Community-based ongoing study: small fibroids linked to early pregnancy loss; Interim results suggest fibroids < 3 cm in diameter may raise miscarriage risk fourfold

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

HOUSTON -- Fibroids so small they are ignored by the widely used Muram ultrasound criteria appear to have a profound association with spontaneous abortion, perhaps explaining many early pregnancy losses, especially among African American women.

Interim results of a community-based study reveal almost a fourfold risk of spontaneous abortion among women who were found to have fibroids measuring < 3 cm in diameter during early pregnancy. In contrast, patients with fibroids > 3 cm in early pregnancy had no increased risk of a miscarriage.

"Perhaps our most intriguing finding is that small, entirely intramural fibroids with an average diameter of a centimeter or less may well turn out to be associated with some level of risk," study investigator Dr. Katherine E. Hartmann said at the annual meeting of the Society for Gynecologic Investigation.

If further study confirms that "jelly-bean-sized" fibroids can disrupt a pregnancy, "we [may] need to move beyond purely architectural explanations of how fibroids cause harm," said Dr. Hartmann of the University of North Carolina at Chapel Hill.

Previously, retrospective and case-control studies have supported a link between uterine fibroids and spontaneous abortion, but these generally did not include fibroids < 3 cm, the cutoff established by the Muram ultrasound criteria in the 1980s. Earlier studies also focused on patients in tertiary care settings and generally did not study very early pregnancies, when many spontaneous abortions occur. Some prior research was flawed by failing to establish uniform ultrasound detection standards.

Dr. Hartmann's findings are from the Right From the Start program, an ongoing prospective study of early pregnancy in Raleigh, N.C.; Galveston, Texas; and Memphis.

Women planning a pregnancy or in the early stages of gestation are recruited through private physicians' offices, advertisements, and coupons in pregnancy tests. The average gestational age at enrollment of the first 1,646 participants was 53 days, with those "preenrolling" before conception enrolling at an average of 31 days after their last menstrual period.

During the study, a vaginal ultrasound is performed in week 5 or 6, followed by telephone interviews at weeks 10-12 and weeks 22-24 to determine the viability of the pregnancy. Medical records confirm information provided by patients.

Fibroids that are at least 0.5 cm are measured in all perpendicular diameters three separate times by an experienced ultrasound operator associated with the study. Two study sonographers masked as to loss status review the mapped images of each fibroid and confirm their type and locations.

In interim results presented at the meeting, Dr. Hartmann reported that 167 women with fibroids during pregnancy were older than those who did not have fibroids. They had higher body mass indexes, were less likely to be nulliparous or to be smokers, and were more likely to have had a history of elective abortion.

African Americans had a strikingly higher rate of fibroids than did women of other races. Almost 30% of the study participants were African American, and 16% had detectable fibroids during an early pregnancy vaginal ultrasound. In comparison, 8% of white women had fibroids.

More than three-fourths of women with fibroids had a single myoma and the "vast majority" had no more than two, said Dr. Hartmann. The median diameter was 2.4 cm, with a range of 0.5-12.9 cm.

Intramural fibroids constituted 41% of the myomas; 37% were subserosal; 14% were submucosal; and 7% were pedunculated. Among the nonpedunculated fibroids, 61% were in the corpus, 31% in the fundus, and 8% in the lower uterine segment or cervix.

Overall, about 15% of the cohort suffered a spontaneous abortion, with more than a doubling of risk if a fibroid was seen on an early transvaginal ultrasound. When the odds were adjusted for potential confounders, women with at least one fibroid still had a 55% increase in the likelihood of a pregnancy loss.

The odds ratio for a spontaneous abortion was highest, 3.93, for women with small fibroids with a maximum transverse diameter < 3 cm. The odds ratio for loss associated with a submucosal fibroid of any size versus no fibroids was 2.34. Women with an intramural fibroid had an odds ratio of 1.67 for a pregnancy loss when compared with those with no fibroids.

"These data likely underestimate both prevalence and risk, since half of the women who would have been eligible for this analysis had a loss before the scheduled entry ultrasound," said Dr. Hartmann. "If fibroids are associated with loss, fibroids would be common in that group and our [quoted] risk is artificially low."

When the study is completed, 5,300 women will have been enrolled. The added participants will provide insight into possible interactions between the size and type of fibroids in early pregnancy and subsequent losses.

BY BETSY BATES

Los Angeles Bureau