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Can Embryo Co-Culture Improve IVF Success?
a blog by David Kreiner, M.D., F.A.C.O.G., May 10, 2010
IVF success is dependent on many factors: egg and embryo quality, the placement of the embryo into the uterus, and the environment surrounding implantation. These factors are all paramount to the ultimate goal of creating a pregnancy that leads to a live baby.
Typically, patients present with their own gametes (eggs) so the genetics and pregnancy potential of the eggs and sperm is usually predetermined when patients first walk in the door to an IVF program. As an REI and IVF specialist, I have dedicated my career to optimizing those other factors that we may influence.
In the late 1990’s I recorded data on all my embryo transfers including the distance the catheter tip was placed into the uterine cavity, number of cells and grade of the embryos, difficulty of the transfer, use of tenaculum etc. I presented my results at the ASRM in 2000, highlighting the two-step transfer to the middle of the uterine cavity and the replacement of the tenaculum with a cervical suture when needed which radically improved pregnancy rates.
Optimizing the Uterine Environment
Hormonally, we have supplemented patient’s cycles with progesterone through both vaginal and parenteral (intramuscular) administration as well as estrogen that we monitor closely after embryo transfer and make adjustments when deemed helpful.
The greatest improvement in pregnancy rates for the past several years, however, has been due to a culture revolution in IVF: The media environment bathing and feeding the embryos. All these advances have had a great impact on IVF success rates to the point that 50% of retrievals will result in a pregnancy. Unfortunately, older patients and some younger ones have yet to share in this success.
How Co-Culture Works
Many IVF programs have reintroduced the concept of utilizing a co-culture medium to improve the quality and implantation of embryos. Co-culture is a procedure whereby “helper” cells are grown along with the developing embryo. Today, the most popular cell lines include endometrial cells (from the endometrium, or uterine lining) and cumulus cells from women’s ovaries. Both cell lines are derived from the patient, thereby eliminating any concerns regarding transmission of viruses. Endometrial cells are much more difficult to obtain and process, while cumulus cells are routinely removed along with the oocytes during IVF retrieval.
Cumulus cells play an important role in the maturation and development of oocytes. After ovulation, cumulus cells normally produce a chemical called Hyaluronan. Hyaluronan is secreted by many cells of the body and is involved in regulating cell adhesion, growth and development. Recent evidence has shown that Hyaluronan is found normally in the uterus at the time of implantation.
Co-culture of cumulus cells provides an opportunity to detoxify the culture medium that the embryos are growing in and produce growth factors important for cell development. This may explain why some human embryos can experience improved development with the use of co-culture.
Preparation of co-culture cells starts with separation of the cumulus cells from the oocytes after aspirating the follicles. These sheets of cells are washed thoroughly and then placed in a solution that permits the sheets to separate into individual cells. The cells are then washed again and transferred to a culture dish with medium and incubated overnight.
During this time, individual cells will attach to the culture dish and create junctions between adjoining cells. This communication is important for normal development. The following morning, cells are washed again and all normally fertilized oocytes (embryos) are added to the dish. Embryos are grown with the cumulus cells for a period of three days to achieve maximum benefit.
Co-culturing embryos has improved implantation and pregnancy rates above and beyond those seen with the IVF advances previously described. More importantly, it promises to offer advantages for those patients whose previous IVF cycles were unsuccessful.