Cytogenetic profiles: genetics can triage management of recurrent miscarriage

OB/GYN News, July 15, 2004 by Betsy Bates

RANCHO MIRAGE, CALIF. -- A series of studies has helped to shed light on when cytogenetic profiles and preimplantation genetic diagnosis should be ordered for women with recurrent miscarriages.

Cytogenetic abnormalities account for recurrent miscarriages in only about half of patients, but an initial genetic study of the products of conception can help direct management of care for these women, Dr. Mary Stephenson, professor of obstetrics and gynecology at the University of Chicago, said at the annual meeting of the Pacific Coast Reproductive Society.

Cytogenetics profiles are recommended in the following cases:

  • After a second consecutive miscarriage and all subsequent miscarriages at less than 10 weeks' gestation.
  • After all unexplained pregnancy losses at more than 10 weeks' gestation.
  • After all miscarriages following infertility treatments, such as in vitro fertilization.

In a study of 420 specimens from 285 patients who had had recurrent miscarriages, Dr. Stephenson and her associates at her former institution, the University of British Columbia in Vancouver, found that successful cytogenetic analysis was far more likely after D & C than when the products of conception were submitted following expectant management of a miscarriage.

A definitive result was obtained in 91% of D & C cases and just 66% of expectant management cases.

Cytogenetic results found euploidy XX in 26%, euploidy XY in 25%, and trisomy in more than 30% of cases. Polyploidy, monosomy, and unbalanced translocations each accounted for fewer than 10% of cases.

Providing cytogenetic information to a couple not only helps them understand why recurrent miscarriages may have occurred but also provides valuable information to the physician in terms of future management strategies.

Dr. Stephenson’s research has determined that recurrent euploid miscarriages are much more common in women younger than 36 years than in older patients.

"If, in a woman less than 36, there is evidence of recurrent euploidy, that’s not an indication for preimplantation genetic diagnosis. Rather, it’s an indication for evaluation of nonchromosomal factors associated with recurrent miscarriage," she said.

In women 36 or older, the study found no evidence of an elevated rate of trisomies among patients who had had recurrent miscarriages, compared with those who had had just one miscarriage, although the risk of trisomy associated with certain chromosomes increases with maternal age.

"It is important to note that some trisomies increase more than others with advancing maternal age," she said.

"We could not find any evidence of recurrent aneuploidy or recurrent trisomy in women over 35 years of age," she said.

Therefore, she said that advanced maternal age may be an indication for preimplantation genetic diagnosis in women who are undergoing in vitro fertilization, but recurrent miscarriage is not by itself an indication for the expensive procedure.

Patients with recurrent miscarriages in Dr. Stephenson’s studies have a mean age of 35 and have had a mean of 5 miscarriages, with a range of 3-13.

Abnormal cytogenetic results have been found in 49% of samples collected for analysis following the miscarriages.

Chromosomal Abnormalities and Miscarriage

Gestational AgeRisk of Miscarriage% of
Miscarried Fetuses
Cytogenetic Abnormalities
<6 weeks 50% 70%
6-10 weeks 15% 50%
>10 weeks 2-3% 5%

Source: Dr. Mary Stephenson

BY BETSY BATES Los Angeles Bureau

COPYRIGHT 2004 International Medical News Group 
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