E-learning for research capacity strengthening in sexual and reproductive health: the experience of the Geneva Foundation for Medical Education and Research and the Department of Reproductive Health and Research, World Health Organization.

Technological advancement has resulted in the increasing use of e-learning and online education, initially in high-income countries and increasingly in low- and middle-income countries. BACKGROUND: In 2010, the Geneva Foundation for Medical Education and Research, in collaboration with the World Health Organization and partner institutions, developed an online postgraduate course "From Research to Practice: Training Course in Sexual and Reproductive Health Research". This course takes advantage of the advancing Internet technology to provide training opportunities to health professionals mostly from low- and middle-income countries whose access to quality education is constrained by time, financial resources, or both. CASE PRESENTATION: To assess the outcomes of the course, an evaluation was conducted by sending a self-administered questionnaire to graduates of the 2010-2012 programme. The objectives were to determine if the graduates had applied the knowledge gained from the course to their work and whether they had implemented their research project developed during the course. The evaluation also appraised the number of graduates who participated in the design or implementation of a new research project since the course concluded and whether the course had contributed to advancement in their careers. A total of 175 of 219 course graduates answered the questionnaire. The evaluation revealed that the majority of respondents (98%) had utilized the knowledge acquired, with nearly half of them (47%) having published a scientific paper as author or co-author. About a third of respondents (39%) had implemented their course research project and about three quarters of them (74%) have been involved in the design or implementation of a research project after completing the course. Over three quarters (81%) of respondents opined that the course had contributed to their career advancement and almost half of them (46%) had a career promotion as a direct or indirect benefit of the course. CONCLUSION: We surmise that the course positively impacted the participants' knowledge and understanding of sexual and reproductive health, which they applied in their professional work, as well as strengthened their research capacity. Success factors for the e-learning programme include tailor-made content to meet participants' needs, flexibility of access, and ongoing engagement/personal interactivity with course coaches.

Web-based instrument to assess skills in visual inspection of the cervix among healthcare providers.

OBJECTIVE: To validate a web-based instrument for assessing healthcare providers' skills in visual inspection with acetic acid or Lugol iodine (VIA/VILI) for the diagnosis and management of cervical intraepithelial neoplasia. METHODS: An observational cross-sectional study enrolled healthcare providers in a web-based assessment of VIA/VILI skills between August and November 2014. Participants participated in a four-module training course, followed by a multiple-choice test with 70 questions based on cervical photographs of HPV-positive women participating in cervical screening. Logistic regression was used to identify relationships between independent variables and success on the test. RESULTS: Overall, 255 participants completed the test and 99 (38.8%) passed. No correlation was found between age or sex and test performance. Compared with other healthcare workers, physicians (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.01-3.63; P=0.048), and participants with more colposcopy experience (OR 3.62, 95% CI 1.91-6.85; P<0.001) and postgraduate VIA/VILI training (OR 1.95, 95% CI 1.16-3.29; P=0.012) were more likely to pass the test. Participants who repeated the test (31/255 [12.2%]) were five times more likely to succeed on their second repeat (OR 5.89, 95% CI 1.46-23.73; P=0.013). CONCLUSION: Web-based training for VIA/VILI is feasible and can identify healthcare workers who are proficient in this technique.

Medical methods for first trimester abortion.

BACKGROUND: Surgical abortion by vacuum aspiration or dilatation and curettage has been the method of choice for early pregnancy termination since the 1960s. Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostaglandins in the early 1970s and anti-progesterones in the 1980s. The most widely researched drugs are prostaglandins (PGs) alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins and methotrexate with prostaglandins. OBJECTIVES: To compare different medical methods for first trimester abortion. SEARCH METHODS: The Cochrane Controlled Trials Register, MEDLINE and Popline were systematically searched. Reference lists of retrieved papers were also searched. Experts in WHO/HRP were contacted. SELECTION CRITERIA: Types of studies Randomised controlled trials comparing different medical methods for abortion during first trimester (e.g. single drug, combination) were considered. Trials were assessed and included if they had adequate concealment of allocation, randomisation procedure and follow-up. Women, pregnant during the first trimester, undergoing medical abortion were the participants. The outcomes were mortality, failure to achieve complete abortion, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the procedure. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion from the results of the search strategy described previously.The selection of trials for inclusion in the review was performed independently by two reviewers after employing the search strategy described previously. Trials under consideration were evaluated for appropriateness for inclusion and methodological quality without consideration of their results. Data were processed using Revman software. MAIN RESULTS: Fifty-eight trials were included in the review. The effectiveness outcomes below refer to 'failure to achieve complete abortion' with the intended method unless otherwise stated. 1) Combined regimen mifepristone/prostaglandin: Mifepristone 600 mg compared to 200 mg shows similar effectiveness in achieving complete abortion (4 trials, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol administered orally is less effective (more failures) than the vaginal route (RR 3.00, 95% CI 1.44 to 6.24) and may be associated with more frequent side effects such as nausea and diarrhoea. Sublingual and buccal routes were similarly effective compared to the vaginal route, but had higher rates of side effects. 2) Mifepristone alone is less effective when compared to the combined regimen mifepristone/prostaglandin (RR 3.76 95% CI 2.30 to 6.15). 3) Five trials compared prostaglandin alone to the combined regimen (mifepristone/prostaglandin). All but one reported higher effectiveness with the combined regimen. The results of these studies could not be combined but the RR of failure with prostaglandin alone is reportedly between 1.4 to 3.75 with the 95% confidence intervals indicating statistical significance. 4) In one trial comparing gemeprost 0.5 mg with misoprostol 800 mcg, misoprostol was more effective (failure with gemeprost: RR 2.86, 95% CI 1.14 to 7.18). 5) There was no difference in effectiveness with use of a divided dose compared to a single dose of prostaglandin. 6) Combined regimen methotrexate/prostaglandin demonstrates similar rates of failure to complete abortion when comparing intramuscular to oral methotrexate administration (RR 2.04, 95% CI 0.51 to 8.07). Similarly, day 3 vs. day 5 administration of prostaglandin following methotrexate administration showed no significant differences (RR 0.72, 95% CI 0.36 to 1.43). One trial compared the effect of tamoxifen vs. methotrexate and no statistically significant differences were observed in effectiveness between the groups. AUTHORS' CONCLUSIONS: Safe and effective medical abortion methods are available. Combined regimens are more effective than single agents. In the combined regimen, the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness. Vaginal misoprostol is more effective than oral administration, and has less side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all trials were conducted in settings with good access to emergency services, which may limit the generalizability of these results.

Early and late half-life of human chorionic gonadotropin as a predictor of persistent trophoblast after laparoscopic conservative surgery for tubal pregnancy.

BACKGROUND: To determine if the early or late half-lives (T0.5) of human chorionic gonadotropin (hCG) can identify patients with persistent trophoblastic activity after conservative surgery for tubal pregnancy. DESIGN: Prospective cohort study. SETTING: Department of obstetrics and gynecology of a university hospital. METHODS: All patients with a tubal pregnancy treated by laparoscopic salpingostomy between June 1997 and September 2000 were enrolled in the study. Postoperative sequential hCG sampling was performed at days 0, 2 (+/- 1) and 7 (+/- 2) and followed until levels were undetectable. Taking the biexponential hCG declining curve as a model, we calculated the early (days 0-2) and late (days 2-7) T0.5 hCG values. MAIN OUTCOME MEASURE: To assess success or failure of surgical treatment. RESULTS: Seventy-three patients with an ectopic pregnancy were managed by conservative surgery. Early and late T0.5 allowed us to identify 2/10 and 9/10 women, respectively, with persistent trophoblast. Late T0.5 levels revealed two patients with false-positive values, but one patient showed a secondary increase in hCG after day 7 (false-negative) despite a normal late T0.5. CONCLUSIONS: Early and late half-lives of hCG do not identify all women at risk for persistent ectopic pregnancy. To exclude persistent trophoblast, postoperative serum hCG determination should be performed until levels are undetectable.

Contraceptive practice before and after termination of pregnancy: a prospective study.

This study is part of a larger prospective research program focusing on termination of pregnancy (TOP). One hundred and three women requesting TOP were interviewed before the intervention and 6 months later using open and closed questions and psychological tests. This paper focuses on contraceptive practices before and after abortion. The analysis took into account specific aspects of contraceptive practices and patients' behaviors. The aims were to assess: the level of women's knowledge and practice of contraception at the time of request for a TOP; the behavioral modifications following professional counseling 6 months after TOP; the influence of psychological and sexual factors, and those linked to the women's use of contraception. Most women (n = 101) had already used recommended contraception. During the cycle that had resulted in pregnancy, more than half (n = 58) had used recommended contraception and one third had not used any contraception. Six months later, 86 women used recommended contraception, and 17 did not. The majority of women reported changes in their contraceptive methods (n = 82). Most changes were within recommended methods. The women (n = 10) who continued to practice unprotected intercourse post-TOP were slightly older, satisfied with their sexual relations with their partner, often involved in a long-term and good relationship. During post-TOP period, it is essential to take into account the psychological dynamics involved in the choice of contraceptive methods. Counseling should emphasize not only protection against an unwanted pregnancy but also protection against sexually transmitted diseases, which is often perceived as a less important issue following TOP.

Feasibility of cytology-based cervical cancer screening in rural Cameroon.

OBJECTIVE: To determine the prevalence of cervical cancer and its precursors in a rural population in Cameroon and to evaluate the feasibility of a cytology-based screening program in such areas. STUDY DESIGN: A prospective study was conducted in the rural town of Bafang. Following an advocacy campaign, 750 women were recruited. After a clinical examination, all women had a Pap smear with the Cervex Brush. Each sample had two preparations, conventional and liquid based. The conventional smears were interpreted in Bafang. Cytologically abnormal cases, those with clinical inflammation and/or macroscopic cervical lesions, had a colposcopic examination and directed biopsy. HSIL and colposcopically abnormal cases were treated with large loop excision of the transformation zone (LLETZ). The liquid-based preparations and histopathology were performed in Geneva and the results sent to Cameroon for patient follow-up. RESULTS: Mean age and parity of the women screened were 43.7 years and 7.8, respectively. The conventional smears showed 3.6% cervical abnormalities: 2% (15/740) ASCUS/LSIL and 1.6% (12/740) HSIL. The liquid-based preparations showed 12.6% (91/722) cervical abnormalities: 10.1% (73/722) ASCUS/LSIL and 2.5% (18/722) HSIL. Fifty percent of samples in both preparations showed evidence of inflammation. Histology was performed on 64 colposcopically directed punch biopsies and LLETZ specimens. The histologic diagnoses agreed with the cytologic findings in 60% (14/23) of conventional smears and 85% (12/14) of liquid-based preparations. CONCLUSION: There is a high rate of cervical intraepithelial neoplasia in the unscreened rural population of Cameroon. The situation is complicated by a high rate of cervical infection. A population-based cytologic screening program for cervical cancer would not be feasible in rural Cameroon because of high cost, low quality and limited technical facilities. Rural Africa requires an algorithm using a simple, low-cost technique of mass screening and an improved cytology service only to triage selected patients.

Are fertility drugs a risk factor for persistent trophoblastic tumour?

BACKGROUND: The introduction of ovulation-inducing drugs has raised concern that women exposed to these therapies may be at increased risk of cancer. We assessed the potential association between exposure to fertility drugs and the risk of developing persistent trophoblastic tumour (PTT). METHODS: We conducted a systematic review of the English and non-English language literature using the National Library of Medicine's Medline to identify all observations of patients with hydatidiform mole (HM) after treatment with ovulation-inducers. RESULTS: Fifty-two cases were considered including 26 singleton molar pregnancies and 26 multiple molar pregnancies consisting of an HM and one or more co-existent fetus(es) (HM-and-CF). PTT occurred in 15% of patients with singleton HM and in 42% of patients with HM-and-CF, 15% of whom had a metastatic disease. Of those patients with HM-and-CF, 16 patients delivered at <24 weeks gestation, mostly because of vaginal haemorrhage. Ten patients delivered at > or = 24 weeks of gestation, six of whom (25%) had a normal live child. These results are similar to spontaneously conceived pregnancies. CONCLUSIONS: Although women having an HM after therapy with ovulation-inducing drugs seem to have no added risk of PTT, multiple pregnancies are more likely to occur, and the overall risk may be increased.

Matrix metalloproteinases and their specific tissue inhibitors in menstruation.

The timely breakdown of extracellular matrix is essential for menstruation. Matrix metalloproteinases, which are able to degrade virtually all components of the extracellular matrix, are spatiotemporally expressed in the cyclic endometrium. The expression of most matrix metalloproteinases is regulated transcriptionally and their proteolytic activities are precisely controlled. The balance between matrix metalloproteinases and their specific tissue inhibitors is believed to be crucial for menstruation. This review focuses on the roles of matrix metalloproteinases and their tissue inhibitors in the initiation of menstruation and on the regulation of matrix metalloproteinase expression and activation. For example, the function of matrix metalloproteinases and their tissue inhibitors in endometrial re-epithelialization and angiogenesis during endometrial regeneration, when cell migration is facilitated to ensure endometrial repair, is discussed. This and other processes, although not fully resolved, serve to illustrate the involvement of matrix metalloproteinases and their tissue inhibitors in the process of menstruation.

Intraperitoneal photodynamic therapy in the Fischer 344 rat using 5-aminolevulinic acid and violet laser light: a toxicity study.

OBJECTIVE: Our study was designed to investigate 5-aminolevulinic acid (ALA) as a candidate for intraperitoneal photodynamic therapy (IP-PDT). The toxicity of IP-PDT and the effects of IP-PDT on abdominal and pelvic organs, particularly the small intestine, were investigated after ALA administration and illumination with violet laser light. STUDY DESIGN AND RESULTS: The toxicity of IP-PDT was evaluated in Fischer 344 rats in two ways. In the first part of the study local PDT effects on the intestine were analyzed histologically. Violet laser light (lambda: 406-415 nm) was applied as a 2 cm diameter spot on the intestine 3 h after intraperitoneal (i.p.) administration of 50 mg/kg ALA. (A) Histological tissue samples were taken 0 min, 6 h and 1, 2 and 3 days after treatment (optical dose 3.2 J/cm(2)). Immediately after local PDT (3.2 J/cm(2), 50 mg/kg ALA) showed no effect on the intestine. However, 6 h post PDT there was complete destruction of the mesothelial lining and the outer (longitudinal) smooth muscle. Ganglion cells of the myenteric (Auerbach) plexus were also destroyed. The inner circular smooth muscle, the muscularis mucosa and the lamina propria were unharmed. Marked lymphectasia was present at this time. (B) To determine the threshold light dose of tissue destruction caused by PDT, different optical doses (1.6, 3.2, 6.4 J/cm(2)) were administered and histologic analysis of tissue samples were obtained 1 day post treatment. Destruction of the entire external musculature, submucosal structures and muscularis mucosa of the intestine at the illumination site could be observed above 1.6 J/cm(2) (50 mg/kg ALA). In the second part of the study whole peritoneal cavity PDT (WPC-PDT) was performed by illumination of the whole peritoneal cavity with 1.6 J/cm(2) violet light 3 h after ALA administration using different drug doses (200, 100 and 50 mg/kg). WPC-PDT showed lethal toxicity with a drug dose above 50 mg/kg ALA at 1.6 J/cm(2). The probable cause of death in the first 3 days after IP-PDT was rhabdomyolysis, whereas when death occurred at longer time intervals, megaintestine associated with significant damage could be observed; however, without perforation of the intestinal wall. CONCLUSION: In rats WPC-PDT with 50 mg/kg ALA, 1.6 J/cm2 at lambda=415 nm was the maximum tolerable light dose. This dose is likely to be above the threshold of destruction of ovarian cancer micrometastasis.

Effect of hydrosalpinx fluid on secretion of trophoblastic matrix metalloproteinases.

OBJECTIVE: To determine if hydrosalpinx fluid affects trophoblastic metalloproteinases (MMPs) secretion. DESIGN: Measurement of the effect of hydrosalpinx and peritoneal fluids (as controls) added to the medium on the MMPs secreted by cytotrophoblastic cells. SETTING: Academic research center. PATIENT(S): Five samples of hydrosalpinx fluid were obtained at the time of ovocyte retrieval. Three samples of peritoneal fluids were collected at laparoscopic sterilization. MAIN OUTCOME MEASURE(S): The concentration and activity of MMP-2 and MMP-9, the concentration of the tissue inhibitor of metalloproteinases (TIMP-1), and the total gelatinolytic activity of the cytotrophoblastic cells were measured in the culture medium. RESULT(S): Hydrosalpinx significantly stimulated MMP-2, MMP-9, and TIMP-1. The net result was a significant stimulation of the total gelatinolytic activity. Peritoneal fluids increased MMP-2, MMP-9, and TIMP-1 concentrations, but the total gelatinolytic activity was not modified. CONCLUSION(S): In contrast to peritoneal fluids, hydrosalpinx stimulates the total gelatinolytic activity of cytotrophoblastic cells. This might indicate that the effect of hydrosalpinx on implantation rates may not be due to an inhibition of the capacity of an embryo to invade the endometrium. However, the stimulatory effect of hydrosalpinx on the net gelatinolytic activity could partly explain the increased incidence of ectopic pregnancies that have been described in the presence of hydrosalpinx.

Use of automated primary screening on liquid-based, thin-layer preparations.

OBJECTIVE: To evaluate the accuracy of the AutoPap System (TriPath Imaging, Inc., Burlington, North Carolina, U.S.A.) (TriPath) in screening AutoCyte PREP liquid-based, thin-layer preparations by comparing the final cytologic diagnoses with instrument slide classification results. STUDY DESIGN: A total of 9,665 AutoCyte PREP thin-layer slides were first independently screened to establish a final cytologic diagnosis (reference diagnosis). The slides were then processed on the AutoPap System. Each slide successfully processed was reported into result categories. The generated report gave a ranking score for each slide designated for "review." Slides designated "no further review" (NFR) were also listed in the report. The reported results were then compared to the reference cytologic diagnoses. RESULTS: Of 9,665 slides initially submitted to the AutoPap, 8,688 (90.8%) were qualified for scanning, and 884 (9.2%) were definitely classified as process review or rerun and excluded from the study. Of high grade squamous intraepithelial lesions and greater (HSIL+), 85.2% were ranked in the first rank, 12.7% in the second, one (2.1%) in the third, none in the fourth and fifth and none in the NFR category. Of low grade squamous intraepithelial lesions, 47.4% were ranked in the first rank, 20.8% in the second, 10.6% in the third, 10.1% in the fourth, 5.3% in the fifth and 5.8% in NFR. Of atypical squamous cells of undetermined significance and atypical glandular cells of undetermined significance, 53.6% were ranked in the first rank, 22.5% in the second, 12.4% in the third, 5.4% in the fourth, 3.8% in the fifth and 2.3% in NFR. Considering a cutoff value at < or = 3rd rank, 84% of cervical abnormalities (RR 6.52, 95% CI 4.96-8.66) and 100% of HSIL+ were identified. CONCLUSION: The AutoPap demonstrates a high capability for detecting cervical abnormalities on AutoCyte PREP thin-layer slides. HSIL+ was associated with the highest instrument scores.

Termination of pregnancy and women's sexuality.

OBJECTIVE: To determine the influence of termination of pregnancy (TOP) on women's sexuality. DESIGN: Prospective qualitative and quantitative study. SUBJECTS: 103 women undergoing induced abortion by vacuum aspiration, interviewed 1-3 weeks before surgery and 6 months later. RESULTS: After TOP, patients described symptoms of fatigue (39%), feelings of guilt (35%), sadness (34%) and anxiety (29%). Thirty-one percent of women presented at least one sexual dysfunction, 18% a decrease in sexual desire, 17% orgasmic disorders, 12% vaginal dryness and 11% dyspareunia. These sexual dysfunctions were correlated with anxiety and symptoms of depression following TOP. Six months after TOP, 57% of the women reported no change in their sexual satisfaction, 17% were 'more satisfied' and 7% 'less satisfied'. Lessening of sexual satisfaction after TOP was correlated with diminished partner satisfaction (p < 0.00001), fatigue (p < 0.0009), feelings of guilt (p < 0.01), low frequency of sexual relations (p < 0.01) and anxiety over sexual relations (p < 0.02). CONCLUSIONS: Six months after TOP some women presented persisting sexual dysfunction. This sexual dysfunction may be explained essentially by the appearance of symptoms of anxiety and depression following TOP. When the quality of the relationship was satisfying, women could cope more easily with the appearance of a sexual dysfunction.

Accuracy of single measurements of pregnancy-associated plasma protein-A, human chorionic gonadotropin and progesterone in the diagnosis of early pregnancy failure.

BACKGROUND: Circulating human chorionic gonadotropin (hCG) and progesterone are commonly used as markers of abnormal pregnancies. Previous studies have shown that pregnancy-associated plasma protein-A (PAPP-A) was also depressed in extrauterine pregnancies (EUP). Previously, PAPP-A was measured with polyclonal antibodies which were later shown to recognise also the pro-form of major basic protein (pro-MBP). OBJECTIVE: To evaluate the clinical usefulness of PAPP-A measurements in early pregnancy. STUDY DESIGN: Circulating PAPP-A, hCG and progesterone were measured in patients with EUP (n=68), abnormal intrauterine pregnancies (abIUP, n=31) and normal intrauterine pregnancies (nIUP, n=72). Gestational age was 30-70 days from the last menstruation. RESULTS: For PAPP-A and hCG, a steep increase was observed from day 30 after last menstrual period onwards, this increase being much less important for abIUP and EUP. The values of PAPP-A and hCG were significantly decreased in abIUP and EUP, from 42 days after LMP onwards. There were no significant differences between abIUP and EUP. Progesterone concentration does not vary with amenorrhoea and was significantly lower in abIUP and EUP. Values in abIUP were significantly (P=0.02) lower compared with EUP for amenorrhoea above 42 days. ROC curves were constructed for amenorrhoea above 42 days. For a specificity of 99%, the sensitivity of PAPP-A, hCG and progesterone were 64.5, 93.3 and 76%, respectively. The threshold values were 14.3mIU/l, 10,400IU/l and 10.1ng/ml for PAPP-A, hCG and progesterone. CONCLUSION: We confirm the decrease of PAPP-A concentrations in pregnancy failure, but hCG and progesterone remain the best clinical tools.