Since the first in vitro fertilization baby was born, over 30 years ago, there have been very significant advances in the field of reproductive technology. Improved drugs, stimulation protocols, culture media to name a few. However, pregnancy rates, although much higher are still not optimum.

Several factors are responsible for this. The most significant is the egg and embryo quality. However, attention has recently focused on the receptivity of the uterus and its impact on pregnancy rates. Investigators have been evaluating the uterus and the different proteins that are secreted during implantation. The field of studying the metabolic (metabolomics) and protein (proteinomics) products is as important as the genetic (genomics) quality of the embryos.

Studies have shown that there may develop a dyssynchrony between the uterus and the embryo. This alters the receptivity of the uterus.

Therefore, pregnancy rates in frozen-thawed embryos cycles have been evaluated further.  Several studies have shown improved clinical pregnancy and delivery rates in frozen thawed cycles.  A recent study by Shapiro et al (Fertility and Sterility 2011) reported ongoing pregnancy rates of 78% in the frozen thawed patients, compared to 50.9% in those who had a fresh transfer.

Patient selection:

Certain patients are better off with a frozen thawed transfer. This includes patients at higher risk of hyperstimulation.  Patients who are good responders, or have polycystic ovarian syndrome do better with thawed embryos. Patients who may experience an elevated progesterone during stimulation (premature luteinization) affecting the endometrium. Patients undergoing a trophectoderm biopsy for preimplantation genetic screening. These embryos are frozen on day 5-6 and then transferred in a subsequent cycle.

Stimulation protocols:

Aggressive protocols used to stimulate the ovaries can result in adverse endometrial development as well as increased abnormal eggs. Several reports have suggested using lower dose stimulation protocols to overcome this, as well as in the interest of patient safety.

Freezing methods:

Slow freezing was the method of freezing used by most centers until recently. Vitrification (rapid freezing) has now been accepted as a more efficient way. Thaw survival rates, as well as pregnancy rates are higher with vitrification of embryos.

Embryo stage for freezing:

The debate is ongoing as to which is the best stage for freezing embryos. Several studies recently have been published showing a definite advantage to freezing the blastocysts on day 5 or 6. Cleavage stage (day 3) embryos fare poorer with thaw transfer cycles. Obviously, waiting to day 5 allows the best embryos to be chosen and decreases the number of excess embryos for freezing.

In conclusion, it is too early to tell if this will become a standard approach in all IVF cycles in the future. But there are many benefits to transferring embryos in a subsequent cycle.

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