Understanding Unexplained Infertility: Diagnosis, Treatment, and Support at OU Health

In quiet bedrooms across America, millions of couples stare at negative pregnancy tests month after month, their hope fading with each disappointing result.

The World Health Organization reports that one in six people globally face infertility, with similar rates in the U.S. About one in seven American women struggle to conceive or maintain a pregnancy. The frustration is acute for the 15 to 30% diagnosed with unexplained infertility, where all tests are normal, yet pregnancy remains elusive.

For these estimated 1.5 to 2 million U.S. couples with unexplained infertility, the journey is particularly challenging. They face a medical puzzle where one-third of infertility cases stem from male factors, one-third from female factors, and one-third — the unexplained cases — remain mysterious even to medical experts.

The question "Why can't we get pregnant?" lingers without a clear answer, leaving couples feeling isolated and helpless.

At OU Health, experts see patients with this diagnosis every day. They understand the emotional toll of unexplained infertility and offer both compassionate support and evidence-based treatment options.

What is Unexplained Infertility?

Reproductive endocrinology and infertility physicians Dr. M. Blake Evans, D.O., FACOG and Dr. Claire Reynolds, M.D., said unexplained infertility is diagnosed in a couple that has undergone an infertility evaluation in which everything is seemingly normal, hence the name “unexplained.”

Diagnosis criteria include normal menstrual cycles, at least one open fallopian tube, no conception after 12 months (under 35) or six months (35 or older), and a normal semen analysis.

Comprehensive Diagnostic Testing at OU Health

Fertility specialists at OU Health conduct thorough evaluations to investigate potential causes of infertility.

"A basic workup usually involves a thorough history, a transvaginal ultrasound and hysterosalpingogram (fallopian tube evaluation) for women and a semen analysis for men," said Dr. Evans.

Additional testing available at OU Health includes:

• Comprehensive hormonal panels
• Endocrine marker evaluations
• Advanced ultrasound monitoring
• Specialized tubal assessments
• Detailed semen analysis

These tests help identify the four main factors that can affect fertility.

Research and Clinical Advances

OU Health and the University of Oklahoma remain at the forefront of fertility research.

"OU Health has multiple ongoing clinical trials to help us better understand certain conditions that can lead to infertility and ultimately help to improve a patient's chances of conceiving,” Dr. Evans said.

One previously conducted study through the Reproductive Medicine Network helped establish evidence-based treatment protocols for unexplained infertility, guiding OU Health’s current treatment approach. This model emphasizes starting with less invasive therapies before advancing to more complex procedures.

OU Health’s progressive approach to treating unexplained infertility includes:

1. Ovulation Induction with Intrauterine Insemination (IUI) This first-line treatment combines oral medications with intrauterine insemination.

"We've studied these different options,” said Dr. Reynolds. “OU Health was part of a very large study that was done on unexplained infertility, and we found that using both oral medications and insemination can significantly improve pregnancy rates—from about 5% to 15–18% per cycle, representing a significant improvement in conception chances.

2. Advanced Reproductive Technologies When appropriate, OU Health offers assisted reproductive technologies like In Vitro Fertilization (IVF). While not typically the first recommendation for unexplained infertility, these advanced options have success rates up to to 55-60% per embryo transfer, depending on various factors including patient age. Given that age is the most important prognostic factor with regards to fertility treatment success, some women will not have success rates this high.

"Relying on the evidence that we have to do the lesser invasive treatment options is something that we really pride ourselves on," said Dr. Reynolds.

Support and Lifestyle Recommendations

The journey through infertility treatment can be emotionally challenging. OU Health providers recognize this difficulty and offer comprehensive support:

"I think it's just important to listen to patients and to be there and support them every step of the way," said Dr. Reynolds, acknowledging that women often blame themselves when facing fertility challenges.

While no specific diet or supplement regimen exists exclusively for unexplained infertility, the REI specialists at OU Health recommend:
 

• Prenatal vitamins
• Optimizing overall health, including weight management
• Thyroid screening
• Balanced nutrition and exercise
• Sleep optimization
• Stress reduction techniques

When to Seek Help

The OU Health team of specialists encourage patients to seek evaluation if they are:

• Women under 35: After one year of trying
• Women 35 and older: After six months of trying
• 40 years and above: right away
• Not having regular menstrual cycles
• Known history of/concern for endometriosis
• Known history of/concern for male factor infertility

"Even if you're not ready to start treatment," Dr. Reynolds said, "just getting your foot in the door and getting an evaluation and understanding your fertility gives you more power to be able to make informed decisions about your next steps."

The Reproductive Medicine Clinic at OU Health offers comprehensive care for couples experiencing unexplained infertility, with evidence-based approaches and compassionate support. As Dr. Evans emphasizes, ongoing research continues to improve understanding and treatment options.

Learn more about unexplained infertility treatment options or schedule a consultation with OU Health reproductive medicine specialists like Dr. Evans and Dr. Reynolds or call (572) 244-0203.