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Autosomal dominant hereditary polycystic kidney disease (ADPKD) is the most common inherited kidney disease that causes end-stage renal disease and kidney failure. Preimplantation genetic testing for monogenic (PGT-M) can effectively prevent the transmission of genetic diseases from parents to the offspring before pregnancy. However, PGT-M currently adopts the single nucleotide polymorphism (SNP) linkage analysis for embryo's pathogenic gene carrying status and linkage analysis requires proband of the family. Here we report a new PGT-M strategy using single sperm SNP linkage analysis for male patient with sporadic ADPKD caused by de novo PKD1 mutation. We recruited five couples with male patient with ADPKD caused by de novo PKD1 mutation, and 39 embryos from six PGT-M cycles were detected. The five couples had at least one embryo that does not carry the PKD1 mutation. Within these five couples, the accuracy of carrier status of embryos was confirmed by amniotic fluid gene detection of two couples and two couples successfully delivered healthy fetuses. Therefore, the new PGT-M strategy of using single sperm SNP linkage analysis was proved to be feasible and effective for male patient with ADPKD caused by de novo PKD1 mutation., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: The study aimed to investigate the relationship between elevated maternal body mass index (BMI) and foetal chromosomal aberrations by performing single-nucleotide polymorphism (SNP) array-based genetic testing on products of conception (POC)., Methods: We retrospectively reviewed the data for 1068 assisted reproductive technology (ART)-conceived POC originated from 1068 patients with early spontaneous miscarriage. First, all types of chromosomal abnormalities were defined. Then, the baseline characteristics, including maternal age, BMI, thyroid-stimulating hormone (TSH), gestational age, fertilization method, reasons for fertility treatment, embryo transfer (ET) cycle, stage of embryo development and the embryo morphology grade, were compared between chromosomally normal and abnormal POC groups. Finally, a multivariate logistic regression model was used to analyse various factors affecting the foetal chromosomal abnormality rate., Results: The SNP array results showed that 45.3% (484/1068) of POC were chromosomally normal and that 54.7% (584/1068) of POC presented chromosomal abnormalities. Of these 584 chromosomally abnormal POC, 388 (66.4%) were trisomy, 42 (7.2%) had a monosomy, 68 (11.6%) were found with segmental aneuploidy, 46 (7.9%) were mosaic, 28 (4.8%) were identified as polyploidy and 12 (2.1%) were euploid samples with uniparental disomy (UPD). Multivariate logistic regression results showed that the risk of miscarrying chromosomally abnormal POC increased 1.424-fold in women with normal BMI compared to women with an elevated BMI (≥ 25 kg/m 2 ) (OR = 1.424, 95% CI = 1.074-1.888, p = 0.014)., Conclusion: Women with an elevated BMI (≥ 25 kg/m 2 ) are more likely to miscarry chromosomally normal POC.

Studies have shown that early-follicular phase long-acting gonadotropin-releasing hormone (GnRH) agonist long protocol (EFLL), a popular controlled ovarian hyperstimulation protocol widely used in China, leads to higher rates of implantation and clinical pregnancy, as well as lower rates of spontaneous abortion and ectopic pregnancy in patients undergoing in vitro fertilization treatment. However, the impact of EFLL on euploid embryos and its underlying mechanisms remain unclear. To address these gaps of knowledge, we conducted a retrospective comparative study of 310 preimplantation genetic testing (PGT) cycles with a total of 1,541 embryos using the EFLL protocol or midluteal short-acting GnRH agonist long protocol (MLSL). Patients were matched by PGT subtype [aneuploidies (PGT-A) vs. PGT for chromosomal structural rearrangements (PGT-SR)], age (±2 years), and body mass index (±1 kg/m 2 ). For PGT-A, there was no significant difference in the number of euploid embryos (1.80 ± 1.47 for EFLL vs. 1.84 ± 2.03 for MLSL, p > 0.05) or the rate of euploidy (44.6 vs. 36.9%, p > 0.05). For PGT-SR, the number of euploid embryos in the EFLL group was significantly higher than that in the MLSL group (1.76 ± 1.54 vs. 1.21 ± 1.24, p < 0.05). A higher euploidy rate was also observed with the EFLL protocol compared with that obtained in MLSL (31.9 vs. 25.7%), although the difference was not statistically significant ( p > 0.05). Compared with the MLSL protocol, more euploid embryos were achieved when using the EFLL protocol in PGT-SR, demonstrating the value in PGT-SR. To the best of our knowledge, this study is the first one to compare embryonic outcomes between EFLL and MLSL, providing key insights into the clinical application of EFLL in PGT cycles. In the light of the limited sample size of our study, we recommend that these questions be explored using a larger prospective study., (Copyright © 2020 Li, Wu, Niu, Xu, Hu, Shi and Sun.)

Background: To assess whether preimplantation genetic testing for aneuploidy with next generation sequencing (NGS) outweighs single nucleotide polymorphism (SNP) array in improving clinical outcomes., Methods: A retrospective analysis of the clinical outcomes of patients who underwent PGT-A treatment in a single center from January 2013 to December 2017.A total of 1418 couples who underwent PGT-A treatment were enrolled, of which 805 couples used NGS for PGT-A, while the remaining 613 couples used SNP array for PGT-A. Clinical pregnancy rate, miscarriage rate and healthy baby rate were compared between the MALBAC-NGS-PGT-A and MDA-SNP-PGT-A groups., Results: After testing karyotypes of 5771 biopsied blastocysts, 32.2% (1861/5771) were identified as chromosomally normal, while 67.8% were chromosomally abnormal. In terms of clinical outcomes, women in the MALBAC-NGS-PGT-A group had a significantly higher clinical pregnancy rate (50.5% vs 41.7%, p = 0.002) and healthy baby rate (39.6% vs 31.4%, p = 0.003), and a lower miscarriage rate (15.5% vs 22.8%, p = 0.036)., Conclusion: This is the largest study reporting the extensive application of NGS-based PGT-A, whilst comparing the clinical outcomes of MALBAC-NGS-PGT-A and MDA-SNP-PGT-A. The results provide greater evidence supporting the wider use of NGS in PGT-A, not only for its lower cost but also for its improved clinical outcomes compared to SNP-based PGT-A.

Triploidy occurred about 2-3% in human pregnancies and contributed to approximately 15% of chromosomally caused human early miscarriage. It is essential for preimplantation genetic diagnosis and screen to distinct triploidy sensitively. Here, we performed comparative investigations between MALBAC-NGS and MDA-SNP array sensitivity on triploidy detection. Self-correction and reference-correction algorism were used to analyze the NGS data. We identified 5 triploid embryos in 1198 embryos of 218 PGD and PGS cycles using MDA-SNP array, the rate of tripoidy was 4.17‰ in PGS and PGD patients. Our results indicated that the MDA-SNP array was sensitive to digyny and diandry triploidy, MALBAC-NGS combined with self and reference genome correction strategies analyze were not sensitive to detect triploidy. Our study demonstrated that triploidy occurred at 4.17‰ in PGD and PGS, MDA-SNP array could successfully identify triploidy in PGD and PGS and genomic DNA. MALBAC-NGS combined with self and reference genome correction strategies were not sensitive to triploidy.

Purpose: Providing feasible preimplantation genetic testing strategies for monogenic disorders (PGT-M) for prevention and control of genetic cancers. Methods: Inclusion of families with a specific pathogenic mutation or a clear family history of genetic cancers. Identification of the distribution of hereditary cancer-related mutations in families through genetic testing. After a series of assisted reproductive measures such as down-regulation, stimulation, egg retrieval, and in vitro fertilization, a biopsy of trophectoderm cells from a blastocyst was performed for single-cell level whole-genome amplification (WGA). Then, the detection of chromosomal aneuploidies was performed by karyomapping. Construction of a haplotype-based linkage analysis to determine whether the embryo carries the mutation. Meanwhile, we performed CNV testing. Finally, embryos can be selected for transfer, and the results will be verified in 18–22 weeks after pregnancy. Results: Six couples with a total of 7 cycles were included in our study. Except for cycle 1 of case 5 which did not result in a transferable embryo, the remaining 6 cycles produced transferable embryos and had a successful pregnancy. Four couples have had amniotic fluid tests to confirm that the fetus does not carry the mutation, while 1 couple was not tested due to insufficient pregnancy weeks. And the remaining couples had to induce labor due to fetal megacystis during pregnancy. Conclusion: Our strategy has been proven to be feasible. It can effectively prevent transmission of hereditary cancer-related mutations to offspring during the prenatal stage. [ABSTRACT FROM AUTHOR]

Purpose: Currently, owing to the limitations of high-throughput sequencing depth and the allele dropout caused by the whole-genome amplification, detection of chromosomal variants in embryos with CNVs <5 Mb is unsatisfactory at the single-cell level using only conventional sequencing methods. Therefore, here we aimed to use a strategy of preimplantation genetic testing for monogenic (PGT-M) to compensate for the shortcomings of conventional sequencing methods. The purpose of this study is to report the effectiveness of haplotype linkage analysis by karyomapping for preimplantation diagnosis microdeletion diseases. Methods: Six couples carrying chromosomal microdeletions associated with X-linked ichthyosis were recruited, and all couples entered the PGT process. Multiple displacement amplification (MDA) method was used to amplify the whole-genome DNA of trophectoderm cells. Then karyomapping based on single nucleotide polymorphism (SNP) was used for haplotype linkage analysis to detect alleles carrying microdeletions, and CNVs of embryos were identified to determine euploid identity. Amniotic fluid tests were performed in the second trimester to verify the PGT-M results. Results: All couples were tested for chromosomal microdeletions, with deletion fragments ranging in size from 1.60 to 1.73 Mb, and one partner in each couple did not carry the microdeletion. Three couples successfully underwent PGT-M assisted conception and obtained healthy live births. Conclusion: This study shows that haplotype linkage analysis by karyomapping could effectively detect the carrier status of embryos with microdeletions at the single-cell level. This approach may be applied to the preimplantation diagnosis of various chromosomal microvariation diseases. [ABSTRACT FROM AUTHOR]

Autosomal dominant hereditary polycystic kidney disease (ADPKD) is the most common inherited kidney disease that causes end‐stage renal disease and kidney failure. Preimplantation genetic testing for monogenic (PGT‐M) can effectively prevent the transmission of genetic diseases from parents to the offspring before pregnancy. However, PGT‐M currently adopts the single nucleotide polymorphism (SNP) linkage analysis for embryo's pathogenic gene carrying status and linkage analysis requires proband of the family. Here we report a new PGT‐M strategy using single sperm SNP linkage analysis for male patient with sporadic ADPKD caused by de novo PKD1 mutation. We recruited five couples with male patient with ADPKD caused by de novo PKD1 mutation, and 39 embryos from six PGT‐M cycles were detected. The five couples had at least one embryo that does not carry the PKD1 mutation. Within these five couples, the accuracy of carrier status of embryos was confirmed by amniotic fluid gene detection of two couples and two couples successfully delivered healthy fetuses. Therefore, the new PGT‐M strategy of using single sperm SNP linkage analysis was proved to be feasible and effective for male patient with ADPKD caused by de novo PKD1 mutation. [ABSTRACT FROM AUTHOR]

Traditionally, chromosomal polymorphisms (CPMs) are normal genetic variants in individuals with no phenotypic variations. However, some studies have shown that CPM is related to reproductive diseases. We explored the influence of CPM on embryonic development and molecular karyotype in chromosomal translocation (CT) patients undergoing preimplantation genetic testing (PGT) between February 2013 and May 2019. Twenty-six cases with CPM and 56 controls with normal chromosomes were included. Furthermore, a 1:4 match pair analysis by female age included 39 cases with CTCPM and 185 controls with CT. There was no statistical difference in fertilization rate (78.48% vs. 78.33%), cleavage rate on Day 3 (90.32% vs. 89.16%), blastocyst rate (60.00% vs. 60.80%), and the high-quality blastocyst rate (36.31% vs. 35.22%) between CPM and normal chromosomes. The high-quality blastocyst rate of CTCPM was significantly lower than that for CT (26.78% vs. 38.89%). Moreover, there was no statistical difference in fertilization rate (70.65% vs. 70.37%), cleavage rate on Day 3 (88.67% vs. 89.53%), and blastocyst rate (48.48% vs. 53.17%) between CTCPM and CT. In addition, one CTCPM spouse had a lower high-quality blastocyst rate, especially of males with CTCPM. Abnormal embryo rates of CTCPM were significantly higher than those for CT (78.64% vs. 68.93%). Abnormal embryo rates were higher in both CTCPM and CPM paternal carriers with CT partners, respectively. For CT, CTCPM may have an impact on the high-quality blastocyst rate and embryonic molecular karyotype, especially in male patients. Patients with CTCPM are relatively rare, but this population would benefit from being explored using a larger sample size. [ABSTRACT FROM AUTHOR]

Purpose: The preimplantation genetic testing for monogenic defects (PGT-M) is a beneficial strategy for the patients suffering from a Mendelian disease, which could protect their offspring from inheriting the disease. The purpose of this study is to report the effectiveness of PGT-M based on karyomapping for three cases of dynamic mutation diseases with trinucleotide repeat expansion. Methods: PGT-M was carried out on three couples, whose family members were diagnosed with Huntington's disease or spinocerebellar ataxias 2 or 12. The whole genome amplification was obtained using the multiple displacement amplification (MDA) method. Then, karyomapping was performed to detect the allele that is carrying the trinucleotide repeat expansion using single nucleotide polymorphism (SNP) linkage analyses, and the copy number variations (CNVs) of the embryos were also identified. Prenatal diagnosis was performed to validate the accuracy of PGT-M. Results: PGT-M was successfully performed on the three couples, and they accepted the transfers of euploid blastocysts without the relevant pathogenic allele. The clinical pregnancies were acquired and the prenatal diagnosis of the three families confirmed the effectiveness of karyomapping. The three born babies were healthy and free of the pathogenic alleles HTT, ATXN2, or PPP2R2B corresponding to Huntington's disease, spinocerebellar ataxias 2 or 12, respectively. Conclusion: This study shows that karyomapping is a highly powerful and efficient approach for dynamic mutation detection in preimplantation embryos. In this work, we first report the birth of healthy babies that are free of the pathogenic gene for dynamic mutation diseases in patients receiving PGT-M by karyomapping. [ABSTRACT FROM AUTHOR]

Objective: To assess the potential association between polycystic ovary syndrome (PCOS) and chromosomally aberrant miscarriage during treatment with assisted reproductive technology (ART).Design: A retrospective, single-center study.Setting: University-affiliated reproductive center.Patient(s): A total of 328 patients sent their first trimester miscarried chorionic villus for genetic examination after ART in our center from January 2013 to September 2016, of which 119 cases were women with PCOS and 209 were non-PCOS controls. No known definite miscarriage-related concomitants existed in any study subject.Intervention(s): Single nucleotide polymorphism array analysis was performed on all collected samples.Main Outcome Measure(s): Frequency of aberrant karyotype of miscarried conceptus and the correlation between PCOS and chromosomally aberrant miscarriage.Result(s): A total of 173 (52.7% of 328) conceptuses were identified as chromosomally aberrant by single nucleotide polymorphism array. Chromosomal aberrations were more frequent in conceptuses from PCOS patients compared with controls (61.3% vs. 47.8%). Furthermore, both univariate and multivariable analysis identified PCOS as a risk factor for an embryo/fetus to be chromosomally abnormal, with odds ratios of 1.957 (95% confidence interval, 1.067-3.590) and 2.008 (95% confidence interval, 1.038-3.883), respectively.Conclusion(s): Women with PCOS were at an increased risk of miscarrying a chromosomally aberrant embryo/fetus compared with non-PCOS controls during ART. Mechanisms require further investigation. Preimplantation genetic screening might be an effective approach to decrease the risk of spontaneous miscarriage for women with PCOS. [ABSTRACT FROM AUTHOR]