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Parra, C M; Cascante, S D; Blakemore, J K; DeVore, S; McCulloh, D H; Grifo, J A
Objective: Planned OC is increasing; yet, there is a lack of thaw data to provide an accurate estimate of CLBR.1 We reviewed our AO thaws to determine CLBR by age and #AOs.
Material(s) and Method(s): We reviewed AO thaws at our academic center from 2004-2021. Inclusion criteria: 1) >=1 live birth (LB)/ongoing pregnancy (OP) >12 weeks, or 2) all AOs + embryos from OC consumed. Exclusion criteria: 1) OC for a medical reason, as research, due to lack of sperm or a natural disaster, combined with embryos or for gestational carrier use, or 2) AOs/embryos from OC transported out before a LB. Primary outcome was CLBR (LB + OP). Patients (pts) were stratified by age and #AOs or metaphase II oocytes (M2s) thawed. If pts had >=1 OC cycle, we calculated a weighted age: [SIGMA (#AOs thawed x age at OC)] / [#AOs thawed]. Statistics included multiple logistic regression (MLR), Fischer's exact test, and chi-squared test (p<0.05 significant).
Result(s): 548 pts (median age at OC 38y, range 28-45y; 151 weighted ages used) underwent 767 OC (location: 90% our center, 9% elsewhere, 2% both; method: 77% vitrification, 4% slow cooling, 19% both), 604 thaw and 465 transfer cycles. 40% (n=218) of pts had >=1 LB/OP, resulting in 221 babies + 30 OPs. See table for CLBRs. In pts of all ages and <38y, CLBR increased as #AO/M2s thawed increased from 0-10 to 11-20 to >20 (p<0.03). In pts 38-39y, CLBR was lower if 0-10 vs. 11-20 or >20 AOs were thawed (p<0.01), but was similar if 11-20 vs. >20 AOs (p=0.34) or M2s (p=0.13) were thawed. In pts >=40y, CLBR did not differ based on #AOs (p=0.81) or M2s thawed (p=0.17). For pts with any # or >20 AO/M2s thawed, CLBR was higher in pts <38y and 38-39y vs. pts >=40y (p<0.04). In a MLR model adjusting for effect of age on #AOs, age and age-independent #AOs were predictive of LB.
Conclusion(s): CLBR increases as more AO/M2s are thawed. OC at <38y has a CLBR of ~50%, a reasonable rate in younger pts at an ideal age for OC. Impact Statement: Pts who freeze >20 AOs at <38y can expect >=70% CLBR based on actual outcomes. This is the largest report to date of AO thaw outcomes from a single U.S. center. [Formula presented] REFERENCES:: 1 Practice Committee of the American Society for Reproductive Medicine. Evidence-based outcomes after oocyte cryopreservation for donor oocyte in vitro fertilization and planned oocyte cryopreservation: a guideline. Fertil Steril. 2021 Jul;116(1):36-47.
ISSN: 1556-5653
CID: 5366982


Shaw, J; Grifo, J A; Blakemore, J K
Objective: E2P is a technique for IVF protocols in poor responders to reduce cycle cancelation due to elevated FSH as well as increase stimulation response. Yet data is inconsistent on the impact on clinical pregnancy rates.1 We sought to evaluate if E2P increases euploidy rates in IVF with PGTA.
Material(s) and Method(s): This is a retrospective cohort study of IVF cycles with PGTA from 3/2020-12/2021 at a single academic fertility center. E2P cycles were compared to age and AMH matched controls (CON) (1:2 ratio). The primary outcome was number of euploid embryos. Secondary outcomes were cycle start follicle stimulation hormone level (FSH), total gonadotrophin (GND) dose, number oocytes, mature oocytes (MII), fertilization rate (2PN), and number of embryos biopsied (BX). Mann Whitney and Chi-square tests were performed (p<0.05 significant). Data is reported in median (range) and percentages.
Result(s): 337 E2P cycles were compared to 674 CON. There were fewer microdose lupron (MCD) cycles in E2P patients (E2P: 88% antagonist (ANT), 12% MCD vs CON: 76% ANT, 24% MCD, p<0.01). Similar cancelation rates [E2P: 14% (47/337) vs CON: 12% (82/674), p=0.42] and poor blast formation (defined as nothing for biopsy) [E2P: 18% (60/337) vs CON: 15% (103/674), p=0.24] were seen between groups. Number of euploid embryos were similar across all SART age groups except for 38-40 years (y), with fewer euploids in E2P (Table). Cycle start FSH was lower and total GND dose was higher for E2P (p<0.05). Other cycle outcomes were not different.
Conclusion(s): E2P is a viable tool for PGTA freeze all cycles, but does not improve euploidy rate; larger studies are necessary to determine if E2P produces fewer euploids in >38y. Impact Statement: E2P cycles require higher GND dose without increased yield in euploid embryos. [Formula presented] Support: None REFERENCES: 1. Orvieto R. Pretreatment: Does it improve quantity or quality? Fertil Steril. 2022 Apr;117(4):657-663. Epub 2022 Mar 5. PMID:.
ISSN: 1556-5653
CID: 5367262


Buldo-Licciardi, J; Wiltshire, A M; Tozour, J N; Hamer, D; McCulloh, D H; Grifo, J A; Blakemore, J K
Objective: The use of GnRH-a trigger in antagonist controlled ovarian hyperstimulation (COH) cycles has increased due to its enhanced safety profile. However, response, as measured by the serum LH level post trigger, vary considerably1-6. We investigated the impact of serum LH response to GnRH-a trigger in antagonist COH cycles on oocyte yield, oocyte maturity, blastocyst formation, PGT-A and pregnancy outcomes.
Material(s) and Method(s): This is a retrospective cohort study in a single university-based fertility center of all GnRH-antagonist COH cycles utilizing GnRH-a alone or in combination with 1000u of human chorionic gonadotropin (hCG) for trigger from 2017 to 2020. An optimal response to GnRH-a trigger was defined as LH >= 40 mIU/mL and suboptimal response was defined as LH < 40 mIU/mL on the morning after trigger. Subanalyses with responses of LH >= 15 mIU/mL and LH < 15 mIU/mL were also performed. Primary outcomes included oocyte yield, oocyte maturity rate, blastocyst formation rate, euploidy rate, aneuploidy rate and simple mosaic rate. Secondary outcomes included biochemical pregnancy rate (BPR), spontaneous abortion rate (SABR) and ongoing/pregnancy live birth rate (OP/LBR). Primary and secondary outcomes were also stratified by age, race and BMI. Descriptive statistics (median +/- range for continuous variables), Mann Whitey U and Fisher's Exact tests were performed accordingly with p<0.05 defined as significant.
Result(s): This study included 3,833 retrieval cycles with 1,435 single thawed euploid embryo transfers (STEET) among 2,618 patients. Ten percent (351/3446) of retrieval cycles had suboptimal and 90% (3446/3833) had optimal response to GnRH-a trigger. There was no difference in median oocyte yield (16 vs 17 oocytes per cycle, p=0.92), or oocyte maturity (77% vs 76%, p=0.43), fertilization (76% vs 77%, p=0.48) and blastocyst formation (51% vs 52%, p=0.88) rates by response. There were no significant differences in the rate of euploidy (35% vs 39%, p=0.55), aneuploidy (51% vs 47%, p=0.56) and simple mosaic (11% vs 11%, p=1) between groups. Seven percent (102/1435) of STEETs utilized embryos from a cycle with suboptimal response and 93% (1333/1435) from optimal response to GnRH trigger. There were no significant differences in BPR [19/44 (14%) vs 164/1907 (9%), p=0.2], SABR [11/144 (8%) vs 152/1907 (8%), p=1] and OP/LBR [85/144 (59%) vs 1127/1907 (59%), p=1]. No differences in pregnancy outcomes were found in the subanalyses of LH >= and < 15 mIU/mL and when data were stratified by SART age ranges, race and BMI.
Conclusion(s): A suboptimal response to GnRH-a trigger (LH < 40) is not associated with lower oocyte yield, oocyte maturity rate, blastocyst rate, euploidy rate or worse pregnancy outcomes compared to an optimal response (LH >= 40). Additional studies with larger cohorts are needed to further investigate these findings and with different thresholds of response. Impact Statement: A suboptimal LH response to GnRH-a trigger may not predict poor cycle outcomes. Providers should not hesitate to use GnRH-a trigger, especially in patients with identifiable risk factors for ovarian hyperstimulation syndrome (OHSS)7. Support: None.
ISSN: 1556-5653
CID: 5367272

Disaster preparedness in assisted reproductive technology

Goldman, Kara N; McCaffrey, Caroline; Riley, Joan; Jungheim, Emily; Grifo, Jamie A
The American Society for Reproductive Medicine compels centers providing reproductive medicine care to develop and implement an emergency preparedness plan in the event of a disaster. Reproductive care is vulnerable to disruptions in energy, transportation, and supply chains as well as may have potential destructive impacts on infrastructure. With the relentless progression of events related to climate change, centers can expect a growing number of such disruptive events and must prepare to deal with them. This article provides a case study of the impact of Hurricane Sandy on one center in New York City and proposes recommendations for future preparedness and mitigation.
PMID: 35878943
ISSN: 1556-5653
CID: 5276282

Fifteen years of autologous oocyte thaw outcomes from a large university-based fertility center

Cascante, Sarah Druckenmiller; Blakemore, Jennifer K; DeVore, Shannon; Hodes-Wertz, Brooke; Fino, M Elizabeth; Berkeley, Alan S; Parra, Carlos M; McCaffrey, Caroline; Grifo, James A
OBJECTIVE:To review the outcomes of patients who underwent autologous oocyte thaw after planned oocyte cryopreservation. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Large urban university-affiliated fertility center. PATIENT(S)/METHODS:All patients who underwent ≥1 autologous oocyte thaw before December 31, 2020. INTERVENTION(S)/METHODS:None. MAIN OUTCOME MEASURE(S)/METHODS:The primary outcome was the final live birth rate (FLBR) per patient, and only patients who had a live birth (LB) or consumed all remaining inventory (cryopreserved oocytes and resultant euploid/untested/no result embryos) were included. The secondary outcomes were laboratory outcomes and LB rates per transfer. RESULT(S)/RESULTS:A total of 543 patients underwent 800 oocyte cryopreservations, 605 thaws, and 436 transfers. The median age at the first cryopreservation was 38.3 years. The median time between the first cryopreservation and thaw was 4.2 years. The median numbers of oocytes and metaphase II oocytes (M2s) thawed per patient were 14 and 12, respectively. Overall survival of all thawed oocytes was 79%. Of all patients, 61% underwent ≥1 transfer. Among euploid (n = 262) and nonbiopsied (n = 158) transfers, the LB rates per transfer were 55% and 31%, respectively. The FLBR per patient was 39%. Age at cryopreservation and the number of M2s thawed were predictive of LB; the FLBR per patient was >50% for patients aged <38 years at cryopreservation or who thawed ≥20 M2s. A total of 173 patients (32%) have remaining inventory. CONCLUSION(S)/CONCLUSIONS:Autologous oocyte thaw resulted in a 39% FLBR per patient, which is comparable with age-matched in vitro fertilization outcomes. Studies with larger cohorts are necessary.
PMID: 35597614
ISSN: 1556-5653
CID: 5247762

Investigation of Global Gene Expression of Human Blastocysts Diagnosed as Mosaic using Next-generation Sequencing

Maxwell, Susan M; Lhakhang, Tenzin C; Lin, Ziyan; Kramer, Yael G; Zhang, Yutong; Wang, Fang; Heguy, Adriana; Tsirigos, Aristotelis; Grifo, James A; Licciardi, Frederick
Embryos are diagnosed as mosaic if their chromosomal copy number falls between euploid and aneuploid. The purpose of this study was to investigate the impact of mosaicism on global gene expression. This study included 42 blastocysts that underwent preimplantation genetic testing for aneuploidy (PGT-A) and were donated for IRB approved research. Fourteen blastocysts were diagnosed as mosaic with Next-generation Sequencing (NGS). Three NGS diagnosed euploid embryos, and 25 aneuploid embryos (9 NGS, 14 array Comparative Genomic Hybridization, 2 Single Nucleotide Polymorphism array) were used as comparisons. RNA-sequencing was performed on all of the blastocysts. Differentially expressed genes (DEGs) were calculated using DESeq2/3.5 (R Bioconductor Package) with p < 0.05 considered significantly differentially expressed. Pathway analysis was performed on mosaic embryos using EnrichR with p < 0.05 considered significant. With euploid embryo gene expression used as a control, 12 of 14 mosaic embryos had fewer DEGs compared to aneuploid embryos involving the same chromosome. On principal component analysis (PCA), mosaic embryos mapped separately from aneuploid embryos. Pathways involving cell proliferation, differentiation, and apoptosis were the most disrupted within mosaic embryos. Mosaic embryos have decreased disruption of global gene expression compared to aneuploid embryos. This study was limited by the small sample size, lack of replicate samples for each mosaic abnormality, and use of multiple different PGT-A platforms for the diagnosis of aneuploid embryos.
PMID: 35304731
ISSN: 1933-7205
CID: 5204212

ART outcomes during the COVID-19 pandemic

Chamani, Isaac J.; Grifo, James; Chung, Monica S.; McKenzie, Laurie J.; McCulloh, David H.; Gibbons, William E.; Licciarid, Frederick L.
Background: To evaluate whether the ongoing coronavirus disease 2019 (COVID-19) pandemic has had an impact on assisted reproductive technology (ART) outcomes and assess the possible role of geographic differences in the pandemic's trajectory on these outcomes. Methods: Multi-center retrospective cohort study involving patients who underwent oocyte cryopreservation, in vitro fertilization (IVF), embryo cryopreservation, or frozen euploid embryo transfer in 2019 and 2020 at two academic fertility centers located in regionally distinct areas of the US with high coronavirus infection rates. Patients were screened for infectious symptoms, exposure to sick contacts, and fevers, and tested with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction testing within 5 days of oocyte retrieval. The primary outcomes were the number of oocytes retrieved, embryos fertilized, blastocyst or euploid embryos produced in oocyte retrieval and IVF cycles, and rates of embryo implantation, biochemical pregnancy or no pregnancy following frozen embryo transfer (FET). Results: We found no consistent significant differences in the number of oocytes retrieved, embryos fertilized, blastocysts or euploid embryos produced at either institution over the study period. Furthermore, we did not detect any differences in FET outcomes, including rates of embryo implantation, biochemical pregnancy, or no pregnancy, at either institution during the study time period. Conclusions: There were no significant differences in ART outcomes in patients who received fertility treatment during the pandemic at our centers. Patients and providers can be reassured that with proper testing, sanitizing, and distancing measures, treatments can continue safely during the pandemic without compromising outcomes.
ISSN: 0390-6663
CID: 5313102

Pseudo contrastive labeling for predicting IVF embryo developmental potential

Erlich, I; Ben-Meir, A; Har-Vardi, I; Grifo, J; Wang, F; Mccaffrey, C; McCulloh, D; Or, Y; Wolf, L
In vitro fertilization is typically associated with high failure rates per transfer, leading to an acute need for the identification of embryos with high developmental potential. Current methods are tailored to specific times after fertilization, often require expert inspection, and have low predictive power. Automatic methods are challenged by ambiguous labels, clinical heterogeneity, and the inability to utilize multiple developmental points. In this work, we propose a novel method that trains a classifier conditioned on the time since fertilization. This classifier is then integrated over time and its output is used to assign soft labels to pairs of samples. The classifier obtained by training on these soft labels presents a significant improvement in accuracy, even as early as 30 h post-fertilization. By integrating the classification scores, the predictive power is further improved. Our results are superior to previously reported methods, including the commercial KIDScore-D3 system, and a group of eight senior professionals, in classifying multiple groups of favorable embryos into groups defined as less favorable based on implantation outcomes, expert decisions based on developmental trajectories, and/or genetic tests.
PMID: 35169194
ISSN: 2045-2322
CID: 5163462

Evaluation of clinical parameters as predictors of monozygotic twins after single frozen embryo transfer

Kelly, Amelia G; Blakemore, Jennifer K; McCaffrey, Caroline; Grifo, James A
Objective/UNASSIGNED:To determine if recent evolutions in laboratory protocols, including the increased use of natural cycles and the use of a hyaluronan-containing transfer medium, affected the rate of monozygotic twin (MZT) pregnancies after single frozen embryo transfer (FET). Design/UNASSIGNED:Retrospective cohort study. Setting/UNASSIGNED:Urban university-based fertility center. Patients/UNASSIGNED:Patients who underwent single FET between January 2016 and December 2018 resulting in an intrauterine pregnancy. Interventions/UNASSIGNED:Transition to a transfer protocol with a hyaluronan-containing transfer medium in July 2017. Main Outcome Measures/UNASSIGNED:Number of MZT pregnancies. Results/UNASSIGNED:There were 1,619 cycles that met the inclusion criteria and 31 (1.9%) resulted in MZT pregnancies. A hyaluronan-containing transfer medium was used in 875 (54.1%) cycles. Programmed cycles were used for 1,385 (85.5%) FETs and 234 (14.5%) cycles were natural. The mean age at FET, oocyte age, endometrial echo thickness, inner cell mass grade, trophectoderm grade, expansion, and day of blastocyst vitrification were similar between the groups. The use of a hyaluronan-containing transfer medium resulted in fewer MZTs. After controlling potential confounders with a multivariate regression, the use of the hyaluronan-containing medium still resulted in fewer MZTs. Monozygotic twins were colinear with preimplantation genetic testing (PGT), so PGT was excluded as a variable in our regression. A regression of PGT only cycles showed that the use of the hyaluronan-containing medium was still associated with a reduction in MZT pregnancies. Conclusions/UNASSIGNED:The use of a hyaluronan-containing transfer medium was associated with a lower rate of MZTs. Other clinical parameters, including cycle type, were not associated with changes in the number of MZTs. The use of PGT needs to be further investigated as a risk factor for MZTs.
PMID: 34934983
ISSN: 2666-3341
CID: 5108852

Making it (net)work: a social network analysis of "fertility" in Twitter before and during the COVID-19 pandemic

Smith, Meghan B; Blakemore, Jennifer K; Ho, Jacqueline R; Grifo, James A
Objective/UNASSIGNED:To characterize activity, text sentiment, and online community characteristics regarding "fertility" on Twitter before and during the COVID-19 pandemic using social network analysis. Design/UNASSIGNED:Cross-sectional analysis. Setting/UNASSIGNED:Publicly available Twitter data. Patients/UNASSIGNED:Not applicable. Interventions/UNASSIGNED:Not applicable. Main Outcome Measures/UNASSIGNED:Number of users (vertices); edges (connections, defined as unique and total); self-loops (tweet without connection to another user); connected components (groups of users communicating back and forth frequently); maximum vertices in a connected component (largest group size); maximum and average geodesic distance (number of tweets to connect two users in the network); graph density; positive and negative sentiment tweets; and top 5 hashtags and top 5 word pairs. Results/UNASSIGNED:There were 1426 unique users and 401 groups in the pre-COVID-19 data compared to 1492 unique users and 453 groups in the during COVID-19 data. There was no difference in the number of total connections (96.8% [1381/1426] vs. 96.0% [1433/1492]) or self-loops (20.0% [286/1426] vs. 22.1% [329/1492]) before and during the COVID-19 pandemic. The percentage of unique connections per user decreased during COVID-19 (91.6% [1381/1508] pre-COVID-19 vs. 83.3% [1433/1720] during COVID-19). The average and maximum distance between users in the community increased during COVID-19 (maximum: 5 pre-COVID-19, 8 during COVID-19; average 1.95 pre-COVID-19, 2.43 during COVID-19). The percentage of positive sentiments per total number of tweets increased during COVID-19 (58.1% pre-COVID-19 [773/1331] vs. 64.3% [1198/1863] during COVID-19). The top 5 hashtags changed during COVID-19 to include COVID-19. The top word pairs changed from "family, hereditary; parents, children" to "fertility, treatment; healthcare, decisions." Conclusions/UNASSIGNED:Despite the challenge to the fertility community amidst the COVID-19 pandemic, the overall Twitter sentiment regarding fertility was more positive during than before the pandemic. Top hashtags and word pairs changed to reflect the emergence of COVID-19 and the unique healthcare decision-making challenges faced. While the character, the number of users, and the total connections remained constant, the number of unique connections and the distance between users changed to reflect more self-broadcasting and less tight connections.
PMID: 34934990
ISSN: 2666-3341
CID: 5108862