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Biomedical subjects

D L Walker

Publications and source records attributed to D L Walker.

At least 19 recordsLinked to original sources
PubMed1998

Temporal relationships between oxytocin and 13,14-dihydro-15-keto-prostaglandin F2 alpha pulses in ovariectomized ewes.

The primary objective was to evaluate the role of non-ovarian oxytocin in the initiation of pulses of PGF2 alpha, as measured by peripheral concentrations of 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM). A 2 x 2 factorial arrangement of estradiol and progesterone treatments was administered to groups of five ewes after ovariectomy on Day 12. Progesterone (10 mg) was administered at 0700 and 1900 hr on Day 12, and then either progesterone or its vehicle was administered on Days 13 and 14. Silastic implants, either empty or containing estradiol, was administered at ovariectomy. Oxytocin and PGFM were measured in jugular blood samples withdrawn from an indwelling catheter at 5-min intervals for 8 hr on Day 15. Statistically significant pulses of oxytocin, presumably of posterior pituitary origin, were detected in all ewes. Approximately one-half of the oxytocin pulses preceded a pulse in PGFM concentrations by 10 min or less. These pulses tended (P = 0.09) to have a longer duration than those not linked to pulses of PGFM. The number of PGFM pulses that followed or did not follow an oxytocin pulse by 10 min or less was similar (P > 0.2). The amplitude and duration of oxytocin-linked PGFM pulses were greater (P = 0.05) than non-linked pulses. Although several explanations for the lower than anticipated temporal relationship between oxytocin and PGFM pulses are possible, the finding that oxytocin-related PGFM pulses are distinguishable from other pulses is consistent with the concept that oxytocin initiates robust pulses in PGF2 alpha secretion.

Animals↗
PubMed1998

6-Aminonicotinamide sensitizes human tumor cell lines to cisplatin.

The nicotinamide analogue 6-aminonicotinamide (6AN) is presently undergoing evaluation as a potential modulator of the action of various antineoplastic treatments. Most previous studies of this agent have focused on a three-drug regimen of chemical modulators that includes 6AN. In the present study, the effect of single-agent 6AN on the efficacy of selected antineoplastic drugs was assessed in vitro. Colony-forming assays using human tumor cell lines demonstrated that pretreatment with 30-250 microM 6AN for 18 h resulted in increased sensitivity to the DNA cross-linking agent cisplatin, with 6-, 11-, and 17-fold decreases in the cisplatin dose that diminishes colony formation by 90% being observed in K562 leukemia cells, A549 non-small cell lung cancer cells, and T98G glioblastoma cells, respectively. Morphological examination revealed increased numbers of apoptotic cells after treatment with 6AN and cisplatin compared to cisplatin alone. 6AN also sensitized cells to melphalan and nitrogen mustard but not to chlorambucil, 4-hydroperoxycyclophosphamide, etoposide, or daunorubicin. In additional studies undertaken to elucidate the mechanism underlying the sensitization to cisplatin, atomic absorption spectroscopy revealed that 6AN had no effect on the rate of removal of platinum (Pt) adducts from DNA. Instead, 6AN treatment was accompanied by an increase in Pt-DNA adducts that paralleled the degree of sensitization. This effect was not attributable to 6AN-induced decreases in glutathione or NAD+, because other agents that depleted these detoxification cofactors (buthionine sulfoximine and 3-acetylpyridine, respectively) did not increase Pt-DNA adducts. On the contrary, 6AN treatment increased cellular accumulation of cisplatin. Further experiments revealed that 6AN was metabolized to 6-aminonicotinamide adenine dinucleotide (6ANAD+). Concurrent administration of nicotinamide and 6AN had minimal effect on cellular 6AN accumulation but abolished the formation of 6ANAD+, the increase in Pt-DNA adducts, and the sensitizing effect of 6AN in clonogenic assays. These observations identify 6AN as a potential modulator of cisplatin sensitivity and suggest that the 6AN metabolite 6ANAD+ exerts this effect by increasing cisplatin accumulation and subsequent formation of Pt-DNA adducts.

6-Aminonicotinamide↗
PubMed1997

Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear.

The amplitude of the acoustic startle response is reliably enhanced when elicited in the presence of bright light (light-enhanced startle) or in the presence of cues previously paired with shock (fear-potentiated startle). Light-enhanced startle appears to reflect an unconditioned response to an anxiogenic stimulus, whereas fear-potentiated startle reflects a conditioned response to a fear-eliciting stimulus. We examine the involvement of the basolateral nucleus of the amygdala, the central nucleus of the amygdala, and the bed nucleus of the stria terminalis in both phenomena. Immediately before light-enhanced or fear-potentiated startle testing, rats received intracranial infusions of the AMPA receptor antagonist 2, 3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)-quinoxaline (3 microg) or PBS. Infusions into the central nucleus of the amygdala blocked fear-potentiated but not light-enhanced startle, and infusions into the bed nucleus of the stria terminalis blocked light-enhanced but not fear-potentiated startle. Infusions into the basolateral amygdala disrupted both phenomena. These findings indicate that the neuroanatomical substrates of fear-potentiated and light-enhanced startle, and perhaps more generally of conditioned and unconditioned fear, may be anatomically dissociated.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

Amygdala and bed nucleus of the stria terminalis: differential roles in fear and anxiety measured with the acoustic startle reflex.

Neural stimuli associated with traumatic events can readily become conditioned so as to reinstate the memory of the original trauma. These conditioned fear responses can last a lifetime and may be especially resistant to extinction. A large amount of data from many different laboratories indicate that the amygdala plays a crucial role in conditioned fear. The amygdala receives information from all sensory modalities and projects to a variety of hypothalamic and brainstem target areas known to be critically involved in specific signs that are used to define fear and anxiety. Electrical stimulation of the amygdala elicits a pattern of behaviours that mimic natural or conditioned states of fear. Lesions of the amygdala block innate or conditioned fear and local infusion of drugs into the amygdala have anxiolytic effects in several behavioural tests. Excitatory amino acid receptors in the amygdala are critical for the acquisition, expression and extinction of conditioned fear.

Amygdala↗
PubMed1997

Anxiogenic effects of high illumination levels assessed with the acoustic startle response in rats.

Previous studies have shown that the amplitude of the acoustic startle reflex is increased by the presentation of aversive stimuli. In the present study, the amplitude of acoustic startle in rats was increased by exposure to high illumination levels. The effect was directly related to the intensity (0, 8, 70, and 700 footlamberts) of illumination (experiment I); was blocked by the anxiolytic compound buspirone (experiment II); and showed little or no habituation with repeated testing (experiment III). These results suggest that the elevation of startle amplitude by light may reflect an unconditioned anxiogenic effect of high illumination levels. The possible utility of this phenomenon as an animal model of anxiety is discussed.

Acoustic Stimulation↗
PubMed1997

Opposing roles of the amygdala and dorsolateral periaqueductal gray in fear-potentiated startle.

The whole-body acoustic startle response is a short-latency reflex mediated by a relatively simple neural circuit in the lower brainstem and spinal cord. The amplitude of this reflex is markedly enhanced by moderate fear levels, and less effectively increased by higher fear levels. Extensive evidence indicates that the amygdala plays a key role in the potentiation of startle by moderate fear. More recent evidence suggests that the periaqueductal gray is involved in the loss of potentiated startle at higher levels of fear. The influence of both structures may be mediated by anatomical connections with the acoustic startle circuit, perhaps at the level of the nucleus reticularis pontis caudalis. The present chapter reviews these data.

Amygdala↗
PubMed1997

Involvement of the dorsal periaqueductal gray in the loss of fear-potentiated startle accompanying high footshock training.

The amplitude of acoustic startle is markedly enhanced by cues signaling moderately intense footshocks but, surprisingly, not by cues signaling higher intensity footshocks. Previous findings suggest that the ineffectiveness of high footshock training may involve activation of the dorsal periaqueductal gray (PAG). As a means of evaluating this possibility, rats trained with moderate (0.6 mA) footshocks were later tested after intra-PAG infusion of an excitatory nontoxic dose of kainic acid. Kainic acid significantly reduced fear-potentiated startle relative to vehicle controls. In a 2nd experiment, the effect of dorsal PAG lesions on fear-potentiated startle to cues paired with 0.6-mA and 1.6-mA footshocks was evaluated. Dorsal PAG lesions prevented the disruptive effects of high footshock training. Together, these results suggest that dorsal PAG activation mediates the loss of potentiated startle accompanying high footshock training.

Acoustic Stimulation↗
PubMed1997

Influence of estradiol and progesterone withdrawal on the secretion of and the temporal correlation between pulses of oxytocin and prostaglandin F2(alpha) in ewes.

The primary objective was to examine the effects of estradiol and the progesterone receptor antagonist onapristone on the pulsatile secretion of prostaglandin F(2alpha) (PGF(2alpha)) and ovarian and pituitary oxytocin. A 2 x 2 factorial arrangement of estradiol and onapristone treatments was administered to groups of 5 ewes after destruction of ovarian follicles on Day 8 of the cycle. Estradiol treatments consisted of the administration of a silicone elastomer implant, either containing or not containing estradiol, on Day 8 plus 50 microg of estradiol or corn oil on Days 11 and 12. Onapristone (2 mg/kg) or its vehicle were administered on Day 13, immediately preceding the simultaneous collection of blood samples from the carotid artery, jugular vein, and vena cava at 7.5-min intervals for 7 h. Ewes were immediately killed for measurements of uterine oxytocin receptor concentrations and phosphatidylinositide turnover. More oxytocin pulses were detected in the jugular vein than in the carotid artery (p < 0.01), suggesting that the pituitary is a source of oxytocin. A similar number (p > 0.1) of PGF(2alpha) pulses were correlated with oxytocin pulses as were not. The linked PGF(2alpha) pulses were longer in duration (p = 0.01) with a tendency toward a higher amplitude (p = 0.08). The corresponding vena caval oxytocin pulses had a longer duration (p = 0.02) than those not linked to PGF(2alpha). Estradiol increased oxytocin receptor concentrations and the turnover of phosphatidylinositides (p = 0.02) without affecting PGF(2alpha) pulse characteristics. Onapristone increased (p = 0.03) PGF(2alpha) pulse amplitude. Although a lower than expected temporal correlation between oxytocin and PGF(2alpha) pulses was observed, the distinguishing characteristics of linked pulses may be indicative of their physiological significance.

Animals↗
PubMed1996

Preclinical pharmacology of ecteinascidin 729, a marine natural product with potent antitumor activity.

Ecteinascidins are marine natural products with potent antiproliferative activity under evaluation as chemotherapeutic agents by the National Cancer Institute. Ecteinascidins bind the minor groove of DNA and may form covalent adducts with DNA by binding the N-2 of guanine in a fashion similar to saframycin antibiotics. The most potent ecteinascidin is ET-729 with antitumor activity observed following administration of 3.8 and 10 micrograms/kg to mice bearing P388 leukemia and B16 melanoma, respectively. A reverse-phase high-performance liquid chromatography (HPLC) assay and an L1210 cell bioassay were developed for ET-729 and utilized for stability and murine pharmacokinetic studies. HPLC analysis showed that ET-729 was stable in organic solvents, mobile phase and acidic buffer (t1/2 > 100 h). Stability was diminished under neutral and basic conditions (t1/2 < 14 h). Following a 48-h incubation with L1210 cells in growth medium in the absence and presence of 2.5% murine plasma, the 50% growth inhibitory concentrations (IC50) of ET-729 were 37 and 72 pM, respectively. Following intravenous administration of ET-729 to male CD2F1 mice, the disappearance of antiproliferative activity determined by the bioassay was described by a two-compartment open model. The mean values of the elimination half-life and plasma clearance were 28 min and 39.7 ml/min per kg, respectively. Following intraperitoneal administration, peak plasma concentrations of antiproliferative activity were observed 6-15 min after injection and antiproliferative concentrations remained above 1 nM for longer than 1 h. Intraperitoneal bioavailability varied over a wide range (20-91%). Antiproliferative activity was detected in every urine sample following intravenous and intraperitoneal administration, but the total 48-h urinary recovery was less than 0.1%.

Animals↗
PubMed1995

Transactivation of LAP/NF-IL6 is mediated by an acidic domain in the N-terminal part of the protein.

LAP/NF-IL6 is a member of the C/EBP family of transcriptional activators and has been shown to be involved in the regulation of the acute-phase response. We have previously shown that phosphorylation of the liver-enriched transcriptional activator protein (LAP) Ser-105 enhances the activation of LAP-dependent genes. To identify the region which is important for gene activation, a series of LAP mutants were constructed, and domain swapping experiments with the DNA-binding domain of GAL4 were performed. These experiments point to an acidic region located between amino acids 21 and 105 of LAP/NF-IL6 which activates genes independent of the DNA-binding domain and the leucine zipper of LAP/NF-IL6. Computer-assisted predictions reveal two regions, a helical and a hydrophobic region in the transactivation domain, which could be important in mediating the direct interaction with the basal machinery. Site-directed mutagenesis of acidic residues in both regions demonstrates that the hydrophobic region located between amino acids 85 and 95 is the likely motif for the interaction with the basal machinery. Our results demonstrate that a hydrophobic region in the acidic transactivation domain of LAP/NF-IL6 seems to be relevant in mediating gene activation of LAP-dependent genes.

Base Sequence↗
PubMed1995

Development and experience of a university-based, freestanding birthing center.

OBJECTIVE: To describe our experience with a freestanding birthing center established in conjunction with a university medical center, and to determine the safety and effectiveness of such a program. METHODS: The University of California Irvine Medical Center opened a freestanding birthing center 2 miles from the hospital. The unit provides prenatal, labor, delivery, postpartum and well-baby care 24 hours/day. All direct patient care is provided by certified nurse-midwives. Data were collected prospectively to provide a descriptive account and to evaluate maternal and perinatal morbidity and mortality to determine the safety and efficacy of this approach. RESULTS: During the first 20 months of operation, the University of California Irvine Birthing Center cared for 1830 patients. Approximately 90% were indigent, 85% were Hispanic, and 35% were nulliparas. Of the total patients, 12% were transferred antenatally for high-risk conditions and 19% were transferred intrapartum. The cesarean rate for all patients was 10% (6.5% for those whose intrapartum care began at the birthing center). The perinatal mortality rate was six per 1000. Neonatal morbidity rates, neonatal intensive care unit admissions, and maternal complications were not greater than expected. CONCLUSION: The first 20 months of experience with a university-based, freestanding birthing center suggests that this alternative is safe for delivering obstetric and newborn care to low-risk patients.

Adolescent↗
PubMed1994

Intra-amygdala kinase inhibitors disrupt retention of a learned avoidance response in rats.

To assess the involvement of intra-amygdala kinase activity in aversively motivated learning, rats received intracranial injections of polymixin B sulfate (PMXB)--a protein kinase C (PKC) and calcium/calmodulin-dependent kinase II inhibitor--immediately after inhibitory avoidance training. When tested 48 h later, retention was significantly impaired relative to vehicle-injected controls. Delayed injections (2 h posttraining) and injections made dorsal to the amygdala were ineffective. Immediate posttraining injections of the more selective PKC inhibitor, NPC 15437, also impaired retention. These results suggest that intra-amygdala protein phosphorylation must occur soon after training for learned avoidance responses to be successfully retained.

Amygdala↗
PubMed1994

Preclinical pharmacology of bizelesin, a potent bifunctional analog of the DNA-binding antibiotic CC-1065.

Bizelesin (NSC-615291), a potent, bifunctional analog of the cyclopropylpyrroloindole antitumor antibiotics CC-1065 and adozelesin, has been selected by the National Cancer Institute for evaluation as a potential chemotherapeutic agent. All three compounds bind to and alkylate DNA at the N-3 position of adenine in a sequence-selective manner. Bizelesin is unique among the analogs with bifunctional alkylating capability due to two chloromethyl moieties that are converted to the cyclopropyl alkylating species that interact with DNA. A reverse-phase high-performance liquid chromatography (HPLC) assay and an L1210 cell bioassay were developed for bizelesin and subsequently applied to stability and murine pharmacokinetics studies. Following 48 h of incubation with L1210 cells the 50% growth-inhibitory concentrations (IC50) of bizelesin, adozelesin, and CC-1065 were 2.3, 3.4, and 88.1 pM, respectively. Bizelesin was stable in organic solvents but was less stable in aqueous solutions, with the half-life values obtained in buffers at pH 4, 7, and 10 being 9.6, 2.1, and < 1 h, respectively. By HPLC analysis, bizelesin degradation was associated with the appearance of two peaks, the mono- and dicyclopropyl derivatives formed by base-catalyzed intramolecular alkylation of the chloromethyl groups. Bizelesin and the dicyclopropyl derivative were equipotent in the L1210 cell bioassay. Following i.v. administration of bizelesin (15 micrograms/kg) to male CD2F1 mice, the plasma elimination of cytotoxic activity determined with the bioassay was described by a two compartment open model; the alpha-phase (t1/2 alpha) and beta-phase (t1/2 beta) half-lives, steady-state volume of distribution (VSS), and total body clearance (ClTB) were 3.5 min, 7.3 h, 7,641 ml/kg, and 16.3 ml min-1 kg-1, respectively. The systemic drug exposure following i.p. administration was at least 10 times lower than that resulting from i.v. infusion. Following i.v. or i.p. administration the recovery of material in urine was < 0.1% of the delivered dose.

Alkylating Agents↗
PubMed1994

Intrahippocampal administration of both the D- and the L-isomers of AP5 disrupt spontaneous alternation behavior and evoked potentials.

We previously reported that systemically administered N-methyl-D-aspartate (NMDA) antagonists significantly impair spontaneous alternation behavior. Others have reported that the restricted blockade of hippocampal NMDA receptors disrupts performance on different tests of spatial learning and have suggested that the resulting impairments are attributable to a disruption of endogenous NMDA-dependent long-term potentiation (LTP). In the present study, we determined whether spontaneous alternation performance was disrupted by circumscribed blockade of hippocampal NMDA receptors as well as by a second class of compounds which disrupt LTP, protein kinase inhibitors. The effect of hippocampal NMDA blockade on inhibitory avoidance was also examined insofar as this behavior too is disrupted by systemically administered NMDA antagonists. When injected into the hippocampus 15 min prior to spontaneous alternation testing, the NMDA antagonists CPP and D,L-AP5 each decreased alternation rates. The specific protein kinase C (PKC) inhibitor, NPC 15437, also disrupted spontaneous alternation, whereas the more general kinase inhibitor, PMXB, did not. When injected 15 min prior to inhibitory avoidance training, CPP also impaired inhibitory avoidance learning as assessed during a subsequent test session, 48 h later. Interpretation of these data was complicated by the additional findings that intrahippocampal infusion of L-AP5 (which is inactive with respect to NMDA receptors) also disrupted alternation performance, and that both the D- and the L-isomers of AP5 as well as each kinase inhibitor dramatically disrupted evoked responses (i.e., population spike amplitude, spike latency, and EPSP slope), as recorded in the dentate gyrus and evoked by perforant path stimulation. These data indicate that behaviorally effective doses of AP5 may have effects which extend beyond NMDA blockade. Moreover, the effects of these compounds on hippocampal transmission, in general, suggest that attribution of the amnestic consequences of their administration to impaired LTP may be unwarranted.

2-Amino-5-phosphonovalerate↗
PubMed1993

Maturational asynchrony between oocyte cumulus-coronal morphology and nuclear maturity in gonadotropin-releasing hormone agonist stimulations.

OBJECTIVE: To determine oocyte meiotic maturity and asynchrony between cumulus-coronal morphology and nuclear maturity after gonadotropin-releasing hormone agonist (GnRH-a) and norethindrone-programmed stimulations. DESIGN: Oocyte meiotic maturity was evaluated at follicular aspiration in 4,961 oocytes after GnRH-a/follicle-stimulating hormone (FSH)/human menopausal gonadotropin stimulations (hMG) for in vitro fertilization patients and 299 oocytes after norethindrone-programmed clomiphene citrate (CC)/hMG in oocyte donors. Maturational asynchrony between the oocyte's cumulus-coronal morphology and nuclear maturity was evaluated in 2,336 oocytes. SETTING: In vitro fertilization program at the University of Iowa Hospitals and Clinics; academic tertiary care center. INTERVENTIONS: After evaluating oocyte cumulus-coronal maturity, cumulus masses were spread to determine oocyte nuclear maturity. RESULTS: Fourteen percent, 17%, 50%, 17%, and 2% of oocytes were prophase I, metaphase I, metaphase II, postmature metaphase II, and atretic, respectively. Asynchrony was noted in 28% of prophase I, 71% of metaphase I, 11% of metaphase II, 45% of postmature metaphase II, 32% of atretic, and 28% of all oocytes. Significant differences were not found between GnRH-a and norethindrone-programmed stimulations in asynchrony between cumulus-coronal morphology and nuclear maturity or percentage of prophase I, metaphase I, metaphase II, postmature metaphase II, or atretic oocytes. Sixty-seven percent of oocytes possessed a polar body at retrieval. The rate of fertilization was significantly higher for metaphase II oocytes than postmature metaphase II and metaphase I oocytes > prophase I oocytes. Parthenogenetic activation tended to be highest for postmature metaphase II oocytes. Embryo cleavage was significantly higher for postmature metaphase II, metaphase II, and metaphase I oocytes than for prophase I oocytes. CONCLUSIONS: This is the first report of asynchrony between cumulus-coronal morphology and nuclear maturity at follicular aspiration in GnRH-a and norethindrone-programmed stimulations. Asynchrony was observed in 28% of oocytes. A higher percentage of oocytes possessed a polar body at egg retrieval with these stimulation regimens compared with rates reported previously for FSH, FSH/hMG, and CC/hMG stimulations.

Cell Cycle↗
PubMed1993

Conditions of oocyte storage and use of noninseminated as compared with inseminated, nonfertilized oocytes for the hemizona assay.

OBJECTIVES: To examine differences in sperm binding to the zona and recovery of oocytes from the storage vessel after oocyte preservation for the hemizona assay (HZA) by the method currently in predominant use, salt storage at 4 degrees C, as compared with a new method that should allow for indefinite preservation of zona receptors, dimethylsulphoxide (DMSO)/sucrose in liquid nitrogen (-196 degrees C). A second objective was to compare sperm binding to noninseminated zona as opposed to zona from inseminated, nonfertilized oocytes and to examine whether differences in binding potential were related to the patient's fertilization rate from the cycle in which the oocytes for the HZA originated. DESIGN: Binding and recovery were evaluated after 1, 2, 3, 6, 9, 12, and 17 to 25 months of storage. SETTING: In vitro fertilization and andrology laboratories at the University of Iowa Hospitals and Clinics; academic tertiary care center. RESULTS: Binding of sperm was significantly lower for nonfertilized oocytes stored > 12 months in salt at 4 degrees C than for those stored in liquid nitrogen. Binding was similar after storage for 1, 2, 3, 6, 9, and 12 months. Oocyte recovery was significantly lower after storage in salt for > 12 months as compared with storage in liquid nitrogen. Greater variability in sperm binding was observed between matching zona halves of nonfertilized as compared with noninseminated oocytes. Nonfertilized oocytes also bound fewer total sperm than noninseminated oocytes. The number of sperm bound to noninseminated oocytes was not related to the patient's fertilization rate from the cycle in which the oocytes originated. However, significantly fewer sperm bound to the zona of nonfertilized oocytes when the oocyte originated from a cycle in which the patient's fertilization rate was > 50%. CONCLUSIONS: These results indicate that storage of oocytes in DMSO/sucrose in liquid nitrogen results in superior long-term (> 12 months) preservation of zona receptors for sperm binding and improves oocyte recovery as compared with salt storage at 4 degrees C. Although noninseminated oocytes appear to be optimal for use in the HZA, nonfertilized oocytes can be used successfully if the oocytes originate from an IVF cycle in which the fertilization rate is < or = 50%.

Adult↗
PubMed1992

Prediction of nuclear maturity from cumulus-coronal morphology: influence of embryologist experience.

PURPOSE: A majority of in vitro fertilization (IVF) programs continues to evaluate oocyte maturity on the basis of cumulus-coronal morphology (CCM) even though marked asynchrony has been reported between CCM and nuclear maturity. This study was designed to examine changes in embryologists' ability to correctly predict nuclear maturity from CCM as a function of increasing experience. Nuclear maturity was assessed by inverted microscopy with a modified spreading technique at follicular aspiration. A second objective was to determine the percentage of oocytes which displayed asynchrony between CCM and nuclear maturity as assessed by embryologists with extensive experience in oocyte maturity evaluation. RESULTS: The three participating embryologists had directly evaluated 1304, 75, and 0 oocytes for nuclear maturity and CCM at study initiation and correctly predicted nuclear maturity from CCM in 74, 64, and 47% of oocytes, respectively. Embryologist 1 did not significantly change in predictive ability during the 17-month study period. Embryologist 2 significantly improved in predictive ability during the first 9 months of the study (841 oocytes evaluated) and plateaued thereafter, at a similar percentage of correct predictions as embryologist 1. Embryologist 3 continued to improve in predictive ability throughout the study period, reaching 61% correct predictions at the close of the study after evaluating 223 oocytes. Once embryologists had plateaued in their predictive ability, 72% of oocytes evaluated received the correct nuclear maturity classification based on CCM. Significantly fewer oocytes (54%; 375/690) evaluated by embryologists who had not plateaued in their predictive ability received the correct nuclear maturity classification based on CCM. CONCLUSIONS: These results indicate that embryologists' ability to predict oocyte nuclear maturity correctly from CCM continues to change over several months even when pretraining video recordings are used before beginning direct evaluations. After embryologists plateaued in their predictive ability, nuclear maturity still could not be correctly predicted from CCM in 28% of oocytes due to asynchrony between nuclear and CCM maturity. Based upon this, circumstances in which the spreading technique should be used for direct assessment of nuclear maturity as opposed to assessment of CCM only are discussed.

Cell Differentiation↗