Unexplained Infertility

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People often approach infertility testing with some trepidation, as they may be concerned about discovering abnormalities, and undergoing treatment. However, it is even more frustrating to have completed a fertility evaluation and be told at the end of the process that there is "nothing wrong".

About 85-90% of patients will have at least an educated guess about what is keeping them from conceiving by the end of the evaluation process. For the remaining 10-15% there may be no clear answer. There are causes of infertility that are beyond either our current level of understanding or the present level of sophistication of our testing procedures.

"Unexplained infertility" does not mean "undiagnosed infertility".

"Unexplained infertility" means that all other known diagnoses have been eliminated.

When an individual is diagnosed with "unexplained infertility", a careful review is conducted of their entire infertility evaluation.
• Each test is examined to ensure it was performed correctly and is technically sound.
• The interpretation and/or conclusion drawn from the results is also examined.
• Tests with questionable results may be repeated.
• Further investigation of one or more questionable factors may be conducted.
• If a thorough review still provides no clues or leads, the next treatment strategy is empirical therapy.

Empirical therapy is treatment based on observation or experience with other infertile couples, rather than on conclusive evidence of what is wrong. The justification for empirical therapy is that it frequently works. Through the use of "Assisted Reproductive Technology" or ART, we join hormonal therapy with a form of artificial insemination (i.e. intrauterine insemination, or IVF).

The purpose of ART is to enhance or bypass as many fertility factors as possible. Sometimes these ART techniques are used to overcome known deficiencies, such as using IVF to circumvent damaged fallopian tubes. Because these techniques are based upon enhancement and/or substitution, they can be applied to unexplained infertility patients with the hope that what is being enhanced or substituted is the element responsible for the infertility.

• The following three levels of empirical therapy treatments are presented in the order of increasing success rates, time commitment and cost.
• All steps do not need to be tried before proceeding to the last level.
• Each level involves treatments, which enhance certain factors while bypassing other factors.

The Three Levels of Empirical Therapy Treatments:

Level 1 includes up to three cycles of clomiphene combined with intrauterine insemination, using 100mg/day for 5 days starting on cycle day 3, 4, or 5. Transvaginal ultrasound monitoring will be performed. Half the time there will be two or three mature follicles seen. Once the largest follicle is = 17 mm, hCG is given as a single injection and intrauterine insemination with washed and separated sperm performed 24 to 36 hours later. It is also possible to determine the timing of the IUI based on urinary ovulation predictor kits.

• Using this treatment modality, the ovulatory and male factors are being enhanced while the cervical factor is being bypassed.

Level 2 includes up to three cycles of gonadotropins combined with intrauterine insemination. Gonadotropins (Gonal-F, Follistim, Fertinex, Pergonal or Humagon) are started on cycle day 3 and administered daily as an intramuscular or subcutaneous injection. Transvaginal ultrasound monitoring is begun after four days of treatment and repeated every 1-2 days until 3-6 follicles reach a size of = 17 mm. To induce ovulation, hCG is given as an injection and then intrauterine insemination with washed and separated sperm is performed 24 to 36 hours later. It is also possible to determine the timing of the IUI based on urinary ovulation predictor kits.

• Using this treatment modality, the ovulatory and male factors are being enhanced while the cervical factor is being bypassed.

Level 3 includes up to three cycles of IVF. Gonadotropins are administered as in level 2, but with the addition of Lupron injections or Synarel nasal spray starting either at the same time or one week before the HMG. Transvaginal ultrasound and blood estradiol measurements are done per routine, with hCG administered when at least three mature follicles are detected. Transvaginal ultrasound-guided follicle aspiration is performed 36 hours later, and embryos are transferred into the uterus 3-5 days later. With IVF, further diagnostic information will be obtained, as we are able to observe the fertilization efficiency of the sperm, and the embryo development prior to transfer. This information may provide clues to a prior undiagnosed infertility factor.

• With IVF, the ovulation and male factors are being enhanced and the cervical and tubal factors are being bypassed.
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About the Author

Dr. Herbert is a fertility expert and an innovator in the field.

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