Embryo Transfer

Developments in reproductive technology are occurring at a rapid rate in animal science as well as in human biology. In vitro fertilization, embryo culture, preservation of embryos by freezing (cryopreservation), and cloning technology yield embryos that are produced outside of the female reproductive system. Embryo transfer permits continued survival of embryos by insertion into the female reproductive system.

Traditionally, relatively little scientific attention has been focused on the technique of human embryo transfer, as it is considered an unimportant variable in the success of an in vitro fertilization cycle. Essentially, the characteristics of embryo transfer in the human have changed little during the twenty years since the British physician R. G. Edwards described the technique in the 1980s.

While cell culture in vitro has made remarkable strides, embryos can be sustained in culture for only a few days. Thus, their survival is dependent upon transfer to the hospitable and nurturing environment of the uterus of a foster mother. While embryo transfer may seem to be high technology, it actually got its start well over a century ago and over the past decade, evolution in culture conditions (as well as stage-specific or "sequential" complex media) have significantly increasing the viability of in vitro fertilized embryos.

Embryos may be transferred to the patient on day 1(zygote stage) of development, on day two (two-cells to four-cells stage), on day three (six-cells to eight-cells stage), on day four (morula), or on days five to seven (different blastocyst stages). The process of embryo transfer includes several steps and the overall pregnancy rate is affected by several factors. One of the most difficult considerations of embryo transfer is the determination of which embryos are most suitable for transfer into the uterus. Recent advanced technologies such as micromanipulation yield increased successes in embryo implantation.

Selection of embryos is an important issue, because the higher the number of embryos transferred, the higher the pregnancy rate. The multiple pregnancy rate also increases, a condition that often is not desirable for the survival of all fetuses. To avoid this, it is important that embryos be selected prior to implantation. The embryo is selected for quality of viability and other important characteristics. Embryo scoring techniques have been developed to evaluate the potential for embryo implantation including cell number, fragmentation characteristics, cytoplasmic pitting, blastomere regularity, presence of vacuoles, and blastomere expansion. Cell stages at the time of transfer correlate to embryo survival because its genome activation occurs between the four-cell and eight-cell stages of pre-implantation development. Events used to score the embryos include embryo metabolism assessment and pre-implantation genetic diagnosis. Genetic abnormalities of the embryo as well as defects in uterine receptivity are also factors in the success of embryo transfer. Additional aspects of successful implantation include bed rest following embryo transfer, the absence of hydrosalpinx (blocked, fluid-filled fallopian tubes) that could lead to washing out of the implanted embryos by intermittent leakage of the hydrosalpingeal fluid. Should uterine contractions occur after transfer, the embryos could be expelled down through the cervix, or up into the fallopian tubes, instead of implanting in the uterus. Additionally, the presence of blood on the outside of the transfer catheter tip correlates with lower rates of successful implantation.

The majority of embryo transfers are currently carried out by cannulating (inserting a hollow tube into) the uterine cavity via the cervix (transcervical transfers). A catheter is inserted inside the uterus and the embryos are deposited at least one to two millimetres from the fundus. Disadvantages include possible cervical stenosis, the risk of infection from the introduction of microorganisms, and release of prostaglandins that may cause contractions. Interaction between the embryo and the endometrium is another important topic in determining embryo transfer success. Paracrine modulators are necessary for embryo-uterine interactions and they are more favorable during the so called " implantation window" that generally occurs between days 18 and 24 of the normal menstrual cycle. This time interval can be assessed either by endometrial biopsies or imaging techniques (ultrasound and magnetic resonance imaging).