Role of AMH in Infertility & Other Clinical Situations

Dr. Sharda Jain Dr. Jyoti Bhaskar Dr. Jyoti Agarwal

PUBLICE AWARENESS SERIOUS

OUR TEAM

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AMH is a glycoprotein

Originally known as Mullerian Inhibiting Substance(MIS)

Appears in females at puberty

Produced by granulosa cells of pre-antral and small antral follicles of 4-6 mm

AMH is not expressed in atretic follicles and theca cells.

AMH

BASIS OF AMH Anti-Mullerian hormone (AMH) plasma levels reflect the continuous non-cyclic growth of small follicles,

thereby mirroring the size of the resting primordial follicle pool and

thus acting as useful marker of ovarain reserve.

FACT ABOUTAMH After an initial increase until

early adulthood, AMH concentrations slowly

decrease with increasing age until becoming undetectable 5

years before menopause.

ADVANATAGE OF AMH

It helps in forecasting of reproductive lifespan, ovarian

response to stimulation ovarian dysfunction and gonadotoxic cancer treatment of ovarian

surgery.

Critical Facts which you all should know about AMH

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AMH is produced by the small growing (primary and preantral) follicles in the postnatal ovary and has two sites of action. It inhibits initial

follicle recruitment (1) and inhibits FSH-dependent growth and selection of preantral and small antral follicles (2).

Model of AMH action in the ovary.

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The intrafollicular concentrations of AMH in normal human antral follicles show a gradual reduction as the diameter of the follicle increases, and a sharp decline is observed around 8mm

Physiological function- prevent excessive follicle recruitment. Acts as a Gatekeeper

Not cycle dependant-can be measured any day

Less cycle to cycle variation than FSH.Not altered after down regulation with

GNRH agonist.Pregnancy

AMH – factors that Increase Polycystic ovaries

AMH - unaffected

AMH This renders AMH easy to measure at any

time as opposed to other currently available markers of ovarian aging, such

as inhibin B, estradiol (E2) and FSH, which are all menstrual cycle dependent and

constitute relatively late markers of the ongoing process of primordial follicle

pool depletion.

- Overweight- Ethnicity- Vitamin D status - Polymorphisms of AMH and its receptor - Smoking and Alcohol intake- Genetic variants across the genome.

Factors influencing AMH concentrations are

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High (often PCOS) Over 3.5 ng/ml

Normal Over 1.4 ng/ml

Low Normal Range 0.7 – 1.3 ng/ml

Low 0.3 - 0.6 ng/ml

Very Low Less than 0.3 ng/ml

AMH BLOOD LEVEL

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AMH – NORMAL RANGE

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High (often PCOS) Over 3.5 ng/ml

Normal Over 1.4 ng/ml

Low Normal Range 0.7 – 1.3 ng/ml

Low 0.3 - 0.6 ng/ml

Very Low Less than 0.3 ng/ml

AMH BLOOD LEVEL

AMH of less than 1.36 ng/ml has a sensitivity of 75.5% and specificity of 74.8% in prediction of poor response.

AMH > 3.5 ng/ml has a sensitivity of 88% and

67% specificity in prediction of hyperstimulation

AMH BLOOD LEVEL

AMH of less than 1.36 ng/ml has a sensitivity of 75.5% and specificity of 74.8% in prediction of poor response.

AMH > 3.5 ng/ml has a sensitivity of 88% and

67% specificity in prediction of hyperstimulation

AMH BLOOD LEVEL

AMH LEVELS IN DIFFERENT CLINICAL SITUATIONS

Infertility and AMH BENEFITS OF ORT IN SUBFERTILE COUPLE

ORT guides in prognosticating outcome in individual cases by

Pre-treatment counsellingChoice of infertility treatmentAvoidance of ovarian hyperstimulation

Fecundity / Infertility & AMH

AMH helps to predict fecunity and accurate ovarian reserve. Increasing age means a decreasing AMH level

Lower AMH levels at any given time irrespective of age predicts a poor response to ART.

High AMH levels – candidates prone for OHSS.

Prediction of pregnancy chances in couples presenting with

infertility

Ovarian reserve testing may allow for a better

assessment of the fertility potential of a given

woman.

AMH in IVF AMH is the best currently

available measure of ovarian reserve hence guides in

individualizing dosing for ovarian stimulation thereby improving

the efficiency and safety of IVF.

The dosage is more for a lesser value and less for a higher value to achieve a

desired ovarian response.

AMH in IVF

ADVANTAGE OVER OTHER Ovarian reserve MARKERSIt is the earliest marker to change with ageIt shows the least intercycle and intracycle

variabilityIt can be randomly measured during the cycleIt shows no modifications during GnRHaIt needs no modification in hypothalamic

amenorrheaIt is both more convenient and informative

than basal FSH

AMH is useful predictor of ovarian

hyperstimulation.

AMH in IVF

La Marca reported the AMH level of 0.7 ng/ ml had a good sensitivity and

specificity of indentifying 75% of poor responders.

AMH of > 3.5 ng / ml predicted hyper response and OHSS

Patient management in IVF

1. La Marca A. Hum Reprod 2007 ; 22:766-71

AMH as predictor of ovarian response

Value of AMH (ng/ml) Ovarian response

<0.4 Extremely poor response and cycle should be cancelled

0.4 – 1 Poor response

1 – 2 At risk of poor response and short stimulation protocols should be used

2 – 3.5 Response adequate

3.5 – 6 Chances of hyper stimulation. Caution to be applied

> 6 High chances of severe OHSS

1. La Marca A. Hum Reprod 2007 ; 22:766-71

PROPOSED AMH BASED PROTOCOLS

HIGH AMH (> 3.5 ng/ml) a. Inform about the risk of OHSSb. Avoid depot GnRHac. Low FSH dosed. Antagonist cycle preferrede. Agonist Triggerf. Blastocyst transfer or Freeze all embryos and

transfer later.

Ovarian dysfunction

Assesing AMH concentrations in anovulatory women may

give additional information of follicle dynamics with ovarian

reserve.

PCOS • The magnitude of AMH elevations in PCOS is

associated with the extent of disease, improved reproductive performance in relation to weight loss and improved ovulatory function with age.

• Hence, AMH testing may allow the early detection of subclinical disease in siblings of women diagnosed with PCOS.

1. Broer SL. Et . Hum Reprod. Update 2014 ; 20 (5) : 688-701 . 2. Thomoson RL et al. Hum Reprod 2009 ; 24:1976-1981.

(A)

Other forms of anovulation • Women presenting with functional

hypothalamic amenorrhea were shown to have normal AMH levels suggesting a normal size of the cohort of early growing follicles.

• Initial AMH levels predict chances for recovery of ovarian function following weight gain in women with anorexia nervosa.

1. Broer SL. Et . Hum Reprod. Update 2014 ; 20 (5) : 688-701 . 2. Luisi S et al. Gynecol Endocrinol 2012 :28:34-38.

(B)

Management of women with cancer & AMH

• AMH appears to facilitate establishing which chemotherapeutic agents are particularly toxic to the ovaries.

• They fall during chemotherapy with some recovery 3 – 6 months thereafter.

1. Broer SL. Et al Anti – Mullerian hormone: ovarian reserve teting and its potential clincal implication. Hum Reprod. Update 2014 ; 20 (5) : 688-71.

2. Dillon KE, et al Pretreatment antimullerian hormone levels determine rate of posttherapy ovarian reserve recovery : acute changes in ovarian reserve during and after chemotherapy. Fertil Steril 2013 : 99: 477 – 483

Menopause prediction & AMH

Prediction of at menopause by assessing

AMH at a relatively young age may enable screening and prevention

programs with reference to osteoporosis, breast cancer, congnition and Alzheimer disease, cardiovascular

disease and stroke .

Anti mullerian hormone (AMH) alone or best in combination with antral follicular count (AFC)

is the BETTER INDICATOR

of ovarian reserve than any other hormonal or

sonographic markers available at present.

CONCLUSION

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