What Is Unexplained Infertility?
Quick Answer
Unexplained infertility is diagnosed when standard fertility testing finds no identifiable cause for a couple’s or individual’s inability to conceive. It accounts for 10 to 30% of all infertility cases. Despite the frustrating diagnosis, outcomes are encouraging: a NIH study found that 92% of couples with unexplained infertility who pursued fertility treatment ultimately had a child.
Markham Fertility Centre offers advanced diagnostics including endometriosis screening and reproductive immunology to help uncover hidden contributing factors that standard testing may miss.
How Unexplained Infertility Is Diagnosed
Unexplained infertility is a diagnosis of exclusion. It means your physician has completed a standard fertility workup and everything appears normal:
Standard tests that must return normal results:
- Ovulation assessment: Regular menstrual cycles confirmed by hormone blood work (progesterone, LH)
- Ovarian reserve testing: AMH, FSH, estradiol, and antral follicle count within expected range for age
- Uterine evaluation: Transvaginal ultrasound showing normal uterine anatomy, no fibroids or polyps
- Fallopian tube patency: Hysterosalpingogram (HSG) confirming at least one open tube
- Semen analysis: Normal sperm count, motility, and morphology
- Thyroid function: TSH within normal range
And the couple has:
- Been trying to conceive for 12+ months (under 35) or 6+ months (over 35)
- No known medical condition affecting fertility
If all of the above checks out and pregnancy has not occurred, the diagnosis is unexplained infertility.
Why It Happens: Possible Hidden Factors
“Unexplained” does not mean “no cause.” It means current standard testing has not identified the cause. Potential hidden factors include:
- Subtle egg quality issues: Eggs may appear normal on ultrasound but have chromosomal or developmental problems that affect fertilization or implantation
- Undiagnosed endometriosis: Mild or deep endometriosis can be missed by standard ultrasound. It may cause inflammation that interferes with fertilization without producing obvious symptoms.
- Sperm function defects: Standard semen analysis measures count, motility, and morphology, but does not assess DNA fragmentation, acrosome function, or the sperm’s ability to penetrate the egg
- Implantation problems: The embryo may form but fail to implant due to uterine receptivity issues, immune factors, or endometrial timing mismatches
- Immune or inflammatory factors: Some patients produce antibodies or inflammatory responses that interfere with implantation or early embryo development
- Lifestyle and environmental factors: Subtle impacts from stress, sleep disruption, toxin exposure, or weight that do not show up on standard testing
At Markham Fertility Centre, routine endometriosis screening via specialized ultrasound is now offered to all new infertility patients at no additional cost. MFC also has expertise in reproductive immunology for patients with recurrent implantation failure, helping investigate immune-related causes that standard workups do not cover.
Treatment Options
Treatment for unexplained infertility follows a stepwise approach, starting with less invasive options and progressing as needed:
Step 1: Timed intercourse with ovulation induction
- Oral medications (letrozole or Clomid) stimulate ovulation and improve cycle predictability
- Combined with timed intercourse around ovulation
- Per-cycle success rate: approximately 5 to 10%
- Typically tried for 2 to 3 cycles before moving to IUI
Step 2: Medicated IUI
- Fertility medications combined with intrauterine insemination
- Concentrates the best sperm directly in the uterus at the time of ovulation
- Per-cycle success rate: 10 to 20% for patients under 35
- Most physicians recommend 3 to 5 cycles before reassessing
- In Ontario, IUI is funded with no lifetime limit through the Ontario Fertility Program
Step 3: IVF (with or without ICSI)
- Recommended after failed IUI cycles, or as a first-line option for patients over 38 where time is a factor
- IVF bypasses many potential hidden barriers (tubal function, sperm-egg interaction, fertilization issues)
- Per-cycle success rate: 40 to 50% for patients under 35
- Allows for preimplantation genetic testing (PGT-A) to select chromosomally normal embryos
- One funded IVF cycle per lifetime is available through the Ontario Fertility Program
| Treatment | Per-cycle success (under 35) | Invasiveness | Ontario funding |
| Timed intercourse + medication | 5 to 10% | Low | Medications out-of-pocket |
| Medicated IUI | 10 to 20% | Low | Unlimited funded cycles (OFP) |
| IVF | 40 to 50% | Moderate to high | One funded cycle per lifetime (OFP) |
| IVF + PGT-A | 50 to 60% (per euploid transfer) | Moderate to high | PGT-A cost out-of-pocket |
What to Do If You Receive This Diagnosis
Getting an “unexplained” label can feel frustrating, but there are practical steps you can take:
- Ask about advanced diagnostics: Not all clinics offer specialized endometriosis screening, sperm DNA fragmentation testing, or immune workups. These can uncover factors that standard testing misses.
- Consider a second opinion: Different clinics may have different diagnostic protocols. A fresh set of eyes can sometimes identify something new.
- Discuss your treatment timeline: Your age and goals should guide how quickly you move through the stepwise approach. Patients over 38 may benefit from moving to IVF sooner.
- Know that treatment works: The vast majority of patients with unexplained infertility achieve pregnancy with treatment. The diagnosis is frustrating, but the prognosis is generally good.
Why Patients Choose Markham Fertility Centre for Unexplained Infertility
- Routine endometriosis screening via specialized ultrasound for all new patients at no additional cost
- Reproductive immunology expertise for patients with recurrent implantation failure or suspected immune-related infertility
- On-site genetics program with PGT-A counselling for IVF patients wanting to optimize embryo selection
- Full treatment spectrum on-site: Ovulation induction, IUI, IVF, and ICSI without needing to transfer clinics
- Pain-free egg retrieval with an anesthesiologist at every IVF procedure
- Five locations across Markham, Barrie-Innisfil, Oshawa, Orillia, and Sudbury
Book a consultation at Markham Fertility Centre →
FAQ
How common is unexplained infertility?
It accounts for 10 to 30% of all infertility cases. It is one of the most frequent diagnoses in reproductive medicine.
Can you get pregnant naturally with unexplained infertility?
Yes. One study found that up to 43% of couples with unexplained infertility eventually conceived without treatment. However, this can take years, and success rates decline with age. Most specialists recommend starting treatment within a reasonable timeframe, especially for patients over 35.
Is unexplained infertility the same as “no hope”?
Not at all. A NIH study found that 92% of couples with unexplained infertility who pursued treatment ultimately had a child. The diagnosis simply means standard tests have not found the cause, but treatment options (IUI, IVF) are highly effective regardless.
Should I go straight to IVF with unexplained infertility?
This depends on your age and timeline. Patients under 35 typically start with medicated IUI (3 to 5 cycles) before moving to IVF. Patients over 38 may benefit from moving directly to IVF to maximize per-cycle success and reduce time to pregnancy.
Does unexplained infertility mean the problem is with me?
No. Unexplained infertility is a couple-level diagnosis. It means that no specific cause has been identified in either partner. Both egg and sperm quality, as well as their interaction, can contribute to difficulty conceiving even when individual test results appear normal.
Can advanced testing uncover the cause?
In some cases, yes. Specialized endometriosis screening ultrasound, sperm DNA fragmentation testing, immune panels, and endometrial receptivity testing can identify contributing factors that standard workups miss. Not all clinics offer these advanced diagnostics, so it is worth asking your provider what testing is available.