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. 2011 Apr 15;6(4):e18781.
doi: 10.1371/journal.pone.0018781.

Association of FMR1 genotypes with in vitro fertilization (IVF) outcomes based on ethnicity/race

Norbert Gleicher  1 , Andrea Weghofer, Irene H Lee, David H Barad
Affiliations

Association of FMR1 genotypes with in vitro fertilization (IVF) outcomes based on ethnicity/race

Norbert Gleicher et al. PLoS One. .

Abstract

The FMR1 gene, mapping to an area of the X chromosome closely associated with autoimmunity also affects ovarian reserve, with specific genotypes associated with distinct ovarian aging patterns. They, therefore, could also be associated with differences of in vitro fertilization (IVF) outcomes, reported between races/ethnicities. We analyzed 339 consecutive IVF patients, 232 Caucasian, 59 African and 48 Asian, for FMR1 genotypes, and tested by multiple logistic regressions for associations between race/ethnicity, FMR1 genotype, autoimmunity and pregnancy chances with IVF. FMR1 genotypes were predictive of pregnancy (P = 0.046), het-norm/low most significantly and with decreasing chance in comparison to norm genotypes (OR 0.44; 95% CI 0.23-0.85; P = 0.014). Race/ethnicity was, overall, independently associated (P = 0.03), African demonstrating decreased odds in comparison to Caucasian (OR 0.33. 95%CI 0.13-0.79; P = 0.014). Autoimmunity did not differ but interaction of autoimmunity with FMR1 genotype almost reached significance (P = 0.07). Logistic regression with race/ethnicity and interaction between FMR1 genotype and autoimmunity in the model, demonstrated 2.5-times the odds of being associated with autoimmune positivity (OR 2.5, 1.34-4.55; P = 0.004). FMR1 genotypes offer a possible explanation for differences in IVF outcomes between races/ethnicities.

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Conflict of interest statement

Competing Interests: NG is owner of CHR, a for-profit infertility center, where this research was conducted. NG and DHB are listed co-inventors on a number of pending, and one already awarded, U.S. patents claiming therapeutic benefits from DHEA supplementation in women with diminished ovarian reserve. Both are also co-inventors on a number of pending U.S. patents, claiming diagnostic relevance for the assessment of CGG triple repeats on the FMR1 gene in determining risk toward diminished ovarian reserve and related issues. NG, AW, and DHB have in the past received research support, travel funds, and speakers' honoraria from different pharma and medical device companies, none, however, in any way related to here presented research data. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials, as detailed online in the guide for authors. Only one U.S. user patent has been awarded in regards to the submitted manuscript (November 10, 2009; # 7615544). This patent describes claims benefits from supplementation with dehydroepiandrosterone (DHEA) on ovarian function and pregnancy rates in women with diminished ovarian reserve. An additional claim, that DHEA reduces embryo aneuploidy in such patients, is still pending. Also still pending is a patent application which describes different genotypes of the FMR1 gene and claims that these different genotypes reflect different ovarian aging patterns. Consequently, they are, as a potential test, predictive of future ovarian aging. All patent applications filed by researchers at CHR are 50% "owned" by CHR and 50% by the investigators who did the research that led to the application.

Figures

Figure 1
Figure 1. Prevalence of autoimmunity based on race/ethnicity and FMR1 genotype.
Autoimmunity, overall, did not differ amongst the three races/ethnicities. Panel A, however demonstrates differences in prevalence of autoimmunity within races, while Panel B demonstrates the same data stratified by FMR1 genotype. The interaction between race/ethnicity and FMR1 genotypes, overall, almost reached significance (P = 0.07), suggesting different FMR1 effects in the three races/ethnicities. Logistic regression, with race/ethnicity and interaction between FMR1 genotype and autoimmunity in the model, has 2.5-times the odds of being associated with autoimmune positivity (OR 2.5, 1.34–4.55; P = 0.004).
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