Frozen Embryo Research Articles

P–590 Women with hypothalamic hypogonadism have lower live birth rates following frozen embryo transfer

Abstract Study question How do live birth rates differ in anovulatory women with polycystic ovary syndrome and hypothalamic hypogonadism compared to normo-ovulatory women undergoing fresh or frozen embryo transfer? Summary answer Live birth rates are similar among all groups undergoing fresh embryo transfer but are significantly lower in women with hypothalamic hypogonadism undergoing frozen embryo transfer. What is known already Conflicting data exist regarding pregnancy outcomes in patients with tubal factor infertility versus polycystic ovary syndrome (PCOS). Some studies demonstrate higher pregnancy and live birth rates for women with PCOS undergoing fresh embryo transfer, but other studies demonstrate no difference. Women with PCOS have higher live birth rates than those with tubal factor infertility when undergoing frozen embryo transfer. Fewer data are available regarding IVF outcomes in women with hypothalamic hypogonadism (HH) and tubal factor infertility. Several studies report comparable live birth rates with fresh embryo transfer, but there are no data on frozen embryo transfer outcomes. Study design, size, duration Retrospective cohort study of all fresh and frozen autologous embryo transfers performed for patients with oligo-anovulation (PCOS, n = 380 and HH, n = 39) and normo-ovulation (tubal factor infertility, n = 315) from 1/1/2012 to 6/30/2019. A total of 734 transfers from 653 patients were analyzed. Participants/materials, setting, methods Transfer outcomes, including implantation, miscarriage, clinical pregnancy and live birth rates, were assessed in fresh and frozen embryo transfer cycles. Adjusted relative risks (RR) and 95% confidence intervals (CI) were calculated adjusting for age, BMI, stimulation protocol, number of embryos transferred, embryo quality, endometrial stripe thickness and day of transfer. Poisson regression was used for counts and with an offset for ratios. Generalized estimating equations were used to account for patients contributing multiple cycles. Main results and the role of chance For fresh embryo transfer cycles, live birth rates are similar among patients with tubal factor infertility, PCOS and HH (29.5% vs. 37.9% vs. 35.9%, respectively, aRR 1.15 95% CI: 0.91–1.44 and aRR 1.23 95% CI: 0.81–2.00, respectively). When evaluating frozen embryo transfer cycles, patients with HH have lower live birth rates than patients with tubal factor infertility (26.5% vs. 42.6%, aRR 0.54 95% CI: 0.33–0.88) and patients with PCOS (26.5% vs. 46.7%, aRR 0.55 95% CI: 0.34–0.88). Additionally, patients with HH have higher chemical pregnancy rates and miscarriage rates than patients with tubal factor infertility (26.5% vs. 13.0% and 17.7% vs. 6.5%, respectively, RR 2.71 95% CI: 1.27–5.77 and RR 2.03 95% CI: 1.05–3.80, respectively). Point biserial correlation showed no significant correlation between live birth and endometrial stripe thickness in HH patients undergoing frozen embryo transfer (r = 0.028, p-value 0.876). Limitations, reasons for caution This study is limited by its retrospective nature and the small sample size of women with hypothalamic hypogonadism. Additionally, these data represent outcomes from a single academic center, so generalizability of our findings may be limited. Wider implications of the findings: Lower live birth rates for HH patients undergoing frozen embryo transfer cycles are not correlated with endometrial stripe thickness. This may be due to absent gonadotropin signaling on endometrial receptors. A prospective randomized trial of HH patients to modified natural versus programmed frozen embryo transfer would best support this hypothesis. Trial registration number Not applicable

P–781 Birthweight is not affected by freezing process. Results from a quasi-experimental study using the Oocyte Donation Model

Abstract Study question Is the freezing process responsible to increase the birthweight or the incidence of Large for Gestational Age (LGA) in Frozen Embryo Transfers (FET)? Summary answer Neither the birthweight nor the LGA incidence were different in embryos that underwent the freezing-thawing process. What is known already Freezing-thawing constitutes one of the processes with a potential impact on the health of the newborn. Data coming from register-based studies and metaanalisis have found an increase in birthweight with a higher incidence of LGA in newborns coming from FET. This is a matter of concern since epigenetic alterations have been suggested to explain this finding casting doubts on future health during childhood and adulthood. Clarifying the safety of cryotechniques should be a priority taken into account that at present frozen embryo transfers outnumber fresh embryo transfers in IVF clinics. Study design, size, duration This retrospective cohort study evaluated 670 women oocyte recipients who underwent fresh (367 cycles) or frozen embryo transfer (303 cycles) at Instituto Bernabeu between July 2017 and March 2019. All recipients were prepared with substitutive cycle and received single blastocyst embryo transfers on day five. All of them at the same culture medium, resulting in a singleton live birth. Participants/materials, setting, methods 1637 patients were assessed for eligibility but 967 were excluded. The sample size has been calculated accepting an alpha risk of 5% and a beta risk of 20%. A sample size of 266 patients (133 per group) is required to detect a minimum mean difference of 275 grams with a standard deviation of 800 grams. Pearsońs Chi-square test (univariate) and binary logistic regression (multivariate for confounding factors) were used to analyze association between variables. Main results and the role of chance Maternal age (42.21 ± 4.45; 42.79 ± 3.83 p = 0.519), BMI (23.34 ± 3.69; 24.99 ± 15.52; p = 0.060), maternal parity (Nulliparous 81.5%; 85.5%; Multiparous 18.5%; 14.5% p = 0.177), gestational diabetes (4.9%; 4.3% p = 0.854), preeclampsia (2.7%; 5.6% p = 0.074), hypertensive disorders (3.3%; 2.3% p = 0.494), maternal smoking (10.8%; 13.0% p = 0.475), gestational age (38.96 ± 1.97; 38.77 ± 2.15; p = 0.207) and liveborn gender (Female 44.5%; 48.8%; Male 55.5%; 51.2%p=0.276) do not present statistically significant differences between fresh or frozen groups, respectively. However endometrial thickness was statistically signiticantly different in both groups (8.83mm ± 1.73 fresh; 8.57mm ± 1.59 frozen p = 0.035) The mean birthweight did not present statistically significant differences (3239.21 ± 550.43 fresh; 3224.56 ± 570.83 frozen p = 0.211). There were also no differences regarding macrosomy (7.1% fresh; 6.3% frozen p = 0.317), LGA (6.0% fresh; 6.7% frozen p = 0.866), pre-term birth (10.9% fresh; 9.0% frozen p = 0.988), very pre-term birth (0.8% fresh; 1.3% frozen p = 0.999), and extremely pre-term birth (0% fresh; 1.0% frozen p = 0.998). There were statistically significant differences regarding underweight (10.0% fresh; 7.0% frozen p = 0.020), but there were no differences in very low weight (0.6 fresh; 1.1% frozen p = 0.972) and SGA (1.9% fresh; 0.7% frozen p = 0.432). Limitations, reasons for caution Despite a quasi-experimental design, the synchronization in fresh embryo transfer drove to a longer preparation with a thicker endometrium. It’s not possible to rule-out the influence in the results of this parameter. Wider implications of the findings: As a hypothesis, the increase in birthweight and/or an abnormal placentation in FET could be explained by the endometrial preparation more than the freezing process. Studies must be planned in the future to explore the possibility of changes in the birthweight between embryos transferred in natural vs artificial endometrial preparations. Trial registration number Not applicable

P–554 Reproductive risks and preimplantation genetic testing intervention for X-autosome translocation carriers

Abstract Study question For X-autosome translocation [t(X-A)] carriers, is it a more applicable preimplantation genetic testing (PGT) strategy, that distinguishing noncarrier from euploid/ balanced embryos and prioritized transfer? Summary answer Noncarrier and carrier embryos discrimination in PGT is an applicable strategy to avoid transferring genetic and reproductive risks to the offspring of t(X-A) carriers. What is known already Balanced t(X-A) is a specific reciprocal translocation, with a higher risk of detrimental phenotype and fertility issues compared to individuals with autosomal translocation. Alternative X-chromosome inactivation (XCI) is a specific pathogenic mechanism in this population. For carrier offspring of couples with t(X-A), the genetic counseling is challenged in both the prenatal and postpartum stages, because of the complexity and severity of phenotype outcomes that are unpredictable and associated with the complex XCI mechanism. Therefore, caution is necessary when designing a PGT strategy for couples with t(X-A). Study design, size, duration A retrospective study. We collected a 3-year-old girl with maternal translocation 46,X,t(X;1)(q28;p31.1) presenting with multiple congenital disabilities. Three couples with female t(X-A) carrier requesting for PGT. Participants/materials, setting, methods Karyotype analysis, whole-exome sequencing (WES), and X inactivation analysis were performed for the girl with congenital cardiac anomaly, language defect, and mild neurodevelopmental delay. PGT based on next-generation sequencing following the microdissecting junction region to distinguish noncarrier and carrier embryos were used in three couples with female t(X-A) carrier (Cases 1–3). Main results and the role of chance The girl carried a maternal balanced translocation 46,X,t(X;1)(q28;p31.1). WES revealed none monogenic mutation related to her phenotype, but she carried a rare skewed inactivation of the translocation X chromosome and spread to the adjacent interstitial 1p segment, contrary to her mother. All translocation breakpoints of Cases 1–3 were successfully identified and each couple underwent one PGT cycle. Thirty oocytes were retrieved, and 13 blastocysts were eligible for biopsy, of which 6 (46.15%) embryos were balanced and only 4 were noncarriers. Three frozen embryo transfers with noncarrier embryos resulted in the birth of two healthy children (one girl and one boy), who were subsequently confirmed to have normal karyotypes. We reported a girl with multiple congenital disabilities resulting from maternally balanced t(X-A) and validated that noncarrier and carrier embryo discrimination is an effective and applicable strategy for avoiding transferring genetic and reproductive risks to the offspring from t(X-A) carriers. Limitations, reasons for caution Here, we reported a girl with multiple congenital disabilities resulting from maternally balanced t(X-A) found different XCI patterns, while we did not further determine the mechanism causing the different XCI patterns between the girl and her mother. Wider implications of the findings: We demonstrated passing on a balanced t(X-A) may result in clinical manifestations associated with the X-inactivation, and verified the PGT strategy, that distinguishing normal and carrier embryos in can widely applied in t(X-A) carrier couples to avoid the genetic and reproductive risk of transferring t(X-A) to the next generation. Trial registration number the National Key Research & Developmental Program of China (2018YFC1004900), the National Natural Science Foundation of China (81771645 and 81971447), the Key Grant of Prevention and Treatment of Birth Defect from Hunan Province (2019SK1012), Hunan Provincial Grant for Innovative Province Construction (2019SK4012) and the Research Grant of CITIC-Xiangya (YNXM–201916).

O-001 Delay in IVF treatment up to 180 days does not affect pregnancy outcomes in women with diminished ovarian reserve

textIn clinical practice, infertility treatment delays can occur due to medical, logistical, or financial reasons. Concerns over treatment delays were brought to the forefront in March 2020 when the SARS-CoV-2 pandemic prompted both the ESHRE and ASRM to recommend the suspension of new infertility treatment cycles. At the time, little was known about the risk of viral transmission on reproductive health and necessary medical resources urgently needed to be reallocated to the front lines of the pandemic. These society recommendations were met with resistance from some clinicians and patients that raised valid concerns about whether delaying IVF treatment for a few months could negatively affect pregnancy outcomes.To help answer this question, we designed a retrospective cohort study to assess whether a delay up to 180 days in initiating IVF treatment affects pregnancy outcomes in infertile women with diminished ovarian reserve. This population was selected because their treatment outcomes were the most likely to affected by treatment delays due to the continuous decline in ovarian reserve over time. Infertile women treated at our IVF center were included if they had diminished ovarian reserve and started an ovarian stimulation cycle within 180 days of their initial consultation that resulted in an oocyte retrieval with planned fresh embryo transfer between 1 January 2012 and 31 December 2018. Diminished ovarian reserve was defined as an anti-Mŭllerian hormone (AMH) < 1.1 ng/mL.In total, 1,790 patients met inclusion criteria (1,115 immediate and 675 delayed treatment). Each patient had one included cycle and no subsequent data from additional frozen embryo transfer cycles were included. Since all cycle outcomes evaluated were from fresh embryo transfers, no genetically tested embryos were included. Patients were grouped by whether their cycle started 1-90 days after presentation (immediate) or 91-180 days (delayed). The primary outcome was live birth (≥24 weeks of gestation). A subgroup analysis of more severe forms of diminished ovarian reserve was performed to evaluate outcomes for patients with an AMH < 0.5 and for patients >40 years old with an AMH < 1.1 ng/mL (Bologna criteria for diminished ovarian reserve). Logistic regression analysis, adjusted a priori for patient age, was used to estimate the odds ratio (OR) with a 95% CI. All pregnancy outcomes were additionally adjusted for the number of embryos transferred.The mean ± SD number of days from presentation to IVF start was 50.5 ± 21.9 (immediate) and 128.8 ± 25.9 (delayed). After embryo transfer, the live birth rate was similar between groups (immediate: 23.9%; delayed: 25.6%; OR 1.08, 95% CI 0.85-1.38). Additionally, a similar live birth rate was observed in a subgroup analysis of patients with an AMH < 0.5 ng/mL (immediate: 18.8%; delayed: 19.1%; OR 0.99, 95% CI 0.65-1.51) and in patients >40 years old with an AMH < 1.1 ng/mL (immediate: 12.3%; delayed: 14.7%; OR 1.21, 95% CI 0.77-1.91).Overall, we observed that a delay in initiating IVF treatment up to 180 days does not affect the live birth rate for women with diminished ovarian reserve when compared to women who initiate IVF treatment within 90 days of presentation. This observation persisted for patients who in the highest-risk categories for poor response to ovarian stimulation. Providers and patients should be reassured that when a short-term treatment delay is deemed necessary for medical, logistical, or financial reasons, treatment outcomes will not be negatively affected.

P–520 Live birth rate with a euploid embryo is the same irrespective of the number of oocyte retrievals undertaken to produce a euploid embryo

Abstract Study question Does a euploid embryo from one ovarian stimulation lead to the same live birth rate as a euploid embryo arising from multiple ovarian stimulations? Summary answer The live birth rate of a euploid embryo transferred is comparable irrespective of the number of ovarian stimulations required. What is known already Embryo transfer of a euploid embryo leads to a high live birth rate. Women with low ovarian reserve or poor responders may not have a euploid embryo from one cycle of ovarian stimulation and can be discouraged from undergoing preimplantation genetic testing for aneuploidy (PGT-A). Embryo batching from multiple cycles offers such patients a potential solution to increase their chance of achieving a euploid embryo. Study design, size, duration A retrospective analysis of 506 cycles of single euploid frozen embryo transfers (FET) from January 2015 to March 2020 was carried out. The indication for PGT-A was advanced maternal age, recurrent miscarriages or repetitive IVF failures. Only the first single euploid FETs per patient were included. Participants/materials, setting, methods Group A (N = 323) included women who had a normal ovarian reserve and only one cycle of ovarian stimulation before the FET, whilst Group B (N = 183) had low ovarian reserve or previous poor ovarian response requiring 2 or more cycles of ovarian stimulation. All embryos were biopsied at the blastocyst stage and subjected to a-CGH or NGS. Univariate statistical analysis with Chi-square or Wilcox Man U as required and multivariate logistic regression was performed with SPSS. Main results and the role of chance Group A and Group B were comparable in terms of BMI (average 22.3 vs 22.6), sperm origin, number of blastocysts biopsied (median N = 6, range 4–8), day 5 vs day 6 biopsy (day 5, 81.1% vs 75.4%, p = 0.130) and whether only one euploid embryo was available (42% vs 34%; p = 0.103). There was a significant difference in the number of eggs retrieved per cycle between the two groups (median 15 vs 9, p &amp;lt; 0.001), the total number of eggs retrieved (median 15 vs 20, p &amp;lt; 0.001) and whether a top-quality embryo was transferred (38% vs 25%, p = 0.026). Pregnancy rate, live birth rate and pregnancy loss was equivalent for both groups: 69.3% (224/323) vs 63.9% (178/183) (p = 0.212), 57.6% (186/323) vs 57.4% (105/183) (p = 0.096) and 17.0% (38/224) vs 10.3% (12/117) (p = 0.964), respectively. Multivariate logistic regression was performed to ascertain the effect of the treatment variables on the live birth rate. The number of oocyte collections was not a significant predictive factor (OR 1.19, 95% CI 0.72 - 1.96, p = 0.491), whilst an embryo biopsy performed on day 5 vs day 6, increased significantly the live birth rate (OR 2.58, 95% CI 1.61 - 4.13, p &amp;lt; 0.001). Limitations, reasons for caution The main limitation of this study is that it is retrospective, single centre and therefore vulnerable to confounding factors and bias. Wider implications of the findings: These results can be used to counsel and reassure women with poor response embarking on embryo batching and PGT-A that should a euploid embryo become available, their chance of success is unaffected by the number of cycles they undertake albeit the physical, emotional and financial burden of multiple ovarian stimulations Trial registration number Not applicable

P–649 Should women receive luteal support following natural cycle frozen embryo transfer? A systematic review and meta-analysis

Abstract Study question Should women receive luteal phase support (LPS) following natural cycle frozen embryo transfer (NC-FET)? Summary answer Progesterone LPS following NC-FET increases the live birth rate. There is no evidence to support the administration of hCG for LPS in these cases. What is known already Whether or not women should receive LPS following NC-FET is highly controversial. Previous studies have shown conflicting results. Study design, size, duration We conducted a systematic search of the literature published in Medline/PubMed, Embase and the Cochrane Library, from January 2000 until December 2020. We included all original English, peer-reviewed articles, irrespective of study-design. The search strategy included keywords related to natural cycle frozen embryo transfer and luteal phase support. Studies reporting the results of artificial or stimulated FET cycles were excluded. Participants/materials, setting, methods Our systematic search generated 395 records. After screening, eight studies were included in the review and seven studies were included in the meta-analysis. Two studies (n = 858) used hCG, and 6 studies (n = 1507) used progesterone for luteal support. Four studies were randomized controlled trials (RCTs), whereas the other four were historic cohort studies. Main results and the role of chance In a meta-analysis using random effects model, hCG administration for LPS did not increase the clinical pregnancy rate (two studies, OR 0.85, 95% CI 0.64–1.14). On the other hand, progesterone LPS was associated with a higher clinical pregnancy rate (five studies, OR 1.48, 95% CI 1.14–1.94), and a higher live birth rate (three studies, OR 1.67, 95% CI 1.19–2.36). Limitations, reasons for caution There was large heterogeneity in progesterone dose and route of administration, as well as the methods used for ovulation detection and triggering. Moreover, only four studies were randomized. Finally, both studies examining the use of hCG for LPS were performed by the same group of researchers in a single center. Wider implications of the findings: The available evidence indicates that progesterone administration for LPS is beneficial following natural cycle frozen embryo transfer. There is no evidence to support the administration of hCG for LPS in these cases. Additional Large RCTs are necessary in order to improve the quality of evidence and validate our findings. Trial registration number PROSPERO ID: CRD42020199045

P–682 Serum progesterone level as prognostic factor in frozen-thawed embryo transfer cycles: effect of selected threshold on gestational results. Systematic review, stratified meta-analysis and meta-regression

Abstract Study question Is there an optimum progesterone threshold level below which gestational results are significantly worse in frozen embryo transfer cycles (FET) with hormone replacement therapy (HRT)? Summary answer Low serum progesterone during luteal phase of HRT-FET cycles impairs substantially its gestational outcomes, regardless of threshold level, origin of oocytes and euploidy of embryos. What is known already HRT for endometrial preparation in FET or oocyte donation cycles is widely used. Oestrogen doses are usually patient-tailored varying upon endometrial thickness, whereas the optimal level of progesterone exposure has not been defined. Various studies have found a negative association between serum progesterone levels measured during luteal phase and FET results in terms of pregnancy and miscarriage rates. Most likely there is an optimal level below which results are worse but a standard threshold level is yet to be established, as in almost every study a different threshold has been found. Study design, size, duration Systematic review and stratified meta-analysis with meta-regression following PRISMA guidelines. An electronic search of MEDLINE, EMBASE, Web of Science, Cochrane Gynaecology and Fertility Specialised Register of Controlled Trials and ClinicalTrials.gov was conducted from inception to January 2021. The aim was to identify prospective or retrospective cohort studies measuring serum progesterone levels around frozen embryo transfer date in HRT cycles. A combination of the following key search terms was used: “progesterone”, “serum”, “frozen embryo”, “transfer”, “frozen-thawed”. Participants/materials, setting, methods Studies analyzing association of luteal serum progesterone with FET-HRT outcomes were included. Risk of bias within studies was assessed using the Newcastle-Ottawa Scale (NOS). Clinical/ongoing pregnancy and miscarriage rates (C/OPR,MR) were considered as primary and secondary outcomes respectively. Odds Ratios with 95% Confidence Interval (OR,95%CI) were calculated applying a random effects model meta-analysis. Heterogeneity was assessed using the I2 statistic. A meta-regression was conducted to examine the association of the effect with the threshold level. Main results and the role of chance The systematic search retrieved 792 studies, 494 after duplicates removal of which 343 were screened and 51 assessed for eligibility. 12 studies, reporting 14 threshold levels, were included in the meta-analysis involving 5009 HRT-FET cycles. Two of them were prospective cohort studies while the rest were retrospective. 10 of them have been published in peer review journals and two were conference abstracts. Quality of studies assessed with NOS varied between 5 and 9. The progesterone threshold ranged from 5.0 to 21.94 ng/ml. Low progesterone levels were associated with less C/OPR (OR: 0.52; 95% CI: 0.40 to 0.66; 11 studies, 5009 cycles). Low progesterone was also associated with high MR (OR: 2.01; 95% CI: 1.57 to 2.58; 9 studies, 2560 pregnancies). These effects showed remarkable consistency in specific sub-analyses considering separately studies with progesterone thresholds up to or above 10 mg/mL, and studies carried out in cycles using oocyte donation, autologous oocytes and embryo aneuploidies screening. Meta-regression did not identify significant association between size effect and progesterone threshold, regarding neither C/OPR (regression coefficient: 0.02; CI 95%: –0.02 to 0.06; p: 0.28) nor MR (regression coefficient: 0.11; CI 95%: –0.13 to 0.36; p: 0.32). Limitations, reasons for caution High degree of clinical and statistical heterogeneity was found due to different routes and doses of progesterone administration, date of progesterone analyses and variety of thresholds as well as high diversity of embryo origin. Despite sensibility analysis by embryo origin any of these sources of heterogeneity can preclude the results. Wider implications of the findings: Despite low progesterone levels are significantly associated to lower gestational results, and a threshold of 10 ng/ml constitutes the median value of our distribution, high quality prospective studies are needed to validate the prognostic value of progesterone levels and to establish an standardised threshold level for clinical application. Trial registration number not required

P-295 Does endometriosis affect oocyte quality? An analysis of 13 627 donor oocyte recipient and autologous IVF cycles

Abstract Study question Does endometriosis affect live birth following donor oocyte recipient versus autologous in vitro fertilisation (IVF) cycle. Summary answer There was no significant difference in the live birth rate (LBR) in women with endometriosis undergoing donor oocyte recipient versus autologous IVF cycle. What is known already For infertile women with endometriosis, IVF is often considered as a treatment option. Lower implantation and pregnancy rates have been observed following IVF in women with endometriosis when compared to tubal factor infertility. It has been debated that lower pregnancy rates following IVF in endometriosis is due to both oocyte quality and the endometrium. To delineate whether endometriosis affects oocyte quality or the endometrium, we planned a study using donor oocyte recipient model where the recipient were women with endometriosis. We compared the LBR after oocyte recipient cycle with autologous IVF in women with endometriosis Study design, size, duration We obtained anonymised dataset of all the IVF cycles performed in the UK since 19991 from the Human Fertilization and Embryology Authority (HFEA). Data from 1996 to 2016 comprising a total of 13 627 donor oocyte recipient and autologous IVF cycles with endometriosis and no other cause of infertility were analysed. Participants/materials, setting, methods Data on all women with endometriosis undergoing fresh or frozen IVF treatment cycles were analysed to compare the LBR between donor oocyte recipient and autologous treatment cycles. Logistic regression analysis was performed adjusting for number of previous IVF cycles, previous live birth, period of treatment, day of embryo transfer, number of embryo transferred, fresh and frozen cycle. Main results and the role of chance There was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient fresh cycles compared to women undergoing fresh autologous IVF cycles (31.6% vs. 31.0%; odds ratio, OR 1.03, 99% CI 0.79 – 1.35). After adjusting for confounders listed above, there was no significant difference in LBR in women undergoing donor oocyte recipient fresh cycles versus fresh autologous ART cycles (aOR 1.06, 99% CI 0.79 – 1.42). There was no significant difference in the LBR in women with endometriosis undergoing frozen donor oocyte recipient cycles compared to women undergoing autologous frozen embryo transfer cycles (19.6% vs. 24.0%; OR 0.77, 99% CI 0.47 - 1.25). After adjusting for potential confounders, there was no significant difference in the LBR in women undergoing frozen donor oocyte recipient cycles compared with autologous frozen embryo transfer cycles (aOR 0.84, 99% CI 0.50 - 1.41). Limitations, reasons for caution Although the analysis was adjusted for several potential confounders, there was no information on classification of endometriosis to allow adjustment. Wider implications of the findings The current study design does not indicate endometriosis has an impact on oocyte quality given that the outcomes in donor oocyte recipient cycles are comparable with autologous IVF cycles. These findings need to be further studied and validated. Trial registration number Not applicable

P–484 Progesterone supplementation in modified natural frozen embryo transfer (mNC-FET) does not cause mental health adverse effects - A sub-study of a multicenter RCT

Abstract Study question Do women undergoing mNC-FET with progesterone supplementation experience mental health adverse effects at a greater rate compared to a control group. Summary answer Progesterone supplementation does not affect mental wellbeing in women undergoing mNC-FET. What is known already Women and men undergoing assisted reproductive treatment more likely to experience stress and other adverse psychological effects than the background population. Various factors such as parental age, cause of infertility and treatment method have been shown to affect patient well-being. Progesterone supplementation is known to cause various physical adverse effects, yet few studies have investigated the potential mental health adverse effects of progesterone supplementation in FET. Study design, size, duration This is a sub-study of an ongoing RCT investigating the effect of luteal phase progesterone supplementation in mNC-FET. The aim is to investigate possible mental health adverse effects of progesterone. From 2019–2021 a total of 164 women were included (n = 84 and n = 82 in the progesterone and control group, respectively). The health and wellbeing self-reporting survey was fulfilled after randomization on hCG trigger + 11 days. Participants/materials, setting, methods A validated, electronic questionnaire in Danish was used to measure mental wellbeing in women aged 18–41 years undergoing mNC-FET with and without use of progesterone supplementation in the luteal phase at seven Danish public hospitals. Women were randomized to either progesterone treatment or no progesterone by a computerized randomization algorithm with minimization for female age &amp;gt; =37 years, previous oocyte retrievals and previous FET. Comparisons of survey responses were performed by chi-square tests. Main results and the role of chance The survey response rate was 68%. We observed no significant differences in any of the three items between the progesterone group and the control group. On the first item “to which degree have you felt sensitive due to treatment”, 56% and 52% responded “to a large degree” or “to some degree” sensitive in the progesterone vs. control group, while 25% and 34% vs. 19% and 13% responded “to a lesser extent” or “not at all” sensitive in progesterone vs. controls (P = 0.35). On the second item, “to which degree have you felt aggressive due to treatment”, 10% and 9% responded “to a large degree” or “to some degree”, 29% and 22% answered “to a lesser degree” and 62% and 70% responded “not at all” in the progesterone vs control group (P = 0.57). On the third item “to which degree have you cried unexpectedly due to treatment” 25% and 18% responded “to a large degree” or “to some degree” in the progesterone vs control group, 20% and 27% answered “to a lesser extent”, while 55% in both groups answered “not at all” (P = 0.44). Limitations, reasons for caution In a self-reported survey selection bias, due to a less than 100% response rate, and reporting bias cannot be excluded. However with the possibility to answer the survey online at leisure, the risk of reporting bias is minimized. Wider implications of the findings: A large concern for clinicians working with ART is patient wellbeing. Our study suggests that luteal phase support does not cause extra emotional distress, though further research is needed. Trial registration number NCT03795220

O-212 MACS vs TESA for raised sperm DNA fragmentation index – a RCT

Abstract Study question In Individuals with raised Sperm DNA Fragmentation Index (SDF), will sperm selection by magnetic activated cell sorting (MACS) or surgical retrieval of testicular sperms (TESA) optimize the reproductive outcomes? Summary answer Couples with failed implantation raised SDF, TESA /MACS offer similar results. This RCT doesn’t prove superiority or added benefit with any of the above interventions. What is known already It is evident that raised SDF negatively affects the reproductive outcomes. Management for raised SDF to optimize reproductive outcomes is still elusive. Study design, size, duration This was a Randomized Control Trial (RCT) with prior approval from institutional Ethical Committee and trial registration. Couples undergoing stimulation with raised SDF were randomized to MACS (n = 75) and TESA (n = 75) for sperm selection between April2019 &amp; February2020. Participants/materials, setting, methods Couples with history of one failed IVF had SDF testing and SDF&amp;gt;30% were recruited. SDF test done with SCSA method and randomized using software. ICSI was the method of insemination. Extended embryo culture till blastocyst was done and freeze all policy was opted. Two Blastocysts that showed 100% survival were transferred in a Frozen Embryo transfer (FET) cycle. Embryonic and Reproductive outcomes were compared between both groups. Live birth and Miscarriage were the primary outcomes. Main results and the role of chance Reproductive Outcomes of MACS Vs TESA were: Average Blastocyst conversion - 32% Vs 39% (RR 1.22, CI1.00 to 1.50) Implantation rate (IR) - 50% Vs 35% (RR - 0.71, CI 0.51 to 0.98) Miscarriage rate (MR) - 5.3% Vs 11% (RR1.6333, CI 0.5227 to 5.1039) Multiple Pregnancy rate (MPR) - 8% Vs 4% Live birth Rate (LBR) per Intention to treat (ITT) - 41.3% Vs 44% (RR 0.95, 95% CI 0.72 to 1.26) LBR per ET cycle - 63% Vs 56% (RR 1.23, 95% CI 0.77 to 1.94) Our preliminary results suggest that despite greater availability of blastocysts for transfer in the TESA group, no difference in ART outcomes was observed between the groups. Though the IR was statistically low with TESA, our primary outcomes LBR and MR were comparable. TESA or MACS seem to offer similar outcomes. Considering the invasiveness with TESA, MACS can be offered for better sperm selection for couples with raised sperm DFI &amp; failed implantation. Limitations, reasons for caution Small sample size. TESA is a surgical intervention Wider implications of the findings Optimal intervention for management of SDF still needs further research. Trial registration number CTRI/2019/07/020140

P–360 Blastocyst biopsy day does have an impact on clinical pregnancies in different frozen embryo transfer (FET) regimens: natural cycle (NC) versus hormone replacement therapy (HRT)

Abstract Study question Do euploid blastocysts biopsied on day (D) 5 or D6 differ in clinical pregnancy rates when single FET are performed in NC or HRT cycles? Summary answer In single FET cycles, euploid D5 blastocysts have higher clinical pregnancy rates than D6 in NC, while outcomes are comparable in HRT cycles. What is known already: The synchronization between the endometrium and the embryo development is fundamental for a successful implantation. When performing FET with euploid blastocysts biopsied on D5 or D6, higher clinical pregnancy rates have been reported with D5 blastocysts, however contradictory findings were described due to the study design heterogeneity and endometrial preparation (EP) protocol variabilities. In FET cycles, no consensus has been defined of the superiority of NC over HRT cycles when euploid blastocysts are transferred. Consequently, the question remains unanswered if the clinical pregnancy rates of single euploid FET with D5 or D6 blastocysts differ when the EP protocol remains constant. Study design, size, duration A single center observational study was performed between June 2017 and November 2020, including 1027 single euploid FET with blastocysts biopsied on D5 or D6. All patients with primary or secondary infertility who underwent a FET in a NC or HRT EP protocol, with blastocysts graded ≥ BL3CC (Gardner scoring system) prior to biopsy were included. Vitrified-warmed blastocysts that did not re-expand within 1-hour post-warming were excluded from the analysis. Participants/materials, setting, methods In NCs, vaginal progesterone (P4) (Endometrin®) was administrated (3x100mg) after endocrinological confirmation of ovulation until pregnancy test. For HRT cycles, oral estradiol administration was started on day 2 (4 mg) and increased to 6mg on D5 of the cycle. When endometrial thickness was ≥6 mm, P4 was given (3x100mg) until pregnancy test. All FET were performed on D5 after start of P4 administration. Clinical pregnancy was recorded as the presence of an intrauterine gestational sac. Main results and the role of chance Women’s mean age was 33.8 ± 5.5 years. A total of 651 FETs were performed with D5 euploid blastocysts (37.6% in NC and 62.4% in HRT) and 376 with D6 (43.1% in NC and 56.9% in HRT). Clinical pregnancy rate in NC was higher with D5 blastocysts compared to D6 (66.9% vs 50.0%; OR = 0.494, 95% CI = 0.322–0.758; p &amp;lt; 0.001), while no significant differences were found when vitrified-warmed blastocysts were transferred in HRT cycles (64.3% vs 58.4%; OR = 0.781, 95% CI = 0.548–1.112; p = 0.164). Additionally, clinical miscarriage was significantly higher with D5 euploid blastocysts transferred in NC (D5=10.9% vs D6=3.7%, OR = 0.239, 95% CI = 0.044–0.837; p = 0.019). In HRT, miscarriage outcomes were similar between D5 and D6 euploid blastocysts (D5=18.7% vs D6=20.8%, OR = 0.781, 95% CI = 0.548–1.112; p = 0.164), but significantly higher (p &amp;lt; 0.001) than in NC. From a multinomial logistic regression model including age, blastocyst quality and day of biopsy as confounding factors, the clinical pregnancy rate was significantly affected by D6 blastocyst biopsy (OR = 0.571, 95% CI = 0.360–0.906, p = 0.017) and inner cell mass (ICM) grade A (OR = 3.941, 95% CI = 1.149–10.402; p = 0.006) or B (OR = 2.601, 95% CI = 1.146–5.907, p = 0.022) in NC. In HRT cycles, exclusively ICM was statistically significant (OR = 2.555, 95% CI = 1.214–5.381, p = 0.015 and OR = 2.397, 95% CI = 1.286–4.470, p &amp;lt; 0.001 for grade A and B, respectively). Limitations, reasons for caution The current results are based on an observational retrospective study. Live birth and perinatal outcomes should be considered in a further analysis to evaluate the performance of the NC vs HRT protocols when D5 or D6 euploid blastocysts are transferred in FET cycles. Wider implications of the findings: While the clinical pregnancies of D5 and D6 euploid blastocysts are comparable in HRT protocols only, the miscarriage rates seem to be significantly increased as compared to NC. Further studies are required to personalize EP protocols based on the day of blastocyst biopsy in order to improve clinical outcomes. Trial registration number No

P–668 We aim for one baby, not one embryo: a personalized ET strategy based on embryo score and woman age maximizes LB and minimizes twins

Abstract Study question Is it possible to define a personalized ET model to maximize the chance of live birth (LB) while minimizing the risk of twin pregnancy? Summary answer A model including age and embryo morphological score can inform a personalized ET strategy to maximize LB while minimizing the risk of twin pregnancy. What is known already The morphological score of the transferred embryos affects pregnancy (PR) and LB rates in IVF cycles. Although SET is mainly recommended to avoid multiple pregnancies, DET is still being performed extensively, especially in patients with poor prognosis, with the aim to improve PR per transfer and shorten time to pregnancy. While twin pregnancies are associated with an increased risk of maternal and fetal complications, very low PR may increase patient drop-off, extend time to pregnancy, and increase the cost per successful transfer. A personalized transfer strategy balancing high LB per transfer with low twin pregnancy rates should be defined. Study design, size, duration Retrospective study including 2,470 fresh and frozen embryo transfers (ET) of either one or two embryos at D3 from January 2016 to August 2019 in a single IVF clinic. Biochemical, clinical, multiple pregnancy and live birth rates after SET and DET were analyzed according to the morphological score of the embryos transferred. ETs were divided into 9 groups according to the combinations of their embryo morphological scores. Participants/materials, setting, methods Embryos were assessed on D3 following a national recommended morphological scale. Morphology was categorized as High (H) if A or B+, medium (M) if B or C+, and Low (L) if C or D. The likelihood of biochemical, clinical pregnancy and live birth, and the risk of multiple pregnancy, after SET and DET of embryos of different scores was analyzed. A logistic regression analysis adjusted by age of the woman was ran for each outcome. Main results and the role of chance The distribution of ETs among the 9 groups for SET was: 510 H, 715 M, 346 L; for DET: 142 HH, 148 HM, 29 HL, 268 MM, 164 ML, 148 LL. Mean woman age was similar among groups: 38.7±4.01. Live birth and twin rates increased with embryo score. Considering a SET of category M as reference, the OR of live birth in DET were: 2.76 [1.82, 4.19 95%CI] for HH, and 2.32 [1.51, 3.55 95%CI] for HM, and 1.69 [1.19, 2.40 95%CI] for MM, and in SET: 1.52 [1.12, 2.04 95%CI] for H. Considering a DET of category MM as reference, the OR of twin birth in DET were: 2.8 [1.14, 6.99 95%CI] for HH, 2.5 [0.98, 6.46 95%CI] for HM, and 0.92 [0.11, 7.84 95%CI] for HL. According to this model, a 38y.o. woman with a SET of category M would have a 16% chance of live birth, and no twins. The addition of an M (DET: MM) increases her chance of live birth to 24% with a 2.9% risk of twins. The addition of a H (DET:MH) would increase further her chance of live birth to 30.8%, however, the increase would be due almost exclusively to twins (7%). Limitations, reasons for caution The limitations of this study are its retrospective nature and the small size of some categories. Embryos were classified using a national morphological scale; other morphological classifications could influence the results. The development and validation of site-specific models, using local patients’ data, is recommended before their use in clinical practice. Wider implications of the findings: A personalized assessment of embryo quality and woman age, at a minimum, are necessary to identify the best ET strategy for each patient; this strategy allows to maximize live birth rates while keeping the risk of twin birth as low as possibl. Trial registration number Not applicable

O-075 The association between high birth weight and long-term outcomes-implications for Assisted Reproductive Technologies: a systematic review and meta-analysis

Abstract Study question Do high birth weight or large for gestational age (LGS) increase the risk of serious disease later in life? Summary answer High birth weight and/or LGA were associated with elevated risks for certain child malignancies, breast cancer, psychiatric disorders, childhood hypertension and diabetes type 1. What is known already Previous studies have shown that children born after frozen embryo transfer (FET) have an increased risk of being born LGA or having a high birth weight. In recent years the practice of FET in Assisted Reproductive Technology (ART) has increased rapidly. The perinatal risks of being born LGA or with a high birth weight are well studied, however less is known about the impact on long-term health and morbidity. Study design, size, duration Pubmed, Scopus and Web of Science were searched until December 2020. 11 748 abstracts were screened, 172 publications were selected for systematic review and 63 for meta-analyses. The methodological quality in terms of risk of bias was assessed by pairs of reviewers. Robin-I (www.methods.cochrane.org) was used for assessing risk of bias in original articles. For systematic reviews AMSTAR was used. For certainty of evidence the GRADE system was used. Participants/materials, setting, methods Exposures were LGA and high birth weight. Long-term morbidity outcomes were cancer, metabolic disease, cardiovascular disease and psychiatric disorders. Cancer was focused on breast cancer, child malignancies in the central nervous system (CNS), hematological malignancies and Wilm´s tumor. Metabolic diseases included diabetes type 1 and type 2. Cardiovascular diseases were focused on hypertension and other cardiovascular disorders and psychiatric disorders on schizophrenia/psychosis and cognitive disorders. Main results and the role of chance Pooled Adjusted Odds Ratios (AOR) for outcome variables were compared for birth weights &amp;gt;4000 or &amp;gt; 4500 g versus &amp;lt; 4000 g. For cancer, meta-analyses showed AOR of 1.24 (95% 1.11-1.39) for development of breast cancer, AOR of 1.15 (95% CI 1.05-1.27) for development of CNS tumors, AOR of 1.29 (95% CI 1.20-1.39) for childhood leukemia and AOR 1.68 (95% CI 1.38-2.06 ) for Wilm´s tumor. For metabolic disease a meta-analysis showed AOR of 1.15 (95%CI 1.05-1.26) for the association between high birth weight and type 1 diabetes. For psychiatric diseases an association was found between high birth weight and/or LGA and schizophrenia and depression. For cardiovascular disease, an association was found between high birth weight and hypertension in childhood with an inverse association in adulthood. No difference in the risk of coronary heart disease in adults born with high birth weight compared to normal birth Limitations, reasons for caution The main limitation is that all data are based on observational studies with their inborn risk of selection bias. Our conclusions are however, mainly based on meta-analyses and/or studies with low risk of bias. Wider implications of the findings Even though high birth weight and LGA are associated with an increased risk of serious diseases, both in childhood and in adulthood, the size of these effects seems modest. However, the identified risk associations should be taken into account in stimulation strategies and when considering fresh or frozen embryo transfer. Trial registration number Not applicable

P–635 Standard versus mild ovarian stimulation in women with polycystic ovaries (PCO): Impact on outcomes in subsequent frozen embryo treatment cycles (FET)

Abstract Study question Does mild ovarian stimulation in women with PCO result in higher live birth rates during subsequent FET cycles? Summary answer Mild ovarian stimulation with FSH doses &amp;lt;150IU did not result in higher clinical pregnancy or livebirth rates in subsequent FET. What is known already Ovarian stimulation during IVF in women with PCO is associated with an exaggerated response, ovarian hyperstimulation syndrome, poor egg to follicle ratio, low fertilisation rates and poor blastocyst conversion. Mild ovarian stimulation, often referred to as protocols with FSH doses under 150IU, is often employed to overcome these challenges. One of the perceived benefits of this approach is improved oocyte and embryo quality reflected in lower aneuploidy rates. Study design, size, duration This was a retrospective observational study looking at 99 FET between January 2011 and Jan 2021 that followed a fresh cycle in women with a pre-treatment antral follicle count of 12 + 12 or greater. Patients were identified through the antral follicle count at the pre-treatment investigation ultrasound scan. Ultrasound findings, treatment cycle details and clinical outcomes were entered prospectively into a dedicated clinic database. Data was retrieved and analysed using SPSS V25. Participants/materials, setting, methods The study was conducted in a large IVF centre. Data on women with an AFC of 12 + 12 or above, undergoing an autologous FET cycle following a fresh cycle were collected. Women were split into those receiving &amp;lt;150IU of FSH (Group1, n = 51) and those receiving FSH ³150 IU (Group 2, n = 48). Binary logistic regression analysis was performed to control for confounders. Live birth was the primary outcome, with biochemical and clinical pregnancy being secondary outcomes. Main results and the role of chance Women in Group 1 were younger (30.8±3.6 v 33.8±3.65, p &amp;lt; 0.005) but had a similar antral follicle count (38.2±11.7 v 34.2±9.1, p = 0.07). The total number of eggs collected (24.1±13.8 v 25.9±8.8, p = 0.45) and fertilisation rate (0.59±0.2 v 0.58±0.18, p = 0.77) during their fresh cycle were comparable. Women in Group 2 had a larger number of embryos suitable for cryopreservation (7.36±4.2 v 4.8±3.5, p = 0.001) In the subsequent frozen embryo replacement cycle, there was no difference in the number or quality of embryos transferred with most women having a single embryo transfer (63% v 48%, p = 0.14) and at least one top quality embryo transferred (68.6% v 81%, p = 0.15). There was a higher biochemical pregnancy rate in Group 1 (84% v 66%, p = 0.035) but with no difference in clinical pregnancy rate (53% v 44%, p = 0.37) or live birth rate (49% v 42%, p = 0.76). Live birth rates remained comparable even after controlling for age, and number and quality of embryos transferred (OR: 1.21 (95% CI 0.50–2.94). Limitations, reasons for caution This was a retrospective analysis raising the risk of allocation bias. This study was also at risk of information bias as it relied on accurate documentation of the AFC at the pre-treatment scan. Wider implications of the findings: Patients can be reassured that both stimulation protocols result in similar live birth rates in subsequent frozen embryo replacement cycles. Prospective trials using PGT-A are required to assess whether aneuploidy could account for the discrepancy in biochemical pregnancy rates in the two groups considering the subsequent comparable clinical pregnancy rates. Trial registration number Not applicable

P–728 Can in couples with unexplained infertility the use of a prediction model to triage assisted reproduction technology save costs?

Abstract Study question Can in couples with unexplained infertility a prognosis-tailored management strategy, that delays treatment if natural conception prospects are good, reduce costs without affecting live-birth rate? Summary answer In couples with unexplained infertility, use of a prognostic tool for natural conception followed by expectant management in good-prognosis couples is cost-effective. What is known already Few countries have guidelines for the assessment of the likelihood of natural conception to determine access to publicly funded ART. In the Netherlands and New-Zealand, couples with unexplained infertility who have a good prognosis for natural conception are encouraged to delay starting ART. However, the cost-effectiveness of this prognosis-tailored treatment strategy has not been determined. Study design, size, duration We studied couples with unexplained infertility to compare a prognosis-tailored strategy to care-as-usual. In the prognosis-tailored strategy, couples were assessed using Hunault’s prediction model. In good-prognosis couples (12-months natural conception &amp;gt;40%), outcomes without ART were modelled by censoring observations after start of ART. We then assumed that poor-prognosis couples (&amp;lt;40% natural conception) were treated, while good-prognosis couples delayed the start of treatment for 12 months. Data for the care-as-usual model were based on real observations. Participants/materials, setting, methods We studied 272 couples with unexplained infertility. Costs of in vitro fertilisation (IVF) and intra-uterine insemination (IUI) were calculated based on the out-of-pocket costs and Australian Medicare costs. In a cost-effectiveness model, we compared costs and effects of both strategies. Main results and the role of chance The prognostic model classified 272 couples with unexplained infertility as favourable (N = 107 (39.3%) or unfavourable prognosis (N = 165 (60.7%)) for natural conception. In the prognosis-tailored strategy, the cumulative live-birth rate was 71.1% (95% CI 64.7% - 76.4%) while the number of ART cycles was 393 (353 IVF; 40 IUI). In care-as-usual strategy, the cumulative conception rate leading to live-birth for the cohort of 272 couples, who underwent a total of 398 IVF cycles and 48 IUI cycles, was 72.1% (95% CI 65.7% - 77.4%). Mean time to conception leading to live birth was 388 days in the prognosis-tailored strategy and 419 days in the care-as-usual strategy. This translated for the 272 couples into potential savings of 45 IVF cycles and eight IUI cycles, which cost a total of AUD$ 125,817 for out-of-pocket and AUD$ 264,497 for Australian Medicare. The average cost savings per couple was AUD$ 1,435 (out-of-pocket AUD$ 463 per couple and Australian Medicare AUD$ 962 per couple). The incremental cost-effectiveness ratio, which was calculated as the total costs per additional live-births, was AUD$ 143,497 per additional live birth. Limitations, reasons for caution This study was limited to couples at a single IVF clinic. The modelling was also based on several key assumptions, particularly the number of fresh and frozen embryo transfer cycles for each couple. Wider implications of the findings: Our results show that in couples with unexplained infertility the use of a prognostic model guiding the start of an IVF-treatment reduces costs without compromising live birth rates. Trial registration number Not applicable

P–626 A freeze-all strategy improves clinical pregnancy rate in patients with few available embryos

Abstract Study question Is elective frozen blastocyst transfer an advantageous strategy for all patients? Summary answer A freeze-all strategy improves the outcomes in patients with few available embryos. What is known already With the aim of defining the best moment to perform embryo transfer, in recent years, relevance has been given to the understanding of the implantation window, however oocyte and embryo quality are key factors that are not to be disregarded. It has been suggested that a freeze-all strategy and subsequent frozen embryo transfers improve pregnancy rates. However, it is unclear whether this strategy benefits all kind of patients (i.e. with or without surplus embryos, etc). In this study, we aim to provide an answer on which patients may benefit of a freeze-all policy and a subsequent frozen embryo transfer. Study design, size, duration This retrospective cohort study includes infertile patients aged 21 to 44 years old, without previous history of recurrent failure of ART (including recurrent miscarriages). Enrolments took place between January 2015 and November 2019 and cycles with oocyte donation and PGT were excluded. Embryo transfers were performed in: 1) a fresh cycle (ET) or 2) a deferred cycle with surplus frozen embryos (FET) or embryos that were frozen in a freeze-all policy (FET-FA). Participants/materials, setting, methods Patients with blastocysts transfer were included. PGT cycles were excluded. The number of cycles complying with the inclusion criteria were: 617 ICSI cycles. Fresh embryo transfers (ET) were performed in 396 cycles (43 with a subsequent Frozen embryo transfer, FET). Frozen embryo transfers following a freeze-all strategy (FET-FA) were performed in 221 cycles. Clinical pregnancy rates (CPR) and Cumulative clinical pregnancy rates (CCPR) were calculated and compared among those groups. Main results and the role of chance Mean age of patients was 36.1 ± 3.7 years old (mean ± SD). In average, 1.83 ± 0.41 (mean ± SD) embryos were transferred. Following the first transfer (either ET and FET-FA), CPR was 40.4% and 58.4% (ET and FET-FA, respectively). Following the subset analysis of 2 age groups (≤38 &amp; &amp;gt;38 years-old); in the ≤38-group, CPR was 45.2% and 58.9% (ET and FET-FA, respectively), while in &amp;gt; 38-group, the rates were 30.8% and 54.8% (ET and FET-FA, respectively); p &amp;lt; 0.05. CCPR were also significantly better in the FET-FA group: 51.3% vs 66.8% and 33.8% vs 58.1% in the ≤38-group and &amp;gt;38-group, respectively. Additionally, CPR was analysed independently for patients with ≤2 usable embryos (1 attempt) or ≥ 3 usable embryos (surplus embryos after first attempt). When a single attempt was possible; in the ≤38-group, CPR was 36.1% and 56.9% (ET and FET-FA, respectively) while in the &amp;gt;38-group, the rates were 24.7% and 63.6% (ET and FET-FA, respectively); p &amp;lt; 0.05. When surplus embryos were available, no difference in CPR (or CCPR) between ET and FET-FA groups were observed. After first attempt CPR were 58.4% and 48.2% in the ≤38-group &amp; &amp;gt;38-group, respectively; while CCPR were 69.8% and 57.1% in the ≤38-group &amp; &amp;gt;38-group, respectively. Limitations, reasons for caution Although the authors consider that the patient population is of optimal size, a detailed analysis of the stimulation protocol and hormonal values (estradiol and progesterone) during treatment, and its potential relation to the outcomes, should follow. Wider implications of the findings: In our setting, the data suggests that freeze-all strategy (with subsequent frozen embryo transfer) over fresh transfer is advantageous for patients with few available embryos (1 or 2 embryos for a single attempt). This increases the chances to pregnancy in 30.3% in the ≤38-group and 77.9% in the &amp;gt;38-group. Trial registration number Not applicable

Endometrial preparation does not affect the risk of hypertensive disorders of pregnancy in low-risk women undergoing frozen embryo transfer

Objective Frozen embryo transfer (FET) is associated with a higher risk of hypertensive disorders in pregnancy. The objective of the present study is to evaluate the effect of different protocols of endometrial preparation on the risk of these disorders. Methods We conducted a retrospective cohort study on 594 singleton pregnancies achieved by embryo transfer of single frozen-thawed blastocysts. Women with preexisting risk factors for hypertensive disorders were excluded. Women were divided into two groups according to the endometrial preparation protocol: either natural cycle (n = 495) or programming cycle with hormonal replacement therapy (n = 97). The primary outcome was the frequency of hypertensive disorders in pregnancy: specifically, gestational hypertension and preeclampsia. Results No differences emerged between women following the natural cycle and those following the programming cycle in the frequency of gestational hypertension (5 vs. 4%) and preeclampsia (1.1 vs. 1.2%). No impact emerged also after multivariate analyses. Conclusions Women receiving hormonal replacement therapy have the same risk of gestational hypertension and preeclampsia as women following natural cycles when considering low-risk singleton pregnancies.

Educational needs of fertility healthcare professionals using ART: a multi-country mixed-methods study

Research question: What are the most pressing educational needs of fertility healthcare professionals using assisted reproductive technologies (ART)?Design: This mixed-methods study combined qualitative interviews with quantitative surveys. Participants included physicians and nurses specialized in reproductive endocrinology or in obstetrics/gynaecology, and laboratory specialists, with a minimum of 3 years of experience, practising in Australia, Brazil, Canada, China, France, Germany, India, Italy, Japan, Mexico, Spain or the UK. Maximum variation purposive sampling was used to ensure a mix of experience and settings. Interviews were transcribed and coded through thematic analysis. Quantitative data were analysed using frequency tables, cross-tabulations and chi-squared tests to compare results by reimbursement context.Results: A total of 535 participants were included (273 physicians, 145 nurses and 117 laboratory specialists). Knowledge gaps, skills gaps and attitude issues were identified in relation to: (i) ovarian stimulation (e.g. knowledge of treatments and instruction protocols for ovarian stimulation), (ii) embryo culture and cryopreservation/vitrification (e.g. diverging opinions on embryo freezing, (iii) embryo assessment (e.g. performing genetic testing), (iv) support of luteal phase and optimizing pregnancy outcomes (e.g. knowledge of assessment methods for endometrial receptivity), and (v) communication with patients (e.g. reluctance to address emotional distress).Conclusions: This descriptive, exploratory study corroborates previously reported gaps in fertility care and identifies potential causes of these gaps. Findings provide evidence to inform educational programmes for healthcare professionals who use ART in their practice and calls for the development of case-based education and interprofessional training programmes to improve care for patients with fertility issues.

Comparison The Clinical Pregnancy Rate (CPR) And Ongoing Pregnancy Rate (OPR) In Frozen Embryo Transfers (FETs) Following Either FreezeAll Policy To Prevent Ovarian Hyperstimulation Syndrome

Introduction: Patients undergoing in vitro fertilization (IVF) cycles may not receive embryo transfer (ET) at that controlled ovarian stim-ulation (COS) cycle for several reasons. Focusing on the FET cycle, it is uncertain whether there is a difference in the pregnancy outcome between the cycles following either freeze-all policy or failed fresh ET. Whether the ET in that cycle was unsuccessful or ET was not per-formed, frozen embryo transfer (FET) would be performed thereafter if the embryos have been cryopreserved. Objective: To compare the clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR) in frozen embryo transfers (FETs) following either freeze-all policy to prevent ovarian hyperstimulation syndrome (OHSS; freeze-all group) or excess embryo cryopreservation after fresh embryo transfer (surplus group). Methods: The freeze-all group comprised 44 FET cycles performed in 25 women between January to December-2020. The surplus group comprised 53 FET cycles performed in 47 women during the same period. The cumulative CPR and OPR according to duration of cryopreservation (interval between cryopreservation and FET) was estimated using Kaplan-Meier plots. Cox regression analysis was used for identifying factor to affect to cryopreservation duration in cycles with pregnancy. Results: In day 2–4 transfer cycles, the crude CPR (40% vs. 18.2%) and OPR (20% vs. 4.5%) were similar between the 2 groups. In day 5 transfer, the crude CPR (33.3% vs. 38.7%) and OPR (33.3% vs. 29%) were also similar between the 2 groups. The cumulative CPR (100% vs. 47.5%) and OPR (100% vs. 33.3%) in day 2–4 transfer as well as the cumulative CPR (46.7% vs. 100%) and OPR (46.7% and 74.8%) in day 5 transfer were also similar between the 2 groups. The median duration of cryopreservation was significantly shorter in the freeze-all group than in the surplus group (19.8 vs. 36.9 weeks, P=0.04). Previous history of delivery was the only factor associated with a shorter cryopreservation duration in cycles with pregnancy (hazard ratio, 0.18; 95% confidence interval, 0.05–0.65; P=0.01). Conclusion: Freezing embryos to prevent OHSS and transferring the frozen embryos later may guarantee an acceptable reproductive outcome.

Male and Female Fertility: Prevention and Monitoring Hodgkin' Lymphoma and Diffuse Large B-Cell Lymphoma Adult Survivors. A Systematic Review by the Fondazione Italiana Linfomi.

Simple SummaryPatients with Hodgkin lymphoma or diffuse large B-cell lymphoma treated with chemotherapy, with or without radiation therapy on pelvic nodes, may suffer permanent damage to their reproductive function, which significantly affects their quality of life. Established gamete cryopreservation techniques, including the freezing of embryos, oocytes, spermatozoa, ovarian and testicular tissue, can, nowadays, be offered to any adult patient candidate receiving gonadotoxic therapy who is interested in preserving future fertility. In order to offer updated information on anticancer treatment harm and to better advise patients on fertility preservation options, Fondazione Italiana Linfomi (FIL) researchers conducted this systematic review to evaluate the frequency of treatment-related infertility, fertility preservation options, fertility assessment measures, and the optimal interval between end of treatment and conception in adult lymphoma patients.Background: Adult patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) have prolonged survival but face the risk of treatment-induced impaired fertility. This systematic review, conducted by Fondazione Italiana Linfomi (FIL) researchers, aims to evaluate the incidence of treatment-related infertility, fertility preservation options, fertility assessment measures, and the optimal interval between the end of treatment and conception. Methods: MEDLINE, the Cochrane Library, and EMBASE were systematically searched up to September 2020 for published cohort, case–control, and cross-sectional studies on fertility issues. Results: Forty-five eligible studies were identified. Gonadotoxicity was related to sex, type and dosage of treatment, and, in females, to age. After receiving alkylating-agent-containing regimens, less than 30% of males recovered spermatogenesis, and 45% of females ≥30 years in age retained regular menstrual cycles. Sperm cryopreservation was offered to the majority of patients; sperm utilization resulted in a 33–61% pregnancy rate. After ovarian tissue transplantation, the spontaneous pregnancy and live birth rates were 38% and 23%; after IVF, the live birth rate was 38.4%. No data could be extracted on the utilization rate of cryopreserved mature oocytes. The results of studies on GnRH analogs are controversial; therefore, their use should not be considered an alternative to established cryopreservation techniques. Sperm count, FSH, and inhibin-B levels were appropriate measures to investigate male fertility; serum AMH levels and antral follicle count were the most appropriate markers for ovarian reserve. No data could be found regarding the optimal interval between the end of treatment and conception. Conclusions: The risk of infertility should be discussed with adult lymphoma patients at the time of diagnosis, and fertility preservation options should be proposed before first-line treatment with alkylating-agent-containing regimens.