Hidden Burden of Subclinical Pelvic Inflammatory Disease: Its Impact on Fertility and Reproductive Outcomes: A Cross-Sectional and Clinical Correlation Study

Pelvic inflammatory disease (PID) continues to be one of the most significant, yet under-recognized causes of reproductive morbidity in women of reproductive age worldwide.[1] It is an ascending infection of the upper female genital tract of the endometrium, tubes, ovary and the surrounding pelvic structures.[2] A large number of cases of acute PID are diagnosed late and are subclinical or may be without any symptoms or signs, and present with pelvic pain, fever and abnormal vaginal discharge.[3] This often asymptomatic or mildly symptomatic form of PID, or subclinical PID (SPID), has become an important public health issue due to its slow progression and long-term reproductive ramifications.[4]

Sexually transmitted infections (STIs) such as Chlamydia trachomatis and Neisseria gonorrhoeae are significant factors involved in the development of PID worldwide.[5] It is estimated that over 374 million new curable STIs occur annually globally, which results in a significant reservoir of upper genital tract infections.[6] Research indicates that about 10-20% of untreated chlamydial infections develop into PID, and a significant number of these cases are subclinical.[7]

Subclinical PID is important because it causes inflammation and progressive damage to the reproductive tract, but it does not have enough symptoms to seek medical care.[8] Chronic inflammatory processes may cause fibrosis, scarring of the tubes, peritubal adhesions, and changes to the endometrial receptivity.[9] These changes have a negative impact on fertility potential and reproductive success. Moreover, tubal factor infertility contributes to about 25–35% of all female cases of infertility

A total of 131 women were included in this study, and the distribution of mean age was primarily in the group aged 26–35 years. Slightly more than half of the participants were from urban areas, while the remaining belonged to rural settings. Education-wise, a significant number of women did not have a secondary level of education and almost 75% were housewives. The majority of participants were from low-to-middle socioeconomic status groups, and represented a middle- and lower-class reproductive population. (Table 1)

The majority of women were multiparous and married for more than five years; a significant proportion of women had been married for over 10 years in terms of marital history. A significant number of the participants reported experiencing infertility, and fewer reported having experienced a miscarriage or ectopic pregnancy. More than a third of women experienced chronic pelvic pain and about a quarter had a history suggestive of sexually transmitted infection. (Table 2)

Nearly one-third of the population of the study showed evidence suggestive of silent upper genital tract inflammation, with an overall prevalence of 29.0% for subclinical PID. The majority did not have clinical or investigational characteristics of subclinical PID. (Table 3)

Infertility was found to be significantly related to subclinical PID. Women with subclinical PID had a significantly larger percentage of infertility than those without subclinical PID, suggesting a significant reproductive consequences of silent pelvic infection. (Table 4)

Likewise, subclinical PID was found to be a statistically significant factor in recurrent pregnancy loss, with women having recurrent pregnancy loss exhibiting more pregnancy losses than women without PID. This is indicative of the potential importance of chronic pelvic inflammation in the causation of early pregnancy loss. (Table 5)

Another significant relationship was found between tubal damage and abnormal implantation as ectopic pregnancy was more common among women with subclinical PID than those without it. (Table 6)

Those women who developed subclinical PID had significantly higher rates of chronic pelvic pain, indicating that the subclinical inflammation remains an important factor in chronic pelvic morbidity and affecting women's quality of life. (Table 7)

After crude odds ratio analysis, a number of sociodemographic and reproductive factors were found to be significant for subclinical PID. Older age group, lower educational status, low socioeconomic status, longer duration of marriage, positive history of sexually transmitted infections, and infertility were all associated with higher odds of subclinical PID while chronic pelvic pain was not. Chronic pelvic pain, infertility and history of sexually transmitted infections showed the strongest associations with the presence of subclinical pelvic inflammation. (Table 8)

Subclinical PID was shown to be strongly and consistently linked with adverse reproductive outcomes. Women with subclinical PID were significantly more likely to be infertile, experience recurrent pregnancy loss, ectopic pregnancy and chronic pelvic pain than those without PID. Association was greatest for chronic pelvic pain and infertility and was also present with ectopic pregnancy, highlighting the potential for long-term reproductive and clinical impacts of the silent pelvic infection. The results highlight the significant reproductive consequences associated with subclinical PID. (Table 9).

Table 1: Socio-demographic Characteristics of Study Participants (n = 131)

Table 2: Reproductive and Gynecological History of Participants (n = 131)

Table 3: Prevalence of Subclinical Pelvic Inflammatory Disease (SPID) (n = 131)

Table 4: Association of Subclinical PID with Infertility (n = 131)

Table 5: Association of Subclinical PID with Recurrent Pregnancy Loss (n = 131)

Table 6: Association of Subclinical PID with Ectopic Pregnancy (n = 131)

Table 7: Association of Subclinical PID with Chronic Pelvic Pain (n = 131)

Table 8: Crude Odds Ratios (ORs) for Factors Associated with Subclinical PID

Table 9: Crude Odds Ratios for Association between Subclinical PID and Reproductive Outcomes

The present study showed that the prevalence of subclinical PID was 29% and was significantly correlated with poor reproductive outcomes such as infertility, recurrent pregnancy loss, ectopic pregnancy, and chronic pelvic pain. The findings underscore the significant unrecognized morbidity and impact of subclinical PID on women of reproductive age.

The current study found a prevalence of subclinical PID similar to that seen in previous studies. Haggerty et al. found that subclinical endometritis was present in about 20-35% of women with a risk of sexually transmitted infections, and was significantly associated with poorer fertility outcomes, reinforcing the notion of this condition being underdiagnosed in routine gynecologic care.[16] Likewise, a prospective cohort study by Hunt et al. 2023 showed that women with subclinical PID had a significantly decreased chance of conception, which further confirms the direct effect of PID on women's fertility potential.[11]

The present study revealed the strong association of subclinical PID with infertility (OR 6.85), similar to findings in the large cohort studies. In a retrospective study performed by Price et al., women who had previously been infected with PID were almost twice as likely as women who had not been infected to become infertile, and even more likely to be infertile if the infection occurred repeatedly or was not treated.[17] Likewise, a case-control study from China identified by Liu et al. showed that PID-related tubal damage is also a major contributor to the risk of infertility, especially in women who had been previously infected with C. trachomatis.[7]

The correlation between subclinical PID and ectopic pregnancy found in the current study is also reflected in the worldwide literature. A population-based cohort study found that women with prior PID were 1.8 to 2.5 times more likely to have ectopic pregnancy because of the tubal scarring and decreased embryo transport.[18] Also, an epidemiological study conducted by Gandotra et al. revealed that delayed diagnosis was one of the most independent risk factors for ectopic pregnancy in reproductive-age women, with PID being one of the strongest when performed in low-resource areas.[19] This is consistent with our observation that even subclinical infections were associated with a significant increase in ectopic implantation risk.

Subclinical PID was found to be significantly associated with recurrent pregnancy loss in the present study. This is supported by studies that show chronic endometrial inflammation may be harmful to implantation and initial placental development.[20] Several inflammatory pathways have been suggested in the recent literature, involving chronic cytokinesis and endometrial receptivity alterations, which are associated with early pregnancy failure.[21, 22]

In this study, chronic pelvic pain was also strongly associated with subclinical PID (OR 6.93). This occurs in line with several studies that have indicated chronic pelvic pain is one of the most frequent sequelae of PID. A study in the hospital setting had previously shown that women with previous PID suffered from chronic pelvic pain and a significant decrease in quality of life because of pelvic adhesion and persistent inflammation.[23] In addition, cohort studies conducted in other countries have shown that chronic pain syndromes are a major factor in the pathogenesis of both clinical and subclinical PID when inflammation persists and leads to pelvic adhesions.

The present study shows that subclinical PID is not an innocuous disease, but a significant, unrecognized cause of infertility and reproductive morbidity worldwide. In this study the consistency of the associations with several outcomes further supports the biological plausibility of damage to the tubal and endometrial tissues due to chronic inflammation as the underlying mechanism.

Several limitations in this study should be taken into consideration for the interpretation of the results. Most importantly, because of the cross-sectional study design, it is difficult to draw causal inferences between subclinical PID and adverse reproductive outcomes because exposure and outcome were measured concurrently. Second, the study was conducted at a single tertiary care hospital and utilized non-probability consecutive sampling due to limitations in time, resources, and access to multiple healthcare centers during the study period. Third, subclinical PID was based on clinical assessment and available investigations in all patients and not on laparoscopy or histopathology, and this could have contributed to misclassification. Additionally, self-reported reproductive and infection histories could have been subject to recall bias. Moreover, unmeasured confounding variables (partner-related infections and detailed microbiological profiling) were insufficiently investigated.

The importance of subclinical pelvic inflammatory disease as a major and frequently unrecognized cause of female reproductive morbidity was stressed in the present study, and a significant number of women had evidence of silent pelvic infection. The link between subclinical PID and poor reproductive outcomes was significant and consistent, highlighting the subclinical nature of its effects on reproductive health, such as infertility, recurrent pregnancy loss, ectopic pregnancy, and chronic pelvic pain. The results highlight the importance of increased clinical vigilance, timely screening protocols, and reproductive health prevention measures, especially among vulnerable groups. Early intervention for subclinical PID could be critical to maintain fertility and reproductive outcomes for women of reproductive age.