Oxidative Stress and Unexplained Infertility

Being told “you have unexplained infertility” is one of the hardest realities a couple can face. Not only have those couples been trying for months or, in many cases even years, but now they are wondering if their dream of having a child will ever happen. 

But here’s the thing, unexplained infertility, otherwise known as idiopathic infertility, is actually a controversial term because it is simply a diagnosis of exclusion not a true diagnosis. This means that your doctor, most likely your reproductive endocrinologist, has completed a thorough evaluation and determined that you are ovulating, have unobstructed fallopian tubes (tubal patency), have a normal uterine cavity, adequate ovarian oocyte (egg) reserve and your partner has a normal semen analysis. So in other words, no obvious findings during a routine fertility evaluation were found. That being said, instead of giving patients with “unexplained infertility” no other solution,, we should be digging deeper into some of the possible causes. 

Some of the suspected causes of “unexplained infertility” include subtle changes in follicle development, ovulatory dysfunction, and changes in the luteal phase. Another common cause includes a suboptimal semen analysis. In other words, your partner’s semen analysis showed sperm concentration and motility were considered “normal” but still on the lower end of normal. Other factors we should also investigate include implantation failure, subtle cervical factors, as well as, other sperm and egg interactions concerns.

Although couples with “unexplained infertility” are usually recommended to undergo in vitro fertilization (IVF) treatments, the reality is, not only is this an expensive option, but because we are not addressing the root cause, many couples who undergo IVF due to unexplained infertility, end up experiencing reduced oocyte fertilization and embryo cleavage rates. In other words, they have lower success rates from IVF. This was demonstrated in a recent study that showed that the oocyte fertilization and the embryo cleavage rate for unexplained vs.tubal factor (explained) infertility were 52 and 60 percent, respectively. These results suggested that couples with unexplained infertility likely had subtle functional abnormalities in oocytes and/or sperm function and in a sense, IVF was actually used as a diagnostic procedure rather than a treatment option. 

So, what causes abnormalities in oocyte and sperm function and is there anything we can do to address it? One proposed theory is our environment, specifically oxidative stress seems to have a significant impact on egg and sperm function.. For those who are unfamiliar, oxidative stress is considered an imbalance between pro-oxidant molecules (including reactive oxygen and nitrogen species) and antioxidant defenses found in our body. This oxidative stress has long been known as playing a key role in infertility, especially unexplained infertility, not only in women but men as well. S, this doesn’t only apply to you ladies, but also your partner. The adverse effects of oxidative stress have been well documented to impact both sperm quality and function. In females, although also impactful on reproductive function, the exact mechanism is still unclear. What researchers have found is that not only does oxidative stress in females appears to impact fertility but has been associated with other reproductive diseases including endometriosis and polycystic ovary syndrome (PCOS). Researchers also believe that pregnancy complications including miscarriages, recurrent pregnancy loss and preeclampsia are also associated in response to the development of oxidative stress. 

So what causes this oxidative stress? I am glad you asked. Studies have shown that there are a variety of modifiable factors that impact oxidative stress the most including: extreme changes in body weight (rapid weight gain or loss ), as well as other lifestyle factors such as cigarette smoking, obesity, alcohol use, malnutrition and recreational drug use. And although these are extremely important to avoid, for most of our patients, they don’t smoke, use recreational drugs and they often keep alcohol to a bare minimum. So, what other factors can be impacting oxidative stress and what can we do about it? 

Physiological pathways that use oxygen as a substrate, such as oxygenase reactions and electron transfer (ET) reactions, create large amounts of reactive oxygen species (ROS). Some of the common factors including environmental pollutants and, in theory, other factors including inflammatory and processed foods, stress, malabsorption  and sedentary lifestyles all appear to have an impact on oxidative stress. 

Now although we can’t live in a glass box and avoid all causes of reactive oxygen species, many of the causes of reactive oxygen species can be avoided. Now, it’s also important to discuss the powerful defense our body uses to fight reactive oxygen species, known as antioxidants. Think of antioxidants as scavengers that detoxify our body of excess ROS. 

When it comes to antioxidants, there are two many types: enzymatic and non-enzymatic. Enzymatic antioxidants are unique because they contain a metallic center which gives them the ability to neutralize excess ROS and prevent damage to cell structures. Non-enzymatic antioxidants, on the other hand, consist of dietary supplements and synthetic antioxidants including Vitamin C, Glutathione, Vitamin E, Zinc and Selenium. 

Since non-enzymatic antioxidants seem to improve oxidative stress, could they be considered a treatment for couples experiencing unexplained infertility? Researchers believe it could. 

Now before you go adding antioxidants to your amazon cart, it’s important to remember that although supplements are “natural” and currently over-the-counter, they can be dangerous.This is where adding a licensed functional medicine or naturopathic doctor to your healthcare team is extremely valuable. Proper micronutrient testing helps us better determine exactly what antioxidants you may need. At NMD Wellness of Scottsdale, micronutrient testing is included in our membership for this exact reason. We want patients to receive personalized recommendations based on their unique needs. Once micronutrient testing has been performed, we are more qualified to establish which antioxidants are best and in what form they are most likely absorbed. 

About the Author: Meet Dr. ZenAlissia Zenhausern- Pfeiffer, NMD, FABNE, (commonly known by her patients as Dr. Zen), is a licensed naturopathic doctor board certified in naturopathic endocrinology and the founder of NMD Wellness of Scottsdale, a premier naturopathic medical practice that focuses on helping women to take a proactive approach to their hormone and fertility health. Dr. Zen has been featured as a lead expert in Forbes, Shape Magazine, and Instyle and is deeply passionate about bridging the gap between traditional and natural medicine in the world of fertility. She works with a variety of hormone related issues including PCOS, endometriosis and unexplained infertility. Her goal is to help more women get back into the driver’s seat of their own health to make lasting transformational changes to their health to bring more cute and adorable babies into this world. Read More About Dr. Zen...