Indications

Initially IVF was developed to overcome infertility due to problems of the fallopian tube, but it turned out that it was successful in many other infertility situations as well. The introduction of intracytoplasmic sperm injection (ICSI) addresses the problem of male infertility to a large extent. Thus, for IVF to be successful it may be easier to say that it requires healthy ova, sperm that can fertilize, and a uterus that can maintain a pregnancy. Cost considerations generally place IVF as a treatment when other less expensive options have failed. This means that IVF can be used for females already gone through pregnancy. The donated oocyte can be fertilized in a crucible. If the fertilization is successful, the fertilized egg will be transferred into the uterus, within which it will develop into an embryo.

Method

Ovarian stimulation

Treatment cycles are typically started on the third day of menstruation and consist of a regimen of fertility medications to stimulate the development of multiple follicles of the ovaries. In most patients injectable gonadotropins (usually FSH analogues) are used under close monitoring. Such monitoring frequently checks the estradiol level and, by means of gynecological ultrasonography, follicular growth. Typically approximately 10 days of injections will be necessary. Endogenous ovulation is blocked by the use of  GnRH agonists or GnRH antagonists.

Oocyte retrieval

When follicular maturation is judged to be adequate, human chorionic gonadotropin (β-hCG) is given. This agent, which acts as an analogue of luteinising hormone, would cause ovulation about 36 hours after injection, but a retrieval procedure takes place just prior to that, in order to recover the egg cells from the ovary. The eggs are retrieved from the patient using a transvaginal technique involving an ultrasound-guided needle piercing the vaginal wall to reach the ovaries. Through this needle follicles can be aspirated, and the follicular fluid is handed to the IVF laboratory to identify ova. The retrieval procedure takes about 20 minutes and is usually done under conscious sedation or general anesthesia.

IVF laboratory

In the laboratory, the identified eggs are stripped of surrounding cells and prepared for fertilization. In the meantime, semen is prepared for fertilization by removing inactive cells and seminal fluid. The sperm and the egg are incubated together (at a ratio of about 75,000:1) in the Culture media for about 18 hours. By that time fertilization should have taken place and the fertilized egg would show two pronuclei. In situations where the sperm count is low a single sperm is injected directly into the egg using intracytoplasmic sperm injection (ICSI). The fertilized egg is passed to a special growth medium and left for about 48 hours until the egg has reached the 6-8 cell stage.

Laboratories have developed grading methods to judge oocyte and embryo quality. Typically, embryos that have reached the 6-8 cell stage are transferred three days after retrieval. In many American and Australian programs, however, embryos are placed into an extended culture system with a transfer done at the blastocyst stage, especially if many good-quality day-3 embryos are available. Blastocysts may give higher pregnancy rates if embryo quality is in doubt. However, many studies have shown no difference in pregnancy rates between day-3 and day-5 transfers.

Embryo transfer

Embryos are graded by the embryologist based on the number of cells, evenness of growth and degree of fragmentation. The number to be transferred depends on the number available, the age of the woman and other health and diagnostic factors. In countries such as the UK and New Zealand, a maximum of two embryos are transferred except in unusual circumstances. This is to limit the number of multiple pregnancies. The embryos judged to be the "best" are transferred to the patient's uterus through a thin, plastic catheter, which goes through her vagina and cervix. Often, several embryos are passed into the uterus to improve chances of implantation and pregnancy.

Post-transfer

The patient has to wait two weeks before she returns to the clinic for the pregnancy test. During this time she may receive progesterone—a hormone that keeps the uterus lining thickened and suitable for implantation. Many IVF programs provide additional medications as part of their protocol.

Success rates

Chance of a successful pregnancy is approximately 20-30% for each IVF cycle, although selected clinics are now able to quote rates up to 50% per cycle. There are many factors that determine success rates including the age of the patient, the quality of the eggs and sperm, the duration of the infertility, the health of the uterus, and the medical expertise. It is a common practice for IVF programs to boost the pregnancy rate by placing multiple embryos during embryo transfer. A flip side of this practice is a higher risk of multiple pregnancy, itself associated with obstetric complications.

IVF programs generally publish their pregnancy rates. However, comparisons between clinics are difficult as many variables determine outcome. Furthermore, these statistics depend strongly on the type of patients selected.

There are many reasons why pregnancy may not occur following IVF and embryo transfer, including

• The timing of ovulation may be misjudged, or ovulation may not be able to be predicted or may not occur
• Attempts to obtain eggs that develop during the monitored cycle may be unsuccessful
• The eggs obtained may be abnormal or may have been damaged during the retrieval process
• A semen specimen may not be able to be provided
• Fertilization of eggs to form embryos may not occur
• Cleavage or cell division of the fertilized eggs may not take place
• The embryo may not develop normally
• Implantation may not occur
• Equipment failure, infection and/or human error or other unforeseen and uncontrollable factors, which may result in the loss of or damage to the eggs, the semen sample and/or the embryos