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Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF

by Dr. Geoffrey Sher on February 8, 2016

Anti-Müllerian hormone also known as AMH is a protein that, is encoded by the AMH gene located on chromosome 19p13.3,. There is an important interaction between AM and its receptor AMHR2 on chromosome 12. AMH is a glycoprotein hormone secreted by Granulosa cells in developing follicles. AMH blood levels in a woman’s blood is an indicator of the remaining quantity of eggs (ovarian reserve) and potentially the number of fertile years the woman may have left and thus provides a valuable tool by which to strategically design a safe and individualized protocol for ovarian stimulation, one that will optimize both egg quantity and quality, AMH levels do  does not change during  the menstrual cycle, so the blood can be done at any time of the month – even while using oral contraception.

In males: AMH inhibits the development of the Müllerian (paramesonephric) ducts (i.e. embryological rests that develop into the female reproductive apparatus. In males AMH is responsible for irreversible regression of the Müllerian ducts (that are programmed to develop into uterus, Fallopian tubes, cervix and upper two thirds of the vaginal canal) a process that is vital to male sex differentiation. Albeit infrequent, mutations of the AMH gene and certain AMH receptors sometimes lead to failure of the Mullerian system to regress and their subsequent persistence in affected male concepti resulting in failed virilization and phenotypic intersexuality, undescended testes, rudimentary uterus and cryptorchidism. AMH is produced by Sertoli cells in the testicles where it helps facilitate spermatogenesis.

In Females: AMH is produced by ovarian (Granulosa) cells present in early primary follicles that advance from the primordial follicle stage. AMH production decreases and then ultimately eases off as follicles grow beyond 8mm, becoming virtually undetectable in larger follicles. AMH production is greatest in preantral and in small antral stages of < 5mm in diameter. Evidence points to the fact that the size of the cohort of recruited (growing) available follicles in a given cycle is strongly influenced by the size of the remaining pool of primordial (sleeping) follicles. It is against this background that AMH blood levels reflect the size of the remaining egg supply or OR.”

A normal blood concentration of AMH points towards a good OR, an abundance of remaining eggs and primordial follicles, that menopause is not imminent and to robust follicular response to ovarian stimulation. A high AMH suggests (often seen in women with irregular menstruation, those with polycystic ovarian syndrome and in very young women) the presence who have very many primordial follicles and are at risk of over-responding to gonadotropin stimulation, placing them at risk of developing very severe ovarian hyperstimulation syndrome (and thus require low dosage stimulation protocols, in readiness for “prolonged coasting”). Below normal AMH levels on the other hand, point to a diminishing ovarian reserve (DOR) suggest an acceleration in the march towards ovarian failure (menopause) , that response to ovarian stimulation with gonadotropins (FSH) is likely to be blunted and accordingly that a more robust stimulation protocol with gonadotropins is called for. It follows that any suggestion that women with DOR (low AMH) might benefit from using “low or mini” stimulation protocols is my opinion, illogical, counter-intuitive and misinformative.

AMH levels probably do not reflect egg competency” This is more a function of the woman’s age, intraovarian environment impacted by the underlying cause of infertility and the protocol used for ovarian stimulation (see elsewhere on this blog the article; “IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation”). This having been said, harvesting more eggs at egg retrieval provides the opportunity for a greater number of eggs to fertilize.. However, this does not always translate into more good quality embryos. Nor does it in any way translate into better quality embryos. When it comes to fertilization rate and embryo quality (the rate limiting factor in IVF outcome) egg quality plays the most important role and here, the selection and implementation of a strategic and individualized approach to ovarian stimulation is vital to optimizing IVF outcome.

if the person being measured is vitamin D deficient.

The table below provides guidelines. Cut-offs are not necessarily as exact as suggested by the compartments below

AMH-LEVEL (NTERPRETATION)

  • Low blood Vitamin D levels can falsely lower AMH
  • AMH can be measured any time in the cycle.

AMH is not the only test that measures ovarian reserve. Measurement of basal FSH, inhibin B and the antral follicle count should also be considered.

Recommended complementary articles for reading elsewhere on this blog:

  1. Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
  2. Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
  3. IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
  4. The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF
  5. Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
  6. Launching Ovarian Stimulation with a BCP: How Does it Affect Response?
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