Aydın T., Akcay B., Yazar S., Dogan S., Bican G., Koroglu N.
HUMAN REPRODUCTION, cilt.41, sa.Supplement_1, ss.813, 2026 (SCI-Expanded, Scopus)
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Yayın Türü:
Makale / Tam Makale
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Cilt numarası:
41
Sayı:
Supplement_1
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Basım Tarihi:
2026
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Doi Numarası:
10.1093/humrep/deag083.1140
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Dergi Adı:
HUMAN REPRODUCTION
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Derginin Tarandığı İndeksler:
Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Scopus, Pharma Collection (ProQuest), Science Citation Index Expanded (SCI-EXPANDED), BIOSIS, CINAHL, EMBASE, Gender Studies Database, MEDLINE
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Sayfa Sayıları:
ss.813
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Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli:
Evet
Özet
Abstract
Study question
Does heavy metal exposure affect serum Klotho levels and embryo quality in infertile women diagnosed with diminished ovarian reserve (DOR)?
Summary answer
Higher follicular fluid zinc and chromium levels were observed in women with DOR and associated with poorer embryo quality, serum Klotho levels similar between groups.
What is known already
Environmental exposure to heavy metals has been increasingly recognized as a contributor to impaired IVF outcomes through mechanisms involving oxidative stress, inflammation, and altered cellular homeostasis. Elevated concentrations of heavy metal such as lead (Pb), cadmium (Cd), nickel (Ni) and Cr in serum and follicular fluid have been associated with reduced oocyte competence, delayed cleavage kinetics, lower blastocyst quality and decreased implantation live birth rates. Klotho, an anti-aging protein involved in oxidative stress regulation and metabolic balance, has been associated with ovarian reserve and reproductive aging; however, its interaction with environmental toxic exposure remains insufficiently explored.
Study design, size, duration
This prospective observational study was conducted between 2024 and 2025 and included 128 women aged 18-39 years undergoing IVF treatment (64 with DOR and 64 controls).
Participants/materials, setting, methods
DOR was defined according to Bologna criteria; to minimize confounding effect of age on ovarian reserve and embryo quality, women aged>40 years were excluded. Controls had normal ovarian reserve. Serum Klotho levels were measured using ELISA, and follicular fluid heavy metals concentrations were analyzed by ICP-MS. Embryo quality was assessed at the blastocyst stage using Gardner criteria. Associations between heavy metals, Klotho levels, and embryo development parameters were assessed using correlation and multivariable regression analyses.
Main results and the role of chance
Baseline lifestyle characteristics, including smoking status, chemical exposure and infertility duration, were comparable between the DOR and control groups; however, cosmetic product use was significantly more frequent in the control group (p < 0.05). Women with DOR had significantly lower numbers of total oocytes, mature oocytes, and day-5 embryos compared to controls. Follicular fluid Zn and Cr levels were significantly higher in the DOR group (p < 0.05), while follicular fluid Pb, Cd, Ni, and serum Klotho levels were similar between groups. Higher follicular fluid Zn levels were weakly associated with blastocyst quality parameters and independently predicted day-5 embryo formation in multivariable analysis. When stratified by smoking status, smokers exhibited significantly higher follicular fluid levels of Ni, Zn, Cd, and Pb compared with non-smokers (all p < 0,001), whereas Cr levels did not differ between groups. Serum klotho levels were significantly lower in smokers than in non-smokers (p = 0.007). Spearman correlation analysis demonstrated a weak negative association between serum Klotho and Cd levels (p=-0.269, p = 0.015), while no significant correlations were observed between Klotho and Cr, Ni, Zn, or Pb (all p > 0.05).
Limitations, reasons for caution
The single-center design may limit generalizability of the findings. Although the study was prospectively conducted, its observational nature does not allow for causal inference. In addition, heavy metal concentrations were not measured in serum, limiting conclusions regarding systemic exposure.
Wider implications of the findings
These findings highlight the potential impact of environmental and lifestyle-related exposures on the follicular microenvironment and embryo developmental competence, particularly in women with DOR. Assessment of environmental toxic exposure and targeted counseling on smoking cessation and lifestyle modification could contribute to optimize IVF outcomes in this patient population.
Trial registration number
No