FertilityAnswers.com - infertility, in vitro fertilization, assisted reproduction, GIFT, ICSI

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Assisted Reproductive Technologies

Assisted Reproductive Technologies (ART's) are a group of treatment options used for couples with infertility that cannot be treated using simpler methods. These procedures have excellent success rates but require significant effort and can be expensive. For all these reasons, advanced treatment options can be stressful. These natural stresses can be minimized if you understand the nuances of the various procedures. We encourage you to learn more and to freely ask questions of your medical team. Understanding the applications for each procedure will help you obtain the appropriate treatment and maximize your chance for success.

There are a number of different types of treatments encompassed under the ART umbrella. These include:

In Vitro Fertilization (IVF)
Gamete Intrafallopian Transfer (GIFT)
Zygote Intrafallopian Transfer (ZIFT) and Tubal Embryo Transfer (TET)
IVF vs. GIFT, ZIFT and TET
Micromanipulation

For additional information on ART, IVF and Success Rates, please follow the links below:

Conventional In Vitro Fertilization (IVF)Therapy

In vitro fertilization, also commonly known as IVF, is the treatment of choice in cases of infertility when both fallopian tubes are blocked. However, IVF may also be used for unexplained infertility, endometriosis, cervical factor infertility, ovulation disorders, or when a man has a low sperm count. Basically, IVF involves taking mature eggs from the woman, fertilizing them with sperm in a dish in a laboratory and then transferring the resulting embryos back to the woman's uterus 2 to 6 days after fertilization is confirmed. Nationwide, approximately 25 percent to 35 percent of women who try in vitro fertilization conceive. At FWHCLA, this number in 2002 was 63.5%. Please see Success Rates for Assisted Reproductive Technologies.

In conventional IVF therapy, a woman' ovaries are hyperstimulated and the mature oocytes (eggs) are retrieved from the woman's ovary. The yield may vary anywhere from one to 30 or more eggs that may be retrieved depending on the responsiveness of the ovaries to the gonadotropins used to stimulate them. These eggs are gathered by the embryologist into an appropriately balanced salt solution and maintained at body temperature (37°C) until such time as they are ready to be inseminated. Meanwhile, a sample of semen containing the sperm destined to be used for each specific set of eggs is collected and processed by cell separation techniques to provide as clean and active a sample of sperm(atozoa) as possible. A major emphasis of the IVF laboratory is directed toward guaranteeing that the correct sperm go with the right eggs through good labeling and check systems. Ultimately, following several hours in culture, eggs and sperm can be mixed and allowed to bind and fertilize in a relatively natural fashion. Depending on the quality and maturity of both eggs and sperm, it is common for fertilization rates to vary considerably relative to the original number of eggs collected. Twenty eggs retrieved in no way guarantees 20 embryos. Likewise, 20 fertilized eggs in no way guarantees that there will be 20 embryos of sufficient quality for both cryopreservation and fresh transfer to the woman's body.

Central to the question of how many embryos are actually utilized in any IVF treatment cycle is the period during which the embryos are cultured in vitro. This can be as little as one day, or up to seven in the case of blastocyst growth and transfer. Assuming that culture conditions are relatively optimal, there is less and less reason not to culture embryos throughout their pre-implantation stages to allow the embryos to "select" themselves for transfer or cryopreservation. The blastocyst is the term given to the very last stage of an embryo prior to it implanting into the endometrial lining of the uterus. The poorer the rates of blastocyst growth are, the more restricted the choice of embryo is at this stage of development. In any event, growth of any embryos to the blastocyst stage improves the level of discrimination of embryo viability available to the embryologist, and is key to reducing the numbers of embryos used for uterine transfer. The more confidence a clinic has in the viability of the embryos it transfers, the less need there is for multiple transfers of three or more embryos. Thus with the transfer of three or less embryos, the risk of multiple pregnancies is significantly reduced, in turn minimizing risks of pregnancy loss or fetal abnormalities common in multi-fetal pregnancies.

For more in-depth information on the IVF process, please see In Vitro Fertilization.

Gamete Intrafallopian Transfer (GIFT)

This is a type of ART in which eggs and sperm are placed into the fallopian tube. The same method of ovulation induction is used as for IVF, and the egg retrieval is performed in the same manner as for IVF. Once the eggs have been retrieved they are placed, unfertilized, along with sperm into the fallopian tube by laparoscopy. This treatment requires a surgical procedure and is performed in an operating room. GIFT can only be performed if the fallopian tubes are open and normal. It is usually not as successful as IVF.

Zygote Intrafallopian Transfer (ZIFT)/Tubal Embryo Transfer (TET)

ZIFT, a combination of IVF and GIFT, transfers fertilized eggs (zygotes) into the fallopian tube. The ovulation induction process, egg retrieval, and insemination in the laboratory are performed in the same fashion as an IVF cycle. However, the zygotes are transferred into the fallopian tube the day after egg retrieval. In TET, more mature pre-embryos are placed in the fallopian tubes on day 2 or 3 after fertilization. ZIFT and TET require a laparoscopic procedure, like GIFT. These procedures are now only rarely used. We will sometimes recommend ZIFT or TET when there is a severe cervical obstruction. ZIFT and TET, like GIFT, can only be performed if fallopian tubes are normal.

IVF Versus GIFT/ZIFT/TET

If tubal disease is a factor then only IVF can be performed and GIFT, ZIFT, or TET are not an option. Because the fallopian tube is the natural site of fertilization and early embryo development, the tubal procedures are theoretically advantageous. However, many well-controlled studies have shown no advantage in using GIFT, ZIFT, or TET over IVF. The experience of many ART programs around the world now support the contention that IVF is the procedure of choice if the embryology laboratory is of the highest quality. Many programs have good GIFT, ZIFT, or TET success rates, but due to subtle laboratory factors, are less successful with IVF. Another major difference between GIFT and IVF, ZIFT, or TET is that with GIFT there is no documentation of fertilization. This procedure should therefore not be performed if a significant egg or sperm problem exists, or if there is any possibility that the fallopian tubes are not perfect.

A major benefit of IVF to the patient is the avoidance of a laparoscopy and the general anesthesia required for GIFT, ZIFT, and TET. We feel that the quality of our laboratory and the success of our IVF program allow us to avoid these unnecessary surgeries for our patients. The ability to transfer fewer embryos with a greater potential for implantation should make GIFT, ZIFT, and TET less appealing. GIFT procedures CAN, however, be performed if indicated or desired by the patient.

Micromanipulation in IVF Therapy

Micromanipulation is the technique whereby sperm, eggs and embryos can be handled on an inverted microscope stage, performing minute procedures at the microscopic level via joysticks that hydraulically operate glass microtools. With the advent of assisted fertilization through micromanipulation, fertilization itself is no longer a hit-and-miss affair. Additionally, embryos can be micro-manipulated for cell biopsy to determine their genetic status as well as aid in their ability to implant through drilling into their outer shell (assisted hatching).

IVF with Intracytoplasmic Sperm Injection (ICSI)

Micromanipulation first saw clinical use in IVF for purposes of assisted fertilization in the treatment of male factor infertility, where fertilization potential was low in cases of poor sperm quality. The ultimate evolution of this approach has been the development of the single sperm injection procedure referred to as Intracytoplasmic Sperm Injection, or ICSI. Using the ICSI technique, the embryologist uses micromanipulation to pick up a single sperm and inject it directly into the egg. This technique is used to fertilize mature eggs in the event of sperm or egg abnormalities. ICSI allows couples with very low sperm counts or poor quality sperm to achieve fertilization and pregnancy rates equal to traditional IVF. It is also recommended for couples who have not achieved fertilization in prior IVF attempts. Sperm of virtually any quality and from any level of the male reproductive tract may be used with the only criterion for use being that the sperm is alive even if it is not moving (motile). Dead sperm may be able to achieve fertilization; however, the DNA or genetic material from such sperm is too degenerate to form a viable embryo. Immature sperm from the testicle or the epididymis can be retrieved for use with ICSI for men who possess no sperm in their ejaculated semen (azoospermia). This azoospermia is either due to an obstruction in the tract (obstructive), or to extremely low production of sperm in the testicle itself (non-obstructive). In certain cases, men may produce sufficient sperm, but they do not survive to the point of ejaculation (necrozoospermia). Consequently, instead of using non-viable sperm from the ejaculate, testicular biopsy will provide a ready source of freshly produced viable sperm.

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ICSI for Non-Male Factor Infertility

The use of ICSI is now routinely applied to a range of clinical situations wherever there is a possibility that conventional in vitro fertilization may be suppressed or not occur. Such situations include the following: idiopathic or unexplained fertility; hyper-responsive ovarian stimulation cases where egg quality may be reduced; post-thaw sperm samples that survive poorly; post-thaw egg insemination; generation of embryos for pre-implantation genetic screening where embryos "clean" from any extraneous contaminating sperm is needed; or, indeed, any case where there is an extreme need to maximize normal fertilization, for example, when a woman has only a few eggs retrieved. It is possible to "rescue" cases following complete failed conventional fertilization with ICSI. The viability potential of these "late-fertilized" embryos is approximately half of timely fertilized embryos; nevertheless, they do generate successful live births. ICSI has become such a common feature of IVF therapy that it is fast becoming the insemination technique of choice.

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Micromanipulation and Assisted Hatching

It has been proposed that a certain number of otherwise viable embryos do not implant simply because they are unable to break free from the surrounding "jelly coat" (zona pellucida) when they reach the blastocyst stage of development. Around an unfertilized egg there exists a transparent glyco-protein coat that acts to protect the egg and regulate normal fertilization by any penetrating sperm. This jelly-like coat continues to protect the early preimplantation embryo until, as a blastocyst, the embryo fills itself up with fluid like a water-filled balloon, pumping itself larger and larger until it ruptures and "hatches" from the zona pellucida. The embryo is now ready to make contact in its naked form with the endometrium and implant. Inappropriate ovarian environment due to advanced maternal age or other factors that may compromise the follicular environment may in certain cases render the zona pellucida thicker or tougher. Such IVF cases may benefit from the application of a form of micromanipulation referred to as "assisted hatching" In this process, the embryo has a hole made in the surrounding zona pellucida prior to transfer to enable it to "hatch" free from the zona pellucida more easily when it expands as a blastocyst in the uterus. This technique has never been unconditionally proven to be effective in any well-defined group of IVF patients, and as such remains essentially an experimental procedure. Holes in the zona pellucida may be made mechanically, chemically, or by laser. With the advent of more routine transfer of blastocyst stage embryos, the future of this technique, usually carried out on day three of development, may seem in question. Indeed, at the blastocyst stage in vitro, it may be most appropriate to dissolve off the entire zona pellucida prior to transferring naked embryos into the uterus. This could be considered the ultimate form of assisted hatching without the need for micromanipulation. Currently, however, assisted hatching can be easily performed using a infrared laser to create a hole in the zona pellucida that allows the embryo an easy means of escape when it is time to try and implant into the uterine wall.

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Embryo Biopsy

Briefly, it is of relevance in any discussion of micromanipulation techniques to mention the potential to biopsy both eggs and embryos. This approach is known as preimplantation genetic diagnosis (PGD) and enables the screening of both the unfertilized egg by removal of the first polar body, or the fertilized multi-cellular embryo by removal of one or more cells either at the 6-12 cell stage or from the trophectoderm of the blastocyst. This material can be probed for both genetic mutations or gross chromosomal errors. This technology remains in its infancy and can be of profound importance clinically, but at this time only for cases with very clear medically-defined needs. The biopsy procedure requires very exacting skills of the IVF laboratory, and the egg or embryo is not entirely free of risk during the procedure. Hence, couples whose offspring have a high chance of inheriting a genetic disorder may have their embryos screened. Women who are at risk of generating eggs with a high risk of chromosomal anomalies can benefit from having their eggs or embryos screened for chromosomal normality. While embryos can have their sex determined through this procedure, the GRS team considers it inappropriate to do so except in cases of sex chromosome-linked disorders.

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Date Page Last Edited: 10/18/2008