Diagnosing Infertility

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Evaluation

Age & Fertility

Semen Evaluation

Semen Analysis-WHO Minimal Standards of Adequacy

Morphology

Urologic Examination

Antisperm Antibodies

Unexplained Infertility

Infertility is defined as the "failure to conceive following one year of unprotected sexual intercourse." For young and healthy couples having frequent intercourse, about 85% will be pregnant after one year of trying and about 93% will be pregnant after two years of trying to conceive. Mid-Iowa Fertility believes infertility to be defined as failure to conceive following one year of unprotected intercourse if under age 35 or six months if over age 35.

This definition is a useful guideline for who should be evaluated for infertility; rigid adherence to the definition can be a disservice to many people desiring to create a family. Some insurance companies and health plan administrators set policies on fertility coverage based on one year's definition even though it does not apply to everyone in every situation. For example, couples with specific infertility risk factors, such as women with a history of endometriosis or irregular menstrual periods should be evaluated as soon as they plan on starting a family. In these cases it is likely they would require some form of assistance in achieving a pregnancy. Other cases include single women or lesbian couples who may need the services of fertility specialists, but may not qualify under their insurance policy's definition of infertility.

Evaluation

A couple's medical history and age of the female partner will be taken into consideration when our physicians begin the initial evaluation. Mid-Iowa Fertility begins evaluation of infertility when:

• Women less than 35 years of age: Begin after one year of trying
• Women 35-39: Begin after approximately six months of adequately timed intercourse or inseminations.
• Women 40 and over: We do this because we recognize that female age is one of the most important predictors of subsequent conception. When female age is a factor, moving more aggressively towards completing the evaluation and initiating treatment can help to maximize the chances of pregnancy.

Age & Fertility

More and more women are having their first child after the age of 35. This time also coincides with the biological decline in fertility potential. One of the most challenging clinical scenarios is the impact of the aging egg on pregnancy chances. This decline in fertility potential, or "ovarian reserve", is the natural consequence of the aging process on human eggs.

The human ovary has two major functions. One is the reproductive function or production of eggs (oocytes). The second is the steroidogenic function or production of hormones, mostly estrogens. The reproductive function of the ovary has a much shorter lifespan that the steroidogenic function. Therefore fertility potential declines in the 30s, even though menopause occurs in the late 40s to early 50s. Each woman is born with a set number of eggs, predetermined before birth. This pool of eggs is never replenished. A female fetus will have the greatest number of eggs around 16-20 weeks of pregnancy (6-7 million); at birth this number decreases to about 2 million, and by puberty to about 300,000. This constant and dynamic process of decline continues until menopause, and is not interrupted by birth control pills, pregnancy, or ovulation. From this reservoir of eggs, fewer than 500 eggs will ovulate during a woman's reproductive years.

Lower pregnancy rates and higher miscarriage rates are both the consequences of the aging process, and reflective of a decline in egg quality. Women ovulate their healthiest eggs during their 20s and early 30s. By the mid 30s the remaining eggs are of lower quality, and by the early 40s only eggs with very low fertility potential are available for ovulation or ovulation induction. This phenomenon is a normal biological process, which neither fertility medications nor lifestyle changes can halt. A healthy egg has two functions necessary for a successful pregnancy. First, it must have normal chromosomes, and second, it must be able to combine its chromosomes with those of the sperm in a correct and efficient manner to produce a normally dividing and growing embryo.

For some patients, we may recommend a Clomid Challenge Test (CCCT), which is a more sensitive test for assessing ovarian reserve. For this test we assess the hormones FSH and Estradiol on cycle day 3, then administer Clomid (Clomiphene Citrate 100 mg/day) from cycle days 5-9, and then reassess the FSH value on day 10. All three blood test results must be in a normal range for the overall test result to be normal. Any abnormal value indicates an abnormal Clomid Challenge Test. The FSH value on cycle day 10 should be less than 10 mIU/ml, and if elevated indicates diminished ovarian reserve. See FAQs

Semen Evaluation

Most men will initially be diagnosed with a potential male factor problem based on the results of an ejaculated sperm specimen. Normal values for the sperm analysis, as defined by the World Health Organization (WHO):

Semen Analysis-WHO Minimal Standards of Adequacy

• Ejaculate volume - 1.5-5.0cc (milliliters)
• Ejaculate volume----------1.5-5.0cc (milliliters)
• Sperm Concentration----->20 million sperm per cc
• Motility--------------------->50%
• Forward Progression------2 (scale 1-4)
• Morphology----------------30% normal forms (WHO criteria)
• Morphology---------------->4% normal forms (Krueger criteria)

Morphology

Another important parameter in the semen analysis is the morphology, or shape of the sperm. The shape of the sperm is a reflection of proper sperm development in the testicle, or spermatogenesis. Men with a defect in sperm maturation tend to have problems with sperm morphology and may then be at risk for failure of their sperm to fertilize their partner's eggs.

Urologic Examination

Once an abnormal finding on a semen analysis is identified, the male partner should be referred to an urologist for an examination and a review of his medical history. Usually, a repeat semen analysis will be recommended by the urologist as there is significant variability from specimen to specimen. The urologist will usually want to examine a urine sample to rule out infection or evidence of kidney or bladder problems.

If the size of the testicles is less than expected, the male will be tested for hormone levels and he will also be examined to see if he might have a varicocele, a set of dilated veins in the scrotum that is associated with infertility. If a blockage of the sperm collection or transport system anatomy is suspected, additional tests may be recommended.

Antisperm Antibodies

One other test worth mentioning is the direct anti-sperm antibody test. It is well known that men who have undergone a vasectomy and a subsequent vasectomy reversal frequently develop antibodies against their own sperm. If a large number of these antibodies bind to the head of the sperm, it becomes increasingly difficult for fertilization to take place. In about 5% of men with unexplained infertility who have no prior surgery will have anti-sperm antibodies which may cause fertilization defects. Therefore, some physicians and urologists will recommend the direct anti-sperm antibody test be performed on the sperm of men who have otherwise unexplained infertility. If the sperm sample shows significant amounts of agglutination (sperm stuck to each other) this test should be performed.

Unexplained Infertility

People often approach infertility testing with some anxiety, 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 are 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).