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

 For all recorded time, the human menstrual cycle has been kind of a mystery. Is your period too long? Is your period too short? Are you bleeding too much? Is there too much pain? It's hard to answer these questions because I'm not sure it makes sense to compare yourself to some, quote, "average woman," because the menstrual cycle is so integrally involved in so many different systems in your body. It makes more sense to look at how your cycle is changing over time, but we don't even have very much data about that. Can we experiment with mice? Sure. But our system is different from the system of a mouse. Can we look at samples of the uterine linings of different women over time? Sure. But that approach tells a story that's not the same as whatever is going on in one person's uterus over time. Today's guest is ushering in a new era of uterine lining exploration that will allow for a much more dynamic, human-centered examination of this amazing tissue that's critical for both a successful pregnancy and integral to women's health. She is opening up the black box of the human menstrual cycle. An in vitro menstrual cycle using organoids captures epithelial cell transitions during menstruation and regeneration of the human endometrium: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(26)00145-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1934590926001451%3Fshowall%3Dtrue

 Your menstrual cycle is incredibly important for your overall health and for your best chance at a successful pregnancy. Creating a high-tech uterine lining each month that you will either continue to develop through a pregnancy or you'll eliminate if pregnancy isn't on the menu, is a biologically intensive and complex process. And there are a select few among all placental mammals who run this process the way humans do. Scientists estimate that less than 2% of placental mammals menstruate the way we do. Something like 84 species out of more than 5,000. All the primate species are relatively closely related, and we menstruate in a similar way, but there's also unexpected attendance at this intimate gathering of placental mammals that menstruate like us, including the spiny mouse, some species of bat, and the elephant shrew. This week's topic is focused on why we essentially organize so many bodily functions around the way that we have a menstrual cycle, how on God's green earth we do it, and what information we can glean from keeping track of cycle to cycle variation.

 In many things in life, timing matters. That's also true in labor. If we can align when we induce labor with what's known about the circadian rhythms of our body, we may be able to take advantage of times at which our bodies are more receptive to these interventions, and turn that advantage into shorter labors or fewer C-sections.Based on this retrospective study, these outcomes came with no costs to the newborns. Today we talk about some of the details of this work, how circadian rhythms show up in different ways for women of different weights, and what might be driving the induction impacts in the first stage of labor.

 If I told you that I've heard of a free way  to reduce the length of labor, to reduce the C-section rate for those most at risk of a C section, all without increasing the risk for the baby, you'd likely tell me to sell my magic beans to someone else. But labor and delivery do not arrive in a uniform way at all hours of the day. In fact, spontaneous labors tend to occur at night, with birth in the early hours of the morning. Using this fact, the researchers I speak with in this episode share what they found by dissecting the time of day into 1 hour slots to measure how the starting time of induction impacts labor outcomes like duration and mode of delivery.  It turns out that timing can have dramatic effects on these outcomes--which may significantly impact a mother's experience of birth.Time of Day of Induction Impacts the Total Duration of Labor: https://www.ajogmfm.org/article/S2589-9333(26)00009-1/fulltext

 Miscarriage is very much a part of pregnancy. It's really common. Roughly 20% of implanted embryos are estimated to miscarry. Unfortunately, stillbirth is also part of the process. The odds are 1 in 175. But for most women who experience these outcomes, it feels like a shock, something you couldn't imagine would happen. In today's episode, I continue my conversation with Dr. Harvey Kliman, who explains why miscarriage and stillbirths happen and offers ways we can try to understand and mitigate the situation.Find the paper and the density plot here, too:Placenal Pathology Findings in Unexplained Pregnancy Loss: https://pmc.ncbi.nlm.nih.gov/articles/PMC10827979/

 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.Let’s Talk about Placental Sex, Baby: Understanding Mechanisms That Drive Female- and Male-Specific Fetal Growth and Developmental Outcomes: https://pmc.ncbi.nlm.nih.gov/articles/PMC8232290/

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.

Although your OB usually doesn’t want to see you in the early weeks of pregnancy—there’s a lot going on that is of critical importance to the ease or complications of a pregnancy—specifically , the introduction of fetus to your uterine lining, and the subsequent merging, if implantation happens. The weeks that follow are equally consequential. Exactly how those cells of your uterine lining negotiate the migration of trophoblast cells, fetal cells that are building the placenta can be the difference between preeclampsia, premature birth intra uterine growth restriction and a normal pregnancy. One main negotiator of this migration is a specific type of immune cell, uNK cells. Today we talk to a world expert on how certain elements of the immune cell function in early pregnancy.  Dr. Ashley Moffett's 2022 paper in Nature Review Immunology: https://pmc.ncbi.nlm.nih.gov/articles/PMC9527719/#Sec1

We are going to talk about the menstrual cycle, aka the result of the conversation between your brain, pituitary and ovaries that’s going on each months to create the conditions for you to build a human. How does your body accomplish this amazing feat? You likely experience your menstrual cycle, and your period in particular, as an inconvenience, but evolution put a lot of hard work into this process and it turns out to be pretty nifty. We’ll also talk about the why today. Most mammals don’t have a menstrual cycle. Why do we think humans do? And how are the ways we have figured out to control that cycle operating in this complicated chemical conversation going on in your body? Are the movers and shakers of the menstrual cycle, the specialized cells that make all these changes happen each month, are they good for anything else? We’ll walk through these topics today.Questions or comments? write to [email protected], or find me on instagram @makingsenseofpregnancy

Current statistics suggest that postpartum depression is one of the most common complications of pregnancy in the US, estimated at between 1 in 10 and 1 and 5 women--and this estimate is mostly based on the response to survey responses.  The Edinburgh Postnatal Depression Scale (EPDS) is the most widely used screening tool for postpartum depression (PPD), recommended by ACOG, USPSTF, and PSI for universal screening at the 1-12 week postpartum visit, and is an imperfect tool to catch all cases.Contrast that to childbirth related PTSD--which is believed to be nearly as common, and for which no standardized screening tool exists. It's important to distinguish one from the other because the treatment is different for PPD and CB-PTSD.Dr. Dekel shares why the distinction is important and ways we might use to catch CB-PTSD early.

 The very first construction project in pregnancy is the placenta. It's critical to the embryo's development, and problems with the placenta can have significant consequences for the baby. Since doctors have been able to identify fetal growth restriction in the course of pregnancy--which started in about the 1970s-- the medical response has been to prescribe bedrest and or early delivery.In the second half of my conversation with Dr. Helen Jones, we talk about how this response to fetal growth restriction may give way to new gene therapy that can fix the placenta during pregnancy. 

 If you're listening to this episode on placental gene therapy, you may wanna sit down. Today's guest walks us through a gene therapy that (a) doesn't change the chromosomal DNA of the mother or the fetus; that (b) can reverse (you heard that right)--REVERSE placental insufficiency after it has taken hold, and as if that weren't enough, (c) has successfully restored fetal weight in growth, restricted Guinea pigs, passed safety checks in macaques and maybe in clinics as soon as five years from now.To look at Dr. Helen Jones' work, see: https://physiology.med.ufl.edu/profile/jones-helen/The paper we use as a scaffold for our conversation today: Placental Gene Therapy in Nonhuman primates: a pilot study of maternal, placental and fetal response to non-viral, polymeric nanoparticle delivery of IGF1: https://academic.oup.com/molehr/article/30/11/gaae038/7876288?login=false 

 Many headlines exclaim the wonders of AI and medical research. What better place to leverage the advantages of AI than in research about pregnancy that positively impacts everyone's health, both in the present and the future? And by that I mean the mother and the baby during the pregnancy and the baby's health trajectory into the future--and maybe also the mothers as well. Today's guests are an uncommon duo, a computer scientist, and an OB who are using big data algorithms and clinical experience to uncover the biological basis for some of the biggest issues in pregnancy. In particular, they're interested in the root causes of vascular issues that may develop into preeclampsia and or preterm birth.Today we talk about a new way for researchers to approach some of the biggest puzzles in pregnancy. 

 Never before in the history of humanity have we been able to examine a pregnancy in process and predict the risk of conditions before clinical symptoms have developed. Even 10 years ago, if you told an OB that you could reliably predict which pregnant women were most likely to encounter preterm birth in their first pregnancy, you'd likely be written off as a kook. The power to predict complications in pregnancy, premature birth, postpartum depression, and other postpartum states is a marker of phenomenal progress.For the second part of the end of the season recap, let's walk through some more of the amazing research and findings we talked about in the first season of the show that will change how we think about and manage pregnancy going forward.

 Looking through some of the research I highlighted on the podcast this year gives me a real sense of hope about the future of pregnancy, and I hope it does for you too. There's good news and bad news. Let's get the bad news outta the way first. It's true that women's health has gotten the short end of the stick in terms of federal funding and research interest for far too long, and research on pregnant women has gotten an even shorter version of that stick. It's still considered niche research in many quarters, despite the fact that. Every existing person owes their existence to a pregnancy, and what happened in that pregnancy likely affected important aspects of their lifelong health. That's the bad news. The good news is research on topics around fertility, pregnancy, birth, and postpartum have dramatically increased over the last 30 years. So for today's end of the year episode, I'm gonna take a walk through a theoretical pregnancy that's happening today with a tourist's eye for some of the amazing research we covered on the show this year. Of course, I can't distill 50 conversations into a half an hour, but let's walk through early pregnancy and see how this research may reshape how we think about and manage the first trimester.  

I am both hopeful and moved, AND filled with disbelief after my conversation with today's guest. He is an OB who has done an inordinate amount of work to make birth safer first for Californians, then for women across the country. His work, which you'll hear about and be able to use in your own pregnancy, is inspiring. What I can't get my head around is the state of maternity care he set out to change in 2006, some of which remains unchanged. Does it make sense that you don't really know the quality of care you'll get at your birth because hospitals didn't keep track of their health outcomes in a useable way? Does it make sense that C section rates vary widely between hospitals? No dear listener, it does not. We talk about the importance of data being collected and quickly disseminated so that hospitals actually know the quality of their maternal care and can compare their care with the care neighboring, and what should be competing hospitals, do, and you, too, as the consumer, can get a better handle on what you are walking into when you pick a hospital in which to give birth. 

 Many pregnancy complications cluster around issues with the placenta, the first fetal organ to form in a pregnancy. Here at the end of 2025, this organ still holds a significant amount of mystery. It's a wily organ that comes in many different forms across the animal kingdom. Even looking at how other mammals have handled the job of nutrient delivery, gas exchange, and waste removal during pregnancy, suggests a diversity of ways these jobs can be managed, emphasizing different benefits and costs in a pregnancy.Looking at how these benefits and costs show up in a cellular conversation between the placenta and the cells of the maternal uterine lining across a select group of mammals, including humans is a new way to understand this organ.

 How the placenta develops and the ways in which that development affect both the mother and the pregnancy have been a mystery since pregnancy became a subject of study. Much of medicine focuses on the symptoms that come from pregnancy complications and tries to find a way to fix if not the problem, then the symptom. Today's guest who looks at pregnancy with an evolutionary biology perspective that asks not only how the system works, but why the system works the way it does i.e. why are human placentas so invasive when other mammals have placentas that are not as invasive. Answers to the why questions can shape the ways in which we manage the how. To find the paper we're discussion today, Cell ype and cell signalling innovations underlying mammalian pregnancy, see: https://www.nature.com/articles/s41559-025-02748-x

We all know the placenta as this life giving organ, the first to develop in pregnancy; a critical connection between mother and fetus that sends food and oxygen to the baby and eliminates the fetal waste products. Only recently did I trip over the fact that it takes a minute to make this incredible organ.How long does it take and while its under construction?How exactly is the embryo and then fetus being fed ? In fact, it takes about eight or nine weeks for your body to build a placenta and then a few weeks to get the hookup to the mother's body, which takes us to roughly the end of the first trimester, 10 to 12 weeks or so.So if that's the case, you might be wondering: how is that embryo getting food for the first 12 weeks? Doesn't it need food to grow and oxygen maybe. What are we doing with the waste? How is all this managed before the placenta is the onsite perfect and all powerful fetal growth manager in a word, womb milk, or histotrophThis is the subject of today's episode. To contact me with questions or suggestions, find me at:[email protected] or @makingsenseofpregnancy

 Why is an active immune system important both in pregnancy and before pregnancy when you're trying to prepare the uterine lining, AKA, the decidua? That was the topic of last week's conversation with Dr. Berg's, and this week we talk about what we do and don't know about how to create a uterine lining that's hospitable to pregnancy, and the challenges of being able to predict when the uterine lining contributes to or detracts from pregnancy opportunity.

  Talk to any person who does research on pregnancy, and you may get a variety of different answers about the source of different pregnancy complications, and at what point in pregnancy we would have to turn back the clock to effectively intervene and increase the chances of a healthy pregnancy? Today's guest dates that time at the period before pregnancy even starts.She and her colleagues are investigating the importance of the process of creating a uterine lining, AKA, decidualization, that will, if many things fall into place, support implantation, placentation, and ultimately a healthy pregnancy, looking particularly at how our immune systems make our bodies fertile ground. Endometrial Decidualization: the primary driver of pregnancy health: https://www.mdpi.com/1422-0067/21/11/4092

   The very important role of a certain type of immune cell called neutrophils in pregnancy is the topic of today's episode. This is a continuation of the conversation we had last week with Dr. Suta NAD Carney, , who  is a researcher at the William Harvey Research Institute, faculty of Medicine and Dentistry at the Queen Mary University of London.We were talking about, the work she's done to uncover the role of the most common immune cell in your body, the neutrophil in pregnancy, and the way that it might contribute to one of the most common birth defects, which are heart defects.To briefly recap here, we used to think that neutrophils didn't play much of a role in pregnancy. The research we're talking about today highlights the role of neutrophils. Basically, they direct other immune cells to behave in an anti-inflammatory way, at the point at which the maternal tissue meets the fetal tissue.If neutrophils aren't around to send signals that generate this anti-inflammatory environment. The environment becomes too inflammatory, which affects the collagen that's protecting the placental barrier. That barrier becomes dysfunctional and maternal immune cells get loose and interrupt.Placental Inflammation leads to Abnormal Embryonic Heart Development: https://pmc.ncbi.nlm.nih.gov/articles/PMC10022676/

 Many pregnancy complications have a whodunit quality to them. Scientists don't yet understand exactly why things go wrong when they go wrong, but researchers tend to agree at this point that if there are issues with the placenta, the lifeline for the fetus, they can reverberate through the pregnancy into well-known conditions like preeclampsia, intrauterine growth restriction, in some cases preterm birth, as well as playing a role in the most common congenital birth defect, which are heart defects.When we are looking for culprits for these pregnancy complications, some scientists have considered the role of your immune system in pregnancy, but those who study the immune landscape have left out the most common white blood cell in your body: the neutrophil. Of all the white blood cells in your body, around 60% of them are neutrophils.They're part of the innate immune system, the first responders, and they're super important in everyday life. And as it turns out, also in pregnancy. Today's guest talks about the critical role played by the neutrophil in placental development and downstream in fetal cardiac development.Dr. Suchita Nadkarni: https://www.qmul.ac.uk/whri/people/academic-staff/items/nadkarnisuchita.htmlPlacental Inflammation leads to abnormal fetal heart development in the journal Circulation: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.061934Neutrophils induce proangiogenic T cells with a regulatory phenotype in Pregnancy in PNAS: https://www.pnas.org/doi/10.1073/pnas.1611944114

 Miscarriage and the failure of an embryo to implant are often attributed to issues with an aggressive immune system. Today I'm gonna tell you some stories about your immune system, and in particular how your immune system behaves in pregnancy, TLDR, you could not get pregnant without significant immune activity.Your body is reliant on your immune system to help it manage the development of a genetically distinct person inside the confines of your body. The immune system is important for many different stages of development, and different players are critical at different times. Today we'll focus on the first step in this process. The first meeting of the uterine lining and the embryo. Conversation with Dr. Jan Brosen's about the specific preparation of the uterine lining for pregnancy:  (part 1) https://podcasts.apple.com/us/podcast/understanding-miscarriage-through-evolutionary-biology/id1779600854?i=1000730772552(part 2) https://podcasts.apple.com/us/podcast/your-uterine-lining-determines-if-and-how-a/id1779600854?i=1000731948247

 If you wanna know what factors contribute to miscarriages, you need to understand what factors contribute to and detract from making the uterus into a hospitable place for pregnancy, both implantation and development. My guest last week, Dr. Jan Brosens, spoke about some of the key conditions that make implantation and development more and less likely, namely the presence of the just right mix of endometrial cells, some of which are progesterone responsive and progesterone resistant. But a fuller picture of the process suggests that there are other critical dimensions in this process of making the uterus hospitable. It's not just timing, but location that's important. 

Since women have been having babies they've experienced miscarriages. For nearly as long, we have not had a useful way to address miscarriage. Often doctors shrug at your first miscarriage and say it's a normal part of pregnancy. And if it arises because of aneuploidy, the fertilized egg has the wrong number of chromosomes, at this point there is not much we can do about that. But there are many routes to miscarriage. Today's guest is working to better understand other mechanisms at play in miscarriage. One of his guiding principles is to recognize that pregnancy in humans works according to its own rules. Adaptations that the human body has made that allow for a 9 month relationship between a fetus developing entirely inside it's mother's body don't exist in any other part of the body. Take, for example, the case of the placenta. there are a class of cells in the placenta that rapidly divide, invade uterine tissue and evade the immune system; this is critical to the development of a maternal fetal interface, but a similar pattern of cell growth outside of the context of pregnancy is often called cancer.  Understanding how human reproduction has evolved to address the challenge of a long pregnancy inside a woman's body has guided today's guest in his work to identify the specific factors that contribute to or prevent implantation, pregnancy and miscarriage.Here's a link to the 2025 paper in Science Advances with more details: https://www.science.org/doi/10.1126/sciadv.adv1988

Last week we talked about the technology, originally used to look at inflammation in the brain and heart, applied to the placenta. This amazing form of MRI, which is both non invasive and safe, allows for real time information about inflammation in a pregnancy in progress. Today I'll finish my conversation with Dr. Yong Wang about what he and his team found in the study that used this technology in pregnant patients.  

The placenta is critically important for the success of a pregnancy, being the physical connection between the mother's body and the developing fetus. Defects in the placenta tend to have significant consequences for the pregnancy and the fetus, including things like preeclampsia, preterm birth and maybe also congenital heart defects. So understanding what's going on in the placenta before these conditions develop has enormous potential to drastically improve the health of the fetus and future child. But figuring out that a problem is a foot before physical signs of that problem show themselves in the form of preterm contractions or high blood pressure in pregnancy has been a challenge. Today I'm talking to a researcher I'm describing as the Magellen of pregnancy, an explorer of sorts showing us new details of changes in inflammation during pregnancies in progress that we haven't been able to see before by adapting a specific type of MRI to image inflammation in the placenta in real time.To read the paper, you can find it here: https://pmc.ncbi.nlm.nih.gov/articles/PMC11698687/

This week we will focus on what in G-ds good name is going on in the uterus during your cycle. I don’t think I’m going too far out on a ledge to say that most of us consider our period an inconvenience at best, but when you hear some of the details of what’s actually going on, you may look at it differently. what’s happening in your uterus each month reads like science fiction–cells following hormone signals with a cult like fervency, multiplying like crazy and transforming into other cell types, building blood vessels on the fly and awakening glands to produce uterine milk. Not only are these cells responding to chemistry, to hormones, but they are also responding to the mechanical signals around them– they feel and respond to the physical pressure of the other cells around them–and it turns out these magic tricks, which, when they are working, can help your body to produce a new human life, and when they aren’t working may significantly contribute to; the risk of miscarriage, the risk of pregnancy complications (endometrial spectrum disorder) and, but also, at the same time, these cells may provide serious prospects for regenerative medicine as a “cure” for some sources of infertility. Here's a link to the episode on implantation: https://podcasts.apple.com/us/podcast/your-placentas-origin-story/id1779600854?i=1000701864045

Pregnancy can appear smooth when everything, or nearly everything goes according to plan--basically. But if you're part of the group of people for which it has not gone smoothly, in pursuit of what may have gone wrong, you find that this process is actually ridiculously complicated.One opportunity to appreciate this comes with IVF when doctors efforts to manage more aspects of this process can lead to insights about how it works.Today's guest talks about a theory that might explain a constellation of infertility, problems from repeated implantation, failure to preeclampsia, and even endometriosis.  

This week’s episode is the ‘Making Sense of Pregnancy’ version of the broadway play (and now movie) Wicked: it provides the back story of a critical character in pregnancy that you likely didn’t know enough about. It also serves as a useful introduction to next week’s show that features the work of a scientist who is trying to untangle one possible path to preeclampsia that seems to arise in women who undergo a certain form of IVF.  And that story hinges, critically on this temporary organ you are making every month called the corpus luteum. Today I’ll share the current state of research on how the corpus luteum is formed and what it does or, alternatively, all the things I didn’t know about how these temporary organ, critical for the survival of our species, is formed and managed inside a woman’s body.

If we wanted to bury the phrase “bounce back” to describe our expectation about how a body should respond in postpartum, I think today’s conversation can effectively do that. I talk to a researcher who has gathered the largest sample of data about women, before, during and after pregnancy, tracking 76 different lab values for 300,000 women between 2003 and 2020. His work shows the significant changes to physiology during pregnancy, and importantly, how long it takes different physical aspects to recover from pregnancy. Spoiler alert: the vast majority of tests take more than 3 months to recover. We’ll also talk about how some complications may well be related to preexisting issues, as seen in the preconception labs.You can find more of Dr. Alon's work here: https://www.weizmann.ac.il/mcb/alon/The previous episode that examines a blood biomarker for depression with Dr. Jennifer Payne: https://podcasts.apple.com/us/podcast/can-we-predict-postpartum-depression-from-inside-the/id1779600854?i=1000711126548

When it comes to categorizing pregnant women as high or low risk, we leave so much information on the table--which keeps us limited to the model where doctors use broad averages to triage care for pregnant women. Age is a definitive way to categorize pregnant women. On average a woman who is 35 or older is considered of advanced maternal age and may be watched more carefully throughout the pregnancy. But the number 35 is no magic line crossed; If you have encountered gestational hypertension or preterm birth in a previous pregnancy, you are “at risk” to experience it again, but that view of a second pregnancy is a rough cut of the information we could be using.If you knew more about your body’s response to pregnancy, could you turn that risk down?  Some aspects of personalized medicine have reached other areas of health care, and it now seems to be reaching pregnancy.In today’s episode I finish my conversation with Professor Benjamin Smarr, about his studies of pregnant women using data collected through an activity tracker. He shares some of his surprising results about miscarriage and age in pregnancy.Find more of Professor Smarr's work here: https://smarr.ucsd.edu/ 

In the olden days, women measured something called basal body temperature (BBT), which is core temperature, to track ovulation by measuring their temperature right when they wake up--it's the first thing you'd do-- with a special thermometer that measured to at least one-tenth of a degree, and record it on a chart  (maybe on your phone, maybe on paper) to identify a subtle temperature shift. But those were the horse and buggy days of biohacking. Now we can wear a ring that provides a continuous read out of your temperature and sends it to an app on your phone; and not only can it tell you if you are ovulating, it may be able to tell you if you are pregnant. Today we talk to Dr. Benjamin Smarr, PhD, who has used sensor data to uncover some of the dynamics of your body in pregnancy. You can find Dr. Smarr's work here: https://smarr.ucsd.edu/

The uterus has really lurked in the shadows of gestational research. We imagined that it was just a place where the fertilized egg decided to settle and grow. But recent research has recast the uterus in a more prominent role. To hear about how this research has overturned what we thought about pregnancy and placental function, I talked with a biologist who has focused on this topic for much of his career. A better understanding of the role of the uterus and how the placenta and uterus encourage each other's development in early pregnancy could help us understand infertility, miscarriage and maybe the genesis of some significant pregnancy complications.You can find Dr. Graham Burton's work here: https://www.trophoblast.cam.ac.uk/people/grahamburton

The how and when of uterine contractions--how are uterine contractions initiated? Whats the trigger or triggers? And when it happens too early, why does it happen too early?  are questions we haven't been able to answer as of yet.  Or maybe more accurately, we have a bunch of different possible answers, but we don't know how they interact with one another. Today I finish my conversation with Dr. Polina Lishko, who shares some of her research on a key mechanism for this trigger, and the other puzzles she and her team have been able to solve by understanding how this particular trigger works.

One of the big unknowns in pregnancy, and there are many, is what initiates labor. Researchers point to many different possible triggers, and likely it is some combination of signals from the placenta, the fetus and the mother that kick off productive contractions. This is a highly sought after bit of information in part because if we knew what initiated labor, maybe, just maybe we could turn it off in teh case of preterm labor. preterm labor is a significant issue in the US. 1 in 10 births are premature. And presently we don't have a successful approach to turning labor off once it's started--which is why my conversation with a researcher today, whose group has identified one of the switches that turns contractions on, is so exciting and inspiring.To read more about Dr. Lishko's work, you can find her here: https://cellbiology.wustl.edu/people/polina-lishko-phd/

Today we are all about fetal programming. It's also known as the Barker Hypothesis or Fetal Origins of Health and Disease. This theory suggests that the uterine environment can impact not just immediate health for the baby, but long-term health as well.The theory suggests that the nine month window of pregnancy is a particularly critical time in the body's development. It is when all organs are being formed and any physical or mental health issue for the mother that affects this sensitive environment of the uterus, leaves its mark on organ and system formation in the fetus.For a pregnant woman, I feel like this theory might spark ambivalence. There's something hopeful in it because it suggests some indirect control over something as important as long-term health, and you're not entirely beholden to the genetics you're passing on. But at the same time, this theory also comes with a lot of responsibility for the pregnant person.You may think I've already given up alcohol and sushi and cheese, and whatever your long list is while I'm sharing my body for nine months, not counting breastfeeding. Now, I'm also responsible for the baby's lifelong health. Let's dive into this topic and see what the state of the research is today.Episode with Dr. Alison Paquette testing Barker Hypothesis issues: https://podcasts.apple.com/us/podcast/the-connection-between-the-womb-and/id1779600854?i=1000697820556

It should not ALSO be a mother's job to catch her own depression after delivery.In pregnancy care in the future, imagine if you walked into your OBs office in your third trimester and you got a blood test that could predict how likely you are to run into postpartum depression? Among all your other novel and challenging responsibilites as the caretaker of a newborn, it would not be your responsibility while operating on very little sleep to also be carefully monitoring and analyzing your emotional state so that you can reach out to a doctor if anything seems awry--and that's making the sometimes large leap in imagining that amidst all the change and newness you'd be able to tell whether the change you may be feeling is typical or one that requires help. Today's guest will talk about this future.You can find Dr. Payne's work here, at the Reproductive Psychiatry Research Program: https://med.virginia.edu/psychiatry/research/reproductive-psychiatry-research-program/

 This week's episode is kind of a how to episode. It's how do you grow a placenta, an entirely new organ, and quickly. Probably a more accurate title would be how do we think we might grow a placenta? How does a placenta develop? Maybe because in truth we have by no means worked out all of the details about how this critical life-giving organ is formed.Having said that, let's run through some of what we think we know today.Growing the placenta is kind of like establishing a fetal embassy inside the united organs of you. It's subject to the laws and customs of the mother country expressed through her chemistry and the condition of her body. But the embassy has ways to get what it needs. Today, I'll highlight what we think is going on and the ways in which we're able to track this progress while it's going on, and what we can do if we run into trouble.

I admit that I love a cross over event, especially when it comes to pregnancy and birth research. Today's crossover involves the use of sports medicine to think about issues that come up in delivery. In particular, we'll talk to both the CEO and one of the co-founders of a company making a device to predict postpartum hemorrhage before it happens. Something like 40% of cases happen to women who are considered low risk, so a tool that helps to flag these people could be significant.Find more about vasowatch here: https://www.vasowatch.com/Find more about Dr. Weimer's internet-of-medical-things lab here: https://jamesweimer.net/

The human placenta is a superhero of organs. It's a master regulator of hormones, a negotiator with the maternal immune system, and capable of adapting structurally and metabolically--in real time--to changes in it's environment to cater to the fetus. But it also has a lot of black box features, in part because it is a difficult organ to study. My guest today talks about an amazing paradigm shift in the way we can examine the placenta, using organ on a chip technology that frees us from the petri dish, and takes advantage of organ on a chip technology to create a 3-D proto placenta that responds to mechanical pressure and allows for investigation of the interaction between multiple cell types grown from induced human pluripotent stem cells. This kind of model will allow us to ask lots of important questions about how the placenta interacts with different drugs and maybe too what factors influence how the developing placenta invades the mother's body, providing more clues about preeclampsia, among other things.You can find more about Dr. Colin Murdoch's work here: https://www.dundee.ac.uk/people/colin-murdoch