Complete and partial luteinized unruptured follicle syndrome after ovarian stimulation with clomiphene citrate/human menopausal gonadotrophin/human chorionic gonadotrophin

A total of 31 clomiphene citrate/human menopausal gonadotrophin(HMG)/human chorionic gonadotrophin (HCG)-stimulated cyclesin 28 patients were investigated to determine the fate of eachof the matured follicles. A standard stimulation regimen wasadhered to, and ultrasound as well as hormonal monitoring wasperformed. All follicles were measured by vaginal ultrasoundat –12, +35 and +45 h relative to HCG administration andat 7 days after HCG administration. Of the 220 follicles, 107(48.6%) ruptured. The number of ruptured follicles per cyclewas correlated with the mid-luteal progesterone concentration(r = 0.63, P = 0.0005). The probability of follicular rupturewas related to follicular diameter at 12 h before HCG administration;6% of follicles <12 mm in diameter ruptured compared with87% of follicles 18–19 mm. A complete luteinized unrupturedfollicle (LUF) syndrome was observed in six cycles (20%). Inthese cycles, follicular growth and oestradiol, progesterone,luteinizing hormone (LH) and follicle stimulating hormone (FSH)concentrations at 12 h before HCG administration were similarto those in cycles with follicular rupture. However, mid-lutealprogesterone concentrations were lower in complete LUF cycles(46.97 ± 8.95 nmol/1 versus 108.74 ± 12.27 nmol/1;P = 0.02). These data demonstrate that in stimulated cyclesmany follicles, usually the smaller ones, fail to rupture, evenafter HCG administration. Complete LUF syndrome, despite a strongexogenous ovulatory signal, and the absence of any differencein peri-ovulatory hormonal parameters, indicates that the defectcausing LUF resides in the follicle itself and/or hormonal changesduring the follicular phase.     

Single embryo transfer and multiple pregnancy rate reduction in IVF/ICSI: a 5-year appraisal

One of the most problematic issues of assisted reproduction is the high incidence of multiple pregnancies, resulting from the transfer of more than one embryo. Particularly at risk are young women who have good quality embryos. The only strategy to reduce the incidence of multiple pregnancies, including twin pregnancies, after assisted reproduction is single embryo transfer (SET). In 1997, the present authors therefore introduced elective SET (eSET) in this particular target group. The proportion of eSET increased from 1.5 (1997-1998) to 17.5% (1999-2002) of all transfers. In 2002, 20% of all transfers were SET. Comparing these two periods, an overall pregnancy rate of 35 and 34% per transfer, respectively, was obtained, while the overall twinning rate dropped from 30 to 21%. The twinning rate dropped to 14% in 2002, and in the eSET group there was only one monozygotic twin. These results demonstrate that a decline in the twinning rate is feasible without a drop in overall pregnancy rates. Comparing eSET with elective double embryo transfer (eDET), it was found that ongoing pregnancy and implantation rates were the same in both groups, but the proportion of twins was clearly different. It was further observed that the mean birthweight of singleton children born after eSET was significantly higher than that after DET. This could reflect a better developmental or implantation potential of these embryos, but this finding remains to be confirmed.     

Transport-in-vitro fertilization/intracellular sperm injection: a prospective randomized study

We performed a prospective randomized clinical trial to investigate whether long distance oocyte transport prior to an intracytoplasmic sperm injection (ICSI) procedure influences fertilization rates, embryo quality and/or embryo implantation rates. After informed consent, 100 infertile couples booked for ICSI treatment were randomized into two groups. In group 1 (n = 50), patients were stimulated and monitored in Rotterdam (The Netherlands), and oocyte retrieval, ICSI procedure and embryo transfer took place in Gent (Belgium). In group 2 (n = 50), patients were stimulated, monitored and punctured in Rotterdam and the oocytes were transported in their follicular fluid in an isothermic transport box to Gent, where the ICSI procedure and the embryo transfer took place. In both groups the stimulation and monitoring regimen, puncture technique, laboratory conditions and transfer policy were identical. In both groups, the number of fertilized oocytes (7.13 +/- 0.65 versus 5.53 +/- 0.60, P = 0.08), the number of transferred embryos (2.36 +/- 0.09 versus 2.40 +/- 0.11, P = 0.87) and the embryo implantation rate [20/113 (17.7%) versus 19/103 (18.4%), P = 0.89] was similar. In group 1, the number of retrieved oocytes was higher (10.83 +/- 0.95 versus 8.44 +/- 0.93, P = 0.05). The total score of the embryos obtained (18.90 +/- 1.73 versus 12.64 +/- 1.26, P = 0.01), the number of good quality embryos (4.63 +/- 0.49 versus 2.98 +/- 0.38, P = 0.02), the mean score of the transferred embryos (3.32 +/- 0.11 versus 2.94 +/- 0.13, P = 0.05) and the number of embryos available for cryopreservation (2.70 +/- 0.45 versus 1.48 +/- 0.38, P = 0.03) were significantly higher in group 1. Therefore, long distance transport of oocytes prior to ICSI does not affect oocyte fertilization and embryo implantation rates, although a negative effect on embryo quality cannot be excluded.      

Medical students' personality characteristics and academic performance: a five-factor model perspective

OBJECTIVES: This study investigates: (1) which personality traits are typical of medical students as compared to other students, and (2) which personality traits predict medical student performance in pre-clinical years. DESIGN: This paper reports a cross-sectional inventory study of students in nine academic majors and a prospective longitudinal study of one cohort of medical students assessed by inventory during their first preclinical year and by university examination at the end of each pre-clinical year. SUBJECTS AND METHODS: In 1997, a combined total of 785 students entered medical studies courses in five Flemish universities. Of these, 631 (80.4%) completed the NEO-PI-R (i.e. a measure of the Five-Factor Model of Personality). This was also completed by 914 Year 1 students of seven other academic majors at Ghent University. Year end scores for medical students were obtained for 607 students in Year 1, for 413 in Year 2, and for 341 in Year 3. RESULTS: Medical studies falls into the group of majors where students score highest on extraversion and agreeableness. Conscientiousness (i.e. self-achievement and self-discipline) significantly predicts final scores in each pre-clinical year. Medical students who score low on conscientiousness and high on gregariousness and excitement-seeking are significantly less likely to sit examinations successfully. CONCLUSIONS: The higher scores for extraversion and agreeableness, two dimensions defining the interpersonal dynamic, may be beneficial for doctors' collaboration and communication skills in future professional practice. Because conscientiousness affects examination results and can be reliably assessed at the start of a medical study career, personality assessment may be a useful tool in student counselling and guidance.     

Immunological analysis of the components of the antigen complex A60 of Mycobacterium bovis BCG.

The antigen complex of A60 of Mycobacterium bovis BCG was analyzed by different immunological techniques to assess its relevance to tuberculosis and the involvement of its components in the immune reactions elicited in humans by tuberculous infection. A60 is composed of about 30 components, of which 8 were identified by available monoclonal antibodies (lipoarabinomannan, a glycolipid, and proteins of 65, 40, 38, 35, 19, and 14 kDa). The majority (87.5%) of anti-mycobacterial antibodies in sera from tuberculosis patients was directed against A60. Western blot (immunoblot) analysis indicated that the majority of the highly antigenic proteins present in mycobacterial homogenates were components of the A60 complex. A small percentage (7.8%) of A60 epitopes proved to be species specific. Thus, A60 proteins of 66, 41, 38, 37, 35, 34, 32, and 22 kDa were found to contain B-cell epitopes specific for M. bovis and not shared by Mycobacterium leprae oR Mycobacterium avium.     

Duplex PCR for differential identification of Mycobacterium bovis, M. avium, and M. avium subsp. paratuberculosis in formalin- fixed paraffin-embedded tissues from cattle

We previously isolated and sequenced two genomic segments of Mycobacterium avium subsp. paratuberculosis, namely, f57, a species-specific sequence, and the p34 gene, coding for a 34-kDa antigenic protein. Comparison of sequences upstream of the p34 open reading frame (us-p34) from M. avium subsp. paratuberculosis and M. tuberculosis showed a 79-base deletion in M. tuberculosis. Sequence analysis of the p34 genes in another two species, M. bovis (strain BCG) and M. avium (strain D4), confirmed the differences observed between tuberculous and nontuberculous species. A duplex diagnostic PCR strategy based on coamplification of nonhomologous us-p34 and species-specific f57 sequences was therefore developed. Duplex PCR yielded three different patterns, specific either for tuberculous bacilli (M. tuberculosis, M. bovis, and M. africanum), for both nontuberculous mycobacteria M. avium and M. intracellulare, or for M. avium subsp. paratuberculosis. The specificity of this single-step DNA-based assay was assessed on DNA from cultured mycobacterial strains, as well as on a panel of formalin-fixed and paraffin-embedded tissues from cattle. Molecular assay results from tissular DNA were compared to conventional bacteriological and histological test results, including those obtained by Ziehl-Neelsen staining on tissue biopsy specimens. Molecular discrimination was successful and confirmed the value of duplex us-p34 and f57 sequence amplification for differential diagnosis of tuberculosis, paratuberculosis, or infections caused by other members of the M. avium complex.     

Evolution of cumulative live birth and dropout rates over six complete IVF/ICSI cycles: a large prospective cohort study

Research questionHow do cumulative live birth rates (CLBR), cumulative multiple live birth rates (CMLBR) and dropout rates over six IVF and intracytoplasmic sperm injection (ICSI) cycles change over time?DesignProspective longitudinal cohort (n = 16,073 patients; 48,946 cycles) starting a first fresh assisted reproductive technology cycle between 1 January 2014 and 31 December 2016, with follow-up until 31 December 2017. Outcomes between the periods 2014–2017 and 2009–2012 were compared.ResultsConservative estimates of CLBR after six complete cycles were significantly higher in women younger than 35 years after every cycle: one to three, adjusted P-value [p adj] < 0.0001; four, p = 0.01; five, p adj = 0.03; six, p adj = 0.04) and after the first cycle in women aged 35–37 years (p adj = 0.04) in 2014–2017 versus 2009–2012. For an optimal estimate, the CLBR was significantly higher after the first three cycles in women younger than 35 years (all p adj < 0.0001) and after the first cycle in women aged 35–37 years (p adj = 0.04). The CMLBR rate decreased from 5.1% ± 0.19 (SE) to 4.1% ± 0.16 for the conservative estimate and from 8.6% ±0.37 (SE) to 6.7% ± 0.30 for the optimal estimate after six complete cycles for the whole cohort. Dropout rates of complete cycles were 26.5% 29.4%, 33.4%, 38.9% and 47.3% after the first to fifth cycle, respectively. Compared with 2009–2012, the dropout rate in the current period was significantly higher for the first (P < 0.0001) and second (P = 0.0124) cycle.ConclusionOver six complete IVF/ICSI cycles, CLBR and dropout rates increased and multiple live birth rates decreased when 2014–2017 was compared with 2009–2012.     

Propofol anaesthesia for ultrasound guided oocyte retrieval: accumulation of the anaesthetic agent in follicular fluid.

Propofol (2,6-diisopropylphenol, Diprivan, ICI-Pharmaceuticals, Manchester, UK) is widely used either as an adjunct in general anaesthesia or as sole anaesthetic agent by the continuous intravenous route and intermittent bolus injections for minor surgical interventions. For several years, we have been using this kind of anaesthesia in transvaginal oocyte retrieval for in-vitro fertilization (IVF), allowing a completely painless puncture on an out-patient basis. From in-vitro studies on mouse oocytes, it appeared that propofol could be deleterious for fertilization in a dose- and time-dependent manner. We therefore investigated the concentrations of propofol in follicular fluid during oocyte retrieval in women. We measured propofol levels in serum and follicular fluid of nine patients at fixed intervals during ultrasound guided oocyte retrieval. Serum levels fluctuated randomly, due to interference from top-off doses of propofol. In follicular fluid, however, we found a steady increase of propofol levels, which was proportional to the total dose of propofol administered. These data indicate that propofol accumulates in follicular fluid. Although it seems unlikely that propofol as used in the present protocol exerts a clinically significant unfavourable effect on IVF, we suggest that the oocyte retrieval procedure should be kept as short as possible, in order to limit the accumulation of the anaesthetic in follicular fluid.