External validation of a model for selecting day 3 embryos for transfer based upon deep learning and time-lapse imaging.

RESEARCH QUESTION: Could objective embryo assessment using iDAScore Version 2.0 perform as well as conventional morphological assessment? DESIGN: A retrospective cohort study of fresh day 3 embryo transfer cycles was conducted at a large reproductive medicine centre. In total, 7786 embryos from 4328 cycles with known implantation data were cultured in a time-lapse incubator and included in the study. Fetal heartbeat (FHB) rate was analysed retrospectively using iDAScore Version 2.0 and conventional morphological assessment associated with the transferred embryos. The pregnancy-prediction performance of the two assessment methods was compared using area under the curve (AUC) values for predicting FHB. RESULTS: AUC values were significantly higher for iDAScore compared with morphological assessment for all cycles (0.62 versus 0.60; P = 0.005), single-embryo transfer cycles (0.63 versus 0.60; P = 0.043) and double-embryo transfer cycles (0.61 versus 0.59; P = 0.012). For the age subgroups, AUC values were significantly higher for iDAScore compared with morphological assessment in the <35 years subgroup (0.62 versus 0.60; P = 0.009); however, no significant difference was found in the ≥35 years subgroup. In terms of the number of blastomeres, AUC values were significantly higher for iDAScore compared with morphological assessment for both the <8c subgroup (0.67 versus 0.56; P < 0.001) and the ≥8c subgroup (0.58 versus 0.55; P = 0.012). CONCLUSIONS: iDAScore Version 2.0 performed as well as, or better than, conventional morphological assessment in fresh day 3 embryo transfer cycles. iDAScore Version 2.0 may therefore constitute a promising tool for selecting embryos with the highest likelihood of implantation.

Prediction model for day 3 embryo implantation potential based on metabolites in spent embryo culture medium.

BACKGROUND: Metabolites in spent embryo culture medium correlate with the embryo's viability. However, there is no widely accepted method using metabolite dada to predict successful implantation. We sought to combine metabolomic profiling of spent embryo culture medium and clinical variables to create an implantation prediction model as an adjunct to morphological screening of day 3 embryos. METHODS: This investigation was a prospective, nested case-control study. Forty-two day 3 embryos from 34 patients were transferred, and the spent embryo culture medium was collected. Twenty-two embryos implanted successfully, and the others failed. Metabolites in the medium relevant to implantation were detected and measured by Liquid Chromatography-Mass Spectrometry. Clinical signatures relevant to embryo implantation were subjected to univariate analysis to select candidates for a prediction model. Multivariate logistical regression of the clinical and metabolomic candidates was used to construct a prediction model for embryo implantation potential. RESULTS: The levels of 13 metabolites were significantly different between the successful and failed groups, among which five were most relevant and interpretable selected by Least Absolute Shrinkage and Selection Operator regression analysis. None of the clinical variables significantly affected day 3 embryo implantation. The most relevant and interpretable set of metabolites was used to construct a prediction model for day 3 embryo implantation potential with an accuracy of 0.88. CONCLUSIONS: Day 3 embryos'implantation potential could be noninvasively predicted by the spent embryo culture medium's metabolites measured by LC-MS. This approach may become a useful adjunct to morphological evaluation of day 3 embryos.

Doble transferencia embrionaria consecutiva D3/D5-6: una alternativa para mejorar las tasas de embarazo en pacientes sometidas a fertilización in vitro/transferencia embrionaria (FIV/TE)

Objetivo: Evaluar la doble transferencia embrionaria consecutiva D3/D5-6 (DTEC D3/D5-6) como alternativa para mejorar las tasas de embarazo en pacientes sometidas a un programa de fertilización in vitro/transferencia embrionaria (FIV/TE) que obtengan más de dos embriones de día 3 (D3), independientemente del número de intentos previos, de la edad y de los criterios de inclusión al programa. Métodos: Estudio observacional prospectivo realizado en un centro de fertilidad privado. Se aplicó la técnica de la DTEC D3/D5-6 de acuerdo al protocolo del Centro Valenciano de Fertilidad y Esterilidad (CEVALFES) a 58 pacientes durante el período septiembre 2012-2014 y que obtuvieron dos o más embriones de buena calidad. Resultados: La tasa de éxito general fue de un 39,65 %. Estos resultados se compararon con las tasas de éxito de la aplicación de la TE de D3 y de D5-6 de un solo embrión y de dos y tres embriones llevadas a cabo en un solo momento. La tasa de éxito general fue superior a las obtenidas con las TE D3 dobles y triples (29,23 % y 31,01 % respectivamente) y a las TE de blastocistos desvitrificados únicas y dobles (15,38 % y 15,15 % respectivamente). Conclusiones: La doble transferencia embrionaria consecutiva D3/D5-6 se perfila como una técnica eficaz para tomar la decisión de cuántos embriones transferir y el momento de hacerlo cuando la pareja cuenta con dos o más embriones de D3. Ello se traduce en una alternativa que puede mejorar los resultados de las técnicas de reproducción asistida en la actualidad.

Objective: The aim of this study was to evaluate a double consecutive embryo transfer day 3/ day 5-6 as an alternative to improve pregnancy rates among patients undergoing an IVF/ET program who obtain more than two day-3 embryos, without taking into account the number of previous attempts, age or IVF/ET program inclusion criteria. Method: Prospective observational study at a private fertility center. The double consecutive embryo transfer day 3/ day 5-6 approach was performed, according to the protocol outlined at CEVALFES, on 58 patients of our fertility center who obtained two or more good quality embryos between September 2012 and September 2014. Results: The overall pregnancy rate was 39,65%. These results were compared with single embryo transfers day 3 and day 5-6 and double and triple embryo transfers performed either on day 3 or on day 5-6. This overall pregnancy rate was higher than the rates obtained for double and triple day-3 ET (29,23% and 31,01% respectively) and for single and double thawed blastocyst ET (15,38% and 15,15% respectively). Conclusions: The double consecutive embryo transfer day 3 and day 5-6 approach presents itself as an effective alternative to inform decision making when two or more day-3 embryos are available: how many day-3 embryos are to be transferred and if ET can be performed consecutively on day 3 and day-5-6. This, in turn, becomes a choice that can improve current pregnancy rates.

Day-3 embryo metabolomics in the spent culture media is altered in obese women undergoing in vitro fertilization.

OBJECTIVE: To determine whether the global metabolomic profile of the spent culture media (SCM) of day-3 embryos is different in obese and normoweight women undergoing in vitro fertilization (IVF). DESIGN: Prospective cohort analysis. SETTING: IVF clinic. PATIENT(S): Twenty-eight young, nonsmoking women with normoweight, nonsmoking male partners with mild/normal sperm factors undergoing a first IVF attempt for idiopathic infertility, tubal factor infertility, or failed ovulation induction: obese ovulatory women (n = 12); obese women with polycystic ovary syndrome (PCOS; n = 4); normoweight ovulatory women (n = 12). INTERVENTION(S): Fifty µl of SCM collected from two day-3 embryos of each cohort. MAIN OUTCOME MEASURE(S): Metabolomic profiling via ultrahigh performance liquid chromatography coupled to mass spectrometry of SCM from a total of 56 embryos. RESULT(S): The untargeted metabolomic profile was different in obese and normoweight women. Partial least squares discriminant analysis resulted in a clear separation of samples when a total of 551 differential metabolites were considered. A prediction model was generated using the most consistent metabolites. Most of the metabolites identified were saturated fatty acids, which were detected in lower concentrations in the SCM of embryos from obese women. The metabolomic profile was similar in obese women with or without PCOS. CONCLUSION(S): The metabolomic profile in the SCM of day-3 embryos is different in normoweight and obese women. Saturated fatty acids seem to be reduced when embryos from obese patients are present. CLINICAL TRIAL REGISTRATION NUMBER: NCT01448863.