Female digit length ratio (2D:4D) and time-to-pregnancy.

study questionIs the female 2th- to 4th-finger ratio (2D:4D) associated with fecundity as measured by time-to-pregnancy (TTP)? SUMMARY ANSWER: Our study does not support an association between female 2D:4D and TTP. WHAT IS KNOWN ALREADY: The 2th- to 4th-finger ratio (2D:4D) has been proposed as a potential indicator of greater androgen exposure during fetal development. Women exposed in utero to unbalanced steroid hormones may have impaired fecundity in the adulthood. Fecundity is often measured by TTP, an epidemiological tool commonly used to assess the impact of environmental factors in human conception. STUDY DESIGN, SIZE, DURATION: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study is a pregnancy and birth cohort of 2001 women recruited before 14 weeks of gestation in 10 cities across Canada between 2008 and 2011. The present analysis is part of MIREC-CD Plus, a follow-up study in a subsample of some 800 MIREC mothers and their children from 2012 to 2015. PARTICIPANTS/MATERIALS, SETTING,

methodsTTP and maternal characteristics were collected from questionnaires administered during the first trimester of pregnancy as part of the MIREC study. Digital pictures of the ventral surface of both hands were obtained in the MIREC mothers at the MIREC-CD Plus follow-up study. The 2D:4D was calculated as the ratio of the second and fourth fingers of each hand. The exposure of interest was the 2D:4D of the women categorized by tertiles, or dichotomized as ≥1 (index finger longer than the ring finger) or <1 (ring finger longer than the index finger, implying greater androgen exposure during fetal development). The final sample included 696 mothers. Statistical analyses included discrete-time Cox proportional hazard models, allowing adjustment for potential confounding factors. MAIN RESULTS AND THE ROLE OF CHANCE: There was no evidence of diminished/increased fecundability according to the 2D:4D, neither on the right nor on the left hand. In our analysis by tertiles, the smallest 2D:4D (i.e. higher androgen exposure during fetal life) resulted in FORs higher than 1 (i.e. shorter TTP) in both hands, although this was not statistically significant (FOR 1.19 [95% CI 0.93, 1.51] in the right hand and 1.16 [95% CI 0.91, 1.47] in the left hand). In the dichotomous analysis, 2D:4D <1 resulted in FORs higher than 1 (i.e. shorter TTP), but this was also not statistically significant (FOR 1.08 [95% CI 0.88, 1.33] in the right hand and 1.14 [95% CI 0.92, 1.42] in the left hand). Our large sample size resulted in a high statistical power to exclude an association between female 2D:4D and TTP. LIMITATIONS, REASONS FOR CAUTION: The MIREC Study is a cohort of pregnant women, and therefore, women with infertility were excluded by design from our study. WIDER IMPLICATIONS OF THE

findingsOur data do not provide evidence for an association between female 2D:4D and fecundity as measured by TTP. Whether the female 2D:4D is a marker of in utero androgen exposure and whether it is associated with fecundity have yet to be determined. STUDY FUNDING/COMPETING INTEREST: The MIREC Study was funded by Health Canada's Chemicals Management Plan, the Canadian Institute of Health Research (CIHR grant # MOP - 81285), and the Ontario Ministry of the Environment. MIREC-CD Plus was funded by Health Canada's Chemicals Management Plan Research Fund. The 2D:4D component was funded by a research grant from the CIHR-Quebec Training Network in Perinatal Research (QTNPR). M.P. Vélez was supported by a CIHR Fellowship Award, and a QTNPR scholarship. P. Monnier is supported by the Research Institute of the McGill University Health Centre. W.D Fraser is supported by a CIHR Canada Research Chair. There are no conflicts of interest to declare.