Aroldo F. Camargos

Detection of Chronic Endometritis by Diagnostic Hysteroscopy in Asymptomatic Infertile Patients

Chronic endometritis has been related to infertility and recurrent abortion. It is usually asymptomatic, and the diagnosis is rarely clinically suspected. We performed a prospective study to evaluate both the role of diagnostic hysteroscopy in the detection of chronic endometritis in infertile patients and Chlamydia trachomatis is a potential etiologic factor. Fifty consecutive patients who sought treatment for infertility in a tertiary academic hospital were submitted to diagnostic hysteroscopy and an endometrial biopsy for histopathological study and for diagnosis of C. trachomatis by polymerase chain reaction. The patients’ mean age was 33.7 ± (SD) 5.4 years, and the duration of the couples’ infertility ranged from 1 to 18 years. The overall prevalence of chronic endometritis was 12% (6 patients). Among all patients, no cases of chlamydial infection were detected by polymerase chain reaction. In the detection of chronic endometritis, with 95% confidence intervals, the hysteroscopy sensitivity was 16.7% (range 0.9–63,5%), the specificity was 93.2% (range 80.3–98.2%), the positive predictive value was 25% (range 1.3–78.1%), and the negative predictive value was 89.1% (range 65.6–95.9%). These data suggest that hysteroscopy is not useful in the screening for chronic endometritis in asymptomatic infertile women. Further studies are needed to establish the etiology of endometritis in infertile patients.

Activin, inhibin and the human breast.

Activins and inhibins are growth factors involved in cell differentiation and proliferation. Human breast tissues such as normal mammary tissue, fibroadenoma, and breast cancer express inhibin and activin mRNA and proteins. Activin A and its binding protein, follistatin, are also present in human milk during the first week of lactation. Using immunohistochemistry, we have observed that the inhibin/activin alpha, betaA, and betaB subunits are present in normal breast tissue regardless of menstrual cycle phase or menopause, as well as in fibrocystic disease, and breast tumors. The mRNAs encoding all three activin/inhibin subunits are expressed in breast carcinoma, fibroadenoma, and normal mammary tissue. The betaA subunit gene expression is higher in either local or metastatic breast carcinoma than in normal tissue. In addition, dimeric activin A is detectable in homogenates of breast cancer tissue at concentrations twice as high as in non-neoplastic adjoining tissue. Recent evidence suggests that some of the activin A produced by breast carcinoma is released into systemic circulation. In women with breast cancer, serum activin A levels are often elevated, and a significant decrease is observed in the first and second days following tumor excision. The role of activin and inhibin as endocrine and/or paracrine factors in the breast is still uncertain. Activin has complex effects on cell growth during branching morphogenesis, but it is generally considered as an inhibitor of cell proliferation as in vitro studies have shown that activin A treatment of breast cancer cells arrests cell growth. Inhibin is generally considered as a tumor suppressor, but its possible role in the breast is less understood.

Angiotensin-(1-7), its receptor Mas, and the angiotensin-converting enzyme type 2 are expressed in the human ovary

OBJECTIVE To investigate whether angiotensin (Ang)-(1-7), its receptor Mas, and angiotensin-converting enzyme type 2 (ACE2) are present in human ovary. DESIGN Cross-sectional study. SETTING Academic hospital. PATIENT(S) Twelve reproductive-age women and five postmenopausal women undergoing oophorectomy for nonovarian diseases and seven women having controlled ovarian hyperstimulation for IVF. INTERVENTION(S) Ovarian tissue was obtained from the reproductive-age women and postmenopausal women undergoing oophorectomy for nonovarian diseases. Follicular fluid (FF) samples were obtained from the women having controlled ovarian hyperstimulation for IVF. MAIN OUTCOME MEASURE(S) Localization of Ang-(1-7) and Mas by immunohistochemistry; measurement of Ang-(1-7) in ovarian FF by RIA; detection of messenger RNAs encoding Mas and ACE2 with use of real-time polymerase chain reaction; assessment of 125I-labeled Ang-(1-7) binding to ovarian sections with use of autoradiographic binding assay. RESULT(S) Angiotensin-(1-7) and the receptor Mas were localized to primordial, primary, secondary, and antral follicles, stroma, and corpora lutea of reproductive-age ovaries. Postmenopausal women expressed both the peptide and its receptor in the ovarian stroma. Angiotensin-(1-7) was detectable in FF (mean±SE: 191±54 pg/mL). Both Mas and ACE2 messenger RNAs were expressed in ovarian tissue, as revealed by real-time polymerase chain reaction, and ovarian binding sites for 125I-labeled Ang-(1-7) were identified by autoradiography. CONCLUSION(S) Angiotensin-(1-7), its receptor Mas, and ACE2 are expressed in the human ovary. The peptide is present in several ovarian compartments and can be quantified in FF.

Development and prevention of postsurgical adhesions in a chimeric mouse model of experimental endometriosis

OBJECTIVE To examine the impact of a recent surgery on development of endometriosis-related adhesions in a chimeric model and to determine the therapeutic efficacy of pioglitazone (PIO). DESIGN Human endometrial biopsies were maintained in E(2) with or without PIO for 24 h before intraperitoneal injection into immunocompromised mice also treated with or without PIO at multiple time points after peritoneal surgery. The presence and extent of adhesions were examined in animals relative to the initial establishment of experimental endometriosis. SETTING Medical school research center. PATIENT(S) Endometrial biopsies for experimental studies were provided by normally cycling women without a medical history indicative of endometriosis or adhesions. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Examination of the development of endometriosis-related adhesions in an experimental model. RESULT(S) Without therapeutic intervention, injection of E(2)-treated human endometrial tissue into mice near the time of peritoneal surgery resulted in multiple adhesions and extensive endometriotic-like disease. In contrast, PIO treatment reduced adhesive disease and experimental endometriosis related to surgical injury. CONCLUSION(S) The presence of human endometrial tissue fragments in the peritoneal cavity of mice with a recent surgical injury promoted development of both adhesive disease and experimental endometriosis. Targeting inflammation and angiogenesis with PIO therapy limited the development of postsurgical adhesions associated with ectopic endometrial growth.

A randomized prospective trial comparing the levonorgestrel-releasing intrauterine system with thermal balloon ablation for the treatment of heavy menstrual bleeding

BACKGROUND Use of the levonorgestrel-releasing intrauterine system (LNG-IUS) was compared with thermal balloon ablation (TBA) for the treatment of heavy menstrual bleeding (HMB). STUDY DESIGN A prospective randomized trial comparing the LNG-IUS (n=30 women) and TBA (n=28 women). RESULTS Hemoglobin levels increased (p<.001) and blood loss was reduced (p<.001) in both groups after 1 year of treatment. Menstrual bleeding was less in the LNG-IUS group compared to the TBA group at 6 and 12 months of treatment (p=.035 and p=.048, respectively). Intermenstrual bleeding was significantly less in the TBA group at 6 months compared to the LNG-IUS group (p=.044); however, there was no significant difference at 12 months (p=.129). No difference was found in psychological aspects between pre- and posttreatment variables in either of the groups (p=.537). CONCLUSIONS Both the LNG-IUS and TBA appear to be effective in controlling HMB; however, posttreatment uterine bleeding patterns are different.

Androgen receptor and 5α-reductase are expressed in pelvic endometriosis

The aim of this study was to evaluate whether androgen receptor (AR) and the enzymes that convert testosterone into the more potent androgen dihydrotestosterone, 5α‐reductases (5α‐R1 and 5α‐R2) are expressed in pelvic endometriosis. The study involved 21 infertile women who underwent laparoscopy and were divided into two groups: control (n= 13) and endometriosis (n= 8) according to the histological and laparoscopic findings. Endometrial and endometriotic implant biopsies were performed. By reverse transcription polymerase chain reaction and immunohistochemistry, AR, 5α‐R1 and 5α‐R2 messenger RNA and protein were detected in biopsies of pelvic endometriosis, as well as in the eutopic endometrium of both groups. These findings suggest that active androgens may be formed within the endometriotic tissue and that both local and systemic androgens have the potential to act on endometriotic cells.

Assessment of fertility protection and ovarian reserve with GnRH antagonist in rats undergoing chemotherapy with cyclophosphamide

BackgroundReproductive function following chemotherapy is of increasing importance given that survival rates are improving. We assessed whether a gonadotropin-releasing hormone antagonist (GnRHant; cetrorelix) could promote ovarian protection against damage due to chemotherapy.MethodsForty-two female Wistar rats were used in this study. Animals were divided into four groups: group I (n = 9) received placebo twice; group II (n = 12) received placebo + cyclophosphamide (CPA); group III (n = 12) received GnRHant + CPA; and group IV (n = 9) received GnRHant + placebo. After medication, the estrous cycle was studied through vaginal smears. Rats were mated, pregnancy was documented and the number of live pups evaluated. Afterwards, rat ovaries were removed and prepared for histological studies. The ovarian cross-sectional area was measured and follicles were counted.ResultsCyclic changes in vaginal smears were observed in all but one animal after treatment, but group II had a significantly lower rate of animals with proestrus or estrus (p < 0.01). The offspring was markedly reduced by CPA treatment (group II, 3.00 +/- 1.33 pups vs. group I, 11.44 +/- 0.78 pups, p < 0.01) and this effect was partly reversed by pre-treatment with GnRHant (group III, 7.00 +/- 1.31 pups). The ovarian cross-sectional area was not significantly different between groups, neither was the number of individual follicle types. However, rats in Group IV had a higher total number of ovarian follicles than those in the control group (17.1 +/- 1.22 vs. 10.9 +/- 0.70, p < 0.05).ConclusionThe use of a GnRHant before CPA chemotherapy provided protection of fertility.

Efficacy and tolerance of metronidazole and miconazole nitrate in treatment of vaginitis

To evaluate the efficacy and tolerability of a vaginal pessary containing 750 mg of metronidazole and 200 mg of miconazole nitrate used daily for 7 days in the treatment of vaginitis.

Expression of 17beta-hydroxysteroid dehydrogenase type 2 in pelvic endometriosis.

Lack of expression or a deficiency of 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2), a key enzyme in estradiol inactivation, could be involved in the pathophysiology of endometriosis. The aim of the present study was to evaluate expression of the gene (17β-Hsd2) encoding 17β-HSD2 in eutopic and ectopic endometrial tissues of women with endometriosis. Thirty-four infertile women were divided into a control group, without any clinical or laparoscopic evidence of endometriosis (n = 19), and a group with pelvic endometriosis (n = 15). Diagnosis was confirmed by histological examination of the endometriotic lesions. 17β-Hsd2 mRNA expression was detected by reverse transcription–polymerase chain reaction in the control group (54% of the samples), in the eutopic endometrium of patients with endometriosis (83% of the specimens analyzed) and in all endometriotic lesions. The semi-quantitative analysis of 17β-Hsd2 mRNA showed a significantly higher gene expression in the endometriotic implants compared with the intrauterine endometrium of the control group (p < 0.05). 17β-HSD2 protein was localized to the glandular epithelium of both eutopic endometrium and endometriotic implants. The present results refute the hypothesis of lower or absent 17β-HSD2 expression in pelvic endometriosis; therefore further studies are needed to assess other potential mechanisms leading to increased estrogenic activity within endometriotic implants.

Five-year follow-up of levonorgestrel-releasing intrauterine system versus thermal balloon ablation for the treatment of heavy menstrual bleeding: a randomized controlled trial

BACKGROUND The study was conducted to compare 5-year follow-up of levonorgestrel-releasing intrauterine system (LNG-IUS) or thermal balloon ablation (TBA) for the treatment of heavy menstrual bleeding (HMB). STUDY DESIGN A prospective, randomized controlled trial comparing LNG-IUS (n=30) and TBA (n=28) was performed. Hysterectomy rates, hemoglobin level, bleeding pattern, well-being status and satisfaction rates were assessed. Comparisons between groups were performed by χ(2) test and by unpaired and paired t tests. RESULTS After 5 years of follow-up, women treated with a TBA had higher rates of hysterectomy (24%) compared to the LNG-IUS group (3.7%) due to treatment failure (p=.039). Use of LNG-IUS resulted in higher mean hemoglobin (±SD) levels in comparison to the TBA group (14.1±0.3 vs 12.7±0.4 g/dL, p=.009). Menstrual blood loss was significantly higher in the TBA when compared to the LNG-IUS group (45.5% vs 0.0% p<.001). The psychological general well-being index scores were similar. Patient acceptability, perceived clinical improvement and overall satisfaction rates were significantly higher in women using LNG-IUS. CONCLUSION Five-year follow-up of HMB treatment with LNG-IUS was associated with higher efficacy and satisfaction ratings compared to TBA.