title: A comparison of molecular and cytogenetic techniques for the diagnosis of pregnancy loss.
abstract: OBJECTIVE
  To evaluate the sensitivity, specificity, advantages, and limitations of multiplex ligation-dependent probe amplification compared with conventional karyotype analysis in the investigation of contributing factors to recurrent pregnancy loss.
  
  
  METHODS
  A cohort of 284 patients underwent side-by-side analysis of products of conception by both conventional karyotyping and multiplex ligation-dependent probe amplification with direct comparison of results.
  
  
  RESULTS
  Multiplex ligation-dependent probe amplification was shown to enable a diagnosis for an additional 47 (16.5%) patients compared with conventional karyotype analysis. However, this advantage was offset by some disadvantages of the method, including a high false-positive rate (8/104; 7.7%), as demonstrated by single-arm probe abnormalities of uncertain clinical significance, as well as the inability to characterize structural rearrangements, such as Robertsonian translocations, which comprised 2.46% of samples (99% confidence interval = 0.09-4.83), and ploidy changes. The calculated performance characteristics of multiplex ligation-dependent probe amplification in this cohort yielded a sensitivity of 86.9% and specificity of 92.4%.
  
  
  CONCLUSIONS
  The advantages of now widely accepted molecular methodologies, such as lower failure rates, faster turnaround times, and lower cost, must be complemented by adequate counseling, family follow-up, and specific diagnostic reporting practices. It is particularly important to specifically address the important limitations of the methodology, including the inability to characterize balanced structural rearrangements and ploidy changes, especially if multiplex ligation-dependent probe amplification is to be performed alone.
authors.affiliation: Department of Haematology and Genetics, South Eastern Area Laboratory Services, The Prince of Wales and Sydney Children's hospitals, Randwick, Sydney, Australia. melody.caramins@sesiahs.health.nsw.gov.au
authors.forename: Melody C
authors.initials: MC
authors.lastname: Caramins
authors.forename: Toni
authors.initials: T
authors.lastname: Saville
authors.forename: Rebecca
authors.initials: R
authors.lastname: Shakeshaft
authors.forename: Glenda L
authors.initials: GL
authors.lastname: Mullan
authors.forename: Briar
authors.initials: B
authors.lastname: Miller
authors.forename: Moh-Ying
authors.initials: MY
authors.lastname: Yip
authors.forename: Michael F
authors.initials: MF
authors.lastname: Buckley
mesh_terms: D000026:Abortion, Habitual / Q000175:diagnosis*; D000782:Aneuploidy; D020732:Cytogenetic Analysis; D005260:Female; D005821:Genetic Techniques / Q000592:standards*; D006801:Humans; D007621:Karyotyping; D009030:Mosaicism; D021141:Nucleic Acid Amplification Techniques; D011123:Polyploidy; D011247:Pregnancy; D012680:Sensitivity and Specificity