Tubal flushing with oil-based or water-based contrast at hysterosalpingography for infertility: long-term reproductive outcomes of a randomized trial.

OBJECTIVE: To determine the impact of oil-based versus water-based contrast on pregnancy and live birth rates ≤5 years after hysterosalpingography (HSG) in infertile women. DESIGN: A 5-year follow-up study of a multicenter randomized trial. SETTING: Hospitals. PATIENT(S): Infertile women with an ovulatory cycle, 18-39 years of age, and having a low risk of tubal pathology. INTERVENTION(S): Use of oil-based versus water-based contrast during HSG. MAIN OUTCOME MEASURE(S): Ongoing pregnancy, live births, time to ongoing pregnancy, second ongoing pregnancy. RESULT(S): A total of 1,119 women were randomly assigned to HSG with oil-based contrast (n = 557) or water-based contrast (n = 562). After 5 years, 444 of 555 women in the oil group (80.0%) and 419 of 559 women in the water group (75.0%) had an ongoing pregnancy (relative risk [RR] 1.07; 95% confidence interval [CI] 1.00-1.14), and 415 of 555 women in the oil group (74.8%) and 376 of 559 women in the water group (67.3%) had live births (RR 1.11; 95% CI 1.03-1.20). In the oil group, 228 pregnancies (41.1%) were conceived naturally versus 194 (34.7%) pregnancies in the water group (RR 1.18; 95% CI 1.02-1.38). The time to ongoing pregnancy was significantly shorter in the oil group versus the water group (10.0 vs. 13.7 months; hazard ratio, 1.25; 95% CI 1.09-1.43). No difference was found in the occurrence of a second ongoing pregnancy. CONCLUSION(S): During a 5-year time frame, ongoing pregnancy and live birth rates are higher after tubal flushing with oil-based contrast during HSG compared with water-based contrast. More pregnancies are naturally conceived and time to ongoing pregnancy is shorter after HSG with oil-based contrast. CLINICAL TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NTR) 3270 and NTR6577(www.trialregister.nl).

[Acute fatty liver of pregnancy]. / Acute leververvetting tijdens de zwangerschap.

BACKGROUND: Acute fatty liver of pregnancy (AFLP) is a rare complication of pregnancy which is potentially fatal to mother and child. CASE DESCRIPTION: A primigravida at term with gestational diabetes presented at hospital complaining mainly of nausea and vomiting. Test results were consistent with acute fatty liver of pregnancy (AFLP). Due to the seriousness and rapid progression of the disease, we strove for a rapid delivery. The patient was admitted to the intensive care unit, but was eventually able to leave hospital in a good condition with a healthy child. CONCLUSION: AFLP is a rare and potentially dangerous condition of pregnancy and requires multidisciplinary collaboration. Knowledge of clinical symptoms, early diagnosis, treatment and anticipation of expected complications is essential to prevent the death of mother and child. Diabetes gravidarum can complicate the making of the diagnosis. More research into potential early diagnostics or screening instruments and the long-term outcomes for mother and child is necessary.

First Successful Conception Induced by a Male Cystinosis Patient.

Cystinosis is a rare autosomal recessive lysosomal storage disease characterized by multi-organ cystine accumulation, leading to renal failure and extra-renal organ dysfunction. Azoospermia of unknown origin is the main cause of infertility in all male cystinosis patients. Although spermatogenesis has shown to be intact at the testicular level in some patients, no male cystinosis patient has been reported yet to have successfully induced conception.We present the first successful conception ever reported, induced by a 27-year-old male renal transplant infantile nephropathic cystinosis patient through percutaneous epididymal sperm aspiration (PESA) followed by intracytoplasmatic sperm injection (ICSI). After 36 weeks and 6 days of an uncomplicated pregnancy, a dichorial diamniotic (DCDA) twin was born with an appropriate weight for gestational age and in an apparently healthy status. Moreover, we demonstrate that the sperm of epididymal origin in selected male cystinosis patients can be viable for inducing successful conception.Our observation opens a new perspective in life for many male cystinosis patients whom nowadays have become adults, by showing that despite azoospermia fathering a child can be realized. In addition, our findings raise questions about the possibility of sperm cryopreservation at a young age in these patients.

e-Therapy to reduce emotional distress in women undergoing assisted reproductive technology (ART): a feasibility randomized controlled trial.

STUDY QUESTION: Is it feasible to evaluate a personalized e-therapy program (Internet based) for women during fertility treatment aimed to reduce the chance of having clinically relevant symptoms of anxiety and/or depression after unsuccessful assisted reproductive technology (ART) treatment within a randomized controlled trial (RCT)? STUDY ANSWER: The evaluation of a personalized e-therapy program is feasible, reflected by good acceptability and integration within current guidelines, but adjustments to the e-therapy program and study design of the RCT have to be made to enhance demand, practicality and efficacy. WHAT IS KNOWN ALREADY: Internet-based interventions are promising in reducing psychological distress, especially when treatment is personalized to specific risk profiles of patients. However in fertility care, the beneficial effects of personalized e-therapy on psychological distress and its implementation in daily clinical care still have to be evaluated. STUDY DESIGN, SIZE, DURATION: To evaluate the feasibility of a personalized e-therapy program, we conducted a two-arm, parallel group, single-blind feasibility randomized controlled trial with a 1:1 allocation. Feasibility was assessed in terms of demand, acceptability, practicality, implementation, integration and limited efficacy. Women were included between 1 February 2011 and 1 June 2013. Women in the control group received care as usual, whereas women in the intervention group received in addition to their usual care access to a personalized e-therapy program. Women were monitored until 3 months after the start of their first ART cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: In a university hospital in the Netherlands women who were screened as at risk for emotional adjustment problems and intended to start their first ART cycle were invited, and of them 120 were randomized. Of these women, 48% in the intervention group were compliant to the intervention. Outcome measures associated with the feasibility to analyse this e-therapy program within an RCT were assessed. MAIN RESULTS AND THE ROLE OF CHANCE: It is feasible to evaluate a personalized e-therapy program within an RCT. The acceptability was good, as was the integration within current clinical guidelines and care. However, the demand reflected by a participation rate of 44% was low, since most women declined participation because they felt no need for support at that moment. The practicality of the intervention was moderate illustrated by a relatively high dropout rate (30%) due to practical concerns. The intervention was effective, shown by a reduction in the percentage women having clinically relevant symptoms of anxiety and/or depression in the compliant intervention group compared with the control group 3 months after the first ART cycle; risk difference of 24% (95% CI: 2-46%; ITALIC! P = 0.03). LIMITATIONS, REASONS FOR CAUTION: The large non-participation rate (56%) needs further evaluation. This also could have influenced results on limited efficacy. Barriers for participation could be assessed more in-depth. Moreover, ∼30% dropped out. This percentage is comparable with other e-health studies. Finally, this is a single-centre study. Generalizability could be enlarged by a multi-centre approach. WIDER IMPLICATIONS OF THE FINDINGS: In clinical fertility care, personalizing an e-therapy program to the patients' risk profile is promising and feasible. However, in future studies, we recommend modification of the study protocol by for example offering the intervention to the preferred moment in the treatment process. Moreover, adjustment of the study protocol tailored to the found barriers and facilitators is needed. When performing a multi-centre consecutive RCT to assess the effectiveness of personalized e-therapy in fertility care, the findings of this study, for example concerning the preferred timing or reasons for non-participation, could be helpful. STUDY FUNDING/COMPETING INTERESTS: NutsOhra (Study Number 0702-94) funded this study with an unrestricted grant. There were no competing interests. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT 01283607. TRIAL REGISTRATION DATE: 21 January 2011. DATE OF FIRST PATIENT'S ENROLMENT: February, 2011.

Identification of TDRD1 as a direct target gene of ERG in primary prostate cancer.

Molecular classification of ERG-rearranged prostate cancer clarifies the role of TMPRSS2-ERG in the development and progression of prostate cancer. The objective of our study was to identify direct ERG target genes in ERG-rearranged prostate cancer. Two independent cohorts of primary prostate cancer (Cohort A, n=48; Cohort B, n=31), a cohort of late-stage prostate cancer (n=51) and expression array data of a cohort of primary prostate tumors from a different institute (n=128) were analyzed for expression of genes that were coexpressed with ERG overexpression. By genome-wide expression analysis and Q-RT-PCR it was shown that the gene Tudor domain containing 1 (TDRD1) was by far the strongest correlated gene with ERG overexpression in both Cohort A and B. Expression array analysis of the patient cohort from a different institute showed a large overlap in genes that were positively correlated with ERG overexpression, including TDRD1. In late-stage prostate cancer, TDRD1 was also coexpressed with ERG overexpression, although a proportion of ERG-negative late-stage samples expressed TDRD1. TDRD1 expression was not associated with ETV1 overexpression. In the prostate cancer cell line VCaP, downregulation of ERG by shRNA lead to a lower expression level of TDRD1 and resulted in a decreased activity of the TDRD1 promoter. By mutation analysis we identified a functional ERG binding site in the TDRD1 promoter. Our findings show TDRD1 as the first identified upregulated direct ERG target gene that is strongly associated with ERG overexpression in primary prostate cancer.

Prolate-spherical shape coexistence at N=28 in 44S.

The structure of 44S has been studied by using delayed γ and electron spectroscopy. The decay rates of the 02+ isomeric state to the 2(1)+ and 0(1)+ states, measured for the first time, lead to a reduced transition probability B(E2: 2(1)+→0(2)+)=8.4(26) e(2) fm4 and a monopole strength ρ2(E0: 0(2)+→0(1)+)=8.7(7)×10(-3). Comparisons to shell model calculations point towards prolate-spherical shape coexistence, and a two-level mixing model is used to extract a weak mixing between the two configurations.

Reasons for dropping out from a waiting list for in vitro fertilization.

OBJECTIVE: To determine the incidence of couples dropping out of the in vitro fertilization (IVF) waiting list and to describe the couples' reasons. DESIGN: Prospective cohort study. SETTING: Fertility center in an academic hospital. PATIENT(S): 674 women placed consecutively on the IVF waiting list between June 2000 and July 2003. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of dropouts and reasons for dropping out. RESULT(S): Follow-up information was collected in 2005 and 2008. Of the 674 couples on the waiting list, 87% started IVF, and 13% dropped out before starting their first IVF cycle. Follow-up data were obtained for 85 of 86 patients (98.8%): 37% dropped out because of spontaneous pregnancy, 36% for personal reasons (passive censoring), and 27% for medical reasons (active censoring). Most of the pregnancies occurred within 3 months after the patient had been placed on the waiting list (30 of 32, 94%). Of the 54 censored couples, four became pregnant. CONCLUSION(S): On a 6-month waiting list for IVF, 13% of the couples dropped out before starting treatment. The single most important reason for dropout was (spontaneous) pregnancy. Most of these pregnancies occurred within 3 months, which suggests that psychological factors such as stress relief after being placed on the waiting list might be operative.

Shell Erosion and Shape Coexistence in (16)43S27.

We report on the g-factor measurement of the first isomeric state in (16)43S27 [Ex=320.5(5) keV, T1/2=415(5) ns, and g=0.317(4)]. The 7/2- spin-parity of the isomer and the intruder nature of the ground state of the nucleus are experimentally established for the first time, providing direct and unambiguous evidence of the collapse of the N=28 shell closure in neutron-rich nuclei. The shell model, beyond the mean-field and semiempirical calculations, provides a very consistent description of this nucleus showing that a well deformed prolate and quasispherical states coexist at low energy.

Collapse of the N=28 shell closure in (42)Si.

The energies of the excited states in very neutron-rich (42)Si and (41,43)P have been measured using in-beam gamma-ray spectroscopy from the fragmentation of secondary beams of (42,44)S at 39A MeV. The low 2(+) energy of (42)Si, 770(19) keV, together with the level schemes of (41,43)P, provides evidence for the disappearance of the Z=14 and N=28 spherical shell closures, which is ascribed mainly to the action of proton-neutron tensor forces. New shell model calculations indicate that (42)Si is best described as a well-deformed oblate rotor.

Structure of 12Be: intruder d-wave strength at N=8.

The breaking of the N=8 shell-model magic number in the 12Be ground state has been determined to include significant occupancy of the intruder d-wave orbital. This is in marked contrast with all other N=8 isotones, both more and less exotic than 12Be. The occupancies of the [FORMULA: SEE TEXT]orbital and the [FORMULA: SEE TEXT], intruder orbital were deduced from a measurement of neutron removal from a high-energy 12Be beam leading to bound and unbound states in 11Be.

Expression in the placenta of neuronal markers for perinatal brain damage.

Determination of S-100 a and b and neuron-specific enolase (NSE) in (cord) blood and amniotic fluid has been used to assess neonatal neuronal damage after compromising conditions. However, these proteins are not only found in nervous tissue, and their expression in placenta and umbilical cord has never been investigated. In this study, S-100 (a and b) and NSE expression in human cord and placental tissue was studied by immunohistochemical analysis. Similar analysis was performed using two other brain-specific markers: glial fibrillary acidic protein and growth-associated protein B-50 (also known as GAP-43 or neuromodulin). Tissue was derived after elective cesarean section in seven women of different gestational ages after uncomplicated or complicated pregnancy. S-100 a and b and NSE immunoreactivity was found in several cell types and structures in the umbilical cord as well as in the placenta of all seven cases. Glial fibrillary acidic protein and B-50 showed no immunoreactivity. These data are of importance for interpreting findings of studies in which S-100 or NSE levels in cord blood or amniotic fluid have been related to neuronal damage in the neonate. The increased levels found may just as well be caused by leakage from placenta or umbilical cord as be caused by brain damage. We conclude that S-100 a and b and NSE are not suitable markers for neonatal brain damage. Brain-restricted proteins such as glial fibrillary acidic protein and B-50 seem more promising.

Radiative proton capture on (6)He.

Radiative capture of protons is investigated as a probe of clustering in nuclei far from stability. The first such measurement on a halo nucleus is reported here for the reaction 6He(p,gamma) at 40 MeV. Capture into 7Li is observed as the strongest channel. In addition, events have been recorded that may be described by quasifree capture on a halo neutron, the alpha core, and 5He. The possibility of describing such events by capture into the continuum of 7Li is also discussed.

Halo structure of (14)Be.

The two-neutron halo nucleus (14)Be has been investigated in a kinematically complete measurement of the fragments ((12)Be and neutrons) produced in dissociation at 35 MeV/nucleon on C and Pb targets. Two-neutron removal cross sections, neutron angular distributions, and invariant mass spectra were measured, and the contributions from electromagnetic dissociation (EMD) were deduced. Comparison with three-body model calculations suggests that the halo wave function contains a large nu(2s(1/2))(2) admixture. The EMD invariant mass spectrum exhibited enhanced strength near threshold consistent with a nonresonant soft-dipole excitation.