Endometrial expression of LIF and its receptor and peritoneal fluid levels of IL-1α and IL-6 in women with endometriosis are associated with the probability of pregnancy

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Reduced endometrial LIF, LIFR, and gp130 expression and elevated peritoneal IL-1α and IL-6 levels were observed in women with endometriosis and subfertility, correlating with a lower probability of pregnancy.

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This study examined whether eutopic endometrial expression of leukemia inhibitory factor (LIF), its receptor (LIFR), and gp130, along with peritoneal fluid (PF) levels of IL-1α and IL-6, are associated with the probability of spontaneous pregnancy in subfertile women with minimal–mild (rASRM stage I–II) endometriosis and healthy controls. Eutopic endometrial biopsies and PF were collected at laparoscopy, with endometrial protein assessed by immunostaining and pregnancy tracked over 6 months after combined postoperative laparoscopy/goserelin acetate treatment; endometrial biopsies were repeated after goserelin. In endometriosis patients without recorded pregnancy, reduced staining of LIF, LIFR, and gp130 was observed and PF IL-6 and particularly IL-1α were elevated, and surgery plus goserelin did not restore these LIF-pathway markers. Relevance to endometriosis: the paper directly analyzes endometriosis patients’ eutopic endometrial LIF/LIFR/gp130 expression and PF IL-1α/IL-6 in relation to pregnancy probability, finding an association with endometriosis-related subfertility.

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Abstract

PURPOSE: To investigate whether eutopic endometrial expression of leukaemia inhibitory factor (LIF), LIF receptor (LIFR) and glycoprotein 130 (gp130) in subfertile women with endometriosis and in healthy controls is related to the probability of spontaneous pregnancy. In addition, we aimed to study peritoneal fluid (PF) levels of interleukin (IL)-1α and IL-6 in the same subsets of women. METHODS: Eutopic endometrial biopsy and PF samples were taken from patients with rASRM stage I-II endometriosis and healthy controls undergoing laparoscopy. Endometrial LIF, LIFR and gp130 immunostaining and PF levels of IL-1α and IL-6 were assessed. Endometrial biopsy samples were obtained again after postoperative goserelin acetate treatment and on-going pregnancies were registered during a 6-month follow-up period. RESULTS: Reduced endometrial staining of LIF, LIFR and gp130, unaffected by surgery and goserelin, was seen in endometriosis patients without a recorded pregnancy during the study. Elevated PF levels of IL-6 and, in particular, IL-1α were detected in these patients. CONCLUSIONS: Reduced eutopic endometrial LIF, LIFR and gp130 protein expression may be associated with subfertility in women with minimal-mild endometriosis. Combined surgical and goserelin acetate treatment does not seem to restore the expression of these members of the IL-6 cytokine superfamily. Elevated peritoneal fluid levels of IL-1α and IL-6 may further contribute to the difficulties of achieving pregnancy in these patients.
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Abstract

Purpose To investigate whether eutopic endometrial expression of leukaemia inhibitory factor (LIF), LIF receptor (LIFR) and glycoprotein 130 (gp130) in subfertile women with endometriosis and in healthy controls is related to the probability of spontaneous pregnancy. In addition, we aimed to study peritoneal fluid (PF) levels of interleukin (IL)-1α and IL-6 in the same subsets of women.

Methods

Eutopic endometrial biopsy and PF samples were taken from patients with rASRM stage I–II endometriosis and healthy controls undergoing laparoscopy. Endometrial LIF, LIFR and gp130 immunostaining and PF levels of IL-1α and IL-6 were assessed. Endometrial biopsy samples were obtained again after postoperative goserelin acetate treatment and on-going pregnancies were registered during a 6-month follow-up period.

Results

Reduced endometrial staining of LIF, LIFR and gp130, unaffected by surgery and goserelin, was seen in endometriosis patients without a recorded pregnancy during the study. Elevated PF levels of IL-6 and, in particular, IL-1α were detected in these patients.

Conclusions

Reduced eutopic endometrial LIF, LIFR and gp130 protein expression may be associated with subfertility in women with minimal–mild endometriosis. Combined surgical and goserelin acetate treatment does not seem to restore the expression of these members of the IL-6 cytokine superfamily. Elevated peritoneal fluid levels of IL-1α and IL-6 may further contribute to the difficulties of achieving pregnancy in these patients. Similar content being viewed by others

References

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Author information Authors and Affiliations Corresponding author Additional information C. Moberg and V. Bourlev contributed equally to this work. Rights and permissions About this article Cite this article Moberg, C., Bourlev, V., Ilyasova, N. et al. Endometrial expression of LIF and its receptor and peritoneal fluid levels of IL-1α and IL-6 in women with endometriosis are associated with the probability of pregnancy. Arch Gynecol Obstet 292, 429–437 (2015). https://doi.org/10.1007/s00404-015-3626-0 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-015-3626-0

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Outcome instruments

rASRM

Condition tags

endometriosis

MeSH descriptors

Endometriosis Infertility, Female Interleukin-1alpha Interleukin-6 Leukemia Inhibitory Factor Adult Ascitic Fluid Ascitic Fluid Ascitic Fluid Case-Control Studies Cytokines Cytokines Endometriosis Endometriosis Endometrium Endometrium Female Follow-Up Studies Humans Infertility, Female

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