The addition of anti-Müllerian hormone in an algorithm for individualized hormone dosage did not improve the prediction of ovarian response-a randomized, controlled trial.

Study question: Does the addition of anti-Müllerian hormone (AMH) to a conventional dosage regimen, including age, antral follicle count (AFC) and BMI, improve the rate of targeted ovarian response, defined as 5-12 oocytes after IVF? Summary answer: The addition of AMH did not alter the rate of targeted ovarian response, 5-12 oocytes, or decreased the rate of ovarian hyperstimulation syndrome (OHSS) or cancelled cycles due to poor ovarian response. What is known already: Controlled ovarian hyperstimulation (COH) in connection with IVF is sometimes associated with poor ovarian response resulting in low pregnancy and live birth rates or leading to cycle cancellations, but also associated with excessive ovarian response, causing an increased risk of OHSS. Even though it is well-established that both AMH and AFC are strong predictors of ovarian response in IVF, few randomized trials have investigated their impact on achieving an optimal number of oocytes. Study design, size and duration: Between January 2013 and May 2016, 308 patients starting their first IVF treatment were randomly assigned, using a computerized randomization program with concealed allocation of patients and in the proportions of 1:1, to one of two dosage algorithms for decisions on hormone starting dose, an algorithm, including AMH, AFC, age and BMI (intervention group), or an algorithm, including only AFC, age and BMI (control group). The study was blinded to patients and treating physicians. Participants/materials, setting, methods: Women aged >18 and <40 years, with a BMI above 18.0 and below 35.0 kg/m2 starting their first IVF cycle where standard IVF was planned, were eligible. All patients were treated with a GnRH agonist protocol and recombinant FSH was used for stimulation. The study was performed as a single-centre study at a large IVF unit at a university hospital. Main results and the role of chance: The rate of patients having the targeted number of oocytes retrieved was 81/152 (53.3%) in the intervention group versus 96/155 (61.9%) in the control group (P = 0.16, difference: -8.6, 95% CI: -20.3; 3.0). Cycles with poor response (<5 oocytes) were more frequent in the AMH group, 39/152 (25.7%) versus the non-AMH group, 17/155 (11.0%) (P < 0.01), while the number of cancelled cycles due to poor ovarian response did not differ 7/152 (4.6%) and 4/155 (2.6%) (P = 0.52). An excessive response (>12 oocytes) was seen in 32/152 (21.1%) and 42/155 (27.1%) patients, respectively (P = 0.27). Moderate or severe OHSS was observed among 5/152 (3.3%) and 6/155 (3.9%) patients, respectively (P = 1.0). Live birth rates were 48/152 (31.6%) and 42/155 (27.1%) per started cycle. Limitations, reasons for caution: The categorization of AMH values in predicted low, normal and high responders was originally established using the Diagnostic Systems Laboratories assay and was translated to more recently released assays, lacking international standards and well-established reference intervals. The interpretation of AMH values between different assays should therefore be made with some caution. Wider implications of the findings: An individualised dosage regimen including AMH compared with a non-AMH dosage regimen in an unselected patient population did not alter the number of women achieving the targeted number of oocytes, or the cancellation rate due to poor response or the occurrence of moderate/severe OHSS. However, this study cannot answer the question if using an algorithm for dose decision of FSH is superior to a standard dose and neither which ovarian reserve test is the most effective. Study funding/competing interest: Financial support was received through Sahlgrenska University Hospital (ALFGBG-70 940) and unrestricted grants from Ferring Pharmaceuticals and the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest. Trial registration: The study was registered at www.clinicaltrials.gov NCT02013973. Trial registration date: 6 December 2013. DATE OF FIRST PATIENT RANDOMIZED: 14 January 2013.

The correlation between AMH assays differs depending on actual AMH levels.

STUDY QUESTION: What is the correlation of serum anti-Müllerian hormone (AMH) levels between two frequently used laboratory assays? SUMMARY ANSWER: A considerable difference was found in serum AMH levels measured with the two different assays, particularly for low AMH values. WHAT IS KNOWN ALREADY: AMH is regarded as being a robust, highly sensitive and specific biomarker for ovarian response and has become widely used as the basis for fertility treatment decisions. However, several available assays with different reference values, in addition to inter-laboratory variations and issues of sample stability, make interpretation of the AMH values and their clinical implications complicated. STUDY DESIGN SIZE DURATION: An observational study was performed including 269 serum samples from infertile women, originating from a RCT conducted in 2013-2016 (www.clinicaltrials.gov NCT02013973). PARTICIPANTS/MATERIALS SETTING METHOD: Serum AMH levels analysed with the Modified Beckman Coulter Gen II ELISA assay (Premix method) were compared to AMH levels analysed with the Beckman Coulter Gen II ELISA original assay (Gen II original). All samples were handled identically and analysed with the two assays in a parallel setting. MAIN RESULTS AND THE ROLE OF CHANCE: The slope of the regression line showed a mean of 18% higher values with the Premix method compared to the Gen II original assay, and more than 40% higher values for AMH levels in the lower range. LIMITATIONS REASONS FOR CAUTION: The Gen II original assay is no longer in clinical use as it has been replaced by the Premix method, which, in turn, recently has been further developed into an automated method. WIDER IMPLICATIONS OF THE FINDINGS: The finding of differences in AMH levels between assays is clinically important and may imply an incorrect classification in the assessment of ovarian reserve. The robustness of serum AMH as a marker for ovarian reserve and as a tool for fertility counselling has to be investigated further. There is an urgent need for international standards on interpretation of AMH values for different assays. STUDY FUNDING/COMPETING INTERESTS: Financial support was received through Sahlgrenska University Hospital (ALFGBG-70940) and the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest.

The vitamin D status in ankylosing spondylitis in relation to intestinal inflammation, disease activity, and bone health: a cross-sectional study.

UNLABELLED: We assessed the vitamin D status in ankylosing spondylitis (AS) patients and healthy controls in the late winter when no vitamin D is produced by the sunlight. The vitamin D status was often poor, but not lower in AS and not associated with disease activity or signs of gut inflammation. INTRODUCTION: The aims of the study were to investigate the vitamin D levels attained mainly by dietary intake in ankylosing spondylitis (AS) in comparison with healthy controls and in relation to gut inflammation, measured indirectly by fecal calprotectin, disease activity, osteoproliferation, bone mineral density (BMD), and vertebral fractures. METHODS: Serum 25-hydroxy vitamin D (25(OH)D) was measured in 203 AS patients and 120 healthy controls at the end of "the vitamin D winter," when the out-door UVB irradiation is too low to allow synthesis of vitamin D3 in the skin at the latitude of Gothenburg, Sweden. Fecal calprotectin was measured in stool samples. Disease activity was assessed with CRP, ESR, ASDASCRP, BASDAI, BAS-G, BASFI, and BASMI. Lateral spine radiographs were scored for osteoproliferation and vertebral fractures using the mSASSS and Genant scores. BMD was measured in the lumbar spine and femoral neck. RESULTS: Vitamin D insufficiency (a serum 25(OH)D <50 nmol/L) was found in approximately 50 % of the AS patients, but serum 25(OH)D was not different from healthy controls and not significantly correlated with fecal calprotectin, gastrointestinal symptoms, disease activity parameters, mSASSS, BMD, or vertebral fractures. CONCLUSIONS: The vitamin D status was often poor in the late winter in AS but not different from the healthy controls. No evidence for a connection between subclinical gut inflammation, malabsorption, and hypovitaminosis D was found. Serum 25(OH)D was not associated with disease activity, osteoproliferation, BMD, or vertebral fractures. We suggest that the lower vitamin D levels in AS, previously found by others, may be caused by reduced out-door UVB exposure.

Serum IGF-1 is higher in patients with idiopathic normal pressure hydrocephalus than in the population.

BACKGROUND: Hypopituitarism has been reported in patients with idiopathic normal pressure hydrocephalus (iNPH), which could enhance characteristic symptoms like impaired wakefulness, gait, body balance, and subcortical cognitive deterioration. PURPOSE: To compare basal serum levels of pituitary and sex hormones and serum insulin-like growth factor-1 (S-IGF-1) in patients with iNPH and an age-matched control population, and to correlate the preoperative hormone levels with symptoms and signs pre-operatively and three months after surgery. METHODS: A cross-sectional case control design was used. Patients diagnosed with iNPH, n=108 (65 men and 43 women, mean age 72.3 years), were consecutively included during 2006-2011 at Sahlgrenska University Hospital, Gothenburg, Sweden. S-TSH, S-free T4, S-FSH, S-LH, S-prolactin, plasma ACTH, S-testosterone, S-oestradiol and S-IGF-1 were examined. Symptoms and signs were scored using the iNPH scale score. Population controls, n=146, were recruited from the WHO MONICA project, Gothenburg in 2008. RESULTS: Men and women with iNPH had higher S-IGF-1 than controls (p<0.001). Women with iNPH had lower S-TSH (p=0.016) than controls, but the frequency of levothyroxine substitution was similar. Among men, a higher level of S-IGF-1 was associated with milder symptoms, while higher levels of S-FSH and S-LH were associated with more severe symptoms. CONCLUSIONS: Patients with iNPH did not have lower levels of pituitary or sex hormones but presented with higher levels of S-IGF-1, compared with healthy, age-matched controls. Higher S-IGF-1 in men was related to milder mental and physical symptoms and signs.