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

This is part two of a two-part mini-series on fertility and reproductive health. Paula Amato is a leading expert in female reproductive health and infertility, widely recognized for her contributions to advancing fertility treatment and research. In this episode, which follows last week’s conversation on male fertility, Paula explores the biology of female fertility, including how hormonal changes regulate the menstrual cycle and ovulation, what those patterns reveal about fertility potential, and why both partners should be evaluated early in infertility workups. She discusses the role of the fallopian tubes, the causes of miscarriage, the impact of age and lifestyle on fertility, and treatment options for conditions like PCOS—including the emerging use of GLP-1 agonists. The episode also covers the evolution of IVF, advances in pre-implantation genetic testing, egg freezing, and the promise and limitations of next-generation reproductive technologies.

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We discuss:

• The finite nature of a woman’s egg reserve, how it changes over time, and the basic process of ovulation and fertilization [3:00];
• How hormones influence egg selection, and how and why chromosomal errors lead to most miscarriages [5:30];
• The full journey of conception—from hormonal cues triggering ovulation to fertilization, embryo development, implantation, and early pregnancy risks [16:30];
• How infertility is defined and diagnosed, and the broader trends contributing to rising infertility rates [25:15];
• Fallopian tube damage: how STDs and scarring impact fertility and raise ectopic pregnancy risk [31:30];
• Unexplained infertility: how doctors evaluate ovulation and cycles—and why more research on women’s health is needed [41:00];
• The defining symptoms of polycystic ovary syndrome (PCOS), its hormonal characteristics, and its relationship with insulin resistance [44:00];
• Managing PCOS without pregnancy: cycle regulation, androgen suppression, and insulin resistance treatment [46:00];
• The treatment approach for women with PCOS who are trying to conceive: GLP-1 use, ovulation induction, and timing protocols [49:45];
• Barriers to getting informed fertility care for PCOS: limited provider knowledge and access, insurance gaps, and next steps when ovulation treatments don’t lead to pregnancy [55:45];
• Fertility treatment for women with unexplained infertility, risk of multiple pregnancies with superovulation, and more [1:03:00];
• Intrauterine insemination (IUI): process, success rates, and when in vitro fertilization (IVF) becomes the better option [1:07:00];
• The history of in vitro fertilization (IVF), and how access and acceptance have evolved over time [1:16:45];
• The step-by-step process of IVF [1:19:30];
• The IVF lab process: egg retrieval, fertilization, embryo culture, and freezing [1:26:30];
• Genetic testing and embryo selection in IVF: aneuploidy screening, polygenic traits, and ethical concerns [1:41:15];
• Embryo transfer in IVF: timing, uterine preparation, and implantation support [1:47:30];
• Egg donation in IVF: indications, donor guidelines, and other considerations [1:50:45];
• How to choose the right IVF clinic [1:54:45];
• Innovations in fertility on the horizon, advice about freezing eggs, and more [2:02:00];
• Optimizing fertility through lifestyle: diet, stress management, sleep, exercise, and supplementation [2:07:45];
• Promising areas of fertility research [2:15:45]; and
• More.

The finite nature of a woman’s egg reserve, how it changes over time, and the basic process of ovulation and fertilization [3:00]

• The physiology in women is different from men, but no less complex, and there are some pretty unique things about it
• Sperm seem to be an infinite resource, men are constantly generating billions of these 
• The opposite is true for women

Women have a limited number of eggs 

• When an embryo or fetus develops, the gonad differentiates into either a testes or an ovary
• The main difference is that sperm is produced throughout a man’s lifetime, whereas women are born with a finite number of eggs

⇒ 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 2 million or so eggs, and by the time you start menstruating, you’re down to maybe 400,000 

A 5-fold reduction in the number of eggs occurs from birth to age 12-14, and most eggs in ovaries undergo a process called atresia (they die) 

• Once 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
  • Normally if there’s not sperm around, the egg just reabsorbs and there’s no pregnancy;  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
    • Then that now zygote or embryo travels down the tube into the uterus and some of the time implants into the the lining of the uterus and establishes a pregnancy

How hormones influence egg selection, and how and why chromosomal errors lead to most miscarriages [5:30]

The cycle of what’s happening in a woman of prime reproductive age (age 20) and the role hormones are playing 

• One of the things that has always fascinated Peter is the selection 
• With males, we don’t think about that problem
  • The selection tends to be more metabolic or stochastic
  • The sperm that makes it isn’t really predetermined
• At day 0, a woman begins her menstrual cycle, and she’s about 14 days from ovulation
• We start to see the interplay of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), particularly FSH
  • [The figure below shows how hormone levels change throughout the menstrual cycle]

Figure 1. Hormone levels during the menstrual cycle. Image credit: OpenStax Anatomy & Physiology Figure 27.15

Walk through what’s happening in that period of time that ultimately leads to one and only one egg being the chosen one 

• It’s a little random in women as well
• It’s true that the pituitary hormones (FSH and LH) are what drives growth of what we call the follicles
  • The eggs are inside the follicles
• Usually a cohort of eggs start to grow
  • The follicles start to get bigger and the cells surrounding the egg start to divide

Peter asks, “What do they look like prior to all of that happening? These are cells that only have 50% of the genetic material. They’ve already undergone meiosis.”

• Yes, they’re arrested in meiosis, and meiosis is not completed until they ovulate (and then in some cases are fertilized)
  • We have an arrested cell that has one of each of the mother’s chromosomes
    • Including one X chromosome by definition (one of her two sex chromosomes)

{end of show notes preview}

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Paula Amato, M.D.

Paula Amato, earned her Medical Degree and completed her residency in obstetrics and gynecology at the University of Toronto. She did a fellowship in reproductive endocrinology and infertility at the University of California-San Diego. Dr. Amato is a physician scientist. She is Professor of Obstetrics and Gynecology and Division Head of Reproductive Endocrinology and Infertility at Oregon Health & Science University. She sees patients at Spring Fertility in Portland, Oregon.  She served as president of the American Society for Reproductive Medicine from 2023-2024. 

Dr. Amato specializes in caring for patients with infertility, polycystic ovary syndrome, and menopausal issues. Her research focuses on innovative assisted reproductive technologies for the treatment of infertility and ovarian aging. Dr. Amato is an expert in the science of reproductive endocrinology and infertility. [Spring Fertility]

LinkedIn: Paula Amato

X: @PaolaAmato