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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
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
DOES EXCESS SPERM CAUSE CONTAMINATION IN PGT-A AFTER CONVENTIONAL INSEMINATION? [Meeting Abstract]
Yoder, N D; Robins, C; Jalas, C; McCaffrey, C; Besser, A G; Blakemore, J K; Zhan, Y; Tao, X; Grifo, J A
OBJECTIVE: Many preimplantation genetic testing (PGT) labs require intracytoplasmic sperm injection (ICSI) for PGT for aneuploidy (PGT-A) due to concern for paternal cell contamination. We sought to determine if sperm lysis occurs during PGT-A and assess the rate of paternal cell contamination in trophectoderm (TE) biopsies in embryos from insemination. MATERIALS AND METHODS: Sixty-two tripronuclear (3PN) embryos donated to research were collected from IVF with either insemination or ICSI from January - April, 2021. Embryos were cultured and assessed for development to blastocyst stage on days 5, 6 and 7 of culture. Embryos that developed into blastocysts underwent two separate TE biopsies. Biopsy procedure consisted of zona ablation on day 4 followed by TE biopsy using 2-3 pulses of laser beam at the cell junction. Biopsy samples were washed with drops of buffer 2-3 times and placed in a PCR tube. Arrested embryos were collected and assessed for approximate cell number. One group of arrested embryos was collected without washing (unwashed) and a second group was collected after removal of the zona (washed). TE biopsies, arrested embryos, and maternal and paternal samples were sent to a PGT lab to determine the genetic ploidy composition of the embryo biopsies and arrested embryos including the parent of origin. Testing included PGT-A using the PGTseq platform and SNP allele sharing that can detect parental origin of abnormalities and contamination.
RESULT(S): Of the 62 3PN embryos cultured, 17 developed into blastocysts with 4 from ICSI and 13 from insemination. There were 45 arrested embryos with 6 from ICSI (2 washed, 4 unwashed) and 39 from insemination (14 washed, 25 unwashed). PGT analysis showed varying degrees of paternal cell contamination in unwashed arrested embryos from insemination, and no paternal cell contamination in washed arrested embryos (ICSI or insemination) or unwashed ICSI embryos. Two washed arrested embryos from insemination showed no amplification. There was no paternal cell contamination in TE biopsies from either ICSI or insemination.
CONCLUSION(S): Analysis of unwashed arrested embryos from insemination demonstrates that excess sperm can lyse and cause paternal cell contamination during PGT-A. However, TE biopsies of embryos from insemination showed no evidence of paternal cell contamination, indicating that when properly washed and processed, paternal cell contamination is unlikely in inseminated embryos undergoing PGT-A. While this study was not powered to draw definitive conclusions or assess levels of contamination that interfere with PGT-A, preliminary results indicate that ICSI is not necessary for PGT-A. It should be noted that these findings are specific to the PGTseq platform, and may not translate to other methods. IMPACT STATEMENT: This study demonstrates that sperm have the ability to lyse and are a potential source of paternal cell contamination in PGT-A. However, this study also showed a 0% rate of paternal cell contamination in inseminated embryos when embryo biopsies were washed and processed as described, suggesting that ICSI is not necessary for patients desiring PGT-A
EMBASE:638130079
ISSN: 1556-5653
CID: 5250722
FIRST ONGOING THIRD TRIMESTER PREGNANCY FROM METAPHASE I (M1) OOCYTE CRYOPRESERVATION (CRYO) - M1 OOCYTE CRYO CAN RESULT IN USEABLE EMBRYOS AND PREGNANCY, BUT LESS FREQUENTLY THAN METAPHASE II (M2) OOCYTE CRYO [Meeting Abstract]
Cascante, S D; Grifo, J A; DeVore, S; Parra, C M; McCaffrey, C; Blakemore, J K
OBJECTIVE: Oocyte cryo is widely used for fertility preservation, but the value of M1 cryo remains unclear. We evaluated the utility and efficiency of M1 compared to M2 cryo. MATERIALS AND METHODS: Patients (pts) who thawed autologous oocytes at our academic center from 2004-2020 were reviewed. Pts were excluded if cryo was performed for a medical indication, as research, due to no sperm or a natural disaster, in combination with embryos or for use with a gestational carrier. At our center, all M1s retrieved from 2004-2015 were cryopreserved; after 2015, M1s were only cryopreserved if <15 M2s were retrieved during the same cryo cycle. Outcomes included survival rate, useable embryo rate and embryo transfer (ET) results.Auseable embryo was defined as an embryo that was transferred, biopsied or cryopreserved for future use. Statistics included Fisher's exact test.
RESULT(S): 543 pts (median age at 1st cryo 38y, interquartile range 37-40y) underwent 800 cryo, 605 thaw and 416 ET cycles. Cryo was performed with vitrification for 72%, slow freezing for 4% and both technologies for 24% of pts. In total, 8511 oocytes (1019M1s + 7492 M2s)were thawed.All pts thawed >=1 M2, and 60% (n=327) thawed >=1 M1. See table for thaw outcomes of M1s vs. M2s. For 30 pts, >=1 M1 led to a useable embryo (n=32 useable embryos). Vitrification was used for 69% of these M1s (n=22) and slow freezing was used for 31% (n=10). Of the 32 useable embryos from M1s, 69% (n=22) underwent PGTand 4were euploid (17 aneuploid, 1 mosaic). Therewere 3 single ETs of euploid embryos from M1s, which led to 1 spontaneous abortion (SAB) and 2 biochemical pregnancies. Therewere 3 single ETs of untested embryos from M1s, which led to 1 negative result, 1 SAB and 1 singleton ongoing pregnancy. The ongoing pregnancy is from an ETof a day 5 morula and is now in the third trimester. There were 6 ETs in which untested embryos from M1s were transferred alongwith untested embryos fromM2s, resulting in 3 negative results, 1 SAB, 1 singleton live birth and 1 unknown outcome (ongoing singleton pregnancy at last contact).
CONCLUSION(S): Cryopreserved M1s can result in useable embryos and pregnancies, but are less likely to survive or form useable embryos than cryopreserved M2s. To our knowledge, this is the first report of an ongoing third trimester pregnancy from a cryopreserved M1. This information may be helpful for pt counselling and designing oocyte cryo protocols for embryology labs. IMPACT STATEMENT: Cryopreserved M1s may be a viable option for pts with a low M2 yield. (Table Presented)
EMBASE:638130069
ISSN: 1556-5653
CID: 5250732
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
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
A MACHINE LEARNING BASED MORPHOLOGY VERSUS AUTOMATIC MORPHOKINETIC ALGORITHMS FOR IMPLANTATION PREDICTION [Meeting Abstract]
Ben-Meir, A; Har-Vardi, I; Karavani, G; Levitas, E; Grifo, J A; Wang, F; Erlich, I
OBJECTIVE: To compare three different implantation prediction models using artificial intelligence algorithms (AI) that analyze (I) morphology only, (II) morphokinetic events only using an automatic AI-based annotation model, and (III) a combination of both, in a retrospective multi-center study. MATERIALS AND METHODS: The automatic morphokinetic evaluation tool was trained on 36561 annotated embryos obtained between 2014 - 2019 (34132 in training set and 2429 in test set). Morphokinetic annotation and morphology evaluation of 6938 embryos with known implantation data (KID) were used to train and test KID+TM, an AI algorithm. The training set consisted of 6363 embryos (1078 KID-positive and 5285 KID-negative). The blind test set consisted of 575 embryos (171 KID-positive and 404 KID-negative). KID+TM scored the embryos for implantation potential based on an automatic evaluation of morphokinetic and morphology data. We compared our combined morphokinetic and morphology model KID+TM to (I) a model that only considers morphokinetic events and (II) a model that only considers morphology from the last frame of embryo development.
RESULT(S): We aimed to compare the implantation prediction potential of algorithms that analyze morphokinetic features only, morphology features only, and a combination of both. To accomplish this, we trained a convolutional neural network (CNN) to perform automatic annotations of embryo development events (r2 =0.95). Analysis of these estimated annotations revealed a robust implantation prediction tool with an area under curve (AUC) continuously increasing from 30 to 116 hours post insemination, reaching a maximal AUC of 0.65 at 116 hours. However, single image analysis of the last frame of the embryo video after the morula stage demonstrated better prediction with AUC of 0.68 at 116 hours. Thus, the combined morphokinetic and morphology algorithm was valuable for implantation prediction until the start of blastulation (~90 hours). After the start of blastulation, the combined algorithm did not demonstrate a superior AUC relative to the morphology only algorithm with an AUC of 0.68 at 116 hours.
CONCLUSION(S): The combined morphokinetic and morphology algorithm was more effective for implantation prediction at the cleavage stage than the morphology only algorithm. Thus, the combined algorithm has the potential to improve the embryo selection process for day 3 transfers. In the later stages of embryo development, the morphology only algorithm was as effective for implantation prediction as the combined algorithm. IMPACT STATEMENT: AI models have the potential to eliminate the high degree of inter- and intra-observer variability associated with embryo assessment by automating morphokinetic and morphology evaluation to accurately predict embryo outcomes, thereby improving IVF outcomes. In addition, AI models leveraging morphokinetic and morphology data may be able to accurately evaluate embryos in earlier stages of development to improve selection for day 3 transfers
EMBASE:638129740
ISSN: 1556-5653
CID: 5250782
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
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
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