Clomiphene citrate changes metabolite content of follicular fluid of PCOS women

To determine whether clomiphene citrate (CC) treatment affects the metabolite contents of a dominant follicle in polycystic ovary syndrome (PCOS).

Twenty non-obese primary infertile anovulatory PCOS women undergoing CC treatment and ten fertile women were enrolled. 6 out of 20 patients had impaired glucose tolerance test (IGT). CC was given at a dose of 150 mg on days 3-7 of cycles in the first group. 10 fertile women with a regular menstrual cycle and normal ovaries during ultrasound examination were accepted as control group. They were not given any drug for ovarian stimulation. Transvaginal sonography and follicular tracking were done to each group of participant. Both groups of subjects underwent magnetic resonance spectroscopy when the dominant follicle with a mean diameter of at least 16-18 mm was detected. Lactate (Lac), N-acetylaspartate (NAA), creatine 1 (Cr1), creatine 2 (Cr2) and choline (Cho) signal of dominant follicles were measured. Peak of each metabolite was measured in units. Voxels were placed in the center of dominant follicle.

Compared to control group significantly decreased Cho signal was found in follicular fluid of PCOS subjects taking clomiphene. Almost three-fold decline in Cho signal was detected in PCOS group compared to Cho signal of control group (0.64±1.01 vs. 2.01 ±1.13). On the other hand, significantly increased Lac signal was detected in the dominant follicle of PCOS subjects taking clomiphene compared to control group. Almost 2 fold increase in Lac signal was noted after clomiphene treatment (1.90±0.32 vs. 0.93±2.21). The results of spectroscopy signals obtained from PCOS subjects without IGT and PCOS subjects with IGT were similar.

Unbalanced production of Cho signal in the follicular fluid may have occurred secondary to membrane damage of cumulus-oocyte-complexes due to CC therapy.