What is female infertility?

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The inability to achieve a desired pregnancy as a result of dysfunction of female reproductive organs.
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Causes and Symptoms

Infertility is defined as the failure of a woman to conceive despite regular sexual activity over the course of at least one year. Studies have estimated that in the United States, 10 to 15 percent of couples are infertile. In about half of these couples, it is the woman who is affected.

Female infertility may be caused by hormonal problems, or it may originate in the reproductive organs: the ovaries, oviducts, uterus, cervix, and vagina. The frequency of specific problems among infertile women is as follows: ovarian problems, 20 percent to 30 percent; damage to the Fallopian tubes, 30 percent to 50 percent; uterine problems, 5 percent to 10 percent; and cervical or vaginal abnormalities, 5 percent to 10 percent. Another 10 percent of women have unexplained infertility. Behavioral factors, such as diet and exercise and the use of tobacco, alcohol, or drugs, also play a role in infertility.

The ovaries have two important roles in conception: the production of ova (egg cells), culminating in ovulation, and the production of hormones. Ovulation usually occurs halfway through a woman’s four-week menstrual cycle. In the two weeks preceding ovulation, follicle-stimulating hormone (FSH) from the pituitary gland causes follicles in the ovaries to grow and the ova within them to mature. As the follicles grow, they produce increasing amounts of estrogen. Near the middle of the cycle, the estrogen causes the pituitary gland to release a surge of luteinizing hormone (LH), which causes ovulation of the largest follicle in the ovary.

Anovulation (lack of ovulation) can result either directly, from an inability to produce LH, FSH, or estrogen, or indirectly, because of the presence of other hormones that interfere with the signaling systems between the pituitary and ovaries. For example, the woman may have an excess production of androgen (testosterone-like) hormones, either in her ovaries or in her adrenal glands, or her pituitary may produce too much prolactin, a hormone that is normally secreted in large amounts only after the birth of a child.

Besides ovulation, the ovaries have another critical role in conception, since they produce hormones that act on the uterus to allow it to support an embryo. In the first two weeks of the menstrual cycle, the uterine lining is prepared for a possible pregnancy by estrogen from the ovaries. Following ovulation, the uterus is maintained in a state that can support an embryo by progesterone, which is produced in the ovary by the follicle that just ovulated, now called a corpus luteum. Because of the effects of hormones from the corpus luteum on the uterus, the corpus luteum is essential to the survival of the embryo. If conception does not occur, the corpus luteum disintegrates and stops producing progesterone. As progesterone levels decline, the uterine lining can no longer be maintained and is shed as the menstrual flow.

Failure of the pregnancy can result from improper function of the corpus luteum, such as an inability to produce enough progesterone to sustain the uterine lining. The corpus luteum may also produce progesterone initially but then disintegrate too early. These problems in corpus luteum function, referred to as luteal phase insufficiency, may be caused by the same types of hormonal abnormalities that cause lack of ovulation.

Some cases of infertility may be associated with an abnormally shaped uterus or vagina. Such malformations of the reproductive organs are common in women whose mothers took diethylstilbestrol (DES) during pregnancy. DES was prescribed to many pregnant women from 1941 to about 1970 as a protection against miscarriage; infertility and other problems have occurred in the offspring of these women.

Conception depends on normal function of the oviducts (or Fallopian tubes), thin tubes with an inner diameter of only a few millimeters; they are attached to the top of the uterus and curve upward toward the ovaries. The inner end of each tube, located near one of the ovaries, waves back and forth at the time of ovulation, drawing the mature ovum into the opening of the oviduct. Once in the oviduct, the ovum is propelled along by movements of the oviduct wall. Meanwhile, if intercourse has occurred recently, the man’s sperm will be moving upward in the female system, swimming through the uterus and the oviducts. Fertilization, the union of the sperm and ovum, will occur in the oviduct, and then the fertilized ovum will pass down the oviduct and reach the uterus about three days after ovulation.

Infertility can result from scar tissue formation inside the oviduct, resulting in physical blockage and inability to transport the ovum, sperm, or both. The most common cause of scar tissue formation in the reproductive organs is pelvic inflammatory disease (PID), a condition characterized by inflammation that spreads throughout the female reproductive tract. PID may be initiated by a sexually transmitted disease such as gonorrhea or chlamydia. Physicians in the United States have documented an increase in infertility attributable to tubal damage caused by sexually transmitted diseases.

Damage to the outside of the oviduct can also cause infertility, because such damage can interfere with the mobility of the oviduct, which is necessary to the capture of the ovum at the time of ovulation. External damage to the oviduct may occur as an aftermath of abdominal surgery, when adhesions induced by surgical cutting are likely to form. An adhesion is an abnormal scar tissue connection between adjacent structures.

Another possible cause of damage to the oviduct that can result in infertility is the presence of endometriosis. Endometriosis refers to a condition in which patches of the uterine lining implant outside the uterus, in or on the surface of other organs. These patches are thought to arise during menstruation, when the uterine lining (endometrium) is normally shed from the body through the cervix and vagina; in a woman with endometriosis, for unknown reasons, the endometrium is carried to the interior of the pelvic cavity by passing up the oviducts. The endometrial patches can lodge in the oviduct itself, causing blockage, or can adhere to the outer surface of the oviducts, interfering with mobility.

Endometriosis can cause infertility by interfering with organs other than the oviducts. Endometrial patches on the outside of the uterus can cause distortions in the shape or placement of the uterus, interfering with embryonic implantation. Ovulation may be prevented by the presence of the endometrial tissues on the surface of the ovary. The presence of endometriosis, however, is not always associated with infertility: Thirty percent to forty percent of women with endometriosis cannot conceive, but the remainder appear to be fertile.

Another critical site in conception is the cervix. The cervix, the entryway to the uterus from the vagina, represents the first barrier through which sperm must pass on their way to the ovum. The cervix consists of a ring of strong, elastic tissue with a narrow canal. Glands in the cervix produce the mucus that fills the cervical canal and through which sperm swim en route to the ovum. The amount and quality of the cervical mucus change throughout the menstrual cycle, under the influence of hormones from the ovary. At ovulation, the mucus is in a state that is most easily penetrated by sperm; after ovulation, the mucus becomes almost impenetrable.

Cervical problems that can lead to infertility include production of a mucus that does not allow sperm passage at the time of ovulation (hostile mucus syndrome) and interference with sperm transport caused by narrowing of the cervical canal. Such narrowing may be the result of a developmental abnormality or the presence of an infection, possibly a sexually transmitted disease.

Treatment and Therapy

The diagnosis of the exact cause of a woman’s infertility is crucial to successful treatment. A complete medical history should reveal any obvious problems of previous infection or menstrual cycle irregularity. Adequacy of ovulation and luteal phase function can be determined from records of menstrual cycle length and changes in body temperature (body temperature is higher after ovulation). Hormone levels can be measured with tests of blood or urine samples. If damage to the oviducts or uterus is suspected, a hysterosalpingography will be performed. In this procedure, the injection of a special fluid into the uterus is followed by x-ray analysis of the fluid movement to reveal the shape of the uterine cavity and the oviducts. Cervical functioning can be assessed with the postcoital test, in which the physician attempts to recover sperm from the woman’s uterus some hours after she has had intercourse with her partner. If a uterine problem is suspected, the woman may have an endometrial biopsy, in which a small sample of the uterine lining is removed and examined for abnormalities. Sometimes, exploratory surgery is performed to pinpoint the location of scar tissue or the location of endometrial patches.

Surgery may be used for treatment as well as diagnosis. Damage to the oviducts can sometimes be repaired surgically, and surgical removal of endometrial patches is a standard treatment for endometriosis. Often, however, surgery is a last resort because of the likelihood of the development of postsurgical adhesions, which can further complicate the infertility. Newer forms of surgery using lasers and freezing offer better success because of a reduced risk of adhesions.

Some women with hormonal difficulties can be treated successfully with so-called fertility drugs, which are intended to stimulate ovulation. There are several different drugs and hormones that fall under this heading: Clomiphene citrate (Clomid), human menopausal gonadotropin (hMG), gonadotropin-releasing hormone (GnRH), and bromocriptine mesylate (Parlodel) are among the medications commonly used, with the exact choice depending on the woman’s particular problem. One problem with some of the drugs is the risk of multiple pregnancy (more than one fetus in the uterus). Other possible problems include nausea, dizziness, headache, and general malaise.

Aside from fertility drugs, there are a variety of methods in use to try to achieve pregnancy with external assistance, known collectively as assisted reproductive technology (ART). One example of this, artificial insemination , also known as intrauterine insemination (IUI), is an old technique that is still useful in various types of infertility. A previously collected sperm sample is placed in the woman’s vagina or uterus using a special tube. Artificial insemination is always performed at the time of ovulation, in order to maximize the chance of conception. The ovulation date can be determined with body temperature records or by hormone measurements. In some cases, this procedure is combined with fertility drug treatment. Since the sperm can be placed directly in the uterus, it is useful in treating hostile mucus syndrome and certain types of male infertility. The sperm sample can be provided either by the woman’s partner or by a donor. The pregnancy rate after artificial insemination is highly variable (anywhere from 10 to 70 percent), depending on the particular infertility problem in the couple.

Another assisted reproductive technology is Gamete intrafallopian transfer (GIFT), the surgical placement of ova and sperm directly into the woman’s oviducts. To be a candidate for this procedure, the woman must have at least one partially undamaged oviduct and a functional uterus. Ova are collected surgically from the ovaries after stimulation with a fertility drug, and a semen sample is collected from the male. The ova and the sperm are introduced into the oviducts through the same abdominal incision used to collect the ova. This procedure is useful in certain types of male infertility, if the woman produces an impenetrable cervical mucus, or if the ovarian ends of the oviducts are damaged. The range of infertility problems that may be resolved with GIFT can be extended by using donated ova or sperm. The pregnancy rate is about 33 percent overall, but the rate varies with the type of infertility present.

The most common assisted reproductive technology is in vitro fertilization (IVF), or the fertilization of the sperm and egg outside the woman's body, followed by implantation of the fertilized egg in the woman's uterus. In this procedure, ova are collected surgically after stimulation with fertility drugs and then placed in a laboratory dish and combined with sperm from the man. The actual fertilization, when a sperm penetrates the ovum, will occur in the dish. The resulting embryo is allowed to remain in the dish for two days, during which time it will have grown to two to four cells. Then, the embryo is placed in the woman’s uterine cavity using a flexible tube. In vitro fertilization can be used in women who are infertile because of endometriosis, damaged oviducts, impenetrable cervical mucus, or ovarian failure. As with GIFT, in vitro fertilization may utilize donated ova or donated sperm, or extra embryos that have been produced by one couple may be implanted in a second woman. Embryos created through IVF can either be used immediately or frozen for later implantation. Success rates for in vitro fertilization have improved greatly over time, and in the United States in 2010, the proportion of IVF procedures that resulted in live births was about 56 percent for fresh embryos and 35 percent for frozen embryos, according to the Centers for Disease Control and Prevention.

Some women may benefit from nonsurgical embryo transfer. In this procedure, a fertile woman is artificially inseminated at the time of her ovulation; five days later, her uterus is flushed with a sterile solution, washing out the resulting embryo before it implants in the uterus. The retrieved embryo is then transferred to the uterus of another woman, who will carry it to term. Typically, the sperm provider and the woman who receives the embryo are the infertile couple who wish to rear the child, but the technique can be used in other circumstances as well. Embryo transfer can be used if the woman has damaged oviducts or is unable to ovulate, or if she has a genetic disease that could be passed to her offspring, because in this case the baby is not genetically related to the woman who carries it.

Some infertile women who are unable to achieve a pregnancy themselves turn to the use of a surrogate, a woman who will agree to bear a child and then turn it over to the infertile woman to rear as her own. In the typical situation, the surrogate is artificially inseminated with the sperm of the infertile woman’s husband. The surrogate then proceeds with pregnancy and delivery as normal, but relinquishes the child to the infertile couple after its birth.

Perspective and Prospects

One of the biggest problems that infertile couples face is the emotional upheaval that comes with the diagnosis of infertility, as bearing and rearing children is an experience that most people treasure. In addition to the emotional difficulty that may come with the recognition of infertility, more stress may be in store as the couple proceeds through treatment. The various treatments can cause embarrassment and sometimes physical pain, and fertility drugs themselves are known to cause emotional swings. For these reasons, a couple with an infertility problem is often advised to seek help from a private counselor or a support group.

Along with the emotional and physical challenges of infertility treatment, there is a considerable financial burden. Infertility treatments, in general, are expensive, especially for more sophisticated procedures such as in vitro fertilization and GIFT. Since the chances of a single procedure resulting in a pregnancy are often low, the couple may be faced with submitting to multiple procedures repeated many times. The cost over several years of treatment—a realistic possibility—can be very high. Many health insurance companies in the United States refuse to cover the costs of such treatment and are required to do so in only a few states.

Some of the treatments are accompanied by unresolved legal questions. In the case of nonsurgical embryo transfer, is the legal mother of the child the ovum donor or the woman who gives birth to the child? The same question of legal parentage arises in cases of surrogacy. Does a child born using donated ovum or sperm have a legal right to any information about the donor, such as medical history? How extensive should governmental regulation of infertility clinics be? For example, should there be standards for ensuring that donated sperm or ova are free from genetic defects? In the United States, some states have begun to address these issues, but no uniform policies have been set at the federal level.

The legal questions are largely unresolved because American society is still involved in religious and philosophical debates over the propriety of various infertility treatments. Some religions hold that any interference in conception is unacceptable. To these denominations, even artificial insemination is wrong. Other groups approve of treatments confined to a husband and wife, but disapprove of a third party being involved as a donor or surrogate. Many people disapprove of any infertility treatment to help an individual who is not married. Almost all these issues stem from the fact that these reproductive technologies challenge the traditional definitions of parenthood.

Bibliography

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