Time-lapse deselection model for human day 3 in vitro fertilization embryos: The combination of qualitative and quantitative measures of embryo growth

Objective To present a time-lapse deselection model involving both qualitative and quantitative parameters for assessing embryos on day 3. Design Retrospective cohort study and prospective validation. Setting Private IVF center. Patient(s) A total of 270 embryos with known implantation data (KID) after day 3 transfer from 212 IVF/intracytoplasmic sperm injection (ICSI) cycles were retrospectively analyzed for building the proposed deselection model, followed by prospective validation using an additional 66 KID embryos. Intervention(s) None. Main Outcome Measure(s) Morphological score on day 3, embryo morphokinetic parameters, abnormal cleavage patterns, and known implantation results. Result(s) All included embryos were categorized either retrospectively or prospectively into 7 grades (A+, A, B, C, D, E, F). Qualitative deselection parameters included poor conventional day 3 morphology, abnormal cleavage patterns identified via time-lapse monitoring, and(PNF) to 5-cell stage and duration of 3-cell stage. KID implantation rates of embryos graded from A+ to F were 52.9%, 36.1%, 25.0%, 13.8%, 15.6%, 3.1%, and 0 respectively (area under the curve [AUC] = 0.762; 95% confidence interval [CI], 0.701-0.824), and a similar pattern was seen in either IVF (AUC = 0.721; 95% CI, 0.622-0.821) or ICSI embryos (AUC = 0.790; 95% CI, 0.711-0.868). Preliminary prospective validation using 66 KID embryos also showed statistically significant prediction in Medicult (AUC = 0.750; 95% CI, 0.588-0.912) and Vitrolife G-Series (AUC = 0.820; 95% CI, 0.671-0.969) suites of culture media. Conclusion(s) The proposed model involving both qualitative and quantitative deselection effectively predicts day 3 embryo implantation potential and is applicable to all IVF embryos regardless of insemination method by using PNF as the reference starting time point

Time-lapse videography reveals different morphokinetic profiles of human embryos displaying direct or reverse cleavage at different stages of development: A retrospective sibling embryo study

© 2020 Wolters Kluwer Medknow Publications. All rights reserved. Objective: To investigate morphokinetic characteristics of embryos displaying either reverse cleavage or direct cleavage during the first, second or third cleavage cycle. Methods: A total of 167 in vitro fertilization and/or intracytoplasmic sperm injection treatment cycles undertaken by 167 women [aged (35.0±4.6) years] were included for reverse cleavage analysis, and a total of 167 in vitro fertilization and/or intracytoplasmic sperm injection treatment cycles undertaken by 167 women [aged (33.8 ±4.3) years] were included for direct cleavage analysis in this study. Using a sibling-embryo design, morphokinetic profiles (both before and after the onset of abnormal event) of embryos displaying reverse cleavage (n=241) or direct cleavage (n=244) were compared with their unaffected siblings (the controls) in the first, second and third cell cycles (n=32, n=142, n=562; n=195, n=412, n=205, respectively), at different developmental stages up to day 3. Results: Direct cleavage embryos demonstrated significantly delayed cleavage rates prior to the event regardless of developmental stage of the occurrence, while reverse cleavage embryos showed similar cleavage rates to their unaffected siblings. Post event, direct cleavage embryos sped up cleavage rates while reverse cleavage embryos slowed down. Conclusions: Altered morphokinetic profiles are displayed by direct cleavage embryos both before and after their occurrence and reverse cleavage embryos after the occurrence, which could potentially confound morphokinetic comparisons if not separated from their unaffected sibling embryos. Further study is warranted in order to fully understand the biological mechanisms of such events

The relationship between embryo quality assessed using routine embryology or time–lapse videography and serum progesterone concentration on the day of ovulatory trigger in in vitro fertilization cycles

Objective: To investigate the relationship between elevated serum progesterone levels (EP) on the day of ovulatory trigger, live birth rates, and the growth of resulting embryos. Methods: A total of 836 in vitro fertilization (IVF) cycles with 4 478 embryos in conventional culture were retrospectively analyzed, together with an additional 90 IVF cycles producing 618 embryos from culture and assessment using the Embryoscope™ time-lapse system. Results: In cycles using conventional culture, serum progesterone per follicle ≥14 mm (median 0.42 nmol/L/follicle, range 0.05-3.50 nmol/L/follicle) was a significant negative predictor of live-birth (ROC AUC = 0.395, 95% CI 0.345-0.445; P=0.000) as were progesterone/estradiol ratio (0.442, 0.391-0.494; P=0.027) and progesterone per oocyte (0.374, 0.326-0.421; P=0.000) but not progesterone alone (0.470, 0.419-0.521; P>0.05). Women with an EP/follicle (>0.42 nmol/L/follicle) had reduced live birth rates if they were ≥35 yrs (14.4% vs. 24.2%, P<0.05) but not <35 years (35.3% vs. 37.4%, ns). Despite reduced pregnancy rates, cycles with EP/follicle in women ≥35 years produced similar proportions of “good” and “top” quality embryos in conventional culture compared to women with low progesterone/follicle, and no difference in abnormalities of cleavage (direct cleavage or reverse cleavage), multinucleation or timings of division (pronuclear fading to 2-cell, 3-cell, 4-cell and 5-cell; cc2 and S2) observed with time-lapse videography. Conclusions: EP/follicle ≥14 mm (>0.42 nmol/L/follicle) adversely affects embryo implantation in women aged ≥35 years, but not <35 yrs. However, no adverse features were seen in the embryos from these affected cycles in terms of morphological appearance, abnormal patterns of cleavage, or morphokinetic timings