**1. Introduction**

#### **1.1. Inflammation and implantation**

Implantation has a complex and multistep process and mechanism, resulting in the blastocyst being embedded in the uterine endometrium, which is often viewed as the rate-limiting step for the in vitro fertilization (IVF) success. Implantation failure is related to either maternal factors or embryonic causes. Maternal factors include uterine anatomic abnormalities, thrombophilia, non-receptive endometrium and immunological factors.

Although uterine abnormalities are considered to have a relevant impact on the chances to conceive through IVF, conventional infertility investigations, based on ultrasound and hysterosalpingography (HSG), may miss subtle intrauterine lesions. Fatemi et al. demonstrat‐ ed that the prevalence of unsuspected intrauterine abnormalities in hysteroscopy before IVF ranges from 11 to 45% accordingly, recent reports suggest that hysteroscopy in the cycle preceding ovarian stimulation, could be useful for patients with recurrent implantation failure (RIF). It is well established that the success of embryo implantation depends on embryo quality and uterine integrity, including endometrial receptivity.

Although embryo quality is the most consistent factor for predicting implantation and pregnancy rates in IVF patients, this cannot be evaluated independently from uterine integrity or endometrial receptivity [1, 2].

The definition of RIF remains controversial, generally being defined as failure to conceive following two or three embryo transfer (ET) cycles, or cumulative transfer of >10 good-quality embryos [3].

Patients with RIF comprise a heterogeneous group that presents with diverse clinical problems, and need a thorough evaluation.

Evaluation of a couple with RIF includes assessment of maternal and paternal karyotypes, testing for antiphospholipid antibodies, and thorough assessment of the uterine cavity, including sampling of the endometrial lining.

Endometrial biopsy is one inexpensive and minimally invasive method to assess and study the physical and hormonal endometrial environment. If abnormalities are identified and corrected, implantation rates can be improved.

ber of detected species by up to fivefold. The detection of bacteria in the intrauterine cavi‐ ty by PCR, in the absence of signs of infection, confirms the proposition of a non-sterile

This chapter will focus on chronic endometritis, uterine microbiome and hydrosalpinges and will review the diagnosis, pathophysiology and the recommended treatments of

**Keywords:** Uterine Microbiome, Chronic Endometritis, Hydrosalpinges, Implantation

Implantation has a complex and multistep process and mechanism, resulting in the blastocyst being embedded in the uterine endometrium, which is often viewed as the rate-limiting step for the in vitro fertilization (IVF) success. Implantation failure is related to either maternal factors or embryonic causes. Maternal factors include uterine anatomic abnormalities,

Although uterine abnormalities are considered to have a relevant impact on the chances to conceive through IVF, conventional infertility investigations, based on ultrasound and hysterosalpingography (HSG), may miss subtle intrauterine lesions. Fatemi et al. demonstrat‐ ed that the prevalence of unsuspected intrauterine abnormalities in hysteroscopy before IVF ranges from 11 to 45% accordingly, recent reports suggest that hysteroscopy in the cycle preceding ovarian stimulation, could be useful for patients with recurrent implantation failure (RIF). It is well established that the success of embryo implantation depends on embryo quality

Although embryo quality is the most consistent factor for predicting implantation and pregnancy rates in IVF patients, this cannot be evaluated independently from uterine integrity

The definition of RIF remains controversial, generally being defined as failure to conceive following two or three embryo transfer (ET) cycles, or cumulative transfer of >10 good-quality

Patients with RIF comprise a heterogeneous group that presents with diverse clinical problems,

Evaluation of a couple with RIF includes assessment of maternal and paternal karyotypes, testing for antiphospholipid antibodies, and thorough assessment of the uterine cavity,

these specific inflammatory processes that contribute to implantation failure.

thrombophilia, non-receptive endometrium and immunological factors.

and uterine integrity, including endometrial receptivity.

uterus.

100 Genital Infections and Infertility

**1. Introduction**

Failure, Infertility

**1.1. Inflammation and implantation**

or endometrial receptivity [1, 2].

and need a thorough evaluation.

including sampling of the endometrial lining.

embryos [3].

Chronic endometritis (CE) is a persistent inflammation of the endometrial lining. Histologi‐ cally, the diagnosis of CE is generally based on finding plasma cells, which infiltrates in endometrial biopsies [4]. CE is thought to be related to infertility and spontaneous abortion, and is mostly asymptomatic and rarely suspected clinically [2, 5, 6].

Implantation is believed to be a process with physiologic inflammation, involved with inflammatory mediators, such as leukocytes, chemokines and other pro inflammatory mediators [7].

The great effect of inflammation on implantation was shown in mice by the localized implan‐ tation defect after the blockade of the pre-implantation cellular influx into one of the two uterine horns [8]. There is also notable histologic [9] and biochemical [10] supports on the role of physiologic inflammation in labor at term.

The decidua in human uterus has a great number of immune cells such as macrophages [11], natural killer (NK) cells [12, 13], T cells [14] and stromal cells [15] capable to produce soluble factors (e.g., prostaglandins, chemokines and cytokines) involved in regulating the immune response [16].

Wegmann et al. [17], through the classification of T cells into two subgroups by their cytokine profile (Th-1 producing INF, interleukin (IL)-2, and Th-2 producing IL-4, IL-5), suggested that pregnancy takes place in the content of a predominant Th-2 response, and that increase toward Th-1 levels would decrease the chance of successful pregnancy [11].

Although the discovery of newer cytokines and complexity of the inflammatory response at the feto-maternal interface has increased the understanding of the role of specific cellular subtypes (e.g., dendritic cells, natural killer cells, and regulatory T cells) [16] on implantation and pregnancy, the evidence that a Th-1 response in the human decidua may lead to sponta‐ neous abortion remains substantial.

Regardless of how the micro organisms and inflammation effect the implantation, one thing is clear: the cause, prevalence and results of subclinical infection and inflammation in the endometrium and their effect on pregnancy failure (infertility, implantation failure, sponta‐ neous abortion, preterm birth) deserve great attention as a mechanism of pathology [12].

The presence of high concentrations of endotoxins (components of gram negative Bacteria) induces a reaction of TH1 inflammatory cells. TH1 cells may predispose a hostile endometrial environment and thereby cause implantation failure, spontaneous abortion or even premature labor. Endometritis is also considered to be an inflammatory reaction. In contrast to acute endometritis, in CE, usually no causal pathogen can be identified.
