The clinical task force: Improving quality of medical students' internship.

Background: Up to 40% of young medical doctors feel that the internships prepared them insufficiently for the clinical work. This study investigated whether a Clinical Task Force (CTF) could improve internship quality. Methods: The CTF visited internship departments with a triple-targeted approach: first, departments pre-filled a self-evaluating questionnaire; secondly, CTF visited departments to discuss the self-evaluation and previous student evaluations; and thirdly, CTF and departments agreed on several quality-improving focus points to work on after the meeting. Focus points were followed-up after three and 12 months. The impact on internship quality was assessed with departments' student evaluation scores, number of completed focus points, and the effect of completed focus points on a range of learning parameters. The CTF learned several things along the way, that potentially could affect the quality of internships. A shortlist of these was provided to illustrate unmeasurable benefits. Results: The CTF met with 53 out of 60 eligible departments. The CTF and departments agreed upon 197 focus points of which 64% were completed. The three most frequent categories of focus points were Introduction of the students, The departments' evaluation percentage, and The departments' function as an educational site. The mean student evaluation scores did not change significantly, but the individual evaluation parameters changed significantly in two categories. It decreased in the category regarding the students' satisfaction with the clinical lecturers and the scheduled teaching and increased in the category regarding the percentage of students evaluating the department. Conclusion: The CTF's triple-targeted approach did not increase the mean student evaluation score significantly. For departments that completed the agreed focus points, one category increased and another decreased. However, the unmeasurable benefits illustrated that CTF was a good viable linking element between the faculty, departments, and students with the potential of improving other aspects of the quality of internships.

No effect of oral sucrose or IV glucose during exercise in phosphorylase b kinase deficiency.

This case report investigated exercise metabolism and the effect of oral sucrose and intravenous glucose supplementation in a 30-year-old, mildly affected man with muscle phosphorylase b kinase (PHK) deficiency caused by a novel c.586G>A mutation in the PHKA1 gene. Only 12 patients with PHK deficiency have been reported and it is unclear to what extent patients exhibit symptoms during exercise. Carbohydrate and fat metabolism were measured during 30 min of exercise at ∼ 70% of peak oxidative capacity using stabile isotope technique and signaling proteins and enzymes in the energy pathway were analyzed by Western blot. Results were compared to four healthy subjects. These studies show that neither oral nor intravenous glucose improved exercise tolerance in this patient with PHK deficiency. Despite Western blots indicated affected metabolism on protein level, systemic substrate turnover studies showed that carbohydrate and fatty acid oxidations were normal.

Time to pregnancy and semen parameters: a cross-sectional study among fertile couples from four European cities.

BACKGROUND: In fertile populations, little is known about the association between semen parameters and time to pregnancy (TTP). METHODS: Pregnant women from Copenhagen, Edinburgh, Paris and Turku who conceived without medical intervention were asked for their TTP (942 couples), and their partners provided a semen sample. The proportion of morphologically normal sperm and the multiple anomalies index (MAI, ratio of the total number of anomalies to the number of abnormal sperm) were centrally estimated. We estimated rate ratios for the occurrence of a pregnancy by a discrete survival model, adjusted for sexual activity and female factors affecting fecundity. RESULTS: Increasing sperm concentration influenced TTP up to 55 x 10(6)/ml. The proportion of morphologically normal sperm influenced TTP up to 39% according to David's criteria, and this association held among the subjects with a sperm concentration >55 x 10(6)/ml. For strict criteria, the threshold value was 19% normal sperm. An increase of 0.5 in MAI was associated with an adjusted rate ratio for the occurrence of a pregnancy of 0.68 (95% confidence interval: 0.54-0.85). CONCLUSIONS: These results highlight the importance of sperm morphology parameters and indicate that the effect of proportion of normal sperm on TTP may be independent of sperm concentration.

Time to pregnancy in relation to semen quality assessed by CASA before and after sperm separation.

BACKGROUND: In order to provide a reference for infertile men, we defined normal values of semen quality in a population of fertile men, using computer-assisted semen analysis (CASA) before and after sperm separation. Additionally, we investigated the relationship between semen quality and time to pregnancy (TTP). METHODS AND RESULTS: Semen samples were obtained from 315 proven fertile men. The median sperm concentration in fresh samples was 107 x 10(6)/ml (5-95 percentiles: 16-322 x 10(6)/ml), the median percentage of motile sperm cells was 65% (14-87%) and the median percentage of progressively motile cells was 37% (5-64%). After density gradient sperm separation, the median total sperm count was 46 x 10(6) (4-350 x 10(6)), the median percentage of motile sperm cells was 77% (16-95%) and the median percentage of progressively motile cells was 63% (11-84%). No significant associations were found between TTP and sperm counts or sperm motility, either before or after sperm separation. This may be due in part to the fact that the study comprised couples with proven fertility. CONCLUSION: We have defined semen parameters, including the results of density gradient separation, in a population of normal fertile men which may be of interest in the evaluation of semen samples from infertile men.

Regional differences in waiting time to pregnancy among fertile couples from four European cities.

BACKGROUND: A previous European study found a longer time to pregnancy (TTP) among fertile women from Paris compared with women from other Western European countries. A co-ordinated, cross-sectional study of pregnant couples from Denmark (Copenhagen), France (Paris), Scotland (Edinburgh) and Finland (Turku) was therefore undertaken to assess differences in waiting TTP among couples from these cities. METHODS: Pregnant women were invited to participate when they showed up for their first antenatal visit in one of the four centres. Inclusion criteria included that their partner was 20-45 years of age and born in the country in which he was currently living and that the pregnancy was achieved without fertility treatment. Both partners filled in a questionnaire and the man underwent a physical examination and delivered a semen sample (Turku: n = 237, Copenhagen: n = 302, Edinburgh: n = 212, Paris: n = 191). RESULTS: French couples had a decreased probability of conception compared with couples from the other three countries, although only after adjustment for confounders. No significant differences between couples from the three other countries were found. CONCLUSION: The observed geographical differences in TTP remain unexplained and were not due to differences in semen quality, but may be caused by varying exposures to environmental factors or psychological distress. In addition, selection bias due to the low participation rates cannot be ruled out. Future studies examining the causes for geographical differences in TTP are needed.

Sperm morphological defects related to environment, lifestyle and medical history of 1001 male partners of pregnant women from four European cities.

BACKGROUND: Recently, differences in semen quality have been found among the partners of pregnant women from four European cities: Turku, Copenhagen, Edinburgh and Paris. METHODS: During this study, slides from the four centres were subjected to a centralized assessment of sperm morphology. The percentages of sperm defects were recorded using a multiple-entry classification enabling the calculation of the multiple anomalies index (MAI), which is the mean number of anomalies per abnormal sperm. The relationships between various sperm abnormalities and self-reported data on medical history, lifestyle and occupational factors were examined. RESULTS: Significant differences in the MAI and most of the sperm defects were found between the four cities, and more abnormalities were found in spring than in winter. An increase in some sperm abnormalities was related to medical treatment of the mother during pregnancy, higher birthweight and previous treatment for cryptorchidism. Significant variations of several sperm defects were related to stress, weekly working time, occupational posture and metal welding, suggesting directions for further exposure studies. CONCLUSION: The present study indicated that the detailed assessment of sperm abnormalities is a useful biomarker of the effect of various external factors which may qualitatively affect human spermatogenesis.

Regional differences in semen quality in Europe.

Recent reports have indicated a decrease in semen quality of men in some countries, and suggested regional differences. A study was undertaken of semen samples from 1082 fertile men from four European cities (Copenhagen, Denmark; Paris, France; Edinburgh, Scotland; and Turku, Finland). Semen analysis was standardized, inter-laboratory differences in assessment of sperm concentration were evaluated, and morphology assessment centralized. Lowest sperm concentrations and total counts were detected for Danish men, followed by French and Scottish men. Finnish men had the highest sperm counts. Men from Edinburgh had the highest proportion of motile spermatozoa, followed by men from Turku, Copenhagen and Paris. Only the differences between Paris/Edinburgh and Paris/Turku were statistically significant (P < 0.003 and P < 0.002 respectively). No significant differences in morphology were detected. A general seasonal variation in sperm concentration (summer 70% of winter) and total sperm count (summer 72% of winter) was detected. Semen quality of a 'standardized' man (30 years old, fertile, ejaculation abstinence of 96 h) were estimated. Typically, sperm concentrations (x 10(6)/ml) for winter/summer were: Turku 132/93; Edinburgh 119/84; Paris 103/73; and Copenhagen 98/69. These differences in semen quality may indicate different environmental exposures or lifestyle changes in the four populations. However, it remains to be seen whether such changes can account for these differences. These data may also serve as a reference point for future studies on time trends in semen quality in Europe.

Embryo quality and developmental potential is compromised by age.

AIMS: The aim of this retrospective study was to assess whether and how the age of the woman affects the quality and developmental potential of the oocytes and embryos in an ART program. METHOD AND MATERIAL: A total of 878 IVF cycles was included as a consecutive series of single transfers (n=292), dual transfers (n=366) and triple transfers (n=220), where all the transferred embryos in each cycle were of identical quality score and identical cleavage stage. RESULTS: We found a highly significant decrease in oocyte recovery with increasing age with about one oocyte per 2.3 years (95% CI 1.8 years to 3.1 years, p<0.0001). Further, we found that the number of oocytes that cleaved declined significantly with increasing age with one per 3.7 years (95% CI 2.7 years to 5.5 years, p<0.0001). This decline was mainly due to the decline in number of oocytes retrieved as the ratio of aspirated oocytes that cleaved with increasing age (approx. -0.04/10 year 95% CI: -0.10; +0.009) was not significantly different (p=0.10). The percentage of transfers using fragmented embryos did not increase significantly with increasing age (p=0.08). The odds of fragmentation increased by 3% per year. The average number of embryos transferred decreased significantly (p=0.03) with age from approximately 2.1 at the age of 25 to approximately 1.8 at the age of 40. In a selected subgroup of embryos all consisting of good quality embryos, a significant decrease was found in implantation rate with increasing age (approx. -0.08/10 years, 95% CI: -1.6; +0.00, p=0.05). Of the 357 pregnancies achieved in this study we found a significantly decreased ongoing pregnancy rate and a significantly increased abortion rate with increasing age (p=0.03). The decrease in the rate of ongoing pregnancies was almost linear, decreasing by approximately 1.5% per year. CONCLUSIONS: We conclude that age has an impact throughout a woman's reproductive life and that it is important to realize that the age-related decline in fertility may start already in the late twenties and not in the mid-thirties as is generally assumed.

Inter-observer variation in the results of the clinical andrological examination including estimation of testicular size.

Inter-observer variation in andrological examination by 10 clinical investigators from five Nordic and Baltic countries was investigated. In addition, information on intra-observer variation was obtained for six of the 10 investigators. Testicular size was measured using Prader's orchidometer and one of the investigators also performed an ultrasound estimate of testicular size. A highly significant difference (p < 0.001) between observers was found with an inter-observer error of 16% in estimating testicular size in 23 young men. The difference in the estimate tended to increase with increasing testicular size. There was no significant intra-observer difference in two measurements performed on consecutive days. Only differences in median testis size, which were greater than 31% between measurements by two investigators, were found to be significant at the 5% level. The ultrasound estimate of testicular size was significantly lower than the orchidometer estimate, with a mean difference of 3.6 mL for the left testis and 4.3 mL for the right testis. Tanner staging of genitalia and diagnosis of a varicocele was subject to great inter-observer variation, and for the diagnosis of varicocele only one-third of the investigators was able to reproduce their results on a second examination. In conclusion, it was found that the clinical andrological examination of young men is subject to great inter-observer variation. This should be kept in mind when results from different studies are compared as well as in daily clinical practice.

High frequency of sub-optimal semen quality in an unselected population of young men.

Male reproductive function seems to have deteriorated considerably during the past 4-5 decades. However, studies of the reproductive function in unselected populations have not previously been reported. As the large majority of young men in Denmark are subjected to a compulsory medical examination for military service, this provided a unique opportunity to study the reproductive function in an unbiased population. Altogether 891 young men delivered a blood sample in which reproductive hormones were measured. From 708 of these men data were also obtained on semen quality and testis size. The median sperm concentration was 41 x 10(6)/ml (mean 57.4 x 10(6)/ml). Men with ejaculation abstinence above 48 h had slightly higher sperm concentrations (median 45 x10(6)/ml, mean 63.2 x 10(6)/ml), but even in this subgroup, 21 and 43% respectively had sperm counts below 20 x 10(6)/ml and 40 x 10(6)/ml. Among men with no history of reproductive diseases and a period of abstinence above 48 h, as many as 18 and 40% respectively had concentrations below 20 and 40 x 10(6)/ml. Sperm counts were positively correlated with testis size, percentage normal spermatozoa and inhibin B, and negatively correlated with percentage immotile spermatozoa and follicle stimulating hormone. Possible causes for this high frequency of young men with suboptimal semen quality are obscure and need to be explored. Whether these findings apply for young male populations of comparable countries remains to be seen.

[Adolescents and sexuality in family practice. A pilot study]. / Unge og seksualitet i almen praksis. Et pilotstudie.

It is well established that teenagers are generally dissatisfied with the sexual education they receive from school and parents. While several alternative sources of sex counselling have been suggested (i.e. an anonymous and semi-official telephone hot-line), the role of the general practitioner in sexual guidance of youngsters is only poorly evaluated. One hundred and sixty-eight teenage callers of "The Adolescent Sexuality Hot-line" were asked about their experience with sexual counselling by their family doctor. One third had actually discussed such topics with their g.p., and a total of 44.6% (significantly more girls than boys) regarded their g.p. as a desirable interlocutor on these issues. The reasons for having approached a g.p. for counselling differed according to gender, as did the causes for not wanting to involve a g.p. in sexual matters: boys tended to state shyness and lack of anonymity as main causes, whereas girls more often pointed to personal aspects of the doctor.

Germ cell cancer and disorders of spermatogenesis: an environmental connection?

Why is there a small peak of germ cell tumours in the postnatal period and a major peak in young age, starting at puberty? And, paradoxically, small risk in old age, although spermatogenesis is a lifelong process? Why is this type of cancer more common in individuals with maldeveloped gonads, including undescended testis, gonadal dysgenesis and androgen insensitivity syndrome? Why has there, during the past 50 years, been a quite dramatic increase in testicular cancer in many developed countries? These are just a few of many questions concerning testicular cancer. However, the recent progress in research in the early stages of testicular cancer (carcinoma in situ testis (CIS)) allows us to begin to answer some of these questions. There is more and more evidence that the CIS cell is a gonocyte with stem cell potential, which explains why an adult man can develop a non-seminoma, which is a neoplastic caricature of embryonic growth. We consider the possibility that CIS cells may loose their stem cell potential with ageing. Along these lines, a seminoma is regarded a gonocytoma where the single gonocytes have little or no stem cell potential. The Sertoli and Leydig cells, which are activated postnatally and during and after puberty, may play a crucial role for both the development of the CIS gonocyte and progression of the neoplasm to invasiveness. The reported increase in testicular cancer is not the only sign that male reproductive health is at risk. There are reports that undescended testis and hypospadias have become more common. Also semen quality has deteriorated, at least in some countries. The epidemiological evidence suggests that environmental factors may play a role. Are the environmental hormone disrupters (e.g. DDT, PCB, nonylphenol, bisphenol A) to be blamed for the apparently synchronised deterioration in these aspects of male reproductive health?

Embryo morphology or cleavage stage: how to select the best embryos for transfer after in-vitro fertilization.

This retrospective study of 1001 in-vitro fertilization (IVF) cycles included a consecutive series of single transfers (n = 341), dual transfers (n = 410) and triple transfers (n = 250) where all the transferred embryos in each cycle were of identical quality score and identical cleavage stage. In our 2 day culture system, transfer of 4-cell embryos resulted in a significantly higher implantation rate and pregnancy rate (23 and 49%) compared with 2-cell embryos (12 and 22%) and 3-cell embryos (7 and 15%). Furthermore, the transfer of 4-cell embryos resulted in a significantly higher pregnancy rate compared with embryos that had cleaved beyond the 4-cell stage (28%). The implantation rate (21%) and pregnancy rate (43%) after transfer of embryos of score 1.0 were significantly higher than after transfer of embryos of score 2.0 (14 and 32% respectively). Transferring embryos of score 2.1 resulted in significantly higher implantation rates (26%) and similar pregnancy rates compared with score 1.0. Transferring embryos of score 2.2-3.0 resulted in a significantly lower implantation rate (5%) and pregnancy rate (15%). A striking finding was that embryos of quality score 2.0 had a significantly lower implantation rate compared with embryos of quality score 1.0 and 2.1 and a significantly lower pregnancy rate compared to embryos of quality score 1.0. We also found a lower implantation rate and pregnancy rate when transferring 3-cell embryos. These findings may indicate periods of increased sensitivity to damage during the cell cycle. In conclusion, these results substantiate the idea of the superiority of 4-cell embryos and demonstrate that minor amounts of fragments in the embryo may not be of any importance. These findings may call for a shift when weighing the two main morphological components (quality score and cleavage stage) in the sense that reaching a 4-cell cleavage stage even with the presence of a minor amount of fragments should be preferred to a 2-cell embryo with no fragments.

Results of intracytoplasmic sperm injection in relation to indication.

BACKGROUND: Intracytoplasmic sperm injection (ICSI) was first introduced as a treatment to couples that were infertile due to severe male factors. Later, the ICSI technic has also been used on other indications like low or no fertilization in previous IVF cycles. METHODS: A total of 262 ICSI cycles performed in 180 patients were reviewed and the results related to the indications. The indications were severely impaired semen quality (182 cycles) or absent or low fertilization in previous IVF attempts (80 cycles). RESULTS: A total of 2298 oocytes were aspirated and 1939 oocytes were injected resulting in 1172 fertilized (60%) and 995 cleaved oocytes (51%). Of these, 547 preembryos were transferred in 240 cycles and 287 preembryos were cryopreserved. We obtained 99 pregnancies (41%/transfer) of which 63 were ongoing pregnancies (26%/transfer). The pregnancy rate was significantly lower (p = 0.025) in couples referred for ICSI due to previously failed IVF (29%/ transfer) compared to couples with impaired semen quality (46%/transfer). Seventy-seven children have been born. Forty-eight healthy children were born from singleton pregnancies with a mean gestational age of 39.8 weeks and an average birthweight of 3561 g. Thirteen sets of healthy twins and one set of healthy triplets were born. In 29 of the 63 ongoing pregnancies amniocenteses were performed and all karyotypes were normal. CONCLUSION: IVF with ICSI gave good clinical results in couples with severe male factor infertility. The technic can also be used in couples with unexplained fertilization failure, but the pregnancy rate may be lower.

[Micro-insemination with intracytoplasmic sperm injection]. / Mikroinsemination med intracytoplasmatisk saedcelleinjektion.

Intracytoplasmic sperm injection (ICSI) is now established in the treatment of infertility. Fertilization is achieved by microinjection of a single spermatozoon into the ooplasma. Oligoasthenoteratozoospermia is the main indication, but ICSI is also used in cases of failed fertilization after standard IVF, retrograde ejaculation and male immunological infertility. In obstructive azoospermia ICSI is performed after aspiration of epididymal or testicular spermatozoa. In some anejaculatoric men spermatozon can be obtained following penile vibration or electro-stimulation, but they often have poor motility and ICSI may be used for fertilization. ICSI may also be used after thawing of semen cryopreserved prior to treatment of a malignant disease. Since 1991 the ICSI technique has been improved, and today the pregnancy rates are at least as good as after standard IVF. So far, studies of the foetuses and children born after ICSI show that the number of malformations and abnormal karyotypes is within the range of the normal population.

[The Adolescent Sexuality Hot-line--a 4-year study]. / Sexlinien for unge--en fireårsopgørelse.

The first Adolescent Sexuality Hot-Line in Denmark was launched in January 1992. The hot-line offers anonymous, professional telephone counselling to teenagers. During its initial four years, 6174 persons called, consisting of approximately 60% boys and 40% girls. Four major categories were: "basic information" (22.8%), "sexual problems" (21.5%), "contraception" (11.3%) and "pregnancy" (9.1%). Characteristically, callers (especially boys) have become significantly older over the four-year-period, coincident with a significant prolongation of the length of the calls. This might be seen as a reflection of a genuine-but as yet unaccommodated-need for sexual counselling in age groups older than the intended target-group. The need for sufficient sexological counselling in a mature population is well established in several other Danish studies.

Time interval from human chorionic gonadotrophin (HCG) injection to follicular rupture.

The aim of this study was to estimate the time interval from human chorionic gonadotrophin (HCG) injection to follicular rupture. Furthermore, it was observed whether there was any effect on the pregnancy rate if the insemination was performed at the time of follicular rupture. In a programme of intrauterine insemination 37 consecutive cycles in 32 patients were monitored after stimulation with clomiphene citrate. HCG was administered by i.m. injection when a leading follicle of at least 18 mm in diameter was observed sonographically. All patients were monitored by sonography with 1 h intervals from 32 h after HCG injection until the first rupture of a follicle. Insemination was performed immediately after the first follicular rupture. The pregnancy rate was 16% (5/32). In 66%, the largest follicle was the first to rupture. The mean time interval from HCG administration to first follicular rupture was 38.3 h (SEM = 0.54; range = 34-46). Our findings support the concept that ovulation occurs about 38 h after HCG administration. The pregnancy rate was within the normal range, although insemination was performed at the time of follicular rupture. The largest follicle was not always the first to rupture.