Failure of embryo implantation in In-vitro fertilization
The first baby from In-vitro fertilisation was born in 1978 through the research efforts of Steptoe and Edwards. Since then the process has been improved through numerous technologies, which has modified it to better standards. It has gone through series of research to become what we know it to be today.
A lot of work has been dedicated to research, especially in the areas of ovarian stimulation, oocyte retrieval, embryo culture and transfer and embryo implantation which in turn improved IVF success rate to 40 per cent per cycle.
In reference to the four areas mentioned above, one can say that ovarian stimulation, oocyte retrieval, embryo culture and transfer has been further developed to almost 99 per cent success rate, while embryo implantation still have grey areas and much work still needs to be done.
It is believed that once this last area gets close to achieving 99 per cent success rate, then we can expect the success in IVF to approach 99 per cent. This brings us to our subject below and what we have done to improve embryo implantation in our centre.
Mrs. A.O is a 42 year-old woman with secondary infertility due to advanced age and multiple myomectomy. Physical examination only revealed abnormal discharge from the breasts. The results of her IVF screening, hysterosonogram (which helps to visualise the womb under ultrasound) and hormone profile all came out normal. The Seminal Fluid Analysis of her husband indicated oligospermia, a condition of low sperm count. The plan was to do IVF/ICSI (IVF with Intracytoplasmic Sperm Injection) with Pre-Genetic Diagnosis and family balancing as requested by patient.
The patient underwent the stimulation process and a total of 32 egg cells were retrieved, out of which 23 were fertilised. The embryos were sent for PGD to detect any chromosomal abnormality as previously recommended. Unfortunately, the test revealed there were no normal embryos thus transfer had to be cancelled.
A second stimulation process was initiated about a month later and 31 egg cells were retrieved, out of which 24 fertilised (12 blastocysts were biopsied and vitrified). Frozen Embryo Transfer was scheduled after the embryos were tested. Three grade B euploid blastocysts were warmed and transferred into a well prepared womb with adequate lining. The patient was subsequently placed on relevant medications following successful transfer. Blood pregnancy tests done on the 12th and 14th days after the transfer were negative.
Mrs. A.O. came back two months later and another FET was done. Two embryos were transferred this time, but, unfortunately, her blood pregnancy test done on day 13 and 15 after transfer remained negative.
With this turn of events, a quantitative immunological test was carried out, testing for IgG, IgM, IgA, anti-phospholipids antibody and anti-cardiolipins. Also a Thyroid Function Test was done and it showed sub-clinical hyperthyroidism, which may have contributed to implantation failure. A repeat hysterosonogram done found polyps in the womb and these were surgically removed.
After this, a 3rd stimulation process was commenced and 25 egg cells were retrieved, out of which 23 fertilised and 12 made it to freezing stage. One the third day, two embryos were transferred into the womb, which had a thickness of 10.4mm. The patient was given relevant medication after the transfer for her thyroid hormone stabilisation. Blood pregnancy test done 14 days after still showed a negative result.
Mrs. A.O. was programmed for another FET cycle from the leftover embryos and this time around, between five and six sessions of the Hypoxicator, as well as orthomolecular supplements at the Modern Mayr Therapy Centre, were given. The Hypoxicator sessions were done to aid cell division and implantation by acting on the mitochondria of the cells. Thereafter, IV immunoglobulin was given prior to and after embryo transfer. Two embryos were warmed and transferred with luteal support. Pregnancy test done showed positive results, with evident heart beat at 6 weeks.
Pregnancy progressed as expected without complications. Mrs. A.O. gave birth to a bouncing baby girl. Mother and child are doing very well till date.
Based on this patient’s outcome and a good number of others, more research is being done to determine the effect of Hypoxicator, orthomolecular supplement and IVIG on mitochondrial cells and pregnancy outcome.
It is known that the main function of the mitochondrion (a membrane-bound organelle found inside the cells) is to produce energy for cellular activity. Eggs have more mitochondria than other cells in the body and they need many mitochondria, in part to produce the energy required for cell division during early embryo development and embryo implantation process.
It is thus suggested that the hypoxicator and the orthomolecular supplements work in synchrony to improve the quality of mitochondrial energy. These orthomolecular substances are potent antioxidants that are naturally made in the cells of the body for cellular energy production and they can be augmented using various techniques. IVIG in turn aids embryo receptivity and implantation and thus reduces embryo rejection and implantation failure to the minimum by protecting the embryo from natural killer cells produced by the mother to be and work in concert with all the co-factors associated with successful implantation.
A possible role for the above mentioned processes in fertility makes sense for all these reasons and more as these recent studies have the potential to help with infertility.
It is now being suggested that the last important step in the development of Assisted Reproductive Technology is the advancement of knowledge on embryo implantation.
Current thinking is that, like most events in the reproductive cycle, the process of implantation is also controlled by several hormones, co-factors, enzymes, and adhesion molecules and more. They work like an orchestra in symphony, so that all tunes must be in harmony for successful implantation. When we understand all the various factors and are able to mimic them our IVF success rates globally would reach almost 95 per cent success (quote from several scholars).