Granulocyte-Colony Stimulating Factor Administration Shows Promise in Treating Unexplained Recurrent Miscarriage
July 30, 2009
Miscarriage occurs in 10%-25% of all clinically recognized pregnancies, with around <5% of women reporting 2 consecutive miscarriages and nearly 1% women experiencing ≥3 recurrent episodes of pregnancy loss. The etiology of miscarriage is unexplained in approximately 50%-75% of couples with recurrent pregnancy loss. Now a randomized controlled study, published in the recent issue of Human Reproduction, reports the potential of subcutaneous administration of granulocyte-colony stimulating factor (G-CSF) as an effective strategy to improve the pregnancy outcome in patients with idiopathic recurrent miscarriages.
Fabio Scarpellini and Marco Sbracia from the Hungaria Center for Endocrinology and Reproductive Medicine, Rome, Italy, conducted the trial to evaluate the efficiency of G-CSF in treating unexplained recurrent miscarriage. The study comprised of 68 women with a minimum of four unexplained recurrent pregnancy losses. The study candidates were subjected to either ubcutaneous G-CSF, 1 μg/kg/day (n=35), initiated on the sixth day following ovulation, or placebo (n=33).
The primary outcome measure was the delivery of a healthy baby with no major or minor abnormalities. The investigators observed that 82.8% women in the G-CSF group (n=29) delivered a healthy baby, in contrast to only 48.5% women (n=16) in the placebo group (P=0.0061; OR=5.1). Women in the G-CSF group showed significantly higher levels of beta human chorionic gonadotropin (β-hCG) in 5-9 gestational weeks when compared to those in the placebo group (P<0.001). Based on their data, the researchers suggested that G-CSF could be indicated for the treatment of unexplained recurrent miscarriage.
Several cytokines, including G-CSF, granulocyte-macrophage CSF (GM-CSF), and interleukin-6, regulate fetal placental unit and have a key role in maintaining pregnancy. Earlier, Perricone et al (American Journal of Reproductive Immunology, 2003) assessed the levels of GM-CSF in women with normal pregnancies and those with unexplained recurrent miscarriage, and determined the effects of treatment with intravenous immunoglobulin (IVIg). The investigators measured the peripheral blood free GM-CSF in 39 healthy women (26 pregnant and 13 non-pregnant), and 53 women with recurrent miscarriage (42 pregnant and 11 non-pregnant). The levels of GM-CSF were measured in 14 pregnant women with recurrent miscarriages even after first infusion of 0.5 g/kg IVIg. A significantly high level of GM-CSF was observed in healthy pregnant women; however, similar findings were not noted in pregnant subjects with recurrent miscarriage. The researchers also found that the IVIg administration led to an increase in GM-CSF level by almost two-fold in pregnant recurrent aborters.
Recurrent miscarriage, characterized by the loss of three or more successive pregnancies during the first trimester, has a huge psychological impact on both the parents. Since the exact etiology and pathogenesis are unclear, the treatment of recurrent miscarriages remains debatable. Few studies have demonstrated the efficacy of corticosteroids, aspirin, heparin or immunotherapy, in treatment. However, further clinical studies based on large cohorts are mandatory to affirm the potential benefits of these strategies in preventing unexplained recurrent miscarriages before recommending them in mainstream clinical practice.
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http://clinicaltrials.gov/ct2/show/NCT00772122
The G-CSF group of 35 women, underwent a daily sub-cutaneous administration of the filgrastim (Neupogen, Dompe', Italy), the recombinant G-CSF, at a dosage of 1 microgram (100000 IU)/kg/day from the 6th day after ovulation till the occurrence of menstruation or to the end of the 9th week of gestation.