P-436 Non-Essential Trace Elements in women’s biofluids are associated with worse IVF outcomes in euploid single embryo transfer cycles.
Authors: González-Martín R , Palomar A , Perez-Deben S , Salsano S , Quiñonero A , Bellver J , Vidal C , Giles J , Dominguez F 
Published: June 2023

Abstract

Study question
What is the non-essential trace element exposure impact on the reproductive outcomes of women undergoing IVF treatment?

Summary answer
Increased blood and urinary non-essential trace element concentration were associated with worse IVF outcomes.

What is known already
Lower fertility rates have been observed in recent decades in industrialized regions, increasing the need for assisted reproductive techniques. Factors responsible for this decline in human fertility include exposure to non-essential trace elements. Since these elements have no known biological functions, they are considered detrimental to the normal function of the organism. The most common elements evaluated so far have been those traditionally considered toxic, such as heavy metals and metalloids (mercury, lead, cadmium and arsenic), for which inconsistent negative associations with different IVF treatment variables have been described.

Study design, size, duration
51 women who underwent an euploid single-embryo transfer (SET) after PGT-A analysis, were included. Nine non-essential elements (barium (Ba), strontium (Sr), rubidum (Rb), arsenic (As), tin (Sn), cesium (Cs), mercury (Hg), lead (Pb), antimonium (Sb)) were measured in follicular fluid (FF), whole blood (B) and urine (Urine-VOR), all collected at vaginal oocyte retrieval day (VOR), and urine collected at transfer day (Urine-T). These measurements were correlated with IVF clinical outcomes.

Participants/materials, setting, methods
Quantification of non-essential elements in the four biofluids were performed by inductively coupled plasma mass spectrometry (ICP-MS). Urine concentrations were normalized by creatinine, quantified by Jaffe reaction. Generalized linear models were employed to explore ovarian response variables and embryological IVF outcomes (associations, estimated as percentile 20th to 80th increase (95% confidence intervals (CI)). Associations with IVF clinical outcomes were estimated by odds ratio (95%CI). Both unadjusted and age-BMI-race-smoking-adjusted models were applied.

Main results and the role of chance
Participants had a median age of 39 years [Inter Quartile Range (IQR): 31.37, 36.50] and BMI of 22.97 kg/m2 [IQR: 20.63, 25.12], and 50% had never smoked. In adjusted models, significantly negative associations were found between blood Hg concentration and relative frequency of fertilized embryos [0.73 (0.56,0.96), p = 0.024], blastocyst arrival [0.64 (0.44,0.93), p = 0.019], and euploid embryos [0.60 (0.37,0.98), p = 0.044]. We also found negative associations for urine-VOR Sn and blastocyst arrival [0.72 (0.53,0.98) p = 0.038] and euploid embryos [0.55 (0.39,0.77), p &lt; 0.001]. In the case of urine-T, higher concentrations of St were associated with lower number of retrieved oocytes [0.71 (0.57,0.90), p = 0.006], relative frequency of mature oocytes [0.75 (0.62,0.90), p = 0.003], fertilized embryos [0.72 (0.62,0.83), p &lt; 0.001], blastocyst arrival [0.68 (0.56,0.84), p &lt; 0.001] and euploid embryos [0.83 (0.69,1.00), p = 0.048]. urine-T Cs was associated with lower proportion of mature oocytes retrieved [0.65 (0.42,0.99), p = 0.046] while both Rb and Cs was associated with lower proportion of euploid embryos [0.066 (0.44,0.99), p = 0.048; 0.55 (0.34,0.89), p = 0.019, respectively]. Regarding IVF clinical outcomes, in fully adjusted models, our results suggest that higher concentrations of As in urine-T were associated with lower probability of live birth [0.03 (0.00,0.36); p = 0.038] and reproductive goal (live birth/all participants) [0.03 (0.00,0.36); p = 0.038].

Limitations, reasons for caution
Further studies are needed to confirm this association in greater populations, including the measurement of different element species.

Wider implications of the findings
Exposure and circulating levels of these non-essential elements have a significant impact on IVF outcomes. These data highlight the need to further study non-essential trace elements to identify and characterize how may be affecting IVF.

Trial registration number
not applicable