Journal of Assisted Reproduction and Genetics

, Volume 30, Issue 11, pp 1439–1444 | Cite as

Live birth following serial vitrification of embryos and PGD for fragile X syndrome in a patient with the premutation and decreased ovarian reserve

  • Dan Nayot
  • Jin Tae Chung
  • Weon-Young Son
  • Assangla Ao
  • Mark Hughes
  • Michael H. DahanEmail author
Assisted Reproduction Technologies



To present a live birth resulting from serial vitrification of embryos and pre-implantation genetic diagnosis (PGD).


A 31-year-old with primary infertility, fragile-X premutation, and decreased ovarian reserve (DOR) (baseline FSH level 33 IU/L), presented after failing to stimulate to follicle diameters >10 mm with three cycles of invitro fertilization (IVF). After counseling, the couple opted for serial in-vitro maturation (IVM), embryo vitrification, and genetic testing using array comparative genomic hybridization (aCGH) and PGD. Embryos were vitrified 2 days after intra-cytoplasmic sperm injection (ICSI). Thawed embryos were biopsied on day-three and transferred on day-five.


The couple underwent 20 cycles of assisted reproductive technology. A total of 23 in-vivo mature and five immature oocytes were retrieved, of which one matured in-vitro. Of 24 embryos, 17/24 (71 %) developed to day two and 11/24 (46 %) survived to blastocyst stage with a biopsy result available. Four blastocysts had normal PGD and aCGH results. Both single embryo transfers resulted in a successful implantation, one a blighted ovum and the other in a live birth.


Young patients with DOR have potential for live birth as long as oocytes can be obtained and embryos created. Serial vitrification may be the mechanism of choice in these patients when PGD is needed.


In-vitro maturation (IVM) Embryo vitrification Diminished Ovarian Reserve (DOR) Fragile X Syndrome (FXS) Preimplantation Genetic Diagnosis (PGD) Array Comparative Genomic Hybridization (aCGH) 


  1. 1.
    Aanesen A, Nygren KG, Nylund L. Modified natural cycle IVF and mild IVF: a 10 year Swedish experience. Reprod Biomed Online. 2010;20(1):156–62.PubMedCrossRefGoogle Scholar
  2. 2.
    Ao A, Jin S, Rao D, Son WY, Chian RC, Tan SL. First successful pregnancy outcome after preimplantation genetic diagnosis for aneuploidy screening in embryos generated from natural-cycle in vitro fertilization combined with an in vitro maturation procedure. Fertil Steril. 2006;85(5):1510-e9–11.CrossRefGoogle Scholar
  3. 3.
    Ao A, Zhang XY, Tan SL. First successful pregnancy following PGD for chromosome translocation on embryos generated from in-vitro matured oocytes: a case report. Reprod Biomed Online. 2011;22(4):371–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Buckett WM, Chian RC, Dean NL, Sylvestre C, Holzer HE, et al. Pregnancy loss in pregnancies conceived after in vitro oocyte maturation, conventional in vitro fertilization, and intracytoplasmic sperm injection. Fertil Steril. 2008;90(3):546–50.PubMedCrossRefGoogle Scholar
  5. 5.
    Fridén B, Hreinsson J, Hovatta O. Birth of a healthy infant after in vitro oocyte maturation and ICSI in a woman with diminished ovarian response: case report. Hum Reprod. 2005;20(9):2556–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Gallagher A, Hallahan B. Fragile X-associated disorders: a clinical overview. J Neurol. 2012;259(3):401–13.PubMedCrossRefGoogle Scholar
  7. 7.
    Gleicher N, Barad DH. The FMR1 gene as regulator of ovarian recruitment and ovarian reserve. Obstet Gynecol Surv. 2010;65(8):523–30.PubMedCrossRefGoogle Scholar
  8. 8.
    Gleicher N, Kim A, Weghofer A, Barad DH. Differences in ovarian aging patterns between races are associated with ovarian genotypes and sub-genotypes of the FMR1 gene. Reprod Biol Endocrinol. 2012;10:77.PubMedCrossRefGoogle Scholar
  9. 9.
    Gleicher N, Weghofer A, Barad DH. Defining ovarian reserve to better understand ovarian aging. Reprod Biol Endocrinol. 2011;9:23.PubMedCrossRefGoogle Scholar
  10. 10.
    Li J, Xu Y, Zhou G, Guo J, Xin N. Natural cycle IVF/IVM may be more desirable for poor responder patients after failure of stimulated cycles. J Assist Reprod Genet. 2011;28(9):791–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Liu J, Lu G, Qian Y, Mao Y, Ding W. Pregnancies and births achieved from in vitro matured oocytes retrieved from poor responders undergoing stimulation in in vitro fertilization cycles. Fertil Steril. 2003;80(2):447–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Lukaszuk K, Kunicki M, Liss J, Lukaszuk M, Jakiel G. Use of ovarian reserve parameters for predicting live births in women undergoing in vitro fertilization. Eur J Obstet Gynecol Reprod Biol. 2013;168(2):173–7.Google Scholar
  13. 13.
    Nolin SL, Brown WT, Glicksman A, Houck Jr GE, Gargano AD, et al. Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles. Am J Hum Genet. 2003;72(2):454–64.PubMedCrossRefGoogle Scholar
  14. 14.
    Requena A, Bronet F, Guillén A, Agudo D, Bou C, et al. The impact of in-vitro maturation of oocytes on aneuploidy rate. Reprod Biomed Online. 2009;18(6):777–83.PubMedCrossRefGoogle Scholar
  15. 15.
    Schoolcraft WB, Fragouli E, Stevens J, Munne S, Katz-Jaffe MG, et al. Clinical application of comprehensive chromosomal screening at the blastocyst stage. Fertil Steril. 2010;94(5):1700–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Son WY, Chung JT, Chian RC, Herrero B, Demirtas E, Elizur S, et al. A 38 h interval between hCG priming and oocyte retrieval increases in vivo and in vitro oocyte maturation rate in programmed IVM cycles. Hum Reprod. 2008;23(9):2010–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Son WY, Chung JT, Dahan M, Reinblatt S, Tan SL, et al. Comparison of fertilization and embryonic development in sibling in-vivo matured oocytes retrieved from different sizes follicles from in vitro maturation cycles. J Assist Reprod Genet. 2011;28(6):539–44.PubMedCrossRefGoogle Scholar
  18. 18.
    Son WY, Chung JT, Das M, Buckett W, Demirtas E, Holzer H. Fertilization, embryo development, and clinical outcome of immature oocytes obtained from natural cycle in vitro fertilization. J Assist Reprod Genet. 2013;30(1):43–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Son WY, Chung JT, Gidoni Y, Holzer H, Levin D, et al. Comparison of survival rate of cleavage stage embryos produced from in vitro maturation cycles after slow freezing and after vitrification. Fertil Steril. 2009;92(3):956–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Son WY, Yoon SH, Lim JH. Effect of gonadotrophin priming on in-vitro maturation of oocytes collected from women at risk of OHSS. Reprod Biomed Online. 2006;13(3):340–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Van Esch H. The Fragile X premutation: new insights and clinical consequences. Eur J Med Genet. 2006;49(1):1–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Yakut T, Karkucak M, Sher G, Keskintepe L. Comparison of aneuploidy frequencies between in vitro matured and unstimulated cycles oocytes by metaphase comparative genomic hybridization (mCGH). Mol Biol Rep. 2012;39(5):6187–91.PubMedCrossRefGoogle Scholar
  23. 23.
    Zhang XY, Ata B, Son WY, Buckett WM, Tan SL, et al. Chromosome abnormality rates in human embryos obtained from in-vitro maturation and IVF treatment cycles. Reprod Biomed Online. 2010;21(4):552–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Zhang L, Yilmaz A, Chian RC, Son WY, Zhang XY, Kong D, et al. Reliable preimplantation genetic diagnosis in thawed human embryos vitrified at cleavage stages without biopsy. J Assist Reprod Genet. 2011;28(7):597–602.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Dan Nayot
    • 1
  • Jin Tae Chung
    • 1
  • Weon-Young Son
    • 1
  • Assangla Ao
    • 2
  • Mark Hughes
    • 3
  • Michael H. Dahan
    • 1
    Email author
  1. 1.Royal Victoria Hospital, Department of Obstetrics and Gynecology, Division of Reproductive, Endocrinology and InfertilityMcGill University Health CenterMontrealCanada
  2. 2.Royal Victoria Hospital, Departments of Obstetrics and Gynecology and Human GeneticsMcGill University Health CenterMontrealCanada
  3. 3.Applied Genomic Technology of MichiganDetroitUSA

Personalised recommendations