Association of Serum and Follicular Zinc Levels With Stimulation Response in Intracytoplasmic Sperm Injection: A Prospective Cohort Study

Abstract

Objectives: To evaluate the associations between serum and follicular zinc levels and the response to intracytoplasmic sperm injection (ICSI). Patients and Methods: A prospective cohort study was conducted between May 2022 and May 2023 on 120 infertile women randomly selected based on specific criteria. The patients were classified into three groups according to stimulation response. Serum zinc level was measured in all patients on the day of ovarian stimulation, and follicular fluid zinc level was measured at the time of pickup. We monitored the patients to evaluate the correlation between serum and follicular zinc levels, as well as the reaction to ovarian stimulation. We assessed oocyte quality and quantity, fertilization rate, embryo quality, and clinical pregnancy rate. Results: The participants were homogenized at comparable ages. The 120 patients were classified into three groups according to the number of oocytes retrieved after ovum pick-up: four oocytes were categorized as poor responders (n = 40), 4-15 retrieved oocytes were categorized as normal responders (n = 40), and >15 retrieved oocytes were categorized as hyper-responders (n = 40). The poor responders had significantly lower serum and follicular zinc levels than the others. There was a significant difference between the three groups (P value = 0.0001). There was a direct positive correlation between serum and follicular zinc levels. However, there was a moderately negative correlation between the serum and follicular zinc levels and the total gonadotropin dose. On the other hand, there was a slightly positive link between the amount of zinc in the serum and follicles and the response to stimulation in the ICSI cycle in terms of the number of oocytes, ovarian sensitivity index (OSI), follicular output rate (FORT), and follicle-to-oocyte index (FOI). There was a strong positive correlation between serum and follicular zinc levels and the fertilization rate and number of MII but a weak positive correlation with the number of MI. All significant correlations between serum and follicular zinc levels were found to be predictors of clinical pregnancy. Conclusions: The serum zinc level at stimulation day was reflected in the follicular fluid zinc levels after stimulation and at the time of ovum pick-up. Both of them predict the success of an ICSI cycle, including the response to stimulation and the pregnancy rate. The serum zinc level can also indicate cases that may progress to clinical pregnancy. It is crucial to measure the blood zinc levels of women preparing to undergo ICSI. The start of ICSI program should be delayed until the serum zinc level is optimal, as it is a predictor of the response to stimulation and the outcome of the ICSI cycle. Encouraging adequate zinc intake prevents the potential impact of altered zinc levels on the success rate of these women’s responses to stimulation.