Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials

STUDY QUESTION What is an objective approach that employs measurable and reproducible physiologic changes as the basis for the classification of ovarian hyperstimulation syndrome (OHSS) in order to facilitate more accurate reporting of incidence rates within and across clinical trials? SUMMARY ANSWER The OHSS flow diagram is an objective approach that will facilitate consistent capture, classification and reporting of OHSS within and across clinical trials. WHAT IS KNOWN ALREADY OHSS is a potentially life-threatening iatrogenic complication of the early luteal phase and/or early pregnancy after ovulation induction (OI) or ovarian stimulation (OS). The clinical picture of OHSS (the constellation of symptoms associated with each stage of the disease) is highly variable, hampering its appropriate classification in clinical trials. Although some degree of ovarian hyperstimulation is normal after stimulation, the point at which symptoms transition from those anticipated to those of a disease state is nebulous. STUDY DESIGN, SIZE, DURATION An OHSS working group, comprised of subject matter experts and clinical researchers who have significantly contributed to the field of fertility, was convened in April and November 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS The OHSS working group was tasked with reaching a consensus on the definition and the classification of OHSS for reporting in clinical trials. The group engaged in targeted discussion regarding the scientific background of OHSS, the criteria proposed for the definition and the rationale for universal adoption. An agreement was reached after discussion with all members. MAIN RESULTS AND THE ROLE OF CHANCE One of the following conditions must be met prior to making the diagnosis of OHSS in the context of a clinical trial: (i) the subject has undergone OS (either controlled OS or OI) AND has received a trigger shot for final oocyte maturation (e.g. hCG, GnRH agonist [GnRHa] or kisspeptin) followed by either fresh transfer or segmentation (cryopreservation of embryos) or (ii) the subject has undergone OS or OI AND has a positive pregnancy test. All study patients who develop symptoms of OHSS should undergo a thorough examination. An OHSS flow diagram was designed to be implemented for all subjects with pelvic or abdominal complaints, such as lower abdominal discomfort or distention, nausea, vomiting and diarrhea, and/or for subjects suspected of having OHSS. The diagnosis of OHSS should be based on the flow diagram. LIMITATIONS, REASONS FOR CAUTION This classification system is primarily intended to address the needs of the clinical investigator undertaking clinical trials in the field of OS and may not be applicable for the use in clinical practice or with OHSS occurring under natural circumstances. WIDER IMPLICATIONS OF THE FINDINGS The proposed OHSS classification system will enable an accurate estimate of the incidence and severity of OHSS within and across clinical trials performed in women with infertility. STUDY FUNDING/COMPETING INTERESTS Financial support for the advisory group meetings was provided by Merck & Co., Inc., Kenilworth, NJ, USA. P.H. reports unrestricted research grants from MSD, Merck and Ferring, and honoraria for lectures from MSD, Merck and IBSA. S.M.N. reports that he has received fees and grant support from the following companies (in alphabetic order): Beckman Coulter, Besins, EMD Serono, Ferring Pharmaceuticals, Finox, MSD and Roche Diagnostics over the previous 5 years. P.D., C.C.C., J.L.F., H.M.F., and P.L. report no relationships that present a potential conflict of interest. B.C.T. reports: grants and honorarium from Merck Serono; unrestricted research grants, travel grants and honorarium, and participation in a company-sponsored speaker's bureau from Merck Sharp & Dohme; grants, travel grants, honoraria and advisory board membership from IBSA; travel grants from Ferring; and advisory board membership from Ovascience. L.B.S. reports current employment with Merck & Co, Inc., Kenilworth, NJ, USA, and owns stock in the company. K.G. and B.J.S. report prior employment with Merck & Co., Inc., Kenilworth, NJ, USA, and own stock in the company. All reported that competing interests are outside the submitted work. No other relationships or activities exist that could appear to have influenced the submitted work

Magnetic enhancement of Co0.2_{0.2}Zn0.8_{0.8}Fe2_2O4_4 spinel oxide by mechanical milling

We report the magnetic properties of mechanically milled Co$_{0.2}$Zn$_{0.8}$Fe$_2$O$_4$ spinel oxide. After 24 hours milling of the bulk sample, the XRD spectra show nanostructure with average particle size $\approx$ 20 nm. The as milled sample shows an enhancement in magnetization and ordering temperature compared to the bulk sample. If the as milled sample is annealed at different temperatures for the same duration, recrystallization process occurs and approaches to the bulk structure on increasing the annealing temperatures. The magnetization of the annealed samples first increases and then decreases. At higher annealing temperature ($\sim$ 1000$^{0}$C) the system shows two coexisting magnetic phases {\it i.e.}, spin glass state and ferrimagnetic state, similar to the as prepared bulk sample. The room temperature M\"{o}ssbauer spectra of the as milled sample, annealed at 300$^{0}$C for different durations (upto 575 hours), suggest that the observed change in magnetic behaviour is strongly related with cations redistribution between tetrahedral (A) and octahedral (O) sites in the spinel structure. Apart from the cation redistribution, we suggest that the enhancement of magnetization and ordering temperature is related with the reduction of B site spin canting and increase of strain induced anisotropic energy during mechanical milling.Comment: 14 pages LaTeX, 10 ps figure

Model study on the photoassociation of a pair of trapped atoms into an ultralong-range molecule

Using the method of quantum-defect theory, we calculate the ultralong-range molecular vibrational states near the dissociation threshold of a diatomic molecular potential which asymptotically varies as $-1/R^3$. The properties of these states are of considerable interest as they can be formed by photoassociation (PA) of two ground state atoms. The Franck-Condon overlap integrals between the harmonically trapped atom-pair states and the ultralong-range molecular vibrational states are estimated and compared with their values for a pair of untrapped free atoms in the low-energy scattering state. We find that the binding between a pair of ground-state atoms by a harmonic trap has significant effect on the Franck-Condon integrals and thus can be used to influence PA. Trap-induced binding between two ground-state atoms may facilitate coherent PA dynamics between the two atoms and the photoassociated diatomic molecule.Comment: 11 pages, 4 figures, to appear in Phys. Rev. A (September, 2003

Demonstration of the temporal matter-wave Talbot effect for trapped matter waves

We demonstrate the temporal Talbot effect for trapped matter waves using ultracold atoms in an optical lattice. We investigate the phase evolution of an array of essentially non-interacting matter waves and observe matter-wave collapse and revival in the form of a Talbot interference pattern. By using long expansion times, we image momentum space with sub-recoil resolution, allowing us to observe fractional Talbot fringes up to 10th order.Comment: 17 pages, 7 figure

Pion, kaon, proton and anti-proton transverse momentum distributions from p+p and d+Au collisions at sNN=200\sqrt{s_{NN}} = 200 GeV

Identified mid-rapidity particle spectra of $\pi^{\pm}$, $K^{\pm}$, and $p(\bar{p})$ from 200 GeV p+p and d+Au collisions are reported. A time-of-flight detector based on multi-gap resistive plate chamber technology is used for particle identification. The particle-species dependence of the Cronin effect is observed to be significantly smaller than that at lower energies. The ratio of the nuclear modification factor ($R_{dAu}$) between protons $(p+\bar{p})$ and charged hadrons ($h$) in the transverse momentum range $1.2<{p_{T}}<3.0$ GeV/c is measured to be $1.19\pm0.05$(stat)$\pm0.03$(syst) in minimum-bias collisions and shows little centrality dependence. The yield ratio of $(p+\bar{p})/h$ in minimum-bias d+Au collisions is found to be a factor of 2 lower than that in Au+Au collisions, indicating that the Cronin effect alone is not enough to account for the relative baryon enhancement observed in heavy ion collisions at RHIC.Comment: 6 pages, 4 figures, 1 table. We extended the pion spectra from transverse momentum 1.8 GeV/c to 3. GeV/

Single Spin Asymmetry ANA_N in Polarized Proton-Proton Elastic Scattering at s=200\sqrt{s}=200 GeV

We report a high precision measurement of the transverse single spin asymmetry $A_N$ at the center of mass energy $\sqrt{s}=200$ GeV in elastic proton-proton scattering by the STAR experiment at RHIC. The $A_N$ was measured in the four-momentum transfer squared $t$ range $0.003 \leqslant |t| \leqslant 0.035$ \GeVcSq, the region of a significant interference between the electromagnetic and hadronic scattering amplitudes. The measured values of $A_N$ and its $t$-dependence are consistent with a vanishing hadronic spin-flip amplitude, thus providing strong constraints on the ratio of the single spin-flip to the non-flip amplitudes. Since the hadronic amplitude is dominated by the Pomeron amplitude at this $\sqrt{s}$, we conclude that this measurement addresses the question about the presence of a hadronic spin flip due to the Pomeron exchange in polarized proton-proton elastic scattering.Comment: 12 pages, 6 figure

Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV

We report a measurement of the longitudinal double-spin asymmetry A_LL and the differential cross section for inclusive Pi0 production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV. The cross section was measured over a transverse momentum range of 1 < p_T < 17 GeV/c and found to be in good agreement with a next-to-leading order perturbative QCD calculation. The longitudinal double-spin asymmetry was measured in the range of 3.7 < p_T < 11 GeV/c and excludes a maximal positive gluon polarization in the proton. The mean transverse momentum fraction of Pi0's in their parent jets was found to be around 0.7 for electromagnetically triggered events.Comment: 6 pages, 3 figures, submitted to Phys. Rev. D (RC

Azimuthal anisotropy and correlations in p+p, d+Au and Au+Au collisions at 200 GeV

We present the first measurement of directed flow ($v_1$) at RHIC. $v_1$ is found to be consistent with zero at pseudorapidities $\eta$ from -1.2 to 1.2, then rises to the level of a couple of percent over the range $2.4 < |\eta| < 4$. The latter observation is similar to data from NA49 if the SPS rapidities are shifted by the difference in beam rapidity between RHIC and SPS. Back-to-back jets emitted out-of-plane are found to be suppressed more if compared to those emitted in-plane, which is consistent with {\it jet quenching}. Using the scalar product method, we systematically compared azimuthal correlations from p+p, d+Au and Au+Au collisions. Flow and non-flow from these three different collision systems are discussed.Comment: Quark Matter 2004 proceeding, 4 pages, 3 figure

Azimuthal anisotropy: the higher harmonics

We report the first observations of the fourth harmonic (v_4) in the azimuthal distribution of particles at RHIC. The measurement was done taking advantage of the large elliptic flow generated at RHIC. The integrated v_4 is about a factor of 10 smaller than v_2. For the sixth (v_6) and eighth (v_8) harmonics upper limits on the magnitudes are reported.Comment: 4 pages, 6 figures, contribution to the Quark Matter 2004 proceeding

Plasma Wakefield Acceleration with a Modulated Proton Bunch

The plasma wakefield amplitudes which could be achieved via the modulation of a long proton bunch are investigated. We find that in the limit of long bunches compared to the plasma wavelength, the strength of the accelerating fields is directly proportional to the number of particles in the drive bunch and inversely proportional to the square of the transverse bunch size. The scaling laws were tested and verified in detailed simulations using parameters of existing proton accelerators, and large electric fields were achieved, reaching 1 GV/m for LHC bunches. Energy gains for test electrons beyond 6 TeV were found in this case.Comment: 9 pages, 7 figure