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Leukocyte populations in patients undergoing in vitro fertilization: responses to hormone treatment and relation to outcome
Linköping University, Department of Clinical and Experimental Medicine. 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)Manuscript (preprint) (Other academic)
Abstract [en]

We aimed to prospectively investigate circulating leukocyte populations in infertile women undergoing IVF treatment and to determine whether any differences in cell proportions were associated with the IVF outcome. We also assessed the effect of IVF-based ovarian stimulation on the leukocyte populations. Twenty-five women were included and IVF treatment was successful in six and unsuccessful in 19 women. Blood samples were collected before IVF treatment, at the time of embryo transfer and four weeks after embryo transfer. The numbers and proportions of lymphocytes, T cells, NK cells, monocytes and granulocytes were analysed by flow cytometry, as well as the following lymphocyte subpopulations: CD3+HLA-DR+, CD4+CD45RA+, CD4+CD45R0+, CD8+CD45RA+, CD8+CD45R0+, CD4+CD25+, CD4dimCD25bright regulatory T cells, CD3-CD56bright and CD3-CD56dim NK cells. The proportions and numbers of leukocytes during IVF treatment were not related to the IVF outcome, although pregnant women (four weeks after ET) had a lower proportion of lymphocytes than the non-pregnant women. The absolute counts of lymphocytes, T cells, granulocytes and monocytes, as well as the proportions of granulocytes and T cells, increased at the time of ET, coinciding with high FSH and hCG levels. In conclusion, the proportions and numbers of leukocyte populations were not associated with the IVF outcome, although a larger study should be conducted to confirm this conclusion. Changes in both proportions and numbers of several leukocyte populations were observed during the course of IVF treatment, suggesting a stimulatory effect of the hormonal influence.

Place, publisher, year, edition, pages
2012.
Keyword [en]
IVF, pregnancy, regulatory T cells, immune regulation, leukocyte populations, hormones
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-85641OAI: oai:DiVA.org:liu-85641DiVA: diva2:572117
Available from: 2012-11-26 Created: 2012-11-26 Last updated: 2013-08-29
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)
Opponent
Supervisors
Available from: 2012-11-26 Created: 2012-11-26 Last updated: 2013-08-29Bibliographically approved

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Persson, MarieEkerfelt, ChristinaJablonowska, BarbaraJonsson, YvonneBerg, GöranErnerudh, JanJenmalm, Maria C.

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Persson, MarieEkerfelt, ChristinaJablonowska, BarbaraJonsson, YvonneBerg, GöranErnerudh, JanJenmalm, Maria C.
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Department of Clinical and Experimental MedicineFaculty of Health SciencesClinical ImmunologyObstetrics and gynecologyDepartment of Gynecology and Obstetrics in LinköpingDepartment of Clinical Immunology and Transfusion MedicinePediatrics
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