Double vitrification and warming does not compromise the chance of live birth after single unbiopsied blastocyst transfer.

STUDY QUESTION: Does double vitrification and thawing of an embryo compromise the chance of live birth after a single blastocyst transfer? SUMMARY ANSWER: The live birth rate (LBR) obtained after double vitrification was comparable to that obtained after single vitrification. WHAT IS KNOWN ALREADY: Double vitrification-warming (DVW) is commonly practiced to accommodate surplus viable embryos suitable for transfer, to allow retesting of inconclusively diagnosed blastocysts in preimplantation genetic testing (PGT), and to circumvent limitations associated with national policies on embryo culture in certain countries. Despite its popularity, the evidence concerning the impact of DVW practice on ART outcomes is limited and lacking credibility. This is the first thorough investigation of clinical pregnancy and LBR following DVW in the case where the first round of vitrification occurred at the zygote stage and the second round occurred at the blastocyst stage in the absence of biopsy. STUDY DESIGN SIZE DURATION: This is a retrospective observational analysis of n = 407 single blastocyst transfers whereby embryos created by IVF/ICSI were vitrified-warmed once (single vitrification-warming (SVW) n = 310) or twice (DVW, n = 97) between January 2017 and December 2021. PARTICIPANTS/MATERIALS SETTING METHODS: In the SVW group, blastocysts were vitrified on Day 5/6 and warmed on the day of embryo transfer (ET). In the DVW group, two pronuclear (2PN) zygotes were first vitrified-warmed and then re-vitrified on Day 5/6 and warmed on the day of ET. Exclusion criteria were ETs from PGT and vitrified-warmed oocyte cycles. All of the ETs were single blastocyst transfers performed at the University Hospital Zurich in Switzerland following natural or artificial endometrial preparation. MAIN RESULTS AND THE ROLE OF CHANCE: The biochemical pregnancy rate, clinical pregnancy rate (CPR), and LBR were all comparable between the DVW and SVW groups. The CPR for DVW was 44.3% and for SVW it was 42.3% (P = 0.719). The LBR for DVW was 30.9% and for SVW it was 28.7% (P = 0.675). The miscarriage rate was additionally similar between the groups: 27.9% for DVW and 32.1% for SVW groups (P = 0.765). LIMITATIONS REASONS FOR CAUTION: The study is limited by its retrospective nature. Caution should be taken concerning interpretation of these findings in cases where DVW occurs at different stages of embryo development. WIDER IMPLICATIONS OF THE FINDINGS: The result of the present study on DVW procedure provides a framework for counselling couples on their chance of clinical pregnancy per warming cycle. It additionally provides confidence and reassurance to laboratory professionals in certain countries where national policies limit embryo culture strategies making DVW inevitable. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the University Research Priority Program 'Human Reproduction Reloaded' of the University of Zurich. The authors have no conflict of interest related to this study to declare. TRIAL REGISTRATION NUMBER: N/A.

Higher miscarriage rate in subfertile women with endometriosis receiving unbiopsied frozen-warmed single blastocyst transfers.

Background: Assisted reproductive technology treatment is recommended to overcome endometriosis-associated infertility but current evidence is controversial. Endometriosis is associated with lower antral follicle count (AFC) and oocyte yield but similar clinical outcomes compared to controls. Unaffected ovarian stimulation response and embryological outcomes but lower clinical pregnancy and live birth rates and higher miscarriage rates have been reported, implying direct impact on endometrial receptivity. With evidence emerging on the benefit of frozen-warmed and blastocyst stage transfer, we investigated ART outcomes in endometriosis using homogeneous case-control groups. Methods: This is a retrospective observational case-control study including n = 66 frozen-warmed unbiopsied single blastocyst transfers of patients with endometriosis and n = 96 of women exhibiting idiopathic sterility. All frozen-warmed transfers followed artificial endometrial preparation. Results: In control women, the mean number of oocytes recovered at oocyte pick up was higher compared to women with endometriosis (15.3 ± 7.1 vs. 12.7 ± 5.2, p = 0.025) but oocyte maturation index (mature oocytes/total oocytes at oocyte pick up) was significantly higher for endometriosis (48.2% vs. 34.0%, p = 0.005). The same was shown for the subgroup of 44 endometriosis patients after endometrioma surgery when compared with controls (49.1% vs. 34.0%, p = 0.014). Clinical pregnancy rate was not higher in endometriosis but was close to significance (47.0% vs. 32.3%, p = 0.059) while live birth rate was comparable (27.3% vs. 32.3%, p = 0.746). Miscarriage rate was higher in the endometriosis group (19.7% vs. 7.3%, p = 0.018). A significantly higher AFC was observed in the control group in comparison with the endometriosis group (16.3 ± 7.6 vs. 13.4 ± 7.0, p = 0.014). Live birth rate did not differ when comparing all endometriosis cases (p = 0.746), ASRM Stage I/II and Stage III/IV (p = 0.348 and p = 0.888) with the control group but the overall pregnancy rate was higher in ASRM Stage I/II (p = 0.034) and miscarriage rate was higher in ASRM Stage III/IV (p = 0.030) versus control. Conclusion: Blastocyst transfers in women with endometriosis originate from cycles with lower AFC but higher share of mature oocytes than in control women, suggesting that endometriosis might impair ovarian reserve but not stimulation response. A higher miscarriage rate, independent of blastocyst quality may be attributed to an impact of endometriosis on the endometrium beyond the timing of implantation.

Primary atony of the lower uterine segment as a distinct cause of early postpartum haemorrhage: a case series and management recommendations.

Primary atony of the lower uterine segment appears to be a distinct cause of postpartum haemorrhage. We report a case series of women with postpartum haemorrhage where ultrasound and clinical findings revealed a well contracted fundus and upper uterine segment and a ballooned out lower uterine segment, a condition we have called primary atony of the lower uterine segment. We hope that this case series will lead to increased recognition of this condition, stimulate others to report their experience and lead to additional studies to better characterise this entity, and develop more effective therapies.

Effect of propofol anesthesia on pallidal neuronal discharges in generalized dystonia.

We present the results of continuous microelectrode recordings from individual pallidal neurons in patients with idiopathic torsion dystonia under different levels of propofol anesthesia. Neither the estimated plasma concentration of propofol nor the level of consciousness had a consistent effect on abnormally low neuronal firing rates. Our data support the pathophysiological model of a decreased basal ganglia output in dystonia and argue against a possible pharmacological artifact.

Treatment options and results in cervical myelopathy.

Cervical myelopathy is a clinical entity resulting from external compression of the cervical medulla. The clinical course can be divided into the acute form (secondary to trauma) versus subacute (progression within weeks to months) and chronic cervical myelopathy (months to years). The clinical picture of myelopathy is that of unsteady gait with long-tract signs, such as hyperreflexia, spasticity and extensor plantar responses. Between 1997 and 2000, 359 consecutive patients have been operated on in our department presenting with a variety of symptoms related to compression of the cervical medulla. Beside of standard MRI for all patients we applied SSEPs, gait analysis and dynamic MRI studies as additional helpful tools in evaluating selected patients pre- and postoperatively. We prefer the anterior approach as first-line approach because in the majority of patients the osteophytic spurs are more dominant anteriorly, and after anterior decompression and stabilization the posterior approach appears safer. We also favor the more extended approach of spondylectomy versus multilevel decompression in patients with bisegmental or multisegmental spinal canal stenosis. However it seems to be that radicular decompression is better achieved through multilevel decompression than through spondylectomy.

Prenatal diagnosis of portal vein thrombosis by ultrasound.

Neonatal portal vein thrombosis (PVT) is a rare condition seen in the setting of thrombophilia or after umbilical vein catheterization. We report a case of fetal PVT with abnormal antenatal ultrasound findings at 27 weeks of gestation. This presented initially as dilation of the intrahepatic umbilical vein. To our knowledge, this is the first reported case evaluated prenatally. Color Doppler ultrasound was valuable in detecting constriction of the vessel with a high-velocity jet seen past the obstruction site. A discussion of this condition and differential diagnosis is presented.

Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures.

UNLABELLED: Remifentanil hydrochloride is an ultra-short-acting opioid that undergoes rapid metabolism by tissue and plasma esterases. We aimed to characterize the pharmacokinetics and determine the hemodynamic profile of remifentanil after a single-bolus dose in children aged 0 to 18 yr. Forty-two children undergoing elective surgical procedures received remifentanil 5 microg/kg infused over 1 min. Patients were divided into age groups as follows: young infants (< or =2 mo), older infants (> 2 mo to < 2 yr), young children (2 to < 7 yr), older children (7 to < 13 yr), adolescents (13 to < 16 yr), and young adults (16 to < 18 yr). Arterial blood samples were collected and analyzed by mass spectroscopy to determine remifentanil pharmacokinetic profiles. Hemodynamic measurements for remifentanil's effect were made after the infusion. Methods of statistical analysis included analysis of variance and linear regression, with significance at P < or = 0.05. Complete remifentanil pharmacokinetic data were obtained from 34 patients. The volume of distribution was largest in the infants < 2 mo (mean, 452 mL/kg) and decreased to means of 223 to 308 mL/kg in the older patients. There was a more rapid clearance in the infants < 2 mo of age (90 mL. kg(-1). min(-1)) and infants 2 mo to 2 yr (92 mL. kg(-1). min(-1)) than in the other groups (means, 46 to 76 mL. kg(-1). min(-1)). The half-life was similar in all age groups, with means of 3.4 to 5.7 min. Seven subjects (17%) developed hypotension related to the remifentanil bolus. Remifentanil showed an extremely rapid elimination similar to that in adults. The fast clearance rates observed in neonates and infants, as well as the lack of age-related changes in half-life, are in sharp contrast to the pharmacokinetic profile of other opioids. Remifentanil in a bolus dose of 5 microg/kg may cause hypotension in anesthetized children. IMPLICATIONS: The pharmacokinetics of remifentanil were studied in children from birth to 18 yr. Remifentanil was found to have age-related changes in clearance and volume of distribution, but not half-life. The increased clearance observed in young infants is in contrast to other opioids.

[Quality of praenatal diagnostic ultrasound - comparison of sonographically detected foetal anomalies with diagnostic findings verified post-partum in Switzerland]. / Qualität der pränatalen sonographischen Diagnostik - Vergleich sonographisch erfasster Fehlbildungen mit dem tatsächlichen fetalen Outcome in der Schweiz.

AIM: Comparison of all praenatally detected cases of foetal anomalies to actual diagnostic findings post partum during a one year period in Switzerland. METHODS: A retrospective questionnaire-based evaluation including the 5 university hospitals and 6 large hospitals in Switzerland as a population-based study. Analysis of all foetal anomalies detected praenatally by ultrasound in the year of 1995 in these centres. RESULTS: 347 cases have been included in the study. 89 % of cases were detected using screening methods. (2/3) were referred by obstetrical practitioners and GPs. 62 % of the pregnancies were completed and 33 % terminated, while the rest resulted in abortion or stillbirth. In terminated pregnancies there was a 82 % agreement between praenatal and postmortem findings. Sonographic results and clinical/post-mortem diagnosis were in agreement about the presence of major foetal anomalies in 18 % of cases. Additional minor anomalies unperceived by sonography, however, were seen post mortem. There was no false positive case. CONCLUSIONS: Without ultrasound screening almost 90 % of anomalies would have been missed due to the absence of clinical symptoms. The Swiss two-step system for praenatal ultrasound screening, based on screening scans done by the obstetrician and GP in practice, or residents in the public outpatient clinics respectively, and the detailed scan done by a subspecialized perinatologist shows excellent results especially in the subgroup of terminated pregnancies.

Ursodeoxycholic acid for the treatment of intrahepatic cholestasis of pregnancy.

OBJECTIVE: To report our experience in managing intrahepatic cholestasis of pregnancy with ursodeoxycholic acid. METHODS: All cases of intrahepatic cholestasis of pregnancy that were diagnosed at Bridgeport Hospital from January 1997 to August 1999 were identified. Information was abstracted on demographics, medical and obstetric history, symptoms, laboratory data, therapy and pregnancy outcome. Statistical analysis was primarily descriptive; continuous variables were analyzed with t tests. RESULTS: A total of 20 cases of intrahepatic cholestasis of pregnancy were identified (0.32% of live births). All patients presented with pruritus. The mean gestational age at onset of symptoms was 31.1 weeks (range 13-38.4, median 32.4). Bile acids were measured in 18 cases and were elevated in all. The mean gestational age at delivery was 36.4 weeks (32.3-39.9). Eight patients were treated with ursodeoxycholic acid (600-1200 mg). All eight patients experienced subjective improvement in pruritus after initiation of treatment with ursodeoxycholic acid. Ursodeoxycholic acid was associated with a decrease in bile acids in most patients (p = 0.16) and with a significant decrease in serum transaminases (p = 0.03). CONCLUSIONS: Ursodeoxycholic acid is an effective therapy for relief of pruritus and improvement of the liver dysfunction that occurs with intrahepatic cholestasis of pregnancy.

Indicated preterm birth: a possible contribution to group B streptococcal sepsis prophylaxis protocol failures. A case report.

BACKGROUND: Despite the acceptance of protocols for the prevention of group B streptococcal (GBS) sepsis for the newborn, protocol violations, with subsequent failure to initiate intrapartum antibiotic therapy, occur at many institutions. The causes for GBS prophylaxis protocol violations are not well understood. CASES: We report two cases of indicated preterm birth in which appropriate antibiotic prophylaxis for GBS sepsis was not initiated. CONCLUSION: In the setting of indicated preterm birth, GBS prophylaxis may be overlooked. We suspect that the attention given to the medical or fetal complications of indicated preterm birth may contribute to the omission of GBS sepsis prophylaxis in these situations.

A randomized, prospective evaluation of noninvasive ventilation for acute respiratory failure.

We compared noninvasive positive-pressure ventilation (NPPV), using bilevel positive airway pressure, with usual medical care (UMC) in the therapy of patients with acute respiratory failure (ARF) in a prospective, randomized trial. Patients were subgrouped according to the disease leading to ARF (chronic obstructive pulmonary disease [COPD], a non-COPD-related pulmonary process, neuromuscular disease, and status postextubation), and were then randomized to NPPV or UMC. Thirty-two patients were evaluated in the NPPV group and 29 in the UMC group. The rate of endotracheal intubation (ETI) was significantly lower in the NPPV than in the UMC group (6.38 intubations versus 21.25 intubations per 100 ICU days, p = 0.002). Mortality rates in the intensive care unit (ICU) were similar for the two treatment groups (2.39 deaths versus 4.27 deaths per 100 ICU days, p = 0.21, NPPV versus UMC, respectively). Patients with hypoxemic ARF in the NPPV group had a significantly lower ETI rate than those in the UMC group (7.46 intubations versus 22.64 intubations per 100 ICU days, p = 0.026); a similar trend was noted for patients with hypercapnic ARF (5.41 intubations versus 18.52 intubations per 100 ICU days, p = 0.064, NPPV versus UMC, respectively). Patients with ARF in the non-COPD category had a lower rate of ETI with NPPV than with UMC (8.45 intubations versus 30.30 intubations per 100 ICU days, p = 0.01). Although the rate of ETI was lower among COPD patients receiving NPPV, this trend did not reach statistical significance (5.26 intubations versus 15.63 intubations per 100 ICU days, p = 0.12, NPPV versus UMC, respectively). In conclusion, NPPV with bilevel positive airway pressure reduces the rate of ETI in patients with ARF of various etiologies.

Successful pregnancy after suspected anaphylactoid syndrome of pregnancy (amniotic fluid embolus). A case report.

BACKGROUND: Limited information is available on the recurrence risk of anaphylactoid syndrome of pregnancy. CASE: A successful pregnancy followed suspected anaphylactoid syndrome of pregnancy. CONCLUSION: A review of the literature revealed five cases of successful subsequent pregnancies following anaphylactoid syndrome of pregnancy. No instances of recurrent anaphylactoid syndrome of pregnancy have been reported.

Pregnancy outcome after successful external cephalic version.

OBJECTIVE: Recent studies have suggested that the rate of cesarean delivery in patients who have undergone a successful external cephalic version is higher than expected. This study compares the incidence of cesarean delivery in patients who underwent successful external cephalic version and patients with primary cephalic presentations. STUDY DESIGN: We identified and reviewed the charts of 92 patients who underwent a successful external cephalic version. We identified a control population of 184 patients from the delivery room logs. We collected outcome data and information on additional risk factors that may affect cesarean delivery rates. RESULTS: There were no significant differences between study and control populations. There was no significant difference in the cesarean delivery rate between study patients (22.8%) and control patients (23.4%). CONCLUSIONS: We could not demonstrate a significant increase in the cesarean delivery rate for women who underwent successful external cephalic version in comparison with patients in labor with primary cephalic presentations.

The association of increased fetal nuchal translucency and spinal muscular atrophy type I.

We report a fetus with spinal muscular atrophy type I, who presented with an increased nuchal translucency at 13 weeks' gestation. A review of the literature reveals additional cases of spinal muscular atrophy type I associated with increased nuchal translucency and suggests increased nuchal translucency may be an early finding in this disorder.

Effects of central and peripheral nicotinic blockade on human nicotine discrimination.

Nicotine produces interoceptive stimulus effects in humans, which may be critical in understanding tobacco use. It has not yet clearly been demonstrated that discrimination of nicotine, or any drug, in humans is due to its central effects. We compared effects of mecamylamine (10 mg p.o.), a central and peripheral nicotine antagonist, on nicotine discrimination with those of trimethaphan (10-40 microg/kg per min i.v.), a peripheral nicotine antagonist only, and placebo. Smokers (n = 6) were first trained to reliably discriminate 0 versus 20 microg/kg nicotine by nasal spray and then tested on generalization of this discrimination across a range of nicotine doses (0, 3, 6, 12, 20 microg/kg) following antagonist/placebo pretreatment. Nicotine self-administration was also assessed after generalization testing by having participants intermittently choose between nicotine versus placebo spray. Compared with responding following placebo pre-treatment, discrimination of the highest dose of nicotine was significantly attenuated following mecamylamine but not trimethaphan. Similar results were observed for some subjective responses to nicotine. Mecamylamine also tended to increase nicotine self-administration. Consistent with previous animal studies, these results suggest that discriminative stimulus effects of nicotine in humans are mediated at least in part by its central effects.

Calibration of a reflectance pulse oximeter in fetal lambs for arterial oxygen saturations below 70%.

OBJECTIVE: To calibrate a reflectance pulse oximeter developed at the Division of Perinatal Physiology, University Hospital of Zurich, for monitoring of oxygen saturations below 70%. METHODS: Oxygen saturation measured noninvasively with the reflectance pulse oximeter in fetal sheep was compared with oxygen saturation of arterial blood samples measured by a conventional two-wavelength oximeter. Oxygen saturation was varied by stepwise reduction of the inspired oxygen concentration of the ewe. RESULTS: A total of 58 data pairs was obtained from five fetuses, with a range of 10.9-73.5% for the reference method and 6.8-69.2% for the pulse oximetry oxygen saturation values. There was good correlation between the results obtained by the two methods (r2 = .89, P < .0001), with a 95% confidence interval of +/- 12.5%. The pulse oximeter showed a precision of 6.2% oxygen saturation. CONCLUSION: The Zurich reflectance pulse oximeter offers valid measurements of oxygen saturation levels down to 10% oxygen saturation, and is therefore suitable for monitoring the fetus during delivery.

The effects of lithium on a potential cycling model of bipolar disorder.

1. Although bipolar disorder constitutes a major public health problem, with a high risk of suicide and an economic cost exceeding that of unipolar depression, it has received comparatively little attention, particularly at the basic science level. Perhaps as a result of this neglect, there is currently no animal model able to simulate the cyclicity which is its defining characteristic. 2. Consequently, drug development in this area is meager and has proceeded serendipitously rather than empirically. 3. The authors have recently reported that repeated exposure to cocaine and other stressors can induce an oscillation or cycling in a host of neurochemical and physiological systems. 4. In order to test whether such cycling might be of potential relevance to bipolar disorder, the authors examined whether cocaine-induced cyclicity of amphetamine-evoked efflux of dopamine from slices of rat nucleus accumbens and striatum and/or cocaine induced oscillation of a behavior, stress-induced hypoalgesia, could be prevented by lithium, the agent of choice in treating this disease. 5. The authors report that prophylactic treatment with lithium, completely and specifically prevented oscillations in each instance. This may represent an important initial step toward the development of the first cycling model of bipolar disorder.

Oscillatory-sensitization model of repeated drug exposure: cocaine's effects on shock-induced hypoalgesia.

1. The authors have recently proposed that the sensitization produced by repeated exposure to drugs or stress may give way to an alternating pattern of increases and decreases in the response to each subsequent exposure (i.e., oscillate), as the limits of the physiological system are approached. 2. Evidence for oscillation has been obtained for 6 drug/non-drug stressors and 9 neurochemical or endocrine endpoints. This paper extends the model to a behavioral outcome. 3. In the first experiment, rats were given 0, 1, 2 or 3 pretreatments with cocaine hydrochloride (COC; 12 mg/kg i.p.), separated by 1-week intervals, and then were tested for footshock-induced hypoalgesia (5-sec, 2-mA), as measured by withdrawal latencies from a hot-plate. 4. The second experiment replicated the first and extended the pretreatment sequence to 5 COC injections. 5. In both experiments, shock significantly increased latencies over the no-shock controls. COC enhanced shock-induced hypoalgesia and this sensitization reached its maximum after 2 COC pretreatments. Thereafter, oscillation developed such that the sensitization was attenuated by 3 as compared to 2 COC injections, enhanced by 4 injections, and reattenuated after 5 COC pretreatments. 6. These data complement other findings by demonstrating that the oscillation model extends to a stress-induced behavioral outcome.