Anti Mullerian hormone and ovarian reserve (OR)

• ovarian Reserve (OR)
  • a term which describes the functional potential of the ovary, which constitutes the size of the ovarian follicle pool and reflects the number and quality of the oocytes which are within it
    • on an average, a female foetus contains about 7 million oocytes at birth, million at puberty and about 40,0000 oocytes at the onset of the menstrual cycle
      
    • a fixed proportion of the remaining oocytes become recruited i.e sensitized to the gonadotrophins, from which one or two will achieve dominance and will progress to ovulation
      
      
• assessment of the OR helps in reflecting the reproductive potential of women - anti Mullerian hormone
  • various markers are available for assessing the OR and the best marker is the Anti Mullerian Hormone (AMH) which reflects the ovarian follicular pool in the ovary
    
    
    • anti mullerian hormone / mullerian inhibiting substance (AMH/MIS) is a glycoprotein dimer which consists of 72 KD monomers which are linked by disulphide bonds
      • belongs to the member of the Transforming Growth Factor (TGF) superfamily
        
        
    • during the foetal development, the embryo consists of mullerian and wolfian ducts
      
      
      • mullerian ducts are the precursors of the uterus, the fallopian tubes and the upper part of the vagina and the wolfian ducts give rise to the epididymis and the seminal vesicles
        
        
        • in males, during the embryonic development, AMH is secreted by the Sertoli cells of the testis and it is responsible for the regression of the mullerian ducts
          
          
        • in the female embryogenesis , the absence of AMH /MIS allows the development of the female sex organs
          • after birth, AMH is produced in small amounts by the ovarian granulosa cells and it becomes undetectable after menopause
          • AMH inhibits the recruitment of the primordial follicles - decreases the responsivenesss of the growing follicles to the FSH
            • in contrast to most of the hormonal biomarkers with a follicular status, AMH is exclusively produced by the granulosa cells, with the follicles ranging from the primary to the early antral stages
          • AMH concentration in the serum is directly related to the antral follicle count and that it is a better indicator of the ovarian reserve than the 3rd day FSH, Inhibin B or the oestradiol levels
            • the concentration of AMH is higher in the small antral follicles than in the preovulatory follicles, suggesting that the circulating AMH levels reflect both the quantity and the quality of the remaining follicles
            • there is no change in the AMH levels in response to the gonodatrophins, therefore it can be measured throughout the cycle in contrast to the other hormones- the AMH intracycle and the cycle to cycle variation is also negligible
              
              
          • all these features support the feasibility of the AMH assessment throughout the cycle
            • AMH levels accurately reflect the ovarian follicular reserve and is a sensitive marker of ovarian aging and ovarian reserve
            • evaluation of the level of AMH has clinical value in predicting the success of in-vitro fertilization (IVF)
              • hyper-response/ovarian hyperstimulation syndrome (OHSS) might be anticipated as about 3.5 ng/ml or above
              • cycle stability and operator independency make AMH a most appealing single marker of ovarian reserve. Use of AMH to paint tailored stimulation protocol could result in a reduced risk of OHSS, optimized treatment burden and maintained pregnancy rates

Notes:

• various markers are available to assess the OR, which include age, the serum FSH, serum oestradiol and the serum anti mullerian hormone levels, the ovarian volume, the antral follicular count, etc
  • cycle fluctuation of the day 3 FSH level makes the OR estimation difficult and a single day 3 FSH measurement may not be very accurate
  • E2 is never used alone as a marker for the OR
  • ovarian volume and the antral follicular count are the predictors of the number of oocytes which is retrieved in the controlled ovarian hyperstimulation protocols and the cancellation rates in IVF rather than assessing OR

Reference:

• 1) Usta T, Oral E.Is the measurement of anti-Müllerian hormone essential? Curr Opin Obstet Gynecol. 2012 Jun;24(3):151-7.
• 2) La Marca A et al. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART).Hum Reprod Update. 2010 Mar-Apr;16(2):113-30.