Jovana Lekovich1, Limor Man1, Kangpu Xu1, Chelsea Canon2, Debra Lilienthal1, Joshua D Stewart1, Nigel Pereira1, Zev Rosenwaks1, Jeannine Gerhardt3,4. 1. The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York, USA. 2. Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, New York, USA. 3. The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York, USA. jeg2039@med.cornell.edu. 4. Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, New York, USA. jeg2039@med.cornell.edu.
Abstract
PURPOSE: Fragile X premutation (PM) carriers may experience difficulties conceiving a child probably due to fragile X-associated diminished ovarian reserve (FXDOR). We investigated which subgroups of carriers with a PM are at higher risk of FXDOR, and whether the number of AGG interruptions within the repeat sequence further ameliorates the risk. METHODS: We compared markers of ovarian reserve, including anti-Müllerian hormone, antral follicle count, and number of oocytes retrieved between different subgroups of patients with a PM. RESULTS: We found that carriers with midrange repeats size (70-90 CGG) demonstrate significantly lower ovarian reserve. Additionally, the number of AGG interruptions directly correlated with parameters of ovarian reserve. Patients with longer uninterrupted CGG repeats post-AGG interruptions had the lowest ovarian reserve. CONCLUSION: This study connects AGG interruptions and certain CGG repeat length to reduced ovarian reserve in carriers with a PM. A possible explanation for our findings is the proposed gonadotoxicity of the FMR1 transcripts. Reduction of AGG interruptions could increase the likelihood that secondary RNA structures in the FMR1 messenger RNA are formed, which could cause cell dysfunction within the ovaries. These findings may provide women with guidance regarding their fertility potential and accordingly assist with their family planning.
PURPOSE: Fragile X premutation (PM) carriers may experience difficulties conceiving a child probably due to fragile X-associated diminished ovarian reserve (FXDOR). We investigated which subgroups of carriers with a PM are at higher risk of FXDOR, and whether the number of AGG interruptions within the repeat sequence further ameliorates the risk. METHODS: We compared markers of ovarian reserve, including anti-Müllerian hormone, antral follicle count, and number of oocytes retrieved between different subgroups of patients with a PM. RESULTS: We found that carriers with midrange repeats size (70-90 CGG) demonstrate significantly lower ovarian reserve. Additionally, the number of AGG interruptions directly correlated with parameters of ovarian reserve. Patients with longer uninterrupted CGG repeats post-AGG interruptions had the lowest ovarian reserve. CONCLUSION: This study connects AGG interruptions and certain CGG repeat length to reduced ovarian reserve in carriers with a PM. A possible explanation for our findings is the proposed gonadotoxicity of the FMR1 transcripts. Reduction of AGG interruptions could increase the likelihood that secondary RNA structures in the FMR1 messenger RNA are formed, which could cause cell dysfunction within the ovaries. These findings may provide women with guidance regarding their fertility potential and accordingly assist with their family planning.
Authors: M Friedman-Gohas; M Kirshenbaum; A Michaeli; N Domniz; S Elizur; H Raanani; R Orvieto; Y Cohen Journal: J Assist Reprod Genet Date: 2020-02-24 Impact factor: 3.412
Authors: Emily G Allen; Anne Glicksman; Nicole Tortora; Krista Charen; Weiya He; Ashima Amin; Heather Hipp; Lisa Shubeck; Sarah L Nolin; Stephanie L Sherman Journal: Front Genet Date: 2018-08-03 Impact factor: 4.599
Authors: Dorothy A Fink; Lawrence M Nelson; Reed Pyeritz; Josh Johnson; Stephanie L Sherman; Yoram Cohen; Shai E Elizur Journal: Front Genet Date: 2018-11-27 Impact factor: 4.599