Is there a relationship between morphokinetic parameters and neonatal sex in fresh embryo transfers?

To investigate whether morphokinetic parameters differ between male and female embryos in IVF embryos resulting in live births, a retrospective cohort study was undertaken. Files of all live births resulting from a single embryo transfer (SET) cultured in time-lapse incubators between 2013 and 2019 in two tertiary care centres were reviewed. The study group consisted of 187 SETs resulted in 187 live births, of which 100 were females (53.5%) and 87 were males (46.5%). Embryo selection for transfer was based on the known implantation data (KID) score provided by the Embryoscope and morphological assessment by experienced embryologists. Neonatal sex was confirmed through live birth documentation. Morphokinetic parameters and day 3 and day 5 KID scores of male and female embryos were compared. Maternal baseline and treatment characteristics were similar between groups. Morphokinetic time-lapse parameters of male and female embryos including: pronuclei fading; cleavage timings (t2-t9); second and third cell cycle durations; synchrony of the second and third cleavages; late morphokinetic parameters and KID scores did not differ between groups. In conclusion, time-lapse morphokinetic parameters and embryo selection methods do not seem to differ between male and female embryos, and their utilization does not bias towards any neonatal sex.

A matched propensity score study of embryo morphokinetics following gonadotropin-releasing hormone agonist versus human chorionic gonadotropin trigger.

PURPOSE: To compare morphokinetic parameters and quality of embryos derived from GnRH antagonist ICSI cycles triggered either with GnRH agonist or standard hCG between matched groups of patients. METHODS: Morphokinetic parameters of embryos derived from matched first GnRH antagonist ICSI cycles triggered by GnRH agonist or standard hCG between 2013 and 2016 were compared. Matching was performed for maternal age, peak estradiol levels, and number of oocytes retrieved. Outcome measures were: time to pronucleus fading (tPNf), cleavage timings (t2-t8), synchrony of the second and third cycles (S2 and S3), duration of the second and third cycle (CC2 and CC3), optimal cell cycle division parameters, and known implantation data (KID) scoring for embryo quality. Multivariate linear and logistic regression analyses were performed for confounding factors. RESULTS: We analyzed 824 embryos from 84 GnRH agonist trigger cycles and 746 embryos from 84 matched hCG trigger cycles. Embryos derived from the cycles triggered with hCG triggering cleaved faster than those deriving from GnRH agonist trigger. The differences were significant throughout most stages of embryo development (t3-t6), and a shorter second cell cycle duration of the hCG trigger embryos was observed. There was no difference in synchrony of the second and third cell cycles and the optimal cell cycle division parameters between the two groups, but there was a higher percentage of embryos without multinucleation in the hCG trigger group (27.8% vs. 21.6%, p < 0.001). CONCLUSION: The type of trigger in matched antagonist ICSI cycles was found to affect early embryo cleavage times but not embryo quality.

Does 'Dual Trigger' Increase Oocyte Maturation Rate?

The aim of this study was to evaluate the oocyte maturation rate when GnRH-a and hCG (dual trigger) are co-administered, compared to the standard hCG trigger within the same patient. Included in the study were GnRH antagonist ICSI cycles performed in 137 patients who had a standard hCG trigger cycle and a dual trigger cycle between 1/1/2013 and 31/12/2017. The mean patient age (35.9 ± 5.6 and 35.2 ± 5.9; <0.001), FSH dose (4140 ± 2065 and 3585 ± 1858; <0.01), number of retrieved oocytes (10.3 ± 6.2 and 8.9 ± 6.1; 0.011) were higher in the dual trigger group compared to the hCG trigger group, oocyte maturation rate was identical. Maturation rate following dual trigger was significantly higher among 34 patients who had a maturation rate of <70% following hCG triggering and among 16 patients with a maturation rate <50% rate following hCG trigger (54% vs. 74%, p < .001 and 44% vs. 73%, p = .006; respectively). In conclusion, co-administration of GnRH agonist and hCG for final oocyte maturation substantially increased the oocyte maturation rate in patients with low oocyte maturation rate in their hCG triggered cycle, but not in an unselected population of patients.IMPACT STATEMENTWhat is already known on this subject? The co-administration of GnRH agonist and hCG for final oocyte maturation prior to oocyte retrieval may improve IVF outcome in patients with a high proportion of immature oocytes. The few studies on dual trigger in patients with a high proportion of immature oocytes or in normal responders have shown conflicting results.What do the results of this study add? We found that co-administration of GnRH agonist and hCG for final oocyte maturation substantially increased the oocyte maturation rate in patients with low oocyte maturation rate in their hCG triggered cycle, but not in an unselected population of patients.What are the implications of these findings for clinical practice and/or further research? The results of this study implicate that in selected population with low oocyte maturation rate, there is an advantage in using dual trigger. However, larger prospective trials are warranted to better assess oocyte response in dual trigger.

Morphokinetic characteristics of embryos derived from in-vitro-matured oocytes and their in-vivo-matured siblings after ovarian stimulation.

RESEARCH QUESTION: Does delayed maturation of aspirated metaphase I (MI) oocytes, completed in vitro, adversely affect early embryo development? DESIGN: Time-lapse microscopy was used to compare morphokinetic variables between embryos derived from oocytes with delayed maturation after ovarian stimulation and from in-vivo-matured metaphase II (MII) sibling oocytes from the same IVF and intracytoplasmic sperm injection cycle. RESULTS: A total of 1545 injected oocytes in 169 cycles from 149 patients were included. The in-vitro-matured oocytes had lower normal fertilization rates than the MII aspirated oocytes (50.2% versus 68.0%; P < 0.001). Early key developmental events were significantly delayed in the normally fertilized in-vitro-matured compared with in-vivo-matured oocytes (polar body extrusion: 5.4 ± 3 versus 3.9 ± 1.8 h; P < 0.001; pronuclear fading: 27.2 ± 4.7 versus 25.1 ± 4.2 h; P < 0.001, respectively) and synchrony of the second cell cycle was adversely affected. The proportions of embryos with optimal second cell cycle length and second cell cycle were similar but with fewer top-quality embryos, based on an algorithm, for the delayed in-vitro-matured oocytes compared with their in-vivo-matured sibling oocytes (14% versus 29.1%; P < 0.001). CONCLUSIONS: Embryos derived from oocytes that failed to mature in-vivo in standard treatment after ovarian stimulation may show a different morphokinetic profile from their sibling oocytes aspirated at the MII stage after completing maturation in-vivo.

Dual nucleotide specificity determinants of an infection aborting anticodon nuclease.

The anticodon nuclease (ACNase) PrrC is silenced by a DNA restriction-modification (RM) protein and activated by a phage T4-encoded restriction inhibitor. The activation is driven by GTP hydrolysis while dTTP, which accumulates during the infection, stabilizes the active form. We show here, first, that the ABC-ATPase N-domains of PrrC can accommodate the two nucleotides simultaneously. Second, mutating a sequence motif that distinguishes the N-domain of PrrC from typical ABC-ATPases implicates three residues in the specificity for dTTP. Third, failure to bind dTTP or its deprivation hastened the centrifugal sedimentation of PrrC, possibly due to exposed sticky PrrC surfaces. Fourth, dTTP inhibited the GTPase activity of PrrC, probably by preventing GDP from leaving. These observations, correlated with relevant traits of a related ACNase, further suggest that PrrC utilizes GTP at canonical ABC-ATPase sites and binds dTTP to distinct sites exposed upon disruption of the ACNase-silencing interaction with the RM partner.