The HERA (Hyper-response Risk Assessment) Delphi consensus for the management of hyper-responders in in vitro fertilization

Abstract

Purpose: To provide agreed-upon guidelines on the management of a hyper-responsive patient undergoing ovarian stimulation (OS) METHODS: A literature search was performed regarding the management of hyper-response to OS for assisted reproductive technology. A scientific committee consisting of 4 experts discussed, amended, and selected the final statements. A priori, it was decided that consensus would be reached when ≥66% of the participants agreed, and ≤3 rounds would be used to obtain this consensus. A total of 28/31 experts responded (selected for global coverage), anonymous to each other.

Results: A total of 26/28 statements reached consensus. The most relevant are summarized here. The target number of oocytes to be collected in a stimulation cycle for IVF in an anticipated hyper-responder is 15-19 (89.3% consensus). For a potential hyper-responder, it is preferable to achieve a hyper-response and freeze all than aim for a fresh transfer (71.4% consensus). GnRH agonists should be avoided for pituitary suppression in anticipated hyper-responders performing IVF (96.4% consensus). The preferred starting dose in the first IVF stimulation cycle of an anticipated hyper-responder of average weight is 150 IU/day (82.1% consensus). ICoasting in order to decrease the risk of OHSS should not be used (89.7% consensus). Metformin should be added before/during ovarian stimulation to anticipated hyper-responders only if the patient has PCOS and is insulin resistant (82.1% consensus). In the case of a hyper-response, a dopaminergic agent should be used only if hCG will be used as a trigger (including dual/double trigger) with or without a fresh transfer (67.9% consensus). After using a GnRH agonist trigger due to a perceived risk of OHSS, luteal phase rescue with hCG and an attempt of a fresh transfer is discouraged regardless of the number of oocytes collected (72.4% consensus). The choice of the FET protocol is not influenced by the fact that the patient is a hyper-responder (82.8% consensus). In the cases of freeze all due to OHSS risk, a FET cycle can be performed in the immediate first menstrual cycle (92.9% consensus).

Conclusion: These guidelines for the management of hyper-response can be useful for tailoring patient care and for harmonizing future research.

Keywords: Hyper-response; Ovarian hyperstimulation syndrome; Ovarian stimulation.