IVF with Delayed Embryo Transfer
The prospect of storing gametes whether they are eggs or embryos was until recently, good in theory but not great in practice because the method of freezing that has been used for the last 25 years resulted in the loss of up to 30% and also produced eggs or embryos that were significantly devitalized by the process. As a result, a frozen transfer was always a bonus but the success rates were lower than a fresh transfer.
This all changed over the last six to ten years with the development of the ultra rapid cryopreservation method called vitrification, developed and perfected in Japan.
With the introduction of vitrification, the survival rates for both eggs and embryos has risen to better than 95% and the resulting gametes appear to be almost as good as they were in the fresh state. This single innovation allows us to consider the option of banking either eggs or embryos without compromising success when these gametes are ultimately used.
In IVF centers with access to advanced laboratory facilities and vitrification, frozen embryo transfer procedures now yield the same or even better success rates compared with the transfer of fresh embryos when the egg provider has herself been stimulated and undergone egg retrieval.
As the success rate with frozen/thawed embryos approaches and surpasses the pregnancy rate in fresh cycles, more and more cycles of conventional IVF, where a woman provides the eggs and carries the embryos herself, will now become cycles where embryos are banked by vitrification, and the patient then returns the following month for a frozen embryo transfer either with natural ovulation if this is predictable or else with a controlled frozen transfer where natural estrogen and progesterone is supplied in sequence allowing for a planned frozen embryo transfer.
Experts from Aberdeen University reviewed 11 previous studies which followed to birth, more than 37,000 pregnancies resulting from the transfer of either fresh or frozen thawed embryos. When frozen embryos were used, there was a 30% lower risk of bleeding during pregnancy, 30 to 40 percent less chance of the baby being born underweight, 20% lower chance of premature delivery and 20% less likelihood of dying in the neonatal period. The study by Dr. Abha Maheshwari at the Aberdeen University was published in the journal, Fertility and Sterility, and was presented at the British Science Festival in Aberdeen in 2012. Dr. Maheshwari said: “We found pregnancies arising from the transfer of frozen thawed embryos seem to have better outcomes both for mothers and babies when compared to those after fresh embryo transfer.” “If pregnancy rates are equal and outcomes in pregnancies are better, our results question whether one should consider freezing all embryos and transfer them at a later date, rather than transferring fresh embryos,” Maheshwari said.
At Zouves Fertility Center, we have been monitoring our pregnancy rates in fresh and frozen transfers when a woman provides the eggs herself. We have noticed a steady increase in the success rates in the frozen transfers over the last three years, and for the first time, in the first six months of 2012, frozen success rates surpassed fresh. This is due mainly to the benefits of vitrification which we do across the board for all gametes in our program. Knowing that the pregnancy rates are higher in the frozen cycle and also when looking at the data from Europe, showing improved pregnancy outcome in frozen transfers versus fresh, it is a logical progression to stop doing fresh embryo transfers when a woman has been stimulated and rather to vitrify the embryos and transfer them during a future non-stimulated cycle.
The options for transferring the frozen embryos back to the uterus include the following:
- Natural frozen embryo transfer where the patient tracks her ovulation and once the LH surge has been identified on urine testing, blood work and an ultrasound scan are performed confirming the LH surge as well as an optimal triple pattern on the endometrial lining and the presence of a dominant follicle in the ovary. The embryos are then transferred approximately one week later given that embryos are generally stored on day five or six after fertilization.
- Controlled frozen embryo transfer does not rely on natural ovulation and the natural hormones. Estrogen and progesterone are added in sequence, thereby preparing a lining of the uterus which is not dependent upon hormones from the ovary. The controlled frozen transfer is more suitable when patients live far away from the clinic or in patients where the ovulation is unpredictable.
Vitrification
Vitrification is a new technique for egg and embryo cryopreservation that was developed and perfected in Japan. The traditional “slow freeze” method of cryopreserving eggs and embryos was tedious to perform and survival rates for eggs was only 10% and for embryos approximately 70%. The new technique of vitrification literally means “changing into glass” and is similar to what is commonly known as “flash freezing”.
With vitrification, the egg or embryo goes from room temperature to -196 Celsius in a matter of mille seconds, too fast for any significant ice crystal formation and this has increased the survival rate to approximately 98%. This has resulted in two major changes in the way that we practice assisted reproduction.
The first major change that has resulted from the breakthrough of vitrification is the ability to freeze unfertilized eggs that can be thawed at a later stage and fertilized resulting in very good quality embryos and ongoing pregnancies. This has huge implications for women to be able to bank their unfertilized eggs, allowing them to suspend the biological clock and to have their own genetic children at an age when their fresh eggs may have deteriorated or even when they have become menopausal.
When embryos are vitrified and thawed, survival is approximately 98% and the quality of the thawed embryos is almost as good as fresh. We have seen the pregnancy rates from frozen embryo transfers rising steadily over the last year, and we are now at the point where the success rate of frozen cycles exceeds the success rate of fresh transfers when a woman is stimulated and supplies eggs for her own IVF cycle.
This has resulted in the second major change in the way that we practice. We have moved from viewing the fresh embryo transfer as the best chance of success, to knowing that the frozen embryo transfers are now producing higher success rates and as a result, we will be doing very few fresh embryo transfers when women provide their own eggs through stimulation. All advanced embryos will be vitrified and transfer will be performed once the negative effects of the fertility drugs have left the body usually by the very next cycle.
Another added bonus is the recent analysis of pregnancy outcome when a fresh embryo transfer was performed in a stimulated cycle versus a frozen embryo transfer. The data shows that the frozen embryo pregnancies appear to be less complicated by problems like bleeding in pregnancy and the frozen embryo pregnancies tend to go two weeks longer and the babies are approximately 200 g heavier for the same gestational time. 
Zouves Fertility Center offers the very latest advances in IVF treatment, and therefore, the greatest chance for success. This video gives you an overview of our breakthrough procedures and a glimpse into our state-of-the-art IVF Laboratory.
Comprehensive Chromosomal Screening
Zouves Fertility Center (ZFC) is pleased to offer comprehensive chromosomal screening (CCS) in combination with IVF as well as IVF with Delayed Embryo Transfer. This allows for the selection of chromosomally normal embryos for transfer given that approximately 60% of early miscarriages are associated with chromosomal abnormalities or aneuploidy.
Since the first IVF baby was conceived and delivered in 1978, there have been a number of seminal breakthroughs in Assisted Reproduction. These breakthroughs include:
- improved embryo culture methods
- introduction of egg donation and surrogacy
- intracytoplasmic sperm injection (ICSI)
- embryo biopsy for preimplantation screening
- vitrification for storage of gametes
The latest breakthrough and arguably one of the most useful, is the ability to identify which embryos are chromosomally normal by analyzing all 24 chromosomes (22 autosomes, X and Y). Comprehensive Chromosomal Screening (CCS) is probably the “holy grail” of assisted reproduction in that it allows us to transfer one single embryo while achieving outstanding pregnancy rates, a lowered rate of miscarriage and all but eliminating the risk of multiple pregnancy.
The commonest cause of pregnancy failure is aneuploidy, which is a term that describes any embryo which has either extra or absent chromosomes. Embryos that result from aneuploid gametes have little potential to produce a healthy baby, but these embryos cannot be distinguished from chromosomally normal embryos using the standard morphological evaluation. Since the late 90s, the preimplantation genetic screening (PGS) method used to identify abnormal embryos was based on cell biopsy followed by fluorescent in situ hybridization or FISH, which allowed less than half of the chromosomes to be screened.
With the ability to analyze the entire chromosomal complement of an embryo, using comparative genomic hybridization (CGH) there has been a dramatic increase in embryo implantation following this comprehensive screening. The method of screening is based on microarrays and is chip based. Some microarray platforms also allow for combined screening for a single gene disorder as well as screening for aneuploidy.
The introduction of vitrification for embryo cryopreservation allows us to store embryos and achieve 98% survival upon thawing. Blastocyst biopsy allows us to remove approximately 5 cells from an embryo on day five when it contains approximately 150 cells, vitrify the embryo while sending the biopsied cells for comprehensive chromosomal screening (CCS) using comparative genomic hybridization (CGH ) for analysis. The combination of CGH and vitrification also fits very well with IVF with Delayed Transfer which has been shown to further increase implantation and also to produce pregnancies that are less complicated from the perinatal point of view, resulting in healthier babies.
Microarray methods of chromosomal screening are continuing to evolve and at ZFC we are using the BlueGnome bacterial artificial chromosome (BAC) arrays. We are also evaluating analysis based on single nucleotide polymorphisms (SNPs) and it remains to be seen which method will ultimately offer the best combination of accuracy speed and cost.
At ZFC when the egg provider is under age 40, ongoing pregnancy rates when utilizing CCS and IVF with Delayed Transfer, are running at 70% per transfer and more than half of transfers are single embryo transfers (SETs).
