First-in-human study to assess the pharmacokinetics, tolerability, and safety of single-dose oxybutynin hydrochloride administered via a microprocessor-controlled intravaginal ring.

Polymeric drug-releasing vaginal rings are useful for both local and systemic administration of drugs via the intravaginal route. Typically, they provide continuous sustained or controlled release of drug(s) over extended time periods, thereby avoiding overdose and improving adherence. This first-in-human study (EudraCT number: 2020-0050044-30) evaluated the pharmacokinetics, safety, and tolerability of a single dose of oxybutynin administered by a novel microprocessor-controlled vaginal ring (MedRing). Eight healthy female subjects received an electronically controlled single intravaginal dose of 3 mg oxybutynin hydrochloride (100 mg/mL) dissolved in 1:1 water/propylene glycol administered via MedRing. Following dosing, MedRing was kept in situ for up to 6 h. Blood samples were collected 1 h prior to oxybutynin dosing and subsequently at regular intervals post-dose for the assessment of plasma concentrations of oxybutynin and its active metabolite N-desethyloxybutynin. The results showed that MedRing efficiently administered oxybutynin via the intravaginal route, resulting in plasma oxybutynin levels comparable to orally administered oxybutynin. The mean ± standard deviation pharmacokinetic parameters for oxybutynin were Cmax 5.4 ± 2.7 ng/mL, AUCinf 34.9 ± 17.4 h ng/mL, t1/2 8.5 ± 3.5 h and for N-desethyloxybutynin were Cmax 3.9 ± 2.5 ng/mL, AUCinf 51.1 ± 43.1 h ng/mL, t1/2 7.7 ± 5.9 h. No serious adverse events were reported. The study demonstrates that intravaginal administration of oxybutynin hydrochloride using the MedRing device was well tolerated.

Performance of OncoE6 cervical test with collection methods enabling self-sampling.

BACKGROUND: The paradigm shift from cytological screening to Human Papillomavirus (HPV)-based screening for cervical cancer allows the introduction of new technologies in sample collection and diagnostics. The OncoE6™ Cervical Test (OncoE6 Test) is a rapid, easy-to-use lateral flow method detecting HPV16/18 E6 oncoproteins that has proven to detect high-grade cervical lesions with high specificity. If compatible with self-collection samples, this technology might allow for decentralized screening of hard-to-reach populations. METHODS: For technical validation, cervicovaginal lavages were collected from 20 patients with confirmed HPV16+ or HPV18+ invasive cervical cancer. Cervical smears were collected by polyester-tipped swabs and cytobrushes. All samples were applied to the OncoE6 Test and cytobrush samples additionally genotyped. RESULTS: Lavage, swab, and cytobrush revealed concordant outcome in 18/20 samples. HPV types corresponded with the HPV genotyping by GP5+/6+ PCR analyses. Due to a rare mutation found in the E6 antibody binding site one sample was not detected, another sample had very low cellularity. CONCLUSIONS: Overall, vaginal lavages are technically adequate for the OncoE6 Test. Combining self-sampling with oncoprotein rapid testing to detect women with highest risk for severe dysplasia or cancer may allow for secondary cancer prevention in settings where other screening modalities were unsuccessful to date.

Pregnancy outcomes and prognostic factors from tubal sterilization reversal by sutureless laparoscopical re-anastomosis: a retrospective cohort study.

BACKGROUND: Female sterilization is a widely used contraceptive method but in a small group of women, post-sterilization regret occurs. A dilemma for these women is the choice between surgical re-anastomosis and IVF. We evaluated the factors that affected pregnancy rate after laparoscopic tubal re-anastomosis for sterilization regret. METHODS: We included women who underwent a laparoscopic tubal re-anastomosis between January 1997 and March 2008 at Máxima Medical Centre, The Netherlands, in a retrospective cohort study. Microsurgical laparoscopic re-anastomosis was performed using a serosa-muscular fixation/biological glue technique. The primary outcome was time to clinical pregnancy (TTP). Other outcomes were ongoing pregnancy and ectopic pregnancy. We studied whether clinical characteristics, including age, fertility history, BMI, semen quality, remaining tubal length and type of anastomosis, could predict the chance of pregnancy. RESULTS: Data from 127 patients were analysed. The 40-month cumulative clinical pregnancy rate was 74%, whereas the ongoing pregnancy rate was 59%. There were five ectopic pregnancies (3.9%). Only age was found to influence the probability of a positive pregnancy test, hazard rate ratio (HRR): 0.32 [95% confidence interval (CI) 0.12-0.88] and ongoing pregnancy [HRR 0.21 (95% CI 0.05-0.87)]. Previous pregnancy increased pregnancy probability [HRR: 2.2 (95% CI 0.51-9.8)]. A total sperm motility count of <20 million was related to prolonged TTP. CONCLUSIONS: Sutureless laparoscopic tubal re-anastomosis is an effective treatment for women who regret sterilization. Age, previous pregnancies and sperm quality should be considered when counselling for tubal sterilization reversal versus IVF. A randomized prospective trial comparing success rates of surgical reversal and IVF after sterilization regret should be conducted.

High concordance of results of testing for human papillomavirus in cervicovaginal samples collected by two methods, with comparison of a novel self-sampling device to a conventional endocervical brush.

A user-friendly self-sampling method for collecting representative cervical cell material would lower the threshold for women to respond to the invitation for cervical screening. In the present article, we introduce such a device; we have evaluated its sensitivity and specificity to detect high-grade cervical intraepithelial neoplasia (CIN), via high-risk human papillomavirus (hrHPV) detection and liquid-based cytology (LBC), compared to endocervical brush samples obtained by gynecologists. Women who had a cervical smear reading of moderate dyskaryosis or worse or a repeat equivocal Pap smear result in the cervical screening program (n=64) and healthy volunteers (n=32) took a self-obtained sample at home prior to their visit to the gynecological outpatient department. At the outpatient department, an endocervical brush smear was taken, followed by colposcopy and biopsy whenever applicable. Both self-obtained samples and endocervical brush samples were immediately collected in Surepath preservation solution and used for LBC and hrHPV testing (by general primer-mediated GP5+/6+PCR). hrHPV test results showed a good concordance between the two sample types (87%; kappa=0.71), with sensitivities for prevalent high-grade CIN that did not differ significantly (92% and 95%; P=1.0). The hrHPV test on self-obtained samples proved to be at least as sensitive for high-grade CIN as cytology on endocervical brush samples (34/37 versus 31/37; P=0.5). LBC showed a poor concordance between self-obtained and endocervical brush samples (60%; kappa=0.27). In conclusion, self-obtained samples taken by this novel device are highly representative of the hrHPV status of the cervix. In combination with hrHPV testing, the use of this device may have implications for increasing the attendance rate for cervical screening programs.

Sutureless re-anastomosis by laparoscopy versus microsurgical re-anastomosis by laparotomy for sterilization reversal: a matched cohort study.

BACKGROUND: Sutureless re-anastomosis per laparoscopy is an alternative for microsurgical re-anastomosis by laparotomy in the treatment of sterilized women with renewed child wish. Our aim was to compare pregnancy rates after both surgical techniques. METHODS: We performed a retrospective cohort study in which consecutive women who underwent sutureless re-anastomosis per laparoscopy were compared to women who underwent microsurgical re-anastomosis by laparotomy. Both procedures were performed in neighbouring hospitals in Northern-Brabant, The Netherlands, and women were matched for age. The primary outcome was time to ongoing pregnancy. RESULTS: Overall, we included 41 women who had sutureless re-anastomosis by laparoscopy, and 41 age-matched women who underwent microsurgical re-anastomosis by laparotomy. The number of women who conceived was 20 (15 ongoing pregnancies) in the sutureless laparoscopic group versus 26 (24 ongoing pregnancies) in the laparotomic group, a difference due to a longer follow-up period in the laparotomic group. Time to ongoing pregnancy was comparable in both groups (P=0.46), with 3 year cumulative ongoing pregnancy rates of 45 and 52% respectively. After adjustment for other prognostic factors, the fecundity rate ratio was 0.97 (95% CI 0.26-3.6), indicating a similar performance of the two techniques. CONCLUSION: The simplified stitchless laparoscopic procedure for reversal of tubal sterilization with the use of a tubal splint, clip fixation of the muscularis and fibrin glue resulted in a promising pregnancy rate, which was similar to the pregnancy rate obtained with the microsurgical re-anastomosis per laparotomy.