Involvement of Interleukin-1 and the Interleukin-1 Receptor Antagonist in In Vitro Embryo Development Among Women Undergoing In Vitro Fertilization–Embryo Transfer

Spandorfer, S.D.; Neuer, A.; Liu, H.-C.; Rosenwaks, Zev

doi:10.1023/b:jarg.0000013650.76052.ae

Cited by 22 publications

(17 citation statements)

References 9 publications

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“…Presently, there is accumulating evidence suggesting that individual cytokines in human follicular fluid can be used as predictors of IVF outcome [30]. A positive association of IL-6 with oocyte maturation [31] and IL-1β with embryo development and pregnancy [32] is documented. A majority of findings have indicated that IL-12 is negatively associated with folliculogenesis, oocyte quality, and implantation [30,33,34].…”

Section: Discussionmentioning

confidence: 99%

Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis

Singh

Dutta

Chattopadhyay

et al. 2016

J Assist Reprod Genet

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Purpose The study aimed to investigate key intrafollicular prognostic factors among various cytokines and angiogenic molecules for prediction of mature oocytes and good-quality embryos in women with endometriosis undergoing in vitro fertilization (IVF). Methods Paired follicular fluid and serum samples were collected from 200 women with advanced stage endometriosis and 140 normal ovulating women during oocyte retrieval. The concentrations of cytokines (pro-inflammatory: IL-1β, TNF-α, IL-2, IL-8, IL-12, IFN-γ; anti-inflammatory: IL-4, IL-6, IL-10) and angiogenic molecules (vascular endothelial growth factor (VEGF), adrenomedullin, angiogenin) were determined in follicular fluid and serum using ELISA. Expression of these molecules was subjected to multivariate analysis for the identification of major predictive markers of oocyte and embryo quality. Receiver operating characteristic (ROC) curve was applied to determine the best cutoff point for the discrimination between mature and immature oocytes in these women. Results Significant increases in levels of cytokines and angiogenic molecules were observed in women with endometriosis compared to controls (P < 0.001). From the validated partial least squares-discriminant analysis (PLS-DA) model, IL-8, IL-12, and adrenomedullin were identified as the most important factors contributing to endometriosis and were negatively associated with oocyte maturity and embryo quality. Conclusion The levels of IL-8, IL-12, and adrenomedullin may be good indicators of embryo and oocyte quality in endometriosis patients undergoing IVF. Further studies are necessary to ascertain the potential of these markers for oocyte and embryo developmental competence which may help improve the chances of a successful IVF in endometriosis patients.

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Section: Discussionmentioning

confidence: 99%

Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis

Singh

Dutta

Chattopadhyay

et al. 2016

J Assist Reprod Genet

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“…In the present study, the expression level of IL-1β in the fallopian tubes was found to be higher in the stimulated groups than in the unstimulated control group. Several studies have indicated that higher levels of IL-1β negatively affect the fertilization process (14-16), embryonic implantation, and pregnancy outcomes (18)(19)(20), and can cause several different complications during pregnancy (21) and can be employed as a marker for tubal pregnancy (22). The elevated inflammatory response observed within the fallopian tube due to higher IL-1β levels, accompanied by the disturbed histoarchitecture of the fallopian tube, might directly affect the fertilization process.…”

Section: Discussionmentioning

confidence: 99%

Ovarian stimulation induces high expression of interleukin-1β and disrupts the histological features of the fallopian tube

Moussa¹,

Farouk²

2019

Turk J Vet Anim Sci

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The objective of this study was to investigate whether there is an association between ovarian stimulation and interrupted gamete interaction in the rat fallopian tube in vivo. We evaluated the protein expression of interleukin-1β (IL-1β) via immunohistochemistry and assessed the key histological features of the ovaries, fallopian tubes, and uteri of the rats following treatment with mild (15 IU) and high (30 IU) doses of gonadotropins compared to an unstimulated control group. The serum concentration of estradiol was also determined by immunoassay. The results revealed that high levels of circulating estrogen were associated with higher expression of the IL-1β protein in the ovaries and fallopian tubes of highly stimulated rats than in those of the mildly stimulated and unstimulated control groups. In contrast, endometrial IL-1β immunoexpression was not affected by ovarian stimulation. The histological features of the fallopian tubes were also dramatically altered upon ovarian stimulation, reducing the efficiency of the fallopian tube. In conclusion, the resulting high circulating estrogen level disrupts the histological features of the fallopian tubes and can lead to higher expression of IL-1β, thus negatively affecting gamete interactions in vivo. These results provide useful information regarding the lower fertilization rate observed following ovarian stimulation.

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“…Cytokines play an important role in implantation and early pregnancy [ 16 , 28 ] . For example, IL-1 receptors have been shown to be located on the early human embryo, emphasizing the important role of IL1-ra in early pregnancy [ 18 ]. Therefore, we aimed to establish chemokines as biomarkers at the time of pregnancy testing, some of which were found to be changed in patients with proven abortions.…”

Section: Discussionmentioning

confidence: 99%

“…For example, lower levels of interleukin 1-receptor antagonist (IL-1ra) prior to embryo transfer were associated with lower pregnancy rates [ 18 ] . Higher levels of Thyreoperoxidase (TPO) and lower concentrations of Granulocyte-Colony Stimulating Factor (GCSF) were significantly associated with the risk of spontaneous abortion in women prior to report of miscarriage.…”

Section: Introductionmentioning

confidence: 99%

Cytokines in relation to hCG are significantly altered in asymptomatic women with miscarriage – a pilot study

Freis

Schlegel

Daniel

et al. 2018

Reprod Biol Endocrinol

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BackgroundSpontaneous abortion is one of the most common complications in early pregnancy. A preventive test to identify women who will experience a miscarriage, even before first symptoms occur, is not established. Activation of maternal immunological tolerance seems to be essential for early fetal development and various cytokines have been described in different stages of pregnancy. Therefore, we aimed to investigate if chemokine levels at the time of pregnancy testing relative to human Choriogonadotropin (hCG) are altered in patients who will experience a miscarriage in this pregnancy.MethodsWe obtained blood samples from 39 women. Dependent on the follow-up, patients with a positive pregnancy test were subsequently divided in two groups: ongoing pregnancy (n = 22) and miscarriage (n = 17) in this pregnancy. Immunological and endocrine profiling of maternal plasma at the time of pregnancy testing (5th week of gestation) was performed for each group at the time of pregnancy test using Multiplex and ELISA analysis.ResultshCG was significantly decreased in patients with abortion whereas levels of IL-1ra, MIP-1a and TNF-alpha were significantly increased. GCSF/ IL-1ra-ratio was 1.66-fold increased in patients with ongoing pregnancy. TGF-beta /MIP1a-ratio was significantly 3.45-times higher in patients with miscarriage. Comparing patients with ongoing pregnancy to patients experiencing a miscarriage, we could demonstrate significant alterations of the ratios MIP1a/hCG, IL-1ra/hCG, TNFalpha/hCG, MCP1/hCG, IL-6/hCG, TPO/hCG and TGF-beta1/hCG. The strongest effects were seen for the ratio MIP1a/hCG, IL-1ra/hCG and TNFalpha/hCG.ConclusionsWe have shown that cytokines in relation to hCG after 4 weeks of gestation are significantly altered in women with miscarriage, promising potential as a prognostic biomarker.

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Involvement of Interleukin-1 and the Interleukin-1 Receptor Antagonist in In Vitro Embryo Development Among Women Undergoing In Vitro Fertilization–Embryo Transfer

Cited by 22 publications

References 9 publications

Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis

Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis

Ovarian stimulation induces high expression of interleukin-1β and disrupts the histological features of the fallopian tube

Cytokines in relation to hCG are significantly altered in asymptomatic women with miscarriage – a pilot study

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