Correlation between three assay systems for anti-Mullerian hormone (AMH) determination

PURPOSE: Analysis of anti-Müllerian hormone (AMH) is becoming of recognized importance in reproductive medicine, but assays are not standardized. We have evaluated the correlation between the new Gen II ELISA kit (Beckman-Coutler) and the older ELISA kits by Immunotech (IOT) and Diagnostic Systems Laboratories (DSL). METHODS: A total of 56 archived serum samples from patients with subfertility or reproductive endocrine disorders were retrieved and assayed in duplicate using the three AMH ELISA kits . The samples covered a wide range of AMH concentrations (1.9 to 142.5 pmol/L). RESULTS: We observed good correlations between the new (AMH Gen II) and old AMH assay kits by IOT and DSL (R(2) = 0.971 and 0.930 respectively). The regression equations were AMH (Gen II) = 1.353 × AMH (IOT) + 0.051 and AMH (Gen II) = 1.223 × AMH (DSL) – 1.270 respectively. CONCLUSIONS: AMH concentrations using the Gen II kit are slightly higher than those from the IOT and DSL kits. Standardization of assay results worldwide is urgently required but this analysis facilitates the interpretation of values obtained historically and in future studies using any of the 3 assays available. Meanwhile, adapting clinical cut-offs from previously published work by direct conversion is not recommended

External validation and calibration of IVFpredict:A national prospective cohort study of 130,960 in vitro fertilisation Cycles

© 2015 Smith et al. Background Accurately predicting the probability of a live birth after in vitro fertilisation (IVF) is important for patients, healthcare providers and policy makers. Two prediction models (Templeton and IVFpredict) have been previously developed from UK data and are widely used internationally. The more recent of these, IVFpredict, was shown to have greater predictive power in the development dataset. The aim of this study was external validation of the two models and comparison of their predictive ability. Methods and Findings 130,960 IVF cycles undertaken in the UK in 2008-2010 were used to validate and compare the Templeton and IVFpredict models. Discriminatory power was calculated using the area under the receiver-operator curve and calibration assessed using a calibration plot and Hosmer-Lemeshow statistic. The scaled modified Brier score, with measures of reliability and resolution, were calculated to assess overall accuracy. Both models were compared after updating for current live birth rates to ensure that the average observed and predicted live birth rates were equal. The discriminative power of both methods was comparable: the area under the receiver-operator curve was 0.628 (95% confidence interval (CI): 0.625-0.631) for IVFpredict and 0.616 (95% CI: 0.613-0.620) for the Templeton model. IVFpredict had markedly better calibration and higher diagnostic accuracy, with calibration plot intercept of 0.040 (95% CI: 0.017-0.063) and slope of 0.932 (95% CI: 0.839 - 1.025) compared with 0.080 (95% CI: 0.044-0.117) and 1.419 (95% CI: 1.149-1.690) for the Templeton model. Both models underestimated the live birth rate, but this was particularly marked in the Templeton model. Updating the models to reflect improvements in live birth rates since the models were developed enhanced their performance, but IVFpredict remained superior. Conclusion External validation in a large population cohort confirms IVFpredict has superior discrimination and calibration for informing patients, clinicians and healthcare policy makers of the probability of live birth following IVF

Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome

Both vitamin D deficiency and polycystic ovary syndrome (PCOS) are associated with aspects of metabolic syndrome, but it is unclear whether vitamin D deficiency contributes to the metabolic disturbances commonly found in women with PCOS. This study sought to investigate (1) the prevalence of vitamin D deficiency in PCOS women in Scotland and (2) the relationship between vitamin D status and metabolic risk factors. This was an observational study on 52 women (25 in PCOS group and 27 in control group). Serum 25-hydroxyvitamin D concentrations less than 25 nmol/L were classified as severe vitamin D deficiency and were found in 44.0% and 11.2% of subjects in the PCOS and control groups, respectively (P =.047). Among the PCOS subjects, 25-hydroxyvitamin D concentrations were negatively correlated with body mass index (P =.033), C-reactive protein (P =.027), and free androgen index (P =.025) and positively correlated with quantitative insulin sensitivity check index (P =.035), high-density lipoprotein cholesterol (HDL-C) (P =.033), and sex hormone binding globulin (P =.038). Associations of vitamin D deficiency with quantitative insulin sensitivity check index and HDL-C were independent of body mass index and waist-to-hip ratio. Vitamin D deficiency is highly prevalent in PCOS women in Scotland, and a larger proportion of PCOS patients than control women were found to be vitamin D deficient. We also demonstrate correlations of vitamin D status with insulin sensitivity, HDL-C, and C-reactive protein in PCOS patients, which support the increasing evidence that vitamin D deficiency is associated with multiple metabolic risk factors in PCOS women. © 2011 Elsevier Inc.link_to_subscribed_fulltex

Serum anti-müllerian hormone level is not altered in women using hormonal contraceptives

Background: Anti-müllerian hormone (AMH) is secreted from granulosa cells of antral follicles into the circulation of adult women and hence could serve as an ovarian function test. This would be of value to hormonal contraceptive users if its serum level is unaffected by the use of hormonal contraceptives. Study Design: We prospectively recruited 95 women using combined oral contraceptive (n=23), combined injectable contraceptive (n=23), progestogen-only pills (n=9), progestogen-only injectable (n=20) and levonorgestrel intrauterine system (n=20), and measured their serum AMH concentration before and 3-4 months after treatment. Results: No significant difference in pre- and post-treatment serum AMH level was evident in all the treatment groups studied. Conclusions: Being unaffected by hormonal contraceptives, serum AMH measurement is potentially a useful clinical test in hormonal contraceptive users for the differential diagnosis of anovulatory disorders and determination of menopause. © 2011 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

Evaluating the performance of serum antimullerian hormone concentration in predicting the live birth rate of controlled ovarian stimulation and intrauterine insemination

Objective: To evaluate the role of serum antimullerian hormone (AMH) concentration in predicting live birth outcome in controlled ovarian stimulation and intrauterine insemination (IUI). Design: Retrospective analysis. Setting: Tertiary assisted reproduction unit. Patients: 243 patients undergoing IUI treatment. Intervention(s): Archived early follicular phase serum samples taken at the start of the first treatment cycle before ovarian stimulation were retrieved from patients undergoing IUI treatment. Main Outcome Measure(s): First-cycle and cumulative live birth rates. Result(s): Patients attaining a successful live birth, either in the first cycle or cumulatively after three cycles, had significantly higher serum AMH concentrations than those failing treatment. Serum AMH concentration correlated positively with antral follicle count (AFC) and duration of stimulation and inversely with maternal age, serum FSH concentration, and total dose of gonadotropin used. After controlling for age, body mass index, AFC, and FSH, AMH remained the only significant predictor of cumulative live birth. The area under the receiver operating characteristic curve was 0.668 in predicting cumulative live birth. Serum AMH concentration was significantly higher in overresponders. Conclusion(s): Serum AMH concentration was significantly higher in subjects with a live birth from the first cycle or after three cycles of stimulated IUI treatment compared with those failing treatment. Serum AMH concentration has a modest predictive value on ovarian overresponse. Copyright © 2010 American Society for Reproductive Medicine, Published by Elsevier Inc.link_to_subscribed_fulltex

Effect of leptin on motility, capacitation and acrosome reaction of human spermatozoa

Leptin is a polypeptide hormone with important roles in reproduction. It has been detected in human seminal plasma as well as on human ejaculated spermatozoa. This study aimed at studying the possible role of leptin in regulating human sperm functions. Immunofluorescent staining was used to study the expression of leptin and its receptor. The correlation between the concentration of leptin and soluble leptin receptor (ObRs) in seminal plasma as measured by enzyme-linked immunosorbant assay and sperm motility parameters measured by computer-assisted sperm analyais (CASA) was determined. The effects of recombinant leptin on human sperm motility, capacitation and acrosome reaction as measured by chlortetracycline staing were also studied. Leptin immunoreactivity was demonstrated at the equatorial and neck regions of human spermatozoa, whereas that of ObRs was shown up on the tail. After Percoll separation, spermatozoa with high density had more intense leptin immunoreactivity compared with those with low density. No significant correlation was found between seminal plasma concentration of leptin/ObRs and sperm motility parameters. After incubation with recombinant human leptin for either 3 h or overnight, there was no change in all the CASA motility parameters determined and percentages of capacitated and acrosome-reacted spermatozoa. We concluded that leptin does not have a significant effect on motility and capacitation/acrosome reaction in human ejaculated mature spermatozoa. Its role in male reproduction is yet to be determined. © 2009 European Academy of Andrology.link_to_subscribed_fulltex

Response to letter to the editor: Serum anti-Mullerian hormone level is not altered in women using hormonal contraceptives

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Evaluation of serum antimullerian hormone and inhibin B concentrations in the differential diagnosis of secondary oligoamenorrhea

Objective: To evaluate the performance of antimullerian hormone (AMH) and inhibin B as ovarian function markers for differentiating common causes of secondary oligoamenorrhea, namely hypogonadotrophic hypogonadism (HH), polycystic ovary syndrome (PCOS), premature ovarian failure (POF), and hyperprolactinemia (HPRL). Design: Retrospective analysis. Setting: Two university hospitals. Patient(s): A total of 124 women with secondary oligoamenorrhea and 26 women with normal ovulation. Intervention(s): Serum samples from the subjects were analyzed for AMH and inhibin B. Main Outcome Measure(s): Serum AMH and inhibin B concentrations. Result(s): Serum AMH concentration was significantly raised in women having World Health Organization group 2 anovulation, either with or without PCOS, and was significantly decreased to very low levels in POF; the diagnostic accuracy in both conditions was excellent, with areas under the receiver operating characteristic curve (AUC) of 0.913 and 0.977, respectively. The discriminatory performance between HH and PCOS was also good, with AUC 0.861. AMH remained unchanged in HH and HPRL compared with ovulatory control subjects. There were large overlap of serum inhibin B levels in the different conditions, and a significant difference from control subjects existed only in the POF group. Conclusion(s): Serum AMH, but not inhibin B concentration, serves as a useful diagnostic tool in the differential diagnosis of secondary oligoamenorrhea. Copyright © 2011 American Society for Reproductive Medicine, Published by Elsevier Inc.link_to_subscribed_fulltex

Area of residence is associated with Australian women's uptake of long-acting contraception [Conference Abstract]

Objective: Several new types of contraception became available in Australia over the last twelve years (the implant in 2001, progestogen intra-uterine device (IUD) in 2003, and vaginal contraceptive ring in 2007). Most methods of contraception require access to health services. Permanent sterilisation and the insertion of an implant or IUD involve a surgical procedure. Access to health professionals providing these specialised services may be more difficult in rural areas. This paper examines uptake of permanent or long-acting reversible contraception (LARCs) among Australian women in rural areas compared to women in urban areas. Method: Participants in the Australian Longitudinal Study on Women's Health born in 1973-78 reported on their contraceptive use at three surveys: 2003, 2006 and 2009. Contraceptive methods included permanent sterilisation (tubal ligation, vasectomy), non-daily or LARC methods (implant, IUD, injection, vaginal ring), and other methods including daily, barrier or "natural" methods (oral contraceptive pills, condoms, withdrawal, safe period). Sociodemographic, reproductive history and health service use factors associated with using permanent, LARC or other methods were examined using a multivariable logistic regression analysis. Results: Of 9,081 women aged 25-30 in 2003, 3% used permanent methods and 4% used LARCs. Six years later in 2009, of 8,200 women (aged 31-36), 11% used permanent methods and 9% used LARCs. The fully adjusted parsimonious regression model showed that the likelihood of a woman using LARCs and permanent methods increased with number of children. Women whose youngest child was school-age were more likely to use LARCs (OR=1.83, 95%CI 1.43-2.33) or permanent methods (OR=4.39, 95%CI 3.54-5.46) compared to women with pre-school children. Compared to women living in major cities, women in inner regional areas were more likely to use LARCs (OR=1.26, 95%CI 1.03-1.55) or permanent methods (OR=1.43, 95%CI 1.17-1.76). Women living in outer regional and remote areas were more likely than women living in cities to use LARCs (OR=1.65, 95%CI 1.31-2.08) or permanent methods (OR=1.69, 95%CI 1.43-2.14). Women with poorer access to GPs were more likely to use permanent methods (OR=1.27, 95%CI 1.07-1.52). Conclusions: Location of residence and access to health services are important factors in women's choices about long-acting contraception in addition to the number and age of their children. There is a low level of uptake of non-daily, long-acting methods of contraception among Australian women in their mid-thirties