Embryo Transfer Process
Embryo transfer is a critical rate-limiting step in IVF. However, the level of expertise in performing this important procedure varies widely. It is difficult to standardize a procedure that combines dexterity and skill with know-how. Alarmingly, there are still IVF practitioners who routinely perform ET without using ultrasound guidance to make certain that the embryo(s) is/are deposited in the uterus with precision. In some cases, where the uterine cavity cannot be adequately visualized, the experienced physician can be successful doing the embryo transfer by feel, but this represents the exception rather than the rule. All embryo transfers should be performed under direct ultrasound guidance to ensure proper placement within the uterine cavity. This practice will significantly enhance embryo implantation and pregnancy rates. Although an embryo can migrate after initial placement; ideal conditions should minimize the chance of this occurring.
We prefer to perform all embryo transfers when the woman has a full bladder. This facilitates the visualization of the uterus by abdominal ultrasound and causes reflex nervous suppression of uterine contractility. The patient is allowed to empty her bladder 10 minutes following the embryo transfer.
It is important that the woman be as relaxed as possible during the embryo transfer because many of the hormones that are released during times of stress, such as adrenaline, can cause the uterus to contract. Accordingly, we offer our patients 5mg of oral diazepam (Valium) or comparable muscle relaxing anti-anxiety medications about a half-hour prior to the embryo transfer. This helps to relax the patient and reduce her apprehension.
Some IVF programs believe that guided imagery helps the woman relax and feel positive about the embryo transfer; thereby reducing the stress level even further. This therapy involves a counselor, clinical coordinator or the future father assisting the patient to focus on visual imagery for a few minutes immediately prior to embryo transfer so as to enhance her relaxation. There are also various pre-recorded programs available that can be listened to for similar results.
Once sufficiently relaxed, the patient is helped into the position familiar to women that have received a pap smear, but taking care to make her as comfortable as possible. For patients that choose assistance from relaxation therapy, a counselor or nurse is usually present at the bedside, coaching her in relaxation exercises during the procedure. After confirmation that her bladder is adequately full to provide clear ultrasound images, the physician first inserts a speculum into the vagina to expose the cervix and then may clean the cervix with a solution to remove any mucus or other secretions. The abdominal ultrasound transducer is held against the lower abdomen so that the uterus is clearly visualized.
Once properly prepared, the physician then informs the embryology laboratory that all is well and awaits the arrival of the transfer catheter that will be loaded with the embryos. The physician gently guides the catheter through the woman’s cervix into the uterine cavity. When the catheter is in place, the embryologist carefully injects the embryos into the uterus, and the physician slowly withdraws the catheter. The catheter is immediately returned to the laboratory, where it is examined under the microscope to make sure that all the embryos have been deposited. Any residual embryos would be re-incubated, and the transfer process would usually be repeated to deliver the remaining embryos. The male partner or another companion is requested to remain with the patient for emotional support and otherwise tend to her needs for the one hour she remains recumbent. Immediately prior to being discharged following the embryo transfer procedure, an exit interview is conducted whereby the patient is given directions.
Hormonal supplementation is usually recommended and involves the administration of intramuscular injections of progesterone and/or vaginal suppositories (comprising estradiol valerate and micronized progesterone) until a blood pregnancy test is performed approximately eight days later (the chemical diagnosis of pregnancy). In selected cases, such progesterone treatment can be replaced with Crinone vaginal gel or Endometrin vaginal inserts. If the pregnancy test is negative or the plasma HCG levels fail to rise appropriately in the ensuing days, all hormonal support is abruptly discontinued.
If an appropriate rise in HCG concentrations has been confirmed, oral dexamethasone and heparin are continued until the 8th week of pregnancy. At this point heparin treatment is stopped, while dexamethasone is tapered down and stopped within a week or two.
An ultrasound examination is performed approximately three weeks after the chemical diagnosis of pregnancy. This examination will accurately indicate the number of gestational sacs and therefore the number of embryos that have successfully implanted. Some patients remain under the care of their RE throughout the duration of the first trimester, whereas others will be referred to an OB/GYN from this point forward.
It has long been debated whether to transfer embryos on day 3 or on day 5-6 (as blastocysts) post fertilization. In 1997, researchers in Australia, Scandinavia and the USA concurrently developed a new generation of culture media that can reliably support embryo growth until the fifth or sixth day of culture. This achievement was based on the premise that the metabolic needs of the early embryo change as it moves through the fallopian tube to the endometrial cavity. These new-generation media are designed to more closely mimic the environment with the fallopian tube-the natural site of the first week of development. Using “sequential culture systems,” approximately 40-50% of “good quality” day-3 embryos (7-9 cells with minimal fragmentation) can now be reliably grown to the expanded blastocyst stage, making it possible for blastocyst transfer to be more widely available. Since in a natural pregnancy, it is typically at the blastocyst stage that an embryo arrives in a fertile uterus, we have every reason to believe it should be the goal of IVF therapy as well.
One goal of culturing embryos to the blastocyst stage is to cull the poor quality (chromosomally abnormal or aneuploid) embryos in the process of prolonged culture. However, this is not meant to imply that all “expanded blastocysts” are chromosomally normal. However, embryos that do not survive to the blastocyst stage are almost invariably chromosomally abnormal (aneuploid) and thus even if they had been transferred to the uterus earlier on in their developmental stage, could not have propagated a successful pregnancy. It follows that because so many aneuploid embryos are culled out in the culturing process, an embryo that survives to the blastocyst stage is much more likely to propagate a pregnancy.
Simply stated, the major benefit from extended embryo culture to the blastocyst stage is that it facilitates natural selection of the best quality embryos. It is most useful among patients with multiple good quality embryos to choose from on day 3.
It is well accepted that cell number and morphologic appearance on day 3 alone are not predictive of blastocyst development or pregnancy. Unfortunately, some women will not have any embryos that survive to blastocyst, despite the fact that they appear good on day 3. However, in reality, these additional two days add tremendous diagnostic information that aids the physician in counseling couples regarding future cycles. Some would consider the risk of not having a transfer as an argument against the use of blastocyst culture. However, we feel that it is best instead to consider the associated diagnostic and therapeutic value, as well as the cost savings of not transferring or storing incompetent embryos. Again, it must be emphasized that embryos that do not survive to the blastocyst stage are in the vast majority of cases chromosomally abnormal (aneuploid) and as such would not result in a viable pregnancy anyway.