Infertility In Women

Description

Alternative Names

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) are procedures that either place sperm inside the woman or uses donated eggs or employ techniques that retrieve eggs from the ovary and reimplant them. Fertilization may occur either in the laboratory or in the uterus. The number of live birth deliveries from ART increased by 73% between 1996 and 2000. And currently, 1% of all American babies--more than 35,000--are born each year using assisted reproductive technologies. In general, ART now achieves live births in more than 25% of cycles using fresh, nondonor eggs or embryos--up from 12% in 1988. (Actual pregnancy rates were higher, but some failed to come to term.)

The standard ART procedures are generally called artificial insemination (AI) and in vitro fertilization (IVF). To date no studies have compared the two approaches.

Artificial Insemination

Artificial insemination (AI) it is the least complex of the assisted reproductive technologies and is often tried first in uncomplicated cases of infertility. AI either involves placing the sperm directly in the cervix (called intracervical insemination) or into the uterus (called intrauterine insemination, or IUI). IUI is the standard AI procedure.

It is useful under the following circumstances:

• When the woman's cervical mucus is unreceptive.
• When donor sperm are required.
• If the man's sperm count is very low (although it is preferable if at least five million per milliliter are motile).
• When unexplained infertility exists in both partners.

Those in whom AI fails, couples with specific fertility defects, or when the woman is older may be candidates for more advanced reproductive technologies. (One 2002 study reported, however, that IUI may be effective even in women over 40.)

Pregnancy Rates. A review of 45 studies reported that in unexplained infertility cases, the per-cycle pregnancy rates were 4% for intrauterine insemination (IUI) alone and 8% to 17% per cycle for IUI combined with superovulation, a procedure that uses fertility drugs to bolster egg recovery.

Researchers in 2002 study suggested IUI as a reasonable first option for many women under age 43. It is less expensive and poses less risk for multiple births than the more advanced assisted reproductive technologies (ART), such as in vitro fertilization. Although IVF procedures are more effective per cycle, couples tend to be able to afford more IUI cycles, so the pregnancy rates over time are very similar.

The Artificial Insemination Procedure. The AI procedure is as follows:

• A woman usually (but not always) takes fertility drugs in advance.
• The man must produce sperm at the time the woman is ovulating.
• The sperm are subjected to certain so-called washing procedures. They are then inserted into the uterine cavity through a long, thin catheter.

The administration of fertility drugs and sperm retrieval is timed so that the process can be administered at the time of ovulation. Of interest was a 2000 study in which women who lay quietly for 10 minutes after sperm were implanted had a significantly higher rate of pregnancy than those who got up immediately.

Standard In Vitro Fertilization (IVF)

About 71% of ART procedures now use in vitro fertilization (IVF) with the woman's own eggs. An in vitro procedure is one that is performed in the laboratory. Advances in these procedures have dramatically increased the rate of live births.

The best candidates for IVF are women with damaged fallopian tubes, and some experts believe it is a better option than attempting surgical repair. IVF is also used when infertility is unexplained or when the male partner has the infertility problem. A typical IVF procedure is as follows:

• The physician first induces superovulation using fertility drugs so that several eggs can be harvested from the ovary before they have been released from the follicles. Higher doses of fertility drugs for subsequent cycles do not appear to add any advantage in women who have a poor response the first time.
• To harvest eggs, the physician generally inserts a probe into the vagina and is guided by ultrasound. A needle is then used to drain the liquid from the follicles, and several eggs are retrieved.
• The eggs and sperm are combined in a Petri dish. Between 48 to 72 hours later the eggs are usually fertilized.
• The resulting embryos (the first stage toward the development of the fetus) are reimplanted into the womans uterus.
• It takes about two weeks to determine if the process is successful.

IVF success rates for the first three cycles of treatment are about equal. They then decline modestly for the fourth cycle and drop significantly after the fifth cycle.

Gamete/Zygote Intrafallopian Transfer. Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) are adaptations of IVF. GIFT and ZIFT are used in unexplained female infertility and in mild male infertility. The success rates are similar to those of IVF, but a woman must have at least one functioning fallopian tube.

GIFT: The procedure is as follows:

• The eggs are harvested as in IVF.
• They are mixed with the sperm but not actively fertilized.
• They are immediately injected back into the woman. Laparoscopy, a technique that employs a miniature viewing device, is used with this procedure to guide the placement of the embryos or egg through a long, thin catheter into the fallopian tubes.
• The sperm and egg are placed exactly where they would be in natural fertilization.

ZIFT: The procedure is as follows.

• The eggs are harvested as in IVF.
• They are then mixed with the sperm and, in this case, are fertilized in the laboratory.
• They are then implanted in the fallopian tubes as in GIFT. (The advantage of this procedure over GIFT is that the physician and couple are assured that fertilization has taken place and the eggs can be examined for defects before implantation.)

Success Rates for Standard IVF Procedures

In 2000, 1% of all American babies--more than 35,000--were born using IVF. In general, assisted reproductive technologies achieves live births in more than 25% of cycles using fresh, nondonor eggs or embryos--up from 12% in 1988. (Actual pregnancy rates were higher, but some failed to come to term.) About 35% of the ART-assisted live births in 2000 were multiple ones, with 4.3% being triplets or more.

Success rates have increased in all age groups (although they are still considerably lower in older than in younger women.) Chances for ART success are also greater among women who do not have uterine abnormalities and have had previous successful pregnancies.

The 2000 live-birth success rates by age are given in the following table:

Success rates are also higher or lower depending on whether the woman uses her own eggs or whether they are donated and also whether the eggs are fresh or frozen. The highest rates are with donated fresh eggs (an average of 43.4% per transfer) and the lowest rates are when the woman's uses her own frozen eggs (a range of 22.3% per transfer for women under 35 to 14.6% for women 41 to 42.) It should be noted, however, that using frozen eggs is less expensive than fresh eggs, so the couple may be able to afford more cycles with frozen eggs.

Use of Donor Eggs. Older women are more likely to use donor eggs. In a 2002 study, success rates were the same for women who used donors with an age range of 20 to 40. There were also no differences in delivery rates for recipients up to age 45. Women over 45, however, increasingly had problems with implantation, pregnancy, and delivery.

Use of Frozen Eggs. Frozen eggs tend to have lower success rates because of toxins released by cells damaged in the freezing and thawing tissues. An interesting study in 2002 suggested that the use of lasers to remove these dead cells may increase the chances of success in the thawed embryos.

Other IVF Techniques

In Vitro Maturation. A new technique called in vitro maturation allows fertilization without the use of fertility drugs. In this process, follicles are harvested a few days before ovulation. In such cases, up to 50 have already begun to mature. At this time, about 15 of these maturing follicles can be removed, out of which two or three can produce healthy embryos.

Blastocyst Transfer. Blastocyst transfer is very promising. Instead of implanting the standard two- or three-day-old embryos in the uterus, the procedure implants blastocysts, which are more complex, five-day-old embryos. Fewer blastocysts than embryos need to be implanted, reducing the risk for multiple births. (There is, however, a higher risk for identical twins compared to other procedures.) Offspring may be more likely to be males than females. Pregnancy rates are about 36% with a first attempt but then drop significantly. The procedure is more likely to be successful in younger than older women.

In Vitro Fertilization with Intracytoplasmic Sperm Injection (ICSI). Intracytoplasmic sperm injection (ICSI) is one of a highly sophisticated group of techniques referred to as micromanipulation. ICSI injects one single sperm into an egg using microscopic instruments. It is used for couples who have failed IVF or when the man has severe infertility problems. It is proving to be effective even in some severe female fertility cases, and pregnancy rates are now equivalent to other ART techniques. The procedure itself is deceptively simple.

• A tiny glass tube (called a holding pipet) stabilizes the egg.
• A second glass tube (called the injection pipet) is employed to penetrate the egg's membrane and deposit a single sperm into the egg.
• The egg is released into a drop of cultured medium.
• If fertilized, the egg is allowed to develop for one or two days and then is either frozen or implanted.

The greatest concern with this procedure, if it is successful, is the risk of passing on any male genetic defects that caused infertility in the first place to the offspring. Studies in 2002 and 2003 reported no higher risks in birth defects in children born using ICSI procedures. One study that followed children to age five and reported a higher rate of certain rare disorders, notably Beckwith-Wiedemann syndrome. In such cases, the babies tend to be large with enlarged organs and a higher risk for certain cancers. Research is ongoing and more should be known s the procedure becomes more widespread and children get older.

Immature sperm (spermatids) are now being used in ICSI as well, and the long-term genetic implications of this remain unknown.

Ooplasmic Transfer. Ooplasmic transfer is an experimental procedure that uses the woman's own egg and a female donor's egg and the male sperm for fertilization. Genetic material from the donor's egg plus the sperm are added to the woman's own egg. This has been successful in a few cases, but studies are very early and long-term effects are unknown. Research on this and similar procedures are currently conducted outside the US, where regulations have hindered investigation.