6k took this course

Fertility 101

Lesson 4 of 5

Diagnosing Fertility Issues & Getting Help

Video Lesson

Written Lesson

When to See a Doctor If You're Trying to Conceive

The official guidelines say that if a woman is under 35, see a doctor after a year of well-timed intercourse without success, and if a woman is 35 or older, see a doctor after six months of trying without success. We’ll unpackage those guidelines and discuss when they should be ignored.

First, there are situations when it’s best to see a doctor earlier, rather than waiting the full six or twelve months. These situations include the following:

  • If a woman hasn’t had a period in three months, that means ovulation isn’t happening, so unassisted pregnancy is very unlikely
  • If there’s a history of multiple miscarriages
  • If either a male or female partner has received chemotherapy (which can damage the ovaries or testicles)
  • If there’s a family history of infertility or early menopause
  • If there’s a reason to believe that a woman might have endometriosis
  • When a man has had any damage or injury to the groin area or has been exposed to toxic chemicals
  • Prior surgery to the uterus or ovaries
  • Female history of appendicitis
  • Prior hernia surgery for men

These recommendations were made based on the likelihood of becoming pregnant in any given month, assuming that unprotected intercourse is well-timed. The first few months of trying to conceive offer the greatest probability per cycle of getting pregnant. Every additional month of trying after those first few months, the odds of conceiving decrease.

A vast majority of women who are under 35 years old will get pregnant after six months of trying. The Gnoth study found 88% of women between the ages of 31 and 34 conceived in 12 months of trying. And for those in the bracket of 35–44 years old, 73% found success in 12 cycles. In both of these groups, continuing to try after the first six cycles can still be somewhat productive.
Time to Pregnancy Broken Down by Maternal Age
Specifically, for women who are over 35 and approaching 40 or beyond, the first six months of trying is still worthwhile as about 30% conceive naturally. As you can see below, the next 6–12 months of trying can still be useful, but by month 18 or so, success rates will have stalled out at 60%.

One could argue that between months 6 and 12 these women should continue to keep trying naturally because rates do still clearly climb. However, that optimism needs to be tempered against the reality that if the woman does not succeed (nearly a coin flip that she won’t) and needs to resort to IVF, that year of delaying treatment can be costly. As you can see below, after every two years success rates decline by half and ultimately settle in below 5% per cycle.
Impact of Age on IVF Success Rates

Another question that comes into play when you’ve decided to see a doctor when trying to conceive, is whether you should seek out your OB/GYN or a “fertility specialist” who is a reproductive endocrinologist (RE).

In our opinion, if it’s available to you, having diagnostics run by a reproductive endocrinologist has benefits, and it’s worth going straight to the doctors who spend all day, every day helping people conceive.

A big difference between an OB/GYN and an RE is that REs can run a lot more diagnostics in-house like the semen analysis, HSG, hysteroscopy & more. They have more experience interpreting the results, and overall, it's just more likely that they've seen patients who are like you are.

Reproductive endocrinologists are able to do the full range of fertility treatments, which won't be available to you at your OB/GYN. So we think it's better to get established with an RE that you really like sooner rather than later.

And for those with male factor infertility, it actually may be more beneficial to seek out a reproductive urologist over an RE. For more information on the topic, you can see our dedicated lesson here.

The reality is that fertility doctors have more effective tools (which we’ll cover in depth in later chapters) in their arsenal to diagnose and treat patients. OB/GYNs can prescribe less powerful drugs like clomid or Letrozole and couple them with intrauterine insemination (IUI). On the other hand, reproductive endocrinologists can prescribe a wide range of medications and are equipped to perform the full spectrum of fertility treatments from IUI to IVF.

As you can see below, the range of treatments (and costs) offered by an RE is wide-ranging and so patients must be discerning about which treatment makes the most sense for them. It’s common for fertility doctors to steer patients immediately to IVF which is the most effective, but also the mostly costly (for you) and profitable (for them) option on the menu.

A lot of in-demand REs have waiting lists of three to six months for new patients. So, even if you’re a few months shy of when the guidelines tell you to see a doctor, you might want to get an appointment on the calendar for a few months down the line. Hopefully, you’ll never need it and can just cancel, but if you do need it you’ll probably be happy to have it on the books.

Diagnostics: Finding What’s Not Working

The goal of fertility diagnostics is to identify where the reproductive systems might not be working properly.

Remember, the key components of human reproduction are the following:

  1. A high quality egg
  2. Healthy sperm
  3. A functional fallopian tube
  4. A uterus that is ready and able to hold a pregnancy
  5. Hormonal support for each event

Like so much with fertility, diagnostics are not clear cut—there are several ways of trying to investigate each part of our reproductive systems and each method has strengths and weaknesses. Unfortunately, there are generally no silver bullet tests that give us all the information we wish we knew.

Diagnostics for Eggs or Ovarian Reserve

There are three main tests that are focused on the eggs or more formally, ovarian reserve. These tests can be really confusing, and they're often misrepresented by the media and the companies that sell these tests. So it's important to understand some core concepts.

First, there is no diagnostic test at this point in time that can tell us the quality of a woman's eggs.

Also, there aren't any tests that can perfectly tell us the quantity of eggs a woman has left. At least not in any actionable sense. What we mean is that there's no test that tells you how long you have before the clock runs out on your individual fertility.

When it comes to egg quality, age is probably the most predictive marker, but that's far from perfect. IVF, especially with genetic testing, can give you insights about egg quality, but using IVF as a diagnostic tool is really expensive and invasive.

So, to sum it up, there are no ovarian reserve tests a woman can take that will tell her whether she'll be able to conceive naturally.

The three main tests that doctors use for ovarian reserve are blood tests called AMH and FSH and a vaginal ultrasound to count the number of small follicles on the ovaries. That's called the AFC.

We'll give you a high-level summary of each one here. These tests are mostly a measure of how well you'll respond to hormones for fertility treatments, if those treatments are needed.

Data currently shows that they are not correlated with the ability to get pregnant naturally. So don't freak out or get complacent about your ability to conceive naturally based on what these tests say.

AMH for Ovarian Reserve Testing

AMH, or Anti-Müllerian Hormone, is a widely used test to help doctors investigate ovarian reserve to predict a woman’s response to fertility treatments—namely, how many eggs she will produce if given medication to stimulate her ovaries.

On the positive side, AMH levels typically do not change a lot during the menstrual cycle, so there’s no specific time window when it needs to be done.

To understand AMH, it’s best to start with the concept of how eggs are stored in the ovary. Long before eggs are selected to be matured and ovulated, they exist in a dormant state in the ovary. These dormant follicles that house immature eggs in the ovary release the AMH hormone. The blood test for AMH gives a rough sense for how many dormant follicles are left—a high AMH means there are many follicles left on the ovaries and a low AMH means there are fewer.

In the context of an egg retrieval, AMH is a good indicator of the quantity of eggs the cycle will yield. Remember, the higher the AMH, the more follicles are present. When fertility medications are taken, these follicles respond, eggs mature, and can then be retrieved.

The big negatives of AMH, which we’ll unpack a little further, are (1) it does not give a window into natural fertility; (2) it does not give us information about egg quality; (3) the test scores can be different depending on which lab runs it; and (4) AMH levels can be influenced by birth control pills.

AMH Doesn’t Predict Natural Fertility

A study published in JAMA concluded that AMH did not predict time to natural pregnancy. This study followed a group of women who were 30–44 years old and attempting to conceive, measuring their AMH levels and tracking how long it took them to get pregnant.

The data showed that women with “diminished ovarian reserve” (as indicated by a low AMH reading) were no less likely to conceive than women with normal or high AMH levels. After correcting for variables, the data didn’t even come close to showing statistical significance, much less a trend.

One important caveat, though, is that this study only followed up through pregnancy, and there’s a chance that low AMH might correlate with higher rates of miscarriage—we really wish the study investigators had netted this all out for us by focusing on live birth rates.

AMH Doesn’t Predict Egg Quality

There is no true definition of egg quality, but the three general categories of egg quality that we can see are (1) does an embryo derived from a given egg survive in a laboratory; (2) does the embryo from a given egg have the right DNA blueprint; and (3) does transfer of that embryo into a woman’s uterus produce a live birth.

The largest study that examined the association between AMH and these factors demonstrated that there was no difference between low AMH versus normal AMH. To put a fine point on it, there is good evidence that AMH does not predict egg quality.

AMH Levels Can Vary Based on Birth Control Use or on Lab Technique

The final issue is the accuracy or reproducibility of the test itself.

AMH levels from the same blood sample can come back different from different laboratories. While “assays” to test AMH in labs have improved in recent years, there can be a wide divergence of readings based on where the test is performed. So, if you’re relying heavily on an AMH number, it’s best to take the test more than once at a lab that runs this test regularly and possibly have it run at different labs.

Finally, if a woman is taking hormonal birth control, AMH could appear artificially low. The longer someone has been on the pill, the lower AMH levels will be. It’s important your doctor knows you’re on birth control pills if you’re doing an AMH test.

FSH for Ovarian Reserve Testing

Follicle stimulating hormone, or FSH, is the hormone released by the brain to signal the ovarian follicles to grow and develop. This is the hormone that starts the process of recruiting follicles towards the end of a menstrual cycle. It continues to rise at the beginning of the next cycle to select a dominant follicle to develop towards ovulation.

If the ovary is functioning properly, just a small amount of FSH (a gentle nudge to the ovary) is needed to signal a dominant follicle to grow. If that ovary isn’t functioning properly, it will take a larger amount of FSH (a loud FSH message) to kick-start a dominant follicle to begin maturing an egg—this means a higher level of FSH is needed (and found) in the bloodstream.

The basis of the FSH test is to look at the FSH level on day 3 of a menstrual cycle to see how much FSH there is encouraging development of the one follicle housing the egg for ovulation that month.

Logistics of FSH Testing

Typically you will call your fertility clinic to let them know when you start your period (day 1 of your cycle). On the third day of bleeding, a blood draw for FSH can be done. The timing is critical here in terms of interpreting what an FSH level means. Day 3 is the most common day to do FSH testing, but some clinics also do it on day 2 or day 4.

FSH is tested along with estradiol levels. Estradiol levels will tell us whether a dominant follicle has already started the process of developing—if it’s high (over 80), this process has already started, which means that a loud FSH message is no longer needed and it begins to go down. In this case, if on day 3 a follicle has gotten a fast start out of the gates, FSH levels might appear normal, not reflecting a true picture of how loud the FSH message needed to be to jumpstart follicular recruitment in the first place.

What FSH Does & Doesn’t Tell Us

FSH levels do not predict one’s ability to conceive naturally—this was demonstrated in the same JAMA study that came to this conclusion about AMH.

What FSH is more correlated with is outcomes with fertility treatments. A high FSH (more than 10) is associated with a lower number of eggs retrieved in an IVF cycle.

While this correlation is true across large numbers of patients, it’s not necessarily true for individual patients—meaning that a high FSH might not predict that you personally will have a bad outcome.

Some studies have shown poor sensitivity for identifying women who will have a poor response to treatment. In other words, a reasonable number of women with high FSH levels produce a normal number of eggs, and a reasonable number of women with normal FSH levels produce a low number of eggs.

Basically, we’ll net this out to say that a slightly elevated FSH probably isn’t something to get too stressed out about.

Antral Follicle Count (AFC) as an Indicator of Ovarian Reserve

Unlike the previous two ovarian reserve tests, antral follicle count, or AFC, is not a blood test—it’s a visual diagnostic that requires a transvaginal ultrasound.

This ultrasound is performed during the first few days of the menstrual cycle before a dominant follicle has been selected for development. At this stage, multiple small follicles should be seen on the ultrasound screen—these are the follicles that have reached the developmental stage where they are vying to be the dominant follicle that’s ovulated that month.

The person (either sonographer or doctor) doing the ultrasound will count the number of small follicles they see—that number is the AFC.

Just like the other two markers of ovarian reserve, AFC doesn’t give a window into egg quality or the chance of becoming pregnant spontaneously.

A low AFC is generally predictive of a poor response to fertility medications. If there are six or fewer follicles, that’s often associated with a low egg yield in IVF.

There is some variability in AFC between cycles—but—it’s entirely possible that this can be attributed to the difference between different sonographers—some might be very stringent in what they count towards AFC while others might count anything that looks like it could be a follicle.

Evaluating Fallopian Tubes

Fallopian tubes are crucial to getting pregnant naturally or with fertility treatments—with the exception of IVF. So unless you know that you're going to be doing IVF, evaluating the tubes is part of a standard fertility evaluation.

There are three options for seeing if the tubes are open; unfortunately, none are perfect, and none tell us if the tubes actually work like they should. The first, and most widely used test, is called a hysterosalpingogram or HSG.

HSG

HSG is usually a first line diagnostic; the test is performed between days 4 and 10 of the menstrual cycle. Most clinics do this test in-house which is likely better than going to an outside radiologist—typically radiologists have less experience with pelvic exams than a clinic focusing on reproductive interventions.

For this test, a woman has dye injected through her uterus and fallopian tubes while x-ray images are taken. On the positive side, it's good at showing if the tubes are open, and it's both diagnostic and therapeutic. So women who have their tubes flushed are nearly 3 times more likely to get pregnant the following month than similar women who don't have their tubes flushed. Another benefit is that you get a limited view of the uterus at the same time.

The negatives are that it's pretty painful, and it can incorrectly diagnose the status of the tubes. Tubal blockage is misdiagnosed a little more than a third of the time, and when tubes are thought to be open, HSG can be wrong about 15% of the time. Finding blockages right where the uterus meets the tubes can be more challenging, and this can lead to more incorrect diagnoses.

HyCoSy

Another option is the hysterosalpingo contrast sonography or HyCoSy. This is basically a pelvic ultrasound where a liquid containing bubbles fills the uterus and an ultrasound shows the bubbles going through the tubes if they're open.

The positives are that it's a bit less painful than the HSG, and you can do a 3-D ultrasound at the same time which will show the muscular part of the uterus. The negative is it's more dependent on the experience of the person who's doing the test.

Chromotubation

Finally, chromotubation is looking at the tubes during a laparoscopic surgery. It's the most accurate way to evaluate the tubes, but it's too risky to do it unless you're already having pelvic surgery for another reason.

Evaluating the Uterine Cavity

There are a few methods for evaluating the uterine cavity, and different doctors and clinics are often partial to one over another, usually because they choose to offer a particular test in-house. Some of these methods show the inside of the uterus, or the cavity, and others can also show us the outside of the uterus.

Hysteroscopy

First, there's a diagnostic hysteroscopy. For this test, a fiber optic camera actually goes into the uterus, allowing the doctor to see directly inside the uterine cavity. This is the only way to definitively diagnose some abnormalities because you can actually see them directly inside the uterus.

Sometimes there is anesthesia and sometimes there’s not—it depends on the clinic. If there is anesthesia and the procedure happens in an operating room, some small issues can be treated during diagnosis, like removing small polyps.

Two downsides to a diagnostic hysteroscopy: it doesn't show us the outside of the uterus, and it’s expensive. Some doctors view this test as an overkill for a first-line look at the uterus if there aren't other red flags.

Saline Sonogram

Next, there's a saline sonogram. This is where saline is injected into the uterus, and a transvaginal ultrasound is performed.

It shows information about the shape of the uterus, can identify problems like fibroids or polyps, and it's possible to do a 3-D ultrasound at the same time.

HSG

Finally, the HSG which you might already be doing to look at the fallopian tubes, can give us some information about the uterus. For example, it can uncover congenital anomalies like a T-shaped uterus or a unicornuate uterus. The downside is that an HSG doesn't provide a ton of detail, and you can’t see the outside of the uterus.

If an HSG raises any questions, there will probably need to be a follow-up with a hysteroscopy or a 3-D ultrasound.

Evaluating Sperm

We've spent a lot of time focusing on female fertility, but male factor infertility is actually entirely responsible for 30% of infertility cases. And half of the time, it's at least a contributing factor. We have a spectacular course devoted just to male factor infertility, and we suggest you give it a look. One of our best lessons in the course is on diagnosing male factor infertility. But while you're here, let's cover some of the basics in the male fertility work-up.

The first-line diagnostic for male factor infertility is a semen analysis. A semen analysis provides a good overview of sperm production. Before doing a semen analysis, abstinence is suggested for between two and five days. Men typically give a semen sample at a fertility clinic, and the clinic's onsite andrology lab will process the sample.

Sometimes clinics will let you collect a sample at home and bring it in, but it's usually done at the clinic. It's important to make sure you get everything in the cup or you could get an inaccurately low count. If you miss some, make sure to tell the clinic.

A semen analysis focuses on a few key areas of sperm, the concentration which is the amount of sperm produced within a milliliter of semen, the morphology which is the percentage of sperm that are of the correct shape, and the motility which is the percentage of sperm that can swim forward. Doctors will use that information to calculate something called the total motile count or TMC. To calculate the TMC, the concentration is multiplied by the motility and then multiplied by the volume or the number of milliliters of semen produced.

This information is roughly used to decide which treatment might be necessary. For example, most doctors think that if a TMC is 20–40 million per milliliter, a man can conceive naturally. If it’s in the 3–5 million range, it’s very unlikely naturally, but might be possible with IUI. Below that range, a doctor may suggest moving right to IVF since with these numbers, natural pregnancies happen less than 1% of the time.

That said, if anything looks abnormal on a first semen analysis, it definitely makes sense to repeat the test because there is a lot of variability between semen analyses. One study by Agarawl looked at one man's samples over 36 days. His sperm counts ranged from 50 million to 200 million per milliliter and his motility ranged from 55% to 85%. So there's some natural variability each time—the test is also very subjective.

Results can also differ between laboratories—with less experienced labs having 2.9x more variability with counts than experienced labs. So it's best to have this test done at a fertility clinic or a lab that specializes in male fertility testing.

In addition to the semen analysis, evaluating a male’s comprehensive history like lifestyle factors, exposures to current or past toxins, and even the medications he’s taking can be incredibly valuable. Be sure to bring up these topics with your RE or reproductive urologist.

In some cases, a sperm DNA fragmentation analysis can be ordered when IVF has resulted in no pregnancy or unreasonably low fertilization rate. The sperm are subjected to stress and the DNA’s susceptibility to fragmentation is observed. A high percentage of fragmentation seems to correlate with lower implantation and pregnancy rates. There is still debate on how to move forward with the findings of this test, so it’s not the first line of diagnostics, but is something used selectively.