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.
Highlights
Infertility treatment outcomes vary in different races/ethnicities [1,2,3,4,5,6,7,8,9], and disparities increase with improving outcomes [10]
Asians present with milder polycystic ovary (PCO) phenotype than Caucasians and Africans [14], and African women in general experience excessive infertility [15]
Logistic regression confirmed FMR1 genotypes overall as predictive of pregnancy rate (P = 0.046), with most significance through het-norm/low in comparison to norm
Summary
Infertility treatment outcomes vary in different races/ethnicities [1,2,3,4,5,6,7,8,9], and disparities increase with improving outcomes [10]. This does not surprise: For example, primary ovarian insufficiency (POI, called premature ovarian failure, POF) varies [11], menopause differs [12] and Chinese oocytes donors demonstrate more premature ovarian aging (POA, called occult primary ovarian insufficiency, OPOI) than Caucasians [13] and higher estradiol levels [9]. For example, myotonic dystrophy and Huntington’s disease [20]
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