April 5, 2016

MALE INFERTILITY (Continued)

Diagnosis
In any fertility work-up, both male and female partners are tested if pregnancy fails to occur after a year of regular unprotected sexual intercourse. It should be done earlier if a woman is over age 35 or if either partner has known risk factors for infertility. A work-up can not only uncover the causes of infertility but also detect other potentially serious medical problems, including genetic mutations, cancer, or diabetes.

Fertility History
The doctor will ask about any medical or sexual factors that might affect fertility:
    -Frequency and timing of sexual intercourse
    -Duration of infertility and any previous fertility events
    -Childhood illnesses and any problems in development
    -Any serious illness (such as diabetes, respiratory infections, cancer, or previous surgeries)
    -Sexual history, including any sexually transmitted diseases
    -Any exposure to toxins, such as chemicals or radiation
    -History of any medications and allergies
    -Any family history of reproductive problems
Physical Exam
A fertility specialist, usually a urologist, will perform a physical examination. A physical examination of the scrotum, including the testes, is essential for any male fertility work-up. It is useful for detecting large varicoceles, undescended testes, absence of vas deferens, cysts, or other physical abnormalities.
    Varicoceles large enough to possibly interfere with fertility can be felt during examination of the scrotum. In such cases, they are described as feeling like "a bag of worms." They disappear or are greatly reduced when the patient lies down, so the patient should be examined for varicocele while standing.
    Checking the size of the testicles is helpful. Smaller-sized and softer testicles along with tests that show low sperm count are strongly associated with problems in sperm formation. Normal testicles accompanied by a low sperm count, however, suggest possible obstruction. The doctor may also take the temperature of the scrotum with a test called scrotal thermography.
    The doctor will also check the prostate gland for abnormalities.
    The penis is checked for warts, discharge from the urinary tract, and hypospadias (incorrect location of the urethra opening).
Post-Ejaculatory Urine Sample
A urine sample to detect sperm after ejaculation may rule out or indicate retrograde ejaculation. It also may be used to test for infections.
Semen Analysis
The basic test to evaluate a man's fertility is a semen analysis. The sperm collection test for men who can produce semen involves the following steps:
    -A man should abstain from ejaculation for several days before the test because each ejaculation can reduce the number of sperm by as much as a third. To ensure an accurate sample, most doctors recommend abstaining from ejaculation for at least 2 days, but not more than 5 days, prior to semen collection.
    -A man collects a sample of his semen in a collection jar during masturbation either at home or at the doctor's office. Proper collection procedure is important, since the highest concentration of sperm is contained in the initial portion of the ejaculate. Specially designed condoms are also available that enable collection of a sample during sexual intercourse. (Regular condoms are not useful, since they often contain substances that kill sperm.)
    -The sample should be kept at body temperature and delivered promptly. If the sperm are not analyzed within 2 hours or kept reasonably warm, a large proportion may die or lose motility.
    -A semen analysis should be repeated at least three times over several months.
Semen analysis:
The sperm count test is performed if a man's fertility is in question. It is helpful in determining if there is a problem in sperm production or quality of the sperm as a cause of infertility. The test may also be used after a vasectomy to make sure there are no sperm in the semen.
The man and woman should both be present when the doctor discusses the results of this analysis so that both partners understand the implications. The analysis report should contain results of any abnormalities in sperm count, motility, and morphology as well as any problem in the semen. However, semen analysis alone is not necessarily a definitive indicator of either infertility or fertility.
A semen analysis will provide information on:
    Amount of semen produced (volume)
    Number of sperm per milliliter of semen (concentration)
    Total number of sperm in the sample (count)
    Percentage of moving sperm (motility)
    Shape of sperm (morphology)
Semen Volume and Concentration. The seminal fluid (semen) itself is analyzed for abnormalities. The color is checked and should be whitish-gray.
The amount of semen is important. Most men ejaculate 2.5 - 5 milliliters (mL) (1/2 - 1 teaspoon) of semen. Either significantly higher or lower amounts can be a sign of prostate problems, blockage, or retrograde ejaculation.
The semen will be tested for how liquid it is. Abnormal results may suggest prostate gland problems or lack of sperm.
Other factors may also be measured:
    -An absence of semen fructose (sugar) may indicate obstruction in the vas deferens or epididymis.
    -Low levels of a substance called inhibin B, which is produced only in the testes, may indicate blockage or other defects in the seminiferous tubules.
    -Low levels of another compound, alpha-glucosidase, may also indicate blockage in the epididymis.
Sperm Count. A low sperm count should not be viewed as a definitive diagnosis of infertility but rather as one indicator of a fertility problem. In general, a normal sperm count is considered to be 20 million per milliliter of semen.
Sperm Motility. Motility (the speed and quality of movement) is graded on a 1 - 4 ranking system. For fertility, motility should be greater than 2.
    Grade 1 sperm wriggle sluggishly and make little forward progress. (Sperm that, in fact, clump together may indicate that antibodies to the sperm are present.)
    Grade 2 sperm move forward, but they are either very slow or do not move in a straight line.
    Grade 3 sperm move in a straight line at a reasonable speed and can home in on an egg accurately.
    Grade 4 sperm are as accurate as Grade 3 sperm, but move at a very rapid speed.
More than 63% of sperm should be motile for normal fertility, but even men whose motile sperm constitutes only about a third of the total sperm count should not rule out conception. Testing for sperm motility is important for predicting the success of assisted reproductive technologies and which men might be candidates for the intracytoplasmic sperm injection (ICSI ) fertilization technique, in which the sperm is inserted directly into the egg and motility plays almost no role.
Sperm Morphology.
Morphology is the shape and structure of the sperm. Determining the morphology of the sperm is particularly important for the success of the fertility treatments in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).
Blood Tests
Blood tests are used for measuring several factors that might affect fertility:
Hormonal Levels. Men produce both male hormones (testosterone) as well as pituitary hormones (FSH and LH). Tests for these hormone levels are indicated if semen analysis is abnormal (especially if sperm concentration is less than 10 million per milliliter) or there are other indications of hormonal disorders.
    Blood tests for testosterone and follicle-stimulating hormone (FSH) levels are usually taken first.
    If testosterone levels are low, then luteinizing hormone (LH) is measured.
Low levels of FSH, LH, and testosterone may indicate a diagnosis of hypogonadotropic hypogonadism. Very high FSH levels with normal levels of other hormones indicate abnormalities in initial sperm production. Usually this occurs only if the testicles are severely defective, causing Sertoli cell-only syndrome, in which sperm-manufacturing cells are absent. Other hormones, such as prolactin, estrogen, or stress hormones may be measured if there are symptoms of other problems, such as low sexual drive or the presence of breasts.
Infections. Blood tests can determine the presence of any infections that might affect fertility, including HIV, hepatitis, and Chlamydia.
Ultrasound
Ultrasound imaging may be used to accurately determine the size of the testes or to detect cysts, tumors, abnormal blood flow, or varicoceles that are too small for physical detection (although such small veins may have little or no effect on fertility). It can also help detect testicular cancer.
  
Sperm Penetration Tests
Cervical Mucus Penetration Test. This post-coital test is designed to evaluate the effect of a woman's cervical mucus on a man's sperm. Typically, a woman is asked to come into the doctor's office within 2 - 24 hours after intercourse at mid-cycle (when ovulation should occur). A small sample of her cervical mucus is examined under a microscope. If the doctor observes no surviving sperm or no sperm at all, the cervical mucus will then be cultured for the presence of infection. The test cannot evaluate sperm movement from the cervix into the fallopian tubes or the sperm's ability to fertilize an egg.
Cervical Mucus Penetration Test.
This test checks to see if sperm can penetrate hamster eggs that have had their covering removed. If fewer than 5 - 20% of the eggs are penetrated, infertility is diagnosed. It may be useful for determining the best assisted reproductive treatment options for men with infertility.
Genetic Testing
Genetic testing may be warranted in men who are severely deficient in sperm and who show no evidence of obstruction, particularly in men undergoing the intracytoplasmic sperm injection (ICSI) procedure. Genetic testing can help identify sperm DNA fragmentation, chromosomal defects, or the possibility of genetic diseases that can be passed on to children. If genetic abnormalities are suspected in either partner, counseling is recommended.
Treatment
Treatment for infertility should first address any underlying medical conditions that may be contributing to fertility problems. Drug therapy may be used to treat hypogonadism and other hormonally related conditions. Surgery is used to repair varicoceles and correct any obstructions in the reproductive tract. However, there is some controversy over whether varicocele embolisation or surgery actually improves fertility. Some studies indicate that varicocele treatment may not help improve a couple’s chances of conception.
If fertility issues remain unresolved, intrauterine insemination (also called artificial insemination) and assisted reproductive technologies such as in vitro fertilization should be considered. Intracytoplasmic sperm injection is commonly used in combination with in vitro fertilization in cases of male factor infertility. The couple can also discuss with a fertility specialist other options such as donor sperm or eggs.
Choosing a Fertility Clinic
Choosing a good fertility clinic is important. Those offering assisted reproductive techniques are not always regulated by the government, 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.)
Special Considerations for Patients with Cancer
Adolescents and adult men undergoing cancer treatments who may want to father children in the future should consider banking and freezing their sperm for later use in assisted reproductive therapies. This technique is called sperm cryopreservation. Sperm cryopreservation is recommended by the American Society of Clinical Oncology as the method with the highest likelihood of success for male cancer survivors. However, these banking methods are not appropriate for pre-adolescent boys being treated for childhood cancers such as leukemia. Researchers are investigating ways that stem cell transplantation may someday help these children regain their fertility while avoiding leukemia relapse.
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 has dramatically increased in the last decade.
Technically, the term ART refers only to fertility treatments, such as in vitro fertilization (IVF) and its variants, which handle both egg and sperm. Therefore intrauterine insemination (artificial insemination) is not officially considered a form of ART.
Sperm Retrieval Procedures
Before fertilization using intrauterine insemination (IUI) or intracytoplasmic sperm injection (ICSI) can take place, the sperm must be collected and prepared.
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 used 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. Most procedures can be done on an outpatient basis, and the patient returns home the same day. There is no conclusive evidence that one procedure works better than another.
Testicular Fine Needle Aspiration. With testicular fine needle aspiration (TFNA), the surgeon uses a fine needle to remove sperm. This can be performed with local anesthetic and by surgeons who do not have experience in microsurgeries.
Microsurgical Epididymal Sperm Aspiration. Microsurgical epididymal sperm aspiration (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. Percutaneous epididymal sperm aspiration (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 performed 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.
Testicular sperm extraction (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, and the sperm are extracted. It is a complex process, however, and may cause more pain than other sperm retrieval procedures.
Testicular Sperm Aspiration.
Testicular sperm aspiration (TESA) uses a needle-like biopsy device to draw a small sample of testicular tissue. Multiple attempts are sometimes required to retrieve sperm.
Sperm Washing
Sperm washing is done to prepare the sperm for use in ART procedures. Methods for washing sperm can help remove chemicals (prostaglandins) that can cause the woman’s uterus to contract and cramp. Sperm washing can also help remove sexually transmitted viruses, such as HIV and hepatitis, which could potentially be transmitted to the woman during fertility treatment. There are three basic methods for sperm washing:
    Simple sperm wash dilutes sperm in a test tube and then uses a centrifuge to retrieve sperm cells
    Density gradient sperm wash is similar to the simple sperm wash but is better for separating dead sperm from live, healthy sperm cells
    Swim-up technique does not use a centrifuge. Instead, it uses a culture dish with a medium that attracts sperm powerful enough to swim up to the nutrient mixture. This technique is useful for harvesting healthy sperm with good motility. It is not helpful for men who have low sperm counts or poorly motile sperm.
Freezing Sperm
Sperm can be fresh or frozen in advance. Frozen sperm provide excellent results for fertilization procedures. Fresh sperm, however, are preferred by some centers for cases when low sperm count is not caused by obstruction.
Intrauterine Insemination (Artificial Insemination)
Artificial insemination (AI) is the least complex of fertility procedures and is often tried first in uncomplicated cases of infertility. AI 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.
Intrauterine insemination may be used 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.
    -If there is decreased sperm motility.
    -When unexplained infertility exists in both partners.
The intrauterine insemination procedure is as follows:
    -A woman usually 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.
If a woman fails to conceive after IUI, she may be a candidate for in vitro fertilization (IVF). 
Intracytoplasmic Sperm Injection (ICSI)
Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology (ART) used for couples when male infertility is the main factor. It is used in combination with in vitro fertilization (IVF). It involves injecting a single sperm into an egg obtained from IVF.
Lifestyle Changes
-Timing and Monitoring Sexual Activity for Best Results
Both male and female hormone levels fluctuate according to the time of day, and they also vary from day to day and month to month. Some timing tips might be helpful.
Fertility and Seasonal Changes.
Some studies have reported higher sperm counts in the winter than in the summer. For women, fertility rates as measured by treatment success are highest in months when days are longest.
Monitoring Basal Body Temperature.
To determine the most likely time of ovulation and therefore the time of fertility, a woman should take her body temperature, called her basal body temperature. This is the body's temperature as it rises and falls in accord with hormonal fluctuations.
By studying the temperature patterns after a few months, couples can begin to anticipate ovulation and plan their sexual activity accordingly.
Frequency of Intercourse.
It is not clear how often a couple should have intercourse in order to conceive. Some doctors think that having sex more than 2 days a week adds no benefits. In addition, frequent sexual activity lowers sperm count per ejaculation. Some studies have indicated, however, that having intercourse every day, or even several times a day, before and during ovulation, improves pregnancy rates. Although sperm count per ejaculation is low, a constantly replenished semen supply is more likely to result in a fertilized egg.
Dietary Considerations
Everyone should eat a healthy diet rich in fresh fruits, vegetables, and whole grains. Replace animal fats with monounsaturated oils, such as olive oil. Certain specific nutrients and vitamins have been studied for their effects on male infertility and sperm health. They include antioxidant vitamins (vitamin C, vitamin E) and the dietary supplements L-carnitine and L-acetylcarnitine. To date, there is no conclusive evidence that they are effective.
Other Lifestyle Changes
Other tips for helping fertility include:
   Avoid cigarettes and any drugs that may affect sperm count or reduce '- function.
    Overweight men should try to reduce their weight as obesity may be associated with infertility.
    Get sufficient rest, and exercise moderately but regularly. (Excessive exercise can impair fertility.)
    Stress may contribute to reduced sperm quality. It is not known if stress reduction techniques can improve fertility, but they may help couples endure the difficult processes involved in fertility treatments.
    Although studies indicate that tight underwear and pants pose no threat to male fertility, there is no harm in wearing looser clothing.
    To prevent overheating of the testes, men should avoid hot baths, showers, and steam rooms.
    Avoid use of sexual lubricants (Astroglide, KY-jelly) as they may affect sperm motility.
Dealing with Stress
The fertility treatment process presents a roller coaster of emotions. There are almost no sure ways to predict which couples will eventually conceive. Some couples with multiple problems will overcome great odds, while other, seemingly fertile, couples fail to conceive. Many of the new treatments are remarkable, but a live birth is never guaranteed. The emotional burden on the couple is considerable, and some planning is helpful:
    Decide in advance how many and what kind of procedures will be emotionally and financially acceptable and attempt to determine a final limit. Fertility treatments are expensive. A successful pregnancy often depends on repeated attempts.
    Prepare for multiple births as a possible outcome for successful pregnancy (especially if assisted reproductive technologies are used). A pregnancy that results in a multiple birth introduces new complexities and emotional problems.
    Determine alternatives (adoption, donor sperm or egg, or having no children) as early as possible in the fertility process. This can reduce anxiety during treatments and feelings of disappointment if conception does not occur.

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