Right from the Start (RFTS) is an ongoing cohort study of pregnancy outcomes that has included women from four metropolitan areas in three states (North Carolina, Tennessee and Texas).
The four academic institutions provided institutional review board approval. Recruitment strategies included newsletters, advertisements, direct home mailings and print material in community practices. The recruitment strategies mentioned only pregnancy outcomes and did not specifically mention leiomyomata or fertility (Promislow et al., 2004
Eligible women were older than 17 years, spoke English or Spanish, did not plan to move from the study area within the next 18 months, enrolled before 13 weeks gestation based on last menstrual period, did not use assisted reproductive technology or ovulation inducing medication and intended to carry the pregnancy to term. Women could enroll in the study for more than one pregnancy, but only the first enrollment was included in this analysis.
Upon enrollment, women completed a computer-assisted telephone interview that included questions about demographic characteristics, health behaviors and medical and reproductive history, women self-reported race and ethnicity. The interview also asked women whether they became pregnant within the first, second or third menstrual cycle; if not within three cycles, they were asked to estimate the number of cycles, months or years that it took them to conceive. We treated months and cycles as equivalent in all analyses.
The time-to-pregnancy data among women who enrolled very early in the study were left truncated to take into account that women were only eligible to enroll in the study if they were in the first trimester. Time-to-pregnancy months that were accrued prior to 3 months (approximate length of first trimester) before the date that the study began at that site were left truncated. For example, if a woman reported trying to conceive for 6 months before the study start date, her first 3 months were truncated from the analysis and she would start accruing person-time during her fourth cycle of her time to pregnancy. Because of the retrospective design of the study, this hypothetical woman would not have been eligible to enroll had she become pregnant in her first three cycles because she would have been in the second trimester by the time the study began. These cycles that occurred prior to 3 months of study initiation are cycles during which a woman who ended up enrolling in RFTS could not have conceived and are therefore excluded from analysis. If a woman accrued all of her cycles attempting to become pregnant prior to this date, she was excluded from the study (n = 78). Though we present results from this design, the results did not change when all time-to pregnancy data were included with no left truncation.
Baseline interview data were available for the first pregnancy of 4683 women. Women were excluded from the analysis if they had not intended to become pregnant and therefore could not provide us with information about how long they had attempted to conceive (n= 1176); did not provide information on whether they were attempting to become pregnant (n= 12); did not provide information on the number of cycles it took them to conceive (n= 268) or did not have ultrasound data (n= 319). These exclusions resulted in 3000 women with person-time eligible for the analysis.
Participants were all scheduled as early as possible for endovaginal ultrasonography (supplemented if needed by transabdominal images) starting at the sixth week of gestation. Sonographers were required to have more than 2 years of pelvic sonography experience including obstetric and gynecologic sonography. Specific research instruction on identifying and measuring uterine leiomyomata was provided for the sonographers. They were trained not to discuss any history of uterine leiomyomata with participants.
Uterine leiomyomata were defined by the Muram criteria (Muram et al., 1980
) with the addition of including masses with a maximum diameter of 0.5 cm or greater. All leiomyomata were measured in three perpendicular planes. Sonographers repeated the measurement of each plane three times separated by measurements of the gestation to reduce the chance that focal contractions would be misclassified as leiomyomata. The three measurements in each plane were averaged to determine three leiomyoma diameters and a total leiomyoma volume was calculated using the ellipsoid formula. A mean leiomyoma diameter (the average of the three planes) was also calculated and used for size measurement.
Leiomyomata were drawn onto a uterine diagram based on appearance on ultrasound and were categorized by location (fundus, corpus, cervix) and position (anterior, posterior, right and left). Leiomyoma type was defined as submucous if distorting the uterine cavity without identifiable myometrium between the leiomyoma and the endometrium, subserous if distorting the external contour of the uterus, intramural if within the myometrium but not distorting the outer contour or cavity, and subserosal pedunculated if attached to the outside of the uterus with an identifiable stalk. Leiomyoma and fetal images were saved initially as print images. Later, digital images with both still and video clips were available for review by study investigators (S.K.L., K.E.H.).