The influence of supraphysiologic estradiol levels on human nidation
Exogenous estradiol (E2) has a well-recognized interceptive action when administered shortly after ovulation. The influence of extremely elevated levels of endogenous E2 on human oocyte fertilization and implantation are unclear. The purpose of this study was to evaluate a potential antinidatory role of extremely high endogenous E2 concentrations on implantation and pregnancy duringin vitro fertilization-embryo transfer (IVF-ET).
Twenty-five patients receiving human menopausal gonadotropins (hMG) following midluteal GnRHa administration for IVF-ET, in which the maximal E2 concentration was >5000 pg/ml (range 5358–16,344 pg/ml) were studied. Cycle parameters including oocyte and embryo characteristics, fertilization, cleavage, and implantation rates as well as pregnancy outcomes were compared to those of 25 patients treated contemporaneously whose treatment cycles had peak E2 values <3500 pg/ml. Patients groups were matched for age, infertility diagnoses, duration of infertility and stimulation protocol.
Cycles characterized by very high endogenous E2 levels resulted in significantly more oocytes per retrieval (21.4± 1.7 versus 8.4± 0.6;P < 0.0001), fewer postmature oocytes (1.6%± 1.0% versus 14%± 5.0%;P < 0.03), and a decreased fertilization rate (63%±4.0% versus 73%±3.0%;P < 0.04) compared to control cycles. There were no differences in the overall mean morphologic grade or cleavage rates between groups. However, high E2 cycles were associated with a significantly increased implantation rate (14%±4.0% versus 8.0%±4.0%;P < 0.01) and pregnancy rate per embryo transfer (62%±16% versus 36%±16%;P < 0.01) compared to controls. The incidence of spontaneous abortion did not differ between groups.
Extremely high endogenous E2 levels do not appear to adversely affect implantation or overall cycle pregnancy rates in IVF-ET cycles. However, impaired fertilization rates in such cycles support a potential adverse effect on oocyte quality.
Key wordsin vitro fertilization estradiol fertilization rates pregnancy rates
Unable to display preview. Download preview PDF.
- 1.Wood C, McMaster R, Rennie G, Trounson A, Leeton J: Factors influencing pregnancy rates following in vitro fertilization and embryo transfer. Fertil Steril 1985;43:245–250Google Scholar
- 2.Gidley-Baird AA, O'Neill C, Sinosich MJ, Porter RN, Pike IL, Saunders DM: Failure of implantation in human in vitro fertilization and embryo transfer patients: the effects of altered progesterone/estrogen ratios in humans and mice. Fertil Steril 1986;45:69–74Google Scholar
- 3.Forman R, Fries N, Testart J, Belaisch-Allart J, Hazout A, Frydman R: Evidence for an adverse effect of elevated serum estradiol concentrations on embryo implantation. Fertil Steril 1988;49:118–122Google Scholar
- 4.Morris JM, Van Wagenen G: Interception: the use of post-ovulatory estrogens to prevent implantation. Am J Obstet Gynecol 1973;115:101–106Google Scholar
- 5.Diamond MP, Bucholtz T, Boyers SP, Lavy G, Shapiro BS, DeCherney AH: Super high estradiol response to gonadotropin stimulation in patients undergoing in vitro fertilization. J In Vitro Fert Embryo Transfer 1989;6:81–84Google Scholar
- 6.Chenette PE, Sauer MV, Paulson RI: Very high serum estradiol levels are not detrimental to clinical outcome of in vitro fertilization. Fertil Steril 1990;54:858–863Google Scholar
- 7.San Roman GA, Surrey ES, Judd HL, Kerin JF: A prospective randomized comparison of luteal phase versus concurrent follicular phase initiation of gonadotropin-releasing hormone agonist for in vitro fertilization. Fertil Steril 1992;58:744–749Google Scholar
- 8.Marrs RP, Saito H, Yee B, Sato F, Brown J: Effect of variation of in vitro culture techniques upon oocyte fertilization and embryo development in human in vitro fertilization procedures. Fertil Steril 1984;41:519–523Google Scholar
- 9.Veeck LL, Wortham JWE Jr, Witmyer J,et al: Maturation and fertilization of morphologically immature oocytes in a program of in vitro fertilization. Fertil Steril 1983;39:594–602Google Scholar
- 10.Jones HW Jr, Acosta A, Andrews MC,et al: The importance of the follicular phase to success and failure in in vitro fertilization. Fertil Steril 1983;40:317–321Google Scholar
- 11.Pellicer A, Ruiz A, Castellvi RM,et al: Is the retrieval of high number of oocytes desirable in patients treated with gonadotropin releasing hormone analogues (GnRH-a) and gonadotropins? Hum Reprod 1989;4:536–540Google Scholar
- 12.Tarin JJ, Pellicer A: Consequences of high ovarian response to gonadotropins: a cytogenetic analysis of unfertilized human oocytes. Fertil Steril 1990;54:665–670Google Scholar
- 13.Testart J, Belaisch-Allart JC, Forman R, Gazengel A, Strubb N, Hazout A, Frydman R: Influence of different stimulation treatments on oocyte characteristics and in vitro fertilizing ability. Hum Reprod 1989;4:192–197Google Scholar
- 14.Testart J, Forman R, Belaisch-Allart J,et al: Embryo quality and uterine receptivity in in-vitro fertilization cycles with or without agonists of gonadotrophin-releasing hormone. Hum Reprod 1989;4:198–201Google Scholar
- 15.Rosenwaks Z: Donor eggs: their application in modern reproductive technologies. Fertil Steril 1987;47:895–909Google Scholar
- 16.Navot D, Bergh PA, Williams M,et al: An insight into early reproductive processes through the in vivo model of ovum donation. J Clin Endocrinol Metab 1991;72:408–414Google Scholar
- 17.Navot D, Bergh PA, Laufer N: Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment. Fertil Steril 1992;58:249–261Google Scholar
- 18.Asch RH, Ivery G, Goldsman M, Frederick JL, Stone SC, Balmaceda JP: The use of intravenous albumin in patients at high risk for severe ovarian hyperstimulation syndrome. Hum Reprod 1993;8:1015–1020Google Scholar
- 19.Wu T-CJ, Gelety TJ, Ming JH, Fournet N, Buyalos R: Successful management of predicted severe ovarian hyperstimulation syndrome with gonadotropin-releasing hormone agonist. J Assist Reprod Genet 1992;9:281–283Google Scholar
- 20.Amso NN, Ahuja KK, Morris N, Shaw RW: The management of predicted ovarian hyperstimulation involving gonadotropin-releasing hormone analog with elective cryopreservation of all pre-embryos. Fertil Steril 1990;53:1087–1090Google Scholar