Fertility and Sterility
Volume 89, Issue 6 , Pages 1694-1701 , June 2008

Less is more: increased gonadotropin use for ovarian stimulation adversely influences clinical pregnancy and live birth after in vitro fertilization

  • Lubna Pal, M.B.B.S., M.R.C.O.G., M.S.

      Affiliations

    • Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, New York
    • Corresponding Author InformationReprint requests: Lubna Pal, M.B.B.S., M.R.C.O.G., M.S., Assistant Professor, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 300 George Street, New Haven, Connecticut 06520. (FAX: 203-785-7134).
    • ,
  • Sangita Jindal, Ph.D.

      Affiliations

    • Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, New York
    • ,
  • Barry R. Witt, M.D.

      Affiliations

    • Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York
    • ,
  • Nanette Santoro, M.D.

      Affiliations

    • Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, New York

Received 2 February 2007 ,Revised 29 May 2007 ,Accepted 29 May 2007.

References 

  1. Toner JP, Philput CB, Jones GS, Muasher SJ. Basal follicle stimulating hormone level is a better predictor of in vitro fertilization performance than age. Fertil Steril. 1991;55:784–791
  2. Check JH, Peymer M, Lurie D. Effect of age on pregnancy outcome without assisted reproductive technology in women with elevated early follicular phase serum follicle stimulating hormone levels. Gynecol Obstet Invest. 1998;45:217–220
  3. Chuang CC, Chen CD, Chao KH, Chen SU, Ho HN, Yang YS. Age is a better predictor of pregnancy potential than basal follicle stimulating hormone levels in women undergoing in vitro fertilization. Fertil Steril. 2003;79:63–68
  4. El-Toukhy T, Khalaf Y, Hart R, Taylor A, Braude P. Young age does not protect against the adverse effects of reduced ovarian reserve—an eight year study. Hum Reprod. 2002;17:1519–1524
  5. Scott RT, Opsahl MS, Leonardi MR, Neall GS, Illions EH, Navot D. Life table analysis of pregnancy rates in a general infertility population relative to ovarian reserve and patient age. Hum Reprod. 1995;10:1706–1710
  6. Nasseri A, Mukerjee T, Grifo JA, Noyes N, Krey L, Copperman AB. Elevated day 3 serum follicle stimulating hormone and/or estradiol may predict fetal aneuploidy. Fertil Steril. 1999;71:715–718
  7. van Montfrans JM, van Hooff MH, Martens F, Lambalk CB. Basal FSH, estradiol and inhibin B concentrations in women with a previous Down's syndrome affected pregnancy. Hum Reprod. 2002;17:44–47
  8. Freeman SB, Yang Q, Allran K, Taft LF, Sherman SL. Women with a reduced ovarian complement may have an increased risk for a child with Down's syndrome. Am J Hum Genet. 2000;66:1680–1683
  9. Levi AJ, Raynault MF, Bergh PA, Drews MR, Miller BT, Scott RT. Reproductive outcome in patients with diminished ovarian reserve. Fertil Steril. 2001;76:666–669
  10. Abdalla H, Thum MY. An elevated basal FSH reflects a quantitative rather than a qualitative decline of the ovarian reserve. Hum Reprod. 2004;19:893–898
  11. Gurbuz B, Yalti S, Ozden S, Ficicioglu C. High basal estradiol level and FSH/LH ratio in unexplained recurrent pregnancy loss. Arch Gynecol Obstet. 2004;270:37–39
  12. Hanoch J, Lavy Y, Holzer H, Hurwitz A, Simon A, Revel A, et al. Young low responders protected from untoward effects of reduced ovarian response. Fertil Steril. 1998;69:1001–1004
  13. Faddy MJ, Gosden RG. A model confirming the decline in the follicle numbers to the age of menopause in women. Hum Reprod. 1996;11:1484–1486
  14. Hock DL, Louie H, Shelden RM, Ananth CV, Kemmann E. The need to step up the gonadotropin dosage in the stimulation phase of IVF treatment predicts a poor outcome. J Assist Reprod Genet. 1998;15:427–430
  15. Tan SL, Child TJ, Cheung AP, Fluker MR, Yuzpe A, Casper R, et al. A randomized, double-blind, multicenter study comparing a starting dose of 100 IU or 200 IU of recombinant follicle stimulating hormone (PuregonR) in women undergoing controlled ovarian hyperstimulation for IVF treatment. J Assist Reprod Genet. 2005;22:81–88
  16. van Hooff MH, Alberda AT, Huisman GJ, Zeilmaker GH, Leerentveld RA. Doubling the human menopausal gonadotrophin dose in the course of an in vitro fertilization treatment cycle in low responders: a randomized study. Hum Reprod. 1993;8:369–373
  17. Edwards RG, Lobo RA, Bouchard P. Why delay the obvious need for milder forms of ovarian stimulation?. Hum Reprod. 1997;12:399–401
  18. Department of Health and Social Services, Centers for Disease Control and Prevention. 2004 Assisted Reproductive Technology (ART) Report. Updated February 2, 2007. Available at: http://www.cdc.gov/ART/ART2004/index.htm. Accessed June 13, 2007.
  19. Miller BG, Armstrong DT. Superovulatory doses of pregnant mare serum gonadotropin cause delayed implantation and infertility in immature rats. Biol Reprod. 1981;25:253–260
  20. Ertzeid G, Storeng R. Adverse effects of gonadotrophin treatment on pre- and postimplantation development in mice. J Reprod Fertil. 1992;96:649–655
  21. Ertzeid G, Storeng R, Lyberg T. Treatment with gonadotropins impaired implantation and fetal development in mice. J Assist Reprod Genet. 1993;10:286–291
  22. Roberts R, Iatropoulou A, Ciantar D, Stark J, Becker DL, Franks S, et al. Follicle-stimulating hormone affects metaphase I chromosome alignment and increases aneuploidy in mouse oocytes matured in vitro. Biol Reprod. 2005;72:107–118
  23. Kaleli S, Yanikkaya-Demirel G, Erel CT, Senturk LM, Topcuoglu A, Irez T. High rate of aneuploidy in luteinized granulosa cells obtained from follicular fluid in women who underwent controlled ovarian hyperstimulation. Fertil Steril. 2005;84:802–804
  24. Sibug RM, Helmerhorst FM, Tijssen AMI, de Kloet ER, Koning J de. Gonadotropin stimulation reduces VEGF120 expression in the mouse uterus during the peri-implantation period. Hum Reprod 2002; 17:1643–8.
  25. Warburton D. Biological aging and the etiology of aneuploidy. Cytogenet Genome Res. 2005;111:266–272

 Supported in part by National Institutes of Health K12 (to L.P.).

 The current address for Lubna Pal, M.B.B.S., M.R.C.O.G., M.S., is Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut.

PII: S0015-0282(07)01226-5

doi: 10.1016/j.fertnstert.2007.05.055

Fertility and Sterility
Volume 89, Issue 6 , Pages 1694-1701 , June 2008

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