Mediator in the Embryo-endometrium Cross-talk: Granulocyte Colony-stimulating Factor in Infertility

Abstract

Successful implantation requires a receptive endometrium and a good quality egg. The challenges a physician encounters with regard to this in assisted reproductive technology are obtaining good quality embryo, achieving optimal endometrial thickness (EMT), and subsequently implantation, which is denotive of a receptive endometrium. Granulocyte colony-stimulating factor (G-CSF) has been observed to be a biomarker of oocyte quality and has been shown to enhance EMT and implantation because of its immunological effects. A systematic search for all relevant articles on G-CSF in follicular fluid and its therapeutic benefit in thin endometrium and recurrent implantation failure was performed, and peer-reviewed, full-text articles related to humans were included in the study. As a tool to determine the potentiality of oocyte, G-CSF shows promise with its predictability increasing in combination with morphological embryo scoring or interleukin 15. For the thin endometrium, G-CSF is especially useful in patients who are refractory to other treatment modalities. In recurrent implantation failure (RIF), G-CSF showed potential in a subset of patients with immunological deficiency lacking killer cell immunoglobulin-like receptor genes. This review highlights the various forms of usage of G-CSF and the effectiveness of G-CSF in infertility. G-CSF equips embryologists with a tool to determine the potentiality of oocyte and physicians with therapy for thin endometrium and RIF, especially since the available treatment options are ineffective.

Approaches to Improve Endometrial Receptivity in Case of Repeated Implantation Failures

“…The role of G-CSF in reproductive physiology has been mainly studied the last two decades. G-CSF is produced by the granulosa cells during ovulation ( Robert et al, 2019 ). It can be identified in the uterus mainly on the uterine NK cells, which play a major role during implantation both by enhancing receptivity and enabling endometrial synchronization ( Sharma and Das, 2014 ; Robert et al, 2019 ).…”

“…G-CSF is produced by the granulosa cells during ovulation ( Robert et al, 2019 ). It can be identified in the uterus mainly on the uterine NK cells, which play a major role during implantation both by enhancing receptivity and enabling endometrial synchronization ( Sharma and Das, 2014 ; Robert et al, 2019 ). More importantly, G-CSF has been shown to regulate Th2 immunity, contributing to maternal-fetal immuno-tolerance ( Moldenhauer et al, 2010 ).…”

A paracrine interaction between granulosa cells and leukocytes in the preovulatory follicle causes the increase in follicular G-CSF levels

“…G-CSF is a multifunctional cytokine, best known for stimulating the production and differentiation of neutrophils during hematopoiesis and promoting their activation, with key roles in immunity and inflammatory responses [10][11][12]. G-CSF also has a recognized role in several aspects of human reproduction [13][14][15][16]. In a recent trial with an ultra-sensitive ELISA specifically designed for the quantification of follicular G-CSF, the probability of successful implantation was 3.3-fold higher for embryos derived from follicles with high G-CSF levels than for those derived from follicles with low G-CSF levels [17].…”