Infertility and women

Definition
Infertility is defined as the inability to conceive after one year or more of regular, unprotected sexual intercourse. In the United States, about 15 percent of couples are considered infertile. Infertility affects men and women equally.

Physiology
Ovulation is the ripening and rupture of a mature egg from one of the ovaries, the female organs that produce sex hormones and eggs for reproduction. Ovulation typically takes place midway through a 28-day menstrual cycle or about 14 or 15 days before the next menstrual cycle. Some women notice a discharge of slippery, clear cervical mucus at the time of ovulation.
Sperm is released in the seminal fluid with ejaculation by the male during sexual intercourse. Millions of sperm are deposited in the woman's vagina with each ejaculation. Some sperm then travel through the cervix, uterus and fallopian tubes (the tubes located on each side of the woman's uterus that lead from the ovaries to the top of the uterus).

After leaving the ovary, an egg is capable of being fertilized for up to about 24 hours. Sperm are capable of fertilizing an egg for about 72 hours after ejaculation. Conception occurs when a sperm penetrates an egg in the fallopian tube to form an embryo, which travels to the uterus and implants itself in the lining.


Causes/associated factors
Fertilization depends on a series of complex events. For example, timing and frequency of intercourse are important for pregnancy to occur naturally. If you're trying to conceive, the best time to have sex is daily around the time of ovulation. To help target the best time to conceive each month, keep a diary of your sexual activity, as well as a log of when you're likely to be ovulating.
If you haven't conceived after 10 to 12 months, you and your partner may want to contact your doctor. If you're older than 35, you may want to consult your doctor after six months. If either partner has a health problem that's known to interfere with fertility, talk to your doctor right away.

For women, infertility can be related to various factors, as described below.

Ovulation disorder
The most common cause of female infertility is failure to ovulate. Ovulation is the ripening and rupture of a mature egg from one of the ovaries. Most women who have regular periods usually ovulate, but not always. Because there are many reasons why ovulation may not take place, a medical evaluation should be done.

Hormone imbalances
Endocrine (hormonal) causes of infertility can be related to dysfunction of the hypothalamus, pituitary, thyroid, adrenal gland or ovaries. These glands work together to produce hormones and regulate female reproductive function.

Scarring or blockage
A blocked fallopian tube can prevent the sperm from reaching the egg or prevent the embryo from traveling to the uterus for implantation. Blockages may be caused by various factors, including structural abnormalities or injuries. Scar tissue may develop after surgery or an infection, such as pelvic inflammatory disease (PID). PID affects the upper genital tract and is often caused by a sexually transmitted disease, such as chlamydia or gonorrhea. When it affects the fallopian tubes, PID is known as salpingitis. This condition can lead to infertility. In some cases, endometriosis (when the tissue that lines the uterus grows outside the uterus) is responsible. If the tissue surrounds the fallopian tubes, for example, it can change the shape of the fallopian tube and possibility cause scar tissue.

Scar tissue may also develop in the uterus after procedures such as dilation and curettage (a minor surgical procedure used to expand the opening of the cervix and scrape the lining of the uterine wall) or removal of fibroid tumors. Rarely, a polyp blocks the cervix, preventing sperm from entering the uterus.

Uterine shape
If your uterus doesn't have the proper shape, it may be unable to sustain a pregnancy. Sometimes, abnormal uterine shape is simply a congenital abnormality (birth defect). In other cases, a change in uterine shape could be due to a tumor or exposure to diethylstilbestrol (DES, a synthetic estrogen used in the past to treat certain medical conditions).

Cervical mucus
The cervical mucus needs to be the correct consistency and have the right acid-base balance for sperm to travel and survive. If the cervical mucus is thick, the sperm have a difficult time penetrating through the cervix.

Immunology
Rarely, a woman may develop antibodies (compounds that help neutralize or destroy foreign substances in the blood) to her partner's sperm. These antibodies can be present in the cervical mucus or vaginal secretions and attack the sperm.

Age
You're born with all the eggs you'll ever have. Additional eggs cannot be produced. In turn, as you age, so do your eggs. A significant decline in the quality and fertilization potential of your eggs begins at about age 35. This decline becomes even more pronounced after age 40.

Lubricants
Many women use vaginal lubricants if they don't produce enough natural lubrication. Many of these products impair the ability of sperm to perform properly, including KY jelly or Lubafax. It's better to prolong foreplay and avoid all artificial vaginal lubricants.

Other factors
Chronic diseases can affect fertility, including diabetes, inflammatory bowel disease, kidney disease and sickle cell disease. Cancer and related treatments may also lead to infertility.

In addition to your general medical condition, obesity, excessive weight loss or gain, extreme exercise, stress and poor dietary habits can also affect fertility. Exposure to toxins such as radiation or pesticides may play a role. Cigarette smoking and alcohol use may also decrease fertility.

In many situations, the cause of infertility is unknown.


Diagnosis
Infertility is best diagnosed and treated by an infertility specialist (a doctor who is board-certified in obstetrics, gynecology or reproductive endocrinology). The infertility specialist will want to initially evaluate both you and your partner together. If the man is found to have a problem that's contributing to the infertility, he may be referred to a urologist (a doctor who specializes in conditions of the male genital tract, as well as the urinary tracts of both men and women). Be sure to discuss any concerns you may have with your doctor about the specialists' training and experience in evaluating and treating infertility.
Making the correct diagnosis regarding the cause of infertility is critical to finding the best treatment. The doctor will ask you and your partner about your health histories, past illnesses or injuries, medication use, sexual habits and basic lifestyle patterns. You'll both also need a complete physical exam.

Based on findings from the physical exam, the doctor may suggest monitoring your basal body temperature to determine when you're ovulating. The process is simple -- you record your temperature using a special basal body thermometer every morning before eating, drinking or getting out of bed. An elevation of ½ to 1 degree may indicate that ovulation has occurred.

Home ovulation kits are more helpful in identifying when ovulation occurs by measuring the level of luteinizing hormone (LH) in your urine. LH plays a role in ovulation and actually tells you when ovulation is about to occur. If you opt for this method, be sure to follow package instructions completely.

Your doctor may also recommend one or more of the following evaluations:

Pelvic ultrasound monitoring (an ultrasound uses sound waves to create images of internal body parts) can help determine how large the follicle is getting and when ovulation is about to occur. The follicle is the part of the ovary where the egg matures.

Blood tests, specifically prolactin and thyriod-stimulating hormone, can provide information about the endocrine glands that regulate reproduction. Sometimes, it may be necessary to evaluate hormones as well.

Hysterosalpingogram (HSG) can help determine if the fallopian tubes are blocked, as well as the shape of the uterus. With this procedure, an X-ray of the uterus and fallopian tubes is taken after a special dye is injected into these areas through a small tube that's inserted through the vagina and cervix. It's usually done two to five days after your period ends.

Laparoscopy is a surgical procedure that allows the doctor to see inside the abdomen and evaluate the uterus and fallopian tubes for any abnormalities or diseases that could contribute to infertility. A laparoscope (a thin tube equipped with a camera lens and light) is inserted through a small incision below the navel. It's done as an outpatient procedure, usually with general anesthesia.

Hysteroscopy is a procedure that allows the doctor to look directly inside the uterus to evaluate and treat specific uterine problems. A hysteroscope is a slender telescope-like tube with a light on the end. It's passed through the vagina and cervical canal, and then into the uterus. Occasionally, an endometrial biopsy (as described below) is done along with a hysteroscopic evaluation.

An endometrial biopsy (taking a tissue sample of the lining of the uterus for evaluation) can help the doctor determine if ovulation has occurred and if the lining of the uterus was adequately prepared for egg implantation. The biopsy is taken 10 to 12 days after ovulation. If the uterine tissue wasn't ready for a fertilized egg, this could suggest an inadequate production or action of the hormone progesterone.

A postcoital (after sex) test of the cervical mucus may also be recommended. During ovulation, cervical mucus allows the sperm to enter the uterus. At other times, the mucus blocks entry. The postcoital test is used to determine if the cervical mucus will sustain active, motile sperm. The sample of cervical mucus is usually taken two to eight hours after sex.

Treatment
Treatment is aimed at correcting the cause of infertility to improve or restore fertility. If natural reproduction is not possible, alternative treatments and options are available. Before making a treatment decision, be sure to discuss with your doctor the risks and benefits, success rates and how these rates are defined. It's important to address any concerns, such as finding the right doctor, determining how much time and effort you're willing to commit to treatment and the cost. Also consider the emotional stress that's and your available support system, as well as any other personal issues.
Medication
Medications can be used to treat various infertility problems, such as lack of ovulation, hormonal imbalances and problems that develop during the luteal phase (the time of the menstrual cycle responsible for supporting early pregnancy). Be sure you understand how and when to take the medication, as well as the potential side effects.

Clomiphene citrate (brand names Clomid and Serophene), human menopausal gonadotropin or hMG (Repronex and Pergonal, for example), and human chorionic gonadotropin or hCG (Pergnyl or Profasi, for example) can be used to induce ovulation.

Bromocriptine mesylate (Parlodel, for example) may be used if the pituitary gland secretes too much prolactin, an important fertility hormone. An overproduction of prolactin can affect ovulation and even lead to lack of menstruation.

Natural progesterone is often used to treat problems with the luteal phase of the menstrual cycle to help maintain and support an early pregnancy. It's available in many forms, including vaginal suppositories or gels, pills and shots.

Medications are occasionally used to treat problems with cervical mucus. If the mucus is too thick for the sperm to travel through, for example, estrogen is sometimes used to help thin the secretions. Low doses of steroids may be prescribed if sperm antibodies are thought to contribute to infertility.
Medication benefits:

Successful therapy may result in pregnancy.
Medication risks:

Infertility medications can be expensive. Frequent and careful monitoring by an infertility treatment specialist is often required.

General side effects may include blurred vision, breast enlargement and hot flashes. Side effects of hormone therapy may include nausea, vomiting, weight gain, acne, increased amount of body hair and mood swings.

Prolonged use of the infertility drugs used to stimulate ovulation is thought by some to slightly increase the risk of ovarian cancer. This has not been definitively proven, however.

Fertility drugs may lead to the development of ovarian hyperstimulation syndrome (OHSS), a potentially serious condition. Early warning signs of OHSS include abdominal pain and swelling, nausea, vomiting, diarrhea and weight gain. Complications of OHSS can include acute respiratory distress, renal failure, deep vein thrombosis, torsion (twisting) of the ovary and intraperitoneal hemorrhage. In some cases, the condition may be fatal.

With Clomid and human menopausal gonadotropin, there is an increased chance of multiple births.

With bromocriptine mesylate, there is a risk of gastric distress, headache, nausea, low blood pressure, heart attack and stroke.
Surgery
The goal of surgery is to correct or reverse the cause of infertility. Remember, surgery cannot guarantee fertility. Ask your doctor or surgeon for details on success rates of surgery compared to assisted reproductive technologies (ART).

Transcervical balloon tuboplasty is a procedure occasionally used to open blocked fallopian tubes. A balloon catheter is inserted through the cervix, into the uterus and up into the fallopian tubes. Once it reaches the blocked area, the balloon is inflated to try to open up the tube.

Various surgical procedures can be done to correct problems such as scarring, adhesions or endometriosis. For example, blocked or damaged fallopian tubes can sometimes be repaired. Laparoscopy or hysteroscopy can be used to remove endometrial tissue, pelvic adhesions, endometrial polyps or fibroids within or around the uterus or fallopian tubes.

Surgery benefits:

Successful surgery may result in pregnancy.
Surgery risks:

general risks associated with anesthesia
infection
bleeding
perforation of the uterus or other organs, including the bladder and bowel
continued infertility
Assisted reproductive technologies
You may be a candidate for assisted reproductive technologies (ART). Many different methods are available, including those described below.

Artificial insemination: With this method, washed and motile sperm are placed directly into the uterus during ovulation. The sperm are placed in the uterus with a special tube during the most fertile part of your menstrual cycle. Artificial insemination may be combined with fertility drug stimulation to treat certain conditions or unexplained infertility. Multiple attempts may be necessary. If you don't become pregnant after about six months, other options should be considered.

Artificial insemination benefits:

Successful insemination may result in pregnancy.
Artificial insemination with your partner's sperm may be an option if the cause of infertility is your partner's physical inability to place sperm high in the vagina. Donor sperm may be an option if your partner can't produce sperm, he carries a dominant genetic abnormality, or the abnormality doesn't respond to treatment.
Artificial insemination risks:

You may experience discomfort, such as mild cramping.
Infection or uterine perforation are rare, but possible.
Infections (such as AIDS) were transmitted in a small percent of artificial inseminations using donor sperm before 1986. Thanks to screening procedures for HIV, the virus that causes AIDS, there have been no documented cases of AIDS transmission from artificial insemination since 1986. Make sure your donor sperm comes from a reputable facility, and discuss with your doctor any concerns you may have regarding this risk.
In vitro fertilization: With this method, you'll take fertility medications to stimulate the ovaries to release several eggs. The doctor will remove the eggs with the help of an ultrasound or a laparoscope and send them to a lab for fertilization. The eggs and sperm will be combined in a test tube and cultured for about 40 hours. Then, the embryos will be transferred to your uterus. Any remaining embryos can be frozen in liquid nitrogen for possible future use. Pregnancy testing is usually done about 10 days after the transfer.

In vitro fertilization benefits:

Successful fertilization may result in pregnancy.
The procedure may be an option if you have a tubal disease, sperm antibodies or endometriosis.
It may also be an option if your partner's sperm quality is insufficient or the cause of infertility is unexplained.
In vitro fertilization risks:

The procedure is expensive.
Gamete intrafallopian tube transfer (GIFT): With this method, the sperm and eggs are placed directly into the fallopian tube for fertilization, instead of in the uterus. This procedure is only an option if you have normal tubal function.

Zygote intrafallopian tube transfer (ZIFT) or tubal embryo transfer (TET): With this method, the egg is fertilized in the lab and the embryo is then placed into the fallopian tube.

GIFT and ZIFT benefits:

Successful treatment may result in pregnancy.
GIFT and ZIFT risks:

The procedure is expensive.
Success rates (as measured by live births) are often low, but are improving.
Intracytoplasmic sperm injection (ICSI): With this relatively new procedure, a single sperm is injected into a single egg to produce an embryo. ICSI improves the results of in vitro fertilization and reduces the need to use donor sperm.

Donor eggs can be used in cases of advanced maternal age or when normal egg production is impaired, you carry a genetic disease, in vitro fertilization fails, or your eggs are unsuitable for other types of assisted reproductive technologies. The donor eggs are mixed with sperm in the lab and then transferred to your uterus. Your doctor will prescribe hormone medication after the transfer until a pregnancy test is done, usually about 10 to 14 days later.

Alternative options may include using a surrogate mother or adoption.


Considerations
People struggling with infertility may experience frustration, sadness and a loss of control, as well as symptoms of depression, guilt or shame. They may become obsessed or preoccupied by their infertility and efforts to get pregnant, often cycling between hope and despair. For some couples, the difficulty associated with infertility provides an opportunity to grow closer to each other. Others may need to grieve individually. You may find yourself withdrawing from personal relationships or pouring your energy into your career. In addition to medical treatment from an infertility specialist, mental health counseling may be helpful. Finding a supportive network of people you trust may help ease the depression and frustration of infertility, along with the ups and downs of treatment.

Prevention
In some cases, infertility can't be avoided or prevented. You can help preserve fertility, however, by making healthy lifestyle choices. For example, help protect yourself from sexually transmitted diseases by using condoms before you want to conceive a child. You can also minimize the risk of STDs by remaining monogamous or limiting your number of sexual partners.
Avoid using vaginal lubricants that are harmful to sperm. Limit alcohol and caffeine use, and avoid recreational drugs, including marijuana and cocaine. Don't smoke, and avoid exposure to toxic environmental or occupational substances, such as harsh chemicals, pesticides and herbicides. Finally, eat a balanced diet and exercise regularly.