Catherine M. Leclair

Histologic and receptor analysis of primary and secondary vestibulodynia and controls: a prospective study

OBJECTIVE The objective of the study was to assess the association between hormone receptor densities, pain nerves, and inflammation in vestibulodynia patients. STUDY DESIGN In a prospective study, tender and nontender biopsies from 10 primary and 10 secondary vestibulodynia patients were compared with biopsies in 4 nontender controls. Hormone receptors were evaluated using immunohistochemistry for estrogen receptor-alpha and -beta, androgen, and progesterone receptors. Inflammation, nerves, and mast cells were assessed histologically. Statistical analysis was by Fishers exact test, analysis of variance, paired Student t test, and Wilcoxon rank test. RESULTS Tender sites from primary vestibulodynia had increased nerve density compared with secondary and control biopsies (P = .01). Tender sites in secondary vestibulodynia had more lymphocytes than tender primary sites and control biopsies (P < .0001). Mast cells were increased in tender sites compared with nontender and controls. There were no differences in hormone receptor expression. CONCLUSION Markers of inflammation differed between primary and secondary vestibulodynia and controls.

Differences in Primary Compared With Secondary Vestibulodynia by Immunohistochemistry

OBJECTIVE: To assess whether primary and secondary vestibulodynia represent different pathologic pathways. METHODS: This was an analysis of archived vestibulectomy specimens from 88 premenopausal women with vestibulodynia (2002–2008). Patient records were reviewed to classify the type of vestibulodynia, duration of symptoms, and hormone status. Histologic sections were stained for hematoxylin and eosin to grade inflammation, S100 to highlight nerves, CD117 for mast cells, estrogen receptor &agr;, and progesterone receptor. Differences between primary and secondary vestibulodynia were tested by t tests, chi-square analysis, and linear and logistic regression. RESULTS: Primary vestibulodynia showed significant neural hypertrophy and hyperplasia (P=.02, adjusted odds ratio [OR] 3.01, 95% confidence interval [CI] 1.2–7.6) and increased progesterone receptor nuclear immunostaining (P=.004, adjusted OR 3.94, CI 1.6–9.9) compared with secondary vestibulodynia. Estrogen receptor &agr; expression was also greater in primary vestibulodynia when symptom diagnosis was less than 5 years (P=.004, adjusted OR 5.53 CI 1.71–17.91). CONCLUSION: Primary and secondary vestibulodynia have significantly different histologic features, suggesting that they may have separate mechanistic pathways. Clinically, this may mean the discovery of distinct conditions. LEVEL OF EVIDENCE: II

Intrauterine lidocaine infusion for pain management in first-trimester abortions

OBJECTIVE: To study the effects of an intrauterine lidocaine infusion on perceived patient pain in first-trimester abortions and to measure serum lidocaine levels. METHODS: A randomized, double-blind, placebo control trial of 80 women receiving either a 10-mL 1% lidocaine (n = 40) or saline (n = 40) intrauterine infusion and a standard paracervical block before first-trimester abortion was undertaken. Women completed a series of 100-mm visual analogue scales to measure their perceived pain (anticipated pain, after speculum insertion, after intrauterine infusion, after cervical dilation, after suction aspiration, and 30 minutes after procedure). Twenty women (10 in each group) volunteered for serum lidocaine levels at 10, 20, 30, 45, and 60 minutes after the lidocaine infusion. RESULTS: Groups were similar in respect to age, parity, prior abortion, ethnicity, gestational age, level of dysmenorrhea, and complications. Pain scores by visual analogue scale demonstrated no significant difference between groups at any time point during the procedure; in particular, pain during aspiration (saline infusion 51 ± 26 mm, lidocaine infusion 47 ± 28 mm; P = .51). Peak serum levels occurred at approximately 10 minutes after lidocaine infusion. The highest level recorded (lidocaine group) was 2.5 μg/mL (toxicity more than 5 μg/mL). CONCLUSION: Compared with paracervical block alone, the addition of a 1% intrauterine lidocaine infusion resulted in no improvement in patient perception of pain during first-trimester abortion. No subjects demonstrated symptoms or serum levels of lidocaine toxicity. LEVEL OF EVIDENCE: I

Four percent intrauterine lidocaine infusion for pain management in first-trimester abortions.

OBJECTIVE: To study the effects of a 4% intrauterine lidocaine infusion on perceived patient pain in first-trimester abortions. METHODS: A randomized, double-blind, placebo-controlled trial of 80 women receiving either a 5-mL 4% lidocaine (n = 40) or saline (n = 40) intrauterine infusion and a standard paracervical block before first-trimester abortion. Women completed a series of 100-mm visual analog scales (anchors: 0 = none, 100 mm = worst imaginable) to measure their perceived pain (anticipated pain, after speculum insertion, after intrauterine infusion, after cervical dilation, after suction aspiration, and 30 minutes postprocedure). Eight women volunteered for serum lidocaine levels after the lidocaine infusion. RESULTS: Groups were similar in respect to age, parity, prior abortion, ethnicity, gestational age, and level of dysmenorrhea. Pain scores demonstrated a significant difference between groups during cervical dilation (saline 55 mm ± 26, lidocaine 35 mm ± 30, P < .01) and during aspiration (saline 71 mm ± 20, lidocaine 43 mm ± 30, P < .01). The lidocaine group reported significantly more symptoms (ie, oral numbness and tingling) than the saline group (saline 0/39, lidocaine 16/38, 42%, P < .01). The highest serum lidocaine level recorded was 4.0 &mgr;g/mL (lidocaine group). There was no difference in overall satisfaction between the 2 groups. CONCLUSION: Compared with paracervical block alone, the addition of a 4% intrauterine lidocaine infusion resulted in a significant reduction in patient perception of pain during first-trimester abortion. Although subjective symptoms of systemic lidocaine effect were common, no subjects demonstrated serum levels consistent with lidocaine toxicity. However, further studies to determine safety are needed. LEVEL OF EVIDENCE: I

Dyspareunia and sexual dysfunction in women seeking fertility treatment

OBJECTIVE To compare rates of dyspareunia in infertile women and healthy controls. Secondary aims are to determine whether demographic characteristics, rates of sexual dysfunction, and baseline depression status differ between the two groups. DESIGN A case-control study. SETTING University-based faculty fertility and OB/GYN generalist clinics. PATIENT(S) Seventy-five infertile female subjects presenting to the infertility clinic and 210 women presenting to the generalist clinic for their annual exam. INTERVENTION(S) Completion of an anonymous survey including demographic information, the Female Sexual Function Index (FSFI), Patient-Health Questionnaire-9 (PHQ-9), and original questions regarding sexual pain. MAIN OUTCOME MEASURE(S) Rate of dyspareunia and sexual dysfunction. RESULT(S) There were no significant differences in rates of dyspareunia (37.6% controls vs. 30.7% study) or the rate of sexual dysfunction (31.9% controls vs. 37.3% study). Infertile women had more frequent intercourse than controls and were more likely to be married. There were otherwise no differences in baseline rates of depression, demographic characteristics, or individual domain scores of the FSFI. CONCLUSION(S) Women seeking fertility treatment had similar rates of dyspareunia and sexual dysfunction compared with controls.

Pain experienced using two different methods of endometrial biopsy: a randomized controlled trial.

OBJECTIVE: To compare patient-reported pain, provider- reported ease of use, and tissue sampling adequacy between endometrial biopsy instruments. METHODS: Women presenting for endometrial biopsy were randomized to either Pipelle or Explora curette. The primary outcome was patient-reported pain with biopsy as measured by a 100-mm visual analog scale. Secondary outcomes included the adequacy of biopsy sample and provider-reported ease of instrument use. RESULTS: Groups were similar in respect to age, parity, ethnicity, level of dysmenorrhea, menopausal status, and biopsy indication. The most common indication for biopsy was abnormal uterine bleeding. Subject reported pain with biopsy was similar between groups (Pipelle, 6.21±2.41 cm; Explora, 6.91±2.88 cm; P=.14), as was provider-reported ease of use. Although procedure length was significantly shorter for patients in the Pipelle group (4.05±1.48 minutes compared with 5.27±2.53 minutes; P=.007), 38% of Pipelle procedures required two or more passes to obtain a sample compared with only 9% using the Explora (P=.004). The Explora group had a higher proportion of adequate samples (97% compared with 91%; P=.33). CONCLUSION: Womens pain during endometrial biopsy does not differ by type of biopsy instrument used. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov NCT00613925. LEVEL OF EVIDENCE: I

CD4-positive T-cell recruitment in primary-provoked localized vulvodynia: potential insights into disease triggers.

Objective To better understand the potential disease triggers of neurogenic inflammation in provoked localized vulvodynia (PLV), our objective was to determine whether the types of infiltrating lymphocytes were different in vestibular biopsies from women with primary PLV, secondary PLV, and unaffected controls. Methods Secondary retrospective analysis of archived vestibular biopsies from a series of adult premenopausal women with primary PLV (n = 10), secondary PLV (n = 10), and unaffected controls (n = 4) was performed. All study patients had severe entry dyspareunia for more than 1 year. Subjects were excluded if pregnant, or they had a known infection, or history of generalized vulvodynia. Biopsies were performed during the midfollicular phase. Lymphocyte subtypes were highlighted in histologic sections using antibodies against CD3, CD4, and CD8 and scored as the mean number of T-cell subtypes per high-power field. Flow cytometry was also used to test fresh biopsies from a de novo prospective series of primary PLV (n = 4) and unaffected controls (n = 2). Results Unaffected control biopsies showed more CD8-positive than CD4-positive T cells, similar to previous reports of the gynecologic tract. In contrast, biopsies from women with primary PLV showed significantly more CD4-positive T cells than those from women with secondary PLV and unaffected controls (p = .003). This observation was further supported by flow cytometry. Conclusions CD4-positive T cells are more numerous in vestibular biopsies from premenopausal women with primary PLV. This may be important because subtypes of CD4-positive T cells are specifically recruited by infectious, allergic, or autoimmune triggers. Future studies distinguishing these subtypes may lead to new insights into this common disease.

Low-grade fibromyxoid sarcoma of the vulva: a case report.

Objective The study aimed to describe a case of low-grade fibromyxoid sarcoma arising from the vulva and to discuss the diagnostic challenges, clinical management, and epidemiology of this rare malignancy. Case A 36-year-old woman presented to 3 separate emergency departments with complaints of a painful and slowly enlarging vulvar mass. Eventual gynecologic referral resulted in excision of a 6-cm, noncystic vulvar mass. Pathological diagnosis revealed low-grade fibromyxoid sarcoma. Later, a right radical hemivulvectomy ensured adequate margins, and 2 years later, the patient is free of recurrent and metastatic disease. Conclusions Low-grade fibromyxoid sarcoma is a rare malignancy that may present in the lower genital tract. Definitive diagnosis is essential because low-grade fibromyxoid sarcoma may metastasize many years after diagnosis, thereby requiring indefinite clinical surveillance.

Group B streptococcus: prevalence in a non-obstetric population.

Objective. To establish and compare the prevalence of group B streptococcus (GBS) colonization in the vaginas of nonobstetric women with and without vaginitis. Materials and Methods. Cross-sectional analysis GBS vaginal culture status of nonpregnant, estrogen-replete women 18 years or older presenting for annual gynecological examinations or vaginal infection. Subjects were classified into 3 groups: no vaginitis if symptoms were absent and examination results was normal; common vaginitis (CV) if microscopic examination revealed yeast, bacterial vaginosis, or trichomonads; or inflammatory vaginitis (IV) if examination revealed inflammation and immature squamous cells but no pathogens. Results. Of the 215 women recruited, 147 (68.4%) showed no evidence of vaginitis, 41 (19.1%) had CV, and 27 (12.6%) showed evidence of IV. The overall prevalence rate of GBS was 22.8%. Vaginitis was associated with a significantly increased risk of GBS colonization (adjusted odds ratio: CV = 2.7, 95% CI = 1.1-6.2; IV = 2.9, 95% CI = 1.1-8.0). Logistic regression revealed pH higher than 4.5, presence of abnormal discharge on examination, and a womens complaint of current symptoms as significant predicators of the presence of GBS. Conclusions. Group B streptococcus colonization occurs more commonly in women with vaginitis. This suggests that disruption of the normal vaginal bacterial environment is an important predictor for GBS colonization.

Red Rashes of the Vulva

Red patches and plaques of the vulva may be manifestations of neoplasms, infections, or inflammatory skin diseases. These diseases can mimic one another clinically; features that generally allow the diseases to be identified on most cutaneous surfaces can be altered in the moist, occluded vulvar environment, making clinical diagnosis difficult. A detailed history and thorough physical examination can point to the likely diagnosis, but biopsy and culture may be needed for diagnosis especially in refractory disease. It is not uncommon for several of these processes to be present concomitantly or complicating other vulvar diseases.