Your Guide to Infertility
Infertility is the inability to get pregnant after a year of unprotected intercourse.
How Does Age Affect Fertility?
Women are born with a finite number of eggs. Thus, as the reproductive years progress, the number and quality of the eggs diminish. The chances of having a baby decrease by 3% to 5% per year after the age of 30. This reduction in fertility is noted to a much greater extent after age 40.
What Causes Female Infertility?
Female infertility can be also be caused by a number of factors, including the following:
Damage to fallopian tubes. Damage to the fallopian tubes (which carry the eggs from the ovaries to the uterus) can prevent contact between the egg and sperm. Pelvic infections, endometriosis, and pelvic surgeries may lead to scar formation and fallopian tube damage.
Hormonal causes. Some women have problems with ovulation. Synchronized hormonal changes leading to the release of an egg from the ovary and the thickening of the endometrium (lining of the uterus) in preparation for the fertilized egg do not occur. These problems may be detected using basal body temperature charts, ovulation predictor kits, and blood tests to detect hormone levels.
Cervical causes. A small group of women may have a cervical condition in which the sperm cannot pass through the cervical canal. Whether due to abnormal mucus production or a prior cervical surgical procedure, this problem may be treated with intrauterine inseminations.
Uterine causes. Abnormal anatomy of the uterus; the presence of polyps and fibroids.
Unexplained infertility. The cause of infertility in approximately 20% of couples will not be determined using the currently available methods of investigation.
How Is the Cause of Infertility Determined?
If male infertility is suspected, a semen analysis is performed. This test will evaluate the number and health of his sperm. A blood test can also be performed to check his level of testosterone and other male hormones.
If female infertility is suspected, your doctor may order several tests, including:
A blood test to check hormone levels
An endometrial biopsy to check the lining of the uterus
Two diagnostic tests that may be helpful in detecting scar tissue and tubal obstruction are hysterosalpingography and laparoscopy.
Hysterosalpingography (HSG). This procedure involves either ultrasound or X-rays taken of the reproductive organs. Either dye or saline and air are injected into the cervix and travel up through the fallopian tubes. This enables the ultrasound or X-ray to reveal if the fallopian tubes are open or blocked.
Laparoscopy. In this procedure, a laparoscope (a slender tube fitted with a fiberoptic camera) is inserted into the abdomen through a small incision near the belly button. The laparoscope enables the doctor to view the outside of the uterus, ovaries, and fallopian tubes to detect abnormal growths, as in endometriosis. The doctor can also check to see if the fallopian tubes are open at the same time.
What goes into a fertility evaluation?
A standard fertility evaluation includes physical exams and medical and sexual histories of both partners. Men undergo a semen analysis that evaluates sperm count and sperm movement. “We look at the percent that are moving and how they are moving — are the sperm sluggish? Are they wandering?” says Robert G. Brzyski, M.D., Ph.D., associate professor of obstetrics and gynecology at the University of Texas Health Science Center at San Antonio. “Often, it’s not possible to identify a specific reason for a sperm disorder,” he says. “But there is new recognition that very low sperm or no sperm may be related to genetics — an abnormality of the Y chromosome.”
For women, doctors first check to see whether ovulation is occurring. This can be determined and monitored through blood tests that detect hormones, ultrasound exams of the ovaries, or an ovulation home test kit. “An irregular menstrual pattern would make us suspicious of an ovulation problem, but it’s also possible for a woman with regular periods to have an ovulation disorder,” Brzyski says.
If a woman is ovulating, doctors then move to a standard test called the hysterosalpingogram, a type of X-ray of the fallopian tubes and uterus. This test involves placing a radiographic dye solution into the uterine cavity. Multiple X-rays are taken. If the fallopian tubes are open, the dye will flow through the tubes and be visible in the abdominal cavity. If the fallopian tubes are blocked, the dye will be retained in the uterus or fallopian tubes, depending on the location of the blockage.
Other tests give doctors more information. For example, ultrasound can be used to examine the female reproductive structures. Hysterosonography is a more complicated type of ultrasound that involves putting salt water (saline) into the uterus during an ultrasound exam. “This is more likely to reveal structural abnormalities than regular vaginal sonography will show alone,” Brzyski says. One such abnormality that hysterosonography may identify is fibroid tumors, which may distort the shape of the uterine cavity.
A surgical procedure called laparoscopy also allows doctors to examine the ovaries, uterus, fallopian tubes, and abdominal cavity. This involves inserting a fiber-optic telescope into the abdomen. One advantage of laparoscopy is that it allows doctors to both diagnose and treat conditions such as endometriosis, when uterine cells attach to tissue outside of the uterus. Adhesions, abnormal attachments between two surfaces inside the body, can also be treated in this way.
Doctors have begun to assess the ovarian reserve by measuring hormone levels and seeing how the ovaries respond to various fertility treatments. This helps evaluate the availability of eggs and the likelihood that a healthy pregnancy will result. “Some women who are 35 are fertile while others are not because their supply of eggs is depleted,” Brzyski says. “In the last decade, we’ve learned this can be investigated through a blood test on the third day of the menstrual cycle. If the numbers are normal, it doesn’t guarantee fertility. But if the numbers are abnormal, it points to a serious problem. Up to 20% of women who seek infertility care have an abnormal ovarian reserve test.”
There are also tests that evaluate how sperm and eggs interact, as well as whether either party is developing antibodies to the sperm. This occurs when the man’s or the woman’s immune system recognizes the sperm as something foreign and attacks it.
How Is Female Infertility Treated?
Female infertility can be treated in several ways, including:
Laparoscopy. Women who have been diagnosed with tubal or pelvic disease can either undergo surgery to reconstruct the reproductive organs or try to conceive through in vitro fertilization (IVF). Using a laparoscope inserted through a cut near the belly button, scar tissue can be removed, endometriosis treated, ovarian cysts removed, and blocked tubes opened.
Hysteroscopy. A hysteroscope placed into the uterus through the cervix can be used to remove polyps and fibroid tumors, divide scar tissue, and open blocked tubes.
Medical therapy. Women suffering from ovulation problems may be prescribed drugs such as clompiphene citrate (Clomid, Serophene) or gonadotropins (such as Gonal F, Follistim, Humegon and Pregnyl), which can lead to ovulation. Gonadotropins can induce ovulation when Clomid or Serophene do not work. These drugs also can enhance fertility by causing multiple eggs to ovulate during the cycle (normally, only one egg is released each month). Gonadotropin therapy may be offered for unexplained infertility or when other factors have been corrected without resulting in pregnancy. Metformin (glucophage) is another type of medication that may restore or normalize ovulation in women who have insulin resistance and/or PCOS (polycystic ovarian syndrome).
Intrauterine insemination. Intrauterine insemination refers to an office procedure in which semen is collected, rinsed with a special solution, and then placed into the uterus at the time of ovulation. The sperm are deposited into the uterus through a slender plastic catheter that is inserted through the cervix. This procedure can be done in combination with the previously listed medications that stimulate ovulation.
In vitro fertilization. In vitro fertilization, or IVF, involves fertilization in a laboratory and then the transfer of embryos into the uterus. This procedure was first used for humans in 1977 at Bourne Hall in Cambridge, England, and tens of thousands of babies have been delivered worldwide as a result of IVF treatment.
IVF refers to a procedure in which eggs are fertilized in a culture dish and placed into the uterus. The woman takes gonadotropins to stimulate multiple egg development. When monitoring indicates that the eggs are mature, they are collected using a vaginal ultrasound probe with a needle guide. The sperm are collected, washed, and added to the eggs in a culture dish. Several days later, embryos — or fertilized eggs — are returned to the uterus using an intrauterine insemination catheter. Any extra embryos can be frozen for later use, upon the consent of the couple.
Over the years, IVF procedures have become increasingly simple, safe and more successful.
To accomplish pregnancy as a result of IVF, several steps are involved:
Step 1: Stimulation of the ovary to produce several fertilizable oocytes (eggs)
Step 2: Retrieval of the oocytes from the ovary
Step 3: Fertilization of the oocytes and culture of the embryos in the IVF laboratory
Step 4: Placement of the embryos into the uterus for implantation, called embryo transfer (ET)
Some types of infertility that may be helped with IVF include:
Absent fallopian tubes or tubal disease that can’t be treated by surgery
Endometriosis that doesn’t respond to treatment
Genetic diseases that result in miscarriage or abnormal births
Infertility secondary to sperm antibodies
Male infertility caused by a low sperm count, but with enough active sperm to fertilize in the laboratory
Male infertility in which sperm must be obtained surgically
Unexplained infertility that doesn’t respond to other treatments
ICSI. Intracytoplasmic sperm injection is used when there is sperm-related infertility. The sperm are injected directly into the egg in a culture dish and then placed into the woman’s uterus.
Intracytoplasmic sperm injection, or ICSI, is the direct microinjection of a single sperm into a single egg to achieve fertilization. It was originally developed in 1992 to assist fertilization in couples with severe male factor infertility or couples who failed to fertilize in a previous IVF attempt.
The procedure overcomes many barriers to fertilization and allows couples with little hope of pregnancy to obtain fertilized embryos.
The technique involves very precise maneuvers to pick a single live sperm and inject it directly into the center of a human egg. The procedure requires that the female partner undergo ovarian stimulation with fertility medications so several mature eggs develop. These eggs are suctioned through the vagina, using vaginal ultrasound, and incubated under precise conditions in the embryology lab.
The semen sample is prepared by spinning the sperm cells through a special medium. This solution separates live sperm from debris and most of the dead sperm. The specialist picks up the single live sperm in a glass needle and injects it directly into the egg.
The current fertilization rate of eggs injected is 70 to 80 percent, and pregnancy rates are comparable to those seen with IVF in couples with no male factor infertility.
Egg donation. Egg donation helps women who do not have normally functioning ovaries (but who have a normal uterus) to achieve pregnancy. Egg donation involves the removal of eggs — also called oocytes — from the ovary of a donor who has undergone ovarian stimulation with the use of fertility drugs. The donor’s eggs are then placed together with the sperm from the recipient’s partner for in vitro fertilization. The resulting fertilized eggs are transferred to the recipient’s uterus.
This is an option when other infertility therapies haven’t worked or when hormonal tests indicate a woman is unlikely to successfully conceive with her own eggs. Ovum donation may be appropriate for women born without ovaries, or whose ovaries were removed or damaged by surgery, chemotherapy or radiation. It also can be an option for patients who’d like to eliminate the risk of passing on a genetic condition carried by the female partner.
Because the chance of having a baby is strongly related to the age of the egg, using donor eggs can increase the likelihood of having a baby from in vitro fertilization, or IVF. The chance of having a baby from a single ovum donation cycle is greater than 60 percent. Many cycles using donated eggs result in surplus embryos to freeze, and when you include later attempts with frozen embryos, the pregnancy rate is about 80 percent.
Ovum donation allows couples to experience pregnancy, childbirth and breastfeeding, and to have a child who is genetically related to the father. Parents will have control over many aspects of the process, including when to try to become pregnant and the choice of the donor.
Ovum donors offer an amazing gift to couples struggling to become parents. The knowledge that she has had the ability to make a profound difference for a family is frequently one of the most compelling reasons young women participate so generously in this process.
Being a donor entails committing to a thorough health and psychological screening. The medical procedures include injecting medications to stimulate your ovaries, undergoing ultrasound monitoring over the course of 10 to 14 days and undergoing an outpatient procedure to remove the stimulated eggs from your ovaries.
Surgical sperm aspiration. This technique involves removing sperm from part of the male reproductive tract, such as the epididymis, vas deferens or testicle. This allows retrieval of sperm if the ejaculatory duct is blocked.
Embryo and semen freezing (cryopreservation)
Embryo freezing preserves embryos by cooling and storing them at low temperatures. They can be thawed later and transferred to the uterus, providing additional opportunities for conception.
During the in vitro fertilization (IVF) process, multiple eggs are stimulated to grow, then recovered from the ovary and fertilized. This may result in more embryos or fertilized eggs than a couple wants at one time. If the additional embryos are of sufficiently good quality to undergo freezing, they can be used later if the first IVF isn’t successful. If the IVF is successful, the extra embryos can be stored for several years to be used if the couple decides to have more children.
Ejaculated sperm or sperm obtained from fluid extracted during surgical procedures (vasal, epididymal and testicular sperm specimens) can be frozen. The sperm is usually frozen for one year. Longer term storage can be arranged after the first year. Thawed sperm are no more likely to result in birth defects than freshly ejaculated sperm.
Pre-implantation genetic diagnosis
Pre-implantation genetic diagnosis (PGD) is a laboratory procedure, used in conjunction with in vitro fertilization (IVF), to reduce the risk of passing on inherited conditions. Some of the most common reasons for PGD are specific single gene conditions (such as cystic fibrosis or sickle cell anemia) or structural changes of a parent’s chromosomes. Families may also use PGD when a member of the family needs a bone marrow donor, as a way to have a child who can provide matching stem cells.
Typically, couples in need of these techniques are not infertile but have a family history of a condition and want to reduce the risk of having another child with significant health issues or early death. Through generally available genetic screening, however, occasionally couples who are seeking fertility treatment are found to be at risk of passing on an inherited condition, and PGD may be an option for them.
PGD is available for almost any inherited condition for which the exact mutation is known. A unique test must be developed for each couple, however. This test design may take up to several months to complete before beginning an IVF cycle.
PGD uses IVF, where multiple eggs are matured and retrieved. The oocytes — or primitive egg cells — are inseminated with a single sperm using intracytoplasmic sperm injection.
The resulting embryos are grown in culture until the six-to-eight-cell stage, which is day three of embryo development. At this point, the embryo is biopsied with the removal of one to two cells. This process does not damage the cells remaining within the embryo.
The isolated cells are evaluated for the specific genetic conditions. Embryos that are found to be unaffected are transferred back to the woman’s uterus on day five of embryo development.
Two main techniques are used for the genetic assessment:
Polymerase chain reaction (PCR) — In PCR, multiple copies of the gene of interest are made by a process of amplification. This amplification process allows the identification of very small amounts of DNA to make the diagnosis.
Fluorescent in situ hybridization (FISH) — FISH allows the laboratory to count the number of chromosomes in an isolated cell. This technique is used primarily for expected abnormalities in chromosome number, such as Down syndrome, or translocations (defects in the structure of the chromosome).
Medical therapy and in vitro fertilization can increase the chance of pregnancy in women diagnosed with unexplained infertility.
Assisted hatching involves mechanical or chemical thinning of the outer shell, called the zona pellucida, of the fertilized egg prior to transfer into the uterus. The technique is used to enhance the embryo’s ability to hatch or break out of its protective shell and implant in the uterus.
The procedure involves measuring the thickness of the outer shell of embryos. If an embryo has not initiated the thinning process naturally, a small “window” or hole is created chemically using a dilute acidic solution on the embryo surface. The embryos are then implanted normally into the uterus.
The most extensive experience with assisted hatching has been reported from Cornell University where implantation rates are 25 percent per embryo, as compared to 18 percent per embryo with regular IVF in non-assisted cycles.
You may be a candidate for assisted hatching if you are 38 years of age or older, or if you have previously had one or more IVF cycles with failure of your embryos to implant despite otherwise good results.
Blastocyst (Embryo) Culturing
Blastocyst culturing is a technique to grow embryos beyond the third day of culture. Typically, we transfer embryos into the uterus about three days after the egg retrieval, which is several days earlier than would occur in nature. On the third day, embryos generally are between six to eight cells. We now have the ability to keep the embryos two additional days in a culturing material before implanting in the uterus. During this additional culture period, the embryos continue to grow to become “blastocysts.”
The natural process of embryo development begins with fertilization of the egg in the outer part of the fallopian tube. As the newly formed embryo develops, it moves slowly toward the uterine cavity where it will ultimately implant. This process takes about six to seven days. When the embryo reaches the “blastocyst” stage, it is ready to implant.
In certain patients, blastocyst culturing allows optimal selection of embryos for transfer and an increased implant rate. However, this technology may not necessarily increase your chance for pregnancy. The main advantage is that fewer embryos may be transferred to eliminate the possibility of triplet and quadruplet pregnancies, while maintaining a high pregnancy rate.
Embryo co-culturing improves the quality of embryos prior to transfer into the womb. It involves using a buffalo rat liver cell line to secrete nutritional products that help growing embryos improve their chances for survival. This technique is only recommended to patients who have had unsuccessful IVF cycles with poor embryo quality.
Historically, oral drugs containing hormones were designed to induce ovulation in women with irregular menstrual cycles who didn’t ovulate. The goal was to stimulate the body to produce and release an egg ready to be fertilized.
Later, injected hormones were developed to increase the number of eggs reaching maturity in a single cycle, increasing chances for conception. These drugs increase the risk of multiple conceptions, are more expensive, require more time and may cause ovarian over stimulation.
In the mid-90s, oral drugs were used in women with regular menstrual cycles who ovulate but who have “unexplained infertility.” The drugs may treat subtle unidentified defects in ovulation and induce the maturity of two to three eggs, instead of just one, to improve both the quality and quantity of ovulation and enhance pregnancy rates.
Ovulation induction is always combined with intrauterine insemination, and it should only be considered after a complete and thorough evaluation. All underlying hormonal disorders such as thyroid dysfunction should be treated prior to resorting to using fertility drugs.
Fertility drugs are the main treatment for women who are infertile due to ovulation disorders. These medications regulate or induce ovulation. In general, they work like natural hormones — such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH) — to trigger ovulation. Commonly used fertility drugs include:
Clomiphene citrate (Clomid, Serophene). This drug is taken orally and stimulates ovulation in women who have polycystic ovary syndrome (PCOS) or other ovulatory disorders. It causes the pituitary gland to release more FSH and LH, which stimulate the growth of an ovarian follicle containing an egg.
Human menopausal gonadotropin (Repronex, Menopur). This injected medication is for women who don’t ovulate on their own due to the failure of the pituitary gland to stimulate ovulation. Unlike clomiphene, which stimulates the pituitary gland, human menopausal gonadotropin (hMG) and other gonadotropins directly stimulate the ovaries. This drug contains both FSH and LH.
Follicle-stimulating hormone (Bravelle). FSH works by stimulating maturation of egg follicles the ovaries.
Human chorionic gonadotropin (Ovidrel, Pregnyl). Used in combination with clomiphene, hMG and FSH, human chorionic gonadotropin (HCG) stimulates the follicle to release its egg (ovulate).
Gonadotropin-releasing hormone analogs. This treatment is for women with irregular ovulatory cycles or who ovulate prematurely — before the lead follicle is mature enough — during hMG treatment. Gonadotropin-releasing hormone (Gn-RH) analogs suppress pituitary gland activity, which alters hormone production so that a doctor can induce follicle growth with FSH.
Aromatase inhibitors. This class of medications, which includes letrozole (Femara) and anastrozole (Arimidex), is approved for treatment of advanced breast cancer. Doctors sometimes prescribe them for women who don’t ovulate on their own and who haven’t responded to treatment with clomiphene citrate. These drugs are not approved by the Food and Drug Administration for inducing ovulation, and their effect on early pregnancy isn’t yet known.
Metformin (Glucophage). This oral drug is taken to boost ovulation. It’s used when insulin resistance is a known or suspected cause of infertility. Insulin resistance may play a role in the development of PCOS.
Bromocriptine (Parlodel). This medication is for women whose ovulation cycles are irregular due to elevated levels of prolactin, the hormone that stimulates milk production in new mothers. Bromocriptine inhibits prolactin production.
Depending on the cause, surgery may be a treatment option for infertility. Blockages or other problems in the fallopian tubes can often be surgically repaired. Laparoscopic techniques allow delicate operations on the fallopian tubes.
If you have endometriosis, your doctor may treat you with ovulation therapy, in which medication is used to stimulate or regulate ovulation, or in vitro fertilization, in which the egg and sperm are joined in the laboratory and transferred to the uterus.
Complications of treatment
Certain complications exist with the treatment of infertility. These include:
Multiple pregnancy. The most common complication of ART is a multiple fetus pregnancy. Generally, the greater the number of fetuses, the higher the risk of premature labor. Babies born prematurely are at increased risk of health and developmental problems.
The number of quality embryos kept and matured to fetuses and birth ultimately is a decision made by the couple. If too many are conceived, the removal of one or more fetuses (multifetal pregnancy reduction) is possible to improve survival odds for the other fetuses.
Ovarian hyperstimulation syndrome (OHSS). If overstimulated, a woman’s ovaries may enlarge and cause pain and bloating. Mild to moderate symptoms often resolve without treatment, but severe cases — marked by abdominal swelling and shortness of breath — require emergency treatment. Younger women and those who have polycystic ovary syndrome have a higher risk of developing OHSS than do other women.
Bleeding or infection. As with any invasive procedure, there is a risk of bleeding or infection with assisted reproductive technology.
Low birth weight. The greatest risk factor for low birth weight is a multiple fetus pregnancy. In single live births, there may be a greater chance of low birth weight associated with ART.
Birth defects. There is some concern about the possible relationship between ART and birth defects. More research is necessary to confirm this possible connection. Weigh this factor if you’re considering whether to take advantage of this treatment. ART is the most successful fertility-enhancing therapy to date.