as fibroids and tubal occlusion. In combination with delayed access to fertility care, this may contribute to the lower live birth rates seen in Black patients in the UK. Study design, size, duration A retrospective observational study conducted on 143,251 Hertility Health users who completed a virtual health assessment between September 2020 and January 2023. The health assessment collected self-reported data on age, ethnicity, pre-existing diagnoses of reproductive health conditions, whether they were actively trying to conceive (TTC) and the length of time they had been actively TTC. Participants/materials, setting, methods A total of 25.9% users (n = 37,170) indicated they were TTC. The majority of those TTC self-identified as White (82.9%), followed by Asian (7.4%), Mixed (3.6%), Black (4.6%) and ‘Other’ (1.5%). Summary statistics (mean ± SD and %) regarding age and prevalence of pre-existing conditions of users TTC have been reported. Additional statistical analysis of the associations of time spent TTC between ethnicities was conducted via Chi-squared test (χ2); p values &amp;lt;0.05 were considered significant. Main results and the role of chance A significant relationship was observed between time spent TTC and ethnicity; the strongest association was observed between Black and White users χ2 (16, n = 34,706)=120, p &amp;lt; 0.0001). Comparison of time spent TTC, and average age showed that fewer Black women undertook the virtual health assessment at &amp;lt; 6 months of TTC than White women (29.3%, n = 469 vs 34.1%, n = 9820) at a moderately older age (31.3±6.5 years vs 29.8±5.7 years). A higher percentage of Black women were TTC for &amp;gt;5 years compared to White women (14.2%, n = 227 vs 8.8%, n = 2544). Additionally, Black women at this time point were approximately four years older than White women (36.9 years ± 6.0 years vs 33.0 ± 5.1 years). Secondary analysis of the prevalence of reproductive health conditions associated with infertility indicated that 20.1% (n = 133) and 22.5% (n = 149) of Black women had a preexisting condition at &amp;lt; 6 months and &amp;gt;5 years of TTC, respectively, vs 22.6% (n = 1363) and 19.2% (n = 1158) of White women in the corresponding TTC length groups. Limitations, reasons for caution As the virtual health assessment data was self-reported, there is a risk of recall bias and false reporting. Data was stratified via the main ethnicities and did not take the heterogeneity within ethnic groups or mixed ethnicities into account. Wider implications of the findings This data suggests that Black women approach fertility testing services later than White women, which may contribute to the disparities between pregnancy outcomes in the UK and cannot fully be accounted for by preexisting diagnoses associated with infertility. Further investigations are needed to outline the underlying reasons for this. Trial registration number not applicable

Accessing publicly funded donor insemination treatment in the UK: is funding information available on fertility clinic websites?

We sought to find out if information about public funding for regulated donor insemination (DI) was available on UK fertility clinic websites, and if so, what information was provided for same-sex couples and single women; and if the available information was easily readable. The ‘Choose a fertility clinic’ pages of the Human Fertilisation and Embryology Authority (HFEA) website were used to identify all licensed fertility clinics in the UK, and any available text on public funding for DI treatment was extracted. The Flesch reading ease scores were calculated to determine the readability of the extracted text. Of the 52 clinics included in the synthesis, 23 mentioned public funding, and for 16 of these, it was unclear whether public funding was available. Six of the 23 clinics mentioned public funding for same-sex couples, and two mentioned public funding for single women. The Flesch reading ease scores indicated that none of the text about funding for DI treatment on any of the clinic websites met the NHS-advised level of readability for health information. Fertility clinic websites should specify whether they offer publicly funded treatment, and to whom, as well as clearly stating the eligibility criteria, using suitably readable language to communicate this.

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MP48-15 ARE UROLOGISTS UNDERREPRESENTED ON FERTILITY CLINIC WEBSITES? A WEB-BASED ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023MP48-15 ARE UROLOGISTS UNDERREPRESENTED ON FERTILITY CLINIC WEBSITES? A WEB-BASED ANALYSIS Bassel Bachir, Lina El Taha, and Fadi Choucair Bassel BachirBassel Bachir More articles by this author , Lina El TahaLina El Taha More articles by this author , and Fadi ChoucairFadi Choucair More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003294.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Infertile couples invariably use the internet to seek different fertility clinics and explore their fertility options. Online information about healthcare providers has made self-referral popular among patients. As there is almost an equal distribution of male and female factor infertility, this information is vital for both partners. To this end, the objective of this study was to identify the visibility of male infertility specialists (urologists) on fertility clinic websites, as compared to other team members. METHODS: Information was retrieved from two publicly available online registries. The Society for Assisted Reproductive Technology (SART) in the United States and the Human Fertilization and Embryology Authority (HFEA) in the United Kingdom. We examined all available websites, looking especially at the online representations of the different team members. RESULTS: A total of 447 clinic websites were analyzed. Out of those websites, only 36 (8%) included the profiles of male infertility specialists (urologists). In contrast, the overwhelming majority of websites, 429 (96%) included the profiles of female infertility specialists (Reproductive Endocrinology and Infertility specialists). Male infertility specialists were also grossly underrepresented compared to other clinic staff members including nurses, 249 (55.7%, p<0.0001), embryology lab directors, 208 (46.5%, p<0.0001), administrative staff, 177 (39.6%, p<0.0001) and embryologists ,133 (29.7%, p<0.0001). CONCLUSIONS: Urologists specialized in male infertility are profoundly underrepresented on fertility clinic websites, despite the fact that male factor infertility accounts for almost half of all infertility cases. Addressing this shortcoming can help fertility clinics attract more patients through a higher visibility of all care team members involved. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e661 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bassel Bachir More articles by this author Lina El Taha More articles by this author Fadi Choucair More articles by this author Expand All Advertisement PDF downloadLoading ...

Early pregnancy outcomes of IVF cycles using donor versus partner sperm: analysis of 1376454 cycles recorded by the Human Fertilisation and Embryology Authority (1991-2016).

Are the early pregnancy outcomes of IVF pregnancies conceived with donor sperm different to those conceived with partner sperm? Pregnancies conceived with donor sperm have a lower odds of early pregnancy loss and ectopic pregnancy compared to pregnancies conceived with partner sperm. The number of cycles using donor sperm has risen significantly in recent years. Adverse early pregnancy outcomes have a negative impact on women and their partners. The evidence available to date regarding early pregnancy outcomes for pregnancies conceived with IVF donor sperm is limited by low numbers and lower-quality studies. This is a retrospective cohort study of 1376454 cycles conceived with either donor or partner sperm between 1991 and 2016 as recorded in the Human Fertilisation and Embryology Authority (HFEA) Register. The HFEA has recorded data on all fertility treatments carried out in the UK from 1991 onwards, and it publishes this data in an anonymized form. This study assessed the outcomes of all pregnancies conceived with donor sperm and compared them to those conceived with partner sperm among IVF cycles recorded in the HFEA anonymized dataset from 1991 to 2016. Cycles that included intrauterine insemination, donor oocytes, preimplantation genetic testing, oocyte thaw cycles and alternative fertility treatments were excluded. The outcomes of interest were biochemical pregnancy, miscarriage, ectopic pregnancy, stillbirth and live birth. Logistic regression was used to adjust for confounding factors including age of the female partner, cause of infertility, history of previous pregnancy, fresh or frozen cycle, IVF or ICSI, number of embryos transferred, and year of treatment. Results are reported as adjusted odds ratios (aOR) and 95% CIs. This study found reductions in the odds of biochemical pregnancy (aOR 0.82, 95% CI 0.78-0.86), miscarriage (aOR 0.93, 95% CI 0.89-0.97), and ectopic pregnancy (aOR 0.77, 95% CI 0.66-0.90) among pregnancies as a result of the use of donor sperm as opposed to partner sperm. This study is retrospective and limited by the constraints of routinely collected data. No data were available for maternal characteristics such as BMI, smoking and partner age, which could all be potential confounders. Clustering of multiple pregnancies within women could not be accounted for as the data are reported only at the cycle level with no maternal identifiers. This study has demonstrated that there are no increased risks of adverse pregnancy outcome with donor sperm pregnancies. The reduction in miscarriage in pregnancies using donor sperm suggests that sperm could have a role in miscarriage, as the selection process for being accepted as donor is stringent. No external funding was sought for this study. C.A. has received funding from Ferring to attend a UK meeting for trainees in reproductive Medicine. A.M. has received funding from Ferring, Cook, Merck Serono, Geodon Ritcher, and Pharmasure for speaking at, or attending, meetings relating to reproductive medicine. She has also participated in a Ferring advisory board. S.B. has received grants from Tenovus and the UK Medical Research Council. She has also been supported with a Medical Research Scotland PhD studentship. N/A.

A comparison of perinatal outcomes following fresh blastocyst or cleavage stage embryo transfer in singletons and twins and between singleton siblings.

Are perinatal outcomes following fresh blastocyst versus fresh cleavage stage embryo transfer (ET) different in singletons, twins, and between singleton siblings? Singleton babies conceived following fresh blastocyst, versus cleavage stage, ET are less likely to be small for gestational age (SGA) or to have a congenital anomaly (a result confirmed by comparing singleton siblings), while singletons born following fresh blastocyst ET were at a higher risk of being large for gestational age (LGA) than their sibling born following fresh cleavage stage ET. Blastocyst stage transfer is now the preferred strategy in most IVF units. Previous studies have suggested that babies conceived through blastocyst transfer are at increased risk of preterm birth and LGA. A national population-based retrospective cohort study was performed using linked Human Fertilisation and Embryology Authority (HFEA) data on 130 516 IVF and ICSI livebirths occurring from 103 062 women between 2000 and 2017. We included women who had at least one singleton livebirth resulting from IVF/ICSI fresh embryo treatment, using their own eggs and partner's sperm. A linked HFEA dataset was analysed using a multilevel framework, which accommodated repeated IVF cycles resulting in livebirths in the same woman. A population-averaged robust Poisson model was used for binary outcomes and a multinomial logistic regression model was used for categorical outcomes. Unadjusted and adjusted risk ratios (aRRs) (95% CI) were calculated. There were 130 516 livebirths in 103 062 women, including 86 630 singletons, 43 886 twin births, and 5384 pairs of singleton siblings. In comparison with fresh cleavage stage ET, fresh blastocyst stage transfer in singletons was associated with a lower risk of low birthweight (aRR = 0.92; 95% CI 0.86, 0.99), lower risk of being SGA (0.83; 0.78, 0.89), and lower risk of congenital anomaly (0.79; 0.71, 0.89). This analysis did not show an increase in risk associated with preterm birth (1.00; 0.94, 1.06), high birthweight (0.99; 0.93, 1.06), LGA (0.99; 0.93, 1.05), and the chance of healthy singleton baby (1.00; 1.00, 1.02). Twins resulting from fresh blastocyst stage ET were at slightly higher risk of preterm birth (1.05; 1.02, 1.10) compared with twins conceived following fresh cleavage stage ET. There was insufficient evidence for an association with the other perinatal outcomes. Singleton siblings born following fresh blastocyst stage ET were at a higher risk of being LGA (1.57; 1.01, 2.46) and at lower risk of having a congenital anomaly (0.52; 0.28, 0.97) compared to their singleton siblings born following cleavage stage ET. There was some evidence of excess risk of preterm birth (1.42; 0.97, 2.23) associated with blastocyst stage transfer. However, we could not confirm an association between blastocyst stage ET and low birthweight (1.35; 0.81, 2.27), high birthweight (1.19; 0.80, 1.77), and the chance of being a healthy baby (0.97; 0.86, 1.09). This was an observational study where we were unable to adjust for some key confounders, such as maternal smoking status and BMI, which may change from one pregnancy to another and are not recorded in the HFEA dataset. In the largest study of its kind, our analysis of singleton siblings, corrected for unmeasured, non-time varying maternal factors, confirms the previously reported association between blastocyst transfer and LGA babies, and shows a reduced risk of congenital anomaly following blastocyst transfer. Our sibling analysis did not confirm a decreased risk of low birthweight following blastocyst transfer. Overall, absolute risks are low and there is insufficient evidence to challenge the practice of extended culture of embryos. This project is financed by an NHS Grampian Endowment Research Grant, project number 17/052. One of the authors, S.B., was the Editor in Chief of HROpen until 31 December 2022 and would have been in that role when the paper was first submitted. As an invited speaker, S.B. has received travel expenses, accommodation and honoraria from Merck, Organon, and Ferring. A.M. has received travel expenses, accommodation, and honoraria from Merck Serono, Cook Medical, Pharmasure, Gedeon Richter, and Ferring. D.J.M. is currently a HROpen Associate Editor. N/A.

B v University of Aberdeen [2020] CSIH 62: Where there's a will, there's a way.

The area of posthumous reproduction—the process by which assisted reproductive technologies are used to achieve conception, pregnancy, and childbirth after the death of one or both biological parents—raises complex questions for the law. B v University of Aberdeen1 (Aberdeen) adds to an increasing line of cases that grapple with the delicate legal issues involving posthumous reproduction.2 The storage and use of gametes and embryos, including their storage and use posthumously, are regulated by a detailed statutory framework contained principally in the Human Fertilisation and Embryology (HFE) Acts 1990 and 2008. The HFE Act 1990 places significant emphasis on consent,3 which is regarded as one of the twin pillars supporting Parliamentary regulation of this field.4 The specific requirements needed for an effective consent are contained in Schedule (Sch) 3 of the HFE Act 1990, which stipulates, amongst other things, that consent must be in writing.5

‘It takes a village’ – fertility treatment using donor gametes, embryos and/or surrogacy

Key content Fertility treatment using donated gametes and embryos is increasingly common. Indications for the use of donated sperm and oocytes include azoospermia, single women and women in same‐sex relationships, inherited conditions, poor quality embryos or failed fertilisation in previous cycles of assisted reproductive technology, and ovarian insufficiency. Causes of azoospermia and ovarian insufficiency include congenital and genetic disorders, infectious and traumatic conditions, iatrogenic causes and age‐related decline. These treatment cycles have ethical and legal implications and require appropriate pre‐conception counselling and completion of Human Fertilisation and Embryology Authority (HFEA)‐mandated forms to ensure the safety of donors, recipients and any children born as a result of treatment. All donors are screened for infectious diseases and can also be screened for genetic conditions. Sperm donation can be organised outside of recognised fertility clinic settings, which increases the possibility of infection transmission. Compared with cycles using autologous gametes and embryos, treatment outcomes can increase live birth rates and reduce incidence of low birthweight, but may increase hypertensive disorders of pregnancy. Learning objectives To understand the clinical indications for the use of gamete and embryo donation, including potential risks to donors and recipients, and success rates. To learn the practical considerations of donation and procurement processes, screening, quarantine, legal and regulatory aspects in the UK and international comparison. To appreciate special issues, including psychological assessment and support requirements, ethical considerations, intrafamilial donation, commercial DNA testing and family tracing implications. Ethical issues Donors must be made fully aware of the implications of donation and the lack of anonymity once resulting children reach the age of 18, according to UK law. Recipients must be thoroughly counselled regarding the implications and psychological impact of treatment. The HFEA obliges all clinics to offer implications counselling to those undergoing treatment in terms of the impact of treatment on them and how to broach the subject with future children.

Association of extended culture to blastocyst and pre-malignant gestational trophoblastic disease risk following IVF/ICSI-assisted reproduction cycles: an analysis of large UK national database.

To assess whether there is an association between extended in vitro culture based on embryo developmental stage at transfer and pre-malignant gestational trophoblastic disease (GTD) risk of molar pregnancy during assisted reproduction. A retrospective study was carried out using Human Fertilization and Embryology Authority (HFEA) anonymized register from 1999 to 2016. A total of 540,376 cycles were eligible to be included in the study after excluding any kind of donor treatment or surrogacy, frozen embryo transfers, and cycles with incomplete data. Subgroup analysis was carried out in subjects with primary infertility aiming to exclude an increased risk in those with a previous GTD. Multivariate logistic regression analysis was used to adjust for possible confounders, and the effect of day of embryo transfer in IVF (in vitro fertilization)/ICSI (intracytoplasmic sperm injection) treatment on a molar pregnancy GTD outcome was analyzed. The prevalence of a molar pregnancy GTD among the study population was 3.4/10,000 livebirths (53/156,683) with a higher risk in the over 40 age category. No significant difference of pre-malignant GTD incidence was seen between IVF and ICSI (0.01% vs 0.009% respectively). No association was seen with GTD based on type/cause of infertility or number of embryos transferred. Crude (1.06; 95% CI 0.852-1.31) and adjusted (1.07; 95% CI (0.857-1.32) odds ratios were calculated to see an association between day of embryo transfer and the occurrence of a GTD. There was no association between day of embryo transfer and molar GTD risk after adjusting for age and secondary infertility. No significant association between pre-malignant molar gestational trophoblastic disease and extended in vitro embryo culture was found after analyzing 540,376 cycles of IVF and ICSI.

Predicting cumulative live birth for couples beginning their second complete cycle of in vitro fertilization treatment.

STUDY QUESTIONCan we develop an IVF prediction model to estimate individualized chances of a live birth over multiple complete cycles of IVF in couples embarking on their second complete cycle of treatment?SUMMARY ANSWERYes, our prediction model can estimate individualized chances of cumulative live birth over three additional complete cycles of IVF.WHAT IS KNOWN ALREADYAfter the completion of a first complete cycle of IVF, couples who are unsuccessful may choose to undergo further treatment to have their first child, while those who have had a live birth may decide to have more children. Existing prediction models can estimate the overall chances of success in couples before commencing IVF but are unable to revise these chances on the basis of the couple’s response to a first treatment cycle in terms of the number of eggs retrieved and pregnancy outcome. This makes it difficult for couples to plan and prepare emotionally and financially for the next step in their treatment.STUDY DESIGN, SIZE, DURATIONFor model development, a population-based cohort was used of 49 314 women who started their second cycle of IVF including ICSI in the UK from 1999 to 2008 using their own oocytes and their partners’ sperm. External validation was performed on data from 39 442 women who underwent their second cycle from 2010 to 2016.PARTICIPANTS/MATERIALS, SETTING, METHODSData about all UK IVF treatments were obtained from the Human Fertilisation and Embryology Authority (HFEA) database. Using a discrete time logistic regression model, we predicted the cumulative probability of live birth from the second up to and including the fourth complete cycles of IVF. Inverse probability weighting was used to account for treatment discontinuation. Discrimination was assessed using c-statistic and calibration was assessed using calibration-in-the-large and calibration slope.MAIN RESULTS AND THE ROLE OF CHANCEFollowing exclusions, 49 314 women with 73 053 complete cycles were included. 12 408 (25.2%) had a live birth resulting from their second complete cycle. Cumulatively, 17 394 (35.3%) had a live birth over complete cycles two to four. The model showed moderate discriminative ability (c-statistic: 0.65, 95% CI: 0.64 to 0.65) and evidence of overprediction (calibration-in-the-large = −0.08) and overfitting (calibration slope 0.85, 95% CI: 0.81 to 0.88) in the validation cohort. However, after recalibration the fit was much improved. The recalibrated model identified the following key predictors of live birth: female age (38 versus 32 years—adjusted odds ratio: 0.59, 95% CI: 0.57 to 0.62), number of eggs retrieved in the first complete cycle (12 versus 4 eggs; 1.34, 1.30 to 1.37) and outcome of the first complete cycle (live birth versus no pregnancy; 1.78, 1.66 to 1.91; live birth versus pregnancy loss; 1.29, 1.23 to 1.36). As an example, a 32-year-old with 2 years of non-tubal infertility who had 12 eggs retrieved from her first stimulation and had a live birth during her first complete cycle has a 46% chance of having a further live birth from the second complete cycle of IVF and an 81% chance over a further three cycles.LIMITATIONS, REASONS FOR CAUTIONThe developed model was updated using validation data that was 6 to 12 years old. IVF practice continues to evolve over time, which may affect the accuracy of predictions from the model. We were unable to adjust for some potentially important predictors, e.g. BMI, smoking and alcohol intake in women, as well as measures of ovarian reserve such as antral follicle count. These were not available in the linked HFEA dataset.WIDER IMPLICATIONS OF THE FINDINGSBy appropriately adjusting for couples who discontinue treatment, our novel prediction model will provide more realistic chances of live birth in couples starting a second complete cycle of IVF. Clinicians can use these predictions to inform discussion with couples who wish to plan ahead. This prediction tool will enable couples to prepare emotionally, financially and logistically for IVF treatment.STUDY FUNDING/COMPETING INTEREST(S)This study was supported by an Elphinstone scholarship scheme at the University of Aberdeen and Aberdeen Fertility Centre, University of Aberdeen. The authors have no conflict of interest.TRIAL REGISTRATION NUMBERN/A.

The Application of Artificial Intelligence in Predicting Embryo Transfer Outcome of Recurrent Implantation Failure.

Background: Recurrent implantation failure (RIF) refers to that infertile patients have undergone multiple in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles and transferred multiple embryos without embryo implantation or clinical pregnancy. Due to the lack of clear evidence-based medical guidelines for the number of embryos to be transferred in RIF patients, how to obtain the highest single cycle pregnancy success rate with as few embryos transferred as possible while avoiding multiple pregnancy as much as possible, that is, how to balance the pregnancy success rate and multiple pregnancy rate, is a great challenge for clinicians and RIF patients. We urgently need an effective and reliable assisted decision-making method to help clinicians find this balance, and an artificial intelligence (AI) system will provide an efficient solution. Design and Methods: In this research, we filtered out the RIF data set (n = 45,921) from the Human Fertilisation and Embryology Authority (HFEA) database from 2005 to 2016. The data set was divided into two groups according to the number of embryos transferred, Group A and B. Group A included 34,175 cycles with two embryos transferred, while Group B included 11,746 cycles with only one embryo transferred, each containing 44 features and a prediction label (pregnancy). Four machine learning algorithms (RF, GBDT, AdaBoost, and MLP) were used to train Group A and Group B data set respectively and 10-folder cross validation method was used to validate the models. Results: The results revealed that the AdaBoost model of Group A obtained the best performance, while the GBDT model in Group B was proved to be the best model. Both models had been proved to provide accurate prediction of transfer outcome. Conclusion: Our research provided a new approach for targeted and personalized treatment of RIF patients to help them achieve efficient and reliable pregnancy. And an AI-assisted decision-making system will be designed to help clinicians and RIF patients develop personalized transfer strategies, which not only guarantees efficient and reliable pregnancy, but also avoids the risk of multiple pregnancy as much as possible.

O-297 Does advanced paternal age influence live birth rate independent of woman’s age: analysis of 18, 825 fresh IVF/ICSI cycles from a national (HFEA) database

Abstract Study question Does advanced paternal age (APA) impact live birth rates (LBRs) in IVF/ICSI treatment independent of female partner’s age? Summary answer LBRs decline with paternal age ≥40 years, but not when female partner is &amp;lt; 35 or ≥ 40 years. What is known already APA, particularly over 40 years, has been shown to be associated with declining sperm parameters, impaired embryo development, aneuploidy, compromised pregnancy outcomes and mental health abnormalities in the offspring in IVF/ICSI cycles. However, no significant effect of APA on pregnancy outcomes has been noted in donor oocyte cycles, indicating possible positive effect of female age counteracting negative male age-related IVF/ICSI outcomes. Data on whether female and male age influence each other, or are independently related to LBR, are limited and inconclusive. Study design, size, duration Retrospective analysis of 18, 825 autologous IVF or ICSI with fresh single embryo transfer (SET) cycles from the UK’s national anonymised registry, published online by the Human Fertilisation and Embryology Authority (HFEA). Study period: 2 years starting from 1st January 2017 to 31st December 2018. Participants/materials, setting, methods Couples underwent IVF/ ICSI with fresh SET due to unexplained or tubal infertility. Cycles with male factor, donor sperm and preimplantation genetic testing were excluded. Female age was grouped to &amp;lt; 35 years, 35-39 years and 40-44 years; male age to &amp;lt; 35 years (control group), 35-39 years, 40-44 years, 45-50 years, 51-55 years and &amp;gt;55 years. Chi-square to compare binominal data; multiple logistic regression to find correlation of male and female age on LBR adjusting confounders. Main results and the role of chance Overall, LBR per SET declined from 39.1% in men &amp;lt;35 years (control group) to 25.9% (p &amp;lt; 0.0001), 23.0% (p &amp;lt; 0.0001), 22.9% (p &amp;lt; 0.0001) and 25.4% (p = 0.002) in 40-44, 45-50, 51-55 and &amp;gt;55 years, respectively. However, in the subgroups of women &amp;lt;35 years, the LBRs were no different whether men were of &amp;lt; 35 (41.3%), 40-45 (40.8%) or &amp;gt; 55 (41.7%) years. Similar trend was observed in women aged 40-44 years: LBRs were 12.3%, 11.9%, and 17.4% in men aged &amp;lt;35, 40-44, and &amp;gt;55 year, respectively. Only in women aged 35-40 years, LBRs dropped from 32.8% in men aged &amp;lt;35 years down to 27.9% (p = 0.004), 28.1% (p = 0.04), 28.7% (p = 0.33) and 25% (p = 0.22) in 40-44, 45-50, 51-55 and &amp;gt;55 years, respectively. The findings remained the same with ICSI only cycles. Individually, male age, female age, treatment-type (IVF or ICSI) and day of transfer were significantly correlated with LBR. Overall, after adjusting for confounders, both male (p = 0.01) and female’s age (p &amp;lt; 0.0001) remained independently related to LBRs.; male age did not correlate with LBRs in women aged &amp;lt;35 years or 40-44 years. Limitations, reasons for caution Information on ovarian reserve and treatment protocols were not available. However, this may have little impact, given large population studied. Exclusion of male infertility might have reduced the ‘effect-size’ but was important to eliminate non-age-related male factors, in order to assess only men’s age on the pregnancy outcome. Wider implications of the findings Oocytes in women &amp;lt;35 appear to reduce the negative impact of older sperm on LBR, but not in women 35-39 years of age. This is useful information when counselling couples and in fertility education setting. Further research is needed to clarity the mechanism underlying our findings. Trial registration number Does advanced paternal age influence live birth rate independent of woman’s age: analysis of 18, 825 fresh IVF/ICSI cycles from a national (HFEA) database

P-761 Perinatal outcomes following blastocyst versus cleavage-stage transfer of fresh embryos: an updated analysis of UK national data

Abstract Study question Are there differences in perinatal outcomes in singleton live births following transfer of fresh embryos at blastocyst versus cleavage-stage? Summary answer In singleton live births arising from fresh embryos, blastocyst transfer is not associated with higher perinatal risks than cleavage-stage transfer. What is known already Extended culture involves prolonged exposure to culture media. Although blastocyst transfer is currently the default strategy for many fertility clinics, there is a paucity of perinatal data from randomised trials. Previous observational research, including an earlier analysis of United Kingdom (UK) national data (up to 2012) by our group, has been suggestive of increased perinatal risks following blastocyst transfer. As laboratory practices have continued to evolve over time, we felt it was important to address this question again using more contemporary data (up to 2018) which have been recently made available by the UK Human Fertilisation and Embryology Authority (HFEA). Study design, size, duration A retrospective cohort study was undertaken using anonymised HFEA data on all fresh in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) cycles resulting in a singleton live birth (127,632) between 1999 and 2018. Perinatal outcomes were compared in babies conceived from the transfer of fresh embryos which were either at cleavage-stage (2-3 days of culture) or blastocyst-stage (5-6 days). Participants/materials, setting, methods All IVF/ICSI cycles resulting in singleton live births following the transfer of fresh blastocysts or cleavage-stage embryos were included. Logistic regression was used to calculate adjusted risk ratios (aRRs) with 95% confidence intervals (CIs) for perinatal outcomes including a healthy baby (term delivery, normal birth weight, no congenital anomalies) following either blastocyst or cleavage-stage transfer. Outcomes were separately compared in women who had a singleton live birth after their first fresh cycle of IVF/ICSI. Main results and the role of chance Of 127,632 singleton live births, 54,688 occurred after blastocyst transfer while 72,944 resulted from cleavage-stage transfer. The corresponding numbers in 64,812 women who underwent their first cycle of IVF/ICSI were 25,452 (blastocyst) and 39,360 (cleavage-stage). Outcomes following blastocyst and cleavage-stage transfer were comparable in terms of low birth weight (7.2% vs. 7.5%, aRR 0.98, 95% CI 0.93-1.05), very low birth weight (1.7% vs. 1.8%, aRR 0.95, 95% CI 0.82-1.10), high birth weight (6.4% vs. 7.3%, aRR 0.98, 95% CI 0.92-1.04), very high birth weight (1.2% vs. 1.4%, aRR 0.99, 95% CI 0.87-1.14), very preterm birth (1.7% vs. 1.7%, aRR 1.04, 95% CI 0.92-1.17) and congenital anomalies (0.6% vs. 2.5%, aRR 0.93, 95% CI 0.80-1.08). These findings were confirmed in the sensitivity analysis involving women undergoing their first fresh embryo transfer. In the general population, the risk of preterm birth was higher following blastocyst transfer (7.7% vs. 7.3%, aRR 1.07, 95% CI 1.01-1.13) but this difference was not maintained in the sensitivity analysis (aRR 1.05, 95% CI 0.96-1.14). The chance to deliver a healthy singleton was similar across both groups in both primary cycle-based analysis (aRR 1.00, 95% CI 0.98-1.02) and sensitivity analysis (aRR 1.00, 95% CI 0.97-1.02). Limitations, reasons for caution The primary analysis was unable to discriminate between cycles and women or to adjust for clustering of women within cycles. Data were unavailable for some key confounders (body mass index, smoking status, previous medical history and complications during pregnancy). Wider implications of the findings While our findings provide some reassurance to patients undergoing blastocyst transfer, the limitations of the current study mean that further research is needed using women based rather than cycle based data. Trial registration number not applicable