‘Defined as a condition in which no eggs are retrieved from mature ovarian follicles with apparently normal follicular development ..’

Emobileclinic Trending Topic :Empty follicle syndrome.

Empty follicle syndrome (EFS) has been defined as a condition in which no eggs are retrieved from mature ovarian follicles with apparently normal follicular development and oestradiol levels, after controlled ovarian hyperstimulation for an assisted reproductive technology (ART) cycle, despite repeated aspiration and flushing.


It is rare with an incidence of 0.2-7% and thought to be a complex phenomenon that can not be explained by low bio-availability.y of human chorionic gonadotrophin alone. The diagnosis of EFS is retrospective.
It is evident that 2 types of EFS exist: genuine (GEFS) and false (FEFS). About 67% of all cases are FEFS suggesting that GEFS is an even rarer event than previously speculated. GEFS is defined as a failure to retrieve eggs from mature follicles after apparently normal folliculogenesis and sterogenesis with optimal beta hCG levels on the day of egg retrieval. Such patients are unlikely to respond to a rescue protocol. FEFS is defined as failure to retrieve eggs in the presence of low BhCG due to an error in the administration or bio-availability of hCG. Such patients are more likely to respond to rescue protocol.
Possible aetilogies for EFS include;

  •   dysfunctional folliculogensesis, in which early oocyte atresia occurs with apparently normal hormonal response.

  •   Biological abnormality in the supply of mature oocytes that can be retrieved despite normal bioavailability of hCG. 

  • Genetic factors in some cases.

  •   Drug related causes due to an abnormality in the in vivo biological activity of some batches of commercially available hCG or GnRH agonist; inappropriate timing of hCG or rapid clearance of hCG by the liver.

  • Advanced ovarian ageing through altered folliculogenesis.

 EFS does not predict a reduce fertility potential in next cycle. If EFS has occurred once, the risk of recurrence is 20%, the risk being higher with advancing age. The risk of recurrence in patients between 35 and 39yrs of age has been reported to be 24% as against 57% for those aged 40yrs and above. In such patients donor cycle may be needed to achieve pregnancy.
Strategies to prevent recurrence of EFS in subsequent ART cycle include;

  •  Using recombinent hCG to trigger an endogenous LH surge.

  •  Changing the batch of hCG.

  •  Use of antagonist protocol.

  • Using a GnRH agonist in antagonist cycle to induce LH surge.

  •  A rescue protocol by administration of 2nd dose of hCG and rescheduling egg retrieval 24-36hrs later. 

  • A rescheduled follicle puncture is feasible as EFS is related to timing of hCG.

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