Outcome of twin babies free of Von Hippel-Lindau disease after a double-factor preimplantation genetic diagnosis: monogenetic mutation analysis and comprehensive aneuploidy screening

Fertil Steril. 2009 Mar;91(3):933.e1-7. doi: 10.1016/j.fertnstert.2008.11.013. Epub 2009 Jan 10.


Objective: To increase the embryo implantation rate, a double-factor preimplantation genetic diagnosis (DF-PGD) was performed, selecting for transfer potentially euploid evolved embryos free of the mutation responsible for Von Hippel-Lindau syndrome (VHL).

Design: Case report.

Settings: Medical university center and a private IVF center.

Patient(s): A patient carrier of the R161Q mutation on the VHL gene.

Intervention(s): After first polar body (1PB) biopsy, it was analyzed using comparative genomic hybridization (1PB-CGH). On day +3, mutation detection using minisequencing and short tandem repeat analysis was performed in multiple displacement amplification products of a single blastomere per embryo.

Main outcome measure(s): Transfering embryos free of the disease and originating from euploid oocytes.

Result(s): Nine of the twelve oocytes obtained were successfully analyzed using 1PB-CGH. One of them was aneuploid (1PB #1: 29XX,+2,+10,+12,+17,+19), and the rest were euploid. All of the oocytes were fertilized and became evolved embryos. Six of the embryos were VHL unaffected and had good quality. Five (83%) of them were potentially euploid. According to cytogenetic results, two of the evolved and healthy embryos were transfered, achieving the birth of healthy twin babies.

Conclusion(s): The DF-PGD can be a useful tool to increase implantation of transfered embryos in PGD for monogenic diseases.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy*
  • Comparative Genomic Hybridization
  • DNA Mutational Analysis*
  • Embryo Implantation
  • Embryo Transfer
  • Female
  • Fertilization in Vitro
  • Genetic Testing*
  • Humans
  • Live Birth
  • Microsatellite Repeats
  • Mutation
  • Oocytes*
  • Polymerase Chain Reaction
  • Pregnancy
  • Preimplantation Diagnosis / methods*
  • Twins / genetics*
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics*
  • von Hippel-Lindau Disease / diagnosis*
  • von Hippel-Lindau Disease / genetics


  • Von Hippel-Lindau Tumor Suppressor Protein
  • VHL protein, human