Some questions about human ovulation

[Drum_God]

I’ve been listening to a podcast called “The Retrievals”. The podcast is by the people who brought us Serial and other podcasts. In this one, it discusses a crime in which some women undergoing IVF treatment are the victims. My questions really have nothing to do with the crime or the consequences thereof, but about some human biology questions.

• In the beginning, the women are given hormone treatments to increase their number of eggs available for the retrieval procedure. I thought that human females were born with all the eggs they were ever going to have. So, why is there a need to increase this number and how does it work?

• During the retrieval procedure, a long needle is inserted through the vaginal opening, through the uterus, piercing the uterine wall, and into the ovary to retrieve eggs. This is very time-sensitive and the women are eager to have this procedure during a specific window of time. If they miss the window, the woman will ovulate and lose the eggs. I get the ovulate part, but, again, doesn’t a human female already have all the eggs she is going to have? I can see one egg lost as it goes on its merry way, but why would lots of eggs be lost?

• While on this subject, most humans ovulate only one egg at a time. How do the ovaries know whose turn it is in a given month? How does the fertility doctor know which ovary to visit for egg retrieval, or does he/she visit both ovaries?

(The crime committed is that a nurse diverted fentanyl to be used to manage the pain during the retrieval procedure. These women ended up having their retrievals without receiving the pain management that the doctors and nurses thought they were administering. There is lots more to this problem, but that is the basic, underlying issue.)

[DSeid]

The goal is to get several of the eggs to mature into harvestable follicles in that cycle. Generally just one ripens enough to be released at a time and the others wither back. It’s a competition. The dominant follicle releases estrogen and something called inhibin to block the others getting as much FSH, causing them to fall back.

The ovaries have plenty of eggs sure, but ones ready for harvesting are in shorter supply.

The whole feedback loops that choreograph the process to ovulation is really complicated. Back in med school I spent a long time diagramming it out to get it down and no way I could still do it now!

But this much I still got down.

[RivkahChaya]

Dr. DS?

Something I always wondered about ova retrieval for things like IVF, is this: when women are given something to stimulate more ova to ripen, does this happen only in the ovary whose “turn” it is that month, or does the drug cause ripening in both ovaries?

Also, something I just now thought of-- I’ve got a friend who had one ovary removed due to a benign, but invasive, tumor (don’t ask me for any details-- that’s all I know). Does (or, did, I guess-- she had the surgery around age 30, but she’s 61 now) this mean she ovulates only every other month? or does the remaining ovary pick up the slack, so she continues to ovulate every month?

[DSeid]

Not my area of expertise but I don’t think that ovulation is strictly alternating sides and I am pretty sure that a woman with a single ovary will still ovulate monthly. The competition for being the dominant follicle will just be on one side only.

[DSeid]

Found this which is interesting.

… * Studies have suggested that the side which ovulates is determined by the length of the previous menstrual cycle. Formation of a dominant follicle, the one that will eventually become a mature egg and ovulated, is more likely in the ovary which has lower levels of progesterone during the follicular phase – that is, the phase that starts on day one of the menstrual cycle and culminates in ovulation. During this phase, Follicle Stimulating Hormone (FSH) produced by the pituitary gland prompts the development of several follicles, one of which will become the dominant one.

• Studies have further observed that ovulation tends to alternate between ovaries during short cycles but that during longer cycles, ovulation occurs randomly, making prediction difficult. …

ETA no idea if there is some ripening that starts on both sides but strongly suspect only one side gets to harvestable follicles.

[BigT]

@Drum_God

I thought that human females were born with all the eggs they were ever going to have. So, why is there a need to increase this number and how does it work?

While it doesn’t affect the other answers, my understanding is that this is no longer considered to be true. However, when searching now on Google, I’m seeing conflicting reports. In particular, a study in 2012 suggests that human women can make more eggs, but then sites that are much newer say they can’t. But I’m not finding anything saying anything was wrong with the previous study.

Does anyone here know more about this?

[Kimstu]

@BigT

In particular, a study in 2012 suggests that human women can make more eggs, but then sites that are much newer say they can’t. But I’m not finding anything saying anything was wrong with the previous study.

Is it this debate you’re thinking of? That article’s from 2008, but I wouldn’t be surprised if it was still a debated issue four years later.

This traditional narrative of oogenesis was recently challenged; indeed, the paper by Johnson et al. 1highlighted here suggests the radical notion that the adult ovary must and does have the capacity to create new oocytes. […]

The prevailing dogma of mammalian reproduction states that females lose the capacity to produce germ cells during fetal development and are born with a finite number of follicle-enclosed oocytes, only a small number of which will be ovulated after puberty […]. Several recent studies from the laboratory of Jonathan Tilly at Harvard led to the hypothesis that adult mice are capable of regenerating oocytes, suggesting the existence of adult germline stem cells […]. These papers created a schism within the reproductive science community that is now coming to a resolution. […]

The publication of the initial adult oogenesis paper created a splash in the journal and in the media, suggesting that young women facing life-preserving but sometimes fertility-threatening cancer treatments might have an option for restoring their fertility. However, the ability to repopulate the ovary with a bone marrow transplant or stem cell transfusion now seems unachievable. […]

The field has moved forward by affirming what it knew—that making an egg is a biological puzzle that has yet to be entirely solved.

[DSeid]

There’s this 2015 article about the possibility of postnatal human ovaries having cells capable of differentiating into oocytes. “Not excluded” as a possibility.

https://scholar.google.com/scholar?q=related:0tYbXOFvCjwJ:scholar.google.com/&scioq=human+adult+oogenesis+&hl=en&as_sdt=0,14#d=gs_qabs&t=1692599138696&u=%23p%3D0tYbXOFvCjwJ

These small stem cells were pushed into the germinal direction of development and formed primitive oocyte-like cells in vitro. Moreover, oocyte-like cells were also formed in vitro from embryonic stem cells and induced pluripotent stem cells. This indicates that postnatal oogenesis is not excluded. It is further supported by the occurrence of mesenchymal stem cells that can restore the function of sterilized ovaries and lead to the formation of new follicles and oocytes in animal models.

Or possibly this?

https://scholar.google.com/scholar?start=10&q=human+egg+quantity+menopause+&hl=en&as_sdt=0,14#d=gs_qabs&t=1692598624014&u=%23p%3DHuEXVmbS1ygJ

The traditional view is that menopause hits when eggs literally run out, with maybe one out of ten getting to ovulation and the others all losing the race. But it seems there are still some there in early menopause at least that can be pushed into action with significant prodding.