Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis: SERENE UC Trial Results.

BACKGROUND & AIMS: SERENE UC (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Ulcerative Colitis) evaluated the efficacy of higher adalimumab induction and maintenance dose regimens in patients with ulcerative colitis. METHODS: This phase 3, double-blind, randomized trial included induction and maintenance studies, with a main study (ex-Japan) and Japan substudy. Eligible patients (18-75 years, full Mayo score 6-12, centrally read endoscopy subscore 2-3) were randomized 3:2 to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3) or standard induction regimen (160 mg at week 0 and 80 mg at week 2); all received 40 mg at weeks 4 and 6. At week 8, all patients were rerandomized 2:2:1 (main study) to 40 mg every week (ew), 40 mg every other week (eow), or exploratory therapeutic drug monitoring; or 1:1 (Japan substudy) to 40 mg ew or 40 mg eow maintenance regimens. RESULTS: In the main study, 13.3% vs 10.9% of patients receiving the higher induction regimen vs standard induction regimen achieved clinical remission (full Mayo score ≤2 with no subscore >1) at week 8 (induction primary end point; P = .265); among week-8 responders, 39.5% vs 29.0% receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (maintenance primary end point; P = .069). In the integrated (main + Japan) population, 41.1% vs 30.1% of week-8 responders receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (nominal P = .045). Safety profiles were comparable between dosing regimens. CONCLUSION: Although primary end points were not met, a >10% absolute difference in clinical remission was demonstrated with higher adalimumab maintenance dosing. Higher dosing regimens were generally well tolerated and consistent with the known safety profile of adalimumab in ulcerative colitis. CLINICALTRIALS: gov, Number: NCT002209456.

Hysterosalpingosonography Is Not as Effective as Hysterosalpingography to Increase Chances of Pregnancy.

OBJECTIVE: This study sought to examine whether hysterosalpingosonography (sono-HSG) is as effective as hysterosalpingography (HSG) in facilitating conception by comparing pregnancy rates in the 6 months following the procedures. METHODS: This retrospective noninferiority study (Canadian Task Force classification II-2) was conducted at a tertiary university centre. The investigators studied 440 consecutive eligible infertile women. Bilateral tubal occlusion, severe male infertility, and having undergone both procedures were exclusion criteria. Tubal testing, as part of the infertility workup, was performed by either sono-HSG or HSG. The primary outcome was pregnancy, defined as a positive fetal heartbeat on ultrasonographic examination, in the 6 months following the procedure. RESULTS: A total of 57 pregnancies (26%) were observed in the HSG group and 33 (15%) in the sono-HSG group. Adjusted and non-adjusted relative risks of pregnancy in the 6 months following sono-HSG compared with HSG were 0.61 (95% CI 0.42-0.89) and 0.58 (95% CI 0.39-0.85). Adverse events were infrequent with both procedures (sono-HSG, 1%; HSG, 4%; P = 0.16). CONCLUSION: This study suggests that uterine flushing as performed during sono-HSG is not as effective as when performed during HSG to increase the chances of pregnancy, but further studies will be required because of bias related to the retrospective study design.

Treatment of Secondary Vestibulodynia with Conjugated Estrogen Cream: A Pilot, Double-Blind, Randomized Placebo-Controlled Trial.

OBJECTIVE: To assess the efficacy of conjugated equine estrogen cream in reducing dyspareunia associated with secondary provoked vestibulodynia. METHODS: We conducted a randomized, double-blind, placebo-controlled trial that included women with secondary provoked vestibulodynia. Participants were randomly allocated to daily application of conjugated equine estrogen cream on the vulvar vestibule (estrogen group) or daily application of a similar placebo cream (placebo group). All patients were evaluated before and after eight weeks of treatment, using a visual analogue scale for superficial dyspareunia (primary outcome), the McGill Pain Questionnaire for superficial dyspareunia, the Female Sexual Function Index for sexual satisfaction, and vulvoscopy for vestibular erythema. RESULTS: The targeted recruitment for this study was 44 women, but because of funding shortfalls recruitment was limited to 20 women. These 20 participants were randomly assigned to two groups of 10. Improvement of superficial dyspareunia on the visual analogue scale was not significantly different between the two groups (estrogen group: 27% improvement vs. placebo group: 3% improvement, P = 0.29). However, the use of conjugated equine estrogen cream was associated with a significant post-treatment improvement in superficial dyspareunia and in all three secondary outcomes (P < 0.05), whereas this was not the case with the use of placebo. CONCLUSION: Daily application of conjugated equine estrogen cream to the vulvar vestibule could potentially reduce superficial dyspareunia in women with secondary provoked vestibulodynia, but a randomized trial with adequate statistical power will be required to demonstrate this.

Evaluation of predictor factors of psychological distress in women with unexplained infertility.

Objective: The objective of this study was to establish the frequency of anxiety and depressive symptoms among women diagnosed with unexplained infertility and to identify risk factors. Methods: We conducted a descriptive cross-sectional study. Forty-two women from the CHU de Quebec fertility clinic were recruited. Women completed the 'Hospital Anxiety and Depression Scale' (HADS) self-administered questionnaire, used to estimate prevalence of anxiety and depressive symptoms (score ≥ 8). Results: Overall, 55% (n = 23) of participants were identified with anxiety or depressive symptoms according to the HADS questionnaire. Anxiety symptoms were more frequent (55%) compared with depressive symptoms (10%). According to a logistic regression model, being under 35 years old [odds ratio (OR) = 16.6, confidence interval (CI): 1.9-25.0], never had a previous spontaneous abortion (OR = 5.6, CI: 1.1-43.5) and never sought fertility treatment (OR = 5.5, CI: 1.1-45.4) were associated with a higher risk of anxiety and depressive symptoms. Conclusion: Anxiety and depressive symptoms are common among women with unexplained infertility, and strategies should be developed to better support and treat this high-risk population.

[Evaluation of an estrogen vaginal cream for the treatment of dyspareunia: a double-blind randomized trial]. / [Évaluation d'une crème œstrogénique vaginale dans le traitement de la vestibulodynie provoquée : essai randomisé à double insu].

OBJECTIVE: Our objective was to assess the short-term effect of an estrogen cream on symptoms associated with provoked vestibulodynia. METHODS: We undertook a double-blind randomized trial in women who had experienced dyspareunia satisfying the Friedrichcriteria for at least three months. We compared the daily application of 3 g of vaginal cream containing 1.875 g of conjugated estrogens for six weeks (estrogen group) with the application of a comparable cream without estrogens (placebo group). The main outcome was modification of dyspareunia,determined by a visual analogue scale of pain from the pretreatment period to the post-treatment period. Secondary outcomes were colposcopic evaluation of the vulva and pain reported during the swab test. RESULTS: Of 69 women randomized, 61 participated for the full duration of the trial. Dyspareunia was significantly lessened in both groups (estrogen group: 7.4 ± 1.9 pre-treatment vs. 4.8 ± 3.0 post-treatment, P < 0. 01; placebo group:7.1 ± 1.9 vs. 4.9 ± 2. 7, P < 0.01), but the difference observed in terms of decrease between the two groups was not found to be significant (P = 0.5). Alternatively, the group treated with estrogen cream showed (1) a more substantial decrease of the pain reported at the orifices of the Bartholin's glands when palpated with a swab (P < 0.01), and (2) a decrease of the inflammation observed at the orifices of the Bartholin's glands orifices and the posterior fourchette (P < 0.01). CONCLUSION: Applying a vaginal cream, whether it contains estrogens or not, for six weeks lessens dyspareunia. Adding estrogens to such a cream could facilitate a decrease of the inflammation observed at the orifices of the Bartholin's glands and the vestibule.

Impact of a Pozzi tenaculum forceps use on the success rate of intrauterine insemination (IUI) : protocol for a randomised control trial.

INTRODUCTION: A therapeutic option frequently proposed for infertility is to proceed first with intrauterine insemination (IUI) cycles. Little is known on the effect of uterine contractions on IUI success rates. We postulated that uterine contractions may help with sperm migration in the women's genital tract. Our objective is to compare the efficacy of IUI when performed with and without a tenaculum forceps on the cervix. METHODS AND ANALYSIS: We are conducting a randomised controlled trial with women aged 18-40 years old, diagnosed with primary or secondary infertility due to endometriosis, mild to moderate male factor, unexplained infertility or ovulatory dysfunction, receiving IUI treatments. On the day of their IUI, women will receive standard care treatment plus or minus the planned use of a Pozzi tenaculum forceps on the cervix. Each of the 800 women will be randomised only once for their first three IUI. They will be randomised in one of the following sequences: tenaculum-no tenaculum-tenaculum or, no tenaculum-tenaculum-no tenaculum. We will compare the live birth rate (primary outcome) and the clinical pregnancy rate (secondary outcome) after IUI treatment. We also plan on assessing global satisfaction of women, pain levels felt during IUI and discrepancies in primary and secondary outcomes in interventions performed by attendings compared with trainees. ETHICS AND DISSEMINATION: This research project was approved by the Centre Hospitalier Universitaire de Québec's ethics review board (no 2018-4084). Pozzi tenaculum application is associated with mild pain, estimated at 33 on a Visual Analogue Scale ranging from 0 to 100. We plan on publishing an article to present our findings in a peer-reviewed journal as well as presenting the research abstract at conferences. TRIAL REGISTRATION NUMBER: NCT03435809.

Preovulatory uterine flushing with saline as a treatment for unexplained infertility: a randomised controlled trial protocol.

INTRODUCTION: In vitro fertilisation (IVF) is the treatment of choice for unexplained infertility. Preovulatory uterine flushing could reduce intrauterine debris and inflammatory factors preventing pregnancy and constitute an alternative to IVF. Our objective is to assess the efficacy of preovulatory uterine flushing with physiological saline for the treatment of unexplained infertility. METHODS AND ANALYSIS: We will perform a randomised controlled trial based on consecutive women aged between 18 and 37 years consulting for unexplained infertility for at least 1 year. On the day of their luteinising hormone surge, 192 participants will be randomised in two equal groups to either receive 20 mL of physiological saline by an intrauterine catheter or 10 mL of saline intravaginally. We will assess relative risk of live birth (primary outcome), as well as pregnancy (secondary outcome) over one cycle of treatment. We will report the side effects, complications and acceptability of the intervention. ETHICS AND DISSEMINATION: This project was approved by the Ethics committee of the Centre Hospitatlier Universitaire de Quebec (no 2015-1146). Uterine flushing is usually well tolerated by women and would constitute a simple, affordable and minimally invasive treatment for unexplained infertility. We plan to communicate the results of the review by presenting research abstracts at conferences and by publishing the results in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02539290; Pre-results.

450 IU versus 600 IU gonadotropin for controlled ovarian stimulation in poor responders: a randomized controlled trial.

OBJECTIVE: To compare the outcomes of controlled ovarian stimulation/in vitro fertilization cycles using 450 IU and 600 IU gonadotropin per day in women at risk of poor ovarian response. DESIGN: Prospective randomized controlled nonblinded study. SETTING: University-affiliated private IVF center. PATIENT(S): Women considered to be at risk of poor ovarian response: aged <41 years with basal FSH >10 IU/L, antimüllerian hormone <1 ng/mL, antral follicle count ≤ 8, or a previous IVF cycle with ≥ 300 IU/d gonadotropin that resulted in a cancellation, <8 follicles, or <5 oocytes. INTERVENTION(S): A total of 356 patients underwent a microdose GnRH agonist flare-up IVF/intracytoplasmic sperm injection protocol with a fixed daily dose of either 450 IU FSH (n = 176) or 600 IU FSH (n = 180) equally divided between Menopur and Bravelle. MAIN OUTCOME MEASURE(S): Number of mature oocytes retrieved. RESULT(S): The two groups were similar in terms of age, ovarian reserve, cause of infertility, duration of stimulation, and cycle cancellation rate. There were no significant differences in the number of metaphase II oocytes retrieved (4 [range 0-6] vs. 4 [range 2-7]), fertilization rate (62.4% vs. 57.0%), biochemical pregnancy rate (20.5% vs. 22.9%), clinical pregnancy rate (16.4% vs. 18.3%), and implantation rate (29.8% vs. 30.4%) between the 450 IU and 600 IU groups, respectively. CONCLUSION(S): Gonadotropin of 600 IU/d does not improve outcome of IVF cycles compared with 450 IU/d in women at risk of poor ovarian response. CLINICAL TRIAL REGISTRATION NUMBER: NCT00971152.