'Curing' empty follicle syndrome

Abstract

We report a novel method of rescuing empty follicle syndrome (EFS) and provide evidence that it is a drug-related problem rather than a clinical dysfunction. In a preliminary study we established that in EFS the serum beta-human chorionic gonadotrophin (beta-HCG) concentrations 36 h after HCG administration never exceeded 10 mIU/ ml. beta-HCG concentrations were thus used to confirm EFS when oocytes were not retrieved from one ovary after controlled ovarian hyperstimulation. The procedure was suspended leaving intact all follicles in the second, ovary. After confirmation of EFS, a second HCG from a different batch was administered and 36 h later mature oocytes were retrieved from the intact ovary, suggesting a fault with the HCG previously administered. Three patients have been treated in this way. In the first case, four out of five mature eggs were fertilized after intracytoplasmic sperm injection (ICSI) resulting in the transfer of three top grade (grade 1) embryos. In the second case all seven mature oocytes fertilized after in-vitro fertilization (IVF) and three grade 1 embryos were transferred resulting in a twin pregnancy, now delivered. In the third case, five out of nine oocytes were fertilized after ICSI and one out of the three treated with high insemination concentration IVF fertilized, resulting in the transfer of three ICSI embryos.

Empty follicle syndrome: the reality of a controversial syndrome, a systematic review

“…Some have postulated that EFS is a drug-related problem rather than a clinical dysfunction (11,12), whereas others suggested that the occurrence of EFS in IVF can be attributed to a failure in [1] accurate timing of induction of final oocyte maturation, [2] properly scheduled ovarian hyperstimulation, or [3] instruction of patients and doctors (23). However, by differentiating between the false and genuine types, these suggestions become less relevant.…”

“…The mechanisms responsible for EFS remain obscure, though many hypotheses have been put forward ranging from human error (6,(9)(10)(11) to pharmacologic problems (8,11,12).…”

“…It is also thought that the granulosa cells' function and/or metabolism in older women may lead to altered oocyte growth and maturation and consequently EFS. Some have proposed that genetic factors could be responsible for some cases of EFS (14,15), whereas others reported a drug-related cause associated with low bioavailability of the administered hCG (11). However, normal levels of b-hCG on the day of oocyte recovery have been reported in EFS patients (4).…”

Empty follicle syndrome after GnRHa triggering versus hCG triggering in COS

“…The available literature describes two subtypes of EFS; the so called genuine EFSpresumably related to intrinsic ovarian factors -and false EFS, mainly related to pharmacological problems or human administration error. Several hypotheses as to the background of EFS after hCG triggering of final oocyte maturation in gonadotropin stimulated cycles have been proposed: early oocyte atresia due to a dysfunctional folliculogenesis in the presence of an apparently normal hormonal response [4], a biological abnormality in the supply of mature oocytes to be retrieved despite normal bioavailability of hCG [5], genetic factors such as LH/hCG receptor mutations [6, REF 22 from Yariz 2011], abnormalities in the in vivo biological activity of some batches of commercially available hCG or GnRHa [7], rapid clearance of hCG by the liver [7], pharmacological problems [5,8,9] and human error [5,7,10] -in particular inappropriate timing of the triggering bolus of hCG [8]. Moreover, advanced ovarian ageing is considered a risk factor for EFS recurrence, probably due to altered folliculogenesis [6].…”

Recurrent genuine empty follicle syndrome: a rare case report

“…A rescue protocol can be used to salvage the cycle when the β-hCG concentration is <100 mIU/ml (Zegershochschild); Ndukwe et al, trying to predict EFS, stated that serum hCG levels were < 10 mIU/ml in cases of EFS but Stevenson and Lashen in a comprehensive review, offered that hCG levels of 40 mIU/ml should be the cutoff between normal to low hCG levels on the day of ovum pickup (OPU). 4,8,16 But In our patient in both cycles serum β hCG level was > 40 mIU/ml. Patients with EFS present a challenge to the treating physician.…”