Hormonal Induction of Endometrial Receptivity for Fresh or Frozen Embryo Transfer Part I
Video
Runtime: 5 min 35 sec
Speaker: Richard J. Paulson MD
Transcript
Dr. Richard Paulson delves into the intricacies of endometrial preparation for assisted reproductive technology (ART). He discusses the historical evolution of hormonal induction of endometrial receptivity, from its early applications in egg donation to its current use in frozen embryo transfer. Dr. Paulson also explores the optimal methods of estrogen and progesterone administration, including oral, transdermal, intramuscular, and vaginal routes.
Hello, I'm Dr. Richard Paulson from the University of Southern California. I've been doing IVF and egg donation and all of these other things that we all do for a very long time. One of my areas of interest for a long time has been the question of endometrial receptivity and in particular the hormonal induction of endometrial receptivity.
Now this procedure, if you will, really was first invented in the context of egg donation because remember embryo cryopreservation wasn't very efficient. So it was when IVF first started and people saw that you could have sperm in one dish and egg in another dish that it didn't take a huge leap of the imagination to say, oh gosh, we could be donating eggs from one person to another. And of course the early recipients were all young women with premature ovarian failure.
So they had no ovarian function and the only way to induce receptivity to embryo implantation was with the progesterone. So the world's first pregnancy in an agonadal recipient took place in 1983. The patient took oral estrogen and vaginal progesterone, 50 milligrams twice a day.
Remember that, 50 milligrams twice a day. And one two-cell embryo was transferred on the second day of progesterone. Second day of progesterone, that means the progesterone started when that embryo was at the pre-nuclear stage.
So remember that, that's actually 24 hours after ovulation. The procedure, or if you will, the preparation of the endometrium was then extended to surrogacy. Same kind of idea, eggs being donated from one person to another.
And when embryo cryopreservation became more efficient, we started using it for preparation of the endometrium prior to frozen embryo transfer. And indeed, that is what it's being used for mostly nowadays. In fact, egg donation and gestational surrogacy, as most of you know, has really shifted towards frozen embryo transfer in any event.
So let's talk about how it is we prepare the endometrium. You need estrogen and you need progesterone. You don't need anything else.
People have tried, but estrogen and progesterone is all that has ever been shown to be necessary and nothing added to it has actually been shown to make a difference. So apparently, that's how that works. So how do you give somebody estrogen? So there's lots of options.
Estradiol in the circulation is relatively low quantities, and as a consequence, you don't have to give that much medication. So we can use oral estrogen. Typically, we use two milligram oral doses, maybe twice a day or three times a day.
You can use transdermal, and because transdermal is absorbed much more efficiently, the dose is lower. So estrogen patches that are used are typically 100 microgram doses. 0.1 milligram dose by a patch is equivalent to about two milligrams orally.
So two milligrams twice a day, for example, orally translates into two patches at one time, and that's how it can be used. The patches actually are more physiologic. They provide the right kind of ratio of estrone and estradiol, but I would say that the majority of cycles in the United States still use oral, and that is because we're more comfortable with it.
It's easier for the patients to take it via pill. You can also use intramuscular, or you can use vaginal administration. We won't go into depth on those.
Those do produce actually higher levels. So estrogen has to be given for some period of time to prepare the endometrium, and specifically to prepare the endometrial cells and to allow them to develop progesterone receptors, because it is progesterone that actually causes the luteinization and opens the window of implantation. So most of us give estrogen for about 10-12 days.
We look for an endometrial thickness of seven millimeters, but you should know that no one has ever correlated endometrial thickness with the presence of progesterone receptors and so on. So the thickness is not all there is to it. Let's move on to progesterone.
So progesterone is present in the body in much higher levels. Remember, we measure progesterone in nanogram quantities, nanogram per mil, and therefore the doses that are given are much higher. So intramuscular doses are typically 50 milligrams, 50 milligrams per ml.
That's a dose. Vaginal doses then typically are around 100 or 200 a day. So oral is not really a reality.
Really, we're stuck with intramuscular or vaginal. The transdermal administration for progesterone also doesn't work. First of all, you have to think about how big that patch would have to be.
I often like to joke that you'd have to have a progesterone jacket to wear. And still, of course, there's five alpha reductase in the skin, which metabolizes the progesterone and makes it be inactivated. So we're going to stick with intramuscular and vaginal.
So that's it for the options that we have for progesterone administration. So I've been investigating progesterone administration for a very long time, and I want to tell you more about that and particularly about the uterine first pass effect that was discovered as a consequence of measuring endometrial tissue levels rather than serum levels of progesterone. And we're going to talk about that in the next video.
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