Female fertility: optimizing reproductive health, diagnosing and treating infertility and PCOS, and understanding the IVF process | Paula Amato, M.D.

**Peter Attia** (0:11)
Hey everyone, welcome to the Drive podcast. I'm your host, Peter Attia. This podcast, my website and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen. It is extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive member-only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of a subscription. If you want to learn more about the benefits of our premium membership, head over to peterattiamd.com/subscribe. My guest this week is Dr. Paula Amato. Paula is a professor of OBGYN at Oregon Health and Science University and a leading expert in reproductive endocrinology and infertility. She's been on the forefront of research and clinical practice of IVF, fertility, preservation and reproductive aging. And today we then continue our two-part series on infertility. Last week, of course, we covered the male side of this with Dr. Paul Turek, and this week we're talking more about female infertility with Paula. In this episode, we discussed the biology of female fertility, how hormonal shifts drive the menstrual cycle and regulate ovulation, and what those patterns reveal about fertility potential, how infertility is defined, where to begin a workup, and why both partners should be evaluated early, the role of the fallopian tube in natural conception, and how infections and or structural issues can lead to infertility or ectopic pregnancy, the reality of miscarriage, and why most early losses are due to chromosomal abnormalities, not anything the patient is doing wrong, increasing impact of age, lifestyle, and environmental factors on fertility, especially as more people delay childbearing, causes and treatment options for polycystic ovarian syndrome, PCOS, the emergence of GLP-1 agonists in PCOS, and what we know and don't know yet about their impact on fertility and pregnancy safety, the nuances of diagnosing and treating unexplained infertility and how age and ovarian reserve shape clinical decisions, the evolution of IVF from early methods of today's technologies, including the use of pre-implantation genetic testing, considerations around egg freezing, how timing, age and egg quantity influence outcomes and decision making, promise and limitations of next-gen reproductive technologies such as mitochondrial replacement and many other things. So without further delay, please enjoy my conversation with Dr. Paula Amato.
Hey Paula, thank you so much for coming to Austin and sitting down to share some remarkable insights. Listeners last week will have heard us talk about all things that pertain to male fertility. And as promised, we're going to now talk about fertility, but from the female perspective. The physiology here is different, but no less complex. And there was some pretty unique things about it. One of them being that unlike sperm, which seemed to be an infinite resource, men are constantly generating literally billions of these things. The exact opposite is the case with women. Tell us a bit about that.

**Paula Amato** (3:44)
That's right. First, thanks for having me. Thanks for inviting me. It is true that when an embryo or fetus develops, the gonad differentiates into either a testes, or an ovary, and the main difference, as you said, is that sperm is produced throughout a man's lifetime, whereas women are born with a finite number of eggs. Actually, the most eggs you'll ever have is when you're in your mom's womb as a fetus, and by the time you're born, there's about two million or so eggs, and by the time you start menstruating, you're down to maybe 400,000 or so.

**Peter Attia** (4:18)
Wow. So a five-fold reduction from birth to, say, an average age would be maybe 14?

**Paula Amato** (4:24)
Yeah, 12 to 14 And we don't know why exactly that happens, but most of the eggs in the ovaries actually undergo a process we call atresia. They basically die. So once a woman goes through puberty, or a girl goes through puberty, every month, if she's not on hormonal contraception, one of those eggs grows. Actually, probably a group of eggs every month starts to grow, but then one takes over and is released from the ovary, and usually finds its way into the fallopian tubes. That's the tube connecting the ovary and the uterus. And then normally, if there's not sperm around, the egg just resorbs, and there's no pregnancy, and the lining of the uterus sheds, and a girl or woman has a period every month. If there's sperm around, there's a chance that that egg might fertilize, and that fertilization usually happens in the fallopian tube, actually. And then that, now, zygote or embryo travels down the tube into the uterus and some of the time implants into the wall of the uterus or the lining of the uterus and establishes a pregnancy.