Abstract
Sixty-four infertile women underwent diagnostic laparoscopy in the periovulatory period at time-bracketed intervals following their endogenous luteinizing hormone (LH) surge. Forty-eight of these women were studied during natural cycles and 16 had mild oligoovulation and were administered clomiphene citrate (CC) to regulate their cycles. No patient received human chorionic gonadotropin. No patient was undergoing either in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). Follicle puncture was performed and the oocytes were observed immediately for stage of maturation. Oocytes obtained from follicles exposed to CC were found to require an increased interval of time to reach metaphase I compared to oocytes obtained from natural cycles (27.75±2.2 vs 22.5 hr; mean±SE). Furthermore, the interval of time required for metaphase I oocytes to achieve metaphase II was statistically significantly shortened for CC cycles (2.4 hr for CC vs 10 hr for natural cycles. Nevertheless, there was no difference between natural and CC cycles in the time interval between LH surge onset and ovulation. These in vivo findings suggest a direct effect of CC on human oocyte maturation and may help explain the wellestablished discrepancy between the relatively high ovulation rate and the relatively low conception rate in clomiphene-induced cycles.
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References
Speroff L, Glass RH, Kase NG: Induction of ovulation.In Clinical Gynecological Endocrinology and Infertility, Vol 3, L. Speroff, RH Glass, NG Kase (eds). Baltimore, Williams & Wilkins, 1983, p 531
Laufer N, Reich R, Braw R, Shenker JG, Tsafriri A: Effect of clomiphene citrate on preovulatory rat follicles in culture. Biol Reprod 1982;27:463–471
Laufer N, Pratt BM, DeCherney AH, Naftolin FM, Merino M, Markert CL: The in vivo in vitro effects of clomiphene citrate on ovulation, fertilization, and development of cultured mouse oocytes. Am J Obstet Gynecol 1983;147:633–639
Seibel MM, Levesque LA, Taymor ML: A rapid radioimmunoassay method for serum luteinizing hormone using polyethylene glycol (PEG) and a double antibody method of separation. Fertil Steril 1981;35:36–40
Seibel MM, Shine W, Smith DM, Taymor ML: Biological rhythm of the luteinizing hormone surge 1982;37:709–711
Seibel MM, Smith DM, Levesque LA, Borten M, Taymor ML: The temporal relationship between the luteinizing hormone surge and human oocyte maturation. Am J Obstet Gynecol 1982;147:568–572
Uebele-Kallhardt BM: Human Oocytes and Their Chromosomes Berlin, Springer-Verlag, 1978, pp 88–91
Grayson K: An improved method for staining mammalian oocytes. Stain Technol 1978;53:115
Edwards RG: Maturation in vitro of human ovarian oocytes. Lancet 1985;2:926–927
Jagiello G, Karnicki J, Ryan RJ: Superovulation with pituitary gonadotropins: Method for obtaining meiotic metaphase figures in himan ova. Lancet 1968;1:178–180
Steptoe PC, Edwards RG: Laproscopic recovery of preovulatory human oocytes after priming of ovaries with gonadotropins. Lancet 1970;1:638
Smith DM, Tenny DY: Effects of steroids on mouse oocyte maturation in vitro. J Reprod Fert 1980;60:331–338
Seibel MM, Smith DM, Levesque LA, Taymor ML: Periovulatory follicular fluid hormone levels in clomiphene stimulated cycles (submitted for publication)
Westergaard L, Byskov AG, Anderson CY, Grinsted J, McNatty KP: Is resumption of meiosis in the human preovulatory oocyte triggered by a meiosis-inducing substance (MIS) in the follicular fluid. Fertil Steril 1984;41:377–381
Bomsel-Helmreich O, Huyen LVN, Durand-Gasselin I, Salat-Baroux J, Antoine J-M: Timing of nuclear maturation and cumulus dissociation in human oocytes stimulated with clomiphene citrate, human menopausal gonadotropin, and human chorionic gonadotropin. Fertil Steril 1987;48:586–595
Bomsel-Helmreich O, Huyen LVN, Durand-Gasselin I, Salat-Baroux J, Antoine J-M: Mature and immature oocytes in large and medium follicles after clomiphene citrate and human menopausal gonadotropin stimulation without human chorionic gonadotropin. Fertil Steril 1987;48:595–604
Wramsby H, Fredga K, Liedholm P: Chromosome analysis of human oocytes recovered from preovulatory follicles in stimulated cycles. N Engl J Med 1987;316:121–124
Schmidt GE, Sites C, Mansour R, FRiedman CI, Kim M: Embryo toxicity of clomiphene citrate on mouse embryos fertilized in vitro and in vivo. Am J Obstet Gynecol 1985; 153:679–684
Boue JG, Boue A: Increased frequency of chromosomal anomalies in abortions after induced ovulation. Lancet 1973;1:679–680
Mor-Joseph S, Anteby SO, Granat M, Brzezinsky A, Evron S: Recurrent molor pregnancies associated with clomiphene citrate and human gonadotropins. Am J Obstet Gynecol 1985;151:1095–1086
Harlap S: Ovulation induction and congenital malformations. Lancet 1976;2:961
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Seibel, M.M., Smith, D.M. The effect of clomiphene citrate on human preovulatory oocyte maturation in vivo. J Assist Reprod Genet 6, 3–6 (1989). https://doi.org/10.1007/BF01134573
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DOI: https://doi.org/10.1007/BF01134573