Clinical Utility of Anti Müllerian Hormone in Veterinary Practice
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19/05/2021 Clinical Utility of Anti‐Müllerian Hormone in Veterinary Practice Dr Jenny Hill Dr Jason Stayt 1 Anti‐Müllerian Hormone • Hormone belonging to the transforming growth factor family • In males secreted by precursor and mature Sertoli cells • In females secreted by the granulosa cells in primary and secondary follicles • In male embryos AMH is associated with regression of the Mullerian ducts (these develop into the cervix, uterus and fallopian tubes) • In females AMH has an inhibitory effect on the recruitment of primordial follicles and the responsiveness of developing follicles to FSH 2 1
19/05/2021 Medical use • Indication of functional ovarian reserve • Predict the onset of menopause • An ancillary test in investigation of polycystic ovarian syndrome • Monitoring patients with ovarian cancer • Investigating ambiguous genitalia • Ancillary tests for investigating male fertility and sex differentiation disorders 3 Assay systems • The range of concentrations in animal species varies according to the test used • This relates to cross reaction with the antibody used • Species specific assays therefore give higher concentrations e.g. canine specific ELISA (Ansh Labs) • In practice most testing utilises human based test systems e.g. AMH Gen II Beckman Coulter • This can give unreliable results before puberty when concentrations are likely to be lower 4 2
19/05/2021 AMH and Companion Animals • Sterilization status • Detection of ovarian remnants • Detection of testicular remnants • Screening for retained testicles • Ancillary testing in patients with testicular masses • Assessing response to ”chemical castration” e.g. use of deslorelin for prostatic hyperplasia in dogs • Limited application as a fertility marker 5 Sterilisation status • Data from the AVA shows approximately 78% of owned dogs and 93% of owned cats are desexed • Sterilisation is strongly supported by animal welfare and veterinary groups across Australia • Benefits include reductions in unwanted animals and moderation of undesirable behaviours including aggression, wandering and “calling” • Significant reduction to protection from mammary and urogenital tumours • Performed by ovariectomy, ovariohysterectomy or orchidectomy 6 3
19/05/2021 Sterilisation status • External indicators of sterilization may be inconclusive which is a challenge in animal shelters • Estimates in 2014 suggested that approximately 200,000 dogs per year enter shelters • In Queensland of the 11,976 dogs only 21% were listed as having been sterilized • Policy is that animals cannot be rehomed unless desexed • AMH is a cost effective, non‐invasive and reliable test for screening of sterilization status • In our lab we have screened dogs, cats, rabbits and guinea pigs 7 Ovarian (and testicular) remnants • Residual, functional ovarian and less commonly testicular tissue may remain following surgical desexing • These animals may present with symptoms including pro‐oestrus bleeding, vulval swelling, attractiveness to males and mammary gland development • Besides the behavioural implications, these animals are also at risk of ovarian disease and stump pyometra • Treatment requires exploratory laparotomy • Initial screening with AMH assists with clinical decision making • Problems with diagnostic sensitivity prior to puberty 8 4
19/05/2021 Retained testicles • Affects up to 10% of dogs and 2% of cats • Associated with behavioural and medical issues • AMH reliable in differentiating between castrated and cryptorchid animals • AMH concentrations have been shown to be significantly higher in inguinal and abdominal cryptorchids compared to sterilized and intact dogs • Large number of immature Sertoli cells in retained vs scrotal testicles (non‐ neoplastic Sertoli cell– only syndrome) 9 Sertoli cell tumours • Non‐invasive means of screening for Sertoli cell tumours, however, this is complicated by Sertoli‐only syndrome in retained testicles. • In the case of testicular masses in scrotal testicles is a useful ancillary test, often combined with FNA cytology 10 5
19/05/2021 AMH and Horses • Screening for ”proud cut” geldings and cryptorchids • Screening for granulosa cell tumours in mares • Measure of fertility in breeding mares 11 Geldings and cryptorchids • “Proud cut” geldings and cryptorchids may display stallion like behaviour which can vary from undesirable to dangerous • Appropriate handling and housing may be required for stallions • Some events require stallions to be clearly identified and handlers/ riders to be over 18 • AMH can provide clarity regarding sterilization status particularly when animals are sold 12 6
19/05/2021 Granulosa cell tumours • Most common tumour of the equine ovary • Associated with fertility and behavioural problems • AMH concentrations are significantly higher in mares with granulosa cell tumours • Not affected by the stage of the oestrus cycle • Higher sensitivity (approximately 98%) when compared with inhibin and testosterone which were previously used 13 Fertility in breeding mares • AMH is positively correlated with follicle diameter, oocyte quality and conception rate • Allows for selection of mares for breeding with expensive bloodstock • Super‐ovulation and embryo transfer not permitted in thoroughbred breeding • Assist in selecting mares for assisted reproduction in other breeds 14 7
19/05/2021 AMH and Production Animals • The AMH gene has been mapped in some species • Cattle and goats: chromosome 7 • Sheep: chromosome 5 • Pig: chromosome 2 • Buffalo: chromosome 9 • Primarily used in the investigation of fertility competence (fertility, superovulation, ovarian disorders) in farmed animal species • The utility of AMH however it is variable due to limited research in production animals and reproductive cycle variability between species • Most of the research has been conducted in cattle 15 Dairy and Beef Cattle • Australia is the second largest beef exporter in the world • Estimated value in 2019 $10.8 billion • Australia ranks fourth in the world in terms of dairy trade • Estimated value in 2019/ 2020 $4.8 billion • Fertility management is crucial for both industries • Fun fact…..To produce milk, a cow must first be pregnant 16 8
19/05/2021 AMH in Cattle Reproduction • Over the past decade AMH has increasingly been utilised in fertility management • AMH is reliable – variations in concentration are minimal during the oestrus cycle and it is repeatable across multiple cycles • Circulating AMH concentrations have positive associations with several measures of fertility 17 AMH in cattle reproduction • It is a marker of the quality of developing follicles • Healthy follicles at all stages of secondary and early antral development produce more AMH than unhealthy follicles • Low AMH lower pregnancy rates • Predictive response to superovulation and embryo yield • Predictor of longevity • Young cows with low AMH is associated with fewer lactations and therefore shorter productive herd life 18 9
19/05/2021 AMH in cattle reproduction • It is used in the selection of replacement heifers • The reproductive rate of young cows can be predicted • Used to replace older cows with declining/ failing reproductive performance • Antral follicular count (AFC) is a heritable trait in cattle • AFC and AMH are highly correlated • Perhaps AMH is also heritable ? 19 AMH and Ovarian Disorders • Cystic ovarian disease • In cattle, aetiology is poorly understood/ not well investigated • No difference in AMH in follicular fluid and AMH expression by granulosa cells between large early dominant follicles and cysts • Possibly driven by lutenising processes (similar to women) • Intrafollicular AMH not a marker of cystic development (unlike in women) • However, processes leading to PCOS are studied in bovine models 20 10
19/05/2021 AMH and Ovarian Disorders • Granulosa cell tumour • Cattle – most common neoplasm involving the ovaries • Rare in sheep, goats, camels • Typically higher diagnostic accuracy, sensitivity and specificity than other markers (inhibin, ovarian steroids) 21 Thank you …. …to the WA branch of the Australasian Association for Clinical Biochemistry and Laboratory Medicine for inviting us to speak today. 22 11
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