Relationship Between Number of Oocytes Retrieved and Embryo Euploidy Rate in Controlled Ovarian Stimulation Cycles.

This cohort study is aimed to determine if higher number of oocytes retrieved affects the rate of euploidy in the embryos of women undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF) with preimplantation genetic testing for aneuploidy (PGT-A). A negative trend between the number of oocytes retrieved and embryo euploidy rate was observed using Visual Analytics software, especially when a higher number of oocytes were retrieved. After regression analysis, patient age was the only variable found to have a statistically significant negative effect (p < 0.0001) on euploidy rate in all regression models. Number of oocytes retrieved was not found to have a statistically significant effect on euploidy rate when analyzed per number of biopsied blastocysts (p = 0.5356), per number of oocytes retrieved (p = 0.1025), and per number of fertilized oocytes (p = 0.7241). The parameter estimates in the linear regression models were negative for number of oocytes retrieved. This study shows a statistically significant effect between patient age and embryo euploidy rate, which is already known. There is some evidence to suggest that higher number of oocytes retrieved may negatively impact the number of euploid embryos per number of oocytes retrieved based on the visual analytic graphs, p value approaching significance, and the negative parameter estimates in the regression models.

Cumulus cell acetyl-CoA metabolism from acetate is associated with maternal age but only partially with oocyte maturity.

Cumulus cell (CC) clumps that associate with oocytes provide the oocytes with growth and signaling factors. Thus, the metabolism of the CCs may influence oocyte function, and CC metabolism may be predictive of oocyte competence for in vitro fertilization. CCs are thought to be highly glycolytic, but data on the use of other potential carbon substrates are lacking in humans. This prospective and blinded cohort study was designed to examine the substrate utilization of CCs by age and oocyte competence. Individual sets of CC clumps from participants were removed after oocyte retrieval procedure then, incubated with stable isotope labeled substrates, and analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for isotopologue enrichment of major metabolic intermediates, including acetyl-CoA. The acyl-chain of acetyl-CoA contains 2 carbons that can be derived from 13C-labeled substrates resulting in an M + 2 isotopologue that contains 2 13C atoms. Comparing the fate of three major carbon sources, mean enrichment of M + 2 acetyl-CoA (mean, standard deviation) was for glucose (3.6, 7.7), for glutamine (9.4, 6.2), and for acetate (20.7, 13.9). Due to this unexpected high and variable labeling from acetate, we then examined acetyl-CoA mean % enrichment from acetate in 278 CCs from 21 women ≤34 (49.06, 12.73) decreased with age compared to 124 CCs from 10 women >34 (43.48, 16.20) (p = 0.0004, t-test). The CCs associated with the immature prophase I oocytes had significantly lower enrichment in M + 2 acetyl CoA compared to the CCs associated with the metaphase I and metaphase II oocytes (difference: -6.02, CI: -1.74,-13.79, p = 0.013). Acetate metabolism in individual CC clumps was positively correlated with oocyte maturity and decreased with maternal age. These findings indicate that CC metabolism of non-glucose substrates should be investigated relative to oocyte function and age-related fertility.Abbreviations: CCs: cumulus cells; COC: cumulus-oocyte complex; LC-MS: liquid chromatography-mass spectrometry; acetyl-CoA: acetyl-Coenzyme A; CoA: Coenzyme A.

Validation study of the Access antimüllerian hormone assay for the prediction of poor ovarian response to controlled ovarian stimulation.

OBJECTIVE: To evaluate the diagnostic performance of the antimüllerian hormone (AMH) level determined using the Access AMH assay for predicting poor ovarian response (POR) defined as ≤4 oocytes retrieved, including the validation of the predefined AMH cutoff of 0.93 ng/mL in both serum and plasma. DESIGN: Prospective cohort study. SETTING: Fifteen private and academic fertility centers (14 in the United States and 1 in Canada). PATIENT(S): Women aged 21-45 years planning controlled ovarian stimulation for in vitro fertilization. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, categorized as POR and normal-to-high ovarian response (non-POR). The correlation of AMH level and antral follicle count. RESULT(S): Data were available for 472 participants who completed the study (74 with POR and 398 non-POR). The mean AMH serum level among those with POR was 0.99 ng/mL (median 0.76 ng/mL) compared with 2.83 ng/mL (median 2.36 ng/mL) among the normal-to-high responders. For confirmation of the 0.93 ng/mL AMH level cutoff as a predictor of POR, a receiver operating characteristic analysis gave an area under the curve of 0.852, with corresponding sensitivity and specificity of 63.5% and 89.2%, respectively. The associated positive predictive value was 52.2% and the negative predictive value was 92.9%. The AMH plasma values demonstrated a strong correlation with AMH serum values with an r value = 0.9980. The previously established AMH cutoff of 1.77 ng/mL for antral follicle count >15 resulted in a sensitivity of 83.8% (95% confidence interval [CI] 77.7-88.5) and a specificity of 59.9% (95% CI 54.2-65.4). CONCLUSION(S): This study validated the previously established AMH cut-point for the prediction of POR. Because this cut-point may vary depending on the assay used, the specific AMH assay should be reported in the literature whenever possible.

Respirometric reserve capacity of cumulus cell mitochondria correlates with oocyte maturity.

PURPOSE: Oocyte competence is critical in success of assisted reproduction. Metabolic signaling between oocyte and cumulus cells within the cumulus-oocyte complex procure oocyte development. This study evaluated the relationship between respirometric activity of cumulus cells and maturity of corresponding oocytes. METHODS: In prospective cohort study, 20 women of age 28-42 undergoing IVF procedure were involved. To evaluate oocyte maturity, the cumulus cells from individual oocytes were assessed flow cytometrically by double labeling of cells with mitochondria specific dyes. The respirometric stress analysis using ATPase inhibitor oligomycin was applied to assess mitochondria metabolic abnormalities. RESULTS: The cumulus cells from each of 327 oocytes were analyzed. The respirometric index of cumulus cells (O'R) strongly correlates with maternal ovarian reserve, showing to be higher in patients with higher AMH (p < 0.0017). Cumulus cells from immature oocytes had severe mitochondria deficiency, i.e., low O'R, than those from mature oocytes (p < 0.02). No significant difference in respirometric capacity was found between cumulus cells associated with good vs poor-quality embryos. CONCLUSIONS: The oocyte maturity is potentially related to the mitochondria activity of cumulus cells.

Multicenter evaluation of the Access AMH antimüllerian hormone assay for the prediction of antral follicle count and poor ovarian response to controlled ovarian stimulation.

OBJECTIVE: To evaluate a new fully automated antimüllerian hormone (AMH) assay for prediction of poor ovarian response (POR) to ovarian stimulation defined as four or fewer oocytes retrieved. DESIGN: Prospective cohort study. SETTING: Thirteen private and academic fertility centers in the United States. PATIENTS(S): A total of 178 women undergoing their first in vitro fertilization (IVF) cycle eligible for the study were consented and enrolled, with data available from 160 women for prediction of POR and 164 women for AMH correlation with antral follicle count (AFC). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cutoff point for AMH that predicts POR. Correlation of AMH with AFC, and cutoff point for AMH that correlates with antral follicle count >15. RESULT(S): The mean AMH among the poor responders was 0.74 ng/mL, compared with 3.20 ng/mL for normal to high responders. The AMH cutoff at 90% specificity for predicting POR with the use of the receiver operating characteristic (ROC) curve was 0.93 ng/mL, with an associated sensitivity of 74.1%. For prediction of POR, ROC analysis showed that AMH (area under the ROC curve [AUC] = 0.929) was significantly better than FSH (AUC = 0.615; P<.0001). AMH was positively correlated with AFC (Spearman rho = 0.756). The AMH at 90% sensitivity for AFC >15 was 1.75, with specificity of 59.1%. CONCLUSION(S): A fully automated AMH assay can be a useful biomarker for predicting POR in IVF cycles. Because AMH cutoff points vary depending on the assay used, future studies should continue to calibrate test results to clinically important outcomes.

Hemivaginal septum resection in a patient with a rare variant of Herlyn-Werner-Wunderlich syndrome.

Herlyn-Werner-Wunderlich syndrome is characterized by a triad of uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. The syndrome should be suspected in any young woman with abdominal pain or cyclic dysmenorrhea, and radiologic evidence of müllerian duct and renal anomalies. Herein is presented the case of a 25-year-old woman with a rare variant of Herlyn-Werner-Wunderlich syndrome, characterized by an anomalous connection between the 2 endocervical canals, who underwent hemivaginal septum resection to relieve progressively worsening dysmenorrhea. The right hemivaginal septum was resected medially from the left cervix and laterally off the right vaginal wall. Hydrodissection between the hemivaginal septum and right cervix facilitated surgical resection. After resection of the hemivaginal septum there was complete resolution of dysmenorrhea and no recurrence of hematometra or hematocolpos.

The utility of embryo banking in order to increase the number of embryos available for preimplantation genetic screening in advanced maternal age patients.

PURPOSE: to determine if embryo banking with PGS is more optimal than proceeding with PGS regardless of embryo number. METHODS: patients were divided into 2 groups, group 1 were those that banked embryos and proceeded through another round of IVF prior to PGS, and group 2 underwent PGS regardless of embryo number. Group 2 was divided into group 2A (patients with >10 embryos) and group 2B (patients who had <10 embryos). RESULTS: there was no difference in embryos biopsied, normal embryos, number transferred, and pregnancy rate between group 1 and 2. A significant number of patients did not have a transfer in group 2B (6/11) compared to group 1 (3/19) (P = 0.0419). There was no significance between pregnancy rates per transfer between group 1 (6/16) and group 2B (2/5). CONCLUSION: our data suggests that banking will increase the odds of going to transfer but there was no increase in pregnancy rates.

The effects of different laser pulse lengths on the embryo biopsy procedure and embryo development to the blastocyst stage.

PURPOSE: a laser is commonly used to remove a blastomere from an embryo for genetic testing. The laser uses intense heat which could possibly disrupt embryo development. It is the goal of this study to test the effects of different laser pulse lengths (and consequently heat) on the embryo biopsy procedure and embryo development. METHODS: each embryo biopsy was performed randomly utilizing laser pulse lengths of 0.604mS (group I), 0.708mS (group II), and 1.010mS (group III). RESULTS: for groups I, II, and III, 83, 86, and 71 embryos were biopsied, respectively. There was no difference in day 5 embryo quality or lysed blastomeres between groups. Average number of blastomeres biopsied between group I (1.0 ± 0.0), II (1.0 ± 0.2), and III (1.1 ± 0.2) was significant (0.0001). CONCLUSION: our data demonstrates that laser pulse length does not influence the embryo biopsy procedure or embryo development.