Recent developments in genetics and medically assisted reproduction: From research to clinical applications

European Journal of Human Genetics

Volumn 26, Issue 1, 2018, Pages 12-33

  Harper, J C ^a   Aittomaki K ^b   Borry, P ^c   Cornel, M C ^d   De Wert, G ^e   Dondorp, W ^e   Geraedts, J ^f   Gianaroli, L ^g   Ketterson, K ^h   Liebaers, I ^i,m   Lundin, K ^j   Mertes, H ^k   Morris, M ^l   Pennings, G ^k   Sermon, K ^m   Spits, C ^m   Soini, S ^b   Van Montfoort, A P A ⁿ   Veiga, A ^o,p   Vermeesch, J R ^c   Viville, S ^q,r   Macek, M ^a,s   more..

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

^c UNIVERSITY OF LEUVEN   (Belgium)

^d VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^e MAASTRICHT UNIVERSITY   (Netherlands)

^f MAASTRICHT UNIVERSITY   (Netherlands)

^g SISMeR Reproductive Medicine Unit   (Italy)

^h Althea Science Inc   (United Kingdom)

ⁱ UNIVERSITY HOSPITAL BRUSSELS   (Belgium)

^j SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

^k GHENT UNIVERSITY   (Belgium)

^l SYNLAB ACADEMY   (Germany)

^m VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

ⁿ MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

^o HOSPITAL DURAN I REYNALS   (Spain)

^p Reproductive Medicine Service of Dexeus Woman Health   (Spain)

^q UNIVERSITÉ DE STRASBOURG   (France)

^r HÔPITAL CIVIL   (France)

^s UNIVERSITY HOSPITAL MOTOL   (Czech Republic)

more..

Author keywords

Assisted reproductive technology; Epigenetics; Expanded carrier screening; Female infertility; Gamete donor anonymity; Germline genome editing; Male infertility; Mitochondrial replacement therapy; Non invasive prenatal testing; Preimplantation genetic testing

Indexed keywords

MITOCHONDRIAL DNA;

AUTOTRANSPLANTATION; CLINICAL PRACTICE; CLINICAL RESEARCH; COPY NUMBER VARIATION; DISEASE ASSOCIATION; DISEASE TRANSMISSION; EMBRYO DEVELOPMENT; EPIGENETICS; EXPANDED CARRIER SCREENING; FEMALE INFERTILITY; FETUS DEVELOPMENT; GAMETE; GENE EDITING; GENETIC ANALYSIS; GENETIC RISK; GENETIC SCREENING; GENETIC VARIATION; GENETICS; GERMLINE MUTATION; HUMAN; INFERTILITY THERAPY; INHERITANCE; MALE INFERTILITY; MANAGED CARE; MICTURITION; MITOCHONDRION; NON INVASIVE PROCEDURE; NONHUMAN; PREIMPLANTATION GENETIC DIAGNOSIS; PREIMPLANTATION GENETIC TESTING; PRENATAL DIAGNOSIS; PRENATAL SCREENING; PREPREGNANCY CARE; PRIORITY JOURNAL; REVIEW; SPERM DONOR; MEDICAL GENETICS; ORGANIZATION; PROCEDURES;

CONGRESSES AS TOPIC; GENETIC TESTING; GENETICS, MEDICAL; HUMANS; REPRODUCTIVE TECHNIQUES, ASSISTED;

EID: 85036534648     PISSN: 10184813     EISSN: 14765438     Source Type: Journal    
DOI: 10.1038/s41431-017-0016-z     Document Type: Review

References (225)

1. ESHG: European Society for Human Genetics. (2017). https:// www. eshg. org (Accessed 14 Sep 2017).
2. ESHRE: European Society for Human Reproduction and Embryology. (2017). https://www. eshre. eu (Accessed 14 Sep 2017).
3. Harper JC, Geraedts J, Borry P, et al. Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policyeuropean society of human genetics and european society of human reproduction and embryology. Eur J Hum Genet. 2013;21:S1-21.
4. Soini S, Ibarreta D, Anastasiadou V, et al. The interface between assisted reproductive technologies and genetics: technical, social, ethical and legal issues. Eur J Hum Genet. 2006;14:588-645.
5. Calhaz-Jorge C, de Geyter C, et al. European IVF-Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Assisted reproductive technology in Europe, 2012: results generated from European registers by ESHRE. Hum Reprod. 2016; 31: 1638-52.
6. Brownstein CA, Beggs AH, Homer N, et al. An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY challenge. Genome Biol. 2014;15:R53.
7. Harper J, Jackson E, Sermon K, et al. Adjuncts in the IVF laboratory: where is the evidence for 'add-on' interventions? Hum Reprod. 2017;32:485-91.
8. Committee Opinion No. 690: Carrier screening in the age of genomic medicine American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;129:e35-40.
9. Edwards JG, Feldman G, Goldberg J, et al. Expanded carrier screening in reproductive medicine-points to consider. Obstet Gynecol. 2015;125:653-62.
10. Henneman L, Borry P, Chokoshvili D, et al. Responsible implementation of expanded carrier screening. Eur J Hum Genet 2016;24:e1-12.
11. Abulí A, Boada M, Rodríguez-Santiago B, et al. NGS-based assay for the identification of individuals carrying recessive genetic mutations in reproductive medicine. Hum Mutat. 2016;37:516-23.
12. Borry P, Henneman L, Lakeman P, ten Kate LP, Cornel MC, Howard HC. Preconceptional genetic carrier testing and the commercial offer directly-to-consumers. Hum Reprod. 2011;26:972-7.
13. Castellani C, Picci L, Tridello G, et al. Cystic fibrosis carrier screening effects on birth prevalence and newborn screening. Genet Med. 2016;18:145-51.
14. Janssens S, Chokoshvili D, Vears D, De Paepe A, Borry P. Attitudes of european geneticists regarding expanded carrier screening. J Obstet Gynecol neonatal Nurs. 2017;46:63-71.
15. De Wert G, Dondorp W, Pennings G, Shenfield F, Devroey P, Tarlatzis B, Barri P, Diedrich K. ESHRE Task Force on Ethics and Law. Intrafamilial medically assisted reproduction. Hum Reprod 2011;26(3):504-509.
16. Holtkamp KCA, Mathijssen IB, Lakeman P, et al. Factors for successful implementation of population-based expanded carrier screening: learning from existing initiatives. Eur J Public Health. 2017;27:372-7.
17. Acuna-Hidalgo R, Veltman JA, Hoischen A. New insights into the generation and role of de novo mutations in health and disease. Genome Biol. 2016;17:241.
18. Dubov T, Toledano-Alhadef H, Bokstein F, Constantini S, Ben-Shachar S. The effect of parental age on the presence of de novo mutations-Lessons from neurofibromatosis type I. Mol Genet genomic Med. 2016;4:480-6.
19. Howard HC, Knoppers BM, Cornel MC, et al. Whole-genome sequencing in newborn screening? A statement on the continued importance of targeted approaches in newborn screening programmes. Eur J Hum Genet 2015;23:1593-600.
20. ESHG: Staffing of medical genetics centres across Europe. 201). https://www. eshg. org/index. php?id=111. (Accessed 14 Sep 2017).
21. Boeldt DL, Schork NJ, Topol EJ, Bloss CS. Influence of individual differences in disease perception on consumer response to direct-to-consumer genomic testing. Clin Genet. 2015;87:225-32.
22. El-Hazmi MAF. Ethics of genetic counseling-basic concepts and relevance to Islamic communities. Ann. Saudi Med. 2004;24:84-92.
23. Dondorp W, De Wert G, Pennings G, et al. ESHRE Task Force on Ethics and Law 21: genetic screening of gamete donors: ethical issues. Hum Reprod. 2014;29:1353-9.
24. Bachelot A, Grouthier V, Courtillot C, Dulon J, Touraine P. MANAGEMENT OF ENDOCRINE DISEASE: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: update on the management of adult patients and prenatal treatment. Eur J Endocrinol. 2017;176:R167-81.
25. Simpson JL, Rechitsky S. Preimplantation diagnosis and other modern methods for prenatal diagnosis. J Steroid Biochem Mol Biol. 2017;165:124-30.
26. Campbell IM, Shaw CA, Stankiewicz P, Lupski JR. Somatic mosaicism: implications for disease and transmission genetics. Trends Genet. 2015;31:382-92.
27. Campbell IM, Stewart JR, James RA, et al. Parent of origin, mosaicism, and recurrence risk: probabilistic modeling explains the broken symmetry of transmission genetics. Am J Hum Genet. 2014;95:345-59.
28. Blake L, Jadva V, Golombok S. Parent psychological adjustment, donor conception and disclosure: a follow-up over 10 years. Hum Reprod. 2014;29:2487-96.
29. Sälevaara M, Suikkari A-M, Söderström-Anttila V. Attitudes and disclosure decisions of Finnish parents with children conceived using donor sperm. Hum Reprod. 2013;28:2746-54.
30. Harper JC, Kennett D, Reisel D. The end of donor anonymity: how genetic testing is likely to drive anonymous gamete donation out of business. Hum Reprod. 2016;31:1135-40.
31. DSR: Donor Sibling Registry. 2017. www. donorsiblingregistry. com (Accessed 14 Sep 2017).
32. DCR: Donor Conceived Registry. 2017. www. donorconceiveregistry. org. uk (Accessed 14 Sep 2017).
33. FTDNA: Family Tree DNA. https://www. familytreedna. com (Accessed 14 Sep 2017).
34. Baptista NM, Christensen KD, Carere DA, Broadley SA, Roberts JS, Green RC. Adopting genetics: motivations and outcomes of personal genomic testing in adult adoptees. Genet Med. 2016;18:924-32.
35. Zadeh S. Disclosure of donor conception in the era of nonanonymity: safeguarding and promoting the interests of donorconceived individuals? Hum Reprod. 2016;31:2416-20.
36. Abbott A. Genome test slammed for assessing 'racial purity'. Nature. 2012;486:167.
37. Patrinos GP, Baker DJ, Al-Mulla F, Vasiliou V, Cooper DN. Genetic tests obtainable through pharmacies: the good, the bad, and the ugly. Hum Genomics. 2013;7:17.
38. Borry P, Rusu O, Dondorp W, De Wert G, Knoppers BM, Howard HC. Anonymity 2. 0: direct-to-consumer genetic testing and donor conception. Fertil Steril. 2014;101:630-2.
39. Millbank J. Numerical limits in donor conception regimes: genetic links and 'extended family' in the era of identity disclosure. Med Law Rev. 2014;22:325-56.
40. Bieniek JM, Lo KC. Recent advances in understanding & amp; managing male infertility. F1000Research. 2016;5:2756.
41. Hanson B, Johnstone E, Dorais J, Silver B, Peterson CM, Hotaling J. Female infertility, infertility-associated diagnoses, and comorbidities: a review. J Assist Reprod Genet. 2017;34:167-77.
42. Krausz C, Escamilla AR, Chianese C. Genetics of male infertility: from research to clinic. Reproduction. 2015;150:R159-74.
43. Ankolkar M, Balasinor NH. Endocrine control of epigenetic mechanisms in male reproduction. Horm Mol Biol Clin Investig. 2016;25:65-70.
44. Girard SL, Bourassa CV, Lemieux Perreault L-P, et al. Paternal age explains a major portion of de novo germline mutation rate variability in healthy individuals. PLoS One. 2016;11:e0164212.
45. Punab M, Poolamets O, Paju P, et al. Causes of male infertility: a 9-year prospective monocentre study on 1737 patients with reduced total sperm counts. Hum Reprod. 2017;32:18-31.
46. Carrell DT, Aston KI, Oliva R, Emery BR, De Jonge CJ. The 'omics' of human male infertility: integrating big data in a systems biology approach. Cell Tissue Res. 2016;363:295-12.
47. MGI: Mouse Genome Informatics. 2017. http://www. informa tics. jax. org/. (Accessed 20 Apr 2017).
48. Franasiak JM, Scott RT. Reproductive tract microbiome in assisted reproductive technologies. Fertil Steril. 2015;104:1364-71.
49. Hotaling J, Carrell DT. Clinical genetic testing for male factor infertility: current applications and future directions. Andrology. 2014;2:339-50.
50. Aston KI. Genetic susceptibility to male infertility: news from genome-wide association studies. Andrology. 2014;2:315-21.
51. Ghédir H, Ibala-Romdhane S, Okutman O, Viot G, Saad A, Viville S. Identification of a new DPY19L2 mutation and a better definition of DPY19L2 deletion breakpoints leading to globozoospermia. Mol Hum Reprod. 2016;22:35-45.
52. ElInati E, Fossard C, Okutman O, et al. A new mutation identified in SPATA16 in two globozoospermic patients. J Assist Reprod Genet. 2016;33:815-20.
53. Ben Khelifa M, Coutton C, Blum MGB, et al. Identification of a new recurrent aurora kinase C mutation in both European and African men with macrozoospermia. Hum Reprod. 2012;27:3337-46.
54. Amiri-Yekta A, Coutton C, Kherraf Z-E, et al. Whole-exome sequencing of familial cases of multiple morphological abnormalities of the sperm flagella (MMAF) reveals new DNAH1 mutations. Hum Reprod. 2016;31:2872-80.
55. Takasaki N, Tachibana K, Ogasawara S, et al. A heterozygous mutation of GALNTL5 affects male infertility with impairment of sperm motility. Proc Natl Acad Sci U S A. 2014;111:1120-5.
56. Okutman O, Muller J, Baert Y, et al. Exome sequencing reveals a nonsense mutation in TEX15 causing spermatogenic failure in a Turkish family. Hum Mol Genet. 2015;24:5581-8.
57. Yatsenko AN, Georgiadis AP, Röpke A, et al. X-Linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men. N Engl J Med. 2015;372:2097-107.
58. Quaynor SD, Bosley ME, Duckworth CG, et al. Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and kallmann syndrome. Mol Cell Endocrinol. 2016;437:86-96.
59. D'Aurora M, Ferlin A, Di Nicola M, et al. Deregulation of sertoli and leydig cells function in patients with Klinefelter syndrome as evidenced by testis transcriptome analysis. BMC Genomics. 2015;16:156.
60. Pevec U, Rozman N, Gorsek B, Kunej T. RASopathies: presentation at the genome, interactome, and phenome levels. Mol Syndromol. 2016;7:72-9.
61. Guo Y-W, Chiu C-Y, Liu C-L, Jap T-S, Lin L-Y. Novel mutation of RUNX2 gene in a patient with cleidocranial dysplasia. Int J Clin Exp Pathol. 2015;8:1057-62.
62. Liu T, Huang J. DNA end resection: facts and mechanisms. Genomics Proteomics Bioinformatics. 2016;14:126-30.
63. Giabicani E, Netchine I, Brioude F. New clinical and molecular insights into silver-russell syndrome. Curr Opin Pediatr. 2016;28:529-35.
64. Marshall CR, Scherer SW, Zariwala MA, et al. Whole-exome sequencing and targeted copy number analysis in primary ciliary dyskinesia. G3 (Bethesda). 2015;5:1775-81.
65. Santoro M, Masciullo M, Silvestri G, Novelli G, Botta A. Myotonic dystrophy type 1: role of CCG, CTC and CGG interruptions within DMPK alleles in the pathogenesis and molecular diagnosis. Clin Genet. 2016. http://oi:10. 1111/ cge. 12954.
66. Laissue P. Aetiological coding sequence variants in nonsyndromic premature ovarian failure: From genetic linkage analysis to next generation sequencing. Mol Cell Endocrinol. 2015;411:243-57.
67. Pelosi E, Forabosco A, Schlessinger D. Genetics of the ovarian reserve. Front Genet. 2015;6:308.
68. Yatsenko SA, Rajkovic A. Chromosomal causes of infertility: the story continues. In: Sermon K, Viville S, editors. Textbook of Human Reproductive Genetics. Cambridge: Cambridge University Press; 2014. p. 97.
69. Tucker EJ, Grover SR, Bachelot A, Touraine P, Sinclair AH. Premature ovarian insufficiency: new perspectives on genetic cause and phenotypic spectrum. Endocr Rev. 2016;37:609-35.
70. Liebaers I, El Inati E, Lissens W, Viville S. Genes and infertility. In: Sermon K, Viville S, editors. Textbook of Human Reproductive Genetics. Cambridge: Cambridge University Press; 2014; p. 113.
71. McAllister JM, Legro RS, Modi BP, Strauss JF. Functional genomics of PCOS: from GWAS to molecular mechanisms. Trends Endocrinol Metab. 2015;26:118-24.
72. Pau CT, Mosbruger T, Saxena R, Welt CK. Phenotype and tissue expression as a function of genetic risk in polycystic ovary syndrome. PLoS One. 2017;12:e0168870.
73. Yotova I, Hsu E, Do C, et al. Epigenetic alterations affecting transcription factors and signaling pathways in stromal cells of endometriosis. PLoS One. 2017;12:e0170859.
74. Rossetti R, Ferrari I, Bonomi M, Persani L. Genetics of primary ovarian insufficiency. Clin Genet. 2017;91:183-98.
75. Qin Y, Jiao X, Simpson JL, Chen Z-J. Genetics of primary ovarian insufficiency: new developments and opportunities. Hum Reprod Update. 2015;21:787-808.
76. Bouilly J, Beau I, Barraud S, et al. Identification of multiple gene mutations accounts for a new genetic architecture of primary ovarian insufficiency. J Clin Endocrinol Metab. 2016;101:4541-50.
77. Caburet S, Arboleda VA, Llano E, et al. Mutant cohesin in premature ovarian failure. N Engl J Med. 2014;370:943-49.
78. de Vries L, Behar DM, Smirin-Yosef P, Lagovsky I, Tzur S, Basel-Vanagaite L. Exome sequencing reveals SYCE1 mutation associated with autosomal recessive primary ovarian insufficiency. J Clin Endocrinol Metab. 2014;99:E2129-32.
79. Wang J, Zhang W, Jiang H, Wu B-L. Primary ovarian insufficiency collaboration. mutations in HFM1 in recessive primary ovarian insufficiency. N Engl J Med. 2014;370:972-4.
80. Desai S, Wood-Trageser M, Matic J, et al. MCM8 and MCM9 nucleotide variants in women with primary ovarian insufficiency. J Clin Endocrinol Metab. 2017;102:576-82.
81. Laven J. Genetics of early and normal menopause. Semin Reprod Med. 2015;33:377-83.
82. Demain LAM, Conway GS, Newman WG. Genetics of mitochondrial dysfunction and infertility. Clin Genet. 2017;91:199-207.
83. Demain LAM, Urquhart JE, O'Sullivan J, et al. Expanding the genotypic spectrum of Perrault syndrome. Clin Genet 2017;91:302-12.
84. Feng R, Yan Z, Li B, et al. Mutations in TUBB8 cause a multiplicity of phenotypes in human oocytes and early embryos. J Med Genet. 2016;53:662-71.
85. Alazami AM, Awad SM, Coskun S, et al. TLE6 mutation causes the earliest known human embryonic lethality. Genome Biol. 2015;16:240.
86. Yuan P, He Z, Zheng L, et al. Genetic evidence of 'genuine' empty follicle syndrome: a novel effective mutation in the LHCGR gene and review of the literature. Hum Reprod. 2017;32:1-10.
87. Tang H, Yan Y, Wang T, Zhang T, Shi W, Fan R, Yao Y, Zhai S. Effect of follicle-stimulating hormone receptor Asn680Ser polymorphism on the outcomes of controlled ovarian hyperstimulation: an updated meta-analysis of 16 cohort studies. J Assist Reprod Genet. 2015;32(12):1801-10. https://doi. org/10. 1007/s10815-015-0600-5. Epub 2015 Oct 19.
88. Cordts EB, Santos MC, Bianco B, Barbosa CP, Christofolini DM. Are FSHR polymorphisms risk factors to premature ovarian insufficiency? Gynecol Endocrinol. 2015;31:663-6.
89. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The International Glossary on Infertility and Fertility Care, 2017. Fertil Steril 2017;108(3):393-406. https://doi. org/10. 1016/j. fertnstert. 2017. 06. 005. Epub 2017 Jul 29
90. Traeger-Synodinos J. Pre-implantation genetic diagnosis. Best Pract Res Clin Obstet Gynaecol. 2017;39:74-88.
91. Geraedts J, Sermon K. Preimplantation genetic screening 2. 0: the theory. Mol Hum Reprod. 2016;22:839-44.
92. Dahdouh EM, Balayla J, García-Velasco JA. Comprehensive chromosome screening improves embryo selection: a metaanalysis. Fertil Steril. 2015;104:1503-12.
93. Vajta G, Rienzi L, Ubaldi FM. Open versus closed systems for vitrification of human oocytes and embryos. Reprod Biomed Online. 2015;30:325-33.
94. Coates A, Kung A, Mounts E, et al. Optimal euploid embryo transfer strategy, fresh versus frozen, after preimplantation genetic screening with next generation sequencing: a randomized controlled trial. Fertil Steril 2017;107:723-e3.
95. Wilkinson J, Roberts SA, Vail A. Developments in IVF warrant the adoption of new performance indicators for ART clinics, but do not justify the abandonment of patient-centred measures. Hum Reprod. 2017; 1-5.
96. Natesan SA, Handyside AH, Thornhill AR, et al. Live birth after PGD with confirmation by a comprehensive approach (karyomapping) for simultaneous detection of monogenic and chromosomal disorders. Reprod Biomed Online. 2014;29:600-5.
97. Natesan SA, Bladon AJ, Coskun S, et al. Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro. Genet Med. 2014;16:838-45.
98. Thornhill AR, Handyside AH, Ottolini C, et al. Karyomapping-a comprehensive means of simultaneous monogenic and cytogenetic PGD: comparison with standard approaches in real time for Marfan syndrome. J Assist Reprod Genet. 2015;32:347-56.
99. Zamani Esteki M, Dimitriadou E, Mateiu L, et al. Concurrent whole-genome haplotyping and copy-number profiling of single cells. Am J Hum Genet. 2015;96:894-912.
100. Zheng H, Jin H, Liu L, Liu J, Wang W-H. Application of nextgeneration sequencing for 24-chromosome aneuploidy screening of human preimplantation embryos. Mol Cytogenet. 2015;8:38.
101. Sermon K, Capalbo A, Cohen J, et al. The why, the how and the when of PGS 2. 0: current practices and expert opinions of fertility specialists, molecular biologists, and embryologists. Mol Hum Reprod. 2016;22:845-57.
102. Vermeesch JR, Voet T, Devriendt K. Prenatal and preimplantation genetic diagnosis. Nat Rev Genet 2016;17:643-56.
103. Hens K, Dondorp W, Handyside AH, et al. Dynamics and ethics of comprehensive preimplantation genetic testing: a review of the challenges. Hum Reprod Update. 2013;19:366-75.
104. Van den Veyver IB. Recent advances in prenatal genetic screening and testing. F1000Research. 2016;5:2591.
105. Harper JC, SenGupta S, Vesela K, et al. Accreditation of the PGD laboratory. Hum Reprod. 2010;25:1051-65.
106. Marianowski P, D?browski FA, Zygu?a A, Wielgo? M, Szymusik I. Do we pay enough attention to culture conditions in context of perinatal outcome after in vitro fertilization? up-todate literature review. Biomed Res Int. 2016;2016:3285179.
107. Matthijs G, Souche E, Alders M, et al. Guidelines for diagnostic next-generation sequencing. Eur J Hum Genet. 2016;24:1515-15.
108. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the american college of medical genetics and genomics and the association for molecular pathology. Genet Med. 2015;17:405-23.
109. HGVS: Human Genome Variation Society. 2017. http://va rnomen. hgvs. org (Accessed 14 Sep 2017).
110. Claustres M, Kožich V, Dequeker E, et al. Recommendations for reporting results of diagnostic genetic testing (biochemical, cytogenetic and molecular genetic). Eur J Hum Genet. 2014;22:160-70.
111. Kamps R, Brandão R, Bosch B, et al. Next-generation sequencing in oncology: genetic diagnosis, risk prediction and cancer classification. Int J Mol Sci. 2017;18:308.
112. Fragouli E, Wells D. Aneuploidy in the human blastocyst. Cytogenet Genome Res. 2011;133:149-59.
113. Scott RT, Galliano D. The challenge of embryonic mosaicism in preimplantation genetic screening. Fertil Steril. 2016;105:1150-52.
114. Greco E, Minasi MG, Fiorentino F. Healthy babies after intrauterine transfer of mosaic aneuploid blastocysts. N Engl J Med. 2015;373:2089-90.
115. Albertini DF, Gleicher N. A detour in the quest for oogonial stem cells: methods matter. Nat Med. 2015;21:1126-7.
116. PGDIS. Preimplantation Genetic Diagnosis International Society Position Statement on Chromosome Mosaicism and Preimplantation Aneuploidy Testing at the Blastocyst Stage. 2016. 1-2. http://www. pgdis. org/docs/newsletter-071816. html (Accessed 14 Sep 2017).
117. Maxwell SM, Colls P, Hodes-Wertz B, et al. Why do euploid embryos miscarry? A case-control study comparing the rate of aneuploidy within presumed euploid embryos that resulted in miscarriage or live birth using next-generation sequencing. Fertil Steril. 2016;106:1414-19. e5.
118. Munné S, Cohen J. Advanced maternal age patients benefit from preimplantation genetic diagnosis of aneuploidy. Fertil Steril. 2017; http://oi:10. 1016/j. fertnstert. 2017. 03. 015.
119. Gleicher N, Kushnir VA, Barad DH. Preimplantation genetic screening (PGS) still in search of a clinical application: a systematic review. Reprod Biol Endocrinol. 2014;12:22.
120. Murugappan G, Shahine LK, Perfetto CO, Hickok LR, Lathi RB. Intent to treat analysis of in vitro fertilization and preimplantation genetic screening versus expectant management in patients with recurrent pregnancy loss. Hum Reprod. 2016;31:1668-74.
121. Gleicher N, Orvieto R. Is the hypothesis of preimplantation genetic screening (PGS) still supportable? A review. J Ovarian Res. 2017;10:21.
122. Gianaroli L, Magli MC, Pomante A, et al. Blastocentesis: a source of DNA for preimplantation genetic testing. Results from a pilot study. Fertil Steril. 2014;102:1692-9. e6.
123. Magli MC, Pomante A, Cafueri G, et al. Preimplantation genetic testing: polar bodies, blastomeres, trophectoderm cells, or blastocoelic fluid? Fertil Steril. 2016;105:676-83. e5.
124. Zhang Y, Li N, Wang L, et al. Molecular analysis of DNA in blastocoele fluid using next-generation sequencing. J Assist Reprod Genet. 2016;33:637-45.
125. Lin R, Feng G, Shu J, et al. Blastocoele re-expansion time in vitrified-warmed cycles is a strong predictor of clinical pregnancy outcome. J Obstet Gynaecol Res. 2017;43:689-95.
126. Galluzzi L, Palini S, Stefani SDe, et al. Extracellular embryo genomic DNA and its potential for genotyping applications. Futur Sci OA. 2015;1:FSO62.
127. Hammond ER, McGillivray BC, Wicker SM, et al. Characterizing nuclear and mitochondrial DNA in spent embryo culture media: genetic contamination identified. Fertil Steril. 2017;107:220-28. e5.
128. Lo YMD, Corbetta N, Chamberlain PF, et al. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997;350:485-87.
129. Tamminga S, van Maarle M, Henneman L, Oudejans CBM, Cornel MC, Sistermans EA. Maternal plasma DNA and RNA sequencing for prenatal testing. In: Advances in clinical chemistry. 2016; p. 63-102.
130. Van Opstal D, Srebniak MI. Cytogenetic confirmation of a positive NIPT result: evidence-based choice between chorionic villus sampling and amniocentesis depending on chromosome aberration. Expert Rev Mol Diagn. 2016;16:513-20.
131. Drury S, Hill M, Chitty LS. Cell-free fetal DNA testing for prenatal diagnosis. Adv Clin Chem. 2016;76:1-35.
132. Verhoef TI, Hill M, Drury S, et al. Non-invasive prenatal diagnosis (NIPD) for single gene disorders: cost analysis of NIPD and invasive testing pathways. Prenat Diagn. 2016;36:636-42.
133. Gregg AR, Skotko BG, Benkendorf JL, et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016;18:1056-65.
134. Wilson KL, Czerwinski JL, Hoskovec JM, et al. NSGC practice guideline: prenatal screening and diagnostic testing options for chromosome aneuploidy. J Genet Couns. 2013;22:4-15.
135. ISPD: International Society of Prenatal Diagnosis-"Position statement from the chromosome abnormality screening committee on behalf of the board of the International Society for Prenatal Diagnosis. 2015. https://www. ispdhome. org/docs/ISPD/ SocietyStatements/PositionStatement-Current-8Apr2015. pdf (Accessed 14 Sep 2017).
136. Brewer J, Demers L, Musci T. Survey of US obstetrician opinions regarding NIPT use in general practice: implementation and barriers. J Matern Fetal Neonatal Med. 2016;30:1-4.
137. Minear MA, Lewis C, Pradhan S, Chandrasekharan S. Global perspectives on clinical adoption of NIPT. Prenat Diagn. 2015;35:959-67.
138. Bustamante-Aragones A, Perlado-Marina S, Trujillo-Tiebas MJ, et al. Non-invasive prenatal diagnosis in the management of preimplantation genetic diagnosis pregnancies. J Clin Med. 2014;3:913-22.
139. Dondorp W, de Wert G, Bombard Y, et al. Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening. Eur J Hum Genet. 2015;23:1592-92.
140. Nuffield Council on Bioethics. Non-invasive prenatal testing: ethical issues. 2017. http://nuffieldbioethics. org/wp-content/ uploads/NIPT-ethical-issues-full-report. pdf (Accessed 14 Sep 2017).
141. Chitty LS, Bianchi DW. Next generation sequencing and the next generation: how genomics is revolutionizing reproduction. Prenat Diagn 2015;35:929-30.
142. Mersy E, Smits LJM, van Winden LAAP, et al. Noninvasive detection of fetal trisomy 21: systematic review and report of quality and outcomes of diagnostic accuracy studies performed between 1997 and 2012. Hum Reprod Update. 2013;19:318-29.
143. Wald NJ, Bestwick JP, Huttly WJ. Improvements in antenatal screening for Down's syndrome. J Med Screen. 2013;20:7-14.
144. Gil M, Accurti V, Santacruz B, Plana M, Nicolaides K. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol. 2017. http:// doi:10. 1002/uog. 17484.
145. Norton ME, Wapner RJ. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. 2015;373:2581-82.
146. Taylor-Phillips S, Freeman K, Geppert J, et al. Accuracy of noninvasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis. BMJ Open 2016;6:e010002.
147. Wald NJ, Huttly WJ, Bestwick JP, Aquilina J, Peregrine E. Reflex antenatal DNA screening for Down syndrome. Prenat Diagn. 2015;35:1154-1154.
148. Gil MM, Revello R, Poon LC, Akolekar R, Nicolaides KH. Clinical implementation of routine screening for fetal trisomies in the UKNHS: cell-free DNA test contingent on results from first-trimester combined test. Ultrasound Obstet Gynecol. 2016;47:45-52.
149. Hill M, Wright D, Daley R, et al. Evaluation of non-invasive prenatal testing (NIPT) for aneuploidy in an NHS setting: a reliable accurate prenatal non-invasive diagnosis (RAPID) protocol. BMC Pregnancy Childbirth. 2014;14:229.
150. Liehr T, Lauten A, Schneider U, Schleussner EWA. Noninvasive prenataltesting-when is it advantageous to apply? Biomed Hub. 2017;2:458432.
151. Amant F, Verheecke M, Wlodarska I, et al. Presymptomatic identification of cancers in pregnant women during noninvasive prenatal testing. JAMA Oncol. 2015;1:814-9.
152. Bianchi DW, Chudova D, Sehnert AJ, et al. Noninvasive prenatal testing and incidental detection of occult maternal malignancies. JAMA. 2015;314:162-9.
153. Salvi S, Gurioli G, De Giorgi U, et al. Cell-free DNA as a diagnostic marker for cancer: current insights. Onco Targets Ther. 2016;9:6549-59.
154. Morris S, Karlsen S, Chung N, Hill M, Chitty LS. Model-based analysis of costs and outcomes of non-invasive prenatal testing for Down's syndrome using cell free fetal DNA in the UK national health service. PLoS One. 2014;9:e93559.
155. Gyselaers W, Hulstaert F, Neyt M. Contingent non-invasive prenatal testing: an opportunity to improve non-genetic aspects of fetal aneuploidy screening. Prenat Diagn. 2015;35:1347-52.
156. Petersen OB, Vogel I, Ekelund C, et al. Potential diagnostic consequences of applying non-invasive prenatal testing: population-based study from a country with existing firsttrimester screening. Ultrasound Obstet Gynecol. 2014;43:265-71.
157. O'Brien BM, Halliday J, Lambert-Messerlian G, Eklund EE, Kloza E, Palomaki GE. Nuchal translucency measurement in the era of prenatal screening for aneuploidy using cell free (cf)DNA. Prenat Diagn. 2017;37:303-05.
158. Palomaki GE, Kloza EM, O'Brien BM, Eklund EE, Lambert-Messerlian GM. The clinical utility of DNA-based screening for fetal aneuploidy by primary obstetrical care providers in the general pregnancy population. Genet Med. 2017. http:// doi:10. 1038/gim. 2016. 194.
159. Benn P. Expanding non-invasive prenatal testing beyond chromosomes 21, 18, 13, X and Y. Clin Genet. 2016;90:477-85.
160. Rose NC, Benn P, Milunsky A. Current controversies in prenatal diagnosis 1: should NIPT routinely include microdeletions/ microduplications? Prenat Diagn. 2016;36:10-4.
161. Rijnders RJ, van der Schoot CE, Bossers B, de Vroede MA, Christiaens GC. Fetal sex determination from maternal plasma in pregnancies at risk for congenital adrenal hyperplasia. Obstet Gynecol. 2001;98:374-8.
162. Miura K, Higashijima A, Shimada T, et al. Clinical application of fetal sex determination using cell-free fetal DNA in pregnant carriers of X-linked genetic disorders. J Hum Genet. 2011;56:296-9.
163. Donley G, Hull SC, Berkman BE. Prenatal whole genome sequencing: just because we can, should we? Hastings Cent Rep. 2012;42:28-40.
164. Deans Z, Clarke AJ, Newson AJ. For your interest? The ethical acceptability of using non-invasive prenatal testing to test 'purely for information'. Bioethics. 2015;29:19-25.
165. de Wert G, Dondorp W, Bianchi DW. Fetal therapy for Down syndrome: an ethical exploration. Prenat Diagn. 2017;37:222-28.
166. Otten ABC, Smeets HJM. Evolutionary defined role of the mitochondrial DNA in fertility, disease and ageing. Hum Reprod Update. 2015;21:671-89.
167. Richardson J, Irving L, Hyslop LA, et al. Concise reviews: Assisted reproductive technologies to prevent transmission of mitochondrial DNA disease. Stem Cells. 2015;33:639-45.
168. Hellebrekers DMEI, Wolfe R, Hendrickx ATM, et al. PGD and heteroplasmic mitochondrial DNA point mutations: a systematic review estimating the chance of healthy offspring. Hum Reprod Update. 2012;18:341-9.
169. Reznichenko A, Huyser C, Pepper M. Mitochondrial transfer: Implications for assisted reproductive technologies. Appl Transl Genomics. 2016;11:40-47.
170. Wolf DP, Mitalipov N, Mitalipov S. Mitochondrial replacement therapy in reproductive medicine. Trends Mol Med. 2015;21:68-76.
171. McGrath J, Solter D. Nuclear transplantation in the mouse embryo by microsurgery and cell fusion. Science. 1983;220:1300-2.
172. Hyslop LA, Blakeley P, Craven L, et al. Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease. Nature. 2016;534:383-86.
173. Tachibana M, Sparman M, Sritanaudomchai H, et al. Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature. 2009;461:367-72.
174. Tachibana M, Amato P, Sparman M, et al. Human embryonic stem cells derived by somatic cell nuclear transfer. Cell 2013;153:1228-38.
175. Tachibana M, Amato P, Sparman M, et al. Towards germline gene therapy of inherited mitochondrial diseases. Nature. 2012;493:627-31.
176. Zhang J, Liu H, Luo S, et al. Live birth derived from oocyte spindle transfer to prevent mitochondrial disease. Reprod Biomed Online. 2017;34:361-68.
177. Zhang J, Zhuang G, Zeng Y, et al. Pregnancy derived from human zygote pronuclear transfer in a patient who had arrested embryos after IVF. Reprod Biomed Online. 2016;33:529-33.
178. Zhang S-P, Lu C-F, Gong F et al. Polar body transfer restores the developmental potential of oocytes to blastocyst stage in a case of repeated embryo fragmentation. J Assist Reprod Genet. 2017. http://doi:10. 1007/s10815-017-0881-y.
179. Palacios-González C. Ethics of mitochondrial replacement techniques: a habermasian perspective. Bioethics. 2017;31:27-36.
180. Nuffield Council on Bioethics. Novel techniques for the prevention of mitochondrial DNA disorders: an ethical review-2012. http://nuffieldbioethics. org/project/mitochondrial-dna-disorders (Accessed 14 Sep 2017).
181. Bredenoord AL, Hyun I. The road to mitochondrial gene transfer: follow the middle lane. Mol Ther 2015;23:975-6.
182. Fogleman S, Santana C, Bishop C, Miller A, Capco DG. CRISPR/Cas9 and mitochondrial gene replacement therapy: promising techniques and ethical considerations. Am J Stem Cells. 2016;5:39-52.
183. Gómez-Tatay L, Hernández-Andreu J, Aznar J. Mitochondrial modification techniques and ethical issues. J Clin Med. 2017;6:25.
184. Barritt JA, Willadsen S, Brenner C, Cohen J. Cytoplasmic transfer in assisted reproduction. Hum Reprod Update. 2001;7:428-35.
185. White YAR, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med. 2012;18:413-21.
186. Woods DC, Tilly JL. Autologous germline mitochondrial energy transfer (AUGMENT) in human assisted reproduction. Semin Reprod Med. 2015;33:410-21.
187. Erler P, Sweeney A, Monaghan JR. Regulation of injury-induced ovarian regeneration by activation of oogonial stem cells. Stem Cells. 2017;35:236-47.
188. Diez-Juan A, Rubio C, Marin C, et al. Mitochondrial DNA content as a viability score in human euploid embryos: less is better. Fertil Steril. 2015;104:534-41. e1.
189. Fragouli E, Wells D. Mitochondrial DNA assessment to determine oocyte and embryo viability. Semin Reprod Med. 2015;33:401-09.
190. Victor AR, Brake AJ, Tyndall JC, et al. Accurate quantitation of mitochondrial DNA reveals uniform levels in human blastocysts irrespective of ploidy, age, or implantation potential. Fertil Steril. 2017;107:34-42. e3.
191. St. John JC. Mitochondrial DNA copy number and replication in reprogramming and differentiation. Semin Cell Dev Biol. 2016;52:93-101.
192. Stigliani S, Persico L, Lagazio C, Anserini P, Venturini PL, Scaruffi P. Mitochondrial DNA in Day 3 embryo culture medium is a novel, non-invasive biomarker of blastocyst potential and implantation outcome. Mol Hum Reprod. 2014;20:1238-46.
193. Hammoud SS, Cairns BR, Carrell DT. Analysis of gene-specific and genome-wide sperm DNA methylation. Methods Mol Biol 2013;927:451-458.
194. Seisenberger S, Peat JR, Hore TA, Santos F, Dean W, Reik W. Reprogramming DNA methylation in the mammalian life cycle: building and breaking epigenetic barriers. Philos Trans R Soc Lond B Biol Sci. 2013;368:20110330.
195. Smith ZD, Chan MM, Humm KC, et al. DNA methylation dynamics of the human preimplantation embryo. Nature. 2014;511:611-15.
196. Kelsey G, Feil R. New insights into establishment and maintenance of DNA methylation imprints in mammals. Philos Trans R Soc B Biol Sci. 2012;368:20110336-20110336.
197. Smallwood SA, Kelsey G. De novo DNA methylation: a germ cell perspective. Trends Genet 2012;28:33-42.
198. Fleming TP, Kwong WY, Porter R, et al. The Embryo and Its Future1. Biol Reprod. 2004;71:1046-54.
199. Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet. 2012;13:97-109.
200. Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR. Distinctive chromatin in human sperm packages genes for embryo development. Nature. 2009;460:473-8.
201. Krausz C, Sandoval J, Sayols S, et al. Novel insights into DNA methylation features in spermatozoa: stability and peculiarities. PLoS One. 2012;7:e44479.
202. Clarke HJ, Vieux K-F. Epigenetic inheritance through the female germ-line: The known, the unknown, and the possible. Semin Cell Dev Biol. 2015;43:106-16.
203. Smallwood SA, Tomizawa S-I, Krueger F, et al. Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nat Genet. 2011;43:811-4.
204. Gifford WD, Pfaff SL, Macfarlan TS. Transposable elements as genetic regulatory substrates in early development. Trends Cell Biol. 2013;23:218-26.
205. Zamudio N, Barau J, Teissandier A, et al. DNA methylation restrains transposons from adopting a chromatin signature permissive for meiotic recombination. Genes Dev. 2015;29:1256-70.
206. Hancks DC, Kazazian HH. Roles for retrotransposon insertions in human disease. Mob DNA. 2016;7:9.
207. Sunde A, Brison D, Dumoulin J, et al. Time to take human embryo culture seriously. Hum Reprod. 2016;31:2174-82.
208. van Montfoort APA, Hanssen LLP, de Sutter P, Viville S, Geraedts JPM, de Boer P. Assisted reproduction treatment and epigenetic inheritance. Hum Reprod Update. 2012;18:171-97.
209. Bunkar N, Pathak N, Lohiya NK, Mishra PK. Epigenetics: A key paradigm in reproductive health. Clin Exp Reprod Med. 2016;43:59.
210. Ghosh J, Mainigi M, Coutifaris C, Sapienza C. Outlier DNA methylation levels as an indicator of environmental exposure and risk of undesirable birth outcome. Hum Mol Genet. 2016;25:123-9.
211. de Waal E, Mak W, Calhoun S, et al. In vitro culture increases the frequency of stochastic epigenetic errors at imprinted genes in placental tissues from mouse concepti produced through assisted reproductive technologies. Biol Reprod. 2014;90:22.
212. Pennisi E. The CRISPR Craze. Science. 2013;341:833-36.
213. Vassena R, Heindryckx B, Peco R, et al. Genome engineering through CRISPR/Cas9 technology in the human germline and pluripotent stem cells. Hum Reprod Update. 2016;22:411-9.
214. Liang P, Xu Y, Zhang X, et al. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 2015;6:363-72.
215. Kang X, He W, Huang Y, et al. Introducing precise genetic modifications into human 3PN embryos by CRISPR/Cas-mediated genome editing. J Assist Reprod Genet. 2016;33:581-8.
216. Ishii T. Reproductive medicine involving genome editing: clinical uncertainties and embryological needs. Reprod Biomed Online. 2017;34:27-31.
217. Ma H, Marti-Gutierrez N, Park SW, Wu J, Lee Y, Suzuki K, Koski A, Ji D, Hayama T, Ahmed R, Darby H, Van Dyken C, Li Y, Kang E, Park AR, Kim D, Kim ST, Gong J, Gu Y, Xu X, Battaglia D, Krieg SA, Lee DM, Wu DH, Wolf DP, Heitner SB, Belmonte JC, Amato P, Kim JS, Kaul S, Mitalipov S. Correction of a pathogenic gene mutation in human embryos. 2149 Nature. 2017;548:413-9. https://doi. org/10. 1038/nature23305
218. Strong A, Musunuru K. Genome editing in cardiovascular diseases. Nat Rev Cardiol. 2016;14:11-20.
219. Ormond KE, Mortlock DP, Scholes DT, Bombard Y, Brody LC, Faucett WA, Garrison NA, Hercher L, Isasi R, Middleton A, Musunuru K, Shriner D, Virani A, Young CE. Human Germline Genome Editing. Am J Hum Genet. 2017;101(2):167-176. https://doi. org/10. 1016/j. ajhg. 2017. 06. 012
220. Evitt NH, Mascharak S, Altman RB. Human germline CRISPRcas modification: toward a regulatory framework. Am J Bioeth. 2015;15:25-29.
221. Hildt E. Human germline interventions-think first. Front Genet. 2016;7:81.
222. Lunshof JE. Human germ line editing-roles and responsibilities. Protein Cell. 2016;7:7-10.
223. Nuffield Council on Bioethics-Genome editing: an ethical review 2016. http://nuffieldbioethics. org/project/genome-editing/ ethical-review-published-september-2016 (Accessed 14 Sep 2017).
224. Sherkow JS. CRISPR: Pursuit of profit poisons collaboration. Nature. 2016;532:172-3.
225. Walton D. The slippery slope argument in the ethical debate on genetic engineering of humans. Sci Eng Ethics. 2016. https://doi. org/10. 1007/s11948-016-9861-3.