Pharmacist recommendations for emergency contraception in Belgium: a simulated user study.

BACKGROUND: Emergency contraception reduces the risk of unintended pregnancy, after unprotected sexual intercourse or contraceptive failure. In Belgium, emergency contraception is available without a prescription and pharmacists play therefore a crucial role in dispensing emergency contraception. AIM: This study assesses the dispensing practices of emergency contraception by pharmacists in two regions of Belgium. METHOD AND DESIGN: Simulated patient study, using a predefined scenario, evaluating a request for emergency contraception. The scenario involves a 25-year-old woman not using contraception, who had unprotected sexual intercourse 84 h (3.5 days) ago. Her last menstrual period was 10 days ago. POPULATION: 260 pharmacies were randomly selected. Principal outcome: proportion of pharmacists who deliver the adequate emergency contraception. We considered the following responses as adequate: Prescribing ulipristal acetate or redirecting to another pharmacy, in case of unavailability, or referring for a copper IUD. RESULTS: We analysed the data obtained in 216 pharmacies (216/260 = 83.1%). In 64% of cases, adequate dispensing of emergency contraception (dispensing of ulipristal acetate or referral for intrauterine device insertion) occurred. There was an association between correct dispensing and asking appropriate questions, such as the date of the last menstrual period and the date of the risky sexual intercourse. CONCLUSION: More than one-third of visited pharmacies did not distribute appropriate emergency contraception, underlining the need for improvement. We hypothesise that this may be achieved with appropriate training, use a dispensing checklist.

We assesses the dispensing of emergency contraception by pharmacists using a simulated patient. More than one-third of visited pharmacies did not distribute appropriate emergency contraception, underlining the need for improvement.

Rarity of fetal cells in exocervical samples for noninvasive prenatal diagnosis.

OBJECTIVES: The possibility to isolate fetal cells from pregnant women cervical samples has been discussed for five decades but is not currently applied in clinical practice. This study aimed at offering prenatal genetic diagnosis from fetal cells obtained through noninvasive exocervical sampling and immuno-sorted based on expression of HLA-G. METHODS: We first developed and validated robust protocols for cell detection and isolation on control cell lines expressing (JEG-3) or not (JAR) the HLA-G antigen, a specific marker for extravillous trophoblasts. We then applied these protocols to noninvasive exocervical samples collected from pregnant women between 6 and 14 weeks of gestational age. Sampling was performed through insertion and rotation of a brush at the ectocervix close to the external os of the endocervical canal. Finally, we attempted to detect and quantify trophoblasts in exocervical samples from pregnant women by ddPCR targeting the male SRY locus. RESULTS: For immunohistochemistry, a strong specific signal for HLA-G was observed in the positive control cell line and for rare cells in exocervical samples, but only in non-fixative conditions. HLA-G positive cells diluted in HLA-G negative cells were isolated by flow cytometry or magnetic cell sorting. However, no HLA-G positive cells could be recovered from exocervical samples. SRY gene was detected by ddPCR in exocervical samples from male (50%) but also female (27%) pregnancies. CONCLUSIONS: Our data suggest that trophoblasts are too rarely and inconstantly present in noninvasive exocervical samples to be reliably retrieved by standard immunoisolation techniques and therefore cannot replace the current practice for prenatal screening and diagnosis.

Impact of Covid-lockdown on abortion management at a family planning in Brussels.

INTRODUCTION: In response to the Covid-19 lockdown, we developed a new abortion protocol in a family planning in Brussels. This study evaluates the effects of the lockdown on the abortion management and its impact on patients' characteristics. METHODS: A retrospective study compared the characteristics and management of patients who terminated their pregnancies at the same family planning (CHU Saint-Pierre Brussels) between 14 March and 6 May 2020 and during the same time period in 2019. RESULTS: Patients having an abortion in 2020 (n = 87) were in average two years older compared to patients having abortions in 2019 (n = 93) (31 years ± 13 vs 29 years ± 13 p < .011), the number of abortions was similar to those of previous years, and the characteristics of the population were identical. The management of abortions has changed significantly as the patients terminated their pregnancies earlier in 2020 than in 2019 (7 W and 1 day ± 3 days versus 8 W and 5 days ± 3 days p < .01), mostly with medication and at home (61.4% versus 2% p < .001), but with similar effectiveness. CONCLUSION: Due to the lockdown, we have accelerated the time required to obtain an appointment and shortened the delay between the abortion request and the pregnancy termination, permitting an earlier management mainly through the use of medical- and at home abortion. Given the satisfactory results, we consider now to implement this new protocol beyond the lockdown period.

Should the management of high grade cervical squamous intraepithelial lesion (HSIL) be different in HIV-positive women?

BACKGROUND: This study compares the management and outcome of high grade squamous intraepithelial lesions (HSIL) in HIV-positive and -negative women and identifies risk factors for treatment failure. METHODS: This retrospective, controlled study includes 146 HIV-positive women, matched for HSIL, age and year of diagnosis, with 146 HIV-negative women. Differences were analysed using parametric and non-parametric tests and Kaplan-Meier survival curves. A binary logistic regression was used to assess risk factors for treatment failure. RESULTS: Persistence of cervical disease was observed most frequently in HIV-positive women (42 versus 17%) (p < 0.001) and the cone biopsy margins were more often invaded in HIV-positive-women than in HIV-negative ones. (37 versus 16%; p < 0.05). HIV-positive women, with successful cervical treatment had better HIV disease control: with significantly longer periods of undetectable HIV viral loads (VL) (19 versus 5 months; p < 0.001) and higher CD4 counts (491 versus 320 cells/mm3; p < 0.001). HIV-positive women with detectable VL at the time of dysplasia had 3.5 times (95% IC: 1.5-8.3) increased risk of treatment failure. Being treated through ablative therapy was associated with a 7.4, four-fold (95% IC: 3.2-17.3) increased risk of treatment failure compared to conization CONCLUSION: HIV-positive women have a higher risk of treatment failure of HSIL than do HIV-negative women, especially when ablative therapy is used and in women with poor control of their HIV infection. The management and the follow- up of HSIL's guidelines in this high-risk population should be adapted consequently: for HIV-positive women with uncontrolled viral load, excisional treatment should be the preferred therapy, whereas for women with undetectable viral load, CD4 + lymphocytes higher than 500 cells/mm3 and with a desire of pregnancy, ablative therapy may be considered.

In vitro fertilization for women infected by hepatitis C virus: a matched case-control study and a systematic literature review.

PURPOSE: The aim of this study was to investigate whether infection of women by the hepatitis C virus (HCV) reduces the chance of conceiving after in vitro fertilization (IVF). METHODS: We performed a retrospective blind matched case-control study where IVF outcomes for the first 37 cycles of HCV sero-positive women were compared to those of 107 cycles of an uninfected control group. Our results were included in a systematic literature review. RESULTS: Out of five eligible studies, ours included, three observed an impact of HCV infection, though at various levels including response to stimulation, fertilization, implantation, and pregnancy rates. Two studies differentiated results for patients with confirmed active viral replication. Matching criteria and populations studied varied between studies. CONCLUSIONS: More and larger studies with well-defined groups are needed to clarify the eventual impact of the HCV on IVF outcomes. Data concerning the infectious status of a patient as well as her health state should be systematically recorded. A multi-disciplinary approach as well as a thorough knowledge of the patient's general health state might prove useful in the management and counseling of these patients in terms of success in conceiving.

In vitro fertilization when men, women, or both partners are positive for HIV: a case-control study.

PURPOSE: The aim of this study was to compare the outcomes of in vitro fertilization (IVF) for couples where one or both partners were positive for the human immunodeficiency virus (HIV) to matched control couples. METHODS: A matched case-control retrospective study was performed. Data for 104 couples where the woman was HIV-positive; for 90 couples where the man was HIV-positive; and for 33 couples where both partners were HIV-positive were prospectively analyzed in comparison to matched controls treated in our center during the same period. The main outcomes were clinical pregnancy and live birth rates. RESULTS: For couples involving an HIV-positive man, clinical outcomes were comparable to controls and resulted in the birth of 18 healthy babies after 90 cycles. When the woman was affected, cycle cancelation, number of retrieved oocytes, and on-going clinical pregnancy rates per transfer were statistically reduced. Implantation rates were comparable to those of non-affected controls. Seven healthy babies for 104 cycles were obtained. For a couple in which both partners were HIV-positive, only one healthy birth occurred after 33 cycles. Pregnancy rates were systematically reduced though not significantly probably due to sample size. CONCLUSIONS: Our data suggest that IVF outcomes were similar to controls when men were HIV-positive and remain acceptable when women were HIV-positive. IVF outcomes were severely reduced in our sero-concordant couples; however, many patients had severe HIV disease previously, and therefore, these results should be reassessed in patients treated early in their disease.

The use of selective progestin receptor modulators (SPRMs) and more specifically ulipristal acetate in the practice of gynaecology.

This review discusses the development of selective progestin receptor modulators (SPRMs) for use in women's health and specifically the use of ulipristal acetate (UPA) as emergency contraception (EC) and as a treatment for symptomatic fibroids in women who want to preserve their fertility or avoid a hysterectomy. As an EC, UPA 30 mg should be recommended for women, within 102 h of unprotected intercourse. As a treatment of fibroids, UPA (5 mg daily dose) should be administered for periods of three months as a pre-surgical strategy, reducing bleeding and fibroid size and facilitating surgery. A proportion of these patients may even avoid surgery. Future developments will demonstrate whether UPA can be used for other indications such as endometriosis and breast cancer prevention or treatment.

Sustained viral suppression and higher CD4+ T-cell count reduces the risk of persistent cervical high-risk human papillomavirus infection in HIV-positive women.

BACKGROUND: Studies analyzing the impact of combination antiretroviral therapy (cART) on cervical infection with high-risk human papillomavirus (HR-HPV) have generated conflicting results. We assessed the long-term impact of cART on persistent cervical HR-HPV infection in a very large cohort of 652 women who underwent follow-up of HIV infection for a median duration of 104 months. METHODS: Prospective cohort of HIV-infected women undergoing HIV infection follow-up who had HR-HPV screening and cytology by Papanicolaou smear performed yearly between 2002 and 2011. RESULTS: At baseline, the median age was 38 years, the race/ethnic origin was sub-Sarahan Africa for 84%, the median CD4(+) T-cell count was 426 cells/µL, 79% were receiving cART, and the HR-HPV prevalence was 43%. The median interval of having had an HIV load of <50 copies/mL was 40.6 months at the time of a HR-HPV-negative test result, compared with 17 months at the time of a HR-HPV-positive test result (P < .0001, by univariate analysis). The median interval of having had a CD4(+) T-cell count of >500 cells/µL was 18.4 months at the time of a HR-HPV-negative test result, compared with 4.45 months at the time of a HR-HPV-positive test result (P < .0001). In multivariate analysis, having had an HIV load of <50 copies/mL for >40 months (odds ratio [OR], 0.81; 95% confidence interval [CI], .76-.86; P < .0001) and having had a CD4(+) T-cell count of >500 cells/µL for >18 months (OR, 0.88; 95% CI, .82-.94; P = .0002) were associated with a significantly decreased risk of HR-HPV infection. CONCLUSION: Sustained HIV suppression for >40 months and a sustained CD4(+) T-cell count of >500 cells/µL for >18 months are independently and significantly associated with a decreased risk of persistent cervical HR-HPV infection.

An audit about labour induction, using prostaglandin, in women with a scarred uterus.

OBJECTIVES: Induction of labour after a previous caesarean section is still controversial. We aim to analyse, in a population of women who have a uterine scar, the maternal, foetal and neonatal complications in relation to the mode of labour and delivery. STUDY DESIGN: Retrospective analysis of collected data from all the singleton deliveries of patients with a scarred uterus (N=798), admitted to the hospital between August 2006 and March 2009. OUTCOMES: maternal and perinatal complications. RESULTS: Among 798 singleton deliveries, 36.1% had a spontaneous labour, 12.6% a prostaglandin-induced labour and 2.9% an ocytocin-induced labour, and 48.4% had an elective caesarean section. The chance of delivering vaginally was respectively 84.4% for those who had a spontaneous labour, 75.2% for those who were induced using prostaglandin, 82.6% after induction using ocytocin. There were eight uterine ruptures, four after spontaneous labour (1.4%), two after prostaglandin induction (2%) and two at the time of an iterative caesarean section (0.5%). There were no differences between groups, except the risk of haemorrhage (17.4% after spontaneously induced labour, 34.8% after ocytocin, 17.8% after prostaglandin and 44.6% after iterative caesarean section; p<0.005) and the neonatal admissions when analysed by intention to treat only (8.3% after spontaneously induced labour, 9.1% after ocytocin, 12% after prostaglandin and 16.8% after iterative caesarean section; p<0.009). CONCLUSION: Although no increase in maternal or perinatal outcome was observed in relation to prostaglandin-induced labour after caesarean section, this study is too underpowered to exclude an increased risk.

HPV genotyping in biopsies of HSIL and invasive cervical cancers in women living with HIV: A cohort- and a nested -case control study.

OBJECTIVE: To characterize HPV genotype distribution in HSIL and ICC- biopsies, of WLWH, in Europe, as compared to HIV-negative women. DESIGN: Cohort- and nested -case control study. METHOD: We characterized HPV genotype distribution by performing PCR on HSIL and ICC biopsies from WLWH (n = 170); 85 cases were compared to 85 HIV-negative matched controls. The proportion of patients that might be protected by HPV vaccines was estimated. RESULTS: Among WLWH (median age 36 years-old, median duration of HIV infection 70,5 months, 79% under cART): the most frequently detected HPV were HPV16 (30%), HPV35 (16%), HPV58 (14,7%), HPV31 (13,5%), and HPV52 (11,7%). HPV16 was less frequently found in WLWH, originating from Central Africa (20,5%) compared to other African regions (35,5%) (p = 0,05) or world regions (38,8%) (p = 0,007). Multiple versus single high-risk HPV infections were associated with younger age (≤35 years)(odds ratio (OR) 2,65 (95%IC: 1,3-5,2,p = 0,002), lymphocyte CD4 count < 350 cells / µL (OR 2,7 (95%IC: 2-8,5; p = 0,005), use of cART for < 18 month OR 2,2 (95%IC: 1,1-4,5),p = 0,04) or a cumulative time with undetectable HIV viral load of less than 12 months (OR 4,2 (95%IC: 2-8.5,p = 0,001). HPV 31, 33 and 35 were more frequently detected in samples from WLWH than in HIV-negative controls (p < 0,05). The 9-valent vaccine would increase HPV protection, in HIV-positive and negative women (p < 0,001). CONCLUSION: WLWH are more frequently infected with high-risk HPV other than 16 and 18 than HIV-negative ones. The use of 9-valent vaccine may prevent HSIL or ICC in up to 85% of the women. Adding HPV 35 to the HPV vaccine panel, might improve vaccine effectiveness in WLWH.

Cervical, anal and oral human papillomavirus (HPV) infection in young women: A case control study between women with perinatally HIV infection and women with non-perinatally HIV infection.

OBJECTIVES: HPV infection may differ in women who are HIV-positive since birth (perinatally infected, P-HIV) and those who acquire HIV later in life (non-perinatally infected, NP-HIV). We assessed the HPV prevalence in relation to the HIV acquisition route and HPV vaccination status. STUDY DESIGN: Case control study comparing 22 P-HIV with 22 NP-HIV patients. Cervical, anal and oral specimen were collected for HPV PCRs. The primary outcome was the prevalence of cervical, oral and anal HPV in P-HIV and NP-HIV patients. The secondary outcome was to identify risk factors for HPV infection. Comparative statistics for two independent groups, univariate and multivariable logistic regression analyses were used. RESULTS: There were no differences between perinatally and non-perinatally infected women. Cervical dysplasia was found in 12/44 (27 %) patients and high-risk HPV (hrHPV) in 30 % of cervical (of which 89 % were hrHPV other than 16 and 18), in 3 % of oral and 65 % of anal specimens. All woman were using combined antiretroviral therapy (cART) and 64 % had HIVRNA < 20 cp/ml. A CD4 count <350/mm³ was associated with cytological abnormalities (OR: 13.52, p = 0.002) and with cervical HPV (OR: 6.11; p = 0.04); anal HPV was associated with a previous cervical dysplasia and concomitant cervical HPV infection. None of thirteen vaccinated patients had a 6/11/16/18 HPV infection. CONCLUSION: In this small series of women under cART, we did not observe a difference in HPV infection in relation to the route of HIV acquisition. The high prevalence of hrHPV other than 16 and 18 support the use of a 9-valent vaccine.

Implementation of a protocol and staff educational sessions improves the care of survivors of sexual assault.

OBJECTIVE: We previously conducted an audit of the care provided for survivors of sexual violence seen at our emergency department and observed that 90% of them did not receive optimal care. This study analysed whether the implementation of a new protocol and educational sessions for staff increased the proportion of such patients who received optimal medical care. METHODS: A computerized chart detailing a new care protocol was developed specifically for rape survivors. Educational sessions focusing on the use of the new protocol were organized for healthcare providers. We then conducted another audit that reviewed retrospectively the charts of all survivors of sexual violence who were cared for at a public university hospital. MAIN OUTCOME MEASURE: Optimal medical care was defined as including systematic investigations for sexually transmitted diseases, and the provision of prophylactic antibiotics, a pregnancy test, emergency contraception, and psychological and medical follow-up. RESULTS: We analysed the charts of 362 survivors of sexual violence and observed that all of the required procedures were completed for 337 patients (93%) and the required preventive measures were provided to 325 patients (90%). CONCLUSION: After the implementation of the new protocol and educational sessions, the proportion of survivors who received optimal medical care increased from 10% to 90%. Nevertheless, optimal management also implies social, psychological and legal support. We hope that the establishment of specialist sexual assault centres will further improve management.

High-risk human papillomavirus genotypes distribution in a cohort of HIV-positive women living in Europe: epidemiological implication for vaccination against human papillomavirus.

BACKGROUND: Worldwide, human papillomavirus (HPV) 16 and 18 represents 70% of high-risk (HR) HPV found in cervical cancer. However HIV-positive women are more frequently infected by HRHPV other than HPV 16 or 18 (OHR). We aimed to analyse the HRHPV genotype distribution in a cohort of HIV-positive women and to estimate the potential protection offered by the different HPV vaccines. METHODS: HRHPV genotypes by PCR and cytology were assessed in cervical samples from 508 HIV-positive women prospectively followed in Brussels. RESULTS: Women characteristics were as follows: African origin (84%), median age 42 years, median CD4 T 555/µl, 89% under combined antiretroviral therapy and 73% with HIVRNA less than 20 copies/ml. HRHPV prevalence was 23% (116/508): 38% had abnormal cytology, 76% carried OHR without HPV 16 or 18 and 11% had concomitant infection by OHR and HPV 16 or 18. The most frequent HRHPV were HPV52 (19.8%), HPV18 (14.6%), HPV31/35/51/58 (12.1% each), HPV56 (9.9%) and HPV16 (9.5%). Less than 30% of women had their HRHPV genotypes included in the bivalent or quadrivalent vaccines against HRHPV 16 and 18; however, 79% had their HRHPV covered by the ninevalent vaccine against HRHPV 16/18/31/33/45/52/58. CONCLUSION: The HRHPV genotypes distribution found in these women living in Europe with a successfully treated HIV is similar to the one found in Central Africa with HRHPV other than HPV16 or 18 retrieved in 87%. In this population, the bivalent or quadrivalent vaccines could offer protection in only 30% of women; however this protection could be extended up to 80% with the ninevalent vaccine.

High-risk human papillomavirus infection in HIV-positive African women living in Europe.

INTRODUCTION: Cervical infection with high-risk human papillomavirus (HRHPV) induces cervical cancer and is present in 14% of women in Europe. We assessed the prevalence and incidence of cervical HRHPV in a cohort of HIV-positive women living in Belgium. METHODS: Prospective observational program of screening and follow up of HRHPV cervical infection performed by Hybrid Capture in 825 HIV-positive women between 2002 and 2011. Women without normal cervix at baseline were excluded. RESULTS: The final analysis included 652 women: median age 38 years, African origin (81%), median HIV follow-up (66 months), median CD4 count (426 cells/µL) and 79% on antiretroviral therapy (cART). At baseline, HRHPV prevalence was 43% and decreased significantly as both age and CD4 cell count increased: highest prevalence (100%) in women <30 years and <200 CD4/µL and lowest (19%) in women >40 years and >500 CD4/µL (p<0.0001, multivariate analysis). The relative risk (RR) to carry HRHPV at baseline decreases proportionally by 11% for each 5 years-age increase and by 11% for each 100 CD4 cells/µL rise (RR=0.89, 95% CI: 0.85-0.93; p<0.0001, Poisson regression for both). During follow-up, incidence rate of HRHPV was 13.4 per 100 women-years. CONCLUSION: We found a high HRHPV prevalence of 43% and an incidence rate of 13 per 100 women-years in this cohort of HIV-positive women living in Europe and on cART. Women under 40 years-age had the highest prevalence even with CD4 count >350 cells/µL. The magnitude of HRHPV epidemiology should prompt to evaluate the clinical efficacy of vaccines against HPV in HIV-infected women.

Optimal management of HIV-infected women during pregnancy and delivery: an audit of compliance with recommendations.

BACKGROUND: The improvement in quality of life of HIV-infected patients and a reduced risk of vertical transmission have led to an increase in the desire for pregnancy among infected women. We assessed whether local recommendations were followed by HIV-infected mothers and their reasons for noncompliance. METHODS: Data on HIV-infected women who delivered between 2002 and 2006 in a large public university hospital in Brussels were collected and analyzed for compliance with recommendations and outcomes. RESULTS: The evidence suggests that current recommendations were followed in two thirds of the 203 recorded deliveries, as the patients in question (n = 140) came to term with an undetectable viral load and an uninfected newborn. About half of these women delivered vaginally, and 67% had ruptured membranes for less than 4 hours and required no instrumental delivery. Among those for whom optimal conditions for delivery were not met, two newborns were infected. CONCLUSIONS: The current recommendations were followed in only two thirds of the recorded deliveries. To improve results for the future, we have adapted our protocol both by starting antiviral therapy earlier and by assigning nurses to the patients' follow-up to try to promote better compliance to treatment during pregnancy.

Ovarian response to stimulation of HIV-positive patients during IVF treatment: a matched, controlled study.

BACKGROUND: Our aim was to compare the ovarian response of HIV-positive and -negative patients during IVF. METHODS: Setting - HIV and IVF reference university hospital. Twenty-seven HIV-infected patients who had undergone IVF between March 2000 and March 2005 were matched with 77 HIV-negative patients for age, aetiology of infertility, whether it was primary or secondary infertility, duration of infertility, history of pelvic surgery and type of pituitary inhibition. Outcome - poor responders were defined using one of the following criteria: a cancelled cycle (for insufficient ovarian response), less than four mature follicles (> or = 16 mm), peak serum levels of E2 lower than 1000 pg/ml. RESULTS: There were no differences between the two groups of patients for the matched criteria. The proportion of African women and of women with a history of pelvic inflammatory disease was significantly higher among HIV patients than among the control group. With the exception of a lower number of transferred embryos among HIV-positive patients versus HIV-negative ones (1.3 versus 1.9; P = 0.035), there was no significant difference between the two groups of patients regarding ovarian response parameters. CONCLUSION: HIV-infected patients who are in good general condition and who are matched to a control group present a similar ovarian response to stimulation, suggesting the existence of a similar ovarian reserve.

Management and outcome of cervical intraepithelial neoplasia lesions: a study of matched cases according to HIV status.

OBJECTIVES: To assess whether adequate strategies are used for the management of cervical intraepithelial neoplasia (CIN) in HIV-positive patients. SETTING: Retrospective study in a HIV reference university hospital. Sixty-eight HIV-infected patients who had undergone a cervical biopsy between January 1995 and March 2002 were matched for CIN and age with HIV-negative patients. OUTCOME: Assess mean of treatment strategy. Assess mean of treatment failure by immediate follow-up PAP smear and recurrence rate by long-term follow-up smears. RESULTS: Both groups of patients received similar treatments for their cervical anomalies. HIV-positive women were two times more likely to have involved margins after conisation than HIV-negative women (P < 0.01). Globally, two thirds of HIV-negative patients had a first follow-up PAP smear that was normal, while this was the case in only one third of HIV-positive women. These proportions were also significantly different after conisation (P < 0.01). The same differences were also observed after sustained follow-up. HIV-infected women who showed a recurrence of dysplasia were more likely to have failed antiviral therapy (9/44) than those without any recurrence (7/12) (P < 0.01). CONCLUSIONS: Higher rates of recurrence were observed among HIV-infected women, indicating that CIN management is more difficult and may require adapted guidelines in HIV-positive patients. In HIV-infected patients, an association was found between the absence of recurrence and a viral response to antiviral therapy.