The simple answer is yes. Approximately 10 to 15 percent of couples experience infertility, with more than half of these cases being due to an underlying genetic issue. Licensed genetic counselor Betsy Swope answers all your questions.

 

By Betsy Swope, MS, LCGC

Can I inherit genes that will make it harder to get pregnant?

The simple answer is yes. Approximately 10 to 15 percent of couples experience infertility, with more than half of these cases being due to an underlying genetic issue. In these instances, the genetic cause could have been inherited. However, infertility is a complex condition, and most cases are not due to a specific known inherited cause.  

Are there specific genes that are known to be tied to fertility?

Changes in the structure of our chromosomes (epigenetics), as well as genetic variants within the genes on our chromosomes, can stunt sperm or egg development or significantly impact the chances for an embryo to implant or develop within the uterus.  

Many individuals that have chromosomal rearrangements (inversions, translocations, duplications) are healthy as their chromosomes contain all the genetic information they need. Although these structural changes can happen by chance, they can also be passed down through generations. Individuals with chromosomal rearrangements have an increased risk of conceiving a pregnancy with too much or too little chromosomal material. 

Additionally, there are some genetic syndromes that can impact fertility, such as cystic fibrosis (CF), congenital adrenal hyperplasia (CAH), and Fragile X syndrome. Individuals with a personal or family history of these conditions may have impacted fertility due to reduced or absent sperm (such as males affected with CF) or premature ovarian failure (POI) (in some females that are carriers of Fragile X). Of note, typically when a person has one of these conditions, they exhibit other symptoms as well; therefore, an otherwise healthy individual is unlikely to be diagnosed with one of these conditions. 

Finally, changes in genes associated with primary infertility are being discovered, but their potential effect and inheritance are still being researched. 

If my mom had difficulty getting pregnant, will I? If my husband's parents had trouble getting pregnant, will I? 

Certain conditions can make it more difficult for one to get pregnant, and having these conditions in your family history can influence your own fertility.

It all depends on the actual cause of infertility in your family. We know that certain conditions can make it more difficult for one to get pregnant, and having these conditions in your family history can influence your own fertility. The genetics of some of these conditions are not completely understood and are influenced by multiple factors, including the environment, genetics, and other acquired factors. In many cases, there are multiple genes involved (called a polygenic trait), so it is difficult to identify the specific genetic cause. Some examples include polycystic ovary syndrome (PCOS), endometriosis, uterine fibroids, and POI. If either your mother or your sister had endometriosis, then the risk that you will also develop the condition is about five to seven times greater than someone without this family history. In addition, research has found that in 10 to 15 percent of individuals diagnosed with POI, an immediate family member was also affected with the condition.

If my mom was able to have a child later in life, does that mean I will be able to?

Not necessarily. Being part of a ‘fertile family’ doesn’t necessarily mean you will be fertile as well. Our personal age is one of the most relevant predictors of fertility. Females are born with all of their eggs, and as they get older, their eggs age along with them. As expected, women experience a natural decline in fertility as they age. The age and speed at which eggs decline likely has a genetic component.   

What data do we have around fertility and genetics? Have there been any landmark studies?

In reproductive medicine, genetic testing is commonly used to screen individuals to see if they are carriers of genetic conditions that could affect their children. It is also used to screen embryos for chromosomal conditions prior to implantation (preimplantation genetic testing) in order to increase success rates for pregnancy. To date, however, genetic information has not been widely used to identify individuals at risk for infertility. This is mostly due to the fact that infertility is a complex condition, and an approach to identify a single genetic cause is very difficult. Fortunately, there has been an increase in published studies over the past decade reporting evidence that genetic factors can influence fertility. Genome-wide association studies search all of a person’s DNA for small variations that occur more frequently in people with a particular condition, in this case infertility, than in people without the condition. The data emerging from these studies are promising and have identified genes that are known to be involved in reproduction. These landmark studies have been imperative in identifying variants in genes that can influence our risk of developing conditions such as PCOS, endometriosis, and POI.  

What predictive fertility tests can and should I take? What are the downsides of those tests?

There are a number of tests that are available that can potentially predict one’s fertility and help to guide your fertility timeline. Some of these tests are hormone based, whereas others involve testing genetic markers. Hormone-based tests typically measure levels of anti-mullerian hormone (AMH), follicle-stimulating hormones (FSH), and other hormones. Measuring these hormones can help determine the number of eggs females may have left in their available ovarian pool. However, the American Society of Reproductive Medicine (ASRM) has warned of an increase in false positives for hormone-based tests when performed in low-risk populations.   

Other types of testing look at genetic markers, or indicators, that have been associated with reproductive factors such as POI, recurrent pregnancy loss, endometriosis, or implantation failure. These genetic tests use prediction models to help determine the odds or likelihood that you would develop a certain reproductive condition, though the results of these tests can be difficult to understand without counseling. For example, a result may indicate that you are five times more likely to develop POI. In order to understand your  chance to develop this condition based on this result, you must first know the population risk to develop POI. In talking with the appropriate medical professional, you would learn that POI is rare in the general population, with an estimated incidence of 1 in 1000. Therefore, with this result, your risk to develop POI is 1 in 250 (or 0.5%). This example is meant to show that just because a result predicts an elevated relative risk for a condition doesn’t mean that your absolute risk will be staggeringly high. The main purpose of these screenings is to identify persons at risk for disease in order to guide your doctor to additional tests and evaluations. Because genetic risk can be challenging for patients to understand, it may be beneficial to speak to a genetic counselor both before and after these tests are performed.

What questions should I ask my doctor to better understand the genetics of  female fertility?

If you have questions regarding your fertility, you may want to discuss your concerns with your obstetrician-gynecologist. (Read Dr. Shah’s post, How to Know When It’s Time to See a Fertility Specialist). The American College of Obstetrics and Gynecology (ACOG) and ASRM have recently published guidelines regarding the initial work-up that should be performed by your doctor if infertility is suspected. This workup includes obtaining a medical history, physical examination, and additional tests that evaluate ovarian reserve, ovulatory function, and structural abnormalities. 

It is important to have a good understanding of your family history of both women’s health  and fertility outcomes. Ask your doctor at these appointments if your family history is concerning, and if there are any available genetic tests or evaluations you should consider to determine if your own fertility could be at risk. If genetic testing is recommended, ask how accurate the testing is, and if it is only predicting your risk or diagnosing a specific condition. Additionally, ask what type of follow-up testing or evaluations would be performed in light of a positive or increased risk result.  (Read Dr. McQueen’s post, Preparing for Your First Fertility Clinic Appointment for more.) 

How can the genetic counselors at Genome Medical play a part in understanding my fertility?

Genome Medical is a nationwide practice of genetic experts that can assess your concerns regarding your family history and discuss the potential benefits of genetic testing. A Genome Medical genetic counselor will interpret your personal and  family history and genetic test results into a clinical action plan for your doctor. Lastly, Genome Medical can support the entire family and help them understand the impact of their family health information as well.

 

Betsy Swope, MS, LCGC, is a licensed and certified genetic counselor with more than 18 years of experience and has been Genome Medical’s reproductive services lead for the past two years. She previously worked at the University of Michigan, the University of North Carolina, and Progenity, Inc.

 

Photo by Daniel Dorsa.