Higher Concentrations of Essential Trace Elements in Women Undergoing IVF May Be Associated with Poor Reproductive Outcomes Following Single Euploid Embryo Transfer

Abstract

Essential trace elements are micronutrients whose deficiency has been associated with altered fertility and/or adverse pregnancy outcomes, while surplus may be toxic. The concentrations of eight essential trace elements were measured using inductively coupled mass spectrometry (ICP-MS) and assessed with respect to clinical in vitro fertilization (IVF) outcomes in a population of 51 women undergoing IVF with intracytoplasmic sperm injection (ICSI), pre-implantation genetic screening for aneuploidy (PGT-A), and single frozen euploid embryo transfer (SET/FET). Specifically, copper (Cu), zinc (Zn), molybdenum, selenium, lithium, iron, chromium, and manganese were quantified in follicular fluid and whole blood collected the day of vaginal oocyte retrieval (VOR) and in urine collected the day of VOR and embryo transfer. We found that the whole blood Cu/Zn ratio was significantly associated with superior responses to ovarian stimulation. Conversely, the whole blood zinc and selenium concentrations were significantly associated with poor ovarian response outcomes. Higher levels of whole blood zinc and selenium, urinary selenium, lithium, and iron had significant negative associations with embryologic outcomes following IVF. Regarding clinical IVF outcomes, higher urinary molybdenum concentrations the day of VOR were associated with significantly lower odds of implantation and live birth, while higher urinary Cu/Mo ratios on the day of VOR were associated with significantly higher odds of implantation, clinical pregnancy, and live birth. Our results suggest that essential trace element levels may directly influence the IVF outcomes of Spanish patients, with selenium and molybdenum exerting negative effects and copper-related ratios exerting positive effects. Additional studies are warranted to confirm these relationships in other human populations.

Keywords: ICP-MS; IVF outcomes; biofluids; essential trace elements; ovarian response.

Figure 1

Forest plots representing the mean differences (95% confidence interval) in ovarian response-related outcomes by essential trace element concentrations. The mean differences (95% CI) are presented for the trigger day estradiol (E2) levels, the total number of retrieved oocytes, and the relative proportion of mature (MII) oocytes across the essential trace elements quantified in each biofluid. The data were adjusted for age (continuous), BMI (continuous), and smoking status (never, former, or current). * p < 0.05. ET, embryo transfer; VOR, vaginal oocyte retrieval.

Figure 2

Forest plots representing the mean differences (95% confidence interval) in the preimplantation IVF outcomes by essential trace element concentrations. The mean differences (95% CI) for the relative proportions of mature (MII) oocytes that successfully fertilized, embryos developing to the blastocyst stage, and euploid blastocysts across the essential trace elements were quantified in each biofluid. The data were adjusted for age (continuous), BMI (continuous), and smoking status (never, former, or current). * p < 0.05. ET, embryo transfer; VOR, vaginal oocyte retrieval.

Figure 3

Forest plot representing the odds ratios (95% confidence interval) for the clinical reproductive outcomes. The odds ratios (95% CI) are presented for embryo transfer, implantation, clinical pregnancy, live birth, and reproductive goal (achievement of a live birth in a given cycle) following single frozen euploid embryo transfer across the essential trace elements quantified in each biofluid. The data were adjusted for age (continuous), BMI (continuous), and smoking status (never, former, or current). * p < 0.05. ET, embryo transfer; VOR, vaginal oocyte retrieval.