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Reproductive Endocrinology and Infertility: Treating Infertility
Treatment Options
Fertility Medications- The basics of fertility pills and
injectable medications
Intrauterine Insemination- Insertion of processed sperm into
the uterus
In Vitro Fertilization (IVF)- Retrieval, fertilization, and
transfer of
embryos
Intracytoplasmic Sperm Injection (ICSI)- Direct injection of a
single
sperm into the egg
Embryo Cryopreservation- Freezing of fertilized eggs for later
transfer
into an appropriately prepared uterus
Ovum (Egg) Donation- Donated eggs are fertilized and transferred
into a
recipient woman's uterus
Operative Laparoscopy- Minimally invasive surgical evaluation
and
treatment of the ovaries and Fallopian tubes
Operative Hysteroscopy- Surgical treatment of fibroids,
polyps, and
other abnormalities that affect the uterus
Myomectomy- Surgical removal of uterine fibroids
Embryo Micromanipulation: Assisted Hatching- a form of embryo micromanipulation that
involves the thinning and creation of an opening in the outer covering
of the embryo to help the embryo implant
Gamete Intrafallopian Transfer (GIFT)- A variation of IVF that
involves placing a mixture of sperm and eggs directly into the
fallopian tubes
Fertility Medications
Clomiphene Citrate, or "Clomid," is often referred to as the "fertility pill." It is used to treat infertile women who have an ovulation problem. It works by helping the pituitary gland (located at the base of the brain) improve the stimulation of developing follicles (eggs) in the ovaries. Clomiphene is most often prescribed to patients who have been found to have an abnormality with their cycle, though combined with intrauterine insemination, it may be useful in the treatment of unexplained infertility.
Clomiphene is usually prescribed for five days each cycle, usually beginning on day three or five. Of all women treated with Clomiphene 60% to 80% will ovulate normally. Nearly 10% of women treated with Clomiphene may experience mild side effects, including hot flashes, blurred vision, nausea, bloating sensation, and headaches. Serious side effects are rarely seen with Clomiphene therapy. The frequency of twins occurring in women who conceive while taking Clomiphene has been reported to be as high as 10%. New studies suggest that long-term use of Clomiphene for more than 12 cycles may place patients at an increased risk of developing ovarian cancer.
A number of studies have confirmed a significantly improved pregnancy rate with injectable medications that stimulate "superovulation." This improvement in pregnancy rate is primarily a result of the increased number of eggs produced. "Fertility drugs," including Pergonal, Humegon, Metrodin, Gonal-F, and Follistim, are administered beginning on the second or third cycle day and are given for six to nine consecutive days. Response to these drugs is monitored by frequent vaginal ultrasounds and blood estrogen determinations. At a time in the cycle when the ovarian follicles reach a designated size, and estrogen levels are appropriate, an injection of the hormone HCG is given to trigger ovulation. Ovulation usually occurs 36-48 hours after the HCG injection. Thus, intercourse or insemination should be timed accordingly.
Performing intrauterine insemination may result in an increase in the number of sperm at the site of fertilization in the fallopian tube. Generally only 1 of 2000 sperm ejaculated into the vagina can later be found in the fallopian tube. Therefore, adding insemination to stimulated cycles may further improve the pregnancy rate. A possible side effect of the injectable fertility drugs is ovarian hyperstimulation, a condition in which the ovaries are tender and enlarged. In severe cases, a woman may have swelling from retaining excessive amounts of body fluid in the tissues. Fortunately, severe hyperstimulation is rare, occurring in less than one percent of treatment cycles.
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Intrauterine Insemination (IUI)
Intrauterine Insemination is often an important part of treatment for couples who are infertile because of sperm disorders. IUI involves injecting sperm through a narrow catheter into the wife's reproductive tract. For most couples, artificial insemination is performed with the husband's sperm. Depending on the husband's sperm count and motility, the wife's cervical mucus quality at the fertile time of her cycle, and the estimated time to egg release from the ovarian follicle, a well timed-IUI can be very effective. In a laboratory, the sperm can be separated from the seminal fluid and resuspended in a very small volume of sterile medium that will keep the sperm alive and actively mobile. Often, preparation involves a "swim-up" procedure, in which only the fastest swimmers are selected for insemination. The insemination is performed by passing a sterile catheter through the cervical canal into the uterine cavity and then injecting the sperm suspension into the uterine cavity. Usually the insemination itself causes little, if any, discomfort.
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In Vitro Fertilization (IVF)
 In vitro fertilization, or IVF, is a procedure that involves retrieving eggs and sperm from the bodies of the male and female partners and placing them together in a laboratory dish to enhance fertilization. Fertilized eggs are then transferred several days later into the female partner's uterus, where implantation and embryo development will hopefully occur as in a normal pregnancy. IVF is performed by physicians who specialize in reproductive medicine and have received additional education and training in the evaluation and treatment of male and female infertility. IVF was originally developed in the early 1970s to treat infertility caused by blocked or damaged fallopian tubes. In 1978, the first IVF baby, Louise Brown, was born in the United Kingdom. Since then, the number of IVF procedures performed each year has increased, and the success rate has improved significantly. IVF involves several different treatment stages:
Stage One: Ovarian Stimulation and Monitoring
In order to maximize the patient's chances for successful fertilization, a patient undergoing IVF usually takes hormones in the form of injections to increase the number of eggs produced in a given month. Physicians monitor the woman to follow her ovarian response continuously, allowing them to adjust and time medication dosage appropriately.
Stage Two: Ovum Retrieval
With the patient sedated and comfortable, the ova, or eggs, are retrieved through the vagina under ultrasound guidance.
Stage Three: Culture and Fertilization
The oocytes, or egg cells, are fertilized with sperm from the male partner. At times, the sperm are put down on top of the oocyte. In other cases, especially when there are fewer than one million living sperm, ICSI, or intracytoplasmic sperm injection, is used catch a single sperm and inject it directly into the oocyte.
Stage Four: Embryo Transfer
Three or four of the best embryos are transferred directly into the uterus and allowed to implant. The remaining healthy embryos may be cryopreserved (frozen). The pregnancy test is performed eleven days after embryo transfer. In a good program with a high quality laboratory, there is a ~50% success rate of pregnancy for a woman under the age of 40.
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Intracytoplasmic Sperm Injection (ICSI)
At times, there are not enough normal sperm to fertilize the eggs retrieved during an IVF cycle. Over the past several years, embryologists have developed a technique to catch a single sperm and inject it directly into an egg. Candidates for use of ICSI include men with extremely low concentrations of sperm (fewer than 6 million motile sperm), men whose sperm have failed to fertilize eggs in previous cycles of IVF, and men with complete absence of seminal sperm (azoospermia) who need the sperm to be retrieved directly from the testicle and then injected into the egg. In a good program with a high quality laboratory, the success rate for IVF should not be reduced when ICSI is required.
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Embryo Cryopreservation
Embryo cryopreservation is preserving embryos by cooling and storing them at low temperatures. The benefit of embryo cryopreservation is that it permits the use of thawed embryos in an otherwise natural cycle, sparing the patient from undergoing ovulation induction, egg retrieval, and the associated costs. Unfortunately, nearly 50% of all cryopreserved embryos do not survive the freezing and thawing process intact. There does not appear to be any increased risk of birth defects in cryopreserved embryos, and there does not appear to be a maximum length of time that the embryos can be stored.
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Ovum (Egg) Donation
More than 150,000 women in the United States can't bear children because of ovarian problems. Many women do not produce eggs, or have had their ovaries removed, have had radiation therapy or chemotherapy for cancer that destroyed their ovarian function, or have dysfunctional ovaries, and are no longer producing fertilization-quality eggs. Other women have deferred pregnancy until their late thirties or forties. Since the ovaries age at such dramatically different rates in different women, while some conceive quickly, others are no longer able to conceive using their own eggs and require donated eggs to conceive. Egg donation is a treatment that uses the male partner's sperm to fertilize eggs donated by an anonymous female donor, and is followed by transfer of the fertilized egg into the female partner's uterus.
Egg donors are typically healthy women between ages 21 and 31 who have no known genetic or sexually transmitted diseases. They should be screened for genetic, hormonal, psychological, infectious, and physical diseases. Egg donors usually take injectable hormones for eight to ten days to increase their egg production. Donor eggs are retrieved transvaginally using an ultrasound to guide the procedure. The recipient of the donated eggs usually takes hormones to synchronize her cycle with the donor's cycle and to prepare her uterus to receive the embryos and thus enhance the likelihood of implantation. These hormones include estrogen, which can be taken orally or administered in patches that attach to the skin, and progesterone, which is administered by injections. As in IVF, three embryos are normally transferred to increase the couple's chances of pregnancy. In a good program, more than 50% of ovum recipients should receive positive pregnancy tests on their first attempt.
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Operative Laparoscopy
A fiber optic telescope, called a laparoscope, is inserted into the female's abdomen below the navel to look for endometriosis, scarring, adhesions, and other pelvic disease. At times, the procedure is performed to look for the cause of pelvic pain or infertility and is called a "diagnostic" laparoscopy. Once disease is identified, however, the surgeon should be capable of performing an "operative" laparoscopy, and actually treat the disease. Instruments such as a laser can be useful in some cases to treat adhesions and endometriosis. The primary advantages of laparoscopy include rapid patient recovery (because of the extremely small incision) and reduced cost (since the patient nearly always goes home the same day). Aside from the treatment of extremely large fibroids, most pelvic surgery can be performed laparoscopically.
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Operative Hysteroscopy
If a uterine abnormality is suspected following the hysterosalpingogram, your doctor may recommend hysteroscopy. Hysteroscopy is performed with a thin telescope, called a hysteroscope, equipped with a fiber optic light. The hysteroscope is inserted through the cervix into the uterus to enable the doctor to see any uterine abnormalities or growths, some of which can be repaired by operative hysteroscopy (e.g., hysteroscopic myomectomy). Photographs or videotape may be taken for future reference. This procedure is usually performed in the early half of a woman's cycle so that the build-up of the endometrium does not obscure the doctor's view. This procedure is usually performed on an outpatient basis with moderate sedation. The patient recovers fully within days.
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Myomectomy
One of the most common causes of infertility in women, uterine fibroids are abnormal growths in the uterus that almost always are noncancerous. 40% of hysterectomies are performed for the treatment of uterine fibroids. New microsurgical techniques have been developed to make myomectomy a choice for some women. Myomectomy is a surgery that removes the fibroid tumor and leaves the female organs intact. Reconstruction of the uterus is often part of the procedure. Specialists who perform myomectomies can discuss whether or not this is a procedure to resolve your problem and whether or not the procedure can be done on an outpatient basis. Medications are another option for treating fibroid tumors in some women. Prescription medications are available that can shrink the size of the fibroid and lessen heavy bleeding and pain. These medications can be used for a limited period of time and require careful monitoring by a physician.
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Embryo Micromanipulation: Assisted Hatching
Assisted hatching is a form of embryo micromanipulation that involves the thinning and creation of an opening in the outer covering of the embryo. This procedure is used to help a normal growing embryo to emerge from its covering in order to implant in the uterus properly. Assisted hatching can be used following in vitro fertilization and appears to be helpful in certain groups of women, including those who are older, those with high baseline FSH levels, and those who have had previously unsuccessful IVF cycles. Assisted hatching increases the likelihood of achieving pregnancy when performed in the laboratory prior to transfer of the fertilized embryo to the female's reproductive tract.
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Gamete Intrafallopian Transfer (GIFT)
Gamete intrafallopian transfer, or GIFT, was developed in 1984 as a variation of in vitro fertilization, or IVF. GIFT is a procedure that involves ovarian stimulation, egg retrieval, and placing a mixture of the sperm and eggs directly into the tubes to foster fertilization inside the female's body. This procedure used to be recommended for couples with unexplained infertility where the female partner had at least one open fallopian tube. Over the past several years, however, the success rate of IVF has dramatically increased, while the success rate of GIFT has stayed the same. Physicians with access to high quality laboratories, therefore, are finding fewer and fewer indications to perform GIFT. In rare cases, it may still be recommended in cases of severe cervical factor infertility. The primary difference between IVF and GIFT is that with GIFT, fertilization occurs naturally within the fallopian tube, instead of in the laboratory.
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