Alkali and alkaline earth elements in follicular fluid and the likelihood of diminished ovarian reserve in reproductive-aged women: a case‒control study

Abstract

Background: Imbalances in alkali elements (AEs) and alkaline earth elements (AEEs) cause reproductive disorders. However, it remains unclear whether AEs/AEEs in follicular fluid have a relationship with the serious reproductive disorder known as diminished ovarian reserve (DOR).

Methods: A nested case‒control study was carried out in China. Follicular fluid samples from 154 DOR patients and 154 controls were collected and assessed for nine AEs/AEE levels. Both the mixed and single effects of the elements on DOR were estimated with a Bayesian kernel machine (BKMR) and logistic regressions.

Results: The DOR group had higher median concentrations of Li, Na, and K in follicular fluid (all P values < 0.05). The logistic regression showed that compared with their lowest tertile, the high tertiles of K [OR:2.45 (1.67-4.43)], Li [OR: 1.89 (1.06-3.42)], and Cs [OR: 1.97 (1.10-3.54)] were significantly associated with the odds of DOR. The BKMR model reported that the DOR likelihood increased linearly across the 25th through 75th percentiles of the nine-AE/AEE mixture, while the AE group contributed more to the overall effect.

Conclusion: This study revealed an association in which the likelihood of DOR increased with higher overall concentrations of AE/AEEs in follicular fluid. Among the nine detected elements, K, Li, and Cs exhibited significant individual associations with DOR. We provide new clues for the environmental factors on female fertility decline.

Trial registration: Retrospectively registered.

Keywords: Alkali elements; Alkaline earth elements; Bayesian kernel machine regression (BKMR); Diminished ovarian reserve; Female fertility; Follicular fluid.

Fig. 1

Associations between the levels of alkali elements and alkaline earth elements in follicular fluid and odds of a diminished ovarian reserve

Fig. 2

The overall effect of elements on the likelihood of a diminished ovarian reserve. Bayesian kernel machine regression was used to investigate the association between exposure to a mixture of 9 elements/5AEs/4 AEEs and DOR. The odds ratios were calculated where the mixture of elements was at a specific quantile level compared to when the mixture is at the 50th percentile. The estimated β-probit was transformed into an odds ratio using the formula OR = exp (1.6 x βprobit). The points refer to odds ratios (ORs), while the vertical lines represent the 95% CIs. The associations were adjusted for infertility type and BMI

Fig. 3

Associations between single element exposure and the likelihood of a diminished ovarian reserve according to the BKMR model: (A) This figure shows the estimated effect of a single element on the likelihood of DOR (est, expressed in βprobit) by comparing its 75th percentile to its 25th percentile, with all other elements being fixed at their 25th, 50th, or 75th percentile. The confounding factors adjusted for in this model include BMI and infertility type; (B) This figure shows the Univariate exposure–response function for each alkali element or alkaline earth element (95%CIs) with the remaining elements set at their medians. h(exposure) is defined as the association between a specific element as a continuous variable and a latent continuous outcome (continuous marker of the binary DOR outcome). The models were adjusted for infertility type and age. K, potassium; Na, sodium; Rb, rubidium; Cs, cesium; Ca, calcium; Mg, magnesium; Sr, strontium; Ba, barium