Definition

The term in vitro refers to a biological procedure that is performed outside of the organism it would normally occur in (in this case the woman). In vitro fertilization (IVF) is the process whereby a woman's egg(s) are fertilized by either her partner's or a donor's sperm outside of her body, (in vitro). After incubation for usually between three and five days, the resultant embryo(s) are transferred into the woman's uterus with the intent that they will implant and result in a pregnancy. IVF is usually the most successful treatment for infertility when other approaches have either failed or will not be of value. The process involves hormonally stimulating the ovaries, aspirating ova (eggs) from the follicles in the woman's ovaries, and incubating them with specially prepared sperm in order that they fertilize.

Applications

IVF was initially developed to treat infertility caused by severely damaged or absent fallopian tubes. However, with many advances in this technology and the resultant significant improvements in success rates, IVF has become a very effective treatment for most other causes of infertility. Furthermore, with the introduction of Intra-Cytoplasmic Sperm Injection (ICSI) where a single sperm is injected into a single egg as in the picture below, the treatment of male factor infertility has been revolutionized.

This technology can be extended to treat women who are unable to produce or cannot use their own eggs (a recipient). Another woman (a fertile donor) is hormonally stimulated, her eggs are collected and fertilized in a laboratory with the recipient's partner's sperm, and the resulting embryos are transferred into the recipient's uterus with the intent of producing a viable pregnancy. This is called donor egg therapy.

History

The first pregnancy resulting from in vitro fertilization was reported in 1973 in The Lancet by the Monash team. This pregnancy resulted in a miscarriage, and subsequently Steptoe and Edwards were successful in creating an IVF pregnancy that resulted in the birth of Louise Brown in 1978. Eight of the first ten babies in the world born following IVF treatment resulted from women treated by the Monash IVF team.

Approaches to Treatment

There are many different approaches to hormonally stimulating the ovaries during IVF treatment. In general, women are initially given medicine to make their ovaries quiescent (down regulation) and then the ovaries are subsequently hormonally stimulated. Spontaneous ovulation during the cycle is usually prevented by blocking the natural ovulation process. Hormonal stimulation is monitored closely by a combination of ultrasound examinations to measure the number and size of follicles that are developing on the woman's ovaries (as in the image below), and the oestrogen level in her blood stream. 

When both of these measures suggest that egg(s) are nearing maturity, the woman is given a "trigger" injection to finally prepare egg(s) for the collection procedure. Following collection the woman is usually given medication to help prepare the lining of the uterus (endometrium) to receive and support embryo(s) after transfer.

Egg Collection Procedure

Under either conscious sedation or a general anaesthetic, egg(s) are usually retrieved from the woman using a transvaginal ultrasound guided technique, where a very thin needle pierces the vaginal wall in order to reach the ovaries as in the video below. Through this needle follicles are drained (aspirated), and the follicular fluid is handed to the IVF scientist in order to identify ova (eggs). The retrieval procedure usually takes about 15-30 minutes.

Laboratory Processes

After fertilization of egg(s) in the IVF laboratory, embryos are generally cultured for between three (the eight cell stage) and five days (the blastocyst stage as in the picture below). The embryos are graded on quality, and then the best quality embryo(s) are transferred into the woman's uterus with any extra good quality embryos, if available, being frozen for use at another time (cryo-preserved). In order to determine the quality of embryos, they are graded by the embryologist (scientist) based on the number of cells, degree of fragmentation and other cellular characteristics.

Embryo Transfer

The transfer is a relatively straightforward procedure, where a very thin and floppy catheter that contains the embryo is inserted into the uterus via the woman's cervix (very similar to having a PAP smear and then the embryo is placed into the uterus in a tiny bubble of fluid (medium) as in the schematic diagram below.

The number of embryos transferred depends on a number of factors such as the age of the woman, the number of good quality embryos and past response(s) to treatment. In Australia there is a progressive trend towards transferring one embryo (elective single embryo transfer or ESET) in order to minimize the risk of multiple pregnancy and the resultant risk(s)/complication(s) for the mother and babies. Considerable training and skill in the embryo transfer technique is required by the Fertility Specialist in order to achieve high pregnancy rates.

Potential Complications

As indicated above, a major complication of IVF is the risk of multiple and high order multiple birth. The level of risk is directly related to the practice of transferring multiple embryos at the time of embryo transfer. Multiple births are associated with an increased risk of miscarriage, prematurity, obstetrical complications, and long-term complications for babies as a consequence of premature birth. In order to avoid these risks there is an ever increasing frequency of elective single embryo transfer as previously described. Even with ESET, there is approximately a 5% chance of a multiple or higher order multiple birth when a single blastocyst is transferred. Other possible risks include the development of ovarian hyperstimulation syndrome (OHSS) in 1-3% of women, ectopic pregnancy in 1-3% of women, and rarely trauma, bleeding or infection related to the egg collection procedure. In a proportion of cases (9%), a treatment cycle is cancelled as the women either under or over responds to the medication used to stimulate her ovaries. Frequently, following a cancelled cycle another treatment is planned a few months later where the drug regime is modified in order to achieve a better response.

The issue of birth defects remains a controversial topic in IVF. A majority of studies do not show a significant increase after use of IVF. Some studies suggest higher rates for ICSI, while others do not support this finding.

Cryopreservation

As mentioned above, if multiple good quality embryos are generated, patients may choose to cryopreserve (freeze) embryos that are not transferred. Those embryos are stored in liquid nitrogen and can be preserved for a number of years. Patients who do not become pregnant or want another child following a successful treatment can then aim to become pregnant using such embryos without having to go through a full (stimulated) IVF treatment cycle. Provided certain criteria are met, "spare" embryos resulting from fertility treatments may also be donated to another woman or couple.

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