Unexplained Infertility: What to Consider Before IVF
Dr. Matthew Lewis
Unexplained Infertility, IVF, Holistic Doctor, Fertility, Functional Medicine
Conventional fertility treatments—including ovulation-stimulating medications, intrauterine insemination (IUI), and in vitro fertilization (IVF)—have helped many people successfully build families. There are patients who certainly benefit from these treatments, and timely referral is particularly important when age, diminished ovarian reserve, tubal obstruction, significant male-factor infertility, or another recognized condition reduces the likelihood of natural conception.
However, there is also substantial evidence that some couples with unexplained infertility are referred to fertility interventions prematurely, particularly when their evaluation is normal and they retain a reasonable probability of natural conception.
I've worked with many women over the years who arrived at our clinic after being told that IVF was their only option. It’s true that some women do need help getting pregnant with reproductive technologies. However, we’ve seen many women who have underlying health issues that deserve further investigation before moving to more invasive treatment. This case illustrates one such example.
Patient details have been limited to protect privacy. Individual outcomes vary, and a single case study cannot establish that any particular intervention caused a pregnancy.
Why I'm Sharing This Case
This article incorporates my years of observing clinical patterns as a Functional Medicine provider. The observation is simply that some women who receive IVF did not always need it.
In fact, they were able to become pregnant and conceive naturally, even after IVF failed.
It does not mean that IVF is not a miracle for those who benefit and require the treatment.
IVF is a science. Figuring out who requires IVF to conceive and who does not is often an art.
Her Goals When She Came to Provoke Health
In October 2025, the patient stated the following goals on her intake:
Improve suspected anemia and thyroid problems
Balance hormones
Improve her hopes of achieving pregnancy
She reported infertility since 2024. Her mother was already an active patient at Provoke Health and was being seen for hypothyroidism and autoimmunity.
Health Concerns and History
The patient reported the following health concerns:
Possible anemia
Thyroid concerns
Hormone-balance problems
Symptoms associated with high cortisol and chronic stress
When asked about her stress levels, she reported chronic stress related to her career and long commute. She had also experienced a recent trauma in her life and was stressed about being 35 and not having a child—or being fearful that she might not be able to have one.
Her husband had been evaluated. His sperm count was normal, although some sperm characteristics were reported as atypical.
She also reported a history of hormonal imbalance since childhood and taking hormonal birth control as a teenager. She had been diagnosed with moderate-to-severe endometriosis in 2023.
Her Experience With Endometriosis
The patient stated the following regarding her endometriosis diagnosis and treatment:
“The doctors kept saying, ‘You’re in range.’ There was a completely dismissive attitude from other physicians.”
For suspected endometriosis problems, her gynecologist suggested hormonal birth control to reduce her symptoms. This seemed to mask the symptoms for many years, but she eventually felt that the novelty wore off and wanted a more holistic approach.
She used the hormonal birth-control medication Portia 28 from 2012 through 2023.
At the time of consultation, her hormonal and menstrual symptoms included:
Painful periods
Excessive bloating and cramping during cycles
Use of Motrin or similar medication for menstrual pain
Heavy bleeding
Changes in her period
Irregular periods
Spotting between cycles
Breast soreness
Vaginal discharge
Mood swings
Decreased sex drive
Headaches
Palpitations
Identifying and Treating a Previously Missed Infection
The patient was referred back to her gynecologist because of symptoms that included pain at the vaginal entrance during intercourse, occasional dysuria after sex, and abdominal cramping and pain.
She noted that these symptoms had been present for years but had previously been dismissed. After learning about Ureaplasma through social media, she requested testing from her gynecologist. Her Ureaplasma vaginal swab came back positive, and antibiotic therapy was initiated.
She had also been experiencing increased bruising and slow healing. After several rounds of antibiotics, her vaginal and urinary symptoms were alleviated.
This was an important piece of the overall clinical picture. It also demonstrates why persistent symptoms should not automatically be attributed to hormones, stress, or endometriosis without appropriate gynecologic evaluation.
The Provoke Health Evaluation
At Provoke Health, we completed a comprehensive workup that included:
A full thyroid panel with thyroid antibodies
A comprehensive hormonal panel
Vitamin and mineral testing
Cortisol levels
In fact, all of her laboratory results were within conventional reference ranges.
At Provoke Health, however, we take a more functional approach to laboratory interpretation. We consider laboratory findings alongside the patient’s symptoms, menstrual history, lifestyle, nutrition, stress, sleep, medical history, and other potential contributors.
Based on her symptoms and borderline-low progesterone, she was started on low-dose progesterone under appropriate clinical supervision to help normalize her menses and decrease pain. Progesterone may also help oppose some of estrogen’s effects in appropriately selected patients with endometriosis, although it is not suitable for everyone and should be prescribed and monitored individually.
Addressing the Broader Fertility Picture
The patient was placed on a Mediterranean-style diet and counseled regarding ways to reduce stress.
One pattern I've observed repeatedly in clinical practice is that women with unexplained infertility are often carrying an extraordinary amount of chronic stress, not because stress is the sole cause of infertility, but because prolonged stress frequently overlaps with poor sleep, hormonal symptoms, inflammation, and nutritional deficiencies. While every patient is different, this combination appears often enough that I believe it deserves careful evaluation.
Stress should not be presented as the sole cause of infertility or used to imply that a patient is responsible for not becoming pregnant. Nevertheless, chronic emotional stress can affect sleep, sexual health, health behaviors, menstrual symptoms, and the hormonal signaling involved in reproduction. It deserves to be addressed as one part of a complete fertility plan.
I advise patients to take a vacation when possible, reconsider an unsustainable career or commute if needed, and, of course, support any hormonal imbalances that may be taking place.
One lesson I've learned after evaluating many complex patients is that fertility challenges rarely stem from a single issue. More often, there are several overlapping contributors that may seem unrelated at first: stress, sleep disruption, nutritional deficiencies, chronic inflammation, hormonal imbalance, or undiagnosed infections. Individually, each factor may appear modest, but together they can significantly affect a person's overall health.
In this case, we also identified infection and vaginosis-related concerns. If you think of fertility from a root-cause perspective, as we do with many other health concerns, there are usually multiple, overlapping contributors. Tackling as many of these factors as possible is what may ultimately help improve the patient’s health and reproductive environment.
Putting the Pieces Into Place
This is exactly how her case was handled.
Supplements were provided to support a healthy cortisol rhythm and sleep cycle. Dietary guidance was given to provide the healthy fats, protein, micronutrients, and overall nutritional foundation needed when preparing for pregnancy.
She was able to get away for a vacation and change her job to a virtual position, which reduced her commute and stress levels.
Throughout this time, we met once a month to review her status, adjust her protocol, and provide the support needed to put all the pieces into place.
After approximately six months on this protocol, she became pregnant. In April 2026, she learned that she was pregnant, and as of today, she is doing great.
We cannot say that one specific treatment caused the pregnancy. Natural conception may still occur in couples with unexplained infertility, and the purpose of a case study is to describe an individual experience, not prove cause and effect. What this case demonstrates is the value of listening carefully, investigating persistent symptoms, addressing modifiable contributors, and supporting the patient as a whole.
Are Couples With Unexplained Infertility Sometimes Overtreated?
There is substantial evidence that couples with unexplained infertility are sometimes referred to medical fertility interventions prematurely, particularly when normal findings suggest a reasonable probability of natural conception.
A landmark Dutch retrospective cohort study conducted across 25 fertility clinics found that 36% of couples with unexplained infertility who were considered eligible for at least six months of expectant management began medically assisted reproduction too early.[1]
A perspective published in Human Reproduction argued that the structure of infertility care can create a favorable situation for overdiagnosis and overtreatment. The authors noted that “unexplained subfertility” is itself prone to overdiagnosis and that IVF may sometimes be applied prematurely.[2]
This does not mean couples should simply wait indefinitely. Age, ovarian reserve, the duration of infertility, prior pregnancy history, semen findings, tubal health, endometriosis, desired family size, and other clinical factors must be considered. Current professional guidance generally recommends beginning an infertility evaluation after 12 months of trying in women younger than 35 and after six months in women 35 or older—or sooner when a known condition may affect fertility.
The goal is to consider each person’s unique situation and chances of conceiving naturally before moving forward with treatment.
Natural Conception Rates Can Remain Meaningful
Research shows that some couples with unexplained infertility may still conceive naturally, even without fertility treatments:
One review found that about 27% conceived within 12 months after completing fertility testing.[3]
A Dutch study found that about 60% had a live birth within three years, with most pregnancies occurring naturally.[4]
Another study found that 34% conceived within six months, 76% within two years, and 87% within five years without treatment.[5]
An individual-participant-data meta-analysis of women age 35 and older found that natural-conception rates remained clinically meaningful, particularly among women with unexplained infertility. A 35-year-old woman with two years of primary unexplained infertility was estimated to have approximately a 24% probability of natural conception leading to ongoing pregnancy or live birth within the following 12 months.[6]
A review of unexplained infertility reported that, even after 12 months of unsuccessful attempts, approximately 50% of couples may conceive during the following 12 months, with another 12% conceiving in the year after that.[7]
These are population estimates, not guarantees for an individual couple. Prognosis changes with age, the duration of infertility, reproductive history, test results, and specific medical conditions.
Factors That May Be Missed in a Typical Fertility Setting
Here is a list of potential contributors to infertility or impaired reproductive health that may not always receive adequate attention in a conventional fertility setting:
Chronic or acute emotional stress
Dietary and micronutrient deficiencies
Endocrine disruption associated with certain plastics, personal-care products, environmental exposures, or other toxicants
Mold or water-damaged-building exposure in appropriately evaluated cases
Chronic or hidden infection
Long COVID or other post-viral health changes
Overt or subclinical hypothyroidism
Autoimmune conditions
Sleep disruption
Metabolic and blood-sugar dysfunction
Vaginal, urinary, or reproductive-tract symptoms requiring gynecologic evaluation
These factors should be looked at carefully, as their presence doesn’t necessarily mean they are causing infertility. Testing and treatment should be based on each person’s health history and symptoms to determine the best route of care.
Holistic Care Can Be an Adjunct or a Stand-Alone Strategy
Of course, not all patients meet the description in this case, and each person needs to be treated individually.
However, from a holistic perspective, there are women who may be reaching out to fertility clinics prematurely or who have failed conventional approaches because potentially important contributors—sometimes simple and sometimes complex—have been missed and replaced with a standardized approach that favors aggressive and expensive therapies.
There are also patients who clearly benefit from conventional fertility treatment, including hormonal therapy, IUI, IVF, surgery, and other procedures. A holistic approach should not be positioned as a universal substitute for reproductive endocrinology or medically necessary fertility care.
Holistic care can be used as either an adjunct or, in appropriately selected cases, a stand-alone initial strategy. The safest approach is collaborative: identifying when natural conception remains reasonably likely and addressing modifiable health factors.
While we recognize that natural methods can be effective for fertility, when they are not, it’s important to refer the patient to a specialist to explore all avenues of care. We believe the patient has the best treatment when there is good collaboration between what conventional health care can offer and functional or holistic treatment.
At Provoke Health, we assist patients who have not responded to conventional treatment with hormones, IVF, or other invasive procedures, as well as those who are looking for a different perspective and treatment option.
The objective is not to reject conventional fertility care. It is to make sure that the whole patient—and the whole story—has been considered before moving forward.
References
Kersten FAM, Hermens RPGM, Braat DDM, et al. Overtreatment in couples with unexplained infertility. Human Reproduction. 2015;30(1):71–80.
Annual Capri Workshop Group. Towards a more pragmatic and wiser approach to infertility care. Human Reproduction. 2019.
Wang R, Danhof NA, Tjon-Kon-Fat RI, et al. Interventions for unexplained infertility: a systematic review and network meta-analysis. Cochrane Database of Systematic Reviews. 2019.
Brandes M, Hamilton CJCM, van der Steen JOM, et al. Unexplained infertility: overall ongoing pregnancy rate and mode of conception. Human Reproduction. 2011.
Barnea ER, Holford TR, McInnes DR. Long-term prognosis of infertile couples with normal basic investigations: a life-table analysis. Obstetrics & Gynecology. 1985;66(1):24–26.
Chua SJ, Danhof NA, Mochtar MH, et al. Age-related natural fertility outcomes in women over 35 years: a systematic review and individual participant data meta-analysis. Human Reproduction. 2020;35(8):1808–1820.
Gelbaya TA, Potdar N, Jeve YB, Nardo LG. Definition and epidemiology of unexplained infertility. Obstetrical & Gynecological Survey. 2014;69(2):109–115.
Shingshetty L, et al. Should we adopt a prognosis-based approach to unexplained infertility?. Human Reproduction Open. 2022.
American Society for Reproductive Medicine. Evidence-based treatments for couples with unexplained infertility: a guideline. 2020.
American Society for Reproductive Medicine. Optimizing natural fertility: a committee opinion. 2022.
This article is for educational purposes only. It does not provide medical advice, diagnose infertility, or replace evaluation by a gynecologist or reproductive endocrinologist. Fertility evaluation and treatment decisions should be individualized according to age, medical history, reproductive goals, test results, and other clinical factors.
