OE is a common benign gynecological disease, but a secondary TOA formation is seldom reported. Schmidt et al. reported the incidence of OE-TOA to be 2.15% in 1981;13 this was consistent with previous reports that indicated that the incidence of OE-TOA was 2.3%.14 Of the 5,595 patients with OE in this study, 44 (0.79%) were diagnosed with OE-TOA. The incidence in this study was lower compared to that in previous reports. Although OE-TOA is rare, it is serious and sometimes fatal. This area of study requires our attention, as it has long been neglected.
Patients with OE are more susceptible than the general population to TOA.14 Possible pathogeneses are as follows. (1) OE, which is itself is an immunodeficiency disease, leading to impairment in the ability of the immune system to wade off infections, at which point TOA easily emerges. (2) The OE capsule wall is thin and delicate, making it easy for bacteria to penetrate. (3) At the same time, OE blood content is an ideal culture medium that facilitates bacterial growth.15 (4) The “bacterial contamination hypothesis” states that the incidence and occurrence of intrauterine microbial colonization and endometritis are significantly higher among women with endometriosis, especially after gonadotrophin-releasing hormone agonist treatment.16
We observed a more than 5-fold increase in OE-TOA risk after lower genital tract infection, which is in line with reports of previous studies. This may be because the cervical mucosal barrier is impaired during pathogenic microorganism infection; hence, infection can spread along the endometrium to other pelvic organs such as the fallopian tubes and ovaries.17 This is a classic pattern of spread. According to related studies in the United States and Nordic countries, the pathogenic microorganisms of PID or TOA most commonly identified were Neisseria gonorrhea and Chlamydia trachomatis.18,19 This is not the case in China. Several domestic studies have indicated low detection rates for both microbes. A new study focusing on next-generation sequencing analysis of cervical mucus indicates that in a variable microbiota, two organisms, Enterobacteriaceae and Streptococcus, are more frequently detected in women with endometriosis.20 Results of this study show that the microbial detection rate in the lower genital tract was significantly higher in cases than in controls. Furthermore, the main pathogen was Escherichia coli (50%), followed by Mycoplasma genitalium (21.4%) and Gardnerella vaginalis (21.4%). This is partially in agreement with reports of previous studies, emphasizing the need to promptly investigate and effectively treat these infections with appropriate antibiotics.
Spontaneous rupture of ovarian endometriotic cysts was found to be a significant contributor to the risk of OE-TOA (OR = 2.572). To the best of our knowledge, rupturing of an ovarian endometriotic cyst as a risk factor for TOA has not been previously evaluated. Spontaneous rupture of an OE cyst is not usually a gynecological emergency. The incidence rate is seldom available in the literature from different countries, and the incidence rates reported in Chinese studies are inconsistent. The disease, characterized by abdominal pain and inflammation,21 is easily misdiagnosed due to its nonspecific clinical features and the lack of knowledge regarding biomarkers for early diagnosis.22 Through analysis, our data shows that the incidence rates of OE cyst rupture in the case and control groups were 9.1% and 1.5%, respectively. Women with spontaneous rupture of ovarian endometriotic cysts had an increased risk of developing TOA. The exact underlying mechanism of this remains unclear. One possible explanation is that the capsule wall easily ruptures because of bleeding of the cyst and increased pressure during the pre-menstruation and menstruation phases of the menstrual cycle.23 When the cyst bursts, a chocolate-like fluid pours into the abdominal cavity, leading to peritonitis. In addition, the blood content of an OE cyst is a good culture medium for mixed anaerobic bacteria, aerobic bacteria, and facultative bacterial infections.24 If treatment is not initiated promptly, this could progress to a much more severe condition such as a TOA.
Finally, whether a patient with OE will develop TOA after IVF has been a controversial topic. Several studies propose that IVF and oocyte retrieval are major risk factors for the development of OE-TOA. Moreover, the condition is often more serious in these cases. The above conclusions are supported by the theory that the blood in an endometrioma offers a nutrient-rich culture for bacterial growth after transvaginal inoculation.25 However, it is thought that the rate of TOA is low in patients suspected of having an ovarian endometriotic cyst after IVF and egg retrieval, even though no such patients have undergone laparoscopic exploration.26,27 Another view is that endometriosis-related infectious disease may be unrelated to assisted reproductive technology and that once OE-TOA occurs, the best form of intervention is early surgical drainage combined with intravenous antibiotics.28 The results of our study directly contradict the view that patients with OE are more likely to have TOA after IVF or oocyte retrieval. These patients may benefit from comprehensive disinfection, antibiotic treatment, and ultrasound guidance to avoid intestinal puncture during oocyte retrieval.
This was a pilot study, and further studies with larger sample sizes are needed to confirm our findings. Some limitations of this work are its single-institutional retrospective design and the lack of larger clinical evidence.