{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:31:39Z","timestamp":1784867499807,"version":"3.55.0"},"reference-count":97,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union-Next Generation EU-PNRR M6C2-Investimento 2.1 Valorizzazione e potenziamento della ricerca biomedica del SSN","award":["PNRR-MR!-2022-12376108"],"award-info":[{"award-number":["PNRR-MR!-2022-12376108"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Primary ovarian failure (POF) is caused by follicle exhaustion and is associated with menstrual irregularities and elevated gonadotropin levels, which lead to infertility before the age of 40 years. The etiology of POI is mostly unknown, but a heterogeneous genetic and familial background can be identified in a subset of cases. Abnormalities in the fragile X mental retardation 1 gene (FMR1) are among the most prevalent monogenic causes of POI. These abnormalities are caused by the expansion of an unstable CGG repeat in the 5\u2032 untranslated region of FMR1. Expansions over 200 repeats cause fragile X syndrome (FXS), whereas expansions between 55 and 200 CGG repeats, which are defined as a fragile X premutation, have been associated with premature ovarian failure type 1 (POF1) in heterozygous females. Preimplantation genetic testing for monogenic diseases (PGT-M) can be proposed when the female carries a premutation or a full mutation. In this narrative review, we aim to recapitulate the clinical and molecular features of POF1 and their implications in the context of PGT-M.<\/jats:p>","DOI":"10.3390\/genes15010006","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T11:17:24Z","timestamp":1702984644000},"page":"6","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["PGT-M for Premature Ovarian Failure Related to CGG Repeat Expansion of the FMR1 Gene"],"prefix":"10.3390","volume":"15","author":[{"given":"Tiziana","family":"Persico","sequence":"first","affiliation":[{"name":"Medically Assisted Procreation Center, Maternal and Child Department, Beauregard Hospital, Valle D\u2019Aosta Local Public Health, 11100 Aoste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Lucrezia","family":"Tranquillo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7487-1333","authenticated-orcid":false,"given":"Renato","family":"Seracchioli","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"},{"name":"Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-6715","authenticated-orcid":false,"given":"Daniela","family":"Zuccarello","sequence":"additional","affiliation":[{"name":"Clinical Genetics and Epidemiology Unit, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8139-6198","authenticated-orcid":false,"given":"Ugo","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Clinical Genetics and Epidemiology Unit, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American College of Obstetricians and Gynecologists (2014). Primary ovarian insufficiency in adolescents and young women. Obs. Gynecol., 124, 193\u2013197.","DOI":"10.1097\/01.AOG.0000451757.51964.98"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI, Webber, L., Davies, M., Anderson, R., Bartlett, J., Braat, D., Cartwright, B., Cifkova, R., de Muinck Keizer-Schrama, S., and Hogervorst, E. (2016). Management of women with premature ovarian insufficiency. Hum. Reprod., 31, 926\u2013937.","DOI":"10.1093\/humrep\/dew027"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"626924","DOI":"10.3389\/fendo.2021.626924","article-title":"Current Understanding of the Etiology, Symptomatology, and Treatment Options in Premature Ovarian Insufficiency (POI)","volume":"12","author":"Ishizuka","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1055\/s-0031-1280916","article-title":"Mechanisms and models of immune tolerance breakdown in the ovary","volume":"29","author":"Cheng","year":"2011","journal-title":"Semin. Reprod. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1093\/humupd\/dmv036","article-title":"Genetics of primary ovarian insufficiency: New developments and opportunities","volume":"21","author":"Qin","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/0092-8674(95)90275-9","article-title":"Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure","volume":"82","author":"Lucena","year":"1995","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0140-6736(95)92194-X","article-title":"Fragile X premutation in familial premature ovarian failure","volume":"346","author":"Conway","year":"1995","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/ajmg.1320510419","article-title":"Obstetrical and gynecological complication in fragile X carriers: A multicenter study","volume":"51","author":"Schwartz","year":"1994","journal-title":"Am. J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/0092-8674(91)90397-H","article-title":"Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome","volume":"65","author":"Verkerk","year":"1991","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.ajhg.2012.02.018","article-title":"Fragile X and X-linked intellectual disability: Four decades of discovery","volume":"90","author":"Lubs","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/349624a0","article-title":"Abnormal pattern detected in fragile-X patients by pulsed-field gel electrophoresis","volume":"349","author":"Vincent","year":"1991","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/0092-8674(91)90514-Y","article-title":"Physical mapping across the fragile X: Hypermethylation and clinical expression of the fragile X syndrome","volume":"64","author":"Bell","year":"1991","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S1357-4310(00)01674-9","article-title":"Fragile X syndrome at turn of the century","volume":"6","author":"Kooy","year":"2000","journal-title":"Mol. Med. Today"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"899","DOI":"10.12740\/PP\/65778","article-title":"Health problems in females carriers of premutation in the FMR1 gene","volume":"51","author":"Lisik","year":"2017","journal-title":"Psychiatr. Pol."},{"key":"ref_15","unstructured":"Hunter, J.E., Berry-Kravis, E., Hipp, H., and Todd, P.K. (1993). FMR1 disorders. Gene Rev., 202."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1126\/science.252.5009.1179","article-title":"Fragile X genotype characterized by an unstable region of DNA","volume":"252","author":"Yu","year":"1991","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s004390050179","article-title":"Stability of triplet repeats of myotonic dystrophy and fragile X loci in human mutator mismatch repair cell lines","volume":"98","author":"Kramer","year":"1996","journal-title":"Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.neuron.2013.02.022","article-title":"The unstable repeats three evolving faces of neurological disease","volume":"77","author":"Nelson","year":"2013","journal-title":"Neuron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1086\/367713","article-title":"Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles","volume":"72","author":"Nolin","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/gim.2014.106","article-title":"Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers","volume":"17","author":"Nolin","year":"2014","journal-title":"Genet. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/ng0994-88","article-title":"Length of uninterrupted CGG repeats determines instability in the FMR1 gene","volume":"8","author":"Eichler","year":"1994","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/gim.2012.34","article-title":"AGG interruptions within the maternal FMR1 gene reduce the risk of offspring with fragile X syndrome","volume":"14","author":"Yrigollen","year":"2012","journal-title":"Genet. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"606","DOI":"10.3389\/fgene.2018.00606","article-title":"Absence of AGG interruptions is a risk factor for full mutation expansion among Israeli FMR1 premutation carriers","volume":"9","author":"Domniz","year":"2018","journal-title":"Front. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.fertnstert.2006.09.004","article-title":"The FMR1 premutation and reproduction","volume":"87","author":"Wittenberger","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1002\/mds.21493","article-title":"Fragile X-associated tremor\/ataxia syndrome: Clinical features, genetics, and testing guidelines","volume":"22","author":"Abrams","year":"2007","journal-title":"Mov. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/nrneurol.2016.82","article-title":"Fragile X -associated tremor\/ataxia syndrome-features, mechanism and management","volume":"12","author":"Hangerman","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.neuron.2013.03.026","article-title":"CGG repeated-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome","volume":"78","author":"Todd","year":"2013","journal-title":"Neuron"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/978-3-642-21649-7_18","article-title":"The fragile X-associated tremor ataxia syndrome","volume":"54","author":"Tassone","year":"2012","journal-title":"Results Probl. Cell Differ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/S1474-4422(13)70125-X","article-title":"Advances in clinical and molecular understanding of the FMR1 premutation and fragile-X-associated tremor\/ataxia syndrome","volume":"12","author":"Hangerman","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1086\/386296","article-title":"The fragile-X premutation: A maturing perspective","volume":"74","author":"Hagerman","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1086\/374321","article-title":"Fragile X premutation tremor\/ataxia syndrome: Molecular, clinical and neuroimaging correlates","volume":"72","author":"Jacquemont","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Tassone, F., Protic, D., Allen, E.G., Archibald, A.D., Baud, A., Brown, T.W., Budimirovic, D.B., Cohen, J., Dufour, B., and Eiges, R. (2023). Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation. Cells, 12.","DOI":"10.3390\/cells12182330"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1056\/NEJMcp0808697","article-title":"Clinical practice. Primary ovarian insufficiency","volume":"360","author":"Nelson","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1093\/humrep\/deh635","article-title":"Association of FMR1 repeat size with ovarian dysfunction","volume":"20","author":"Sullivan","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1002\/(SICI)1096-8628(19990402)83:4<322::AID-AJMG17>3.0.CO;2-B","article-title":"Fragile X Premutation Is a Significant Risk Factor for Premature Ovarian Failure","volume":"83","author":"Chitayat","year":"1999","journal-title":"Am. J. Med. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/ajmg.1320380221","article-title":"Heterozygous fragile X female: Historical, physical, cognitive, and cytogenetic features","volume":"38","author":"Cronister","year":"1991","journal-title":"Am. J. Med. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/j.1365-2265.2007.03073.x","article-title":"Primary ovarian insufficiency: A more accurate term for premature ovarian failure","volume":"68","author":"Welt","year":"2008","journal-title":"Clin. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1093\/humrep\/dei432","article-title":"Influence of intermediate and uninterrupted FMR1 CGG expansions in premature ovarian failure manifestation","volume":"21","author":"Bodega","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.fertnstert.2008.07.007","article-title":"Intermediate and premutation FMR1 alleles in women with occult primary ovarian insufficiency","volume":"92","author":"Streuli","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Barasoain, M., Barrenetxea, G., Huerta, I., T\u00e9lez, M., Criado, B., and Arrieta, I. (2016). Study of the Genetic Etiology of Primary Ovarian Insufficiency: FMR1 Gene. Genes, 7.","DOI":"10.3390\/genes7120123"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/(SICI)1096-8628(19990528)84:3<300::AID-AJMG27>3.0.CO;2-5","article-title":"Premature ovarian failure (POF) and fragile X premutation females: From POF to fragile X carrier identification, from fragile X carrier diagnosis to POF association data","volume":"84","author":"Guarducci","year":"1999","journal-title":"Am. J. Med. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/sj.ejhg.5201510","article-title":"Nonlinear association between CGG repeat number and age of menopause in FMR1 premutation carriers","volume":"14","author":"Ennis","year":"2006","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1038\/s41436-021-01177-y","article-title":"Refining the risk for fragile X-associated primary ovarian insufficiency (POF1) by FMR1 CGG repeat size","volume":"23","author":"Allen","year":"2021","journal-title":"Genet. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/gm401","article-title":"FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States","volume":"4","author":"Tassone","year":"2012","journal-title":"Genome Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/j.fertnstert.2011.08.028","article-title":"Number of CGG repeats in the FMR1 gene of Japanese patients with primary ovarian insufficiency","volume":"96","author":"Ishizuka","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/j.fertnstert.2008.01.098","article-title":"Apilot study of premature ovarian senescence: Correlation of triple CGG repeats on the FMR1 gene to ovarian reserve parameters FSH and anti-Mullerian hormone","volume":"91","author":"Gleicher","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1007\/s00439-005-1326-8","article-title":"FMR1 repeat sizes in the gray zone and high end of the normal range are associated with premature ovarian failure","volume":"117","author":"Bretherick","year":"2005","journal-title":"Hum. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1177\/1933719112446074","article-title":"Elevated prevalence of 35-44 FMR1 trinucleotide repeats in women with diminished ovarian reserve","volume":"19","author":"Pastore","year":"2012","journal-title":"Reprod. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1093\/humrep\/deq058","article-title":"Intermediate sized CGG repeats are not a common cause of idiopathic premature ovarian failure","volume":"25","author":"Bennet","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1093\/humrep\/deu095","article-title":"The significance of fragile X mental retardation gene I CGG repeats sizes in the normal and intermediate range in women with primary ovarian insufficiency","volume":"29","author":"Voorhuis","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1086\/302985","article-title":"Premature ovarian failure among fragile X premutation carriers: Parent of origin effect?","volume":"67","author":"Sherman","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1590\/S1415-47571999000400002","article-title":"Premature ovarian failure (POF) in Brazilian fragile X carriers","volume":"22","author":"Costa","year":"1999","journal-title":"Genet. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/sj.ejhg.5200451","article-title":"Reproductive and menstrual history of females with fragile X expansions","volume":"8","author":"Murray","year":"2000","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1097\/00042192-200103000-00005","article-title":"Implications of the FMR1 gene in menopause: Study of 147 Spanish women","volume":"8","author":"Mallolas","year":"2001","journal-title":"Menopause"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/ajmg.a.10862","article-title":"Female carriers of fragile X premutations have no increased risk for additional diseases other than premature ovarian failure","volume":"117A","author":"Hundscheid","year":"2003","journal-title":"Am. J. Med. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/gim.2017.220","article-title":"CGG repeat length and AGG interruptions as indicators of fragile X-associated diminished ovarian reserve","volume":"20","author":"Lekovich","year":"2018","journal-title":"Genet. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1055\/s-2000-13476","article-title":"Premature ovarian failure and the FMR1 gene","volume":"18","author":"Murray","year":"2000","journal-title":"Semin. Reprod. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1097\/gme.0b013e31804c793d","article-title":"Effect of early menopause on bone mineral density and fractures","volume":"14","author":"Gallagher","year":"2007","journal-title":"Menopause"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3907","DOI":"10.1210\/jc.2004-0015","article-title":"Impaired endothelial function in young women with premature ovarian failure: Normalization with hormone therapy","volume":"89","author":"Kalantaridou","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1097\/01.gme.0000218683.97338.ea","article-title":"Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: A meta-analysis","volume":"13","author":"Atsma","year":"2006","journal-title":"Menopause"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00439-004-1086-x","article-title":"A Study of the distributional characteristics of FMR1 transcript levels in 238 individuals","volume":"114","author":"Allen","year":"2004","journal-title":"Hum. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1261\/rna.280807","article-title":"Elevated FMR1 mRNA in premutation carriers is due to increased transcription","volume":"13","author":"Tassone","year":"2007","journal-title":"RNA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1093\/hmg\/10.14.1449","article-title":"Reduced FMRP and increased FMR1 transcription is proportionally associated with CGG repeat number in intermediate-length and premutation carriers","volume":"10","author":"Kenneson","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/jhg.2009.121","article-title":"Examination of FMR1 transcript and protein levels among 74 premutation carriers","volume":"55","author":"Peprah","year":"2010","journal-title":"J. Hum. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1261\/rna.206307","article-title":"Analysis of FMR1 gene expression in female premutation carriers using robust segmented linear regression models","volume":"13","author":"Ibanez","year":"2007","journal-title":"RNA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1212\/WNL.57.1.127","article-title":"Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X","volume":"57","author":"Hagerman","year":"2001","journal-title":"Neurology"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Elizur, S.E., Lebovitz, O., Derech-Haim, S., Dratviman-Storobinsky, O., Feldman, B., Dor, J., Orvieto, T., and Cohen, Y. (2014). Elevated levels of FMR1 mRNA in granulosa cells are associated with low ovarian reserve in FMR1 premutation carriers. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105121"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1093\/humrep\/dem148","article-title":"Examination of reproductive aging milestones among women who carry the FMR1 premutation","volume":"22","author":"Allen","year":"2007","journal-title":"Hum. Reprod."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1093\/humrep\/dev280","article-title":"Presence of inclusions positive for polyglycine containing protein, FMRpolyG, indicates that repeat-associated non-AUG translation plays a role in fragile X-associated primary ovarian insufficiency","volume":"31","author":"Buijsen","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1093\/nar\/gki186","article-title":"Facile FMR1 mRNA structure regulation by interruptions in CGG repeats","volume":"33","author":"Napierala","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1093\/humrep\/deab214","article-title":"What is the threshold of mature oocytes to obtain at least one healthy transferable cleavage-stage embryo after preimplantation genetic testing for fragile X syndrome?","volume":"36","author":"Sonigo","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/s10815-021-02067-7","article-title":"Fertility preservation for genetic diseases leading to premature ovarian insufficiency (POI)","volume":"38","author":"Mastellari","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1093\/humrep\/13.11.3169","article-title":"Successful preimplantation genetic diagnosis is related to the number of available cumulus-oocyte complexes","volume":"13","author":"Vandervorst","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"300","DOI":"10.3389\/fgene.2014.00300","article-title":"Health and reproductive experiences of women with an FMR1 premutation with and without fragile X premature ovarian insufficiency","volume":"5","author":"Wheeler","year":"2014","journal-title":"Front. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/S0015-0282(99)00396-9","article-title":"Antral follicle counts by transvaginal ultrasonography are related to age in women with proven natural fertility","volume":"72","author":"Scheffer","year":"1999","journal-title":"Fertil. Steril."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0015-0282(16)53707-8","article-title":"Intercycle variability of day 3 follicle-stimulating hormone levels and its effect on stimulation quality in in vitro fertilization","volume":"54","author":"Scott","year":"1990","journal-title":"Fertil. Steril."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.fertnstert.2010.10.011","article-title":"Age-specific serum anti-M\u00fcllerian hormone values for 17,120 women presenting to fertility centers within the United States","volume":"95","author":"Seifer","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_78","first-page":"19","article-title":"Psychological Impact of Abortion due to Fetal Anomaly: A Review of Published Research","volume":"32","author":"Sullivan","year":"2017","journal-title":"Issues Law. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1007\/s10815-020-01809-3","article-title":"Are ovarian response and pregnancy rates similar in selected FMR1 premutated and mutated patients undergoing preimplantation genetic testing?","volume":"37","author":"Ranisavljevic","year":"2020","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1093\/humrep\/17.11.2807","article-title":"Preimplantation genetic diagnosis for fragile X syndrome: Difficult but not impossible","volume":"17","author":"Platteau","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/humrep\/deq265","article-title":"ESHRE PGD Consortium\/Embryology Special Interest Group\u2013Best practice guidelines for polar body and embryo biopsy for preimplantation genetic diagnosis\/screening (PGD\/PGS)","volume":"26","author":"Harton","year":"2011","journal-title":"Hum. Reprod."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1002\/(SICI)1097-0223(199912)19:13<1223::AID-PD724>3.0.CO;2-0","article-title":"Preimplantation diagnosis for fragile X syndrome based on the detection of the non-expanded paternal and maternal CGG","volume":"19","author":"Sermon","year":"1999","journal-title":"Prenat. Diagn."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/gim.2015.185","article-title":"Identification of microsatellite markers <1 Mb from the FMR1 CGG repeat and development of a single-tube tetradecaplex PCR panel of highly polymorphic markers for preimplantation genetic diagnosis of fragile X syndrome","volume":"18","author":"Chen","year":"2016","journal-title":"Genet. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1093\/molehr\/6.5.391","article-title":"Multiplex PCR of polymorphic markers flanking the CFTR gene; a general approach for preimplantation genetic diagnosis of cystic fibrosis","volume":"6","author":"Dreesen","year":"2000","journal-title":"Mol. Hum. Reprod."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/pd.111","article-title":"Preimplantation genetic diagnosis of the fragile X syndrome by use of linked polymorphic markers","volume":"21","author":"Apessos","year":"2001","journal-title":"Prenat. Diagn."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S1472-6483(10)60901-7","article-title":"Preimplantation genetic diagnosis for fragile X syndrome using multiplex nested PCR","volume":"14","author":"Malcov","year":"2007","journal-title":"Reprod. Biomed. Online"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/ejhg.2015.96","article-title":"Improving preimplantation genetic diagnosis for Fragile X syndrome: Two new powerful single-round multiplex indirect and direct tests","volume":"24","author":"Kieffer","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e10","DOI":"10.1017\/erm.2017.10","article-title":"FMR1 CGG repeat expansion mutation detection and linked haplotype analysis for reliable and accurate preimplantation genetic diagnosis of fragile X syndrome","volume":"19","author":"Lian","year":"2017","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"143","DOI":"10.11622\/smedj.2020009","article-title":"Repeat expansion and methylation-sensitive triplet-primed polymerase chain reaction for fragile X mental retardation 1 gene screening in institutionalised intellectually disabled individuals","volume":"62","author":"Sihombing","year":"2021","journal-title":"Singap. Med. J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1016\/j.fertnstert.2021.07.276","article-title":"Observed outcomes of fmr1 pgt-m analysis with incorporation ofCGG repeat expansion can lead to extra embryos suitable for transfer","volume":"116","author":"Discenza","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1159\/000455849","article-title":"Impact of FMR1 Pre-Mutation Status on Blastocyst Development in Patients Undergoing Pre-Implantation Genetic Diagnosis","volume":"83","author":"Hutchinson","year":"2018","journal-title":"Gynecol. Obs. Investig."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1093\/humrep\/deq203","article-title":"PGD for fragile X syndrome: Ovarian function is the main determinant of success","volume":"10","author":"Tsafrir","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1093\/humrep\/dex090","article-title":"The ovarian response in fragile X patients and premutation carriers undergoing IVF-PGD: Reappraisal","volume":"32","author":"Avraham","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s10815-020-01701-0","article-title":"Does the presence of AGG interruptions within the CGG repeat tract have a protective effect on the fertility phenotype of female FMR1 premutation carriers?","volume":"37","year":"2020","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.fertnstert.2009.04.047","article-title":"The effect of CGG repeat number on ovarian response among fragile X premutation carriers undergoing preimPlantation genetic diagnosis","volume":"94","author":"Bibi","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1093\/molehr\/gal069","article-title":"Multiple displacement amplification improves PGD for fragile X syndrome","volume":"12","author":"Burlet","year":"2006","journal-title":"Mol. Hum. Reprod."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1007\/s10815-013-0079-x","article-title":"Live birth following serial vitrification of embryos and PGD for fragile X syndrome in a patient with the premutation and decreased ovarian reserve","volume":"30","author":"Nayot","year":"2013","journal-title":"J. Assist. Reprod. 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