Optimal Embryo Selection: The Irreplaceable Role of the Embryologist in an Age of Advancing Technology.

Background: Time-lapse incubators allow for ongoing evaluation of embryos without culture condition disruption. The use of time-lapse incubation has been shown to improve outcomes either by improving overall conditions or providing additional information to aid in embryo selection for transfer. Time-lapse incubators can also utilise morphokinetic models to rank embryos based on morphokinetic parameters. We sought to compare a morphokinetic model for embryo comparison to traditional morphologic evaluation. Aims: The aim of the study is to compare a morphokinetic model for embryo comparison to traditional morphologic evaluation. Settings and Design: This is a retrospective cohort design. Materials and Methods: Embryos cultured in a time-lapse culture system that had traditional morphologic evaluation, morphokinetic modelling and known live birth outcomes were included in this study. Embryos with unknown competence were excluded, including when two embryos were transferred with a single live birth resulted. Statistical Analysis Used: Receiver operating characteristic (ROC) curves were determined for both the morphologic analysis and the morphokinetic model on culture day 3 and day 5. Using the ROC-determined cutoff that optimised both sensitivity and specificity, a binary outcome for each test was analysed using agreement statistics to determine if one method of embryo evaluation was superior to the other. Results: Morphological and morphokinetic grading were both predictive of embryo competence on days 3 and 5. However, on day 3, morphologic grading was superior to morphokinetic grading with area under the curve (AUC) of 0.66 (P < 0.001) and 0.58 (P = 0.009), respectively. Contrarily, on day 5, the morphokinetic model had a higher AUC of 0.65 (P = 0.03) compared to the morphologic grading, AUC 0.56 (P = 0.02). Conclusion: Traditional morphology was noted to be a better diagnostic tool (higher AUC) on culture day 3 while a morphokinetic model was superior on day 5.

Clinical implementation of algorithm-based embryo selection is associated with improved pregnancy outcomes in single vitrified warmed euploid embryo transfers.

PURPOSE: To assess whether utilization of a mathematical ranking algorithm for assistance with embryo selection improves clinical outcomes compared with traditional embryo selection via morphologic grading in single vitrified warmed euploid embryo transfers (euploid SETs). METHODS: A retrospective cohort study in a single, academic center from September 2016 to February 2020 was performed. A total of 4320 euploid SETs met inclusion criteria and were included in the study. Controls included all euploid SETs in which embryo selection was performed by a senior embryologist based on modified Gardner grading (traditional approach). Cases included euploid SETs in which embryo selection was performed using an automated algorithm-based approach (algorithm-based approach). Our primary outcome was implantation rate. Secondary outcomes included ongoing pregnancy/live birth rate and clinical loss rate. RESULTS: The implantation rate and ongoing pregnancy/live birth rate were significantly higher when using the algorithm-based approach compared with the traditional approach (65.3% vs 57.8%, p<0.0001 and 54.7% vs 48.1%, p=0.0001, respectively). After adjusting for potential confounding variables, utilization of the algorithm remained significantly associated with improved odds of implantation (aOR 1.51, 95% CI 1.04, 2.18, p=0.03) ongoing pregnancy/live birth (aOR 1.99, 95% CI 1.38, 2.86, p=0.0002), and decreased odds of clinical loss (aOR 0.42, 95% CI 0.21, 0.84, p=0.01). CONCLUSIONS: Clinical implementation of an automated mathematical algorithm for embryo ranking and selection is significantly associated with improved implantation and ongoing pregnancy/live birth as compared with traditional embryo selection in euploid SETs.

Clinical pregnancy rates and experience with in vitro fertilization after uterus transplantation: Dallas Uterus Transplant Study.

BACKGROUND: The clinical pregnancy rates among patients with uterus transplantation have been reported by only a limited number of centers, and those centers have not used preimplantation genetic testing for aneuploidy in their protocol. OBJECTIVE: This study examined clinical pregnancy rates among women with absolute uterine-factor infertility undergoing in vitro fertilization using good-quality, expanded-blastocyst-stage, euploid embryos after uterus transplantation. STUDY DESIGN: This cohort observational study involved 20 women who underwent uterus transplantation over 3 years. Notably, 14 of these patients had successful transplants and were followed prospectively for a median of 14.1 months (range, 11-34.8 months). In vitro fertilization was performed before subjects underwent uterus transplantation, and good-quality expanded-blastocyst-stage euploid embryos were obtained and frozen for future embryo transfer. Interventions consisted of in vitro fertilization, preimplantation genetic testing for aneuploidy, uterus transplantation, and frozen embryo transfer. RESULTS: All 14 subjects with successful transplants underwent single embryo transfer of a warmed, good-quality, euploid, expanded blastocyst and had at least 1 documented clinical pregnancy within the uterus. In 71.4%, the first embryo transfer resulted in clinical pregnancy. The median time from successful uterus transplantation to first embryo transfer was 4.5 months; from successful uterus transplantation to first clinical pregnancy, 7.3 months; and from successful uterus transplantation to first live birth, 14.1 months. A total of 13 live births have occurred in 12 subjects. CONCLUSION: Women with absolute uterine-factor infertility who have surgically successful uterus transplantation and in vitro fertilization using preimplantation genetic testing for aneuploidy can achieve high clinical pregnancy rates. We have reduced the time interval from uterus transplantation to embryo transfer by at least 50% and the interval from uterus transplantation to clinical pregnancy by >6 months compared with previous studies. We believe our approach may shorten the time from transplant to clinical pregnancy and therefore decrease patient exposure to immunosuppressant therapies.

Association between morphologic grading and implantation rate of Euploid blastocyst.

BACKGROUND: Standard morphologic evaluation has been the most widely adopted approach to embryo selection, and remains the most common strategy.The objective of the study to determine the association between the morphologic grading and implantation rate of euploid blastocysts in single frozen-thawed embryo transfer (SET) cycles. METHODS: A total of 271 patients aged 20-40 years undergoing euploid SET from January 2017 to December 2019 were included in retrospective cohort study.The cycles were divided into three groups based on their morphologic grading before cryopreservation: good-quality (n = 58), average-quality (n = 88) and poor-quality blastocysts (n = 125). The pregnancy outcome of the three morphologic groups were analyzed and a logistic regression of implantation rate was conducted. RESULTS: Good-quality blastocysts yielded statistically significantly higher implantation rates than poor-quality (79.31% vs. 48%; P<0.001). Planned subgroup analyses by age and the day of TE biopsy were conducted. Logistic regression analyses that adjusted for these variables identified higher implantation rates (adjusted odds ratio(aOR) = 4.083, 95% confidence interval (CI):1.836-9.082, P<0.001) for the good-quality blastocysts than for those that underwent poor-quality cycles in women aged < 35 years, but not in women aged ≥35 years (aOR = 6.074, 95% CI: 0.456-80.919, P = 0.172). The implantation rates were higher among women with good-quality blastocysts on both Day 5 and Day 6 of TE biopsy than among those with poor-quality blastocysts (Day 5, aOR = 3.294, 95% CI:1.260-8.616, P = 0.015; Day 6, aOR = 4.179, 95% CI:1.004 ~ 17.399, P = 0.049). Day 5 euploid blastocysts had no significant difference in implantation potential and early spontaneous abortion rate compared with similarly graded Day 6 euploid blastocysts. CONCLUSIONS: Blastocyst morphologic grading was associated with implantation rate for euploid embryo transfers after adjustment for potential confounders. These findings suggest that evaluating blastocyst morphology is critical when selecting the best euploid blastocyst.

Correlation between Morphologic Grading and Euploidy Rates of Blastocysts, and Clinical Outcomes in In Vitro Fertilization Preimplantation Genetic Screening.

BACKGROUND: The standard morphological evaluation has been widely used for embryo selection, but it has limitations. This study aimed to investigate the correlation between morphologic grading and euploidy rate of in vitro fertilization (IVF) preimplantation genetic screening (PGS) and compare the pregnancy rates in young and old ages. METHODS: This is a retrospective study using the medical records of patients who underwent IVF procedures with PGS between January 2016 and February 2017 in a single center. The embryo grades were categorized into 4 groups: excellent, good, fair, and poor. Basic characteristics, euploidy rates, clinical pregnancy (CP) rates and ongoing pregnancy rates were analyzed. RESULTS: The excellent group had significantly higher rate of euploid embryos than fair group (47.82% vs. 29.33%; P = 0.023) and poor group (47.82% vs. 29.60%; P = 0.005). When the four groups were recategorized into two groups (excellent and good vs. fair and poor), they also showed significant difference in euploidy rates (44.52% vs. 29.53%; P = 0.002). When the patients were divided into two groups by age 35, the CP rates for those under and over 35 years old were 44.74% and 47.83%, respectively, which showed no significant difference. CONCLUSION: The significant differences among the euploidy rates of different morphologic embryo grades demonstrated the positive correlations between the morphologic grading of the embryo and the euploidy rate of PGS. Additionally, there was no significant difference between the younger and older patients' CP rates. These findings emphasize the fact that old age patients might benefit from PGS whatever the indication of PGS is.

Blastocyst development rate influences implantation and live birth rates of similarly graded euploid blastocysts.

OBJECTIVE: To determine whether the blastocyst development rate, as assessed by the day of trophectoderm biopsy (day 5 vs. day 6), affects the live birth rate (LBR) of similarly graded euploid blastocysts. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): Patients who underwent frozen-thawed single euploid blastocyst transfers from 2013 to 2016 were included. Blastocyst morphologic grading was performed on day 5 or day 6 before the biopsy, with embryos designated into the following groups: good (3-6AA, 3-6AB, and 3-6BA), average (2-6BB), and poor (2-6BC and 2-6CB). INTERVENTION(S): Frozen-thawed embryo transfer. MAIN OUTCOME MEASURE(S): Implantation rate (IR) and LBR. RESULT(S): A total of 701 frozen-thawed single euploid blastocyst transfer cycles were included. Cycles in which day 5 blastocysts were transferred (n = 366) were associated with a significantly higher LBR than those in which day 6 blastocysts were transferred (n = 335; 60.4% vs. 44.8%). The odds ratio remained significant after controlling for all confounders, including the blastocyst grading. Furthermore, there was a significant difference in LBRs between good-quality, average-quality, and poor-quality blastocysts (67.8%, 53.4%, and 29.5%, respectively). Embryos reaching good-quality blastocysts on day 5 yielded significantly higher LBR (72.8% vs. 56.5%) and IR (77.7% vs. 58.7%) compared with those reaching similar quality blastocysts on day 6. Similarly, day 5 average-quality embryos conveyed a significantly higher IR compared with day 6 embryos of the same quality (64.4% vs. 53.4%). CONCLUSION(S): In addition to aneuploidy assessment, the speed of embryo development to the blastocyst stage and an evaluation of blastocyst morphology are critical to selecting the best embryo.

Morphologic grading of euploid blastocysts influences implantation and ongoing pregnancy rates.

OBJECTIVE: To determine whether blastocyst grading can predict pregnancy outcomes in the frozen-thawed embryo transfer (FET) of euploid blastocysts. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): Women who underwent FET of euploid embryo(s) between January 2013 and December 2015, with blastocysts were divided into four groups based on their morphologic grading before cryopreservation: excellent (≥3AA), good (3-6AB, 3-6BA, 1-2AA), average (3-6BB, 3-6AC, 3-6CA, 1-2AB, 1-2BA), and poor (1-6BC, 1-6CB, 1-6CC, 1-2BB). INTERVENTION(S): FET. MAIN OUTCOMES MEASURE(S): Ongoing pregnancy rate (OPR). RESULT(S): A total of 417 FET cycles (477 embryos) were included. Excellent-quality embryos (n = 38) yielded a statistically significantly higher OPR than poor-quality embryos (n = 106) (84.2% vs. 35.8%; adjusted odds ratio 11.0; 95% confidence interval, 3.8-32.1) and average-quality embryos (n = 197) (84.2% vs. 55.8%; adjusted odds ratio 4.8; 95% confidence interval, 1.7-13.3). Good-quality embryos (n = 76) were associated with a statistically significantly higher OPR than poor-quality embryos (61.8% vs. 35.8%). These odds ratios were adjusted for patient's age, body mass index, number of transferred embryos, type of frozen cycle, peak endometrial thickness, day of trophectoderm biopsy (5 or 6), and total number of euploid embryos for each patient. An inner cell mass grade of A yielded a statistically significantly higher OPR than ICM grade C (76.2% vs. 13.5%) or grade B (76.2% vs. 53.6%) after controlling for all confounders. CONCLUSION(S): Contrary to prior published studies, the current data suggest that blastocyst morphologic grading and particularly inner cell mass grade is a useful predictor of OPR per euploid embryo. Morphologic grading should be used to help in the selection among euploid blastocysts.

Non-invasive metabolomic profiling of embryo culture media and morphology grading to predict implantation outcome in frozen-thawed embryo transfer cycles.

PURPOSE: Assessment of embryo viability is a crucial component of in vitro fertilization and currently relies largely on embryo morphology and cleavage rate. Because morphological assessment remains highly subjective, it can be unreliable in predicting embryo viability. This study investigated the metabolomic profiling of embryo culture media using near-infrared (NIR) spectroscopy for predicting the implantation potential of human embryos in frozen-thawed embryo transfer (FET) cycles. METHODS: Spent embryo culture media was collected on day 4 after thawed embryo transfer (n = 621) and analysed using NIR spectroscopy. Viability scores were calculated using a predictive multivariate algorithm of fresh embryos with known pregnancy outcomes. RESULTS: The mean viability indices of embryos resulting in clinical pregnancy following FET were significantly higher than those of non-implanted embryos and differed between the 0, 50, and 100 % implantation groups. Notably, the 0 % group index was significantly lower than the 100 % implantation group index (-0.787 ± 0.382 vs. 1.064 ± 0.331, P < 0.01). To predict implantation outcomes, we examined the area under the ROC curve (AUCROC), which was significantly higher for the viability than for the morphology score (0.94 vs. 0.55; P < 0.01); however, the AUCROCs for the composite and viability scores did not differ significantly (0.92 vs. 0.94; P > 0.05). CONCLUSIONS: NIR metabolomic profiling of thawed embryo culture media is independent of morphology and correlates with embryo implantation potential in FET cycles. The viability score alone or in conjunction with morphologic grading is a more objective marker for implantation outcome in FET cycles than morphology alone.