Impact of follicular G-CSF quantification on subsequent embryo transfer decisions: a proof of concept study

Abstract

BACKGROUNDPrevious experiments have shown that granulocyte colony-stimulating factor (G-CSF), quantified in the follicular fluid (FF) of individual oocytes, correlates with the potential for an ongoing pregnancy of the corresponding fertilized oocytes among selected transferred embryos. Here we present a proof of concept study aimed at evaluating the impact of including FF G-CSF quantification in the embryo transfer decisions.METHODSFF G-CSF was quantified with the Luminex XMap technology in 523 individual FF samples corresponding to 116 fresh transferred embryos, 275 frozen embryos and 131 destroyed embryos from 78 patients undergoing ICSI.RESULTSFollicular G-CSF was highly predictive of subsequent implantation. The receiving operator characteristics curve methodology showed its higher discriminatory power to predict ongoing pregnancy in multivariate logistic regression analysis for FF G-CSF compared with embryo morphology [0.77 (0.69–0.83), P < 0.001 versus 0.66 (0.58–0.73), P = 0.01)]. Embryos were classified by their FF G-CSF concentration: Class I over 30 pg/ml (a highest positive predictive value for implantation), Class II from 30 to 18.4 pg/ml and Class III <18.4 pg/ml (a highest negative predictive value). Embryos derived from Class I follicles had a significantly higher implantation rate (IR) than those from Class II and III follicles (36 versus 16.6 and 6%, P < 0.001). Embryos derived from Class I follicles with an optimal morphology reached an IR of 54%. Frozen-thawed embryos transfer derived from Class I follicles had an IR of 37% significantly higher than those from Class II and III follicles, respectively, of 8 and 5% (P < 0.001). Thirty-five per cent of the frozen embryos but also 10% of the destroyed embryos were derived from G-CSF Class I follicles. Non-optimal embryos appear to have been transferred in 28% (22/78) of the women, and their pregnancy rate was significantly lower than that of women who received at least one optimal embryo (18 versus 36%, P = 0.04).CONCLUSIONSMonitoring FF G-CSF for the selection of embryos with a better potential for pregnancy might improve the effectiveness of IVF by reducing the time and cost required for obtaining a pregnancy.

Granulocyte-colony stimulating factor may improve pregnancy outcome in patients with history of unexplained recurrent implantation failure: An RCT

“…Balanced local immune system is required during the implantation window to enable the embryo not only to attach but also to regulate the invasion phase. G-CSF stimulates type 2 T helper cytokine secretion and activation of T regulatory cells so it could be the effective treatment in patient with history of implantation failure (3). In the present study, the pregnancy outcome improved in women used single dose of G-CSF, although this difference was not statistically significant compared with women in the control group.…”

“…Endometrial receptivity is the limiting factor for implantation and success of IVF programs (2). Granulocyte-colony stimulating factors (G-CSF) is a hematopoietic lineage-specific cytokine and known for its specific effects on the activation of intracellular signaling pathways that are associated with the cell proliferation, differentiation, and stimulation of hematopoietic cells of the neutrophilic granulocyte lineage (3, 4). Several non-hematopoietic cell types, such as reproductive tissue cells, also have shown to produce G-CSF (5- 7).…”

“…The highest G-CSF receptor expression occurs in the first trimester (8). G-CSF effect on recruitment of type 2 T helper cytokine secretion, activation of T regulatory cells, modulation of uterine natural killer cells cytotoxicity and endometrium angiogenesis as a result has an essential role on early cross talk between embryo and uterine endometrium (3, 7-9). Studies showed that elevated G-CSF concentrations on follicular fluid increased implantation rate and can improve IVF outcome (10-15).…”

Additive Verfahren in der Reproduktionsmedizin

“…Eine Rolle als prädiktiver Marker in der Follikelflüssigkeit bei IVF/ICSI-Patientinnen wird ebenso diskutiert [7,19].…”

Preimplantation and postimplantation therapy for the treatment of reproductive failure

“…Lédée et al , presented proof regarding the importance of quantification of follicular fluid G-CSF in ET decision. [23] It reflected the necessity of analysis and monitoring of follicular fluid G-CSF in embryo selection process because if used to an advantage, it will drastically reduce the cost of treatment in achieving a successful pregnancy.…”