Pro-inflammatory Cytokines and Implantation Process in Women With Primary Idiopathic Infertility

Infertility is a common, worldwide problem. In about 20% of couples, the causative agent of infertility cannot be identified after routine diagnostic tests. One of the causes of idiopathic infertility may be implantation disorders.

Implantation can take place at a strictly defined moment in the menstrual cycle, when the capacity of the blastocyst to implant is overlapped with readiness for its acceptance by the endometrium, the so-called endometrial receptivity.The time interval in which the endometrium exhibits this property is called the implantation window.

The acquisition of receptivity by the endometrium is reflected in cellular and structural changes.The changes taking place at the cellular and molecular levels within the endometrium are compared to processes such as wound healing and degradation of the matrix during the neoplastic process.In considering the role of local inflammation in fertility, it is essential to distinguish between acute and chronic inflammation of moderate or low intensity.The profile of the molecules seen in a given inflammation depends on the severity, duration and mechanisms involved in the inflammation process, as well as the ability of the body's immune system to respond and adapt.IL-18 is a pro-inflammatory cytokine that mediates a type 1 cellular response. In the context of fertilization, IL-18 is a bivalent cytokine. Outside of the implantation window, IL-18 acts as an IFN-gamma inducer and is seen as a detrimental factor in the implantation process. During the implantation window, IL-18 becomes one of the main factors involved in the proper preparation of the spiral arteries. Histamine meets all the criteria of an inflammatory mediator. Histamine expression is also expressed in the endometrium, where it plays the role of a paracrine messenger during embryo decision-making and implantation. Adequate glucose uptake and metabolism are essential for the proper differentiation of the uterine endometrium towards a receptive state that allows the implantation of the embryo. The best described and most abundant glucose transporter in the endometrial stroma is GLUT1. However, there are no data on the role of GLUT4 in undetermined infertility.

GLUT4 is one of the better studied transporters because of its major role in whole body glucose homeostasis and the pathogenesis of type II diabetes.

Aims:1. Analysis of the level of interleukin 18 and histamine as molecules with a postulated role in the implantation process in the receptive endometrium in women with primary infertility of unknown etiology and comparing it to the group of women with naturally conceived offspring.

2. Assessment of the correlation of the levels of interleukin 18 and histamine in the receptive endometrium and in the blood as an attempt to find a diagnostic useful marker of receptivity.

3. Analysis of GLUT4 level in the receptive endometrium between two groups.

Materials and Methods:

Patients recruited from among women hospitalized at the CMUJ Gynecological Endocrinology Clinic for hormonal diagnostics.

1. The patient's visit during the implantation window (appropriate time of the cycle determined on the basis of ultrasound ovulation monitoring)
2. Endometrial aspiration biopsy, venous blood collection (5 ml). Preparation of material.
3. Analysis of the collected material.