Options for Women

Fertility Medications

Clomiphene Citrate (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 often prescribed to those patients who have been found to have an abnormality with their cycle.  When combined with intrauterine insemination, it may be useful in the treatment of unexplained infertility.

Clomiphene is usually prescribed for 5 days each cycle, usually beginning on day 3 or 5. 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%. In addition, 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.  It is not recommended to use clomiphene for more than 6 cycles.

A number of studies have confirmed a significantly improved pregnancy rate with injectable medications that stimulate "superovulation". This improvement in pregnancy rate is due primarily to the increased number of eggs produced.  Injectables including Bravelle, Gonal-F, and Follistim are administered beginning on the 3^rd cycle day and given for 6 to 9 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 1% of treatment cycles.

Intrauterine Insemination

Intrauterine insemination is often an important part of treatment for couples that are infertile due to sperm disorders. IUI involves injecting sperm through a narrow catheter into the woman's uterus. Typically, artificial insemination is performed with the partner's sperm; however, donor sperm may also be used. Depending on the sperm count and motility 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. 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.

In Vitro Fertilization

In vitro fertilization, or IVF, is a procedure that involves retrieving eggs and sperm from the bodies of a male and female and placing them together in a laboratory dish to enhance fertilization. Fertilized eggs are then transferred several days later into the female's uterus where implantation and embryo development will hopefully occur as in a normal pregnancy. The IVF process 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.

The IVF process was originally developed in the early 1970s to treat infertility caused by blocked or damaged fallopian tubes. By 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 rates have improved significantly. IVF involves several different treatment stages:

1.  Stage 1: 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. Monitoring is performed to continuously follow a woman's ovarian response, allowing the physician to adjust and time medication dosage appropriately.

2.  Stage 2: Ovum Retrieval: With the patient sedated and comfortable, the ova (eggs) are retrieved through the vagina under ultrasound guidance.

3.  Stage 3: Culture and Fertilization: The oocytes are fertilized with sperm. At times, the sperm are put down on top of the oocyte. In other cases, ICSI (intracytoplasmic sperm injection) is used catch a single sperm and inject it directly into the oocyte.

4.  Stage 4: Embryo Transfer: Between 1 to 3 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 11 days after embryo transfer. In a good program with a high quality laboratory, a woman under the age of 38 should become pregnant approximately 50% of the time.

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. Indications for ICSI include men with low concentrations of sperm, men whose sperm have failed to fertilize eggs in previous cycles of IVF, and men with complete absence of 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 should not be reduced when ICSI is required.

Embryo Cryopreservation

Embryo cryopreservation is a method used to preserve 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. Fortunately, only less than 5% 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 from cryopreserved embryos, and there does not appear to be a maximum length of time that the embryos can be stored.

Ovum Donation

More than 150,000 women in the United States can't bear children because of ovarian problems. Many women do not produce eggs, 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 high 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, some conceive quickly while others are no longer able to conceive using their own eggs and require donated eggs to conceive. Egg donation is a treatment that uses sperm to fertilize eggs donated by an anonymous female donor, and is followed by transfer of the fertilized egg into the female's uterus.

Egg donors are typically healthy women between ages 21 and 32 who have no known genetic or sexually transmitted diseases. They are screened for genetic, hormonal, psychological, infectious, and physical diseases. Egg donors usually take injectable hormones for 8 to 10 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 occurring. These hormones include estrogen which can be taken orally or administered in patches that attach to the skin and progesterone administered by injections. Due to high chances of conceiving, 1 to 2 embryos are normally transferred into the uterus. In a good program, more than 50% of ovum recipients should receive positive pregnancy tests on their first attempt.

Operative Laparoscopy

A fiber optic telescope called a laparoscope is inserted into the female's abdomen at 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. However, once disease is identified the surgeon may be capable of performing an "operative" laparoscopy, and actually treat the disease. Instruments such as laser can be useful in some cases to treat adhesions and endometriosis. The primary advantages of laparoscopy include rapid patient recovery (due to the extremely small incisions) and decreased cost (since the patient nearly always goes home the same day). Aside from the treatment of some fibroids, most pelvic surgery can be performed laparoscopically.

Operative Hysteroscopy

If a uterine abnormality is suspected following the hysterosalpingogram (HSG) or saline ultrasound, 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 and enables the doctor to see any uterine abnormalities or growths. Photographs 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 out-patient basis. Full recovery of the patient occurs within days.

Myomectomy

Uterine fibroids are abnormal growths in the uterus and almost always are non-cancerous. Uterine fibroids are also one of the most common causes of infertility in women. 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.

Preimplantation Genetic Diagnosis (PGD) and Comprehnsive Chromosome Screening (CCS)

Preimplantation Genetic Diagnosis (PGD) and Comprehensive Chromosome Screening are advanced genetic techniques which allow an individual embryo to be analyzed. PGD is a recommended procedure for patients who are carriers of a genetic anomaly or are affected by a genetic condition that drastically reduces the probability of passing the anomaly to their offspring. Additionally, some patients with advanced maternal age or a history of recurrent miscarriages use CCS to select embryos that do not possess chromosomal abnormalities.

PGD or CCS involves the removal and analysis of a limited number of cells from a developing embryo. The analysis of these cells may be performed by fluorescent in situ hybridization (FISH) or polymerase chain reaction (PCR), which allows a geneticist to provide information on the individual embryo's chromosomal make-up. PGD or CCS cases may require extended embryo culture to allow for enough time for genetic analysis to be performed. In consultation with the patient's physician and embryology laboratory, the decision of which embryo(s) and how many embryos to transfer will be made.

Blastocyst Transfer and Culture

A blastocyst is an embryo that has developed 2 different cell types and also contains a central fluid-filled cavity. The outer cells, called the trophectoderm, will become the placenta, and the inner cells will become the fetus. Blastocyst formation in the human usually occurs on the 5^th day after fertilization. By the end of the 6^th day, healthy blastocyst should hatch from its outer shell (the zona pellucida), and within another 24 hours the hatched blastocyst begins to implant in the lining of the mother's uterus.

Over the first 2 decades of experience with in vitro fertilization, embryos were routinely cultured for 2 to 3 days in the laboratory and then transferred to the uterus. This is quite different than when embryos normally enter the uterus (day 5 or 6). After 2 or 3 days of growth inside the body, embryos are found in the fallopian tubes and may not be ready to enter the uterus. Recently, laboratory culture conditions have been improved so that embryos can develop to the blastocyst stage in the laboratory, and therefore be replaced into the uterus at the more "natural" time, Day 5 or 6 after fertilization.

The additional benefit of waiting longer to transfer embryos is reducing the number of embryos needed to be transferred to result in a viable pregnancy. By culturing embryos to the blastocyst stage, we have more opportunity to choose the healthiest ones for transfer. So, optimal pregnancies rates may be obtained by transferring fewer embryos and reducing multiple pregnancy rates.