scholarly journals A Rapid NGS-Based Preimplantation Genetic Testing for Chromosomal Abnormalities in Day-3 Blastomere Biopsy Allows Embryo Transfer Within the Same Treatment Cycle

2021 ◽  
Vol 12 ◽  
Author(s):  
Yinghui Ye ◽  
Jieliang Ma ◽  
Long Cui ◽  
Sijia Lu ◽  
Fan Jin

Nowadays, most of the preimplantation genetic testing (PGT) is performed with a strategy of comprehensive chromosome screening and trophectoderm biopsy. Nevertheless, patients with ovarian insufficiency may not have competent blastocysts. In the present study, we aimed to establish the value of multiple annealing and looping-based amplification cycle (MALBAC)-based next-generation sequencing (NGS) for PGT in day-3 embryos. A total of 94.3% (1168/1239) of embryos yielded informative results, and the overall embryo euploid rate was 21.9% (256/1168). Overall, 225 embryos were transferred in 169 cycles with a clinical pregnancy rate of 49.1% (83/169). The live birth and implantation rates were 47.3% (80/169) and 44.4% (100/225), respectively. Double embryos transfer showed higher clinical pregnancy and live birth rates compared with single embryo transfer, but the implantation rates were similar (44.2% vs. 44.6%, P > 0.05). The euploid rate for reciprocal translocations (16.1%) was significantly lower than that for Robertsonian translocations (28.0%, P < 0.01) and inversions (28.0%, P < 0.01). However, higher percentages of embryos with de novo abnormalities were observed with Robertsonian translocations (23.3%, P < 0.01) and inversions (30.5%, P < 0.01) than with reciprocal translocations (11.6%). We demonstrated that NGS for PGT on day-3 embryos is an effective clinical application, particularly for patients with a diminished ovarian reserve and limited embryos.

2020 ◽  
Vol 35 (10) ◽  
pp. 2356-2364
Author(s):  
Miriam J Haviland ◽  
Lauren A Murphy ◽  
Anna M Modest ◽  
Matthew P Fox ◽  
Lauren A Wise ◽  
...  

Abstract STUDY QUESTION Does preimplantation genetic testing for aneuploidy (PGT-A) increase the likelihood of live birth among women undergoing autologous IVF who have fertilized embryos? SUMMARY ANSWER PGT-A is associated with a greater probability of live birth among women 35 years old and older who are undergoing IVF. WHAT IS KNOWN ALREADY Previous studies evaluating the association between PGT-A and the incidence of live birth may be prone to confounding by indication, as women whose embryos undergo PGT-A may have a lower probability of live birth due to other factors associated with their increased risk of aneuploidy (e.g. advancing age, history of miscarriage). Propensity score matching can reduce bias where strong confounding by indication is expected. STUDY DESIGN, SIZE, DURATION We conducted a retrospective cohort study utilizing data from women who underwent autologous IVF treatment, had their first oocyte retrieval at our institution from 1 January 2011 through 31 October 2017 and had fertilized embryos from this retrieval. If a woman elected to use PGT-A, all good quality embryos (defined as an embryo between Stages 3 and 6 with Grade A or B inner or outer cell mass) were tested. We only evaluated cycles associated with the first oocyte retrieval in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Our analytic cohort included 8227 women. We used multivariable logistic regression to calculate a propensity score for PGT-A based on relevant demographic and clinical factors available to the IVF provider at the time of PGT-A or embryo transfer. We used the propensity score to match women who did and did not utilize PGT-A in a 1:1 ratio. We then used log-binomial regression to compare the cumulative incidence of embryo transfer, clinical pregnancy, miscarriage and live birth between women who did and did not utilize PGT-A. Because the risk of aneuploidy increases with age, we repeated these analyses among women <35, 35–37 and ≥38 years old based on the Society for Assisted Reproductive Technology’s standards. MAIN RESULTS AND THE ROLE OF CHANCE Overall, women with fertilized embryos who used PGT-A were significantly less likely to have an embryo transfer (risk ratios (RR): 0.78; 95% CI: 0.73, 0.82) but were more likely to have a cycle that resulted in a clinical pregnancy (RR: 1.15; 95% CI: 1.04, 1.28) and live birth (RR: 1.21; 95% CI: 1.08, 1.35) than women who did not use PGT-A. Among women aged ≥38 years, those who used PGT-A were 67% (RR: 1.67; 95% CI: 1.31, 2.13) more likely to have a live birth than women who did not use PGT-A. Among women aged 35–37 years, those who used PGT-A were also more likely to have a live birth (RR: 1.27; 95% CI: 1.05, 1.54) than women who did not use PGT-A. In contrast, women <35 years old who used PGT-A were as likely to have a live birth (RR: 0.91; 95% CI: 0.78, 1.06) as women <35 years old who did not use PGT-A. LIMITATIONS, REASONS FOR CAUTION We were unable to abstract several potential confounding variables from patients’ records (e.g. anti-Mullerian hormone levels and prior IVF treatment), which may have resulted in residual confounding. Additionally, by restricting our analyses to cycles associated with the first oocyte retrieval, we were unable to estimate the cumulative incidence of live birth over multiple oocyte retrieval cycles. WIDER IMPLICATIONS OF THE FINDINGS Women aged 35 years or older are likely to benefit from PGT-A. Larger studies might identify additional subgroups of women who might benefit from PGT-A. STUDY FUNDING/COMPETING INTEREST(S) No funding was received for this study. D.S. reports that he is a member of the Cooper Surgical Advisory Board. The other authors report no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.


Zygote ◽  
2021 ◽  
pp. 1-6
Author(s):  
Linjun Chen ◽  
Zhenyu Diao ◽  
Jie Wang ◽  
Zhipeng Xu ◽  
Ningyuan Zhang ◽  
...  

Summary This study analyzed the effects of the day of trophectoderm (TE) biopsy and blastocyst grade on clinical and neonatal outcomes. The results showed that the implantation and live birth rates of day 5 (D5) TE biopsy were significantly higher compared with those of D6 TE biopsy. The miscarriage rate of the former was lower than that of the latter, but there was no statistically significant difference. Higher quality blastocysts can achieve better implantation and live birth rates. Among good quality blastocysts, the implantation and live birth rates of D5 and D6 TE biopsy were not significantly different. Among fair quality and poor quality blastocysts, the implantation and live birth rates of D5 TE biopsy were significantly higher compared with those of D6 TE biopsy. Neither blastocyst grade nor the day of TE biopsy significantly affected the miscarriage rate. Neonatal outcomes, including newborn sex, gestational age, preterm birth, birth weight and low birth weight in the D5 and D6 TE biopsies were not significantly different. Both blastocyst grade and the day of TE biopsy must be considered at the same time when performing preimplantation genetic testing–frozen embryo transfer.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shaoqin Zhang ◽  
Jianjiang Zhu ◽  
Hong Qi ◽  
Limei Xu ◽  
Lirong Cai ◽  
...  

Abstract Introduction De novo balanced reciprocal translocations mosaicism in fetus conceived using preimplantation genetic testing from a different balanced translocation carrier parent has been rarely reported. Methods Chromosomal microarray analysis, karyotype analysis and fluorescent in situ hybridization were performed to verify the type and heredity of the rearrangement. STR analysis was conducted to identify potential contamination and verify kinship. In addition, a local BLAST engine was performed to locate potentially homologous segments which might contribute to the translocation in breakpoints of chromosome. Results A rare de novo balanced reciprocal translocations mosaicism mos 46,XY,t(1;3)(q42;q25)[40]/46,XY[39] was diagnosed in a fetus conceived using preimplantation genetic testing due to a 46,XY,t(12;14)(q22;q13) balanced translocation carrier father through multiplatform genetic techniques. Two of the largest continuous high homology segments were identified in chromosomal band 1q42.12 and 3q25.2. At the 21-months follow up, infant has achieved all psychomotor development milestones as well as growth within the normal reference range. Conclusion We present a prenatal diagnosis of a rare de novo balanced reciprocal translocations mosaicism in a fetus who conceived by preimplantation genetic testing. The most reasonable driving mechanism was that a de novo mitotic error caused by nonallelic homologous recombination between 1q42.12 and 3q25.2 in a zygote within the first or early cell divisions, which results in a mosaic embryo with the variant present in a half proportion of cells.


2018 ◽  
Vol 30 (12) ◽  
pp. 1720 ◽  
Author(s):  
Joanna Liss ◽  
Ewa Pastuszek ◽  
Sebastian Pukszta ◽  
Eva Hoffmann ◽  
Waldemar Kuczynski ◽  
...  

The present study analysed live birth ratios in frozen embryo transfer (FET) cycles where embryo ploidy status was determined with preimplantation genetic testing (PGT) using next-generation sequencing (NGS). PGT was performed on trophectoderm cells biopsied at the blastocyst stage. The present prospective cohort study included 112 women undergoing frozen embryo transfer, with NGS PGT. The control group consisted of 85 patients who underwent the IVF procedure with FET planned for a subsequent cycle. The live birth rate per cycle was higher by ~18.5 percentage points in the investigated compared with control group (42.0% vs 23.5% respectively; P = 0.012). The differences between the study and control groups were also significant for clinical pregnancy (42.0% vs 23.5% respectively; P = 0.012), implantation (41.2% vs 22.2% respectively; P = 0.001) and pregnancy loss rates (9.6% vs 28.6% respectively; P = 0.027). The results show that PGT NGS is a useful method for embryo selection and it may be implemented in routine clinical practice with propitious results.


2021 ◽  
pp. 1-6
Author(s):  
Tam M. Luu ◽  
Nhung C. Nguyen ◽  
Cam T. Tran ◽  
Anh H. Le ◽  
Bao G. Huynh ◽  
...  

Embryonic mosaicism is defined as two or more distinct cell lines within an embryo, which is originally developed from a zygote. Although the potential of mosaic embryos still remain unclear, recent reports have proved that mosaic embryo transfer can achieve healthy live-births. Up to now, there is no report of a live-birth having mosaic trisomy of full chromosome 5 following in-vitro fertilization (IVF). Our case is the first case proving that the transfer of medium-mosaicism embryo can result in a healthy live-birth. The couple are both carriers of balanced reciprocal translocations (46,XX,t(2;8)(p23;q24.3) and 46,XY,t(12;16)(q13.2;q23)). They had three IVF cycles combined with PGT-SR (Preimplantation Genetic Testing for Structural Rearrangement). A total of 18 blastocysts were biopsied and no euploid embryo was found. After the conselling, the patients chose to transfer a 40% mosaic trisomy chromosome 5 embryo. The follow-up pregnancy including prenatal diagnosis, amniocentesis and peripheral blood chromosome analysis of the newborn revealed no trisomy chromosome 5.


2021 ◽  
Author(s):  
xiliang wang ◽  
Yankun Wang ◽  
kaibo hou ◽  
dongmei hao ◽  
jinyan zhang ◽  
...  

Abstract BackgroundMicrodeletions of AZF are the most common factor causing male infertility except Klinefelter syndrome. AZF patients are able to father babies through intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF), and the ICSI embryos for IVF can be scored based on morphological criteria. However, the clinical pregnancy rate and the live birth rate are unsatisfactory.ResultsHere, we investigated the outcomes of using preimplantation genetic testing for aneuploidies (PGT-A) in families with AZFc microdeletions. A total of 26 intracytoplasmic sperm injection (ICSI) cycles were performed in 22 families, 25 ICSI cycles were performed, and 81 embryos underwent PGT-A. Among them, 48 were euploid embryos (23 females and 25 males), 30 were aneuploid embryos, and three embryos did not meet the quality control standards. Thirteen ICSI cycles with female euploid embryos and one ICSI cycle with male euploid embryos entered the stage of embryo implantation. Finally, the clinical pregnancy rate was 100% (14/14), and the live birth rate was 85.7% (12/14).ConclusionCompared with other published results, PGT-A increased the chance of fertility in AZFc microdeletion patients.


2021 ◽  
pp. 1-9
Author(s):  
Hongfang Liu ◽  
Bin Mao ◽  
Xiaojuan Xu ◽  
Lin Liu ◽  
Xiaoling Ma ◽  
...  

The purpose of this study was to evaluate the effectiveness of next-generation sequencing (NGS)-based preimplantation genetic testing (PGT) for balanced translocation carriers to identify normal/balanced blastocysts and to measure pregnancy outcomes following euploid embryo transfer. We enrolled 75 couples with a balanced translocation who underwent 83 PGT cycles (58 cycles for carriers with reciprocal translocations and 25 cycles for carriers with Robertsonian translocations) and 388 blastocysts were diagnosed. Moreover, we transferred single euploid blastocysts through frozen embryo transfer and calculated the biochemical pregnancy, clinical pregnancy, miscarriage, and ongoing pregnancy rates per embryo transfer cycle. Despite a mean maternal age of 29.8 years and mean of 4.34 embryos biopsied, there was a 32.8% chance of recording no chromosomally normal/balanced embryos for reciprocal translocation carriers. The proportion of normal/balanced embryos was significantly higher (44.1 vs. 27.8%) in Robertsonian translocation carriers than in reciprocal translocation carriers. Female carriers had a significantly lower (23.3 vs. 42.4%, 34.7 vs. 54.7%, respectively) percentage of normal/balanced embryos than male carriers, regardless of the translocation. After transfering single blastocysts, we obtained a 64.4% clinical pregnancy rate per transfer, and the clinical miscarriage rate was 5.7%. Amniocentesis results showed that all karyotypes of the fetuses were consistent with PGT results. The clinical outcomes are probably not influenced by the type of translocation, maternal age, and blastocyst morphology following the transfer of euploid blastocysts. Therefore, we conclude that NGS-based PGT is an efficient method for analyzing balanced translocation carriers, and aneuploidy screening had good clinical outcomes.


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