Making Sense of Pregnancy: What Experts Want you To Know About Your Body

 Miscarriage is a well-known secret that you may not be aware of until it happens to you or to a close friend, but it's incredibly common. 

Studies suggest something like 15 to 20% of recognized pregnancies end in miscarriage or stillbirth, with the vast majority of miscarriages happening in the first trimester, about 80%, and most stillbirths occurring in the third trimester.

 Scientists have compared human pregnancy to the pregnancy rates of other mammals and found that the way we "do pregnancy" is incredibly inefficient. This 15 to 20% number I just mentioned reflects errors in pregnancy that we can measure. But researchers who estimate conception rates suggest that an even more common outcome for an embryo is that it fails to implant entirely, leaving no sign of a missed pregnancy. 

Given that this is a biological reality, how we appreciate our own experience of pregnancy and loss depends importantly on if and how we understand the loss.

 Today's guest has made a major advance in how pathologists categorize pregnancy loss by recognizing a hallmark of chromosomal abnormality that shows up in pathologies and often isn't well-identified, giving couple's who've experienced a loss a way to better understand that loss.

 As scientists have come to learn more about serious pregnancy complications like preeclampsia and premature birth, they believe that some of those complicated issues are born in the very earliest days of pregnancy. 

But the goings-on in the early first trimester have been a mystery for most of human history. 

Recent technological advancements, like the special microscope used by the researcher I talk with today, uses techniques that attempt to "essentially" add audio to the video, allowing us to know more about both what cells are present in these early weeks (with a focus on maternal immune cells and different types of EVTs) and what kinds of conversations they may be having with each other.

A Spatially Resolved Timeline of the Human Maternal-Fetal Interface: https://www.nature.com/articles/s41586-023-06298-9

 We can initiate a pregnancy by handling eggs and sperm outside the human body. We can remove these elemental factors from people fundamentally changing the way eggs and sperm were built to interact and reinsert them into a woman's body to produce a pregnancy and eventually a baby. 

It's an audacious and remarkable feat if you think about it, something that all generations of living creatures before us could not do. As if that wasn't enough, we can do it despite the fact that not all the details of fertility and pregnancy have been worked out. 

Helping people manage fertility has been around for nearly 250 years, starting with aides to insemination, just handling sperm, which are, accessible enough. But in the last 50 years, the increasingly complicated ways in which we can interact with eggs and sperm to create a pregnancy is mind blowing. This week we're gonna talk about some of the groundbreaking technologies that have been developed over the last three or four decades to maintain and extend fertility, we'll also look at what this process teaches us about fertility and pregnancy. 

 Question, are ovaries the most underrated organ? Answer: Yes. They're the workhorse of your menstrual cycle, this critical process that happens again and again and again to preserve your fertility, which may or may not be a top priority for you, but it is of top priority for the embryo that made you. 

And today I'm gonna focus on this workhorse. Your ovaries, not only are they critical to health overall, but obviously also critical to the success of a pregnancy since they're the living vault of your fertility. 

We'll talk about how eggs are formed, how they stay quiet for decades, how they're chosen in each cycle, and the relationship between aging and the ovarian reserve. 

 Today we'll continue our conversation about Project Implantation. 

In last week's episode, we were focused on how the model of the uterine lining was created and what it could do. This part of the conversation focuses more on what the blastoids, the embryo models and actual blastocysts (five day old embryos)  are doing with the model uterine lining. 

 Dr. Irene Zorzan is a postdoctoral Leverhulme Fellow at the Bainbridge Institute in Cambridge. 

She's got a PhD in molecular medicine and was focused on the factors that help guide cells in the blastocyst to specialize into the epiblast and trophoblast cell lineages and some of the development that follows. She also studied reprogramming fibroblasts into pluripotent stem cells. And is working on Dr.
Peter Rugg's team to better understand the conversation between the uterine lining and the blast assist to manage implantation and early placental development.

Here is a link to the paper. Scroll down in the paper to see the video we talk about in this episode: Modeling Human Embryo Implantation in Vitro: https://www.cell.com/cell/fulltext/S0092-8674(25)01232-2

Today we're going to talk about what I'm calling Project Implantation. 

It's a bold experimental model that creates a 3D version of a uterine lining as it would exist during the window of implantation--that period in the cycle when you can actually get pregnant. This model, the first of its kind, is being used to better understand the hows of early placental construction:  how that embryo talks to the cells in a model uterine lining and how these placental and uterine lining cells negotiate the terms of the implantation that follows. 

Given how critical a functioning placenta is to a successful pregnancy, a better understanding of this early process, this early conversation between the embryo and the uterine lining may lead to real insight into the development of serious pregnancy complications like preeclampsia, intrauterine growth restriction, and preterm birth.

Modeling Human Embryo Implantation in Vitro: https://www.cell.com/cell/fulltext/S0092-8674(25)01232-2

 The sex of the fetus often isn't even mentioned until the 20 week scan, but as my conversation with Dr. Clifton suggests, fetal sex can have real impacts on how the fetus negotiates intrauterine life, especially if there are challenges.

Today we talk about the ways in which fetal sex may affect how pregnancy complications are managed by the fetus and the placenta in the womb, in particular with respect to maternal asthma, preeclampsia, and IUGR. We also talk about the possibility of treating pregnancy complications based on fetal sex. 

 Dr. Clifton is a National Health and Medical research council, senior research Fellow, and a senior research fellow at Mader Research. Professor Clifton leads the pregnancy and Development research group and is the scientific director of the Queensland Family Cohort Study.

Questions or comments? find me at [email protected]

 Lots of research has been done trying to understand how the human placenta is similar to and different from placentas of other mammals; to specifically tease out exactly how the placenta contributes to a pregnancy, and how its formation affects the success or failure of a pregnancy. 

Another attribute of the placenta that's of increasingly recognized significance is the sex of the placenta and how that affects its strategy to enhance the chances of fetal development and survival. That's the topic of today's episode.

Postpartum depression is the most common complication of pregnancy.

Given our current ability to measure it we think it will affect 10-15% of pregnancies, but it can be a tricky condition to diagnose because in the past, diagnosis has depended on the postpartum person answering a survey meant to identify it, or recognizing the condition in themselves and seeking help. 

There are relatable reasons why women may not answer this survey in a way that reflects their true feelings, and it may be a real challenge to catch it in yourself given everything else a postpartum mother is doing. 

But these obstacles to diagnosis are changing. 

I interviewed this researcher when she was working on securing  FDA approval of her blood test that can use biomarkers to predict the risk of PPD before symptoms arise. Now that test is available in limited release for clinical use in select states: California, Texas and Florida. It's called myLuma. I’m re releasing this episode, originally released last summer, so that you can get a sense of some of the science underlying this potentially pregnancy changing test.

MyLuma: https://myluma.health/

Note: I have no connection with this company, but am so excited to see progress on physical tests for depression, especially in the context of pregnancy.

 One of the first things on an embryo's to-do list is to make a placenta, but to do this, it will need to work well with the decidual cells occupying the future Placenta construction site, otherwise known as the decidua or uterine lining that's beefed up for pregnancy.

There are likely many contributors to this process, but how this negotiation goes down between a specific set of immune cells called uterine natural killer cells, or uNK cells and the fetal cells from the embryo that set up the bridge between the mother's body and the placenta called the trophoblast cells, or EVTs is the subject of today's episode.

Also: why great obstetrical syndromes (preeclampsia, IUGR, stillbirth) is more of an issue for humans than other mammals.