Manuel Viotti1, Andrea R Victor2, Frank L Barnes3, Christo G Zouves3, Andria G Besser4, James A Grifo4, En-Hui Cheng5, Maw-Sheng Lee6, Jose A Horcajadas7, Laura Corti8, Francesco Fiorentino9, Francesca Spinella9, Maria Giulia Minasi10, Ermanno Greco10, Santiago Munné11. 1. Zouves Foundation for Reproductive Medicine, Foster City, California; Zouves Fertility Center, Foster City, California. Electronic address: mviotti@zouvesfoundation.org. 2. Zouves Foundation for Reproductive Medicine, Foster City, California. 3. Zouves Foundation for Reproductive Medicine, Foster City, California; Zouves Fertility Center, Foster City, California. 4. New York University Langone Fertility Center, New York, New York. 5. Lee Women's Hospital, Taichung, Taiwan. 6. Lee Women's Hospital, Taichung, Taiwan; Chung Shan Medical University, Institute of Medicine, Taichung, Taiwan. 7. Overture Life, New York, New York. 8. IRCCS San Raffaele Scientific Institute, Milan, Italy. 9. Eurofins Genoma Group, Molecular Genetics Laboratories, Rome, Italy. 10. European Hospital, Centre For Reproductive Medicine, Rome, Italy; Villa Mafalda, Center For Reproductive Medicine, Rome, Italy. 11. Cooper Genomics, Livingston, New Jersey.
Abstract
OBJECTIVE: To study how the attributes of mosaicism identified during preimplantation genetic testing for aneuploidy relate to clinical outcomes, in order to formulate a ranking system of mosaic embryos for intrauterine transfer. DESIGN: Compiled analysis. SETTING: Multi-center. PATIENT(S): A total of 5,561 euploid blastocysts and 1,000 mosaic blastocysts used in clinical transfers in patients undergoing fertility treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation (gestational sac), ongoing pregnancy, birth, and spontaneous abortion (miscarriage before 20 weeks of gestation). RESULT(S): The euploid group had significantly more favorable rates of implantation and ongoing pregnancy/birth (OP/B) compared with the combined mosaic group or the mosaic group affecting only whole chromosomes (implantation: 57.2% vs. 46.5% vs. 41.8%; OP/B: 52.3% vs. 37.0% vs. 31.3%), as well as lower likelihood of spontaneous abortion (8.6% vs. 20.4% vs. 25%). Whole-chromosome mosaic embryos with level (percent aneuploid cells) <50% had significantly more favorable outcomes than the ≥50% group (implantation: 44.5% vs. 30.4%; OP/B: 36.1% vs. 19.3%). Mosaic type (nature of the aneuploidy implicated in mosaicism) affected outcomes, with a significant correlation between number of affected chromosomes and unfavorable outcomes. This ranged from mosaicism involving segmental abnormalities to complex aneuploidies affecting three or more chromosomes (implantation: 51.6% vs. 30.4%; OP/B: 43.1% vs. 20.8%). Combining mosaic level, type, and embryo morphology revealed the order of subcategories regarding likelihood of positive outcome. CONCLUSION(S): This compiled analysis revealed traits of mosaicism identified with preimplantation genetic testing for aneuploidy that affected outcomes in a statistically significant manner, enabling the formulation of an evidence-based prioritization scheme for mosaic embryos in the clinic.
OBJECTIVE: To study how the attributes of mosaicism identified during preimplantation genetic testing for aneuploidy relate to clinical outcomes, in order to formulate a ranking system of mosaic embryos for intrauterine transfer. DESIGN: Compiled analysis. SETTING: Multi-center. PATIENT(S): A total of 5,561 euploid blastocysts and 1,000 mosaic blastocysts used in clinical transfers in patients undergoing fertility treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation (gestational sac), ongoing pregnancy, birth, and spontaneous abortion (miscarriage before 20 weeks of gestation). RESULT(S): The euploid group had significantly more favorable rates of implantation and ongoing pregnancy/birth (OP/B) compared with the combined mosaic group or the mosaic group affecting only whole chromosomes (implantation: 57.2% vs. 46.5% vs. 41.8%; OP/B: 52.3% vs. 37.0% vs. 31.3%), as well as lower likelihood of spontaneous abortion (8.6% vs. 20.4% vs. 25%). Whole-chromosome mosaic embryos with level (percent aneuploid cells) <50% had significantly more favorable outcomes than the ≥50% group (implantation: 44.5% vs. 30.4%; OP/B: 36.1% vs. 19.3%). Mosaic type (nature of the aneuploidy implicated in mosaicism) affected outcomes, with a significant correlation between number of affected chromosomes and unfavorable outcomes. This ranged from mosaicism involving segmental abnormalities to complex aneuploidies affecting three or more chromosomes (implantation: 51.6% vs. 30.4%; OP/B: 43.1% vs. 20.8%). Combining mosaic level, type, and embryo morphology revealed the order of subcategories regarding likelihood of positive outcome. CONCLUSION(S): This compiled analysis revealed traits of mosaicism identified with preimplantation genetic testing for aneuploidy that affected outcomes in a statistically significant manner, enabling the formulation of an evidence-based prioritization scheme for mosaic embryos in the clinic.
Authors: Daniel Ariad; Stephanie M Yan; Andrea R Victor; Frank L Barnes; Christo G Zouves; Manuel Viotti; Rajiv C McCoy Journal: Proc Natl Acad Sci U S A Date: 2021-11-16 Impact factor: 11.205
Authors: Antonio Capalbo; Maurizio Poli; Laura Rienzi; Laura Girardi; Cristina Patassini; Marco Fabiani; Danilo Cimadomo; Francesca Benini; Alessio Farcomeni; Juliana Cuzzi; Carmen Rubio; Elena Albani; Laura Sacchi; Alberto Vaiarelli; Matteo Figliuzzi; Necati Findikli; Onder Coban; Fazilet K Boynukalin; Ivan Vogel; Eva Hoffmann; Claudia Livi; Paolo E Levi-Setti; Filippo M Ubaldi; Carlos Simón Journal: Am J Hum Genet Date: 2021-11-18 Impact factor: 11.025