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

NCT05190250 | Completed

• 1 other identifier: K / DSC / 0042
• Study Type: observational
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Infertility, Female; Infertility Unexplained; Inflammatory Response

Keywords

infertility; inflammation; endometrial receptivity

Outcome Measures

Primary Outcomes (6)

• Il-18 in the blood

  Level of IL-18 in the blood in women with idiopathic infertility compared to women with children

  July 2017- December 2020

• Il-18 in endometrium

  Level of IL18 in endometrium in women who have children compared to women with idiopathic infertility

  July 2017- December 2020

• Histamine in the blood

  Histamine levels in the blood of women with idiopathic infertility compared to women who had children

  July 2017- December 2020

• Histamine in endometrium

  Histamine levels in the receptive endometrium of women with idiopathic infertility compared to women with children

  July 2017- December 2020

• GLUT4 in endometrium

  GLUT4 levels in the receptive endometrium of women with idiopathic infertility compared to women with children

  July 2017- December 2020

• Endometrium vs blood levels of histamine and Il-18

  Correlation between the level of IL-18 in the endometrium and its level in the blood. Correlation between the level of histamine in the endometrium and its level in the blood.

  July 2017- December 2020

Study Arms (2)

Study group - women with idiopathic infertility

Endometrial biopsy during implantation window Blood analysis

Diagnostic Test: Pipelle biopsy

Control group - women with naturally conceived offspring

Endometrial biopsy during implantation window Blood analysis

Diagnostic Test: Pipelle biopsy

Interventions

Pipelle biopsy DIAGNOSTIC_TEST

Ultrasonographically confirmed implantation window. Collection of material with use of Pipelle biopsy. Collection of 5 ml venous blood.

Also known as: Blood sampling

Control group - women with naturally conceived offspring; Study group - women with idiopathic infertility

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study group consisted of 58 women diagnosed with primary infertility, and a control group consisted of 8 patients with naturally conceived offspring. Patients were recruited from among women hospitalized at the Gynecological Endocrinology and Gynecology Clinic, consulted at the Gynecological Endocrinology Clinic and diagnosed under the Comprehensive Reproductive Health Program

You may qualify if:

• primary infertility (unsuccessfully trying to become pregnant for more than a year)
• regular menstruation

You may not qualify if:

• female homronal therapy
• established male factor of infertility
• tubal factor
• endometriosis
• inflammation in the pelvic area - currently and in the history
• hormonal background of infertility
• obesity
• insulin resistance
• status post at least one miscarriage
• chronic autoimmune diseases.
• Control group
• naturally conceived offspring up to three years of age
• regular menstruation
• status post surgery on the uterus, including curettage of the uterine cavity
• endometriosis

Sponsors & Collaborators

• Jagiellonian University: lead

Study Sites (1)

Clinic Of Endocrynological Gynecology

Krakow, Malopolska, 30-501, Poland

Location

Biospecimen

Retention: SAMPLES WITH DNA

Endometrial tissue - aspiration biopsy Blood sample 5ml

MeSH Terms

Conditions

Infertility, Female; Infertility; Inflammation

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 22, 2021
• First Posted: January 13, 2022
• Study Start: November 1, 2017
• Primary Completion: March 1, 2020
• Study Completion: November 1, 2020
• Last Updated: January 13, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)