F&S science · 2024
Blood-based inflammatory markers in female infertility: evidence from Mendelian randomization analysis.
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Alesi Simon, Teede Helena, Enticott Joanne, De Silva Kushan, Mousa Aya
Аннотация
OBJECTIVE: To investigate causal associations between blood-based inflammatory markers and female infertility using Mendelian randomization (MR).
DESIGN: Mendelian randomization using genome-wide association study data.
SUBJECTS: Large female-only cohorts of European ancestry.
EXPOSURE: Blood-based inflammatory markers (C-reactive protein, interleukins, monocyte chemoattractant protein-1, tumor necrosis factor-α, interferon-γ).
MAIN OUTCOME MEASURES: Anovulatory infertility (1,054 cases and 117,098 controls); female infertility of other/unspecified origin (5,667 cases and 117,098 controls); and medical treatment for female infertility (2,706 cases and 120,873 controls). Total causal effects were assessed using univariable two-sample methods including inverse variance weighted (IVW) as the primary analysis, as well as other secondary analyses (MR-Egger, weighted median, etc.), with relevant quality assessments.
RESULTS: Interleukin-8 demonstrated a positive association with anovulatory infertility via IVW (odds ratio, 95% confidence interval; 1.51, 1.04-2.21) and weighted median (1.64, 1.05-2.57) methods. Monocyte chemoattractant protein-1 was associated with anovulatory infertility via MR-Egger (2.06, 1.13-3.77). Inverse associations were found for interleukins-12 and -18 via IVW, with higher interleukin-12 being associated with lower medical treatment for female infertility (0.75, 0.59-0.94), whereas higher interleukin-18 was associated with lower female infertility of other/unspecified origin (0.90, 0.83-0.97).
CONCLUSIONS: This is the first study to examine causal relationships between inflammation and female infertility using MR. Monocyte chemoattractant protein-1 and interleukin-8 are implicated in anovulatory infertility; however, only the relationship with interleukin-8 was evident in the primary analysis. Interleukins-12 and -18 demonstrated inverse associations with infertility outcomes. Further research is needed to uncover the mechanistic functions of these markers to confirm causality and examine their therapeutic potential for female infertility.
DESIGN: Mendelian randomization using genome-wide association study data.
SUBJECTS: Large female-only cohorts of European ancestry.
EXPOSURE: Blood-based inflammatory markers (C-reactive protein, interleukins, monocyte chemoattractant protein-1, tumor necrosis factor-α, interferon-γ).
MAIN OUTCOME MEASURES: Anovulatory infertility (1,054 cases and 117,098 controls); female infertility of other/unspecified origin (5,667 cases and 117,098 controls); and medical treatment for female infertility (2,706 cases and 120,873 controls). Total causal effects were assessed using univariable two-sample methods including inverse variance weighted (IVW) as the primary analysis, as well as other secondary analyses (MR-Egger, weighted median, etc.), with relevant quality assessments.
RESULTS: Interleukin-8 demonstrated a positive association with anovulatory infertility via IVW (odds ratio, 95% confidence interval; 1.51, 1.04-2.21) and weighted median (1.64, 1.05-2.57) methods. Monocyte chemoattractant protein-1 was associated with anovulatory infertility via MR-Egger (2.06, 1.13-3.77). Inverse associations were found for interleukins-12 and -18 via IVW, with higher interleukin-12 being associated with lower medical treatment for female infertility (0.75, 0.59-0.94), whereas higher interleukin-18 was associated with lower female infertility of other/unspecified origin (0.90, 0.83-0.97).
CONCLUSIONS: This is the first study to examine causal relationships between inflammation and female infertility using MR. Monocyte chemoattractant protein-1 and interleukin-8 are implicated in anovulatory infertility; however, only the relationship with interleukin-8 was evident in the primary analysis. Interleukins-12 and -18 demonstrated inverse associations with infertility outcomes. Further research is needed to uncover the mechanistic functions of these markers to confirm causality and examine their therapeutic potential for female infertility.