AMH or ‘Anti-Müllerian Hormone’ is a blood test taken as part of a fertility work-up. Levels below normal ‘may’ reflect low ovarian reserve and levels above normal reflect polycystic ovaries. AMH levels peak at age 25 and then slowly decline until menopause. 1.
According to the Cleveland Clinic typical levels of AMH based on age are:
25 years old: 3.0 ng/mL. (21.43 pmol/L)
30 years old: 2.5 ng/mL. (17.85 pmol/L)
35 years old: 1.5 ng/ mL. (10.71 pmol/L)
40 years old: 1 ng/mL. (7.1 pmol/L)
45 years old: 0.5 ng/mL. (3.5 pmol/L)
AMH is a hormone produced in the ovarian follicles. As women age, the number of follicles decrease causing a decrease in AMH levels. AMH levels are used to predict ovarian reserve and ovarian response to fertility treatments. It is considered a marker of ovarian age. IF AMH levels are low, In-Vitro Stimulation (IVF) is considered the most effective fertility treatment. Yet, it is generally agreed that there is much variability in AMH levels due to a number of factors and that this test cannot clearly predict fertility.
There are a number of factors that influence AMH levels aside from age including:
Endometriosis,
genetic factors,
auto-immune diseases,
cancer treatments,
smoking,
environmental causes like pollution,
obesity,
women taking birth control pills may show falsely low AMH levels,
pregnancy (suppresses AMH levels),
recurrent pregnancy loss (associated with low AMH levels independent of age).
AMH and Endometriosis:
Endometriosis occurs when tissue similar to the tissue that normally lines the inside of the uterus — the endometrium — grows outside the uterus. This endometrial-like tissue thickens, breaks down and bleeds with each menstrual cycle but has no way to exit the body. The surrounding tissues become irritated, eventually developing scar tissue and adhesions that can cause pelvic tissues and organs to stick to each other.
The relationship between AMH levels and endometriosis is not fully understood but it has been observed that women with endometriosis have lower AMH levels. This can occur both in women who have had surgery to remove endometrial growth on the ovary (and in the process damage the ovary) and in women who simply have endometrial growth. In the later case it is assumed that inflammation and possible autoimmune processes associated with endometriosis may damage the ovarian follicles leading to lower AMH levels. 2.
Studies of younger women with severe endometriosis showed diminished ‘oocyte yield’ (or number of follicles) but not a reduction in embryo quality and pregnancy outcomes.3.
If women do require surgery for endometriosis it has been shown that AMH levels can recover 12 months post-op if surgery is done on one ovary (rather than both). 4
AMH and Genetic Factors
There are a number of genetic factors or variants that have been linked with low ovarian reserve. This is a complicated and relatively new area of research. Different genetic changes are linked to low ovarian reserve such as:
Chromosomal differences
Single-nucleotide polymorphisms that code for hormonal receptors and influence expression of hormones such as AMH, Follicle Stimulating Hormone (FSH), Lutenising Hormone (LH) and estrogen, contributing to varied ovarian response and diminished reserve
Genes involved in formation of ovarian follicles
Genes that influence gene expression and genetic susceptibility to the environment (epigenetics)
Genes responsible for DNA repair – the widely know BRCA gene is associated with declines in ovarian reserve, premature ovarian aging and mutations in DNA
No two genetic ‘reasons’ for low ovarian reserve are the same and potential treatments vary depending on the specific gene involved.
AMH and Auto-Immune Disease
The ovaries are a common target for autoimmune attack. It is thought that autoimmunity can be linked to premature ovarian failure, POF (depletion of ovarian follicles before age 40) in up to 30% of cases. 5. Autoimmune involvement should be suspected in women with low AMH and other forms of autoimmunity including:
Autoimmune thyroid conditions,
Autoimmune adrenal gland conditions
Autoimmune polyendocrine syndromes
Type 1 Diabetes
Celiac Disease
Crohn’s Disease
Lupus
Premature Ovarian Failure is associated with autoimmunity. Anti-oocyte antibodies (AOAs) are found in 24–73% of patients with confirmed Premature Ovarian Insufficiency. AMH is considered a reliable tool in patients with other autoimmune diseases for recognition and risk assessment of developing premature ovarian insufficiency. 5.
AMH and Cancer Treatments
AMH can fall during cancer treatment with variable recovery thereafter depending on the degree of toxicity of the treatment used. Studies have shown that AMH levels do increase in the initial two years after cancer treatment, although the values remain low. There still is a ways to go in being able to use this AMH level to predict the window of fertility in recovered cancer patients. 6.
AMH and Lifestyle Factors
AMH levels are known to be impacted by a number of environmental factors.
Heavy Smoking: A history of heavy smoking is generally associated with diminished ovarian reserve although there is conflicting evidence. The relationship between smoking and AMH levels are also unclear. However, given the toxicity associated with smoking, it is still best practice to stop smoking as part of any preconception plan.7.
Urban Living and Pollution: There is a growing body of evidence linking urban living and exposure to pollution with adverse fertility and pregnancy outcomes, including stillbirth, miscarriage and fetal loss, impaired fetal growth, preterm delivery and reduced fertility rate. Likewise, there is evidence that proximity to green space has positive reproductive and pregnancy outcomes. AMH has been found to be higher in individuals who live further from major roads and closer to green space. 8.
Obesity: Obesity is another potential factor influencing AMH. It is know that increasing body mass index has a range of health consequences. When it comes to prenatal health - being overweight is associated with menstrual cycle irregularity, abnormal uterine bleeding, endometrial hyperplasia, infertility, and pregnancy complications. The infertility observed in women with obesity is commonly associated with ovulatory disturbances and irregular menstrual cycles. And some studies have shown a relationship between increasing Body Mass Index (BMI) and decreasing AMH levels. 9.
Contraceptive Use: Lastly, the birth control pill is associated with a temporary decrease in AMH levels. In one study including 27,125 US-based women aged 20 to 46 years, all forms of contraception were associated with reduced AMH levels (with the exception of the copper IUD). 10.
Does AMH predict pregnancy outcomes?
Interestingly, while AMH levels are helpful in predicting response to fertility treatment, time to menopause and possibly polycystic ovarian syndrome – it is not the best predictors of who will get pregnant naturally. In one study of 750 women aged 30-44 years of age without a history of infertility who had tried to conceive for 3 months or less – there was no significant difference in conception rate between those with low and normal AMH levels. This was also the case for other markers of ovarian reserve such as Follicle-Stimulating Hormone. 11.
It is likely the case that AMH is predicting follicle quantity rather than quality. Regular ovulation and quality may hold more importance in natural pregnancy than ovarian reserve values. 12.
It is also the case that AMH levels vary significantly within and between menstrual cycles. A single measurement may not be enough upon which to base clinical judgements because (12, 13, 14, 15.):
AMH May be higher in the follicular phase than the luteal phase
These variations within the cycle may be different for younger and older women
AMH levels are influenced and modified by other hormonal factors such as androgen (DHEA-S) and insulin levels.
AMH value have been shown to vary within cycles by 16-20% and between cycles by as much as 28%
More recent research has been looking at the relationship between AMH levels and recurrent miscarriage. Low AMH levels do seem to predict the risk of recurrent miscarriage and may be used clinically to assess this risk but more research is required. 16.
With this in mind, it likely matters when AMH is measured within a cycle. It makes sense to take multiple measures of AMH across menstrual cycles to get a clearer picture of ovarian reserve although this is rarely done due to cost. It is also important to keep in mind that these numbers may reflect quantity and not quality. All of these factors should be taken into consideration if women are basing their preconception planning on these lab values.
References:
1. Moolhuijsen LME, Visser JA. Anti-Müllerian Hormone and Ovarian Reserve: Update on Assessing Ovarian Function. J Clin Endocrinol Metab. 2020 Nov 1;105(11):3361–73. doi: 10.1210/clinem/dgaa513.
2. Romanski PA, Brady PC, Farland LV, Thomas AM, Hornstein MD. The effect of endometriosis on the antimüllerian hormone level in the infertile population. J Assist Reprod Genet. 2019 Jun;36(6):1179-1184. doi: 10.1007/s10815-019-01450-9.
3. Pacchiarotti A, Iaconianni P, Caporali S, Vitillo M, Meledandri M, Monaco G, Sergio C, Boza M, Saccucci P. Severe endometriosis: low value of AMH did not affect oocyte quality and pregnancy outcome in IVF patients. Eur Rev Med Pharmacol Sci. 2020 Nov;24(22):11488-11495. doi: 10.26355/eurrev_202011_23790.
4. Anh, N.D., Ha, N.T.T., Tri, N.M., Huynh, D.K., Dat, D.T., Thuong, P.T.H., Toan, N.K., Duc, T.A., Hinh, N.D., Tong, H.V. (2022). Long-Term Follow-Up Of Anti-Mullerian Hormone Levels After Laparoscopic Endometrioma Cystectomy. International Journal of Medical Sciences, 19(4), 651-658. https://doi.org/10.7150/ijms.69830.
5. Szeliga A, Calik-Ksepka A, Maciejewska-Jeske M, Grymowicz M, Smolarczyk K, Kostrzak A, Smolarczyk R, Rudnicka E, Meczekalski B. Autoimmune Diseases in Patients with Premature Ovarian Insufficiency-Our Current State of Knowledge. Int J Mol Sci. 2021 Mar 5;22(5):2594. doi: 10.3390/ijms22052594.
6. Yasmin L. Jayasinghe, W. Hamish B. Wallace & Richard A. Anderson (2018) Ovarian function, fertility and reproductive lifespan in cancer patients, Expert Review of Endocrinology & Metabolism, 13:3, 125-136, DOI: 10.1080/17446651.2018.1455498
7. Bhide P, Timlick E, Kulkarni A, et alEffect of cigarette smoking on serum anti-Mullerian hormone and antral follicle count in women seeking fertility treatment: a prospective cross-sectional study BMJ Open 2022; 12:e049646. doi: 10.1136/bmjopen-2021-049646
8. Fatemeh Abareshi, Zahra Sharifi, Reza Hekmatshoar, Majid Fallahi, Moslem Lari Najafi, Akbar Ahmadi Asour, Forough Mortazavi, Rahim Akrami, Mohammad Miri, Payam Dadvand,Association of exposure to air pollution and green space with ovarian reserve hormones levels,Environmental Research,Volume 184, 2020, 109342,ISSN 0013-9351, https://doi.org/10.1016/j.envres.2020.109342.
9. Oldfield AL, Kazemi M, Lujan ME. Impact of Obesity on Anti-Mullerian Hormone (AMH) Levels in Women of Reproductive Age. J Clin Med. 2021 Jul 20;10(14):3192. doi: 10.3390/jcm10143192.
10. Hariton, E., Shirazi, T. N., Douglas, N. C., Hershlag, A., & Briggs, S. F. (2021). Anti-Müllerian hormone levels among contraceptive users: evidence from a cross-sectional cohort of 27,125 individuals. American Journal of Obstetrics and Gynecology, 225(5), 515.e1-515.e10. https://doi.org/10.1016/j.ajog.2021.06.052
11. Steiner AZ, Pritchard D, Stanczyk FZ, et al. Association Between Biomarkers of Ovarian Reserve and Infertility Among Older Women of Reproductive Age. JAMA. 2017;318(14):1367–1376. doi:10.1001/jama.2017.14588
12. Lin C, Jing M, Zhu W, Tu X, Chen Q, Wang X, Zheng Y, Zhang R. The Value of Anti-Müllerian Hormone in the Prediction of Spontaneous Pregnancy: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2021 Oct 13;12:695157. doi: 10.3389/fendo.2021.695157.
13. Lin LT, Tsui KH. The Relationships Between Serum DHEA-S and AMH Levels in Infertile Women: A Retrospective Cross-Sectional Study. J Clin Med. 2021 Mar 15;10(6):1211. doi: 10.3390/jcm10061211.
14. Melado L, Lawrenz B, Sibal J, Abu E, Coughlan C, Navarro AT, Fatemi HM. Anti-müllerian Hormone During Natural Cycle Presents Significant Intra and Intercycle Variations When Measured With Fully Automated Assay. Front Endocrinol (Lausanne). 2018 Nov 27;9:686. doi: 10.3389/fendo.2018.00686.
15. Narelle Hadlow, Suzanne J. Brown, Afsana Habib, Robert Wardrop, John Joseph, Melissa Gillett, Rhonda Maguire, Johan Conradie, Quantifying the intraindividual variation of antimüllerian hormone in the ovarian cycle, Fertility and Sterility, Volume 106, Issue 5, 2016, Pg. 1230-1237, https://doi.org/10.1016/j.fertnstert.2016.06.009.
16. McCormack, Catherine & Leemaqz, Shalem & Furness, Denise & Dekker, Gustaaf & Roberts, Claire. (2019). Anti-Müllerian hormone levels in recurrent embryonic miscarriage patients are frequently abnormal, and may affect pregnancy outcomes. Journal of Obstetrics and Gynaecology. 39. 1-5. 10.1080/01443615.2018.1552669.