The effect of G-CSF on infertile women undergoing IVF treatment: A meta-analysis

Figures & data

Table 1. Characteristics of controlled trials on G-CSF and pregnant outcomes included in the meta-analysis.

		Interventions			Study group		Control group
Authors	Study design/Race	Cases	Controls	Analysis endpoints	Events/Mean ± SD	Total	Events/Mean ± SD	Total	Treatment protocol	Basic information
		300 microgram of G-CSF was administered on the morning of hCG administration before noon	placebo (normal saline)	Endometrium	10.23 ± 2.01	73	10.37 ± 2.22	68	Undergoing IVF and frozen embryo transfer in a first study cycle.	Unselected IVF patients with normal endometrial thickness. Endometrial thickness was assessed 5 days later after G-CSF infusion.
				Implantation	22	176	28	168
Barad et al. (2014)	RCT/Mixed			Biochemical pregnancy	18	73	19	68
				Clinical pregnancy	17	73	16	68
Eftekhar et al. (2014)	Case-control/Asian	300 microgram G-CSF was administered before embryo transfer	without G-CSF	Endometrium	7.91 ± 0.55	34	8.23 ± 0.82	34	Undergoing frozen embryo transfer	Endometrial thickness below 7mm at 12-13 day of frozen embryo transfer cycle. Endometrial thickness was assessed at the first day of progesterone injection.
				Biochemical pregnancy	11	34	4	34
				Clinical pregnancy	9	34	3	34
Li et al. (2014)	Case-control/Asian	100 microgram G-CSF was used only on the day of ovulation or administration of progesterone or hCG	without G-CSF	Implantation	13	82	14	105	Undergoing frozen embryo transfer	Endometrial thickness below 7mm prior to ovulation. Endometrial thickness was assessed 5 days later after G-CSF infusion.
				Clinical pregnancy	10	40	12	80
Xu et al. (2015)	Case-control/Asian	300 microgram G-CSF was carried out on the day that one follicle became dominant	without G-CSF	Implantation	9	28	15	108	Undergoing frozen embryo transfer	Endometrial thickness below 7mm prior to ovulation. Endometrial thickness was assessed 24 or 48 h later after G-CSF infusion.
				Clinical pregnancy	1	14	1	52
Aleyasin et al. (2016)	RCT/Asian	300 microgram G-CSF was administered before embryo transfer	without G-CSF	Endometrium	11.2 ± 2	56	11.5±2.3	56	Undergoing IVF	IVF patients with repeated IVF failure
				Implantation	24	133	10	138
				Biochemical pregnancy	25	56	11	56
				Clinical pregnancy	21	56	8	56
Eftekhar et al. (2016)	RCT/Asian	300 microgram G-CSF was administered at the oocyte retrieval day	without G-CSF	Biochemical pregnancy	9	50	10	50	Undergoing IVF	Unselected IVF patients with normal endometrial thickness who were undergoing IVF
				Clinical pregnancy	9	50	9	50

G-CSF: granulocyte colony-stimulating factor; RCT: randomized controlled trials; Mixed: American population.

Figure 1. The process flow diagram of selected studies.

Table 2. Comparing G-CSF treatment versus placebo for infertile women undergoing IVF.

	Fixed/Random model			Sensitivity analysis
Outcomes	Pooled relative risk (95% CI)	I^2 (%)	Heterogeneity (P)	Pooled relative risk (95% CI)	I^2 (%)	Heterogeneity (P)
Implantation	1.461 (0.801,2.664)	70.7	0.017	1.887 (1.256,2.833)	23.2	0.272
Biochemical pregnancy	1.426 (0.795,2.559)	61.9	0.049	1.800 (1.172,2.765)	50.2	0.134
Clinical pregnancy	1.563 (1.122,2.176)	26.8	0.234	1.897 (1.267,2.840)	0	0.417
Mean difference (95% CI)
Endometrium	-0.173 (-0.393,0.46)	0	0.411	-0.260 (-0.564,0.043)	5.5	0.304

Table 3. Subgroup analysis of pregnant outcomes.

		Fixed/Random model
Outcomes	Subgroups analysis	Pooled relative risk (95% CI)	I^2 (%)	Heterogeneity (P)
Implantation	Thin endometrium/RIF	1.887 (1.256,2.833)	23.2	0.272
	Normal IVF	0.750 (0.447,1.258)	NA	NA
	Overall	1.461 (0.801,2.664)	70.7	0.017
Biochemical pregnancy	Thin endometrium/RIF	2.385 (1.414,4.023)	0	0.756
	Normal IVF	0.888 (0.562,1.403)	0	0.969
	Overall	1.426 (0.795,2.559)	61.9	0.049
Clinical pregnancy	Thin endometrium/RIF	2.312 (1.444,3.701)	0	0.766
	Normal IVF	0.993 (0.611,1.616)	0	0.984
	Overall	1.563 (1.122,2.176)	26.8	0.234

NA: Not applicable.

Figure 2. The pooled risk ratios (RRs) or the standardized mean difference (SMD) with 95% confidence intervals (CIs) of the relationship between G-CSF/placebo or no treatment and implantation rate with random models (A), clinical pregnancy rate with fixed models (B), endometrial thickness (C), and funnel plots for clinical pregnancy rate (D).

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