Does the dysregulation of matrix metalloproteinases contribute to recurrent implantation failure?

Benkhalifa, M.; Zayani, Y.; Bach, Véronique; Copin, Henri; Feki, Moncef; Benkhalifa, Moncef; Allal-Elasmi, Monia

doi:10.1080/14789450.2018.1464915

Cited by 17 publications

(12 citation statements)

References 131 publications

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“…Today numerous studies have generated much information concerning the relation between the varied proteins at the site of implantation such as cytokines, growth factors, adhesion molecules and MMPs. However, the precise role of the MMPs in embryo implantation and the effect of their dysregulation in recurrent implantation failure have yet to be characterized but it seems that the balance between the matrix metalloproteinase (MMPs) and their tissue inhibitors (TIMPs) appear to play a crucial role in both the process of embryo implantation and invasion (Benkhalifa et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Endometrium immunomodulation by intrauterine insemination administration of treated peripheral blood mononuclear cell prior frozen/thawed embryos in patients with repeated implantation failure

Nobijari

Arefi

Moini

et al. 2019

Zygote

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SummaryIn assisted reproductive technology (ART) programmes, approximately 10% of infertile patients have at least two or three repeated implantation failures (RIFs) after an in vitro fertilization (IVF) protocol. Successful implantation mainly depends on local immune tolerance mechanisms involving a spectrum of cytokines, interleukins and growth factors. The latter have played pivotal roles in the recruitment of immune cells (and notably T-lymphocyte cells). In total, 250 couples participating in frozen–thawed embryo transfer programme were incorporated in a randomized clinical trial (peripheral blood mononuclear cells (PBMC) subgroup: n=122; control subgroup: n=128). In the PBMC group, a blood sample was collected 5 days before the scheduled frozen–thawed embryo transfer; PBMCs were isolated using Ficoll separation and then cultured for 72 h. Two days prior to embryo transfer, 0.4 ml of cultured PBMCs were transferred into the patient’s uterus. Although the clinical pregnancy rate was higher in the PBMC group (34.4%) than in the control group (23.4%), this difference was not statistically significant (P=0.05 in a chi-squared test). Nevertheless, when we limited the analysis to patients with ≥3 RIFs (n=138), there was a significant difference in the clinical pregnancy rate between the PBMC group (38.6%) and the control group (19.7%; P=0.01). Our results imply that PBMC transfer can be part of effective fertility treatment for patients with RIF.

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Section: Discussionmentioning

confidence: 99%

Endometrium immunomodulation by intrauterine insemination administration of treated peripheral blood mononuclear cell prior frozen/thawed embryos in patients with repeated implantation failure

Nobijari

Arefi

Moini

et al. 2019

Zygote

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“…Furthermore, the activation of phosphatidyl-inositol three kinase by IGF1 will initiate trophoblast invasion and the activation of E-cadherins by this biomarker in conjunction with metalloproteinases ADAM 10 will activate pro-inflammatory cytokines obligatory for peri-implantation ( Peron et al, 2018 ). IGF1 also participates in the modulation of the secretion of matrix metalloproteinases (MMP) and their specific inhibitors; the tissue inhibitors of matrix metalloproteinases (TIMP), which are also involved in the human trophoblast cells invasion, as well as follicular development in oocyte level ( Benkhalifa et al, 2018 ). On the other side, IGF2 is more likely associated with implantation rate than IGF1.…”

Section: Discussionmentioning

confidence: 99%

Follicular Fluid Growth Factors and Interleukin Profiling as Potential Predictors of IVF Outcomes

et al. 2022

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Growth hormone (GH) has gained attention as an anti-aging compound enhancing oocyte quality. In fact, GH is known to activate intrafollicular metabolic events for oocyte maturation. Insulin growth factor I (IGF1) is another ovarian growth factor that mediates the FSH and GH actions. Cytokines could also increase IVF outcomes. Indeed, IL-6 is a pleiotropic cytokine with multiple cellular effects that can vary based on the physiological environment. IL-6 may also play an important role in follicular development (Yang et al., J Assist Reprod Genet, 2020, 37 (5), 1171–1176). Clinical studies have been performed to explore the potential role of IL-6 in human oocyte maturation and subsequent embryonic development. To date, the answers are not conclusive. During peri-implantation, many cytokines balances are regulated like pro-inflammatory and anti-inflammatory interleukins. The pro-inflammatory properties of IL-17 and its impact on the tumor microenvironment or autoimmune diseases are characterized, but new dimensions of IL-17 activity that promotes embryo implantation are not well explored. In the search for answers, our study compared concentrations of growth factors IGF1, GH, and interleukins IL-6 and IL-17 in the follicular fluid (FF) from 140 women divided into two groups depending on bad (G1) or good prognosis (G2) and investigated the relationships between these FF components’ levels and the main parameters of IVF. GH, IGF1, and IL-6 were significantly higher for G2. For GH, it was negatively correlated to patient age and positively correlated to maturity rate and IGF1. Moreover, GH and IGF1 were correlated to the top embryo rate and cumulative pregnancy rate. Regarding IL-6, it was correlated to IGF1 level, endometrium thickness, and implantation rate. As for IL-17, it was only correlated to IL-6. Consequently, all these FF components were predictive of oocyte quality except IL-17. GH seemed to be the best biomarker of this quality.

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“…MMP-2 and MMP-9 promote follicular development, as well as play an indispensable role in the selection of dominant follicles [ 86 ]. MMP-2 can further facilitate trophoblastic infiltration and embryo implantation [ 11 ].…”

Section: Characteristics Of Endometrial Receptivity Markers In Pcos Patients During the Implantation Windowmentioning

confidence: 99%

Research progress of endometrial receptivity in patients with polycystic ovary syndrome: a systematic review

Bai

Zheng

et al. 2021

Reprod Biol Endocrinol

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Polycystic ovary syndrome (PCOS) is a neuroendocrine heterogeneous disease that frequently occurs in women of reproductive age, causing serious damage to the fertility, quality of life, and physical and mental health of patients. The current studies have proved that satisfactory endometrial receptivity is one of the conditions that must be met during the process of spermatovum position, adhesion and invasion, as well as the subsequent blastocyst division and embryo development. Women with PCOS may suffer a series of pathological processes such as changes in the expression levels of hormones and related receptors, imbalances in the proportion of miscellaneous cytokines, insulin resistance, low-grade chronic inflammation and endometrial morphological changes, which will damage endometrial receptivity from various aspects and obstruct fertilized egg nidation and embryonic development, thus causing adverse reproductive health events including infertility and abortion. This article reviews the research progress about characteristics and related influencing factors of endometrial receptivity in PCOS patients.

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Does the dysregulation of matrix metalloproteinases contribute to recurrent implantation failure?

Cited by 17 publications

References 131 publications

Endometrium immunomodulation by intrauterine insemination administration of treated peripheral blood mononuclear cell prior frozen/thawed embryos in patients with repeated implantation failure

Endometrium immunomodulation by intrauterine insemination administration of treated peripheral blood mononuclear cell prior frozen/thawed embryos in patients with repeated implantation failure

Follicular Fluid Growth Factors and Interleukin Profiling as Potential Predictors of IVF Outcomes

Research progress of endometrial receptivity in patients with polycystic ovary syndrome: a systematic review

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