Infertility is a loaded word. Being diagnosed with it isn’t simple either. There are many causes or contributing factors to fertility problems, and in many cases, there are multiple issues to contend with, which we'll cover in this article.
Infertility is one of the most internet-searched medical conditions because patients often feel confused and alone. Maybe you’re dealing with multiple diagnoses, which can mean several different healthcare providers who may or may not agree on your treatment plan. Or perhaps both partners have fertility challenges, and diagnoses are accumulating faster than solutions.
The bottom line is that educating yourself as a patient can give you more clarity in asking your doctors’ questions and finding a clear path forward. In this blog post, we’ll overview ten common causes of infertility.
What is Infertility?
Infertility can mean many things, but the actual medical definition is being unable to get pregnant after a year of trying to conceive (or, after six months if you’re a woman over age 35).
However, men can also be diagnosed with infertility, as can women who get pregnant but have recurrent miscarriages. To make matters more complex, women who have already had a child but have trouble conceiving again can be diagnosed with something known as secondary infertility.
Women and men are equally as likely to struggle with infertility. (1)
Overall, one-third of infertility can be attributed to women’s health issues and one-third to men’s health issues. The last third is either a combination of issues between both partners or unexplained factors that can’t necessarily be tied to either partner specifically.
The manner in which infertility is treated depends on the cause and the factors contributing to it. There can be physical causes, hormonal causes, genetic factors, immunological triggers, and more. Treatments aim to resolve the problem(s) and lead to a successful pregnancy outcome.
Of course, treatments themselves can be stressful and don’t come with guarantees. This leads many patients here: internet-searching or doing their own research to try to get ahead in understanding and solutions. Surprisingly, sometimes patients can be given one diagnosis as if it’s the only issue, only to find out down the road that something else was the bigger issue all along.
Being a proactive patient in the infertility world is often required, primarily because you know your body better than anyone else.
Understanding the conditions you’re asking about can improve your communication with doctors and healthcare providers, leading to overall better results and faster interventions.
10 Causes of Infertility
There are many triggers for infertility, and no single blog post could cover them all. These are the most common conditions and diagnoses that are associated with trouble conceiving or staying pregnant.
Women’s infertility issues tend to come down to a few key categories: physical problems, hormone-related problems, immune issues, or other factors that can decrease fertility, like getting older.
Men can deal with the same types of problems, though for the purposes of this post, we’ve condensed male fertility factors to one section, and will look more closely at the most common causes of female infertility first.
1. PCOS (Polycystic Ovary Syndrome)
Polycystic ovary syndrome is a hormone-driven condition that, confusingly, doesn’t even necessarily involve cysts. You can also have cysts in your ovaries and not have PCOS.
PCOS occurs when there is an imbalance between estrogen, progesterone, and testosterone.
It leads to ovulation problems and irregular menstrual cycles. Since you can only get pregnant after ovulation, not being able to naturally and regularly ovulate can significantly impact the ability to get pregnant.
PCOS is not always easily diagnosed, nor is there a single definitive cause, although genetics, other hormone-related conditions, and inflammatory processes may play a role. (2, 3)
The most common signs of PCOS are:
- Missed or irregular periods
- Excessive hair growth on face, back, arms
- Acne
- Weight gain or trouble losing weight
- Frequent headaches
PCOS is typically diagnosed when a woman has at least two of these factors: irregular periods, high levels of androgen hormones, and/or cysts in the ovaries. In spite of the name, you can have PCOS without having cysts if you have the other two factors.
Treatment for PCOS often includes medications that help to normalize hormone levels, including those that balance insulin and glucose. (4) Ovulation triggers may be used to normalize a cycle for conception. In vitro fertilization (IVF) may also be recommended for women with other factors or who are older.
How does MTHFR affect risk for PCOS? Depending on ethnicity, it can lead to an increased risk, decreased risk, or no change in risk. A meta-analysis of 14 studies concluded that MTHFR C677T: (5)
- Decreases the risk of PCOS for Caucasians
- Increases the risk of PCOS for Asian people
- Does not alter or affect the risk for people of Middle Eastern descent
2. Endometriosis
Endometriosis is a condition where the tissue that lines the inside of the uterus may appear and grow where it is not supposed to be. This can occur on the outside of the uterus, the ovaries, fallopian tubes, and even the intestines. Endometriosis causes symptoms like heavy and severe periods, back pain, and cramping. It is a common cause of infertility, and as many as 11 percent of women of reproductive age may have it. (6)
What causes endometriosis has not been established, although theories revolve around cellular changes that may be driven by structural problems, immune disorders, or genetics.
Variants in the MTHFR and PEMT genes, as well as in others that control folate and choline metabolism, may play a role in the development of endometriosis. (7)
Running a home genetic test can give you insights into your MTHFR, PEMT, and other important fertility- and health-related genes.
When it comes to treating endometriosis for infertility, it depends on the severity of the disease. Some women may be able to conceive without assistance but may be prone to higher miscarriage risk. Women with more severe endometriosis may require IVF.
Adenomyosis is another type of uterine tissue abnormality that involves the thickening of the uterine lining. This happens because the endometrium, or inner lining of the uterus, grows into the myometrium, the outer muscular layer. It has many of the same symptoms of endometriosis, and may also be associated with infertility. (8)
3. Fibroids
Fibroids are non-cancerous growths that can occur inside or on the uterus. The cause of fibroids is not known, but they are common. As many as 80 percent of all women will have one or more by the time she is 50 years old. (9) Fibroids can come and go on their own. They can also grow or shrink based on numerous factors. Not all fibroids that occur need to be medically addressed.
For some women, fibroids can be a contributing factor to infertility.
They may require surgical removal, depending on where they are located. Some fibroids may also interfere with sperm implantation or may increase the risk of pregnancy loss.
Risk factors for fibroids include having a family history of them, being older than age 30, being overweight, and being African-American. Pregnancy can also increase the chance of growth or development of fibroids because of the higher estrogen levels.
Small fibroids that come and go on their own may produce no symptoms. When fibroids are a problem, they will likely produce symptoms that may include: (10)
- Heavy, clotty periods
- Lower back pain
- Painful intercourse
- Abdomen pressure or pain
- An enlarged abdomen that may even appear pregnant
Fibroids can typically be seen on ultrasounds, so if they’re contributing to your infertility or problems getting pregnant, they will likely be discovered by your OBGYN or fertility specialist.
Fibroid treatment depends on the severity and location. Smaller ones may be treated with lifestyle adjustments like yoga, stress management, weight loss, and/or dietary changes. Eating more vegetables and fiber can help. Mayo Clinic also notes that vitamin D deficiency may contribute to fibroids, as well as a diet that is higher in red meat and lower in vegetables and fruits. (11) Alcohol intake can also influence fibroid growth and development.
4. Physical Problems with Fallopian Tubes, Ovaries, Uterus, or Cervix
Any type of physical abnormalities with the structure or position of the uterus, fallopian tubes, cervix, and ovaries can influence the ease of conception. Previous complications can also influence the structure and function of reproductive anatomy. These can include losing a fallopian tube to ectopic pregnancy or having scars from previous surgical procedures, including C-sections.
A healthy pregnancy relies on fertilization and implantation.
Most of these physical problems affect whether or not an egg can be properly released and fertilized, or they influence how well an embryo can implant and grow into the uterine lining.
According to the CDC, pelvic inflammatory disease and other infections can also lead to blocked fallopian tubes. These can include sexually transmitted infections (STIs) like gonorrhea and chlamydia. (12) Endometriosis can be another cause of blocked fallopian tubes.
Assisted reproductive technology (ART) is often needed for overcoming physical reproductive system problems. IVF is often a solution for structural or physical challenges that prevent pregnancy since these can present barriers that cannot be overcome by diet, lifestyle, or other forms of treatment.
5. Thyroid & Other Female Hormone Problems
Fertility relies heavily on several hormones: estrogen, progesterone, testosterone, and also thyroid hormones. Any imbalance in these hormones can lead to trouble getting or staying pregnant.
The thyroid regulates metabolism, but it’s also essential for maintaining fertility and regulating a healthy pregnancy. Thyroid hormones that are too low or too high can lead to infertility, miscarriage, and pregnancy complications, including intrauterine growth restriction (IUGR). Thyroid hormones also contribute to your other hormones working in balance, so a thyroid problem becomes a systemic hormone problem in a hurry.
Low thyroid hormones and other related factors may be responsible for up to 12 percent of all miscarriages. (13)
One study found that more than 53 percent of infertile women were hypothyroid. After being treated with levothyroxine, or thyroid hormone replacement, more than 33 percent went on to conceive within 6 weeks to 2 years. (14) That study only assessed TSH, or thyroid-stimulating hormone.
When other factors are taken into account, the thyroid could be more thoroughly assessed earlier in the process of seeking fertility help. For example, testing thyroid antibodies could help determine if a thyroid issue is rooted in autoimmunity. Checking free T3 and free T4 levels can identify the degree of hypothyroidism or thyroid hormone imbalance, and can even help to identify whether a woman has too much thyroid hormone.
Optimal fertility requires a balanced thyroid.
Not all fertility specialists will do a full thyroid workup as part of fertility treatments, so it’s worth asking your healthcare provider. If you’re already getting a full assessment to determine what’s causing your infertility, you might as well make sure your thyroid is in optimal shape. If it’s not, addressing it sooner rather than later can shorten your time to conception. (15)
6. Advanced Maternal Age and Premature Ovarian Failure
Aging impacts female fertility. Women are born with all the eggs they’ll ever have, and by the time they approach their early 40s, egg quality starts to decline. Unfortunately, some women can experience a more pronounced decline when they’re younger, and this can be known as premature ovarian failure.
Whether the cause is advanced maternal age or premature ovarian failure, egg quality is an essential part of leading to a healthy pregnancy. However, you’re not doomed to the inability to conceive even if your egg reserve is low.
Myo-inositol and melatonin have been studied as ways to support egg quality, even in women of advanced maternal age. (16) While studies show mixed results, it’s impossible to ignore the fact that individual factors such as methylation status, lifestyle, stress, diet, and nutrient status could impact egg quality.
It takes roughly 90 days for an egg to mature before fertilization, so optimizing your health—especially during this window—can support an overall better chance at a healthy pregnancy.
In spite of the irritating terminology of being at “advanced maternal age” when you’re 35 or older, it’s not true that fertility falls off a cliff for everyone. Your own factors will create your own fertility profile, and that’s why it’s important to work with a practitioner who will view you from a complete perspective, not just someone who is treating one aspect of your health.
7. Blood Clotting Disorders & MTHFR
Blood clotting disorders may play a role in infertility or recurrent miscarriages. Some of them are genetic, while others have roots in autoimmunity. Clotting disorders may not be known prior to infertility treatment or investigating the cause of recurrent pregnancy loss.
The primary reason that clotting problems are associated with trouble conceiving is that they can change the way that the uterine blood supply interacts with the embryo, or they may cause problems with early implantation or the formation of the placenta. They can cause problems later in pregnancy, too, if subchorionic hematomas develop.
Types of clotting disorders include: (17)
- Antiphospholipid syndrome
- Sticky platelet syndrome
- Tissue plasminogen activator deficiency
- Factor V Leiden
- Elevated levels of PAI-1
- Elevated lipoprotein(a)
While MTHFR in and of itself is not a clotting disorder, those who have MTHFR variants that are not well-controlled can lead to elevated levels of homocysteine. When homocysteine is high, this can lead to blood vessel changes that may increase the risk for clot formation. (18) Research does find that MTHFR variants can lead to clotting problems even when they’re present in the father, so if both parents have polymorphisms, the risk may increase.
Some doctors don’t automatically consider MTHFR or methylation status, but since this is crucial in embryo formation and growth, it should be considered in anyone who is struggling to get or stay pregnant.
While clotting problems can sound scary, they can be successfully treated in many cases. Women who have clotting disorders are often given low-dose aspirin and/or blood thinners like heparin or enoxaparin (Lovenox). More than 98 percent of women who have infertility due to these factors will go on to carry a healthy term pregnancy when treated with blood thinners. (19) Supporting healthy methylation by avoiding folic acid and taking methylated folate may also play a role in supporting healthy homocysteine levels and overall fertility.†
8. Recurrent Pregnancy Loss (RPL)
Overall, one or two percent of women may experience what is known as recurrent pregnancy loss, or RPL. This means the loss of three or more consecutive pregnancies, although some experts expand it to include back-to-back miscarriages. (20)
Infertility includes recurrent miscarriage because the ability to conceive does not guarantee the ability to carry a pregnancy to term.
If you can easily get pregnant but can’t stay pregnant, there are fertility experts who will investigate this and seek to find answers to help you maintain a healthy pregnancy.
Recurrent miscarriage can happen for many reasons, including:
- Genetics
- Blood clotting disorders
- Poor embryo quality (which could include sperm and/or egg factors)
- Chromosome abnormalities
- Structural or physical problems with the uterus
When it comes to recurrent loss, there is not one single test to run, but a whole plethora of factors to investigate in both partners. Still, there are experts who primarily investigate this type of infertility, and even with many miscarriages, most women who experience miscarriage will go on to carry a healthy pregnancy to term. (21)
9. Secondary and Unexplained Infertility
The ambiguous infertility diagnoses—secondary infertility or unexplained infertility—are undoubtedly some of the most frustrating. How do you fix something if you don’t know what’s causing it?
Secondary infertility occurs when a woman has already successfully had one child but struggles to conceive or carry another to term. In many cases, secondary infertility is not actually unexplained, and investigating the above reasons usually leads to a diagnosis. Women who’ve already had babies can develop thyroid problems, PCOS, fibroids, or other hormone problems that may affect future fertility.
As many as 15 to 30 percent of infertile couples may receive a diagnosis of unexplained infertility, but this only means that straightforward causes have been ruled out. (22) This does not mean that there are no answers to be found.
Unexplained infertility is more challenging because, in essence, it means all typical avenues have been investigated, and no clear answers have been found. If you’re in this position, make sure that your providers have fully investigated things like methylation, MTHFR, and clotting factors, since these are not always part of a typical infertility workup. Even a full thyroid assessment is often not part of a fertility assessment.
If someone says they don’t know how to help you, that only means that they don’t know how to help you. A second or third opinion can often yield different insights or results, so don’t be afraid to find someone who is willing to do a deeper dive into your and your partner’s fertility.
10. Male Infertility Factors
Men can experience infertility just like women. It generally comes down to physical or hormonal abnormalities, but genetic variants may also play a role.
Common diagnoses for male factor infertility include: (23)
- Low sperm count
- Low sperm movement (motility)
- Problems with sperm production
- Problems with the shape of the sperm (morphology)
- Varicocele (enlarged veins that lead to blockages which may decrease sperm quality and volume)
- Other physical factors that involve the testicles and testicular function
- Low testosterone levels
Male infertility is, in some ways, more straightforward to investigate and treat since there are fewer components. In women, the causes can be physical, hormonal, or genetic but can also be related to implantation, which can be harder to investigate.
No man wants to find out that he may have fertility problems, but women don’t want to either.
For too long, the burden of infertility has been more heavily placed on women, yet research shows that male fertility factors are just as important when it comes to investigating conception challenges.
Even recurrent miscarriages are attributable to the father’s health, too, so sperm does play a role that goes beyond the moment of conception. (24)
MTHFR and other genes can also play a role in male factor infertility. A meta-analysis of 26 studies found a significant association between MTHFR C677T and several common male factor infertility diagnoses. (25)
It’s not just that one variant, though. Being homozygous for MTHFR A1298C can be an elevated risk factor for men who have little or no sperm in their semen. (26) Having the MTHFR C677T variant has also been found in men with oligoasthenoteratozoospermia (OAT), a condition in which sperm are found in low numbers along with abnormal shape and motility. (27) Any type of defective methylation can be associated with elevated sperm measurements that are associated with male infertility, the recommended therapeutic approach for which is methylated folate.† (28)
Risk factors for male factor infertility include:
- Age
- Methylation status
- Heavy alcohol use
- Cigarette smoke or exposure
- Marijuana exposure
- Being overweight
- Regular exposure to toxins, chemicals, or pesticides
- Hormonal imbalances
- Side effects of certain medications (such as certain medical treatments, blood pressure medications, steroids) and illegal drugs
There are many ways to test for male infertility, but the most common starting points are semen analysis and lab work to check for testosterone levels or related factors. You can also get MTHFR tested via blood or saliva.
If trouble conceiving is caused by male factors alone, some treatment options may include IUI (intrauterine insemination), ICSI (intracytoplasmic sperm injection), or IVF. Addressing other factors like hormones or methylation can be done with medications and supplements. Diet may also play a role, as well as lifestyle changes, especially when it comes to alcohol, cigarette exposure, and chemicals.
The Bottom Line
If you’re struggling with infertility, don’t give up hope. You may need to seek advice from multiple healthcare practitioners before finding one (or more) people who can evaluate you and find the root cause of your infertility. There are many factors that can contribute to infertility, including physical, hormonal, genetic, and structural disorders in both men and women. Seek out an MFM (Maternal Fetal Medicine) doctor, an RE (Reproductive Endocrinologist), or an OBGYN who specializes in infertility or recurrent pregnancy loss. While not every infertility journey ends in an expected way, there are many ways to become a parent or find a happy ending.
References
- https://www.womenshealth.gov/a-z-topics/infertility
- https://pubmed.ncbi.nlm.nih.gov/19910321/
- https://www.sciencedirect.com/science/article/pii/S2213596016300447#bb0010
- https://www.mayoclinic.org/diseases-conditions/pcos/symptoms-causes/syc-20353439
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601750/
- https://www.womenshealth.gov/a-z-topics/endometriosis
- https://pubmed.ncbi.nlm.nih.gov/21429654/
- https://www.mayoclinic.org/diseases-conditions/adenomyosis/symptoms-causes/syc-20369138
- https://www.womenshealth.gov/a-z-topics/uterine-fibroids
- https://www.mayoclinic.org/diseases-conditions/uterine-fibroids/symptoms-causes/syc-20354288
- https://www.mayoclinic.org/diseases-conditions/uterine-fibroids/symptoms-causes/syc-20354288
- https://www.cdc.gov/reproductivehealth/infertility/index.htm
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603072/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481657/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5961023/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019888/
- https://pubmed.ncbi.nlm.nih.gov/10898270/
- https://rarediseases.info.nih.gov/diseases/10953/mthfr-gene-variant/cases/36452
- https://pubmed.ncbi.nlm.nih.gov/10898270/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709325/
- https://www.mayoclinic.org/healthy-lifestyle/getting-pregnant/in-depth/pregnancy-after-miscarriage/art-20044134
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2505167/
- https://www.mayoclinic.org/diseases-conditions/male-infertility/symptoms-causes/syc-20374773
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610348/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368707/
- https://pubmed.ncbi.nlm.nih.gov/20935396/
- https://pubmed.ncbi.nlm.nih.gov/16247718/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633564/
† This information is for educational purposes only. No product results are implied.