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Immunological status in patients undergoing in vitro fertilisation: responses to hormone treatment and relationship to outcome
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0002-3993-9985
Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
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2012 (English)In: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 96, no 1-2, 58-67 p.Article in journal (Refereed) Published
Abstract [en]

We aimed to prospectively investigate the paternal antigen-induced cytokine secretion by peripheral blood mononuclear cells (PBMCs) in response to hormone treatment in women undergoing in vitro fertilisation (IVF) and to examine the predictive value of the cytokine secretion profile in the outcome of IVF treatment, in a pilot study. Twenty-five women were included and IVF treatment was successful for six and unsuccessful for 19 women. Blood samples were collected before IVF treatment, on four occasions during IVF and four weeks after embryo transfer. The numbers of Th1-, Th2- and Th17-associated cytokine-secreting cells and cytokine levels in cell supernatants were analysed by enzyme-linked immunospot-forming (ELISpot), enzyme-linked immune-sorbent (ELISA) or Luminex assay. None of the cytokines (IFN-γ, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, TNF and GM-CSF) had any predictive value regarding IVF outcome. The majority of the cytokines reached their peak levels at ovum pick-up, suggesting an enhancing influence of the hormonal stimulation. Pregnancy was associated with a high number of IL-4-, IL-5- and IL-13-secreting cells four weeks after ET. In conclusion, the results do not support our hypothesis of a more pronounced peripheral Th1 and Th17 deviation towards paternal antigens in infertile women with an unsuccessful IVF outcome, although this is based on a small number of observations. A larger study is required to confirm this conclusion. Higher numbers of Th2-associated cytokine-secreting cells in pregnant women four weeks after ET do corroborate the hypothesis of a Th2 deviation during pregnancy.

Place, publisher, year, edition, pages
Elsevier , 2012. Vol. 96, no 1-2, 58-67 p.
Keyword [en]
IVF; Th1; Th2; Th17; Immune regulation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-85640DOI: 10.1016/j.jri.2012.07.005ISI: 000312969900007OAI: oai:DiVA.org:liu-85640DiVA: diva2:572112
Available from: 2012-11-26 Created: 2012-11-26 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Immune regulation during pregnancy in relation to allergy and in women undergoing in vitro fertilization
Open this publication in new window or tab >>Immune regulation during pregnancy in relation to allergy and in women undergoing in vitro fertilization
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

During pregnancy, the fetus expresses both maternal and paternal antigens. To the mother, the paternal antigens are foreign, providing her immune system with an interesting challenge. The fact that the fetus is not normally attacked and rejected implies that mechanisms of tolerance must exist. Pregnancy has long been considered to cause a redirection of the maternal immune responses towards a less aggressive type. Allergic disease has also been associated with that same redirection of immune responses, suggesting that this deviation may be more pronounced in allergic women during pregnancy. Several observations support the concept of a role of the immune system in the etiology of unexplained infertility, associating a redirection of the immune responses towards a more aggressive type with pregnancy loss and pregnancy failure.

The aim of this thesis was to investigate the immune responses during pregnancy in allergic and non-allergic women, and in infertile women undergoing IVF treatment. We hypothesized that allergic women would have a more pronounced Th2-deviation than non-allergic women towards paternal antigens during pregnancy and that an unsuccessful outcome of IVF treatment would be associated with aberrations in circulating leukocyte populations and a paternal antigen-specific Th1 and Th17 bias.

An increased number of both spontaneous and paternal antigen-induced Th2-like cytokine-secreting cells in peripheral blood was associated with pregnancy in 54 women with pregnancies defined as normal. The allergic pregnant women did not have a more pronounced Th2-deviation than the non-allergic women, as measured by numbers of cytokine-secreting cells. However, when analyzing cytokine levels in cell supernatants, we did observe lower Th1 responses towards paternal antigens in the allergic compared with non-allergic women. Additionally, allergy was associated with a reduced capacity to induce anti-inflammatory IL-10 responses towards paternal antigens.

In 25 infertile women undergoing IVF, the peak levels of the majority of paternal antigen-induced cytokines and leukocyte populations investigated coincided with the maximal levels of gonadotropins administered during IVF treatment, suggesting that controlled ovarian hyper-stimulation has a general stimulatory effect on the immune system and that it may be regarded as an inflammatory state. During the treatment, no differences were found regarding cytokine responses to paternal antigens in peripheral blood or the numbers or proportions of circulating leukocyte populations between women with a successful or unsuccessful outcome of IVF. We did see higher numbers of Th2-associated cytokine secreting cells and a lower proportion of lymphocytes in the pregnant compared with the non-pregnant women four weeks after embryo transfer, however, in line with previous findings of immune modulation during pregnancy.

In conclusion, normal pregnancy seems to be characterized by a less aggressive type of immune responses, possibly more pronounced in allergic women. This may be of importance for the in utero influences on childhood allergy development. An unsuccessful outcome of IVF does not appear to be associated with a more aggressive type of immune responses towards paternal antigens or aberrations in circulating leukocyte populations, although this should be confirmed in a larger study. The results in this thesis also indicate that the hormonal therapy during IVF treatment has a stimulatory effect on the immune system, generating an inflammatory state.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. 71 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1346
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85642 (URN)978-91-7519-736-4 (ISBN)
Public defence
2012-12-05, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
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Supervisors
Available from: 2012-11-26 Created: 2012-11-26 Last updated: 2013-08-29Bibliographically approved

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Persson, MarieEkerfelt, ChristinaJablonowska, BarbaraJonsson, YvonneErnerudh, JanJenmalm, Maria C.Berg, Göran

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Persson, MarieEkerfelt, ChristinaJablonowska, BarbaraJonsson, YvonneErnerudh, JanJenmalm, Maria C.Berg, Göran
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Clinical ImmunologyFaculty of Health SciencesObstetrics and gynecologyDepartment of Clinical Immunology and Transfusion MedicineDepartment of Gynaecology and Obstetrics in Linköping
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