Anti-Mullerian hormone normal, AMH decreased, increased

AMG. Anti-Mullerian hormone in questions and answers.

• Is an AMH test necessary for every woman? If not, then to whom is it indicated as a screening test?
• Can contraceptives (COCs) preserve follicular reserve and increase AMH?
• Which IVF stimulation protocol is best suited for patients with high AMH?
• Is it true that in conditions of high AMH and excess follicular reserve, urinary gonadotropins (hMG) cannot be used, as the risk of developing OHSS increases?
• Is AMH a good predictor of pregnancy in IVF? In other words, can AMH concentration predict the likelihood of pregnancy in an IVF cycle?

Everyone is well aware that sexual differences, so characteristic of all mammals in general, and humans in particular, do not appear immediately. Thus, in the early stages of embryonic development, without special research, it is completely impossible to identify gender normal embryo. The point is that the beginnings reproductive system The early embryo has derivatives of both the duct of the primary kidney, the Wolffian duct (literally, the male principle), and the paramesonephric duct, the Müllerian duct, (literally, the female principle). And only further processes of differentiation and morphogenesis of the reproductive tract form sexual differences. Already in the 40s of the last century, it was shown that the development of the male reproductive system involves regression of the Müllerian ducts (Alfred Jost). But only 50 years later (1986) it was possible to establish a factor that inhibits the Müllerian ducts. Given the described effects on the developing embryo, this factor has been named "Anti-Mullerian hormone", "Mullerian inhibitory factor", "Anti-Mullerian substance" or "Anti-Mullerian factor".

As it turned out, AMH is a fairly universal hormone; in addition to mammals, it performs a similar function in fish, reptiles, and birds.
Soon the structure of the new hormone was described. It has been shown that AMG is a glycoprotein of the transforming growth factor-beta (TGF-B) family, with molecular weight 140 kDa, represented by a structure of two homologous subunits (Hampl et al., 2011). The molecular biophysical mechanisms of action of AMH show great similarity with other relatives of the TGF-B group. Signal transmission involves the binding of a ligand to the extracellular part of the transmembrane AMH type II receptor, which induces phosphorylation and subsequent signal transmission through intracellular Smad proteins (Teixeira et al., 2001; Salhi et al., 2004).

The locus of the location of the gene encoding AMH was established on the short arm of chromosome 19 - 19q13.3 (Cate RL et al., 1986) and its type II receptor (chromosome 12).

The effects of AMH are limited to the reproductive system. It has been demonstrated that AMH is responsible for sexual differentiation during embryonic development. In male fetuses (boys), AMH expression is recorded from 8 weeks of gestation (Lee et al., 1997), which is explained by the presence and function of Sertoli cells responsible for its production. It is obvious that, thanks to AMH, boys experience regression in the development of the Müllerian duct and other Müllerian structures (Behringer RR, 1994). The effect is ipsilateral, that is, suggesting that each testicle suppresses the development of Müllerian structures only on its side (Walter F., PhD. Boron, 2003). At the embryonic stage, developing Leydig cells secrete testosterone, which is responsible for further development Wolffian duct (Wilson et al., 1981).

In the complete absence of AMH, fetuses of both sexes of mammals develop the fallopian tubes, uterus and upper third of the vagina, while the Wolffian duct, responsible for the development of the male reproductive tract, is automatically reduced not only in girls, but also in boys (An Introduction to Behavioral Endocrinology, Randy J Nelson, 3rd edition).

If the concentration of AMH is insufficient during embryonic development, genetic programs for the formation of the basic reproductive structures of both sexes are implemented. As a result, the child acquires undifferentiated genitalia that do not allow clear identification of gender. In this case, assessing the plasma concentration of AMH levels can be useful in determining sex, but is still inferior in terms of information content to a cytogenetic study.

Responsible for sexual differentiation at the stage of early embryonic development and organogenesis of the entire reproductive system during the rest of the gestation period, in boys AMH is recorded in a fairly high concentration for about two years after birth, when it begins to gradually decline, sharply disappearing from the period of puberty maturation.

In female fetuses (girls), AMH secretion appears much later, in the prenatal period (Rajpert-De Meyts et al., 1999). In the follicular fluid of antral follicles, AMH accumulates in high concentrations, reaching sufficient levels to ensure its detection in peripheral blood (Hudson et al., 1990; JOSSO et al., 1990; Lee et al., 1997; Jeppesen et al., 2013 ). However, when compared with boys, AMH is present in much lower concentrations, which does not allow it to inhibit normal organogenesis of the female reproductive tract. In girls, AMH is secreted by granulosa cells of the follicles. After birth, AMH production in girls is extremely low, which is explained by the planned period of follicle dormancy. The picture changes from puberty, when dormant follicles successively enter the growth phase - folliculogenesis. It is noted that the basis of AMH-secretory activity of granulosa tissue is recorded during the period from the primary to preantral stages of follicular differentiation, that is, at gonadotropin-independent stages. An immunohistochemical study of ovarian tissue showed the absence of AMH staining in primordial follicles, along with the demonstration of high AMH expression in primary, secondary and early antral follicles up to 4 mm in diameter. AMH staining gradually disappeared in follicles between 4 and 8 mm in diameter (Weenen et al., 2004). A recent study confirmed this finding, demonstrating that AMH gene expression and AMH hormone concentrations in follicular fluid increased up to 8 mm diameter follicles, after which they declined sharply (Jeppesen et al., 2013), noting that follicles 5 mm in diameter -8 mm provided about 60% of the total circulating AMH (Jeppesen et al., 2013). It has also been shown that antral follicles that become sensitive to FSH gradually lose their ability to produce AMH. Therefore it is determined inverse relationship between the production of AMH and estradiol by granulosa cells of the growing follicle (Broekmans FJ et al., 2008). In IVF protocols of ovarian hyperstimulation, when the majority of antral follicles are recruited to large dominant follicles, there is a significant decrease in serum AMH concentrations (Fanchin et al., 2003).

It should be noted that for a long time the role of AMH in the functioning of the female reproductive system was not clear. It has been suggested that AMH does not have much meaning and was acquired by a woman as a side burden only due to genetic proximity to a man.

Subsequently, evidence was found of the important role of AMH in the processes of folliculogenesis. It was postulated that through AMH there is a paracrine regulation of not only the selection of primordial follicles, but also further early stages of folliculogenesis in the preantral stages of the pregonadotropin-dependent period (La Marca A et al., 2006). It is assumed that AMH limits the formation of a pool of primary follicles and prevents excessive follicular FSH recruitment (Dewailly D et al., 2014; Weenen C et al., 2004). In mice, switching off AMH was accompanied by an increase in the rate of selection of primary follicles, which ultimately led to premature depletion of the total follicular pool of resting primordial follicles (Durlinger et al., 1999, 2001).
By the way, it must be said that these stages of folliculogenesis are not yet understood in many respects, and AMH is perhaps the most studied agent, so we still have to learn the true biomechanism and the role of AMH in it.

Meanwhile, it is extremely clear that the total supply of primordial follicles decreases with age, and the number of follicles that enter the growth phase every day decreases in proportion to this. And since the number of antral follicles is directly proportional to the total follicular reserve (Gougeon, 1984), the AMH level can be considered as a marker of the total follicular reserve.

During a woman's life, AMH secretion changes significantly. In the first two years of a girl’s life, the AMH level is so low that it is practically undetectable. Starting from the 3-4th year, the AMH content, having increased slightly, remains at a plateau level until the onset of puberty (Kelsey TW et al., 2011; Nelson et al., 2011). Probably, such dynamics reflect the general neurohormonal mechanisms of the formation of sexual dimorphism of the brain and the correct orientation of the processes of development and formation of gender-specific behavior (Wang PY et al., 2009). This assumption can be supported by the fact that functional extragonadal AMH receptors are found in addition to breast and endometrial tissues, also in the brain (Segev et al., 2000; Lebeurrier et al., 2008; Wang et al., 2009).

In the future, the dynamics of AMH levels in women is much more active. Increasing since becoming regular menstrual function, AMH enters the highest phase of its plasma concentration. Reflecting the number of follicles invisible to the eye armed with ultrasound, AMH will acquire a slightly perceptible downward trend almost immediately after its peak level, but clearly falls after a critical reduction in the number of primordial follicles available for activation, which is tantamount to demonstrating ovarian decline. The subsequent trend of AMH levels is always only negative, and already in menopause it ceases to be determined at all (Kelsey TW et al., 2011).

Taken generally, there is a surprising negative association of AMH levels between sexes. At the moment when a high plasma concentration of AMH is recorded during the period of fetal development in boys, it is practically not detected in girls. On the contrary, during the period of approaching reproductive viability, the level of AMH in boys is characterized by a constant downward trend; in girls and women, on the contrary, it is determined in rather high concentrations.

During a woman’s life, AMH has an understandable and natural dynamics (the average annual decline from the age of 21 is 5.6% (Bentzen et al., 2013)), according to the consumption of the total follicular reserve, but this hormone has another feature that is attractive for practical orientation. Due to the fact that AMH does not take part in the hypothalamic-pituitary-ovarian axis of regulation, changes in its level in the serum during natural menstrual cycle are not clinically significant (Hehenkamp WJ et al., 2006; La Marca A et al., 2006), it is also more or less constant when recorded in different short-term cycles of the same woman, especially when compared with other serum determinants of ovarian reserve (Renato Fanchin, Taieb J et al., 2005). However, for the sake of objectivity, it should be noted that not all authors agree with the fact of the stable constancy of AMH levels. So Wunder et al. (2007) showed significant fluctuations in plasma concentrations of AMH levels during the menstrual cycle, especially in young women, therefore it is proposed to measure AMH only in the early follicular phase. And Overbeek et al. (2012) noted significant fluctuations in AMH levels over a longer period of time, which also needs to be taken into account when using the test in a clinical setting.

Due to such characteristics, in terms of sensitivity and specificity, AMH is unanimously recognized as the best marker of ovarian functional activity and a diagnostic criterion for the preservation of the follicular reserve (ASRM Practical Committee, 2012). That is why, frankly, not a purely female hormone, moreover, a hormone that blocks the embryonic formation of the female phenotype has long been universally associated only with the female follicular reserve, which is generally equivalent to reproductive potential.

AMH was first detected in human serum a little over 20 years ago (Lee et al., 1993). Meanwhile, wide interest in the topic, which prompted a large number of discussions in a relatively short period of time using the AMH test, resulted in a large number of statements, sometimes having dubious evidence base. The purpose of this discussion is an attempt to objectively answer the main practical questions related to the determination of AMH (AMH test).

What is an AMH test and how is it performed?

The AMH test involves a laboratory determination of the hormone content in the blood plasma. Various methods using antibodies imply high sensitivity and accuracy in determining the level of the hormone, in the vast majority of clinical cases, covering the practical need. Most modern methods(AMH Gen II and the newest Anhs Labs ultra-sensitive AMH and pico AMH ELISA (Welsh et al., 2014)) are characterized by sensitivity up to 0.08 ng/ml and very low cross-reactivity with other relatives in the group (Kumar et al. , 2010). However, the lack of a unified standard and common calibration still ensures differences between laboratories, which makes its own adjustments to the interpretation of the result. In addition, the result of the AMH test may be additionally affected by technical factors associated with differences in the conditions of transportation and storage of the blood sample (Rustamov et al., 2012).

Should every child, especially girls, be tested for AMH?

No, testing only makes sense to clarify gender if this issue arises.

What is the typical AMH level in women?

• Age over 34 but under 38 years of age. Between 20 and 34 years of age, there was no significant correlation between AMH levels and duration of pregnancy (Hagen et al., 2012). Postponing pregnancy beyond the age of 38 is not logical by definition and in itself has potential risks of infertility, increased incidence of pregnancy loss and genetically determined pathologies of the offspring. This condition is especially relevant for women who smoke, in a group of whom it is probably worth reducing the age threshold for testing to 30-32 years.
• A history of surgical interventions on the pelvic organs, especially the ovaries (Raffi et al., 2012), after embolization of the uterine arteries (Berkane et al., 2010), as well as a condition after cytotoxic therapy (Andersen C. Y., et al., 2014 ).
• The presence of genetically determined indications of possible earlier depletion of the follicular reserve. For example, previously ovarian failure sister or moms.
• Extreme prematurity and low birth weight (Sir-Petermann et al., 2010)
• Type 1 diabetes mellitus (Soto et al., 2009)
• Autoimmune diseases and systemic lupus erythematosus (Lawrenz et al., 2011)

Laboratory:

• Test Method
• Calibration
• Conditions for transporting and storing blood

• Excess body weight (Freeman et al., 2007; Su et al., 2008; Piouka et al., 2009; Buyuk et al., 2011)
• Ethnicity (Seifer et al., 2009)
• Vitamin D status (Dennis et al., 2012; Merhi et al., 2012),
• Polymorphisms of AMH and its receptor (Kevenaar et al., 2007)
• Smoking (Dolleman et al., 2013)
• Long-term use of some medicines, such as COCs (Dolleman et al., 2013) or GnRH agonists (Hagen et al., 2012; Su et al., 2013).

The large scatter of individual values ​​under conditions of a short period of use of the AMH test does not yet allow us to objectively agree on exact normative reference values.

The table below presents summary interpretations of literature data and our own clinical experience. However, it is necessary to understand that cutoff values, for example 0.9 and 1.1 ng/ml, which formally classify women into different groups, are in reality practically indistinguishable in terms of fertility. In a practical sense, it is a continuum rather than a precise classification.

What should you do if you have a low AMH level? Who needs to be afraid of low AMH?

Comparison of individual AMH levels relative to the average is useful from the perspective of assessing fertility potential, as it carries information about the volume of follicular reserve. Registration of reduced AMH should serve as a guide to early childbearing, or to resolve the issue of cryopreservation of oocytes or embryos, in order to implement reproductive function in the future, if by that time the effective part of the follicles has already been used up (Cupisti S, Dittrich R et al., 2007).

Could a very low AMH level indicate premature depletion of the ovarian follicular reserve?

Taking into account that AMH in women is synthesized only by granulosa cells of small follicles, it becomes obvious that its decrease to menopausal values ​​earlier than expected (40 years) clearly indicates a stop in the functional activity of the ovaries (Massin N et al., 2008; Méduri G and al., 2007).

Can contraceptives (COCs) preserve follicular reserve and increase AMH?

The effects of COC drugs are realized on later phases follicular growth, by modulating the hypothalamic-pituitary-ovarian loop and inhibiting the maturation of the dominant follicle. As is known, AMH itself and the follicles that produce it do not directly participate in gonadotropin-dependent processes. Accordingly, COCs are not able to actively control the cohort of AMH-secreting follicles and, moreover, cannot have any effect on the follicular reserve in general. Therefore, it has been suggested that AMH levels should remain unchanged by sex steroid oral contraceptives (Somunkiran et al., 2007; Streuli et al., 2008; Steiner et al., 2010; Li et al., 2011; Deb et al. , 2012). A recent large study demonstrated that serum AMH concentrations, on the contrary, tended to decrease under the influence of long-term use COC (Dolleman et al., 2013), which was likely explained by a decrease in the average volume of antral follicles, known to be the main contributor to AMH levels. A similar effect has also been demonstrated in other studies (Arbo et al., 2007; Shawet et al., 2011; Kristensen et al., 2012). And in general, it is natural that the abolition of COCs was accompanied by a restoration of the plasma concentration of AMH (Dolleman et al., 2013), and in some cases its level even increased briefly (van den Berg et al., 2010), documenting the well-known rebound effect.

How to generally increase low AMH?

It is necessary to understand that the AMH test is only a marker that indirectly reflects the general follicular reserve of the ovaries. Taking into account that this value during a woman’s life changes only in the direction of decrease, a low AMH value must be regarded as an incentive to take some action, but one must simply agree with the fact of a low supply of follicles; it is not possible to increase it.

Does AMH predict menopause?

Considering that AMH is secreted by granulosa cells of the developing follicle, its level is directly proportional to the volume of granulosa cells of follicles in the early stages of growth (up to 4-8 mm), and the number of developing follicles, in turn, is theoretically directly proportional to the number of resting follicles, it becomes obvious that a decrease in AMH levels should indicate not only a decrease in the overall functional activity of the ovaries, but also their actual aging (van Rooij IA et al., 2005; Hale GE et al., 2007). That is why AMH is considered to be sufficiently objective and important indicator not only a decrease in a woman’s reproductive potential with age, but also a prognostic criterion for the timing of menopause (Broer et al., 2011; Tehrani et al., 2011; Freeman et al., 2012). Moreover, of the hormonal markers used today, AMH is the most reliable indicator (Sowers MR et al., 2008). For example, very low AMH before age 40 years predicts earlier menopause than the population average. What, among other things, can be useful for planning optimal tactics dispensary observation for the purpose of preventing diseases associated with menopause, in particular musculoskeletal, cardiovascular and nervous systems organs. Currently, large studies are being conducted to accurately assess the prognostic role of AMH in combination with other important characteristics such as age and negative factors such as smoking (Dolleman et al., 2013; La Marca et al., 2013).

Is it bad to have elevated AMH levels?

Increased level AMH indicates a good volume of follicles, therefore a good supply of eggs. In general, provided the normal regularity of the natural menstrual cycle is good.

Does a high AMH level indicate polycystic ovary syndrome?

There is some truth in this statement. The fact is that PCOS is characterized by a large number of growing follicles, and, accordingly, a large total volume of granulosa tissue in them, which is known to synthesize AMH. In addition, in PCOS there is an altered activity of granulosa cells, which probably also has a positive effect on plasma AMH levels (Pellatt L et al., 2007). That is why it is completely logical that the AMH content in patients with PCOS significantly exceeds the average values ​​in the general group of women of the same age (Visser J et al., 2006; Pigny P et al., 2003; Cook CL et al., 2002)

However, despite the fact that such proposals are periodically heard (Dewailly et al., 2011, 2013; Eilertsen et al., 2012), AMH is not considered an absolute diagnostic criterion for PCOS. Let's try to figure out why, perhaps something is missing here, or obvious concepts are simply ignored.

If we recall the criteria approved by the consensus of the ESHRE/ASRM Working Group Symposium (2003).
“PCOS is made as a clinical diagnosis if two of three manifestations are present:

1. anovulation or oligoovulation;
2. clinical and/or biochemical signs of hyperandrogenism;
3. presence of multifollicular ovaries according to pelvic ultrasound data"

Meanwhile, AMH is not a bad fit as an additional criterion for PCOS. Thus, in a meta-analysis (Iliodromiti et al., 2013), it was shown that using a cut-off level of 4.7 ng/ml, PCOS was confirmed with a sensitivity and specificity of 82.8 and 79.4%, respectively. In addition, the AMH value is likely associated with the severity of the disease (Laven et al., 2004; Piouka et al., 2009) and reflects the dynamics of the condition, for example, after weight loss (Thomson et al., 2009) or surgical treatment, correcting polycystic ovaries (Elmashad, 2011). AMH is also elevated in the prepubertal period in adolescent girls who subsequently develop PCOS (Villarroel et al., 2011), which may facilitate earlier detection of subclinical disease, for example in the daughters of women with PCOS.

Does AMH level predict response to induction and follicle number?

A number of studies have immediately demonstrated that a yield of between 9-13 or 6-15 oocytes provided the highest pregnancy or birth rates (van der Gaast et al., 2006; Sunkara et al., 2011; Ji et al., 2013). It is therefore not surprising that fertility specialists are interested in predicting the response to ovarian hyperstimulation. According to NICE, a low AMH level (less than or equal to 5.4 pmol/l (0.8 ng/ml)) suggests a weak ovarian follicular response to induction in an IVF cycle, while a high level of the hormone (greater than or equal to 25. 0 pmol/l (3.6 ng/ml)) predicts excessive ovarian response (Fertility: assessment and treatment for people with fertility problems. NICE clinical guideline, 2013). And despite the fact that in the literature there are different opinions regarding threshold concentrations (La Marca A, Sunkara S K, 2013) predicting an inadequate response, in general it can be fundamentally stated that AMH can be considered a valuable hormonal predictor of ovarian response in an IVF cycle, reflecting not only absence, but also excessive follicular response to induction, which can be useful in selecting the optimal dose of the inducer (Broer et al., 2013; Seifer DB et al., 2002; Nelson SM et al., 2007; Nardo LG et al., 2008).

Today, active research is underway to develop algorithms for individual ovarian hyperstimulation in IVF, based on AMH levels. This treatment strategy has resulted in a reduction in both overresponse and OHSS, cycle cancellations, and increased pregnancy and delivery rates, in addition to reducing costs (Nelson et al., 2009; Yates et al., 2011; La Marca et al., 2011). al., 2012).

Which IVF stimulation protocol is best for patients with low AMH?

The answer to this question will seem paradoxical at first glance, but all induction protocols are not good enough, and each of them can be used with approximately the same effectiveness. Despite the fact that statements are periodically made that one protocol is much better than others, it must be said that so far these statements are unfounded. In addition, often these opinions are more marketing than clinical and are associated with the name of a center. In fact, for poor defendants today, there is simply no better protocol.

As an example, consider one ingrained misconception:

GnRH agonists in a long protocol reduce the follicular reserve available for stimulation

Studies conducted to evaluate the effect of pituitary desensitization with GnRH agonists in long-term IVF protocols have demonstrated that two-week pituitary desensitization, on the contrary, is characterized by a tendency to increase AMH, which clearly indicates that there is no decrease in the number of follicles available for stimulation (Jayaprakasan K et al., 2008).

Which IVF stimulation protocol is best suited for patients with high AMH?

Patients with high AMH from the standpoint of induction in IVF are considered to be at risk of developing OHSS, which is known to be an extremely serious complication of treatment with ART methods. It has been noted that the use of GnRH antagonists is associated with a statistically significant reduction in the incidence of ovarian hyperstimulation syndrome, especially its severe forms (Ludwig M et al., 2001; Al-Inany H et al., 2002; Kolibianakis EM et al., 2006). In addition, protocols with GnRH antagonists allow relatively greater maneuverability, from delaying the day of induction and reducing total doses of gonadotropins, to replacing the ovulation trigger with a GnRH agonist, which also positions this protocol as optimal in the group of women with excess follicular reserve (high AMH ).

Is it true that in conditions of high AMH and excess follicular reserve, urinary gonadotropins (hMG) cannot be used, as the risk of developing OHSS increases?

When analyzing studies (La Marca A et al., 2012) (level of evidence 1a) in patients with high AMH, data were obtained comparing the effectiveness of hMG stimulation protocols and recombinant FSH (rFSH) with the use of GnRH agonists (MERIT study) (Andersen AN et al. ., 2006) and GnRH antagonists (MEGASET study) (Devroey P et al., 2012). hCG-driven LH activity of hMG during ovulation stimulation reduces the number of intermediate follicle sizes, which may predispose patients to the development of complications such as ovarian hyperstimulation syndrome, providing positive influence on the safety of ovulation induction protocols (Andersen AN et al., 2006; Filicori M et al., 2002; Peter Platteau et al., 2006). However, the smaller number of follicles obtained during hMG stimulation does not affect the cohort of dominant follicles (Hompes et al., 2008; Trew et al., 2010).
In stimulation protocols using GnRH agonists or GnRH antagonists, the use of hMG in women with high AMH had a significantly lower incidence of excess response than rFSH. This leads to an improvement in the fertility rate when using a single hMG protocol in patients with high ovarian reserve (Joan-Carles Arce et al., 2014; La Marca A et al., 2012).

Is AMH a good predictor of pregnancy in IVF?
In other words, can AMH concentration predict the likelihood of pregnancy in an IVF cycle?

Numerous arguments supported by voluminous clinical studies, confirm that the level of AMH, maintained by the activity of granulosa cells of growing follicles, quite objectively characterizes the available for induction and probably the total follicular reserves. However, despite the apparent dependence, the question of the quality of the oocytes located inside the follicles remains unclear. Indeed, on the one hand, it is known that clinical situations with a large volume of available antral follicles do not necessarily end in pregnancy in IVF with the most high frequency, and this can sometimes be observed in the group of patients with PCOS and, on the contrary, in the group of patients with single follicles that responded to induction, it is often possible to obtain the very desired oocyte and embryo good quality, sufficient for the successful completion of the treatment cycle.

Meanwhile, everyone knows that the quantity, but above all the quality of oocytes is directly related to the woman’s age. And it is the woman’s age that is the main factor in reproductive success, including the frequency of pregnancy in the ART cycle.

Regarding the significance of AMH in the outcome of IVF attempts, the following has been clearly established:

• At each specific age, women with high and normal AMH become pregnant more often than their peers with low and very low AMH. This was explained by the low frequency of cycle cancellations, obtaining more oocytes and good quality embryos (Nelson et al., 2007; Gleicher et al., 2010; La Marca et al., 2010; Majumder et al., 2010).
• Under 35 years of age, low AMH levels (alone) do not predict poor IVF cycle success
• Over the age of 41, high AMH levels do not correlate with high IVF success rates

Does AMH level affect fertility rates?

It has recently been confirmed that women with higher AMH levels have higher pregnancy rates as well as higher fertility rates (Arce et al., 2013; Brodin et al., 2013), a trend that persisted even after adjusting for age and number of oocytes obtained.

So:

• AMH is an important tool for realizing the male genotype in terms of correct formation reproductive organs
• AMH is one of the main paracrine tools for regulating the early stages of folliculogenesis
• AMH is the most sensitive indicator of total and active (available for stimulation) follicular reserves, since the dynamics of its level correlates well with the number of developing follicles and allows an objective representation of the pool of remaining primordial follicles
• AMH does not participate in the hypothalamic-pituitary-ovarian endocrine regulation, therefore its level is relatively stable throughout the menstrual cycle, as well as from cycle to cycle of one woman over a relatively short period of time
• In addition to the follicular reserve, the quality indicator of the AMH test depends on the testing method, calibration, conditions of transportation and storage of the blood sample, and is also determined by a number of factors: individual characteristics patients, such as excess body weight, ethnicity, vitamin D status, AMH and its receptor polymorphisms, smoking, and taking certain medications.
• Screening determination of AMH levels does not need to be carried out for everyone without exception.
• Screening determination of AMH levels is indicated for women from 34 to 38 years of age who are postponing childbearing, as well as younger women with a history of surgical interventions on the pelvic organs, especially the ovaries, UAE, chemotherapy, risk premature exhaustion ovaries, and also women who smoke, women with autoimmune diseases and type I diabetes.
• Registration of low AMH should serve as a reason for more active actions towards the implementation of reproductive function or safety cryopreservation of oocytes/embryos.
• AMH correlates with age and has high reliability in determining premature depletion of ovarian follicular reserve and predicting the age of menopause.
• Elevated AMH indicates a good follicular reserve of the ovaries and, in conditions of a regular menstrual cycle, cannot be considered a negative manifestation
• High AMH correlates well with PCOS, but is not the gold standard for diagnosing this condition
• AMH can be useful in predicting the follicular response of the ovaries to induction in an IVF cycle, as it well demonstrates both insufficient and excessive ovarian potential, which helps determine the protocol and dose of gonadotropins.
• There is no best protocol for ovarian stimulation in the setting of low AMH. All widely used protocols have comparable effectiveness.
• The ovarian stimulation protocol with GnRH antagonists can be considered optimal in conditions of high AMH.
• The use of urinary gonadotropins, when compared with recombinant FSH in conditions of high AMH and follicular reserve, does not increase the risk of complications (OHSS) and has a positive effect on the fertility rate.
• AMH best predicts the pregnancy rate in IVF when the patient is between 35 and 41 years of age. And it loses its main prognostic significance in extreme age categories of women (up to 35 years and over 41 years), when age itself is a reliable predictor of effectiveness. Despite this, women with low AMH always get pregnant less often than their peers with normal AMH.
• The level of AMH is directly proportional to the fertility rate in IVF.

The ability to get pregnant in a certain period of time determines. For conception, its amount must be within the normal range. In a woman’s body, from birth until menopause, AMH is produced by the ovaries.. This substance is special because the brain does not control its secretion.

Norm, table by age

The AMH norm in women is determined by a wide range of indicators, since the numerical value of the ovarian reserve is individual. The amount of the substance is not affected by the phase of the menstrual cycle, lifestyle and other external factors. In the table, AMH norms are presented depending on the woman’s age:

Indications for analysis

From a physiological point of view, the norm of anti-Mullerian hormone in women is an indicator of immature (resting) follicles. Every month one of them matures, releasing a mature egg for conception.. Mature follicles do not release AMH into the blood.

We can reasonably talk about reproductive dysfunction if a woman of childbearing age has difficulty conceiving a child for a long time under favorable conditions. Deviations from normal values ​​of anti-Mullerian hormone in women may be associated with an insufficient number of mature eggs (decreased ovarian reserve), developmental pathologies, and diseases of the reproductive system.

An anti-Mullerian hormone test is prescribed in following cases:

• unexpressed causes of infertility;
• unsuccessful IVF attempts;
• early menopause;
• carrying out antiandrogen therapy;
• diagnostics malignant tumors ovaries.

Analysis

On what day of the cycle to take anti-Mullerian hormone depends on the disease for which the test is prescribed. As a rule, it taken on the 3rd day of the cycle, since in parallel they study the level of other hormones (for example, FSH (follicle-stimulating hormone), the concentration of which is determined by the phase of the uterine cycle.

This rule is followed during a normal cycle, during artificial stimulation of the ovaries for IVF, and in diseases that cause cycle disruption. In some cases, the study may be scheduled on the 4th or 5th day.

To take the AMH hormone test, you must follow several rules that will help you obtain reliable results:

• venous blood is donated in the morning on an empty stomach;
• three days before the study, it is necessary to avoid physical activity, stressful situations;
• the analysis is not carried out in the presence of acute diseases or after recent illnesses;
• one hour before blood sampling, you should not smoke,
• should not be consumed the day before alcoholic drinks, fried, fatty;
• Your doctor can give you additional recommendations for preparing for blood sampling.

Direct blood testing involves several stages:

1. Analysis of FSH and AMH.
2. Determining the number of eggs ready for fertilization.
3. Calculation of ovarian volume.

The results of a laboratory blood test are issued in 2-3 days, in some cases it can take up to 7 days. The results are interpreted by the attending physician.

The normal level of anti-Mullerian hormone in a woman’s blood significantly increases the chances of conceiving a child. The concentration of this substance depends on the number of immature follicles, since it is secreted directly by them.

This is an indicator of mature eggs that can be used for fertilization. Women should remember that their number decreases every month and to plan a pregnancy it would not be superfluous to conduct research hormonal levels, including determination of AMH levels. For this purpose, laboratory research is carried out venous blood.

Displays the number of mature eggs.

If the levels of this hormone are abnormal, this significantly reduces the chances of a successful outcome of the in vitro fertilization procedure.

The purpose of anti-Mullerian hormone in the body

Anti-Mullerian hormone (AMH) is active substance, produced by the female body during the period of functioning of the reproductive system.

The protein molecule is produced by specialized cells of the ovaries until the onset of menopause. This is a hormone that affects growth factor.

AMH begins to be released during puberty, which is medically called puberty. This process ends in girls with the appearance of the first menstrual flow.

This hormone is an indicator of ovarian reserve. This is the number of eggs in the follicles ready for fertilization.

AMH is a marker of ovarian dysfunction. This condition occurs when it is impossible to produce hormones and germ cells. Usually the cause of this pathology is hormonal imbalance.

Using an AMH test, you can find out the ovarian response (the number of mature eggs that can develop into healthy embryos). This study is usually performed during in vitro fertilization.

Functions of anti-Mullerian hormone:

1. Regulation of follicle output in a calm state.
2. Impact on the rate of decline in the primary reserve.

Today, this hormone is used to diagnose infertility, the causes of which have not been clarified by doctors.

Research on the amount of this biological substance in the female body, it is done in case of unsuccessful attempts at in vitro fertilization.

Based on the results of AMH, it is possible to understand the reasons for the increase in follicle-stimulating hormone.

Today, analysis for this substance is used to diagnose granul cell cancer of the female gonads. This tumor most often develops in women after 40 years of age.

Normal AMH level

The normal range is 2.1 to 7.3 ng/ml (nanograms per milliliter). This concentration indicates that the woman is of reproductive age, that is, she can become pregnant on her own.

Low levels of the hormone indicate ovarian depletion. This pathology indicates premature development of menopause.

With increased AMH levels, the number of small antral follicles increases.

This condition is caused by polycystic ovary syndrome. With this disease, the hypothalamic regulation of the female reproductive glands is disrupted.

For IVF, AMG must be taken on days 3–5 of the menstrual cycle.

Before the study it is prohibited:

• Smoking.
• Drink alcohol.
• Be nervous.
• Exercise.
• Take hormonal medications.

The analysis involves taking blood from a vein. AMH is determined using a special serum.

The results are interpreted by an endocrinologist. The AGM norm for IVF is not less than 0.8 ng/ml.

Deviations from the norm during IVF

Anti-Mullerian hormone levels play an important role during in vitro fertilization.

After all, they help to find out the number of ready eggs and make a forecast regarding future conception.

Low AMG

According to reviews, IVF with low AMH less often ends in successful fertilization. The reason for this is the smaller number of eggs produced by the gonads.

The result of IVF with low AMH depends primarily on the qualifications of the reproductologist and the reaction female body for stimulation.

It is necessary for the maturation of several follicles with eggs, which are then collected using a puncture for further artificial fertilization.

Successful IVF with low AMH is only possible if the indicators are normal. If follicostimulating hormone is too high, it will not occur.

The FSH norm for IVF is 1.37-9.90 mU/l. Fertilization in case of deviation from the norm will not occur due to the impossibility of collecting the required number of mature eggs.

The chances of IVF with low AMH are considered minimal. Doctors focus on the fact that in case of deviations, conception occurs in 20% of cases, but in 85% the pregnancy fails due to abruption ovum from the endometrium of the uterus.

There are also cases where, due to low rate anti-Mullerian hormone, children were born with chromosomal abnormalities (Down syndrome, Patau, Edwards and others). Most often, children with pathologies are born from mothers whose age is over 35 years.

If the AMH level is below 0.8 ng/ml, then the woman’s reproductive specialist prescribes special hormone-based therapy, which increases the number of mature eggs.

To increase AMH for IVF, use medicines based on menopausal gonadotropin: “Menogon”, “Pergonal”, “Manopur”. The drugs “Puregon” and “Gonal” are also used.

To suppress the production of estrogen, the following drugs are used: Clostilbegit, Serofen and Clomid.

If a woman has problems with the amount of human chorionic gonadotropin, then the following drugs are prescribed: Prophase, Ovitrel, Choragol and Pregnil.

Reasons for the downgrade:

Elevated levels of anti-Mullerian hormone due to polycystic ovary syndrome

With such indicators, treatment is first prescribed, and then only IVF is done.

Conclusion

To undergo IVF, women's AMH must be normal. If the level of this hormone is low, then doctors will not be able to collect eggs, so the chances of fertilization are automatically reduced. If results are poor, therapy is prescribed.

Many women, after being diagnosed with infertility, managed to get pregnant even with low AMH, but reproductive specialists note that these cases are not patterns.

The ability to fertilize directly depends on the age of the expectant mother, the strength of her body and susceptibility to hormonal drugs. P

approved drugs to increase the protein molecule can provoke ovarian hyperstimulation syndrome.

It is very dangerous for women and can have the following consequences:

1. Development of ascites.
2. Premature ovarian failure.
3. Rupture of the gonads.
4. Blood thickening.
5. Torsion of the ovary.
6. Accumulation of fluid in the abdominal cavity.

Video: Anti-Mullerian Hormone (AMH)

One of the most important hormones that begins to be produced by the human body in utero. Anti-Mullerian hormone - what is it? It has an influence on the synthesis of all cells of the body, but its greatest role is noted in the formation of genital organs in men and eggs in women. This hormone accompanies men from birth until full puberty, after which its production subsides. In women, active creation of the hormone occurs until menopause.

What is anti-Mullerian hormone

The human body constantly produces various substances responsible for one or another function. Hormones rarely perform only one job, but are aimed at solving problems of a different nature. Biologists can only establish the connection of a certain substance with processes in the body, but this does not mean that its role ends there. Anti-Mullerian hormone is an indicator of the condition, and not the root cause of the manifestation of diseases.

A direct relationship has been proven between the amount of anti-Mullerian hormone in women and the possibility of fertilization. Deviations in the sexual development of boys with low levels of hormone (inguinal hernia, undescended testicles) have been established. But this is not proof that addiction has feedback. With an artificial increase in AMH (anti-Mullerian hormone), recovery does not occur. This is only one of the markers of the state of the reproductive system, helping to identify the cause of infertility.

In what cases is an AMH test prescribed?

There are several reasons why testing for the amount of this hormone is prescribed and they may differ for men and women, but are always related to the functioning of the reproductive system:

1. boys under 12 years of age with frequent (more than once a year) cases of inguinal hernias;
2. boys diagnosed with undescended testicles (cryptorchidism) after the first year of life;
3. men diagnosed with infertility, when the origin of the disease is not established;
4. to determine the true gender of a person;
5. diagnosing premature puberty;
6. diagnosis of delayed puberty;
7. assessment of a woman's ability to become pregnant;
8. diagnosis of ovarian cancer;
9. unsuccessful attempts at artificial conception (IVF).

AMH level norms

The AMH content largely depends on the gender and age of the patient. The norm of anti-Mullerian hormone in women at the age of puberty (before the first menstruation) is considered to be from 0.23 to 0.7 ng/ml. At the age of 13-14 years, the level of the hormone increases and is established within 1.0 – 2.50 ng/ml, remains unchanged and is produced by the body until the onset of menopause.

In men, the hormone plays a different role. Its main function is the formation of the male reproductive system, stimulating the descent of the testicles into the scrotum in boys. AMH levels in newborn boys are normally very high, ranging from 32 to 65 ng/ml in the first year of life. Subsequently, along with puberty, this indicator decreases to 0.49 ng/ml and remains low, because Its main function is performed in the first years of a man’s life.

How to take the test correctly

You need to know when to take a hormone test to get exact result. The AMH level is determined by collecting the patient's venous blood. There are several rules on how to take hormones correctly:

• Alcohol consumption - analysis may show a significantly underestimated result that does not correspond to reality. Avoid drinking alcohol 3 days before your test.
• Smoking can also reduce the hormone level, so do not smoke the day before the test.
• Stress – depending on the characteristics of the body, can either lower or increase the level of the hormone several times. 3 days without stress – required condition correct determination of the level of this hormone.
• Excessive physical activity can affect hormone levels, so 2 days before the test, do not subject your body to exercise and skip the fitness training.
• Past illness. Not necessarily related to gynecology. Even common cold influences AMH levels. Do not take the test while sick or immediately after recovery.
• Eating. Do not eat on the day of your test until your blood is drawn. This is a prerequisite for correctly determining the AMH level.

What does deviation from the norm indicate?

Only the attending physician should decipher the test results. Exceeding the limit values AMH hormone men or women may indicate pathological processes in the body, a delay or, conversely, premature puberty. The AMH level cannot be the only sign of a particular disease. To determine the actual level of the hormone, the test is performed 2 times with a period of at least 2 weeks between blood draws. It is important to test for AMH during and after the course of treatment, if one was prescribed.

Above normal

An increase in hormone levels in women may indicate several ailments present in the body.

• Polycystic ovary syndrome. As noted, AMH is involved in the construction of new cells in the body and reproductive system. Elevated hormone levels may indicate the presence of benign neoplasms in the ovaries. To confirm the diagnosis, additional ultrasound examination.
• Delayed puberty occurs only in girls. If there is a delay in the onset of menstruation, a high level of anti-Mullerian hormone indicates underdevelopment of the reproductive system.
• Granulosa tumors of the ovaries. Unlike polycystic disease or cysts, such neoplasms arise on the outer wall of the ovary and are dangerous due to their ability to degenerate into malignant formations.

Below normal

Low level Anti-Mullerian hormone deficiency can be caused by a very large number of factors that are pathological and situational in nature. Stress, drinking alcohol, smoking, excessive exercise, past illness– all this can lead to a decrease in the level of this hormone. The main pathological reasons leading to a decrease in AMH include:

• Menopause. During this period of a woman’s life, the production of AMH almost completely stops and the body becomes incapable of fertilization.
• Premenopausal processes. Menopause does not occur suddenly and a decrease in AMH levels before this phenomenon, along with other processes - normal phenomenon. A decrease in hormone limits indicates wilting reproductive function female body.
• Obesity. If you are overweight, the human body is not able to secrete a number of hormones, and AMH is one of them. A hormone level test can help determine whether obesity is causing a woman's infertility.

What to do if indicators deviate

A slight excess of the patient's AMH level limits does not require any adjustment. The role of the hormone in the normal functioning of the reproductive system has not yet been sufficiently studied; only the connection between its level and the ability to fertilize has been noted. Artificially increasing this indicator with drugs does not bring success in the treatment of infertility and does not affect the synthesis of eggs. It is necessary to treat the cause of the deviation, the pathology that led to an increase/decrease in the hormone. There is no universal answer to how to increase AMH in women.

Where to do the analysis and how much it costs in Moscow

If your attending physician has prescribed an AMH test, you can choose one of the clinics in the table, taking into account your location and the price for the service provided. There will be no fundamental difference in the results. All blades work with modern equipment and you will learn the results 2-3 days after the test. Addresses of clinics in Moscow: