The effects of levonorgestrel on various sperm functions.
ABSTRACT Two doses of 750-microg levonorgestrel at 12 h apart is one of the regimens for emergency contraception. The mechanism of action of this regimen is not fully known. We investigated whether levonorgestrel influences sperm functions and thereby, exerts contraceptive activity. The motility, acrosome reaction, zona binding capacity, and oocyte fusion capacity of human spermatozoa treated with 1, 10, and 100 ng/mL levonorgestrel for 3 h were evaluated. Levonorgestrel decreased the curvilinear velocity of the treated spermatozoa in a dose-dependent manner. A significant decrease in straight-line velocity, average path velocity and linearity were also found with 100 ng/mL levonorgestrel treatment. This concentration of levonorgestrel, but not others, also marginally decreased (p = 0.045) the zona binding capacity of the treated spermatozoa. The steroid had no effect on acrosome reaction but had a dose-dependent inhibition on spermatozoa-oocyte fusion. These data show that levonorgestrel affects sperm function only at high concentration and the contribution of these effects to emergency contraception is unlikely to be significant.
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ABSTRACT: One retrospective and two prospective studies were conducted among 218 couples treated with in-vitro fertilization (IVF) to establish the reproducibility and diagnostic accuracy of computer-assisted sperm analysis (CASA) with swim-up spermatozoa for the prediction of the fertilization rate of oocytes in vitro. Based on the results of a preliminary retrospective analysis in 49 patients, the 'curvilinear velocity' (VCL) was chosen as the most distinctive motion parameter of sperm function and the median was used to represent the entire sperm population. The number of inseminated motile spermatozoa was then adjusted to median VCL during two subsequent prospective studies with clinical IVF. Whereas in the first prospective study (90 couples) the threshold values of VCL with regard to the number of spermatozoa inseminated were based on the results of the preliminary retrospective study (49 couples), in the second prospective study (79 couples) the settings were based on the results of the first prospective study. The reproducibility of CASA was tested by analysing the motion characteristics of spermatozoa at different intervals after termination of swim-up, by repeated analysis of the same video-recording of the incubated spermatozoa by different observers, and by the repeated video-recording of the freshly prepared sperm samples and analysis of both video-recordings by the same observer. Under these conditions the frequency of disagreement between two measurements varied between 2.0 and 8.2%. In both prospective studies the sensitivity of CASA for the prediction of fertilization was high (74.0%), whereas the specificity was low (40.0%). In contrast to successful fertilization, unsuccessful fertilization of oocytes in vitro could not be predicted reliably with CASA. However, the pregnancy rate per cycle among patients with predicted low fertilization rates was significantly lower (5.3%) than in couples with high predicted fertilization rates (24.3%, P < 0.001). Therefore, CASA of washed spermatozoa may still help to identify couples who would benefit more from intracytoplasmic sperm injection (ICSI) than from IVF. A definite threshold level could not be identified for any of the motion parameters to distinguish the motion characteristics of fertilizing and non-fertilizing spermatozoa. Using various algorithms for hyperactivated motility, the percentage of hyperactivated spermatozoa was significantly higher among the successfully fertilizing patients than among the nonfertilizing group. However, the absolute number of hyperactivated spermatozoa added to the oocytes was higher in non-fertilizing couples. Therefore, the lack of fertilization in some patients may be caused by a generalized defect in sperm function rather than by insufficient hyperactivation.Human Reproduction 09/1998; 13(9):2512-20. · 4.67 Impact Factor
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ABSTRACT: To visualize progesterone (P) binding sites on the sperm surface, examine the relationship between hormone binding and hormone action (acrosome reaction), and determine the size of the hormone-responsive sperm subpopulation. Kinetic analysis of P binding was combined with the assessment of the hormone effect using a fluorescent acrosomal marker. Private hospital, medical research center, and a university-based andrological laboratory. Sperm samples were from healthy volunteers with normal spermiogram values. None. Progesterone binding was analyzed by fluorescence microscopy and flow cytometry using P coupled to fluorescein isothiocyanate-labeled bovine serum albumin. Tetramethylrhodamine isothiocyanate-labeled Pisum sativum agglutinin was used as acrosomal marker in double-labeling experiments. After in vitro capacitation, only few spermatozoa (approximately 10%) were able to bind P to the cell surface, but most of these cells subsequently generated the acrosome reaction in response to hormone binding. The expression of P receptor sites on the human sperm surface is a major factor controlling the P-induced acrosome reaction. Further studies are warranted to explore if defective expression of the receptor can compromise fertility.Fertility and Sterility 11/1992; 58(4):784-92. · 4.17 Impact Factor
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ABSTRACT: The progestational and androgenic in vitro receptor binding affinity and the in vivo activity of norgestimate was compared with that of its metabolites and other progestins. The relative binding affinities (RBAs) of norgestimate and its 17-deacetylated metabolite for rabbit uterine progestin receptors were similar to that of progesterone (P); those of 3-keto norgestimate and levonorgestrel were about five times that of P; those of gestodene and 3-keto desogestrel were about nine times that of P. The RBAs of norgestimate, P, and 3-keto norgestimate for rat prostatic androgen receptors were from 0.003 to 0.025 times that of dihydrotestosterone (DHT); those of 3-keto desogestrel, gestodene, and levonorgestrel were from 0.118 to 0.220 times that of DHT. The order of receptor level selectivity represented by the ratio of androgen:progestin IC50 values (with a greater ratio value reflecting a better selectivity) was norgestimate greater than P = 3-keto norgestimate greater than 17-deacetylated norgestimate greater than 3-keto desogestrel greater than gestodene greater than levonorgestrel. In vivo studies demonstrated similar profiles for norgestimate and its 17-deacetylated metabolite. These latter two steroids were equally potent as progestins in stimulating rabbit endometrium, and compared with the other progestins, both steroids exhibited minimal androgenicity as measured by the stimulation of rat prostate growth. In conclusion, these studies, as well as previous preclinical and clinical studies, provide evidence of the selectivity of norgestimate based on minimal androgenicity, indicating an improvement over other progestins used in oral contraceptives.Contraception 05/1990; 41(4):399-410. · 3.09 Impact Factor