Genetic anomalies account for majority of miscarriages



BOSTON – A substantial majority of miscarriages appear to be caused by genetic abnormalities rather than the usual suspects of thrombophilias, antiphospholipid syndromes, immunologic problems, or other maternal factors, study results suggest.

A decade of microscopic studies of placental tissues obtained after pregnancy losses showed that of 615 samples, 495 cases (80.5%) were caused by genetic abnormalities, determined by the presence of markers for genetic abnormalities, said Dr. Harvey J. Kliman, director of the reproductive and placental research unit at Yale University in New Haven, Conn.

Data from a second study of the karyotypes of embryos from spontaneous abortions showed that embryonic chromosomal abnormalities accounted for a significant portion of the miscarriages, and that two-thirds of women with prior loss of an aneuploid embryo went on to have a live birth, said Dr. Ruth B. Lathi, director of the recurrent pregnancy loss program at the Stanford (Calif.) Fertility and Reproductive Medicine Center.

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Dr. Harvey J. Kliman

The studies were reported at the conjoint meeting of the International Federation of Fertility Societies and the American Society for Reproductive Medicine.

Although standard workups fail to identify the cause of recurrent pregnancy losses in more than half of all cases, the findings should be reassuring to patients, Dr. Lathi said in an interview.

"The vast majority of miscarriages are chromosomally or somehow morphologically or genetically abnormal – even if we can’t prove it, we all believe it. Luckily, these genetic abnormalities for the most part are random, and women can have a combination of abnormal pregnancies and normal pregnancies," Dr. Lathi said.

"Each new pregnancy is a new set of genetics: It’s a new egg, it’s a new sperm, and what was wrong in the last pregnancy may not carry over to the next pregnancy," she added.

Dr. Kliman said that if women know that recurrent miscarriages are unlikely to be related to something they have done, such as having a cocktail or smoking marijuana when they weren’t even aware that they were pregnant, they will be better able to cope emotionally and resume trying.

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Dr. Ruth A. Lathi

"I have a lot of families that have six pregnancies: three perfectly normal children and three losses, and the losses always happen at the same time, because it’s a programming error; that’s another hint that it’s genetic," he said.

Dr. Kliman and Kristin M. Milano, director of laboratory services in the reproductive and placental research unit at Yale, reported data on 615 pregnancy losses that occurred from 7 to 20 weeks’ gestational age. The samples were fixed, sectioned, stained, and then examined microscopically for abnormalities.

The primary diagnosis in 495 of the 615 samples examined was dysmorphic trophoblastic invaginations and inclusions. In 55 cases (8.9%) there were no chorionic villi, 53 cases (8.6%) had no pathologic abnormalities, 10 cases (1.6%) were apparently due to thrombosis, 1 (0.2%) was due to abruption, and 1 to chronic villitis.

"This study validates the importance of pathologic examination of all pregnancy losses," Dr. Kliman said in a poster.

Dr. Lathi and her colleague, Dr. Jamie Massie, examined the live birth rate by embryonic karyotype among 95 women with a self-reported history of recurrent pregnancy loss.

They found that 40 of the women (42%) had a miscarriage of a euploid embryo, and 55 (58%) lost a pregnancy with an aneuploid embryo. Of the aneuploid abnormalities, 95% were numeric (for example, monosomies and trisomies), and 5% were structural.

In all, 21 of the 40 women (52.5%) with loss of a euploid embryo had a subsequent live birth, compared with 37 of 55 (67.3%) of those with loss of an aneuploid pregnancy.

The findings, which need to be validated in larger studies, suggest that aneuploidy may be a good prognostic indicator for the success of future live births, the investigators concluded.

Dr. Lathi was coauthor of a separate study of 87 women with two or more recurrent pregnancy losses from either explained or unexplained causes, which found that 59.7% of the patients had a healthy term delivery, with obstetrical outcomes similar to those in women with infertility problems.

Dr. Kliman’s study was supported by the reproductive and placental research unit at Yale. He reported having no relevant financial disclosures. The funding sources for Dr. Lathi’s studies were not disclosed. She reported having no relevant conflicts of interest.

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