Infertility

Definition

Infertility is the failure of a couple to conceive a pregnancy after trying to do so for at least one full year. In primary infertility, pregnancy has never occurred. In secondary infertility, one or both members of the couple have previously conceived, but are unable to conceive again after a full year of trying.

Description

Approximately 20% of couples struggle with infertility at any given time. Infertility has increased as a problem over the last 30 years. Some studies blame this increase on social phenomena, including the tendency for marriage and starting a family to occur at a later age. For women, fertility decreases with increasing age:

• Infertility in married women ages 16–20 = 4.5%.
• Infertility in married women ages 35–40 = 31.8%.
• Infertility in married women over the age of 40 = 70%.

Presently, individuals often have several sexual partners before they marry and try to have children. This increase in numbers of sexual partners has led to an increase in sexually transmitted diseases. Scarring from these infections , especially from pelvic inflammatory disease (infection of the female reproductive organs) seems to be in part responsible for the rise in infertility. Furthermore, use of some forms of the contraceptive called the intrauterine device (IUD) has contributed to an increased rate of pelvic inflammatory disease, with subsequent scarring. A study in 2001 found that copper IUDs have probably been wrongfully blamed for tubal infertility, while infection from the sexually transmitted disease chlamydia was likely the cause.

To understand the causes of infertility, it is first necessary to understand the basics of human reproduction. Fertilization occurs when a sperm from the male merges with an egg (ovum) from the female, creating a zygote that contains genetic material (DNA) from both the father and the mother. If pregnancy is then established, the zygote will develop into an embryo, then a fetus, and ultimately, if all goes well, a baby will be born.

Sperm are small cells that carry the father's genetic material. The sperm are mixed into a fluid called semen, which is discharged from the penis during sexual intercourse. The whiplike tail of the sperm allows the sperm to swim up the female reproductive tract, in search of an egg.

The ovum is the cell that carries the mother's genetic material. Once a month, a single mature ovum is produced, and leaves the ovary in a process called ovulation. This ovum enters a tube leading to the uterus (the fallopian tube) where fertilization occurs.

When fertilization occurs, the resulting cell (which now contains genetic material from both the mother and the father) is called the zygote. This single cell will divide into multiple cells and the resulting cluster of cells (called a blastocyst) moves into the womb (uterus). The uterine lining (endometrium) has been preparing itself to receive a pregnancy by growing thicker. If the blastocyst successfully attaches itself to the wall of the uterus, then pregnancy has been achieved.

Causes & symptoms

Unlike most medical problems, infertility is an issue requiring the careful evaluation of two separate individuals, as well as an evaluation of their interactions with each other. In about 3–4% of couples, no cause for their infertility will be discovered. About 40% of the time, infertility is due to a problem with the male; about 40% of the time, infertility is due to the female; and about 20% of the time, there are fertility problems with both the male and the female.

The main factors involved in causing infertility include:

• male problems: 35%
• ovulation problems: 20%
• tubal problems: 20%
• endometriosis : 10%
• cervical factors: 5%

Male factors

Male infertility can be caused by a number of different characteristics of the sperm. To check for these characteristics, a sample of semen is obtained and examined under the microscope (semen analysis). Four basic characteristics are usually evaluated:

• Sperm count refers to the number of sperm present in a semen sample. The normal number of sperm present in just 1 ml of semen is over 20 million. A man with only 5–20 million sperm is considered subfertile and a man with fewer than 5 million sperm is considered infertile.
• Sperm are also examined to see how well they swim (sperm motility) and to be sure that most have normal structure.
• Not all sperm within a specimen of semen will be perfectly normal. Some may be immature, and some may have abnormalities of the head or tail. A normal semen sample will contain no more than 25% abnormal forms of sperm.
• Volume of the semen sample is important. An abnormal amount of semen could affect the ability of the sperm to successfully fertilize an ovum.

Any number of conditions result in abnormal findings in the semen analysis. Men can be born with testicles that have not descended properly from the abdominal cavity (where testicles develop originally) into the scrotal sac, or may be born with only one instead of the normal two testicles. Testicle size can be smaller than normal. Past infection (including mumps ) can affect testicular function, as can a past injury. The presence of abnormally large veins (varicocele) in the testicles can increase testicular temperature, which decreases sperm count. History of having been exposed to various toxins, drug use, excess alcohol use, use of anabolic steroids, certain medications, diabetes, thyroid problems, or other endocrine disturbances can have direct effects on the formation of sperm (spermatogenesis). A study published in late 2001 linked certain organic solvents that men encounter in the workplace as possible causes of low sperm count. The types of solvents are most likely encountered in such occupations as those of professional printers, painters, and decorators. Theories suggest solvents like glycol ethers, which are know to affect animals' reproductive systems, are the most harmful.

Problems with the male anatomy can cause sperm to be ejaculated not out of the penis, but into the bladder; and scarring from past infections can interfere with ejaculation.

Studies continue to uncover reasons for male infertility. In 2001, researchers reported that a certain protein lacking in the sperm could prevent formation of the structure on the head of the sperm that contains enzymes that help penetrate the egg, allowing conception. The finding should lead to further study of the molecular basis of male fertility.

Ovulatory problems

The first step in diagnosing ovulatory problems is to make sure that an ovum is being produced each month. A woman's morning body temperature is slightly higher around the time of ovulation. A woman can measure and record her temperatures daily and a chart can be drawn to show whether or not ovulation has occurred. Luteinizing hormone (LH) is released just before ovulation. A simple urine test can be done to check if LH has been released around the time that ovulation is expected.

Pelvic adhesions & endometriosis

Pelvic adhesions cause infertility by blocking the fallopian tubes and preventing the sperm from reaching the egg. Pelvic adhesions are fibrous scars. These scars can be the result of past infections, such as pelvic inflammatory disease, or infections following abortions or prior births. Previous abdominal surgeries can also leave behind scarring.

Endometriosis is the abnormal location of uterine tissue outside of the uterus. When uterine tissue is planted elsewhere in the pelvis, it still bleeds on a monthly basis with the start of the normal menstrual period. This leads to irritation within the pelvis around the site of this abnormal tissue and bleeding, and may cause scarring. Endometriosis may lead to pelvic adhesions.

A hysterosalpingogram (HSG) can show if the fallopian tubes are blocked. This is an x-ray exam that tests whether dye material can travel through the patient's fallopian tubes. Scarring also can be diagnosed by examining the pelvic area through the use of a laparoscope that is inserted into the abdomen through a tiny incision made near the navel.

Cervical factors

The cervix is the opening from the vagina into the uterus through which the sperm must pass. Mucus produced by the cervix helps to transport the sperm into the uterus. Injury to the cervix or scarring of the cervix after surgery or infection can result in a smaller than normal cervical opening, making it difficult for the sperm to enter. Injury or infection can also decrease the number of glands in the cervix, leading to a smaller amount of cervical mucus. In other situations, the mucus produced is the wrong consistency (perhaps too thick) to allow sperm to travel through. In addition, some women produce antibodies (immune cells) that are specifically directed to identify sperm as foreign invaders and to kill them.

Cervical mucus can be examined under a microscope to diagnose whether cervical factors are contributing to infertility. The interaction of a live sperm sample from the male partner and a sample of cervical mucus from the female partner can also be examined. This procedure is called a post-coital test.

Treatment

Conventional treatment for infertility usually involves invasive and, expensive procedures. There are many alternative treatments available that can increase the chance of conception. Some have been proven effective in clinical studies.

General measures to increase fertility include monitoring ovulation and timing intercourse (optimal chance for conception is within six days prior to and including the day of ovulation); and quitting smoking , excessive drinking, and drug use. To improve sperm quality, men can wear boxer shorts instead of briefs.

Both men and women can increase fertility by eating a well-balanced diet. Good food choices include legumes (especially soy), dark-colored vegetables, fruits, seeds, nuts, and sufficient good quality protein including meat, fish, and eggs. Some people think that refined sugar, processed cheeses, foods made with white flour, and chemical preservatives should be avoided. Adequate sleep is also important.

Supplements

Dietary supplements that can enhance fertility include:

• Multivitamins can help treat infertility in women.
• Vitamin E has antioxidant activity that prevents reproductive damage in men and women. It can increase sperm count and motility in men and balance hormones in women.
• Vitamin C has antioxidant activity that prevents reproductive damage in men and women. Also, a study found that vitamin C supplementation led to improved sperm count and decreased sperm clumping in infertile men.
• Folic acid (with a multivitamin) improved fertility in a study of infertile women.
• Zinc deficiency is often associated with low sperm count. Studies have found that zinc supplementation can improve male fertility.
• Arginine supplementation led to major increases in sperm count and motility in a study of infertile men.
• Selenium has antioxidant activity. Selenium supplementation led to increased sperm count and motility and decreased number of abnormal sperm in a study of infertile men.
• Beta-carotene supplementation can increase sperm count and motility.
• B vitamins (B₂, B₆, and B₁₂) are important for optimal fertility.

Herbal and Chinese medicine

The following may be taken by women to treat infertility:

• Dong quai (Angelica sinensis ) has been used to regulate menstrual cycles and for infertility.
• Licorice helps to balance levels of estrogen and testosterone and is used for infertility.
• Red clover (Trifolium pratense ) has a beneficial effect on the uterus, can calm the nervous system, and can balance hormone levels.
• Nettle (Urtica dioica ) supports the uterus and hormonal system.
• Raspberry leaf strengthens the mucous lining of the uterus.
• Chasteberry (Vitex agnus-castus ) balances hormone production.
• Ladies mantle (Alchemilla vulgaris ) balances hormone production.
• Shatavari (Asparagus racemosus ) is an Ayurvedic remedy for infertility and works by balancing hormones.
• Rehmannia is an Ayurvedic remedy for infertility.
• Myrrh (Commiphora myrrha ) is an Ayurvedic remedy for infertility.
• False unicorn (Chamaelirium luteum ) balances hormone levels.
• Pomegranate essence balances the reproductive system.

The following may be taken by men to treat infertility:

• Ginseng may increase the formation of sperm, testosterone levels, and sexual activity.
• Pygeum may help infertile men who have a reduced secretion of semen.
• Pine bark extract improves sperm shape.
• Chasteberry (Vitex agnus-castus ) balances hormone production.
• Shatavari (Asparagus racemosus ) is an Ayurvedic remedy for infertility and works by balancing hormones. May increase sperm production.
• Saw palmetto (Serenoa serrulata ) increases the production of testosterone and strengthens the reproductive system.
• Ashwaganda (Withania omnifera ) is an Ayurvedic remedy that improves the quality of semen and sperm count.
• Chinese herbals must be specifically designed and used to treat infertility in males.

Other treatments

A variety of other alternative treatments may be used for infertility:

• stress reduction
• cognitive behavior therapy
• visualization
• homeopathy
• reflexology
• essential oils
• acupuncture

Allopathic treatment

The first step in the treatment of infertility is to perform thorough physical exams and testing of both partners in the hope of finding the source of infertility. For the woman this involves blood testing and ultrasound examinations at specific days during the menstrual cycle. This may include an endometrial biopsy in which a sample of the lining of the uterus is taken and examined. Hysteroscopy, in which a special camera examines the inside of the uterus, may be performed.

Pelvic adhesions can be treated during laparoscopy. The adhesions are cut using special instruments. Endometriosis can be treated with certain medications, but may also require surgery to repair any obstruction caused by adhesions.

Treatment of cervical factors includes antibiotics in the case of an infection, steroids to decrease production of anti-sperm antibodies, and artificial insemination techniques to completely bypass the cervical mucus.

Treatment of ovulatory problems depends on the cause. If a thyroid or pituitary problem is responsible, simply treating that problem can restore fertility. Medications that stimulate ovulation are clomiphene citrate (Clomid) that is taken by mouth and follicle stimulating hormone (Pergonal, Fertinex, and Follistim) that is given by injection. These drugs increase the risk of multiple births (twins, triplets, etc.) and may cause side effects.

Treatment of male infertility includes addressing known reversible factors first; for example, discontinuing any medication known to have an effect on spermatogenesis or ejaculation, as well as decreasing alcohol intake, and treating thyroid or other endocrine disease. Varicoceles can be treated surgically. Testosterone in low doses can improve sperm motility.

Other treatments of male infertility include collecting semen samples from multiple ejaculations, pooling them, and depositing them into the female's uterus during ovulation. When the male partner's sperm is proven to be absolutely unable to produce pregnancy, donor sperm may be used. Depositing the male partner's sperm or donor sperm by mechanical means into the female is called artificial insemination.

Assisted reproductive techniques include in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), and zygote intrafallopian tube transfer (ZIFT). These are usually used after other techniques to treat infertility (surgery, medications, and/or insemination) have failed.

IVF involves the use of drugs to induce the simultaneous production of many eggs from the ovaries, which are retrieved surgically or via ultrasound-guided needle aspiration through the vaginal wall. The ova and sperm are combined in a laboratory, where several of the ova may be fertilized. Cell division is allowed to take place up to the pre-embryo stage. While this takes place, the female may be given progesterone to ensure that her uterus is ready for implantation. Two or more pre-embryos are transferred to the female's uterus.

Success rates of IVF are still rather low. The national average success rate of IVF is approximately 27% but some centers have higher pregnancy rates. Because most IVF procedures put more than one embryo into the uterus, the chance for a multiple birth (twins or more) is greatly increased.

GIFT involves retrieval of both multiple ova and semen, and the mechanical placement of both within the female's fallopian tubes, where fertilization may occur. ZIFT involves the same retrieval of ova and semen, and fertilization and growth in the laboratory up to the zygote stage, at which point the zygotes are placed in the fallopian tubes. Both GIFT and ZIFT have higher success rates than IVF.

Expected results

In general, it is believed that about half of the couples who undergo a complete evaluation of infertility followed by treatment will ultimately have a successful pregnancy. About 5% of those couples who choose to not undergo evaluation or treatment will go on to conceive after a year or more.

Resources

BOOKS

Hornstein, Mark D., and Daniel Schust. "Infertility." In Novak's Gynecology, edited by Jonathan S. Berek. Baltimore: Williams and Wilkins, 1996.

Maleskey, Gale. "Infertility." Nature's Medicines: from Asthma to Weight Gain, from Colds to High Cholesterol—the Most Powerful All-Natural Cures. Emmaus, PA: Rodale Press, 1999.

Martin, Mary C. "Infertility" In Current Obstetric and Gynecologic Diagnosis and Treatment, edited by Alan H. Cecherney and Martin L. Pernoll. Norwalk, CT: Appleton & Lange, 1994.

Ying, Zhou Zhong, and Jin Hui De. "Common Diseases of Gynecology." In Clinical Manual of Chinese Herbal Medicine and Acupuncture. New York: Churchill Livingston, 1997.

PERIODICALS

Alfieri, Rosemarie Gionta. "Natural Options for Fertility." Let's Live, 67 (May 1999): 37+.

"Copper IUD Not the Cause of Tubal Occlusion." Contemporary OB/GYN 46, no. 12 (December 2001): 111.

"Low Sperm Count Linked to Organic Solvents." Health and Medicine Week (October 1, 2001).

"New Study Provides Insight into Male Infertility." Gene Therapy Weekly (December 13, 2001).

Rosenbaum, Joshua. "Beat the Clock: Treatments for Infertility." American Health (December 1995): 70+.

Trantham, Patricia. "The Infertile Couple." American Family Physician (September 1, 1996): 1001+.

Veal, Lowana. "Complementary Therapy and Infertility: an Icelandic Perspective." Complementary Therapies in Nursing & Midwifery 4 (1998): 3–6.

ORGANIZATIONS

American Society for Reproductive Medicine. 1209 Montgomery Highway, Birmingham, AL 35216-2809. (205) 978-5000. <http://www.asrm.com>.

International Center for Infertility Information Dissemination. <http://www.inciid.org>.

RESOLVE. 1310 Broadway, Somerville, MA 02144-1779. (617) 623-1156. <www.resolve.org>.

Belinda Rowland

Teresa Norris

Infertility

Definition

Infertility is the failure of a couple to conceive a pregnancy after trying to do so for at least one full year. In primary infertility, pregnancy has never occurred. In secondary infertility, one or both members of the couple have previously conceived, but are unable to conceive again after a full year of trying.

Description

Currently, in the United States, about 20% of couples struggle with infertility at any given time. Infertility has increased as a problem over the last 30 years. Some studies pin the blame for this increase on social phenomena, including the tendency for marriage to occur at a later age, which means that couples are trying to start families at a later age. It is well known that fertility in women decreases with increasing age, as illustrated by the following statistics:

• Infertility in married women ages 16-20 = 4.5%
• Infertility in married women ages 35-40 = 31.8%
• Infertility in married women over the age of 40 = 70%.

Today, individuals often have multiple sexual partners before they marry and try to have children. This increase in numbers of sexual partners has led to an increase in sexually transmitted diseases. Scarring from these infections, especially from pelvic inflammatory disease (a serious infection of the female reproductive organs, most commonly caused by gonorrhea ) seems to be in part responsible for the increase in infertility noted. Furthermore, use of some forms of a contraceptive called the intrauterine device (IUD ) contributed to an increased rate of pelvic inflammatory disease, with subsequent scarring. However, newer IUDs do not lead to this increased rate of infection.

To understand issues of infertility, it is first necessary to understand the basics of human reproduction. Fertilization occurs when a sperm from the male merges with an egg (ovum) from the female, creating a zygote that contains genetic material (DNA) from both the father and the mother. If pregnancy is then established, the zygote will develop into an embryo, then a fetus, and ultimately a baby will be born.

The male contribution to fertilization and the establishment of pregnancy is the sperm. Sperm are small cells that carry the father's genetic material. This genetic material is contained within the oval head of the sperm. The sperm are mixed into a fluid called semen, which is discharged from the penis during sexual intercourse. The whip-like tail of the sperm allows the sperm to swim up the female reproductive tract, in search of the egg it will try to fertilize.

The female makes many contributions to fertilization and the establishment of pregnancy. The ovum is the cell that carries the mother's genetic material. These ova develop within the ovaries. Once a month, a single mature ovum is produced, and leaves the ovary in a process called ovulation. This ovum enters a tube leading to the uterus (the fallopian tube). The ovum needs to meet up with the sperm in the fallopian tube if fertilization is to occur.

When fertilization occurs, the resulting cell (which now contains genetic material from both the mother and the father) is called the zygote. This single cell will divide into multiple other cells within the fallopian tube, and the resulting cluster of cells (called a blastocyst) will then move into the womb (uterus). The uterine lining (endometrium) has been preparing itself to receive a pregnancy by growing thicker. If the blastocyst successfully reaches the inside of the uterus and attaches itself to the wall of the uterus, then implantation and pregnancy have been achieved.

Causes and symptoms

Unlike most medical problems, infertility is an issue requiring the careful evaluation of two separate individuals, as well as an evaluation of their interactions with each other. In about 3-4% of couples, no cause for their infertility will be discovered. About 40% of the time, the root of the couple's infertility is due to a problem with the male partner; about 40% of the time, the root of the infertility is due to the female partner; and about 20% of the time, there are fertility problems with both the man and the woman. Recently, a study in Great Britain reported that smoking adds to infertility problems for both men and women. In addition, men and women who smoke are less likely to respond to infertility treatment.

The main factors involved in causing infertility, listing from the most to the least common, include:

• Male problems: 35%
• Ovulation problems: 20%
• Tubal problems: 20%
• Endometriosis: 10%
• Cervical factors: 5%.

Male factors

Male infertility can be caused by a number of different characteristics of the sperm. To check for these characteristics, a sample of semen is obtained and examined under the microscope (semen analysis ). Four basic characteristics are usually evaluated:

• Sperm count refers to the number of sperm present in a semen sample. The normal number of sperm present in just one milliliter (ml) of semen is more than 20 million. An individual with only 5-20 million sperm per ml of semen is considered subfertile, an individual with less than 5 million sperm per ml of semen is considered infertile.
• Sperm are also examined to see how well they swim (sperm motility) and to be sure that most have normal structure.
• Not all sperm within a specimen of semen will be perfectly normal. Some may be immature, and some may have abnormalities of the head or tail. A normal semen sample will contain no more than 25% abnormal forms of sperm.
• Volume of the semen sample is important. An abnormal amount of semen could affect the ability of the sperm to successfully fertilize an ovum.

Another test can be performed to evaluate the ability of the sperm to penetrate the outer coat of the ovum. This is done by observing whether sperm in a semen sample can penetrate the outer coat of a guinea pig ovum; fertilization cannot occur, of course, but this test is useful in predicting the ability of the individual's sperm to penetrate a human ovum.

Any number of conditions result in abnormal findings in the semen analysis. Men can be born with testicles that have not descended properly from the abdominal cavity (where testicles develop originally) into the scrotal sac, or may be born with only one instead of the normal two testicles. Testicle size can be smaller than normal. Past infection (including mumps ) can affect testicular function, as can a past injury. The presence of abnormally large veins (varicocele) in the testicles can increase testicular temperature, which decreases sperm count. History of having been exposed to various toxins, drug use, excess alcohol use, use of anabolic steroids, certain medications, diabetes, thyroid problems, or other endocrine disturbances can have direct effects on the formation of sperm (spermatogenesis). Problems with the male anatomy can cause sperm to be ejaculated not out of the penis, but into the bladder, and scarring from past infections can interfere with ejaculation.

Treatment of male infertility includes addressing known reversible factors first; for example, discontinuing any medication known to have an effect on spermatogenesis or ejaculation, as well as decreasing alcohol intake, and treating thyroid or other endocrine disease. Varicoceles can be treated surgically. Testosterone in low doses can improve sperm motility.

Other treatments of male infertility include collecting semen samples from multiple ejaculations, after which the semen is put through a process that allows the most motile sperm to be sorted out. These motile sperm are pooled together to create a concentrate that can be deposited into the female partner's uterus at a time that coincides with ovulation. In cases where the male partner's sperm is proven to be absolutely unable to cause pregnancy in the female partner, and with the consent of both partners, donor sperm may be used for this process. Depositing the male partner's sperm or donor sperm by mechanical means into the female partner are both forms of artificial insemination.

Ovulatory problems

The first step in diagnosing ovulatory problems is to make sure that an ovum is being produced each month. A woman's morning body temperature is slightly higher around the time of ovulation. A woman can measure and record her temperatures daily and a chart can be drawn to show whether or not ovulation has occurred. Luteinizing hormone (LH) is released just before ovulation. A simple urine test can be done to check if LH has been released around the time that ovulation is expected.

Treatment of ovulatory problems depends on the cause. If a thyroid or pituitary problem is responsible, simply treating that problem can restore fertility. (The thyroid and pituitary glands release hormones that also are involved in regulating a woman's menstrual cycle.) Medication can also be used to stimulate fertility. The most commonly used of these are called Clomid and Pergonal. These drugs increase the risk of multiple births (twins, triplets, etc.). Other possible medications include gonadotropin medications, which are injected medications made up of hormones produced in the pituitary glands. They may directly stimulate the ovaries to produce eggs. Follicle stimulating hormone (FSH) has a 95% chance of simulating ovulation in women with an ovulatory problem. However, its use does not guarantee a successful pregnancy and may lead to multiple pregnancies.

Pelvic adhesions and endometriosis

Pelvic adhesions and endometriosis can cause infertility by preventing the sperm from reaching the egg or interfering with fertilization.

Pelvic adhesions are fibrous scars. These scars can be the result of past infections, such as pelvic inflammatory disease, or infections following abortions or prior births. Previous surgeries can also leave behind scarring.

Endometriosis may lead to pelvic adhesions. Endometriosis is the abnormal location of uterine tissue outside of the uterus. When uterine tissue is planted elsewhere in the pelvis, it still bleeds on a monthly basis with the start of the normal menstrual period. This leads to irritation within the pelvis around the site of this abnormal tissue and bleeding, and may cause scarring.

Pelvic adhesions cause infertility by blocking the fallopian tubes. The ovum may be prevented from traveling down the fallopian tube from the ovary or the sperm may be prevented from traveling up the fallopian tube from the uterus.

A hysterosalpingogram (HSG) can show if the fallopian tubes are blocked. This is an x-ray exam that tests whether dye material can travel through the patient's fallopian tubes. A few women become pregnant following this x-ray exam. It is thought that the dye material in some way helps flush out the tubes, decreasing any existing obstruction. Scarring also can be diagnosed by examining the pelvic area through the use of a scope that can be inserted into the abdomen through a tiny incision made near the naval. This scoping technique is called laparoscopy.

Pelvic adhesions can be treated during laparoscopy. The adhesions are cut using special instruments. Endometriosis can be treated with certain medications, but may also require surgery to repair any obstruction caused by adhesions.

Cervical factors

The cervix is the opening from the vagina into the uterus through which the sperm must pass. Mucus produced by the cervix helps to transport the sperm into the uterus. Injury to the cervix or scarring of the cervix after surgery or infection can result in a smaller than normal cervical opening, making it difficult for the sperm to enter. Injury or infection can also decrease the number of glands in the cervix, leading to a smaller amount of cervical mucus. In other situations, the mucus produced is the wrong consistency (perhaps too thick) to allow sperm to travel through. In addition, some women produce antibodies (immune cells) that are specifically directed to identify sperm as foreign invaders and to kill them.

Cervical mucus can be examined under a microscope to diagnose whether cervical factors are contributing to infertility. The interaction of a live sperm sample from the male partner and a sample of cervical mucus from the female partner can also be examined. This procedure is called a post-coital test.

Treatment of cervical factors includes antibiotics in the case of an infection, steroids to decrease production of anti-sperm antibodies, and artificial insemination techniques to completely bypass the cervical mucus.

Treatment

Assisted reproductive techniques include in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), and zygote intrafallopian tube transfer (ZIFT). These are usually used after other techniques to treat infertility have failed.

In vitro fertilization involves the use of a drug to induce the simultaneous release of many eggs from the female's ovaries, which are retrieved surgically. Meanwhile, several semen samples are obtained from the male partner, and a sperm concentrate is prepared. The ova and sperm are then combined in a laboratory, where several of the ova may be fertilized. Cell division is allowed to take place up to the embryo stage. While this takes place, the female may be given drugs to ensure that her uterus is ready to receive an embryo. Three or four of the embryos are transferred to the female's uterus, and the wait begins to see if any or all of them implant and result in an actual pregnancy.

Success rates of IVF are still rather low. Most centers report pregnancy rates between 10-20%. Since most IVF procedures put more than one embryo into the uterus, the chance for a multiple birth (twins or more) is greatly increased in couples undergoing IVF.

GIFT involves retrieval of both multiple ova and semen, and the mechanical placement of both within the female partner's fallopian tubes, where one hopes that fertilization will occur. ZIFT involves the same retrieval of ova and semen, and fertilization and growth in the laboratory up to the zygote stage, at which point the zygotes are placed in the fallopian tubes. Both GIFT and ZIFT seem to have higher success rates than IVF.

Prognosis

It is very hard to obtain statistics regarding the prognosis of infertility because many different problems may exist within and individual or couple trying to conceive. In general, it is believed that of all couples who undergo a complete evaluation of infertility followed by treatment, about half will ultimately have a successful pregnancy. Of those couples who do not choose to undergo evaluation or treatment, about 5% will go on to conceive after a year or more of infertility.

Resources

BOOKS

Martin, Mary C. "Infertility." In Current Obstetric and Gynecologic Diagnosis and Treatment, edited by Alan H. Cecherney and Martin L. Pernoll. Norwalk, CT: 1994.

PERIODICALS

"Infertility; Treatment." NWHRC Health Center March 10, 2004.

Kmietowicz, Zosia. "Smoking is Causing Impotence, Miscarriages, and Infertility." British Medical Journal February 14, 2004: 364.

ORGANIZATIONS

American Society for Reproductive Medicine. 1209 Montgomery Highway, Birmingham, AL 35216-2809. (205) 978-5000. 〈http://www.asrm.com〉.

International Center for Infertility Information Dissemination. 〈http://www.inciid.org〉.

KEY TERMS

Blastocyst— A cluster of cells representing multiple cell divisions that have occurred in the fallopian tube after successful fertilization of an ovum by a sperm. This is the developmental form which must leave the fallopian tube, enter the uterus, and implant itself in the uterus to achieve actual pregnancy.

Cervix— The opening from the vagina, which leads into the uterus.

Embryo— The stage of development of a baby between the second and eighth weeks after conception.

Endometrium— The lining of the uterus.

Fallopian tube— The tube leading from the ovary into the uterus. Just as there are two ovaries, there are two Fallopian tubes.

Fetus— A baby developing in the uterus from the third month to birth.

Ovary— The female organ in which eggs (ova) are stored and mature.

Ovum (plural: ova)— The reproductive cell of the female, which contains genetic information and participates in the act of fertilization. Also popularly called the egg.

Semen— The fluid that contains sperm, which is ejaculated by the male.

Sperm— The reproductive cell of the male, which contains genetic information and participates in the act of fertilization of an ovum.

Spermatogenesis— The process by which sperm develop to become mature sperm, capable of fertilizing an ovum.

Zygote— The result of the sperm successfully fertilizing the ovum. The zygote is a single cell that contains the genetic material of both the mother and the father.

infertility may be primary or secondary. Primary infertility is when no pregnancy has ever occurred. Secondary infertility is when there have been one or more pregnancies but a further pregnancy has proved impossible. It has been estimated that the chances of conception for a given couple having regular sexual intercourse without any contraception are 80% and 90% after 12 months and 18 months respectively. It is therefore usual to begin investigations after one year. At this time some problems may be discovered and it should be possible, the basic tests having been done, to offer a realistic prognosis and a possible treatment outline. It is important to discover if there are any obvious abnormalities because with the new methods of treatment that have become available over the last twenty years it is frequently possible to offer real hope of success.

Female physiology

The Fallopian tubes lead from the ovaries, where the eggs are made, to the uterus. Each month, around 12–14 days from the last menstrual period, an egg (ovum) is released from the ovary. The ovum passes down the tube and its passage is facilitated by the moving cilia of the lining cells, which waft the ovum along. If intercourse occurs around this time the sperm swims up through the uterus to the tube and one of them joins the egg in the tube. The fertilized egg then continues down the tube to the uterus which has been prepared by hormones to receive the egg.

Causes of infertility

Unexplained infertility

is not easy to define. The more investigations that a clinic is able to perform the lower is the incidence of unexplained infertility. Hopefully some time in the future all will be explained.

Male infertility

It is not always recognized how commonly the male partner is the infertile one. The average amount of seminal fluid ejaculated each time is 2–5 ml. Persistent low volume may indicate an abnormality. If the number of sperm is less than 10 million/ml this makes fertilization less likely. The mobility of the sperm is also a factor, as is the ability of the sperm to penetrate the egg. These factors can all be tested in the laboratory. An important cause of reduced sperm numbers is a history of mumps, as the testicles are damaged in some cases.

Anovulation

means that for some reason no ovum is produced in each menstrual cycle.

Tubal factors

The main tubal factor is blockage, which may result from infection from sexually transmitted disease or a previous miscarriage. The blockage prevents the union of sperm and ovum so that no pregnancy occurs. Sometimes, although the tube may not be blocked, the cilia, which assist the passage of the ovum down the tube, are damaged so that the ovum gets stuck in the tube and union with the sperm does not occur. Sometimes the sperm does manage to fertilize the stuck egg and this results in a pregnancy occurring in the tube — an ectopic pregnancy. As this pregnancy grows the tube may rupture, with serious consequences due to bleeding into the abdominal cavity.

Endometriosis

is a condition where, for unknown reasons, portions of the lining of the uterus grow in other parts of the pelvis such as the ovaries. The reason why this causes infertility is not clear.

Sexual dysfunction

occurs sometimes due to psychological factors that prevent proper intercourse.

Mucus hostility

means that the secretion from the neck of the womb (cervix) is abnormal, and kills the sperm so that they cannot travel through the uterus to the tubes.

Investigations

At an infertility clinic both partners are given a full physical examination and a detailed medical history is taken.

In the male a good proportion of infertility is due to deficiencies in semen, so a proper seminal examination is essential. This involves measurement of the volume of the ejaculate — the sperm count — which should be 20 million/ml or more; the swimming ability of the sperm; and the numbers of abnormal forms present. A history of mumps or sexually transmitted disease or genital trauma are important, as are previous hernia operations. A social history of drug and alcohol intake may be relevant, as may occupations involving working at extremes of temperature or at altitude. Physical examinations may reveal some testicular or penile abnormality.

There is still controversy as to what constitutes normal semen. With modern methods of assisted reproduction many men with very low sperm counts can produce enough sperm which can be used to fertilize eggs ‘in vitro’ (IVF). Our ideas as to what constitutes an infertile male have radically altered in the last twenty years.

In the case of the female partner the occurrence of ovulation can be tested by Basal Body Temperature measurement (the temperature rises 1 degree following ovulation in the second half of the menstrual cycle) and by measurement of the female hormones, oestrogen and progesterone. The use of ultrasound can visualize the ovum in the ovary, and taking a sample of the lining of the uterus can show whether or not the uterus is being prepared properly in each cycle for reception of a fertilized ovum. Assessment of the state of the tubes can be achieved by injecting dye through the cervix. This fills the uterine cavity, and, with the use of a small telescope (laparoscope) inserted into the abdomen, dye will be seen flowing from the tubal opening at the ovary if the tube is patent. If no dye is seen the tube is blocked. A newer method, falloscopy, involves the introduction of a tiny telescope (falloscope) into the tube through the tubal opening in the uterus and allows evaluation of the state of the tubal lining — so important for the transport of the egg. The mucus at the cervix can be sampled and tested to see if it kills sperm; if it does, there are methods of avoiding this.

A small telescope (hysteroscope) can also be used to examine the inside of the uterus to see if there any abnormalities of shape and to exclude the presence of tumours. All these tests are available at properly equipped infertility centres.

A history of pelvic infection may be relevant — perhaps after a miscarriage or previous abdominal operation, or due to sexually transmitted disease. An abnormal menstrual history may suggest a hormonal disturbance. Previous use of hormonal contraception (the Pill) can result in anovulation, and use of the intrauterine device can cause infection and blocked tubes.

The success of infertility treatment varies enormously depending on the cause. In the most favourable cases treatment may be 90% successful. In cases it may be quite unsuccessful. Nowadays, with proper investigation and treatment the results are incomparably better than a quarter of a century ago.

Malcolm Macnaughton

infertility inability to conceive or carry a child to delivery. The term is usually limited to situations where the couple has had intercourse regularly for one year without using birth control . The term sterility is restricted to lack of sperm production or inability to ovulate. Approximately 40% of reported cases of infertility are due to problems in the male; another 40% to problems in the female; the remaining 20% are of unknown cause or due to problems in both the male and female.

Causes

Infertility can be caused by any interruption in the usual process of fertilization, pregnancy , and birth , which includes ejaculation of normal amounts of healthy sperm , passage of the sperm through the cervix and into the fallopian tube of the female, passage of an ovum (egg) down the fallopian tube from an ovary, fertilization in the fallopian tube, implantation of the fertilized egg in a receptive uterus , and the ability to carry the fetus to term. In women, the most common problems are failure to ovulate and blockage of the fallopian tubes. In men, low sperm count is the most common problem.

Underlying problems include disease, such as diabetes or mumps in adult men, hormonal imbalances, endometriosis, pelvic inflammatory disease (often caused by sexually transmitted diseases , e.g., chlamydia ), the abuse of alcohol and other drugs, and exposure to workplace hazards or environmental toxins. Uterine irritation or infection that sometimes accompanies IUD use can also reduce fertility. Occasionally there is a chemical or immunological incompatibility between male and female. Psychological factors are difficult to evaluate because of the stressful nature of infertility itself.

The number of couples seeking treatment for infertility has increased as more of them have postponed childbearing to a later age. In women, fertility begins to decline in the mid-twenties, and continues to decline, more and more sharply, until menopause . Male fertility declines gradually until age forty, then declines more quickly.

Evaluation and Treatment

Evaluation includes examination of sperm, observation of basal body temperature or luteinizing hormone peaks (see gonadotropic hormone ) in the female to determine whether ovulation is taking place, the ruling out of obstructions of the fallopian tubes or vas deferens, and blood tests that measure hormone levels. Treatment is geared to the specific problem. The first step may be treatment of underlying disease and, in men, avoidance of substances that might affect sperm count. Fertility drugs , some of which increase the likelihood of multiple births , are often prescribed. If necessary, surgical correction of blocked tubes can be attempted.

Artificial insemination , in which the man's sperm or donor sperm from a sperm bank is inserted directly into the woman or a surrogate mother may be attempted. Another method is in vitro fertilization , in which an egg is taken from the mother or an egg donor and fertilized outside the body by the father's sperm. The resulting embryo is then inserted into the mother's uterus. Gamete intrafallopian transfer (GIFT) mixes the egg and sperm outside the body, then, using laparoscopic surgery (see endoscope ), introduces them into the fallopian tube. For men with low sperm count or sperm of low quality, a procedure called intracytoplasmic sperm injection can help by inserting a single sperm directly into an egg. If none of these measures succeeds, adoption is sometimes considered.

Some controversy has surrounded infertility treatment. Many of the procedures are very expensive, and some question whether insurance plans should be responsible for the cost. The multiple births that sometimes occur with fertility drugs can put great strain on a family's resources. The legal rights of surrogate mothers and sperm donors are also of concern to all parties and have sometimes been resolved only after extended court cases. The wisdom of stretching the definition of "the childbearing years" has come into question as well, as methods used for treating infertility have been used to allow postmenopausal women to have children. Some are uncomfortable with the ability to choose the sex of the child or the screening of sperm or egg donors for characteristics such as height and intelligence.

See also gynecology ; obstetrics .

Infertility

What Is Infertility?

How Is Infertility Diagnosed?

How Is Infertility Treated?

Coping with Infertility: Jim and Sarah’s Story

Resources

Infertility (in-fer-TIL-i-tee) means that a couple has difficulty conceiving a child after approximately a year of trying. The man, woman, or both may have problems with their reproductive system that causes them to be infertile.

KEYWORDS

for searching the Internet and other reference sources

Artificial insemination

Assisted reproductive technology

Gynecology

In vitro fertilization

Reproductive medicine

What Is Infertility?

Infertility is defined as the failure to become pregnant after about a year of trying many times without using contraception*. Infertility problems increase as a person gets older, and they are becoming more widespread as many women are waiting to have babies until they are in their thirties and forties. Currently, fertility problems affect at least 6.1 million couples in the United States. For people who cannot imagine their lives without children and are not considering adoption, the condition may be heartbreaking.

* contraception

(kon-tra-SEP-shun) is the deliberate prevention of conception or impregnation.

Doctors can find no medical cause for up to 20 percent of infertility cases. In 15 to 20 percent of infertility cases, both the man and the woman have fertility problems. The rest of the time, infertility is caused by problems with either the male or the female reproductive system. Some doctors believe that smoking, drinking a lot of alcohol, poor eating habits, stress, excess weight, and generally poor health can make the physical problems causing infertility even worse.

Male factor infertility

Roughly 35 to 40 percent of infertile couples are unable to conceive because of a problem with the male reproductive system. Infertility can result when a man does not produce enough sperm*, or when the sperm have too short a life span, they do not move properly, or they cannot penetrate the egg to fertilize it. These problems can be caused by many factors, including abnormalities of reproductive organs, a varicose vein* in the scrotum*, inflammation* in the male genitals, and sexually transmitted diseases, such as chlamydial (kla-MID-e-al) infections, gonorrhea (gon-o-REE-a), and syphilis (SIF-i-lis). Some men have trouble ejaculating (discharging sperm), which also can cause infertility. In rare cases, the immune system* of the man or woman may produce antibodies* that kill sperm.

* sperm

are the tiny, tadpole-like cells in the fluid males produce in their testicles (TES-ti-kulz) that can unite with a female’s egg to result eventually in the birth of a child.

* varicose vein

(VAR-i-kose VAYN) is an abnormally swollen or dilated vein.

* scrotum

(SKRO-tum) is the pouch on a male body that contains the testes (TES-teez) and their accessory organs.

* inflammation

(in-fla-MAY-shun) is the body’s response to infection or irritation.

* immune system

is the body system that fights disease.

* antibodies

(AN-te-bod-eez) are proteins produced by the immune system to fight specific infections. In certain disorders, antibodies attack some of the body’s own proteins and cells.

Infertility in women

Another 35 to 40 percent of couples are infertile because of a problem with the female reproductive tract. Problems can occur in any part of the system:

• Ovaries: The ovaries (O-va-reez) are a pair of organs where egg cells develop and mature. About 25 percent of female infertility is caused by the failure of a mature egg to leave the ovary (a process called ovulation).
• Hormones: Problems with hormone* production can prevent pregnancy.
• Fallopian tubes: A woman has two fallopian (fa-LO-pe-an) tubes (one associated with each ovary), which carry eggs from the ovaries to the uterus (YOO-ter-us). Infertility can occur when one or both of the fallopian tubes are blocked, scarred, or collapsed.
• Pelvic inflammatory disease (PID): Infertility also is common in women with PID, which is an infection of the female reproductive organs (especially the fallopian tubes).
• Uterus: The uterus is the muscular organ in which a fertilized egg develops into a fetus (FEE-tus; developing baby). If the uterus contains scar tissue or a piece of tissue dividing it in half, the fertilized egg might not be able to implant and grow.
• Endometriosis: Women also can have infertility problems because of conditions such as endometriosis (en-do-me-tree-O-sis), which occurs when pieces of the lining of the uterus grow outside of the uterus.
• Fibroids: Fibroids (FY-broidz) are noncancerous tumors* that also can cause infertility.
• Cervix: The cervix (SER-viks) is the opening between the uterus and the vagina. Infertility can occur if the cervix does not produce enough mucus* to allow sperm to pass into the uterus.
• Vaginal infections: The vagina (va-JY-na) is the tubular canal that runs from the cervix to the outside of the body. Certain vaginal infections that spread to the uterus and fallopian tubes can cause infertility.

* hormone

is a chemical that is produced by different glands in the body. A hormone is like the body’s ambassador: it is created in one place but is sent through the body to have specific regulatory effects in different places.

* tumors

(TOO-morz) usually refer to abnormal growths of body tissue that have no known cause or physiologic purpose. Tumors may or may not be cancerous.

* mucus

(MU-kus) is a kind of body slime. It is thick and slippery, and it lines the inside of many parts of the body.

How Is Infertility Diagnosed?

The first step in treating infertility is finding out the cause. Both the man and the woman require a complete physical examination to determine if a physical disorder is causing infertility.

The first test for male infertility is an analysis of the sperm for shape, movement, and number. The first test for a woman is to find out if she is ovulating. Home ovulation* kits are available for this purpose, as are body temperature charts (the body temperature fluctuates during the menstrual cycle*). Tests of a woman’s blood and urine also help doctors to determine if a woman is having normal menstrual cycles. An x-ray of the uterus and fallopian tubes can reveal any blockage that might prevent the egg from being fertilized. In some cases, the doctor may look inside the body with a laparoscope*, which is a viewing tube that is inserted into the abdomen* through a small incision.

* ovulation

(ov-yoo-LAY-shun) is the release of a mature egg from the ovary.

* menstrual cycle

(MEN-stroo-al SYkul) culminates in menstruation (men-stroo-AY-shun), the discharging through the vagina of blood, secretions, and tissue debris from the uterus that recurs at approximately monthly intervals in females of breeding age.

* laparoscope

(LAP-a-ro-skope) is a fiber-optic instrument inserted into an incision in the abdominal wall to perform a visual examination.

* abdomen

(AB-do-men), commonly called the belly is the portion of the body between the thorax (THOR-aks) and the pelvis.

How Is Infertility Treated?

Difficulty conceiving a baby may not be a permanent condition, and many couples with fertility problems eventually have a child without medical intervention. However, some couples need medical help to become pregnant, and the treatment depends on the cause of infertility. If a hormone deficiency causes infertility, treatment may involve taking hormones prescribed by a doctor. If there is damage or an abnormality in the female organs, they sometimes can be repaired surgically. For other couples, treatment can range from taking fertility drugs to using assisted reproductive technology (ART). Many treatments for infertility exist; only a few are described in the following.

Multiple Births

One of the major problems facing couples undergoing fertility treatment is that of multiple births. Fertility drugs may result in multiple births, because they can stimulate release of multiple eggs. For example, as many as 10 percent of women who become pregnant with the help of the drug Clomid (KLO-mid), or clomiphene citrate (KLO-mi-feen SY-trayt), have twins, and 1 in 400 women have triplets.

Assisted reproductive technologies such as in vitro fertilization usually place two to five eggs inside the woman’s reproductive tract, because not all are expected to survive—but sometimes they all do. In the 1990s, several women who underwent fertility treatment had as many as eight babies at once.

The more embryos that develop at one time in the uterus, the more likely they are to be born prematurely, to be small, and to have serious health problems such as cerebral palsy (se-REE-bral PAWL-zee) and brain damage. Because of such health problems, and because of ethical and financial issues associated with multiple births, fertility treatment can be controversial.

Artificial insemination

Artificial insemination (in-sem-i-NAY-shun) is the introduction of a man’s sperm into the opening of a woman’s uterus with a tube called a catheter (CATH-e-ter). Before insemination, antibodies and unhealthy sperm are removed from the semen (SEE-men), the fluid containing sperm. The sperm used in artificial insemination ideally comes from the woman’s male partner. However, in cases where the man is infertile or carries a genetic disorder, sperm from a donor may be used.

Fertility drugs

Fertility drugs can be used to treat problems with ovulation. A number of different medications have been developed that help to stimulate the maturation and release of ova (eggs).

In vitro fertilization (IVF)

“In vitro” literally means “in glass” (as in a test tube) and therefore refers to a procedure performed outside the body. In vitro fertilization (IVF) occurs when eggs are removed from the woman and mixed with sperm in the laboratory. Fertilized eggs, or embryos, then are placed in the woman’s uterus. This procedure bypasses the fallopian tubes.

Before IVF, women usually take fertility drugs in order to produce multiple eggs. Eggs are taken from a woman’s ovaries using a needle inserted through the vagina. The male partner provides a sperm sample, which is mixed with the eggs in a dish in the laboratory. After several days, if the eggs have been fertilized and have developed into embryos, two to five embryos (usually) are placed into the uterus (not all are expected to develop into fetuses). About two weeks later, the woman takes a pregnancy test to see if the procedure was successful.

Coping with Infertility: Jim and Sarah’s Story

Jim and Sarah Albertson are among the 10 to 20 percent of the reproductive-aged population in the United States who have difficulty having a baby. Even though pregnancy is possible in more than half of couples pursuing fertility treatment, it does not seem possible for them.

Jim and Sarah began trying to have a baby on their honeymoon, when they were both 34. Five years later, they still have no children. Sarah has had surgery to remove fibroids, and she has taken hormones and fertility pills. Jim has done everything possible to increase his sperm count. They have tried artificial insemination. It seems their whole lives revolve around trying to get pregnant, but nothing is working.

As Jim and Sarah watch one friend after another have a baby, their own home begins to feel empty. They try not to blame each other, but it is hard not to. Even though their health plan does not cover in vitro fertilization, they decided to spend their own money to try to get pregnant that way. Three tries and $30,000 later, they still have no baby. With the help of marital counseling and the support of other couples with the same problem, Jim and Sarah are learning to accept that they may not have biological children.

See also

Chlamydial Infections

Endometriosis

Gonorrhea

Menstrual Disorders

Pelvic Inflammatory Disease (PID)

Pregnancy, Complications of

Prematurity

Sexually Transmitted Diseases

Syphilis

Varicose Veins

Resources

Books

Cooper, Susan, and Ellen Sarasohn Glazer. Choosing Assisted Reproduction: Social, Emotional, and Ethical Considerations. Indianapolis, IN: Perspectives Press, 1999.

Turiel, Judith Steinberg. Beyond Second Opinions: Making Choices about Fertility Treatment. Berkeley, CA: University of California Press, 1998.

Organizations

American Society for Reproductive Medicine, 1209 Montgomery Highway, Birmingham, AL 35216-2809. Telephone 205-978-5000 http://www.asrm.org

InterNational Council on Infertility Information Dissemination, Inc. (INCIID), P.O. Box 6836, Arlington, VA 22206. Telephone 703-379-9178 http://www.inciid.org

RESOLVE, The National Infertility Association, 1310 Broadway, Somerville, MA 02144. Telephone 617-623-0744 http://www.resolve.org

infertility Inability to reproduce. In a woman it may be due to a failure to ovulate (the release of an ovum for fertilization), obstruction of the Fallopian tube, or disease of the endometrium; in a man it is due to inadequate sperm production. In plants, the term refers to inability to reproduce sexually. Infertility occurs in a hybrid between different species, which are unable to produce viable gametes.

infertility (in-fer-til-iti) n. inability of a woman to conceive or of a man to induce conception after regular unprotected sexual intercourse for two years. See also sterility.

Infertility

SeeChildlessness; Family Planning; Fertility