One of the commonest questions I get is from women with low AMH (anti mullerian hormone) levels who are having trouble getting pregnant. These women are often frantic and worried that they will never be able to get pregnant.
They often feel that having a low AMH level is the end of the world and it makes pregnancy impossible. Not necessarily true! Read on.
What is AMH and What Does it Tell Us?
Granulosa cells that surround the eggs in the ovary release AMH. It is now well established that AMH levels reflect the number of eggs (oocyte pool) that remain in the ovary (ies). Early studies showed that AMH levels do not show cyclic variation and (unlike follicle stimulating hormone (FSH) levels) can be measured any day during the menstrual cycle. AMH levels were not affected by being on birth control pills, gonadotropin-releasing hormone agonists (e.g. leuprolide acetate or Lupron) or pregnancy. Some of these assumptions are no longer true as previously discussed. Large follicles do not release AMH and AMH levels will decrease in the later stages of stimulated cycles. Obese women have low AMH levels. Patients with Vitamin D deficiency may have low AMH levels.
Measuring an AMH level thus very quickly became a part of a basic infertility work up. A low AMH level was considered consistent with a diagnosis of diminished ovarian reserve. AMH levels were found to correlate very nicely with the number of eggs retrieved during IVF and also with IVF pregnancy rates. It was possible that we had finally come up with a simple blood test that assessed ovarian reserve. It could be done at anytime during the menstrual cycle and was relatively inexpensive. I wish!
AMH Levels Fluctuate
As we gained more clinical experience with the use of AMH levels, some things became clear. AMH levels seemed to vary when repeated in the same patient. We have seen wide variations in AMH levels with levels varying in a short period of time from 0.5 ng/mL to even as high as 2.0 ng/mL. I have discussed this in a previous blog. The problem seems to be with the new Gen II AMH assay. Hopefully, the manufacturers are addressing this and we a new more reliable assay will soon be available.
With this background, what can be done for patients with low AMH levels who continue to have trouble getting pregnant?
It is reasonable to get a second (confirmatory) AMH level. At InVia, we no longer rely on AMH levels alone for assessing ovarian reserve. This may change once the problems with the current AMH assay are resolved. We instead use a combination of AMH level and antral follicle count and day-3 FSH level. Other factors that are considered include age, BMI, smoking status, previous ovarian surgery and previous ovarian response to stimulation.
When is AMH Not As Important a Factor?
Patient age is a huge factor that affects the prognosis. Young patients (< age 30 y) with low AMH levels have been shown to have a fairly good chance of getting pregnant naturally. It is therefore NOT a good idea to get an AMH level as a “fertility check” in a young, otherwise healthy woman who may not even be trying to get pregnant. A low level unnecessarily induces panic in a patient who may not have difficulty conceiving.
In patients older than age 40 years the situation is a bit complicated. Age is an independent variable that MUST be considered. A 41 year old with an AMH level of 3.0 ng/mL does not have the same chance of getting pregnant as a 25 year old with the same AMH level. At the same time, a low AMH level in this age group is generally associated with a poor prognosis.
If you are overweight and have a low AMH level, it makes sense to lose weight. It is possible your AMH level will improve. Overweight patients have lower pregnancy rates with IVF.
Vitamin D deficiency is associated with low AMH levels. This is easily diagnosed with a blood test and can be corrected with Vitamin D supplements.
Is IVF necessary for treatment of low AMH level?
The rationale for recommending IVF is to pursue pregnancy aggressively in these patients. IVF is the option with the highest per cycle pregnancy rate when compared to clomiphene citrate / intrauterine insemination (IUI) or FSH/IUI. However, especially in younger patients, it is reasonable to start with three cycles of IUI before considering IVF for this indication.
What are the IVF pregnancy rates for patients with low AMH?
Not bad. The group from Cornell under the leadership of Dr Zev Rosenwaks has shown reasonable pregnancy rates in IVF patients with low AMH levels. These have been presented in a previous blog.
We will generally use an aggressive stimulation protocol to stimulate these patients. Priming with DHEA or testosterone may also be considered. Another approach is to use a combination of clomiphene citrate and gonadotropins (IVF lite) to stimulate these patients.
If you truly have diminished ovarian reserve, at some point, you may have to consider options such as donor eggs, donor embryos, adoption or child free living.
To see a fertility specialist who is versed in the complexities of AMH level testing, make an appointment at one of InVia's four Chicago area fertility clinics.