P-76: Important Role of Macrophage Colony-Stimulating Factor during Menstrual Cycle and Early Pregnancy Phase in Oovarian Stimulated IVF-Ppatients

Background: M-CSF is a cytokine mediating the growth, proliferation and differentiation of various cell types including macrophages, trophoblast cells, and osteoclasts. It plays an important role in immunity reproduction, follicle development and ovulation. In the present study, we describe the important role of the changes in serum M-CSF levels during the menstrual cycle, in the process of follicular maturation, ovulation, implantation, pregnancy and their response to ovarian stimulation with recombinant (r) FSH. Materials and Methods: Granulosa cells (GC) were separated from follicular fluid (FF) by the Percoll technique (n=21). The protein expression of M-CSF and its receptor in GC were detected by immunocytochemistry and by RT-PCR technique. From an original sample of 95 patients (age from 20 to 42), serum and follicular fluid (FF) were collected on the day of follicular puncture (FP). The aetiology of patients was tubal or male factor infertility. These patients were divided into two groups as follows: In group 1: a) correlation between serum and FF with respect to M-CSF and correlation between M-CSF and estradiol (E2) in serum; and b) comparison of M-CSF level in serum in response to ovarian stimulation and comparison of M-CSF level in serum between pregnant and non-pregnant patients. In group 2: Patients (n=23) were monitored throughout the menstrual cycle until 4 weeks after embryo transfer. In this group, M-CSF levels in serum were analysed throughout the different ovarian cycle phases and gestation. Results: RT-PCR and immunocytochemical results demonstrated that human follicular GCs express M-CSF and its receptor. In group 1 the M-CSF in FF was higher than in serum (p=0.01). M-CSF levels in serum increased from low, through moderate, to high response patients (p=0.001); pregnancy rates were 11.5%, 22.5% and 51.7%, respectively. In group 2 the levels of M-CSF in serum increased throughout stimulation, reached a peak on the day of oocyte retrieval (p=0.006) and decreased until embryo transfer (ET, p=0.03). In the post-retrieval days, from the day of ET, through implantation, to the day of confirmation of pregnancy, the M-CSF levels of those patients who became pregnant (n=13) increased significantly (p=0.03) and reached their highest level. After implantation the M-CSF level decreased slightly and reached a plateau during gestation. Conclusion: Our data show that M-CSF is involved in follicle development and ovulation and plays an important role in the maintenance of pregnancy. It could also be a predictor of embryo implantation for IVF outcome.