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

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.

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.

Eligibility Criteria:
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.