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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

Evidence-based management of preimplantation chromosomal mosaicism: lessons from the clinic

Besser, Andria G; Mounts, Emily L; Grifo, James A
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.
PMID: 34373104
ISSN: 1556-5653
CID: 5006122

Universal SARS-CoV-2 polymerase chain reaction screening and assisted reproductive technology in a coronavirus disease 2019 pandemic epicenter: screening and cycle outcomes from a New York City fertility center

Shaw, Jacquelyn; Tozour, Jessica; Blakemore, Jennifer K; Grifo, James
OBJECTIVE:To evaluate the prevalence of coronavirus disease 2019 (COVID-19) and efficacy of a universal screening program in patients undergoing controlled ovarian stimulation (COS). DESIGN:Single-center retrospective cohort study. SETTING:Academic fertility center in an epicenter of the COVID-19 pandemic. PATIENT(S):All patients undergoing COS from June 17, 2019, to February 28, 2021. INTERVENTION(S):Universal COVID-19 screening starting June 17, 2020, with SARS-CoV-2 polymerase chain reaction testing within 5 days of oocyte retrieval, patient-reported symptom screening, and temperature monitoring. MAIN OUTCOMES MEASURE(S):The primary outcome was the number of positive COVID-19 cases in patients undergoing COS cycles. The secondary outcomes were cycle outcomes compared with before COVID-19 COS cycles, adverse outcomes in COVID-canceled cycles, and center-specific COVID-19 detection rates compared with New York City cases. RESULT(S):From June 17, 2020, to February 28, 2021, 1,696 COS cycles were initiated with only seven positive COVID-19 cases for an overall positivity rate of 0.4%. When compared with before COVID cycles from June 17, 2019, to February 28, 2020, the volume of COS cycles were higher, while the overall cycle cancelation rate was lower during COVID-19. Cycle outcomes including oocyte yield and blast utilization rates were unchanged from pre-COVID cycles. Cases of COVID-19, while very low, occurred more frequently during surges in New York City rates. CONCLUSION(S):Assisted reproductive technology can be performed during the COVID-19 pandemic utilizing frequent universal screening and safe practices with low SARS-CoV-2 positivity, low cycle cancelation rates, and positive patient outcomes.
PMID: 34238573
ISSN: 1556-5653
CID: 5038832

Planned oocyte cryopreservation-10-15-year follow-up: return rates and cycle outcomes

Blakemore, Jennifer K; Grifo, James A; DeVore, Shannon M; Hodes-Wertz, Brooke; Berkeley, Alan S
OBJECTIVE:To evaluate the outcomes of planned oocyte cryopreservation patients most likely to have a final disposition. DESIGN/METHODS:Retrospective cohort study of all patients who underwent at least 1 cycle of planned oocyte cryopreservation between Jan 2005 and December 2009. SETTING/METHODS:Large urban University-affiliated fertility center PATIENT(S): All patients who underwent ≥1 cycle of planned oocyte cryopreservation in the study period. INTERVENTION(S)/METHODS:None MAIN OUTCOME MEASURE(S): Primary outcome was the disposition of oocytes at 10-15 years. Secondary outcomes included thaw/warming types, laboratory outcomes, and live birth rates. Outcomes and variables treated per patient. RESULT(S)/RESULTS:A total of 231 patients with 280 cycles were included. The mean age at the first retrieval was 38.2 years (range 23-45). A total of 3,250 oocytes were retrieved, with an average of 10 metaphase II frozen/retrieval. To date, the oocytes of 88 patients (38.1%) have been thawed/warmed, 109 (47.2%) remain in storage, 27 (11.7%) have been discarded, and 7 (3.0%) have been transported elsewhere. The return rate (patients who thawed/warmed oocytes) was similar by Society for Assisted Reproductive Technology age group. The mean age of patients discarding oocytes was 47.4 years (range, 40-57). Of the 88 patients who thawed/warmed oocytes, the mean age at the time of thaw/warming was 43.9 years (range, 38-50) with a mean of 5.9 years frozen (range, 1-12). Nine patients (10.2%) thawed/warmed for secondary infertility. A total of 62.5% of patients created embryos with a partner, and 37.5% used donor sperm. On average, 14.3 oocytes were thawed/warmed per patient, with 74.2% survival (range, 0%-100%) and a mean fertilization rate of 68.8% of surviving oocytes. Of 88 patients, 39 (44.3%) planned a fresh embryo transfer (ET); 36 of 39 patients had at least 1 embryo for fresh ET, and 11 had a total of 14 infants. Forty-nine of 88 patients (55.7%) planned for preimplantation genetic testing for aneuploidy, with a mean of 4.2 embryos biopsied (range, 0-14) and a euploidy rate of 28.9%. Of the 49 patients, 17 (34.7%) had all aneuploidy or no embryos biopsied. Twenty-four patients underwent a total of 36 single euploid ET with 18 live births from 16 patients. Notably, 8 PGT-A patients had a euploid embryo but no ET, affecting the future cumulative pregnancy rate. Overall, 80 patients with thaw/warming embryos had a final outcome. Of these, 20 had nothing for ET (arrested/aneuploid), and of the 60 who had ≥1 ET, 27 had a total of 32 infants, with a live birth rate of 33.8% (27/80). CONCLUSION(S)/CONCLUSIONS:We report the final outcomes of patients most likely to have returned, which is useful for patient counseling: a utilization rate of 38.1% and a no-use rate of 58.9%, similar across age groups. Further studies with larger cohorts as well as epidemiologic comparisons to patients currently cryopreserving are needed.
PMID: 33712289
ISSN: 1556-5653
CID: 4817192

Clinical application of sequencing-based methods for parallel preimplantation genetic testing for mitochondrial DNA disease and aneuploidy

Spath, Katharina; Babariya, Dhruti; Konstantinidis, Michalis; Lowndes, Jo; Child, Tim; Grifo, James A; Poulton, Joanna; Wells, Dagan
OBJECTIVE:To validate and apply a strategy permitting parallel preimplantation genetic testing (PGT) for mitochondrial DNA (mtDNA) disease and aneuploidy (PGT-A). DESIGN/METHODS:Preclinical test validation and case reports. SETTING/METHODS:Fertility centers. Diagnostics laboratory. PATIENTS/METHODS:Four patients at risk of transmitting mtDNA disease caused by m.8993T>G (Patients A and B), m.10191T>G (Patient C), and m.3243A>G (Patient D). Patients A, B, and C had affected children. Patients A and D displayed somatic heteroplasmy for mtDNA mutations. INTERVENTIONS/METHODS:Embryo biopsy, genetic testing, and uterine transfer of embryos predicted to be euploid and mutation-free. MAIN OUTCOME MEASURES/METHODS:Test accuracy, treatment outcomes, and mutation segregation. RESULTS:Accuracy of mtDNA mutation quantification was confirmed. The test was compatible with PGT-A, and half of the embryos tested were shown to be aneuploid (16/33). Mutations were detected in approximately 40% of embryo biopsies from Patients A and D (10/24) but in none from Patients B and C (n = 29). Patients B and C had healthy children following PGT and natural conception, respectively. The m.8993T>G mutation displayed skewed segregation, whereas m.3243A>G mutation levels were relatively low and potentially impacted embryo development. CONCLUSIONS:Considering the high aneuploidy rate, strategies providing a combination of PGT for mtDNA disease and aneuploidy may be advantageous compared with approaches that consider only mtDNA. Heteroplasmic women had a higher incidence of affected embryos than those with undetectable somatic mutant mtDNA but were still able to produce mutation-free embryos. While not conclusive, the results are consistent with the existence of mutation-specific segregation mechanisms occurring during oogenesis and possibly embryogenesis.
PMID: 33745725
ISSN: 1556-5653
CID: 4822192

The effect of endometrial thickness on live birth outcomes in women undergoing hormone-replaced frozen embryo transfer

Martel, Rachel A; Blakemore, Jennifer K; Grifo, James A
Objective/UNASSIGNED:To determine the impact of endometrial thickness on live birth outcomes and obstetric complication rate after hormone-replaced frozen embryo transfer. Design/UNASSIGNED:Retrospective cohort study. Setting/UNASSIGNED:Large, urban, academic fertility center. Patients/UNASSIGNED:All patients with a singleton live birth after single euploid embryo transfer (by array comparative genomic hybridization or next-generation sequencing) in a hormone-replaced frozen embryo transfer cycle between January 2017 and December 2018 were reviewed. Interventions/UNASSIGNED:None. Main Outcome measures/UNASSIGNED:The primary outcomes were birth weight and obstetric complication rate. Results/UNASSIGNED:A total of 492 patients were included. The median endometrial thickness was 8.60 mm (range, 6.0-20.0). The median gestational age at live birth was 39.4 weeks with a median birth weight of 3,345.2 g. Endometrial thickness was significantly correlated with birth weight. When patients were dichotomized into groups (those with an endometrial thickness of <7 mm and those with an endometrial thickness of >7 mm), neonates born from endometria with a thickness of <7 mm were born earlier (37.3 vs. 39.4 weeks and born with lower birth weights (2,749.9 vs. 3,345.2 g). It should be noted that only seven patients had an endometrium measuring <7 mm. Moreover, 7.1% (n = 35) of patients had an obstetric complication. Endometrial thickness was not significantly associated with obstetric complications, even with adjustments for age and medical history. Conclusions/UNASSIGNED:Endometrial thickness may be a valuable predictor of placental health and birth weight. Further study is required to examine the relationship with individual obstetric complications, as our study may not have been powered to observe differences in obstetric complication rate, as well as the relationship between endometrial thickness and outcomes in natural frozen embryo transfer cycles.
PMID: 34278346
ISSN: 2666-3341
CID: 4947852

Using outcome data from one thousand mosaic embryo transfers to formulate an embryo ranking system for clinical use

Viotti, Manuel; Victor, Andrea R; Barnes, Frank L; Zouves, Christo G; Besser, Andria G; Grifo, James A; Cheng, En-Hui; Lee, Maw-Sheng; Horcajadas, Jose A; Corti, Laura; Fiorentino, Francesco; Spinella, Francesca; Minasi, Maria Giulia; Greco, Ermanno; Munné, Santiago
OBJECTIVE:To study how the attributes of mosaicism identified during preimplantation genetic testing for aneuploidy relate to clinical outcomes, in order to formulate a ranking system of mosaic embryos for intrauterine transfer. DESIGN/METHODS:Compiled analysis. SETTING/METHODS:Multi-center. PATIENT(S)/METHODS:A total of 5,561 euploid blastocysts and 1,000 mosaic blastocysts used in clinical transfers in patients undergoing fertility treatment. INTERVENTION(S)/METHODS:None. MAIN OUTCOME MEASURE(S)/METHODS:Implantation (gestational sac), ongoing pregnancy, birth, and spontaneous abortion (miscarriage before 20 weeks of gestation). RESULT(S)/RESULTS:The euploid group had significantly more favorable rates of implantation and ongoing pregnancy/birth (OP/B) compared with the combined mosaic group or the mosaic group affecting only whole chromosomes (implantation: 57.2% vs. 46.5% vs. 41.8%; OP/B: 52.3% vs. 37.0% vs. 31.3%), as well as lower likelihood of spontaneous abortion (8.6% vs. 20.4% vs. 25%). Whole-chromosome mosaic embryos with level (percent aneuploid cells) <50% had significantly more favorable outcomes than the ≥50% group (implantation: 44.5% vs. 30.4%; OP/B: 36.1% vs. 19.3%). Mosaic type (nature of the aneuploidy implicated in mosaicism) affected outcomes, with a significant correlation between number of affected chromosomes and unfavorable outcomes. This ranged from mosaicism involving segmental abnormalities to complex aneuploidies affecting three or more chromosomes (implantation: 51.6% vs. 30.4%; OP/B: 43.1% vs. 20.8%). Combining mosaic level, type, and embryo morphology revealed the order of subcategories regarding likelihood of positive outcome. CONCLUSION(S)/CONCLUSIONS:This compiled analysis revealed traits of mosaicism identified with preimplantation genetic testing for aneuploidy that affected outcomes in a statistically significant manner, enabling the formulation of an evidence-based prioritization scheme for mosaic embryos in the clinic.
PMID: 33685629
ISSN: 1556-5653
CID: 4809162

Prospective analysis of progesterone exposure in programmed single thawed euploid embryo transfer cycles and outcomes

Hirschberg, Carly I; Blakemore, Jennifer K; Fino, Elizabeth; Grifo, Jamie A
PURPOSE/OBJECTIVE:In the era of personalized medicine and the increased use of frozen embryo transfer (FET), assay of the endometrium's receptivity prior to transfer has gained popularity, especially among patients. However, the optimal timing for single thawed euploid embryo transfers (STEET) in a programmed FET has yet to be determined Mackens et al. (Hum Reprod. 32(11):2234-42, 2017). We sought to examine the outcomes of euploid FETs by length of progesterone (P4) exposure. METHODS:Prospective cohort study of programmed FETs of single euploid embryos between June 1, 2018, and December, 18, 2018, at our center. Subjects reported the exact start time for initiating progesterone. The transfer time was noted to calculate the primary independent variable, duration of progesterone exposure. Statistical analysis included ANOVA and Spearman's rho correlation, with p < 0.05 considered significant. RESULTS:Inclusion criteria were met for 253 programmed STEET cycles in the analysis. There was no significant difference in P4 duration when comparing outcome groups (112.8 ± 3.1 ongoing pregnancy (OP), 112.4 ± 4.4 spontaneous abortion (SAB), 111.6 ± 1.7 biochemical pregnancy (BP), 113.9 ± 5.7 no pregnancy (NP), F 1.76, df 3, p = 0.16). An ROC curve assessing the ability of P4 duration to predict ongoing pregnancy (OP) had an area under the curve of 0.467 (p = 0.38). CONCLUSION/CONCLUSIONS:Duration of P4 was not associated with outcome. Of the cycles, 65.6% resulted in ongoing pregnancy with our center's instructions resulting in an average progesterone exposure of 112.8 h, with a range of 98.3-123.7 h. With growing popularity for individualized testing, these results provide evidence for patient counseling of the high likelihood of ongoing pregnancy without personalized testing.
PMID: 33566261
ISSN: 1573-7330
CID: 4836322

Comparison of subchorionic hematoma in medicated or natural single euploid frozen embryo transfer cycles

Reich, Jenna; Blakemore, Jennifer K; Grifo, James A
OBJECTIVE:To study the effect of frozen embryo transfer (FET) preparation protocol on incidence of subchorionic hematoma (SCH) and serum hormone levels. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:University-affiliated fertility center. PATIENT(S)/METHODS:Patients who underwent FET at the New York University Langone Fertility Center. INTERVENTION(S)/METHODS:None. MAIN OUTCOME MEASURE(S)/METHODS:The primary outcome was incidence of SCH by protocol in FET cycles. RESULT(S)/RESULTS:There were 1,273 FET cycles that met criteria for inclusion. The frequency of SCH was lower in natural compared with programmed cycles (P<.05; relative risk = 0.4 [0.27-0.78]; odds ratio = 0.4 [0.23-0.75]). Serum estrogen level was higher in programmed compared with natural cycles on day of progesterone initiation (P<.001) and cycle day 28 (P<.001). However, serum estrogen levels at the same time points were not associated with formation of SCH in programmed or natural cycles. CONCLUSION(S)/CONCLUSIONS:This is the first study to evaluate the formation of SCHs by FET protocol type. Our results highlight that high serum estradiol levels do not independently lead to an increase in rate of SCH. Further research must be done to understand other clinical, or perhaps molecular, differences between natural and programmed FET cycle preparations that can be better associated with SCH formation.
PMID: 32709380
ISSN: 1556-5653
CID: 4539872