Is granulocyte colony-stimulating factor level predictive for human IVF outcome?

Salmassi, Ali; Schmutzler, A. G.; Schaefer, S.; Koch, Kerstin; Hedderich, Jürgen; Jonat, W.; Mettler, Liselotte

doi:10.1093/humrep/dei071

Cited by 82 publications

(60 citation statements)

References 34 publications

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“…The majority of the cytokines reached their peak levels at the time of OPU, coinciding with the maximal levels of FSH and HCG. In support of our findings, previous studies have found a gradual increase of serum macrophage colony-stimulating factor (M-CSF) and granulocyte colonystimulating factor (G-CSF) throughout ovarian stimulation in IVF cycles (Nishimura et al, 1998;Salmassi et al, 2005;Salmassi et al, 2010). IFN-γ, IL-4 and TNF have been studied after lymphocyte activation with PMA/ionomycin before and after ovarian stimulation (Kalu et al, 2008), and IL-10 has been analyzed in serum during IVF treatment (Wu et al, 2001).…”

Section: Discussionsupporting

confidence: 87%

Immunological status in patients undergoing in vitro fertilisation: responses to hormone treatment and relationship to outcome

Persson

Ekerfelt

Jablonowska

et al. 2012

Journal of Reproductive Immunology

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We aimed to prospectively investigate the paternal antigen-induced cytokine secretion by peripheral blood mononuclear cells (PBMC) in response to hormone treatment in women undergoing in vitro fertilization (IVF) and to examine the predictive value of the cytokine secretion in the outcome of IVF treatment in a pilot study. Twenty-five women were included and IVF treatment was successful for six and unsuccessful for 19 women. Blood samples were collected before IVF treatment, on four occasions during IVF and 4 weeks after embryo transfer. The numbers of Th1-, Th2-and Th17-associated cytokine secreting cells and cytokine levels in cell supernatants were analyzed by enzyme linked immunospot-forming (ELISpot), enzyme-linked immune-sorbent (ELISA) or Luminex assay. None of the cytokines (IFN-γ, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, TNF and GM-CSF) had any predictive value regarding IVF outcome. The majority of the cytokines reached their peak levels at ovum pickup, suggesting an enhancing influence of the hormonal stimulation. Pregnancy was associated with a high number of IL-4-, IL-5-and IL-13-secreting cells four weeks after ET. In conclusion, the results do not support our hypothesis of a more pronounced peripheral Th1 and Th17 deviation towards paternal antigens in infertile women with an unsuccessful IVF outcome, although this is based on a small number of observations. Thus, a larger study should be conducted to confirm this conclusion. Higher numbers of Th2-associated cytokinesecreting cells in pregnant women four weeks after ET do corroborate the hypothesis of a Th2 deviation during pregnancy.

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Section: Discussionsupporting

confidence: 87%

Immunological status in patients undergoing in vitro fertilisation: responses to hormone treatment and relationship to outcome

Persson

Ekerfelt

Jablonowska

et al. 2012

Journal of Reproductive Immunology

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Section: The Role Of Gcsf In Implantation and Pregnancymentioning

confidence: 99%

“…Salmassi et al evaluated 93 women who underwent IVF; in their study, patients who became pregnant revealed a continuous increase in serum GCSF level from the day of embryo transfer to the day of implantation and from the day of confirmation of pregnancy to gestation; in contrast, those patients who did not become pregnant initially showed a slight increase in GCSF level, then with the failure of implantation as the GCSF level decreased significantly (Salmassi et al 2005). The authors concluded that this cytokine could have an important function in achieving or maintaining pregnancy (Salmassi et al 2005). In another study, Rahmati and coworkers demonstrated significantly lower levels of GCSF receptors at the maternal-fetal interface in infertile women with implantation failure, and interestingly, stimulation with high-dose GCSF was able to increase the expression of GCSF receptors in these patients (Rahmati et al 2014).…”

Section: The Role Of Gcsf In Implantation and Pregnancymentioning

confidence: 99%

“…Many couples still remain unsuccessful after several IVF attempts causing deep effect on quality of life and a heavy financial burden (Zeyneloglu & Onalan 2014). With the recent advances in understanding the important role of granulocyte colony-stimulating factor (GCSF) in reproduction, and the detection of GCSF receptors in placental cytotrophoblasts, syncytiotrophoblasts, decidual stromal cells, endometrial gland cells, and follicular cells (Saito et al 1994, Miyama et al 1998, McCracken et al 1999, Salmassi et al 2005, Ledee et al 2008, Rahmati et al 2014, GCSF started to attract attentions in gynecology, especially in patients with recurrent abortions and/or infertility.…”

Section: Introductionmentioning

confidence: 99%

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Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial

Aleyasin¹,

Abediasl²,

Nazari³

et al. 2016

Reproduction

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Recent studies have revealed key roles for granulocyte colony-stimulating factor (GCSF) in embryo implantation process and maintenance of pregnancy, and some studies showed promising results by using local intrauterine infusion of GCSF in patients undergoing in vitro fertilization (IVF). This multicenter, randomized, controlled trial included 112 infertile women with repeated IVF failure to evaluate the efficacy of systemic single-dose subcutaneous GCSF administration on IVF success in these women. In this study, the Long Protocol of ovarian stimulation was used for all participants. Sealed, numbered envelopes assigned 56 patients to receive subcutaneous 300 µg GCSF before implantation and 56 in the control group. The implantation (number of gestational sacs on the total number of transferred embryos), chemical pregnancy (positive serum β-HCG), and clinical pregnancy (gestational sac and fetal heart) rates were compared between the two groups. This trial is registered at www.irct.ir (IRCT201503119568N11). The successful implantation (18% vs 7.2%, P = 0.007), chemical pregnancy (44.6% vs 19.6%, P = 0.005), and clinical pregnancy (37.5% vs 14.3%, P = 0.005) rates were significantly higher in the intervention group than in the control group. After adjustment for participants' age, endometrial thickness, good-quality oocyte counts, number of transferred embryos, and anti-Mullerian hormone levels, GCSF treatment remained significantly associated with successful implantation (OR = 2.63, 95% CI = 1.09-6.96), having chemical pregnancy (OR= 2.74, 95% CI = 1.11-7.38) and clinical pregnancy (OR = 2.94, 95% CI = 1.23-8.33). In conclusion, administration of single-dose systemic subcutaneous GCSF before implantation significantly increases the IVF success, implantation, and pregnancy rates in infertile women with repeated IVF failure.

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“…G-CSF is also secreted by cells of the reproductive tract: human luteinized follicular granulosa cells (12), endometrial cells (13), and cells from decidual, placental (14) and various foetal tissues (15). At ovulation, G-CSF concentrations are much higher in FF than in serum (6). Studies using western blot and immunohistochemistry techniques have located the G-CSF protein and its receptor in the ovary, mainly in the granulosa cells of the follicle and in luteal cells (12).…”

Section: Introductionmentioning

confidence: 99%

Cumulus oophorus T cells: a possible source of follicular fluid G-CSF, biomarker predictive for embryo implantation in IVF/ICSI cycles

Piccinni¹

2015

CCE

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SummaryGranulocyte-colony stimulating factor (G-CSF) in individual follicular fluid (FF) may provide a non-invasive biomarker of implantation to be evaluated, to select the oocyte and hence the embryo with the highest implantation potential to transfer in IVF/ICSI (In Vitro Fertilization/ Intracytoplasmatic Sperm Injection) cycles. We wonder what could be the source of FF-G-CSF. Since cytokines preferentially act locally, the source of FF G-CSF could be located nearest the oocyte. Cumulus oophorus surrounds the oocyte and then in physiological pregnancy surrounds, breaking up progressively, the derived embryo during the first 72 hours until its implantation. Thus, cumulus could have a strong influence particularly on oocyte and then on embryo development and quality. We found that cumulus T cells produce G-CSF, which could be: a) the source of FF G-CSF induced by IL-4 produced by T cells in response to cumulus-derived progesterone and b) responsible together with cumulus derived-progesterone for the cumulus T cells IL-4 production, which in turn could induce the production of LIF by these T cells. Cumulus T cell-derived LIF, which increases the quality of embryos, may provide a microenvironment suitable for embryo pre-implantation development and may explain the increased implantation rate of the embryos associated with high levels FF G-CSF.

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Is granulocyte colony-stimulating factor level predictive for human IVF outcome?

Abstract: G-CSF is involved in follicle development and may be a predictor of IVF outcome.

Cited by 82 publications

References 34 publications

Immunological status in patients undergoing in vitro fertilisation: responses to hormone treatment and relationship to outcome

Immunological status in patients undergoing in vitro fertilisation: responses to hormone treatment and relationship to outcome

Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial

Cumulus oophorus T cells: a possible source of follicular fluid G-CSF, biomarker predictive for embryo implantation in IVF/ICSI cycles

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