No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture.

STUDY QUESTION: Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception? SUMMARY ANSWER: There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study. WHAT IS KNOWN ALREADY: Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions. STUDY DESIGN, SIZE, DURATION: This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia). PARTICIPANTS/MATERIALS, SETTING, METHODS: From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders. MAIN RESULTS AND THE ROLE OF CHANCE: In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer. LIMITATIONS, REASONS FOR CAUTION: This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables. WIDER IMPLICATIONS OF THE FINDINGS: Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation. STUDY FUNDING/COMPETING INTEREST(S): The study was financed by a research grant from Gedeon Richter. There are no conflicts of interest for all authors to declare. TRIAL REGISTRATION NUMBER: N/A.

Non-invasive metabolomic profiling of Day 2 and 5 embryo culture medium: a prospective randomized trial.

BACKGROUND: Near infrared (NIR) spectroscopy is a technology proposed to facilitate non-invasive screening for the most optimal human embryo for uterine transfer. It has been proposed that the NIR spectral profile of an embryo's spent culture medium can be used to generate a viability score that correlates to implantation potential. As the initial proof of principle studies were all retrospective, our aim was to investigate whether NIR spectroscopy on spent embryo culture medium in an on-site, prospective setting could improve the ongoing single embryo transfer (SET) pregnancy rate after Day 2 and 5 transfers. METHODS: We conducted a single-centre, double-blinded, randomized controlled trial in which the NIR group was compared with a control group. The primary outcome was the clinical pregnancy rate after 6-7 weeks of gestation per randomized patient. In the control group embryo selection was based only on traditional morphological evaluation while in the treatment group NIR spectroscopy was added to the morphological evaluation. RESULTS: The study was terminated early as the analysis of the Data Safety Monitoring Board showed a very low conditional power of superiority for the primary outcome. Of the 752 patients calculated to be included in the study, 164 and 163 patients were randomized into the NIR and control groups, respectively. No significant difference in the ongoing pregnancy rate per randomized patient was found between the NIR and the control group, 34.8 versus 35.6%, (P= 0.97). The proportional difference between the study groups mean was -0.8% (95% confidence interval -11.4 to 10.2). CONCLUSIONS: This study shows that adding NIR spectroscopy, in its present form, to embryo morphology does not improve the chance of a viable pregnancy when performing SET. The NIR technology appears to need further development before it can be used as an objective marker of embryo viability. CLINICAL TRIALS IDENTIFIER: ISRCTN23817363.

Obstetric outcomes after transfer of vitrified blastocysts.

BACKGROUND: It has been claimed that the risks to the child resulting from vitrification as compared with the slow-freezing technique, may be higher owing to the high concentrations of potentially toxic cryoprotectants. We therefore retrospectively compared the obstetric and neonatal outcomes in a cohort of children born after transfer of vitrified blastocysts, fresh blastocysts and slow-frozen early cleavage stage embryos. METHODS: All children born after transfer of vitrified blastocysts (n = 106), fresh blastocysts (n = 207) and slow-frozen early cleavage stage embryos (n = 206) during the period January 2006 to May 2008 at Fertility Center Scandinavia were included. Data on obstetric and neonatal outcomes were obtained from medical records from the antenatal and delivery clinics. RESULTS: For singletons, there were no significant differences between the groups in gestational age, mortality or birth defects. After adjustment for parity and BMI, birthweight was significantly higher in singletons born after transfer of vitrified blastocysts as compared with after transfer of fresh blastocysts (median 3560 versus 3510 g, P = 0.0311). More singletons born after transfer of fresh blastocysts were small for gestational age compared with singletons born after transfer of vitrified blastocysts (12.1 versus 3.0%, P = 0.0085). A higher rate of major post-partum haemorrhage was observed in the vitrified blastocyst group as compared with the other two groups (25.0 versus 6.0 and 7.5%). CONCLUSIONS: No adverse neonatal outcomes were observed in children born after transfer of vitrified, as compared with fresh blastocysts or after transfer of slow-frozen early cleavage stage embryos.

Testicular ultrasonography and extended chromosome analysis in men with nonmosaic Klinefelter syndrome: a prospective study of possible predictive factors for successful sperm recovery.

OBJECTIVE: To investigate whether extended chromosome analysis or testicular sonography, including flow Doppler imaging, before diagnostic testicular sperm extraction have predictive value for successful sperm retrieval in men with nonmosaic Klinefelter syndrome. DESIGN: Prospective clinical study. SETTING: IVF clinic and genetics laboratory at a university hospital. PATIENT(S): Nineteen patients with nonmosaic Klinefelter syndrome and azoospermia. INTERVENTION(S): Collection of blood samples; histopathologic examination of testicular tissue; fluorescence in situ hybridization; sonography, including Doppler imaging; and testicular sperm extraction. MAIN OUTCOME MEASURE(S): Testicular volume, serum FSH and serum testosterone levels, percentage of normal XY cells, ultrasound echogenicity, intratesticular blood flow resistance, and sperm recovery. RESULT(S): Testicular volume and levels of serum FSH and serum testosterone levels did not differ significantly. No differences in testicular echogenicity or intratesticular blood flow resistance were found between 47,XXY men in whom sperm recovery was successful and those in whom sperm recovery failed. Significant differences were seen between all patients with the Klinefelter syndrome and controls with normal sperm values. Fluorescence in situ hybridization of peripheral lymphocytes and buccal tissue showed no correlation between frequency of normal 46,XY cells and testicular spermatogenesis. CONCLUSION(S): In azoospermic men with the Klinefelter syndrome, histopathologic findings seem to be predictive for successful sperm recovery. Infertility work-up, including diagnostic testicular sperm recovery, is recommended, and, if possible, viable sperm should be cryopreserved.

Organizational change and health at work.

The focus of this article is the link between organizational change and individual working conditions. In some organizational development projects health aspects may be left to chance, in others they may be to some extent respected, and in still others they are the main theme of the process and direction of change. Along this line, the author presents and discusses a number of Swedish cases. The analysis aims at emphasizing a necessary characteristic of occupational health experts, namely, to be sensitive to the differences between the goals of various projects in organizational development. Preventive work must be based on a careful identification of the sort of health aspects that are overlooked in every effort at organizational change.

Means, goals, and outcomes of a comprehensive occupational health program for telephone operators.

A means-goals analysis requires a plan with some degree of distinctness, which is worked out beforehand and specifies reasonably clear goals and intended means. This article draws its material from a broadly designed strategy for organizational change that meets these criteria. A service division of Swedish Telecom underwent a program of comprehensive organizational change; major efforts were made to improve the occupational health of 300 telephone operators in manual service operations. Over a full three-year period, a number of specific problems were to be resolved. An independent research team evaluated the implementation of the program prospectively. The team followed an evaluation model in which stringent distinction was made between: (1) action areas, (2) intended specific means, (3) intended immediate goals, and (4) the longer-term favorable effects of achieving these immediate goals. In addition, an attempt was made to interpret and understand the findings of the means-goals evaluation by paying systematic attention to the implementation process and factors that might permit an understanding of the final outcomes of the program. Compared with other efforts to improve telephone operators' work conditions as reported in the research literature, this strategy for the promotion of change is broad and ambitious.

Evaluation of an ergonomics intervention programme in VDT workplaces.

This paper focuses on an intervention programme based on the concept of participatory ergonomics. The study was designed within the framework of a multidisciplinary project concerned with identifying the work conditions and problems necessary to improve the working life of VDT operators with routine data-entry and data-dialogue tasks. The intervention programme was evaluated in two follow-up studies. The evaluation criteria covered the proposals for improvement emerging from (1) the intervention programme's final joint decisions (of experts and employees) on measures needed, and (2) workers' views of the effectiveness of the programme itself. As the implementation period was marked by increasing turbulence caused by recession in many branches of the Swedish economy, attention was paid to the impact of the restructuring and rationalization effected by company management in the workplaces under study. To obtain a better understanding of the outcome of the intervention programme, the follow-up was extended systematically to explore the disturbing organizational factors operating during the implementation period. The results of the evaluation offer increased knowledge of organizational barriers to the implementation of ergonomics measures decided upon within the framework of intervention research.

The psychological background of pregnancy outcome: a critical evaluation of research.

This paper concentrates on the scientific attempts to find psychological interpretations of pregnancy outcome. The author presents a critical discussion of the literature based on an extensive evaluation undertaken during 1988. The aim of the analysis was to clarify the state-of-the-art and choices of methodologies in studies exploring and identifying the non-medical factors behind pregnancy outcome. Three distinctive psychology based approaches are found, which are based on personality theory, psychosocial theory and life-event theory. These bases argue for very different causal contexts of pregnancy outcome and are, therefore, according to the author's view, very important to recognize, particularly when it comes to occupational health research on work environment and pregnancy outcome.

Swedish women and new technology.

This paper provides information and analysis on the overall situation of women in Sweden with regard to computer based new technology. It is based on a survey of computer use in Sweden, carried out in June 1984 by Statistics Sweden. The aim of the study was to ascertain the knowledge base and experience with computers of the Swedish population. In order to study whether sex differences exist a special analysis of the data was carried out. Women are involved in new technology in Sweden to a very great extent, however, there is male dominance in both the initiation and development of the technology. This may be as much reflective of general male and female roles in the workplace as of the nature of new technology itself.

Inhibition of peritonitis by amide local anesthetics.

Peritonitis was induced in rats by exposing the peritoneal surface to 0.1 M hydrochloric acid (HCl). Peritonitis was quantified by extraction of Evans blue-bound albumin from the tissue exposed to HCl and analyzed by a spectrophotometric technique. In the first set of experiments, one group of rats had the peritoneal surface exposed to HCl following local pretreatment with isotonic saline; a second group of rats had the peritoneum exposed to HCl after topical pretreatment with an equal volume of lidocaine 1%, whereas in a third group the peritoneal surface was exposed only to saline without HCl. The experimental design in the second set of experiments was similar to that of the first set except that bupivacaine 0.5% was used instead of lidocaine in the second group. Results show a significant inhibition of peritonitis in the groups pretreated with lidocaine (P less than 0.01) and bupivacaine (P less than 0.05) compared with rats in the saline pretreated group. In the lidocaine-pretreated group Evans blue-albumin extravasation did not differ significantly from the rats not receiving HCl, whereas the bupivacaine-pretreated group showed a slightly but significantly (P less than 0.05) more pronounced peritonitis than control rats not exposed to HCl. In the third set of experiments the peritoneum was topically treated with either lidocaine 1%, bupivacaine 0.5%, or isotonic saline after first having exposed the peritoneal surface to HCl. A significant inhibition of albumin extravasation was seen following lidocaine (P less than 0.001) or bupivacaine (P less than 0.001) treatment compared with treatment with isotonic saline.(ABSTRACT TRUNCATED AT 250 WORDS)

Different fertilization rates between immotile testicular spermatozoa and immotile ejaculated spermatozoa for ICSI in men with Kartagener's syndrome: case reports.

We report two cases of infertility treatment in couples where males suffered from Kartagener's syndrome (KS) and a total absence of motile sperm in the ejaculate. A total of three ICSI cycles was carried out. In all cycles, viable ejaculated or testicular spermatozoa were selected using the hypo-osmotic swelling (HOS) test. Case 1: In the first ICSI cycle total fertilization failure occurred after using ejaculated spermatozoa. In the following cycle testicular spermatozoa were used for ICSI, resulting in 75% fertilized oocytes and a pregnancy. Case 2: In the same ICSI cycle 50% of the oocytes were injected with ejaculated and 50% with testicular spermatozoa. The fertilization rates were 44 and 56% respectively and high quality embryos were achieved in both groups. One single embryo derived from testicular sperm was transferred with a resulting singleton pregnancy. In conclusion, testicular sperm for ICSI seem to have reliable fertilization capacity in men with KS, while ejaculated sperm, even if tested viable, seem more unpredictable. HOS test for selection of viable sperm for ICSI is recommended when ejaculated as well as testicular sperm are used for ICSI.

Attitudes of different groups of women in Sweden to oocyte donation and oocyte research.

OBJECTIVES: To evaluate attitudes of Swedish women towards oocyte donation and oocyte research. METHODS: Five different groups of women, with approximately 50 patients in each, were asked anonymously about their attitudes to legislation, tentative roles as donors or recipients, anonymity, suitable donors or recipients, research on fetuses and cadavers as a source of oocytes, age limits and economic aspects. The groups were: 1. Women undergoing IVF treatment (IVF). 2. Infertile women during work-up (INF). 3. Recently delivered women attending a maternity unit (MAT). 4. Women attending a family planning center applying for therapeutic abortion (FPC). 5. Women with Turner's syndrome (TUR). RESULTS: More than 90% of women in all groups investigated advocated amendment of the law in order to permit oocyte donation. The women of infertile groups were more in favor of donating oocytes compared to women of fertile groups (p<0.05). A great majority would prefer anonymity both if they were donors and if they were recipients. If no anonymity was guaranteed, the acceptance of both the donor and recipient groups decreased but more than half of the women in all groups would still donate/accept oocytes. There was a significant difference in attitude towards non-anonymous oocyte donation, with the highest acceptance among Turner patients and the lowest among IVF patients (p<0.01). A majority in all groups were more motivated to donate/accept oocytes from a close relative, with the exception of Turner patients (p<0.01). All groups had a negative attitude to the use of donated fetuses and cadavers as sources of oocytes. IVF patients, close relatives and volunteers were all regarded as suitable donors by a majority of women in all groups. Women of fertile age, with ovarian failure or a genetic disorder, were accepted as recipients by all groups. Postmenopausal women were not accepted as recipients by a great majority in all groups. All groups preferred an age limit for recipients. More than 70% set the limit to the interval 40 to 45 years of age. A majority in all groups believed that donors should be paid to cover medication and loss of income. The recipients were expected, by a majority of women, to pay for some of the costs of the oocyte donation program. CONCLUSIONS: A great majority wanted a change in the Swedish legislation to permit oocyte donation. All groups had a generous attitude to donation of oocytes although anonymity would be preferred. Ovarian dysfunction and genetic disorders among women of fertile age were regarded as major indications for oocyte donation. IVF patients, close relatives and volunteers were all regarded as acceptable donors.

Postoperative pain relief by topical lidocaine in the surgical wound of hysterectomized patients.

BACKGROUND: To improve postoperative analgesia, local anesthetics have been administered perioperatively as infiltration or as aerosol in the surgical area. A previous study showed good analgesic effects by topical lidocaine in the wound in minor extraabdominal surgery (herniorraphy), while the same treatment in minor lower laparothomies did not improve postoperative analgesia. The present study investigated the effect of topical wound anesthesia using lidocaine aerosol on postoperative pain following major lower abdominal surgery. METHODS: Postoperative pain and analgesic requirements were studied in a double-blind randomized trial including 30 hysterectomized patients. Patients were randomized to receive single wound treatment either with lidocaine aerosol 500 mg (100 mg/ml; Xylocain aerosol, ASTRA, Sweden) (n = 15) or placebo aerosol (n = 15). Postoperative pain was evaluated by visual analogue scale (VAS). Requirements of opiate analgesics (buprenorphine) after surgery were monitored. RESULTS: Lidocaine aerosol induced a significantly (P < 0.001) better analgesia at rest (VAS) and a significant (P < 0.001) reduction in postoperative requirements of buprenorphine during the first 24 hours after surgery compared to placebo aerosol. Differences between the groups in pain scores (VAS) and buprenorphine requirements during the second postoperative day were not significant. Mean pain scores upon mobilization 24 h after surgery were significantly lower in the group receiving lidocaine aerosol (P < 0.05). The plasma lidocaine concentration 4 h after the administration of lidocaine was well below toxic level and plasma lidocaine was detectable 48 h postoperatively. No drug-related side effects were reported. CONCLUSION: A single dose of lidocaine aerosol topically administered in the surgical wound of hysterectomy patients improved analgesia during the first postoperative day with minimal risk of side effects.

The adrenergic nervous control of fluid transport in the small intestine of normotensive and spontaneously hypertensive rats.

Intestinal net fluid transport in normotensive Wistar Kyoto rats (WKR) and spontaneously hypertensive rats of the Okamoto strain (SHR) were studied during 'rest', during electrical stimulation of the regional sympathetic fibres as well as after acute denervation and alpha-adrenergic receptor blockade (phentolamine). During 'rest' no statistically significant difference in fluid transport rate could be demonstrated between WKR and SHR. Cutting the left splanchnic nerve, severing the periarterial nerves or giving phentolamine turned net fluid absorption to net fluid secretion in most SHR, whereas fluid absorption was little influenced in WKR by these procedures. Stimulating the left splanchnic nerve (2, 4, 8 Hz) markedly increased net fluid uptake or decreased net fluid secretion in SHR in a frequency-dependent manner. A small effect was seen in WKR at a stimulation rate of 4 Hz. The 'spontaneous' fluid secretion in denervated intestinal segments of SHR was accompanied by a net chloride secretion. Giving hexamethonium i.v. turned net fluid and chloride secretion into water and ion absorption, suggesting that the secretion was evoked by secretory nervous pathways in the enteric nervous system. It is concluded that the 'spontaneous' fluid and electrolyte secretion seen in denervated intestines of SHR is normally 'concealed' by an augmented rate of firing in the regional adrenergic nerve fibres controlling fluid and electrolyte transport. The possible importance of the 'spontaneous' intestinal secretion in SHR in the pathophysiology of arterial hypertension is tentatively discussed.

Intestinal fluid and electrolyte transport in man during reduced circulating blood volume.

The effect on intestinal net transport of fluid and electrolytes of a reduced circulating blood volume was studied in the human jejunum with the triple lumen perfusion technique. The blood volume was reduced by changing the lower extremities from an elevated to a dependent position combined with a venous stasis. The tilting manoeuvre, probably resembling a bleeding of about 600-800 ml, significantly increased net absorption of fluid, sodium and chloride while glucose transport was unaffected. Concomitantly the blood flow decreased and vascular resistance increased in the forearm vascular bed. The results are consistent with the hypothesis that activity in the sympathetic nervous system initiated from unloading of the cardiopulmonary volume receptors enhances intestinal absorption of fluid and electrolytes. The results also indicate that the human intestines are an important target organ in the compensatory mechanisms activated during hypovolaemia due to - for example, haemorrhage.

Obstetric outcome of pregnancies following ICSI, classified according to sperm origin and quality.

The aim of this study was to report the outcome of all clinical pregnancies obtained after intracytoplasmic sperm injection (ICSI) performed during a 5 year period at two fertility clinics, with special reference to delivery outcome associated with different sperm origin and quality and the transfer of fresh or frozen-thawed pre-embryos. A total of 1293 clinical pregnancies was analysed. Deliveries occurred in 75.9% (n = 982) and early spontaneous abortion, late spontaneous abortion and ectopic pregnancy in 21.4, 1.0 and 1.2% respectively. Multiple birth occurred in 21.3% (208 sets of twins and one set of triplets) of the deliveries, with the highest incidence in the epididymal sperm group (30.2%) and lowest in the cryopreserved group (13.7%). A total of 1192 infants was born. Preterm birth occurred in 15.7% of all deliveries. Preterm birth was not related to sperm origin or quality but was related to multiple birth. The prematurity rate was 8.4%, 42.3% and 100% for singletons, twins and triplets respectively. Singleton infants born after cryopreservation as embryos had a significantly higher birthweight than the ejaculated sperm group with fresh embryo transfer. The perinatal mortality rate was 11.7 per 1000 born infants. Eighty-seven of the 1192 infants (7.3%) had a malformation, 40 of which were minor. The perinatal mortality rate and the malformation rate were similar in the different subgroups. Prenatal karyotyping was performed on 149 fetuses (12.5%) and abnormal results were found in four cases (2.7%). In conclusion, obstetric outcome of ICSI pregnancies was similar to that of conventional IVF and was not influenced by sperm origin or quality. The high incidence of multiple births is still the major concern.