Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-02T20:52:00.341Z Has data issue: false hasContentIssue false
  • English
  • Français

Robust evidence reveals the reliable rate of normal/balanced embryos for identifying reciprocal translocation and Robertsonian translocation carriers

Published online by Cambridge University Press:  12 December 2023

Zhihua Tian Open the ORCID record for Zhihua Tian [Opens in a new window] ,
Wenchang Lian ,
Li Xu ,
Yanxi Long ,
Li Tang  and
Huawei Wang
Zhihua Tian
Affiliation:
Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
Wenchang Lian
Affiliation:
Department of Medical Genetics, Yikon Genomics Company, Ltd, Jiangsu Suzhou 215021, China
Li Xu
Affiliation:
Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
Yanxi Long
Affiliation:
Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
Li Tang*
Affiliation:
Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
Huawei Wang*
Affiliation:
Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
*
Corresponding authors: Li Tang; Email: [email protected] and Huawei Wang; Email: [email protected]
Corresponding authors: Li Tang; Email: [email protected] and Huawei Wang; Email: [email protected]
Rights & Permissions [Opens in a new window]

Summary

We aimed to evaluate the reliable rate of normal/balanced embryos for reciprocal translocation and Robertsonian translocation carriers and to provide convincing evidence for clinical staff to conduct genetic counselling regarding common structural rearrangements to alleviate patient anxiety. The characteristics of 39,459 embryos that were sourced from unpublished data and literature were analyzed. The samples consisted of 17,536 embryo karyotypes that were not published and 21,923 embryo karyotypes obtained from the literature. Using the PubMed, Cochrane Library, Web of Science, and Embase databases, specific keywords were used to screen the literature for reciprocal translocation and Robertsonian translocation. The ratio of normal/balanced embryos in the overall data was calculated and analyzed, and we grouped the results according to gender to confirm if there were gender differences. We also divided the data into the cleavage stage and blastocyst stage according to the biopsy period to verify if there was a difference in the ratio of normal/balanced embryos. By combining the unpublished data and data derived from the literature, the average rates of normal/balanced embryos for reciprocal translocation and Robertsonian translocation carriers were observed to be 26.96% (7953/29,495) and 41.59% (4144/9964), respectively. Reciprocal translocation and Robertson translocation exhibited higher rates in male carriers than they did in female carriers (49.60% vs. 37.44%; 29.84% vs. 27.67%). Additionally, the data for both translocations exhibited differences in the normal/balanced embryo ratios between the cleavage and blastocyst stages of carriers for both Robertsonian translocation and reciprocal translocation (36.07% vs 43.43%; 24.88% vs 27.67%). The differences between the two location types were statistically significant (P < 0.05). The normal/balanced ratio of embryos in carriers of reciprocal and RobT was higher than the theoretical ratio, and the values ranged from 26.96% to 41.59%. Moreover, the male carriers possessed a higher number of embryos that were normal or balanced. The ratio of normal/balanced embryos in the blastocyst stage was higher than that in the cleavage stage. The results of this study provide a reliable suggestion for future clinic genetic consulting regarding the rate of normal/balanced embryos of reciprocal translocation and Robertsonian translocation carriers.

Keywords

Balanced chromosome embryosGenetic consultingReciprocal translocationRobertsonian translocationUnbalanced chromosome embryos
Type
Research Article
Information
Zygote , Volume 32 , Issue 1 , February 2024 , pp. 58 - 65
Check for updates
Copyright
© The Author(s), 2023. Published by Cambridge University Press

Introduction

In couples of childbearing age, reciprocal translocation (RecT) and Robertsonian translocation (RobT) are the two major chromosomal abnormalities responsible for the high occurrence of abortion (Xu et al., Reference Xu, Zhang, Niu, Yang, Yao, Shi, Jin, Song, Chen, Zhang, Guo, Su, Hu, Zhai, Zhang, Dong, Gao, Li and Bo2017). Its incidence is higher in newborns and couples of childbearing age and ranges from 0.1% to 0.2% and 0.4%, respectively (Alfarawati et al., Reference Alfarawati, Fragouli, Colls and Wells2012). According to published studies, the miscarriage rates for RecT and RobT are ∼2–5% (Zhai et al., Reference Zhai, Wang, Li, Wang, Zhu, Kuo, Guan, Li, Song, He, An, Zhi, Lian, Huang, Li, Qiao, Yan and Yan2022). RecT is caused by the translocation of two chromosome segments on both sides of the breakpoint and can occur in all chromosomes. The formation of RobT is related to the centromere region and involves the long-arm connection of two chromosomes that were restricted to chromosomes 13, 14, 15, and 21 (Xu et al., Reference Xu, Zhang, Niu, Yang, Yao, Shi, Jin, Song, Chen, Zhang, Guo, Su, Hu, Zhai, Zhang, Dong, Gao, Li and Bo2017; Zhai et al., Reference Zhai, Wang, Li, Wang, Zhu, Kuo, Guan, Li, Song, He, An, Zhi, Lian, Huang, Li, Qiao, Yan and Yan2022). Previous studies have revealed the occurrence of RecT/RobT during gamete formation (including oocytes or sperm), therefore indicating that the onset of most RecT/RobT was novel.

The intrinsic characteristic of RecT/RobT is the change in chromosome fragments; however, the majority of patients did not exhibit a loss of key genes. Therefore, RecT/RobT carriers do not possess any genetic diseases (Findikli et al., Reference Findikli, Gultomruk, Boynukalin and Ogur2019). Most RecT/RobT carriers were detected using chromosomal karyotype analysis of peripheral blood for recurrent abortion and infertility. However, RecT/RobT carriers can exhibit a higher frequency of chromosomal abnormalities in oocytes and sperm, ultimately resulting in offspring with congenital diseases such as Down’s syndrome and Pato syndrome (Xu et al., Reference Xu, Zhang, Niu, Yang, Yao, Shi, Jin, Song, Chen, Zhang, Guo, Su, Hu, Zhai, Zhang, Dong, Gao, Li and Bo2017). According to the adjacent and 3:1 theory for RobT carriers, they may possess 1/6 normal and 1/6 balanced gametes (Liu et al., Reference Liu, Mao, Xu, Liu, Ma and Zhang2020), and this results in phenotypically normal offspring based on the normal and balanced gametes possessing normal expression of genes from the entire genome (Jin et al., Reference Jin, Ping, Jie, Ying and Yongjian2010). For RecT, to ensure proper alignment of translocated chromosomes and homologous sequences, quadrivalents were formed and generated alternately, an adjacent-1, adjacent-2, 3:1, and 4:0 segregation could be performed (Kushnick, Reference Kushnick1992; Yuan et al., Reference Yuan, Zheng, Ou, Zhao, Li, Luo, Tan, Zhang and Wang2021). Therefore, 1/18 normal and 1/18 balanced gametes were ultimately formed, and the remaining 16/18 unbalanced gametes would theoretically cause recurrent abortion in RecT carrier couples. Sex can also exert different effects on the formation of normal, carrier, and unbalanced gametes (Ko et al., Reference Ko, Cho, Park, Kim, Koong, Song, Kang and Lim2010; Zhang et al., Reference Zhang, Lei, Wu, Sun, Zhou, Zhu, Wu, Fu, Sun, Lu, Sun and Zhang2018). Preimplantation genetic testing (PGT) for aneuploidies (PGT-A) and structural rearrangement (PGT-SR) can select embryos by performing a genetic test to identify and abandon those with chromosomal abnormalities and transfer the normal embryos to the uterus of patients with IVF in a suitable situation, and this can improve the outcomes of IVF (Xu et al., Reference Xu, Zhang, Niu, Yang, Yao, Shi, Jin, Song, Chen, Zhang, Guo, Su, Hu, Zhai, Zhang, Dong, Gao, Li and Bo2017; Zhang et al., Reference Zhang, Lei, Wu, Sun, Zhou, Zhu, Wu, Fu, Sun, Lu, Sun and Zhang2018; Findikli et al., Reference Findikli, Gultomruk, Boynukalin and Ogur2019; Shi et al., Reference Shi, Jiang, Zhou, Ye, Qin, Huang, Chen and Xu2021).

However, the theoretical rate of normal/balanced gametes for RecT/RobT carriers did not represent the true situation of normal/balanced gametes and embryos of these carriers, as several of the theoretical gametes were eliminated directly during the formation stage. Therefore, the rate of normal/balanced embryos in RecT/RobT carriers was not consistent with the theoretical results. The normal/balanced embryo rates among patients with RecT/RobT were observed to be different in previous studies (Boynukalin et al., Reference Boynukalin, Gultomruk, Turgut, Rubio, Rodrigo, Yarkiner, Ecemis, Karlikaya, Findikli and Bahceci2021; Yuan et al., Reference Yuan, Zheng, Ou, Zhao, Li, Luo, Tan, Zhang and Wang2021; Zhai et al., Reference Zhai, Wang, Li, Wang, Zhu, Kuo, Guan, Li, Song, He, An, Zhi, Lian, Huang, Li, Qiao, Yan and Yan2022), and it remains controversial if sex could affect the rate of normal/balanced embryos of patients with RecT/RobT. Certain scholars believe that there are differences in the normal/balanced ratio results among different embryos during the biopsy period (Beyer and Willats, Reference Beyer and Willats2017; Wang et al., Reference Wang, Li, Xu, Diao, Zhou, Lin and Zhang2019). The normal/balanced embryo ratio during the cleavage stage is lower than that during the blastocyst stage, and this can ensure that doctors provide more accurate genetic counselling services. Consequently, the genetic consultation of RecT/RobT carriers has primarily been based on the theoretical rate of gametes that was much lower than the reported normal/balanced embryos of patients with RecT/RobT, and this may also cause anxiety in patients. Accordingly, in this study the rates of normal/balanced embryos of 39,063 embryos were analyzed, and among 39,063 embryos, 9568 RobT carriers and 29,495 RecT carriers were included. Additionally, sex was considered in our study to reveal the plausible effect of sex on the rate of normal/balanced embryos in patients with RecT or RobT, and we verified the difference in the normal/balanced embryo ratio between the cleavage and blastocyst stages.

Materials and methods

Editorial policies and ethical considerations

This study was approved by the reproductive ethics board of the First Affiliated Hospital of Kunming Medical University, and informed consent was obtained from all patients.

To determine the normal/balanced embryo rate of patients with RecT/RobT with PGT, 9568 embryos from RobT carriers and 29,495 embryos from RecT carriers were analyzed. In this study, 4158 embryos from 856 RobT carriers and 13,378 embryos from 2924 RecT carriers were newly reported and provided by the Department of Medical Genetics of the Yikon Genomics Company in Jiangsu Suzhou, China. As presented in Tables 1 and 2, 5410 embryos from RobT carriers and 16,117 RecT carriers were retrieved from the literature (Tables 1 and 2). RecT and RobT carriers with preimplantation genetic testing (PGT)/preimplantation genetic diagnosis (PGD) were used as keywords to screen the literature in the PubMed, Cochrane Library, Web of Science, and Embase databases, respectively, and October 2022 was deemed as the deadline for the published literature. The abstract of each study was read, and balanced/normal embryo data of RecT and RobT carriers with PGT were retrieved from the literature to evaluate the rate of normal/balanced embryos from patients with RecT/RobT with PGT that were analyzed in this study. To further reveal the effect of sex, 856 RobT carriers and 2924 RecT carriers were grouped according to sex. Of the 856 RobT carriers, 420 were male and 436 were female. Similarly, 2924 RecT carriers included 1336 male and 1558 female carriers. Additionally, to verify the effect of the biopsy period on embryo karyotype, we divided all embryo data into two groups based on the biopsy period (cleavage stage and blastocyst stage). The cleavage and blastocyst stage embryos from both groups are recorded in detail in Table 5. Some of the embryonic karyotypes were not included for two reasons: they were obtained using methods other than biopsy; there were no detailed records of the biopsy period in the literature.

Table 1. Basic information obtained from the literature on RobT carriers

NA, Not available.

Table 2. Basic information obtained from the literature on Rec. T carriers

NA, Not available.

Statistical analysis

The ratio of normal to balanced embryos to the total embryos was recorded and calculated. The numbers of normal/balanced and unbalanced embryos were compared using the chi-squared test. A P-value < 0.05 was considered statistically significant in this study.

Results

General characteristics of the subjects

Normal/balanced embryos possess the common gene expression of the entire human genome, and this would not result in any clinical characteristics in patients. These types of embryos could be used for translation of couples suffering from RobT/RecT, despite the possibility that the offspring of the balanced carrier embryo could experience complications such as recurrent abortion. However, most RobT/RecT carriers with PGT might not possess sufficient embryos for transfer. Therefore, balanced embryos were also considered for transplantation. To determine the rate of normal/balanced embryos of RobT/RecT carriers and provide reliable genetic evidence for genetic consultation in clinics, 3780 patients with RobT/RecT were recruited for this study (856 RobT carriers and 2924 RecT carriers). In total, 4158 RobT carriers and 13,378 embryos RecT carrier embryos were identified. Averages of 4.86 (2924/856) embryos of RobT carriers and 4.56 (13,178/2924) embryos for each RecT carrier were subjected to PGT-A/PGT-SR. The average number of embryos in RobT carriers was higher than that in RecT carriers with PGT.

The rate of normal/balanced embryos from RobT/RecT carriers

The transfer of normal/balanced embryos from RobT/RecT carriers with PGT produced offspring without a phenotype. Therefore, normal/balanced embryos were present. However, the rate of normal/balanced embryos exhibited a large range of fluctuations, and this was not conducive for clinicians in regard to performing genetic counselling. Accordingly, to determine the probability of normal/balanced embryos in RobT/RecT carriers, the rate was analyzed among 39,063 embryos from patients with PGT. Among 856 RobT carriers, in total, 4158 embryos were retrieved with 1817 embryos characterized as normal/balanced embryos, and the rate of normal/balanced embryos was 43.70% (1817/4158) for RobT carriers. The limited embryos from the literature may not reflect the plausible rate of normal/balanced carrier embryos among all the embryos from RobT/RecT carriers. Therefore, the data for normal/balanced embryos were retrieved from the literature as presented in Table 3. By combining with the datasets from the literature, 2141 normal/balanced embryos were identified from 5140 embryos, and the rate of normal/balanced embryos was 39.57% (2141/5140). The total rate of normal/balanced embryos was 41.37% (3958/9568), and this was much higher than that based on the theory of gamete production.

Table 3. The rate of abnormal and normal phenotype embryos from RobT carriers and RecT carriers

* Chromosome normal or balanced embryos from RobT and RecT carriers.

Stratified analysis of normal/balanced embryo distribution based on carrier gender

It is well established that male RecT/RobT carriers produce a larger number of gametes each month compared with those of females, and this may cause less of an effect on normal or balanced embryos. Therefore, male RecT/RobT carriers may exhibit a higher proportion of normal/balanced embryos than female carriers. To explore if sex could affect the rate of normal/balanced embryos from RecT/RobT carriers, RecT/RobT carriers were grouped according to sex. Our data revealed that the rate of normal/balanced embryos in male RobT carriers was higher than that in female RobT carriers (49.60% vs. 37.44%), and a significant difference was detected between the two subgroups (P < 0.01) as presented in Table 4. Furthermore, the RecT carriers of PGT were also divided into male and female groups, and the data indicated a similar rate to that of RobT carriers (29.84% vs. 27.67%) (Table 4).

Table 4. The rate of abnormal and normal phenotype embryos from RobT carriers and RecT carriers

* Chromosome normal or balanced embryos from RobT and RecT carriers.

Table 5. The rate of normal/balanced embryos selected for biopsy during blastomere or trophoblast stages

* Chromosome normal or balanced embryos from RobT and RecT carriers.

Stratified analysis of normal/balanced embryo distribution of the biopsy period

Embryo cells from the third and fifth/sixth day of development were selected for biopsy during the cleavage and blastocyst stages, respectively. The number of fertilized egg cells on the third day of development was relatively small (only 6–8). Therefore, to reduce the effect on the embryo, only a small number of cells can be biopsied, and this leads to low accuracy of the results. On the fifth/sixth day of development there were more trophoblast cells, and 5–10 cells can be selected for biopsy, therefore greatly improving the accuracy and success rate of the results. Additionally, certain studies have reported that the normal/balanced rate of embryos in the blastocyst stage biopsy is slightly higher than that in the cleavage stage, and this is consistent with the results of the present study. There were 2534 cleavage-stage embryos in the Robertson translocation group. Of these, 914 were normal/balanced. There were 4571 embryos in the blastocyst stage, and of these 1985 were normal/balanced. For RecT, there were, in total, 6769 cleavage stage embryos and, of these, 1684 were normal/balanced embryos. In total, 18,064 embryos were in the blastocyst stage and, of these, 4998 were normal/balanced. The proportions of normal/balanced embryos at different biopsy periods in both groups were statistically significant (36.07% vs. 43.43% and 24.88% vs. 27.67%, respectively).

Discussion

Carrying RecT or RobT is the major reason for abortion and infertility due to the risk of generating imbalanced chromosome gametes. Natural pregnancy combined with prenatal diagnosis after pregnancy, oocyte or sperm donation, and PGT are different strategies to produce a phenotypically normal infant with a normal or balanced chromosome karyotype. Additionally, PGT has been widely approved by the carriers of RecT/RobT for producing phenotypically normal and genetic material that is consistent with that of the parents. However, most PGT procedures were performed by genetic diagnosis of blastula trophoblast cells for the blastosphere, and the culture of embryos from the cleavage-stage to the blastocyst stage led to the loss of embryos. This enhances the anxiety of patients with PGT during assisted reproductive technology (ART) and also increases the difficulty for doctors who perform genetic counselling. Due to the lack of large-scale datasets for normal/balanced embryos from RecT/RobT carriers with PGT, the theoretical probability rate of normal/balanced gametes of these carriers remains uncertain. For example, RobT carriers could possess 1/6 gametes with normal chromosomes, 1/6 gametes with balanced chromosomes, and 4/6 gametes with unbalanced chromosomes. RecT carriers would possess 1/18 gametes with normal chromosomes, 1/18 gametes with balanced chromosomes, and 16/18 gametes with unbalanced chromosomes. The unbalanced gametes would cause recurrent abortions. Accordingly, we aimed to provide robust genetic evidence supporting the proportion of normal/balanced gametes in RobT/RecT carriers and to determine if gender was a factor affecting the proportion of normal/balanced gametes in RobT/RecT carriers.

In total, 4158 embryos from 856 patients were obtained from RobT carriers with PGT, and this was slightly higher than the 13,378 embryos obtained from 2924 RecT carriers with PGT. Furthermore, in this study 4158 embryos from RobT carriers and 13,378 embryos from 2924 RecT carriers were analyzed, and our data revealed that each RobT carrier possessed 4.86 (2924/856) embryos and 4.56 (13,378/2924) embryos for each RecT carrier. Patients with RecT possessed fewer embryos than did RobT PGT carriers. Further analyses indicated that ∼41.37% (3958/9568) of RobT carriers with PGT possessed normal/balanced embryos, and this was higher than that for RecT carriers (26.96%; 7953/29495). Interestingly, the proportion of RobT carriers with PGT in this study was 43.70% (1817/4158), and this was higher than that reported in the literature (39.57%; 2141/5410). The consistent rate of normal/balanced embryos for RobT carriers with PGT from datasets in this study and the literature supported the reliable evidence that RobT carriers may exhibit a rate for obtaining ∼41.37% embryos for embryo transplantation, and this was consistent with that in previous studies (44.1%; 60/136; Liu et al., Reference Liu, Mao, Xu, Liu, Ma and Zhang2020). The pattern for RecT carriers was similar, in which the total rate of normal/balanced embryos for RecT carriers with PGT was 26.96% (7953/29,495), and the rate from datasets in this work was 28.75% (3846/13,378) and was consistent with datasets from literature (25.48%; 4107/16,117). Additionally, this rate is similar to that reported in recent studies (70/252, 27.8%). The rate of normal/balanced embryos in RobT/RecT carriers with PGT was higher than the theoretical value of synaptonemal complex segregation for RobT (2/6, 33.33% vs. 3958/9568; 41.37%) and RecT (2/18, 11.11% vs. 7953/29,495; 26.96%). Natural selection may play a crucial role during the processes of gametogenesis and embryogenesis (Mateu-Brull et al., Reference Mateu-Brull, Rodrigo, Peinado, Mercader, Campos-Galindo, Bronet, García-Herrero, Florensa, Milán and Rubio2019; Liu et al., Reference Liu, Mao, Xu, Liu, Ma and Zhang2020), and the higher ratio of normal/balanced embryos for RobT carriers (41.37%; 3958/9568) compared with that of RecT carriers (26.96%; 7953/29,495) may be caused by the higher alternate segregation of RobT carriers compared with that of RecT carriers (Liu et al., Reference Liu, Mao, Xu, Liu, Ma and Zhang2020). Specifically, both RobT carriers and RecT carriers exhibit a greater chance of obtaining a transferable embryo compared with the theoretical value, and this provides reliable genetic evidence for clinical genetic consulting for RobT/RecT carriers with the aim of performing PGT.

To further determine if sex could affect the rate of normal/balanced embryos, the 856 RobT carriers and 2924 RecT carriers were divided into two groups according to their sex. For RobT carriers, our data indicated that male carriers possess more normal/balanced embryos than female carriers (49.60% vs. 37.44). A significant difference between the two groups was detected with P = 0.000 (P < 0.05), and this indicated that male carriers possess a higher number of transferable embryos than do female carriers. However, for RecT carriers a higher transferable embryo rate was observed in 29.84% (1996/6690) of male carriers than was observed in female carriers (27.67%; 1850/6687) with P = 0.006 (P < 0.05). These data also indicated a higher number of transferable embryos in male RecT carriers. Our data illustrated that male carriers possess more normal/balanced embryos than do female RobT and RecT carriers. This is consistent with the results of a previous study (Liu et al., Reference Liu, Mao, Xu, Liu, Ma and Zhang2020). Therefore, the gender of the carrier should be considered when performing genetic consulting for patients with the aim of PGT. Additionally, according to the results of biopsy period grouping, the normal/balanced ratio of embryos in the blastocyst stage was higher than that in the cleavage stage (36.07% vs 43.43%; 24.88% vs 27.67%) in both groups of carriers for both RobT and RecT, therefore indicating a higher likelihood of obtaining normal/balanced embryos through blastocyst stage biopsy. This phenomenon may be explained by the observation that the process of embryo development from days 3 to 5/6 naturally eliminated poor-quality embryos.

However, the absence of patient information for data retrieved from the literature, including the age of RobT/RecT carriers, the number of patients participating in the research, and the clinical outcomes of PGT, restricts a better understanding of the clinical outcomes of PGT. Additionally, mosaic embryos with a low proportion of unbalanced chromosomes or a high proportion of unbalanced chromosomes were included in the datasets of this study and those from the literature, and this could be caused by technology such as fluorescence in situ hybridization (FISH) used for performing genetic diagnosis in the literature.

In conclusion, the performance of PGT could diagnose the normal/balanced embryos of RobT/RecT carriers, and this could reduce the clinical pregnancy rate of the carriers. However, the conventional genetic consulting of RobT/RecT carriers was primarily explained with theoretical values of 2/6 and 2/18, and this did not reflect the real ratios of the normal/balanced embryos and may cause anxiety to carriers. The plausible ratios were illustrated in previous studies and ranged from 1.79% to 55.56% for RecT carriers (Sampson et al., Reference Sampson, Ouhibi, Lawce, Patton, Battaglia, Burry and Olson2004; Zhang et al., Reference Zhang, Zhao, Zhang, Mao, Kong, Zhang, Liang, Sun and Xu2019) and from 10.00% to 79.66% for RobT carriers (Tulay et al., Reference Tulay, Gultomruk, Findikli and Bahceci2016; Xu et al., Reference Xu, Jin, Qian, Ye, Zhu and Huang2004). The small sample size was the major factor responsible for causing the fluctuations in the normal/balanced embryo rate of RobT/RecT carriers. Consequently, to provide reliable genetic datasets for genetic consulting, the large-scale embryos of RobT/RecT carriers were collected and analyzed in this study. The datasets illustrated that the rates of normal/balanced embryos were 41.37% among 9568 embryos from RobT carriers and 26.96% from 29,495 embryos from RecT. The rates were much higher than the theoretical values of 2/6 and 2/18. The male carriers for both RobT and RecT exhibited a higher rate of normal/balanced embryos compared with that of female groups, and the ratio of normal/balanced embryos in the blastocyst stage was higher than that in the cleavage stage. This supplied robust genetic evidence for performing genetic consulting for RobT/RecT carriers with PGT.

Financial support

This study was supported by funds from the Shanghai Key Laboratory of Embryo Original Diseases (Shelab202003), the Applied Basic Research Joint Project of Yunnan Province Science and Technology Department and Kunming Medical University (202301AY070001-087), the Project of Education Teaching Research of Kunming Medical University(2023-JY-Y-108), and Yunnan Province High-level Personnel Training Programme (RLMY20200017).

Competing interests

The authors declare no conflicts of interest.

Ethical standard

The authors assert that all procedures contributing to this work complied with the ethical standards of the relevant national and institutional committees on human experimentation and the Declaration of Helsinki of 1975 as revised in 2008.

Footnotes

*

Authors contributed equally.

References

Alfarawati, S., Fragouli, E., Colls, P. and Wells, D. (2012). Embryos of robertsonian translocation carriers exhibit a mitotic interchromosomal effect that enhances genetic instability during early development. PLOS Genetics, 8(10), e1003025. doi: 10.1371/journal.pgen.1003025 CrossRefGoogle ScholarPubMed
Alves, C., Sousa, M., Silva, J. and Barros, A. (2002). Preimplantation genetic diagnosis using FISH for carriers of robertsonian translocations: The Portuguese experience. Prenatal Diagnosis, 22(12), 1153–1162. doi: 10.1002/pd.503 CrossRefGoogle ScholarPubMed
Amir, H., Barbash-Hazan, S., Kalma, Y., Frumkin, T., Malcov, M., Samara, N., Hasson, J., Reches, A., Azem, F. and Ben-Yosef, D. (2019). Time-lapse imaging reveals delayed development of embryos carrying unbalanced chromosomal translocations. Journal of Assisted Reproduction and Genetics, 36(2), 315–324. doi: 10.1007/s10815-018-1361-8 CrossRefGoogle ScholarPubMed
Beyer, C. E. and Willats, E. (2017). Natural selection between day 3 and day 5/6 PGD embryos in couples with reciprocal or robertsonian translocations. Journal of Assisted Reproduction and Genetics, 34(11), 1483–1492. doi: 10.1007/s10815-017-1009-0 CrossRefGoogle ScholarPubMed
Bono, S., Biricik, A., Spizzichino, L., Nuccitelli, A., Minasi, M. G., Greco, E., Spinella, F. and Fiorentino, F. (2015). Validation of a semiconductor next-generation sequencing-based protocol for preimplantation genetic diagnosis of reciprocal translocations. Prenatal Diagnosis, 35(10), 938–944. doi: 10.1002/pd.4665 CrossRefGoogle ScholarPubMed
Boynukalin, F. K., Gultomruk, M., Turgut, N. E., Rubio, C., Rodrigo, L., Yarkiner, Z., Ecemis, S., Karlikaya, G., Findikli, N. and Bahceci, M. (2021). The impact of patient, embryo, and translocation characteristics on the ploidy status of young couples undergoing preimplantation genetic testing for structural rearrangements (PGT-SR) by next generation sequencing (NGS). Journal of Assisted Reproduction and Genetics, 38(2), 387–396. doi: 10.1007/s10815-020-02054-4.CrossRefGoogle ScholarPubMed
Celestine, C. K., Werner, M. D., Franasiak, J. M., Juneau, C. R., Treff, N. R., Molinaro, T. and Scott, R. T. (2015). Does the parental origin of translocation impact rates of abnormal embryos? Fertility and Sterility, 104(3), e232. doi: 10.1016/j.fertnstert.2015.07.730 CrossRefGoogle Scholar
Findikli, N., Gultomruk, M., Boynukalin, F. K. & Ogur, C. (2019) Possible impact of interchromosomal effect at the blastocyst stage in cases undergoing PGT-A for translocations. Reproductive Biomedicine Online, 38(Suppl. 1), e56–e57. doi: 10.1016/j.rbmo.2019.03.090 CrossRefGoogle Scholar
Fiorentino, F., Kokkali, G., Biricik, A., Stavrou, D., Ismailoglu, B., De Palma, R., Arizzi, L., Harton, G., Sessa, M. and Pantos, K. (2010). Polymerase chain reaction-based detection of chromosomal imbalances on embryos: The evolution of preimplantation genetic diagnosis for chromosomal translocations. Fertility and Sterility, 94(6). doi: 10.1016/j.fertnstert.2009.12.063.CrossRefGoogle ScholarPubMed
Gianaroli, L., Magli, M. C., Ferraretti, A. P., Munné, S., Balicchia, B., Escudero, T. and Crippa, A. (2002). Possible interchromosomal effect in embryos generated by gametes from translocation carriers. Human Reproduction, 17(12), 3201–3207. doi: 10.1093/humrep/17.12.3201 CrossRefGoogle ScholarPubMed
Jin, H., Ping, L., Jie, Q., Ying, L. and Yongjian, C. (2010). Translocation chromosome karyotypes of the robertsonian translocation carriers’ embryos. Fertility and Sterility, 93(4), 1061–1065. doi: 10.1016/j.fertnstert.2008.11.020 CrossRefGoogle ScholarPubMed
Ko, D. S., Cho, J. W., Park, S. Y., Kim, J. Y., Koong, M. K., Song, I. O., Kang, I. S. and Lim, C. K. (2010). Clinical outcomes of preimplantation genetic diagnosis (PGD) and analysis of meiotic segregation modes in reciprocal translocation carriers. American Journal of Medical Genetics. Part A, 152A(6), 1428–1433. doi: 10.1002/ajmg.a.33368 CrossRefGoogle ScholarPubMed
Kuliev, A., Janzen, J. C., Zlatopolsky, Z., Kirillova, I., Ilkevitch, Y. and Verlinsky, Y. (2010). Conversion and non-conversion approach to preimplantation diagnosis for chromosomal rearrangements in 475 cycles. Reproductive Biomedicine Online, 21(1), 93–99. doi: 10.1016/j.rbmo.2010.04.003 CrossRefGoogle ScholarPubMed
Kushnick, T. (1992). Thompson & Thompson Genetics in Medicine. JAMA 267(15), 2115–2115.CrossRefGoogle Scholar
Kyu Lim, C., Hyun Jun, J., Mi Min, D., Lee, H. S., Young Kim, J., Koong, M. K. and Kang, I. S. (2004). Efficacy and clinical outcome of preimplantation genetic diagnosis using FISH for couples of reciprocal and robertsonian translocations: The Korean experience. Prenatal Diagnosis, 24(7), 556–561. doi: 10.1002/pd.923 CrossRefGoogle ScholarPubMed
Lammers, J., Reignier, A., Splingart, C., Moradkhani, K., Barrière, P. and Fréour, T. (2019). Morphokinetic parameters in chromosomal translocation carriers undergoing preimplantation genetic testing. Reproductive Biomedicine Online, 38(2), 177–183. doi: 10.1016/j.rbmo.2018.11.006 CrossRefGoogle ScholarPubMed
Li, G., Sun, Y. P., Jin, H. X., Xin, Z. M. and Dai, S. J. (2009). Application of sperm fluorescence in situ hybridization in preimplantation genetic diagnosis. Zhonghua Fu Chan Ke Za Zhi, 44(6), 418–421.Google ScholarPubMed
Li, R., Wang, J., Gu, A., Xu, Y., Guo, J., Pan, J., Zeng, Y., Ma, Y., Zhou, C. and Xu, Y. (2021). Feasibility study of using unbalanced embryos as a reference to distinguish euploid carrier from noncarrier embryos by single nucleotide polymorphism array for reciprocal translocations. Prenatal Diagnosis, 41(6), 681–689. doi: 10.1002/pd.5897 CrossRefGoogle ScholarPubMed
Liu, H., Mao, B., Xu, X., Liu, L., Ma, X. and Zhang, X. (2020). The effectiveness of next-generation sequencing-based preimplantation genetic testing for balanced translocation couples. Cytogenetic and Genome Research, 160(11–12), 625–633. doi: 10.1159/000512847 CrossRefGoogle ScholarPubMed
Mardesić, T., Kosarová, M., Zudová, D., Jelínková, L., Sobotka, V. and Gregor, V. (2011). [Preimplantation genetic diagnosis (PGD) in carriers of chromosomal translocations: Possibilities and results]. Ceská Gynekologie, 76(2), 100–103.Google ScholarPubMed
Mateu-Brull, E., Rodrigo, L., Peinado, V., Mercader, A., Campos-Galindo, I., Bronet, F., García-Herrero, S., Florensa, M., Milán, M. and Rubio, C. (2019). Interchromosomal effect in carriers of translocations and inversions assessed by preimplantation genetic testing for structural rearrangements (PGT-SR). Journal of Assisted Reproduction and Genetics, 36(12), 2547–2555. doi: 10.1007/s10815-019-01593-9 CrossRefGoogle ScholarPubMed
McKenzie, L. J., Cisneros, P. L., Torsky, S., Bacino, C. A., Buster, J. E., Carson, S. A., Simpson, J. L. and Bischoff, F. (2003). Preimplantation genetic diagnosis for a known cryptic translocation: Follow-up clinical report and implication of segregation products. American Journal of Medical Genetics. Part A, 121A(1), 56–59. doi: 10.1002/ajmg.a.20159 CrossRefGoogle ScholarPubMed
Munné, S., Sandalinas, M., Escudero, T., Fung, J., Gianaroli, L. and Cohen, J. (2000). Outcome of preimplantation genetic diagnosis of translocations. Fertility and Sterility, 73(6), 1209–1218. doi: 10.1016/s0015-0282(00)00495-7 CrossRefGoogle ScholarPubMed
Pei, Z., Deng, K., Lei, C., Du, D., Yu, G., Sun, X., Xu, C. and Zhang, S. (2021). Identifying balanced chromosomal translocations in human embryos by Oxford nanopore sequencing and breakpoints region analysis. Frontiers in Genetics, 12, 810900. doi: 10.3389/fgene.2021.810900 CrossRefGoogle ScholarPubMed
Sampson, J. E., Ouhibi, N., Lawce, H., Patton, P. E., Battaglia, D. E., Burry, K. A. and Olson, S. B. (2004). The role for preimplantation genetic diagnosis in balanced translocation carriers. American Journal of Obstetrics and Gynecology, 190(6), 1707–1711; discussion 1711–1703. doi: 10.1016/j.ajog.2004.02.063 CrossRefGoogle ScholarPubMed
Sarasa, J., Wheeler, K., Lansdowne, L., Raberi, A., Babariya, D. and Wells, D. (2015). Clinical experience using single nucleotide polymorphism (SNP) arrays for preimplantation genetic diagnosis (PGD) of chromosomal translocations. Human Reproduction, 30, 403–403.Google Scholar
Shi, W. H., Jiang, Z. R., Zhou, Z. Y., Ye, M. J., Qin, N. X., Huang, H. F., Chen, S. C. and Xu, C. M. (2021). Different strategies of preimplantation genetic testing for aneuploidies in women of advanced maternal age: A systematic review and meta-analysis. Journal of Clinical Medicine, 10(17), 3895. doi: 10.3390/jcm10173895 CrossRefGoogle ScholarPubMed
Tan, Y. Q., Tan, K., Zhang, S. P., Gong, F., Cheng, D. H., Xiong, B., Lu, C. F., Tang, X. C., Luo, K. L., Lin, G. and Lu, G. X. (2013). Single-nucleotide polymorphism microarray-based preimplantation genetic diagnosis is likely to improve the clinical outcome for translocation carriers. Human Reproduction, 28(9), 2581–2592. doi: 10.1093/humrep/det271 CrossRefGoogle ScholarPubMed
Tobler, K. J., Brezina, P. R., Benner, A. T., Du, L., Xu, X. and Kearns, W. G. (2014). Two different microarray technologies for preimplantation genetic diagnosis and screening, due to reciprocal translocation imbalances, demonstrate equivalent euploidy and clinical pregnancy rates. Journal of Assisted Reproduction and Genetics, 31(7), 843–850. doi: 10.1007/s10815-014-0230-3 CrossRefGoogle ScholarPubMed
Tulay, P., Gultomruk, M., Findikli, N. and Bahceci, M. (2015). Poor embryo development and preimplantation genetic diagnosis outcomes of translocations involving chromosome 10: Do we blame genetics? Zygote, 23(5), 778–784. doi: 10.1017/S0967199414000422 CrossRefGoogle ScholarPubMed
Tulay, P., Gultomruk, M., Findikli, N. and Bahceci, M. (2016). Number of embryos biopsied as a predictive indicator for the outcome of preimplantation genetic diagnosis by fluorescence in situ hybridisation in translocation cases. Zygote, 24(1), 107–114. doi: 10.1017/S0967199414000793 CrossRefGoogle ScholarPubMed
Verlinsky, Y., Cieslak, J., Evsikov, S., Galat, V. and Kuliev, A. (2002). Nuclear transfer for full karyotyping and preimplantation diagnosis for translocations. Reproductive Biomedicine Online, 5(3), 300–305. doi: 10.1016/s1472-6483(10)61836-6 CrossRefGoogle ScholarPubMed
Wang, Y. Z., Ding, C. H., Wang, J., Zeng, Y. H., Zhou, W., Li, R., Zhou, C. Q., Deng, M. F. and Xu, Y. W. (2017). Number of blastocysts biopsied as a predictive indicator to obtain at least one normal/balanced embryo following preimplantation genetic diagnosis with single nucleotide polymorphism microarray in translocation cases. Journal of Assisted Reproduction and Genetics, 34(1), 51–59. doi: 10.1007/s10815-016-0831-0 CrossRefGoogle ScholarPubMed
Wang, J., Li, D., Xu, Z., Diao, Z., Zhou, J., Lin, F. and Zhang, N. (2019). Analysis of meiotic segregation modes in biopsied blastocysts from preimplantation genetic testing cycles of reciprocal translocations. Molecular Cytogenetics, 12, 11. doi: 10.1186/s13039-019-0423-7 CrossRefGoogle ScholarPubMed
Wiland, E., Hobel, C. J., Hill, D. and Kurpisz, M. (2008). Successful pregnancy after preimplantation genetic diagnosis for carrier of t(2;7)(p11.2;q22) with high rates of unbalanced sperm and embryos: A case report. Prenatal Diagnosis, 28(1), 36–41. doi: 10.1002/pd.1899 CrossRefGoogle Scholar
Xie, Y., Xu, Y., Wang, J., Miao, B., Zeng, Y., Ding, C., Gao, J. and Zhou, C. (2018). Preliminary analysis of numerical chromosome abnormalities in reciprocal and robertsonian translocation preimplantation genetic diagnosis cases with 24-chromosomal analysis with an aCGH/SNP microarray. Journal of Assisted Reproduction and Genetics, 35(1), 177–186. doi: 10.1007/s10815-017-1045-9 CrossRefGoogle ScholarPubMed
Xu, C. M., Jin, F., Qian, Y. L., Ye, Y. H., Zhu, Y. M. and Huang, H. F. (2004). Preimplantation genetic diagnosis of chromosome abnormality by fluorescence in-situ hybridization. Zhonghua Fu Chan Ke Za Zhi, 39(7), 453–456.Google ScholarPubMed
Xu, Y. W., Zhou, C. Q., Zeng, Y. H., Liu, Y., Gao, L. and Zhuang, G. L. (2011). Clinical analysis of 100 preimplantation genetic diagnosis cycles. Zhonghua Fu Chan Ke Za Zhi, 46(4), 255–259.Google ScholarPubMed
Xu, J., Zhang, Z., Niu, W., Yang, Q., Yao, G., Shi, S., Jin, H., Song, W., Chen, L., Zhang, X., Guo, Y., Su, Y., Hu, L., Zhai, J., Zhang, Y., Dong, F., Gao, Y., Li, W., Bo, S., et al. (2017). Mapping allele with resolved carrier status of Robertsonian and reciprocal translocation in human preimplantation embryos. Proceedings of the National Academy of Sciences of the United States of America, 114(41), E8695–E8702. doi: 10.1073/pnas.1715053114 Google ScholarPubMed
Yu-li, Q., Chen-ming, X., Fan, J., Yi-Min, Z., Qiong, L. and He-feng, H. (2008); Preimplantation genetic diagnosis of translocation. Chinese Journal of Obstetrics and Gynecology, 43(8), 581–583.Google Scholar
Yuan, P., Zheng, L., Ou, S., Zhao, H., Li, R., Luo, H., Tan, X., Zhang, Q. and Wang, W. (2021). Evaluation of chromosomal abnormalities from preimplantation genetic testing to the reproductive outcomes: A comparison between three different structural rearrangements based on next-generation sequencing. Journal of Assisted Reproduction and Genetics, 38(3), 709–718. doi: 10.1007/s10815-020-02053-5 CrossRefGoogle Scholar
Zhai, F., Wang, Y., Li, H., Wang, Y., Zhu, X., Kuo, Y., Guan, S., Li, J., Song, S., He, Q., An, J., Zhi, X., Lian, Y., Huang, J., Li, R., Qiao, J., Yan, L. and Yan, Z. (2022). Preimplantation genetic testing for structural rearrangement based on low-coverage next-generation sequencing accurately discriminates between normal and carrier embryos for patients with translocations. Reproductive Biomedicine Online, 45(3), 473–480. doi: 10.1016/j.rbmo.2022.05.012 CrossRefGoogle ScholarPubMed
Zhang, S., Lei, C., Wu, J., Sun, H., Zhou, J., Zhu, S., Wu, J., Fu, J., Sun, Y., Lu, D., Sun, X. and Zhang, Y. (2018). Analysis of segregation patterns of quadrivalent structures and the effect on genome stability during meiosis in reciprocal translocation carriers. Human Reproduction, 33(4), 757–767. doi: 10.1093/humrep/dey036 CrossRefGoogle ScholarPubMed
Zhang, S., Zhao, D., Zhang, J., Mao, Y., Kong, L., Zhang, Y., Liang, B., Sun, X. and Xu, C. (2019). BasePhasing: A highly efficient approach for preimplantation genetic haplotyping in clinical application of balanced translocation carriers. BMC Medical Genomics, 12(1), 52. doi: 10.1186/s12920-019-0495-6 CrossRefGoogle ScholarPubMed
Zhou, Z., Ma, Y. L., Li, Q., Zhang, Y., Huang, Y. H., Tu, Z. H., Ma, N., Chen, X. Y. and Xu, W. (2017). Clinical application of oligo array-CGH for detecting balanced translocations in preimplantation genetic diagnosis. International Journal of Clinical and Experimental Pathology, 10(7), 7821–7835.Google ScholarPubMed
Figure 0

Table 1. Basic information obtained from the literature on RobT carriers

Figure 1

Table 2. Basic information obtained from the literature on Rec. T carriers

Figure 2

Table 3. The rate of abnormal and normal phenotype embryos from RobT carriers and RecT carriers

Figure 3

Table 4. The rate of abnormal and normal phenotype embryos from RobT carriers and RecT carriers

Figure 4

Table 5. The rate of normal/balanced embryos selected for biopsy during blastomere or trophoblast stages