胚胎植入前非整倍体检测(PGT-A)在三大适应人群中的研究异质性与分层研究展望
Heterogeneity and Stratification of Preimplantation Genetic Grafting (PGT-A) Testing in Three Adapted Populations: A Future Study
DOI: 10.12677/jcpm.2026.54221, PDF,    科研立项经费支持
作者: 曹刘慧：济宁医学院临床医学院，山东 济宁；杨爱军*：济宁医学院附属医院生殖医学科，山东 济宁
关键词: 胚胎植入前非整倍体检测；高龄不孕；复发性流产；反复种植失败 ；Preimplantation Aneuploidy Testing； Advanced Maternal Age Infertility； Recurrent Miscarriage； Repeated Implantation Failure
摘要: 背景：高龄(Advanced Maternal Age, AMA)、复发性流产(Recurrent Spontaneous Abortion, RSA)、反复种植失败(Recurrent Implantation Failure, RIF)是胚胎植入前非整倍体检测(Preimplantation Genetic Testing for Aneuploidy, PGT-A)的三大核心适应症。然而，目前针对这三类人群的研究多为独立的单一人群分析，研究设计、纳入标准、结局指标等关键因素存在显著差异，导致研究结论难以横向比较，临床决策缺乏统一证据支持。目的：系统梳理PGT-A在高龄、RSA、RIF三类人群中的研究现状，重点分析研究设计的异质性及其对结论可比性的影响，揭示当前研究的局限性与未来方向。方法：检索国内外相关文献，对三类人群的研究进行归纳，比较不同研究在纳入标准、对照组设置、混杂因素等方面的差异。结果：三类人群的研究在关键设计要素上存在显著异质性，导致不同人群、不同研究间的结论无法直接横向比较。目前尚缺乏将三类人群置于同一研究框架下进行分层比较的高质量研究。结论：开展基于多中心、大样本、规范的统一设计、对三大适应症进行分层比较的临床研究，对于PGT-A的真实临床价值、指导个体化治疗具有重要意义。
Abstract: Background: Advanced maternal age (AMA), recurrent spontaneous abortion (RSA), and recurrent implantation failure (RIF) are the three core indications for preimplantation genetic testing for aneuploidy (PGT-A). However, current studies on these three populations are mostly independent single-population analyses, with significant differences in key factors such as study design, inclusion criteria, and outcome measures, making cross-sectional comparisons of research conclusions difficult and lacking unified evidence to support clinical decisions. Objective: To systematically review the current research status of PGT-A in the three populations of advanced maternal age, RSA, and RIF, focusing on analyzing the heterogeneity of study design and its impact on the comparability of conclusions, revealing the limitations of current research and future directions. Methods: Relevant domestic and international literature was retrieved, and studies on the three populations were summarized, comparing differences in inclusion cri, control group settings, and confounding factors among different studies. Results: Significant heterogeneity exists in key design elements among the studies of the three populations, making direct cross-sectional comparisons of conclusions between different populations and different studies impossible. Currently, there is a lack of high-quality studies that stratify and compare the three population groups within the same research framework. Conclusion: Conducting multi-center, large-sample, standardized, and uniformly designed clinical studies that stratify and compare the three indications is of great significance for understanding the true clinical value of PGT-A and guiding individualized treatment.
文章引用：曹刘慧, 杨爱军. 胚胎植入前非整倍体检测(PGT-A)在三大适应人群中的研究异质性与分层研究展望[J]. 临床个性化医学, 2026, 5(4): 28-37. https://doi.org/10.12677/jcpm.2026.54221

参考文献

[1] Kuznyetsov, V., Madjunkova, S., Antes, R., Abramov, R., Motamedi, G., Ibarrientos, Z., et al. (2018) Evaluation of a Novel Non-Invasive Preimplantation Genetic Screening Approach. PLOS ONE, 13, e0197262.
https://doi.org/10.1371/journal.pone.0197262
[2] 程德华, 谢平原, 胡晓, 等. 胚胎植入前遗传学检测技术的临床应用和发展前景[J]. 实用妇产科杂志, 2023, 39(3): 167-171.
[3] 徐晨明. 胚胎植入前遗传学诊断/筛查技术专家共识[J]. 中国产前诊断杂志(电子版), 2018, 10(2): 57.
[4] 黄色新, 邹洋, 高明, 等. 《胚胎植入前遗传学检测的遗传咨询专家共识》解读[J]. 实用妇产科杂志, 2025(8): 636-640.
[5] Faust, J.S. (2016) Sci-Hub. Annals of Emergency Medicine, 68, A15-A17.
https://doi.org/10.1016/j.annemergmed.2016.05.010
[6] Munné, S., Kaplan, B., Frattarelli, J.L., Child, T., Nakhuda, G., Shamma, F.N., et al. (2019) Preimplantation Genetic Testing for Aneuploidy versus Morphology as Selection Criteria for Single Frozen-Thawed Embryo Transfer in Good-Prognosis Patients: A Multicenter Randomized Clinical Trial. Fertility and Sterility, 112, 1071-1079.e7.
https://doi.org/10.1016/j.fertnstert.2019.07.1346
[7] Porter, T.F. and Scott, J.R. (2005) Evidence-Based Care of Recurrent Miscarriage. Best Practice & Research Clinical Obstetrics & Gynaecology, 19, 85-101.
https://doi.org/10.1016/j.bpobgyn.2004.11.005
[8] Dimitriadis, E., Menkhorst, E., Saito, S., Kutteh, W.H. and Brosens, J.J. (2020) Recurrent Pregnancy Loss. Nature Reviews Disease Primers, 6, Article No. 98.
https://doi.org/10.1038/s41572-020-00228-z
[9] 全松, 刘婧. 反复种植失败的定义及影响因素[J]. 实用妇产科杂志, 2018, 34(5): 321-324.
[10] Dong, L., Teh, D.B.L., Kennedy, B.K. and Huang, Z. (2023) Unraveling Female Reproductive Senescence to Enhance Healthy Longevity. Cell Research, 33, 11-29.
https://doi.org/10.1038/s41422-022-00718-7
[11] Franasiak, J.M., Forman, E.J., Hong, K.H., Werner, M.D., Upham, K.M., Treff, N.R., et al. (2014) The Nature of Aneuploidy with Increasing Age of the Female Partner: A Review of 15,169 Consecutive Trophectoderm Biopsies Evaluated with Comprehensive Chromosomal Screening. Fertility and Sterility, 101, 656-663.e1.
https://doi.org/10.1016/j.fertnstert.2013.11.004
[12] Vitagliano, A., Paffoni, A. and Viganò, P. (2023) Does Maternal Age Affect Assisted Reproduction Technology Success Rates after Euploid Embryo Transfer? A Systematic Review and Meta-Analysis. Fertility and Sterility, 120, 251-265.
https://doi.org/10.1016/j.fertnstert.2023.02.036
[13] 李孟芸, 张婧妤, 周建军. 高龄不孕症患者冷冻单囊胚移植的临床结局分析[J/OL]. 兰州大学学报(医学版), 2025: 1-6.
https://link.cnki.net/urlid/62.1194.R.20251229.1328.004, 2025-12-30.
[14] Youssef, A., Vermeulen, N., Lashley, E.E.L.O., Goddijn, M. and van der Hoorn, M.L.P. (2019) Comparison and Appraisal of (Inter)national Recurrent Pregnancy Loss Guidelines. Reproductive BioMedicine Online, 39, 497-503.
https://doi.org/10.1016/j.rbmo.2019.04.008
[15] 孙晓溪. 胚胎植入前遗传学诊断[J]. 中国产前诊断杂志, 2018, 10(2): 57.
[16] Zhang, C., Deng, X., Zhang, X., Pan, Z., Zhao, W., Zhang, Y., et al. (2016) Association between Serum TNF-α Levels and Recurrent Spontaneous Miscarriage: A Meta-Analysis. American Journal of Reproductive Immunology, 75, 86-93.
https://doi.org/10.1111/aji.12447
[17] Lei, C., Ye, J., Sui, Y., Zhang, Y. and Sun, X. (2019) Retrospective Cohort Study of Preimplantation Genetic Testing for Aneuploidy with Comprehensive Chromosome Screening versus Nonpreimplantation Genetic Testing in Normal Karyotype, Secondary Infertility Patients with Recurrent Pregnancy Loss. Reproductive and Developmental Medicine, 3, 205-212.
https://doi.org/10.4103/2096-2924.274544
[18] Zhao, S., Lyu, C., Liu, Y., Wang, X., Zhang, Z., Lv, H., et al. (2024) Preimplantation Genetic Testing for Aneuploidy Could Not Improve Cumulative Live Birth Rate among 1003 Couples with Recurrent Pregnancy Loss. Chinese Medical Journal, 137, 2134-2136.
https://doi.org/10.1097/cm9.0000000000003041
[19] Wang, A., Kort, J. and Westphal, L. (2019) Miscarriage History Association with Euploid Embryo Transfer Outcomes. Reproductive BioMedicine Online, 39, 617-623.
https://doi.org/10.1016/j.rbmo.2019.05.011
[20] Ni, T., Wu, Q., Zhu, Y., Jiang, W., Zhang, Q., Li, Y., et al. (2020) Comprehensive Analysis of the Associations between Previous Pregnancy Failures and Blastocyst Aneuploidy as Well as Pregnancy Outcomes after PGT-A. Journal of Assisted Reproduction and Genetics, 37, 579-588.
https://doi.org/10.1007/s10815-020-01722-9
[21] Pfeifer, S. and Marc Fritz, J.G. (2012) Evaluation and Treatment of Recurrent Pregnancy Loss: A Committee Opinion. Fertility and Sterility, 98, 1103-1111.
[22] Cimadomo, D., Capalbo, A., Dovere, L., Tacconi, L., Soscia, D., Giancani, A., et al. (2021) Leave the Past Behind: Women’s Reproductive History Shows No Association with Blastocysts’ Euploidy and Limited Association with Live Birth Rates after Euploid Embryo Transfers. Human Reproduction, 36, 929-940.
https://doi.org/10.1093/humrep/deab014
[23] Coughlan, C., Ledger, W., Wang, Q., Liu, F., Demirol, A., Gurgan, T., et al. (2014) Recurrent Implantation Failure: Definition and Management. Reproductive BioMedicine Online, 28, 14-38.
https://doi.org/10.1016/j.rbmo.2013.08.011
[24] ESHRE PGT Consortium Steering Committee, et al. (2020) ESHRE PGT Consortium Good Practice Recommendations for the Organisation of PGT. Human Reproduction Open, 2020, hoaa021.
https://doi.org/10.1093/hropen/hoaa021
[25] Thornhill, A.R., deDie-Smulders, C.E., Geraedts, J.P., Harper, J.C., Harton, G.L., Lavery, S.A., et al. (2005) ESHRE PGD Consortium “Best Practice Guidelines for Clinical Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic Screening (PGS)”. Human Reproduction, 20, 35-48.
https://doi.org/10.1093/humrep/deh579
[26] Polanski, L.T., Baumgarten, M.N., Quenby, S., Brosens, J., Campbell, B.K. and Raine-Fenning, N.J. (2014) What Exactly Do We Mean by “Recurrent Implantation Failure”? A Systematic Review and Opinion. Reproductive BioMedicine Online, 28, 409-423.
https://doi.org/10.1016/j.rbmo.2013.12.006
[27] Sato, T., Sugiura-Ogasawara, M., Ozawa, F., Yamamoto, T., Kato, T., Kurahashi, H., et al. (2019) Preimplantation Genetic Testing for Aneuploidy: A Comparison of Live Birth Rates in Patients with Recurrent Pregnancy Loss Due to Embryonic Aneuploidy or Recurrent Implantation Failure. Human Reproduction, 34, 2340-2348.
https://doi.org/10.1093/humrep/dez229
[28] Fodina, V., Dudorova, A. and Erenpreiss, J. (2021) Evaluation of Embryo Aneuploidy (PGT-A) and Endometrial Receptivity (ERA) Testing in Patients with Recurrent Implantation Failure in ICSI Cycles. Gynecological Endocrinology, 37, 17-20.
https://doi.org/10.1080/09513590.2021.2006466
[29] Busnelli, A., Somigliana, E., Cirillo, F., Baggiani, A. and Levi-Setti, P.E. (2021) Efficacy of Therapies and Interventions for Repeated Embryo Implantation Failure: A Systematic Review and Meta-Analysis. Scientific Reports, 11, Article No. 1747.
https://doi.org/10.1038/s41598-021-81439-6
[30] Blockeel, C., Schutyser, V., De Vos, A., Verpoest, W., De Vos, M., Staessen, C., et al. (2008) Prospectively Randomized Controlled Trial of PGS in IVF/ICSI Patients with Poor Implantation. Reproductive BioMedicine Online, 17, 848-854.
https://doi.org/10.1016/s1472-6483(10)60414-2
[31] Greco, E., Bono, S., Ruberti, A., Lobascio, A.M., Greco, P., Biricik, A., et al. (2014) Comparative Genomic Hybridization Selection of Blastocysts for Repeated Implantation Failure Treatment: A Pilot Study. BioMed Research International, 2014, Article ID: 457913.
https://doi.org/10.1155/2014/457913
[32] Rubio, C., Bellver, J., Rodrigo, L., Bosch, E., Mercader, A., Vidal, C., et al. (2013) Preimplantation Genetic Screening Using Fluorescence in Situ Hybridization in Patients with Repetitive Implantation Failure and Advanced Maternal Age: Two Randomized Trials. Fertility and Sterility, 99, 1400-1407.
https://doi.org/10.1016/j.fertnstert.2012.11.041
[33] Yakin, K., Ata, B., Ercelen, N., Balaban, B. and Urman, B. (2008) The Effect of Preimplantation Genetic Screening on the Probability of Live Birth in Young Women with Recurrent Implantation Failure; a Nonrandomized Parallel Group Trial. European Journal of Obstetrics & Gynecology and Reproductive Biology, 140, 224-229.
https://doi.org/10.1016/j.ejogrb.2008.05.005
[34] Wang, Z., Huang, S., Yang, J., Li, D. and Xu, Y. (2023) Subfertile Chinese Patients with Diminished Ovarian Reserve: An Analysis of Pregnancy Outcomes of ART Cycles. Pakistan Journal of Medical Sciences, 39, 338-343.
https://doi.org/10.12669/pjms.39.2.6226
[35] Li, L., Sun, B., Wang, F., Zhang, Y. and Sun, Y. (2022) Which Factors Are Associated with Reproductive Outcomes of DOR Patients in ART Cycles: An Eight-Year Retrospective Study. Frontiers in Endocrinology, 13, Article ID: 796199.
https://doi.org/10.3389/fendo.2022.796199
[36] Hao, Y., Wang, Y., Yan, L., Xu, X., Chen, D., Zhao, Y., et al. (2023) Synthetic Phenolic Antioxidants and Their Metabolites in Follicular Fluid and Association with Diminished Ovarian Reserve: A Case-Control Study. Environmental Health Perspectives, 131, Article No. 67005.
https://doi.org/10.1289/ehp11309
[37] Devesa-Peiro, A., Sebastian-Leon, P., Parraga-Leo, A., Pellicer, A. and Diaz-Gimeno, P. (2022) Breaking the Ageing Paradigm in Endometrium: Endometrial Gene Expression Related to Cilia and Ageing Hallmarks in Women over 35 Years. Human Reproduction, 37, 762-776.
https://doi.org/10.1093/humrep/deac010
[38] 陈晶晶, 何耀娟, 陈爱兰, 等. 广州地区高龄女性孕前子宫内膜容受性分析及中药干预后的疗效评价[J]. 中国妇幼保健, 2018, 33(8): 1711-1713.
[39] 张滇. PGT-A周期累积活产率预测模型研究和辅助临床决策应用[D]: [硕士学位论文]. 西安: 西安医学院, 2025.
[40] 曹源, 管一春, 张建瑞, 等. 高龄不孕女性(≥ 38岁)不同助孕方案的结局分析[J/OL]. 实用医学杂志, 1-10.
https://link.cnki.net/urlid/44.1193.r.20260211.1453.024, 2026-07-22.
[41] 蒲艳, 郑爱燕, 廖桂芝, 等. 高龄与非高龄复发性流产患者行胚胎植入前非整倍体检测的可行性分析[J]. 中国计划生育和妇产科, 2023, 15(1): 82-87.
[42] 崔永娜. 基于女性年龄及胚胎整倍体率的反复种植失败新模型的验证和拓展[D]: [硕士学位论文]. 石家庄: 河北医科大学, 2022.
[43] Xu, N., Du, Y., Su, Z., Yu, S., Li, W., Guan, Y., et al. (2025) Analysis of Pregnancy Outcomes in Patients with Unexplained Recurrent Miscarriage Assisted by IVF/ICSI with or without PGT-A. Journal of Assisted Reproduction and Genetics, 42, 1679-1687.
https://doi.org/10.1007/s10815-025-03438-0
[44] Listorti, I., Manzo, R., Greco, E., Pirastu, G., Ruberti, A., Colasante, A., et al. (2026) Beyond Aneuploidy: Embryo Morphology, Maternal Age, and Miscarriage Dynamics in PGT-A Selected Single Embryo Transfer. Journal of Assisted Reproduction and Genetics, 43, 143-153.
https://doi.org/10.1007/s10815-025-03744-7
[45] 中国女医师协会生殖医学专业委员会专家共识编写组. 辅助生殖领域拮抗剂方案标准化应用专家共识[J]. 中华生殖与避孕杂志, 2022, 42(2): 109-116.
[46] 成海英, 黄向红, 谭小军, 等. PPOS方案与拮抗剂方案对卵巢高储备者胚胎整倍体率的影响[J]. 中国卫生标准管理, 2025, 16(2): 13-16.
[47] Wang, L., Wang, J., Zhang, Y., Qian, C., Wang, X., Bai, J., et al. (2023) Analysis of Euploidy Rates in Preimplantation Genetic Testing for Aneuploidy Cycles with Progestin-Primed versus GnRH Agonist/Antagonist Protocol. European Journal of Medical Research, 28, Article No. 28.
https://doi.org/10.1186/s40001-023-01000-1
[48] 李小兰, 王艳芳, 张志强. 复发性流产行常规体外受精对胚胎植入前遗传学检测-非整倍体筛查治疗结局的影响[J]. 实用妇产科杂志, 2025, 41(12): 1008-1012.
[49] Palmerola, K.L., Vitez, S.F., Amrane, S., Fischer, C.P. and Forman, E.J. (2018) Minimizing Mosaicism: Assessing the Impact of Fertilization Method on Rate of Mosaicism after Next-Generation Sequencing (NGS) Preimplantation Genetic Testing for Aneuploidy (PGT-A). Journal of Assisted Reproduction and Genetics, 36, 153-157.
https://doi.org/10.1007/s10815-018-1347-6
[50] Deng, J., Kuyoro, O., Zhao, Q., Behr, B. and Lathi, R.B. (2020) Comparison of Aneuploidy Rates between Conventional in Vitro Fertilization and Intracytoplasmic Sperm Injection in in Vitro Fertilization-Intracytoplasmic Sperm Injection Split Insemination Cycles. F&S Reports, 1, 277-281.
https://doi.org/10.1016/j.xfre.2020.07.006