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Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF

by Dr. Geoffrey Sher on March 4, 2016

Until about 15 years ago, we believed that the best and safest way to cryopreserve embryos was by using a slow freezing method. What we subsequently learned was that the slow freezing process caused the formation of intracellular ice and that this, by damaging embryos and compromised their post-thaw survival as well as IVF outcome, significantly. The introduction of ultra-rapid embryo freezing (vitrification) has changed all that. With vitrification, embryos are frozen so fast that ice cannot form and as a result embryos are hardly damaged. In fact, about 90% of pre-vitrified embryos survive the freeze thaw in at least the same state of health as the day they were frozen and upon being transferred to a receptive uterus, have at the very least  the same ability to propagate a viable pregnancy as they would have done, had they been transferred fresh. In fact there are many who believe that the post-FET pregnancy rate is now, perhaps even better than with fresh transfers. This is probably due to the fact that optimal hormonal preparation for FET provides the opportunity to better prepare the uterine lining for implantation than when fresh embryo transfers are done where unpredictably erratic levels of steroid hormones along with other potentially harmful byproducts of ovarian stimulation endometrial development might compromise endometrial development and receptivity. Against this background, and in the absence of prejudice, more and more IVF practitioners are freezing embryos for subsequent dispensation in FET cycles.

There are different ways to prepare the uterus for FET. Some authorities favor the use of commercially available oral estradiol products (e.g. Estrace, Progynova), while others recommend transdermal, transvaginal, or subcutaneous/intramuscular estradiol injections. The problem with oral estradiol administration is firstly that anything taken orally will upon gastrointestinal absorption, first pass through the liver (via the venous portal system) before being delivered into the systemic circulation and to the uterus. It is processed in the liver so what reaches the uterus is an altered substance and is substantially watered down. Secondly, the most commonly used form of estradiol, namely Estrace, readily metabolizes into both estradiol and estrone which could be prejudicial to optimal endometrial development. Trans-vaginal (suppositories) and trans-dermal (skin patches) administration also have drawn-backs that relate to erratic and unpredictable absorption issues. In my opinion, the optimal way to administer estrogen for endometrial development in preparation for embryo reception (FET), egg donor-IVF and gestational surrogacy) is through the twice weekly intramuscular administration of (slow release) estradiol (e.g. Delestrogen). This method of estradiol delivery allows for even absorption and is delivered directly to the uterus via the systemic circulation without having first to pass through the liver. I have advocated the use of

Delestrogen for uterine preparation exclusively for more than 20 years. Results are excellent and I see s no reason to change. Here is how I implement the treatment:

It starts with administering an oral contraceptive (OC) to the recipient. This is later overlapped with Lupron daily for 5-6 days. The oral contraceptive is then withdrawn, but the daily Lupron injections are continued until the onset of menstruation at which point the Lupron dosage is reduced and intramuscular (IM) estradiol valerate (Delestrogen) is administered every 3 days. The objective of the estradiol is to achieve and sustain an optimal plasma E2 concentration of 500pg/ml-1,000pg/ml and a 9mm endometrial lining as assessed by ultrasound examination. Intramuscular and/or intravaginal progesterone is administered daily starting about 6 days prior to the FET and continued along with twice weekly IM Delestrogen until the 10th week of pregnancy or until it has been confirmed that the patient is not pregnant.

Daily oral dexamethasone commences with the Lupron start and continues until a negative pregnancy test or until the completion of the 8th week of pregnancy. Then it is tapered down and discontinued. The recipient also receives prophylactic oral antibiotics starting with the initiation of Progesterone therapy, until the day after ET. Usually we would thaw vitrified blastocysts with the objective of having 1, 2 or 3 for transfer; depending on a couple’s stated preference. Commencing on the day following the ET, the patient inserts a vaginal progesterone suppository daily and this is continued until the completion of the 8th week of pregnancy or until a negative pregnancy test.

As an alternative regimen for women who cannot tolerate intramuscular Progesterone (PIO), we prescribe either Crinone vaginal gel or Endometrin vaginal inserts according to protocol. If you’d like to explore one of these options, talk to your physician. For blastocyst FET’s, the blood pregnancy tests are performed 13 days and 15 days after the first progesterone administration is commenced.

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