What is Staggered IVF?
Staggered IVF is a new approach to IVF. It involves the use of CGH to identify chromosomally normal (“competent”) embryos/blastocysts for selective transfer, thereby markedly improving the efficiency of the entire process. It addresses three important issues: First, it significantly increases the success rate per embryo transferred and thereby allows fewer embryos to be transferred per ET. This reduces the incidence of multiple births. Second, by reducing the risk of aneuploidy, the commonest cause of early pregnancy loss, it significantly lowers the incidence of miscarriages. Third, it minimizes the risk of chromosomal birth defects such as Down’s syndrome.
Staggered-IVF involves dividing the IVF cycle into 2 separate stages. The first segment involves ovarian stimulation and egg retrieval, while the second comprises the embryo transfer (which can be performed weeks, months, or even years later). The purpose of dividing the cycle into two parts is to allow the genetics laboratory sufficient time to complete CGH on one or more of the cells (blastomeres) that were surgically removed from the embryo 3 days after fertilization by intracytoplasmic sperm injection (ICSI).
First Stage of Staggered-IVF:
1. Ovarian stimulation, ultrasound & hormonal monitoring and egg retrieval are conducted in preparation for ICSI, which is performed 4-6 hours later. Three possible approaches can be taken to obtain a DNA specimen for CGH analysis:
a. Polar body (PB) biopsy: Here the PB is removed from immediately under the envelopment (zona) of each mature egg immediately following ER.
b. Blastomere Biopsy: A single cell (blastomere) is removed from each 6-9 cell embryo, 3 days following ET.
c. Blastocyst biopsy: A number of cells (≥5) are removed from the outer layer (trophectoderm) of each expanded blastocyst, 5-6 days post-fertilization.
DNA samples obtained through ether (or a combination) of the above approaches are then processed in preparation for CGH analysis which is a highly complex process that takes several weeks to complete.
2. All fertilized eggs and embryos remain in culture for up to six days. Those that develop into healthy expanded blastocysts (the most advanced stage of pre-implantation development) are cryopreserved (frozen) using a new ultra-rapid and highly efficient method known as vitrification. Until 2003, the preferred method for cryopreserving embryos was by using “conventional” (slow) freezing methodology. This, unfortunately, results in ice crystal formation inside blastomeres, damaging them and reducing embryo “competency”. The introduction of vitrification-whereby the embryo is frozen 600 times faster than with conventional freezing-is so rapid that there is no time for intracellular crystallization and its resulting cell damage to occur. With conventional slow freezing 30%-40% of embryos are lost during the freeze/thaw process. By contrast, <10% are lost with vitrification.
3. Fully developed blastocysts, determined through CGH to have all twenty three pairs (46) chromosomes intact (euploid), are retained in the vitrified state (cryostored), while those determined by CGH to be chromosomally abnormal (aneuploid) are discarded.
4. The patient is subsequently informed of the CGH test results and a date is set for the transfer of up to two euploid embryos.
Second Stage of Staggered IVF:
Patients who have at least one “competent” blastocyst in cryostorage return for clinical assessment, ultrasound, and hormonal monitoring in preparation for embryo transfer (ET). The “competent” vitrified blastocyst(s) selected for transfer is/are warmed (thawed) and transferred to the recipient’s uterus under ultrasound guidance.