Chance Of Live Birth Research Articles

Live birth and maternity outcome in childhood and adolescent cancer survivors under 18 years at diagnosis: a 40-year population-based cohort study.

Survival from childhood and adolescent cancer has increased, but the chance of a livebirth in female survivors under 18 years at diagnosis may be reduced. We performed a national population-based analysis, including all female cancer survivors diagnosed in Scotland before the age of 18 years between 1981 and 2012. Scottish Cancer Registry records were linked to Scottish maternity records. Females from the exposed group with no pregnancies before cancer diagnosis (n = 2118) were compared with three general population controls matched for age and year of diagnosis. The cumulative incidence of a livebirth for all diagnoses was reduced to 37% (95% CI 33-40%) for cancer survivors at 30 years of age vs 58% (57-60%) for controls. The deficit varying by diagnosis: for lymphoid leukaemia, the cumulative incidence at 30 years was 29% (23-36%) vs 57% (52-61%) for controls with similar deficits in CNS tumours and retinoblastoma. There was a steady improvement in the chance of livebirth in those diagnosed more recently. We have shown a reduced chance of livebirth in female survivors of cancer diagnosed before age 18. The deficit is present for all diagnoses.

Correlation of adenomyosis features to live birth rates after the first IVF/ICSI treatment, when using the revised Morphological Uterus Sonographic Assessment group definitions.

Data regarding the impact of adenomyosis on the outcomes after invitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment are conflicting. Standardized diagnostic criteria are prerequisites for studying a potential association between adenomyosis and IVF/ICSI treatment outcomes. This study aims to examine the cumulative live birth rate (CLBR) after the first IVF/ICSI treatment in women with or without direct or indirect features of adenomyosis, using the revised Morphological Uterus Sonographic Assessment (MUSA) group definitions. This was a prospective cohort study of 1037 women aged 25-≤39 years, undergoing their first IVF/ICSI treatment between January 2019 and October 2022. The presence of MUSA features of adenomyosis was assessed prior to treatment start. The CLBR after the first IVF/ICSI treatment was 424/1037 (40.9%, 95% CI, 37.9-43.8) in the total cohort. Women with direct features of adenomyosis had lower CLBR, 25/102 (24.5%; 95% CI, 17.5-31.5) than women without, 399/935 (42.7%; 95% CI, 39.5-45.8), p < 0.001. The adjusted relative risk (aRR) for live birth for women with direct features of adenomyosis compared to women without was 0.62 (95% CI, 0.43-0.88), p = 0.007. Direct features were associated with a higher risk of miscarriage after frozen embryo transfer, aRR 2.88 (95% CI, 1.49-5.57), p = 0.002. Women with indirect features had a lower CLBR [50/188 (26.6%, 95% CI, 20.3-32.9)] than women without [399/935, (42.7%, 95% CI, 39.5-45.8)], aRR 0.58 (95% CI, 0.45-0.75), p < 0.001. For features located in the inner myometrium, the aRR for live birth was 0.29 (95% CI 0.11-0.74), p = 0.010 and for the outer myometrium 2.61 (95% CI 1.42-4.8), p = 0.002. An interrupted junctional zone was the single feature that impacted CLBR the most. The presence of direct or indirect MUSA features of adenomyosis correlates to reduced live birth rates in women undergoing their first IVF/ICSI treatment. Features located in the inner myometrium, particularly an interrupted junctional zone, reduced the chance of live birth the most, whereas location in the outer myometrium was associated with higher chances of live birth. Systematic ultrasound examinations should be considered for women scheduled for IVF/ICSI treatment, for adequate counseling on the chances of successful treatment.

Steady morphokinetic progression is an independent predictor of live birth: a descriptive reference for euploid embryos.

Can modelling the longitudinal morphokinetic pattern of euploid embryos during time-lapse monitoring (TLM) be helpful for selecting embryos with the highest live birth potential? Longitudinal reference ranges of morphokinetic development of euploid embryos have been identified, and embryos with steadier progression during TLM are associated with higher chances of live birth. TLM imaging is increasingly adopted by fertility clinics as an attempt to improve the ability of selecting embryos with the highest potential for implantation. Many markers of embryonic morphokinetics have been incorporated into decision algorithms for embryo (de)selection. However, longitudinal changes during this temporal process, and the impact of such changes on embryonic competence remain unknown. Aiming to model the reference ranges of morphokinetic development of euploid embryos and using it as a single longitudinal trajectory might provide an additive value to the blastocyst morphological grade in identifying highly competent embryos. This observational, retrospective cohort study was performed in a single IVF clinic between October 2017 and June 2021 and included only autologous single euploid frozen embryo transfers (seFET). Reference ranges were developed from [hours post-insemination (hpi)] of the standard morphokinetic parameters of euploid embryos assessed as tPB2, tPNa, tPNf, t2-t9, tSC, tM, tSB, and tB. Variance in morphokinetic patterns was measured and reported as morphokinetic variance score (MVS). Nuclear errors (micronucleation, binucleation, and multinucleation) were annotated when present in at least one blastomere at the two- or four-cell stages. The blastocyst grade of expansion, trophectoderm (TE), and inner cell mass (ICM) were assessed immediately before biopsy using Gardner's criteria. Pre-implantation genetic diagnosis for aneuploidy (PGT-A) was performed by next-generation sequencing. All euploid embryos were singly transferred in a frozen transferred cycle and outcomes were assessed as live birth, pregnancy loss, or not pregnant. Association of MVS with live birth was investigated with regression analyses. TLM data from 340 seFET blastocysts were included in the study, of which 189 (55.6%) resulted in a live birth. The median time for euploid embryos to reach blastulation was 109.9 hpi (95% CI: 98.8-121.0 hpi). The MVS was calculated from the variance in time taken for the embryo to reach all morphokinetic points and reflects the total morphokinetic variability it exhibits during its development. Embryos with more erratic kinetics, i.e. higher morphokinetic variance, had higher rates of pregnancy loss (P = 0.004) and no pregnancy (P < 0.001) compared to embryos with steadier morphokinetic patterns. In the multivariable analysis adjusting for ICM, TE grade, presence of nuclear errors, and time of blastulation, MVS was independently associated with live birth (odds ratio [OR]: 0.62, 95% CI: 0.46-0.84, P = 0.002) along with ICM quality. Live birth rate of embryos with the same ICM grading but different morphokinetic variance patterns differed significantly. Live birth rates of embryos exhibiting low MVS with ICM grades A, B, and C were 85%, 76%, and 67%, respectively. However, ICM grades A, B, and C embryos with high MVS had live birth rates of 65%, 48%, and 21% (P < 0.001). The addition of the MVS to embryo morphology score (ICM and TE grading) significantly improved the model's AUC value (0.67 vs 0.62, P = 0.015) and this finding persisted through repeat cross-validation (0.64 ± 0.08 vs 0.60 ± 0.07, P < 0.001). The exclusion of IVF cases limits, for now, the utility of the model to only ICSI-derived embryos. The utility of these reference ranges and the association of MVS with various clinical outcomes should be further investigated. We have developed reference ranges for morphokinetic development of euploid embryos and a marker for measuring total morphokinetic variability exhibited by developed blastocysts. Longitudinal assessment of embryonic morphokinetics rather than static time points may provide more insight about which embryos have higher live birth potential. The developed reference ranges and MVS show an association with live birth that is independent of known morphological factors and could emerge as a valuable tool in prioritizing embryos for transfer. This study received no external funding. The authors declare no conflicting interests. N/A.

Neurodevelopmental outcomes of school-age children conceived after hysterosalpingography with oil-based or water-based iodinated contrast: long-term follow-up of a nationwide randomized controlled trial.

Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives? Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives. HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women's iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG. This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012-2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228). The study included 69 children aged 6-9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups. School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant. The small sample size of this follow-up study limited statistical power. This study provides evidence for the absence of large-sized differences between preconceptional exposure to the two contrast media types but does not rule out more subtle effects on neurodevelopment compared to naturally conceived children without preconceptional exposure to HSG. This study contributes to our knowledge about the long-term effects of different types of iodinated contrast media used in fertility work-up, indicating that choosing oil-based over water-based iodinated contrast media is unlikely to have major effect on the long-term neurodevelopmental outcomes of children conceived shortly after HSG. However, further research should focus on the overall safety of iodine exposure during HSG, comparing children conceived after HSG to those conceived naturally as both types of contrast contain high amounts of iodine. The original H2Oil randomized controlled trial was an investigator-initiated study that was funded by the two academic hospitals now merged into the Amsterdam University Medical Centre. The current follow-up study (Neuro-H2Oil) is funded through a research grant awarded to the authors by the Amsterdam Reproduction & Development (AR&D) research institute. S.K. is funded by a AMC MD/PhD Scholarship from the Amsterdam UMC. S.K. reports holding voluntary roles in the civil society organizations Universities Allied for Essential Medicines and People's Health Movement. V.M. reports receiving travel and speaker fees as well as research grants from Guerbet, Merck and Ferring. K.D. reports receiving travel and speaker fees as well as research grants from Guerbet. BWM is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy, travel support and research funding from Merck, consultancy for Organon and Norgine, and holding stock from ObsEva. The other authors report no conflict of interest. NCT05168228.

Embryo retention and live birth in frozen embryo transfer cycles: a cohort study

To study the effect of embryo retention in the transfer catheter on pregnancy outcomes in frozen embryo transfer (FET) cycles. Retrospective cohort study. Tertiary-care academic medical center. This retrospective study involved a total of 39,118 women who underwent FET cycles at a tertiary-care academic medical from January 2016 to December 2022. Women were divided into a control group (n = 38,933) and embryo retention group (n = 185). The women in the embryo retention group had been propensity scores matched with those in the control group at a 1:4 ratio. The primary outcome was live birth (LB). The secondary outcomes were biochemical pregnancy, clinical pregnancy (CP), miscarriage, and ectopic pregnancy. The overall incidence of embryo retention in the transfer catheter was 0.47% (185/39,118). The pregnancy outcome in the embryo retention group after propensity score matching (PSM) was comparable to that before PSM, with a reduced likelihood of biochemical pregnancy (odds ratio [OR], 0.83; 95% confidence interval [CI], 0.72-0.95), CP (OR, 0.81; 95% CI, 0.69-0.96), and LB (OR, 0.80; 95% CI, 0.66-0.97). In addition, the birth weight in the embryo retention group was higher compared with the control group. However, no differences were observed in terms of miscarriage, ectopic pregnancy, cesarean delivery, as well as gestational age both before and after PSM. Embryo retention in the transfer catheter decreases the chance of biochemical pregnancy, CP, and LB in FET cycles.

Reproductive Outcomes After Hysteroscopic Adhesiolysis in Patients Experiencing Recurrent Pregnancy Loss and Intrauterine Adhesions

ObjectiveThis study aims to evaluate the reproductive outcomes after hysteroscopic adhesiolysis in patients experiencing recurrent pregnancy loss (RPL) combined with intrauterine adhesions (IUA). DesignSingle-center retrospective cohort study. SettingInternational referral hospital for women with IUA and RPL. PatientsBetween January 2018 and June 2022, a cohort of 64 women diagnosed with RPL and IUA were studied, with a follow-up period of at least one year after hysteroscopic adhesiolysis. InterventionsAll patients had a diagnosis of IUA from the diagnostic hysteroscopy and were treated with hysteroscopic adhesiolysis, utilizing intraoperative ultrasound monitoring as required. Main MeasurementsLive birth rate and menstrual pattern change (subjective assessment) after hysteroscopic adhesiolysis. ResultsIn our cohort, 59.38% (38/64) achieved pregnancy following hysteroscopic adhesiolysis, with 92.11% (35/38) conceiving within two years of the procedure. The miscarriage rate was recorded at 17.19% (11/64), and the live birth rate stood at 42.19% (27/64). Throughout the extended follow-up period, 64.06% (41/64) of the patients reported increased menstrual blood volume and improvements in menstrual patterns posthysteroscopic adhesiolysis. Univariate analysis indicated that being aged ≥35 years (p = .026), having a history of infertility (p = .003), the presence of moderate or severe IUA (p = .023), and experiencing menstrual improvements postsurgery (p = .001) were independent predictors of live birth. Multivariate analysis further identified that women with a history of infertility had a reduced chance of live birth following hysteroscopic adhesiolysis (p = .008), while those who reported menstrual pattern improvements postoperatively had an increased probability of achieving a live birth (p = .031). ConclusionsOur findings indicate that RPL and IUA patients without prior infertility and showing menstrual pattern improvement after hysteroscopic adhesiolysis, are more likely to achieve live births. Standardized hysteroscopic treatment, postoperative antiadhesion care, and early pregnancy planning are key to improving fertility outcomes in these patients.

The oocyte microenvironment is altered in adolescents compared to oocyte donors.

Do the molecular signatures of cumulus cells (CCs) and follicular fluid (FF) of adolescents undergoing fertility preservation differ from that of oocyte donors? The microenvironment immediately surrounding the oocyte, including the CCs and FF, is altered in adolescents undergoing fertility preservation compared to oocyte donors. Adolescents experience a period of subfecundity following menarche. Recent evidence suggests that this may be at least partially due to increased oocyte aneuploidy. Reproductive juvenescence in mammals is associated with suboptimal oocyte quality. This was a prospective cohort study. Adolescents (10-19 years old, n = 23) and oocyte donors (22-30 years old, n = 31) undergoing ovarian stimulation and oocyte retrieval at a single center between 1 November 2020 and 1 May 2023 were enrolled in this study. Patient demographics, ovarian stimulation, and oocyte retrieval outcomes were collected for all participants. The transcriptome of CCs associated with mature oocytes was compared between adolescents (10-19 years old, n = 19) and oocyte donors (22-30 years old, n = 19) using bulk RNA-sequencing. FF cytokine profiles (10-19 years old, n = 18 vs 25-30 years old, n = 16) were compared using cytokine arrays. RNA-seq analysis revealed 581 differentially expressed genes in CCs of adolescents relative to oocyte donors, with 361 genes downregulated and 220 upregulated. Genes enriched in pathways involved in cell cycle and cell division (e.g. GO: 1903047, P = 3.5 × 10-43; GO: 0051983, P = 4.1 × 10-30; GO: 0000281, P = 7.7 × 10-15; GO: 0044839, P = 5.3 × 10-13) were significantly downregulated, while genes enriched in several pathways involved in cellular and vesicle organization (e.g. GO: 0010256, P = 1.2 × 10-8; GO: 0051129, P = 6.8 × 10-7; GO: 0016050, P = 7.4 × 10-7; GO: 0051640, P = 8.1 × 10-7) were upregulated in CCs of adolescents compared to oocyte donors. The levels of nine cytokines were significantly increased in FF of adolescents compared to oocyte donors: IL-1 alpha (2-fold), IL-1 beta (1.7-fold), I-309 (2-fold), IL-15 (1.6-fold), TARC (1.9-fold), TPO (2.1-fold), IGFBP-4 (2-fold), IL-12-p40 (1.7-fold), and ENA-78 (1.4-fold). Interestingly, seven of these cytokines have known pro-inflammatory roles. Importantly, neither the CC transcriptomes nor FF cytokine profiles were different in adolescents with or without cancer. Original high-throughput sequencing data have been deposited in Gene Expression Omnibus (GEO) database with the accession number GSE265995. This study aims to gain insights into the associated gamete quality by studying the immediate oocyte microenvironment. The direct study of oocytes is more challenging due to sample scarcity, as they are cryopreserved for future use, but would provide a more accurate assessment of oocyte reproductive potential. Our findings have implications for the adolescent fertility preservation cycles. Understanding the expected quality of cryopreserved eggs in this age group will lead to better counseling of these patients about their reproductive potential and may help to determine the number of eggs that is recommended to be banked to achieve a reasonable chance of future live birth(s). This project was supported by Friends of Prentice organization SP0061324 (M.M.L. and E.B.), Gesualdo Family Foundation (Research Scholar: M.M.L.), and NIH/NICHD K12 HD050121 (E.B.). The authors have declared that no conflict of interest exists.

The association between paternal diabetes mellitus and successful pregnancy-Examined in a nationwide population undergoing reproductive treatment.

About 15% of all pregnancies end in pregnancy loss. As most studies have focused on maternal factors little is known regarding the influence of paternal factors on the chance of successful pregnancy. This cohort study aims to assess the chance of biochemical pregnancy, clinical pregnancy, and live-born children in couples where the male partner has diabetes mellitus (DM). We performed a nationwide cohort study. Couples undergoing assisted reproductive technology treatment from 2006 to 2019 were included. The exposed cohorts comprised embryo transfers in couples with paternal type 1 DM (T1DM), type 2 DM (T2DM), or mixed type DM (TMDM). The unexposed cohort included embryo transfers in couples without paternal DM. A total of 101,875 embryo transfers were included. Of these, 503 males had T1DM, 225 males had T2DM, 263 males had TMDM, and 100,884 did not have DM. For paternal T1DM, the adjusted OR for achieving a biochemical pregnancy, clinical pregnancy, and live-born child were 0.97 (95% CI 0.77-1.23), 1.08 (95% CI 0.65-1.79), and 0.75 (95% CI 0.49-1.14), respectively. For paternal T2DM, the adjusted OR for achieving a biochemical pregnancy, clinical pregnancy, and live-born child were 0.80 (95% CI 0.56;1.16), 0.67 (95% CI 0.32-1.41), and 1.03 (95% CI 0.48-2.20), respectively. For the paternal TMDM, the adjusted OR for achieving a biochemical pregnancy, clinical pregnancy and livebirth were 0.95 (95% CI 0.67-1.33), 1.31 (95% CI 0.56-2.92), and 1.19 (95% CI 0.59-2.38), respectively. Paternal DM was not associated with a statistically significant decreased chance of biochemical pregnancy, clinical pregnancy, or live birth.

Intracytoplasmic sperm injection versus conventional in vitro insemination in couples with non-male infertility factor in the ‘real-world’ setting: analysis of the HFEA registry

BackgroundIn assisted reproductive technology (ART), the choice between intracytoplasmic sperm injection (ICSI) and conventional in vitro insemination (IVF) remains a pivotal decision for couples with female or unexplained infertility. The hypothesis that ICSI may not confer significant improvements in live birth rates in the absence of a male infertility factor was explored in this study.MethodsThis was a retrospective collection of data recorded by the Human Fertilisation and Embryology Authority (HFEA) in the UK from 2005 to 2018 and analysed through regression analysis models on both the entire dataset and a matched-pair subset. First fresh ART cycles were analysed according to the insemination technique in order to compare live birth as the main outcome. Cycles were included if complete information regarding infertility cause, female age, number of oocytes retrieved, allocation to ICSI or IVF, and treatment outcome in terms of live birth was available. Matching was performed at a 1:1 ratio between IVF and ICSI cycles according to the cause of infertility, female age, number of oocytes, and year of treatment.ResultsThis study, based on 275,825 first cycles, revealed that, compared with IVF, ICSI was associated with higher fertilization rates and lower cycle cancellations rates. However, ICSI was associated with a lower chance of implantation and live birth than IVF in cycles with female-only infertility: in the entire dataset, the adjusted odds of having a live birth decreased by a factor of 0.95 (95% CI 0.91–0.99, p = 0.011), while in the matched-pair analyses it decreased by a factor of 0.91 (95% CI 0.86–0.96, p = 0.003) using ICSI compared to IVF. For unexplained infertility cycles, the adjusted odds ratios for live birth in ICSI compared to IVF cycles were 0.98 (95% CI 0.95–1.01) in the entire dataset and 0.97 (95% CI 0.93–1.01) in the matched-pair analysis.ConclusionsCompared with IVF, ICSI was associated with a reduction in live births when ART was indicated due to female-only factors. Additionally, no significant improvements were associated with the use of ICSI in cycles with unexplained infertility. Our findings impose a critical reevaluation regarding the use of ICSI over IVF for cases with female-only factors and unexplained infertility.

P-727 The impact of antidepressants and anxiolytics on assisted reproductive technology treatment outcomes

Abstract Study question Does antidepressant and anxiolytic use impact the chance of live birth after assisted reproductive technology (ART) treatment? Summary answer For women using antidepressants, ART treatment is as successful as for others. However, concomitant anxiolytic use was associated with failure to succeed. What is known already Infertility and depression are prevalent disorders in women of reproductive age and may occur coincidently. Antidepressants constitute the mainstay in treatment for moderate-severe depression, and selective serotonin reuptake inhibitors (SSRIs) are among the most commonly used antidepressants because they, in general, cause few side effects. However, antidepressant use in women undergoing ART treatment may be considered to balance the possible risks of untreated depression against fetal drug exposure and the efficacy of ART treatment. Furthermore, up to 50% of patients with depression also meet the criteria for anxiety disorders and may be treated with anxiolytics. Study design, size, duration This is an observational cohort study based on the Danish health registries. The use of antidepressants, i.e. as current or recent users, and anxiolytics or hypnotics at embryo transfer was obtained from the prescription register and information on all ART treatments and childbirths between 2006 and 2019 from the Danish ART register and the Danish birth register. Participants/materials, setting, methods The study population included 130,170 embryo transfers in 48,156 women undergoing ART treatment. A total of 1505 women were exposed to antidepressants at the time of embryo transfer, and 1160 women were recent users who discontinued before embryo transfer. We used mixed-effects logistic regression analyses. The association between antidepressants and anxiolytics respectively and ART was analyzed taking potential confounders into account estimating the odds ratios(OR) of either a biochemical pregnancy, clinical pregnancy, or live birth. Main results and the role of chance The adjusted OR(aOR) and corresponding 95% confidence interval (CI) of a biochemical-, and clinical pregnancy in women with current use of antidepressants at time of embryo transfer were 0.87 (95% CI: 0.73-1.04) and 0.84 (95% CI: 0.57-1.20), respectively, and 0.90 (95% CI: 0.67-1.19) for live birth. For women who discontinued antidepressant use before embryo transfer (labeled recent users), the aORs for a biochemical-, clinical pregnancy and live birth were 0.95 (95% CI: 0.76-1.17), 0.71 (95% CI: 0.46-1.09) and 1.02 (95% CI: 0.72-1.45), respectively. When analyzing women who use or recently used antidepressants in combination with anxiolytics or hypnotics the chance of a live birth was decreased markedly with an aOR of 0.15 (95% CI: 0.04-0.51). Based on nationwide data from more than a decade of ART treatments, we found that the use of antidepressants at the time of embryo transfer was not associated with a decreased chance of biochemical or clinical pregnancy, or live birth. However, when women treated with antidepressants also used anxiolytics or hypnotics, the chance of a live birth was significantly decreased though based on a limited number of patients suggesting a point of further investigation and attention. Limitations, reasons for caution As in all observational studies, it can never be ensured that the patients take the medicine, but we used information on prescriptions for antidepressants/anxiolytics from the prescription register using at least two redeemed prescriptions within 182 days before, and until 182 days after the date of embryo transfer. Wider implications of the findings Use of antidepressants at the time of embryo transfer was not associated with a decreased chance of biochemical or clinical pregnancy, or live birth. However, when antidepressants are used concomitantly with anxiolytics or hypnotics, the chance of live birth is significantly decreased suggesting the need for further investigation and attention. Trial registration number The study was funded by The Region of Southern Denmark and Merck.

P-269 Three-dimensional assessment of the inner cell mass is more effective at predicting implantation and live birth than Gardner grading

Abstract Study question 3-dimensional quantitative assessment of the inner cell mass (ICM) is more effective at selecting viable embryos than the widely used Gardner grading system? Summary answer 3-dimensional quantitative assessment of the ICM is significantly more predictive of implantation and live birth than the widely used Gardner grading of the ICM What is known already ICM assessment forms a key part of most widely used blastocyst grading systems. Grading under these systems, however, is often qualitative, subjective, and subject to inter/intra-operator variability. To reduce subjectivity in ICM grading, it has been suggested that quantitative criteria are used. Previous studies have focused on the assessment of such parameters (e.g. ICM area) in 2 dimensions. However, such approaches fail to account for the various embryo orientations which could lead to different measurements. Therefore, quantitative 3-dimensional analysis of the ICM is needed to improve the reliability and consistency of grading. Study design, size, duration This was a retrospective analysis of 153 randomly selected tEB embryos from two clinics. All data was captured on Embryoscope between 2018 and 2020. Data for maternal age, blastocyst grade, blastocyst ploidy, implantation and live birth rates were also recorded. Participants/materials, setting, methods Embryos were imaged at 7+ focal planes and in-focus sections of each ICM were annotated using ImageJ. These sections were combined into a 3D model using Blender, and sphericity (ψ) computed. Embryos were categorised as spheroid (ψ ≥ 0.8), ellipsoid (ψ &amp;lt; 0.8), crescent and irregular. Chi-squared tests were performed, comparing classification and clinical outcome. The predictive power of the system was compared to the Gardner scale (spheroid/ellipsoid classifications and A grades considered predictive of a positive outcome respectively). Main results and the role of chance Most ICM were either ellipsoid (48%) and spheroid (37%) rather than crescent (6%) or irregular (8%, p &amp;lt; 0.001). ICM 3D classification was associated with implantation, X2(3, N = 119)= 11.10, p = 0.01 and live birth, X2(3, N = 119)= 10.78, p = 0.01. Blastocysts with ellipsoid (70%, 28/40) and spheroid (58%, 18/31) shaped ICM had the greatest chances of implantation, whilst those with crescent (40%, 6/15) and irregularly shaped ICM (33%, 11/33) had lower chances of implantation (p &amp;lt; 0.011). Similarly, blastocysts with ellipsoid (58%, 23/40) and spheroid (48%, 15/31) shaped ICM had the greatest chances of live birth, whilst those with crescent (33%, 5/15) and irregularly shaped ICM (21%, 7/33) had lower chances of live birth (p &amp;lt; 0.013). 3D assessment of ICM outperformed Gardner ICM grading with regards to prediction of implantation (accuracy 64.7% vs 49.6%, area-under-the-curve 0.642 vs 0.486, precision 64.8% vs 51.9%, sensitivity 73% vs 65.1%, specificity 55.4% vs 32.1%, F1 score 68.7% vs 57.8%, 3D vs Gardner) and live birth (accuracy 62.2% vs 50.4%, area-under-the-curve 0.641 vs 0.531, precision 53.5% vs 44.3%, sensitivity 76% vs 70%, specificity 52% vs 36.2%, F1 score 62.2% vs 54.3%, 3D vs Gardner). Limitations, reasons for caution Manually rendering the 3D images for each ICM was time consuming, making it impractical for clinical application. Further work is now focusing on automating this process using image recognition and augmented reality. Wider implications of the findings This is a novel ICM assessment that provides an improved perspective of the 3-dimensionality of the ICM which is more consistent and effective than traditional methods of embryo assessment, potentially contributing towards improving embryo selection efficacy and time to pregnancy. Trial registration number none

P-740 Septoplasty versus expectant management in women with septate uterus and a previous history of a live birth

Abstract Study question Does hysteroscopic septoplasty improve reproductive outcome in patients who were diagnosed to have a septate uterus (SU) after a previous live birth? Summary answer This study suggests that hysteroscopic septoplasty improves the chance of a live birth in patients with both SU and a history of previous live birth. What is known already SU accounts for 50% of uterine anomalies and can be associated with adverse pregnancy outcomes. Many observational studies reported significant improvement in pregnancy outcomes following hysteroscopic septoplasty. However, some investigators have reported good reproductive outcome among women with SU without surgical interventions. A recent randomized controlled trial, albeit with a small sample size, reported no difference in reproductive outcomes between patients who underwent hysteroscopic septoplasty and those who had no surgery (Rikken 2021). Therefore, more studies are needed to be able to counsel patients with SU presenting with reproductive failure, especially those with a history of a previous live birth. Study design, size, duration This retrospective study included 114 patients who had a previous live birth and subsequently complained of reproductive failure. A SU was diagnosed during their work up between 2005-2022. Patients presented with secondary infertility (98.3%) or with recurrent pregnancy loss (RPL) [1.7%]. Forty-two patients presented with both secondary infertility and RPL (36.8%). Participants/materials, setting, methods Diagnosis of SU was suspected on transvaginal 3D ultrasound scan and was confirmed on a diagnostic hysteroscopy at an infertility clinic affiliated with an academic hospital. Patients were offered the option of hysteroscopic septoplasty or expectant management. Infertility treatment options depended on the underlying etiology and included spontaneous conception, oral fertility medications, intrauterine insemination, and in-vitro fertilization/embryo transfer. Eighty-two patients underwent hysteroscopic septoplasty (Group 1), while 32 patients declined surgery (Group 2). Main results and the role of chance There were no significant differences in mean age (years), BMI (Kg/m2), infertility duration, baseline FSH levels (mIU/mL), number of miscarriages, and gestational age at delivery before treatment between the two groups. There were no significant differences in incidence of ≤ 3 or ≥ 3 pregnancies, nor incidence of one live birth or &amp;gt; 1 live birth between the two groups. There were no significant differences in the underlying etiology, except for a significantly higher incidence of endometriosis (P = 0.004) and diminished ovarian reserve (P = 0.04) in Group 1 compared to Group 2. There were no significant differences in the incidence of partial septate uterus (PSU) [angle of indentation &amp;lt;90 degrees] and complete septate uterus between the two groups. However, there was significantly lower incidence of PSU with angle of indentation &amp;gt; 90 degrees (P = 0.028) and higher mean septum length in mm (18.9±1.0 vs 13.8±1.1, P = 0.024) on hysteroscopy in Group 1 compared to Group 2. After treatment, there were significantly higher pregnancy (68.3% vs 37.5%, p = 0.003) and live birth (61.7% vs 25%, P = 0.000) rates, but no significant difference in miscarriages (4.9% vs 6.3%), preterm birth (14% vs 25%) rates, or method of pregnancy in Group 1 compared to Group 2. Limitations, reasons for caution Our study has limitations being retrospective in nature with a small sample size. Therefore, more studies are required to support our findings. However, our pilot study explored management options in a particular group of patients with SU who initially proved their fertility and subsequently presented with reproductive failure. Wider implications of the findings Our data support the notion that patients with SU can have a normal reproductive outcome, although those who undergo septoplasty are expected to have a better chance of conception and live birth. During counselling of patients with SU, both surgical and expectant management can be offered. Trial registration number not applicable

O-129 Live birth of Day 7 blastocyst transfers. Another chance to succeed

Abstract Study question Does the reproductive potential, especially live birth probability, of embryos decrease when blastocyst development takes longer than the traditionally accepted 5 and 6 days?. Summary answer The reproductive potential decreases with blastulation time. Day 7 had the worst live birth (LB), aneuploidy and miscarriage rates compared to Day 5 and 6. What is known already Ending culture on Day 6 is current practice in most clinics, it is important to elucidate whether or not this is a good practice. It has been reported that Day 7 blastocysts represent only 5% of useable blastocysts, although slower growing compared to Day 5 and 6 blastocysts.Day 7 blastocysts can be viable, they can be of top morphological grade, euploid and result in a LB. Furthermore, the effects of prolonged culture to Day 7 in regards to embryo development and their reproductive potential are not well established. Study design, size, duration Retrospective cohort study of patients from US RMA clinics attempting conception through ICSI and utilizing preimplantation genetic testing for aneuploidy screening (PGT-A) from January 2022 to January 2023. A total of 6,132 ICSI PGT-A cycles were included in the analysis; three thousand six hundred and eighty frozen single embryo transfer (SET) from those resulting ICSI cycles occurred during that period of time were included in the study. Participants/materials, setting, methods Patients that performed an ICSI cycle with autologous oocytes were included in the study. Patients with frozen oocytes, donor egg recipients, non PGT-A cases, and conventional insemination were excluded. The main outcome measures include euploidy rates, miscarriage rates and LB rates between Days 5, 6 and 7. Statistical tests were conducted through Chi-Square Test and logistic regression methods adjusted for maternal age at time of transfer and morphological quality of the blastocyst. Main results and the role of chance Euploidy rate was worse on D7 than D5 or D6, with 45.5%95%CI(43,46%-47,50%), 78.1% 95%CI(77,02%-79,13%), and 63.2%95%CI(62,42%-63,96%) respectively, p&amp;gt;0.0001. LB rate per ET (embryo transfer) was also worse on D7, 21.6%95%CI(15.05-28.09), than D5, 62.3%95%CI(59.73-64.95), and D6, 53.3%95%CI(51.23-55.40). We found D5 and D6 statistically significant vs D7, p&amp;lt;0.0001. When adjusted for potential confounders, and establishing D7 as reference, for LB AdjORD5=4.127,95%CI(2.671-6.378), and AdjORD6=3.241, 95%CI(2.145-4.898). Clinical miscarriage was 20.8%, 95%CI(9.84-31.67) on D7, and 11.2%, 95%CI(9.38-13.09) and 14.1%, 95%CI(12.41-15.75) for D5 and D6 respectively, with AdjORD5=0.478, 95%CI(0.230-0.994) and AdjORD6, 95%CI(0.619, 95%CI(0.310-1.239), being statistically different only for AdjORD5 (p=0.048). Finally, when we analyzed the quality of the inner cell mass (ICM) and the trophectoderm among Day 7 ETs, we found that blastocysts with an A quality ICM had a higher chance of LB (40%) when compared with B (25%) and C (7.1%) ICM. The adjusted OR comparing A vs C revealed significant difference (p=0.005), when A ICM is established as reference. Also, ET of blastocysts graded with an A trophectoderm had higher probability of a LB (44%) when compared with B and C (17.3% and17%, respectively). The adjusted OR, with A trophectoderm as reference, B and C trophectoderm revealed significant difference (p=0.012 and p=0.007, respectively). Limitations, reasons for caution The primary limitation is the low number of Day 7 blastocyst transfers. To determine whether Day 7 blastocysts are intrinsically worse from Day 5/6 embryos, prospective randomized studies with patients who have at least one embryo developed on day 5, 6 and 7 suitable for transfer are needed. Wider implications of the findings Expanding blastocyst culture increases the number of useable embryos per cycle and provides further opportunity of LB for patients, especially those with a few or low-quality blastocysts. This study demonstrates that Day 7 blastocysts can achieve live births and challenges the predominant practice of ending culture before Day 7. Trial registration number 2206-SFR-079-MC

P-247 Comparison between two deep-learning based artificial intelligence models for time-lapse imaging: study on 814 blastocysts in fresh SET

Abstract Study question Comparison of the positive pregnancy predictibility between 2 deep-learning models of iDAScore (iDA-1 and iDA-2) in the same set of embryos. Summary answer The performances (AUC) to predict implantation are similar in both models with slightly higher sensitivity for iDA-2. Scores &amp;gt;6.4 display the best chances for implantation. What is known already The use of artificial intelligence (AI) is dramatically increasing in automatic annotation of the embryos as an aid to embryologists for evaluation and selection of the best implanting embryo. AI-based methods appear to be objective, standardized, and efficient tools for evaluating human embryos. AI-based automatic annotations need high accuracy and reliability to help securely standardizing and automatizing the process. iDAScore (Vitrolife) is a commercial deep-learning model for scoring embryos based on their implantation potential. Two versions of this model are currently available, iDAScore-1 and iDAScore-2. In this study we compare these two versions with the same cohort of embryos. Study design, size, duration Retrospective evaluation by the two models of 814 fresh SET cycles, from 758 patients, during 2020-2023 in a private hospital setting. Blastocyst selection for transfer was based on morphological grading and morphokinetic annotations (KID-Score, Gardner criteria) by experienced embryologists. Both version of iDAScore for each selected embryo was recorded retrospectively for not to influence the decision-making. Participants/materials, setting, methods The ICSIs incubated in Embryoscope + (Vitrolife) followed by fresh SET during the study period were enrolled. All the selected blastocysts for transfer were retrospectively annotated by well-trained experienced embryologist to iDA-1 and iDA-2. Pregnancy outcome was recorded and statistical analyses were performed with SPSS software using appropriate test, ROC analysis and AUC comparison to find predictibility for implantation and cut-off scores for poorest and best chances of pregnancy.Main results and the role of chance The mean female age was 36.43±0.14. The 814 SET achived 349 pregnancies and resulted in 199 live birth. The mean iDAScore in positive pregnancy, whatever the age, was different between the IDAScore versions. In iDA-1 the mean pregnancy score was 8.54 ± 0.98 and in iDA-2 the score was 6.2 ± 1.9. The mean iDAScore for ongoing pregnancy, regardless of age, was 9 ± 0.64 and 7.2 ± 1.51 and for live birth 8.8 ± 0.67 and 6.8 ± 1.74 respectively for each version. Comparing both versions: the AUC for predicting implantation/pregnancies was 0.652 [0.645-0.679] for iDA-1 and 0.678 [0.659-0.685] for iDA-2, establishing the best cut-off for implantation above 8.8 for iDA-1 and 6.4 for iDA-2. 7 score groups were defined to study pregnancy probability (1.1-2.9, 3-4.9, 5, 6, 7, 8, 9) and our results showed that blastocysts with iDA-1 &amp;lt;6 resulted in 7.1% pregnancy per fresh transfer and with iDA-2 &amp;lt;3 resulted in &amp;lt; 15% pregnancy per transfer. Chances of pregnancy and live birth were equivalent in scores 6-8.7 for iDA-1 and 3-6.3 for iDA-2: respectively 31.6% vs 31.6% and 19.7% vs 20.4%. Limitations, reasons for caution The main limitation of the study was the small size of the sample. However, our findings are concordant with the largest validation cohort of iDAScore-2. Wider implications of the findings iDA-2 appears to have a better pregnancy predictibility compared to the first version. However, the AUCs are quite comparable between the two versions. Setting the cut-off scores under which or above which the pregnancy chances are minimal or maximal is crucial for better management of patients communication and clinical decision-making. Trial registration number not applicable

P-739 Hysteroscopic metroplasty and thin endometrium, some new indication? Results of a multicenter retrospective study

Abstract Study question Is there a place for hysteroscopic metroplasty in the management of thin endometrium? Summary answer Hysteroscopic metroplasty appears to significantly improve the chances of live birth in a population of infertile patients with thin endometrium. What is known already A thin endometrium is found in 1 to 12 % of the cases for patient treated in an infertility center. When a thin endometrium is repeatedly observed there is no specific protocol for resolving the situation. Numerous study have been carried out on this subject but here is insufficient evidence to recommend a specific treatment because the results are inconclusive, or not strong enough. Hysteroscopic-metroplasty is use by several teams to treat infertile women with T-Shaped uterus. We assumed that metroplasty could improve results in patients with a thin endometrium by stimulating endometrial recolonisation as observed in cases of synechia section. Study design, size, duration This is a multi-center retrospective observational study conducted between 1er January 2015 and 31 December 2021 at the Clinique Mutualiste de la Sagesse, Rennes, France and in the University Hospital of the Kremlin Bicêtre, APHP, France. T-Shaped uterus was diagnosed by an ultrasound expert, and a thin endometrium was defined as an endometrium less than 7mm thick after a minimum of 14 days of well-conducted stimulation. Participants/materials, setting, methods Exclusion criteria were age &amp;lt; 18 years, previous hysteroscopic metroplasty, past history of more than one synechia treatment. The primary outcome was first live birth after surgery. Secondary endpoints were pregnancy rate and spontaneous pregnancy rate, surgery complications, neonatal outcomes. This retrospective study used data collected prospectively. Main results and the role of chance Our objective was to evaluate hysteroscopic metroplasty in the management of infertile patients with T-shaped uterus type dysmorphia and / or a thin endometrium. The primary endpoint was the occurrence of a live birth rate post-surgery. One hundred and forty five infertile patients were included, including 126 nulliparous women (86.9%). The post-surgery live birth rate was 40.7% during the total post-operative follow-up, with similar result in case of thin endometrium or in case of T-Shaped uterus. In terms of pregnancy, we recorded 75 post-surgery pregnancies (51.7%), of which one third was obtain spontaneously. The duration of infertility suffered by patients before surgery ranged from 1 to 7 years and the average duration of conception after surgery was less than 1 year. We did not raise any major per or post operative complication for both mother and the future baby. Hysteroscopic metroplasty appears to significantly improve the chances of live birth in a population of infertile patients with at least one uterine pathology such as T-shaped uterus or thin endometrium Limitations, reasons for caution This is a retrospective study, with all the biases that this implies. More robust studies are therefore needed before the practice can be generalised. Furthermore these results were obtained in 2 expert centres. Although the technique is easily reproducible, caution must be exercised before generalising it. Wider implications of the findings This study is the first one to the best of our knowledge to provide an opportunity to consider this new treatment option for thin endometrium, what is still an under-recognised pathology. Our results can be used to justify the initiation of a randomised controlled trial. Trial registration number not applicable

P-655 Live birth rate in the fresh cycle associated with number of oocytes in ovarian stimulation with individualised follitropin delta: an individual patient data meta-analysis

Abstract Study question What is the optimum number of oocytes retrieved to achieve a live birth for women undergoing ovarian stimulation with individualised follitropin delta? Summary answer The live birth rate (LBR) in the fresh cycle was highest in the range of 8-14 oocytes retrieved, peaking at 11 oocytes. What is known already The number of oocytes retrieved following ovarian stimulation for assisted reproductive technologies is regarded a prognostic marker of pregnancy outcome, where high numbers increase chances of live birth but also the risk of complications, especially ovarian hyperstimulation syndrome (OHSS). Thus, an optimum range of oocytes retrieved is essential. Still, there is no consensus regarding this range in fresh cycles. Optimum numbers between 6 and 15 oocytes have been suggested, taking the risk of OHSS into consideration. The individualised dosing algorithm for the recombinant follicle-stimulating hormone follitropin delta has a target range of 8–14 oocytes. Study design, size, duration Individual patient data meta-analysis of 1772 patients from 5 randomised controlled trials using individualised dosing of follitropin delta for ovarian stimulation, with fixed daily dosing based on serum anti-Müllerian hormone (AMH) and body weight. The analysis included patients with ≥1 oocyte retrieved. Outcomes of LBR and OHSS in the fresh stimulation cycle were evaluated in relation to number of oocytes retrieved. Subgroup analyses were performed based on age, AMH and number of oocytes retrieved. Participants/materials, setting, methods Participants were women, 18–42 years, undergoing first or second in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycle in a GnRH antagonist/long agonist protocol with human chorionic gonadotrophin or GnRH agonist triggering and IVF/ICSI. Single or double embryo/blastocyst transfer was performed on Day 3/5. All pregnancies were followed until birth. Predicted live birth was obtained using a logistic regression analysis with fractional polynomials to assess the association between number of oocytes retrieved and live birth. Main results and the role of chance The studied population (n = 1772) had a mean age of 32.6 years and median AMH of 17.7 pmol/l. Mean number of oocytes retrieved was 10.4, the LBR was 32.1% and the OHSS rate (any grade and onset) was 6.6%. The LBR steadily increased with the number of oocytes retrieved up to a plateau starting at 8 oocytes, with a LBR above 34% in the range of 8-14 oocytes retrieved, peaking at 34.9% for 11 oocytes. Beyond 14 oocytes, LBR gradually declined. By number of oocytes (grouped), the LBR was 27.8%, 33.6% and 30.9% at 1-7, 8-14 and ≥15 oocytes. In patients with embryo transfer, corresponding rates were 32.8%, 37.2% and 38.7%. In the subgroup analyses, LBR decreased with increasing age (32.7%, 30.7% and 23.4% at &amp;lt; 35, 35-37 and 38-42 years) while it was similar for AMH &amp;lt;15 and ≥15 pmol/l (30.4% and 31.3%, respectively). LBR was highest at 8-14 oocytes in patients &amp;lt;35 years (28.0%, 36.2% and 32.4% at 1-7, 8-14 and ≥15 oocytes), while it was consistently low (&amp;lt;26%) in patients 38-42 years, irrespective of number of oocytes retrieved. The OHSS rate (any grade) increased from 2.1% with 1-7 oocytes, to 5.2% with 8-14 oocytes and 17.0% with ≥15 oocytes. Limitations, reasons for caution A limitation of this study is the small number of patients with &amp;gt;20 oocytes retrieved in the studied population. Wider implications of the findings The current individual patient data meta-analysis suggests an optimum range of 8-14 oocytes retrieved to achieve a live birth in fresh cycles with follitropin delta. Furthermore, the analysis demonstrates a marked increase in OHSS rate from 15 oocytes retrieved. The results support the appropriateness of individualised follitropin delta dosing regimen. Trial registration number NCT01956110, NCT03228680, NCT03296527, NCT03564509, NCT03809429

P-162 Embryo transfer impact: a comprehensive national cohort analysis comparing maternal outcomes across varied embryo stages in fresh and frozen transfers

Abstract Study question What is the ideal choice between fresh and frozen embryos transfer, and should the transfer be done at the cleavage or blastocyst stage? Summary answer This study highlights the clinical pregnancy and live birth superiority of frozen embryo transfer in blastocysts but not in cleavage stage embryos. What is known already Frozen embryo transfer not only improves reproductive outcomes by increasing the chances of live birth and clinical pregnancy but also enhances safety by reducing the risks of OHSS and multiple pregnancies. Due to the consistent findings, there has been a growing discussion in recent years about whether it is advisable to adopt elective frozen embryo transfer as the standard practice. Study design, size, duration In this retrospective cohort study conducted in Taiwan, a comprehensive dataset from the national assisted reproductive technology (ART) database was utilized, covering the period from January 1st, 2013, to December 31st, 2017. The final cohort study encompassed eligible 51762 female participants who had undergone ART and embryo transfer. Pregnancy outcomes and maternal complications during the follow-up were assessed using the population registry dataset from January 1st, 2013, to December 31st, 2018. Participants/materials, setting, methods The study categorizes cases into groups based on whether they underwent fresh or frozen embryo transfers, with additional subgroups based on cleavage stage and blastocyst stage transfers. Exposure variables include clinical pregnancy rate, live birth rate, ovarian hyperstimulation syndrome (OHSS), pregnancy-induced hypertension, gestational diabetes mellitus (DM), placenta previa, placental abruption, and preterm premature rupture of membranes (PPROM). Main results and the role of chance For pregnancy outcomes, frozen blastocyst transfers exhibited higher rates of clinical pregnancy (OR 1.33, 95%CI 1.25-1.42) and live births (OR 1.27, 95%CI 1.19-1.36) when compared to fresh blastocyst transfers. However, frozen cleavage stage transfers had lower rates of clinical pregnancy (OR 0.73, 95%CI 0.69-0.77) and live births (OR 0.79, 95%CI 0.74-0.84) compared to fresh cleavage stage transfers. For maternal complications, frozen embryo transfers were associated with reduced risks of OHSS (OR 0.02, 95%CI 0.02-0.03 for blastocyst and OR 0.05, 95%CI 0.03-0.09 for cleavage stage) compared to fresh embryo transfers, but were linked to a higher risk of pregnancy-induced hypertension (OR 1.43, 95%CI 1.19-1.73 for blastocyst and OR 1.23, 95%CI 1.29-1.82 for cleavage stage). No significant differences were observed in the incidence of gestational DM and PPROM among the various transfer groups. Limitations, reasons for caution Our retrospective study design may not offer the same level of rigor as a randomized controlled trial. Furthermore, the reproductive database did not provide detailed information on specific endometrial preparation methods (such as hormone replacement therapy or natural cycle), which could potentially influence implantation outcomes. Wider implications of the findings The freeze-all strategy may not be suitable for universal application. When embryos can develop to the blastocyst stage, frozen embryo transfer is a favorable choice, but embryos can only develop to the cleavage stage, fresh embryo transfer becomes a more reasonable option. Trial registration number KMUHIRB-E(I)-20210222

P-195 Euploid embryo transfer in a hyaluronic acid-enriched media results in a higher ongoing pregnancy rate than euploid embryo transfer in media not containing hyaluronic acid

Abstract Study question Will using a hyaluronan-rich transfer medium increase the ongoing pregnancy rate and live birth rate when transferring euploid embryos cultivated in a dry incubator? Summary answer Transferring euploid embryos in a media with high concentrations of hyaluronic acid increases the ongoing pregnancy rate compared with media with no hyaluronic acid. What is known already Cochrane Review found that solutions with high concentrations of hyaluronic acid increase the chance of live birth by adding probably 1 additional live birth for every 14 embryos transferred in a high-concentration hyaluronic acid solution for patients aged 27 to 35. A study involving 85 frozen embryo transfer cycles showed a positive effect of high concentrations of hyaluronic acid on the results of transfer of morphologically poor euploid blastocysts. Previous studies were conducted in humidified incubators where hyaluronic acid-rich media was equilibrated without oil overlay. Our clinic uses dry incubators, necessitating oil overlay with all media, including hyaluronic acid-rich media. Study design, size, duration A randomized prospective study involving 255 patients aged 19-44 undergoing a transfer of a single euploid embryo between June 2023 and November 2023. Patients were randomly assigned to the study and control groups. Blastocysts were incubated after thawing for 3 hours either in a hyaluronic acid-enriched medium or in a medium without hyaluronic acid. Participants/materials, setting, methods Embryos underwent PGT-A at the blastocyst stage on either day 5 or day 6, using the EmbryoMap method. Trophectoderm biopsy was performed using the Flicking technique without a laser. 5-7 cells were removed for analysis. Blastocysts were vitrified following biopsy. Hyaluronic acid-enriched media was equilibrated for 16-18 hours in a 5%O2 6%CO2 atmosphere in a well of 4-well culture dish under oil overlay (600 microliters of media and 500 microliters of oil). Main results and the role of chance In this ongoing study, 127 transfers of euploid blastocysts in a hyaluronic acid-rich media resulted in 70 ongoing pregnancies, with a 55.1% ongoing pregnancy rate. In comparison, 128 transfers of euploid blastocysts in a media with no hyaluronic acid resulted in 65 ongoing pregnancies, with a 50.8% ongoing pregnancy rate. The relative improvement in the ongoing pregnancy rate is 8.5%. Our data suggests that using a hyaluronic acid-rich medium for the transfer of euploid blastocysts of good morphology can improve clinical pregnancy rates, although the effect is less dramatic than was shown in a 2023 study by Nakagawa et al. for morphologically poor euploid blastocysts, where more than twofold increase in clinical pregnancy rates was detected. Limitations, reasons for caution Specific media equilibration protocol is required for the incubation and transfer of embryos in a hyaluronan-rich transfer medium for IVF clinics utilizing dry incubators. Further research is required to confirm results and to establish whether transferring embryos in hyaluronic acid-enriched media increases the live birth rate after euploid embryo transfer. Wider implications of the findings Our results show that it is feasible to use a hyaluronic acid-enriched medium in a dry incubator with an oil overlay and that using it according to described protocol could increase the ongoing pregnancy rate after a single euploid blastocyst transfer. Trial registration number not applicable

P-250 Only euploidy does not ensure optimal chances for successful live birth through single blastocyst cryotransfer

Abstract Study question What does a euploid blastocyst require to provide the greatest probability of successful birth? Summary answer Morphokinetic and morphological features of the inner cell mass (ICM) and trophectoderm (TE) are crucial for optimizing live birth chances in cryo-transferred euploid blastocysts. What is known already Embryo selection through preimplantation genetic testing for aneuploidy (PGT-A) alongside frozen embryo transfer strategy enhances outcomes of single-embryo transfer cycles. While euploidy is a crucial indicator, investigations on the identification of additional criteria influencing implantation and live birth rates remain imperative. Studies suggest morphokinetic and morphological quality may supplement predictive factors for euploid embryo success, with varying correlations. The impact of factors like age or gamete origin on euploid blastocyst success remains uncertain, differentiating it from clear effects on non-diagnosed embryos. Optimizing selection criteria involves navigating the intricate interplay of these variables. Study design, size, duration This retrospective study analyses the pregnancy rate (PR) in 596 single embryo cryotransfers of full euploid blastocysts (without detected mosaicism) between February 2019 and September 2023. From these, 437 had a known outcome, and the live birth rate (LBR) was calculated. The study explored the potential impact of gamete origin, oocyte provider age, recipient age, morphokinetics, and morphological quality of ICM or TE (Gardner score) on the reproductive success of the transferred embryo. Participants/materials, setting, methods All embryos were biopsied at the blastocyst stage and successively vitrified. High-resolution next-generation sequencing was used for PGT-A. Only deferred transferences of single post-thawing intact embryos were included. Morphokinetic was assessed using the KIDscoreD5 3.1. Quantitative variables (oocyte provider age, recipient age, and morphokinetic score) were compared using the t-student test, while qualitative variables (gamete origin, morphological quality of ICM and TE) were assessed using the chi-square test. Main results and the role of chance Oocytes leading to pregnancies and live births were derived from women with ages comparable to those without success (Pregnancy: 30.0±7.1 vs. 30.8±6.8, p = 0.174; Live Birth: 30.1±7.1 vs. 30.5±6.9, p = 0.499). Similar age was also observed among recipients achieving pregnancy (41.5±5.4) and live births (41.1±5.1) compared to those who did not (Pregnancy: 41.8±5.1, p = 0.506; Live Birth: 41.5±5.3, p = 0.411). The origin of oocytes and semen (own or donor) did not significantly affect PR (Oocytes: 199/273 vs. 217/323, p = 0.130; Semen: 328/473 vs. 88/123, p = 0.224) or LBR (Oocytes: 113/205 vs. 116/232, p = 0.285; Semen: 183/347 vs. 46/90, p = 0.783). Morphokinetics played a crucial role, with euploid embryos resulting in pregnancy (7.5±1.7) and live births (7.6±1.6) exhibiting significantly higher scores than those without success (6.9±1.7; 7.1±1.7; p &amp;lt; 0.05).199 ICM quality did not significantly impact PR (A:211/296, B:190/275, C:15/25; p = 0.469). However, higher miscarriage rates in C-quality ICM blastocysts significantly reduced the LBR (A:116/211, B:107/205, C:6/21; p &amp;lt; 0.05). TE quality exhibited significant differences in PR (A:221/289, B:184/289, C:11/18; p &amp;lt; 0.05). Since the miscarriage rate was similar among groups (p = 0.787), LBR remained higher in A-quality TE blastocysts (A:124/209, B:98/213, C:7/17; p &amp;lt; 0.05). Limitations, reasons for caution As a retrospective analysis, this study is inherently limited. The influence of expansion grade on success rates remains unexplored, given the use of assisted hatching on day 3 of culture. Performing assisted hatching at the time of biopsy could potentially overcome this limitation. Wider implications of the findings The pursuit of a euploid embryo often becomes the priority in IVF laboratories. However, once the milestone is achieved, morphokinetics and embryonic morphological quality must continue to be considered. This study provides valuable insights for conveying a detailed message to patients with euploid embryos about their prospects for homebirth success. Trial registration number not applicable

Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction.

Practitioners in the field of assisted reproductive technology (ART) continually seek alternative or adjunct treatments to improve ART outcomes. This Cochrane review investigates the adjunct use of synthetic versions of two naturally produced hormones, dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction. Steroid hormones are proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation. This may lead to a greater oocyte yield and, subsequently, an increased chance of pregnancy. To assess the effectiveness and safety of DHEA and T as pre- or co-treatments in infertile women undergoing assisted reproduction. We searched the following electronic databases up to 8 January 2024: the Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and trial registries for ongoing trials. We also searched citation indexes, Web of Science, PubMed, and OpenGrey. We searched the reference lists of relevant studies and contacted experts in the field for any additional trials. There were no language restrictions. Randomised controlled trials (RCTs) comparing DHEA or T as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction. Two review authors independently selected studies, extracted relevant data, and assessed risk of bias. We pooled data from studies using fixed-effect models. We calculated odds ratios (ORs) for each dichotomous outcome. Analyses were stratified by type of treatment. We assessed the certainty of evidence for the main findings using GRADE methods. We included 29 RCTs. There were 1599 women in the intervention group and 1469 in the control group. Apart from three trials, the trial participants were women identified as 'poor responders' to standard in vitro fertilisation (IVF) protocols. The included trials compared either T or DHEA treatment with placebo or no treatment. Pre-treatment with DHEA versus placebo/no treatment: DHEA likely results in little to no difference in live birth/ongoing pregnancy rates (OR 1.30, 95% confidence interval (CI) 0.95 to 1.76; I² = 16%, 9 RCTs, N = 1433, moderate certainty evidence). This suggests that in women with a 12% chance of live birth/ongoing pregnancy with placebo or no treatment, the live birth/ongoing pregnancy rate in women using DHEA will be between 12% and 20%. DHEA likely does not decrease miscarriage rates (OR 0.85, 95% CI 0.53 to 1.37; I² = 0%, 10 RCTs, N =1601, moderate certainty evidence). DHEA likely results in little to no difference in clinical pregnancy rates (OR 1.18, 95% CI 0.93 to 1.49; I² = 0%, 13 RCTs, N = 1886, moderate certainty evidence). This suggests that in women with a 17% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using DHEA will be between 16% and 24%. We are very uncertain about the effect of DHEA on multiple pregnancy (OR 3.05, 95% CI 0.47 to 19.66; 7 RCTs, N = 463, very low certainty evidence). Pre-treatment with T versus placebo/no treatment: T likely improves live birth rates (OR 2.53, 95% CI 1.61 to 3.99; I² = 0%, 8 RCTs, N = 716, moderate certainty evidence). This suggests that in women with a 10% chance of live birth with placebo or no treatment, the live birth rate in women using T will be between 15% and 30%. T likely does not decrease miscarriage rates (OR 1.63, 95% CI 0.76 to 3.51; I² = 0%, 9 RCTs, N = 755, moderate certainty evidence). T likely increases clinical pregnancy rates (OR 2.17, 95% CI 1.54 to 3.06; I² = 0%, 13 RCTs, N = 1152, moderate certainty evidence). This suggests that in women with a 12% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using T will be between 17% and 29%. We are very uncertain about the effect of T on multiple pregnancy (OR 2.56, 95% CI 0.59 to 11.20; 5 RCTs, N = 449, very low certainty evidence). We are uncertain about the effect of T versus oestradiol or T versus oestradiol + oral contraceptive pills. The certainty of the evidence was moderate to very low, the main limitations being lack of blinding in the included trials, inadequate reporting of study methods, and low event and sample sizes in the trials. Data on adverse events were sparse; any reported events were minor. Pre-treatment with T likely improves, and pre-treatment with DHEA likely results in little to no difference, in live birth and clinical pregnancy rates in women undergoing IVF who have been identified as poor responders. DHEA and T probably do not decrease miscarriage rates in women under IVF treatment. The effects of DHEA and T on multiple pregnancy are uncertain. Data regarding adverse events were very limited; any reported events were minor. Research is needed to identify the optimal duration of treatment with T. Future studies should include data collection on adverse events and multiple pregnancy.