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.

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In Vitro Fertilization (IVF-ET)

History

In Vitro Fertilization Pre-Embryo Transfer (IVF-ET) is a fertility procedure which first succeeded as recently as 1978 by Dr. Edwards (an embryologist) and Dr. Steptoe (a gynecologist) in England. Since then the technology has been further refined and developed by physicians and embryologists, with over 20,000 babies born worldwide. The possibility of a continuing pregnancy being achieved by IVF has improved from practically nil to one chance in 4 to 6 at IVF centers worldwide.

The possibility of a pregnancy being achieved for any one patient cannot be predicted, as it depends on many variables - such as age and the reproductive health of both the wife and the husband. Although the chance of success varies from case to case, a thorough evaluation is required to predict the probability of pregnancy in any given situation.

IVF Without Surgery - Transvaginal Oocyte Retrieval

Due to improvements in ultrasound imaging, surgery is no longer necessary for most In Vitro Fertilization patients. A technique for recovery of eggs from the ovary is described below. It uses a sonographically-guided needle to replace the surgical procedure which previously was used to recover oocytes (eggs). This procedure, called Transvaginal Oocyte Retrieval, requires neither hospitalization nor general anesthesia.

In order to prepare a proper environment in the woman and to increase the chances of recovering several healthy and mature eggs, the woman will undergo about two weeks of intensive preparation. This will include hormonal therapy with "fertility drugs." Blood tests and ultrasound scans of the ovaries are used to determine the optimal time to retrieve the eggs from the ovary. This optimal time is just before ovulation when the oocytes are almost ready for fertilization.

At the proper time, an outpatient procedure under local anesthesia will allow the female's eggs to be visualized by ultrasound and retrieved from the ovary by placing a needle through the vaginal wall. The mild discomfort that the patient feels has been described as similar to a Pap smear or endometrial biopsy. After a short rest, the patient will be able to go home and resume normal activities.

The fluid from the follicles is examined under the microscope by the embryologist, who locates the eggs and keeps them in the laboratory under physiologic conditions. The embryologist will place the sperm with the eggs when they are ready for fertilization. Usually, the eggs will develop into cleaving pre-embryos, whose cells divide 2 or 3 times to become preimplantation embryos (pre-embryos). They are maintained in laboratory dishes, in a nutrient mixture which acts as a substitute for the environment that would otherwise have been provided by the fallopian tubes.

Using a special catheter, the couple's pre-embryos will be passed through the vagina and into the uterus at the time the pre-embryos would normally have reached the uterus (2+ days after retrieval).

After the pre-embryo placement in the uterus, the patient will lie quietly in a bed for about an hour, and then will return home.

IVF-ET- Questions and Answers

Q: Will the IVF technique damage my ovaries?

A: There is no evidence to suggest that either normal laparoscopy or ultrasound egg retrieval damages the ovaries. In fact, some reports in the medical literature suggest that following ovarian biopsy, pregnancies occur in couples with a long-term history of infertility.

Q: Will scar tissue around my ovaries make it impossible to retrieve the eggs?

A: Not ordinarily. The surgeon must be able to see the follicles in order to guide the needle to the proper spot for retrieval of the eggs whether by sonographic (ultrasound) or surgical methods.

Q: What if I ovulate before oocyte (also called egg or ovum) retrieval?

A: Once ovulation has occurred it is impossible to retrieve the eggs. The entire team of physician, nurse and embryologist will monitor your cycle very carefully to avoid premature ovulation.

Q: If an egg is not retrieved or if the technique does not produce a pregnancy on the first attempt, how soon can the procedure be repeated?

A: This depends on the individual. The primary reason for delay is to allow the patient's normal menstrual cycle to resume, which may take 2 to 3 cycles.

Q: How many times will IVF be repeated per couple?

A: There is no specific number. This is determined by the couple together with the physician.

Q: Can we have intercourse during the two-week period before an IVF procedure is performed?

A: Most definitely. We recommend that the husband refrain from ejaculation for at least 48 hours, but for no more than 5 to 6 days preceding egg retrieval. This precaution assures that the semen sample obtained for IVF will contain a maximum number of healthy, motile sperm.

Q: After the IVF procedure, how long must we wait to have intercourse?

A: Although a definite time of abstinence to avoid damage to the pre-embryo has not been determined, most experts recommend abstinence for two to three weeks. Theoretically, the uterine contractions associated with orgasm could interfere with the early stages of implantation. However, intercourse the night before pre-embryo transfer is acceptable. Some physicians will advise intercourse before transfer as they feel that this will improve the chances of a pregnancy.

 

Q: What about other activities? How soon can I resume my normal routine?

A: The IVF team recommends that the patient be sedentary for a full 24 hours following pre-embryo placement in the uterus. Strenuous exercises such as jogging, horseback riding, swimming, etc. should be avoided until pregnancy is confirmed. Otherwise, the patient is free to return to her regular activities.

Q: How soon will I know if I'm pregnant?

A: Pregnancy can be confirmed using blood tests about 13 days after egg aspiration. Pregnancy can be confirmed by ultrasound 30 to 40 days after aspiration.

Q: I had my tubes tied (tubal ligation) several years ago. Would I be a candidate for IVF?

A: Perhaps, in certain situations, IVF may be cheaper and physically less demanding than surgery to repair you fallopian tubes.

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 selectereasons why pregnancy may not occur following In Vitro Fertilization (IVF)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