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.

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

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

Embryologist agreement when assessing blastocyst implantation probability: is data-driven prediction the solution to embryo assessment subjectivity?

STUDY QUESTION: What is the accuracy and agreement of embryologists when assessing the implantation probability of blastocysts using time-lapse imaging (TLI), and can it be improved with a data-driven algorithm? SUMMARY ANSWER: The overall interobserver agreement of a large panel of embryologists was moderate and prediction accuracy was modest, while the purpose-built artificial intelligence model generally resulted in higher performance metrics. WHAT IS KNOWN ALREADY: Previous studies have demonstrated significant interobserver variability amongst embryologists when assessing embryo quality. However, data concerning embryologists' ability to predict implantation probability using TLI is still lacking. Emerging technologies based on data-driven tools have shown great promise for improving embryo selection and predicting clinical outcomes. STUDY DESIGN, SIZE, DURATION: TLI video files of 136 embryos with known implantation data were retrospectively collected from two clinical sites between 2018 and 2019 for the performance assessment of 36 embryologists and comparison with a deep neural network (DNN). PARTICIPANTS/MATERIALS, SETTING, METHODS: We recruited 39 embryologists from 13 different countries. All participants were blinded to clinical outcomes. A total of 136 TLI videos of embryos that reached the blastocyst stage were used for this experiment. Each embryo's likelihood of successfully implanting was assessed by 36 embryologists, providing implantation probability grades (IPGs) from 1 to 5, where 1 indicates a very low likelihood of implantation and 5 indicates a very high likelihood. Subsequently, three embryologists with over 5 years of experience provided Gardner scores. All 136 blastocysts were categorized into three quality groups based on their Gardner scores. Embryologist predictions were then converted into predictions of implantation (IPG ≥ 3) and no implantation (IPG ≤ 2). Embryologists' performance and agreement were assessed using Fleiss kappa coefficient. A 10-fold cross-validation DNN was developed to provide IPGs for TLI video files. The model's performance was compared to that of the embryologists. MAIN RESULTS AND THE ROLE OF CHANCE: Logistic regression was employed for the following confounding variables: country of residence, academic level, embryo scoring system, log years of experience and experience using TLI. None were found to have a statistically significant impact on embryologist performance at α = 0.05. The average implantation prediction accuracy for the embryologists was 51.9% for all embryos (N = 136). The average accuracy of the embryologists when assessing top quality and poor quality embryos (according to the Gardner score categorizations) was 57.5% and 57.4%, respectively, and 44.6% for fair quality embryos. Overall interobserver agreement was moderate (κ = 0.56, N = 136). The best agreement was achieved in the poor + top quality group (κ = 0.65, N = 77), while the agreement in the fair quality group was lower (κ = 0.25, N = 59). The DNN showed an overall accuracy rate of 62.5%, with accuracies of 62.2%, 61% and 65.6% for the poor, fair and top quality groups, respectively. The AUC for the DNN was higher than that of the embryologists overall (0.70 DNN vs 0.61 embryologists) as well as in all of the Gardner groups (DNN vs embryologists-Poor: 0.69 vs 0.62; Fair: 0.67 vs 0.53; Top: 0.77 vs 0.54). LIMITATIONS, REASONS FOR CAUTION: Blastocyst assessment was performed using video files acquired from time-lapse incubators, where each video contained data from a single focal plane. Clinical data regarding the underlying cause of infertility and endometrial thickness before the transfer was not available, yet may explain implantation failure and lower accuracy of IPGs. Implantation was defined as the presence of a gestational sac, whereas the detection of fetal heartbeat is a more robust marker of embryo viability. The raw data were anonymized to the extent that it was not possible to quantify the number of unique patients and cycles included in the study, potentially masking the effect of bias from a limited patient pool. Furthermore, the lack of demographic data makes it difficult to draw conclusions on how representative the dataset was of the wider population. Finally, embryologists were required to assess the implantation potential, not embryo quality. Although this is not the traditional approach to embryo evaluation, morphology/morphokinetics as a means of assessing embryo quality is believed to be strongly correlated with viability and, for some methods, implantation potential. WIDER IMPLICATIONS OF THE FINDINGS: Embryo selection is a key element in IVF success and continues to be a challenge. Improving the predictive ability could assist in optimizing implantation success rates and other clinical outcomes and could minimize the financial and emotional burden on the patient. This study demonstrates moderate agreement rates between embryologists, likely due to the subjective nature of embryo assessment. In particular, we found that average embryologist accuracy and agreement were significantly lower for fair quality embryos when compared with that for top and poor quality embryos. Using data-driven algorithms as an assistive tool may help IVF professionals increase success rates and promote much needed standardization in the IVF clinic. Our results indicate a need for further research regarding technological advancement in this field. STUDY FUNDING/COMPETING INTEREST(S): Embryonics Ltd is an Israel-based company. Funding for the study was partially provided by the Israeli Innovation Authority, grant #74556. TRIAL REGISTRATION NUMBER: N/A.

Does advanced paternal age affect outcomes following assisted reproductive technology? A systematic review and meta-analysis.

Infertility affects more than 14% of couples, 30% being caused by male factor infertility. This meta-analysis includes 28 studies, selected according to PRISMA guidelines. Data were extracted from these studies to collate cycles separating paternal age at 30, 35, 40, 45 and 50 years (±1 year). Primary outcomes of interest were clinical pregnancy, live birth and miscarriage rates. Secondary outcomes were the number of fertilized eggs, cleavage-stage embryos and blastocysts, and embryo quality per cycle. Fixed-effects and random-effects models giving pooled odds ratios (OR) were used to assess the effect of paternal age. This meta-analysis included a total 32,484 cycles from 16 autologous oocyte studies and 12 donor oocyte studies. In autologous cycles, a statistically significant effect of paternal age <40 years was noted in clinical pregnancy (OR 1.65, 95% confidence interval [CI] 1.27-2.15), live birth (OR 2.10, 95% CI 1.25-3.51) and miscarriage (OR 0.74, 95% CI 0.57-0.94) rates. Paternal age <50 years significantly reduced miscarriage rate (OR 0.68, 95% CI 0.54-0.86), and increased blastocyst rate (OR 1.61, 95% CI 1.08-2.38) and number of cleavage-stage embryos (OR 1.67, 95% CI 1.02-2.75) in donor oocyte cycles, where maternal age is controlled. This is an important public and societal health message highlighting the need to also consider paternal age alongside maternal age when planning a family.

Live birth rate following a euploid blastocyst transfer is not affected by double vitrification and warming at cleavage or blastocyst stage.

PURPOSE: To compare reproductive outcomes following a euploid embryo transfer, between those embryos vitrified-warmed twice to those vitrified-warmed once. METHODS: We retrospectively analysed 694 single euploid frozen embryo transfer cycles following preimplantation genetic testing for aneuploidy (PGT-A). For cycles in group 1 (N = 451), embryos were biopsied for PGT-A at blastocyst stage and vitrified. For cycles in group 2 (N = 146), embryos were vitrified at blastocyst stage, before being warmed and biopsied for PGT-A and vitrified again. For cycles in group 3 (N = 97), embryos were vitrified on day-3, before being warmed, cultured to day-5 and biopsied for PGT-A and re-vitrified. RESULTS: The pregnancy, clinical pregnancy and livebirth rate in group 2 were not statistically different to group 1 (pregnancy rate, adjusted OR 1.09, 95% CI 0.62-1.91; clinical pregnancy, aOR 0.89, 95% CI 0.58-1.37; live birth rate, aOR 0.85, 95% CI 0.56-1.28). There was also no significant difference between group 3 and group 1, with similar pregnancy rate (aOR 1.22, 95% CI 0.74-1.99), clinical pregnancy rate (aOR 1.21, 95% CI 0.75-1.96) and live birth rate (aOR 1.15, 95% CI, 0.73-1.80). There was no significant difference in miscarriage rates between all three groups. The age at the oocyte collection, embryo quality and day of biopsy were associated with pregnancy, clinical pregnancy and live birth rate. CONCLUSION: This study suggests that vitrifying and warming embryos twice at blastocyst or at cleavage and then blastocyst stage, can lead to similar reproductive outcomes to embryos vitrified-warmed once, after a single euploid embryo transfer.

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

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

Adding a low-quality blastocyst to a high-quality blastocyst for a double embryo transfer does not decrease pregnancy and live birth rate.

INTRODUCTION: The effect of embryo quality on clinical outcomes of assisted reproductive technology following a double transfer is not well defined, with some studies suggesting that a low-quality embryo transferred with a high-quality embryo decreases the live birth rate (LBR), compared with transferring a single high-quality embryo. Our study examined whether the quality of a second blastocyst transferred affects the outcome, controlling for the number of the available high-quality blastocysts (HQB). MATERIAL AND METHODS: A historical cohort study of 2346 fresh blastocyst transfers in a single fertility clinic between 2013 and 2019. The main outcomes were pregnancy, miscarriage, live birth, and multiple gestation rates. Outcomes were compared between single embryo transfers with a high-quality blastocyst (SET-H), double embryo transfers with two HQBs (DET-HH), and transfers with one high-quality and one low-quality blastocyst (DET-HL). Outcomes were also assessed between SET and DET when only low-quality blastocysts were available. RESULTS: With one HQB available, DET-HL increased LBR (adjusted odds ratio [OR] 1.65, 95% CI 1.09-2.49) compared with SET-H, but increased multiple gestation rate (aOR 23.1, 95% CI 3.0-177.6). With two HQBs available, DET-HH was associated with a higher LBR (aOR 1.62, 95% CI 1.28-2.04) and lower miscarriage rate (aOR 0.56, 95% CI 0.40-0.80), but very high twin rate (aOR 49.8, 95% CI 24.3-102.1) compared with SET-H. A SET-H with at least one or more HQB available to freeze, compared with a SET-H with no other HQB available, had a higher LBR (aOR 1.69, 95% CI 1.17-2.45). When there were no HQBs available, compared with SET-L, a DET-LL had a higher live birth (aOR 3.20, 95% CI 1.78-7.703) and twin rate (aOR 3.72 × 1010 ) and a lower miscarriage rate (aOR 0.24, 95% CI 0.10-0.58). CONCLUSIONS: When there is one HQB available, transferring an additional low-quality blastocyst would only slightly increase the LBR, but significantly increase the twin rate, therefore SET should be recommended. When two or more HQBs are available, SET-H would have a reasonably good chance of success without the very high twin rate associated with DET-HH. DET-LL when compared with SET-L, would increase the LBR, but increase the risk of multiple gestation.

Perceptions, outcomes, and regret following social egg freezing in the UK; a cross-sectional survey.

INTRODUCTION: Social egg freezing enhances reproductive autonomy by empowering women with the capacity to delay their childbearing years, while preserving the opportunity to maintain biological relation with subsequent offspring. However, age-related obstetric complications, economic implications and the risk of unsuccessful future treatment make it a controversial option. Despite the upward trend in women electively cryopreserving their eggs, there is limited data about the women's perceptions, having undergone the process. The aim of this study was to investigate the motivations of women who have undergone social egg freezing, identify their perceptions following treatment, and assess potential feelings of regret. MATERIAL AND METHODS: This cross-sectional survey, based at a fertility clinic in the UK, used an electronic questionnaire to assess the motivations and perceptions of women who underwent social egg freezing between 1 January 2008 and 31 December 2018. RESULTS: One hundred questionnaires were distributed, and 85 women responded (85% response rate). The most frequent reason for freezing oocytes was not having a partner with 56 (70%) women saying it "definitely" influenced their decision. The majority of women (83%; n = 68) knew there was a chance of treatment failure in the future and that a live birth could not be guaranteed. More than half (n = 39; 51%) disagreed or strongly disagreed that the 10-year UK storage limit is fair. One-third of respondents (n = 17; 33%) felt the storage time should be indefinite and 29% (n = 15) believed it should be up to the age of 50. Twenty percent (n = 15) of the women who underwent social egg freezing have successfully had a baby or are currently pregnant, half (n = 8; 53%) of whom conceived spontaneously and a quarter (n = 4; 26%) used their stored oocytes. In all, 91% (n = 73) had no regrets over their decision to undergo social egg freezing. CONCLUSIONS: We demonstrate herein important and novel insights into the motivations and perceptions of women from a UK population who have undergone social egg freezing. Despite potential physical, psychological, and financial burdens, only a small minority of women experience regret after social egg freezing. We also highlight clear discontent with the Human Fertilisation & Embryology Authority storage limit among social egg freezers in the UK.

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

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

The dawn of a new ice age: social egg freezing.

Given the age-related decline in ovarian reserve and oocyte quality, it is unsurprising the global trend of deferring motherhood has resulted in increased levels of involuntary childlessness. The development of oocyte vitrification, with pregnancy and livebirth rates now comparable to using fresh oocytes, has provided an opportunity to cryopreserve oocytes electively for future use, empowering women with the capacity to delay their childbearing years. While it enhances reproductive autonomy, age-related obstetric complications, economic implications and the risk of unsuccessful future treatment make this a controversial therapeutic option. However, some women have no reasonable alternative, such as single women approaching their late thirties, in whom egg freezing, although not a guarantee against involuntary childlessness, offers hope by extending the window of opportunity to find a partner. Given the upward trend in women electively cryopreserving their eggs, it would appear that a new ice age, from a fertility perspective, is upon us.

Karyomapping: a single centre's experience from application of methodology to ongoing pregnancy and live-birth rates.

This study aimed to determine whether karyomapping can be applied to couples requiring preimplantation genetic diagnosis (PGD) for single gene disorder (SGD) and/or chromosomal rearrangement. 75/82 (91.5%) and 6/82 (7.3%) couples were referred for autosomal SGD and X-linked disease, respectively. One couple (1.2%) was referred for SGD and chromosomal rearrangement. Of 608 embryos, 146 (24%, 95% CI 21-28) day-3 and 462 (76%, 95% CI 72-79) blastocyst biopsies were performed. A total of 81 embryo transfers were performed; 16/81 (20%) were following day-3 embryo biopsy, 65/81 (80%) were following blastocyst biopsy and cryopreserved embryo transfer. Of 81 embryo transfers with known pregnancy outcome, 51 (63%, 95% CI 52-73) were on-going pregnancies, 6/81 (7%, 95% CI 3-15) resulted in first trimester miscarriages and 24/81 (30%, 95% CI 21-40) were failed implantations. Of the 51 on-going pregnancies, 15 (29%, 95% CI 19-43) couples had a singleton live birth at the time of write up. There have been no reports of abnormal prenatal, genetic testing or diagnosis of phenotype at birth. Karyomapping is reliable, efficient and accurate for couples requiring PGD for SGD and/or chromosomal rearrangement. Additionally, it provides aneuploidy screening, minimising risks of miscarriage and implantation failure.

Successful preimplantation genetic testing for fibrodysplasia ossificans progressiva: a case report.

PURPOSE OF THE STUDY: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant condition that leads to significant disability and morbidity, characterised by the formation of heterotopic hard tissues within connective tissues. The condition has an incidence of approximately one per two million people worldwide. There is no known single effective treatment available for FOP. We report the world's first case of a healthy infant born following in vitro fertilisation (IVF) and preimplantation genetic testing for monogenic disorder (PGT-M) using Karyomapping for FOP. CASE PRESENTATION: A 30-year-old Caucasian female with FOP presented with her partner seeking IVF with PGT-M to achieve a healthy pregnancy with an embryo unaffected by FOP. METHODS: The couple underwent IVF and PGT-M using Karyomapping as the testing method. A multi-disciplinary team approach was utilised in planning this case, considering the additional risks of oocyte retrieval, pregnancy and childbirth in women with FOP. MAIN FINDINGS: The oocyte retrieval was covered with a 5-day course of prednisolone to reduce the risk of a localised inflammatory reaction, which could result in subsequent heterotopic ossification. This was subsequently weaned down with reducing doses every two days. The patient underwent uncomplicated oocyte retrieval, yielding 12 mature oocytes. Following intracytoplasmic sperm injection (ICSI), ten zygotes having two pro-nuclei were cultured, and six underwent trophoectoderm biopsy and vitrification 5-6 days after retrieval. PGT-M via Karyomapping revealed four out of six (66.7%) of blastocysts were not carriers of the maternal high-risk FOP allele. In total, the patient had three separate embryo transfers. Pregnancy was achieved following the third frozen embryo transfer, which went to 37 weeks' gestation, and delivered by Caesarean section. The baby was born in excellent condition and is unaffected by FOP. CONCLUSION: IVF/ICSI and PGT-M using Karyomapping was successfully implemented to identify embryos carrying the high-risk FOP allele resulting in a healthy livebirth.

Impact of double trophectoderm biopsy on reproductive outcomes following single euploid blastocyst transfer.

OBJECTIVES: To study the effect of double trophectoderm biopsy on clinical outcomes following single euploid blastocyst transfer. STUDY DESIGN: Retrospective cohort study of 2046 single euploid frozen-thawed blastocyst transfers from January 2015 to June 2022 in a single centre. All patients undergoing a frozen-thawed embryo transfer (FTET) cycle with euploid blastocysts, biopsied for any indication, were included. The outcomes were compared for blastocysts which were biopsied and vitrified once (Group 1, n = 1684), biopsied once but vitrified twice (Group 2, n = 312) and biopsied and vitrified twice (Group 3n = 50). We adjusted for confounders and performed subgroup analysis for PGT-A, PGT-M and PGT-SR cycles. The primary outcome was live birth rate. Secondary outcomes included pregnancy, clinical pregnancy, birthweight and sex ratio. RESULTS: After adjusting for confounders (previous failed euploid implantations, embryo quality and day of biopsy), embryos which were biopsied twice had lower OR for clinical pregnancy (0.48, CI 0.26-0.88, p = 0.019) and for live birth (0.50 CI 0.27-0.92, p = 0.025) compared to controls. Embryos which were biopsied once but vitrified twice had no different ORs for all reproductive outcomes compared to controls. No significant difference was observed for neonatal birthweight or sex ratio amongst the three groups. This is a retrospective single centre study with inherent bias and results may not be transferable to all settings. CONCLUSION: This study is the largest to date assessing the outcomes of FTET cycles following double trophectoderm biopsy. The results are in keeping with the existing literature and can be incorporated into patient counselling. Whilst double biopsy seems to adversely impact LBR, it is only one of the many factors that can affect success rates. The subfertility background and embryo characteristics should not be overlooked. This study provides reassuring evidence since double biopsied embryos still result in live births with no difference in sex ratio or birthweight. However, long term follow up of the off-springs is lacking and should be reported in future studies.

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.

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.

Oocyte yield in social, medical and donor oocyte cryopreservation cycles.

To determine if oocyte yield in women undergoing cryopreservation for social (SOC), medical (MOC) and oocyte donation (OD) cycles is comparable when matched for age. 315 oocyte retrievals were performed for SOC, 116 for MOC and 392 for OD. Non-parametric Kruskal-Wallis tests and Poisson regression were used to assess the impact of age stratification. The median ages of women undergoing SOC, MOC, and OD were 38, 31 and 26 years respectively. The median (IQR) number of oocytes in the three categories was 7, 10, and 12. The oocyte yield was significantly higher in women aged 30-34 years undergoing SOC, compared to the MOC group. For the SOC group, age in years, oestradiol levels per 1000 pmol/and follicle count >12mm on the day of trigger were significant predictors of oocyte yield. Women embarking on SOC are significantly older than those undergoing MOC and OD, and thus oocyte yield is reduced when stratified for age. This study highlights the significant predictors of oocyte yield amongst women undergoing oocyte cryopreservation for specific indications. The findings can be used to optimise the yield and overall chance of successful livebirth.

The novel use of fertility quality of life (FertiQoL) treatment subscale to assess treatment acceptability in social egg freezing.

This is the first study to assess the impact of social egg freezing (SEF) on quality of life. This cross-sectional survey utilised the FertiQoL treatment module in women who underwent SEF between January 2008 and October 2019 (n = 94). The mean treatment score was 65.5, whereas the tolerability and environment scores were 62.4 and 68 respectively. Being married or in a relationship was associated with higher, albeit not statistically significant, scores (69.2) when compared to single women (66.3; p = 0.49). However, being separated or divorced was associated with significantly worse scores compared to married women, women in a relationship and single women (43.3 vs. 67.0; p = 0.001). There were no significant differences in scores between younger and older women, low and high number of oocytes stored, duration of stimulation cycles, or in those who had single or multiple cycles. These data suggest SEF is largely tolerable, with favourable FertiQoL scores compared to infertile women undergoing IVF. However, whilst such women are physiologically fertile, their situation renders them socially infertile. As such, women undergoing SEF should be identified as a population that requires additional support, who should be offered extensive counselling, active monitoring throughout the process and additional support if required.