5 Things my Fertility Doctors Didn’t Do to Resolve My Unexplained Infertility

Unexplained infertility and recurrent implantation failure are a physical and psychological burden that too many women face in our current society. I can say that I completely understand the grief and misery associated with these conditions because I had endured unexplained infertility for nearly 5 years. I can relate to the frustration of not understanding, of not finding the answers or not becoming pregnant despite being treated by a team of infertility specialists.

After struggling for nearly 5 years, I was able to uncover the underlying factors for my unexplained infertility and become pregnant naturally. Looking back, my fertility doctors overlooked multiple factors which could have explained my unexplained infertility, prevented recurrent implantation failure and otherwise improved my chances with fertility treatments.

Here are at least 5 things my fertility doctors didn’t do to resolve my unexplained infertility, which ultimately led me to recurrent implantation failure.

1. They didn’t consider my thyroid autoimmunity as a factor for my infertility.

When I raised my concerns on the effects of my Hashimoto’s Thyroiditis on my infertility, I was dismissed by my fertility team on numerous occasions. I was told multiple times that TSH was the only critical factor and that it needed to be within optimal range using my levothyroxine (T4) prescription. More erroneously, my doctor told me there were no studies that indicated Hashimoto’s Thyroiditis patients were at greater risk of implantation failure than patients without thyroid autoimmunity.  

Why is it critical to consider thyroid autoimmunity when resolving infertility?

Autoimmune diseases are characterized by the activation of the immune system against one’s self. It is understood as advanced immune dysfunction resulting in tissue damage in the absence of an external threat to the body. There are over 80 defined autoimmune diseases, including thyroid autoimmunity (namely Hashimoto’s Thyroiditis or Graves’ disease).

In clinical practice, thyroid autoimmunity (thyroid antibodies) have been established as co-factors for high levels of NK cell counts which are associated with a pro-inflammatory environment disruptive for endometrial receptivity. In fact, numerous scientific publications have already linked infertility (explained or unexplained) to immune system disorders.

Chronic inflammation is a common underlying cause of infertility, including conditions such as PCOS and endometriosis. The key point to remember is that even hidden or modest, low-grade chronic inflammation can disrupt fertility by driving immune dysfunction and causing hormone imbalances, simply by interfering with signaling pathways and blocking hormone receptors.

2. They didn’t consider my endometriosis symptoms to be a factor for my infertility.

When I raised concerns about past heavy and painful periods and the possibility of endometriosis, I was swiftly dismissed by my medical team. We didn’t spend time talking about the risks or exploring my symptoms in detail. Instead, I was told there are many different stages of endometriosis and that even with the most severe stage, surgery is not recommended because of its associated risks and also, that it does not necessarily lead to an improvement in infertility.

Why is it critical to consider endometriosis when resolving infertility?

Endometriosis is recognized as a complex, chronic inflammatory disease although some health professionals consider the more severe cases of endometriosis as a syndrome or collection of health issues. The inflammatory nature of endometriosis contributes to the formation of scar tissue and adhesions, which can exacerbate symptoms of inflammation and complicate fertility treatments. 

In addition, recent efforts to better understand the pathology have reclaimed endometriosis as a systemic disease which affects metabolism in the liver and adipose tissue, rather than a disease that predominantly affects only the pelvis. A growing number of women with endometriosis have been identified to have underlying health issues such as irritable bowel syndrome, insulin resistance and immune dysfunction or autoimmunity.

In circumstances of silent or mild endometriosis, some patients often disregard or normalize symptoms which prolong proper diagnosis and otherwise induce misdiagnoses. Also depending on the severity of endometriosis, the symptoms may be diverse, overlap and be associated with other conditions. Thus, the diagnosis of endometriosis is not straightforward.

But the point is that all women with endometriosis, at any of its stages, who are seeking fertility treatments are at particular risk for an inhospitable uterine environment which complicates fertility treatments.

3. In the absence of cystic ovaries, they didn’t use my abnormally high AMH to uncover insulin resistance as a factor for my infertility.

Despite the absence of cystic ovaries, my doctors didn’t offer me any consult on the negative implications of my abnormally high AMH level (10.59 ng/mL). We didn’t discuss its association with insulin resistance and PCOS. Instead, I was instructed to proceed with IVF.

Why is it critical to consider high AMH levels when resolving infertility?

Anti-Mullerian Hormone (AMH) is a hormone produced by the granulosa cells in the ovarian follicles, which helps to reflect a woman’s ovarian reserve, or the remaining quantity of eggs in the ovaries. Normally, AMH levels can provide valuable insight into fertility potential. However, an abnormally high AMH level, even in the absence of cystic ovaries like those seen in Polycystic Ovary Syndrome (PCOS), can be concerning.

Elevated AMH levels may indicate conditions such as excessive follicle development or the presence of ovarian tumors. This could lead to potential issues with fertility, as an imbalance in follicle development can disrupt normal ovulation processes and hormonal balance. High AMH levels can also point hyper-responsiveness to fertility treatments like ovarian stimulation, which can increase the risk of ovarian hyperstimulation syndrome (OHSS).

Elevated AMH levels have been found with higher insulin levels and reduced insulin sensitivity, which are key characteristics of insulin resistance. Studies have shown that there is a relationship between AMH levels and insulin resistance, even in the absence of cystic ovaries commonly found with PCOS. Thus, monitoring AMH levels can provide insights into metabolic health and potential insulin resistance, each of which are vital in addressing when restoring fertility.

Understanding and monitoring AMH levels, even when cystic ovaries are not present, is crucial in understanding underlying factors and managing reproductive health problems.

4. They didn’t consider my inflammatory reaction to fertility medications including progesterone suppositories, as a factor for my infertility.

During my fertility treatments, I noticed adverse reactions to prescribed progesterone suppositories over the “two-week-wait” to pregnancy test. My symptoms included a progression of severe fatigue and inflammation characterized by bloating and swelling.

Over the course of several weeks, by Hashimoto’s thyroid (TPO) antibodies had soared from near 500 IU/mL before embryo transfer to nearly 2100 IU/mL on the day I tested negative for pregnancy. After I had stopped the progesterone suppositories, my symptoms cleared and my TPO antibodies reduced after retesting. I asked my physician about the progesterone suppositories and whether those could be inflammatory for me but they insisted that progesterone suppositories had anti-inflammatory effects and were most likely not contributing to the problem.

Why is it critical to consider progesterone resistance when resolving infertility?

Progesterone suppositories are often used in fertility treatments to support the uterine lining and ensure it is prepared for embryo implantation. They are particularly important in assisted reproductive technologies like IUI, IVF and FET.

Failure to response to progesterone (or progestins), otherwise known as progesterone resistance, has been reported by some patients with endometriosis, where progesterone receptors are dysregulated. In particular, the mechanisms behind progesterone resistance include abnormal progesterone receptor signaling, exacerbated chronic inflammation, epigenetic alterations and environmental toxins – all of which have been investigated as potential causes.

In my experience, progesterone suppositories needed for my embryo transfers were actually increasing inflammation and perpetuating a pro-inflammatory environment, inhospitable for embryo implantation. Thus, progesterone resistance can be a substantial risk factor for failure in patients with endometriosis or unexplained infertility who undergo IUI and IVF treatments.

5. They didn’t look for underlying root causes to explain my infertility after failed IUI and IVF transfer.

After struggling with unexplained infertility for nearly 4 years, failing IUI and experiencing recurrent implantation failure after IVF, I asked my fertility doctors what do we do differently? Is there anything that we can do to calm immune system activity if it was affecting endometrial receptivity?

The answers offered to me:

• We do nothing different. We continue to transfer 1 embryo at a time, perhaps 2 at at time at the next round if you are still not pregnant.
• Do you really want to suppress your immune system (sounds silly)? Hashimoto’s Thyroiditis patients have no greater disadvantage for succession rates in implantation, as long as TSH levels are within optimal range.

These answers and the consults I had with my fertility team weren’t helpful to resolve my unexplained infertility, let along uncover any root causes and improve my health.

Insanity is doing the same thing over and over again and expecting different results. None of the answers my fertility doctors offered made any sense to me. Despite this, I continued to seek answers and fortunately, I become pregnant naturally and my son was born healthy.

Key Takeaway

If you are suffering from infertility, explained or unexplained – I encourage you to keep searching for your underlying causes. Understanding the fundamentals principles of health is key to getting started. If you’re interested in learning more about what to look for in uncovering your root causes and where to begin in restoring your fertility, my book is great place to start.

Stay Tuned: My Signature Program on how to restore your fertility, including a 10-part MasterClass on infertility, explained or unexplained is loading!

References

Ulčová-Gallová Z, Mukenšnabl P, Haschová M, Pešek M, Chaloupka P, Lošan P, Bibková K, Mičanová Z, Cibulka J, Švecová M. NK cells not only in endometrium but also in ovulatory cervical mucus in patients with decreased fertility. Ceska Gynekol. 2019 Spring;84(3):184-189. English. PMID: 31324107.

Poppe K, Glinoer D, Van Steirteghem A, Tournaye H, Devroey P, Schiettecatte J, Velkeniers B. Thyroid dysfunction and autoimmunity in infertile women. Thyroid. 2002 Nov;12(11):997-1001. doi: 10.1089/105072502320908330. PMID: 12490077.

Herman T, Török P, Laganà AS, Chiantera V, Venezia R, Jakab A. Hashimoto’s Thyroiditis Negatively Influences Intracytoplasmic Sperm Injection Outcome in Euthyroid Women on T4 Substitution Therapy: A Retrospective Study. Gynecol Obstet Invest. 2024;89(2):150-158. doi: 10.1159/000537836. Epub 2024 Feb 17. PMID: 38368857.

Luciano G. Nardo, Allen P. Yates, Stephen A. Roberts, Phil Pemberton, Ian Laing, The relationships between AMH, androgens, insulin resistance and basal ovarian follicular status in non-obese subfertile women with and without polycystic ovary syndrome, Human Reproduction, Volume 24, Issue 11, November 2009, Pages 2917–2923, doi.org/10.1093/humrep/dep22