Salivary Estradiol As a Surrogate Marker for Serum Estradiol in Assisted Reproduction Treatment

Introduction: Controlled ovarian hyper-stimulation for in vitro fertilization or intra cytoplasmatic sperm injection necessitates close monitoring using ultrasound and estradiol measurements. Monitoring is also important to prevent or limit the severity of ovarian hyper stimulation syndrome, an iatrogenic and potentially life-threatening complication. Self-operated endovaginal telemonitoring has been shown to offer an attractive and less costly alternative to classic consultation and saliva estradiol measurements could be a stress-free and practical alternative to serial blood determinations. Objectives were to evaluate whether saliva can be a surrogate marker for serum estradiol and its potential applicability in assisted reproduction treatment monitoring.

Material And Methods: Serial blood and saliva samples were collected from 31 patients undergoing ovarian hyper-stimulation. All patients were followed-up using in-house serial vaginal sonograms and immunoassay serum estradiol measurements. Afterwards estradiol was determined in saliva and serum by LC-MS/MS. For a subset equilibrium dialysis and measurement of free serum estradiol was performed.

Results: About 1% of estradiol is present in serum in its free, unbound, form. Salivary estradiol correlates well to both serum free estradiol and serum total estradiol (r=0.80). The concentration of salivary estradiol corresponds to the unbound concentration in serum. The dynamics observed in serum monitoring during treatment are closely mimicked in saliva. ROC analysis on the current limited dataset suggested a saliva cut-off of 22pg/mL (81pmol/L) could help predict risk for OHSS.

Conclusions: Salivary E2 can be considered a surrogate marker for free serum estradiol and total serum estradiol in assisted reproduction treatment. Additionally there might be a role as a prediction marker for OHSS although this finding has to be validated in larger datasets.