Reproducibility and clinical significance of pre-ovulatory serum progesterone level and progesterone/estradiol ratio on the day of human chorionic gonadotropin administration in infertile women undergoing repeated in vitro fertilization cycles

BACKGROUND The objective of this study was to explore the cycle-to-cycle reproducibility of serum progesterone level and progesterone/estradiol (P/E2) ratio in the final step of triggering oocyte maturation in patients undergoing repeated consecutive controlled ovarian hyperstimulation for in vitro fertilization (COH-IVF) treatment and to investigate the clinical parameters associated with serum progesterone concentration and P/E2 ratio. METHODS We retrospectively studied 524 cycles in 203 infertile women who underwent two or more fresh COH-IVF cycles from July 1998 to May 2012 in a university hospital IVF unit. The patients were divided into groups according to the number (2, 3 or >=4) of total successive IVF cycles with successful oocyte retrieval. The within-subject reproducibility of serum P and P/E2 was tested by calculating intra-class correlation coefficients (ICCs). Multiple linear regression analysis was used to assess the association between patient variables and pre-ovulatory serum P level and P/E2 ratio. RESULTS The ICCs in women who underwent 2, 3 and >=4 IVF cycles were -0.052, 0.163 and 0.212, respectively, for serum P concentration and 0.180, 0.168 and 0.148, respectively, for P/E2 ratio. All ICCs for both serum P and P/E2 ratio were indicative of poor reproducibility. The number of oocytes was significantly positively related to P concentration, and endometrial thickness was significantly negatively related to P concentration and P/E2 ratio. CONCLUSION The cycle-to-cycle reproducibility of pre-ovulatory serum P concentration and P/E2 ratio was poor in individual patients, and these fluctuations were more cycle- than patient-dependent. The number of oocytes was the most significant factor relating to P concentration. By using milder stimulation approach to produce fewer oocytes in the next cycle is a strategy to overcome the high serum P concentration, while clinicians should consider each patient's general condition including the age, ovarian reserve, embryo grading and the capacity of frozen-thawed embryo transfer.