Probing the potential of mucus permeability to signify preterm birth risk.

Preterm birth is the leading cause of neonatal mortality, and is frequently associated with intra-amniotic infection hypothesized to arise from bacterial ascension across a dysfunctional cervical mucus plug. To study this dysfunction, we assessed the permeability of cervical mucus from non-pregnant ovulating (n = 20) and high- (n = 9) and low-risk (n = 16) pregnant women to probes of varying sizes and surface chemistries. We found that the motion of negatively charged, carboxylated microspheres in mucus from pregnant patients was significantly restricted compared to ovulating patients, but not significantly different between high- and low-risk pregnant women. In contrast, charged peptide probes small enough to avoid steric interactions, but sensitive to the biochemical modifications of mucus components exhibited significantly different transport profiles through mucus from high- and low-risk patients. Thus, although both microstructural rearrangements of the components of mucus as well as biochemical modifications to their adhesiveness may alter the overall permeability of the cervical mucus plug, our findings suggest that the latter mechanism plays a dominant role in the impairment of the function of this barrier during preterm birth. We expect that these probes may be readily adapted to study the mechanisms underlying disease progression on all mucosal epithelia, including those in the mouth, lungs, and gut.

Predictive value of preimplantation genetic diagnosis for aneuploidy screening in repeated IVF-ET cycles among women with recurrent implantation failure.

OBJECTIVE: To determine the predictive value of euploid embryos in women with recurrent implantation failure undergoing repeated IVF-ET cycles with PGD (PGD). DESIGN: Cohort of IVF-PGD cycles in a tertiary care ART facility. MATERIALS AND METHOD(S): Fifty-five consecutive patients with repeated implantation failure (more than three failed IVF-ET cycles) underwent two or more PGD cycles for aneuploidy testing. Mean maternal age was 37.6+/-5.3 years. Biopsies were performed on day 3. One blastomere was removed from each pre-embryo, fixed and analyzed by multicolor and multi-probe FISH for chromosomes X and Y, 13, 15, 16, 17, 18, 21, and 22. RESULT(S): Forty-three of 55 patients (78%) undergoing PGD had at least one euploid embryo for transfer. Of these 31 patients (72%) also had at least one euploid embryo available for transfer with the second cycle. Of the 12 (28%) patients with no euploid embryos available for transfer with the second IVF/PGD cycle, five had a third cycle of PGD and two of these had euploid embryos available for transfer. Seventeen of the 31 patients (55%) who had euploid embryos on the second PGD cycle conceived. The ongoing pregnancy and implantation rates in patients with at least one euploid embryo were 40% and 18%, respectively. Twelve of the 55 patients (22%) had no euploid embryos available for transfer on the first PGD cycle, but on the second PGD cycle, six (50%) of these had euploid embryos for transfer. Only two pregnancies were achieved among this group of women, yielding a pregnancy rate of 17%, but both conceptions resulted in miscarriage. Of the six patients with no euploid embryos available after the second PGD cycle, four patients had a third IVF/PGD cycle, but none had euploid embryos available for transfer. Also, among women with euploid embryos available only in either the first or second PGD cycle, but not both, no ongoing pregnancy was achieved. No woman who had a PGD cycle productive of no euploid embryos had an ongoing pregnancy. Significant differences were found in terms of ongoing pregnancy (40%, P<0.05) and implantation rates (18%, P<0.05) in women with euploid embryos available for transfer with the first and second IVF/PGD cycles, compared to women with no euploid embryos available for transfer with either the first or second cycle. The positive predictive value of the first euploid cycle predicting a second euploid cycle was 72%, 95% CI 0.66-0.78. The negative predictive value of an aneuploid cycle was 50%, 95% CI 0.27-0.72. The sensitivity and specificity of the first PGD cycle predicting the second was 84%, 95% CI 0.77-0.91 and 33%, 95% CI 0.18-0.48, respectively. CONCLUSION(S): Even with a history of recurrent implantation failure, the availability of euploid embryos, especially on two, consecutive PGD cycles is associated with high ongoing pregnancy and implantation rates. Conversely, the absence of euploid embryos for transfer predicts poor reproductive outcome, even if subsequent cycles do yield euploid embryos.

Vulvar vestibulitis syndrome: reliability of diagnosis and evaluation of current diagnostic criteria.

OBJECTIVE: To assess the reliability of the diagnosis of vulvar vestibulitis as defined by Friedrich and to evaluate the usefulness of Friedrich's criteria in the diagnostic process. METHODS: In a university hospital, 146 women with dyspareunia had two sets of gynecologic examinations involving vulvar pain ratings, took part in structured interviews, and completed the McGill-Melzack Pain Questionnaire. RESULTS: Kappa values for the vulvar vestibulitis diagnosis ranged from 0.66 to 0.68 for inter-rater agreement and from 0.49 to 0.54 for test-retest reliability. Mean vestibular pain ratings ranged from 2.45 at the 12 o'clock site to 7.58 at the 9-12 o'clock site; ratings for all sites correlated significantly between gynecologists. Pain in the labia majora and labia minora was minimal for both sets of examinations, with mean participant pain ratings ranging from 0 to 1.49. Gynecologists' erythema ratings did not correlate significantly with respect to either inter-rater agreement or test-retest reliability. Of Friedrich's three diagnostic criteria, only tenderness to pressure within the vulvar vestibule differentiated dyspareunia patients with and without vulvar vestibulitis. In reference to their coital pain, 88.1% of women with vulvar vestibulitis chose adjectives from the McGill-Melzack Pain Questionnaire describing a thermal quality, and 86.6% chose adjectives describing an incisive pressure sensation. CONCLUSION: Vulvar vestibulitis can be reliably diagnosed in women with dyspareunia. Pain is limited to the vulvar vestibule and can be rated and described in a consistent fashion by these women. Erythema does not appear to be a useful diagnostic criterion.

Vulvar vestibulitis syndrome: a critical review.

OBJECTIVE: Vulvar vestibulitis syndrome (VVS) is thought to be the most frequent cause of dyspareunia in premenopausal women and is one of the major subtypes of vulvodynia. Vulvar vestibulitis is a chronic, persistent clinical syndrome characterized by severe pain on vestibular touch or attempted vaginal entry, exquisite tenderness to a cotton-swab palpation of the vestibular area, and physical findings confined to vestibular erythema. The purpose of this paper is to critically review the descriptive, diagnostic, etiologic, and treatment studies on VVS. Methodological problems are highlighted, and future guidelines for research are proposed. DATA SOURCES: References were obtained from a MEDLINE search covering the period from January 1984 until June 1995. The indexing term "vulvar vestibulitis" was used, and the search was constrained to English-language articles. References from other relevant sources, such as texts and bibliographies, were also included. STUDY SELECTION: All articles pertaining to VVS were reviewed. DATA EXTRACTION: All data relevant to the descriptive, diagnostic, etiologic, and treatment aspects of VVS were included. DATA SYNTHESIS: Pain symptomatology tends to be underemphasized in the current descriptive studies. The trend in etiological research is to focus on biomedical factors such as candidiasis and human papillomavirus (HPV). Only a few studies adopt a nonreductionnist approach. Surgery is the treatment option with the highest reported success rate. Medical management is underinvestigated, considering its widespread use. Pain management techniques such as biofeedback and behavior therapy show promising results. CONCLUSIONS: A pain syndrome conceptualization is suggested as the most useful approach for solving current empirical and clinical problems.

Comparison of reoperation for moderate (stage III) and severe (stage IV) endometriosis-related infertility with in vitro fertilization-embryo transfer.

OBJECTIVE: To evaluate the efficacy of reoperation for stage III or IV endometriosis-related infertility versus IVF-ET. DESIGN: Retrospective analysis. SETTING: In vitro fertilization-embryo transfer unit and tertiary infertility clinic. PATIENTS: Twenty-three couples with stage III or IV endometriosis-related infertility undergoing IVF-ET and 18 women undergoing reoperation for stage III or IV disease, both groups undergoing treatment after failed initial surgery to restore fertility. RESULTS: The cumulative pregnancy rate (CPR) after reoperation for stage III or IV endometriosis-related infertility after 3, 7, and 9 months was 5.9 percent, 18.1 percent and 24.4 percent, respectively. The cumulative PR after one and two cycles of IVF-ET with stage III or IV endometriosis was 33.3 percent and 69.6 percent, respectively. The cumulative PR after one cycle of IVF-ET was higher than with reoperation 33.3 percent versus 24.4 percent. After two cycles the cumulative PR was significantly higher than reoperation 69.6 percent versus 24.4 percent. The mean number of oocytes retrieved was 8.5 +/- 4.6, the mean number of embryos was 4.8 +/- 2.9, and the fertilization rate was 64 percent +/- 21.8 percent. The PR per cycle, per oocyte retrieval and per ET was 38 percent, 42 percent, and 44 percent, respectively, with the implantation rate being 16 percent. The live birth rate per oocyte retrieval and per ET was 29.7 percent and 34.4 percent, respectively. No statistically significant difference could be demonstrated with regard to the fertilization, implantation, nor pregnancy or live birth rates, as compared with IVF-ET outcome with tubal infertility. CONCLUSION: If initial surgery fails to restore fertility in patients with moderate (stage III) or severe (stage IV) endometriosis-related infertility, IVF-ET is an effective alternative; reoperation for asymptomatic patients offers little added benefit.

The effect of antisperm autoantibodies in male or female partners undergoing in vitro fertilization-embryo transfer.

OBJECTIVE: To evaluate the effects of sperm bound autoantibodies on the outcome of IVF-ET. DESIGN: Couples with positive antisperm autoantibodies as determined by the immunobead test were retrospectively classified into two groups: group A, consisting of 15 couples with positive antisperm antibodies in the female sera; and group B, consisting of 16 couples with sperm antibodies bound to motile spermatozoa from the male partner. Both groups were subclassified according to pregnancy outcome, i.e., pregnant and nonpregnant cycles. PATIENTS: Thirty-one couples with positive antisperm autoantibodies were compared with 312 couples with tubal infertility undergoing IVF-ET. RESULTS: No significant correlation could be shown between the mean percent binding of any specific immunoglobulin (Ig) class (G, A, and M) nor localization of sperm binding with regard to fertilization and embryonic development among pregnant and nonpregnant cycles within groups A and B. The mean fertilization rate was 59% in the control group, compared with 62% in group A and 52% in group B. Overall, the pregnancy rate (PR) in IVF-ET cycles with positive sperm autoantibodies did not demonstrate a decreasing trend compared with controls. The PR per cycle, per oocyte retrieval, and per ET was higher in group A (47%, 50%, and 53%, respectively) compared with group B (32%, 33%, and 37%) and to controls (27%, 31%, and 34%). The implantation rate was lowest in the control group (10%) compared with the study groups (group A, 20% and group B, 14%). CONCLUSION: In vitro fertilization-embryo transfer is not significantly affected by the presence of sperm autoantibodies in female sera used to supplement the culture media or antibodies bound to inseminated sperm.

Effects of Ringer's lactate, Interceed(TC7) and Gore-Tex Surgical Membrane on postsurgical adhesion formation.

OBJECTIVE: To evaluate the effects of Ringer's lactate instillation, Interceed(TC7) (Johnson and Johnson Medical, Inc., New Brunswick NJ), and Gore-Tex Surgical Membrane (W. L. Gore and Associates, Inc., Flagstaff, AZ) in a rat uterine horn model. SETTING: Rats were in a conventional laboratory setting. PARTICIPANTS: Sprague-Dawley white rats, weighing 225 to 250 g. INTERVENTIONS: The left uterine horn was subjected to a standardized lesion by serosal denudation and devascularization. The rats were randomly assigned into control group, Interceed(TC7) group, Gore-Tex group, and Ringer's lactate group. MAIN OUTCOME MEASURES: Degree of adhesions was evaluated 2 weeks after the initial surgery. RESULTS: Adhesion score after Ringer's lactate instillation was significantly lower than those of control, Interceed(TC7), and Gore-Tex groups. Gore-Tex was associated with less adhesion formation than control. No difference was found in the adhesion formation between the Interceed(TC7) group and the control group. CONCLUSION: Confirming our previous observations, Ringer's lactate instillation is effective in decreasing adhesion formation. Gore-Tex reduces adhesion formation, but its efficacy is inferior to those of Ringer's lactate. Contrary to previous reports, Interceed(TC7) is ineffective in our animal model.