Identifying Disease Mechanisms Underlying the Association Between Asthma and Infertility - The INFLammation Asthma Mechanism Endometrium (INFLAME) Study (INFLAME)

To investigate if asthma affects the inflammatory balance of the endometrium and thereby interfere with implantation, as indicated by the characteristics of the inflammatory cells in the endometrium and airways in women with asthma who are referred for IUI or IVF due to infertility, compared to otherwise healthy women who are referred for IUI or IVF due to infertility.

Study Overview

• Status: Unknown
• Conditions: Asthma; Infertility, Female
• Intervention / Treatment: Procedure: biopsy

Detailed Description

The link between asthma and fertility may be associated with widespread tissue inflammation, as inflammatory changes are not only affecting the respiratory organs, but also systemically, and here by affecting both the lungs and the reproductive organs in women with asthma.

A likely mechanism involved in infertility among asthmatic women seems to be inflammatory changes found in the endometrium of the uterus. Some studies show high number of mast cells, eosinophil granulocytes and basophil granulocytes in the endometrium[1]. One study found low values of VEGF in endometrial secretion in women with asthma as a possible cause for subfertility [2]. Others assume, that an imbalance of the adaptive immune system (both the Th1 and Th2/TH17 response) is associated with infertility [3].

It has been shown that inflammation in the endometrium with a specific combination of cytokines and chemokines is part of successful implantation [4]. However, If the inflammatory process is characterized by a less optimal combination of cytokines and chemokines the reproductive outcome may be less successful. The systemic inflammation caused by asthma could offset the balance between the cytokines and chemokines in the endometrium and thereby have negative impact on reproductive outcome.

In the present study, our aim is to analyze inflammation in the uterus and in the airways in women with asthma referred to fertility treatment receiving Intrauterine insemination (IUI) or in vitro fertilization (IVF) to characterize and thereby provide knowledge of the mechanisms underlying the association between asthma and reproductive outcomes.

In an explorative non-randomized study, including 30 participants divided into two groups: 15 women with asthma and 15 non-asthmatic controls. The patients will go through an asthma work-up (diagnosis, allergy, medication, and inflammation). Menstrual blood will be collected at home using the menstrual cup and at the 7th-14th day cycle day, an endometrium sample from the uterus lining will be obtained together with sputum, as indicators of the system inflammation expressed both in the lungs and the uterus, and blood samples.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre
    • Copenhagen, Hvidovre, Denmark, 2650
      • Recruiting
      • Department of Respiratory Medicine, Hvidovre University Hospital
      • Contact: Casper Tidemandsen, MD; Phone Number: +4523497817; Email: casper.tidemandsen.02@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

30 participants divided into two groups: 15 women with asthma and 15 non-asthmatic controls. The patients will go through an asthma work-up (diagnosis, allergy, medication, and inflammation). Menstrual blood will be collected at home using the menstrual cup and at the 7th-14th cycle day, an endometrium sample from the uterus lining will be obtained together with sputum, as indicators of the system inflammation expressed both in the lungs and the uterus, and blood samples.

Description

Inclusion criteria:

Asthma n= 15:

• Informed consent.
• Diagnosis of asthma.
• 18-40 years.
• Referred to Intra Uterine Insemination (IUI) or in vitro fertilization (IVF)

Non-asthmatic n= 15:

• Informed consent.
• 18-40 years.
• Referred to Intra Uterine Insemination (IUI) or in vitro fertilization (IVF)

Exclusion criteria:

Asthma only:

• Other respiratory diseases than asthma.
• Other inflammatory disease or a disease that affects fertility.
• Infections requiring antibiotics or anti-viral treatment within 30 days.
• Current smokers and/or life-time tobacco exposure > 10 pack-years.
• Endometriosis.
• Infertility due to other reasons than male factor, tubal factor or unexplained infertility.
• No pelvic inflammatory disease (PID) within the last 6 months.
• No contraceptive intrauterine device (IUD), or other contraceptive for the last 6 months.

Non-asthmatic controls:

• No respiratory diseases.
• Other inflammatory disease or a disease that affects fertility.
• Infections requiring antibiotics or anti-viral treatment within 30 days.
• Current smokers and/or life-time tobacco exposure > 10 pack-years.
• Endometriosis.
• Infertility due to other reasons than male factor, tubal factor or unexplained infertility.
• No pelvic inflammatory disease (PID) within the last 6 months.
• No contraceptive intrauterine device (IUD), or other contraceptive for the last 6 months.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Women with astma; At the 7th -14th cycle day, an endometrium sample from the uterus lining will be obtained together with sputum, as indicators of the system inflammation expressed both in the lungs and the uterus, and blood samples.	Procedure: biopsy; biopsy of the endometrium
Women without asthma; At the 7th - 14th cycle day, an endometrium sample from the uterus lining will be obtained together with sputum, as indicators of the system inflammation expressed both in the lungs and the uterus, and blood samples.	Procedure: biopsy; biopsy of the endometrium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
type of inflammatory cells	To classify the type of inflammatory cells, (ie. cytokines and inflammatory cells), found in the uterine lining (endometrium) in women with asthma suffering from infertility, compared to non-asthmatic controls.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
airway inflammation vs inflammation in the endometrium.	Explore associations between airway inflammation and inflammation in the endometrium.	6 months
systemic inflammation vs local inflammation	Explore associations between systemic inflammation and local inflammation	6 months
Severity	Differences in local inflammation of the endometrium within different severities/phenotypes of asthma.	6 months

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2020
• Primary Completion (Anticipated): September 30, 2021
• Study Completion (Anticipated): October 31, 2021

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): December 3, 2020
• Last Update Submitted That Met QC Criteria: December 1, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Infertility; Inflammation; Asthma; Infertility, Female
• Other Study ID Numbers: H-20029413

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Will be shared upon request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No