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• Highlights
• Introduction
• Male Reproductive System
• Sperm Abnormalities
• Causes
• Diagnosis
• Treatment
• Assisted Reproductive Technologies
• Complications of ART
• Other Treatments
• Resources
• References

Infertility in men

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of male infertility.

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) are medical techniques that help couples conceive. These procedures involve either:

• A couple’s own eggs or sperm
• Donor eggs, sperm, or embryos

Fertilization may occur either in the laboratory or in the uterus. In the U.S., the number of live birth deliveries from ART increased by 128% from 1996 - 2002. More than 45,000 babies are now born in the U.S. each year using assisted reproductive technologies.

ART includes fertility drug treatments, artificial insemination (AI), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and other procedures.

Choosing a Fertility Clinic

Choosing a good fertility clinic is important. The government does not always regulate centers offering assisted reproductive techniques, and abuses have been reported, including lack of informed consent, unauthorized use of embryos, and failure to routinely screen donors for disease.

The clinic should always provide the following information:

• The live-birth rate (not just pregnancy success rate) for other couples with similar infertility problems. (Multiple births, such as twins or triplets, are counted as one live birth.)
• Such statistics should include high-risk women, such as those who are older or fail to produce eggs. (Some disreputable clinics give success percentages that exclude high-risk women from their total, thereby making the percentage of success much higher.)

Advanced fertility procedures and medications are extremely expensive and often not covered by insurance. Couples should be cautious about offers of rebates in the event of failure. The clinics offering them are often significantly more expensive than those that don't.

Artificial Insemination

Artificial insemination (AI) it is the least complex of the assisted reproductive technologies and is often tried first in uncomplicated cases of infertility. AI either involves placing the sperm directly in the cervix (called intracervical insemination) or into the uterus (called intrauterine insemination, or IUI). IUI is the standard AI procedure.

It is useful under the following circumstances:

• When the woman's cervical mucus is unreceptive.
• When donor sperm are required.
• If the man's sperm count is very low (although it is preferable if at least 5 million per milliliter are motile).
• When unexplained infertility exists in both partners.

Those in whom AI fails, couples with specific fertility defects, or older women may be candidates for more advanced reproductive technologies.

Pregnancy Rates. A review of 45 studies reported that in unexplained infertility cases, the per-cycle pregnancy rates were 4% for intrauterine insemination (IUI) alone and 8 - 17% per cycle for IUI combined with superovulation, a procedure that uses fertility drugs to bolster egg recovery.

Researchers in 2002 study suggested IUI as a reasonable first option for many women under age 43. It is less expensive and poses less risk for multiple births than the more advanced assisted reproductive technologies (ART), such as in vitro fertilization. Although IVF procedures are more effective per cycle, couples tend to be able to afford more IUI cycles, so the pregnancy rates over time are very similar.

The Artificial Insemination Procedure. The AI procedure is as follows:

• A woman usually (but not always) takes fertility drugs in advance.
• The man must produce sperm at the time the woman is ovulating.
• The sperm are subjected to certain so-called "washing" procedures. They are then inserted into the uterine cavity through a long, thin catheter.

The administration of fertility drugs and sperm retrieval is timed so that the process can coincide with time of ovulation. A 2000 study suggested that women who lay quietly for 10 minutes after sperm were implanted had a significantly higher rate of pregnancy than those who got up immediately.

Intracytoplasmic Sperm Injection (ICSI)

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology used for couples when male infertility is the main factor. It involves injecting a single sperm into an egg obtained from in vitro fertilization (IVF). The procedure is very simple:

• A tiny glass tube (called a holding pipet) stabilizes the egg.
• A second glass tube (called the injection pipet) is employed to penetrate the egg's membrane and deposit a single sperm into the egg.
• The egg is released into a drop of cultured medium.
• If fertilized, the egg is allowed to develop for 1 - 2 days and then is either frozen or implanted.

The greatest concern with this procedure has been whether it increases the risk for birth defects. However, studies in 2002 and 2003 reported no higher risks of birth defects in children born using ICSI procedures. While some studies have shown a higher number of birth defects in children conceived with ICSI, experts think that this may have more to do with the genetic background of the parents than ICSI itself. Recent research suggests that ICSI children develop normally. A 2006 study of 8-year-old children conceived with ICSI found no important differences between these children and children who were conceived naturally.

In Vitro Fertilization (IVF)

About 71% of ART procedures now use in vitro fertilization (IVF) with the woman's own eggs. An in vitro procedure is one that is performed in the laboratory. Advances in these procedures have dramatically increased the rate of live births.

The best candidates for IVF are women with damaged fallopian tubes, and some experts believe it is a better option than attempting surgical repair. IVF is also used when infertility is unexplained or when the male partner has the infertility problem. A typical IVF procedure is as follows:

• The doctor first induces superovulation using fertility drugs so that several eggs can be harvested from the ovary before they have been released from the follicles. Higher doses of fertility drugs for subsequent cycles do not appear to add any advantage in women who have a poor response the first time.
• To harvest eggs, the doctor generally inserts a probe into the vagina and is guided by ultrasound. A needle is then used to drain the liquid from the follicles, and several eggs are retrieved.
• The eggs and sperm are combined in a Petri dish. Between 48 - 72 hours later the eggs are fertilized.
• The resulting embryos (the first stage toward the development of the fetus) are reimplanted into the woman's uterus.
• It takes about 2 weeks to determine if the process is successful.

IVF success rates for the first three cycles of treatment are about equal. They then decline modestly for the fourth cycle and drop significantly after the fifth cycle.

Gamete/Zygote Intrafallopian Transfer. Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) are adaptations of IVF. GIFT and ZIFT are used in unexplained female infertility and in mild male infertility. The success rates are similar to those of IVF, but a woman must have at least one functioning fallopian tube.

GIFT : The procedure is as follows:

• The eggs are harvested as in IVF.
• They are mixed with the sperm but not actively fertilized.
• They are immediately injected back into the woman. Laparoscopy, a technique that employs a miniature viewing device, is used with this procedure to guide the placement of the embryos or egg through a long, thin catheter into the fallopian tubes.
• The sperm and egg are placed exactly where they would be in natural fertilization.

ZIFT : The procedure is as follows.

• The eggs are harvested as in IVF.
• They are then mixed with the sperm and, in this case, are fertilized in the laboratory.
• They are then implanted in the fallopian tubes as in GIFT. (The advantage of this procedure over GIFT is that the doctor and couple are assured that fertilization has taken place and the eggs can be examined for defects before implantation.)

Success Rates for IVF Procedures

Success rates have increased in all age groups (although they are still considerably lower in older than in younger women). Chances for ART success are also greater among women who do not have uterine abnormalities and have had previous successful pregnancies.

Success rates are also higher or lower depending on whether the woman uses her own eggs or whether they are donated and also whether the eggs are fresh or frozen. The highest live birth rates are with donated fresh eggs (an average of 50% per transfer) and the lowest rates are when a woman uses her own frozen eggs (an average of 29% per transfer). However, using frozen eggs is less expensive than fresh eggs, so a couple may be able to afford more cycles with frozen eggs.

Use of Donor Eggs. Older women are more likely to use donor eggs. In a 2002 study, success rates were the same for women who used donors with an age range of 20 - 40. There were also no differences in delivery rates for recipients up to age 45. Women over age 45, however, increasingly had problems with implantation, pregnancy, and delivery.

Use of Frozen Eggs. Frozen eggs tend to have lower success rates because of toxins released by cells damaged in the freezing and thawing tissues.

Other ART Techniques

In Vitro Maturation. A new technique called in vitro maturation allows fertilization without the use of fertility drugs. In this process, follicles are harvested a few days before ovulation. In such cases, up to 50 have already begun to mature. About 15 of these maturing follicles can be removed, out of which 2 or 3 can produce healthy embryos.

Blastocyst Transfer. Blastocyst transfer is very promising. Instead of implanting the standard 2- or 3-day-old embryos in the uterus, the procedure implants blastocysts, which are more complex, 5-day-old embryos. Fewer blastocysts than embryos need to be implanted, reducing the risk for multiple births. (There is, however, a higher risk for identical twins compared to other procedures.) Offspring may be more likely to be males than females. Pregnancy rates are about 36% with a first attempt but then drop significantly. The procedure is more likely to be successful in younger than older women.

Ooplasmic Transfer. Ooplasmic transfer is a controversial experimental procedure that uses the woman's own egg and a female donor's egg and the male sperm for fertilization. Genetic material from the donor's egg plus the sperm are added to the woman's own egg. This has been successful in a few cases, but studies are very early and long-term effects are unknown. Research on this and similar procedures are currently conducted outside the United States.

Sperm Retrieval and Preparation for ART Before fertilization using intrauterine insemination (IUI) or advanced assisted reproductive technologies (ART) can take place, the sperm must be collected and prepared for optimal chances for success. Retrieval Procedures When a man has no available sperm in the ejaculate (usually from blockage, vasectomy, or lack of vas deferens), the sperm must be retrieved from the testes or the epididymis. Various microsurgical techniques are now available for retrieval. The procedure may be done under local or general anesthesia, using a spring-loaded biopsy device, a thin needle, incisions, or microsurgical techniques. Surgical Biopsy. In men without obstruction, sperm can be retrieved using a surgical testicular biopsy. Testicular Fine Needle Aspiration (TFNA). TFNA employs a fine needle to remove sperm. This can be performed with local anesthetic and by surgeons who do not have to be experienced in microsurgeries. Microsurgical Epididymal Sperm Aspiration (MESA). MESA uses microsurgical techniques to collect sperm that are close to blocked portions of the epididymis. It involves an open incision and may be done under general or spinal anesthesia in a hospital setting, although the patient can often go home the same day. The doctor accesses the epididymis and retrieves sperm with an extremely fine needle-like device. It has the advantage that it can retrieve the largest number of sperm compared to other procedures. However, as with any invasive procedure, it carries some risks of complications, such as bleeding or infection. Percutaneous Epididymal Sperm Aspiration (PESA). PESA uses a needle to obtain mature sperm from areas in the upper parts of the epididymis (the coiled tube where sperm are stored before ejaculation). It is done under local anesthesia, sometimes in the doctor's office, is less expensive than other techniques, and recovery is fairly painless. However, it has less of a chance of achieving sufficient sperm than MESA, and there is also a chance of hitting a blood vessel, causing bleeding. Testicular Sperm Extraction (TESE). TESE is a microsurgery that removes a small amount of tissue from one or more areas of the testes using incisions and microsurgery techniques. The tissue is placed in a culture and chopped into tiny pieces. Sperm are liberated from the tiny tubes and extracted. It is a complex process, however. This is the second best method for men with vasectomies, according to some experts. It is more painful than PESA, however. In addition, if the procedure is repeated too often, it can cause permanent alterations in testicular function that may even reduce male hormone levels. Testicular Sperm Aspiration (TESA). TESA uses a needle-like biopsy device to draw a small sample of testicular tissue. Multiple attempts are sometimes required to retrieve sperm, and it is not as effective or as safe as TESE, although imaging techniques using ultrasound may improve results. Sperm Washing A sperm's energy output is 20 times greater once it is removed from the seminal fluid. Methods for washing sperm can have a dramatic effect on the ability of sperm to move towards the egg. The simplest method involves: The sperm is mixed with a nutrient-rich fluid (or culture media) in a test tube. They are then centrifuged (spun very rapidly) for about 5 minutes. The sperm, which are heavy, settle on the bottom, forming a dense button of millions of pure sperm. The fluid left on top is siphoned off. This procedure may be repeated. This simple method of sperm washing, however, does not eliminate heavy debris, such as dead sperm, white blood cells, or bacteria, which may impair fertility. Scientists are developing new techniques, such as adding a substance called platelet-activating factor during the sperm washing process, which may enhance pregnancy rates. Swim-Up Technique The swim-up technique is not only a useful diagnostic procedure for testing the ability of sperm to escape from the semen into the cervical mucus, but it also achieves the goal of removing sperm from semen. A specially prepared semen sample is placed in a tube. A culture media (a nutrient-rich substance in which cells thrive) is placed on top of the sample. The medium is a hospitable environment for sperm, and those that are healthy will swim up to it. After an hour or more, the culture is examined, and the number of sperm that have reached the medium is compared to the number still remaining in the semen. The result gives a fair estimation of the number of sperm potentially capable of fertilization. It is superior to sperm washing because the live sperm will swim up to the culture media, leaving behind most of the debris, although some may float up into the medium. There is also some evidence that such sperm may have fewer genetic abnormalities than those retrieved through sperm washing. The strongest sperm, which are those at the top of the medium, can be collected for in vitro fertilization or artificial insemination. A good swim test yields about half a million very active sperm. Freezing Sperm Sperm can be fresh or frozen in advance. Studies are reporting that frozen sperm provide excellent results and can be used confidently for fertilization procedures. Fresh sperm, however, are preferred by some centers for cases when low sperm count is not caused by obstruction.

• Review Date: 10/20/2006
• Reviewed By: Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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