Hang Wun Raymond Li

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.

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

PurposeAnalysis 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).MethodsA 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).ResultsWe observed good correlations between the new (AMH Gen II) and old AMH assay kits by IOT and DSL (R2 = 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.ConclusionsAMH 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.

Role of Baseline Antral Follicle Count and Anti-Mullerian Hormone in Prediction of Cumulative Live Birth in the First In Vitro Fertilisation Cycle: A Retrospective Cohort Analysis

Objective This retrospective study determined for the first time the role of baseline antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) level in the first in-vitro fertilisation (IVF) cycle in predicting cumulative live birth from one stimulation cycle. Methods We studied 1,156 women (median age 35 years) undergoing the first IVF cycle. Baseline AFC and AMH level on the day before ovarian stimulation were analysed. The main outcome measure was cumulative live birth in the fresh plus all the frozen embryo transfers after the same stimulation cycle. Results Serum AMH was significantly correlated with AFC. Both AMH and AFC showed significant correlation with age and ovarian response in the stimulated cycle and total number of transferrable embryos. Baseline AFC and serum AMH were significantly higher in subjects attaining a live birth than those who did not in the fresh stimulated cycle, as well as those attaining cumulative live birth. There was a significant trend of higher cumulative live birth rate in women with higher AMH or AFC. However, logistic regression revealed that both AMH and AFC were not significant predictors of cumulative live birth after adjusting for age and number of embryos available for transfer. Considering only one single predictor, the areas under the ROC curves for AMH (0.646, 95% CI 0.616–0.675) and age (0.648, 95% CI 0.618–0.677) were slightly higher than that for AFC (0.617, 95% CI 0.587–0.647) in predicting cumulative live birth. However, a model combining AMH (with or without AFC) and age of the women only classified an addition of less than 2% of subjects correctly compared to the model with age alone. Conclusion Baseline AFC and serum AMH have only modest predictive performance on the occurrence of cumulative live birth, and may not give additional value on top of the womens age.

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.

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.

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 analysis (CASA) was determined. The effects of recombinant leptin on human sperm motility, capacitation and acrosome reaction as measured by chlortetracycline staining 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.

Possible Role of Adrenomedullin In the Pathogenesis of Tubal Ectopic Pregnancy

CONTEXT Tubal ectopic pregnancy (tEP) is currently the leading cause of pregnancy-related deaths during the first trimester. Our current knowledge on the molecular pathogenesis is limited. OBJECTIVE The objective of the study was to find out the possible role of adrenomedullin (ADM) in the pathogenesis of tEP. DESIGN This was an experimental in vitro study on oviductal tissue. SETTING The study was conducted at a university teaching hospital. PATIENTS AND INTERVENTIONS Patients included those having oviducts removed surgically during salpingectomy for tEP or hysterectomy for benign gynecological conditions. Oviductal tissues were incubated in hormonal condition mimicking early pregnancy before used for in vitro experiments. MAIN OUTCOME MEASURES Plasma ADM concentration, oviductal expression of ADM and its receptors, ciliary beat frequency, smooth muscle contraction were measured. RESULTS The ciliary beat frequency and frequency of muscle contraction were lower in the oviducts from patients with tEP than those from simulated normal pregnancy. The plasma and oviductal tissue ADM levels were also lower. The decreases in ciliary beat and frequency of contraction were restored to normal after ADM treatment. CONCLUSIONS The results suggest that the lower ADM level in the oviducts of tEP may lead to the decrease in ciliary beating and muscle contraction, with the result that the embryo is retained and implanted in the oviduct. Our findings explain for the first time the etiology of tubal pregnancy on the basis of an impairment of the transport of the fertilized ovum resulting from an ADM deficiency and raise the possibility of using the plasma ADM level as a predictor for tubal ectopic pregnancy.

Maternal serum anti-Mullerian hormone level is not superior to chronological age in predicting Down syndrome pregnancies.

To compare the difference in maternal serum anti‐Mullerian hormone (AMH) level between Down syndrome pregnancies and unaffected pregnancies, and to evaluate its performance as a screening marker for Down syndrome pregnancy.

Ulipristal acetate resembles mifepristone in modulating human Fallopian tube function

STUDY QUESTION Do ulipristal acetate (UPA) and mifepristone have an effect on ciliary beat frequency and muscular contractions in the human Fallopian tube? SUMMARY ANSWER UPA, in resemblance to mifepristone, inhibits ciliary beat and muscular contraction of the human Fallopian tube, probably through an agonistic effect on the tubal progesterone receptor. WHAT IS KNOWN ALREADY UPA, like mifepristone, acts as an emergency contraceptive mainly by inhibiting ovulation. Little is known about its effects on tubal function. STUDY DESIGN, SIZE, DURATION This was an in vitro experimental study using Fallopian tube samples collected from 11 women undergoing hysterectomy for benign non-tubal gynaecological conditions. PARTICIPANTS/MATERIALS, SETTING, METHODS The tubal epithelium and longitudinal smooth muscle fibres were isolated, cultured and treated with UPA at graded concentrations of 0, 20, 200 and 2000 ng/ml, and mifepristone at graded concentrations of 0, 300, 3000 and 30 000 ng/ml, respectively. After treatment, ciliary beat frequency was determined using a photometric method. Basal tone, amplitude and frequency of muscular contraction were recorded through a force transducer. The mRNA expression of progesterone receptor (total and PR-B isoform), glycodelin and adrenomedullin were determined by real-time quantitative PCR. MAIN RESULTS AND THE ROLE OF CHANCE There was an overall dose-dependent suppressive effect on ciliary beat frequency (P < 0.0001) after treatment with UPA at all concentrations and with mifepristone at 3000 ng/ml or above. The basal tone, amplitude and frequency of muscular contractions were significantly reduced (P < 0.05) after treatment with UPA at 200 ng/ml or above, and with mifepristone at 3000 ng/ml or above. UPA treatment at 200 ng/ml or above significantly up-regulated the mRNA expression of progesterone receptor and glycodelin and down-regulated the mRNA expression of adrenomedullin in Fallopian tube tissue (P < 0.05). LIMITATIONS, REASONS FOR CAUTION Whether or not the tubal effect may translate into additional mechanisms for contraceptive action in vivo is uncertain. WIDER IMPLICATIONS OF THE FINDINGS The clinical relevance of UPA with regard to contraceptive activity is worthy of further exploration. STUDY FUNDING/COMPETING INTERESTS The study was supported by a Seed Fund from the Centre of Reproduction, Development and Growth, Faculty of Medicine, the University of Hong Kong. All authors have no competing interest to declare.

Serum adiponectin is independently associated with the metabolic syndrome in Hong Kong, Chinese women with polycystic ovary syndrome

Abstract Objective: To evaluate the association of serum adiponectin level with the metabolic syndrome in Chinese women with polycystic ovary syndrome (PCOS). Methods: This was a cross-sectional study carried out in Hong Kong Chinese women with PCOS at a university-affiliated tertiary hospital between January 2010 and January 2011. Clinical and biochemical parameters of the women were analysed. Prediction of the metabolic syndrome was determined by receiver–operator characteristic (ROC) curves, univariate and multivariate logistic regression analyses. Results: A total of 116 women diagnosed to have PCOS were analysed. The area under the ROC curve of adiponectin for the prediction of metabolic syndrome was 0.820, 95% confidence interval (CI) 0.737–0.886. Univariate binary logistic regression showed that testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), waist circumference, body mass index (BMI), quantitative insulin-sensitivity check index (QUICKI), homeostasis model assessment of insulin resistance (HOMA-IR) and adiponectin were significantly associated with the metabolic syndrome. On multivariate logistic regression analysis, adiponectin (p =  0.020), HOMA-IR, age (p =  0.011) and BMI (p =  0.019) were independently associated with the metabolic syndrome, but not FAI (p =  0.256). Conclusions: Serum adiponectin is independently associated with the metabolic syndrome in Chinese women with PCOS. Further longitudinal follow-up studies are needed to determine whether serum adiponectin adds to the prediction of long-term cardiometabolic morbidity conferred by age, BMI and measures of insulin resistance.