progesterone production
10 Replies
teri-chan - July 20

Dr. Smith,

This isn't exactly an embryology question, but you tend to give much more complete answers than Dr. Jacobs does, so I'm writing you. (The fact that you actually explain things is so very much appreciated.)

Here's my understanding. Once implantation has occurred, it's the hCG that signals the "yellow bodies" in the ovaries to continue to produce progesterone, so that the uterine lining stays intact. Eventually though the fetus/placenta takes over progesterone production.

My question is this: does the embryo/placenta contribute at all to progesterone levels early on in a preganacy? (I ask this because I had an IVF cycle using my own eggs, in which my progesterone levels were low after implantation. Once we knew this, I was put on a higher dosage of progesterone injection--as high as that given to recipients in donor cycles. Still, my progesterone was low. The end result was a chemical pregnancy. This makes me worry that if I have a donor cycle in the future, I may not get enough progesterone to support a pregnancy. Of course, if a healthy embryo/placenta is contributing some progesterone too, that might make the difference.) Any thoughts you have on this would be appreciated. I will bear in mind that you're not a medical doctor, so don't worry!



Dr Smith - July 21

You are correct that the hCG stimulates the corpus luteum (yellow body) to produce progesterone in the early part of pregnancy. The placenta takes over later on. The problem with progesterone following IVF is that many of the follicular cells that produce progesterone in response to hCG are aspirated along with the egg at the time of retrieval. Accordingly, progesterone must be supplemented to ensure there is an edequate amount to sustain a pregnancy.

Low levels of progesterone in the blood have to be interpreted by taking into consideration the method of administration. Progesterone delivered by vaginal creams or suppositories are absorbed locally and they effect the endometrium directly. Since much of the progesterone is metabolized as it passes through the liver, the levels in the blood can be low, but all is well. Conversely, if the progesterone is administered via IM injection, the levels in the blood should be higher.

No one knows how much progesterone is actually needed to sustain a pregnancy. Since in a natural cycle, only one follicle is producing progesterone, it can't be that much. We tend to overkill the progesterone in IVF to be on the safe side. Even if your levels were lower than expected, it is likely that it was enough to sustain the pregnancy. The chemical pregnancy was probably related to embryo genetics rather than progesterone levels.

In a donor cycle, all the progesterone comes from the shots or vaginal cream. To increase your blood levels of progesterone, injections can be used. But, like I said, the amount actually required is probably quite low compared to what we see with progesterone supplementation.


teri-chan - July 21

Thanks for your reply.

In my IVF cycle I took .25 mg (half a cc of a .50mg/cc preparation) progesterone in oil injections along with morning and evening suppositories. When my hCG came in at 18, but my progesterone only 12.3, they increased my progesterone to .50 mg (a full cc) by injection. My third hcG reading came in at 97, but my progesterone was only 8.9.

My worry isn't that the low progesterone caused the pregnancy not to continue. It seems far more likely to me that there were genetic problems. (I was 41.5 at the time.) But I am worried that in spite of getting a pretty high dosage of progesterone, my blood levels were pretty low. I mean, if I do a donor cycle, all the progesterone will initially have to come from the injections (and suppositories). I need to make sure there's enough coming in that way to sustain a pregnancy. Any thoughts?


Dr Smith - July 21

Your progesterone levels were on the low side; we like to see above 20 ng/ml. I imagine that's their target range as well. We have seen patients with consistently low progesterone levels, even when the dose is increased (just like you). These patients have achieved pregnancies, in spite of the initially low levels. The progesterone often goes up a couple of weeks after the first hCG level. This made us check the literature to find out what the minimum progesterone level is. No results. No one knows. I think you'll be O.K., even with values under 10.


Dr Smith - July 21

Wait! I just came across a paper (cited below) that found that the minimum progesterone level consistent with term pregnancy was 10.83 ng/ml. I must have missed it before.

Reference values for the midluteal plasma progesterone concentration: evidence from human menopausal gonadotropin-stimulated pregnancy cycles.
Sallam HN, Sallam A, Ezzeldin F, Agamia AF, Abou-Ali A.
Fertil Steril. 1999 Apr;71(4):711-4.


teri-chan - July 21

Thanks for the information, although it scares me a bit. I don't really understand how blood levels of progesterone can stay low in spite of taking in a fair bit of progesterone by injection. I mean, the progesterone has to go somewhere. Any thoughts? Would it help to take even more progesterone? Or to do two injections daily?


Dr Smith - July 24

Progesterone is metabolized as it passes through the liver (its call the "first pass" effect). In other words, it goes directly from the injection site to the liver and gets metabolized. This will reduce the amount of circulating progesterone. As long as the circulating level stays above the minimum (~10 ng/ml), you should be O.K..

Where does the progesterone go?

Either the progesterone is not being absorbed very well (patients with a lot of fat back there don't always make it all the way down to the muscle for the IM injection and the progesterone stays lodged in the fat cells) OR your liver is very efficient at metabolizing progesterone, so less shows up in your blood. If you are of average weight, its probably the latter.

You can speak with your doctor about changing your dose or frequency of injections. See what they have to say.


teri-chan - July 25

Thanks much. I guess my liver's efficient at metabolizing the progesterone. I take it that it doesn't really matter so much how much progeserone is in my blood as long as there's enough getting to my uterus to keep the lining intact. Is that right? If I use prometrium inserted vaginally is that apt to get the intended effect on the lining but not not show up in the blood?

Thank you.


Dr Smith - July 25

You are correct that the blood level of progesterone does not necessarily reflect its effect on the endometrium. Progesterone delivered vaginally does not go through the "first pass" metabolism and, instead, acts locally (i.e. absorbed directly by the endometrium from the vagina). Accordingly, the blood level is usually lower than when progesterone is administered by injection, but the progesterone is still having the desired effect.


Asunflower - July 25

So is it better to do PIO IM shots or suppositories? I take 1cc of PIO every night. Is this enough?


Dr Smith - July 28

Some RE's use suppositories/creams only (although this number is getting fewer and fewer), some use injections only and some use both. As long as the progesterone level in the serum remains adequate, no worries.

Most RE's do prescribe the IM shots, even if they are a pain in the a** (literally). You are getting the usual dose, which is probably more than adequate.



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