Embryo freezing has been an essential component of in vitro fertilization (IVF) treatment since the 1980s. Significant developments in egg and embryo freezing have changed the approach to cryopreservation in more recent years. The embryos can now be frozen within 24 hours of fertilization (at the pronucleate stage - 2PN), or on day 5 of embryo development at the blastocyst stage (depending on the preference of the IVF center). We freeze embryos at the blastocyst stage because this is the last stage when embryos can be assessed for quality before cryopreservation in the IVF laboratory. Most of the chromosomally abnormal embryos will stop developing in culture and do not progress to the blast stage (Day 5) based on our published medical studies. It is therefore important to freeze only those embryos that reach the 5th day, as they will be stronger embryos with a better chance of resulting in a pregnancy.
If the embryos are frozen on the first day after fertilization (2-PN), they are thawed and cultured for a few days. Those that reach the blastocyst stage are assessed for quality and considered for embryo transfer. If the embryos were frozen on the 5th day, blastocysts are thawed and transferred on the same day within a few hours. A recent method called vitrification has increased embryo survival rates with an overall significant improvement in pregnancy rates following frozen embryo transfers (FET). Some of the frozen blastocysts will be lost during the freeze-thaw process, although it has been less than 10% in our program. Thus 90% of the embryos survive the process. This does not mean that the pregnancy rate is 90%, but with such high survival rates, pregnancy rates have also improved over the years. Most recent medical evidence suggests that the transfer of frozen-thawed embryos/blastocysts does not increase the risk of birth defects.
Frozen Embryo Transfer Protocols:
The recipient's cycle is initiated with birth control pills (BCP) with the onset of a menstrual priod, which is later overlapped with Lupron daily for 6-7 days. Then, BCP is withdrawn and daily Lupron injections are continued until the onset of BCP induced menstruation, whereupon the Lupron dose can be reduced until progesterone is initiated. Once progesterone is started, premature ovulation is no longer a concern and Lupron is discontinued. If Lupron or similar drugs called Ganirelix or Cetrotide are not used to prepare for a frozen embryo transfer, an egg can mature and ovulate spontaneously. When this happens, the egg releases progesterone hormone, which affects the cellular make up of the uterus (endometrial cells). This causes a dissynchrony between the stage of the embryo and the endometrial cells.
Estradiol valerate (E2V) is administered twice a week intramuscularly (IM) beginning within a few days of induced menstruation. On the day following the second E2V administration, a serum estradiol (E2) level is checked. This allows for adjustment of the E2V dosage for the next scheduled E2V injection. The objective is to achieve an optimal E2 concentration and an adequate endometrial lining as assessed by ultrasound examination. E2V is continued twice a week until the blood pregnancy test. Daily dexamethosone is started generally with Lupron and continued until a negative pregnancy test or until the completion of the 8th week of pregnancy, whereupon it is tapered and discontinued. Prenatal vitamins are taken daily before and throughout the pregnancy. The recipient also receives antibiotics starting with the initiation of progesterone therapy until the day after embryo transfer (ET). Vaginal estrogen and in some cases Viagra vaginal suppositories may be used in cases where there is a thin (< 8 mm) endometrial lining. Luteal support is initiated 5 days prior to the ET with 50 mg daily progesterone injections continuing until the completion of the 12th week of pregnancy or until a negative blood pregnancy test.
An alternative regimen for women who cannot tolerate progesterone or estrogen injections is vaginal estrogen and progesterone suppositories. Vaginal estrogen is used to prepare the endometrial lining and can be combined with oral estrogen for two weeks. An ultrasound examination and measurement of the uterine lining is done to make sure the lining is adequately thick enough (8 mm or thicker) to start progesterone suppositories. Progesterone can be given twice or three times a day and both suppositories are continued until 12 weeks.
Download Dr. Bayrak's published findings on Embryo Freezing here: