Rescue hCG to treat empty follicle syndrome after the use of a GnRH agonist as oocyte maturation trigger: First report on fresh embryo transfer and clinical pregnancy

Abstract

We present a case series and literature review on the use of rescue human chorionic gonadotropin (hCG) in cases of empty follicle syndrome (EFS) after a gonadotropin-releasing hormone agonist (GnRHa) trigger. EFS was diagnosed after failure to collect any oocytes from one ovary. In such cases, a single dose of hCG was administered and the oocyte retrieval was repeated 36 h later. The main outcome measures were the number of mature oocytes (M2) and embryos (2PN), incidence of hospitalisation for severe ovarian hyperstimulation syndrome (OHSS) and clinical pregnancy when fresh embryo transfers occurred. Our population consisted of 322 patients, who had a GnRH agonist as oocyte maturation trigger (2-mg subcutaneous buserelin). Six patients (1.8%) developed EFS after the use of a GnRHa trigger. Mature oocytes were retrieved in 5 patients after the use of rescue hCG. One patient developed severe OHSS. Two patients had a fresh embryo transfer and one clinical pregnancy was reported. This is the first case series to report fresh embryo transfers and a clinical pregnancy with the use of rescue hCG after failure of the GnRHa trigger.

Self-Detection of the LH Surge in Urine After GnRH Agonist Trigger in IVF—How to Minimize Failure to Retrieve Oocytes

“…Interestingly, Christopoulos et al (17) reported six EFS patients after GnRHa trigger, having a mean age of 32.6 years, a mean antral follicle count of 27 and a mean basal FSH level of 4.4 UI/l, rather far from the LH value defining the hypogonadotropic hypogonadal patient.…”

“…This prompted many clinics to recommend donors to have a serum measurement in the fertility clinic 12 h after the GnRHa trigger. However, urine LH measurement performed at home should predict the correct response to the GnRHa trigger, and if needed, the administration of a rescue bolus of hCG (re-trigger) and re-scheduling could avoid EFS or a low follicle mature oocyte ratio (17,18).…”

Empty follicle syndrome revisited: definition, incidence, aetiology, early diagnosis and treatment

“…On the other hand, EFS has also been reported in young patients with normal or high ovarian reserve. Christopoulos et al (2015) reported six patients with EFS having a mean age of 32.6 years, mean basal FSH level of 4.4 Ui/l and mean antral follicle count of 27. These cases, however, were observed after GnRH-agonist trigger, because of a high risk of ovarian hyperstimulation syndrome (more than 18 follicles >11 mm plus serum oestradiol around 5,000 pg/ml).…”

“…Nevertheless, EFS may occur even after GnRH-agonist trigger and the consequent endogenous LH peak (Asada et al, 2013;Christopoulos et al, 2015). In recent years, GnRH-agonist trigger has been used more frequently in the case of high responders who bear a high risk of developing severe OHSS (Banker and Garcia-Velasco, 2015;Engmann and Benadiva, 2012;Humaidan et al, 2013), as its best characteristic is the much lower risk of stimulating the onset of the syndrome in comparison to HCG.…”

“…Furthermore, gonadotrophen-releasing hormone (GnRH) agonist trigger is nowadays largely used in antagonist cycles to prevent severe ovarian hyperstimulation syndrome (OHSS) (Banker and Garcia-Velasco, 2015;Engmann and Benadiva, 2012;Humaidan et al, 2013); however,only few data are available on the incidence of EFS in case of trigger strategies alternative to HCG bolus (Castillo et al, 2012;Christopoulos et al, 2015). Indeed, specific reports about the incidence of EFS after GnRH-agonist trigger of ovulation in IVF are lacking, and cut-off values of circulating LH, allowing a diagnosis of EFS to be made, have not yet been established.…”