A randomized controlled, non-inferiority trial of modified natural versus artificial cycle for cryo-thawed embryo transfer.

STUDY QUESTION: Are live birth rates (LBRs) after artificial cycle frozen-thawed embryo transfer (AC-FET) non-inferior to LBRs after modified natural cycle frozen-thawed embryo transfer (mNC-FET)? SUMMARY ANSWER: AC-FET is non-inferior to mNC-FET with regard to LBRs, clinical and ongoing pregnancy rates (OPRs) but AC-FET does result in higher cancellation rates. WHAT IS ALREADY KNOWN: Pooling prior retrospective studies of AC-FET and mNC-FET results in comparable pregnancy and LBRs. However, these results have not yet been confirmed by a prospective randomized trial. STUDY DESIGN, SIZE AND DURATION: In this non-inferiority prospective randomized controlled trial (acronym 'ANTARCTICA' trial), conducted from February 2009 to April 2014, 1032 patients were included of which 959 were available for analysis. The primary outcome of the study was live birth. Secondary outcomes were clinical and ongoing pregnancy, cycle cancellation and endometrium thickness. A cost-efficiency analysis was performed. PARTICIPANT/MATERIALS, SETTING, METHODS: This study was conducted in both secondary and tertiary fertility centres in the Netherlands. Patients included in this study had to be 18-40 years old, had to have a regular menstruation cycle between 26 and 35 days and frozen-thawed embryos to be transferred had to derive from one of the first three IVF or IVF-ICSI treatment cycles. Patients with a uterine anomaly, a contraindication for one of the prescribed medications in this study or patients undergoing a donor gamete procedure were excluded from participation. Patients were randomized based on a 1:1 allocation to either one cycle of mNC-FET or AC-FET. All embryos were cryopreserved using a slow-freeze technique. MAIN RESULTS AND THE ROLE OF CHANCE: LBR after mNC-FET was 11.5% (57/495) versus 8.8% in AC-FET (41/464) resulting in an absolute difference in LBR of -0.027 in favour of mNC-FET (95% confidence interval (CI) -0.065-0.012; P = 0.171). Clinical pregnancy occurred in 94/495 (19.0%) patients in mNC-FET versus 75/464 (16.0%) patients in AC-FET (odds ratio (OR) 0.8, 95% CI 0.6-1.1, P = 0.25). 57/495 (11.5%) mNC-FET resulted in ongoing pregnancy versus 45/464 (9.6%) AC-FET (OR 0.7, 95% CI 0.5-1.1, P = 0.15). χ(2) test confirmed the lack of superiority. Significantly more cycles were cancelled in AC-FET (124/464 versus 101/495, OR 1.4, 95% CI 1.1-1.9, P = 0.02). The costs of each of the endometrial preparation methods were comparable (€617.50 per cycle in NC-FET versus €625.73 per cycle in AC-FET, P = 0.54). LIMITATIONS, REASONS FOR CAUTION: The minimum of 1150 patients required for adequate statistical power was not achieved. Moreover, LBRs were lower than anticipated in the sample size calculation. WIDER IMPLICATIONS OF THE FINDINGS: LBRs after AC-FET were not inferior to those achieved by mNC-FET. No significant differences in clinical and OPR were observed. The costs of both treatment approaches were comparable. STUDY FUNDING/COMPETING INTERESTS: An educational grant was received during the conduct of this study. Merck Sharpe Dohme had no influence on the design, execution and analyses of this study. E.R.G. received an education grant by Merck Sharpe Dohme (MSD) during the conduct of the present study. B.J.C. reports grants from MSD during the conduct of the study. A.H. reports grants from MSD and Ferring BV the Netherlands and personal fees from MSD. Grants from ZonMW, the Dutch Organization for Health Research and Development. J.S.E.L. reports grants from Ferring, MSD, Organon, Merck Serono and Schering-Plough during the conduct of the study. F.J.M.B. receives monetary compensation as member of the external advisory board for Merck Serono, consultancy work for Gedeon Richter, educational activities for Ferring BV, research cooperation with Ansh Labs and a strategic cooperation with Roche on automated anti Mullerian hormone assay development. N.S.M. reports receiving monetary compensations for external advisory and speaking work for Ferring BV, MSD, Anecova and Merck Serono during the conduct of the study. All reported competing interests are outside the submitted work. No other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: Netherlands trial register, number NTR 1586. TRIAL REGISTRATION DATE: 13 January 2009. FIRST PATIENT INCLUDED: 20 April 2009.

Antibiotic effects on bacterial profile in osteonecrosis of the jaw.

OBJECTIVE: Oral infection is considered to play a critical role in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ), and antibiotic therapy has become a mainstay of BRONJ therapy. This study was aimed to investigate the effect of antibiotics on bacterial diversity in BRONJ tissues. MATERIALS AND METHODS: The bacterial profile from soft tissues associated with the BRONJ lesion was determined using 16S rRNA-based denaturing gradient gel electrophoresis (DGGE) and sequencing. Twenty BRONJ subjects classified as stage 0-2 were enrolled in this study, and patient groups were divided into an antibiotic cohort (n=10) treated with systemic antibiotic and a non-antibiotic cohort (n=10) with no prior antibiotic therapy. RESULTS: The DGGE fingerprints indicated no significant differences in bacterial diversity of BRONJ tissue samples. Patients on antibiotics had higher relative abundance of phylum Firmicutes with bacterial species, Streptococcus intermedius, Lactobacillus gasseri, Mogibacterium timidum, and Solobacterium moorei, whereas patients without antibiotics had greater amounts of Parvimonas micra and Streptococcus anginosus. Thirty percent of bacterial populations were uncultured (yet-to be cultured) phylotypes. CONCLUSION: This study using limited sample size indicated that oral antibiotic therapy may have a limited efficacy on the bacterial population associated with BRONJ lesions.

Dynamic sagittal half-Fourier acquired single-shot turbo spin-echo MR imaging of the temporomandibular joint: initial experience and comparison with sagittal oblique proton-attenuation images.

BACKGROUND AND PURPOSE: Our aim was to assess dynamic half-Fourier acquired single-shot turbo spin-echo (HASTE) MR imaging of the temporomandibular joint (TMJ) using parallel imaging, in comparison with static proton density (Pd) imaging. MATERIALS AND METHODS: Thirty-four TMJs from 17 subjects (7 volunteers, 10 patients) were imaged in a multichannel head coil on a 1.5 T magnet by using a 35-second dynamic sagittal HASTE acquisition (TR/TE, 1180/65 msec; matrix, 128 x 128; section thickness, 7 mm; 30 images) and sagittal oblique Pd in closed- and open-mouthed positions (TR/TE, 1800/12 msec; matrix, 256 x 256; section thickness, 2 mm; 15 sections). Images were reviewed by 3 readers and rated for confidence of disk position, presence of motion artifact, range of motion, and presence of disk displacement on a 5-point scale. Consensus review of cases was also performed to assess disk dislocation and limited range of motion. RESULTS: More static examinations were rated as having motion artifact (19.6% versus 6.9%, P=.016), limited range of motion (30.4% versus 17.7%, P=.016), and disk dislocations (31.4% versus 22.6%, P=.071). Confidence ratings were higher on dynamic examinations (4.11 versus 3.74, P=.018). Chi-squared tests demonstrated no significant difference in consensus reviews of the 2 examination types. CONCLUSION: Dynamic HASTE TMJ MR imaging is a time-efficient adjunct to standard MR imaging protocols, producing fewer motion artifacts, additional range of motion information, and a dynamic assessment of disk position, when compared with static imaging. Further study is needed to evaluate the role of this sequence in diagnosing disk displacement.

Cephalopod Predation Facilitated by Dinoflagellate Luminescence.

Predation by nocturnal cephalopods on nonluminous prey was examined in the presence of dinoflagellate bioluminescence. Sepia officinalis Linnaeus and Euprymna scolopes Berry were tested for predation efficiency in darkness illuminated by the luminescent dinoflagellate Pyrocystis fusiformis Murry. Prey were mysids, Holmesimysis sculpta (Tattersall); grass shrimp, Palaemonetes pugio Holthuis; and mosquito fish, Gambusia affinis Baird and Girard. Tests were conducted in aquaria containing 0-20 cells ml-1 of P. fusiformis. Predation increased as numbers of luminescent dinoflagellates increased. Controls were predation tests in the presence of P. fusiformis during nonluminescent photophase or in the absence of dinoflagellates. Movements of squid and prey readily stimulated luminescence. Behavior and correlated luminescence in infrared-illuminated aquaria were recorded by image-intensified and infrared video cameras. Sepia strikes on prey were common under luminescent conditions--85% occurred in less than 10 min; but strikes in darkness were rare. E. scolopes attacked more frequently than Sepia, and almost 90% obtained prey under luminescent conditions. This study demonstrates the ability of squid to use dinoflagellate bioluminescence to locate and capture nonluminous prey. The burglar alarm theory of the adaptive significance of dinoflagellate bioluminescence is supported.