THE EMPTY FOLLICLE SYNDROME - A PHARMACEUTICAL-INDUSTRY SYNDROME

The purpose of this study is to provide evidence that empty follicle s yndrome (EFS) is a result of an abnormality in the in-vivo biological activity of some batches of commercially available human chorionic gon adotrophin (HCG). This is a comparative study between six consecutive in-vitro fertilization (IVF) cases with EFS (study group) and 10 IVF p regnancy cycles (control group), Both groups received the same ovarian stimulation protocol consisting of leuprolide acetate and human menop ausal gonadotrophin (HMG), An i.m. injection of 10 000 IU of HCG was a dministered once follicles had reached 18-20 mm and oestradiol/follicl e greater than or equal to 16 mm was at least 900 pmol/l. Transvaginal aspiration was performed 36 h later, Plasma HCG prior to and 12 h aft er i.m. injection as well as the follicular fluid (FF) concentrations of oestradiol, progesterone, luteinizing hormone (LH) and HCG were det ermined in the study group and controls, The in-vitro biological activ ity of the batch of HCG used by the EFS cases and the control group wa s determined using a Leydig cell preparation from adult rats, Furtherm ore, the plasma clearance rate after i.v. injection of 5000 IU of HCG, from the same batches, was studied in three male volunteers, In the I VF cycles, no HCG was detected in plasma prior to the injection of com mercial HCG. After 12 h, no HCG was detected in the study group compar ed to a mean of 207.5 IU/I (110-360) in controls, Mean FF concentratio n of LH, BCG, progesterone and oestradiol was 0.9 IU/I, 0 IU/I, 3.1 nm ol/ml and 4.4 nmol/ml in EFS compared to 1.0, 98.3, 32.0 and 3.7 in pr egnancy cycles, The in-vitro biological activity in both HCG batches w as not significantly different; however, immunoreactive HCG used in EF S cases was undetectable in plasma of male volunteers as soon as 10 mi n after i.v injection of 5000 IU of HCG. The endocrine abnormalities f ound in follicular fluids of EFS are not a consequence of an ovarian p roblem but the result of a lack of exposure to biologically active HCG . The rapid clearance of the drug after i.v. injection and the high af finity of desialylated HCG to liver cells suggest this to be a possibl e explanation for this infrequent but unfortunate event.