US Pharm. 2024;49(6):24-27.

Infertility is a disease of the reproductive system that can result in a man, a woman, or both having the inability to conceive a baby. Male infertility means that a male has a problem with his reproductive organs and cannot achieve a pregnancy with a female partner. Problems with producing healthy sperm are the most common causes of male infertility. Sperm may be immature, abnormally shaped, or immobile.¹

A healthy man produces healthy sperm that should normally fertilize an ovum (egg). To achieve fertilization, he must have an erection and ejaculate so that the sperm can reach the egg. Problems in either of these areas may cause infertility.¹

A total motile sperm count (TMSC) above 20 million is considered normal; however, even if a male has over 20 million motile sperm, it may not result in a higher chance of pregnancy. In cases where a male has fewer than 20 million motile sperm, the chances of having a successful pregnancy may decrease. Men with a TMSC consistently fewer than 5 million are said to have severe male factor infertility.²

In many cases, the cause of infertility may be difficult to determine and may include inadequate levels of certain hormones. The main symptom of infertility is an inability to get pregnant, and there may not be any additional symptoms.³

Today, many treatments are available to improve the chances of males becoming fertile. These treatments include hormone treatments, fertility drugs, and surgery. In addition, assisted reproduction with various medical techniques has resulted in fertilizing an egg.^3,4

CAUSES OF MALE INFERTILITY

Sperm Disorders

Problems making healthy sperm are the most common causes of male infertility. In some cases, a man may not have enough sperm or may not make any sperm. Azoospermia (absence of viable sperm in semen) affects nearly 1% of the male population and about 10% to 15% of all males with infertility.⁵ Many untreatable testicular disorders result in azoospermia. It is reported that sperm disorders may be caused by a variety of conditions:

• Hormone or pituitary gland problems
• Mumps virus infection after puberty
• Autoimmune disorders
• Smoking, alcoholism, and use of steroids (environmental factors)
• Genetic diseases, such as cystic fibrosis or hemochromatosis.^5,6

Structural Problems and Abnormal Sperm

Anything that blocks the genital tract can stop the flow of semen. This could be a genetic or birth defect, as well as infection or inflammation from a sexually transmitted disease. Other causes include scar tissue from surgery, twisted or swollen veins in the scrotum, as well as abnormal sperm.^1,6

Abnormal sperm morphology is classified as defects in head, midpiece, or tail of the sperm. Head defects include large, small, tapered, pyriform, round, and amorphous heads; heads with a small acrosomal area and double heads; as well as any combination of these. These defects might affect the ability of sperm to reach and penetrate an egg.^1,6

Major untreatable types of male infertility are found in 70% of infertile men and include oligozoospermia, asthenozoospermia, teratozoospermia, and normospermia with functional defects. In these cases, assisted reproductive techniques will be necessary for reproduction.^1,6

A basic spermogram or semenogram assesses the various aspects of the sample, and if no variation is found, it is declared to be normozoospermia.

Risk Factors

Any of the following issues in the past may cause male infertility¹:

• Inflammation of the prostate or past genital infections
• Injury to or twisting (torsion) of the testicles
• Early or late puberty
• Exposure of the genitals to high temperatures
• Hernia repair
• Undescended testicles.

Research has also shown an association between hypertension and impaired semen quality. Men diagnosed with hypertension had a lower semen volume, sperm motility, total sperm count, and motile sperm count relative to men in the cohort who did not carry a diagnosis of hypertension.⁷

SYMPTOMS

A man may have male infertility if his female partner has not become pregnant after having unprotected sex without any birth control for 12 months. There may be no other obvious signs or symptoms; however, it is reported that a low sperm count, decreased facial or body hair, erectile dysfunction, low desire for sex, and pain, swelling, or a lump in the testicle area may be considered symptoms.¹

DIAGNOSIS

After a clinician reviews a patient’s past medical history and performs a physical exam, he or she may order the following tests for male infertility^8,9:

Sperm Count (Semen Analysis): At least two semen samples are taken on separate days. The provider will check the semen and sperm for many characteristics, including the quantity of semen and sperm that the patient produces, how uniform and acidic the semen is, how well the sperm move, and the shape of the sperm.

Blood Tests: The physician may order special blood tests to check hormone levels and rule out other problems.

Imaging: The provider uses imaging to help find the cause of sperm defects or health problems of the male reproductive system. Imaging tests such as an ultrasound may be used to look at the testicles, blood vessels, and structures inside of the scrotum.

Testicular Biopsy: If semen analysis shows that the patient has few or no sperm, the physician may order a biopsy from each testicle for a microscopic analysis.

TREATMENT

Treatment depends on what is causing the male’s infertility, and the treatment involves helping him to get his partner pregnant. This may be as follows^8,9:

Artificial Insemination: This method places many healthy sperm at the entrance of the cervix, or they are inserted directly into the woman’s uterus. The sperm can then travel to the fallopian tubes.

Fertilization: In vitro fertilization and gamete intrafallopian transfer work similarly to artificial insemination. The provider first collects the male’s sperm. Then he or she mixes the woman’s egg(s) with a large amount of high-quality sperm. The physician may mix the egg(s) and sperm in the laboratory or in the woman’s fallopian tube.

Intracytoplasmic Sperm Injection: In this technique, the doctor injects a single sperm into an egg. Fertilization then takes place under a microscope. The clinician then puts the fertilized egg in the woman’s uterus.

HORMONAL AND DRUG TREATMENT

Hormone treatment may help if a man has a hormone disorder causing infertility. Hormone imbalances can affect how sperm develops. They may be caused by a problem in how the hypothalamus, pituitary gland, and testes interact. Treatment may include gonadotropin therapy. Certain hormones can get male fertility back on track by increasing the amount of testosterone and decreasing the amount of estradiol (estrogen).⁸

Hormonal therapy for infertile men includes human chorionic gonadotropin, human menopausal gonadotropin, and highly purified or recombinant human follicle–stimulating hormone (FSH). The FDA has approved use of these hormones for the treatment of infertility due to gonadotropin deficiency. Hormonal therapies associated with an increase in sperm production focus on optimizing testosterone production from the Leydig cells, increasing FSH levels to stimulate Sertoli cells, spermatogenesis, and normalizing the testosterone-to-estrogen ratio.⁹

An estrogen receptor blocker, such as clomiphene citrate, is commonly prescribed that stimulates the hypothalamus and pituitary gland in the brain. This generates hormone production and the release of FSH and luteinizing hormone, which can increase sperm production.^10,11

SURGICAL PROCEDURES

A surgical procedure may be necessary to fix problems that keep sperm from being made, matured, or ejaculated.

Surgery to remove twisted, swollen veins in the scrotum is called varicocelectomy. This procedure can be performed in various ways. In microscopic varicocelectomy, performed with sedation or general anesthesia, the surgeon makes a small incision over the inguinal canal, which is located on each side of the groin. Next, he or she uses a special microscope to locate and tie off the affected veins inside the spermatic cord, which travels through the inguinal canals. The recovery typically takes 1 to 3 days followed by limited activity for 2 weeks. Sometimes microscopic varicocelectomy is performed using laparoscopic surgery to identify, cut, and tie off the affected veins.

Varicocele embolization is another type of treatment for varicocele and is a minimally invasive procedure that moves blood away from the enlarged varicocele. The procedure is performed by an interventional radiologist and reduces pressure in the varicocele, allowing blood to be directed through other pathways. The procedure is done under light sedation, and the patient can return home the same day.

The third procedure is transurethral ejaculatory duct resection, which may be performed to open the ejaculatory duct—the tube that carries semen from the testicles to the urethra—if it is blocked. It may also be used to remove any obstruction that can affect a man’s ability to ejaculate sperm. An obstruction may occur because of trauma to the pelvis or an infection. The physician analyzes the quality of the semen 1 month after the procedure, assessing semen volume and the number of sperm, their shape, and their motility.

Sometimes, men wish to reverse a vasectomy—a surgery used for birth control that prevents the release of sperm during ejaculation. Different techniques can be used for this reversal surgery, which helps restore fertility by allowing the flow of sperm. After the vasectomy reversal, patients are able to go home the same day. The recovery typically takes 1 to 3 days, followed by 2 weeks of limited activity.

Finally, microsurgical testicular sperm extraction is recommended for some men with severe deficits in sperm production. Only highly trained urologists perform this procedure. For men with severe deficits in sperm production, this surgery may be the only way to have a biological child. Recovery typically takes 1 to 3 days, with limited activity recommended for 2 weeks.¹²

REFERENCES

1. Leslie SW, Soon-Sutton TL, Khan MAB, et al. Male infertility. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2024 Jan-.
2. Hamilton JM, Cissen M, Brandes M, et al. Total motile sperm count: a better indicator for the severity of male factor infertility than the WHO sperm classification system. Hum Reprod. 2015;30(5):1110-1121.
3. Mayo Clinic. Infertility. www.mayoclinic.org/diseases-conditions/infertility/symptoms-causes/syc-20354317. Accessed May 1, 2024.
4. Chen T, Belladelli F, Giudice FD, et al. Male fertility as a marker for health. Reprod Biomed Online. 2022;44:131-144.
5. Mayo Clinic. Male infertility. www.mayoclinic.org/diseases-conditions/male-infertility/symptoms-causes/syc-20374773. Accessed May 1, 2024.
6. WebMD. What is the morphology of sperm? www.webmd.com/infertility-and-reproduction/morphology-of-sperm. Accessed May 1, 2024.
7. Guo D, Li S, Behr B, et al. PD52-12 the impact of hypertension and antihypertensives on semen quality. J Urol. 2015;193:e1117.
8. Naz M, Kamal M. Classification, causes, diagnosis and treatment of male infertility: a review. Orien Pharm Exp Med. 2017;17(2):89-109.
9. Liu PY, Handelsman DJ. The present and future state of hormonal treatment for male infertility. Hum Reprod Update. 2003;9(1):9-23.
10. Kim HJ, Seo JT, Kim KJ, et al. Clinical significance of subclinical varicocelectomy in male infertility: systematic review and meta-analysis. Andrologia. 2016;48(6):654-661.
11. Kobori Y, Suzuki K, Iwahata T, et al. Hormonal therapy (hCG and rhFSH) for infertile men with adult-onset idiopathic hypogonadotropic hypogonadism. Syst Biol Reprod Med. 2015;61(2):110-112.
12. New York University Langone Health. Surgery for male infertility. www.nyulangone.org/conditions/male-infertility/treatments/surgery-for-male-infertility. Accessed May 9, 2024.

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