Patient information: Treatment of infertility in men

MALE INFERTILITY OVERVIEW

Infertility is defined as a couple's inability to become pregnant after one year of unprotected intercourse. In any given year, about 15 percent of couples in North America and Europe who are trying to conceive are infertile.

The fertility of a couple depends upon several factors in both the male and female partner. Among all cases of infertility, about 20 percent can be traced to male factors, 38 percent can be traced to female factors, 27 percent can be traced to factors in both the male and female partners, and 15 percent cannot be traced to obvious factors in either partner.

When infertility occurs, the male and female partners are evaluated to determine the cause and best treatment options. In the past, men with infertility had few options because there was limited information about causes and even less information about successful treatment. However, new tests have made it possible to determine the causes of male infertility and treatments and assisted reproductive techniques (ART) offer hope to many couples.

Separate articles discuss the treatment of female infertility (see "Patient information: Infertility treatment with clomiphene (Clomid® or Serophene®)" and "Patient information: Infertility treatment with gonadotropins" and "Patient information: In vitro fertilization (IVF)".

MALE INFERTILITY CAUSES

Fertility in men requires normal functioning of the hypothalamus, pituitary gland, and testes (figure 1). Therefore, a variety of conditions can lead to infertility.

• 30 to 40 percent of cases are due to problems in the testes (called primary hypogonadism)
• 10 to 20 percent are due to problems with the transport of sperm from the testes to the urethra (usually caused by a blockage) (figure 2)

• 1 to 2 percent of cases are due to conditions of the pituitary gland or hypothalamus (called secondary hypogonadism)
• 40 to 50 percent of cases have no identifiable cause, even after an evaluation

MALE INFERTILITY EVALUATION

A separate article discusses the evaluation of infertility in men. (See "Patient information: Evaluation of the infertile couple".)

MALE INFERTILITY TREATMENT

The treatment of male infertility depends upon the underlying cause. Several months to years of treatment are usually necessary to achieve fertility.

However, treatment is not currently available for all types of male infertility. As an example, there is no known treatment when the seminiferous tubules have been severely damaged or are abnormal. These conditions include Klinefelter syndrome, microdeletions of the Y-chromosome, Sertoli cell only syndrome, and idiopathic infertility associated with azoospermia. In these cases, the couple may consider other options (see 'When infertility cannot be treated' below.

Treatment of hypothalamic or pituitary deficiency — Male infertility can occur when the hypothalamus and pituitary gland (parts of the brain that regulate hormone production) fail to produce normal levels of hormones. In this case, treatment with human chorionic gonadotropin (hCG), recombinant human follicle stimulating hormone (rhFSH) (also called gonadotropin treatment) or gonadotropin-releasing hormone (GnRH) may be recommended.

• Gonadotropin treatment — Gonadotropin treatment is started with injections of hCG three times per week (or sometimes every other day) for up to six months. Blood tests are used to monitor blood testosterone levels and to adjust the dose if necessary.

If sperm counts do not recover after six months of treatment, recombinant human follicle stimulating hormone (rhFSH) is added; this is also given by injection. In many cases, a total of one to two years of treatment is needed to achieve normal fertility. The cost of these treatments can be significant, especially if health insurance does not cover the costs of infertility treatments.

• Pulsatile GnRH treatment — Pulsatile injections of gonadotropin releasing hormone (GnRH) have been successfully used to treat gonadotropin deficient patients. GnRH is delivered in pulses using a portable pump that attaches to the body with thin tubing and a flexible needle that is inserted under the skin. The pump can be carried in a pocket or on a belt, like a pager. Treatment for 12 months to three years is required before sperm are developed. In addition, treatment is only available in selected academic research centers.

Other conditions — Treatments are available for several other conditions (listed below), but their role and effectiveness in reversing male infertility are still being studied. The pregnancy success rate of these treatments can vary from couple to couple. An infertility specialist may be able to predict the likelihood that these treatments will be successful.

Genital infection — If the semen analysis reveals many white blood cells, an infection of the reproductive tract may be present. Infections are treated with antibiotics. However, only certain infections have been clearly linked to infertility, and antibiotic treatment may not be effective in restoring fertility.

Retrograde ejaculation — Certain conditions cause sperm to move in the wrong direction in the male reproductive tract, depositing them in the bladder. In many cases, retrograde ejaculation is a permanent condition. However, sperm can be retrieved from a urine sample that is specially treated. The sperm are washed and used in assisted reproductive techniques such as in vitro fertilization. (See "Patient information: In vitro fertilization (IVF)".)

Varicocele — A varicocele is a dilation of a vein (like a varicose vein) in the scrotum. Many men with varicocele have a low sperm count or abnormal sperm morphology (shape). The reason a varicocele affects the sperm may be related to a higher than normal temperature in the testicles, poor oxygen supply, and poor blood flow in the testes.

Varicocele can be treated surgically by cutting the veins connected to the varicocele. However, surgery does not always improve fertility and is not recommended for most men unless there is a large varicocele. A varicocele that has been present for a long time can cause irreversible damage that cannot be surgically treated.

An alternative to varicocele repair is assisted reproductive techniques (ART), such as intracytoplasmic sperm injection (ICSI). With ICSI, only a small number of sperm are needed (see 'Intracytoplasmic sperm injection (ICSI)' below.

Blockage of the reproductive tract — Surgery may be performed to open or bypass blockages of various parts of the male reproductive tract. Vasectomy (male sterilization) is one type of blockage that can be reversed in up to 85 percent of cases; over 50 percent of couples can achieve pregnancy following vasectomy reversal. However, the more time that has passed since the vasectomy, the less likely vasectomy reversal is to restore fertility.

Other types of blockages (in the epididymis, caused by past infections) tend to be more difficult to treat. Treatment options include surgery to correct the blockage or assisted reproductive technologies.

ASSISTED REPRODUCTIVE TECHNIQUES

If the male partner's semen contains few sperm, no sperm, abnormal sperm, or sperm with poor motility, assisted reproductive techniques can often help. These techniques offer hope to some infertile couples who could not achieve pregnancy without them.

However, the techniques are expensive, require a considerable commitment of time and energy, may pose certain health risks, and may have disappointingly low success rates. Couples should discuss the pros, cons, and success rates of these techniques with an infertility specialist.

In vitro fertilization (IVF) — IVF is a commonly used technique for a variety of infertility problems, including male tubal blockages and unexplained infertility. IVF is usually recommended with ICSI for men with infertility. (See 'Intracytoplasmic sperm injection (ICSI)' below.)

IVF success rates depend upon a number of variables, including the age and health of the woman, health of the male sperm and female egg, and to some extent, the experience of the infertility center. Approximately 28 percent of IVF cycle result in pregnancy, and 82 percent of those pregnancies result in the birth of one or more children. (See "Patient information: In vitro fertilization (IVF)".)

Intracytoplasmic sperm injection (ICSI) — ICSI is a procedure that is performed in conjunction with IVF. With ICSI, a single sperm from the male partner is injected directly into the fluid surrounding a woman's egg (oocyte) in the laboratory. (See "Intracytoplasmic sperm injection".)

This technique can be useful in many cases of low sperm count. If a man's semen completely lacks sperm (azoospermia), sperm can sometimes be directly removed from the testes. This is done in a minor surgery or by using a needle to aspirate semen under local anesthesia. The pregnancy rate with ICSI is approximately 20 to 40 percent per cycle, although the technique is expensive.

Risks of ART — Most patients who undergo ART have no major complications. There are few to no risks for men, depending upon the procedure used to obtain sperm. Men who must undergo a procedure to retrieve sperm have a small risk of bleeding, damage to the testes, and infection.

Risks of ART for women include infection and damage to blood vessels, reproductive, or surrounding organs. The ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication that can occur during the process of IVF. (See "Patient information: In vitro fertilization (IVF)".)

There is some evidence that children of couples who become pregnant after IVF or ICSI have a slightly higher rate of chromosomal or congenital (birth) abnormalities. This potential risk should be discussed with an infertility specialist. For now, couples can be reassured that these conditions are rare and the absolute risk of having a child with a congenital anomaly is low (the population baseline risk is 2 to 4 percent, which is potentially increased by about one-third with ART).

WHEN INFERTILITY CANNOT BE TREATED

Some treatments for male infertility fail, and some cases of male infertility simply cannot be treated at this time. If this is this case, an infertility specialist can advise the couple of available alternatives. Each couple's choice is a very personal one.

Men with irreversible infertility and testosterone deficiency may benefit from testosterone treatment. Although this treatment may not address a couple's goal of having a child, it can improve the male partner's sexual function and mood and help increase and maintain bone and muscle mass. (See "Patient information: Sexual problems in men".)

Artificial insemination with donor sperm — Some couples affected by irreversible male infertility consider artificial insemination of the female partner with donor sperm. Donor sperm may be obtained from a sperm bank, which screens men for infections, certain genetic problems, and provides a complete personal and family history. Most sperm banks keep the identity of their donors confidential; some banks give donors the option to be contacted by the children conceived with their sperm.

The decision to use donor sperm, whether from a known or unknown donor, can be complicated and difficult for a couple. Counseling may be helpful to help both partners discuss their feelings and the potential implications of using donor sperm. The decision to disclose the identity of the biologic parent to the child and the couple's friends and family should also be discussed; some couples are comfortable openly discussing their use of donor sperm while others prefer to tell no one.

The American Society for Reproductive Medicine recommends that parents discuss their child's genetic origins with the child. The optimal age for this discussion is not known, although most experts recommend that the child be told before he or she is an adolescent (before approximately age 13) [1].

The use of donor sperm has a high success rate; pregnancy rates are about 50 percent after six cycles of insemination. Insemination may be done without the use of infertility medications or monitoring in women who have no infertility. Women who have difficulty conceiving may require intrauterine insemination or in vitro fertilization. (See "Patient information: Infertility treatment with gonadotropins".)

Adoption — Some couples affected by irreversible male infertility consider adopting a child. A healthcare provider or social worker can suggest resources for couples who decide to pursue this option. Approximately 2 to 4 percent of American families include an adopted child. There are many ways to adopt a child, many of which include use of adoption agency.

The child's biologic parent(s) may request that their identity remain confidential and that they not be contacted, while other biologic parent(s) request that they be allowed to interact with the child as he or she grows. Prospective adoptive parents should take care to work with a reputable adoption agency.

Childlessness — Some couples affected by irreversible male infertility decide to remain childless. They may explore alternate ways of enjoying children through volunteer or foster opportunities, work to enrich their relationship as a couple, or work to create a support network of other childless couples.

Parents who decide to remain childless often face questions from friends or family regarding their decision. These questions can be hurtful for couples who have struggled with infertility. Couples often benefit from counseling after they decide to stop infertility treatments; communicating openly is important to maintain a healthy relationship.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Infertility treatment with clomiphene (Clomid® or Serophene®)
Patient information: Infertility treatment with gonadotropins
Patient information: In vitro fertilization (IVF)
Patient information: Evaluation of the infertile couple
Patient information: Sexual problems in men

Professional Level Information:
Causes of male infertility
Causes of primary hypogonadism in males
Causes of secondary hypogonadism in males
Clinical features and diagnosis of male hypogonadism
Effects of cytotoxic agents on gonadal function in adult men
Evaluation of male infertility
Evaluation of the infertile couple
Induction of fertility in men with secondary hypogonadism
Intracytoplasmic sperm injection
Treatment of male infertility
Treatment of unexplained infertility

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• The Hormone Foundation

      (www.hormone.org/public/other.cfm, also available in Spanish)

• American Society for Reproductive Medicine

      (www.asrm.com/)

• Resolve: The National Infertility Asoociation

      (www.resolve.org)

• The International Council on Infertility Information Dissemination

      (www.inciid.com)

Patient Support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Infertility Conditions Forum

      (http://infertility.about.com/forum)

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