Psychosocial health and quality of life in ICSI and naturally conceived adolescents: a cross-sectional comparison.

PURPOSE: Psychosocial health (PH) and quality of life (QoL) are important health outcomes. We compared PH and QoL of adolescents conceived with intrazytoplasmatic sperm injection (ICSI) and of naturally conceived controls. The impact of disclosure of ICSI-conception on QoL and PH was quantified. METHODS: The cross-sectional sample consisted of 545 ICSI-conceived adolescents and 427 unmatched singleton controls aged 14-18 years. Adolescents reported PH with the 'Strengths and Difficulties Questionnaire' (low values indicating high PH), and QoL with the KINDL questionnaire (high values indicating high QoL). Because of clustering of multiples within families, adjusted linear regressions with generalized estimating equations were used to compare ICSI- and naturally conceived adolescents. Missing values were treated by multiple imputation. Minimal importance was defined as half a standard deviation. RESULTS: Both ICSI and control adolescents had high PH (low mean 'total difficulties' score: 9 of 40) and high QoL (mean 'total KINDL' score: 75 of 100). Differences were generally in favour of the ICSI group. Significant differences occurred for 'impact of behavioural problems' (p = 0.033), the 'total KINDL' score (p = 0.021) and the dimensions 'physical wellbeing' (p = 0.031) and 'school' (p = 0.005), but all differences were far below minimal importance. About 80% of ICSI adolescents were informed about their mode of conception. PH and QoL were slightly higher in informed adolescents; behavioural difficulties ('total behavioural problems' and 'conduct problems') were significantly lower (p = 0.013 and p = 0.003), behavioural strengths ('prosocial behaviour') and 'physical QoL' significantly higher (p = 0.004 and p = 0.018), but differences remained clearly below minimal importance. CONCLUSIONS: Our results are reassuring for parents using ICSI and their children. Speaking openly about an ICSI conception in the family may be beneficial.

Pubertal development and reproductive hormone levels of singleton ICSI offspring in adolescence: results of a prospective controlled study.

STUDY QUESTION: Are there any differences in the pubertal development and reproductive hormone status during adolescence between singletons following ICSI therapy or spontaneous conception (SC)? SUMMARY ANSWER: Pubertal development and reproductive hormone levels are largely similar between ICSI and SC adolescents, except for a tendency towards lower inhibin B levels as well as significantly higher estradiol levels and a lower testosterone-to-estradiol-ratio in male adolescents. WHAT IS KNOWN ALREADY: Previous data are scarce and partly inconclusive regarding pubertal development in female ICSI adolescents as well as demonstrating a tendency towards lower inhibin B serum levels in male ICSI offspring. STUDY DESIGN, SIZE, DURATION: Prospective controlled study including 274 singleton ICSI-conceived adolescents (141 girls, 133 boys) followed up for the third time, and 273 SC controls (142 girls, 131 boys) from seven German registration offices (Aachen, Eichstätt, Erfurt, Lübeck, Hamburg, Heidelberg and Schwerin). PARTICIPANTS/MATERIALS, SETTING, METHODS: Pubertal development assessed by Tanner staging (breast, genital and pubic hair development), age at menarche and reproductive hormone levels were analyzed in ICSI and SC adolescents at the mean age of 16.5 years. Differences were analyzed by multinomial regression (Tanner stages) or t test and linear regression for hormonal assessments. MAIN RESULTS AND THE ROLE OF CHANCE: Both female and male ICSI and SC adolescents showed adequate pubertal maturation according to their age, and the mean age at menarche (at 12.7 versus 12.8 years) was similar. Tanner stages as well did not display any relevant or significant differences between the groups. Reproductive hormone levels in female adolescents not using hormonal contraception were largely similar before and after adjustment for several factors such as preterm birth, Tanner stages, BMI or physical activity. In male ICSI adolescents, a tendency towards lower inhibin B (-14.8 pg/ml, 95% CI: -34.2 to 4.6 pg/ml), significantly higher estradiol (2.6 ng/l, 95% CI: 0.0 to 5.2 ng/l) and a significantly lower testosterone-to estradiol ratio (-0.047, 95% CI: -0.089 to -0.004) was found. LIMITATIONS, REASONS FOR CAUTION: The all-over response rate and the willingness to participate in the blood test and medical examination were very low in the control group. Participating control families may have greater health awareness, and selection bias cannot be ruled out. Hormonal data in the females were measured irrespective of the cycle day and restricted to those not using hormonal contraception. Some parameters from the questionnaire data such as usage of hormonal contraception might suffer from reporting bias. As this is an observational study, we can draw only limited causal conclusions from the findings. WIDER IMPLICATIONS OF THE FINDINGS: Differences in male reproductive hormones may indicate altered testicular function. However, at this time possible consequences for later reproductive success are unknown. STUDY FUNDING/COMPETING INTEREST(S): DFG research grant KA 1643/4-1. The authors declare no conflict of interest.

Anti-Müllerian hormone in women with hypopituitarism diagnosed before or during adolescence.

In women, anti-Müllerian hormone (AMH) is exclusively expressed in granulosa cells and an established marker of ovarian reserve. In menstrual cycle disorders, low AMH is usually interpreted as an indicator of primary ovarian insufficiency. This study is a case series of 11 patients with hypopituitarism. AMH concentrations were on or below the age-specific 25th percentile in three of the four patients diagnosed in infancy, but not in the remaining seven patients, who were diagnosed during adolescence or later. In patients with hypopituitarism, the detection of low AMH serum concentrations can present a diagnostic pitfall and its value in the interpretation of ovarian reserve in these patients is challenging.

Assessment of follicular development in cryopreserved primate ovarian tissue by xenografting: prepubertal tissues are less sensitive to the choice of cryoprotectant.

Improvements in cancer survival rates have renewed interest in the cryopreservation of ovarian tissue for fertility preservation. We used the marmoset as a non-human primate model to assess the effect of different cryoprotectives on follicular viability of prepubertal compared to adult ovarian tissue following xenografting. Cryopreservation was performed with dimethylsulfoxide (DMSO), 1,2-propanediol (PrOH), or ethylene glycol (EG) using a slow freezing protocol. Subsequently, nude mice received eight grafts per animal from the DMSO and the PrOH groups for a 4-week grafting period. Fresh, cryopreserved-thawed, and xenografted tissues were serially sectioned and evaluated for the number and morphology of follicles. In adult tissue, the percentage of morphologically normal primordial follicles significantly decreased from 41.2 ± 4.5% (fresh) to 13.6 ± 1.8 (DMSO), 9.5 ± 1.7 (PrOH), or 6.8 ± 1.0 (EG) following cryopreservation. After xenografting, the percentage of morphologically normal primordial (26.2 ± 2.5%) and primary follicles (28.1 ± 5.4%) in the DMSO group was significantly higher than that in the PrOH group (12.2 ± 3 and 5.4 ± 2.1% respectively). Proliferating cell nuclear antigen (PCNA) staining suggests the resumption of proliferative activity in all cellular compartments. In prepubertal tissues, primordial but not primary follicles display a similar sensitivity to cryopreservation, and no significant differences between DMSO and PrOH following xenografting were observed. In conclusion, DMSO shows a superior protective effect on follicular morphology compared with PrOH and EG in cryopreserved tissues. Xenografting has confirmed better efficacy of DMSO versus PrOH in adult but not in prepubertal tissues, probably owing to a greater capacity of younger animals to compensate for cryoinjury.

Polymorphism of the FSH receptor and ovarian response to FSH.

Follicle-stimulating hormone (FSH) is a key factor in human reproduction. FSH activates its receptor (FSHR) located exclusively on Sertoli cells in the testis and granulosa cells in the ovary. Two common single nucleotide polymorphisms (SNP) within exon 10 of the human FSHR gene result in two almost equally common allelic variants exhibiting threonine (Thr) or alanine (Ala) at position 307 in the hinge region, respectively, asparagine (Asn) or serine (Ser) at codon 680 of the intracellular domain. Clinical studies have demonstrated that p.N680S polymorphism determines the ovarian response to FSH stimulation in patients undergoing IVF-treatment. Patients with the Ser(680) allele need more FSH during the stimulation phase to reach the serum estradiol levels of Asn(680) patients. A study investigating women with normal, mono-ovulatory menstrual cycles revealed that the Ser(680)/Ser(680) genotype leads to higher FSH serum levels and a prolonged cycle. To date, the molecular mechanism underlying the partial "resistance" of the Ser(680)-FSHR to FSH remains unclear. Future experiments should extend our current understanding of FSH action on follicular selection and dominance, thereby permitting novel, patient-tailored therapies for infertility and fertility preservation.

A common single nucleotide polymorphism in exon 10 of the human follicle stimulating hormone receptor is a major determinant of length and hormonal dynamics of the menstrual cycle.

CONTEXT: FSH is essential for follicular maturation. Data from ovarian hyperstimulation cycles suggest that FSH action is attenuated by a frequent single nucleotide polymorphism of the FSH receptor gene exchanging Asn for Ser at codon 680. OBJECTIVE: We hypothesized that the FSH receptor genotype influences menstrual cycle dynamics. DESIGN: Menstrual cycle was monitored from the midluteal phase through ovulation until the consecutive menstruation. SETTING: The study was conducted at the University research center. SUBJECTS: Women homozygous for the Asn680 (n = 12) and Ser680 (n = 9) variants with normal menstrual cycles volunteered for the study. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASUREMENTS: Follicular growth, serum LH, FSH, estradiol, progesterone, inhibin A, inhibin B and antimullerian hormone were measured. RESULTS: During the luteo-follicular transition, serum levels of estradiol, progesterone, and inhibin A were significantly lower, and FSH started to rise earlier in the Ser680/Ser680 group. FSH levels were steadily and significantly higher, and the mean area under the FSH curve was 31% greater in this group (P < 0.002). No differences were observed in estradiol, inhibin B, and growth velocities of dominant follicles. The time from luteolysis to ovulation was significantly longer in women with the Ser680/Ser680 (13.6 +/- 1.01 d) compared with Asn680/Asn680 (11.3 +/- 0.61 d, P < 0.05) genotype with a significant difference in total menstrual cycle length (29.3 vs. 27.0 d, respectively; P < 0.05). CONCLUSIONS: The FSH receptor Ser680/Ser680 genotype is associated with higher ovarian threshold to FSH, decreased negative feedback of luteal secretion to the pituitary during the intercycle transition, and longer menstrual cycles.

First observation of self-amplified spontaneous emission in a free-electron laser at 109 nm wavelength

We present the first observation of self-amplified spontaneous emission (SASE) in a free-electron laser (FEL) in the vacuum ultraviolet regime at 109 nm wavelength (11 eV). The observed free-electron laser gain (approximately 3000) and the radiation characteristics, such as dependency on bunch charge, angular distribution, spectral width, and intensity fluctuations, are all consistent with the present models for SASE FELs.

Size Selective Feeding in Cyclidium glaucoma (Ciliophora, Scuticociliatida) and Its Effects on Bacterial Community Structure: A Study from a Continuous Cultivation System.

Three aspects of size selective feeding by the scuticociliate Cyclidium glaucoma were studied in continuous cultivation systems. Firstly, grazing-induced changes in abundance, biomass, and size structure of a bacterial community were investigated. Secondly, we studied possible grazing-protection mechanisms of bacteria as a response to permanent presence of the predator. And finally, we were looking for potential feedback mechanisms within this predator-prey relationship, i.e., how the ciliate population reacted to a changed, more grazing-protected bacterial community. The first stage of the cultivation system consisted of the alga Cryptomonas sp. and the accompanying mixed bacterial community. These organisms were transferred to two second stage vessels, a control stage without ciliates and a second one inoculated with C. glaucoma. After the first week, the abundance of bacteria in the latter decreased by 60% and remained stable until the end of the experiment (65 d), whereas bacterial biomass was less affected (393 mg C L-1 during days 0-7, 281 mg C L-1 afterwards). The mean bacterial cell volume doubled from 0.089 mm3 to 0.167 mm3, which was mainly due to increasing cell widths. During the whole investigation period formation of colonies or filaments was not observed, but we found a clear feedback of ciliates on bacterial size. An increase in bacterial cell volume was always followed by a decline of the predator population, resulting in a yet undescribed type of microbial predator-prey relation. Literature and our own data on the optimal food size range grazed by C. glaucoma showed that bacterial cell width rather than length was responsible for that observed phenomenon. Finally, we suggest that uptake rates of spherical latex beads give only limited information on truly ingestible prey volumes and that prey geometry should be considered in future studies on size selective feeding of protists.

Squamous cell carcinoma of the parotid gland.

Squamous cell carcinoma involving the parotid gland is an aggressive and rapidly advancing lesion which if not recognized and treated early will result in a high morbidity and mortality. We reviewed 30 patients with squamous cell carcinoma involving the parotid gland. Twenty-four patients had had previous epidermoid skin lesions in an area known to drain to the parotid gland and three resulted from direct extension into the gland from an overlying skin carcinoma, whereas only three were primary lesions of the gland. Patients who presented with involvement of the gland more than 4 months after excision of the skin lesion had a poor prognosis. Patients with epidermoid skin cancer in areas with a propensity to secondarily involve the parotid gland must be closely followed after treatment of the primary skin lesion.

[Deficits in the treatment of chronic pain. 2. Possibilities for improvement through the Pain Therapy Ambulant Network (STAN)]. / Defizite in der Therapie chronischer Schmerzen (Teil 2). Möglichkeiten zur Verbesserung durch das Schmerztherapeutische ambulante Netzwerk (STAN).

In a regional pain management network in Cologne, the pain clinic of the department of anaesthesiology and the departments of psychosomatic medicine and of informatics, statistics and epidemiology have been cooperating with the regional board of physicians and more than 80 general practitioners since 1996. The program is sponsored by the German Ministry of Health. In this network, guidelines for the management of chronic pain have been implemented for outpatient care in the last three years. Results from the first year confirm the high level of distress of patients with chronic pain. Consultation and education offered by the coordinating office and in training courses were accepted by the practitioners in variable degrees. Some physicians requested consultations frequently while including only a few patients in the study documentation, while other physicians requested consultations rarely and assessed many patients. Participating physicians were also asked to provide analgesic regimens for constructed case reports with chronic headache or cancer pain. The evaluation of these prescriptions showed poor adherence to analgesic guidelines.

[Deficits in the treatment of chronic pain (I)]. / Defizite in der Therapie chronischer Schmerzen (Teil 1).

Pain management by general practitioners often is inadequate. Guidelines for pain management are either not observed or not known at all. Opioids are not prescribed adequately. Differential diagnoses influencing the therapeutic regimen such as drug-induced headache are not sufficiently known. Monotherapies with analgesic drugs are enforced for patients with chronic lower back pain in spite of low efficacy. Improving pain management can be difficult for the general practitioner having no special knowledges or support from pain specialists. However, the general practitioner should remain the patient-coordinator for the patient with chronic pain. Networks with general practitioners and specialised units in the hospital may offer possibilities for improvement of pain management deficits.

Role of the CAG repeat polymorphism of the androgen receptor gene in polycystic ovary syndrome (PCOS).

BACKGROUND: Polycystic ovary syndrome (PCOS) is a frequent heterogenic disorder with a familial background. Androgenic effects, determining the clinical features of the syndrome, are mediated by the androgen receptor (AR), whose activity is modulated by a genetic polymorphism. We investigated the role of the CAG repeat polymorphism of the androgen receptor in PCOS. METHODS: In the infertility unit of a university clinic, 72 PCOS patients were compared with 179 ovulatory controls undergoing a standardized diagnostic work-up. The number of CAG repeats was determined by PCR, labelling with IR-800 and PAGE. X-chromosome inactivation was assessed by a methylation-sensitive assay. RESULTS: Compared to controls, PCOS patients displayed a shorter mean CAG repeat length, encoding for higher AR activity (P=0.001). CAG repeat length correlated inversely with oligomenorrhea, a central androgen dependent feature of the syndrome (P=0.005). In a binomial regression analysis including BMI, LH and free testosterone, CAG repeat length was identified as an independent risk factor for PCOS (P=0.002). CONCLUSIONS: The CAG repeat polymorphism could constitute one of the genetic factors modulating the syndrome's phenotype, contributing to its clinical heterogeneity and associated metabolic consequences.

Spin-orbit mediated interference in the radiative and nonradiative channels of the La 4d core resonances.

Symmetrical fluorescence yield profiles and asymmetrical electron yield profiles of the preresonances at the La N_{IV,V} x-ray absorption edge are experimentally observed in LaPO_{4} nanoparticles. Theoretical studies show that they are caused by interference effects. The spin-orbit interaction and the giant resonance produce symmetry entangled intermediate states that activate coherent scattering and alter the spectral distribution of the oscillator strength. The scattering amplitudes of the electron and fluorescence decays are further modified by the spin-orbit coupling in the final 5p;{5}epsilonl and 5p;{5}4f;{1} states.

The axillary tree as a source of musculocutaneous and fasciocutaneous flaps in a fixed-skin porcine model.

Our understanding of muscle, fascia, and skin flap physiology is based largely on data obtained from rodent, rabbit, or canine models. The presence of a well-developed panniculus carnosus confounds the extrapolation of data from these animals to humans. This study attempted to define microsurgically applicable musculocutaneous and fasciocutaneous flaps in the pig that would be comparable to flaps commonly used in humans. Lead oxide was injected into each axillary artery of three standard white domestic swine. Gross dissection and radiographic studies were used to define the specific anatomic fasciocutaneous territory served by the branches of the circumflex scapular artery. Eight musculocutaneous flaps based on the thoracodorsal artery and eight fasciocutaneous flaps based on the circumflex scapular artery were elevated. Although all flaps survived in their entirety, the fasciocutaneous flaps did not, as in man, have an easily dissectable axial blood supply. This finding suggests that the porcine scapular fasciocutaneous flap, although reliable as a pedicled flap, is difficult to employ as a free tissue transfer.