Euploidy Rates Research Articles

Autologous non-invasively derived stem cells mitochondria transfer shows therapeutic advantages in human embryo quality rescue

BackgroundThe decline in the quantity and quality of mitochondria are closely associated with infertility, particularly in advanced maternal age. Transferring autologous mitochondria into the oocytes of infertile females represents an innovative and viable strategy for treating infertility, with no concerns regarding ethical considerations. As the donor cells of mitochondria, stem cells have biological advantages but research and evidence in this area are quite scarce.MethodsTo screen out suitable human autologous ooplasmic mitochondrial donor cells, we performed comprehensive assessment of mitochondrial physiology, function and metabolic capacity on a varity of autologous adipose, marrow, and urine-derived mesenchymal stromal cells (ADSC, BMSC and USC) and ovarian germline granulosa cells (GC). Further, to explore the biosafety, effect and mechanism of stem cell-derived mitochondria transfer on human early embryo development, randomized in-vitro basic studies were performed in both of the young and aged oocytes from infertile females.ResultsCompared with other types of mesenchymal stromal cells, USC demonstrated a non-fused spherical mitochondrial morphology and low oxidative stress status which resembled the oocyte stage. Moreover, USC mitochondrial content, activity and function were all higher than other cell types and less affected by age, and it also exhibited a biphasic metabolic pattern similar to the pre-implantation stage of embryonic development. After the biosafety identification of the USC mitochondrial genome, early embryos after USC mitochondrial transfer showed improvements in mitochondrial content, activity, and cytoplasmic Ca2+ levels. Further, aging embryos also showed improvements in embryonic morphological indicators, euploidy rates, and oxidative stress status.ConclusionAutologous non-invasively derived USC mitochondria transfer may be an effective strategy to improve embryonic development and metabolism, especially in infertile females with advanced age or repeated pregnancy failure. It provides evidence and possibility for the autologous treatment of infertile females without invasive and ethical concerns.

Optimal antimüllerian hormone levels in oocyte donors: a national database analysis

To study the relationship between high antimüllerian hormone (AMH) levels in oocyte donors and embryo development and pregnancy outcomes among donor oocyte recipients. Retrospective cohort study. Donor Egg Bank Database. Patients undergoing invitro fertilization using vitrified donor oocytes from 35 invitro fertilization centers in the United States between 2013 and 2021. For each recipient, the first oocyte lot that was received with a planned insemination and embryo transfer (ET) was included. Oocyte donor-recipient cycles. Ongoing pregnancy rate (OPR) per ET. A total of 3,871 donor oocyte-recipient thaw cycles were analyzed. On the basis of donor AMH serum concentration, cycles were stratified into the high AMH group (AMH ≥5 ng/mL; n = 1,821) and the referent group (AMH <5 ng/mL; n = 2,050). Generalized estimating equation models were used to account for donors that contributed more than one lot of oocytes. The number of usable embryos per lot (median [interquartile range]) was significantly increased in the high AMH group (2 [2-4]) compared with the referent group (2 [1-3]) (relative risk [RR] 1.06; confidence interval [CI] 1.01-1.12). Among recipients with a planned ET, there was no difference in OPR between the high AMH group (45.4%) and the referent group (43.5%) (RR 1.04; 95% CI 0.94-1.15). Among preimplantation genetic testing for aneuploidy cycles, the embryo euploidy rate per biopsy was similar at 66.7% (50%-100%) in both groups (RR 1.04; CI 0.92-1.17). The OPR per euploid ET among patients who used preimplantation genetic testing for aneuploidy was also comparable, at 52% in the high AMH group and 54.1% in the referent group (RR 0.95; CI 0.74-1.23). This large national database study observed that there was no association between a high level of AMH (≥5 ng/mL) in oocyte donors and an OPR in the recipient after the first ET. On the basis of these findings, recipients and physicians can be reassured that oocyte donors with a high AMH level can be expected to produce outcomes that are at least as good as donors with an AMH level (<5 ng/mL).

The effect of advanced sperm selection methods on euploidy rates and live birth rates in PGT-A cycles

The effect of advanced sperm selection methods on euploidy rates and live birth rates in PGT-A cycles

Compared With Conventional Insemination, Intracytoplasmic Sperm Injection Provides No Benefit in Cases of Nonmale Factor Infertility as Evidenced by Comparable Euploidy Rate

(Abstracted from Fertil Steril 2023;120(2)) Intracytoplasmic sperm injection (ICSI) has dramatically improved fertilization rates for couples with male factor infertility and those with prior failed in vitro fertilization (IVF) cycles. Although several international academic organizations and the cumulative evidence do not suggest the routine use of ICSI for nonmale factor infertility, it is now used frequently for all cases of IVF regardless of the indication.

Adjuvant letrozole administration in gonadotropin releasing hormone antagonist cycles do not affect ploidy status of embryos

ObjectiveTo evaluate the effects of adjuvant letrozole administration on euploid embryo rates in gonadotropin releasing hormone (GnRH) antagonist cycles. MethodsThis retrospective study was conducted by analyzing data of patients that underwent GnRH antagonist cycles with intra-cytoplasmic sperm injection (ICSI) and pre-implantation genetic testing for aneuploidy between 2013 and 2021. Study included a total of 713 patients which 84 of them were received adjuvant letrozole and 629 patients underwent ovulation induction without any adjuvant therapy. ResultsIn patients with letrozole administration, total dose of consumed gonadotropins were significantly lower (2166.80 ± 738.82 IU vs. 2541.96 ± 755.76 IU; p < 0.001, respectively), and duration of stimulation was slightly longer (9.80 ± 1.23 days vs. 9.53 ± 1.38 days; p = 0.037) in comparison to patients without letrozole administration. Overall euploidy rates were found similar among letrozole group and control group (28.02 % ± 31.08 % vs. 23.02 % ± 30.87 %; p = 0.109). Similar rate of euploidy remained even after stratification of patients in accordance with female age. There was no significant difference in terms of live birth rates between letrozole administered group and control group (66.7 % vs 62.2 %, respectively). ConclusionCo-treatment with 5 mg/day letrozole for 5 days does not appear to affect euploidy rates of obtained embryos in GnRH antagonist cycles with ICSI.

Implicit bias in diagnosing mosaicism amongst preimplantation genetic testing providers: results from a multicenter study of 36 395 blastocysts.

Does the diagnosis of mosaicism affect ploidy rates across different providers offering preimplantation genetic testing for aneuploidies (PGT-A)? Our analysis of 36 395 blastocyst biopsies across eight genetic testing laboratories revealed that euploidy rates were significantly higher in providers reporting low rates of mosaicism. Diagnoses consistent with chromosomal mosaicism have emerged as a third category of possible embryo ploidy outcomes following PGT-A. However, in the era of mosaicism, embryo selection has become increasingly complex. Biological, technical, analytical, and clinical complexities in interpreting such results have led to substantial variability in mosaicism rates across PGT-A providers and clinics. Critically, it remains unknown whether these differences impact the number of euploid embryos available for transfer. Ultimately, this may significantly affect clinical outcomes, with important implications for PGT-A patients. In this international, multicenter cohort study, we reviewed 36 395 consecutive PGT-A results, obtained from 10 035 patients across 11 867 treatment cycles, conducted between October 2015 and October 2021. A total of 17 IVF centers, across eight PGT-A providers, five countries and three continents participated in the study. All blastocysts were tested using trophectoderm biopsy and next-generation sequencing. Both autologous and donation cycles were assessed. Cycles using preimplantation genetic testing for structural rearrangements were excluded from the analysis. The PGT-A providers were randomly categorized (A to H). Providers B, C, D, E, F, G, and H all reported mosaicism, whereas Provider A reported embryos as either euploid or aneuploid. Ploidy rates were analyzed using multilevel mixed linear regression. Analyses were adjusted for maternal age, paternal age, oocyte source, number of embryos biopsied, day of biopsy, and PGT-A provider, as appropriate. We compared associations between genetic testing providers and PGT-A outcomes, including the number of chromosomally normal (euploid) embryos determined to be suitable for transfer. The mean maternal age (±SD) across all providers was 36.2 (±5.2). Our findings reveal a strong association between PGT-A provider and the diagnosis of euploidy and mosaicism. Amongst the seven providers that reported mosaicism, the rates varied from 3.1% to 25.0%. After adjusting for confounders, we observed a significant difference in the likelihood of diagnosing mosaicism across providers (P < 0.001), ranging from 6.5% (95% CI: 5.2-7.4%) for Provider B to 35.6% (95% CI: 32.6-38.7%) for Provider E. Notably, adjusted euploidy rates were highest for providers that reported the lowest rates of mosaicism (Provider B: euploidy, 55.7% (95% CI: 54.1-57.4%), mosaicism, 6.5% (95% CI: 5.2-7.4%); Provider H: euploidy, 44.5% (95% CI: 43.6-45.4%), mosaicism, 9.9% (95% CI: 9.2-10.6%)); and Provider D: euploidy, 43.8% (95% CI: 39.2-48.4%), mosaicism, 11.0% (95% CI: 7.5-14.5%)). Moreover, the overall chance of having at least one euploid blastocyst available for transfer was significantly higher when mosaicism was not reported, when we compared Provider A to all other providers (OR = 1.30, 95% CI: 1.13-1.50). Differences in diagnosing and interpreting mosaic results across PGT-A laboratories raise further concerns regarding the accuracy and relevance of mosaicism predictions. While we confirmed equivalent clinical outcomes following the transfer of mosaic and euploid blastocysts, we found that a significant proportion of mosaic embryos are not used for IVF treatment. Due to the retrospective nature of the study, associations can be ascertained, however, causality cannot be established. Certain parameters such as blastocyst grade were not available in the dataset. Furthermore, certain platform-related and clinic-specific factors may not be readily quantifiable or explicitly captured in our dataset. As such, a full elucidation of all potential confounders accounting for variability may not be possible. Our findings highlight the strong need for standardization and quality assurance in the industry. The decision not to transfer mosaic embryos may ultimately reduce the chance of success of a PGT-A cycle by limiting the pool of available embryos. Until we can be certain that mosaic diagnoses accurately reflect biological variability, reporting mosaicism warrants utmost caution. A prudent approach is imperative, as it may determine the difference between success or failure for some patients. This work was supported by the Torres Quevedo Grant, awarded to M.P. (PTQ2019-010494) by the Spanish State Research Agency, Ministry of Science and Innovation, Spain. M.P., L.B., A.R.L., A.L.R.d.C.L., N.P.P., M.P., D.S., F.A., A.P., B.M., L.D., F.V.M., D.S., M.R., E.P.d.l.B., A.R., and R.V. have no competing interests to declare. B.L., R.M., and J.A.O. are full time employees of IB Biotech, the genetics company of the Instituto Bernabeu group, which performs preimplantation genetic testing. M.G. is a full time employee of Novagen, the genetics company of Cegyr, which performs preimplantation genetic testing. N/A.

Multiple embryo manipulations in PGT-A cycles may result in inferior clinical outcomes

Research questionDo embryos that undergo a thaw, biopsy and re-vitrification (TBR) for pre-implantation genetic testing for aneuploidy (PGT-A) have different ploidy and transfer outcomes compared with fresh biopsied embryos? DesignRetrospective cohort study of all embryos that underwent the following procedures: fresh biopsy for PGT-A (fresh biopsy); embryos that were warmed, biopsied for PGT-A and re-vitrified (single biopsy TBR); embryos with a no signal result after initial biopsy that were subsequently warmed, biopsied and re-vitrified (double biopsy TBR). The patients who underwent transfers of those embryos at a single academic institution between March 2013 and December 2021 were also studied. ResultsAbout 30% of embryos planned for TBR underwent attrition. Euploidy rates were similar after biopsy: fresh biopsy (42.7%); single biopsy TBR (47.5%) (adjusted RR: 0.99, 0.88 to 1.12); and double biopsy TBR 50.3% (adjusted RR: 0.99, 0.80 to 1.21). Ongoing pregnancy over 8 weeks was not statistically significant (double biopsy TBR: 6/19 [31.6%] versus fresh biopsy: 650/1062 [61.2%]) (adjusted RR 0.52, 95% CI 0.26 to 1.03). The miscarriage rate increased (double biopsy TBR: 4/19 [21.1%] versus fresh biopsy: 66/1062 [6.2%])(RR 3.39, 95% CI 1.38 to 8.31). Live birth rate was also lower per transfer for the double biopsy TBR group (double biopsy TBR [18.75%] versus fresh biopsy [53.75%]) (RR 0.35, 95% CI 0.12 to 0.98), though not after adjustment (adjusted RR 0.37, 95% CI 0.13 to 1.09). These differences were not seen when single biopsy TBR embryos were transferred. ConclusionsEmbryos that undergo TBR have an equivalent euploidy rate to fresh biopsied embryos. Despite that, double biopsy TBR embryos may have impaired transfer outcomes.

Random-start ovarian stimulation in an oocyte donation programme: a large, single-centre, experience

Research questionDo live birth rates differ between recipients matched with donors using conventional ovarian stimulation compared with those using random-start protocols? DesignRetrospective analysis of 891 ovarian stimulations in egg donors (January–December 2018) and clinical outcomes in matched recipients (n = 935). Donors commenced ovarian stimulation on day 1–3 of the menstrual cycle (n = 223) or in the mid/late-follicular (n = 388) or luteal phase (n = 280) under a conventional antagonist protocol. Live birth rate of matched recipients was the main outcome. ResultsDuration of stimulation and total gonadotrophin dose were comparable between conventional versus random-start groups. The number of collected eggs were similar (17.6 ± 8.8 versus 17.2 ± 8.5, P = 0.6, respectively). Sub-group analysis showed that stimulation length (10.2 ± 1.8 versus 9.8 ± 1.7 versus 10.4 ± 1.7, P < 0.001) and gonadotrophin consumption (2041.5 ± 645.3 versus 2003.2 ± 647.3 versus 2158.2 ± 685.7 IU, P = 0.01) differed significantly between the conventional, mid/late follicular and luteal phase groups, respectively. In matched recipients receiving fresh oocytes and undergoing fresh embryo transfer, the biochemical pregnancy (63.8% and 63.3%; P = 0.9), clinical pregnancy (54.6% and 56.1%; P = 0.8) and live birth rates (47.7% and 46.6%; P = 0.7) per embryo-transfer were similar between conventional versus random groups. Similar results were obtained in recipients receiving vitrified eggs. Euploidy rate was also comparable. ConclusionsNo notable variations were found in clinical outcomes using oocytes obtained from random-start protocols and those proceeding from conventional ovarian stimulation in oocyte donation treatments. Luteal-phase stimulation seems to require longer stimulation and higher FSH consumption. Random-start stimulation strategy does not impair the potential of the oocyte yield or clinical outcomes in oocyte donation cycles.

The impact of the number of previous miscarriages on embryo euploid rate and pregnancy outcomes in patients with unexplained recurrent pregnancy loss

Objective: To investigate the impact of the number of previous miscarriages on embryo euploid rate and pregnancy outcomes after preimplantation genetic testing for aneuploidies (PGT-A) in patients with unexplained recurrent pregnancy loss (uRPL). Methods: A retrospective cohort study was conducted. 799 women with uRPL who underwent PGT-A for the first time between January 2015 and December 2021 at the Reproductive center of Shandong University were enrolled. These patients were divided into three groups according to the number of previous miscarriages (2, 3, and≥4). Stratified analysis was conducted according to female age (≤37 years and>37 years). The embryo euploidy rate, good-quality blastocyst formation rate, cumulative live birth rate, and cumulative clinical pregnancy loss rate of three groups were compared in younger and older patients, respectively. Meanwhile, the cumulative live birth rate, clinical pregnancy loss rate, and embryo euploidy rate were analyzed by multivariate logistic regression analysis. Results: Patients' age was (34.7±5.1) years old. In the three groups with 2, 3 and ≥4 previous miscarriages, there was no significant difference in the embryo euploidy rate between groups in the younger [48.9% (539/1 103), 50.6% (354/700) and 52.1% (152/292), P=0.567] and older [26.2% (103/393), 28.8% (55/191) and 20.5% (16/78), P=0.377] age population. Compared with 2 and 3 previous miscarriages, the cumulative live birth rate was significantly decreased [52.6% (153/291), 52.8% (93/176) and 34.3% (25/73), P=0.014] and the cumulative clinical pregnancy loss rate was significantly increased [15.8% (31/196), 15.3% (18/118) and 46.9% (23/49), P<0.001] in younger women with ≥4 miscarriages. After adjusting for maternal age, BMI, AMH, endometrial thickness on hCG trigger day and antral follicle count, the number of previous miscarriages ≥4 was a relevant factor for cumulative live birth rate (OR=0.461, 95%CI: 0.263-0.807, P=0.007) and the cumulative clinical pregnancy loss rate (OR=4.382, 95%CI: 2.165-8.873, P<0.001) in younger patients, but it was not significantly correlated with the cumulative live birth rate, cumulative clinical pregnancy loss rate and embryo euploidy rate in patients with advanced age. Conclusion: In uRPL patients,≥4 previous miscarriages decreased cumulative live birth rate and increased cumulative clinical pregnancy loss rate in women aged≤37 years old.

Evaluation of pre-implantation genetic testing for aneuploidy outcomes in patients without infertility undergoing in vitro fertilization compared to infertile controls.

To evaluate pre-implantation genetic testing for aneuploidy (PGT-A) outcomes in patients without infertility compared to infertile patients. We performed a retrospective cohort study of all patients without an infertility diagnosis ("fertile" patients) who utilized PGT-A at a large university-affiliated fertility center between 2016 and 2021. Fertile patients were 1-to-3 matched to infertile controls by age and number of oocytes retrieved. The primary outcome was blastocyst aneuploidy rate. Secondary outcomes included ovarian reserve markers, laboratory outcomes, and other PGT-A outcomes [rates of euploidy, mosaicism, and potentially transferrable (euploid + mosaic) embryos]. 283 fertile and 849 infertile patients were included. Median age, anti-Mullerian hormone, and day 2 estradiol levels were equivalent among groups; day 2 follicle-stimulating hormone levels were higher in fertile patients (6.9 vs. 6.5IU/mL, p < 0.01). The aneuploidy rate was similar among fertile and infertile patients (33.7% vs. 31.8%, p = 0.11); the euploidy rate was higher (50.8% vs. 47.0%, p < 0.01), and the mosaicism rate was lower in fertile patients (13.3% vs. 19.2%, p < 0.01). The rate of transferrable embryos was similar among groups (64.0% vs. 66.3%, p = 0.07), as was the percentage of patients yielding ≥ 1 euploid embryo (90.1% vs. 87.3%, p = 0.25). When controlling for significant covariates, multiple linear regression showed that aneuploidy rate was equivalent in both cohorts. Aneuploidy rate was similar in fertile and infertile patients. Fertile patients had slightly higher euploidy and lower mosaicism than infertile patients. Still, compared to fertile patients, infertile patients had equivalent rates of transferrable embryos and were just as likely to yield ≥ 1 euploid embryo.

Chromosomal aneuploidy and pregnancy outcomes for D5/D6 blastocysts from patients undergoing PGT-A treatment

To compare the prevalence of chromosomal aneuploidies and pregnancy outcomes of D5 and D6 blastocysts subjected to preimplantation genetic testing for aneuploidy (PGT-A). Clinical and laboratory data of 268 couples who underwent PGT-A at the Reproductive Center of the First Affiliated Hospital of Zhengzhou University from September 2018 to September 2020 were collected. The prevalence of chromosomal aneuploidies and pregnancy outcomes of D5/D6 biopsied blastocysts were compared. Compared with D6 blastocysts, the euploidy rate of D5 blastocysts was significantly higher (49.1% vs. 41.1%, P = 0.001 1), whilst their aneuploidy rate was significantly lower (50.9% vs. 58.9%, P = 0.001 1). The rate of numerical abnormalities of D6 blastocysts was significantly higher than that of D5 blastocysts (27.9% vs. 20.2%, P = 0.000 5). For patients under 35 years old, the euploidy rate of D5 blastocysts was significantly higher than that of D6 blastocysts (53.8% vs. 44.3%, P = 0.001), whilst the numerical abnormality rate was significantly lower (16.3% vs. 23.9%, P = 0.001). For both D5 and D6 blastocysts, the euploidy rates for patients <= 35 were significantly higher than those for > 35. The elder group had the lowest rates for aneuploidies and live births. Compared with those receiving D6 blastocysts transplantation, the pregnancy rate, implantation rate and live birth rate for those receiving thawed D5 blastocysts transplantation were significantly higher (60.2% vs.37.0%, P = 0.000 3; 59.1% vs.37.0%, P = 0.000 6; 47.7% vs. 28.3%, P = 0.002). For patients undergoing PGT-A, the chromosomal euploidy rate for D5 blastocysts is higher than that for D6 blastocysts, and the clinical outcome of D5 blastocysts with normal signal is better than that of D6 blastocysts. Elder patients have a higher rate of aneuploidies.

Descriptive analysis of Rekovelle® “real-world” experience

Objective(s) To describe the data on “real-world” Rekovelle® administration concerning the response to controlled ovarian stimulation (COS) and clinical intracytoplasmic sperm injection (ICSI) outcomes. Study design This non-interventional study based on secondary use of data included 763 patients undergoing ICSI treatment in a private university-affiliated IVF center from January 2018 to December 2021. Patients undergoing COS with Follitropin delta were given 16mcg Rekovelle® daily (n = 362). Ovarian response to stimulation and laboratory and clinical outcomes of ICSI were described. Two cohorts of patients were added as references: the population included in the ESTHER-1 trial (extern), and a population undergoing COS with follitropin alpha (on-site). Results Patients in the Follitropin delta group showed acceptable outcomes in terms of number of follicles and oocytes, oocyte maturity rate, blastocyst development, and clinical outcomes, irrespective of subgroups of age and BMI. Embryos from women using follitropin delta showed morphokinetic development that seemed equivalent to those from implanted embryos previously reported, demonstrating high implantation potential. This was further corroborated by satisfactory cumulative implantation rates observed for this group of patients. The modified protocol seems to not interfere with oocyte and embryo competence since euploidy rates were also within the expected ranges. OHSS frequencies and rates also seemed acceptable. Conclusions Descriptive data showed that using a starting 16 ug follitropin delta dose for COS results in satisfactory retrieved oocytes and maturity rates across patients in different age ranges and BMI, leading to reasonable cumulative pregnancy rates without increasing OHSS.

Oocyte rescue in-vitro maturation does not adversely affect chromosome segregation during the first meiotic division

Research questionDoes rescue in-vitro maturation (IVM) in the presence or absence of cumulus cells, affect the progress of meiosis I, compared with oocytes that mature in vivo? DesignThis prospective study was conducted in a university-affiliated fertility centre. Ninety-five young oocyte donors (mean age 25.57 ± 4.47) with a normal karyotype and no known fertility problems were included. A total of 390 oocytes (116 mature metaphase II [MII] and 274 immature oocytes) were analysed. The immature oocytes underwent rescue IVM in the presence of cumulus cells (CC; IVM+CC; n = 137) or without them (IVM-CC; n = 137), and IVM rate was calculated. Chromosome copy number analysis using next-generation sequencing (NGS) was performed on all rescue IVM oocytes reaching MII as well as those that were mature at the time of initial denudation (in-vivo-matured oocytes [IVO]). ResultsMaturation rates were similar in IVM+CC and IVM-CC oocytes (62.8 versus 71.5%, P = 0.16). Conclusive cytogenetic results were obtained from 65 MII oocytes from the IVM+CC group, 87 from the IVM-CC group, and 99 from the IVO group. Oocyte euploidy rates for the three groups were similar, at 75.4%, 83.9% and 80.8%, respectively (P = 0.42). ConclusionsThe results suggest that culture of germinal vesicle and metaphase I oocytes in the presence of cumulus cells does not improve rates of IVM. In general, the process of rescue IVM does not appear to alter the frequency of oocytes with a normal chromosome copy number.

Spontaneous collapse as a prognostic marker for human blastocysts: a systematic review and meta-analysis.

Is spontaneous collapse (SC) by human blastocysts a prognostic factor in IVF treatment? SC in human blastocyst is associated with reduced euploid embryo and pregnancy rates. SC of the human blastocyst is a phenomenon that was revealed relatively recently following the clinical application of time-lapse monitoring in IVF laboratories. The ploidy and clinical prognosis of affected blastocysts are still poorly understood, with inconsistent reports. Systematic reviews and meta-analyses on this topic are currently absent in the literature but its potential as a marker of embryo viability holds great clinical value. In this study, we aimed to comprehensively evaluate the potential of SC as a prognostic factor in regard to ploidy status, and pregnancy, live birth and miscarriage rates. A systematic review and meta-analysis were performed according to PRISMA guidelines, with a protocol registered with PROSPERO (CRD42022373749). A search of MEDLINE, EMBASE, and the Cochrane Library for relevant studies was carried out on 10 October 2022, using key words relevant to 'blastocyst collapse' and 'time-lapse imaging'. Two independent reviewers systematically screened and evaluated each study in terms of participants, exposure, comparator, and outcomes (PECO). The Quality In Prognosis Studies tool was used for quality assessment. Data were extracted according to Cochrane methods. Pregnancy, live birth, ploidy, or miscarriage data were summarized by risk ratios (RRs) or odds ratios and their 95% CIs. All meta-analyses were performed with random-effects models. Following removal of duplicates, a total of 196 records were identified by the initial search. After screening according to PECO, 19 articles were included for further eligibility assessment. For meta-analysis, seven retrospective cohort studies were eventually included. After data pooling, the incidence of blastocyst SC was 37.0% (2516/6801) among seven studies (ranging from 17.4% to 56.2%). SC was associated with significantly lower clinical pregnancy rates (two studies, n = 736; RR = 0.77, 95% CI = 0.62-0.95; I2 = 30%), ongoing pregnancy rates (five studies, n = 2503; RR = 0.66, 95% CI = 0.53-0.83; I2 = 60%), and reduced euploidy rates (three studies, n = 3569; RR = 0.70, 95% CI = 0.59-0.83; I2 = 69%). Nevertheless, live birth rates (two studies, n = 816; RR = 0.76, 95% CI = 0.55-1.04; I2 = 56%) and miscarriage rate (four studies, n = 1358; RR = 1.31, 95% CI = 0.95-1.80; I2 = 0%) did not differ between blastocysts with or without SC. There was, however, significant heterogeneity between the studies included for evaluation of ongoing pregnancy rates (I2 = 60%, P = 0.04), live birth rates (I2 = 56%, P = 0.13), and ploidy rates (I2 = 69%, P = 0.04). Subgroup analyses were conducted according to different definitions of SC, number of collapse events, and whether the transferred blastocyst had undergone preimplantation genetic testing for aneuploidy; with inconclusive findings across subgroups. All studies in the meta-analysis were retrospective with varying levels of heterogeneity for different outcomes. Not all studies had accounted for potential confounding factors, therefore only unadjusted data could be used in the main meta-analysis. Studies employed slightly different strategies when defining blastocyst SC. Standardization in the definition for SC is needed to improve comparability between future studies. Our results indicate that blastocyst SC has negative implications for a pregnancy. Such blastocysts should be given a low ranking when selecting from a cohort for intrauterine transfer. Blastocyst SC should be considered as a contributing variable when building blastocyst algorithms to predict pregnancy or live birth. There is no external funding to report. All authors report no conflict of interest. PROSPERO 2022 CRD42022373749.

Embryo ploidy in vitrified versus fresh oocytes: Is there a difference?

To evaluate embryo ploidy in a cohort of patients who underwent preimplantation genetic testing for aneuploidy (PGT-A) with vitrified oocytes compared to fresh oocytes. Patients who underwent their first autologous oocyte vitrification and warming followed by in vitro fertilization (IVF) and trophectoderm biopsy for PGT-A between 1/1/2017 and 12/31/2021 at a single academic institution were included. Patients were compared 1:3 to age-matched controls who underwent their first IVF cycle with fresh oocytes and subsequent trophectoderm biopsy for PGT-A. The primary outcome was the proportions of euploid, mosaic, and aneuploid embryos between those using vitrified versus fresh oocytes. 117 patients who cryopreserved a total of 1,272 mature oocytes were included in the study and were matched with 351 controls using fresh oocytes. The average age was 36.9 ± 2.6years, and the median interval between oocyte vitrification and warming was 38months. There were similar numbers of mature oocytes (10.9 ± 4.9 vs. 11.1 ± 6.3, P = .67), fertilized oocytes (7.8 ± 4.0 vs. 8.7 ± 5.5, P = .10), and blastocysts per patient (5.1 ± 3.1 vs. 5.8 ± 4.3, P = .10) between those using vitrified versus fresh oocytes. In terms of embryo ploidy results, there were no statistically significant differences in rates of euploidy (40.1% vs. 41.6%), mosaicism (15.7% vs. 12.0%), or aneuploidy (44.3% vs. 46.4%) (P = .06) between the two groups. Oocyte vitrification with subsequent warming, fertilization, and trophectoderm biopsy for PGT-A was not associated with adverse chromosomal competence when compared to age-matched controls utilizing fresh oocytes.

Progestin Primed Ovarian Stimulation (PPOS) protocol yields lower euploidy rate in older patients undergoing IVF

BackgroundTo explore if exogenous progestin required for progestin primed ovarian stimulation (PPOS) protocol compromises the euploidy rate of patients who underwent preimplantation genetic testing cycles when compared to those who received the conventional gonadotropin-releasing hormone (GnRH) antagonist protocol.MethodsThis retrospective cohort study analyzed 128 preimplantation genetic testing for aneuploidy (PGT-A) cycles performed from January 2018 to December 2021 in a single university hospital-affiliated fertility center. Infertile women aged 27 to 45 years old requiring PGT-A underwent either PPOS protocol or GnRH-antagonist protocol with in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for fertilization. Frozen embryo transfers were performed following each PGT-A cycle. Data regarding the two groups were analyzed using the Statistical Package for Social Sciences (SPSS) version 22.0 (SPSS Inc., Chicago, IL).ResultsPatients who underwent PPOS treatment had significantly reduced blastocyst formation rate and euploidy rate compared to those who received the GnRH antagonist protocol. Subgroup-analysis was performed by stratifying patients’ age into elder and young subgroups (elder: ≥ 38-year-old, young: < 38-year-old). In the elder sub-population, the blastocyst formation rate of the PPOS group was significantly lower than that of the GnRH-antagonist group (45.8 ± 6.1% vs. 59.9 ± 3.8%, p = 0.036). Moreover, the euploidy rate of the PPOS group was only about 20% of that of the GnRH-antagonist group (5.4% and 26.7%, p = 0.006). In contrast, no significant differences in blastocyst formation rate (63.5 ± 5.7% vs. 67.1 ± 3.2%, p = 0.45) or euploidy rate (30.1% vs. 38.5%, p = 0.221) were observed in the young sub-population. Secondary outcomes, which included implantation rate, biochemical pregnancy rate, clinical pregnancy rate, live birth rate, and miscarriage rate, were comparable between the two treatment groups, regardless of age.ConclusionWhen compared to the conventional GnRH-antagonist approach, PPOS protocol could potentially reduce the euploidy rate in aging IVF patients. However, due to the retrospective nature of this study, the results are to be interpreted with caution. Before the PPOS protocol is widely implemented, further studies exploring its efficacy in larger populations are needed to define the optimal patient selection suitable for this method.Trial registrationHuman Investigation and Ethical Committee of Chang Gung Medical Foundation (202200194B0).

Outcomes of random-start letrozole protocol with PGT-A in women with breast cancer undergoing fertility preservation.

One hundred and seventeen who underwent SSCOS and 39 who underwent RSCOS for oocyte and/or embryo cryopreservation before breast cancer chemotherapy were retrospectively evaluated. Mean number of embryos and blastocyst euploidy rates were the main outcome measures. A majority of RSCOS cycles were initiated in the luteal phase (66.6% luteal vs. 33.3% follicular). While the total dose of gonadotropins was significantly higher in the RSCOS (3720.8 ± 1230.0 vs. 2345.1 ± 803.6IU; P < 0.001), the mean number of mature oocytes and embryos was similar to SSCOS. However, there was a trend for a higher number of mean embryos with luteal start RSCOS (6.9 ± 2.7 in late follicular start vs. 9.4 ± 4.2 in luteal start, P = 0.08). PGT-A was performed in 48% of the cases that underwent embryo cryopreservation in RSCOS (12 women, mean age = 35.3 ± 4.1; 87 blastocysts), revealing a euploidy rate of 36.2 ± 22.3% per patient. This rate was comparable to a 45% aneuploidy rate from similarly aged published data. Of the 7 RSCOS patients who returned for frozen embryo transfer, 5 delivered and one has an ongoing pregnancy, while in SSCOS, 18 out of 40 cycles resulted in live birth. Our data suggests that RSCOS fertility preservation cycle outcomes are similar to those with SSCOS and result in age-appropriate euploidy rates.

The number of prior pregnancy losses does not impact euploidy rates in young patients with idiopathic recurrent pregnancy loss.

Our study aimed to determine the possible factors that might impact the probability of obtaining a euploid blastocyst following intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidy (PGT-A) procedures in idiopathic recurrent pregnancy loss (RPL) patients. This single-center retrospective cohort analysis included 180 oocyte retrieval cycles of 166 women under 35years old and those diagnosed with idiopathic RPL according to American Society of Reproductive Medicine (ASRM) guidelines. Trophectoderm biopsy and next-generation sequencing (NGS) were the techniques used. Patients were stratified by the number of previous losses (Group A: 2, Group B: 3, and Group C: > 3). Baseline and embryological characteristics showed no statistically significant differences. The euploidy rate per analyzed blastocyst was comparable within the groups (63.3%, 58.2%, and 58.5%; p = 0.477). Logistic regression analyses confirmed that only the trophectoderm scores of A and B increased the probability of obtaining a euploid embryo [OR: 1.82, 95% CI (1.120-2.956), p: 0.016]. It is concluded that there was no correlation between the number of previous losses and the chance of finding at least one euploid embryo in ICSI cycles of women younger than 35years.

P-193 Comparison of ICSI outcomes and euploidy rates between AI and non-AI sperm selection

Abstract Study question Can artificial intelligence (AI) assisted sperm selection improve intracytoplasmic sperm injection (ICSI) outcomes and euploidy rates? Summary answer AI selected spermatozoa showed no statistical significance in various measures of ICSI outcomes but an increasing trend in euploidy rate can be observed. What is known already All ICSI practitioners would like to have an objective tool for the selection of sperm to be injected as it is one of the factors in producing successful ICSI. Sperm selection assistant (SiD: (IVF 2.0 Limited, UK) is a real-time AI spermatozoa identifier that assesses all spermatozoa in a visual field based on their motility patterns individually. Mendizabal-Ruiz et. al. (2022) have reported promising data showing SiD may reduce subjectivity in sperm selection, which can potentially be an alternative method to our current practice. Study design, size, duration From June 2022 to December 2022, 89 ICSI cycles (mean age: 35.3; age range: 26.0–47.0) were done in Alpha IVF &amp; Women’s Specialists. A sibling AI (Group A) and non-AI (Group B) assisted sperm selection study with ICSI was performed on the oocytes retrieved from these cycles. Of which, 76 cycles were planned for Preimplantation Genetic Testing for Aneuploidies (PGT-A) on utilizable blastocysts. Participants/materials, setting, methods All matured oocytes were injected using Piezo-ICSI method (Prime Tech Ltd, Japan). Half of the oocytes of each cycle were injected with SiD selected sperm whereas the other half by manual selection. All injected oocytes were cultured up to day-7 and trophectoderm biopsy for PGT-A screening (IonTorrent, USA) was done on utilizable blastocysts prior to vitrification (Cryotec, Japan). The fertilization, blastulation, utilization and euploidy rates were assessed in both groups. Main results and the role of chance In Group A, the fertilization rate (2PN), abnormal fertilization rate ( &amp;gt; 2PN), blastulation rate from 2PN, blastocyst utilization rate from 2PN and euploidy rate from utilizable blastocysts were 81.5% (419/514), 2.1% (11/514) 77.1 (323/419), 57.5% (241/419) and 45.2% (71/157) respectively. In Group B, the fertilization rate (2PN), abnormal fertilization ( &amp;gt; 2PN), blastulation rate from 2PN, blastocyst utilization rate from 2PN and euploidy rate from utilizable blastocysts were 79.7% (427/536), 2.8% (15/536), 75.9% (324/427), 59.0% (252/427) and 35.5% (60/169) respectively. No significant differences were observed in the fertilization rate (p = 0.4828), abnormal fertilization rate (p = 0.5545), blastulation rate from 2PN (p = 0.6861), blastocyst utilization rate (p = 0.7278) and euploidy rate (p = 0.0898). Although the ICSI outcomes are comparable between the two groups, AI assisted sperm selection showed an increasing trend in euploidy rates. SiD may be considered as a tool to assist embryologist in selecting better spermatozoa during ICSI procedures. Limitations, reasons for caution The patient sample size was small but further studies with a larger sample size certainly seem to be justified, particularly in association with PGTA on utilizable blastocysts. The value of SiD shall be greatly enhanced when spermatozoon morphology can also be measured. Wider implications of the findings This is more evidence suggesting that SiD may improve ICSI outcomes and euploidy rate when compared to manual selection by an embryologist. In addition, it could be used to train and assist embryologists learning ICSI procedures. Trial registration number not applicable

P-254 Short-time or overnight co-incubation with sperm in conventional IVF delivers similar pre-implantation development outcomes: a sibling cumulus-oocyte complex study

Abstract Study question Does a short-time co-incubation in conventional IVF improve rates of fertilization, embryo development and euploidy, when compared to overnight co-incubation? Summary answer There is no significant difference in fertilization, embryo development and euploidy rates between sibling oocytes subjected to short co-incubation versus overnight co-incubation. What is known already Conventional IVF usually implies coincubation of cumulus-oocyte complex(es) with sperm for an overnight period. This overnight incubation might create an over exposure of COCs to reactive oxygen species (ROS), which might disturb oocyte homeostasis, and impact on embryonic developmental rate. To this extend, many early studies have compared a short co-incubation time (2-6 hours) with overnight co-incubation, with reported conflicting outcomes. None of the studies combined time-lapse monitoring with short co-incubation, which allows the identification of early morphokinetic events of the inseminated oocytes after conventional IVF, as already known for ICSI oocytes in time-lapse incubators. Study design, size, duration This single center prospective study included 604 COCs in 38 IVF/ICSI cycles with preimplantation genetic testing between December 2020 and November 2022. After oocyte retrieval a min of 6 COCs were assigned for insemination by IVF and equally divided between short(2hrs) and overnight (16-20hrs) co-incubation. Supernumerary oocytes were denuded and inseminated by ICSI. Primary endpoint was fertilization rate; secondary endpoints were maturation rate, ploidy rate after trophectoderm biopsy, embryo development and morphokinetics. Participants/materials, setting, methods Couples with a female age between 18-43 (average:34.4) years, BMI ≤30kg/m2 and normal semen parameters (WHO) in the fresh ejaculate on the day of OR, were eligible for the study. After IVF, all embryos were cultured in a time-lapse imaging system in Global Total LP media. Blastocysts (≥Bl3BCC) were subjected to trophectoderm biopsy on day 5-7 and next generation sequencing (NGS) to determine blastocyst ploidy status. Main results and the role of chance In total, 288 oocytes (47.7%) were denuded for ICSI, whereas 316 (52.3%) oocytes were randomized 1:1 to short and overnight co-incubation groups. Maturation rates (M2/COC) and normal fertilization rates (2PN/COC) in short and overnight co-incubation groups were similar (88.0% vs 83.5%, P = 0.074 and 60.8% vs 62.0%, P = 0.193, respectively). Day-3 embryo cell numbers (P = 0.383), fragmentation rates (P = 0.529), blastulation rates on day 5 (39.9 vs 38.0% P = 0.696), time to blastulation (median: 112.6 vs 111.1 hours after insemination by time lapse, P = 0.544) were similar between short and overnight co-incubation groups. In total, 48 embryos in short and 45 embryos in overnight co-incubation groups were of sufficient quality for biopsy resulting in similar euploidy rates between the groups (39.6 vs 44.4%, P = 0.791). When compared to their siblings in ICSI, short (mean difference: -6.48%, 95% CI: -18.5 to 5.59%, P = 0.290) and overnight co-incubation (mean difference: -0.87%, 95% CI: -12.9 to 11.2%, P = 0.886) attained similar fertilization rates per cycle. No significant differences regarding blastulation and euploidy rates were observed in short or overnight co-incubation compared to ICSI in unadjusted and adjusted analyses. Limitations, reasons for caution This is a prospective study with a limited patient population with a normal ovarian response. Results might not be transferable to patients with high or low ovarian reserve. Wider implications of the findings The present study demonstrated that there is no difference between short and overnight co-incubation in terms of fertilization and euploidy rates. Therefore short co-incubation might allow us to benefit from early denudation, and to investigate early morphokinetics in time lapse monitoring, which are otherwise missed by overnight co-incubation. Trial registration number NCT04627545