Clinical embryologists play a central role in assisted reproductive technology (ART) laboratories and contribute directly to technical processes that influence treatment outcomes. As ART utilization and technological complexity increase, the responsibilities and scope of practice of clinical embryologists have expanded. Despite this role, clinical embryology in the United States lacks a nationally standardized educational pathway, competency framework, or profession-specific licensure model. This expert opinion reviews the current landscape of clinical embryology practice in the United States, including laboratory responsibilities, variability in training pathways, credentialing structures, and the use of laboratory performance indicators in competency assessment. The manuscript also summarizes international approaches to training and credentialing of clinical embryologists and discusses considerations that may inform discussions regarding professional development, workforce sustainability, and laboratory quality in the field.

Objective: To evaluate 20-year outcomes of a structured quality improvement (QI) and risk-management program in a single IVF laboratory, with emphasis on never events, near misses, and longitudinal performance on predefined quality indicators (QIIs). Design: Longitudinal, single-center quality improvement study (2004–2024). Setting: Large healthcare network -affiliated IVF laboratory operating under CAP accreditation. Patients/Cycles: 15,956 ART cycles (8,320 fresh IVF; 7,636 frozen embryo transfer). Interventions: Implementation and continuous refinement of a laboratory QI framework comprising high-risk process mapping; QIIs with thresholds; standardized reporting (verbal escalation → SBAR); structured investigations (RCA) with corrective/preventive actions (CAPA); competency-based staff training; electronic/dual witnessing; cryoinventory reconciliation; equipment maintenance and alarm testing; and a non-punitive reporting culture. Main Outcome Measures: Incidence of never events and intercepted near misses; protocol non-compliance; report errors; cryoinventory accuracy (QIR07); gamete/embryo traceability (QIR10); equipment/handling issues affecting care (QIR16). Results: Across 20 years, one true “never event” occurred (erroneous discard of an embryo intended for cryopreservation with freezing of a lower-quality embryo instead; ≈0.006% of cycles). The event was disclosed, investigated via RCA, corrected per SOPs, and remediated with a no-cost IVF cycle. One intercepted near miss (thaw of an undesired-gender embryo detected pre-transfer) was identified, disclosed, and resolved (refreeze and correct embryo transfer) without clinical impact. Protocol non-compliance declined from 8 cases (2004) to 0 by 2008 and remained at or near zero thereafter. Report errors decreased to 0% in recent years. Cryoinventory performance remained near 0% error with one easily resolved misplacement. Gamete/embryo traceability (QIR10) stayed well below thresholds with no significant missing/untraceable specimens. QIR16 recorded one handling incident (faulty pipette), causing loss of several oocytes, prompting protocol revision, equipment checks, and retraining via RCA/CAPA.Conclusions: A structured, data-driven QI program–embedding SBAR, RCA/CAPA, traceability safeguards, and a just culture–was associated with sustained near-zero serious events and progressive reliability gains over two decades. This reproducible model can inform benchmarking and multi-center learning aimed at further reducing latent risk in IVF laboratories.

To investigate the differential impact of GnRH-agonist (GnRHa), hCG, or dual trigger, on the embryological outcomes in the general infertility population.

There are few published studies that report on the practical application and utility of IVF laboratory KPIs in identifying performance shifts in response to changes in laboratory processes. There are even fewer reports on the potential effects of major changes in patient clinical management upon laboratory quality indicators.The aim of this study is to collect and analyze our IVF laboratory KPIs based on the two newly adopted ovulation trigger regimens during controlled ovarian hyper-stimulation treatment. IVF patients were divided into three study groups based on the medication used for triggering final oocyte maturation: Group A - human chorionic gonadotropin (HCG) (n=837), Group B - GnRH agonist (GnRHa) only (n=78), and Group C – combination of HCG and GnRHa (n=152). Fourteen KPI parameters were collected for three patient groups (Table 1.) Results were compared with thresholds established within our laboratory quality improvement program. KPI results for patients in groups A, B, and C are presented in Table 1. All KPI thresholds were met in Groups A and C. There were three parameters (oocytes retrieved per follicles aspirated, IVF fertilization rate, and IVF fertilization rate of mature oocytes) that were slightly outside acceptable limits in Group B . The type of oocyte maturation trigger does not seem to be associated with a considerable shift in IVF laboratory KPIs. The minor under-performance of some KPIs in Group B can be reflective of potentially diminished oocyte quality in patients triggered with GnRHa only, which warrants further monitoring and more detailed investigation, including a deep dive into potential clinical differences between patient groups.

OBJECTIVE:To determine if an automated time-lapse test (TL-test) combined with traditional morphology for embryo selection and day 3 transfer results in improved clinical outcomes.DESIGN:Prospective concurrent-controlled pilot study.SETTING:IVF clinic and laboratory.PATIENT(S):A total of 319 female patients <41 years old, with day 3 embryo transfer, fewer than three failed IVF cycles, and at least four zygotes (2-pronuclear) on day 1.INTERVENTION(S):Automated time-lapse embryo assessment combined with morphologic assessment in the study (test) group compared with morphologic assessment only (control group).MAIN OUTCOME MEASURE(S):Embryo implantation, pregnancy, and multiple pregnancy rates. Subanalysis of implantation potential of embryos based on the TL-test (TL-high vs. TL-low) scores.RESULT(S):Implantation and clinical pregnancy rates were significantly higher in the test group compared with the control group (implantation rates 30.2% vs. 19.0%, clinical pregnancy rates 46.0% vs. 32.1%, respectively). Multiple pregnancy rates were not statistically different (26.7% vs. 18.3%). Test group patients receiving at least one TL-high embryo had significantly higher implantation rates than patients receiving only TL-low embryos (36.8% vs. 20.6%). TL-high compared with TL-low embryos had significantly higher implantation rates (44.7% vs. 20.5%). Among morphologically good embryos, TL-high embryos were more likely to implant than TL-low embryos (44.1% vs. 20.6%).CONCLUSION(S):This is the first report demonstrating improved implantation rates in patients receiving day 3 embryo transfers based on the combined use of a TL-test along and traditional morphology. Our findings confirm that the noninvasive TL-test adds valuable information to traditional morphologic grading.CLINICAL TRIAL REGISTRATION NUMBER:NCT01671657.

OBJECTIVE:To characterize atypical dynamic embryo phenotypes identified by time-lapse microscopy, evaluate their prevalence, and determine their association with embryo development.DESIGN:Retrospective multicenter cohort study.SETTING:Five IVF clinics in the United States.PATIENT(S):Sixty-seven women undergoing IVF treatment with 651 embryos.INTERVENTION(S):Embryo videos were retrospectively analyzed for atypical phenotypes.MAIN OUTCOME MEASURE(S):Identification of four groups of atypical embryo phenotypes: abnormal syngamy (AS), abnormal first cytokinesis (A1(cyt)), abnormal cleavage (AC), and chaotic cleavage (CC). Prevalence and association with embryo morphology and development potential were evaluated.RESULT(S):A high prevalence of atypical phenotypes was observed among embryos: AS 25.1% (163/649), A1(cyt) 31.0% (195/639), AC 18% (115/639) and CC 15% (96/639). A high percentage of embryos with atypical phenotype(s) had good quality on day 3 (overall grade good or fair): AS 78.6% (70/89); A1(cyt) 79.7% (94/119), AC 86.4% (70/81), and CC 35.2% (19/54), but the blastocyst formation rates for these embryos were significantly lower compared with their respective control groups: AS 21.5% vs. 44.9%, A1(cyt) 21.7% vs. 44.6%, AC 11.7% vs. 43.1%, and CC 14.0% vs. 42.3%.CONCLUSION(S):Embryos exhibiting atypical phenotypes are highly prevalent in human embryos and show significantly lower developmental potential than control embryos.CLINICAL TRIAL REGISTRATION NUMBER:NCT01369446.

Computer-automated time-lapse analysis has been shown to improve embryo selection by providing quantitative and objective information to supplement traditional morphology. In this multi-centre study, the relationship between such computer-derived outputs (High, Medium, Low scores), embryo implantation and clinical pregnancy were examined. Data were collected from six clinics, including 205 patients whose embryos were imaged by the Eeva(TM) System. The Eeva scores were blinded and not considered during embryo selection. Embryos with High and Medium scores had significantly higher implantation rates than those with Low scores (37% and 35% versus 15%; P < 0.0001; P = 0.0004). Similar trends in implantation rates were observed in different IVF centres each using their own protocols. Further analysis revealed that patients with at least one High embryo transferred had significantly higher clinical pregnancy rates than those with only Low embryos transferred (51% versus 34%; P = 0.02), although patients' clinical characteristics across groups were comparable. These data, together with previous research and clinical studies, confirm that computer-automated Eeva scores provide valuable information, which may improve the clinical outcome of IVF procedures and ultimately facilitate the trend of single embryo selection.

ObjectiveIt has been demonstrated that computer-automated measurements of key time-lapse parameters can aid in the selection of embryos with the highest potential to develop to the blastocyst stage (Conaghan et al. 2013). However, the impact of this novel test on clinical outcomes for patients in different age groups remains unclear. The objective of this study was to examine the correlation between computer-automated time-lapse analysis results and embryo implantation for patients in different age groups.DesignBlinded, multi-center study.Materials and Methods205 patients from 6 clinics consented to have embryos imaged using the Eeva® System, a platform technology that automates the analysis of P2 (time between first and second mitosis) and P3 (time between second and third mitosis) and generates a test score of High or Low regarding developmental potential. For this non-selection study, High/Low scores were blinded, and embryos were selected for transfer using only morphology evaluation. Two age groups were analyzed: egg age <35 years and egg age ≥35 years. Implantation was defined by fetal heartbeat at the 6-7 week ultrasound. χ2-test was used for statistical analysis.ResultsTabled 1IR<35 years>=35 yearsEeva High52% (31/60)20% (10/51)Eeva Low35% (34/97)13% (16/123)p-value0.02NS Open table in a new tab ConclusionIt is well known that egg age highly correlates to implantation rates. In this blinded, non-selection study, we have demonstrated that in younger patients Eeva High/Low scores generated from automated cell division timings, correlate well with embryo implantation. We postulate that Eeva Test scores may reflect embryo quality independent of age and that the use of Eeva Test scores to aid embryo selection may improve overall implantation rates. The study is currently ongoing and with increased sample size, will allow us to further evaluate such phenomenon in older patients. ObjectiveIt has been demonstrated that computer-automated measurements of key time-lapse parameters can aid in the selection of embryos with the highest potential to develop to the blastocyst stage (Conaghan et al. 2013). However, the impact of this novel test on clinical outcomes for patients in different age groups remains unclear. The objective of this study was to examine the correlation between computer-automated time-lapse analysis results and embryo implantation for patients in different age groups. It has been demonstrated that computer-automated measurements of key time-lapse parameters can aid in the selection of embryos with the highest potential to develop to the blastocyst stage (Conaghan et al. 2013). However, the impact of this novel test on clinical outcomes for patients in different age groups remains unclear. The objective of this study was to examine the correlation between computer-automated time-lapse analysis results and embryo implantation for patients in different age groups. DesignBlinded, multi-center study. Blinded, multi-center study. Materials and Methods205 patients from 6 clinics consented to have embryos imaged using the Eeva® System, a platform technology that automates the analysis of P2 (time between first and second mitosis) and P3 (time between second and third mitosis) and generates a test score of High or Low regarding developmental potential. For this non-selection study, High/Low scores were blinded, and embryos were selected for transfer using only morphology evaluation. Two age groups were analyzed: egg age <35 years and egg age ≥35 years. Implantation was defined by fetal heartbeat at the 6-7 week ultrasound. χ2-test was used for statistical analysis. 205 patients from 6 clinics consented to have embryos imaged using the Eeva® System, a platform technology that automates the analysis of P2 (time between first and second mitosis) and P3 (time between second and third mitosis) and generates a test score of High or Low regarding developmental potential. For this non-selection study, High/Low scores were blinded, and embryos were selected for transfer using only morphology evaluation. Two age groups were analyzed: egg age <35 years and egg age ≥35 years. Implantation was defined by fetal heartbeat at the 6-7 week ultrasound. χ2-test was used for statistical analysis. ResultsTabled 1IR<35 years>=35 yearsEeva High52% (31/60)20% (10/51)Eeva Low35% (34/97)13% (16/123)p-value0.02NS Open table in a new tab ConclusionIt is well known that egg age highly correlates to implantation rates. In this blinded, non-selection study, we have demonstrated that in younger patients Eeva High/Low scores generated from automated cell division timings, correlate well with embryo implantation. We postulate that Eeva Test scores may reflect embryo quality independent of age and that the use of Eeva Test scores to aid embryo selection may improve overall implantation rates. The study is currently ongoing and with increased sample size, will allow us to further evaluate such phenomenon in older patients. It is well known that egg age highly correlates to implantation rates. In this blinded, non-selection study, we have demonstrated that in younger patients Eeva High/Low scores generated from automated cell division timings, correlate well with embryo implantation. We postulate that Eeva Test scores may reflect embryo quality independent of age and that the use of Eeva Test scores to aid embryo selection may improve overall implantation rates. The study is currently ongoing and with increased sample size, will allow us to further evaluate such phenomenon in older patients.

A recent publication described development of a test that automatically measures key time-lapse parameters and provides quantitative information regarding embryo development (Eeva® Test) (Conaghan et al. 2013). The objective of this study was to determine if use of the test as an adjunct to traditional morphology for day 3 embryo transfer (ET) results in improved clinical outcomes. Pilot cohort study using concurrent controls. IRB approval was obtained. 51 patients consented to using the Eeva Test as an adjunct to morphology for day 3 ET. The Eeva Test generates a High or Low score based on the automatic extraction of key cell division timings from time-lapse videos. Inclusion criteria were: maternal age < 41 years, < 3 previous failed IVF attempts, and ≥4 zygotes available for image analysis. In the Eeva Test group, preference in selection for transfer was given to embryos that had good morphology and exhibited a High score. In the control group, embryos were selected for transfer based on morphology only. Clinical characteristics, implantation and pregnancy were compared. χ2 test was used for statistical analysis. Positive hCG and implantation rates were significantly higher when Eeva Test scores were used as an adjunct to morphology to select embryos for transfer on Day 3. There were no significant differences in clinical characteristics between groups.Tabled 1Eeva TestControlN51131Age (mean ± sd)34.5 ± 3.834.4 ± 3.4Egg #16.5 ± 6.716.5 ± 6.1ET #1.9 ± 0.62.0 ± 0.62PN #8.5 ± 3.48.8 ± 3.3Positive hCG73%60%*Clinical pregnancy rate55%40%Ongoing pregnancy rate49%35%Multiple rate44%28%Implantation rate43%28%***p=0.04, **p=0.01 Open table in a new tab *p=0.04, **p=0.01 This is the first report of improved implantation rates in patients receiving day 3 ET based on the adjunctive use of a time-lapse enabled test and traditional morphology. The adjunctive Eeva Test day 3 implantation rate appears equivalent to published day 5 blastocyst rates. Our findings confirm that the non-invasive Eeva Test can be used to increase the clinician's confidence in recommending eSET on day 3, thereby achieving the benefits of higher pregnancy rates, lower multiple pregnancy rates and improved clinical outcomes. The current study is ongoing and will further evaluate the impact on pregnancy rates and multiple rates with increased sample size.

Time-lapse imaging of embryo development is increasing in popularity and has been shown to predict an embryo's potential for blastocyst formation (1, 2) and implantation (3). The technology could be used to allow the transfer of fewer embryos through improved and objective selection of viable embryos. Currently, the best embryo selection method is subjective morphological assessment, but this is unreliable since most patients are still transferring 2 or more, resulting in twin pregnancy rates consistently above 30% (4). Greater utilization of eSET requires improved and objective selection methods that can reliably identify viable embryos in a cohort. To evaluate if time-lapse imaging could help identify on day 3 (D3) or day 5 (D5) embryos with higher implantation potential. 77 good prognosis patients (antral follicle count >8 and cycle day 3 FSH < 10 IU/ml) were included in the study, for a total of 135 embryos analyzed. Embryos were imaged from Day 1 to 3 using the Early Embryo Viability Assessment System test (EevaTM; Auxogyn, Menlo Park, CA) at 5 clinical sites. Only patients with 100% or 0% of the transferred embryos implanting after D5 transfer were included. During imaging, automated cell tracking software predicted a "high" or "low" blastocyst development probability for each embryo by the afternoon of D2. The addition of an Eeva high result to the D3 morphology assessment predicted slightly higher implantation rates for good D3 embryos (55%) compared with fair/poor embryos (42%). For morphologically good quality blastocysts, the implantation rate was not impacted by the Eeva prediction (56% without Eeva, 55% with an Eeva high and 55% with an Eeva low score). However, Eeva discriminated well among poor quality blastocysts (Eeva high IR was 47%, Eeva low was 31% and morphology only without Eeva was 27%). Similarly, early and expanding blastocysts had better IR's with an Eeva high score (50% and 43%) compared with those scored low by Eeva (30% and 36%) and those scored by morphology only (33% and 36%).Tabled 1Embryo groupImplantation rate (%) after D5 ETGood D3 morphology + Eeva high55%Good D3 morphology + Eeva low40%Good D5 morphology + Eeva high55%Good D5 morphology + Eeva low55%Fair/Poor D5 morphology + Eeva high47%Fair/Poor D5 morphology + Eeva low27%Early blastocyst + Eeva high50%Early blastocyst + Eeva low30% Open table in a new tab For D3 embryos, the information provided by Eeva was a good indicator of which embryos would make blastocysts and which would implant after transfer. If blastocyst morphology was poor, or the blastocysts were not fully expanded, Eeva provided a valuable additional parameter indicating which embryos would implant. Eeva, a computer automated predictor of blastocyst formation, may be effective in selecting embryos for transfer and allowing for fewer embryos to be transferred.

Abnormal cleavage (AC) occurs when 1 cell divides to >2 daughter cells. It is reported that zygote AC is correlated with very low implantation (1%) (Rubio et al. 2012). The objectives of this study were to (1) further address the clinical relevance of zygote AC (AC1) and daughter cell AC (AC2), and (2) examine the potential of using automated time-lapse cleavage analysis to deselect AC. Retrospective cohort study. Patients undergoing D3 embryo transfer from 3 sites (Jun2011-Oct2012) consented to have their embryos monitored using the Eeva™ Test (Auxogyn), a time-lapse enabled system which provides a high or low score of developmental potential based on key P2 (2-to-3 cell) and P3 (3-to-4 cell) time intervals (Wong et al. 2010, Conaghan et al. 2013). AC1 and AC2 were manually evaluated, and clinical relevance was based on implantation and clinical pregnancy (ultrasound at 6 wks). Imaging data of AC embryos were processed using Eeva software. Statistical significance was calculated using Fisher's Exact or χ2 test. A total of 363 embryos from 43 patients were included. The overall prevalence of AC was 20% (AC1:10%, AC2:10%, Both:0.6%). The prevalence of AC among 107 embryos transferred was 29% (AC1:9%, AC2: 19%, Both:1%), because all AC embryos selected for transfer exhibited relatively good morphology (6-10 cell, <25% frag, perfect/moderate symmetry). The implantation rate of AC was 3% (1/30). In patient cohorts, the incidence of AC (0% vs. 1-25% vs. ≥25%) was inversely correlated with clinical pregnancy (50% vs. 29% vs. 16%). Eeva software categorized 87% (53/61) of AC embryos as low, suggesting that automated P2 and P3 timings may inherently capture AC. AC1 and AC2 embryos are often selected for Day 3 transfer due to their overall good morphology, but these embryos rarely implant. Automated time-lapse analysis using predictive cleavage timings may aid in the deselection of AC events to improve pregnancy rates – a prospective trial is currently underway.

Objective: To assess the first computer-automated platform for time-lapse image analysis and blastocyst prediction and to determine how the screening information may assist embryologists in day 3 (D3) embryo selection.Design: Prospective, multicenter, cohort study.Setting: Five IVF clinics in the United States.Patient(s): One hundred sixty women >= 18 years of age undergoing fresh IVF treatment with basal antral follicle count >= 8, basal FSH < 10 IU/mL, and >= 8 normally fertilized oocytes.Intervention(s): A noninvasive test combining time-lapse image analysis with the cell-tracking software, Eeva (Early Embryo Viability Assessment), was used to measure early embryo development and generate usable blastocyst predictions by D3.Main Outcome Measure(s): Improvement in the ability of experienced embryologists to select which embryos are likely to develop to usable blastocysts using D3 morphology alone, compared with morphology plus Eeva.Result(s): Experienced embryologists using Eeva in combination with D3 morphology significantly improved their ability to identify embryos that would reach the usable blastocyst stage (specificity for each of three embryologists using morphology vs. morphology plus Eeva: 59.7% vs. 86.3%, 41.9% vs. 84.0%, 79.5% vs. 86.6%). Adjunctive use of morphology plus Eeva improved embryo selection by enabling embryologists to better discriminate which embryos would be unlikely to develop to blastocyst and was particularly beneficial for improving selection among good-morphology embryos. Adjunctive use of morphology plus Eeva also reduced interindividual variability in embryo selection.Conclusion(s): Previous studies have shown improved implantation rates for blastocyst transfer compared with cleavage-stage transfer. Addition of Eeva to the current embryo grading process may improve the success rates of cleavage-stage ETs. ((c) 2013 by American Society for Reproductive Medicine.)

ObjectiveCombined with timing of the 2nd and 3rd cytokinesis, a prolonged 1st cytokinesis duration has been reported to correlate with low blastocyst formation and reduced expression of cytokinesis genes (Wong et al, 2010). This study determined the incidence of a novel abnormal 1st cytokinesis phenotype, evaluated the duration of 1st cytokinesis, and assessed clinical relevance.DesignMultisite retrospective cohort study.Materials and MethodsPatients from 3 clinics consented to have embryos imaged using the Eeva™ Test (Auxogyn), which performs time-lapse analysis of key cell division timings (Jun2011-Oct 2012). Embryo videos were reviewed for 1st cytokinesis phenotype and duration (P1). Abnormal phenotype was defined as oolema ruffling and/or formation of pseudo cleavage furrows. P1 duration was defined as the time from appearance of the 1st cleavage furrow to completion of the 1st division. Clinical pregnancy was confirmed by ultrasound at 6 wks. Fisher's Exact test was used to assess statistical significance.ResultsA total of 638 embryos from 67 patients were categorized into groups: (1) with normal phenotype (442/638=69%) and (2) with abnormal phenotype (196/638=31%). Both groups had good morphology embryos on D3 (53% and 34% with 6-10 cells, ≤10% frag, p<0.001). Group 2 had a lower blastocyst formation rate (131/305=43% vs. 26/126=20%, p<0.0001) and trended to lower implantation rate (15/91=17% vs. 2/32=6%, p=0.2). Group 2 also exhibited prolonged P1 (0.5± 0.8 vs. 1.8±3.3 hrs, p<0.0001). Within Group 2, a subgroup of embryos with P1≥0.5 hrs had even lower blastocyst formation (6/70=9%; p<0.0001 vs. Group 1, p<0.05 vs. Group 2), and none (0/14) implanted.ConclusionEmbryos exhibiting abnormal 1st cytokinesis phenotypes represent 31% of the embryo population and have significantly lower developmental potential. Since many of these embryos have good morphology at the cleavage stage, using time-lapse to detect abnormal and prolonged 1st cytokinesis phenotypes may improve the success of embryo selection. ObjectiveCombined with timing of the 2nd and 3rd cytokinesis, a prolonged 1st cytokinesis duration has been reported to correlate with low blastocyst formation and reduced expression of cytokinesis genes (Wong et al, 2010). This study determined the incidence of a novel abnormal 1st cytokinesis phenotype, evaluated the duration of 1st cytokinesis, and assessed clinical relevance. Combined with timing of the 2nd and 3rd cytokinesis, a prolonged 1st cytokinesis duration has been reported to correlate with low blastocyst formation and reduced expression of cytokinesis genes (Wong et al, 2010). This study determined the incidence of a novel abnormal 1st cytokinesis phenotype, evaluated the duration of 1st cytokinesis, and assessed clinical relevance. DesignMultisite retrospective cohort study. Multisite retrospective cohort study. Materials and MethodsPatients from 3 clinics consented to have embryos imaged using the Eeva™ Test (Auxogyn), which performs time-lapse analysis of key cell division timings (Jun2011-Oct 2012). Embryo videos were reviewed for 1st cytokinesis phenotype and duration (P1). Abnormal phenotype was defined as oolema ruffling and/or formation of pseudo cleavage furrows. P1 duration was defined as the time from appearance of the 1st cleavage furrow to completion of the 1st division. Clinical pregnancy was confirmed by ultrasound at 6 wks. Fisher's Exact test was used to assess statistical significance. Patients from 3 clinics consented to have embryos imaged using the Eeva™ Test (Auxogyn), which performs time-lapse analysis of key cell division timings (Jun2011-Oct 2012). Embryo videos were reviewed for 1st cytokinesis phenotype and duration (P1). Abnormal phenotype was defined as oolema ruffling and/or formation of pseudo cleavage furrows. P1 duration was defined as the time from appearance of the 1st cleavage furrow to completion of the 1st division. Clinical pregnancy was confirmed by ultrasound at 6 wks. Fisher's Exact test was used to assess statistical significance. ResultsA total of 638 embryos from 67 patients were categorized into groups: (1) with normal phenotype (442/638=69%) and (2) with abnormal phenotype (196/638=31%). Both groups had good morphology embryos on D3 (53% and 34% with 6-10 cells, ≤10% frag, p<0.001). Group 2 had a lower blastocyst formation rate (131/305=43% vs. 26/126=20%, p<0.0001) and trended to lower implantation rate (15/91=17% vs. 2/32=6%, p=0.2). Group 2 also exhibited prolonged P1 (0.5± 0.8 vs. 1.8±3.3 hrs, p<0.0001). Within Group 2, a subgroup of embryos with P1≥0.5 hrs had even lower blastocyst formation (6/70=9%; p<0.0001 vs. Group 1, p<0.05 vs. Group 2), and none (0/14) implanted. A total of 638 embryos from 67 patients were categorized into groups: (1) with normal phenotype (442/638=69%) and (2) with abnormal phenotype (196/638=31%). Both groups had good morphology embryos on D3 (53% and 34% with 6-10 cells, ≤10% frag, p<0.001). Group 2 had a lower blastocyst formation rate (131/305=43% vs. 26/126=20%, p<0.0001) and trended to lower implantation rate (15/91=17% vs. 2/32=6%, p=0.2). Group 2 also exhibited prolonged P1 (0.5± 0.8 vs. 1.8±3.3 hrs, p<0.0001). Within Group 2, a subgroup of embryos with P1≥0.5 hrs had even lower blastocyst formation (6/70=9%; p<0.0001 vs. Group 1, p<0.05 vs. Group 2), and none (0/14) implanted. ConclusionEmbryos exhibiting abnormal 1st cytokinesis phenotypes represent 31% of the embryo population and have significantly lower developmental potential. Since many of these embryos have good morphology at the cleavage stage, using time-lapse to detect abnormal and prolonged 1st cytokinesis phenotypes may improve the success of embryo selection. Embryos exhibiting abnormal 1st cytokinesis phenotypes represent 31% of the embryo population and have significantly lower developmental potential. Since many of these embryos have good morphology at the cleavage stage, using time-lapse to detect abnormal and prolonged 1st cytokinesis phenotypes may improve the success of embryo selection.

Since many transferred embryos with "good morphology" fail to implant, technologies are needed to distinguish embryos with highest developmental competence. We developed and validated an integrated time-lapse and automated image analysis system which measures specific cell division timings and predicts blastocyst development by day 2. The objective of this study was to determine the degree of improvement to viable embryo selection when using our prediction model with traditional morphology. Multi-site, prospective, cohort study. The study included 43 patients (≤42 years old) undergoing in vitro fertilization at 3 clinics. Day 3 morphology and time-lapse image data captured by an integrated imaging system, Eeva (Early Embryo Viability Assessment), were prospectively collected. Eeva generated a blastocyst probability score (Low, High) based on specific cell division timings. Eeva blastocyst probability was determined to be High when all cell division timings were within the defined ranges. Five experienced embryologists made a "blastocyst" or "arrest" prediction for each embryo using Day 3 Morphology only, and then using Morphology and Eeva scores. The prediction results were compared to true blastocyst outcomes. A total of 343 embryos were evaluated. By combining Morphology+Eeva, the average blastocyst prediction accuracy significantly improved. The degree of improvement was augmented for embryos with "good morphology" on day 3.Tabled 1Blastocyst Prediction on Day 3 (% Accuracy, Mean±SD)Embryo GroupsMorphology onlyMorphology+EevaP valueTotal Embryos (n=343)62±680±2<0.0056 to 10-cell, ≤10% Frag, Perfect Symmetry (n=135)37±466±4<0.005 Open table in a new tab Adding Eeva to traditional morphology dramatically improved day 3 blastocyst prediction, particularly among "good morphology embryos". Predictions are non-invasive and available by day 2 using automated analysis. Eeva is a uniquely effective and efficient tool for viable embryo selection that may ultimately improve implantation rates.

The aim of this report is to describe our experience and results with implementation of a cut standard straw technique for vitrification and warming of day 3 cleavage-stage human embryos. Detailed description of the method and results of 63 frozen embryo transfers performed with this technology are discussed, and it is concluded that this method provides a reliable, inexpensive, and effective option of embryo vitrification at a cleaved stage. (Fertil Steril (R) 2011; 95: 2552-3. (C) 2011 by American Society for Reproductive Medicine.)

OBJECTIVE: To compare laboratory and clinical outcomes of human in vitro fertilization (IVF) using a 5% oxygen system versus a 20% oxygen system in various clinical groups.DESIGN: Retrospective analysis of data from IVF cycles performed in a private fertility laboratory setting.MATERIALS AND METHODS: A total of 512 cycles were undertaken using autologous oocytes and 30 cycles were performed using donated oocytes. Oocytes and embryos were randomly assigned for culture in incubators of either a low oxygen system (LOS) or a high oxygen system (HOS). Fertilization rates, embryo cleavage rates, embryo grades, embryo cell numbers, embryo utilization rates, pregnancy rates, and miscarriage rates were compared between LOS and HOS conditions in 12 study groups defined based on maternal age, method of fertilization, prognosis and stimulation protocol. Results were compared within these groups in order to identify patient populations that may benefit from low oxygen culture. Student's t-test and Fisher's exact test were used for statistical analysis.RESULTS: Analysis of the data detected an increase in conventional IVF fertilization rates under LOS conditions, especially in patients of 38-40 years of age (P=0.01). Fertilization rates after intracytoplasmic sperm injection (ICSI) were improved in patients with good prognosis, in the GnRH agonist downregulation group, and in patients of 35-37 years of age. Moreover, we observed a statistically significant increase in the mean number of blastomeres under LOS conditions. This increase was especially significant in patients over 40 years of age and in patients with the Micro-dose flare stimulation protocol (P<0.01 and P=0.01, respectively). Accelerated embryo cleavage under LOS conditions resulted in a significant increase of the rate of embryo utilization in patients who used ICSI (P<0.01).CONCLUSIONS: Based on our data, LOS has positive effects on fertilization rates and embryo quality. Careful separation of the IVF population into homogenous clinical subsets allows for better detection of these benefits in particular groups of patients. Since LOS conditions are more physiological and seem to be beneficial overall for oocyte fertilization and embryo quality, they should be considered by IVF laboratories as preferred methods for human embryo culture. OBJECTIVE: To compare laboratory and clinical outcomes of human in vitro fertilization (IVF) using a 5% oxygen system versus a 20% oxygen system in various clinical groups. DESIGN: Retrospective analysis of data from IVF cycles performed in a private fertility laboratory setting. MATERIALS AND METHODS: A total of 512 cycles were undertaken using autologous oocytes and 30 cycles were performed using donated oocytes. Oocytes and embryos were randomly assigned for culture in incubators of either a low oxygen system (LOS) or a high oxygen system (HOS). Fertilization rates, embryo cleavage rates, embryo grades, embryo cell numbers, embryo utilization rates, pregnancy rates, and miscarriage rates were compared between LOS and HOS conditions in 12 study groups defined based on maternal age, method of fertilization, prognosis and stimulation protocol. Results were compared within these groups in order to identify patient populations that may benefit from low oxygen culture. Student's t-test and Fisher's exact test were used for statistical analysis. RESULTS: Analysis of the data detected an increase in conventional IVF fertilization rates under LOS conditions, especially in patients of 38-40 years of age (P=0.01). Fertilization rates after intracytoplasmic sperm injection (ICSI) were improved in patients with good prognosis, in the GnRH agonist downregulation group, and in patients of 35-37 years of age. Moreover, we observed a statistically significant increase in the mean number of blastomeres under LOS conditions. This increase was especially significant in patients over 40 years of age and in patients with the Micro-dose flare stimulation protocol (P<0.01 and P=0.01, respectively). Accelerated embryo cleavage under LOS conditions resulted in a significant increase of the rate of embryo utilization in patients who used ICSI (P<0.01). CONCLUSIONS: Based on our data, LOS has positive effects on fertilization rates and embryo quality. Careful separation of the IVF population into homogenous clinical subsets allows for better detection of these benefits in particular groups of patients. Since LOS conditions are more physiological and seem to be beneficial overall for oocyte fertilization and embryo quality, they should be considered by IVF laboratories as preferred methods for human embryo culture.