Correlation Study of Inflammatory Factors and Ovarian Reserve Decline in Infertile Women

  

    
Variables 
    
β 
    
S.E.
    
Wald
    
P
    
OR
    
95%CI
  
  

    
Age 
    
-0.120
    
0.037
    
10.698
    
<0.001 
    
0.885
    
0.824~0.951
  
  

    
Infertility years 
    
0.069
    
0.048
    
2.074
    
0.151
    
1.071
    
0.975~1.177
  
  

    
Infertility type 
    
-0.699
    
0.215
    
10.529
    
<0.001 
    
0.497
    
0.326~0.758
  
  

    
BMI (kg/m2) 
    
-0.072
    
0.027
    
7.033
    
0.008
    
0.93
    
0.882~0.981
  
  

    
Endometriosis 
    
0.047
    
0.366
    
0.017
    
0.898
    
1.048
    
0.511~2.150
  
  

    
MONO (109/L) 
    
-0.466
    
0.703
    
0.158
    
0.507
    
0.627
    
0.158~2.486
  
  

    
NEUT (109/L) 
    
0.451
    
0.071
    
1.366
    
<0.001 
    
1.570
    
1.366~1.805
  
  

    
*MONO represents monocyte    count; NEUT neutrophil count. 
  

Table 3: Comparison of infertility types in the two groups.

Discussion

Ovarian reserve function is a measure of the quantity and quality of ovulation in female ovaries, which can directly affect fertility. Current methods for assessing ovarian reserve include hormonal assessments, such as measuring serum levels of anti-mullersonian hormone (Anti-Muller Hormone AMH) and follicular stimulating hormone (Follations Stimulate Hormones FSH), and the imaging technique for transvaginal ultrasound counting [2-4]. Despite advances in these techniques, significant gaps remain in understanding the complex biological mechanisms governing ovarian reserve and its decline with age or pathological conditions. How to seek a valid indicator to evaluate, and this indicator is easily accessible, this is the objective of this study.

Between DOR patients and non-DOR patients, we compared the counts of various indicators in blood routine (Table 2). Median MONO and NEUT, DOR group were lower than non-DOR group, the difference was statistically significant (P <0.001). Through multivariate logistic regression analysis, the effect of NEUT on ovarian reserve function was an independent influencing factor of clinical pregnancy. Although the median MONO was statistically significant in group comparisons, the multivariate logistic regression analysis was not an independent influence of clinical pregnancy and could be influenced by other factors (Table 3). Although the specific regulatory network and mechanisms involved in NEUT in this process are still unclear, further studies are needed to clarify its role in ovarian reserve decline. However, it has reflected its importance in this study, and combined with previous studies, there is a possible correlation between inflammatory factors and ovarian reserve decline, suggesting that chronic inflammation may affect the physiological state of ovary through several mechanisms, such as by changing the endocrine environment or directly damaging ovarian tissue [11]. It causes significant harm to reproductive health, especially in pregnant women, the decline of ovarian function will lead to ovulation disorders, pregnancy complications and abortion problems [12]. In turn, chronic intestinal inflammation is very likely to affect the physiological function of the ovary, and then affect the maintenance of ovarian reserve function in [13-15]. Chronic inflammation may adversely affect ovarian function and the overall success of ART. Studies have shown that elevated levels of proinflammatory cytokines are associated with reduced response to ovarian stimulation and decreased pregnancy rate after entering the sperm injection flow, highlighting the complex relationship between inflammation and fertility outcomes [16-18]. In this study, excluding women with significant PCOS or other inflammatory conditions, we found between DOR and non-DOR infertility (P >0.05), but in the median of NEUT of conventional blood inflammatory indicators, indicating a more clear link between subclinical inflammation and reproductive outcomes, suggesting that even mild inflammatory status can negatively affect fertility. In addition, this study used regression analysis to find NEUT as an independent factor affecting clinical pregnancy, which is of great significance. We may find a way to solve inflammatory conditions and tailored treatment to reduce their effects may improve the success rate, which deserves further exploration in subsequent studies. Several previous studies have shown that polycystic ovary syndrome is a low-grade chronic inflammatory [11] with metabolic dysfunction. At present, the occurrence and development mechanism of inflammatory factors and decreased ovarian reserve function still need to be explored in depth. There may be individual differences in the effects of different types of ovarian diseases, inflammatory status and chemotherapy on ovarian reserve, so these factors need to be taken into account when developing treatment options. Future studies should focus on exploring how inflammatory factors influence ovarian reserve through different pathways and finding potential intervention strategies to actively address the fertility challenges of ovarian reserve decline.

NEUT has a correlation with ovarian reserve, and the lower NEUT is more prone to DOR. The specific mechanism needs further investigation. However, this study still has some limitations. First, patients with endometriosis were not excluded from this study, and previous studies have confirmed the possible correlation between inflammatory factors and endometriosis [19,20]. In addition, the sample size of DOR group still needs to be further expanded.

The sample size gap between DOR group and non-DOR group in this study is large, and more sample data of DOR is still needed to support, which can be solved by multi-center study; Second, the findings may still not be applicable to all infertility subgroups, such as those with unexplained infertility or other specific causes; Furthermore, the exclusion of women with Polycystic Ovary Syndrome (PCOS) may limit the applicability of our findings to populations exhibiting ovarian hyperresponsiveness, thus potentially oversimplifying the complex interplay between inflammation and ovarian reserve in different clinical situations. Finally, the crosssectional nature of the study limits the causal inferences, as the temporal relationship between inflammatory cytokines and ovarian responses remains to be elucidated. Recently, inflammatory factors have played crucial roles in various molecular biology as well as in pathological processes, including the regulation of ovarian reserve function. Studies have shown that there may be a correlation between inflammatory factors such as monocyte count and neutrophil count and decreased ovarian reserve function.

The chronic inflammatory state may lead to blocked follicle development and decreased egg quality by affecting cellular mechanisms within the ovary [16-18]. However, the relationship between NEUT and ovarian reserve function is still not completely defined, and the specific regulatory mechanisms need further investigation. Moreover, therapeutic strategies for decreased ovarian reserve function need to be explored to overcome drug resistance [21- 23].

In conclusion, this study concluded that NEUT, as a simple and clinically measurable routine blood parameter, has a correlation with ovarian reserve decline. And has some correlation with ovarian reserve decline, but its deep mechanism still needs further research.

Author Statements

Acknowledgements

We are indebted to Jing Cai contributions on the data analysis, Yan Sun, Kun Wang and Jia jun Zeng given a great help in the surgical operation and device design.

Authors contributions

Jing Cai, performed the data analyses and wrote the manuscript; Li Ya Song performed the surgeries and contributed significantly to analysis and manuscript preparation; Yan Sun, Kun Wang and Jia jun Zeng helped perform the analysis with constructive discussions. All authors reviewed the manuscript.

Declaration of conflicting interests

Jing Cai, Yan Sun, Kun Wang and Jia jun Zeng have no conflicts of interest or financial ties to disclose.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The General Project of Social Science and Technology Development in Dongguan City of China (Nos.20221800904462).

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