Causes
Causes of infertility can be found in about 90% of infertility cases, but despite extensive tests, about 10% of couples will never know why they cannot conceive. Between 10% and 30% of cases of infertility have more than one cause. Male or female infertility each account for about 30% to 40% of cases. In men, sperm defects (their quality and quantity) are usually responsible. Female infertility is more complex.
Pelvic Inflammatory Disease
Pelvic inflammatory disease (PID) is the major cause of infertility worldwide. PID comprises a variety of infections caused by different bacteria that affect the reproductive organs, appendix, and parts of the intestine that lie in the pelvic area. The sites of infection most often implicated in infertility are in the fallopian tubes, a specific condition referred to as salpingitis.
Causes of PID. PID may result from many different conditions that cause infections. Among them are the following:
- Sexually transmitted diseases (cause of most PIDs). Chlamydia trachomatis is an infectious organism that causes 75% of infertility in the fallopian tubes. Gonorrhea is responsible for most of the remaining cases. Of concern is a 2002 report that suggests these disease may be widely under-diagnosed and undertreated.
- Pelvic tuberculosis (a growing global problem as tuberculosis cases increase).
- Nonsterile abortions.
- Ruptured appendix.
- Herpesvirus (suggested for some cases, but not confirmed as a causal agent).
Symptoms of PID. The infection may be subclinical (occurring without any symptoms), or there may be fever, chills, or pelvic pain indicating inflammation of the entire pelvic area.
Effects of PID. Severe or frequent attacks of PID can eventually cause scarring, abscess formation, and tubal damage that result in infertility. About 20% of women who develop symptomatic PID become infertile. PID also significantly increases the risk of ectopic pregnancy (fertilization in the fallopian tubes). The severity of the infection, not the number of the infections, appears to pose the greater risk for infertility. (A small US study suggests, however, that even mild Chlamydia infection that occurs in the upper genital tract may cause a higher proportion of ectopic pregnancies than previously thought.)
Endometriosis
The medical literature indicates that endometriosis may account for as many as 30% of infertility cases. Some evidence suggests that between 30% and 50% of women with endometriosis are infertile. Often, however, it is difficult to determine if endometriosis is the primary cause of infertility, particularly in women who have mild endometriosis. In an attempt to determine the chances for infertility with endometriosis, researchers have come up with a staging system based on findings during diagnostic surgery.
It should be noted that endometriosis rarely causes an absolute inability to conceive, but, nevertheless, it can contribute to it both directly and indirectly.
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| Endometriosis is the condition in which the tissue that normally lines the uterus (endometrium) grows on other areas of the body causing pain and irregular bleeding. |
Direct Effect of Endometrial Cysts. Endometrial cysts may directly prevent infertility in a number of ways.
- If implants occur in the fallopian tubes, they may block the egg's passage.
- Implants that occur in the ovaries prevent the release of the egg.
- Severe endometriosis can eventually form rigid webs of scar tissue (adhesions) between the uterus, ovaries, and fallopian tubes, thereby preventing the transfer of the egg to the tube.
Immune Factors and the Inflammatory Response. Researchers are focusing on defects in the immune system that not only may be responsible for endometriosis in the first place but may also cause the infertility associated with endometriosis. Even in early stage endometriosis, investigators have observed increased immune system activity.
Other Conditions Linking Endometriosis and Infertility. Researchers have sometimes noted unusually low levels of specific substances that enable a fertilized egg to adhere to the uterine lining. (Such abnormalities are more often a factor in infertility in women with mild to moderate endometriosis than in those with severe cases.)
One study found that the eggs in women with endometriosis appeared to have more genetic abnormalities than those in women without the disorder.
[For more information, see Well-Connected Report #74, Endometriosis.]
Polycystic Ovarian Syndrome
Polycystic ovarian syndrome (PCOS) is a condition in which the ovaries produce high amounts of androgens (male hormones), particularly testosterone. PCOS occurs in about 6% of women, and amenorrhea or oligomenorrhea (infrequent menses) is quite common. According to a 2002 study, nearly 30% of obese women with PCOS had amenorrhea. (The rate was lower--4.7%--in women with normal weight.)
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Click the icon to see an image of polycystic ovarian syndrome. |
In PCOS, increased androgen production produces high LH levels and low FSH levels, so that follicles are prevented from producing a mature egg. Without egg production, the follicles swell with fluid and form into cysts. Every time an egg is trapped within the follicle, another cyst forms, so the ovary swells, sometimes reaching the size of a grapefruit. Without ovulation, progesterone is no longer produced, whereas estrogen levels remain normal.
The elevated levels of androgens (hyperandrogenism) can cause obesity, facial hair, and acne, although not all women with PCOS have such symptoms. Other male characteristics, such as deepening voice and clitoral enlargement, are rare.
PCOS also poses a high risk for insulin resistance, particularly in women who are also obese. Insulin resistance is associated with diabetes type 2, in which insulin levels are normal or high but the body cannot use this hormone efficiently. About half of PCOS patients, in fact, also have diabetes.
The drug valproate used to treat seizures and bipolar disease has been associated with PCOS. In most cases, the cause of PCOS is unknown.
Premature Ovarian Failure (Early Menopause)
Premature ovarian failure (POF) is the early depletion of follicles before age 40, which, in most cases, leads to premature menopause. It affects about 1% of women and is typically preceded by irregular periods, which might continue for years. In this condition follicle-stimulating hormone (FSH) are elevated, as they are during perimenopause. Premature ovarian failure is a significant cause of infertility and women who have this condition have only a 5% to 10% chance to conceive without fertility treatments.
Causes of Premature Ovarian Failure. There are a number of causes of POF. Often the cause of this disorder or other causes of POF is unknown. In some cases may represent an acceleration of the aging process.
The following may conditions may produce POF:
- Adrenal, pituitary, or thyroid gland deficiencies.
- Genetic factors related to the X chromosome. A woman needs two functioning X chromosomes for normal reproduction. When one is abnormal, ovarian function fails. The most severe example is Turner's syndrome, a genetic condition, in which one of the two X-chromosomes is missing or malfunctioning. Milder cases of ovarian failure can occur in fragile X syndrome and other rare inherited conditions that cause partial X-chromosome abnormalities.
- Other genetic factors. Some cases of POF and amenorrhea may be due to other genetic abnormalities. For example, researchers have reported POF in women with genetic defects in the production of growth factors called inhibins, which are produced by the ovaries. As yet, however, investigators have not identified specific genetic factors that might explain many cases of POF.
- Cancer treatments (radiation, chemotherapy, or both). Women who are undergoing such treatments and who want to become pregnant should ask about assisted reproductive technologies, possibly freezing embryos before their cancer treatments, which gives them the best odds. Ovarian transplantation procedures are under investigation. Investigators are testing a hormone called a gonadotropin-releasing hormone analogue that puts women in a temporary pre-pubescent state during chemotherapy and which may preserve fertility in many women.
- Autoimmunity. Autoimmune diseases, including diabetes type 1, systemic lupus erythematosus, autoimmune hypothyroidism, and autoimmune Addison's disease, are associated with a higher risk for early menopause. Autoimmunity, however, may also play a role in some cases of POF without the presence of specific autoimmune diseases. In such cases, antibodies specifically attack the cells that secrete reproductive hormones thus causing ovarian failure.
Other causes: sarcoidoisis, mumps, some sexually transmitted diseases, and tuberculosis. Women with epilepsy are at higher risk for POF.
Idiopathic Hypogonadotropic Hypogonadism
Idiopathic hypogonadotropic hypogonadism is a rare condition in which follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are underproduced and prevent the development of functional ovaries. There are no other abnormalities in the hypothalamus-pituitary axis (such as tumors or abnormal stress hormones or prolactin). In most cases, the causes of hypergonadotropic hypogonadism are unknown. Genetic factors, including Kallman's syndrome, have been identified in about 20% of these cases.
Functional Hypothalamic Amenorrhea (FHA) and Eating Disorders
Functional hypothalamic amenorrhea (FHA) is the absence of menstruation due to disturbances in the thyroid gland and hypothalamus-pituitary-adrenal (HPA) system, which regulates reproduction and other important functions. The eating disorders anorexia and bulimia are most often associated with FHA. FHA may be due to other different factors, most unknown.
Luteal Phase Defect (Implantation Failure)
Luteal phase defect is a general term referring to problems in the corpus luteum that result in inadequate production of progesterone. Because progesterone is necessary for thickening and preparing the uterine lining, the ovum fails to successfully implant in the endometrium. Between 25% and 60% of women who experience recurrent miscarriages may have a luteal phase defect. A luteal phase defect, however, can also occur in fertile women, so other factors may be responsible for implantation failure.
Benign Uterine Fibroids
Benign fibroid tumors in the uterus are extremely common in women in their 30s. The effect of fibroids on fertility is controversial. A 2002 analysis suggested that they may account for infertility in only 1% to 2.4% of women who are having trouble conceiving.
Large fibroids may cause infertility impairing the uterine lining, by blocking the fallopian tube, or by distorting the shape of the uterine cavity or altering the position of the cervix.
Some evidence suggests that even small fibroids may reduce the chances of pregnancy in women who are undergoing assisted reproductive techniques. Treatments to reduce fibroids may be helpful in such women, although there has been little research on this subject. [For more information, see Well-Connected Report # 73, Fibroids: Uterine.]
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Click the icon to see an image of uterine fibroids. |
Elevated Prolactin Levels (Hyperprolactinemia)
Prolactin is a hormone produced in the pituitary gland that stimulates breast development and milk production in association with pregnancy. High levels of prolactin (hyperprolactinemia) reduce gonadotropin hormones and inhibit ovulation. Hyperprolactinemia in women who are not pregnant or nursing can be caused by hypothyroidism or pituitary adenomas. (These are benign tumors that secrete prolactin. They can cause headache and visual problems as well as breast secretions.) Some drugs, including oral contraceptives and some antipsychotic drugs, can also elevate levels of prolactin.
Secretions from the breast not related to pregnancy or nursing (called galactorrhea) is a telltale symptom of high prolactin levels and should be investigated.
Structural Problems Causing Obstruction
Inborn Abnormalities. Inborn genital tract abnormalities may cause infertility. Mullerian agenesis is a specific malformation in which no vagina or uterus develops. Even in these cases, some women can become mothers by undergoing in vitro fertilization and having the fertilized egg implanted in another woman who is willing and able to carry the pregnancy (a surrogate mother).
Uterine or Abdominal Scarring. Bands of scar tissue that bind together after abdominal or pelvic surgery or infection (called adhesions) can restrict the movement of ovaries and fallopian tubes and may cause infertility. Asherman's syndrome, for example, is scarring in the uterus that can cause obstructions and secondary amenorrhea. It may be caused by surgery, repeated injury, or unknown factors. Laparoscopic surgery is less likely to cause adhesions than standard open surgery.
In some of these cases surgery, may be helpful. One technique called pressure lavage under ultrasound guidance (PLUG) may prove to be useful for treating some cases of mild scarring in the uterus (intrauterine adhesions). This technique is based on transvaginal sonohysterography, which uses ultrasound along with saline infused into the uterus to enhance visualization. Continuous accumulation of saline in the procedure is used to break up the scars.
Other Causes of Infertility
Ectopic Pregnancies. Ectopic pregnancies increase the risk for infertility, although subsequent pregnancy rates are quite variable. Ectopic pregnancies that terminate without treatment appear to pose a lower risk for future infertility. Even a ruptured tube does not appear to reduce the chance for a future pregnancy in most women. Such an event however can be dangerous and even life threatening for the woman. Laparoscopic surgery to remove a fallopian tube affected by an ectopic pregnancy may preserve fertility better than traditional abdominal surgery.
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Click the icon to see an image of an ectopic pregnancy. |
Cancer Treatments. Cancer treatments (radiation or chemotherapy) can result in infertility. Women who are undergoing such treatments and who want to become pregnant should ask about assisted reproductive technologies and freezing embryos before their cancer treatments. This gives them the best chances for future child bearing.
Medications. Among the medications that can cause temporary infertility are those used to treat chronic disorders, as well as antidepressants, hormones, pain killers, and antipsychotic drugs.
Inflammatory Bowel Disease. Inflammatory bowel disease (particularly Crohn's disease or surgery for ulcerative colitis) can affect fertility.
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Click the icon to see an image of Crohn's disease. |
Celiac Sprue. Celiac sprue is a disease in which the patient cannot tolerate gluten, a common food chemical. The disorder is also highly associated with infertility in men and women, possibly through multiple effects on nutrition, immune factors, and hormones. The mechanisms are not altogether clear, but infertility is usually reversible with strict dietary control.
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Click the icon to see an image of celiac sprue. |
Epilepsy. In one study of women with epilepsy, fertility rates were 33% lower than among women in the general population, perhaps due to certain antiepileptic drugs that increase the risk for birth defects. The social effects of epilepsy may also lead to marriage at an older age, which can be associated with delayed attempts to get pregnant and thereby affect fertility.
Thyroid Problems. Thyroid problems, either too much thyroid hormone (hyperthyroidism) or too little (hypothyroidism) can interrupt cycles.
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Click the icon to see an image of hyperthyroidism. |
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Click the icon to see an image of hypothyroidism. |
Metabolic Syndrome (also Called Syndrome X). Doctors diagnose this condition when at least three of the there abnormalities are present: abdominal obesity, low HDL (good) cholesterol levels, high triglyceride levels, high blood pressure, and insulin resistance. Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease. A 2002 study also reported that, as with PCOS, women with metabolic syndrome have higher levels of male hormones and are therefore at risk for infertility. A 2002 study estimated that 24% of the population now has this condition.
Other Medical Conditions. Medical conditions associated with delayed puberty and amenorrhea (absence of periods) include Cushing's disease, sickle cell disease, HIV, kidney disease, and diabetes. Genetic mutations that affect luteinizing hormone may also be responsible for some cases of light or absent menstruation. Other rare genetic disorders, such as Kallman syndrome, cause abnormalities in the hypothalamus of the brain.
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