ENGAGE study: ClinicalTrials.gov identifier NTC00696800. PURSUE-study: NCT01144416.

Over the past few years, the use of Gonadotropin-releasing-hormone (GnRH)-agonist for final oocyte maturation in GnRH-antagonist-protocols in stimulated IVF/ICSI cycles has gained worldwide acceptance, as this approach reduces significantly the risk for development of ovarian hyperstimulation syndrome (OHSS). Final oocyte maturation with GnRH-agonist leads to sever luteolysis, which cannot be counterbalanced using standard luteal phase support with purely progesterone (P4) application and therefore administration of hCG or high doses of P4 is considered to be essential to prevent/counteract luteolysis. However, lately publications indicate, that luteolysis is not always complete after GnRH-agonist for trigger. This case-series evaluates the degree of luteolysis in high-responder-patients, who received GnRH-agonist for final oocyte maturation. Assessment of estradiol (E2)- and P4-levels 48 h after oocyte-pick-up (OPU) procedure demonstrate clearly, that luteolysis after GnRH-agonist trigger is individual-specific, even in high-responder patients with the same number of oocytes. Hence, individualization of luteal phase support with the focus on avoiding unnecessary administration of hCG, bearing the risk for development of OHSS, a new concept of luteal coasting needs to be developed, based on severity of luteolysis following luteal coasting.

Ovarian stimulation in a gonadotropin-releasing hormone (GnRH) antagonist protocol with the use of GnRH agonist for final oocyte maturation is the state-of-the-art treatment in patients with an expected or known high response to avoid or at least reduce significantly the risk for development of ovarian hyperstimulation syndrome (OHSS). Due to a shortened LH surge after administration of GnRH agonist in most patients, the luteal phase will be characterized by luteolysis and luteal phase insufficiency. Maintaining a sufficient luteal phase is crucial for achievement of a pregnancy; however, the optimal approach is still under debate. Administration of human chorionic gonadotropin (hCG) within 72 h rescues the corpora lutea function; however, the so far often used 1,500 IU still bear the risk for development of OHSS. The recently introduced concept of “luteal coasting” individualizes the luteal phase support by monitoring the progesterone concentrations and administering a rescue dosage of hCG when progesterone concentrations drop significantly. This retrospective proof-of-concept study explored the correlation between hCG dosages ranging from 375 up to 1,500 IU and the progesterone levels in the early and mid-luteal phases as well as the likelihood of pregnancy, both early and ongoing. The chance of pregnancy is highest with progesterone level ≥13 ng/ml at 48 h postoocyte retrieval. Among the small sample size of 52 women studied, it appears that appropriate progesterone levels can be achieved with hCG dosages as low as 375 IU. This may well optimize the chance of pregnancy while reducing the risk of OHSS associated with higher doses of hCG supplementation in the luteal phase.