Measuring serum hCG levels between hCG injection and egg retrieval is an effective approach to avoiding “empty follicle syndrome”

Abstract

OBJECTIVE: Failure to retrieve eggs from apparently mature follicles (Empty Follicle Syndrome or EFS) has been reported in 0.6%-7% of in vitro fertilization (IVF) cycles. Most cases of EFS occur because sufficient serum hCG (human chorionic gonadotropin) levels are not attained due to patient or pharmaceutical errors. One method to prevent this occurrence is to document appropriate serum hCG values between the time of hCG injection and attempted egg retrieval. Our objective was to examine the efficacy of this approach and to determine the range of hCG levels consistent with appropriate ovulation triggering in IVF patients. DESIGN: Retrospective cohort. MATERIALS AND METHODS: We reviewed 272 fresh IVF cycles performed between June 2006 and April 2008. Women were treated with standard luteal leuprolide acetate (LA), microdose flare LA or ganirelix with the addition of FSH (follicle stimulating hormone) with or without LH (luteinizing hormone) prior to ovulation triggering with intramuscular urinary hCG (7,500-10,000 IU). Patients were excluded if their IVF cycle was incomplete or canceled. Serum hCG levels were measured 8-12 hours after hCG injection. Primary outcomes were oocyte number and number of mature oocytes per mature follicle (>14mm). Other outcomes included embryo number and implantation. Correlation coefficients and Chi-squared tests were used to analyze the relationship of hCG level and these outcomes. RESULTS: Of 272 fresh IVF cycles, 174 cycles (in 151 patients) met our criteria. Mean age was 34.4±4.5 years, and mean BMI was 25.3±5.6 kg/M2. In one patient, hCG was undetectable 12 hours after injection. When questioned, she acknowledged confusion about mixing the injection. This patient received a second hCG injection, and 20 mature oocytes were retrieved 35 hours later. In the remaining patients, serum hCG levels 8-12 hrs after administration were 191±108 IU/mL (range 47-647 IU/mL). The hCG concentration negatively correlated with BMI (R2=-0.3, P<0.0001), but was unrelated to age (P=0.087). There was no correlation of hCG values with number of mature oocytes retrieved, number of follicles >14mm, the ratio of mature oocytes to follicles >14 mm, number of embryos, or implantation rate. CONCLUSIONS: Routine measurement of hCG the day after triggering can avoid EFS due to incorrect hCG administration prior to egg retrieval. Levels of hCG as low as 47 IU/mL the day after IM injection appeared to indicate adequate ovulation triggering. Serum hCG levels at 8-12 hours did not correlate with treatment outcome.