G-CSF (granulocyte colony stimulating factor) is a natural cytokine (chemical messenger) which is normally found in the body, and neupogen (filgrastim) is a synthetic (recombinant) form of G-CSF . Higher levels of natural G-CSF seem to be found in follicles which go on to produce healthy eggs compared to follicles which produce poor eggs. Higher levels of G-CSF are expressed in healthy embryos and in healthy placenta, so it is a marker of embryonic/placental viability that seems to have a role in communicating with the endometrium to allow implantation. It is suggested that it may improve lining thickness and egg quality (although the number of patients he has tried it out on for egg quality is apparently very small), as well as placental growth and may permit a successful live birth for ladies who have failed to respond to IVIG. For patients who respond well to it, he believes it can replace IVIG.
Neupogen is licenced in the UK to treat severe neutropenia (low neutrophil (a type of white blood cell) count). Studies on giving GCSF to pregnant animals showed some problems so pregnant women taking the drug for neutropenia were initally advised to stop it, but then studies showed that pregnancy outcomes (for mother and baby) were much better for neutropenic patients who remained on the drug.
Two significant studies have been performed by doctors in Rome and Munich.
In the Rome study, unexplained repeat miscarriage patients who were trying to conceive naturally who were given GCSF from 6 days post ovulation until the onset of the period (if unsuccessful) or until 9 weeks of pregnancy had The live birth rate was 83% compared to the control group's live birth rate of 49%
In the Munich study G-CSF was administered every 3 days from egg collection onwards in fresh IVF patients who were shown to have a genetic defect (absence of 3 killer cell-like immunoglobulin activator receptors) after 5 or more failed IVF cycles or several years of unexplained infertility. This study showed a very high pregnancy rate 74% but also a high miscarriage rate (38%) - although potentially that might have been because the G-CSF therapy was stopped on test day. However, although the incidence of the KIR defect (3 missing activators) was very high, (78% of the patient group who had 5 or more failed IVF or an average duration of unexplained infertility of 6.8 years - this compares to about 30% of the typical population), when the same G-CSF therapy was used with patients who did not have the KIR defect, the pregnancy rate was much lower (only 10%). This suggests that although about 3/4s of patients with 5 or more failed IVFs or long term unexplained infertility may benefit from G-CSF due to the faulty gene, the other 1/4 may get no benefit from G-CSF. In other studies
There is a research trial currently in progress to test for any enhancement in inplantation/pregnancy rate. The protocol is:
two intrauterine infusions of 300mcg G-CSF 48 hours apart before embryo transfer