Is FMR1 CGG repeat length a predictor of in vitro fertilization stimulation response or outcome?

Abstract

Objective: To study a broad range of FMR1 CGG repeat lengths and assisted reproduction technology (ART) outcomes.

Design: Retrospective cohort study.

Setting: Private ART practice.

Patient(s): Fresh autologous ART stimulation cycles.

Intervention(s): None.

Main outcome measure(s): Oocyte yield, live birth.

Result(s): We screened 14,088 fresh autologous ART cycles from 2012 to 2015, of which 4,690 cycles in 3,290 patients met the inclusion criteria. The FMR1 repeat length was statistically significantly but weakly associated with oocyte yield and other markers of ovarian response. The receiver operating characteristic curve analysis suggested extremely limited predictive ability. Moreover, the FMR1 repeat length was not statistically significantly associated with outcomes in multivariable models, including other markers of ovarian reserve. The FMR1 repeat length was not associated with embryo quality or live birth. Only patient age had a strong ability to predict live birth.

Conclusion(s): The FMR1 repeat length is associated with ART response, but only weakly. It provides no incremental predictive ability beyond the conventionally used predictors, including patient age, antimüllerian hormone concentration, antral follicle count, and follicle-stimulating hormone level. These data suggest a possible role of the FMR1 repeat length within the normal range in ovarian response but demonstrate no clinically relevant indication for testing FMR1 as a predictor of ART outcomes.

Keywords: ART; CGG repeats; FMR1; IVF; ovarian reserve.

FIGURE 1

Scatter plots demonstrating the weak association of (A) FMR1 short alleles and (B) FMR1 long alleles and oocyte yield, and the strong association of (C) antral follicle count and (D) antimüllerian hormone with oocyte yield.

FIGURE 2

Receiver operating characteristic (ROC) curves associating predictor variables with (A) poor ovarian response (<4 oocytes) and (B) hyper ovarian response (>15 oocytes). The area under the curve (AUC) is shown under each ROC curve to demonstrate the association of the predictor variable with the outcome. For demonstrative purposes, an unconventional graphic display is demonstrated, as negative predictive variables are shown as dropping below the 0.50 null line. Note the further the ROC line drifts from the 0.50 null line (either up or down), the stronger it was for predicting the outcome.

FIGURE 3

Graph demonstrating the incidence of the best embryo being good (blue), fair (red), or poor (green) for (A) cleavage embryo transfers and (B) blastocyst embryo transfers/blastocyst freezing cycles.