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Competing Interests: Declaration of Interests V.J. has nothing to disclose. K.S. has nothing to disclose. B.B. has nothing to disclose. M.P. has nothing to disclose. H.J.I. has nothing to disclose. M.R.P. has nothing to disclose. J.F. has nothing to disclose. U.S.K. has received funding from Gedeon Richter Nordic, IBSA, and Merck for studies outside this work; honoraria for teaching from Merck and Thillotts Pharma AB; and travel support and conference expenses covered by Merck.

Objective: To determine whether the aneuploidy risk score from a morphokinetic ploidy prediction model, Predicting Euploidy for Embryos in Reproductive Medicine (PREFER), is associated with miscarriage and live birth outcomes., Design: Multicentre cohort study., Setting: Nine in vitro fertilization clinics in the United Kingdom., Patients: Data were obtained from the treatment of patients from 2016-2019. A total of 3587 fresh single embryo transfers were included; preimplantation genetic testing for aneuploidy) cycles were excluded., Intervention: PREFER is a model developed using 8,147 biopsied blastocyst specimens to predict ploidy status using morphokinetic and clinical biodata. A second model using only morphokinetic (MK) predictors was developed, P PREFER-MK. The models will categorize embryos into the following three risk score categories for aneuploidy: "high risk," "medium risk," and "low risk.", Main Outcome Measures: The primary outcomes are miscarriage and live birth. Secondary outcomes include biochemical clinical pregnancy per single embryo transfer., Results: When applying PREFER, the miscarriage rates were 12%, 14%, and 22% in the "low risk," "moderate risk," and "high risk" categories, respectively. Those embryos deemed "high risk" had a significantly higher egg provider age compared with "low risk," and there was little variation in risk categories in patients of the same age. The trend in miscarriage rate was not seen when using PREFER-MK; however, there was an association with live birth, increasing from 38%-49% and 50% in the "high risk," "moderate risk," and "low risk" groups, respectively. An adjusted logistic regression analysis demonstrated that PREFER-MK was not associated with miscarriage when comparing "high risk" to "moderate risk" embryos (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.63-1.63) or "high risk" to "low risk" embryos (OR, 1.07; 95% CI, 0.79-1.46). An embryo deemed "low risk" by PREFER-MK was significantly more likely to result in a live birth than those embryos graded "high risk" (OR, 1.95; 95% CI, 1.65-2.25)., Conclusion: The PREFER model's risk scores were significantly associated with live births and miscarriages. Importantly, this study also found that this model applied too much weight to clinical factors, such that it could no longer rank a patient's embryos effectively. Therefore, a model including only MKs would be preferred; this was similarly associated with live birth but not miscarriage., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate whether the presence of vacuoles in biopsied blastocysts is associated with the likelihood of aneuploidy and clinical outcomes., Design: Retrospective observational study., Setting: A single reproductive center., Intervention(s): None., Patient(s): This study retrospectively analyzed data obtained through preimplantation genetic testing for aneuploidy performed on 3351 blastocysts from 826 patients at a single reproductive center between August 2018 and July 2020. Ultimately, 167 single euploid blastocyst transfers were performed in these patients. Vacuoles existing in the trophectoderm or inner cell mass were observed using blastocyst biopsy. After the biopsy, all blastocysts were vitrified, and embryo transfer was performed in a subsequent treatment cycle., Main Outcome Measure(s): The associations between vacuoles and euploidy or live birth rates were assessed using logistic regression models and estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs)., Result(s): Of the 3351 blastocysts from 826 patients, 903 (26.9%) were discovered to have vacuoles. The vacuole-positive group had a significantly lower percentage of euploid blastocysts after TE biopsy than the vacuole-negative group (28.8% vs. 35.5%). Embryos with vacuoles were significantly more likely to be poor quality (30.6% vs. 18.2%). Logistic regression analyses revealed that euploid blastocysts were positively associated with the absence of vacuoles, maternal age, and good embryo quality (vacuole-negative group: adjusted OR 1.291; 95% CI: 1.089-1.530; age <38 years: adjusted OR 1.989; 95% CI: 1.692-2.337; good embryo quality: adjusted OR 1.703; 95% CI: 1.405-2.064). The implantation and live birth rates were significantly lower for the transferred single euploid blastocysts with vacuoles than those without (35.5% vs. 56.6%; 29.0% vs. 52.2%, respectively). The live birth rate was positively associated with the absence of vacuoles (adjusted OR 2.792; 95% CI: 1.180-6.608)., Conclusion(s): The formation of vacuoles in blastocysts is associated with lower rates of euploidy and live birth. Blastocysts without vacuoles should thus be prioritized for embryo transfer in vitro fertilization cycles., (Copyright © 2023. Published by Elsevier Inc.)

This statement is offered to update and expand on the prior American Society for Reproductive Medicine preimplantation genetic testing (PGT) opinion, elucidate the current clinical and technical complexities specific to PGT for monogenic conditions, assist providers in supporting patient understanding of and access to this technology, and offer considerations for the development of future clinical and laboratory guidelines on PGT for monogenic conditions., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the association between antimüllerian hormone (AMH) and embryo ploidy rates in 2 cohorts of patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A): the general population of women pursuing IVF with PGT-A (Infertile cohort) and women pursuing IVF with preimplantation genetic testing for monogenic disorders (PGT-M) owing to the risk of hereditary monogenic diseases (Non-infertile cohort)., Design: Retrospective cohort study., Setting: Academic center., Patient(s): Patients undergoing their first cycle of IVF with trophectoderm biopsy and PGT-A or PGT-A and PGT-M in our center between March 2012 and June 2020. Patients of advanced maternal age according to the Bologna criteria (age ≥40 years) and patients who underwent fresh embryo transfers were excluded., Intervention(s): None., Main Outcome Measure(s): Proportion of euploid, mosaic, and aneuploid embryos per cycle., Result(s): "Infertile" (n = 926) and "Non-infertile" (n = 214) patients were stratified on the basis of AMH levels, with low-AMH defined as <1.1 ng/mL in accordance with the Bologna criteria. Age-adjusted regression models showed no relationship between AMH classification and proportion of euploid, mosaic, and aneuploid embryos in the Infertile or Non-infertile cohorts. In the Infertile cohort, no association between AMH classification and embryo ploidy rates was identified in a subgroup analysis of patients aged <35 years, 35-37 years, and 38-39 years. These findings persisted in a sensitivity analysis of infertile patients stratified into AMH (ng/mL) quartile categories., Conclusion(s): No association was found between AMH and the proportion of euploid, mosaic, or aneuploid embryos in 2 large cohorts of patients undergoing IVF with PGT-A (Infertile patients) or PGT-A and PGT-M (Non-infertile patients), suggesting that a quantitative depletion of ovarian reserve does not predict the ploidy status of the embryo cohort., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To evaluate the current evidence of pregnancy outcomes among couples with recurrent pregnancy loss (RPL) with abnormal karyotypes vs. those with normal karyotypes and among couples with RPL and abnormal karyotypes after receiving expectant management vs. preimplantation genetic diagnosis (PGD)., Design: Systematic review and meta-analysis., Setting: Academic medical centers., Patient(s): Pregnancy outcomes in 6,301 couples with RPL who conceived without medical intervention in 11 studies were analyzed. However, only 2 studies addressed the outcomes of couples with RPL and abnormal karyotypes after expectant management (75 cases) vs. PGD (50 cases)., Intervention(s): None., Main Outcome Measure(s): The pregnancy outcomes in couples with RPL with abnormal and normal karyotypes across included studies were evaluated., Result(s): Compared with those with a normal karyotype, a significantly lower first pregnancy live birth rate (LBR) was found in couples with RPL with abnormal karyotypes (58.5% vs. 71.9%; odds ratio [OR], 0.55; 95% confidence interval [CI], 0.46-0.65; I 2 =27%). A markedly decreased first pregnancy LBR was found in couples with a translocation (52.9% vs. 72.4%; OR, 0.44; 95% CI, 0.31-0.61; I 2 =33%) but not in couples with an inversion. However, the differences in accumulated LBR (81.4% vs. 74.8%; OR, 0.96; 95% CI, 0.90-1.03; I 2 = 0) were nonsignificant, whereas the miscarriage rate was distinctly higher in couples with RPL and abnormal karyotypes (53.0% vs. 34.7%; OR, 2.21; 95% CI, 1.69-2.89; I 2 = 0). Compared with those who chose expectant management, differences in accumulated LBR were nonsignificant (60% vs. 68%; OR, 0.55; 95% CI, 0.11-2.62; I 2 =71%), whereas the miscarriage rate (24% vs. 65.3%; OR, 0.15; 95% CI, 0.04-0.51; I 2 = 45) was markedly low in couples with RPL and abnormal karyotypes who chose PGD., Conclusion(s): Couples with RPL and abnormal karyotypes had a higher miscarriage rate than couples with normal karyotypes but achieved a noninferior accumulated LBR through multiple conception attempts. In couples with RPL and abnormal karyotypes, PGD treatment did not increase the accumulated LBR but markedly reduced miscarriage rate compared with expectant management., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the cost-effectiveness of planned oocyte cryopreservation (OC) as a strategy for delayed childbearing to achieve 1 or 2 live births (LB) compared with in vitro fertilization (IVF) and preimplantation genetic testing for aneuploidy (PGT-A) at advanced reproductive age., Design: Decision tree model with sensitivity analyses using data from the Society for Assisted Reproductive Technology Clinical Outcome Reporting System and other clinical sources., Setting: Not applicable., Patient(s): A data-driven simulated cohort of patients desiring delayed childbearing with an ideal family size of 1 or 2 LB., Intervention(s): Not applicable., Main Outcome Measure(s): Probability of achieving ≥1 or 2 LB, average and maximum cost per patient, cost per percentage point increase in chance of LB, and population-level cost/LB., Result(s): For those desiring 1 LB, planned OC at age 33 with warming at age 43 decreased the average total cost per patient from $62,308 to $30,333 and increased the likelihood of LB from 50% to 73% when compared with no OC with up to 3 cycles of IVF/PGT-A at age 43. For those desiring 2 LB, 2 cycles of OC at age 33 and warming at age 40 yielded the lowest cost per patient and highest likelihood of achieving 2 LB ($51,250 and 77%, respectively) when compared withpursuing only 1 cycle of OC ($75,373 and 61%, respectively), no OC and IVF/PGT-A with embryo banking ($79,728 and 48%, respectively), or no OC and IVF/PGT-A without embryo banking ($79,057 and 19%, respectively). Sensitivity analyses showed that OC remained cost-effective across a wide range of ages at cryopreservation. For 1 LB, OC achieved the highest likelihood of success when pursued before age 32 and remained more effective than IVF/PGT-A when pursued before age 39, and for 2 LB, 2 cycles of OC achieved the highest likelihood of success when pursued before age 31 and remained more effective than IVF/PGT-A when pursued before age 39., Conclusion(s): Among patients planning to postpone childbearing, OC is cost-effective and increases the odds of achieving 1 or 2 LB when compared with IVF/PGT-A at a more advanced reproductive age., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine if there is a relationship between paternal factors and embryonic aneuploidy of paternal origin using preimplantation genetic testing for aneuploidy (PGT-A)., Design: Retrospective cohort., Setting: Academic., Participants: Couples undergoing in vitro fertilization with PGT-A., Interventions: None., Main Outcome Measure: To determine if there is an association between paternal age, body mass index (BMI), or semen analysis parameters and paternal aneuploidy., Results: From January 2015-2020, 453 in vitro fertilization cycles (1,720 embryos) underwent PGT-A using single nucleotide polymorphism microarrays with parental support bioinformatics. The mean (±SD) was 36.5 (±3.5) years for maternal age, 39.5 (±5.5) years for paternal age, 24.7 (±5.0) kg/m 2 for maternal BMI, and 27.6 (±4.3) kg/m 2 for paternal BMI. Embryonic aneuploidy of paternal origin was found in 8.4% (144/1,720) embryos. There were 1,533 embryos with a recorded paternal BMI. Rates of embryonic aneuploidy of paternal origin were similar between men across BMI groups: BMI 18-24.9 kg/m 2 was 7.2% (referent); BMI 25-29.9 kg/m 2 was 8.4% (odds ratio [OR], 1.12; 95% confidence interval [CI], 0.79-1.82); and BMI ≥30 kg/m 2 was 9.1% (OR, 1.31; 95% CI, 0.83-2.08). There were 854 embryos from men with a normal and 866 from men with an abnormal semen analysis. No differences were found in the rate of embryonic aneuploidy of paternal origin between men with normal and abnormal sperm concentration, total count, motility, progressive motility, or morphology. No significant difference was seen in rates of aneuploidy between men aged <50 years and those aged ≥50 years (OR, 1.69; 95% CI, 0.96-2.98)., Conclusion: No association was found between paternal age, BMI, or semen analysis parameters and paternal aneuploidy., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the relationship between maternal body mass index (BMI) and embryonic aneuploidy of maternal origin., Design: Retrospective cohort analysis., Setting: University hospital-based reproductive center., Patients: Maternal origin of aneuploidy was available for 453 cycles and 1,717 embryos., Interventions: Data regarding BMI were collected before egg retrieval. Comparison groups included underweight (BMI, <18.5 kg/m 2 ), normal weight (BMI, 18.5-24.9 kg/m 2 ), overweight (BMI, 25-29.9 kg/m 2 ), and obese (BMI, ≥30 kg/m 2 ). Overall embryonic aneuploidy and maternal aneuploidy rates were compared. The aneuploidy rate was the number of embryos with either maternal or mixed (maternal and paternal) aneuploidy divided by the total number of embryos tested., Main Outcome Measures: Overall embryonic aneuploidy and maternal aneuploidy rates., Results: Maternal aneuploidy rate was 51.5% for BMI of ≥30 kg/m 2 and 39.3% for BMI of <30 kg/m 2 . Female age as well as several in vitro fertilization characteristics were significantly different across groups and were included in the adjusted model. Both the overall embryonic aneuploidy rate (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.11-1.59) and the maternal aneuploidy rate (OR, 1.64; 95% CI, 1.25-2.16) increased with increasing maternal BMI. However, after controlling for significant confounders, BMI did not significantly predict the rate of maternal aneuploidy (OR, 1.16; 95% CI, 0.85-1.59)., Conclusions: Maternal BMI did not correlate with embryonic aneuploidy of maternal origin after adjusting for confounders., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine how often the results of a single trophectoderm (TE) biopsy tested by PGTseq, a targeted next-generation sequencing preimplantation genetic testing for aneuploidy technology, reflect the biology of the rest of the embryo., Design: Blinded prospective cohort study., Setting: University-affiliated private practice., Patient(s): A total of 300 blastocysts were donated; 113 of these embryos were euploid; 163 embryos possessed at least one whole chromosome aneuploidy; and 24 embryos were negative for whole chromosome aneuploidy but possessed at least one secondary finding on initial TE biopsy., Intervention(s): All blastocysts underwent rebiopsy and preimplantation genetic testing for aneuploidy on the PGTseq platform., Main Outcome Measure(s): Partial concordance rate per embryo, total concordance rate per embryo, and total concordance rate per chromosomal event., Result(s): An initial TE biopsy result of euploidy or whole chromosome aneuploidy was reconfirmed in >99% of rebiopsied samples, affirming that meiotic errors are manifested in almost the entire embryo. In contrast, results of whole chromosome or segmental mosaicism were confirmed in 15%-18% of subsequent rebiopsies, suggesting that mitotic events are only sporadically seen throughout the embryo. Segmental aneuploidy was confirmed in 56.6% of rebiopsied samples, identifying a mixed meiotic and mitotic etiology for such abnormalities., Conclusion(s): A euploid or aneuploid result on the PGTseq platform is highly concordant with the rest of the embryo's ploidy status. The rarer confirmation of whole chromosome mosaic and segmental mosaic results suggest that these mosaics are suitable for embryo transfer. Segmental aneuploidy, with higher concordance rates throughout the embryo, may represent a different biologic etiology compared to mosaic embryos., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To apply long-read, third-generation sequencing as a part of a general workup strategy for performing structural rearrangement (PGT-SR) and monogenic disease (PGT-M) embryo testing., Design: Prospective study., Setting: In vitro fertilization unit., Patient(s): Couples presenting for PGT-SR (n = 15) and PGT-M (n = 2)., Intervention(s): Blastocyst biopsy with molecular testing for translocation breakpoints or mutations (targets)., Main Outcome Measure(s): Detailed, parental-phased, single-nucleotide polymorphism (SNP) profiles around targets for selection of informative polymorphic markers to simplify and facilitate clinical preimplantation genetic testing (PGT) designs that enable discrimination between carrier and noncarrier embryos., Result(s): High definition of chromosome breakpoints together with closely phased polymorphic markers was achieved for all 15 couples presenting for PGT-SR. Similarly, for the two couples presenting for PGT-M, tightly linked informative markers around the mutations were also simply identified. Three couples with translocations t(1;17)(q21;p13), t(3;13)(p25;q21.2), and t(12;13)(q23;q22) proceeded with PGT-SR, requesting preferential identification of noncarrier embryos for transfer. Following selection of a set of informative SNPs linked to breakpoints, we successfully performed PGT-SR tests, resulting in ongoing pregnancies with a noncarrier fetus for all couples. Similarly, with the use of tests based on informative SNPs linked to the parental mutations, one couple proceeded with PGT-M for maple syrup urine disease, resulting in an ongoing pregnancy with a disease-free fetus., Conclusion(s): For couples contemplating clinical PGT, variant haplophasing around the target reduces the workup process by enabling rapid selection of closely linked informative markers for patient-specific test design., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the association between body mass index (BMI) and embryo aneuploidy and mosaicism in a cohort of patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing technology., Design: Retrospective cohort study., Setting: Academic center., Patients: Patients undergoing their first IVF cycle with trophectoderm biopsy and PGT-A at our center between January 1, 2017, and August 31, 2020. Patients classified as underweight on the basis of BMI (BMI <18.5 kg/m 2 ) and patients who underwent fresh embryo transfers were excluded., Intervention: None., Main Outcome Measures: Number and proportion of aneuploid, mosaic, and euploid embryos., Results: The patients were stratified according to the World Health Organization's BMI classification: normal weight (18.5-24.9 kg/m 2 , n = 1,254), overweight (25-29.9 kg/m 2 , n = 351), and obese (≥30 kg/m 2 , n = 145). Age-adjusted regression models showed no relationship between BMI classification and the number or proportion of aneuploid embryos. There were no statistically significant associations between BMI classifications and the number or proportion of mosaic or euploid embryos. A subgroup analysis of patients classified into age groups of <35, 35-40, and >40 years similarly showed no relationships between BMI and embryo ploidy outcomes., Conclusion: Body mass index was not associated with the number or proportion of aneuploid, mosaic, or euploid embryos in this large cohort of patients undergoing IVF with PGT-A, suggesting that the negative effect of excess weight on reproductive outcomes was independent of the ploidy status of the embryo cohort., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To provide full morphokinetic characterization of embryos ranked with different degrees of chromosomal mosaicism., Design: Retrospective cohort study., Setting: University-affiliated private in vitro fertilization clinic., Patient(s): We analyzed 1,511 embryos from 424 intracytoplasmic sperm injection cycles by culturing embryos in a time-lapse imaging system and performing next-generation sequencing. We assessed 106 mosaic embryos., Intervention(s): None., Main Outcome Measure(s): Comparison of chromosomal, morphological, and morphokinetic characteristics of blastocysts classified as euploid, aneuploid, low-degree mosaic (30% to <50% aneuploid cells in trophectoderm biopsy), and high-degree mosaic (50% to <70% aneuploid cells in trophectoderm biopsy). Statistical analysis was performed using χ 2 , Kruskal-Wallis, or analysis of variance tests according to data type and distribution. A two-way random effects model was used to calculate interoperator correlation of annotations, and a logistic mixed effects model was performed to evaluate the effect of confounders on morphokinetic timing., Result(s): The mosaicism rate was ∼7% regardless of parental age. Mosaicism and uniform aneuploidies were not evenly distributed across chromosomes. The percentage of high-quality blastocysts significantly decreased from euploid (66.9%) to mosaic (52.8%) and aneuploid (47.7%). Aneuploid blastocysts significantly delayed development compared with euploid blastocysts in start of compaction (median, 84.72 hours postmicroinjection [hpm], interquartile range [IQR], 13.2; vs. median, 82.10 hpm, IQR, 11.5), start of blastulation (median, 101 hpm; IQR, 11.7; vs. median, 98.29 hpm, IQR, 10.5), and timing of blastocyst (median, 108.04 hpm, IQR, 11.50; vs. median, 104.71 hpm, IQR, 11.35). However, embryo morphokinetics were not correlated to the degree of mosaicism or to a mosaicism configuration that was apt for embryo transfer., Conclusion(s): Morphokinetic timing of mosaic embryos overlaps with that of euploid and aneuploid embryos, which may reflect their unique genetic and developmental identity. Although this suggests mosaic embryos are not simply a misdiagnosis by-product, further studies are needed to reveal the true identity of this particular type of embryo., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effects of non-Robertsonian translocation with chromosome fusion (N-RBCF) on preimplantation embryos., Design: Case series., Setting: University-affiliated center., Patient(s): Twelve couples with N-RBCF., Intervention(s): Assisted reproduction with preimplantation genetic testing in chromosomal structural rearrangement (PGT-SR)., Main Outcome Measure(s): Normal embryo rate, unbalanced translocation rate., Result(s): PGT was performed in 12 N-RBCF carriers, of whom 4 carried Y-autosome fusions and 8 autosomal fusions. A total of 12 (63.2%) of 19 blastocysts exhibited normal/balanced embryos, and only one (5.3%) embryo exhibited unbalanced translocations among Y-autosome fusion cases. In contrast to these findings, the percentage of normal/balanced blastocysts in 8 autosomal N-RBCF cases was 28.2% (11/39), whereas the unbalanced translocation rate was 53.8%. Furthermore, the percentage of normal/balanced embryos in the Robertsonian translocation group was significantly higher than that of the 8 autosomal N-RBCF (48.7% vs. 28.2%) cases. The rates of abnormality from chromosomal fusion in the 8 autosomal N-RBCF cases were significantly higher than those noted in the Robertsonian translocation (53.8% vs. 31.4%) subjects. The results of the stratified analysis according to the carrier's sex demonstrated that the rates of unbalanced translocation were significantly higher in the male autosomal N-RBCF subjects than those from the corresponding Robertsonian translocation (55% vs. 19.7%) cases., Conclusion(s): A low number of unbalanced translocations was identified in blastocysts from N-RBCF subjects who carried the Y fusion. The risk of unbalanced translocation in autosomal N-RBCF was higher than that of the Robertsonian translocation, notably in male carriers., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To validate and apply a strategy permitting parallel preimplantation genetic testing (PGT) for mitochondrial DNA (mtDNA) disease and aneuploidy (PGT-A)., Design: Preclinical test validation and case reports., Setting: Fertility centers. Diagnostics laboratory., Patients: 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: Embryo biopsy, genetic testing, and uterine transfer of embryos predicted to be euploid and mutation-free., Main Outcome Measures: 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., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether female body mass index (BMI) is associated with an increased risk of miscarriage after euploid embryo transfer., Design: A retrospective, observational, multicenter cohort study., Setting: University-affiliated in vitro fertilization center., Patient(s): In this study, 3,480 cycles of in vitro fertilization with preimplantation genetic testing for aneuploidy (PGT-A) in the blastocyst stage and euploid embryo transfer were divided into four groups according to patient BMI., Intervention(s): In vitro fertilization with PGT-A., Main Outcome Measure(s): The primary outcome was the miscarriage rate, which included both biochemical and clinical miscarriages. Secondary outcomes were implantation, pregnancy, clinical pregnancy, and live birth rates., Result(s): Cycles were divided into four groups according to BMI (kg/m 2 ): underweight (<18.5; n = 155), normal weight (18.5-24.9; n = 2,549), overweight (25-29.9; n = 591), and obese (≥30; n = 185). The number of PGT-A cycles per patient was similar in the four groups. Fertilization rate, day of embryo biopsy, technique of chromosomal analysis, number of euploid embryos, number of transferred embryos, and method of endometrial preparation for embryo transfer were similar in the four BMI groups. Miscarriage rates were significantly higher in women with obesity compared to women with normal weight, mainly due to a significant increase in the clinical miscarriage rates. Live birth rates also were lower in women with obesity. Obesity in women and day 6 trophectoderm biopsy were found to influence the reduced live birth rate., Conclusion(s): Women with obesity experience a higher rate of miscarriage after euploid embryo transfer than women with a normal weight, suggesting that other mechanisms than aneuploidy are responsible for this outcome., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To validate a commercially available noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) assay by investigating the following: prevalence of deoxyribonucleic acid (DNA) amplification failure with niPGT-A; factors affecting amplification failure with niPGT-A; and frequency of discordant results between niPGT-A and traditional preimplantation genetic testing for aneuploidy., Design: Prospective cohort study SETTING: Academic-affiliated private practice PATIENT(S): One hundred sixty-six blastocysts and their surrounding culture media from couples undergoing in vitro fertilization between July 2019 and May 2020 were analyzed., Intervention(s): Blastocyst-stage spent culture media samples underwent niPGT-A using a commercially available kit that used whole-genome amplification with a modified multiple annealing and looping-based amplification cycle protocol followed by next-generation sequencing. Preimplantation genetic testing for aneuploidy of trophectoderm (TE) biopsies was performed using targeted next-generation sequencing., Main Outcome Measure(s): The primary outcome was failure to achieve an interpretable result with niPGT-A. Factors affecting DNA amplification were also assessed. Discrepancies between niPGT-A and TE biopsy results were analyzed, and clinical outcomes were evaluated., Result(s): Deoxyribonucleic acid amplification failures with niPGT-A were observed in 37.3% (62/166) of the samples. With TE biopsy, no embryos exhibited DNA amplification failure. Embryos with a shorter duration of exposure to the culture media and no evidence of whole-chromosome aneuploidy on the TE biopsy displayed high rates of DNA amplification failure with niPGT-A. Of 104 embryos with both niPGT-A and TE biopsy results available, whole-chromosome discordance was noted in 42 cases (40.4%). Three embryos classified as aneuploid based on the niPGT-A result progressed to successful delivery., Conclusion(s): The rates of DNA amplification failure were high among the niPGT-A samples, virtually precluding the clinical applicability of niPGT-A in its current form., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the outcome of preimplantation genetic testing (PGT-A) using their own oocytes in patients with mosaic Turner Syndrome (MTS). The impact of the assisted reproduction technique (ART) performed (PGT-A or oocyte donation) and the type of absence of the X chromosome (total or partial) were considered., Design: Retrospective observational multicenter study., Setting: University-affiliated private in vitro fertilization center., Patient(s): Fifty-six patients with MTS with whom 65 ovarian stimulation cycles for PGT-A (fluorescence in situ hybridization/arrays-next generation sequencing) were performed. The study included 90 women with MTS and 20 women with pure Turner Syndrome (PTS) who underwent 140 and 25 oocyte donation (OD) cycles, respectively., Intervention(s): In vitro fertilization for PGT-A (fluorescence in situ hybridization/arrays-next generation sequencing) or OD., Main Outcome Measure (s): Reproductive outcome and feto-maternal outcomes., Results: The live birth rate (LBR) per embryo transfer in patients with MTS tended to be higher in OD 37.7% (95% confidence interval [CI]: 29.3-46.1) than that observed for PGT-A 22.5% (95% CI 7.8-38.2), and the cumulative LBR (CLBR), with 77.6% vs. 43.3%, respectively. Likewise, the LBR per patient was significant when comparing PGT-A vs. OD, with 12.5% (95 CI 3.9-21.1) vs. 51.1% (40.7-61.4), respectively. While focusing on the X chromosome, partial MTS (PTS), we found significant differences in the CLBR per embryo transfer, with 77.6% vs. 29.2%, and also in the LBR per patient: 51.1% (40.7-61.4) in MTS vs. 15% (95 CI 0.0-30.1) in PTS., Conclusion(s): Oocyte donation is the best reproductive option in females with Turner Syndrome with or without mosaicisms. Nevertheless, PGT-A is a valid therapeutic option in patients with MTS using their own oocytes, and OD should not necessarily be directly recommended., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Intracytoplasmic sperm injection, while typically effective for overcoming low or absent fertilization in couples with a clear abnormality of semen parameters, is frequently used in combination with assisted reproductive technologies for other etiologies of infertility in the presence of semen parameters that meet the World Health Organization 2010 normative reference values. This committee opinion provides a critical review of the literature, where available, to identify situations where this may or may not be of benefit. This document replaces the previously published document of the same name, last published in 2012 (Fertil Steril 2012;98:1395-9)., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate a possible correlation between chromosomal aberrations and paternal age, analyzing embryos derived from young oocyte donors, with available preimplantation genetic testing for aneuploidy results from day 5/6 trophectoderm biopsy obtained by next-generation sequencing for all 24 chromosomes., Design: Retrospective cohort study., Setting: Canadian fertility centre., Patient(s): A total of 3,118 embryos from 407 male patients, allocated into three paternal age groups: group A, ≤39 years (n = 203); group B, 40-49 years (n = 161); group C, ≥50 years (n = 43)., Intervention(s): None., Main Outcome Measure(s): The primary outcomes were aneuploidy, euploidy, mosaicism, and blastocyst formation rates. Secondary endpoints were comparison of specific chromosome aneuploidy, segmental and complex (involving two chromosomes + mosaicism >50%) aneuploidy, and analysis of overall percentage of chromosomal gains and losses within each group., Result(s): The study included 437 in vitro fertilization (IVF) antagonist cycles using 302 oocyte donors in which preimplantation genetic testing for aneuploidy was performed. Overall, 70.04% of embryos were euploid, 13.9% were aneuploid, and 16.06% were mosaic. No significant differences among paternal age groups A, B, and C were found in euploidy rates (69.2%, 70.6%, 71.4%, respectively), aneuploidy rates (14.7%, 12.8%, 13.9%, respectively) or mosaicism rates (16.1%, 16.6%, 13.6%; respectively). The fertilization rate was lower in group C compared with group B (76.35% vs. 80.09%). No difference was found in blastocyst formation rate between the study groups (median 52% [interquartile range, 41%, 67%] vs. 53% [42%, 65%] vs. 52% [42%, 64%], respectively). A generalized linear mixed model regression analysis for embryo ploidy rates found older oocyte donor age to be independently associated with embryo aneuploidy (odds ratio = 1.041; 95% CI, 1.009-1.074). The rate of segmental aneuploidies was significantly higher in the older versus younger paternal age group (36.6% vs. 19.4%)., Conclusion(s): No association was found between paternal age and aneuploidy rates in embryos derived from IVF cycles using young oocyte donors, after adjusting for donor, sperm, and IVF cycle characteristics. Advanced paternal age ≥ 50, compared with younger paternal ages, was associated with a lower fertilization rate and increased rate of segmental aberrations., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To present an effective approach to trophectoderm biopsy for blastocysts of different stages and characteristics by mechanical blunt dissection (MBD)., Design: Stepwise demonstration with still pictures and operational video clips to explain tips and tricks for trophectoderm biopsy. (This demonstration was approved by the Reproductive Study Ethics Committee at Shengjing Hospital of China Medical University.) SETTING: In vitro fertilization laboratory., Patient(s): Patients who underwent preimplantation genetic testing., Intervention(s): The illustrated techniques of blastocyst trophectoderm biopsy using micromanipulation methods include artificial shrinkage, zona pellucida drilling, injecting media from the drilling, aspiration of trophectoderm cells into the biopsy pipette (outer diameter 27 μm for fully expanded blastocysts and peanut-shaped hatching blastocysts; outer diameter 20 μm for 8-shaped hatching and hatched blastocysts), detachment of the trophectoderm cells by laser pulse combined with MBD (performed using the rims of the biopsy and holding pipettes), and release of the biopsy fragment., Main Outcome Measure(s): Successful biopsy rate and survival after warming., Result(s): Our biopsy strategy does not involve assisted hatching on day-3 or day-4 embryos, which can leave the embryo undisturbed in culture up to the expanded blastocyst stage. Notably, this approach demonstrates several noteworthy advantages for sampling blastocysts of different stages and characteristics, and it maintains a desirable successful biopsy rate (95.4%, n = 1,872) and survival rate after warming (100%, n = 440). The MBD method may reduce thermal damage because fewer laser pulses are used, compared with the traditional laser-only biopsy techniques. For noncollapsed blastocysts after artificial shrinkage, the strategy of injecting medium from the zona pellucida drilling helps to separate the trophectoderm cells from the zona pellucida, thus facilitating the biopsy procedure. For peanut-shaped hatching blastocysts, this approach could provide better control over the aspiration of trophectoderm cells into the biopsy pipette. Especially if the inner cell mass is herniating from the zona pellucida, the trophectoderm biopsy can be performed away from the inner cell mass to avoid damaging it. In addition, the MBD approach combined with the biopsy pipette (outer diameter 20 μm) can effectively control the target number of trophectoderm cells, thus simplifying the process of obtaining a biopsy from a hatched blastocyst., Conclusion(s): Our biopsy approach demonstrates several noteworthy advantages. Considering its benefits and the simplicity of its execution, this systematic biopsy method for blastocysts of different stages and characteristic can be widely applied., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the efficacy of sperm disomy rate as a predictor of preimplantation genetic screening (PGT-A) outcomes., Design: Retrospective cohort study., Setting: Andrology laboratory and in vitro fertilization center., Patient(s): All patients (n = 123) who underwent sperm fluorescence in situ hybridization and PGT-A at the China International Trust and Investment Corporation Xiangya Reproductive and Genetic Hospital between January 2015 and November 2018 were included., Intervention(s): Sperm samples of all patients evaluated for elevated disomy levels of 24 chromosomes using multicolor sperm fluorescence in situ hybridization and all embryos were cultured and biopsied at the blastocyst stage for PGT-A., Main Outcome Measure(s): The relationship between the whole genome of sperm disomy rate and PGT-A outcome and the predictive effect of the whole genome of sperm disomy rate on PGT-A outcome., Result(s): A statistically significant correlation was observed between the sperm disomy rate and PGT-A outcome. Many confounders were considered, such as patients' factors, semen or laboratory characteristics, which may affect PGT-A outcome. Regression analysis excluding these confounding factors indicated a 2.071-fold decrease in odds of probability of not obtaining any euploid embryo to transfer for every 1% decrease in total disomy rate. Based on a total disomy rate threshold of 4.84%, the prediction ability of total disomy rate on PGT-A outcome reached 75.6%., Conclusion(s): There is a negative correlation between the whole genome of sperm disomy rate and PGT-A outcome. It is a potential role for whole genome of sperm disomy rate in the PGT-A patients as a predictor, as well as in future genetic counselling. Based on these results, genetic counselors can advise couples on the risk of not obtaining any euploid embryo and help them choose the best reproductive and diagnostic method., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To assess whether the calculated difference in endometrial thickness from the end of the estrogen phase to the day of ET (after 6 days of P in hormonally prepared cycles) is associated with ongoing pregnancy rates in euploid frozen ETs (FETs)., Design: An observational cohort study., Setting: Single tertiary care medical center., Patient(s): Ultrasound images from 234 hormonally prepared FET cycles were assessed. All the transfers were elective single ETs of a euploid embryo, post-preimplantation genetic testing for aneuploidy (PGT-A)., Intervention(s): Ultrasound measurements of peak endometrial thickness at the end of the estrogen phase and again after 6 days of P at the time of ET., Main Outcome Measure(s): Ongoing pregnancy rate in relation to the delta between endometrial thickness at the end of estrogen phase and at the time of ET., Result(s): We calculated the ongoing pregnancy rate in cycles where the endometrial lining decreased (compacted) after addition of P by 5%, 10%, 15%, and 20% and demonstrated a significantly higher pregnancy rate after all rates of compaction of the endometrial lining in comparison with cycles where the endometrial lining did not compact. The ongoing pregnancy rate in this cohort, after compaction of 15% or more, was 51.5%, compared with 30.2% in cycles where the endometrial lining did not compact., Conclusion(s): There is a significant correlation between endometrial lining compaction and ongoing pregnancy rate in FET cycles of euploid embryos. These findings help to explain why some euploid embryos may fail to implant., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the use of preimplantation genetic testing for aneuploidy (PGT-A) among patients pursuing embryo banking (EB) for medically indicated fertility preservation (FP)., Design: Retrospective cohort., Setting: University-affiliated fertility center., Patients: All patients who underwent in vitro fertilization with or without PGT-A for medically indicated FP between January 2014 and April 2018., Interventions: None MAIN OUTCOME MEASURES: EB cycle characteristics, subsequent cycle pursuit/outcomes, and frozen embryo transfer (FET) outcomes., Results: A total of 58 medical EB cycles were compared; 34 cycles used PGT-A. Of the EB patients with breast cancer, 67% used PGT-A; other indications were evenly divided between PGT-A (FP/PGT-A) and no PGT-A (FP). PGT-A use increased over the study period. Groups were similar in age, days of stimulation, and days from initial FP consultation to treatment initiation. Number of oocytes (14.5 [2-63] FP vs. 17.5 [1-64] FP/PGT-A), 2PN zygotes (7 [1-38] FP vs. 9 [0-36] FP/PGT-A), and blastocysts (5.5 [0-22] FP vs. 5 [0-18] FP/PGT-A) cryopreserved were similar between groups. Equal numbers cryopreserved both oocytes and embryos (5 vs. 3). Five FP/PGT-A patients underwent a second EB cycle. Among FP/PGT-A patients, an average of 6.7 ± 5 blastocysts underwent PGT-A, with 3.5 ± 3 (48.2%) euploid embryos cryopreserved for future FET compared to an average of 7.2 ± 7 untested embryos in the FP group., Conclusion: PGT-A in medical EB cycles increased over time and did not limit the use of other FP methods such as oocyte cryopreservation. In some cases, poor PGT-A results informed patients to pursue a second EB cycle. When counseling patients, the prognostic benefits of PGT-A must be weighed against the financial costs and potential for "terminal" fertility diagnosis., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The evaluation of embryo viability is typically based on morphologic and morphometric grading systems, which are known to be heavily affected by differences in subjective judgement. A significant proportion of euploid embryos do not implant even when the endometrium is normal, despite the wide incorporation of preimplantation genetic testing for aneuploidy. The need to improve reproductive outcomes following assisted reproductive treatments is culminating in the emergence of new research and technology with the potential to enhance embryo selection. The assessment of mitochondrial DNA content as a predictor of embryo viability has gained increasing attention among numerous promising approaches. As is common with new tools, this attention has led to both inflated expectations and serious disillusionment. Here we gather evidence to establish the true clinical applicability of this method. Controversy continues to surround this topic, adding both interest and confusion., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether the blastocyst development rate, as assessed by the day of trophectoderm biopsy (day 5 vs. day 6), affects the live birth rate (LBR) of similarly graded euploid blastocysts., Design: Retrospective cohort study., Setting: Academic medical center., Patient(s): Patients who underwent frozen-thawed single euploid blastocyst transfers from 2013 to 2016 were included. Blastocyst morphologic grading was performed on day 5 or day 6 before the biopsy, with embryos designated into the following groups: good (3-6AA, 3-6AB, and 3-6BA), average (2-6BB), and poor (2-6BC and 2-6CB)., Intervention(s): Frozen-thawed embryo transfer., Main Outcome Measure(s): Implantation rate (IR) and LBR., Result(s): A total of 701 frozen-thawed single euploid blastocyst transfer cycles were included. Cycles in which day 5 blastocysts were transferred (n = 366) were associated with a significantly higher LBR than those in which day 6 blastocysts were transferred (n = 335; 60.4% vs. 44.8%). The odds ratio remained significant after controlling for all confounders, including the blastocyst grading. Furthermore, there was a significant difference in LBRs between good-quality, average-quality, and poor-quality blastocysts (67.8%, 53.4%, and 29.5%, respectively). Embryos reaching good-quality blastocysts on day 5 yielded significantly higher LBR (72.8% vs. 56.5%) and IR (77.7% vs. 58.7%) compared with those reaching similar quality blastocysts on day 6. Similarly, day 5 average-quality embryos conveyed a significantly higher IR compared with day 6 embryos of the same quality (64.4% vs. 53.4%)., Conclusion(s): In addition to aneuploidy assessment, the speed of embryo development to the blastocyst stage and an evaluation of blastocyst morphology are critical to selecting the best embryo., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)