Key Takeaways

• Normal fertility testing does not always answer every question. If pregnancy is not happening, implantation repeatedly fails, or losses continue, the article encourages looking at the larger health picture rather than assuming there is nothing else worth exploring.

• Your reproductive organs do not function separately from the rest of your body. Blood sugar, sleep, stress, digestion, immune activity, nutrition, and inflammatory conditions may all be relevant to a comprehensive fertility evaluation.

• Do not assume that stress means “just relax.” The article treats stress as a physiological process and focuses instead on giving the nervous system regular opportunities for recovery.

• Low AMH is information, not a verdict. AMH primarily provides information about ovarian reserve; it does not directly measure egg quality or determine whether pregnancy is possible.

• Whole-body support can happen alongside fertility medicine. Medical treatment and preconception preparation do not need to compete; they can address different parts of the fertility picture at the same time.

What should be considered when infertility or recurrent miscarriage remains unexplained? In addition to standard evaluation of ovulation, sperm, fallopian tubes, the uterus, genetics, and hormones, the article suggests considering metabolic health, insulin resistance, endometriosis, adenomyosis, immune activity, sleep, nutrient status, gut symptoms, and chronic inflammatory conditions. These factors should be investigated appropriately rather than assuming inflammation is the cause of every unexplained fertility problem.

There are few things more frustrating in fertility care than being told that everything looks normal when you know something isn’t working.

The semen analysis is normal. The tubes are open. Hormones fall within the expected ranges. You may even have genetically normal embryos. And still, pregnancy doesn’t happen, implantation fails, or another pregnancy ends far too soon.

“Unexplained” is a diagnosis I have always found unsatisfying. It tells us what conventional testing hasn’t found. It doesn’t necessarily tell us that there is nothing else worth looking for.

In a recent Health Youniversity conversation, I spoke with Dr. Jan Rydfors, a Stanford-trained OB-GYN who has spent decades working with unexplained infertility and recurrent pregnancy loss. Our conversation focused on an area he believes deserves much more attention: chronic inflammation.

Inflammation is a broad subject, and it has many possible sources. Insulin resistance, stress, poor sleep, gut health, autoimmune activity, endometriosis, adenomyosis, nutrient status, and environmental exposures can all contribute to the body's inflammatory burden. For someone trying to conceive, these seemingly separate issues may be important pieces of the same fertility picture.

Why Inflammation Matters in Fertility

Inflammation is part of a healthy immune response. We need it to fight infection, respond to injury, and repair damaged tissue. Problems can develop when that inflammatory response stays activated long after its immediate job is done.

That ongoing activation can influence metabolic health, hormones, circulation, immune signaling, and the environment surrounding the reproductive organs. From a fertility perspective, this matters because developing eggs and sperm, implantation, and early placental development are all taking place within that larger biological environment.

I have talked about this with my fertility patients for years. Your ovaries and uterus do not function independently from the rest of you. Reproductive health is influenced by what is happening with blood sugar, digestion, sleep, stress, circulation, nutrition, and immune function.

Dr. Rydfors takes that same whole-body perspective when he evaluates unexplained infertility and recurrent pregnancy loss.

Pregnancy Requires Sophisticated Immune Communication

Pregnancy asks the immune system to do something rather extraordinary.

An embryo contains genetic material from both parents, so early pregnancy requires carefully coordinated immune tolerance. The immune system still needs to protect the mother while allowing implantation and placental development to proceed.

When inflammatory signaling is already elevated elsewhere in the body, that communication may become more complicated. This is one reason Dr. Rydfors considers chronic inflammation when investigating implantation failure and recurrent pregnancy loss.

There are many causes of miscarriage, including chromosomal abnormalities, which become more common as egg age increases. Inflammation is one possible contributor, particularly when pregnancy losses or implantation failures remain unexplained after the usual evaluation.

Insulin Resistance: A Fertility Issue We Should Be Talking About

One of the first places Dr. Rydfors looks is metabolic health.

When cells become less responsive to insulin, the body compensates by producing more of it. Higher insulin levels can affect ovarian hormone production, including androgen levels, and may interfere with ovulation and normal cycle patterns.

This connection is well recognized in PCOS, but insulin resistance isn't limited to people with a PCOS diagnosis. Changes in blood sugar regulation and metabolic health can occur over time, sometimes before standard laboratory values make the problem obvious.

Your menstrual cycle can offer clues. If cycles are consistently long or ovulation is happening later than expected, I want to know why. The cycle itself gives us useful information about what is happening elsewhere in the body.

Visceral fat also enters this conversation because it is metabolically active tissue. It produces inflammatory signals of its own and is closely associated with insulin resistance. Nutrition, movement, sleep, stress management, and, when appropriate, supplements or medications can all become part of improving the metabolic environment before conception.

Stress Is Physiology

People struggling with infertility have heard “just relax” far too many times.

Stress deserves a more intelligent conversation.

Your nervous system responds to pressure through measurable biological pathways involving cortisol, epinephrine, blood sugar, immune signaling, sleep, and inflammation. Fertility treatment itself can add another layer, with appointments, medications, financial decisions, waiting for results, and the emotional toll of unsuccessful cycles.

The goal isn't to eliminate stress from your life. Few of us could accomplish that even if we tried. We can, however, give the nervous system regular opportunities to shift out of a prolonged stress response.

This is one reason practices such as acupuncture, Qigong, meditation, breath work, walking, adequate sleep, and time in nature can have a place in preconception care. They are ways of working with physiology, rather than simply telling someone to relax.

The Gut-Inflammation Connection

Our conversation also turned to gut health, which makes sense when you consider how closely the digestive and immune systems interact.

A diverse microbiome depends, in part, on what we feed it. Fiber, colorful vegetables and fruits, herbs, spices, and other polyphenol-rich plant foods support the organisms that produce compounds such as butyrate. Butyrate helps nourish the cells lining the intestinal wall.

When that barrier becomes compromised, bacterial components and other substances may cross into circulation and trigger immune activity. This increased intestinal permeability, commonly called “leaky gut,” is one pathway being studied in relation to chronic systemic inflammation.

One of the simplest takeaways from our conversation was variety. Eating nutritious food is important. Eating a greater variety of nutritious foods gives the microbiome an even broader range of substrates to work with.

Endometriosis Can Be Quiet

Endometriosis deserves particular attention because it is fundamentally an inflammatory condition and can exist without the symptoms people commonly associate with it.

Some people experience severe menstrual pain, pelvic pain, or painful intercourse. Others have few obvious symptoms and don't discover endometriosis until they begin investigating infertility.

That means the absence of pain doesn't necessarily rule it out.

Endometriosis can alter the inflammatory environment within the pelvis and may affect ovarian function, egg development, implantation, and fertility outcomes. Adenomyosis can create another inflammatory influence within the uterus itself.

Dr. Rydfors also raised an interesting perspective on AMH. We usually think of AMH primarily as an estimate of ovarian reserve. A low AMH tells us something about egg quantity; it doesn't directly measure egg quality. When ovarian reserve appears lower than expected, however, he believes it is worth asking what else may be happening in the ovarian and pelvic environment rather than stopping at the number itself.

That distinction matters. An AMH result is information. It is not a verdict on your ability to conceive.

The Basics Still Matter

One theme I return to again and again in fertility care is that seemingly ordinary things can have extraordinary biological importance.

Sleep matters. Blood sugar matters. The quality and variety of food matter. Movement matters. Stress resilience matters. Nutrient sufficiency matters.

Magnesium, zinc, omega-3 fatty acids, and other nutrients are involved in immune regulation and inflammatory pathways. Dr. Rydfors specifically discussed omega-3 status and the potential usefulness of testing rather than automatically assuming someone is getting enough.

Supplements should always be individualized, particularly during fertility treatment and pregnancy. More is not automatically better. The purpose of testing and assessment is to understand what your body may actually need.

Where Reproductive Immunology Fits

For some patients with recurrent pregnancy loss or implantation failure, medical treatment may include medications intended to modify immune activity or support early pregnancy.

Dr. Rydfors discussed therapies including progesterone and, in selected circumstances, medications such as prednisone, IVIG, tacrolimus, or low-dose aspirin. These are medical treatments that require appropriate evaluation, prescribing, and monitoring.

What I found especially important in our conversation was the parallel question: what is contributing to the inflammatory burden?

If insulin resistance, endometriosis, gut dysfunction, poor sleep, chronic stress, or nutritional insufficiency is part of the picture, there may be opportunities to address those factors alongside appropriate reproductive medical care.

This is what integrative medicine should do well. We can use conventional medicine when it is needed while also paying attention to the health of the person undergoing treatment.

Can We Measure Inflammation Better?

Dr. Rydfors is also involved in developing a fascinating new approach to measuring systemic inflammation through retinal imaging.

The retina contains a dense network of blood vessels and metabolically active tissue. His company, Bonafia, is exploring whether retinal images analyzed with artificial intelligence can reveal inflammatory patterns associated with conditions and outcomes including endometriosis, preterm birth, IVF success, and miscarriage risk.

This technology is still emerging, so it should not be viewed as a replacement for an appropriate fertility or medical evaluation. I find the concept intriguing because it reflects where medicine is heading: finding better ways to recognize patterns earlier, before they become obvious disease.

Looking Upstream

If you have experienced recurrent pregnancy loss, failed embryo transfers, unexplained infertility, low AMH, long menstrual cycles, or autoimmune concerns, there may be value in widening the lens.

Look at metabolic health. Look at blood sugar. Consider gut health, sleep, nutrient status, stress physiology, and the possibility of inflammatory conditions such as endometriosis or adenomyosis. Some of these areas may need medical investigation; others are things you can begin supporting well before your next fertility treatment.

This is also why I encourage people to think about preconception as a period of preparation rather than simply a countdown to the next cycle.

Eggs and sperm develop within the environment we provide for them. The uterus, immune system, gut, metabolism, nervous system, and reproductive hormones are continuously communicating with one another. Giving yourself several months to work on that environment can create an opportunity to influence many of the factors that are within your control.

There will always be aspects of fertility we cannot control. But “unexplained” does not have to mean there is nothing left to explore.

Sometimes it means we need to ask better questions.

Frequently Asked Questions - FAQs

What is unexplained infertility?

Unexplained infertility generally means standard fertility testing has not identified a clear explanation for why pregnancy has not occurred.

The article emphasizes that “unexplained” describes the limits of what has been identified so far rather than proving that no other relevant factors exist.

Can inflammation cause infertility?

The article discusses chronic inflammation as one possible contributor, not a universal cause of infertility.

Fertility problems can also involve ovulation, sperm, fallopian tubes, uterine factors, endometriosis, age, genetics, ovarian reserve, or other medical conditions.

Can inflammation cause recurrent miscarriage?

Inflammatory or immune factors may be relevant in some cases, but recurrent pregnancy loss has many potential causes.

The article specifically notes that chromosomal abnormalities are an important cause of miscarriage and that inflammation should be considered as one possible part of a broader evaluation.

What causes chronic inflammation?

The article discusses potential contributors including:

• Insulin resistance

• Metabolic dysfunction

• Endometriosis

• Adenomyosis

• Autoimmune activity

• Poor sleep

• Chronic stress

• Gastrointestinal dysfunction

• Nutrient insufficiency

• Environmental exposures

The relevant factors will differ between individuals.

How does insulin resistance affect fertility?

When cells respond less effectively to insulin, the body may compensate by producing more insulin.

The article explains that higher insulin can affect androgen production, ovulation, and menstrual-cycle patterns, particularly in people with metabolic dysfunction or PCOS.

Can I have insulin resistance without PCOS?

Yes.

The article specifically emphasizes that insulin resistance is not limited to people diagnosed with PCOS and may develop before obvious changes appear on standard laboratory tests.

Can long menstrual cycles indicate a metabolic problem?

Long or irregular cycles can have many causes.

The article treats cycle patterns as useful information and encourages asking why ovulation is delayed rather than assuming the cycle pattern is insignificant.

How are stress and inflammation connected?

The article describes stress as a physiological response involving cortisol, adrenaline, sleep, blood sugar, and immune signaling.

Its recommendation is not to eliminate all stress, but to create regular opportunities for nervous-system recovery.

Does stress cause infertility?

The article does not establish stress as a sole cause of infertility.

Fertility patients should not be told that treatment will work if they simply relax. Stress-management strategies are better understood as supportive care for health and well-being.

Can gut health affect inflammation?

The article describes the close relationship between digestive and immune function.

It discusses fiber and plant diversity as factors that support a diverse microbiome and mentions increased intestinal permeability as one possible pathway being researched in systemic inflammation.

What foods support the gut microbiome?

The article highlights:

• Fiber

• Colorful vegetables

• Fruits

• Herbs

• Spices

• Polyphenol-rich plant foods

The main recommendation is dietary diversity rather than relying on one “fertility food.”

What is butyrate?

Butyrate is a compound produced by certain gut bacteria when they ferment dietary fiber.

The article discusses it because butyrate helps nourish cells lining the intestinal wall.

What is “leaky gut”?

“Leaky gut” is a commonly used term for increased intestinal permeability.

The article describes it as a condition in which substances that normally remain within the intestine may cross the intestinal barrier and contribute to immune activity.

Can endometriosis exist without pain?

Yes, according to the article.

Some people have severe pelvic symptoms, while others have few obvious symptoms and may discover endometriosis only during investigation for infertility.

How can endometriosis affect fertility?

The article describes endometriosis as an inflammatory condition that may influence the pelvic environment, ovarian function, egg development, implantation, and fertility.

The effect varies depending on the individual and severity of disease.

What is adenomyosis?

Adenomyosis occurs when tissue similar to the uterine lining grows into the muscular wall of the uterus.

The article discusses it as another potential source of inflammation within the uterine environment.

Does low AMH mean poor egg quality?

No.

The article correctly distinguishes ovarian reserve from egg quality: AMH primarily provides information about egg quantity or ovarian reserve; it does not directly measure egg quality.

Can low AMH cause infertility?

Low AMH can be relevant to fertility planning and expected ovarian response, particularly during IVF, but it does not independently determine whether someone can conceive.

It should be interpreted alongside age, cycle history, antral follicle count, medical history, and other fertility factors.

What nutrients are discussed in relation to inflammation?

The article mentions:

• Magnesium

• Zinc

• Omega-3 fatty acids

It emphasizes testing and individualized supplementation rather than assuming everyone needs the same doses.

Should I take omega-3 supplements for fertility?

The article discusses omega-3 status as something that may be worth evaluating, but does not establish a universal supplement protocol.

Supplements should be reviewed with a qualified healthcare professional, particularly during IVF or pregnancy.

What is reproductive immunology?

Reproductive immunology examines interactions between immune function, implantation, pregnancy, and reproductive health.

The article discusses it particularly in relation to recurrent pregnancy loss and implantation failure.

What medications may be used in reproductive immunology?

The article mentions:

• Progesterone

• Prednisone

• IVIG

• Tacrolimus

• Low-dose aspirin

These are not general fertility supplements. Their risks, benefits, and indications vary substantially and require medical prescribing and monitoring.

Should everyone with recurrent miscarriage take aspirin or prednisone?

No.

The article explicitly presents these as treatments used in selected circumstances, not universal therapies for recurrent pregnancy loss.

What does retinal imaging have to do with fertility?

The article describes emerging work by Bonafia using retinal images and AI to investigate patterns associated with systemic inflammation and outcomes such as endometriosis, preterm birth, IVF success, and miscarriage risk.

It also makes clear that this technology is still emerging and should not replace appropriate fertility or medical evaluation.

How should recurrent pregnancy loss be evaluated?

The source does not provide a complete recurrent-loss testing protocol.

Its emphasis is that recurrent loss may deserve evaluation beyond one isolated factor, including appropriate reproductive, genetic, metabolic, inflammatory, and medical assessment.

What can I do before my next IVF cycle?

The article encourages considering sleep, nutrition, movement, stress support, metabolic health, nutrient status, gut symptoms, and relevant medical investigation before or alongside fertility treatment.

Preparation should complement—not delay medically necessary care.

Look Beyond “Unexplained” and Build a More Complete Fertility Plan

If you've experienced recurrent pregnancy loss, failed implantation, long cycles, low AMH, or unexplained infertility, your next step may involve looking at the fertility picture more broadly—not simply adding another supplement or repeating the same cycle.

The Health Youniversity Preconception Plan brings together Nutrition, Circulation, Lifestyle, and Emotional Support to help you support whole-body and reproductive health before natural conception or alongside fertility treatment.

Explore the Preconception Plan →

If you're unsure which questions to ask next or whether there are areas of your fertility preparation that deserve closer attention, schedule a Fertility Assessment Call with Dr. Susan Fox.

Schedule a Fertility Assessment Call →

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Dr Rydfors received his Medical degree and specialization training from Stanford University Medical Center where he is an Adjunct Clinical Assistant Professor.

Dr Rydfors has extensive experience in the workup and treatment of unexplained infertility and unexplained miscarriages and has founded the Freyja Early Pregnancy Loss Clinic in Redwood City, California, where his team implements multidisciplinary and integrative program to prevent recurrent miscarriages and to solve unexplained Infertility

He is the initial creator and current Co-Author of the popular “Handbook in Obstetrics, Gynecology and Infertility,” now in its sixth edition, the main handbook used by the majority of Obstetricians and Gynecologists in training in the US.

He is a co-founder of Bonafia® an AI company which is using retinal imaging and AI interpretation to evaluate and reduce chronic systemic inflammation. It is using its technology for Endometriosis detection, Preterm Birth risk detection, IVF success prediction and Miscarriage risk prediction.

Freyja Clinic: https://freyjaclinic.com/

Bonafia: https://www.bonafia.com/

MARAbio https://www.marabio.com/

Medical Disclaimer:

By listening to the Health Youniversity podcast, you agree not to use this podcast as medical advice to treat any medical condition for yourself or others. Consult your healthcare provider for any medical issues you may have. This entire disclaimer also pertains to any guests or contributors to any Health Youniversity podcast.