P-673 GnRH Agonist Early Follicular Challenge Test as a Predictor of Ovarian Response in Short Antagonist Cycles for Fertility Preservation
Authors: Yerushalmi G.M , Abraham S , Kedem A , Youngster M , Barkat J , Bruchin O , Gat I , Hourvitz A 
Published: June 2022

Abstract

Study question
Does the response to GnRH agonist can be used to predict ovarian function in short GnRH antagonist cycles in women undergoing oocyte cryopreservation IVF cycles?

Summary answer
Response to a single GnRH agonist dose at the beginning of stimulation during short antagonist cycle can predict the outcome of the fertility preservation cycle

What is known already
There is a need for a reliable test for ovarian reserve. Gonadotrophin agonist stimulation test (GAST) is considered a valid marker for ovarian reserve but the test was never validated for short antagonist protocol. The reported dose for this test was 0.1 mg, however, from the vast experience with GnRH agonist triggering, it is now agreed that the optimal dose for GnRH agonist flare effect is 0.2 mg.

Study design, size, duration
A prospective observational study of fertility preservation cycles patient in an academic hospital setting. Seventy-four Short GnRH antagonist cycles that underwent an oocyte retrieval between 1 December 2020 and 1 January 2022.

Participants/materials, setting, methods
On day 2, blood was sampled for basal FSH, LH, and E2 measurements, followed by a subcutaneous injection of 0.2mg GnRH agonist as part of the initial ovarian stimulation. Twelve hours later blood sampling was repeated. E2 response was used as test parameter. The major outcome was the number of cryopreserved oocytes.

Main results and the role of chance
Participants were divided to groups according to Day 3 E2 to Day 2 E2 response (E3/E2 ratio) to lower and upper third percentiles (&lt;3.32, n = 24 and &gt;5.41, n = 25). Age (32.68 vs. 32.79, p = 0.965), total gonadotropin dose injected 3216.67 vs. 2773.42 IU p = 0.16) and day 3 FSH levels (7.39 vs. 7.16, p = 0.768) were not significantly different between groups. Ovarian response as measured by E2 levels on ovulation trigger (7879.72 vs. 17572.54 pmol/ml, p = 0.001) and number of M2 oocytes retrieved were significantly different (17.92 vs. 6.24, p &lt; 0.001). Linear correlation between E3/E2 ratio and number of M2 oocytes was calculated (R = 0.48, p &lt; 0.001). ROC curve analysis of E3/E2 ratio for more than fifteen M2 oocytes indicate AUC value of 0.82 (cutoff value of 4.22, p &lt; 0.001, 84.6% sensitivity, 70.8% specificity) and for less than five M2 oocytes AUC value of 0.84 (cutoff value of 3.34, p &lt; 0.001, 76.3% sensitivity, 73.3% specificity). The results suggest that the testing response to 0.2mg GnRH agonist positively correlates with treatment outcome of the current cycle.

Limitations, reasons for caution
Although all patients were tested for FSH levels for ovarian reserve, they were not tested for AMH levels.

Wider implications of the findings
The response to single GnRH agonist dose during short antagonist cycle can be used as another biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict accurately the outcome of the specific cycle, and potentially used to adjust the treatment dose.

Trial registration number
NCT04973969