Faculty Bibliography

Objective: Data regarding the chance of more than one LB from oocyte cryopreservation (OC) is lacking. We reviewed outcomes from patients (pts) with >=1 LB from thawed autologous oocytes (AOs) to examine: 1) how many have inventory (AOs or resultant euploid/untested/no result embryos), and 2) embryo transfer (ET) outcomes after 1^st LB.
Material(s) and Method(s): We reviewed all pts who thawed AOs at our center in 2006-2021 and had >=1 resultant LB. Pts were excluded if OC was performed for a medical reason, as research, due to lack of sperm or a natural disaster, with embryo banking or for gestational carrier use.
Result(s): 191 pts had >=1 LB (median # OC cycles 1, median age at 1^st OC 37 years (y), median # cryopreserved AOs 18, median # AOs thawed before 1^st LB 15). After LB, 61% of pts (n=117) had inventory and 39% (n=74) did not; see table. Among pts with inventory, 12% (n=14) discarded or donated, 3% (n=4) transported out and 10% (n=12) consumed all inventory as of 1/2022. 22% of pts with inventory (n=26) had >=1 ET after LB. Among these pts, 21 thawed embryos (median # thawed 1, range 1-2), 4 thawed AOs (median # thawed 11, range 5-40) and 1 thawed both AOs + embryos (15 AOs + 4 embryos). Median time from the ET that led to 1^st LB and next ET was 26 months (range 15-57) and median age at next ET was 44y (range 37-53). This ET resulted in: implantation rate of 63% (19/30), spontaneous abortion rate of 16% (3/19) and ongoing pregnancy (OP) + LB rate of 58% (15/26); 1 pregnancy was terminated for monozygotic twins. Among pts who had a LB from this ET, 66% (10/15) had remaining inventory and 33% (5/15) did not. Among pts who did not have a LB from this ET, 45% (5/11) had remaining inventory and 54% (6/11) did not; 5 of these unsuccessful pts returned for another ET and 2 had a LB. In total, 16 pts had 2 ETs result in OP/LB and 1 pt had 3 ETs result in LB. 10 more pts had >=2 children from a single ET (9 twins, 1 triplet); thus, we report 27 pts with >=2 children from OC. Among pts with >=2 children, median # OC cycles was 1 (range 1-8), median age at 1^st OC was 37y (range 34-41), median # cryopreserved AOs was 20 (range 5-102) and median # thawed AOs was 19 (range 5-58).
Conclusion(s): Most pts (61%) had inventory after their 1^st LB from OC, and most pts (65%) who returned for ET after LB achieved another OP/LB. Further research must explore pts' thoughts regarding OC inventory after LB and its associated storage fees. Impact Statement: OC can help pts achieve their ideal family size, even if >1 child. [Formula presented] Support: None.
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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.
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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.

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.

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.

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.

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.

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.

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.

Mosaic results obtained through preimplantation genetic testing for aneuploidy pose ongoing challenges to clinical practice. Thorough genetic counseling for patients considering mosaic embryo transfer is consistently recommended by many best-practice statements, and providers are charged with the task of assessing and explaining potential prenatal, neonatal, and long-term risks. However, an increasing amount of outcome data from transferred embryos with mosaic results do not show any evidence of increased risk to ongoing pregnancies or newborns. This article examines how to reconcile these data with the current practices for patient education about preimplantation genetic testing for aneuploidy and mosaic embryo risk assessment, through an evidence-based lens.