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Study of serum inhibin levels in two in-vitro fertilization protocols Kwong, Eugene Cheuk Kun


In order to characterize and compare the pattern of inhibin production in the follicular phase between patients of the clomiphene citrate/human menopausal gonadotropin (hMG) and Buserelin/hMG protocols in in-vitro fertilization, serum inhibin levels from 20 patients in each protocol were measured. The patients were matched for age and had tubal diseases only. It was hypothesized that the serum inhibin levels would be different in these two groups due to possible local actions of clomiphene citrate and Buserelin (a GnRH agonist) on the ovary. Serum inhibin levels were measured using an immunoenzymatic assay kit, with the mean interassay and intraassay coefficients of variation being 14.1% and 8.9% respectively. This assay did not cross-react with folliclestimulating hormone, luteinizing hormone, transforming growth factor β, activin A, insulin-like growth factor-1, seminal inhibin like peptide and human chorionic gonadotropin (hCG), but it could detect free a subunits of inhibin in addition to dimric inhibin. Apart from inhibin, serum estradiol-17/3 levels in patients from the two protocols were compiled from patient records. Serum inhibin was found to correlate significantly with serum estradiol-17/3 in the follicular phase (r= 0.844; P< 0.0001). In the clomiphene citrate/HMG protocol, on day 0 (day of ovulation trigger with hCG), day -1 (one day before hCG administration) and day -2 (two days before hCG administration), the serum inhibins were 6.84 +/- 0.76, 5.11 +/- 0.61, and 3.55 +/- 0.31 U/ml respectively; the serum estradiol-170 levels were 5141 +/- 353.6, 3332.7 +/- 192.6, and 2112.5 +/- 117.3 pmol/1 respectively. In the Buserelin/HMG protocol, on days 0, -1, and -2, the serum inhibin levels were 6.48 +/- 0.71, 5.47 +/- 0.49, and 4.0 +/- 0.35 U/ml respectively; the serum estradiol-17/3 levels were 4287.8 +/- 409.4, 2991.7 +/- 259.8, and 2093.5 +/- 151.3 pmol/1 respectively. Serum inhibin and estradiol-17/3 levels in these two protocols were compared by the unpaired t-test. No significant differences were found in serum inhibin and estradiol-17/3 levels on days 0, -1 and -2 between these two groups of patients (inhibin: P= 0.73, 0.639, and 0.37, respectively; estradiol-17/3: P= 0.123, 0.298 and 0.93, respectively). With respect to follicular growth as assessed by ultrasonography, the Buserelin/HMG protocol resulted in significantly greater number of large follicles with diameter greater than or equal to 17 mm on day 0 (2.45 +/- 0.28), compared with that in the corresponding size category of the clomiphene citrate/HMG protocol (1.50+/- 0.21) (P=0.0095). Whereas, in the size category of 10 to 13mm in follicular diameter on day 0, the number of follicles in the Buserelin/HMG protocol (4.7 + /- 0.7) was significantly smaller than that in the clomiphene citrate/HMG protocol (7.1 +/- 0.8) (P= 0.0306). Nevertheless, no significant differences were found in the number of oocytes retrieved, mature and total, between the two groups of patients. In summary, the clomiphene citrate/HMG and "ultra-short" Buserelin/HMG protocols resulted in similar ovarian responses as reflected by serum inhibin and estradiol-17/3 levels. Therefore, the data of the present study did not support the proposed hypothesis, despite the observation that the Buserelin/HMG protocol produced larger follicles.

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