Colposcopy in Evaluating Bleeding During the Second and Third Trimesters: Short-Term and Postpartum Implications.

BACKGROUND: The etiology of vaginal bleeding during pregnancy may be obstetric or non-obstetric. Though colposcopy is generally not part of the routine evaluation of 2nd- or 3rd-trimester vaginal bleeding without obvious obstetrical cause, our department does perform colposcopy and cervical cytology testing in these patients. This study assessed the need and possible contribution of colposcopy in diagnosing the etiology of 2nd- and 3rd-trimester bleeding. METHODS: Retrospective analysis of colposcopy findings from 2012-2015 in patients with 2nd- or 3rd-trimester bleeding where an obstetrical cause was not found. Data collected included demographics, obstetric data, bleeding characteristics, colposcopy results, cervical cytology testing, a sonogram directed at the placenta, and birth details. RESULTS: Of the 168 patients who underwent colposcopy, 29 (17.3%) complained of postcoital bleeding (PCB). The following were the colposcopy results: 5 (3%) had abnormal colposcopy findings, 14 (8.3%) ectropion, 4 (2.4%) polyps, and 1 (0.6%) vaginal varices. Postpartum follow-up of women with PCB or pathologic cervical cytology testing diagnosed 1(0.6%) patient with high-grade cervical intraepithelial neoplasia 2-3, human papillomavirus 18 and 45 positive. CONCLUSIONS: Colposcopy diagnosed the origin of bleeding in 24 cases (13.7%). These findings support the use of colposcopy in evaluating vaginal bleeding of undetermined obstetric origin during pregnancy.

Localized Provoked Vulvodynia: Association With Nerve Growth Factor and Transient Receptor Potential Vanilloid Type 1 Genes Polymorphisms.

OBJECTIVE: The aim of the study was to study the associations between localized provoked vulvodynia (LPV) and several single-nucleotide polymorphisms (SNPs) in the transient receptor potential vanilloid type 1 (TRPV1), nerve growth factor (NGF), and the heparanase (HPSE) genes. MATERIALS AND METHODS: Prevalence of SNPs among 65 women with moderate or severe primary LPV (initial symptoms occur with first provoking physical contact) and 126 healthy, ethnically matched controls was analyzed in an observational case-control study. Each participant answered a questionnaire addressing familial LPV occurrence and comorbid pain conditions. RESULTS: Familial occurrences of LPV, temporomandibular joint (TMJ) symptoms, recurrent vaginitis, and irritable bowel syndrome were significantly higher among LPV women than healthy controls. Genotyping analyses revealed a novel, statistically significant high prevalence of polymorphism c.945G>C (rs222747) of TRPV1 and a SNP in the promoter region of NGF (rs11102930) in LPV women compared with controls. A logistic regression model for rs222747 and rs11102930 frequent alleles indicates significant LPV association within the entire study group and Ashkenazi Jewish women, respectively. Comparison of pain conditions with frequent alleles showed the rs222747 "CC" genotype of TRPV1 associated with women with TMJ, recurrent vaginitis, and LPV. CONCLUSIONS: Our results suggest novel genetic susceptibility to primary LPV associated with specific alleles in genes TRPV1 and NGF and propose the rs222747 "C" allele of TRPV1 as a common genetic predisposition for other pain syndromes.

Enoxaparin treatment for vulvodynia: a randomized controlled trial.

OBJECTIVE: To estimate the effectiveness of enoxaparin-a low-molecular-weight heparin with antiheparanase properties-in treating localized provoked vulvodynia. METHODS: Forty women with severe localized provoked vulvodynia were randomly and blindly assigned to self-administer either 40 mg enoxaparin or saline subcutaneously for 90 days. Dyspareunia and local sensitivity were evaluated before, at the end, and 90 days after treatment. The most painful focus was biopsied at the beginning of the study and a parallel site at the end of study for mast cells, PGP 9.5 nerve fiber staining, and heparanase quantification. RESULTS: The enoxaparin-treated women showed a greater reduction in vestibular sensitivity at the end of treatment and 3 months later (29.6% compared with 11.2%, P=.004). Seventy-five percent (15 of 20) of them reported more than 20% pain reduction compared with 27.8% (five of 18) in the placebo group (P=.004). Seven enoxaparin-treated women compared with three in the placebo group had almost painless intercourse at the end of the study. In women who had improvement of sensitivity at the site parallel to the original biopsy site, there was a histologically documented reduction in the number of intraepithelial-free nerve fibers in the enoxaparin group. CONCLUSION: Enoxaparin reduced the vestibular sensitivity and dyspareunia, concomitant with a reduction in intraepithelial free nerve fibers, in women with localized provoked vulvodynia.

Topical nifedipine for the treatment of localized provoked vulvodynia: a placebo-controlled study.

UNLABELLED: Topical application of the calcium antagonist nifedipine has demonstrated effectiveness in treating chronic anal fissure, without adverse effects. Like chronic anal fissure, vulvodynia is associated with muscle hypertonicity and an inflammatory infiltrate. We conducted a double-blind placebo-controlled study to investigate the effectiveness of 2 concentrations of topical nifedipine cream in the treatment of vulvodynia. Thirty participants were alternately assigned to 3 topical treatment groups: .2% nifedipine, .4% nifedipine, and placebo. All administered the cream to the vestibule 4 times daily for 6 weeks. For all 3 treatment groups, mean pain intensity on vestibular touch, assessed by the Q-tipped cotton test, pain from speculum insertion, and reports of pain during sexual intercourse was reduced at post-treatment compared with pre-treatment. These improvements remained at 3 months' follow-up. The effectiveness of nifedipine in treating vulvodynia did not exceed that of placebo. PERSPECTIVE: The topical application of both nifedipine and a placebo reduced pain in women with vulvodynia. This study highlights the need for controlled trials of treatments for vulvodynia and raises doubts about studies conducted without comparison to placebo.

[Vestibulodynia--the Israeli experience].

The cause of vestibulitis, currently known as vestibulodynia, is still an enigma. Among those attempting to decipher the puzzle, Israeli researchers are well represented. This article reviews the developments in terminology, etiology, treatment, and research directions, with an emphasis on the role of IsraeLi research. Forty-four articles, covering a range of aspects of vestibulodynia, are testimony to the commendable contribution of Israeli research to the understanding of this disease. For example, the finding of mast cell proLiferation and degranulation, enhanced heparanase expression, and the resultant increase and penetration of nerve fibers into the epithelial emanates from Israel. Furthermore, an Israeli first proposed the new name, vestibulodynia. Implemented in the 1980s, immediately after its initiation in the United States, surgical treatment and research in Israel is at the forefront in the world. Israeli teams investigating the effectiveness of surgical treatment conclude that perineoplasty is more successful than any other treatment. Nonetheless, with 57% complete response, and 89% improvement, surgery does not cure all those suffering from vestibulodynia.

Involvement of heparanase in the pathogenesis of localized vulvodynia.

Recently, we have shown that vestibular hyperinnervation and the presence of 8 or more mast cells in a 10 x 10 microscopic field can be used as diagnostic criteria in localized vulvodynia (vulvar vestibulitis). We have also documented that degranulation of mast cells occurs in these cases. The present study further examines the characteristics of vestibular hyperinnervation and mast cell function in localized vulvodynia to elucidate if the 2 processes-hyperinnervation and mast cell increase and degranulation-are related. We examined vestibular tissue from 7 women aged 18 to 48 with severe localized vulvodynia and from 7 healthy control women. Parallel sections were stained by Giemsa and then immunostained for CD117 and heparanase. Nerve fibers that expressed protein gene product 9.5 were examined. Tissues from women with localized vulvodynia documented a significant increase in vestibular mast cells, subepithelial heparanase activity, and intraepithelial hyperinnervation compared with healthy women. This is the first documentation of heparanase activity in localized vulvodynia. Heparanase, which is degranulated from mast cells, is capable of degrading the vestibular stroma and epithelial basement membrane, thus permitting stromal proliferation and intraepithelial extension of nerve fibers, as seen in the present study. The hyperinnervation has been thought to cause the vestibular hyperesthesia distinctive of localized vulvodynia.

A universal combination treatment for vaginitis.

BACKGROUND: We compared a novel vaginal tablet consisting of 100 mg of clotrimazole and 100 mg of metronidazole ('Clo-Met') to a 100-mg clotrimazole tablet in the treatment of vaginitis. METHODS: A multicenter, double-blind, randomized controlled study. Women with vaginal discharge and diagnosed as suffering from vaginitis caused by Trichomonas vaginalis, bacterial vaginosis or Candida albicans, or any combination of the three, and who had not received treatment for vaginitis during the previous month, were studied. RESULTS: 165 patients were enrolled into the study--84 into the combined therapy group, and 81 into the clotrimazole group. In women with Candida vaginitis, Clo-Met was more effective than clotrimazole treatment (p < 0.012 and p < 0.05, respectively). CONCLUSION: A combination vaginal tablet consisting of clotrimazole and metronidazole is therapeutically effective in candidal vaginitis. The effectiveness of Clo-Met on bacterial vaginosis, T. vaginalis infection as well as on vaginal infections due to a combination of these microorganisms should be studied further.

[Vaccination against cervical cancer and diseases caused by Human Papillomavirus].

Developing the vaccine against human papillomavirus (HPV) types 6, 11, 16 and 18 which cause a variety of lesions, in particular cervical cancer, is regarded as a scientific breakthrough and received the FDA and CDC approval. Cervical cancer is the leading cause of death from cancer in women in developing countries. About 490,000 women develop cervical cancer yearly and 230,000 women die yearly of this disease. The vaccine includes a virus-like-particle (VLP) without the genetic core, which could have caused a malignant transformation. The present review describes how HPV causes cancer and how the vaccine has been developed. The large scale studies that have examined the vaccine depicted that it is well received, leads to a high antibody level, and prevents a chronic HPV infection and the diseases that are associated with it. However, several new questions arose, such as: at what age to administer the vaccine and whether it is possible to vaccinate those who had already been infected; for how long the immunity acquired by the vaccine lasts and is it effective in those whose immune system is depressed. Although best results will be achieved if the vaccine is administered to girls prior to sexual intercourse, vaccination at a later age may also be valuable. Previous exposure to the vaccine is not a contraindication to administration of the quadrivalent vaccine and it is not necessary to examine if it has occurred. Cervical cancer screening policy should continue for a few more years.

Tools for post LEEP surveillance.

UNLABELLED: Recurrences of cervical intraepithelial neoplasia (CIN) as well as invasive cervical carcinoma have been reported to arise following ablative or excisional treatment for cervical intraepithelial neoplasia. This review utilizes MEDLINE and National Library of Medicine's PubMed review of the various screening tools used in follow-up protocols for women treated by loop excision for CIN. Cervical cytology, colposcopy, endocervical curettage and HPV typing have been advocated for use as tools for follow up. Involvement of the surgical margins and the presence of HPV-DNA are associated with higher risks of recurrence and should be taken into consideration. The psychological impact of undergoing colposcopy may affect compliance with follow-up visits and should be dealt with appropriately. LEARNING OBJECTIVES: After completion of this article, the reader should be able to list the various tools that can be used for the surveillance of patients after treatment for CIN, to compare the advantages and disadvantages of each surveillance method, and summarize methods to improve compliance with follow-up.

[Large loop excision of the transformation zone in Israel--2001].

BACKGROUND: Large loop excision of the transformation zone (LLETZ) is regarded as the treatment of choice in cases of Cervical Intraepithelial Neoplasia (CIN). Since the method is easy to learn and the equipment is inexpensive, many gynecologists now perform it in the clinic. Concern has been raised regarding the use of this procedure with insufficient indication by physicians who have not been adequately trained in performing LLETZ. AIM: This article aims to verify whether the indications for LLETZ in Israel are similar to those accepted in the updated literature and to discuss the need for licensure to perform LLETZ. Licensure would limit the use of LLETZ only to professionals specifically trained to conduct this procedure. METHOD: A questionnaire was sent to gynecologists, heads of obstetrics and gynecology departments as well as managers of public and private hospitals, regarding LLETZ performed in 2001. Topics covered in the questionnaire included: the number of LLETZ procedures performed, the patient's age, pre- and post-operative histopathological diagnosis, complications, follow-up and recurrence rate. The physicians were asked to complete separate questionnaires for each of the clinics in which he or she worked. RESULTS: The completed questionnaires comprised of 625 LLETZ procedures in eight public and three private colposcopy clinics. The ages of the women ranged from 18 to 70 years old, with 49% in the 18 to 34 age range. Most women (416) who underwent the LLETZ procedure had CIN grades 2 or 3. However, 128 women with CIN 1 were also treated. Among this group, 50% were confirmed CIN 1 according to the surgical specimen but 43 women had normal epithelium, 20 (15.6%) had high grade CIN (2-3) and one had invasive cancer. The most common post-operative short and long-term complication was heavy bleeding. Involvement of the surgical specimen borders was found in one fifth of the cases. CONCLUSIONS: The finding that about half of the women who underwent LLETZ were below the age of 35 years is of particular significance since the health insurance agencies in Israel only cover a pap smear screening test for women between the ages 35-54, once every three years. Therefore, there is an indication to start screening from the age 18. Similar to other countries in the world, the main indication to perform LLETZ in Israel is CIN 2-3. However, performing LLETZ for CIN 1 in many cases, and administering general anesthesia in certain centers, calls for the introduction of licensure for performing LLETZ. Involvement of the margins of the specimen in the neoplastic process in one fifth of the patients was similar to that reported in the literature. The various centers in Israel have different approaches as to the required surveillance period for women following LLETZ. It is suggested that women with involvement of the surgical specimen margins by CIN should be under medical surveillance at colposcopy clinics for a period of at least eight years.