Infertility

Introduction

Planning to start a family sometime in the future?

Wanting to get pregnant now?

Because most couples have little trouble conceiving a child, few consider that they might not be able to have children. Unfortunately, many couples find out that one or both partners is infertile only after they are ready to start a family. In 2002, infertility affected more than 2 million married couples in the United States - more than 7% of adults in the ages most likely to have children, according to information from the American Society for Reproductive Medicine and the National Center for Health Statistics.

What is it?

Often, 'infertility' is the word used to describe a decreased ability to produce children. The word 'infertile' sometimes means sterile (not being able to have children at all) while the term 'subfertility' is used to describe a lower-than-normal ability to reproduce. A more detailed definition of infertility from Resolve: the National Infertility Foundation follows:

Infertility is defined as the inability to conceive after one year of unprotected intercourse (six months if the woman is over age 35) or the inability to carry a pregnancy to live birth.

Women who have stopped taking oral contraceptives (birth control pills) may not regain fertility for up to 15 months, and those who have stopped using injectable methods of contraception may not regain fertility for up to 18 months. Additionally, women over the age of 35 may have more trouble than younger women conceiving a child because female fertility declines with age.

What causes it?

Most couples who are trying actively to have a child experience successful conception rates of about 20%-25% per month. Conception means becoming pregnant. It is the fertilization of a woman's egg by a man's sperm. Surprisingly, though, the biological process of having a child is not always simple. Both the male and female reproductive systems are quite complicated. For successful conception and pregnancy, a series of complex and interconnected hormonal events must take place with relatively precise timing. Even a small disturbance in any one of these processes can result in infertility. Although infertility is not a life-threatening condition, it can be both emotionally and financially difficult.

Either or both members of the couple may have health issues contributing to infertility. The National Women's Health Information Center estimates that about one-third of infertility cases have causes relating to the man (male factors). Roughly another third of cases have causes related to the woman (female factors), and the remaining cases have multiple or unknown causes. Although abnormalities in the reproductive system account for most cases of infertility, other physical factors that can affect fertility include extreme exercise activity, injuries, and being overweight or underweight. In addition, being exposed to certain chemicals, taking certain prescription medications, using illegal drugs, smoking cigarettes, drinking alcohol, or consuming high amounts of caffeine can also decrease fertility. Along with physical causes, fertility can be affected by other factors such as anxiety and stress.

While most infertility results from long-term conditions, some causes of infertility may be temporary. For example, a man who uses a sauna or holds a portable computer on his lap for an extended length of time may be less fertile than usual for several hours or days afterward because heat decreases sperm production and functioning. Also, an active infection of the reproductive tract may interfere with either male or female fertility until the infection is cured.

Male Factors

Although a large percent of infertility in men has no identifiable cause, known causes of male infertility can be classified into four general groups:

1. Spermatogenic disorders, which include decreases in semen volume, sperm count, sperm movement, and the ability of sperm to fertilize an egg, can all lead to male infertility. Semen is the thick, slippery, white fluid secreted by the testicles and prostate gland during sex. Semen contains lubricants and other components as well as sperm, the male cells that can fertilize an egg. Varicoceles (enlargements of the veins in the testicles) are the most common identifiable male infertility factor Varicoceles contribute to low sperm counts in up to 40% of men with fertility problems. After they are detected by clinical examination, most varicoceles are easily removed by surgery. Approximately 6% of infertile men have genetic abnormalities that interfere with sperm formation. For instance, a defect in the receptors for specific male hormone may mean that the man cannot use male hormones even though he is producing them. Azoospermia, the total lack of sperm production, may be caused by failure of the testicles or by other reasons. Low testosterone levels and other disturbances with male sex hormones may account for about 3% of all infertility cases by causing other problems with sperm production. However, half of spermatogenic disorders have no apparent cause.

2. Seminal tract obstruction involves a defect in the vas deferens (the long, thin tubes which carry sperm and semen from the testicles). If one or both of the vas deferens become blocked or twisted, sperm cannot be ejaculated (expelled) effectively. Causes for obstruction may be permanent (such as birth defects or accidental cutting of the vas deferens during abdominal surgery) or temporary (such as an infection in one of the tubes). Vasectomy, which is a deliberate surgical cutting of both vas deferentia, is a form of permanent birth control used by men who do not want to father children.

3. Inflammation of the reproductive tract can also cause male infertility. The testicles, the vas deferens, or other male reproductive structures may be damaged and/or scarred, affecting sperm production, function, and transport. Usually inflammation results from infections of the male reproductive tract or from sexually transmitted diseases (STDs). Also called sexually transmitted infections (STIs), STDs include chlamydia, genital herpes, gonorrhea, and syphilis.

4. Sexual dysfunctions can also lead to male infertility. Sexual dysfunction includes erectile dysfunction (also called impotence), which is the inability to maintain an erect penis long enough to complete sexual intercourse, and ejaculatory dysfunction which is the inability of a male to eject sperm during sexual intercourse. Men with diabetes or spinal cord injuries are at higher risk for sexual dysfunction than men without these conditions.

Female Factors

Uterine Factors
Growths and lesions (sores) inside the uterus can cause female infertility. Abnormal structures on the uterine wall, such as polyps, scars, or tumors, may prevent pregnancy by keeping a fertilized egg from attaching to the uterine wall. Other possible uterine factors that could contribute to infertility are congenital abnormalities (structural deviations that develop before birth) or an intrauterine device (IUD) that has been left in the uterus by mistake.

Endometriosis
As many as 5.5 million American women may have endometriosis, a chronic condition that can lead to fertility problems. Endometriosis occurs when cells from the endometrium (the inner lining of the uterus) become displaced and deposit outside of the uterus. Usually accumulating on pelvic or abdominal organs such as the bladder, intestines, and ovaries, the displaced endometrial tissue swells during the menstrual cycle causing symptoms. These symptoms may include abdominal pain, heavy menstrual periods, spotting between periods, and infertility. Even though the exact ways that endometriosis may cause infertility are not fully understood, endometriosis is believed to damage the ovaries or fallopian tubes. The resulting alterations in menstrual cycles can upset the hormonal balance needed for conception to occur. Endometriosis usually decreases after menopause. Surprisingly, it may also lessen after a full-term pregnancy.

Tubal factors
A number of factors can damage the fallopian tubes, the ducts which carry eggs from the ovaries to the uterus. Fertilization takes place in the fallopian tubes. Injuries and scarring can thicken and stiffen the fallopian tubes, making both egg transport and fertilization more difficult. Infertility may result from some types of fallopian tube damage that may be caused by:

• Appendicitis (especially a ruptured appendix)
• Fallopian tube surgery
• Recurring pelvic inflammatory disease (PID)
• Septic abortion (serious infection of the uterus associated with a miscarriage or abortion procedure)
• Use of an intrauterine device (IUD) for birth control

Cervical Factors
Cervical mucus is a slippery secretion that moistens and protects. It is always present around the cervix (the opening of the uterus into the vagina). In general, cervical mucus forms a soft plug that keeps bacteria and other organisms from invading the uterus. However, the composition of cervical mucus changes throughout the menstrual cycle. The preovulatory phase typically occurs one to three days before ovulation (the release of a mature egg by one ovary). During this phase, cervical mucus changes from its normal thick, gooey form to a thinner form. The more watery mucus allows sperm to penetrate through the cervical opening to the fallopian tube. Normally, cervical mucus contains hormonal and chemical components that promote sperm functioning and help sperm survive in the female reproductive tract. When the composition of the mucus is altered in any way (such as by low estrogen levels), sperm are less likely to penetrate the cervix or survive long enough to reach the egg.

Additionally, antisperm antibodies may be present in cervical mucus, as well as in semen produced by the male partner. Antibodies are proteins made by the body's immune system to fight off invaders such as bacteria. Each type of antibody attacks only one specific type of invader. Although the exact effects of antisperm antibodies are unclear, frequently they are associated with infertility. Studies are currently underway to evaluate whether any treatments targeting these antibodies could help restore fertility.

Ovarian Factors

Ovulation Failure
Failure to ovulate (release mature eggs from the ovaries) may result from numerous causes:

A primary cause of ovulation failure is age-related change in the reproductive system. A woman's fertility declines after the age of 30 years - falling dramatically after the age of 40 years. During the time when a woman is approaching menopause, ovulation typically becomes erratic, making fertilization more difficult. Approximately one-third of the women who attempt to conceive in their mid- to late-thirties will experience infertility problems.

Polycystic Ovarian Syndrome (PCOS) is another common cause of ovulation failure. Formerly called Stein-Leventhal Syndrome, PCOS is a condition in which eggs fail to mature, instead remaining in the ovaries as many small cysts. As the cysts accumulate, the ovaries stretch to as much as five times their normal size. Women with PCOS produce more androgen hormones, such as testosterone, which may result in facial and body hair, a deeper voice, decreased breast size, and other masculine features. Typically, PCOS also causes acne, irregular or absent menstrual periods, and weight gain. In the 1980s, untreated PCOS was found to be related to high cholesterol and lessened ability to use insulin properly.

Premature Ovarian Failure (POF) is essentially early menopause. Occurring in women who are younger than 40 years old, POF has no apparent cause in many cases. For other women, POF may have multiple factors that include genetics and previous pelvic infections. It may also be caused by drug or radiation treatments for cancer. Recently, some cases have been linked to certain autoimmune disorders including diabetes, rheumatoid arthritis, and systemic lupus erythematosus.

Diminished Ovarian Reserve refers to a decrease in both the number and the condition of the eggs in a woman's ovaries as she ages. Unlike men, who make new sperm throughout their life, women are born with a large, but limited number of eggs in their ovaries. Gradually, between about age 35 and menopause, when the egg supply runs out, the ovaries lose the ability to produce mature eggs. Finally, hormonal imbalances can lead to ovulation abnormalities. Disorders of the adrenal, hypothalamus, pituitary, or thyroid glands may change blood levels of hormones such as estrogen, prolactin, or progesterone enough to upset ovarian function.

Luteal Phase Abnormalities
Rarely, female infertility may result from a lack or imbalance of progesterone, one of the main female hormones. During the luteal phase (the phase immediately following ovulation) of the menstrual cycle, the inner lining of the uterus usually responds to increased progesterone levels by becoming thick and wrinkled. The softer, folded texture makes a fertilized egg more likely to stay (implant) in the uterus and start a pregnancy. If progesterone levels are not high enough or if progesterone is not present for an appropriate length of time during the luteal phase, the uterus cannot prepare correctly. Even though ovulation and fertilization may occur normally, the uterus cannot trap and nourish a fertilized egg.

Who has it?

In the United States, the number of individuals treated for infertility problems is on the rise. One reason may be that many individuals are marrying later and couples are waiting to start their families. The chance of infertility is higher in women who are in their late 30s and 40s. Another reason may be that infertile couples are more open about asking for medical help than they might have been a few years ago. Changing sexual practices may also contribute. Having an untreated sexually-transmitted disease (STD), such as chlamydia or syphilis, often leads to scarring in the reproductive tract which results in infertility.

According to a survey conducted in 2002 by the National Center for Health Statistics, approximately 12% of women between 15 and 44 years of age in the United States (over 7 million women) reported fertility problems. About a million of these women reported seeing a doctor specifically to be counseled or treated for infertility. Over their reproductive years, about one-quarter of American women who want to have a child will have some difficulty getting pregnant. In addition, nearly 2 million American men are estimated to have some degree of infertility.

What are the risk factors?

Certain risk factors (traits or actions that contribute to having certain conditions) are associated with infertility. Early detection and treatment of infertility may help to prevent problems that are more serious later, so couples having difficulty conceiving should consult a doctor if any of the following risk factors for infertility are present.

Risk Factors for Men

• Chronic conditions such as diabetes, hypertension, psoriasis, or ulcers (and some of the medications used to treat them)
• Exposure to hazardous chemicals (such as lead, mercury, or pesticides) or other toxins (such as radioactivity or x-rays)
• Having the mumps after puberty (the age when sexual organs mature)
• Heavy alcohol consumption
• Hernia surgery
• Obesity
• Prostate gland infection
• Sexually transmitted diseases (STDs) such as chlamydia, gonorrhea, or syphilis
• Smoking cigarettes or marijuana
• Stress or anxiety
• Traumatic injury
• Undescended testicles (the testicles remain in the abdomen rather than moving into the scrotum before birth; also called cryptorchidism or empty testicles)
• Use of diethylstilbestrol (DES) by the man's mother during her pregnancy
• Use of hot baths, saunas, steam rooms, or whirlpools

Risk Factors for Women

• Abnormal pap smears, especially those that resulted in treatment with cryosurgery (the use of intense cold to destroy abnormal cervical tissue) or a cone biopsy (surgery to remove a small section of abnormal tissue from the cervix)
• Age over 30
• Chronic conditions (such as arthritis, asthma, diabetes, hypertension, systemic lupus erythematosus) and some of the medications used to treat them
• Eating disorders
• Ectopic pregnancy (pregnancy outside the uterus)
• Endometriosis or a family history of endometriosis in close female relatives (mother, sisters)
• Extremely intense regular exercise
• Hair growth on unusual areas such as the face; acne on the face, chest, or abdomen; mannish facial features
• Heavy alcohol consumption
• Irregular menstrual cycles or very heavy menstrual flow
• Multiple miscarriages or abortions
• Obesity
• Ovarian cysts
• Pelvic surgery
• Ruptured appendix
• Sexually transmitted diseases (STDs) such as chlamydia, gonorrhea, or syphilis
• Smoking cigarettes or marijuana
• Stress or anxiety
• Traumatic injury
• Tubal surgery
• Use of an intrauterine device (IUD) for contraception
• Use of diethylstilbestrol (DES) by the woman's mother during her pregnancy
• Very low body fat

What are the symptoms?

Infertility has no easily recognized symptoms. In fact, most individuals do not even realize they are infertile until they try to conceive a child. However, only about 45% of infertile couples seek medical help.

For those undergoing medical evaluation of fertility, the first step is usually complete physical examinations to rule out medical causes, such as sexually transmitted diseases (STDs) for both partners. Each will also be checked for structural abnormalities, such as undescended testicles (for men) and missing or blocked fallopian tubes (for women). Additionally, medical histories will be taken to identify potential contributing factors such as past abdominal infections and previous surgeries. For women, information about menstrual cycles, previous pregnancies, and use of contraceptives will be needed.

Typically, the next steps in evaluating couples for infertility are:

• an analysis of the man's semen
• an evaluation of the woman's ovulation

Semen Analysis

For men who may be infertile, a laboratory test known as a semen analysis (often called a sperm count) is performed on the thick, white liquid that is ejected during sex. After refraining from having sex for 2 to 7 days, the man provides a sample of his semen for testing. Non-prescription home semen-testing kits are available. If sperm testing is done in a laboratory, the sample must be delivered as soon as possible after it is collected (usually within 2 hours). Characteristics such as amount, acidity, and nutrient content of the semen are evaluated. It is also checked for white blood cells that could indicate an infection. In addition, the number, size, shape, movement, and survival time of the sperm contained in the sample are tested. Usually, a second semen analysis is done after a few weeks. If either analysis shows abnormal semen or sperm, the man may need further testing.

Occasionally, postcoital (after sexual intercourse) semen testing may be performed. By examining the woman's cervical mucus after she has had sexual intercourse, a physician may be able to determine the quality of the man's semen, as well as the number of sperm and their ability to move in the mucus. Postcoital testing has fallen out of favor because it is awkward to do and it may not be as reliable as other types of tests.

Ovulation Detection

A woman who may be infertile is often evaluated to find out if her ovaries are working properly. Ovulation (the release of a mature egg from one of her ovaries) typically occurs in the middle of a regular 28-day menstrual cycle. The woman's egg is available for fertilization for 12 to 24 hours after ovulation and sperm can retain their ability to fertilize the mature egg for 24 to 48 hours. Therefore, if the time of ovulation can be determined, sexual intercourse can be planned to have the best chance of successful fertilization.

The most common methods for determining if or when ovulation occurs include:

Charting of Basal Body Temperature (BBT)
Since basal body temperature (the lowest body temperature of the day) varies throughout the menstrual cycle, a woman can keep track of her BBT to estimate when ovulation occurs. BBT is usually measured at about the same time every morning before the woman gets out of bed. BBT is lowest about 2 days before ovulation and then goes up slightly (about one-half a degree) during ovulation. Women measuring BBT usually use special thermometers that make reading the small changes in temperature easier. After tracking BBT for several months, the couple may be able to identify an approximate ovulation period (usually within a 2 to 3 day time frame).

For detailed instructions on how to use a BBT chart, please see http://www.fertilityplus.org/faq/bbt/bbtfaq.html

Ovulation Testing Kits
Several brands of ovulation testing kits are available without a prescription for use at home. Ovulation tests detect the presence of a chemical known as luteinizing hormone (LH) in the woman's urine. During the menstrual cycle, a large increase in LH triggers ovulation. Identifying the LH surge can help pinpoint the time of ovulation, which generally can be expected to occur within 36 hours after LH enters the urine. Most kits contain a series of 5 to 9 daily urine tests that take between a few minutes and an hour to perform each morning, depending on the kit.

Progesterone Levels
Measuring blood levels of progesterone is another method of determining the time of ovulation. Normally, after ovulation occurs, progesterone levels are relatively high because progesterone helps prepare the uterus to receive and implant the fertilized egg. Measuring the amount of progesterone in the blood on day 21 of a 28-day menstrual cycle (about a week after ovulation should have occurred) helps doctors tell if ovulation did take place. Checking progesterone levels is a test that requires doctor's office or clinic visits.

Ultrasound Monitoring Often used to determine when fertility drugs should be taken, ultrasounds also can determine whether or not a woman is ovulating. Ultrasounds are usually done on a hospital outpatient basis. Using high frequency sound waves, ultrasound testing shows the shape of various organs and tissues in the body. For infertility testing, ultrasound assesses the thickness of the uterine lining and the condition of the ovaries. Specifically, an ultrasound image can show the development of follicles, the structures that contain developing eggs inside the ovaries.

Endometrial Biopsy
An endometrial biopsy involves examining a tissue sample from the uterine lining under a microscope. About 2 or 3 days before the menstrual period, a sample of the endometrium is collected in a doctor's office or infertility clinic. Samples may be obtained in several ways that include scraping the uterus or using a suction device. If ovulation has occurred, the sample of tissue is likely to show the effects of progesterone, a hormone that helps prepare the uterus support a fertilized egg. An endometrial biopsy is usually reserved until other ovulation tests have been inconclusive because it is a more invasive procedure and may be uncomfortable (especially for women in their late thirties or forties).

Additional Testing

A hysterosalpingogram (HSG), which is an X-ray picture of the uterus and the fallopian tubes, may also be performed to determine whether the woman's fallopian tubes are blocked. If needed, a closer look at the inside of the uterus may be made with a hysteroscope, which is a tiny telescope inserted through the vagina. Using a hysteroscope, a doctor can see if the lining of the uterus is damaged or if abnormal growths such as fibroids (non-cancerous tumors) are present. A hysteroscope may also show the inside of the fallopian tubes.

If other tests do not show reasons for infertility, an exploratory surgical procedure such as laparoscopy (inserting a tiny camera or telescope through a small cut in the abdomen to look at the outside of the ovaries and uterus) may be done. Very rarely, laproscopy may be performed to observe or repair abnormalities, such as undescended testicles, in men who are infertile. All of these tests must be performed in a clinic, doctor's office, or hospital outpatient department.

How is it treated?

Since infertility has multiple causes, treatment options for it are also varied and many are directed at underlying causes. Timing sexual intercourse for probable dates of ovulation is a common first step. Some study evidence suggests that male hormone levels are higher in the morning and that sperm counts are higher in colder weather than in hot weather. Lifestyle changes (for instance, giving up cigarettes, losing or gaining weight, moderating extremely vigorous exercise programs, and reducing or eliminating the intake of alcohol and caffeine) are recommended for both partners. Counseling and/or medications may relieve anxiety, depression, or other psychological factors contributing to infertility. If the cause is a reproductive-tract infection, antibiotics or antiviral drugs may be enough to restore fertility. Treating health conditions such as diabetes and hypertension, or changing the prescription drugs used to treat them may also reduce infertility for some individuals. Occasionally, blocked reproductive structures may be re-opened by surgery.

If male infertility results from a low sperm count, therapy with male hormones may help. When female infertility is caused by decreased ovulation, certain medications and female hormones can be used to induce ovulation (help stimulate the woman's body to produce mature eggs). It is important to know that most drugs and other infertility treatment options increase the chance that a woman has multiple fetuses (twins, triplets, other multiples). In cases of multiple births, there is an greater chance that the babies will be born early and have developmental and/or health problems. This issue should be discussed with a doctor before starting fertility treatment. For more information about medications used in infertility treatment, click the drug classes links below.

Infertility treatment options other than medications include:

No Treatment

Infertile couples can choose not to undergo specialized treatment. Infertility treatments are often embarrassing and expensive. Also, they may need to be repeated and may not be covered by health insurance. However, for couples who want to conceive a child together, choosing not to be treated may decrease the chance of a successful pregnancy.

Intrauterine Insemination (IUI)

Formerly known as artificial insemination, intrauterine insemination (IUI) has been used for many years as a treatment approach for infertile couples. It may be successful when infertility is caused by certain male factors (such as spermatogenic disorders or sexual dysfunction), by female cervical factors, or by both. In IUI, concentrated sperm (from the male partner or a sperm donor) is introduced directly into the woman's uterus through a tube that is inserted through her vagina.

Performed in a medical facility, the procedure is scheduled to be done during ovulation. Usually, a woman undergoing IUI will take fertility drugs before the procedure to induce ovulation. This assures that she produces mature eggs that can be fertilized. IUI results in successful conception in up to 40% of couples when the male partner's sperm is used. When donor sperm is used, success rates are generally higher averaging between 40% and 70%. If successful conception has not occurred after 6 months of IUI, other treatment options should be explored.

Assisted Reproduction Techniques (ART)

Beginning in the 1980s, scientific advances have led to improvements in treating infertility. Assisted reproduction techniques (ART) may use eggs and sperm from the couple trying to conceive or from donors. Between 1996 and 2002, the number of live births for women using ART more than doubled from about 14,500 to over 33,000. The number of live births is less than the actual number of ART-conceived babies, because a multiple birth (twins, triplets, or more babies born at one time) is counted as only one live birth. Most often, doctors performing ART procedures return fertilized eggs to the couple's female partner. Because more than one fertilized egg is usually returned to the woman, the chance of having a multiple birth increases between 20% and 40% for women who undergo ART.

The Division of Reproductive Health at the Centers for Disease Control and Prevention (CDC) keeps track of U.S. fertility-treatment success rates at each infertility clinic. However, comparing rates between clinics may not be appropriate because patient populations and treatment offerings vary widely. The woman's age also plays a big role in whether or not ART will work. In addition, success rates differ according to the source and storage of the eggs. In general, the highest success rates result from using donated fresh eggs and the lowest rates from using the woman's own frozen eggs. Usually, though, ART procedures that use frozen eggs are less expensive, so the couple may be able to afford more attempts if the first procedure is not successful. According to the most recent available CDC report, over 90,000 ART procedures were attempted in 2002. Overall results were:

ART Procedure Success Rates, United States-2005
	Woman's Age
	Under 35	35 to 37	38 to 40	41 to 42
Pregnancy	43.1%	35.7%	26.8%	17.6%
Live Births	37.3%	29.5%	19.7%	10.%
Results of ART with fresh, nondonor eggs

For more information, see the full report at: http://apps.nccd.cdc.gov/ART2005/nation05.asp

Sometimes, the female partner can get pregnant, but she cannot carry a baby to a live birth. In fewer than 1% of those who have an ART, the couple may decide to use the services of a surrogate mother (a healthy woman who agrees to have the fertilized egg or eggs implanted in her uterus). Surrogate mothers are usually paid and they often sign contracts agreeing to give the couples all parental rights for children that result from successful live births.

Most common current ART techniques include:

Intracytoplasmic Sperm Injection (ICSI)
Best used when sperm numbers, quality, or movement are inadequate, intracytoplasmic sperm injection (ICSI) addresses male factor infertility. In ICSI, healthy, active sperm are isolated from a semen sample and mature eggs are taken from a woman's ovaries. In a laboratory, one sperm is injected into each egg. After a few days, some of the eggs that have been fertilized are transferred to the woman's uterus. If the procedure is successful, one or more eggs will implant in the uterus and a pregnancy will result. Any extra fertilized eggs may be frozen for possible future use. When infertility has both male and female causes, ICSI can be paired with another type of ART, such as in vitro fertilization, to improve the chances of successful conception. In about 50% of couples undergoing fertility treatments, ICSI is used in addition to an ART procedure for the woman.

In Vitro Fertilization (IVF)
In vitro fertilization was first used successfully in the United States in the early 1980s. According to information from the Centers for Disease Control and Prevention, over 99% of women who decided to use ART in 2005 chose IVF as their first treatment option. IVF is estimated to have resulted in the births of over 115,000 American children (who are sometimes called test tube babies) to date. In IVF, several eggs are taken from a woman's ovaries and fertilized in a laboratory dish using sperm from her partner or a sperm donor. If the female partner cannot produce healthy eggs, donor eggs may be used. Two to four (or more) of the fertilized eggs (embryos) are placed into the woman's uterus, where they may implant and grow naturally. Eggs that are fertilized by IVF but not inserted into the uterus may be saved by freezing them. Because each implanted embryo has a 20% to 25% chance of resulting in a birth; IVF frequently produces twins, triplets, or more babies at one time.

Gamete Intrafallopian Transfer (GIFT)
Developed in 1984 to more closely mimic natural conception, gamete intrafallopian transfer (GIFT) is very similar to IVF. The main difference is that fertilization occurs in the woman's body instead of in a laboratory dish. Several eggs are extracted from the ovaries, examined under a microscope for maturity, and then the healthiest, most mature eggs are placed directly into one of the woman's fallopian tubes along with purified and concentrated sperm. Because GIFT requires laparoscopy (surgery using small incisions) and general anesthesia, it is both more involved and more expensive than IVF. In addition, fertilization cannot be confirmed as easily as with other ART procedures. Due to these disadvantages, GIFT is not as common as other ART procedures. However, GIFT may be more successful for women over 40 years of age, who tend to have lower success rates with IVF.

Zygote Intrafallopian Transfer (ZIFT)
During a zygote intrafallopian transfer (ZIFT) procedure, which has aspects of both IVF and GIFT, some of a woman's eggs are taken from her ovaries or from an egg donor. The eggs are fertilized in a laboratory dish where they are allowed to develop into zygotes (an early development stage in which the fertilized egg has divided into two or four cells. Viable zygotes are then transferred to the woman's fallopian tube) usually within one day of fertilization, which is confirmed before the zygotes are returned to the woman's reproductive tract. Like GIFT, ZIFT also requires laparoscopy.

Tubal Embryo Transfer (TET)
Tubal embryo transfer (TET) is nearly identical to ZIFT. Eggs and sperm are united outside the body, but any resulting fertilized eggs are allowed to divide in a laboratory dish for a longer period of time (two or more days) before being placed in one of the woman's fallopian tubes.

Peritoneal Oocyte and Sperm Transfer (PROST)
A somewhat newer procedure known as peritoneal oocyte and sperm transfer (PROST) is also very similar to ZIFT. However, in PROST, eggs that are fertilized by sperm in a laboratory dish are placed into the fallopian tube before cell division occurs.

What is on the horizon?

Much of the current research on infertility involves its causes and the conditions that may contribute to it, in addition to new treatments. For example, fertility researchers at the National Institute of Child Health and Human Development (NICHD) have been looking at several general factors involved in human fertility that include:

• Structures of both male and female reproductive tracts
• Actions of the hormones that regulate fertility
• Functions of the ovaries and testicles
• Mutations of genes responsible for reproductive functions

Researchers continue to try to find ways to improve current treatment options such as assisted reproduction techniques. For example, a screening method known as preimplantation genetic diagnosis (PGD) is being developed and tested so that doctors may identify which embryos are the highest quality for transfer to a woman during in-vitro fertilization.

Aging

In addition, investigators are trying to understand why fertility decreases as a woman ages and how to slow or stop this process. There is also the possibility of a woman being able to freeze her eggs for future use if she wishes to delay pregnancy until she is older.

Uterine Transplantation

Another alternative that is currently being studied is uterine transplantation. This treatment would be an alternative to using a surrogate mother (a healthy woman who agrees to have the fertilized egg or eggs implanted in her uterus). However, like other transplant patients, uterine transplant patients would require drugs to prevent the immune system from rejecting the donor organ. These drugs often have unwanted side effects and need to be taken for life. Although some progress has been made with this and other new treatment options, it is unlikely that they will be widely available to women anytime soon. It will take many years to determine whether these new treatment options are safe and effective.

Nutritional Factors

Other research has uncovered possible nutritional factors that may contribute to infertility that is not explained by physical or emotional factors. For example, low levels of folic acid, a type of vitamin B found in fruits, vegetables and other foods, may be associated with infertility in men. Folic acid has long been known to help prevent birth defects of the spine when pregnant women take it, and taking it may improve female infertility, too. Trace elements are chemicals such as aluminum and zinc that the body needs in very small amounts. Shortages of some of these trace elements are also believed to decrease fertility. Zinc deficiencies may contribute to genetic damage that may result in both male and female infertility because zinc is a component of DNA. One study of infertile men has shown a significant increase in sperm production among men who took supplements containing folic acid and zinc. Essential fatty acids (EFAs) are needed by both men and women to make sex hormones and they may have effects on semen and cervical mucus. Other dietary supplements, such as carnitine (found in meat and milk) and melatonin, have been tested for their effects on infertility in men. Results of studies on the role of nutrients and dietary supplements in infertility are not conclusive.

Antioxidants

Frequently called reactive oxygen species (ROS), oxygen free radicals are highly-active molecules that result from normal body processes. Inside the human body, oxygen free radicals may cause damage to other cells including sperm and eggs. They may also contribute to infertility risk factors, such as endometriosis. Antioxidants, for instance beta carotene, selenium, and vitamin C, are substances that help to limit damage from oxygen free radicals. Studies conducted in Australia and India suggest that naturally-occurring antioxidants such as lycopene seem to help improve fertility in men. Research on the effects of oxygen free radicals on fertility in women is less advanced, but studies are underway for both men and women.

Cancer and Infertility

For individuals who may become infertile due to radiation or chemotherapy treatments for cancer or other diseases, sperm or eggs may now be collected before the therapy begins. In a procedure known as cryopreservation, healthy sperm or eggs are taken from the patient and frozen, before therapy begins. After the damaging treatment, the eggs or sperm may be used for ART procedures. More recently, cells from testicles and ovaries have also been cryopreserved and then re-implanted to restore at least partial reproductive function after treatments are ended. Doctors may also use infertility medications to minimize reproductive organ damage during cancer treatment. In a procedure that is beginning to be used more frequently for children, adolescents, and young adults, FSH and LH levels may be suppressed by drugs known as GnRH analogs during the cancer treatment. As a result, the testicles or ovaries become inactive and, therefore, less likely to be damaged by drug or radiation treatments. After the therapy is over, at least partial normal function may be restored.

Long-term Effects of ART

Finally, researchers are focusing on the long-term effects of ART on all members of the family. If ART is not successful, both partners may suffer psychological consequences, such as depression and loss of self-esteem. Procedures that result in live births - especially those producing three, four, or more babies at the same time - often create unexpected physical, financial, and emotional stresses for the family. Frequently, ART procedures produce multiple-infant pregnancies and women pregnant with more than one child are more likely to develop complications during pregnancy. Both multiple and single children born after ART are more often delivered early. They also tend to be lower in birth weight than other babies. Being born early and/or weighing less than five and a half pounds at birth may contribute to breathing, heart, intestinal, and vision problems. In addition, results of a few studies seem to show that some children born as the result of ART may be at a slightly greater risk of having certain birth defects, developmental abnormalities, genetic conditions, or learning disorders than children who are conceived naturally. Whether the tendency to have these conditions is due to ART, to the factors causing the infertility, or to other causes has yet to be determined.

References

Agarwal A, Allamaneni SS. Role of free radicals in female reproductive diseases and assisted reproduction. Reproductive Biomedicine Online. 2004;9(3):338-347.

Agarwal A, Nallella KP, Allamaneni SS, Said TM. Role of antioxidants in treatment of male infertility: an overview of the literature. Reproductive Biomedicine Online. 2004;8(6):616-627.

American Society for Reproductive Medicine. Frequently asked questions about infertility. Available at: http://www.asrm.org/Patients/faqs.html. Accessed July 24, 2007.

Assisted Reproduction Techniques (ART). Fertilitext. Available at: http://www.fertilitext.org/ Accessed July 24, 2007.

Baker HW. Reproductive effects of nontesticular illness. Endocrinology and Metabolism Clinics of North America. 1998;27(4):831-850.

Bonanomi M, Lucente G, Silvestrini B. Male fertility: core chemical structure in pharmacological research. Contraception. 2002;65(4):317-320.

Brugh VM 3rd, Lipshultz LI. Male factor infertility: evaluation and management. Medical Clinics of North America. 2004;88(2):367-385.

Carr BR, Bradshaw KD. Disorders of the Ovary and Female Reproductive Tract. In: Fauci AS, Braunwalk E, Martin JB, et al., eds. Harrison's Principles of Internal Medicine 14th ed. McGraw-Hill. 1998; 2097-2115.

Carson DS, Bucci KK. Infertility in women: an update. Journal of the American Pharmaceutical Association. 1998; 38(4):480-486.

Chandra A, Martinez GM, Mosher WD, Abma JC, Jones J. Fertility, family planning, and reproductive health of U.S. women: Data from the 2002 National Survey of Family Growth. National Center for Health Statistics. Vital Health Stat 23(25). Dec 2002. Available at: http://www.cdc.gov/nchs/data/series/sr_23/sr23_025.pdf. Accessed September 25, 2006.

Chen P. Polycystic Ovary Disease. MedLine Plus. Updated February 5, 2008. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000369.htm. Accessed August 27, 2008.

Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion. Centers for Disease Control and Prevention. U.S. Department of Health and Human Services. 2003 Assisted Reproductive Technology (ART) Report: 2003 Fertility Clinic Report by State: National Summary. Date last reviewed: March 23, 2006. Available at: http://www.cdc.gov/ART/ART2003/PDF/ART2003.pdf. Accessed September 27, 2006.

El-Tawil AM. Zinc deficiency in men with Crohn's disease may contribute to poor sperm function and male infertility. Andrologia. 2003;35(6):337-341.

e-Medicine. Endometriosis. Last updated September 13, 2005. Available at: http://www.emedicinehealth.com/articles/12239-1.asp. Accessed July 24, 2007.

Fertility researchers discover new gene essential for female fertility. National Institutes of Child Health and Human Development. October 30, 2000. Available at: http://www.nih.gov/news/pr/oct2000/nichd-30.htm. Accessed April 11, 2001.

Forti G, Krausz C. Clinical review 100: Evaluation and treatment of the infertile couple. Journal of Clinical Endocrinology and Metabolism. 1998;83(12):4177-4188.

Frey KA, Patel KS. Initial evaluation and management of infertility by the primary care physician. Mayo Clinic Proceedings. 2004;79(11):1439-1443.

Garolla A, Maiorino M, Roverato A, Roveri A, Ursini F, Foresta C. Oral carnitine supplementation increases sperm motility in asthenozoospermic men with normal sperm phospholipid hydroperoxide glutathione peroxidase levels. Fertility and Sterility. 2005;83(2):355-361.

Hammond CB, Stillman RJ. Infertility and Assisted Reproduction. In: Scott JR, DiSaia PJ, Hammond CB, Spellacy WN, eds. Danforth's Obstetrics and Gynecology. 8th ed. Philadelphia. Lippincott Williams & Wilkins. 1999:649-667.

Hansen M, Bower C, Milne E, de Klerk N, Kurinczuk JJ. Assisted reproductive technologies and the risk of birth defects--a systematic review. Human Reproduction. 2005;20(2):328-338.

Hardy K, Wright C, Rice S, Tachataki M, Roberts R, Morgan D, Spanos S, Taylor D. Future developments in assisted reproduction in humans. Reproduction. 2002;123(2):171-183.

Hassan MA, Killick SR. Negative lifestyle is associated with a significant reduction in fecundity. Fertility and Sterility. 2004;81(2):384-392.

Isaksson R, Tiitinen A. Present concept of unexplained infertility. Gynecology and Endocrinology. 2004;18(5):278-290. Jones HW, Toner JP. The infertile couple. New England Journal of Medicine. 1993; 329:1710-1712.

Jung A, Schill WB. Male infertility. Current life style could be responsible for infertility. [Article in German] MMW Fortschritte der Medizin. 2000;142(37):31-33.

Kempers RD. Where are we going? Fertility and Sterility. 1994;62(4):686-689.

Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. Journal of Clinical Endocrinology and Metabolism 1999;84:165-169.

Lie RT, Lyngstadaas A, Orstavik KH, Bakketeig LS, Jacobsen G, Tanbo T. Birth defects in children conceived by ICSI compared with children conceived by other IVF-methods; a meta-analysis. International Journal of Epidemiology. 2005;34(3):696-701.

Lieu CL and Yoshida T. Infertility. In: DiPiro JT, Talbert RL, Hayes PE, Yee GC, Matzke GR, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 5th ed. New York. McGraw-Hill. 2002:1431-1443.

Linne Y. Effects of obesity on women's reproduction and complications during pregnancy. Obesity Review. 2004;5(3):137-143.

Marmar JL. The diagnosis and treatment of male infertility in the new millennium. International Journal of Fertility and Womens Medicine. 2001;46(3):116-136.

Marshall K. Polycystic ovary syndrome: clinical considerations. Alternative Medicine Review. 2001;6(3):272-292.

Martin J. In-vitro Fertilization: 25 Years Later. Article date Aug 5, 2003. Reviewed on Jan 3, 2005. Available at: http://www.fertilityneighborhood.com. Accessed September 25, 2006.

Mayo Clinic Staff. Infertility. Mayo Clinic. June 29, 2005. Available at: http://www.mayoclinic.com/invoke.cfm?id=DS00310. Accessed July 24, 2007.

McManus MC, Barqawi A, Meacham RB, Furness PD 3rd, Koyle MA. Laparoscopic varicocele ligation: are there advantages compared with the microscopic subinguinal approach? Urology. 2004;64(2):357-361.

Minnesota Men's Health Center. Male infertility. Available at: http://www.mmhc-online.com/articles/male_infertility.html. Accessed January 4, 2005.

Murase M, Uemura T, Gao M, Inada M, Funabashi T, Hirahara F. GnRH antagonist-induced down-regulation of the mRNA expression of pituitary receptors: comparisons with GnRH agonist effects. Endocrinology Journal. 2005;52(1):131-137.

Namiki M. Genetic aspects of male infertility. World Journal of Surgery 2000; 24 (10):1176-1179.

National Center for Health Statistics. Centers for Disease Control and Prevention. U.S. Department of Health and Human Services. Infertility. Last reviewed October 6, 2006. Available at: http://www.cdc.gov/nchs/fastats/fertile.htm. Accessed July 24, 2007.

National Institute of Child Health and Human Development. Disorders associated with infertility. Last modified September 15, 2006. Available at: http://www.nichd.nih.gov/about/womenhealth/infertility.cfm. Accessed July 24, 2007.

National Institute of Child Health and Human Development. From cells to selves. Reproductive health in the 21st century. No date given. Available at: http://www.nichd.nih.gov/strategicplan/cells/Reproductive_Health.pdf.Accessed December 28, 2004.

National Women's Health Information Center. Infertility. U.S Department of Health and Human Services, Office of Women's Health. November 2002. Available at: http://www.4woman.gov/faq/infertility.htm. Accessed December 28, 2004.

Ng CM, Blackman MR, Wang C, Swerdloff RS. The role of carnitine in the male reproductive system. Annals of the New York Academy of Science. 2004;1033:177-188.

Norman RJ, Noakes M, Wu R, Davies MJ, Moran L, Wang JX. Improving reproductive performance in overweight/obese women with effective weight management. Human Reproduction Update. 2004;10(3):267-280.

Partonen T. Melatonin-dependent infertility. Medical Hypotheses. 1999;52(3):269-270.

Pasquali R, Pelusi C, Genghini S, Cacciari M, Gambineri A. Obesity and reproductive disorders in women. Human Reproduction Update. 2003;9(4):359-372.

Pasqualotto FF, Lucon AM, Sobreiro BP, Pasqualotto EB, Arap S. Effects of medical therapy, alcohol, smoking, and endocrine disruptors on male infertility. Rev Hosp Clin Fac Med Sao Paulo. 2004;59(6):375-382.

Pathak P, Kapil U. Role of trace elements zinc, copper and magnesium during pregnancy and its outcome. Indian Journal of Pediatrics. 2004;71(11):1003-1005.

POF Support Group. Premature ovarian failure (POF) fact sheet. Available at: http://www.pofsupport.org/information/factsheet/fact_sheet_english.pdf. Accessed January 21, 2005.

Preserving Your Fertility: Risk Factors. RESOLVE: The National Infertility Association. Available at: http://www.resolve.org/site/PageServer. Accessed August 27, 2008.

Rein MS, Barbieri RL. The Infertile Couple Part I. In: Ryan KJ, Berkowitz RS, Barbieri RL, Dunaif A. Kistners Gynecology and Women's Health, 7th ed. St. Louis, Mosby. 1999:325-354.

Rein MS, Barbieri RL. The Infertile Couple Part II. In: Ryan KJ, Berkowitz RS, Barbieri RL, Dunaif A. Kistners Gynecology and Women's Health, 7th ed. St. Louis, Mosby. 1999:325-354.

Richardson MR. Current Perspectives in Polycystic Ovary Syndrome. American Family Physician. 2003;68(4):697-704.

Sandlow, JI. Shattering the myths about male infertility. Postgraduate Medicine. 2000;107(2): 235-239, 242, and 245.

Schieve LA, Rasmussen SA, Buck GM, Schendel DE, Reynolds MA, Wright VC. Are children born after assisted reproductive technology at increased risk for adverse health outcomes? Obstetrics and Gynecology. 2004;103(6):1154-1163.

Schlatt S, von Schonfeldt V, Schepers AG. Male germ cell transplantation: an experimental approach with a clinical perspective. British Medical Bulletin. 2000;56(3):824-836. Semen analysis. MedLine Plus. Last updated January 19, 2005. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/003627.htm. Accessed April 21, 2005.

Shaeer OK, Shaeer KZ. Laparoscopy-assisted pelvi-scrotal vasovasostomy. Andrologia. 2004;36(5):311-314.

Sheynkin Y, Jung M, Yoo P, Schulsinger D, Komaroff E. Increase in scrotal temperature in laptop computer users. Human Reproduction. 2005;20(2):452-5.

Siddiq FM, Sigman M. A new look at the medical management of infertility. Urology Clinics of North America. 2002;29(4):949-963.

Sigman M, Howards SS. Male Infertility. In: Walsh PC, Retnick AB, Vaughan ED, Wein AJ. Campbell's Urology, 7th ed. Philadelphia, W.B. Saunders 1998: 1287-1330.

Sinclair S. Male infertility: nutritional and environmental considerations. Alternative Medicine Review. 2000;5(1):28-38.

Spitz A, Kim ED, Lipshultz LI. Contemporary approach to the male infertility evaluation. Obstetric and Gynecology Clinics of North America. 2000; 27(3):487-516.

Stephen EH, Chandra A. Updated projections of infertility in the United States: 1995-2025. Fertility and Sterility. 1998;70(1):30-34.

Stephen EH, Chandra A. Use of Infertility Services in the United States: 1995. Family Planning Perspectives. 2000;32(3):132-137.

Talbert LM. Overview of the diagnostic evaluation. In: Hammond MG, Talbert LM, eds. Infertility: A Practical Guide for Physicians. 3rd ed. Boston, Blackwell. 1993:1-10.

Torrents E, Boiso I, Barri PN, Veiga A. Applications of ovarian tissue transplantation in experimental biology and medicine. Human Reproduction Update. 2003;9(5):471-481.

Trounson AO, Wood C. IVF and related technology. The present and the future. Medical Journal of Australia. 1993;158(12):853-857.

Westphal LM, Polan ML, Trant AS, Mooney SB. A nutritional supplement for improving fertility in women: a pilot study. Journal of Reproductive Medicine. 2004;49(4):289-293.

Zini A, Fischer MA, Nam RK, Jarvi K. Use of alternative and hormonal therapies in male infertility. Urology. 2004;63(1):141-143.

Infertility Health Condition Last Updated: September 2008

Note: The above information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist, or other healthcare professional. It is not intended to diagnose a health condition, but it can be used as a guide to help you decide if you should seek professional treatment or to help you learn more about your condition once it has been diagnosed.

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