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Unexplained infertility common questions

If medical evaluation and testing yield no specific cause of infertility, a patient is diagnosed with unexplained infertility. This diagnosis is given after a careful evaluation of several factors such as the uterus, fallopian tubes, ovulation, endocrine disorders and male fertility. 

About 20% of couples who have an infertility evaluation will have the diagnosis of unexplained infertility. According to RESOLVE, approximately one in five couples will be diagnosed with unexplained infertility after completing a full workup.

A standard fertility evaluation includes assessing the structure of the uterus, potential blockage in the fallopian tubes, egg supply, ovulation functionality, endocrine factors such as thyroid function and a semen analysis. All tests will have a normal or abnormal result. If it is abnormal, such as having a blocked tube, then the cause of infertility is tubal factor. If all test results are normal, there is no identifiable cause, pointing to an unexplained infertility diagnosis.

There is a disparity in endometriosis and infertility diagnoses. Roughly half of women with endometriosis experience infertility, however, the diagnosis of endometriosis is listed as only 3-4% of infertility cases by the Society of Assisted Reproductive Technology (SART). The diagnosis and treatment of endometriosis prior to IVF has decreased over the past 20 years due to routine diagnostic laparoscopy falling out of practice.

Without direct visualization of the pelvis via laparoscopy, the gold standard for an endometriosis diagnosis has been replaced by diagnosing from symptoms. While painful periods and/or pelvic pain are symptoms, not everyone with endometriosis has these symptoms. 

Traditional best practices are used due to the absence of a diagnosis. Optimizing conception involves stimulating the ovaries with oral or injectable medication to increase the number of eggs available for fertilization. This is combined with timed intercourse or intrauterine insemination (IUI), which increases the number of healthy sperm in the uterus during ovulation. If these treatments fail, in vitro fertilization (IVF) is recommended. 

The literature has shown that ovarian stimulation with timed intercourse or a natural ovulation cycle with IUI is not any more effective than no treatment at all. For this reason, ovarian stimulation is recommended with IUI.

Traditional best practices are used due to the absence of a diagnosis. Optimizing conception involves stimulating the ovaries with oral or injectable medication to increase the number of eggs available for fertilization. This is combined with timed intercourse or intrauterine insemination (IUI), which increases the number of healthy sperm in the uterus during ovulation. If these treatments fail, in vitro fertilization (IVF) is recommended. 

There is new research looking at less invasive ways to diagnose endometriosis. By taking an endometrial biopsy 6-10 days after a surge of Luteinizing Hormone (ovulation happens 1-2 days after the surge) we can detect the presence of a specific gene (BCL6) that is more common in women with endometriosis. If this gene is present, we can alter treatment accordingly.

Women with unexplained infertility who are treated for endometriosis based on the presence of this gene have similar live birth rates than in women who are BCL6 negative. Treatment options for endometriosis are either surgical removal of endometriotic implants or 2-3 months of treatment with a once-a-month injectable hormone to suppress the endometriosis.

Pregnancy rates will vary based upon the treatment chosen and female age:

  • Oral ovarian stimulation medication with IUI = 10-15%
  • Subcutaneous (injectable) ovarian stimulation medication with IUI = 10-25%
  • IVF: 30%-40%
    It is important to note that while there is a broad range, IVF is a great option because women with unexplained infertility have a good ovarian reserve, and several embryos can be created in one cycle.

Lifestyle changes such as regular exercise and a healthy diet of whole grains, lean proteins and plenty of veggies and fruits can boost your overall health and improve fertility. Quitting smoking for both partners, which includes cigarettes and vaping, can significantly improve the chances of conception and ability to sustain a pregnancy. It is also helpful to limit drinking to a couple drinks per week or less, and to strive for a Body Mass Index in the normal range. 

Supplements can also help both partners. Women should take prenatal vitamins and folic acid every day. Men can also boost sperm health by taking a daily multivitamin (Zinc helps sperm count/function, Vitamin C boosts motility, Vitamin D helps with sperm development), Folic Acid (reduces sperm abnormalities) and 400mg daily of Coenzyme Q10 (improves sperm count/motility).

Medical contribution by Meike Uhler, M.D.

Dr. Uhler feels fortunate to play a role in this stage of her patients’ lives. Her research interests focus on the evaluation and treatment of infertility, as well as raising fertility awareness in the general population.

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