January 2020, Volume XXXIII, No 10

Men’s Health

Male infertility

Considering appropriate evaluation

he drive to have genetically conceived children is very strong for many couples, yet as many as 15% are not able to conceive a child, even with frequent, unprotected intercourse for a year or more. It is an unfortunate but common notion that infertility is a woman’s issue, yet according to the American Society of Reproductive Medicine, 20% of infertile couples are infertile solely due to a male infertility factor. In 30% to 40% of infertility cases, there are combined male and female factors. This means that in at least half of infertile couples, the inability to conceive is at least partially explained by male infertility. For these reasons, I believe that a female fertility evaluation should begin with a semen analysis from the partner.

I often see couples who have been trying to conceive for several years, and the woman has undergone extensive testing. Sometimes, azoospermia (no sperm in the ejaculate) is not diagnosed until the man provides a specimen for an insemination. While most physicians are aware of the prevalence and significance of male factor infertility, many of our patients are not. Moreover, many men are reluctant to be tested, fearing that the results, if unfavorable, might question their masculinity.

In Minnesota, there are only a handful of formally trained male infertility physicians. This shortage contributes to the delay in appropriate evaluation of the infertile man.

Why do we pursue a male infertility evaluation?

There are four main reasons to conduct a thorough male fertility evaluation:

  1. To identify significant and undiagnosed medical problems: Approximately 1% of infertile men have testicular cancers. One or two percent have endocrinologic disorders involving the hypothalamus or pituitary gland.
  2. To identify risk factors for the development of significant medical problems: Some studies suggest that men with abnormal semen parameters have a higher all-cause mortality rate, making semen quality a potential health marker. Moreover, a majority of my patients have not seen a physician within the past five years. The male infertility evaluation represents a precious opportunity to identify correctable risk factors, such as obesity, diabetes, excessive drug and alcohol use, tobacco use, and environmental exposures.
  3. To identify correctable male infertility factors: Studies have demonstrated that treatments for specific male factor conditions are both medically effective and cost-effective.
  4. To identify uncorrectable male infertility factors and direct management toward empiric therapies: When male factor infertility cannot be altered, it is important to recognize that expeditiously and present the couple with other options. We are fortunate to partner with reproductive endocrinologists to offer options with well-established success rates.

Twenty percent of infertile couples are infertile solelydue to a male infertility factor.

Specific causes of male infertility

Many conditions affecting male fertility can be identified and treated effectively. Common medical issues include:

Varicocele. Varicoceles are the number one correctable cause of male infertility. The majority of men who have this condition repaired experience a clinically significant improvement in semen analyses and improved chances of contributing to a pregnancy.

Infection. Infections can include epididymitis, orchitis, gonorrhea, or HIV. If they result in permanent damage to the genital ducts, we can often retrieve sperm after the infection has been eliminated.

Ejaculation issues. Retrograde ejaculation (semen that enters the bladder instead of emerging through the penis during orgasm) can occur as a result of diabetes, spinal injuries, medications, and surgery. Spinal cord injuries can affect ejaculation, but often sperm can be retrieved through surgical and nonsurgical means.

Tumors. Cancers and benign tumors can affect hormones related to reproduction, and treatment with surgery, radiation, or chemotherapy can affect male fertility.

Undescended testicles. When one or both testicles fails to descend, decreased fertility can result.

Hormone imbalance. Diseases of the hypothalamus, pituitary, thyroid, or adrenal glands can affect fertility.

Genetic disorders. Klinefelter syndrome is an inherited disorder in which a man is born with two X chromosomes and one Y chromosome instead of one X and one Y. Other karyotypic abnormalities, cystic fibrosis, Kallmann syndrome (a form of hypogonadotropic hypogonadism), and Kartagener syndrome (a type of primary ciliary dyskinesia) also can affect male fertility.

Sexual factors. Anything that affects sexual intercourse can impact fertility, including the inability to maintain an erection, premature ejaculation, and painful intercourse.

Medications. Certain medications can impair sperm production, such as testosterone replacement therapy, steroid use, and chemotherapy.

Surgery. Surgeries that may affect fertility include hernia repairs, retroperitoneal or pelvic surgeries, and, of course, vasectomies.

Diagnostic procedures

Diagnosing male infertility almost always starts with a detailed medical history and physical exam. This is followed by, ideally, two semen analyses to determine semen volume, sperm count, sperm motility, and sperm morphology. Additional specialized testing may include scrotal ultrasound, hormone testing, post-ejaculation urinalysis, specialized sperm function tests, transrectal ultrasound, and testicular biopsy.

Genetic abnormalities, such as numeric and structural chromosomal variations, can lead to infertility. About 10% of men with nonobstructive azoospermia will have an abnormal karyotype and/or an abnormal Y chromosome microdeletion. It is important for patients with genetic abnormalities to undergo genetic counseling prior to assisted reproduction. There may be implications for their own health, as well as for the health of their children.

Treatment options for men with nonobstructive azoospermia

Obstructive azoospermia, which accounts for about 40% of men with azoospermia, often can be repaired through surgery to bypass the obstruction. Men with non-obstructive azoospermia are either not making any sperm or making so few sperm that none make it to the ejaculate. Non-obstructive azoospermia affects about 1% of the male population. Typically, the history is unremarkable in these men. Physical examination usually, but not always, shows small testes. The semen analyses typically show normal or slightly low volume with no sperm and normal pH. A hormonal assessment generally reveals a high follicle stimulating hormone (FSH). In most cases, a diagnostic biopsy is not needed, since we can determine whether there is an obstruction or not based on the FSH and testicular examination.

The next step is to obtain a karyotype and y-chromosome microdeletion test. If there is an abnormality, genetic counseling is undertaken. At this point, the couple can adopt, they can use donor sperm for intrauterine inseminations, or we can attempt to find some sperm in the testicles. If sperm are found, they are used fresh to fertilize the partner’s ova as part of the IVF process.

The mix of options available to treat epilepsy has  expanded considerably.

This sperm retrieval process is called microsurgical testicle sperm extraction. It involves opening the coating over the testicle to expose the tiny tubules. Using an operating microscope that magnifies the site 30 to 40 times, we identify the largest tubules, process microscopic samples, and look for sperm real time. At least one andrology technician is in the operating room with us during the procedure. In almost all circumstances, this extraction is timed with the partner’s ova retrieval, usually within 12 to 24 hours. Published rates for sperm retrieval range from 40% to 65%, depending upon the patient population.

Other treatments for male infertility

Varicocele is the most common correctable form of male infertility. Most infertility specialists perform varicocele repair using a microsurgical subinguinal approach. This minimally invasive option has fewer adverse effects and similar efficacy compared with the older inguinal approach. For all but the most active work, a weekend off is typically adequate for recuperation.

Men who are fertile but who have had a vasectomy may opt for vasectomy reversal. The use of operating microscopes and the development of extremely fine needles, sutures, and instruments enable precise suture placement for aligning the two ends of the vas deferens or the vas deferens to the epididymis, if a more extensive bypass is needed. Urologists specializing in vasectomy reversal and incorporating these techniques typically achieve sperm in the ejaculate more than 90% of the time after a vasectomy reversal.

Medications

In certain populations, we can improve the overall semen quality, most commonly the count, with medical management. This is especially true for men with low FSH and low testosterone, who frequently respond well to clomiphene citrate, or men with high estradiol levels who may respond to anastrozole.

If we find an elevated prolactin level on our initial workup, we pursue an evaluation for a pituitary adenoma and recommend medical management in collaboration with our endocrinology colleagues.

Focusing on the entire picture

Some men are not proactive when it comes to their health. Because we know that low sperm counts often are associated with all-cause mortality, we focus on more than just helping a couple conceive a child. We view this as a golden opportunity for beneficial intervention, if a patient is open to it.

We collaborate with a man’s primary care physician, if he has one, as well as any specialists who are treating other conditions. We also work with reproductive endocrinologists in a coordinated team approach to provide a complete list of reproductive treatment options. These options may include insemination, IVF, donor insemination, and adoption. Ultimately, only the patients can make the best decisions for their reproductive goals, armed with the information we provide after a thorough assessment.

For many years and for many reasons, male infertility has not received much attention. As male infertility factors into at least half of all cases of infertility, we owe it to our patients to provide them with timely, guidelines-based evaluations. Once that evaluation is complete, patients should receive a full and detailed discussion regarding the risks and benefits of all reasonably possible treatment options. Treating male infertility can be challenging, but the joy of success when a couple achieves their dream makes it all worthwhile.

Aaron Milbank, MD, is a urologist with Minnesota Urology, specializing in male infertility and microsurgery. 

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Aaron Milbank, MD, is a urologist with Minnesota Urology, specializing in male infertility and microsurgery.