**2. Clinical appearance**

Chronic endometritis is often clinically silent. Therefore, it is impossible to accurately deter‐ mine its true prevalence in the general population [5].

In some cases, however, it can be associated with *infertility* [9–11].

Endometrial inflammation seems to interfere with the physiological mechanisms of oocyte fertilization and embryonic implantation.

Repeated implantation failure (RIF) is defined as failure to conceive following two or three embryo transfer cycles or cumulative transfer of 10 good quality embryos [12,13].

In a retrospective study reported by Johnston-MacAnanny [14], women with a history of RIF after in vitro fertilization (IVF) were positively diagnosed with chronic endometritis in about 30% of cases and women diagnosed with chronic endometritis had lower implantation rates (11.5%) after IVF cycles.

In contrast, Kasius et al. [15] reported that the clinical implication of chronic endometritis seems minimal because they diagnosed this condition only in 2.8% of asymptomatic infertile patients with a normal transvaginal ultrasound examination (TVS). The same authors reported that the reproductive outcome at conventional In Vitro Fertilization (IVF) or Intra-cytoplasmic sperm injection (ICSI) cycles was not negatively affected by chronic endometritis, but they underlined that the low prevalence and unknown clinical significance of endometritis warrant further study [15, 16].

Cicinelli et al. [12], in a recent pilot research, demonstrated that chronic endometritis was a condition frequently associated with RIF (66.0%). It was about double compared with 30.3% reported by Johnston-MacAnanny et al. [14]. This discrepancy could be explained by the very strict selection criteria employed in this study (for example, in order to rule out any confound‐ ing factor and inflammatory conditions, they considered clinical or ultrasonographic evidence of ovarian endometrioma as an exclusion criterion) and by the expertise of their group in hysteroscopic and histological diagnosis of chronic endometritis. In this population study, the most prevalent infectious agents were common bacteria and mycoplasma. In addition, the normalization of the hysteroscopic endometrial pattern was associated with a significant improvement of the reproductive outcome of the IVF cycle performed after antibiotic treat‐ ment.

Chronic endometritis is also related to recurrent miscarriage (RM) [17].

RM, defined as three or more miscarriages before 20 weeks of pregnancy, affects about 3% of all couples [4, 18].

In a recent paper, it was demonstrated that in women with repeated abortions, chronic endometritis is a frequent finding (68.3%) and that women who received adequate antibiotic treatment had a significantly higher rate of successful pregnancies compared to women who were not treated or with persistent disease. Also in this population, the most prevalent infectious agents were common bacteria and *Mycoplasma* [12, 18].

In conclusion, untreated chronic endometritis seems to diminish the success rates of both spontaneous conception and IVF cycles, as well as to contribute to adverse obstetrical out‐ comes, as intrauterine infections, preterm delivery, and postpartum endometritis [2–4, 12, 16, 19–21]. Furthermore, all these results suggest that hysteroscopy should be a part of the diagnostic work-up of infertile women complaining of unexplained RM and with RIF [18, 22].

However, the exact mechanisms by which chronic endometritis can lead to a compromised fertility are not yet fully understood and are still the subject of numerous studies.

Very recently, it was shown that in the endometrial mucosa of infertile patients suffering from chronic endometritis, there is an altered distribution of natural killer cells. In particular, in chronic endometritis, there is a decrease in CD56 lymphocytes and an increase in CD16 lymphocytes, hence, an altered maternal immune tolerance towards the embryo, along with adverse effects on the mechanisms of implantation, and a defective trophoblastic invasion [23].

Other symptoms related to chronic endometritis are as follows [24]:


Chronic inflammation may follow the acute stage—which is the most frequently seen—or it may occur more subtly, as chronic inflammation 'ab initio', without passing through an acute

Chronic endometritis can reveal a microbiological origin or a mechanical–chemical origin [5]. In the latter case, the most frequent causative agents are common pyogenic pathogens (streptococci, staphylococci, enterococci, *Escherichia coli*), as well as bacteria such as *Chlamydia trachomatis*, *Neisseria gonorrhoeae*, *Mycoplasma*, and *Ureaplasma urealyticum*. It has also been described in cases of postpartum endometritis secondary to herpes simplex virus (HSV) and

However, although the etiology in most cases is polymicrobial, the results obtained by traditional culture tests are laboratory dependent, and often, given the use of endometrial

Also worth mentioning is tubercular endometritis, because in recent years there has been an increased incidence of tuberculosis in Western countries, owing to migration from countries

Endometritis of chemical–mechanical origin, on the other hand, is generally caused by the

Chronic endometritis is often clinically silent. Therefore, it is impossible to accurately deter‐

Endometrial inflammation seems to interfere with the physiological mechanisms of oocyte

Repeated implantation failure (RIF) is defined as failure to conceive following two or three

In a retrospective study reported by Johnston-MacAnanny [14], women with a history of RIF after in vitro fertilization (IVF) were positively diagnosed with chronic endometritis in about 30% of cases and women diagnosed with chronic endometritis had lower implantation rates

In contrast, Kasius et al. [15] reported that the clinical implication of chronic endometritis seems minimal because they diagnosed this condition only in 2.8% of asymptomatic infertile patients with a normal transvaginal ultrasound examination (TVS). The same authors reported that the reproductive outcome at conventional In Vitro Fertilization (IVF) or Intra-cytoplasmic sperm injection (ICSI) cycles was not negatively affected by chronic endometritis, but they underlined that the low prevalence and unknown clinical significance of endometritis warrant further

embryo transfer cycles or cumulative transfer of 10 good quality embryos [12,13].

cytomegalovirus (CMV) infections, particularly in patients with HIV [6–8].

with a high incidence of endemic tuberculosis.

presence of pessaries or intrauterine devices.

fertilization and embryonic implantation.

mine its true prevalence in the general population [5].

In some cases, however, it can be associated with *infertility* [9–11].

**2. Clinical appearance**

(11.5%) after IVF cycles.

study [15, 16].

sampling devices, vaginal and endocervical contamination cannot be excluded.

stage.

36 Genital Infections and Infertility


Tubercular endometritis merits special mention; this type of chronic endometrial inflammation virtually always occurs secondary to respiratory or abdominal localization, with a clear predilection for adnexal localization. It is generally limited to young women of childbearing age, being rare in the menopause.

The symptomatology varies from overt forms, in which the inflammatory process has affected the appendages, to completely latent forms. In the presence of tubercular endometritis, changes in menstrual flow may occur, ranging from polymenorrhea to amenorrhea, accom‐ panied by an almost universal history of sterility/infertility.
