Fertility specialist Dr. Kolbe Hancock of Spring Fertility covers everything you need to know about diminished ovarian reserve (DOR), including causes, symptoms, diagnosis, and treatment options.

 

By OBGYN and fertility expert Dr. Kolbe Hancock of Spring Fertility

Diminished Ovarian Reserve might sound scary, but please know that a DOR diagnosis does not mean that you’re infertile. If you are young (under 35 years old) and regularly ovulating, your chance of getting pregnant is similar to someone with a “normal” egg reserve. If you are undergoing fertility treatments with DOR, you have options! Let’s break it down below.

What exactly is ovarian reserve?

Your ovarian reserve refers to the number of eggs you have remaining in your ovaries.

Females are born with all the oocytes (aka eggs) that we will ever have. When we are in our mother’s belly, our own little baby ovaries have the maximum number of eggs. We are then born with about two million eggs, and by the time we get our first menstrual period, this number has dropped by about 75% to 500,000 eggs.

Throughout our reproductive years, we progressively lose eggs each month to the point where there are around 1,000 eggs left by the time we reach menopause. How fast we lose eggs during our reproductive years can be unpredictable, but we know for certain that progressive loss occurs.

“Diminished” ovarian reserve is when there are fewer eggs in your ovaries than the average for women your age, and in some cases, you may also lose oocytes at a faster rate. Men have a very different circumstance. They have sperm stem cells in their testes that continually produce sperm every three months from puberty onwards. Unfortunately, women have no such equivalent stem cells, so our egg reserve is finite.

How do we measure ovarian reserve?

Each month, your ovaries offer up a new cohort of eggs for a shot at pregnancy, whether you are actively trying to conceive or not. Your brain secretes hormones which act like food for your eggs to grow and mature, but the brain only secretes enough of this hormone “food” for one egg. The result is that one egg grows and ovulates, and that’s why we humans generally have one baby at a time (as opposed to other species who have litters of babies).

As for the other eggs from the cohort that month? They essentially starve from lack of hormone “food” and then disappear. So, there are actually a ton of wasted eggs each month. I know, this sounds a bit like the Hunger Games, but your body is frugal, meaning if you have a low egg reserve, your ovaries can sense that, and they will offer up fewer eggs per month in an effort to protect their reserve. This is actually one of the ways we measure ovarian reserve. We do an ultrasound early in the menstrual cycle and see how many eggs the ovaries are offering up. If they are offering up a lot, they have a robust reserve. If they are only offering up a few, they likely have a low reserve. This is called your antral follicle count, more commonly abbreviated to AFC.

Another marker to measure ovarian reserve is called Anti-Mullerian Hormone (aka AMH), which is a blood test. All of the very small eggs waiting to be offered up in the ovary each secrete a small amount of AMH into your bloodstream. Your AMH stays steady throughout the menstrual cycle, so we can read AMH levels through a blood draw at any point in a month.  However, it may be inaccurate if you are on oral birth control pills. If this is the case, you may have a falsely decreased AMH which is completely reversible if you discontinue the pill.

The last indicator of egg reserve is called Follicle Stimulating Hormone (aka FSH) which is basically just the hormone “food” that the brain sends down to the ovary to recruit one of the follicles that the ovaries have offered up that month. If the egg reserve is low, and the ovaries are working hard to hold onto them, the brain has to send out more food to entice the follicles out of the ovary. So, ultimately seeing a high FSH read early in the cycle means that the egg reserve is low.

How does ovarian reserve impact fertility?

So if you only need one egg, why does it matter if you have 200 or 20,000 eggs left? Good question! There is an important difference between egg quantity and quality. Unfortunately, both decline with age, and they actually follow different patterns. As we discussed earlier, egg quantity falls in a progressive pattern during our reproductive years. But egg quality is different. Each egg is one cell that contains the genetic information you would pass on to a potential child. 

Egg quality is determined by the structural integrity of the egg and the proper balance of genetic material contained in that egg. We know that egg quality starts to drop in your mid-thirties and then again more sharply around age 40. The reason for this goes back to the fact that your eggs have been in your ovaries since you yourself were a fetus. So your eggs have been exposed to everything that you have—including toxins, radiation, you name it. Time, plus these other factors, take a toll on the egg quality.

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What exactly does this mean? For women under age 35, where the egg quality is good, the chance that the one egg that gets selected is good quality and genetically normal is high. This is a very important fact to understand—low egg reserve below age 35 does not mean you cannot get pregnant. Many women with low egg reserve regularly ovulate good quality eggs and successfully get pregnant.

However, if you are over age 35 with low egg reserve, things can get a bit more complicated. This is because egg quality starts to decline—so the chance that the one egg you ovulate will be good quality goes down, and unfortunately, this is what makes it harder to get pregnant. In Vitro Fertilization (IVF) can often be a solution for women with DOR who are struggling to conceive.

How does IVF work to treat DOR?

When we do IVF, we are not creating new eggs, we’re simply capitalizing on the egg cohort model that I described earlier—the Hunger Games thing. A fertility specialist will work with you to determine the best treatment protocol for your unique biology and will carefully dose you with enough of the egg growing hormone “food” (follicle stimulating hormone or FSH) for all the eggs your ovaries offered up that month to mature and survive. If your egg reserve is low and your ovaries are only presenting with a few eggs per month, then we may get fewer eggs per IVF cycle than someone with a high ovarian reserve

For patients with low ovarian reserve, we have many specialized protocols (read: tricks up our sleeves) to maximize the number of eggs we get on each cycle—no egg left behind! We can also do more than one IVF cycle to stack the numbers in your favor. Lastly, if you know you have low egg reserve and you also know that you will be delaying childbearing for a few years, egg or embryo freezing or banking might be a great option for you. Because we know that both your egg quality and reserve will only go down with time, it makes sense to capitalize on that earlier and bank as many good quality eggs as you think you will need for your family planning goals. To help develop realistic expectations and to estimate the probability of your frozen eggs resulting in a baby, you can find egg calculators online which are based on studies of frozen eggs that have been thawed and how many of those eggs turn into usable embryos or live births.

Are there other non-invasive treatments for DOR?

Unfortunately, we have not found any medications, herbs, or supplements that have been proven to help egg reserve or prevent decline in ovarian reserve. I truly wish there was something we could recommend to our patients (trust me), but nothing has been proven with medical research and data. Certainly, a prenatal vitamin which has all the good stuff including folic acid (folate) is always recommended for any woman of reproductive age, especially those trying to conceive. As it relates to egg quality, CoQ10 is a supplement that has some biologic plausibility. CoQ10 is a cofactor that the egg needs in order to metabolize energy, so it makes sense that it could potentially improve egg quality. There is a small randomized controlled trial from 2018  that demonstrated that supplementing with extra CoQ10 improved the quality of the embryos. The logic here is that because we have no test to determine oocyte/egg quality, we use embryo quality as a surrogate marker since the egg is the main driver of early embryo development. 

What underlying factors impact ovarian reserve?

By now you may be wondering what exactly causes diminished ovarian reserve? For the overwhelming majority of patients who have low egg reserve, a specific cause is not identifiable.  

We think there may be some genetic or heritable component, as proven by similarities between the age at which a mother and a daughter go through menopause. Additionally, there are specific identified genetic mutations that can make your egg reserve low, however, these are exceedingly rare.

Other environmental factors such as oxidative stress from the environment or smoking tobacco products may contribute to diminished ovarian reserve, as well as factors such as radiation exposure, which accumulates over time, and radiation therapy or chemotherapy to treat cancer and other diseases.

Decreased blood flow to the ovary during some types of surgery or removal of an ovary can cause loss of eggs, and we now also suspect that some environmental toxins as well as obesity may have some impact on egg reserve.

What are symptoms of DOR?

There are no overt symptoms of low ovarian reserve; often women get normal monthly menstrual cycles and don’t ever know about it unless they see a fertility specialist as they are having trouble getting pregnant or want to freeze their eggs. So it is a bit hard to say exactly how many women have diminished ovarian reserve because we don’t know about many of them. We do know that about 15% of the population has infertility, and of that specific subset, about 20-25% of infertility cases are due to diminished ovarian reserve.

What’s next?

Ok, so now that you are armed with all this knowledge, what should you do? The best place to start is really to think about the big picture: what life or career goals do you have and what is your timeline for that aspect of your life? What are your family planning goals and what is the timeline for that? It’s beneficial to maintain regular care and contact with your gynecologist, who will likely address these topics with you each year at your annual visit as well as review your menstrual regularity, your family history in terms of menopause, and any risk factors for diminished ovarian reserve. A combination of these factors may prompt a consultation with a fertility specialist to determine your egg reserve. If you have been trying to conceive for six to 12 months and you are younger than 35, or five to six months after age 35, you should consult with a fertility specialist.

More than anything, by arming yourself with information on your body and overall fertility, you’re taking the first (and most important!) step in deciding what’s best for you, based on your goals. Knowledge is power, and understanding what options are on the table is an empowering first step to meeting those goals.

 

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 Featured Image by R Khalil

 

Spring Fertility was founded in 2016 with the goal of delivering best-in-class clinical IVF outcomes, while also providing the most supportive, individualized patient experience anywhere. Over the last five years, they’ve grown from a single clinic in San Francisco, to a network that includes 6 clinic locations serviced by three state-of-the-art laboratories throughout the Bay Area, Vancouver, B.C. and now New York City. Spring was founded on the belief that everyone deserves to have a family if they want one. They believe that a “one size fits all” approach doesn’t work in fertility care and opened their doors to provide patients with care that focuses on them. The Spring team is a passionate, dedicated team of leading physicians and scientists, but they’re also spouses and parents and have been patients too.