Searched for: person:grifoj01
CHARACTERIZATION OF TELOMERES IN HUMAN ANEUPLOID BLASTOCYSTS [Meeting Abstract]
Wang, F; McCulloh, D H; Wiltshire, A M; Fioravanti, Schaal R; Oh, C; McCaffrey, C; Grifo, J A; Keefe, D L
OBJECTIVE: To compare telomere length (TL) and telomerase gene expression in human euploid and aneuploid blastocysts generated from IVF treatment. MATERIALS AND METHODS: TL and telomerase gene expression were measured in cryopreserved aneuploid (N=115) and euploid (N=4) human blastocysts donated by 26 patients who consented research under approval of IRB study #16-00154. Blastocysts were classified according to number of aneuploid chromosomes (A1-one segmental error, A2-one whole chromosome error, A3-two chromosomal errors and A4- >= 3 chromosomal errors). Genomic DNA and messenger RNA were separated simultaneously from individual blastocysts after thawing in vitrification-warming media. Telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) mRNA levels were determined by RT-qPCR with GAPDH as internal control, and TL was measured by qPCR with 5s rDNA as internal control. Relative gene expression and TL were calculated by DELTADELTACt method, and GraphPad Prism 8 software was used for statistical analysis.
RESULT(S): TL and telomerase gene expression were not normally distributed, so nonparametric tests were used to compare the medians among groups (Table 1). Median TL, TERTand TERC levels didn't differ by number of chromosome errors nor between aneuploid and euploid groups. Intriguingly, TL, TERT and TERC levels in aneuploid blastocysts tended to be greater compared to euploid blastocysts. TL in blastocysts correlated with telomerase TERT expression (R2 =0.054, P = 0.011), but not TERC expression (R2 =0.0002, P = 0.865).
CONCLUSION(S): To our knowledge, this is the largest study to measure telomere length and telomerase gene expression in human blastocysts. Our data indicated that telomeres are lengthened and telomerase is activated in aneuploid embryos at blastocyst stage. Moreover, telomere length and telomerase gene TERT in human blastocysts correlate regardless of ploidy status. Like cancer cells, TERT is highly expressed in aneuploid blastocysts. IMPACT STATEMENT: Robust TERT expression and telomere maintenance in aneuploid human blastocysts may explain why extended in vitro culture alone is insufficient to cull out aneuploidy embryos during IVF (Table Presented)
EMBASE:638129675
ISSN: 1556-5653
CID: 5250812
LOCKDOWN UPTICK: DID THE SARS-COV-2 PANDEMIC GENERATE AN INCREASE IN PLANNED OOCYTE CRYOPRESERVATION (POC)? [Meeting Abstract]
Weidenbaum, E M; Cascante, S D; DeVore, S; Hodes-Wertz, B; Grifo, J A; Blakemore, J K
OBJECTIVE: The rise of the SARS-CoV-2 pandemic and temporary closures of fertility centers made the effect on POC cycles uncertain but garnered national attention1,2. We sought to assess the impact of the pandemic on POC cycles in a pandemic epicenter. MATERIALS AND METHODS: This is a retrospective cohort study of all POC cycles at an academic fertility center in New York City from 1/1/2019- 12/31/2020. Primary outcomes were number of POC patients (pts) and cycles. Secondary outcomes were pt relationship status, payment method, AMH, and cycle parameters; with subgroup analyses by age groups. We also examined the relationship between monthly number of POC cycles and national SaRS-CoV-2 cases. Statistical analyses included z-score analysis, Mann-Whitney, and Chi-squared, with p<0.05 significant.
RESULT(S): Despite a 5.5 week center closure in 2020, POC pts increased 14% and POC cycles increased 16% from 2019 to 2020 (Table), with a 32% increase seen between June-Dec, 2020 . There was a 28% increase in POC pts <37yo in 2020 (252 pts vs. 323 pts, p<0.04) and no change in pts >37yo in 2020 (p=0.9). Relationship status did not differ between years (16% partnered, 76% single, 8% unknown in 2019 vs. 16% partnered, 73% single, 11% unknown in 2020; p=0.6). Fewer patients in 2020 had insurance coverage (16% vs. 24%, p<0.001). AMH was higher in 2020 (2.3 vs. 2.1, p<0.03), but days of stimulation, oocytes retrieved, oocytes frozen, total gonadotropins, and maximum estradiol (E2) were not different (Table). While national SARS-CoV-2 cases peaked in April, July, and November 2020, monthly POC cycles at our center did not decrease with surges in SARS-CoV-2 after our center reopened in May (p=0.24). In 2020 there were 23 cycles cancelled, none due a positive SARS-CoV-2 test.
CONCLUSION(S): POC volume increased at our center in 2020, especially in young patients, despite center closures and SARS-CoV-2 surges. IMPACT STATEMENT: More young people pursued POC despite the SARS-CoV-2 pandemic. Further research is needed to understand POC pt motivations and experiences during a pandemic. (Table Presented)
EMBASE:638129262
ISSN: 1556-5653
CID: 5250952
EGG FREEZING UNSCRAMBLED: AUTOLOGOUS OOCYTE (AO) THAW OUTCOMES FROM OVER 500 PATIENTS (PTS) AT A LARGE ACADEMIC FERTILITY CENTER (FC) [Meeting Abstract]
Cascante, S D; Blakemore, J K; DeVore, S; Parra, C M; Hodes-Wertz, B; McCaffrey, C; Grifo, J A
OBJECTIVE: AO cryopreservation (cryo) is widely used, but published thaw data is scarce. We reviewed our elective AO thaws. MATERIALS AND METHODS: Pts who thawed AOs at our FC in 2004- 2020 were reviewed. Pts were excluded if AO cryo was performed for a medical reason, as research, due to no sperm or a natural disaster, with embryo cryo or for use with a gestational carrier. Outcomes included implantation (IR), spontaneous abortion (SABR) and ongoing pregnancy + live birth (LBR) rates / embryo transfer (ET). We calculated a final LBR (FLBR) defined as LBR / pt; FLBR only included pts who a) had live birth (LB) or ongoing pregnancy (OP), or b) consumed all AOs and resultant embryos. Statistics included Mann-Whitney U and Fisher's exact test.
RESULT(S): 543 pts (median age at 1st cryo 38y) underwent 800 cryos (89% our FC, 9% elsewhere, 2% both), 605 thaws and 416 ETs. Cryo used vitrification for 72%, slow freezing for 4% and both for 24% of pts. Median time from 1st cryo to 1st thaw was 4y. In total, we thawed 8511 AOs (7492 M2s). AO survival was 79%, M2 survival was 80% and 2PN fertilization was 66%. When pts returned for thaw, 25% pursued fresh ET, 73% pursued preimplantation genetic testing (PGT), and 2% pursued a combination of both. In pts who pursued fresh ET, 92% had >=1 embryo for ET. In pts who pursued PGT, 57% had >=1 euploid. 13% of pts had no useable embryos (embryos for fresh ET, PGT, cryo). 59% of pts had >=1 ET. 37% of ETs were fresh, with 2% using rush-PGT. 63% of ETs were frozen, with 97% using PGT. In non-biopsied ETs, IR was 29%, SABR was 19% and LBR was 31%. In euploid ETs, IR was 64%, SABR was 10% and LBR was 55%. In our cohort, FLBR was 38%. In total, 178 babies (11 twin, 1 triplet) and 24 OPs resulted. 176 pts have >=1 LB or OP, and 23 pts have >=2 LBs or OPs from AO thaw. 33% of pts have remaining AOs or euploid or untested embryos; 45% of these pts do not have a LB or OP from AO thaw. See table for outcomes by age.
CONCLUSION(S): AO thaw leads to a FLBR of 38%, comparable to our FC's 34% LBR per intended retrieval in pts of similar age1 . IMPACT STATEMENT: Our real thaw data may be more useful than models in pt counseling
EMBASE:638129103
ISSN: 1556-5653
CID: 5250982
IS DAY OF BIOPSY A PREDICTOR OF OUTCOMES FOLLOWING MOSAIC EMBRYO TRANSFER? [Meeting Abstract]
Wiltshire, A M; Besser, A G; Akerman, M; Viotti, M; Grifo, J A
OBJECTIVE: To determine the prognostic utility of day of biopsy on mosaic embryo (ME) transfer outcomes. MATERIALS AND METHODS: Sub-analysis was performed of data collected in the 2021 study by Viotti et al 1. Descriptive statistics (mean +/- standard deviation for continuous variables; frequencies and percentages for categorical variables) were calculated separately by biopsy day (5, 6, or 7). The three groups were compared using the chi-square test or Fisher's exact test, as deemed appropriate, for categorical variables, and analysis of variance (ANOVA) for continuous data. A result was considered statistically significant at p<0.05. All analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC).
RESULT(S): Of the 1000 ME transfers documented, 825 specified day of biopsy (day 5, 6, or 7). There was a significant difference in mosaic type by biopsy day (p<0.0001); day 7 MEs resulted in significantly more complex and single monosomy/trisomy types. Day 6 MEs resulted in significantly more double monosomy/trisomy type. Day 5 MEs resulted in significantly more segmental types overall, including single, double, and complex segmental. There were also significant differences in outcomes; day 7 MEs were significantly less likely to result in pregnancy (p=0.0015), while day 5 MEs were significantly more likely to result in implantation (p= 0.0005) and ongoing pregnancy/live birth (p <0.0001). There was no significant difference in biochemical pregnancy (p= 0.717) or spontaneous abortion (p=0.757) based on biopsy day. There was no significant difference in maternal age (p= 0.455) or percent mosaicism (p=0.319) based on biopsy day. Day 5 MEs had significantly better morphology (p< 0.0001). The difference in ongoing pregnancy rate among the three biopsy days remained statistically significant after adjusting for mosaic type (p<0.0005). However, there was no significant difference in ongoing pregnancy rate between mosaic types after adjusting for biopsy day (p=0.1369).
CONCLUSION(S): MEs biopsied on day 5 are more likely to have segmental type mosaicism, better morphology, and better transfer outcomes. The mechanism for these differences are unclear; however, a hypothesis is that embryos with mosaicism associated with poorer outcomes may be slower to develop into blastocysts. These data can be incorporated into ME prioritization decisions. Further studies are needed to determine whether larger sample sizes would show similar findings, and how biopsy day can be combined with embryo morphology and mosaic type to continue improving ME selection and better inform patient counseling. IMPACT STATEMENT: Day of embryo biopsy is an important predictor of ME transfer success
EMBASE:638129264
ISSN: 1556-5653
CID: 5250942
WHY DO PREGNANCIES FOLLOWING EUPLOID EMBRYO TRANSFER MISCARRY? [Meeting Abstract]
Wiltshire, A M; Schaal, R F; Barrett, F; Wang, F; Akerman, M; Berkeley, A S; Grifo, J A; McCulloh, D H; Keefe, D L
OBJECTIVE: The causes of spontaneous abortion (SAB) following euploid embryo transfer (EET) remain poorly understood. Here we describe the frequency of aneuploidy in products of conception (POC) and endometrial dysfunction in women who miscarried after EET. MATERIALS AND METHODS: Between 1/2018 - 8/2020, 255 dilation and curettage (D&C) procedures were performed at a large academic IVF center for SAB following EET. Retrospective chart review was performed to identify D&Cs followed with genetic analysis of POCs. Information collected from the medical record included assessments of endometrial dysfunction based on Endometrial Receptivity Assay (ERA), CD138 for chronic endometritis (CE), and/or BCL6 for endometriosis. Exclusion criteria included an abnormal endometrial cavity on imaging. Demographic factors, clinical parameters and IVF/FET outcomes were reviewed. Additionally, retrospective chart review was performed of all ERAs completed at our institution from 12/2018-9/2020.
RESULT(S): Genetic analysis of 67 POCs after D&C following EET were identified. Fifty-nine POCs (88%) were euploid by SNP microarray. Eight (12%) of the POCs displayed genetic abnormalities: 3 trisomies, 2 partial duplications, 2 mosaic trisomies and 1 triploidy of paternal origin. Of the 51 patients who had endometrial biopsy (EMB), 28 (55%) had normal results. Twenty-three (45%) had abnormal results: 18 with CE, 2 with elevated BCL6 and 3 with pre-receptive ERA. The proportion of SABs unexplained by endometrial dysfunction or genetically abnormal POCs was 38% (26). A total of 44 patients underwent repeat EET. Eleven live births (LB) occurred, six after correction of endometrial dysfunction. Eight patients currently have ongoing pregnancy, 2 after treatment for CE. Three patients experienced repeat SAB, 1 following correction of pre-receptive ERA, and 1 after CE treatment. Four patients had implantation failure, 3 following normal EMB and 1 after treatment of CE. Two patients conceived spontaneously and delivered, 1 after treatment for CE, the other after a normal EMB. Upon review of all ERAs, 82 single EET following ERA guidance were identified. Fifty-nine percent (n=48) resulted in ongoing pregnancy or LB. There was no significant difference in ERA result or post ERA transfer outcome based on ethnicity (p= 0.7, p=0.4) or BMI (p= 0.8, 0.9), respectively. There was also no difference in post ERA transfer outcome based on blastocyst age (day 5 or 6) (p=0.5)
CONCLUSION(S): Aneuploidy and/or endometrial factor can contribute to SAB following EET. Aneuploid POCs could have arisen de novo and/or have passed undetected by trophectoderm biopsy and NGS. Our results are consistent with the 1-2% false negative rate reported for PGT-A. Further studies are needed to characterize the sub-chromosomal genetic variations associated with euploid embryo SABs, as well as endometrial function testing. IMPACT STATEMENT: The etiology behind failed EET may involve more discrete entities such as sub-chromosomal abnormalities in addition to aneuploidy and endometrial dysfunction
EMBASE:638129070
ISSN: 1556-5653
CID: 5251022
TRENDS IN PREIMPLANTATION GENETIC TESTING FOR MONOGENIC DISORDERS (PGT-M) [Meeting Abstract]
Besser, A G; McCulloh, D H; McCaffrey, C; Grifo, J A
OBJECTIVE: With increased availability of genetic testing, particularly expanded carrier screening (ECS) and hereditary cancer (HC) testing, the scope of conditions for which PGT-M is performed is expanding. Our aim was to report on indications for PGT-M from the past decade in our large academic practice. MATERIALS AND METHODS: All PGT-M cases occurring between January 2010 and April 2021 were reviewed.
RESULT(S): A total of 331 patients were identified for which PGT-M was performed for 124 different genes over 582 cycles. Eighteen patients tested for two genes and one patient tested for three genes; therefore, there were a total of 351 unique PGT-M cases. Of the 124 genes tested, 82 (66.1%) were of childhood onset while 16 (12.9%) were of adult onset, and the remaining 26 (21.0%) were of variable onset. Over the entire study period, 70/351 patients (19.9%) tested for 16 genes related to HC syndromes; between 2010-2017, HC-related PGT-M accounted for 12.6% (20/159) of our total PGT-M volume, and since 2018, it rose to 26.0% (50/192). Overall, BRCA1 was the most common gene tested in our practice, and hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2) accounted for 15.1% (53/351) of our total PGT-M patient population. 181/351 patients (51.6%) tested for 49 genes that are commonly found on ECS, with cystic fibrosis (CFTR) being the most common (34/351) followed by fragile X (FMR1; 32/351); these represented the second and third most common genes tested in our practice (9.7% and 9.1% respectively). Of all patients doing PGT-M for ECS-related conditions, 46.4% (84/181) tested for 41 genes that are not detected by traditional or ethnicity-based carrier screening, with the most common being GJB2-related nonsyndromic hearing loss (the fourth most common condition tested in our practice, representing 6.6% of our total PGT-M volume), followed by 21-hydroxylase deficient congenital adrenal hyperplasia (CYP21A2) and familial Mediterranean fever (MEFV). There were eight patients (2.3%) who either were or could have been identified on our current 283-disease ECS panel but would have been missed on our prior 176-disease ECS panel. Eight patients did PGT-M for HLA matching, and three did non-disclosure PGT-M (two for Huntington's disease/HTT and one for CADASIL/NOTCH3). 80/124 genes tested (64.5%) were unique to a single patient.
CONCLUSION(S): PGT-M is performed for a wide range of genetic conditions, and nearly two-thirds of genes tested in our clinic were unique to a single patient. While most conditions tested are childhood-onset, BRCA1 is the most common gene tested by our patient population, and the proportion of patients testing for HC syndromes has doubled over the past three years. More than half of patients pursued PGT-M for conditions detectable through ECS but not through traditional carrier screening; however, increasing the ECS panel size by more than 100 conditions has only had a minor effect on PGT-M uptake. IMPACT STATEMENT: This large dataset from a single IVF clinic highlights the impact of HC testing and ECS on PGT-M utilization over the past decade
EMBASE:638129922
ISSN: 1556-5653
CID: 5250762
IVF/OOF OUTCOMES DURING THE COVID-19 PANDEMIC [Meeting Abstract]
Chamani, I J; McCulloh, D H; Grifo, J A; Licciardi, F L
OBJECTIVE: COVID-19 has affected nearly every facet of modern life, and has left many wondering what implications, if any, the virus has on reproductive health. Increased levels of psychological stress, concern for viral contamination in embryology labs, and reports of decreased male fertility following COVID infection, have also been thought to contribute negatively to ART outcomes.We sought to determine whether the pandemic resulted in any differences in IVF/OOF outcomes. MATERIALS AND METHODS: Patients who tested negative for COVID-19 and underwent GnRH-antagonist IVF and OOF cycles from January 2020 through December 2020 at NYU Fertility Center, a period marked by the COVID-19 pandemic, were separated by month of treatment and compared with patients from the corresponding month in the prior year. In patients with multiple cycles over this time period, only the first cycle was used. Patient age, AMH, #oocytes retrieved, #oocytes matured, #fertilized, #blastocysts, and #euploid embryos were compared using Student's T-test.
RESULT(S): 2,467 patients were compared. While the number of cycles were remarkably decreased over March and April of 2020 (59 and 25 respectively), the total number of cycles were very similar for the entire year (1,239 in 2019; 1,228 in 2020). There were no consistently significant differences in age, AMH, #oocytes retrieved, #oocytes matured, #blastocysts formed, or #euploid embryos formed, between the two years.
CONCLUSION(S): Despite initial concerns, and prior research suggesting otherwise, we did not detect any consistent quantitative or qualitative differences in retrieval outcomes amongst COVID negative patients receiving care during the pandemic. IMPACT STATEMENT: These results can reassure patients and their providers that IVF/OOF cycles can be continued safely during the pandemic without compromising outcomes
EMBASE:638129960
ISSN: 1556-5653
CID: 5250742
SERUM GONADOTROPIN (GN) LEVELS PREDICT RESPONSE TO GONADOTROPIN-RELEASING HORMONE (GNRH) TRIGGER IN ANTAGONIST CONTROLLED OVARIAN HYPERSTIMULATION (COH) CYCLES [Meeting Abstract]
Wiltshire, A M; Tozour, J N; Akerman, M; Hamer, D; Grifo, J A; McCulloh, D H; Blakemore, J K
OBJECTIVE: The use of a GnRH trigger in COH cycles has increased due to an improved safety profile but not all patients have adequate response1.We sought to investigate the utility of using serum GN levels to predict response to GnRH trigger. MATERIALS AND METHODS: We performed a retrospective cohort study of all GnRH-antagonist COH cycles at an urban university affiliated fertility center from 2017-2020. Cycles that utilized GnRH-agonist (GnRH-a) alone or in combination with human chorionic GN (hCG) for trigger were included. Patient and cycle characteristics were collected from the electronic medical record, including day 2 baseline follicle stimulating hormone (B-FSH) and earliest in-cycle luteinizing hormone (EIC LH). An optimal response to GnRH-a trigger was defined as a LH R40 mIU/mL on the morning after trigger. Descriptive statistics (median +/- range for continuous variables; frequencies and percentages for categorical variables) were calculated by GnRH-a response. Statistical analyses were performed on SAS (v9.4) and included the chi-square test, Fisher's exact test, or Mann Whitney U test, as appropriate with a p<0.05 considered significant.
RESULT(S): A total of 3,865 COH antagonist cycles were included. Ninetyone percent of patients had an optimal response to GnRH-a trigger. Optimal responders had higher B-FSH levels than those with poor response (6.52 mIU/ml vs 4.36 mIU/ml, p<0.001). Similarly, the EIC LH was higher for optimal responders (4.66 mIU/ml vs 2.16 mIU/ml, p<0.001). Optimal response had a positive association with older age (p<0.00001), lower BMI (p<0.0001), less days of stimulation (p<0.001), lower starting serum estradiol (p<0.0007), and lower total gonadotropin dose (p<0.001). Optimal response was also associated with B-FSH >5 mIU/ml (p<0.0001), EIC LH >1 (p<0.0001), and Clomiphene citrate use (p< 0.009). Asian race was associated with poor response (p<0.006). There was no difference in oocyte maturity rate (p=0.6) or fertilization rate (p=0.5) for optimal or poor response. Cutoffs for B-FSH (>5 mIU/mL) and EIC LH ( >1 mIU/mL) were chosen to be reasonable clinical cutoffs to create a tool or aid to predict patient response to GnRH-a trigger. The incidence of patients with B-FSH >5 IU/ ml who had a poor response was 4.9% compared to 16.0% in patients with B-FSH <5 (p<0.0001). Twenty-four percent of patients with an EIC LH <1 had a poor response, compared to 4% of patients with EIC LH >1 (p<0.0001). The combination of B-FSH >5 IU/ml and EIC LH >1 IU/ml had a 71% sensitivity and 96% PPV in predicting an optimal response. When individually compared to a B-FSH >5 mIU/ml, an EIC LH>1 mIU/ ml had a higher sensitivity (91% vs 76%) and higher PPV (96% vs 95%) in predicting optimal response.
CONCLUSION(S): A B-FSH>5 and EIC LH>1 may be an appropriate threshold and helpful guide for physicians when determining trigger medicine for GnRH-antagonist COH cycles. Further studies are needed to understand predictors of poor response above these thresholds. IMPACT STATEMENT: In an era of personalized medicine, cycle and patient characteristics, such as GN levels, may improve cycle outcomes and provide further individualized care
EMBASE:638129660
ISSN: 1556-5653
CID: 5250832
Prenatal and postnatal outcome of mosaic embryo transfers: multicentric study of one thousand mosaic embryos diagnosed by preimplantation genetic testing with trophectoderm biopsy [Meeting Abstract]
Spinella, F; Victor, A; Barnes, F; Zouves, C; Besser, A; Grifo, J A; Cheng, E H; Corti, L; Minasi, M G; Greco, E; Munne, S; Fiorentino, F; Biricik, A; Viotti, M
Study question: To explore the effect of chromosomal mosaicism detected in preimplantation genetic testing (PGT-A) on prenatal and postnatal outcome of mosaic embryo pregnancies Summary answer: No significant difference between euploid and mosaic embryos was observed in terms of weeks of gestation, average weight, and developmental defect of the babies born What is known already: Mosaic embryos have the potential to implant and develop into healthy babies.Transfer of these embryos is now offered as an option for women who undergo IVF resulting in no euploid embryos. While, prenatal diagnosis has shown the depletion of chromosomal mosaicism in mosaic embryos, several concerns remain. For instance, the direct effects of different kind of mosaicism on prenatal/postnatal outcome and the possibility that intra-biopsy mosaicism in the TE is a poor predictor of the ploidy status of the ICM. Thus, there is certainly a need for comprehensive analyses of obstetrical and neonatal outcome data of transferred mosaic embryos. Study design, size, duration: Compiled analysis from multicenter data on transfers of mosaic embryos (n=1,000) and their outcome, with comparison to a euploid control group (n=5,561). To explore the effect of embryonic mosaicism on newborns, we matched mosaic embryos resulting in a birth with a euploid embryo by a series of parameters (maternal age, embryo morphology, and indication for PGT-A). Prenatal tests and birth characteristics of >200 neonates from mosaic embryo transfers were compared to >200 euploid embryos. Participants/materials, setting, methods: PGT-A was performed on blastocyst- stage embryos with 24-Chromosome whole genome amplification (WGA)-based Next Generation Sequencing (NGS). In accordance with established guidelines, embryos were categorized as mosaic when PGT-A results indicated 20-80% aneuploid content. Prenatal testing where performed in 30% of pregnancies with amniocentesis, 4% did an extra analysis for potential UPD for the suspected mosaic chromosome, and an additional 16% performed chorionic villus sampling (CVS) and 9.5% performed noninvasive prenatal testing (NIPT). Main results and the role of chance: Of the 465 mosaic embryos that implanted, about 20% miscarried, and out of those, 75% were early spontaneous abortions. Of the pregnancies, 3 out of 368 were stillborn (2 out of them were twins that were extremely premature at 23 weeks, and the other died during pregnancy from a heart defect). The remaining 99% of those have been born or are late ongoing pregnancies at the time of analysis. Prenatal tests were performed in >200 pregnancies and the vast majority tested normal. All 5 abnormal cases were amniocentesis tests showing microdeletions or insertions of sizes smaller than the resolution used during PGT-A, so they were unrelated to the mosaicism detected with PGT-A. In fact, in none of the cases did the prenatal test reflect the mosaicism detected at the embryonic stage. Matching each of the 162 mosaic embryos resulting in a birth with a euploid embryo, we found that the length of gestation was similar on average, and so was the average weight of the babies at birth. We also gathered information on the routine physical examination performed on babies at birth, and of those 162 babies from mosaic embryo transfers, none had obvious developmental defects or gross abnormalities. Limitations, reasons for caution: Even though newborns resulting from mosaic embryo transfers in this study invariably appeared healthy by routine examination, concerns for long-term health cannot yet be entirely dispelled. The question must therefore be carefully considered by each clinic and patient situation. Wider implications of the findings: Prenatal testing of >200 pregnancies from mosaic embryo transfers showed no incidence of mosaicism that matched the PGT-A findings, indicating the involvement of self-corrective mechanisms. Pregnancy and obstetric data indicates that mosaic embryos prevailing through gestation and birth have similar chromosomal and physiological health compared to euploid embryos
EMBASE:637629377
ISSN: 1460-2350
CID: 5240932
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