by Stephen L. Corson, MD

Here's What You'll Find Below:• In vitro fertilization
• How it works
• Variants of IVF
• Intracytoplasmic sperm injection (ICSI)
• Gamete intrafallopian transfer (GIFT)

In Vitro Fertilization

Assisted reproductive technologies (ART) is a blanket term used to cover in vitro fertilization (IVF) and other procedures designed to produce pregnancy if other methods have failed. The decision to employ IVF comes either after years of frustration with other unsuccessful therapies, or after diagnosis of a specific problem, such as advanced tubal disease or major sperm deficits, which requires IVF to achieve pregnancy. Following is a discussion of IVF, but note that treatment is far from standardized, and clinics vary considerably in their individual approach and philosophy of care.

A Brief History of In Vitro Fertilization

IVF was born in 1978 with the arrival in England of Elizabeth Brown, the first "test-tube" baby, whose mother was infertile as a consequence of fallopian tube closure. This landmark event, however, was preceded by decades of success with IVF in various animal species. Successful fertilization of any kind requires a cell commonly known as an egg (or oocyte) from a female and sperm from a male. Initially used to manage solely obstructions of the fallopian tubes (the tubes that carry the female egg from the ovary to the uterus) that were resistant to surgical correction, it soon became obvious that IVF could be used to solve other reproductive problems. Infertility of unknown causes, infertility caused by endometriosis (a condition where the tissue similar to that of the uterine lining appears elsewhere in the body, usually in the abdomen), and even infertility arising from sperm-related problems can all be treated with IVF and lead to delivery of normal offspring.

How Does IVF Work?

IVF can be divided into four phases:

Phase 1: The first phase consists of stimulating the ovary with hormones injected just beneath the skin or into a muscle in order to cause several eggs to mature. Normally, only one egg matures per menstrual cycle, so additional hormones are usually required to prevent the body (specifically the pituitary gland) from reacting negatively to this excess of eggs. During this stimulation phase, which usually lasts for 8-12 days, blood tests for hormonal levels and ultrasound examinations of the ovaries are carried out in order to monitor the development of the eggs. The doses of the hormone injections, which are usually self-administered or given by the husband after training is received, are determined by the results of the blood tests and ultrasound examinations. The last injection given is that of human chorionic gonadotropin (hCG), the hormone normally produced during pregnancy. Under these conditions hCG serves as the final stimulus for egg maturation.

Phase 2: The second phase, that of egg retrieval, occurs about 34-36 hours after the hCG injection. Oocyte collection used to be performed in an operating room but today almost all retrievals are done in an outpatient, office-type setting. A long, thin needle is inserted through the vagina using ultrasound guidance (where images taken by ultrasound are used to target the needle to the ovary) and the eggs are collected with the needle.

The entire procedure usually takes 8-20 minutes depending on the number of eggs that have developed and the ease of accessing the ovaries. In many centers this is performed with local anesthesia and mild sedation, but some patients prefer to be asleep. Generally, the patient may leave after 30-60 minutes of observation. Once the eggs are harvested, they are isolated from the fluid that surrounds them (called follicular fluid) and placed in a special incubator where temperature, humidity and gas content are tightly controlled.

Phase 3: The third phase involves fertilization of the eggs. In most cases this is simply a process of preparing sperm from a specimen produced by the husband and placing sperm in the same dish as the egg(s). For others, a procedure called ICSI (mentioned below) is employed. About 24 hours later, the eggs are observed for changes suggesting that fertilization has taken place, mainly the presence of two early (pronuclear) masses within the egg.

What takes place over the next few days (in between phase 3 and 4) constitutes the weak link in the IVF process. Simply stated, the soup present in the woman’s tubes and uterus contains many substances which we have not identified to date -- let alone duplicated -- but that normally sustain an egg and early embryo in a woman's body. In natural fertilization, the fertilized egg enters the uterus about four days after ovulation and fertilization, and then does not physically implant in the uterine wall for another two days or so. Until recently, our laboratories could not sustain embryo development for this duration, so clinics were forced to place embryos in the uterus two or three days after egg retrieval.