Determinants of transplantation success with cryopreserved ovarian tissue: data from 196 women of the FertiPROTEKT network.

STUDY QUESTION: What are the pregnancy and live birth rates for ovarian tissue transplantation and which factors are associated with the success rate? SUMMARY ANSWER: Pregnancy and live birth rates per transplanted woman are 32.7% and 26.5% and success rate is associated with female age and first versus repeated transplantation. WHAT IS KNOWN ALREADY: Live birth rates after ovarian tissue transplantations have been reported to be between around 24% and 41% per patient. Success rates seem to be negatively associated with increasing female age at the time of tissue cryopreservation and with pelvic radiation. Success rates are apparently not reduced after overnight transportation of ovarian tissue before freezing. STUDY DESIGN, SIZE, DURATION: Registry analysis of 244 transplantations in 196 women, performed by 26 FertiPROTEKT network centres from 2007 to 2019 with follow-up till December 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Orthotopic ovarian tissue transplantations were performed in 196 women, 191 with previous malignant and 5 with previous non-malignant diseases. Size of transplanting centres varied between 1 and 100 transplantations per centre (median: 2). Factors possibly associated with success rate such as female age, first and repeated transplantation, experience of the transplanting centre and overnight transportation of the ovarian tissue before freezing were analysed. MAIN RESULTS AND THE ROLE OF CHANCE: Average age of all 196 transplanted women was 31.3 years (SD 5.2; range 17-44) at the time of cryopreservation of tissue and 35.9 years (SD 4.8; range 23-47) at the time of transplantation. Pregnancy rate was 30.6% (95% CI, 24.2-37.6%) per first transplantation and 32.7% (95% CI, 26.1-39.7%) per patient. Pregnancy rate was higher after first transplantation (30.6% (95% CI, 24.2-37.6%)) compared to second and subsequent transplantations (11.8% (95% CI, 3.3-27.5%)). Live birth rate per first transplantation was 25.0% (95% CI, 19.1-31.7%) and per patient 26.5% (95% CI, 20.5-33.3%). Success rate decreased with increasing age at the time of ovarian tissue freezing. Live birth rate was 28.2% (95% CI, 20.9-36.3%) in women <35 years and 16.7% (95% CI, 7.9-29.3%) in women >35 years. Pregnancy rates after first transplantation were higher in centres who had performed ≥10 transplantations (35.1%) compared to centres with <10 transplantation (25.4%) (P = 0.12). Corresponding live birth rates were 27.0% and 18.6%. Success rates were not different in women with and without overnight transportation of tissue before cryopreservation. LIMITATIONS, REASONS FOR CAUTION: The data were drawn from a registry analysis. Data such as ovarian reserve and premature ovarian insufficiency were not available for all women. Data might be influenced by different follow-up policies of the centres. WIDER IMPLICATIONS OF THE FINDINGS: The study reveals the high potential of ovarian tissue freezing and transplantation, but only if freezing is performed in younger women. The study suggests focus should be placed on the first and not on repeated transplantations. It also opens the discussion of whether transplantation should rather be performed by experienced centres. STUDY FUNDING/COMPETING INTEREST(S): No funding. No competing interests. TRIAL REGISTRATION NUMBER: N/A.

Refinement of detecting atrial fibrillation in stroke patients: results from the TRACK-AF Study.

BACKGROUND AND PURPOSE: Detection of occult atrial fibrillation (AF) is crucial for optimal secondary prevention in stroke patients. The AF detection rate was determined by implantable cardiac monitor (ICM) and compared to the prediction rate of the probability of incident AF by software based analysis of a continuously monitored electrocardiogram at follow-up (stroke risk analysis, SRA); an optimized AF detection algorithm is proposed by combining both tools. METHODS: In a monocentric prospective study 105 out of 389 patients with cryptogenic stroke despite extensive diagnostic workup were investigated with two additional cardiac monitoring tools: (a) 20 months' monitoring by ICM and (b) SRA during hospitalization at the stroke unit. RESULTS: The detection rate of occult AF was 18% by ICM (n = 19) (range 6-575 days) and 62% (n = 65) had an increased risk for AF predicted by SRA. When comparing the predictive accuracy of SRA to ICM, the sensitivity was 95%, specificity 35%, positive predictive value 27% and negative predictive value 96%. In 18 patients with AF detected by ICM, SRA also showed a medium risk for AF. Only one patient with a very low risk predicted by SRA developed AF revealed by ICM after 417 days. CONCLUSIONS: A combination of SRA and ICM is a promising strategy to detect occult AF. SRA is reliable in predicting incident AF with a high negative predictive value. Thus, SRA may serve as a cost-effective pre-selection tool identifying patients at risk for AF who may benefit from further cardiac monitoring by ICM.

Ninety-five orthotopic transplantations in 74 women of ovarian tissue after cytotoxic treatment in a fertility preservation network: tissue activity, pregnancy and delivery rates.

STUDY QUESTION: What is the success rate in terms of ovarian activity (menstrual cycles) as well as pregnancy and delivery rates 1 year after orthotopic ovarian transplantations conducted in a three-country network? SUMMARY ANSWER: In 49 women with a follow-up >1 year after transplantation, the ovaries were active in 67% of cases and the pregnancy and delivery rates were 33 and 25%, respectively. WHAT IS KNOWN ALREADY: Cryopreservation of ovarian tissue in advance of cytotoxic therapies and later transplantation of the tissue is being performed increasingly often, and the total success rates in terms of pregnancy and delivery have been described in case series. However, published case series have not allowed either a more detailed analysis of patients with premature ovarian insufficiency (POI) or calculation of success rates based on the parameter 'tissue activity'. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of 95 orthotopic transplantations in 74 patients who had been treated for cancer, performed in the FertiPROTEKT network from 2008 to June 2015. Of those 95 transplantations, a first subgroup (Subgroup 1) was defined for further analysis, including 49 women with a follow-up period >1 year after transplantation. Of those 49 women, a second subgroup (Subgroup 5) was further analysed, including 40 women who were transplanted for the first time and who were diagnosed with POI before transplantation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Transplantation was performed in 16 centres and data were transferred to the FertiPROTEKT registry. The transplantations were carried out after oncological treatment had been completed and after a remission period of at least 2 years. Tissue was transplanted orthotopically, either into or onto the residual ovaries or into a pelvic peritoneal pocket. The success rates were defined as tissue activity (menstrual cycles) after 1 year (primary outcome) and as pregnancies and deliveries achieved. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of all transplanted 74 women was 31 ± 5.9 years at the time of cryopreservation and 35 ± 5.2 at the time of transplantation. Twenty-one pregnancies and 17 deliveries were recorded. In Subgroup 1, tissue was cryopreserved at the age of 30 ± 5.6 and transplanted at 34 ± 4.9 years. Ovaries remained active 1 year after transplantation in 67% of cases (n = 33/49), the pregnancy rate was 33% (n = 16/49) and the delivery rate was 25% (n = 12/49). In Subgroup 5, tissue was cryopreserved at the age 30 ± 5.9 years and transplanted at 34 ± 5.2 years. Ovaries remained active 1 year after transplantation in 63% of cases (n = 25/40), the pregnancy rate was 28% (n = 11/40) and the delivery rate was 23% (n = 9/40). The success rates were age dependant with higher success in women who cryopreserved at a younger age. In Subgroup 5, tissue was exclusively transplanted into the ovary in 10% (n = 4/40) of women and into a peritoneal pocket in 75% (n = 30/40), resulting in spontaneous conceptions in 91% of patients (n = 10/11). LIMITATIONS, REASONS FOR CAUTION: The data were drawn from a retrospective analysis. The cryopreservation and transplantation techniques used have changed during the study period. The tissue was stored in many tissue banks and many surgeons were involved, leading to heterogeneity of the procedures. However, this does reflect the realistic situation in many countries. Although patients with POI were evaluated before transplantation to allow specific analysis of the transplanted tissue itself, the possibility cannot be excluded that residual ovarian tissue was also reactivated. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest case series worldwide to date and it confirms that cryopreservation and transplantation of ovarian tissue can be a successful option for preserving fertility. Persistent tissue activity 12 months after transplantation suggests that the pregnancy and delivery rates may increase further in the future. As transplantation into the peritoneum results in a high success rate, this approach may be an alternative to transplantation into the ovary. However, in order to establish the best transplantation site, a randomized study is required. STUDY FUNDING/COMPETING INTEREST: This study was in part funded from the Deutsche Forschungsgemeinschaft (# DI 1525) and the Wilhelm Sander Foundation (2012.127.1) and did not receive any funding from a commercial company. No competing interests. TRIAL REGISTRATION NUMBER: None.

Detection and isolation of Toxoplasma gondii from fresh semen of naturally infected dogs in Southern Brazil.

The aim of this study was to isolate Toxoplasma gondii and determine the viability of the parasite in fresh semen samples of clinically healthy adult dogs naturally infected. Eleven seropositive dogs with T. gondii IgG antibodies from southern Brazil were selected to confirm the presence and viability of T. gondii in fresh semen samples using in vitro isolation in Vero cell culture, polymerase chain reaction (PCR) and sequencing analysis. The presence of viable T. gondii was confirmed by in vitro isolation and PCR in five semen samples. The ITS1 region of the isolated protozoa (TG S4) was amplified and sequenced. The nucleotide sequence obtained was 99% compatible with the T. gondii DNA sequences stored in the GenBank. It has been shown that T. gondii tachyzoites may be isolated in vitro from fresh semen samples of clinically healthy dogs seropositive for T. gondii.

Risk of recurrent cervical artery dissection during pregnancy, childbirth and puerperium.

BACKGROUND AND PURPOSE: Hormonal and mechanical factors might increase the risk for cervical artery dissection (CAD) during pregnancy and the puerperium. There is uncertainty how to counsel women with a previous CAD regarding the risk of CAD recurrence during pregnancy and the puerperium. METHODS: In an observational study of four stroke centers, all women aged 16-45 years with primary CAD in the previous decade were asked to participate in a standardized assessment on long-term follow-up with a special focus on pregnancies and recurrent CAD. RESULTS: Ninety-two women were identified and 53 of them were included in the analysis (60%). Eleven women declined to participate, 28 were untraceable. The 39 non-participants did not differ from participants regarding key baseline characteristics. Average follow-up time was 72 months. Nine women (17%) had recurrent CAD after a median of 14 days (range 2 days to 117 months). Eleven women (20%) had a total of 13 completed pregnancies at a median of 44 months (range 12-84 months) after index CAD. Two of the pregnant women (18%) had suffered recurrent CAD ≥18 months prior to the pregnancy. All 13 pregnancies and puerperia went without recurrent CADs or cerebrovascular events. This includes giving birth by vaginal delivery (n = 6) and caesarean section (n = 7). None of the five women with typical connective tissue disease became pregnant. CONCLUSIONS: Our observation suggests that the risk of recurrent CAD may not be greatly increased with pregnancies starting at least 12 months after CAD in women without typical connective tissue disease.

Comparison of Whole Ovary Cryotreatments for Fertility Preservation.

The goal of this study was to compare a traditional slow-freeze method (TF) with an open unidirectional slow freeze cooling system (UF) for whole ovary cryopreservation. Therefore, whole pig ovaries were randomly assigned to (A) fresh control, (B) traditional slow freeze (TF) or (C) unidirectional slow freeze (UF). Ovaries were perfused with 10% DMSO in Krebs-Ringer. For TF, whole ovaries were placed in specimen jars containing 10% DMSO and placed into a specialized container for freezing filled with propan-2-ol. For UF, whole ovaries were placed within a specially designed container containing 10% DMSO and transferred to a specialized freezing machine (CTE 920). Histological evaluation demonstrated intact morphology of follicles in all groups; however, an overall decrease of follicle numbers in TF (46%) and UF (50%) compared to fresh control. Live/dead assay indicated significantly lower populations of live cells in both TF (60%) and UF (58%) compared to fresh tissue (74%). TUNEL assay confirmed a difference in percentage of apoptotic follicles between fresh and TF, but there was no significant difference between fresh and UF. To improve the structural and functional integrity of whole ovaries, further investigation, especially into directional freezing, is needed. Whole ovary cryopreservation could provide opportunities for women facing fertility loss due to chemo- or radiotherapy treatment.

Vascularization of carotid plaque in recently symptomatic patients is associated with the occurrence of transcranial microembolic signals.

BACKGROUND AND PURPOSE: Microembolic signals (MES) are detectable in the middle cerebral artery by transcranial ultrasound downstream to atherosclerotic lesions of the internal carotid artery (ICA) in patients with stroke or transient ischaemic attack. The occurrence of MES predicts future risk of stroke in patients with symptomatic and asymptomatic carotid stenosis. The detection of intra-plaque neo-vascularization by contrast-enhanced ultrasound (CEUS) in atherosclerotic plaques of the ICA is associated with future cardiovascular/cerebrovascular events. We investigated whether there is an association between both surrogate markers of future vascular events. METHODS: Forty-one patients with symptomatic atherosclerotic plaques underwent ipsilateral transcranial ultrasound MES detection for 30 min followed by a CEUS investigation of the plaque. The occurrence and number of MES was documented, and the degree of intra-plaque neo-vascularization was measured semi-quantitatively. RESULTS: During the 30 min investigation, 17 patients had MES and nine of them showed neo-vascularization of the atherosclerotic plaque. The remaining 24 patients did not have MES, and only in four patients of this group could plaque neo-vascularization be demonstrated (P = 0.020). CONCLUSIONS: We found an association between the occurrence of MES and the presence of neo-vascularization in patients with symptomatic atherosclerotic carotid plaque. Therefore, plaque neo-vascularization might also be a surrogate marker of future stroke risk.

Nanocrystalline spherical hydroxyapatite granules for bone repair: in vitro evaluation with osteoblast-like cells and osteoclasts.

Conventionally sintered hydroxyapatite-based materials for bone repair show poor resorbability due to the loss of nanocrystallinity. The present study describes a method to establish nanocrystalline hydroxyapatite granules. The material was prepared by ionotropic gelation of an alginate sol containing hydroxyapatite (HA) powder. Subsequent thermal elimination of alginate at 650 °C yielded non-sintered, but unexpectedly stable hydroxyapatite granules. By adding stearic acid as an organic filler to the alginate/HA suspension, the granules exhibited macropores after thermal treatment. A third type of material was achieved by additional coating of the granules with silica particles. Microstructure and specific surface area of the different materials were characterized in comparison to the already established granular calcium phosphate material Cerasorb M(®). Cytocompatibility and potential for bone regeneration of the materials was evaluated by in vitro examinations with osteosarcoma cells and osteoclasts. Osteoblast-like SaOS-2 cells proliferated on all examined materials and showed the typical increase of alkaline phosphatase (ALP) activity during cultivation. Expression of bone-related genes coding for ALP, osteonectin, osteopontin, osteocalcin and bone sialoprotein II on the materials was proven by RT-PCR. Human monocytes were seeded onto the different granules and osteoclastogenesis was examined by activity measurement of tartrate-specific acid phosphatase (TRAP). Gene expression analysis after 23 days of cultivation revealed an increased expression of osteoclast-related genes TRAP, vitronectin receptor and cathepsin K, which was on the same level for all examined materials. These results indicate, that the nanocrystalline granular materials are of clinical interest, especially for bone regeneration.

Low inhibin B levels alone are not a reliable marker of dysfunctional spermatogenesis in childhood cancer survivors.

Hormone and semen analyses were carried out to examine the diagnostic value of hormones and hormone combinations as markers of spermatogenesis in male patients who had received oncological treatment in childhood. Hormone analyses from 73 participants and spermiograms from 42 participants were evaluated. Spearman's correlation coefficients and measures of diagnostic accuracy were calculated for the hormone and semen analysis values. Inhibin B levels of <80 ml/ml, follicle-stimulating hormone (FSH) levels of >10 IU l(-1) and a combination of the two parameters showed positive predictive values for azoospermia of 0.423, 0.6154 and 0.6667 respectively. While 32% of the 73 participants showed a combination of abnormal inhibin B and FSH values, which strongly indicates impaired spermatogenesis, 31% of the 42 spermiogram results revealed azoospermia. The hormone and semen analyses showed that approximately one-third of the participants had fertility impairment. Inhibin B alone thus does not reflect spermatogenesis as well as inhibin B in combination with FSH in patients who have undergone cancer treatment in childhood. Both parameters should therefore be evaluated in paediatric cancer follow-up programmes to allow better identification of treatment regimens that cause persistent azoospermia in male childhood cancer survivors.

Extracorporeal perfusion of the swine uterus: effect of human seminal plasma.

The active transport of sperm through the female genital tract is a very important factor in the fertilisation process. There is conflicting evidence as to whether seminal plasma has a positive or a negative effect on reproductive performance regarding the sperm transport in the female genital tract. In this study, we investigated if the perfused swine uterus is an appropriate model to study the effect of human seminal plasma on uterine contractility. It was found that repeated application of human seminal plasma caused a significantly higher rise in pressure and frequency of contractions in perfused swine uteri compared to buffer [a 1.8-fold and 1.5-fold pressure rise (Δt1SP, P = 0.025; Δt2SP, P = 0.004)] after the first and second application of seminal plasma respectively, and even a 2-fold pressure rise after the third application with a statistical significance of P = 0.007. The pressure rise caused by the seminal plasma over the entire period of application was calculated using a mathematical programme and was represented by the integral of the pressure curve over time. This perfusion model as well as the use of pressure-time integrals is suitable for patho-physiological studies of the uterus.

Myometrial response to neurotropic and musculotropic spasmolytic drugs in an extracorporeal perfusion model of swine uteri.

To compare the effects of neurotropic and musculotropic spasmolytic drugs in isolated swine uterus specimens, 80 swine uteri were perfused using an established model for preserving a viable organ that responds to oxytocic hormones and spasmolytic drugs. An intrauterine catheter was used to record pressure changes. Following initiation of rhythmic uterine contractions and recording of spontaneous rhythmic contractions, spasmolytic drugs (butylscopolamine, atropine, denaverine, morphine, metamizole, pethidine and celandine) were administered at various concentrations. The musculotropic relaxant denaverine in particular showed significant results (P ≤ 0.05) for all dosages and parameters investigated. In terms of muscle physiology, musculotropic agents (denaverine and celandine) have clear advantages in comparison with neurotropic (butylscopolamine and atropine) or musculoneurotropic (morphine, metamizole and pethidine) spasmolytic drugs for inhibiting contractions. Experiments with pethidine (Dolantin) also showed promising results; with celandine (Paverysat), an initial increase in contractions was observed that may suggest ways of promoting rapid directed sperm transport. Denaverine and pethidine in particular may in the future be able to play an important role in improving the pregnancy rate after IVF.

[Silent brain infarcts]. / Klinisch stumme Hirninfarkte.

Silent brain infarctions are frequently found by modern cerebral imaging. Up to 30% of persons without a clinical history of stroke were found to have silent brain infarction in epidemiological studies. "Silent" refers to ischemic brain lesions for which no matching clinical syndrome can be found based on history or clinical investigation. Age, education, and ethnic background have a strong impact on noticing and reporting stroke symptoms. The current clinical definition of stroke is insensitive for cognitive deficits which can also be caused by brain infarctions. The majority of silent brain infarctions are localized in the subcortical white matter of the brain; however, about 10% of silent brain infarctions are cortical. Silent brain infarctions are strongly associated with stroke risk factors and comorbidities that are known to cause clinically overt stroke. Silent brain infarctions are 5 to 10 times more frequent than clinically overt strokes. Silent brain infarctions as defined by DWI lesions on MRI imaging are a frequent finding during operative or interventional procedures and their monitoring may help improve the respective techniques in order to decrease the risk of periprocedural stroke.

The intrauterine to intra-arterial pressure ratio: a new parameter for the study of uterine contractility physiology.

The objective of the study was to examine the uterine contractions and the arterial perfusion pressure changes after application of oxytocin, endothelin 1, prostaglandins PGE(1), PGE(2) and PGF(2alpha), in order to identify the substance with the greatest intrauterine pressure (IUP)/intra-arterial pressure (IAP) ratio, which means the substance most suitable for inducing uterine contractility without raising the systemic vascular pressure. Increasing doses of oxytocin, endothelin 1, PGE(1), PGE(2) and PGF(2alpha) were applied as bolus injection through the uterine artery of perfused swine uteri and the intrauterine and intra-arterial pressure rises were recorded. All substances showed a significant cervicofundic pressure gradient and, with the exception of PGF(2alpha), the uterine peristalsis moved towards the cervix uteri. The perfusion pressure after application of oxytocin, PGE(1), PGE(2) and PGF(2alpha) reached a maximum value and started to decrease, whereas endothelin 1 caused a continuous increase in the perfusion pressure. Endothelin 1 showed the lowest IUP/IAP ratio and oxytocin the greatest. In conclusion, the IUP/IAP ratio provides a promising new parameter for the study of uterine contractility physiology. Besides oxytocin, PGE(2) and PGF(2alpha) emerged as the best candidate substances to improve uterine contractility without raising the intra-arterial pressure.

Hormone and Sperm Analyses after Chemo- and Radiotherapy in Childhood and Adolescence.

BACKGROUND: Since prevalence of and reasons for infertility were unclear in survivors of childhood cancer we conducted a two centre survey in 2006 and nationwide in 2008. In 2008/2009 we undertook a study entitled "Hormone and Sperm Analyses after Chemo- and Radiotherapy in Childhood and Adolescence". PATIENTS AND METHODS: Letters were sent to 748 former paediatric oncological patients who were at least 18 years of age at the time of the survey. Serum and sperm samples were analysed. RESULTS: We obtained 159 blood samples (86 women, 73 men). 42 men took part in the sperm analyses. The average participants' age at the time of the survey was 25 years. The anti-Mullerian hormone levels (AMH) in 14/86 female participants (16 %) were < 0.1 ng/ml. The follicular reserve of these women seemed manifestly impaired, which is consistent with suspected infertility. The AMH levels in 21/86 women (24 %) were 0.1 - 1.0 ng/ml indicating limited follicular reserve and therefore suspected early ovarian failure. Inhibin B levels of < 80 pg/ml and FSH levels of > 10 IU/L were found in 23/73 male participants (32 %), which may indicate impaired spermiogenesis with increased risk of infertility. 13/42 sperm analyses (31 %) revealed azoospermia. DISCUSSION: Paediatric oncological therapy seems to have led to fertility impairment in about 1/3 of the participants. Considering this serious impairment, patients and their families should be given comprehensive counselling ahead of therapy to enable fertility-preserving measures. For persons who wish to have children after undergoing therapy we recommend a hormone and sperm analysis. An early analysis may enable a more successful family planning.

Uterus cryopreservation: maintenance of uterine contractility by the use of different cryoprotocols.

Cryopreservation of cells and even tissue is feasible. New exciting findings arise in the promising field of cryobiology, e.g. the cryopreservation of whole ovaries. Uterus cryopreservation would be advantageous not only for experimental biology, but also for transplantation surgery. The objective of this study was to evaluate various cryopreservation protocols as well as various storage temperatures in cryopreservation of whole swine uteri. The used freezing protocol was slow (0.2 degrees C/min) after arterial perfusion with 1%, 5% or 10% dimethyl sulfoxide (DMSO) solution for 10 min and equilibration in this solution for 30 min. Viability of the organs was tested by histological examination, biochemical parameters and by the capability of rhythmical contractions in a perfusion system. Eighty swine uteri were cryopreserved. All uteri that were frozen with 10% and 5% DMSO were viable after thawing for at least 1 h, whereas only 40% survived with the use of 1% DMSO and 0% with the use of 0.5% DMSO, respectively. There was no difference regarding the survival rates after various cryostorage periods for up to 16 weeks or after cryostorage for 2 weeks in -70 degrees C or -130 degrees C. The cryopreservation of a whole organ such as the swine uterus is a valuable method for the study of cryoprotective agents and freezing protocols. This study demonstrates clearly that the perfusion of the organ with cryoprotectants is the only factor which allows the uterus to contract.

Fertility preservation in cancer patients.

Today the vast majority of children and adolescents diagnosed with cancer achieve relatively high rates of remission and long-term survival, due to significant advances in oncological treatment. Oncological surgery, radiotherapy and chemotherapy however, are often detrimental to fertility, thus substantially impacting a patient's quality of life. Concerns about fertility are similar for men and women; however, their opportunities for intervention differ considerably. This article reviews the literature, discusses the etiology and effects of cancer treatment on fertility, and presents the current and emerging options for the preservation of fertility in patients with cancer. The various diagnostic methods of assessing the fertility potential at the time of diagnosis and the efficacy of the different fertility preserving methods after cancer treatment are also presented.

Thyroid-stimulating hormone is associated with insulin resistance independently of body mass index and age in women with polycystic ovary syndrome.

BACKGROUND: The aim of this study was to evaluate the association between thyroid function, reflected by thyroid-stimulating hormone (TSH) levels, and insulin resistance (IR) in 337 women suffering from polycystic ovary syndrome (PCOS). METHODS: Clinical, metabolic and endocrine parameters were obtained and an oral glucose tolerance test was performed, with calculation of IR indices. The association between thyroid function and IR was evaluated with classification analysis using logistic regression and 10-fold cross-validation to identify a possible TSH threshold for IR. Parameters were then compared between women above and below the TSH threshold using two-sample tests. One-way analyses of covariance were performed to explore whether the impact of TSH on IR is independent of other variables. RESULTS: A TSH cut-off value around 2 mIU/l had the best sensitivity and specificity for identifying women with IR. Women with TSH >or= 2 mIU/l were younger, had a higher body mass index (BMI) and were more insulin-resistant compared with women with TSH < 2 mIU/l. This effect of TSH on IR was independent of age and BMI. CONCLUSIONS: In women with PCOS, a significant association between thyroid function, as reflected by TSH >or= 2 mIU/l, and IR was found and the association appeared to be independent of age and BMI.

Obliterating intracranial vasculopathy mimicking multiple sclerosis.

BACKGROUND: The first ever diagnosis of multiple sclerosis (MS) requires consideration of both diagnostic criteria and differential diagnosis. Clinicians are particularly challenged by rare conditions which may mimic MS symptoms and relapses. CASE REPORT: We report the case of a young female patient who presented with relapsing left hemispheric symptoms that were highly suspicious of MS but were caused by an idiopathic occlusive angiopathy of the circle of Willis. CONCLUSION: Occlusive disease of the great cerebral arteries in young patients is a rare but important differential diagnosis of MS. It has to be considered in patients presenting with the first symptoms suspicious of MS as substantial treatment consequences will arise.

Sensitivity of neurovascular ultrasound for the detection of spontaneous cervical artery dissection.

The reported sensitivity of neurovascular ultrasound (nUS) for detecting spontaneous cervical artery dissection (sCAD) varies from 80% to 96% in the internal carotid artery (ICA) and from 70% to 86% in the vertebral arteries (VA). The aim of this study was to assess the sensitivity of nUS compared to MRI of the neck and MR angiography for the detection of sCAD. Forty consecutive patients with sCAD proven by 1.5T MRI were investigated by nUS within 48 hours of admission. A total of 52 cases of sCAD were detected by MRI, equally distributed (n=26, 50%) in the ICA and VA territories. Two sCADs affecting the ICA (n=2, 8%) and two sCADs of the VA (n=2, 8%) had normal initial nUS findings. The sensitivity of nUS in detecting sCAD is high, about 92% for both vascular territories. However, intramural hematomas may be missed either when they are located outside the arterial segments directly visible by nUS or if they are too small to cause hemodynamically significant stenosis.

Polymorphisms in estrogen metabolism and estrogen pathway genes and the risk of miscarriage.

PURPOSE: This study investigated genetic variations in the estrogen pathway and their association with miscarriages. METHODS: A total of 483 patients were recruited from a comprehensive control group for case-control studies. Three variants of the CYP19A1 gene (rs10046, rs4646 and rs700519) and one variant each of the estrogen (ESR1) and progesterone (PGR) receptor genes (rs3020314 and rs1042838) were investigated using polymorphism genotyping. The chi-squared test and one-way analysis of variation (ANOVA) were used for statistical analysis. RESULTS: For rs10046 (CYP19A1), the C/C genotype was associated with a greater frequency of miscarriages (P = 0.017). The other genotypes were not found to be associated with recurrent miscarriage. CONCLUSIONS: This is the first study that has identified a single-nucleotide polymorphism in the aromatase gene that suggests a significant association between genotypes and miscarriage. As aromatase is an essential enzyme in the estrogen pathway, it may be speculated that variations in the aromatase gene in some way give rise to different conditions in the endocrine environment that can lead to impaired fertility.