Evolution of embryo selection for IVF from subjective morphology assessment to objective time-lapse algorithms improves chance of live birth.

RESEARCH QUESTION: Does using an objective time-lapse imaging algorithm (TLIA) after IVF relate to conventional morphological assessment of human blastocysts as a prognosticator for live birth? DESIGN: Prospective use of a TLIA to select embryos in multicentre IVF clinics all using the same strictly controlled laboratory protocols. Each blastocyst was given a ranking from A to D, with the highest rank preferred for fresh transfer. This ranking was retrospectively compared with a given morphological score, which was blinded to the TLIA rank; all embryos were cultured under the same conditions. RESULTS: Using multiple variable logistic regression models, TLIA embryo rank enabled greater discrimination between cycles with and without live births than the conventional morphology grade, even when considered in isolation, and when adjusting for covariates related to treatment and patient criteria. Of the 1810 cycles of single blastocyst transfer, 894 (49.4%) resulted in a live birth. A Vuong non-nested test including covariates showed strong evidence of the superiority of the embryo rank model compared with the transfer grade model (P = 0.0008 [raw], P = 0.0003 [Akaike information criterion - corrected]). From the receiver operating characteristic (ROC) curves across all possible thresholds the TLIA rank showed better true positive and true negative rates and had a higher area under the curve [AUC] of 67.43% compared with 61.74% for the blastocyst morphology grade. The same analysis but excluding covariates demonstrated an AUC of 62.86% versus 54.02%, respectively. CONCLUSION: Objective TLIA is superior for selecting embryos for their propensity to generate a live birth over a conventional, subjective blastocyst morphology scoring system.

Altered expression of BRG1 and histone demethylases, and aberrant H3K4 methylation in less developmentally competent embryos at the time of embryonic genome activation.

Epigenetics is a fundamental regulator underlying many biological functions, such as development and cell differentiation. Epigenetic modifications affect key chromatin regulation, including transcription and DNA repair, which are critical for normal embryo development. In this study, we profiled the expression of epigenetic modifiers and patterns of epigenetic changes in porcine embryos around the period of embryonic genome activation (EGA). We observed that Brahma-related gene 1 (BRG1) and Lysine demethylase 1A (KDM1A), which can alter the methylation status of lysine 4 in histone 3 (H3K4), localize to the nucleus at Day 3-4 of development. We then compared the abundance of epigenetic modifiers between early- and late-cleaving embryos, which were classified based on the time to the first cell cleavage, to investigate if their nuclear localization contributes to developmental competence. The mRNA abundance of BRG1, KDM1A, as well as other lysine demethylases (KDM1B, KDM5A, KDM5B, and KDM5C), were significantly higher in late- compared to early-cleaving embryos near the EGA period, although these difference disappeared at the blastocyst stage. The abundance of H3K4 mono- (H3K4me) and di-methylation (H3K4me2) during the EGA period was reduced in late-cleaving and less developmentally competent embryos. By contrast, BRG1, KDM1A, and H3K4me2 abundance was greater in embryos with more than eight cells at Day 3-4 of development compared to those with fewer than four cells. These findings suggest that altered epigenetic modifications of H3K4 around the EGA period may affect the developmental capacity of porcine embryos to reach the blastocyst stage. Mol. Reprod. Dev. 84: 19-29, 2017. © 2016 Wiley Periodicals, Inc.

Testicular sperm aspiration for nonazoospermic men: sperm retrieval and intracytoplasmic sperm injection outcomes.

OBJECTIVE: To evaluate testicular sperm aspiration (TESA) sperm retrieval rates and intracytoplasmic sperm injection outcomes in nonazoospermic men. MATERIALS AND METHODS: Data were collected retrospectively from 54 consecutive, nonazoospermic, infertile men who underwent TESA between March 2007 and September 2012. Sperm retrieval rates and clinical pregnancy outcomes were recorded. Patients were subgrouped based on clinical diagnosis: group 1, anejaculation (primary, situational); group 2, idiopathic severe oligoasthenozoospermia; and group 3, severe oligoasthenozoospermia after vasovasostomy. RESULTS: Mean (± standard deviation) paternal and maternal ages were 39 ± 7 and 35 ± 5 years, respectively. Using TESA, sperm recovery was successful in 94% (51 of 54) of the men overall and in 100% (17 of 17) of the men in group 1, 90% (28 of 31) in group 2, and 100% (6 of 6) in group 3. Overall, 35% of the couples achieved a clinical pregnancy using TESA sperm (with a mean of 1.7 ± 0.9 embryos transferred per cycle). The clinical pregnancy rates were 40% in group 1, 33% in group 2, and 33% in group 3 with no significant difference in paternal or maternal age between groups. CONCLUSION: The data indicate that TESA yields high sperm retrieval rates in select groups of nonazoospermic infertile men, and this approach results in acceptable pregnancy rates regardless of the male infertility etiology. Randomized controlled trials comparing ejaculated vs testicular sperm are needed to assess the true benefit of TESA-intracytoplasmic sperm injection in these couples.