Infertility is the failure of a couple
to become pregnant after one year of regular, unprotected
intercourse. In both men and women the fertility process is complex.
About 10% of couples who wish to have a baby are still unable to
after a year of unprotected sex. About half of these couples can
achieve pregnancy within 2 years after appropriate treatment of the
woman, the man, or both. Even under ideal circumstances, the
probability that a woman will get pregnant during a single menstrual
cycle is only about 30%. And, when conception does occur, only 50 -
60% of pregnancies advance beyond the 20th week. (The inability of a
woman to produce a live birth because of abnormalities that cause
miscarriages is called infecundity and is not discussed in detail in
Males and females each account for 40% of
infertility. In the remaining 20%, either both partners are
responsible or the cause is unclear. Although this report
specifically addresses infertility in women, it is equally important
for the male partner to be tested at the same time.
Causes of Female Infertility
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 - 30% of cases
of infertility have more than one cause. Male or female infertility
each account for about 30 - 40% of cases. In men, sperm defects
(their quality and quantity) are usually responsible. Female
infertility is more complex.
Pelvic inflammatory disease (PID) is the major cause
of female 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
Causes of PID.
PID may result from many different conditions that cause infections.
Among them are:
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.
Pelvic tuberculosis (a growing
global problem as tuberculosis cases increase)
Herpesvirus (suggested for some cases, but not
confirmed as a cause)
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.
Endometriosis may account for as many
as 30% of infertility cases. Some evidence suggests that between 30
- 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.
Endometriosis rarely causes an absolute inability to conceive, but,
nevertheless, it can contribute to it both directly and indirectly.
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 cause infertility in several 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
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
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.
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.)
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.
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) levels are
elevated, as they are during per menopause. Premature ovarian
failure is a significant cause of infertility, and women who have
this condition have only a 5 - 10% chance to conceive without
Causes of Premature Ovarian Failure.
There are numerous causes of POF. Often the cause of this disorder
or other causes of POF is unknown. In some cases, POF may represent
an acceleration of the aging process.
The following conditions may produce POF:
Adrenal, pituitary, or thyroid
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.
Cancer treatments (radiation,
chemotherapy, or both). Women who are undergoing cancer
treatments and who want to become pregnant should see a
reproductive specialist to discuss their options. According to
the American Society of Clinical Oncology’s 2006 guidelines, the
fertility preservation method with the best chance of success is
embryo cryopreservation. This procedure involves harvesting a
woman’s eggs (oocytes), followed by in vitro fertilization and
freezing of embryos for later use. Other treatments under
investigation include egg preservation, collecting and freezing
unfertilized eggs, removing and freezing a part of the ovary for
later reimplantation, and using hormone therapy to protect the
ovaries during chemotherapy. Women may be able to access these
investigational approaches through enrolling in clinical trials.
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 of POF include
sarcoidosis, mumps, some sexually transmitted diseases, and
tuberculosis. Women with epilepsy are at higher risk for POF.
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
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.
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 - 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 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 - 2.4% of women who are having
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
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
Secretions from the breast not related to pregnancy
or nursing (called galactorrhea ) is a telltale symptom of high
prolactin levels and should be investigated.
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
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
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.
Medications. Among the medications
that can cause temporary infertility are those used to treat chronic
disorders, as well as antidepressants, hormones, pain killers, and
Inflammatory Bowel Disease. Inflammatory bowel
disease (particularly Crohn's disease or surgery for ulcerative
colitis) can affect fertility.
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.
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.
Metabolic Syndrome (also Called Syndrome X). Doctors
diagnose this condition when at least three of the the following
abnormalities are present:
Metabolic syndrome is a pre-diabetic condition that is significantly
associated with heart disease. A 2002 study 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.
In the U.S., an estimated 10.2% of women between the
ages of 15 - 44, or about 6.1 million women, have impaired
fertility, and the incidence is increasing. About 25% of women
experience some period of infertility during their reproductive
As a woman ages, her chances for fertility decline.
Infertility in older women appears to be mostly due to a higher risk
for chromosomal abnormalities that occur in her eggs as they age.
Older women are also more likely to have health problems that may
interfere with fertility. If fertilization occurs, older, healthy
women can usually successfully bear a fetus to term, although they
have a higher risk for miscarriage. Using population studies,
experts have come up with estimated odds for pregnancy at different
ages, given no fertility intervention. A 2002 analysis of pregnancy
rates based on conception on the day of ovulation suggested that
women between ages 19 - 26 have twice the pregnancy rates as those
between 35 - 39.
Chances for Pregnancy by Age
|Up until age 34
|By age 40
||Declining to 67%
|By age 45
||Declining to 15%
Weight Factors and Excessive Exercise
Although most of a woman's estrogen is manufactured
in her ovaries, 30% is produced in fat cells by a process that
transforms circulating adrenal male hormones into estrogen. Because
a normal hormonal balance is essential for the process of
conception, it is not surprising that extreme weight levels, either
high or low, can contribute to infertility.
Being Overweight. Being overweight or obese (fat levels that are 10
- 15% above normal) can contribute to infertility in various ways.
Obesity is highly associated with polycystic ovarian syndrome (PCOS),
which is the cause of infertility in some cases. In one 2003 study,
overweight women without PCOS were classified in one of five grades,
depending on the severity of the obesity. The risk for irregular or
absent periods increased two-fold by each increase in grade. In this
group, amenorrhea (absent periods) was also highly associated with
type 2 diabetes and blood sugar abnormalities.
Being Underweight. Body fat levels 10 - 15% below
normal can completely shut down the reproductive process. Women at
Women with eating disorders, such as anorexia or bulimia.
Women on very low-calorie or
restrictive diets are at risk, especially if their periods are
Strict vegetarians might have difficulties if they lack important
nutrients, such as vitamin B12, zinc, iron, and folic acid.
Marathon runners, dancers, and others who exercise
very intensely. (Lower body fat contributes to menstrual
irregularities in competitive athletes, but other mechanisms are
Exposure to environmental hazards (herbicides, pesticides,
industrial solvents) may affect fertility. Estrogen-like
hormone-disrupting chemicals are of particular concern for
infertility in men and for effects on offspring of women.
Phthalates, chemicals used to soften plastics, are
under particular scrutiny for their ability to disrupt hormones.
Specific phthalates of special concern include dibutyl phthalate (DBP)
and others found in many products, including cosmetics and clay
products sold to children (Fimo, Sculpey). Animals exposed to
phthalates have significantly impaired sperm count and abnormalities
in reproductive structures, such as the testes. In addition, there
is some concern that exposure in pregnant women may affect the
Stress and Fertility
Neurotransmitters (chemical messengers) act in the
hypothalamus gland, which controls both reproductive and stress
hormones. Severely elevated levels of stress hormone can, in fact,
shut down menstruation. Whether stress has any significant effect on
fertility or fertility treatments is unclear. One 2005 study found
that psychological stress does not affect the success or failure of
in vitro fertilization.
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