Infertility

Overview

Infertility means a couple cannot achieve pregnancy after one year of having regular, unprotected sex, or after six months if the woman is older than 35. The term also describes the condition of women who can get pregnant but cannot carry a pregnancy to term because of miscarriage, recurrent pregnancy loss, stillbirth, or other problems. In addition, it includes the need to use donor sperm, eggs, or fertilized embryos to achieve a successful pregnancy as an individual or as a partner.

Related Terms: Subfertility is when a woman or couple has a lower-than-expected chance of becoming pregnant within a given period, but pregnancy remains possible

Causes and Risk Factors

Infertility can be caused by male factors, female factors, a combination of both, or reasons that remain unexplained. Many different medical conditions and other factors can also contribute to fertility problems. An individual case may have a single cause, several causes, or no identifiable cause, known as idiopathic infertility.

Causes of Female Infertility

The most common overall cause of female infertility is failure to ovulate. Causes of ovulatory dysfunction may include:

• Ovarian or gynecological conditions, such as primary ovarian insufficiency (POI) or polycystic ovary syndrome (PCOS), also known as Polyendocrine metabolic ovarian syndrome
• Aging, including “diminished ovarian reserve,” meaning a reduced number of eggs due to normal aging
• Endocrine disorders, such as thyroid disease or problems with the hypothalamus, which can affect hormone levels
• Lifestyle and environmental factors

Structural problems can also contribute to infertility. If the fallopian tubes are blocked, eggs cannot move from the ovaries to the uterus, and sperm cannot reach the egg. Specific structural problems include:

• Endometriosis is a condition in which tissue that normally lines the inside of the uterus grows outside the uterus in other places and may block the fallopian tubes.
• Uterine fibroids are noncancerous growths within or around the wall of the uterus. Most women with fibroids can get pregnant, but some may have difficulty conceiving naturally or may have multiple miscarriages.
• Polyps are noncancerous growths on the inside surface of the uterus that can interfere with the normal function of the uterus.

When a fertilized egg fails to implant in the uterine wall, it is called implantation failure. This may result from several factors:

• Genetic abnormalities in the embryo
• Thin endometrium
• Embryonic defects
• Endometriosis
• Progesterone resistance
• Scarring in the uterus from previous injuries, infections, or surgery
• An unusually shaped uterus

Infections can also contribute to infertility:

• Untreated gonorrhea and chlamydia can lead to pelvic inflammatory disease and cause scarring that blocks the fallopian tubes.
• Untreated syphilis increases the risk of stillbirth.
• Chronic infections of the cervix can reduce the amount or quality of cervical mucus. Surgical treatment of cervical lesions associated with human papillomavirus (HPV) infection can cause this as well.

Autoimmune disorders such as lupus, Hashimoto’s thyroiditis, and rheumatoid arthritis may affect fertility through inflammation in the uterus and placenta or through medicines used to treat these conditions.

Causes of Male Infertility

The cause of male infertility often cannot be determined. The most common issues that lead to infertility in men are problems that affect how the testicles and other components of the male reproductive tract work together to produce functional sperm. These may include:

• A complete lack of sperm, known as aspermia, which may be caused by a hormone imbalance or blockage of sperm transport
• Low sperm count, also known as oligospermia, which may be caused by varicocele, or enlarged veins in the scrotum
• Chromosome defects
• Diabetes
• Overproduction of the hormone prolactin made by the pituitary gland, a condition known as hyperprolactinemia
• Injury to the testicles
• Insensitivity to androgens, including testosterone
• Inflammation or swelling of the testicles from infections such as mumps, gonorrhea, or chlamydia
• Klinefelter syndrome, which is a chromosome disorder caused by the presence of an extra X chromosome in males
• Thyroid disorders
• One or both testicles failing to descend, known as cryptorchidism

Problems with sperm movement can also contribute to infertility:

• Sperm may move too slowly or not at all and die before reaching the egg.
• Seminal fluid may be too thick for sperm to move properly.
• An inability to transport sperm from the testicles to the penis may result from natural blockages or from vasectomy.

Other conditions that can cause male infertility include:

• Erectile dysfunction is a condition defined by difficulty getting or maintaining an erection, which makes having sex difficult.
• Retrograde ejaculation is a condition in which sperm travel into the bladder instead of out through the penis. Some medicines may increase the likelihood of this problem.
• Cystic fibrosis is a genetic disorder that can cause men to be born without the tubes that carry sperm out of the testicles. These men are infertile, but not sterile, because they still produce sperm.

Age-Related Factors

Fertility declines with age in both men and women, but the effects of age are greater in women. Researchers believe that women are born with one million to two million eggs and that this number decreases as they age. In their 30s, women are about half as fertile as they are in their early 20s, and the chance of conception declines significantly after age 35. After menopause, there is no way for a woman to get pregnant naturally.

Male fertility also declines with age, but more gradually.

Increasing age also raises the risk for conditions that can contribute to a loss of fertility, including:

• Uterine fibroids
• Tubal disease, including infections that affect the fallopian tubes
• Endometriosis
• Genetic abnormalities in the remaining eggs, which can make them less viable or increase the likelihood of chromosomal conditions such as Down syndrome

In males, advancing age reduces the quality of sperm, which may affect the sperm’s ability to reach or fertilize an egg. Other age-related causes of reduced fertility in males include:

• Genetic abnormalities of the sperm
• Erectile dysfunction, which may be influenced by decreasing testosterone levels or by medicines used to treat age-related conditions such as high blood pressure
• Changes in the reproductive tissues or organs, such as an age-related decrease in testicle volume or an enlarged prostate that can contribute to problems with ejaculation

Lifestyle and Environmental Factors

Research consistently shows that lifestyle and environmental factors have profound effects on fertility.

• Body weight: Obesity can affect fertility in women and is linked to lower sperm count and sperm quality in men. Being underweight is also linked to infertility and ovarian dysfunction in women.
• Physical activity: Strenuous physical labor may reduce sperm count in men and excessive exercise can affect ovulation and fertility in women.
• Medical treatment: Taking multiple medicines is associated with reduced sperm count in men. Radiation therapy and chemotherapy can also cause infertility in both men and women.
• Substance use: Smoking tobacco, using other tobacco products or marijuana, alcohol misuse, and using illegal drugs such as heroin and cocaine all can reduce fertility in both men and women. In addition, using anabolic steroids (body-building medicines) or androgens can impair sperm production in men.
• Blood pressure: Having high blood pressure can change the shape of sperm and may reduce fertility.
• Environmental factors: Exposure to persistent organic pollutants and endocrine-disrupting chemicals (EDCs) in the environment can affect both male and female fertility. Certain organochlorine pesticides and many polychlorinated biphenyls (PCBs) have been linked to increased time-to-pregnancy or reduced couple fertility.

Prevention Guidance

Although not all causes of infertility can be prevented, certain steps may help reduce risk and support reproductive health.

• Maintain a healthy body weight. Both overweight and underweight status can affect fertility. See our articles on obesity and healthy eating to learn more.
• Control your blood pressure. Managing high blood pressure may support overall reproductive health. See our article on hypertension to learn more.
• Get vaccinated against human papillomavirus (HPV). The Centers for Disease Control and Prevention recommends that all boys and girls age 11 or 12 be vaccinated against HPV. Men and women who were not vaccinated at the recommended age can also get the vaccine through their early to mid-20s.
• Consider fertility preservation before certain medical treatments, such as radiation therapy or chemotherapy. Fertility preservation is the process of saving or protecting eggs, sperm, or reproductive tissue for possible future use to have biological children.

Diagnosis

In most cases, infertility has no outward signs or symptoms other than the inability to conceive within a stated period of time or the inability to carry a pregnancy to a live birth. Healthcare providers evaluate men and women differently when diagnosing infertility.

When to See a Healthcare Provider

Couples should consult a healthcare provider about possible fertility problems if they have had regular, unprotected sex for one year without a successful pregnancy. Earlier evaluation may be appropriate for some people, including:

• Women older than age 35 who have had six months of regular, unprotected sex without achieving a successful pregnancy
• Women who suspect they may have underlying conditions that affect fertility, such as irregular menstrual periods
• Individuals who have been diagnosed with medical conditions known to reduce fertility

For Women

A healthcare provider will ask about health and reproductive history, including:

• Prior pregnancies and miscarriages
• The regularity of her menstrual periods
• The presence of pelvic pain
• Abnormal vaginal bleeding or discharge
• History of pelvic infection or previous pelvic surgery

Initial evaluation may also involve:

• A physical exam, including a pelvic exam or pelvic ultrasound
• A Pap test (also called a Pap smear or cervical cytology), which collects cells from the cervix so they can be checked for abnormalities
• Blood tests to assess overall health

Additional laboratory tests and diagnostic tests may include:

• Blood tests: A blood test around day 23 of the menstrual cycle can measure the hormone progesterone and determine whether ovulation has occurred. Other blood tests can measure follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) can help determine the quantity of a woman’s remaining egg supply.
• Hysterosalpingography is an X-ray procedure in which a healthcare provider injects radiographic dye through the cervix to determine whether the fallopian tubes are open and free of blockages.
• Laparoscopy is a surgical procedure in which a small viewing instrument is inserted through a small cut in the abdomen to examine the female reproductive organs. If blockages are found, they may sometimes be treated during the same procedure.
• Transvaginal ultrasound uses sound waves to provide a view of the uterus and ovaries via a wand inserted into the vagina.
• Hysteroscopy uses a long, thin camera inserted through the vagina and into the uterus to examine the inside of the uterus.
• Saline sonohysterography involves injecting sterile saline through the cervix to fill the uterus, making the inner lining easier to evaluate with transvaginal ultrasound.

For Men

A healthcare provider will ask about health and reproductive history, including:

• Past injury to the testicles or penis
• Recent high fevers
• Childhood diseases, such as mumps
• Low sexual desire (libido)

A physical examination may check for:

• Signs of infection
• Hernia
• Malformed tubes that transport sperm
• Signs of hormone deficiency, such as small testes or a lack of facial and body hair
• A mass in the testicles
• Enlarged veins in the scrotum, called varicocele

Additional tests may include:

• Semen analysis requires the man to provide a semen sample after refraining from ejaculation for about 48 hours to assess the health and quality of his sperm. More than one sample may be needed because sperm production can vary over time.
• Blood hormone tests can measure testosterone, follicle-stimulating hormone (FSH), thyroid hormones, and prolactin.
• Biopsy of the testicle is a procedure in which a healthcare provider uses a needle to extract sperm directly from the testicle.
• Genetic testing may be used when no or very few sperm are found in the semen. This testing can identify genetic abnormalities that may explain the lack of sperm or increase the risk of developmental problems for offspring.

Treatment and Management

Treatments for infertility can range from medicines to embryo implantation through assisted reproductive technology (ART). In most cases, infertility is treated with conventional medical therapies, such as medicine or surgery. If fertility treatments are unsuccessful, it is possible to use eggs or sperm donated by a third party or to have another woman carry a fetus.

Treatments for Women

Whether treatment for female infertility succeeds depends on several factors, including:

• The underlying cause of the problem
• The woman’s age
• Her history of previous pregnancies
• How long she has experienced infertility

The first step in treating infertility is often to address the underlying cause. For example, when a thyroid disorder causes hormone imbalances, treatment of the thyroid disorder may restore fertility.

Medicines that stimulate ovulation include:

• Clomiphene (Clomiphene Citrate) is an oral medicine that causes the body to make more of the hormones that help eggs mature in the ovaries. Women treated with clomiphene have a 10% chance of having twins, while having triplets or higher numbers of multiple babies is rare, occurring in less than 1% of cases. Clomiphene is a common treatment for infertility in women with PCOS.
• Letrozole is an oral medicine that lowers estrogen levels and stimulates the ovaries to release eggs. Some studies have found that letrozole may be more effective than clomiphene in women with PCOS.
• Gonadotropins and human chorionic gonadotropin (hCG) are injectable hormones that directly stimulate egg development in the ovaries. Gonadotropins are typically injected in the early part of the menstrual cycle for 7 to 12 days. About 30% of women who conceive with these medicines have multiple births.
• Bromocriptine or cabergoline are oral medicines that treat abnormally high levels of prolactin, a hormone that can interfere with ovulation. Once prolactin levels become normal, about 85% of women ovulate.

To help women with PCOS get pregnant, doctors may also recommend:

• Weight loss: Women with PCOS who lose weight are more likely to resume ovulation and improve their chances of pregnancy. Among women with obesity who have PCOS, losing 5% of body weight can improve the likelihood of ovulation and pregnancy.
• Metformin: This insulin-sensitizing medicine may help improve menstrual cycles and stimulate ovulation in women with PCOS.

Surgery may be used to treat certain causes of infertility, including:

• Repairing the fallopian tubes or removing blockages, though these increase the risk of ectopic pregnancy, a pregnancy that occurs outside of the uterus (most often in a fallopian tube)
• Surgery to treat endometriosis by removing patches of uterine-like tissue growing outside of the uterus
• Removing uterine fibroids, polyps, or scarring, which may improve fertility when such abnormalities interfere with implantation or normal uterine function
• Ovarian drilling, a surgical treatment that may help stimulate ovulation in women with PCOS

Treatments for Men

Medicine can treat some issues that affect male fertility, including hormone imbalances and erectile dysfunction. Surgery can repair blockages in the tubes that transport sperm and can also correct varicoceles. Current research suggests that surgical repair of varicocele may improve sperm health, although it has not been shown to increase the chances of conception. If surgery does not restore fertility, assisted reproductive technology (ART) may be an effective option.

Assisted Reproductive Technology (ART) 

Assisted Reproductive Technology (ART) refers to treatments and procedures used to help achieve pregnancy. These complex treatments may be an option for people who have tried other infertility treatment options but have not achieved pregnancy.

Although there are currently no medicines or surgical treatments that increase fertility in women with primary ovarian insufficiency (POI), they may still be able to become pregnant through ART with the use of donor eggs.

Intrauterine insemination (IUI) involves placing a man’s sperm directly into a woman’s uterus using a long, narrow tube. IUI may be most effective for treating infertility involving:

• Women who have scarring or defects of the cervix
• Men who have low sperm counts
• Men who have sperm with reduced mobility
• Men who cannot get erections
• Men with retrograde ejaculation
• Couples who have difficulty having intercourse

When insemination is performed monthly with fresh or frozen sperm, success rates may be as high as 20% per cycle.

In vitro fertilization (IVF) involves combining eggs and sperm in a laboratory to create an embryo, followed by placing the embryo into the woman’s uterus. The steps of IVF include:

1. Superovulation: The woman takes injectable medicine for 8 to 14 days to stimulate the ovaries to make multiple mature eggs at one time. An injection of human chorionic gonadotropin (hCG) triggers ovulation, and the eggs are retrieved 34 to 36 hours later.
2. Egg retrieval: This is an outpatient procedure that normally takes about 30 minutes. A mild sedative and pain medicine are often used.
3. Fertilization: Sperm are placed in a dish with the egg and left overnight in an incubator. If fertilization does not occur on its own, a single sperm may be injected directly into an egg using a needle in a process called intracytoplasmic sperm injection (ICSI). About 60% of IVF procedures in the United States use ICSI.
4. Embryo transfer: A healthcare provider inserts a long, thin tube through the vagina and into the uterus to place the embryo in the uterus. Implantation should occur in the uterine lining about 6 to 10 days after egg retrieval.

Third party-assisted assisted reproductive technology (ART) options include:

• Sperm donation: This may be used when a man does not produce sperm, produces very low numbers of sperm, or has a genetic disease. Donated sperm can be used with IUI or IVF.
• Egg donation: This may be an option when a woman does not produce healthy eggs that can be fertilized. Egg donation may be particularly helpful for women with primary ovarian insufficiency, who have received chemotherapy or radiation therapy. It can also be helpful for women who have had their ovaries surgically removed, were born without ovaries, are carriers of known genetic diseases, are infertile because of poor egg quality, or are menopausal.
• Surrogates and gestational carriers: A surrogate is a woman who is inseminated with sperm from the male partner. A gestational carrier is implanted with an embryo that is not biologically related to her.
• Embryo donation (embryo adoption): This allows the recipient mother to experience pregnancy and give birth. According to the CDC, about 50% of transfers using donated frozen embryos result in pregnancy and about 40% result in a live birth.

Find Clinical Trials

Clinical trials uncover better ways to prevent, diagnose, treat, and understand diseases and conditions. To ensure results apply to everyone, volunteers of all ages, sexes, and backgrounds, including both healthy individuals and those with specific medical conditions, are needed. Find clinical trials on infertility.

Research Information

The National Institutes of Health (NIH) is the largest public funder of biomedical research in the world. NIH invests most of its budget in medical research seeking to enhance life and to reduce illness and disability. NIH-funded research has led to breakthroughs and new treatments helping people live longer, healthier lives, and building the research foundation that drives discovery.

NIH conducts and supports research on the causes, characteristics, and impacts of male and female fertility and infertility and on therapies for improving fertility. NIH-funded research also examines typical reproduction, which helps improve basic understanding of factors that can contribute to infertility and can later lead to more effective strategies for diagnosis, management, and prevention of conditions that contribute to infertility.

NIH research programs on fertility and infertility include research on:

• Fertility preservation
• Male reproductive health
• Ovarian function and dysfunction
• Preimplantation genetics and development
• Embryonic gonad and reproductive cell development
• Uterine function and implantation biology
• Diseases and disorders that cause infertility
• Development of novel infertility technologies and improvement of existing technologies

In addition, NIH supports the National Centers for Translational Research in Reproduction and Infertility (NCTRI), a collection of multidisciplinary research centers with a strong focus on translational and clinical solutions that improve reproductive outcomes and/or reduce the cost of infertility care for women and men.

Find NIH-funded research projects using NIH RePORTER, a searchable database of current and past research projects supported by NIH and other federal agencies.