Recombinant human granulocyte-colony stimulating factor (rhG-CSF) is given as an immunomodulatory treatment to suppress an immune response to pregnancy (in which the uterus rejects the embryo or fetus), which is a cause for “unexplained” miscarriage, and hence, prevents recurrent pregnancy loss.
Now, a new study presented at the 34th Annual Meeting of ESHRE (European Society of Human Reproduction and Embryology) has found no evidence that rhG-CSF, when given in the first trimester of pregnancy, improves outcomes in women with a history of unexplained recurrent pregnancy losses.
Results of the large randomized placebo-controlled study – the largest of its kind, the RESPONSE trial, were presented by Abey Eapen, honorary research fellow, Tommy’s National Centre for Miscarriage Research at the University of Birmingham, UK. The study, a controlled randomized trial involved 150 women with a history of unexplained miscarriage and was performed at 21 hospitals in the UK.
rhG-CSF is a drug that is widely used (and licensed) in cancer medicine to increase white blood cells after chemotherapy. It is a regulator of neutrophils and other lymphocytes activating and protecting the immune system.
Miscarriage is a common and distressing complication of pregnancy, especially in IVF. Estimates are that around 1-2% of all couples experience recurrent pregnancy loss, but Eapen said that it is difficult of estimate the actual numbers using rhG-CSF. “It’s a relatively new treatment and is offered mainly through private miscarriage and IVF clinics.”
As background to the study, Eapen said that evidence in favor of rhG-CSF in the prevention of recurrent pregnancy loss was based on just one single-center randomized trial and four further observational studies, which all suggested a statistically significant increase in pregnancy and live birth rates in the treatment groups.
In this study, with an endpoint defined as clinical pregnancy rate at 20 weeks gestation, 76 women were randomized to rhG-CSF and 74 to placebo. All subjects had had at least three unexplained miscarriages, were aged between 18 and 37 years, and were trying to conceive naturally.
At follow-up, results showed a clinical pregnancy rate at 20 weeks of 59.2% in the rhG-CSF group, and of 64.9% in the placebo group, suggesting a neutral effect of the treatment. With further follow-up, these rates were similarly evident in live birth.
“Worldwide, the granulocyte-colony stimulating factor is widely used in reproductive medicine to treat pregnancies conceived both naturally and after assisted reproduction following recurrent miscarriages,” said Eapen. “Some studies have suggested statistically significant improvements in clinical pregnancy rates, but we here have high-quality evidence that rhG-CSF is not an effective treatment for patients with unexplained recurrent miscarriages.”
Even after a diagnosis of recurrent miscarriage, the majority of pregnancies do have a favorable outcome. “But,” said Eapen, “it is still very important that these women are investigated and managed in a specialist miscarriage clinic for counseling, support, evidence-based investigation, and an opportunity to take part in research. Healthy diet and management of modifiable risk factors may also help.”