G-CSF Priming Improves Pregnancy Rate in Assisted Reproductive Technology

Granulocyte colony-stimulating factor (G-CSF) priming improves fertilization and implantation rate and embryonic development in patients with poor ovarian reserve according to study results published in Reproductive Biology and Endocrinology.

Researchers conducted a prospective randomized open-label controlled trial between May 19, 2014, and November 26, 2018, in Japan. Only patients seeking assisted reproductive technology (ART) therapy who had mild to moderately decreased ovarian reserve and anti-Müllerian hormone (AMH) concentrations of less than 2 ng/mL were included in the study. A total of 100 patients were enrolled and randomized; patients and investigators were not blinded in this study. Half of the patients were given G-CSF in 2 consecutive cycles preceding ART therapy, whereas the other half served as the control group. 

Enrolled participants were aged 20 to 42 years and received conventional infertility treatments such as sexual intercourse or intrauterine insemination. Fresh embryo transfer occurred after in vitro fertilization (IVF) or intracytoplasmic sperm injection. AMH serum concentrations that were collected at baseline and post-treatment were compared between groups. Data that were not normally distributed were analyzed using the Mann-Whitney test or Wilcoxon matched-pairs rank test. Normally distributed data were analyzed with the chi-squared test, Fischer’s exact test, or multiple logistic regression analysis. At baseline, there were no significant differences between the 2 groups. 

After conventional infertility treatment, 3 participants in the G-CSF group conceived compared to 0 in the control group. The rest of the participants received ovarian stimulation which resulted in 14 clinical pregnancies compared with 6 in the control group, 12 ongoing pregnancies compared with 5 in the control group, and 9 live deliveries compared with 5 in the control group. Additionally, in the G-CSF group, there was a significantly higher rate of patients achieved clinical pregnancy (30%) and ongoing pregnancy (26%) compared with 12% and 10% in the control group respectively. Cryopreserved embryo transfer was then carried out in the G-CSF and control groups. Twenty-one cycles of embryo transfer in the G-CSF group resulted in 6 clinical pregnancies and 4 live deliveries compared with 14 cycles of embryo transfer leading to 4 clinical pregnancies and 2 live deliveries in the control group. 

The researchers found that the rate of cumulative live delivery was significantly higher in the G-CSF group (32%) compared with the control group (14%; RR, 2.8; 95% CI, 1.04-7.7; P <.05). Miscarriage rates were similar between both groups and G-CSF priming resulted in no adverse events on the participants or the fetuses. 

A logistic regression analysis was used to analyze the associations between fertility-related factors such as age, day-3 follicle-stimulating hormone, AMH, and G-CSF priming with live delivery. The authors found that age (P <.05) and G-CSF (P <.05) were the only factors that were associated with cumulative live delivery. Additionally, G-CSF administration was found to be associated with significantly increased serum AMH concentrations (P <.01).

Limitations of this study include the authors’ decision to utilize once-per-cycle administration of G-CSF as more frequent administration could have resulted in greater efficacy.

 “…G-CSF priming in 2 consecutive cycles preceding ART significantly improved fertilization and embryonic development in ART therapy,” the study authors wrote.