Around the uterus in fourteen days: the luteal phase

mcg1102

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Today we are going to discuss a time of mystery, a time of endless possibility, a time of progesterone: the luteal phase. (Despite my clickbait title, the length of the typical luteal phase can vary from about 10 to about 16 days, and 12 days is actually the most common length. Don’t believe clickbait titles.)

I have made a schematic figure to illustrate this post: follow along here!

The luteal phase begins with ovulation. The “luteal” in luteal phase comes from the cells of the ovary that surround the developing egg cell as it careens toward ovulation; the same cells that provide hormonal support to the egg as it matures are the cells that provide hormonal support after the follicle has ruptured, although the dominant hormone produced by these cells shifts from estrogen to progesterone. After follicular rupture, the support cells turn yellowish (from Latin: luteus, yellow) and form a deflated popped bubble on the ovary that can be visualized via ultrasound. (The egg itself, and the early embryo, is too small to be visualized.)

Ovulation day: ovulation

On ovulation day, the egg is released and (hopefully) is met by sperm at the ovary-side end of the fallopian tube. The newly ovulated egg cannot survive longer than about a day without being fertilized, so it’s best for sperm to be in the uterus and tubes already, waiting for the egg to be released. Since the egg can’t live for more than a day, this means that ovulation day and fertilization day are the same day.

1-5 days post-ovulation: early development

Over the next few days, the developing embryo begins to float down the fallopian tube toward the uterus, reaching the uterus around 3 days post-ovulation. (At this point, it’s correct to refer to it as an embryo or morula – it is no longer a “fertilized egg”.) The embryo is not anchored to the uterus and tubes in any way, but floats down the tube in the world’s most lovely lazy-river-slash-car-wash situation, being gently swept toward the uterus by cilia that line the tubes. Meanwhile, the corpus luteum, which has no knowledge of whether fertilization occurred or not, has started to increase its production of progesterone. Progesterone levels will continue to rise for the next few days, and could begin to cause standard “progesterone symptoms” at any point, but progesterone levels are not different in cycles that will ultimately be successful or unsuccessful.

6-7 days post-ovulation: apposition

By about 6 or 7 days post-ovulation, if an embryo is still healthy and developing, it will begin to line up with the uterine lining in a process called apposition. This is not dissimilar to the process of the space shuttle lining up with the International Space Station; the embryo finds a nice spot to settle down, and extends cellular projections toward the lining, which extends its own projections back. At this point, progesterone levels are at their typical peak, but they are still the same on average between a successful and an unsuccessful cycle – at this point, it’s not possible to tell the difference between a successful cycle and an unsuccessful one by symptoms alone, or even by quantitative progesterone levels, and the lining is prepared for possible implantation each cycle regardless of whether conception happened, or even regardless of whether sex happened. Also, at this point in the luteal phase, a home pregnancy test will be negative, even if conception has occurred. The cells of the embryo that will become the placenta have just started to produce hCG (human chorionic gonadotropin, the embryo’s own hormone), but have no way to get it into the parental bloodstream, since the embryo is still not physically connected with the uterus.

8-9 days post-ovulation: implantation

Around 8-9 days post-ovulation, the process of implantation actually begins. At this point, the embryo, which is continuing to grow and divide all the time, buries itself in the uterine lining, moving progressively deeper over the course of a few days. Now that the embryo is connected with the uterus and surrounded by uterine tissue, it has access to the maternal bloodstream and can receive hormonal and other nutrient support and send its own hormonal messages to the rest of the body. The primary goal the embryo must achieve is to produce enough hCG to signal to the corpus luteum and keep it producing progesterone – without a signal from an embryo, the corpus luteum will soon shut down production of progesterone for the cycle, which will trigger the uterine lining to be trimmed and shed for a period. hCG levels rise rapidly as the embryo continues to grow, and can increase progesterone levels as early as the day of implantation itself. Since hCG is in the bloodstream, it is also being filtered into the urine, and it is possible to get a positive home pregnancy test starting from the day of implantation, although it is more likely to happen the next day or the day after. Progesterone levels will now begin to rise in a successful cycle, and to fall in an unsuccessful one, and it is possible to have progesterone-based symptoms that are truly the result of pregnancy. Indeed, following implantation, it is possible to be pregnant – during the time after fertilization but before implantation, a person can be carrying an embryo, but is not yet pregnant.

Implantation happens most often on 8, 9, or 10 days post-ovulation (about 20%, 35%, and 25% of the time, respectively), so the timeline described above will vary a little according to the individual embryo. How quickly an embryo begins to undergo implantation depends mostly on its own developmental readiness – the embryo must have reached the stage where it is capable of implantation in order for implantation to begin. When the embryo undergoes implantation does not have to do with the length of your luteal phase, and you won’t necessarily get a positive on the same day in two different pregnancies.

10-12 days post-ovulation: opening Schrödinger’s box

At this point in the cycle, you can begin to reliably access information about whether the cycle has been successful or not. In an unsuccessful cycle, progesterone levels will begin to drop, preparing the uterine lining for shedding and a period; progesterone symptoms may lessen or disappear. In a successful cycle, progesterone levels will rise and continue rising, which can cause intensification of progesterone symptoms. hCG levels will also rise rapidly, and about 90% of pregnancies will have urinary hCG levels higher than 15mIU/mL by 12 days post-ovulation. Most pregnancies, then, should be detectable by a sensitive home pregnancy test by this point, but not every pregnancy will be detectable by the same day – since implantation day varies by a few days in either direction, it stands to reason that the day of the first positive home pregnancy test will also vary. Even if you see a lot of 9dpo positive tests on /r/TFABlineporn, it’s not possible to be certain you’re not going to end up pregnant with a negative test at 9dpo.

It might be worth noting here that implantation does place the embryo into contact with the parental body. It is a popular saying around the internet that the embryo does not come into contact with the bloodstream until the placenta forms several weeks after implantation, and therefore it’s not possible for substances in your own blood to affect development until that point. This is not the case: embryo-harming teratogenic substances from the host bloodstream can begin to affect the embryo once implantation occurs, and there are substances that can cause major embryonic abnormalities and loss even within the week or two after implantation occurs (see this figure, from a popular developmental biology text). “[x] ‘til it’s pink” is probably a reasonable strategy for most substances, but once you do see that second line, pregnancy has begun.

13 days post-ovulation and beyond: onward, or back to the beginning

As the time post-ovulation passes, the embryo continues to get bigger and more complex, and begins to spin off major support structures that connect it with the parental body and hCG continues to rise, approximately doubling every 2-3 days. The embryo begins to divide cells among the major cellular lineages, even beginning to lay down plans for the first organs and systems starting by the middle of the third week after ovulation.

In the event that implantation didn’t happen, or if it did and the pregnancy did not continue, progesterone levels will drop as the corpus luteum regresses, and other hormones will return to cycle baseline as well. The drop in progesterone signals to the uterine lining, which is trimmed and shed to start a new cycle. Follicle selection will hopefully take place around 5-7 days into the new cycle, and after follicular maturation, ovulation will happen anew.
 
@mcg1102 So between days 3-5/6 when a possible embryo has made its way out of the tube and into the uterus but before implantation, what is it doing? Hanging out in the uterine cavity?

Your post is fascinating and I’ve saved it to read over again in the future! Also I’m 3DPO so my interest is extra piqued haha.
 
@hal16 Just chilling!

I should have linked this picture, which I love, from the developmental bio text I use in class: panel B is three intrepid pre-implantation blastocysts going on a journey through the uterus.
 
@mcg1102 Amazing post! It’s fascinating what our bodies do (or attempt to do in my case) each month.

I love the point about how the corpus luteum is responsible for releasing progesterone. And of course, if you ovulate, whether or not conception happens, the corpus luteum is going to do it’s thing. That drives home for me the futility of not symptom spotting (not that I still won’t do it… ha).
 
@mcg1102 Thank you for this post! It’s so helpful to understand the mechanics and horomones. Two questions if you know or can recommend further reading:

1) If the sperm are hanging out in the uterus before the egg is available, does something make them start swimming up through the tubes when it is released? Or is it just like luck of where they are located (ideally in the tubes?) that determines if they meet the egg?

2) Do you know any more about the substances that can cause loss in the first two weeks after implantation? i.e. what substances could these be?

Thanks again!!
 
@jschoeman00 Awesomely enough, one of the major signals that sperm use to tell them when and where to go is progesterone itself. This has the dual advantage of telling them that ovulation has happened and also which direction they should swim.

Anything that would cause the death of enough cells in the embryo that it would be unable to recover by growth could cause loss in the first few weeks. The most obvious examples are things with clear reasons not to use during pregnancy — cancer drugs that arrest or kill dividing cells, for example. Once the embryo has started to assign cells to particular eventual functions, canonically 17 days post-ovulation, substances that kill many cells can cause major developmental malformations, because the potential of each cell is now limited, and cells assigned to become one thing cannot compensate for loss of cells assigned to become another thing.
 
@mcg1102 This post was quite timely for my current interests! If anyone wants to dive deeper into implantation steps, my clinic released this video on implantation failure. From 6:00 to 15:00, the stages of implantation are described.
 
@mcg1102 Thank 👏 you 👏 so 👏 much👏! Saved.

I Google this every TWW, right around the 8/9dpo stage when progesterone is testing my sanity. So incredibly helpful to see everything laid out that explains symptoms peaking right when I enter the premeditated murder zone (before 12dpo when the murder zone hits and I still have 2 days to wait for AF).
 
@mcg1102 This is so interesting! What’s happening with (tubal) ectopics? Are they just stuck hanging in the fallopian tube until they’re developed enough and implant? I’ve been wondering if they implant earlier but based on this, it sounds like they wouldn’t because they still need time to develop enough and be ready?
 
@sls2labs Yes, precisely! They can’t undergo implantation until they’re developmentally ready. So they’ll undergo implantation at the normal time, or potentially a little late — the thing about them being not located in the uterus means they generally don’t grow as well as uterine pregnancies once implantation occurs, because they’re like seeds in bad soil, so hCG is often very low for a long time.

But the other thing about them not being in the uterus is that a period will not cause them to be removed — there’s no endometrium in the tubes, and no menstrual flow from there. So by the time people tend to get a positive pregnancy test, it’s actually usually well into the next cycle. As a result, people sometimes think they’ve gotten a positive test very early post-ovulation, but it’s actually a pregnancy from the previous cycle.
 
@mcg1102 In the case of the ectopic not being a structural issue, what causes this? Does the egg make it to the uterus and then bounce back to the tube or does it never leave the tube to begin with? I could ask a thousand questions about ectopics.
 
@mickiio Could be either! Tubal damage does increase the likelihood of an ectopic, and there are likely cases where there's subtle damage that goes undetected, but is still capable of blocking an embryo's way to the uterus. For example, cigarette smoking is a risk factor for ectopic pregnancy, and it's thought that this could be due to impairment of the cilia that usually sweep the embryo down the tube.

Damage to the end of the tube (the fimbria) can also be a risk factor for ectopic pregnancy, since the end of the tube needs to catch the egg/embryo as it is released by the ovary, and failure to catch it can result in implantation on the ovary or elsewhere in the abdominal cavity.

But sometimes the embryo just selects a spot for implantation that's too close to to the uterine end of the tube.
 
@mcg1102 Thank you dor this very informative and useful post ! It helps me so much to know that 7 DPO is too early to feel or detect a pregnancy. I mean, I know that but I get lurrred by progesterone none the less. Reading it every cycle will remind me that the potential embryo is still chilling at this point 😅

I'm wondering why there are so many 8 DPO positives on r/tfablineporn though. Are they wrong about ovulation day or is this just a selection bias ?
 
@okmnhyxxx Probably a little of column A, a little of column B. Some are likely wrong about their ovulation day. But it’s not impossible to get a positive at 8dpo — about 30% of embryos undergo implantation at 8dpo or earlier. Most of those won’t have high enough hCG levels to be positive at 8dp itself, but let’s say 1/3 are. If something happens to 10% of people, it’s going to show up a lot on lineporn, and it’s also pretty memorable when it does show up.
 

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