Fertility Testing and AMH

This page is meant to clarify any misconceptions and answer questions related to general fertility testing. Fertility testing isn't right for everyone.

Background

What are primordial follicles?

Primordial follicles are the earliest stage of follicle development in a female's ovaries. They are tiny structures that contain an immature egg surrounded by a layer of flat, supportive cells known as granulosa cells.

These follicles are present in the ovaries from birth, and a female is born with all the primordial follicles she will ever have. During a woman's reproductive life, some of these primordial follicles will mature into larger follicles that can release an egg during the menstrual cycle, a process known as ovulation.

Most primordial follicles remain dormant and never mature. They play a crucial role in female fertility, and their number can give insights into a woman's ovarian reserve, or the potential number of eggs she has available for future development and possible conception.

What's an 'ooctye'?

An ooctye is an immature egg that develops into a mature egg ('ovum').

What is a Poor Ovarian Responder (POR)?

A poor ovarian responder is someone who is predicted to have a low 'Ooocyte Yield'. Reproductive endocrinologists AKA fertility doctors will sometimes reference the Bologna criteria which states that 2 of the following 3 features must be present to classify someone as a Poor Ovarian Responder.

1. Age > 40

2. Prior poor response to IVF stimulation (less than 3 eggs retrieved)

3. Either

   1. A low Antral Follicle Count (AFC), OR

   2. anti-Mullerian hormone (AMH) ,0.5– 1.1 ng/ml).

What is Antral Follicle Count (AFC)?

AFC is an important measure used to understand a woman's ovarian reserve or the number of remaining eggs. Antral follicles are small follicles in the ovaries that contain immature eggs.

Fertility Testing

Is there a general test for fertility?

Unfortunately no. The best way to determine fertility is to measure your success through attempts at conceiving naturally or undergoing fertility treatments if you fail to conceive naturally.

What is Ovarian Reserve?

Ovarian reserve refers to the total number of 'primordial follicles', though is generally understood to represent a woman's ability to get pregnant based on:

• The total number of eggs

• The quality of eggs available

What is the difference between fertility and ovarian reserve?

Fertility is the ability to conceive and produce offspring. It's a broader concept than ovarian reserve and involves the interplay of multiple physiological systems and factors, including the health of the eggs, sperm, fallopian tubes, uterus, and hormonal balance.

Using cars as an analogy, ovarian reserve can represent the 'gas in your tank' while fertility represents your ability to drive the car. We can measure the gas in the tank (AMH, AFC), but it doesn't mean the car will get to where it needs to go.

Does measuring my ovarian reserve tell me about my fertility?

Ovarian reserve tests do not directly tell a doctor if you are fertile, or will have difficulty conceiving naturally. Women with low markers on ovarian reserve testing can naturally conceive, and women with high ovarian reserve markers can struggle and require the assistance of a fertility specialist.

At what age should I see a fertility specialist or have fertility investigations?

1. Female Age < 35: You have been trying to conceive naturally with timed intercourse for more than 12 months.

2. Female Age 35-40: You have been trying to conceive naturally with timed intercourse for more than 6 months.

3. Female Age 40+: You should be referred immediately to a specialist.

What are 5 reasons I should not complete fertility testing before trying to conceive with my partner?

1. You can conceive naturally with abnormal ovarian reserve measurements.

Having a low AMH, high day-3FSH or low AFC doesn't mean you cannot naturally conceive. Nearly all people who conceive naturally never have fertility investigations prior to conception. Many people who conceive naturally would have had an abnormal test value had testing been completed pre-conception.

Having a receipt of abnormal test values can cause unnecessary stress and anxiety surrounding a process that can already be stressful.

You likely would have gone through life without knowledge of an abnormal value had you not tested that would have had no impact on your fertility.

1. Abnormal test values create anxiety. Anxiety can directly affect natural fertility.

Having abnormal lab test values can actually lead to increased psychological stress in both partners. There is an association between increased stress levels and fertility success. As an example, psychological stress is associated with increased oxidative stress on the body which can have deleterious (i.e. negative) effects on sperm quality.

1. Abnormal test values prompt unnecessary follow-up investigations.

If you didn't time a test properly or are in receipt of a result that is mildly outside of the 'normal range', this can lead you to the false conclusion that you require additional testing. This might mean repeat testing a month later, or several months later and referral to a specialist where one was not needed.

1. There is no lab test that answers the question 'What is my fertility?'

Lab tests that measure ovarian reserve are not an accurate marker for your overall fertility. What really matters is your fertility and ovarian reserve tests are just a component of that.

1. Having normal ovarian reserve markers can lead to ill-informed decision-making and be falsely reassuring.

Having 'high-normal levels' (i.e. AMH levels at the upper level of the normal range) can make you think you have good fertility and delay trying to conceive with a partner. In reality, you may have poor fertility due to other factors (i.e. age).

I consulted with a fertility specialist outside of Canada who says I need fertility tests before trying to get pregnant. Is s/he correct?

With rare exceptions, pre-conception fertility testing (testing before trying) is not required according to Canadian, American and European Practice Guidelines. These guidelines consider current medical evidence, the negative externalities (i.e. harm) both financially and psychologically from testing, and whether test results affect how we approach managing you as a patient.

What percentage of women get pregnant after 12 months of trying?

On average, 85% of women conceive naturally with 12 months of regular intercourse.

Measures of Ovarian Reserve

What are the common examples of hormones involved in measuring ovarian reserve?

Doctors will check levels of Follicle-Stimulating Hormone (FSH), Estradiol, and Anti-Muellerian (AMH) to learn about your ovarian reserve. Inhibin B is not checked because it doesn't give clear or helpful details about this reserve.

Are there ways to measure ovarian reserve with ultrasounds?

An ultrasound can be used to count the number of small follicles present in the ovaries at the start of a menstrual cycle. This measure is called an Antral Follicle Count (AFC).

What is timed intercourse?

This is the practice of having sexual intercourse at specific times when a woman is most fertile, typically around the time of ovulation.

We define the window period as 5 days prior to expected ovulation, the date of ovulation and 1 day afterwards.

Is FSH used as a measure of ovarian reserve?

FSH levels increase on days 2-4 in women as get older and their ovarian reserve decreases. As such, it is used as a measure of ovarian reserve and high values are associated with a poor response to ovarian stimulation and difficulty conceiving.

It's important to note that a woman with a normal (i.e. low) FSH level can have decreased ovarian reserve.

But a woman with an abnormal (i.e. high) FSH level will have decreased ovarian reserve.

Timed Intercourse Guide

This table guides the expected date of ovulation based on your cycle length. This is only applicable to you if you have regular cycles.

Regular Cycles

• Definition: A cycle is considered regular if the length (number of days between bleeding) and patterns of the periods (length of flow) stay roughly the same from cycle to cycle, with variations of only a few days.

1st Day of Cycle

• Definition: 1st day of full menstrual flow (spotting doesn't count)

Cycle length

• Definition: 1st day of the menstrual cycle (full flow) until the 1st day of the next menstrual cycle (full flow)

Average Cycle Length

• Definition: The average number of days in your cycle. For example a woman with the last 3 cycles measuring 29, 30, 31 days would average 30 days.

Days to Have Intercourse

There is no good data to suggest that timing intercourse more frequently, less frequently, or on specific days will improve or worsen fertility outcomes. Different fertility providers might provide different schedules for timed intercourse. Some providers might advise that intercourse is required on the date of expected ovulation. Others might suggest every 2 or 3 days.

The guide below recommends intercourse beginning 5 days before your expected ovulation date, and every 2 days. This naturally implies no intercourse on the day of ovulation. Sperm can survive for up to 5 days in the vaginal cavity, and there is no clear evidence to suggest that intercourse on the day of ovulation results in higher fertilization rates.

Average Cycle Length (Days)	Predicted Ovulation Day	Days to Have Intercourse
26	12	7, 9, 11, 13
27	13	8, 10, 12, 14
28	14	9, 11, 13, 15
29	15	10, 12, 14, 16
30	16	11, 13, 15, 17
31	17	12, 14, 16, 18
32	18	13, 15, 17, 19
33	19	14, 16, 18, 20
34	20	15, 17, 19, 21
35	21	16, 18, 20, 22
36	22	17, 19, 21, 23
37	23	18, 20, 22, 24
38	24	19, 21, 23, 25

Intercourse instructions

1. Single episode of intercourse the recommended dates.

2. No masturbation 2 days prior to, or during the fertility window.

Fertility vs. Ovarian Reserve

Can I have good ovarian reserve but poor fertility?

Yes, you have excellent measures of fertility (AFC, AMH, Day 3 FSH) but still have difficulty conceiving naturally. Examples where this might occur include:

• Your fallopian tubes are scarred or closed (this requires a 'sonohysterogram' to explore whether your fallobian tubes are 'patent' or open for transit of your eggs into the uterus from the ovaries.

• Your partner may have issues with their sperm quality.

• You may have a rare condition like Cystic Fibrosis.

• You may not be ovulating regularly.

*Sonohysterogram = an ultrasound where a fertility specialist injects fluid into the uterus to determine if your uterine cavity has a normal appearance and if your tubes are open.

Can I have poor ovarian reserve but have good fertility?

You can have poor ovarian reserve and still get pregnant naturally, but the likelihood of conceiving naturally is statistically lower in women with poor ovarian reserve.

What happens to AMH and Inhibin B over time?

As the number of ovarian follicles reduces over time, the concentration of 'early phase' Inhibin B (i.e. measured in the 1st 1/2 of the menstrual cycle) and AMH declines.

Is Inhibin B a reliable measure of Ovarian Reserve?

Inhibin B is not a reliable measure of ovarian reserve. There is lots of variability within and between cycles, and it has limited usefulness in identifying women who will be poor responders to IVF medications or ovarian reserve (i.e. AMH is a better test for this), even though there is a correlation between lower inhibin B levels and declining ovarian reserve.

Confirmation of Ovulation

What is the reliability of urine LH testing for the prediction of ovulation?

Measuring LH levels in the urine is a very reliable measure of ovulation, with one study referencing a 97% agreement using ultrasound as a comparison for predicting ovulation. Ultrasound is the 'gold standard' for observing ovulation, as we can see ovulation occurring directly.

What is the reliability of measuring body temperature?

Measuring body temperature is moderately reliable, with two studies referencing a 30% and 77% correlation with ovulation predicted against LH testing.

Are there studies evaluating the use of cervical mucus changes in predicting ovulation?

No, there are no changes in cervical mucus to product changes in ovulation.

Predicting Pregnancy

Trying < 12 Months

Does my ovarian reserve predict my ability to conceive naturally in the next 12 months?

No. It has been consistently demonstrated that your total ovarian reserve does not predict your likelihood of getting pregnant in the next 12 months.

I have decreased ovarian reserve but have regular cycles. Does that mean I'm less likely to get pregnant in the next 12 months?

Women who have regular cycles who have decreased ovarian reserve are just as likely as woman who have normal ovarian reserve to get pregnant naturally over the next 12 months.

Trying > 12 Months

Is Antral Follicle Count (AFC) able to predict if I will get pregnant naturally?

Several studies have found no correlation between AFC and the likelihood of getting pregnant over the next 6-12 months.

Reference studies: Casadei et al., 2013; Depmann et al., 2017; Yücel et al., 2018

Is AMH able to predict if I will get pregnant naturally?

Several studies have found no correlation between AMH levels and the likelihood of becoming pregnant naturally. Women with low AMH levels had similar pregnancy rates as those with higher levels.

AMH Questions

When is AMH testing useful?

AMH testing is useful when a woman is considering pursuing Artificial Reproductive Treatment (ART) - known more commonly as IVF. During IVF treatment, gynecologists will prescribe medications that simulate the ovaries to mature a large number of follicles (immature eggs) into mature eggs (oocytes). Oocytes are then retrieved (by inserting a needle into the ovary) for fertilization in a lab to produce an embryo.

The number of oocytes retrieved is called the 'Ooctyte Yield'.

Low AMH

• Women with low AMH will likely not respond favourably to ovarian stimulation. This means that during an 'IVF cycle', when given stimulating medication, a woman is not likely to retrieve a large number of oocytes (i.e. she might have a low 'Ooctye Yield') if she has a low AMH level.

Is AMH useful for determining how long it will take to get pregnant?

AMH levels do not correlate with the time to achieve pregnancy. AMH is a relatively new hormone measurement, and at present time there isn’t enough evidence to use it for the prediction of pregnancy loss, or for estimating a general fertility status outside of IVF assessments.

What information does AMH tell us about young women and predicting pregnancy?

There are some studies looking at the 'positive predictive value' (i.e. the likelihood of getting pregnant) using different values for AMH levels.

One study found that having an AMH level < 2.7 ng/ml correctly predicted that 6-8 of 10 women would not get pregnant (i.e. predicted these women would not get pregnant and they did not get pregnant), and incorrectly predicted that 2-4 of 10 women would not get pregnant but they did.

Is the a normal or abnormal cut-off value for AMH testing?

At present time, there is no standard 'cut-off' value that doctors agree on for a normal vs. abnormal AMH value. For example, in diabetes, there is a universally agreed upon cutoff value for when a person has diabetes (i.e. > 126 mg/dL or 7.0 mmol/L).

To make things more complicated, each lab uses a different lab kit for measuring AMH so AMH testing done at one lab doesn't necessarily compare to lab .

Does it make sense to test my fertility markers before trying to conceive naturally?

No, it doesn't make sense to test before attempting conception if you have regular menstrual cycles.

Scenario 1: You test before conception and have a low AMH, high FSH or a low AFC level. You are referred to a specialist for an initial appointment. At that appointment, the fertility specialist will review your numbers and tell you to come back in several months (6 months if older than 35, or 12 months if < 35) after trying naturally.

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764725/

https://extendfertility.com/your-fertility/fertility-statistics-by-age/