Abstract

GnRH antagonist does not create flare-up effects such as are seen with GnRH agonist, and secretion of gonadotropin is immediately controllable. However, a decrease in the number or quality of oocytes extracted occurs as a result of the strong effects of GnRH antagonist in some cases. The purpose of our study was to consider what kind of results can be obtained by using hCG at 50 units from the day of GnRH antagonist use in cases that had not previously reached full term pregnancy using the hMG-GnRH antagonist protocol. Retrospective evaluation using the patient’s previous IVF stimulation attempts as a historical control. The subjects were 14 cases on whom IVF was carried out (28 cycles: 14 cycles with oral contraceptive pill-hMG-GnRH antagonist protocol and 14 cycles with oral contraceptive pill-hMG-low dose hCG-GnRH antagonist protocol). All the cases had been unsuccessful even though the antagonist protocol not using low dose hCG had been carried out (full term pregnancies had not resulted). Regarding the ovulation induction method, an oral contraceptive pill was used from day 3 of menstruation in the cycle prior to extracting the eggs. Ovarian stimulation was started from day 4 after completion of a course of oral contraceptive pills. In both antagonist protocols the type of ovulation induction drug was changed depending on the LH level just before beginning ovarian stimulation. When serum LH was more than 1.5mIU/ml, pure urinary FSH or recombinant FSH was used, and when serum LH was less than 1.5mIU/ml hMG (Humegon, Organon, Osaka) was used. Daily hypodermic injections of Cetrorelix 0.25 mg/day were started from the time the leading follicle reached 14 mm. The treatment regime was changed to hMG (Pergogreen:in a ratio of FSH and LH at one to one) from the day Cetrorelix was started. Urinary hCG at 50 units was used together with hMG from the day that use of Cetrorelix was started in the low dose hCG protocol. When the average diameter of the leading follicle reached 20 mm, the type of ovulation induction drug was changed to hCG at 10000 units. No statistical difference was noted between the two groups for the amount of hMG (no low dose hCG group 2680.4±1039.5 vs low dose hCG group 3235.7±1171.5). However, the mean number of oocytes retrieved was significantly higher in the low dose hCG group (no low dose hCG group 9.7±3.7 vs low dose hCG group 14.6±6.3, p<0.05). The fertilization rate was significantly higher in the low dose hCG group (no low dose hCG group 57.1% vs low dose hCG group 69.6%, p<0.05). The blastomere number on the day 3 was significantly higher in the low dose hCG group (no low dose hCG group 6.0±2.4 vs low dose hCG group 7.0±2.2, p<0.05). Moreover, the blastocyst formation rate was significantly higher in the low dose hCG group (no low dose hCG group 37.5% vs low dose hCG group 63.0%, p<0.05). No statistical difference was noted between the two groups for the clinical pregnancy rate (FHM) per ET (no low dose hCG group 7.7% vs low dose hCG group 33.3%). The results of this study suggest that increases in the number of oocytes extracted, the fertilization rate, the average number of day 3 blastomeres, and blastocyst formation rates can all be increased by using low dose hCG to control the overly strong effectiveness of GnRH antagonist in cases that had not reached full term pregnancy using the GnRH antagonist protocol.

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