Serum antimüllerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: A longitudinal study

Objective: The aim of this study was to assess which of the basal ovarian reserve markers provides the best reflection of the changes occurring in ovarian function over time (i.e., reproductive aging). Design: Prospective longitudinal study. Setting: Healthy volunteers in an academic research center. Patient(s): Eighty-one women with normal reproductive performance during the course of their lives were longitudinally assessed. In this select group of women, becoming chronologically older was considered as a proxy variable for becoming older from a reproductive point of view. Intervention(s): The women were assessed twice, with on average a 4-year interval (T 1 and T 2). The number of antral follicles on ultrasound (AFC) and blood levels of antimüllerian hormone (AMH), FSH, inhibin B, and E 2 were assessed. Main Outcome Measure(s): Longitudinal changes of the markers mentioned and the consistency of these parameters over time. Result(s): The mean ages at T 1 and T 2 were 39.6 and 43.6 years, respectively. Although AFC was strongly associated with age in a cross-sectional fashion, it did not change over time. The AMH, FSH, and inhibin B levels showed a significant change over time, in contrast to E 2 levels. The AMH and AFC were highly correlated with age both at T 1 and T 2, whereas FSH and inhibin B predominantly changed in women more than 40 years of age. To assess the consistency of these parameters over time, we investigated whether a woman's individual level above or below the mean of her age group at T 1 remained above or below the mean of her age group at T 2. Serum AMH concentrations showed the best consistency, with AFC as second best. The FSH and inhibin B showed only modest consistency, whereas E 2 showed no consistency at all. Conclusion(s): These results indicate that serum AMH represents the best endocrine marker to assess the age-related decline of reproductive capacity

Cidofovir for BK Virus-Associated Hemorrhagic Cystitis: A Retrospective Study

Background.BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated. Methods.We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation. Results.From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (P=.01) and the use of total body irradiation (P=.03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P<.001 and P=.001, respectively). Conclusions.Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trial

Physical activity for patients undergoing an allogeneic hematopoietic stem cell transplantation: Benefits of a moderate exercise intervention

An allogeneic hematopoietic stem cell transplantation (HSCT) can have profound and lasting adverse effects on a patient’s physical and psychological well-being. So far, only few studies have investigated the effectiveness of physical activity over the entire inpatient phase of an allogeneic HSCT. Purpose: We performed a randomized controlled study to examine the influence of a controlled moderate exercise program starting parallel to chemotherapeutic conditioning and total body irradiation on the patient’s physical and psychological constitution. Patients and methods: Forty-seven patients undergoing an allogeneic HSCT were randomly assigned to an exercise group (EG) or a control group (CG). While the EG took part in an endurance and activity of daily living-training twice a day, the CG received the clinic’s standard physiotherapy program once a day. Results: Significant differences and/or trends in favor of the EG were observed regarding the primary endpoint endurance performance (P = 0.002), muscular strength (P = 0.022), fatigue (P = 0.046), and emotional state (P = 0.028) without posing an additional risk for the individual. Conclusion: The results show that the training program is feasible and seems to have positive influences on physical performance and quality of life in patients undergoing an allogeneic HSCT. However, further studies are necessary to confirm these results

Anti-Mullerian hormone and ovarian dysfunction

Anti-Mullerian hormone (AMH) has important roles in postnatal ovarian function. Produced by ovarian granulosa cells, AMH is involved in initial follicle development. In fact, serum AMH level correlates with ovarian follicle number. In patients with polycystic ovary syndrome (PCOS), AMH levels are elevated, which indicates its potential relevance in PCOS diagnosis and management. AMH represents a useful clinical marker for the assessment of ovarian reserve in cases of subfertility caused by advanced age in women. A potential role for AMH in dominant follicle selection has also been suggested. Future challenges comprise the availability of a well-standardized assay and the development of AMH agonists and antagonists as possible tools to manipulate ovarian function for contraception or ovarian longevity

Anti-Mullerian Hormone Predicts Menopause: A Long-Term Follow-Up Study in Normoovulatory Women

Context: It has been hypothesized that a fixed interval exists between age at natural sterility and age at menopause. Both events show considerable individual variability, with a range of 20 yr. Correct prediction of age at menopause could open avenues of individualized prevention of age-related infertility and other menopause-related conditions, like cardiovascular disease and breast carcinoma. Objective: The aim of this study was to explore the ability of ovarian reserve tests to predict age at menopause. Design and Setting: We conducted a long-term follow-up study at an academic hospital. Participants: A total of 257 normoovulatory women (age, 21-46 yr) were derived from three cohorts with highly comparable selection criteria. Interventions: Anti-Mullerian hormone (AMH), antral follicle count, and FSH were assessed at time 1 (T1). At time 2 (T2), approximately 11 yr later, cycle status (strictly regular, menopausal transition, or postmenopause) and age at menopause were inventoried. Main Outcome Measures: Accuracy of the ovarian reserve tests in predicting time to menopause was assessed by Cox regression, and a nomogram was constructed for the relationship between age-specific AMH concentrations at T1 and age at menopause. Results: A total of 48 (19%) women had reached postmenopause at T2. Age, AMH, and antral follicle count at T1 were significantly related with time to menopause (P < 0.001) and showed a good percentage of correct predictions (C-statistic, 0.87, 0.86, and 0.84, respectively). After adjusting for age, only AMH added to this prediction (C-statistic, 0.90). From the constructed nomogram, it appeared that the normal distribution of age at menopause will shift considerably, depending on the individual Conclusions: AMH is highly predictive for timing of menopause. Using age and AMH, the age range in which menopause will subsequently occur can be individually calculated. (J Clin Endocrinol Metab 96: 2532-2539, 2011

Anti-Mullerian Hormone, Inhibin B, and Antral Follicle Count in Young Women with Ovarian Failure

Context: Ovarian dysfunction is classically categorized on the basis of cycle history, FSH, and estradiol levels. Novel ovarian markers may provide a more direct insight into follicular quantity in hypergonadotropic women. Objective: The objective of the study was to investigate the distribution of novel ovarian markers in young hypergonadotropic women as compared with normogonadotropic regularly menstruating women. Design: This was a nationwide prospective cohort study. Setting: The study was conducted at 10 hospitals in The Netherlands. Patients: Women below age 40 yr with regular menses and normal FSH (controls; n = 83), regular menstrual cycles and elevated FSH [incipient ovarian failure (IOF); n = 68]; oligomenorrhea and elevated FSH [referred to as transitional ovarian failure (TOF); n = 79]; or at least 4 months amenorrhea together with FSH levels exceeding 40 IU/liter [premature ovarian failure (POF); n = 112]. Main Outcome Measures: Serum levels of anti-Mullerian hormone (AMH), inhibin B, and antral follicle count (AFC) was measured. Results: All POF patients showed AMH levels below the fifth percentile (p(5)) of normoovulatory women. Normal AMH levels (>p(5)) could be identified in 75% of IOF, 33% of TOF patients, and 98% of controls. AFC and AMH levels changed with increasing age (P <0.0001), whereas inhibin B did not (P = 0.26). AMH levels were significantly different between TOF and IOF over the entire age range, whereas AFC became similar for TOF and IOF at higher ages. Conclusions: Compared with inhibin B and AFC, AMH was more consistently correlated with the clinical degree of follicle pool depletion in young women presenting with elevated FSH levels. AMH may provide a more accurate assessment of the follicle pool in young hypergonadotropic patients, especially in the clinically challenging subgroups of patients with elevated FSH and regular menses (i.e. IOF) and in hypergonadotropic women with cycle disturbances not fulfilling the POF diagnostic criteria (i.e. TOF). (J Clin Endocrinol Metab 94: 786-792, 2009

A controlled trial of recombinant human erythropoietin after bone marrow transplantation

Recombinant human erythropoietin (rHuEPO) stimulates erythropoietic bone marrow cells and increases erythrocyte production. This prospective study was designed to evaluate the effects of rHuEPO on regeneration of erythropoiesis after allogeneic or autologous bone marrow transplantation (BMT). Seventeen centers participated in this randomized, double-blind, placebo-controlled multicenter trial. The randomization was performed centrally for each center and stratified according to allogeneic or autologous BMT and major ABO-blood group incompatibility. One hundred and six patients received rHuEPO after allogeneic BMT and 109 patients received placebo. After autologous BMT, 57 patients were treated with rHuEPO and 57 with placebo. Patients received either 150 IU/kg/day C127 mouse-cell-derived rHuEPO or placebo as continuous intravenous infusion. Therapy started after bone marrow infusion and lasted until independence from erythrocyte transfusions for 7 consecutive days with stable hemoglobin levels greater than or equal to 9 g/100 mL or until day 41. After allogeneic BMT, the reticulocyte counts were significantly higher with rHuEPO from day 21 to day 42 after BMT. The median time (95% confidence intervals) to erythrocyte transfusion independence was 19 days (range, 16.3 to 21.6) with rHuEPO and 27 days (range, 22.3 to > 42) with placebo (P < .003). The mean (+/-SD) numbers of erythrocyte transfusions until day 20 after BMT were 6.6 +/- 4.8 with rHuEPO and 6.0 +/- 3.8 with placebo. However, from day 21 to day 41, the rHuEPO-treated patients received 1.4 +/- 2.5 (median, 0) transfusions and the control group received 2.7 +/- 4.0 (median, 2) transfusions (P = .004). In the follow-up period from day 42 up to day 100, 2.4 +/- 5.6 transfusions were required with rHuEPO and 4.5 +/- 9.6 were required with placebo (P =.075). A multivariate analysis (ANOVA) showed that acute graft-versus-host disease (GVHD), major ABO-blood group incompatibility, age greater than 35 years, and hemorrhage significantly increased the number of transfusions. However, after day 20, rHuEPO significantly reduced the number of erythrocyte transfusions in these patient groups, as well as reducing incompatibility in the major ABO-blood group. For the whole study period, rHuEPO reduced the transfusion requirements in GVHD III and IV from 18.4 +/- 8.6 to 8.5 +/- 6.8 U (P = .05). After autologous BMT, there was no difference in the time to independence from erythrocyte transfusions and in the regeneration of reticulocytes. Marrow purging strongly increased the requirement for transfusions as well as the time to transfusion independence. rHuEPO had no relevant effect on regeneration of thrombopoiesis after allogeneic or autologous BMT. Overall, no major differences in side effects or complications between rHuEPO-treated and placebo-treated patients occurred. After allogeneic BMT, rHuEPO significantly accelerates the reconstitution of erythropoiesis and reduces the number of erythrocyte transfusions after day 20. The strongest effect occurs in patients with acute GVHD. After autologous BMT, rHuEPO has no clinically relevant effect on regeneration of erythropoiesis. (C) 1994 by The American Society of Hematology