Study Design and Participants
The Institutional Review Board at both the Brigham and Women’s Hospital and the University of Minnesota approved this study. All women signed informed consent forms before joining the study. In brief, the study collected data between the years 2000 and 2003 from women in the Boston area on history of vulvar pain. Women aged 18–64 years were identified using a sampling of the Massachusetts annual census publication containing names, ages, and addresses (called the Massachusetts Town Books). Weighted sampling was employed to reflect the age and community distributions of all communities based on the US Census data. Using this method, 12,047 women with a confirmed residential listing comprised the target population. Of these women, 67.4% (8,125) returned a short screening questionnaire that assessed the history of the following four types of vulvar pain symptoms that lasted for three or more months: itching, burning, knife-like sharp pain, pain on contact (with tampon insertion, intercourse, or pelvic examination).
Vulvodynia Case Determination
Those who reported having symptoms consistent with the International Society for the Study of Vulvovaginal Disease criteria for vulvodynia on their short screening questionnaire were candidates to become a vulvodynia case [5]. These women were screened over the phone for additional vulvodynia-related criteria, including history of vulvar itching, burning, knife-like pain, and pain on contact. Age at onset of symptoms, a brief description of treatments ever used, and intensity were assessed for each pain domain. A specialist in vulvar disease diagnosis (E.G.S.) reviewed all women with vulvar pain symptoms from the self-reported questionnaires and, based on history of pain and other conditions that could have explained the vulvar pain, determined the final group of cases. There were 177 women with chronic (>3 months in duration) vulvar pain symptoms, who agreed to participate in the present study. An additional 65 women who were clinically confirmed to have vulvodynia were identified and enrolled from a vulvovaginal specialty clinic (attended by E.G.S.). For each of the 242 cases, a control was matched on age (±5 years) and area of residence. Previous studies have reported high validity of results when examining population-based cases and clinically confirmed cases [4, 6]. Further details regarding the study methods can be found elsewhere [4, 6].
To determine events, such as pregnancy occurring after onset of vulvar pain symptoms, the authors developed a reference point in time. Age at first onset of vulvar pain symptoms was determined for each woman with vulvodynia. This age was referred to as the “reference age,” and it was assigned to a matched control woman with no vulvar pain history.
Assessing Pregnancy and Delivery Characteristics
As the authors wanted to determine the fertility among women after first onset of vulvar pain (and reference age in controls), the authors restricted the present study population to women with reference ages less than 45 years. This exclusion criterion eliminated 15 women with vulvodynia and 15 control women, leaving 454 women (227 women with vulvodynia and 227 controls) for the analysis.
A telephone-administered questionnaire assessed each pregnancy history, including dates, pregnancy outcome, mode of delivery, and type of anesthesia. If the delivery was vaginal, women were asked, “Did your episiotomy or tear pain subside by 2 months, or were you in pain for a longer time? (≤2 or >2 months).” Vulvar pain after delivery was defined as reporting pain for more than 2 months after vaginal delivery.
The authors determined whether the number of pregnancies and other pregnancy-related characteristics after reference age differed by case–control status. For the analysis of number of pregnancies, the authors included only those after the woman’s reference age. The first pregnancy after reference age was considered the index pregnancy for the assessment of pregnancy-related characteristics (pregnancy outcome, delivery characteristics, and vulvar pain during the postpartum period). The authors lacked specific data on women’s level of pain around conception, during pregnancy, and into the postpartum period.
Statistical Analysis
All analyses were restricted to pregnancies occurring after the reference age (age at first onset of pain for vulvodynia cases and the matched reference age for controls). The authors hypothesized that women with vulvodynia who had their first onset of pain at a young age may be more prone to problems than those with an older age at pain onset. Therefore, in addition to the overall estimates that use the entire sample of women, findings from a restricted dataset that includes only women with reference ages that were less than 30 years are also presented.
The authors sought to investigate three specific aims: first, determine whether vulvodynia was associated with a reduced likelihood of pregnancy; second, among those who became pregnant, determine if vulvodynia was associated with differences in pregnancy outcomes; and third, among women with vulvodynia only, determine if pain-related factors around pregnancy, such as pain that limited intercourse or intermittent (vs. constant) pain, were associated with becoming pregnant.
To address these research aims, the authors conducted three separate analyses. For the first analysis, all 454 women were included (Fig. 1). The authors used univariate conditional logistic regression that accounted for the study’s original matching criteria (town of residence and age at interview) to determine factors associated with a reduction in the likelihood of pregnancy after reference age. For the second aim, only women who became pregnant were eligible; therefore, matching was broken. Due to small sample sizes, for this aim the authors present descriptive data and P values using the Chi square test for categorical variables and the Student’s t test for the difference in means. Finally, for the third aim, only vulvodynia cases were eligible. The authors used multivariate logistic regression to assess independent characteristics of vulvar pain associated with likelihood of becoming pregnant. Variables that were found to be significant in the univariate analysis were considered (P ≤ 0.05), with forward stepwise selection employed (probability of entry set to 0.20) for variable selection into the final models. All analyses were performed using STATA/SE™ v.10 (StataCorp LP, College Station, TX, USA).