Embryo Transfer: The Critical Step in IVF
How important is the embryo transfer during IVF?
Unquestionably, the IVF doctor’s expertise in performing embryo transfer ranks as one of the most important factors that will determine IVF outcome. It takes confidence, dexterity, skill, and above all, experience to do a good transfer. This having been said, of all the procedures in IVF this is the most difficult to teach. It is a true “art” and there is little doubt that many women will fail to conceive following IVF simply because their doctor could not perform this procedure optimally.
Good quality embryos are those whose cells (blastomeres) continue to divide at a regular and predictable rate, such that within 72 hours of fertilization they contain 6-9 cells and within 5-6 days, develop into expanded blastocysts. Such embryos are the ones that are most likely to be “competent” (i.e., able to propagate a pregnancy upon being transferred to a receptive uterus). Those that do not, are the ones least likely to be “competent”. In fact, embryos that fail to develop into expanded blastocysts within 5-6 days of being fertilized are, almost invariably, chromosomally abnormal (aneuploid) and “incompetent”.
The addition of genetic embryo testing by methods such as comparative genomic hybridization (CGH), which assesses all the embryo’s chromosomes, at least doubles the ability to select truly “competent” embryos for transfer. This vastly increases the baby rate per embryo transferred, markedly reduces the likelihood of miscarriage, and minimizes the occurrence of chromosomal birth defects such as Down’s syndrome.
Ultrasound Guided Embryo Transfer: A Must!
Today all embryo transfers should, in my opinion, be performed under direct ultrasound guidance to ensure proper placement in the uterine cavity. All other factors being equal, such practice alone (if properly conducted) will significantly enhance embryo implantation and pregnancy rates.
How Many Embryos Should be Transferred?
There is an overriding need to minimize the occurrence of multiple gestations, especially high order multiples (triplets or greater). This is because the risk of prematurity-related complications increases proportionate to the number of babies in the uterus. Unfortunately, there are several confounding considerations in determining how many embryos to transfer at a time:
- The older the woman who produces the eggs, the greater the likelihood that upon being fertilized, the resulting embryo(s) will be “incompetent:” As an example: in the case of a woman 33 years old, each morphologically “good looking” embryo (those with a “high grade”) would have about a 20-30% chance of initiating a normal pregnancy, while for a woman in her mid-forties, the comparable rate would be no greater than 5-10%. Thus, the transfer of say, three (3) such “high grade” embryos to the uterus of a younger woman would perhaps yield better than a 40% chance of an IVF success, a 20% likelihood of twins and a 5-10% incidence of triplets. In contrast , the transfer of the same number of “high grade” embryos to the uterus of a woman of 45 years would offer well below a 10% chance of success, less than a 5% likelihood of twins, and virtually no chance at all of triplets. It follows that the number of embryos that might safely be transferred per IVF procedure (without resulting in a high-order multiple) should be governed by the age of the egg provider. So, while it would be reasonable to restrict the number of “high grade” embryos transferred to a younger woman to two (2), the same restriction would be inappropriate and unreasonable in the case of a woman in her 40’s receiving embryos derived from the fertilization of her own eggs.
- Another issue relates to the perceived “quality” of the embryo(s) being transferred. When a decision on how many embryos to transfer is based upon the microscopic appearance of such embryos, then their microscopic “grade” should be taken into consideration. Since it is less likely that a “lower grade” embryo would propagate a baby than would be the case for one that was of “high grade,” it follows that when it comes to older women, it would be both appropriate and acceptable to transfer more low-grade embryos at a time than if the embryos were of a high grade.
- The stage of development that the embryos have reached by the time of the transfer must also be taken into account in deciding how many to transfer. The reason for this is that blastocysts (5 or 6 day) are far more likely to propagate pregnancies than are earlier (day 2-3) embryos. Here again, fewer blastocysts need be transferred at a time. Finally since an embryo’s “competence” can all but be assured in cases where it tests CGH-normal (all its chromosomes are present and intact), the transfer of only ONE such embryo is likely to produce a baby about 60% of the time in such cases (regardless of the age of the egg-provider). It is thus completely feasible to restrict the number of CGH-normal embryos that are transferred to 1 or 2.
As a rule of thumb, at SIRM we tend to transfer two day-3 embryos to women under 39 years, three to women 39-42 years and four to women of 43 years or older.
The Embryo Transfer Process as Performed at SIRM
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 also 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 an oral tranquilizer (usually 5mg of oral diazepam or Valium) about a half hour prior to the embryo transfer, to relax the woman and reduce apprehension. Some IVF programs believe that imagery will help the woman relax and feel positive about the process and, in the process, reduce the stress level. In such programs, a counselor and/or clinical coordinator may help the woman focus on visual imagery for a few minutes immediately prior to embryo transfer so as to enhance her relaxation.
Shortly before being transferred, embryos are put together in a single laboratory dish containing growth medium. The laboratory staff informs the clinic coordinator that the embryos are ready for transfer, and the coordinator prepares the patient and informs the physician that a transfer is imminent.
With the woman properly positioned and her bladder full, the physician inserts a speculum into the vagina to expose the cervix. He/she then irrigates the vagina and cleans the cervix with a sterile salt solution to remove any mucus or other secretions. With an abdominal ultrasound transducer placed suprapubically on the lower abdomen to allow clear visualization of the uterus and the transfer catheter loaded with the embryo(s) the physician gently guides the embryo transfer catheter through the cervical opening into the uterine cavity. Once ultrasound examination confirms that the catheter is properly in place, the embryologist carefully injects the embryos into the uterus whereupon the physician slowly withdraws the catheter. The catheter is then immediately returned to the laboratory where it is examined under the microscope to make sure that all the embryos have been released. Should the embryologist find that one or more of the embryos were retained within, or clinging to the outside of the catheter, those residual embryos would be re-incubated, and the transfer would be repeated so as to deliver the remaining embryos to the uterine cavity.
The male partner or other companion is expected to remain with the patient for emotional support and to otherwise help tend to her needs for the one hour that she remains recumbent. Immediately prior to being discharged following the embryo transfer procedure, an exit interview is conducted whereby the patient/couple is/are given directions.
The patient is then able to return home and advised to be a “couch potato” for 12-24 hours. Absolute bedrest is unnecessary. She can return to work a day or two later.
In the case of a fresh cycle using a patient’s own eggs, the first and second blood pregnancy tests are done at 11 and 13 days after the egg retrieval. In the case of a recipient embryo transfer (as with frozen transfers, egg donor cycles or gestational surrogacy) the tests are done at 12 and 14 days after initiating progesterone therapy.