Does theFMR1 gene affect IVF success?

Abstract

Published research suggests that women who carry the FMR1 premutation (about 55 to 200 CGG) may have reduced success with IVF, e.g. fewer retrieved oocytes after ovulatory stimulation regimens. A meta-analysis has revealed no association within subcategories of normal repeat length (<45 CGG) and IVF pregnancy rates. ABSTRACTFMR1 CGG trinucleotide repeat expansions are associated with Fragile X syndrome (full mutations) and primary ovarian insufficiency (premutation range); the effect of FMR1 on the success of fertility treatment is unclear. The effect of FMR1 CGG repeat lengths on IVF outcomes after ovarian stimulation was reviewed. PubMed was searched for studies on IVF-related outcomes reported by FMR1 trinucleotide repeat length published between 2002 and December 2017. For women with CGG repeats in the normal (<45 CGG), intermediate range (45-54 CGG), or both, research supports a minimal effect on IVF outcomes, including pregnancy rates; although one study reported lower oocyte yields after IVF stimulation in women with lower CGG repeat lengths and normal ovarian reserve. Metaanalysis revealed no association within subcategories of normal repeat length (<45 CGG) and IVF pregnancy rates (summary OR 1.0, 95% CI 0.87 to 1.15). Premutation carriers (CGG 55-200) may have reduced success with IVF treatment (lower oocyte yield) than women with a normal CGG repeat length or a full mutation, although findings are inconsistent. Direct implications of the repeat length on inheritance and the risk of Fragile X syndrome have been observed. Patients may require clinical and psychological counselling, and further preimplantation genetic testing options should be considered. Thus, there are clinical and psychological counseling implications for patients and potential further patient decisions regarding preimplantation genetic testing options.

Association between mutations in the FMR1 gene and ovarian dysfunction in Brazilian patients

“…In addition, a recent review suggested that women with FMR1 premutation should be informed that they might have lower chances of success with in vitro fertilization (IVF) due to lower number of retrieved oocytes after ovulatory stimulation regimens; interestingly, IVF outcomes are apparently unaffected by FMR1 repeat lengths smaller than 55 CGG or greater than 200 CGG (Pastore et al, 2019).…”

Fragile X Syndrome Secondary to in Vitro Fertilization with a Family Egg Donor, A Case Report and Review of the Literature

“…They don’t have any distinctive physical features or intellectual disabilities which allow the identification of their PM carrier status. Furthermore, due to the decreasing number of extracted eggs and the need for higher doses of gonadotropin hormone, compared to women without the PM or even with the FM; PM carriers have a lower success rate in IVF protocols ( 33 , 34 ).…”

“…The egg receptor for this case had two previous failed attempts of IVF with her own eggs; she was the donor´s sister and was also a PM carrier. This enhances the need for young women with PM for FXS, even without a reproductive desire, to undergo ovarian reserve tests and in case of a decreased reserve be offered fertility preservation alternatives ( 33 , 34 ).…”

The molecular mechanisms that underlie fragile X-associated premature ovarian insufficiency: is it RNA or protein based?

“…Women carrying midrange repeats (approximately 70–90 repeats) have the highest risk for POI, while carriers of smaller and larger premutation repeat lengths have an increased risk of POI compared to the general population, but not to the same extent as mid-range carriers. It remains contentious whether normal or grey zone CGG repeat lengths are correlated with ovarian reserve parameters, age at natural menopause and IVF outcome ( Gleicher et al , 2009 ; Gleicher et al , 2011 ; Voorhuis et al , 2013 ; Gustin et al , 2015 ; Banks et al , 2016 ; Pastore et al , 2019 ). In addition, X chromosome inactivation ( Sullivan et al , 2005 ; Tejada et al , 2008 ; Spath et al , 2010 ), background genes ( Hunter et al , 2008 ; Spath et al , 2011 ) and smoking ( Spath et al , 2011 ) have all been investigated to explain the incomplete penetrance of POI among premutation carriers.…”