Dr. Natalie Crawford: Female Hormone Health, Fertility & Vitality

Podcast Host: Dr. Andrew Huberman (Stanford Associate Professor - brain development, brain plasticity, and neural regeneration and repair fields).

Podcast Guest: Dr. Natalie Crawford, MD, is a double board-certified physician specializing in obstetrics and gynecology, fertility, and reproductive health and host of the “As a Woman” podcast.

Key Takeaways:

Understanding egg depletion and fertility preservation techniques is crucial for making informed reproductive decisions (Segment 2)
Distinguishing natural puberty from endocrine-disruptor-induced changes and understanding prenatal influences on reproductive health is crucial for reproductive well-being (Segment 3)
Mindful choices about everyday products, especially those involving frequent skin contact, are crucial for children's long-term health (Segment 4)
Breastfeeding during the first six months of an infant's life may have long-term benefits for their immune system and fertility (Segment 5).
Combined oral contraceptives prevent ovulation by suppressing follicle-stimulating hormone (FSH) secretion and are reversible and may even enhance fertility in some cases (Segment 8)
Testosterone levels and high heat exposure significantly impact fertility in both sexes (Segment 9)
Estrogen's surge before ovulation boosts libido and enhances the chances of conception (Segment 12)
Smoking, vaping, cannabis, and excessive alcohol consumption can harm fertility and pregnancy outcomes (Segment 14)
The birth control pills are one of the major causes of polycystic ovarian syndrome (Segment 16)
Egg freezing offers a viable option to preserve fertility, with advancements leading to improved survival rates and cost-effectiveness compared to embryo freezing (Segment 20)
The dual application of donor mitochondrial DNA or eggs is successful in addressing mitochondrial disorders but facing political obstacles in the U.S. regarding embryo research (Segment 24).
Paternal and maternal sex play a crucial role in autism (Segment 26).
Prenatal vitamins, vitamin D, omega-3 fatty acids, and CoQ10 supplements are very important for reproductive health (29).

Summary:

For this particular podcast, the featured guest is Dr. Natalie Crawford, an accomplished medical professional who holds dual board certifications in the fields of obstetrics and gynecology, as well as fertility and reproductive health. Dr. Crawford is also the esteemed host of the widely recognized podcast titled "As a Woman." This discussion encompasses various aspects related to female hormones, diet, supplementation, reproductive health, and fertility. Specifically, we explore the influence of the timing and duration of puberty on a woman's long-term hormone cycles and menopause. In addition, we engage in an examination of the advantages and disadvantages associated with different forms of contraception, as well as an analysis of the impact of hormonal and non-hormonal birth control on reproductive capacity. This article discusses the various factors that influence the quality of eggs and sperm, as well as strategies for optimizing the timing of conception. In addition, we explore methodologies for evaluating female fertility, encompassing assessments of ovarian reserve through egg count and hormone testing, as well as elucidating the intricacies of oocyte cryopreservation, in vitro fertilization (IVF), and alternative reproductive alternatives. This episode provides a thorough examination of female hormones and reproductive health, emphasizing the significance of various tests and screenings, as well as the range of behavioral, nutritional, supplement, and prescription-based interventions available to women of all age groups in order to enhance fertility, hormone regulation, and overall well-being.

1. 00:04:59 Female Puberty & Growth Characteristics, Height

The initiation of female reproductive capacity commences during the prenatal period, whereby the highest quantity of eggs is observed at approximately 20 weeks of gestation, subsequently diminishing considerably by the time of delivery. During the process of early growth and puberty, the ovaries experience a steady depletion of eggs. The commencement of puberty entails the activation of the hypothalamic-pituitary-gonadal axis, wherein the brain communicates with the ovaries to stimulate the production of follicle-stimulating hormone (FSH). This hormonal cascade prompts the formation of ovarian follicles, which house the developing eggs and initiate exposure to estrogen. Consequently, the presence of estrogen triggers the development of secondary sexual characteristics, such as breast growth. Typically, the onset of breast development occurs approximately two years prior to the occurrence of menarche, which refers to the onset of the first menstrual cycle. Additional secondary sexual features encompass the maturation of pubic and axillary hair, concomitant with the initiation of body odor as a result of hormonal fluctuations. During the onset of puberty in males, there is a noticeable emergence of a unique body odor as well as the growth of facial and body hair. The discourse also addresses the phenomenon of early initiation of puberty in females, which may have ramifications for height, and briefly alludes to the utilization of blockers to postpone puberty in instances of precocious puberty [1].

References

Nakamoto, J.M., Myths and variations in normal pubertal development. West J Med, 2000. 172(3): p. 182-5.

2. 00:13:27 Eggs & Ovulation, Harvesting Eggs, In Vitro Fertilization (IVF)

The temporal occurrence of puberty initiation in females does not exert an influence on the entirety of the reproductive lifespan or the potential fall in fertility. The depletion of oocytes initiates during prenatal development and persists on a monthly basis, regardless of the onset of menstruation. The concept of an egg "vault" is employed to elucidate the ongoing nature of egg accessibility and attrition, which remains unaffected by the age at which a female commences menstruation. The comprehension of this idea is of utmost importance in debunking misunderstandings around fertility preservation techniques such as oocyte cryopreservation or in vitro fertilization (IVF). The act of harvesting eggs for these treatments does not expedite the depletion of the egg reserve. Instead, it entails the manipulation of the natural process of egg release in order to optimize efficiency. The pharmaceutical agents employed in vitro fertilization (IVF), namely follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are administered with the objective of inducing the development of oocytes, facilitating their cryopreservation for potential future utilization, while preserving the total ovarian reserve. This clarification aims to address prevalent concerns surrounding fertility preservation and advocate for a better-informed decision-making process regarding reproductive options [2].

Figure 1. In vitro fertilization general protocol [3].

References

Wang, J. and M.V. Sauer, In vitro fertilization (IVF): a review of 3 decades of clinical innovation and technological advancement. Ther Clin Risk Manag, 2006. 2(4): p. 355-64.

3. https://craftivf.com/in-vitro-fertilization-ivf/

3. 00:17:31 Endocrine Disruptors, Fetal Development

Differentiating between the onset of natural puberty and the emergence of secondary sexual traits caused by endocrine-disrupting drugs is of utmost importance. The potential impact of exposure to chemicals such as evening primrose, lavender, or tea tree oil on breast bud development in boys, as a result of estrogen exposure, has been seen. However, it is important to note that this exposure does not begin the onset of puberty. Likewise, it is possible for adolescent females to display initial indications of pubertal development, hence requiring assessment by a specialist in pediatric endocrinology in order to distinguish between extrinsic influences and the genuine onset of puberty. The discourse additionally explores the susceptibility of ovarian development throughout prenatal periods, highlighting the potential influence of maternal behaviors during pregnancy on a child's ovarian reserve and their susceptibility to illnesses such as diminished ovarian reserve, polycystic ovary syndrome (PCOS), or endometriosis. The correlation between the exposure to endocrine disruptors in the 1980s and 1990s and the present occurrence of reproductive health problems underscores the significance of including the prenatal environment into the comprehension of fertility difficulties. The presence of a comparable phenomenon in male fetal development, wherein early hormonal influences contribute to subsequent puberty responses, highlights the significant influence of preconception and fetal phases on total reproductive well-being [4].

Figure 2. Different classes of endocrine-disrupting chemicals (EDCs) [5].

References

Koulivand, P.H., M. Khaleghi Ghadiri, and A. Gorji, Lavender and the nervous system. Evid Based Complement Alternat Med, 2013. 2013: p. 681304.
Padmanabhan, V., Song, W., & Puttabyatappa, M. (2021). Praegnatio perturbatio—impact of endocrine-disrupting chemicals. Endocrine Reviews, 42(3), 295-353.

4. 00:21:39 Lavender, Tea Tree & Evening Primrose Oils, Scents, Diapers

The discourse emphasizes the significance of exercising mindfulness in relation to the goods we utilize, specifically those that involve frequent and extended touch, such as shampoos or soaps. The discussion underscores the need to select unscented items, particularly for children, during crucial developmental periods, by placing emphasis on the potential enduring physiological consequences associated with prolonged exposure to specific chemicals. Recommendations encompass a range of commonplace commodities, including laundry detergent, shampoo, conditioner, soaps, and body oils. Notably, lavender oil is highlighted due to its widespread utilization. This study examines the decision-making process regarding the use of cloth versus non-cloth diapers, taking into consideration the lack of definitive facts regarding the permeability of newborn skin. It acknowledges that the developmental period in early life plays a crucial role in establishing the groundwork for potential future outcomes. The discourse promotes an individualized methodology, acknowledging the various factors associated with both diaper alternatives, and emphasizes the importance of reducing children's exposure to toxins, either by selecting appropriate products or opting for diapers with reduced presence of potentially harmful compounds [6].

References

Martin, C.R., P.R. Ling, and G.L. Blackburn, Review of Infant Feeding: Key Features of Breast Milk and Infant Formula. Nutrients, 2016. 8(5).

5. 00:25:13 Breast Milk vs. Formula & Fertility

Exposure to breast milk throughout the initial six months of an infant's life is of paramount importance in the development of their immune system. The early enhancement of immune response has been found to be associated with a reduced susceptibility to autoimmune disorders, particularly those that are correlated with intestinal permeability. Although it is not explicitly claimed that the absence of nursing directly causes fertility problems, there is a correlation between the preventative benefits of breastfeeding and a reduced probability of certain illnesses. This association may have potential ramifications for female fertility in the future. The discourse highlights the prospective enduring influence of early nutrition and immunological support on overall health and fertility results [7].

Table 1. Advantages and disadvantages of breast and formula milk feeding in babies [7].

References

Bruinvels, G., A.C. Hackney, and C.R. Pedlar, Menstrual Cycle: The Importance of Both the Phases and the Transitions Between Phases on Training and Performance. Sports Medicine, 2022. 52(7): p. 1457-1460.

6. 00:26:04 Menstruation Cycle & Hormones, Timing

The onset of the menstrual cycle is typically identified as day one, which signifies the commencement of uterine bleeding and the subsequent shedding of the endometrial lining. This marks the commencement of the follicular phase, during which eggs, which have become responsive to follicle-stimulating hormone (FSH), begin to develop within follicles and subsequently secrete estrogen. During the estrogen-dominant phase, individuals may have increased energy levels and a more cheerful attitude. Ovulation is triggered by a rise in luteinizing hormone (LH) that occurs when estrogen levels reach their peak. The follicle that has undergone rupture transforms into the Corpus luteum, which is responsible for the production of progesterone during the luteal phase. In the absence of pregnancy, the Corpus luteum undergoes a lifespan of approximately 12 to 14 days. This temporal progression prompts a decline in the levels of estrogen and progesterone, thereby initiating the onset of menstruation and initiating a fresh menstrual cycle. The duration of the luteal phase has a rather stable pattern, whereas the follicular phase is subject to variability. The establishment of a regular cycle is of utmost importance, as any deviations from the norm may indicate potential disruptions in hormonal communication. The act of reducing the duration of menstrual cycles may serve as an indicator of a decrease in the quantity and quality of a woman's ovarian follicles, sometimes referred to as diminishing ovarian reserve. The monitoring of menstruation regularity is regarded as an essential indicator, serving as a reflection of hormonal well-being and possible health issues [8].

Figure 3. Various important phases of the Menstrual Cycle [9].

References

Bruinvels, G., A.C. Hackney, and C.R. Pedlar, Menstrual Cycle: The Importance of Both the Phases and the Transitions Between Phases on Training and Performance. Sports Medicine, 2022. 52(7): p. 1457-1460.
https://helloclue.com/articles/cycle-a-z/the-menstrual-cycle-more-than-just-the-period

7. 00:35:59 Estrogen, Progesterone & Menstrual Cycle

Indeed, the elucidation provided on the follicle as a fluid-filled structure housing the ovum and its subsequent rupture during the process of ovulation is of utmost significance. The structure in question is a transient cyst that ruptures to facilitate the discharge of the egg, subsequently transitioning into the Corpus luteum and initiating the process of tissue repair. The user's observation regarding the roles of estrogen and progesterone is accurate, with estrogen being responsible for promoting the growth of the uterine lining and progesterone playing a crucial role in maintaining its stability for potential implantation. The acknowledgment of the normalcy of estrogen dominance and progesterone deficiency throughout the follicular phase holds significant value, particularly in resolving issues over the interpretation of randomly obtained laboratory tests. A comprehensive comprehension of the cyclicality inherent in hormone production is crucial for the appropriate interpretation of findings and the provision of reassurance to individuals on the inherent fluctuations occurring during distinct phases of the menstrual cycle [10].

Figure 4. The levels of various types of hormones during different stages of ovulation [11].

References

Yen, J.Y., et al., Early- and Late-Luteal-Phase Estrogen and Progesterone Levels of Women with Premenstrual Dysphoric Disorder. Int J Environ Res Public Health, 2019. 16(22).
https://womeninbalance.org/about-hormone-imbalance/

8. 00:38:08 Hormonal Birth Control & Ovarian Reserve, AMH Testing, Fertility

Combined oral contraceptives, commonly known as "the pill," consist of estrogen and progestin components. These contraceptives do not affect the release of eggs from the ovarian follicles. Instead, they exert their contraceptive effect by suppressing the secretion of follicle-stimulating hormone (FSH) from the hypothalamus and pituitary gland, thereby limiting ovulation. The expulsion of eggs remains unchanged; but, in the absence of follicle-stimulating hormone (FSH), they undergo natural degeneration, hence rendering contraception efficacious. Although birth control does not have any negative effects on fertility or the ovarian reserve, it is crucial to take certain factors into account. The extended utilization of oral contraceptives has the potential to transiently inhibit the presence of antimullerian hormone (AMH), which serves as an indicator of ovarian reserve. This occurrence can introduce complexities in the evaluation of fertility. The reversibility of the influence should be taken into account when assessing ovarian reserve in persons using birth control, as the interpretation of results must acknowledge the potential suppression of anti-Müllerian hormone (AMH). It is noteworthy that prolonged utilization of oral contraceptives may potentially enhance fertility in persons diagnosed with illnesses such as endometriosis. The utilization of oral contraceptive pills is frequently observed in in vitro fertilization (IVF) protocols to synchronize the maturation of eggs, hence enabling a controlled and harmonized approach to fertility interventions. In the realm of reproductive health, the pill serves as a highly valuable instrument, providing efficacious contraception and strategic utility in the realm of fertility therapies [12].

References:

12. Hariton, E., et al., Anti-Müllerian hormone levels among contraceptive users: evidence from a cross-sectional cohort of 27,125 individuals. Am J Obstet Gynecol, 2021. 225(5): p. 515.e1-515.e10.

9. 00:42:42 Spermatogenesis & Testosterone; Heat: Ovaries vs Testes

Spermatogenesis is an ongoing and dynamic biological process, wherein the testes exhibit a daily capacity for the production of fresh sperm. In contrast to women, who possess a finite amount of eggs from birth, men exhibit continuous sperm production, affording them more adaptability and the capacity for regeneration. Nonetheless, the occurrence of some variables such as testosterone can interfere with this physiological process by transmitting signals to the brain indicating the presence of an adequate amount of sperm, thereby causing a suppression of FSH and LH, which are essential for the creation of sperm. Extended exposure to testosterone can impede the resumption of sperm production, perhaps leading to a lasting effect. Conversely, apprehensions regarding thermal exposure, such as saunas or hot tubs, predominantly impact the testes owing to their exterior location, which facilitates temperature regulation. In the case of females, whose ovaries are located internally, it can be observed that heat exposure does not exert the same adverse impact on the processes of ovulation or hormone production. It is advisable for pregnant individuals to exercise caution when exposed to high heat since it has the potential to impact the development of the fetus during the early stages of organogenesis. In general, comprehending the discrete mechanisms inside the male and female reproductive systems facilitates the comprehension of how different factors influence fertility [13].

Figure 5. The stimulatory effects of three hormones involved in spermatogenesis [14]

References

13. Walker, W.H., Testosterone signaling and the regulation of spermatogenesis. Spermatogenesis, 2011. 1(2): p. 116-120.

14. https://www.nagwa.com/en/explainers/525185982150/

10. 00:46:11 Period & Pregnancy, Conception Window

The prevailing notion that conception is impossible during menstruation is not totally precise. Although typically less fertile, particularly in persons with regular menstrual cycles, it is possible for sperm to survive in the reproductive canal for a duration of up to five days. However, it is important to note that variations in cycle length or timing of ovulation may result in certain exceptions to this general rule. The period of highest fertility is commonly regarded as the five-day interval preceding and encompassing the day of ovulation. The ovum remains capable of fertilization for around 24 hours following ovulation, whereas spermatozoa can maintain their viability for a duration of up to 5 days. Individuals who possess regular menstrual cycles or engage in active ovulation tracking can enhance their likelihood of pregnancy by focusing sexual intercourse efforts on the day preceding and the day of ovulation. Gaining knowledge about the intricacies of the menstrual cycle and the period of viability enables individuals to make well-informed choices regarding family planning and reproductive capabilities [15].

References

15. Harville, E.W., et al., Vaginal bleeding in very early pregnancy. Human Reproduction, 2003. 18(9): p. 1944-1947.

12. 00:48:56 Estrogen, Libido & Ovulation; Mittelschmerz

The relationship between estrogen, libido, and ovulation in females is closely intertwined. Higher estrogen levels are associated with increased libido, particularly during the peak estrogen levels that trigger the LH surge leading up to ovulation. The body is naturally designed for reproduction, and this surge in estrogen and libido aims to encourage sexual activity during the ovulatory period to enhance the chances of conception. Some individuals claim to sense the moment of ovulation, describing a crampy pain known as mittelschmerz. This phenomenon, experienced by those attuned to their bodies, aligns with the rupture of the ovarian cyst during ovulation, releasing the egg and follicular fluid into the pelvic cavity. The intricate and well-coordinated processes of the reproductive system, including the timing of hormonal surges and the sensations associated with ovulation, highlight the marvels of biological orchestration [16].

References:

16. Cappelletti, M. and K. Wallen, Increasing women's sexual desire: The comparative effectiveness of estrogens and androgens. Horm Behav, 2016. 78: p. 178-93.

13. 00:51:33 Tool: Intercourse Timing & Conception; Artificial Insemination, IVF

Regarding the frequency of sexual intercourse and fertility, maintaining a regular interval between sexual activity is crucial for optimal chances of conception. Daily intercourse, especially during the fertile window, is associated with the highest fertility rates. However, for couples not engaging in daily intercourse, the stress of adhering to a strict schedule can impact both the emotional and physical aspects of the relationship. To alleviate this stress, a recommended approach is to have intercourse every other day throughout the fertile window, starting five or six days before the anticipated ovulation and focusing on the day before and the day of ovulation. This strategy aims to balance sperm exposure and prevent burnout, allowing for a more relaxed and sustainable approach to conception. Additionally, when it comes to semen analysis or procedures like IUI and IVF, specific abstinence periods are recommended to ensure accurate evaluation or enhance the effectiveness of assisted reproductive techniques. Understanding these dynamics can aid individuals in making informed decisions about family planning and fertility treatments [17].

Figure 6. Artificial insemination types and methods [18].

References

17. Radaelli, M.R.M., et al., Timed intercourse in association with controlled ovarian hyperstimulation as the first-line treatment of couples with unexplained subfertility. JBRA Assist Reprod, 2022. 26(4): p. 612-619.

18. https://www.invitra.com/en/artificial-insemination-ai/

14. 00:55:03 Egg/Sperm Quality, Cigarettes, Vaping, Cannabis & Alcohol

Smoking cigarettes, vaping nicotine, and cannabis use, whether edible or smoked, have been linked to adverse effects on both egg and sperm quality, influencing fertility and pregnancy outcomes. Smoking is known to decrease the number of eggs, accelerate entry into menopause, and increase the risk of abnormal chromosomes, impacting egg quality. Vaping, although a relatively newer phenomenon, is associated with poor success rates in IVF cycles, suggesting potential harm to egg quality. Cannabis use negatively affects sperm production, motility, morphology, and DNA integrity, heightening the risk of miscarriage. While individual experiences may vary, these habits are generally considered detrimental to fertility, and optimizing lifestyle choices becomes crucial for those planning pregnancies. Additionally, alcohol consumption, a known toxin requiring liver processing, can lead to chronic inflammation, impacting egg and sperm quality. Moderation is advised, especially during pregnancy, where abstinence is recommended to avoid fetal alcohol syndrome and potential fertility implications. Making informed choices in anticipation of pregnancy is vital for setting the stage for reproductive success [19].

Figure 7. Effects of various types of chemicals and drugs on Male fertility [19].

References

19. Close, C.E., P.L. Roberts, and R.E. Berger, Cigarettes, alcohol and marijuana are related to pyospermia in infertile men. J Urol, 1990. 144(4): p. 900-3.

15. 01:03:29 Intrauterine Device (IUD), Depo-Provera & Fertility

Various birth control methods impact fertility differently, and understanding their mechanisms is crucial. Copper IUDs, causing inflammation without hormonal involvement, create a uterine environment hostile to sperm and less conducive to implantation. Progesterone-based IUDs, like Mirena or Kyleena, mainly work by thinning the uterine lining, inhibiting implantation. While they don't consistently prevent ovulation, prolonged use may lead to a thin endometrium, delaying the return of regular periods once the IUD is removed. The Depo-Provera shot, a high-dose progesterone contraceptive, not only prevents ovulation for three months but can linger in the system for up to 18 months, affecting menstrual patterns. Planning for pregnancy involves considering the timing of contraceptive discontinuation and potential delays in restoring natural menstrual cycles. Proactively managing these factors can optimize fertility when transitioning from contraception to family planning [20].

References:

20. Damtie, Y., et al., Fertility return after hormonal contraceptive discontinuation and associated factors among women attended Family Guidance Association of Ethiopia Dessie model clinic, Northeast Ethiopia: A cross-sectional study. PLoS One, 2023. 18(7): p. e0287440.

16. 01:10:00 Birth Control Risks & Benefits, Cancers, Polycystic Ovarian Syndrome (PCOS)

The birth control pill, a commonly employed contraceptive method, presents a range of dangers and benefits that are subject to individual variation. Consisting of ethinyl estradiol, synthetic estrogen, and progestins, this medication does not accurately mimic the endogenous hormones secreted by the ovaries. The practice of continuous pill usage, which is commonly employed to mitigate hormone swings and prevent menstrual cycles, has the potential to lead to atrophic vaginitis, affecting the overall health of the vagina. Although the contraceptive pill has demonstrated its potential to be beneficial in terms of mental health preservation, management of heavy menstrual cycles, and prevention of specific types of cancers such as endometrial and ovarian cancer, it also raises certain apprehensions. Extended utilization of this substance may potentially elevate the susceptibility to breast cancer, obscure the detection of underlying irregularities in the menstrual cycle, and has been associated with the development of disorders such as leaky gut syndrome or irritable bowel syndrome (IBS). Gaining a comprehensive understanding of the effects of oral contraceptive pills on the body's hormonal and physiological equilibrium is vital in order to make well-informed decisions regarding contraception and overall well-being [21].

Figure 8. PCOS pathways and causes in the reproductive system of women [22].

References

21. Oguz, S.H. and B.O. Yildiz, An Update on Contraception in Polycystic Ovary Syndrome. Endocrinol Metab (Seoul), 2021. 36(2): p. 296-311.

22. https://www.lifeextension.com/protocols/female-reproductive/polycystic-ovary-syndrome-pcos

17. 01:19:39 Blood Clotting & Birth Control Pill; Health Screening

When evaluating the use of oral contraceptives, it is imperative to recognize the potential hazards and account for individual variances. Although the pill is generally considered safe for a majority of individuals, it is important to exercise caution and take essential precautions. For instance, individuals with high blood pressure or those who engage in cigarette smoking should avoid the use of the pill, as these factors can increase the risk of stroke. The practice of routinely screening for hereditary clotting diseases is not commonly performed. However, in cases where an individual develops a blood clot while using oral contraceptives, it becomes crucial to do a thorough investigation, particularly if there is a familial predisposition to clot-related complications. Advocating for one's health and asking inquiries is encouraged. The discourse surrounding ovarian reserve testing explores the intricacies of screening guidelines, underscoring the significance of comprehending and advocating for one's own healthcare. Screening determinations are frequently impacted by considerations of cost-effectiveness, and individuals may be required to navigate the intricacies of healthcare in order to guarantee comprehensive assessment and suitable testing in accordance with their specific circumstances [23].

References

23. Piparva, K.G. and J.G. Buch, Deep vein thrombosis in a woman taking oral combined contraceptive pills. J Pharmacol Pharmacother, 2011. 2(3): p. 185-6.

18. 01:24:50 Tool: AMH Testing, Ovarian Reserve, Antral Follicle Count Ultrasound

The question of ovarian reserve testing, particularly in relation to the measurement of AMH levels, is a subject of intense controversy within academic circles. Although the ACOG discourages routine screening, Dr. Crawford presents a contrasting perspective, advocating for the significance of such screenings. The measurement of AMH levels, acquired by a blood test, provides valuable information regarding ovarian reserve. The average cost associated with this diagnostic procedure amounts to $79. This information has the potential to provide individuals with the necessary knowledge to make well-informed decisions regarding their fertility. The assessment of AFC using ultrasound imaging offers a visual depiction of eggs located outside the ovarian vault, contributing to the comprehensive comprehension of ovarian health. In his explanation, Dr. Crawford delineates the anticipated follicle counts within various age cohorts, placing particular emphasis on the exponential reduction in ovarian reserve subsequent to reaching the age of 37. The dialogue pertains to the significance of assuming the role of a health advocate and the potential advantages of early detection of reproductive status [24.].

References:

24. Jirge, P.R., Ovarian reserve tests. J Hum Reprod Sci, 2011. 4(3): p. 108-13.

19. 01:29:55 IVF, In Vitro Maturation (IVM); Early Ovarian Reserve Screening

In the Huberman Lab podcast, Dr. Natalie Crawford sheds light on the dynamic nature of fertility technologies, with a specific focus on in vitro maturation (IVM). The primary objective is to optimize efficacy for individuals with a limited number of oocytes, a prevalent constraint in reproductive treatments. The discussion returns to the dispute around ovarian reserve testing, specifically the screening of anti-Müllerian hormone (AMH). The ACOG presents arguments opposing routine screening, but Dr. Crawford and the podcast host take a skeptical viewpoint. The focal point of their emphasis lies on the practical choices individuals encounter in their daily lives, encompassing aspects such as interpersonal dynamics, strategic family planning, and the pivotal deliberation surrounding the decision to undergo oocyte cryopreservation. The debate questions the viewpoint of the ACOG, highlighting the possibility of stress that can be acted upon, enabling individuals to make well-informed decisions regarding their journey toward conception. The utilization of the analogy of testing for potential paralysis serves to emphasize the significance of adopting a proactive approach to decision-making, challenging the idea of deferring contemplation of motherhood until complications manifest. Dr. Crawford advocates for the regular administration of annual anti-Müllerian hormone (AMH) tests among individuals considering family planning, indicating a transition toward a more individualized and evidence-based approach to reproductive healthcare [25].

Figure 9. Diagrammatic comparison of conventional IVF and IVM.

References

25. Le, H.L., et al., Live birth after in vitro maturation in women with gonadotropin resistance ovary syndrome: report of two cases. J Assist Reprod Genet, 2021. 38(12): p. 3243-3249.

26. https://fertility.coopersurgical.com/in-vitro-maturation/

20. 01:35:40 Tools: Egg Freezing, IVF; Age & Egg Quality

The methods of egg freezing and in vitro fertilisation (IVF) are often compared due to their shared characteristic of extracting eggs from the body, followed by the subsequent choice of either cryopreserving them or subjecting them to laboratory fertilisation for IVF purposes. The technological advancements in the field of oocyte cryopreservation have seen substantial progress in the last ten years. Presently, the survival rate of thawed eggs stands at an impressive 90%, hence enhancing the feasibility and availability of this approach. The discussion highlights the contrast between cryopreserving eggs and embryos, wherein embryos have greater resilience and display a survival rate of 99% following the process of thawing. The comparative cost-effectiveness of cryopreserving eggs vs creating embryos is being examined, taking into account the recognized decline in egg quality as individuals age, which can affect genetic integrity and elevate the likelihood of chromosomal irregularities. The conversation addresses the significance of early consideration of reproductive choices, particularly due to the noticeable fall in both the amount and quality of eggs after the age of 37. The passage highlights the importance of making well-informed decisions and supports the use of proactive strategies like AMH testing and egg storage to safeguard fertility choices for individuals, particularly women, who may lack a present partner or harbor uncertainties over future parental arrangements [27].

References

27. Chronopoulou, E., et al., Elective oocyte cryopreservation for age-related fertility decline. J Assist Reprod Genet, 2021. 38(5): p. 1177-1186.

21. 01:43:37 Egg Freezing & IVF Procedures, Maternal Age, Success Rates

In her podcast, Dr. Natalie Crawford examines the most advantageous timeframe for oocyte cryopreservation, underscoring the findings of research studies that indicate intervention between the ages of 32 and 33, wherein a favorable convergence of excellent oocyte quality and quantity is observed. The author discusses the method of egg freezing, emphasizing a survival probability of 90% upon thawing. However, the author also emphasizes the inherent uncertainty surrounding future sperm quality. Crawford elucidates the necessity of mitigating this risk through the cryopreservation of additional eggs, given the uncertainty surrounding sperm quality. The discourse examines the rates of success pertaining to fertilization, embryo formation, and implantation, with a particular focus on the significance of a larger quantity of eggs in augmenting the likelihood of achieving positive outcomes. In their analysis, Crawford does a comparative examination of the process of freezing eggs as opposed to creating embryos. The author delves into the intricate considerations surrounding embryo quality, the likelihood of monozygotic twinning, and the statistical benefits associated with single embryo transfers. The essay highlights the significance of comprehending the cumulative probability of achieving success following successive euploid embryo transfers. This understanding enables individuals, particularly those with partners, to make well-informed decisions on family planning, taking into account their objectives and circumstances [20].

References

28. Petropanagos, A., et al., Social egg freezing: risk, benefits and other considerations. Cmaj, 2015. 187(9): p. 666-669.

22. 01:51:30 Tool: Sperm Freezing & Paternal Age, Vasectomy

The podcast underscores the significance of safeguarding gametes, specifically eggs and sperm, in light of the uncertain nature of forthcoming circumstances. The adverse effects of increased paternal age on outcomes are commonly documented at approximately 50 years of age. However, attention is redirected towards situations in which individuals may contemplate initiating a second family or encounter a younger spouse. The process of freezing sperm is commonly depicted as a relatively uncomplicated and financially viable technique, which typically entails undergoing blood tests, observing a short period of sexual abstinence, and undergoing an easy collection procedure. This stands in contrast to the process of freezing eggs, which is notably more complex. The essay advocates for men, namely those who are considering vasectomies, to contemplate the option of cryopreserving their sperm in advance, as a precautionary measure against unexpected events or alterations in personal circumstances. The cost-effectiveness and ease of sperm cryopreservation are emphasized, rendering it a practical alternative in contrast to more complex and costly reproductive interventions such as oocyte cryopreservation [29].

References

29. Sharma, R., et al., Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring. Reprod Biol Endocrinol, 2015. 13: p. 35.

23. 01:55:01 Hormones, Egg Freezing & IVF

In the Huberman podcast, Dr. Natalie Crawford explores the topic of egg freezing, also known as IVF, and emphasizes the hormonal interventions utilized to stimulate the development of eggs. This passage elucidates the process by which the administration of synthetic substances, namely FSH and LH, supersedes the innate physiological mechanisms of the human body, resulting in the development of a coordinated cohort of oocytes. The utilization of the analogy involving the suppression and subsequent stimulation of eggs serves to depict the process as a deliberate and calculated intervention. The tale explores the importance of monitoring the maturation of eggs by measuring blood levels of estradiol and conducting transvaginal ultrasounds throughout the approximately 12-day stimulation period. The concluding phase encompasses the administration of a trigger shot, which serves to induce the segregation of chromosomes in anticipation of the fertilization process. The analogy of meiotic spindles is employed to elucidate the fragility of eggs, specifically in relation to the consequences of aging on the process of chromosomal separation. This highlights the heightened susceptibility to aneuploidy that accompanies advancing age. In general, the article offers a thorough and easily understandable examination of the egg-freezing procedure, elucidating the technical elements while ensuring readability [30].

Figure 10. Testing and Optimization protocol for freezing eggs [21].

References

30. Akhondi, M.M., et al., Knowledge and beliefs about oocyte cryopreservation for medical and social reasons in female students: a cross-sectional survey. BMC Womens Health, 2023. 23(1): p. 336.

31. https://www.scrcivf.com/what-to-expect-in-the-egg-freezing-process/

24. 02:00:42 Three-Parent IVF, Mitochondrial DNA

Dr. Natalie Crawford examines the application of donor mitochondrial DNA (mtDNA) or donor eggs, with a particular focus on the original purpose of this technology, which was to tackle highly debilitating mitochondrial disorders that invariably result in fatality. The primary emphasis was placed on addressing these disorders, which are predominantly transmitted from mothers to their offspring via mitochondria. Although the technology has been effective for its intended purpose, the text acknowledges that its application in mitigating age-related alterations in eggs has not yielded conclusive results. The discourse pertains to the political obstacles encountered in the United States with regard to embryo research, impeded by divergent perspectives on the commencement of life and restrictions on research methods that include destruction. The contentious nature of the topic extends to matters within the field of in vitro fertilization (IVF), wherein a substantial number of unused embryos have the potential to contribute to scientific progress if more viable alternatives were accessible. The essay discusses the intricate nature of utilizing embryo donation for research objectives and the present utilization of embryos for the training of embryologists. It emphasizes the need for more substantial contributions to further scientific comprehension within this domain [32].

Figure 11. Diagram showing three-parent babies [33].

References

32. Lledo, B., et al., Comprehensive mitochondrial DNA analysis and IVF outcome. Hum Reprod Open, 2018. 2018(4): p. hoy023.

33. https://www.thebridgeclinic.com/blog/three-parent-ivf-the-facts-the-benefits-the-concerns-

25. 02:05:21 IVF Embryo Storage & Donation; Donor Education & Consent

Dr. Natalie Crawford explores the contemporary obstacles that have arisen within the realm of assisted reproductive technologies, with a specific focus on IVF and the cryopreservation of embryos. This statement elucidates the progression of IVF techniques, tracing their development from first endeavors that were limited by the absence of modern advancements, to the present-day approaches that incorporate less invasive procedures for oocyte retrieval. This paper examines the storage of excess embryos and the ethical implications associated with their disposal or donation for research and training endeavors. It proposes that embryos should be kept in storage until there is complete certainty over decisions related to family-building. The book further examines the increasing intricacies involved in third-party reproduction, specifically focusing on the challenges associated with sperm and egg donation. It highlights the recent examination of restrictions placed on sperm donors and the potential consequences of technological advancements in connecting persons produced through donor gametes. The monetization of egg donation gives rise to ethical considerations, which encompass several aspects such as remuneration, factors determining payment, and emerging business models that encourage egg donation for personal and donor-related objectives. The challenges encompass the domain of embryo donation, which brings to light the existence of unregulated practices and the convergence of profit objectives with ethical considerations. The passage continues by highlighting the ethical quandaries and unexplored domains associated with gamete and embryo donation, warning against unethical behaviors motivated by financial gain, and emphasizing the significance of scientific investigation keeping up with technical progress [34].

References

34. Samorinha, C. and S. Silva, A patient-centred approach to embryo donation for research. Israel Journal of Health Policy Research, 2016. 5(1): p. 44.

26. 02:14:29 Autism, Developmental Disorders, IVF Babies, Age

In her discourse, Dr. Natalie Crawford examines the progression of IVF techniques and their implications for infant outcomes. The focus is on the transition from fresh embryo transfers, which posed difficulties associated with an artificial uterine environment, to the currently widespread utilization of frozen embryo transfers. The aforementioned alteration has resulted in noteworthy enhancements in neonatal outcomes through the establishment of a more physiologically appropriate hormonal uterine environment for the process of embryo implantation. The discourse also addresses the intricacies of terminology and nomenclature, recognizing the dynamic nature of language within the medical and scientific domains. Moreover, this study investigates the correlation between infertility diagnoses and a marginally elevated likelihood of birth abnormalities and developmental disorders, prompting inquiries into whether these hazards are more prevalent among the general population rather than being particular to certain procedures. The passage concludes by emphasizing the significance of taking into account both paternal and mother age when examining reproductive health, specifically emphasizing the sometimes overlooked influence of advanced paternal age, particularly in regard to autism [35].

References

35. Diop, H., et al., Early Autism Spectrum Disorders in Children Born to Fertile, Subfertile, and ART-Treated Women. Matern Child Health J, 2019. 23(11): p. 1489-1499

27. 02:20:36 Tools: Sleep, Nutrition & Fertility; Dietary Fat

Dr. Natalie Crawford explores the intricate interrelationships among lifestyle factors, hormone function, and reproductive health, thereby questioning the conventional practice of categorizing medicine into discrete organ systems. The author underscores the significance of sleep, with particular emphasis on its role in facilitating cellular repair and mitigating inflammation, which is vital for ensuring optimal egg and sperm quality. Nutrition has a prominent role, emphasizing the consumption of entire foods such as fruits, vegetables, whole grains, and healthy fats. Crawford refutes the fallacy around the perceived negative impact of fruit consumption resulting from its sugar level while underscoring its inherent nutritional advantages. The present discourse acknowledges the inherent difficulties encountered in conducting fertility and nutrition studies, which frequently rely on observational data. However, it emphasizes the favorable influence of dietary choices on fertility outcomes, encompassing reduced inflammation, enhanced ovulation, and increased success rates of IVF. Crawford advocates for a comprehensive perspective on health, aiming to dispel misunderstandings regarding low-fat diets and emphasizing the importance of lipids in facilitating hormone synthesis [26].

References

36. Lindseth, G. and A. Murray, Dietary Macronutrients and Sleep. West J Nurs Res, 2016. 38(8): p. 938-58.

28. 02:27:32 Protein, Meat, Tofu, Fish; Sugar, Artificial Sweeteners; Weight & Miscarriage

Dr. Natalie Crawford endeavors to elucidate prevalent fallacies around the purported influence of specific dietary components on reproductive capacity. Tofu, a food product derived from soybeans, has been subject to concerns over its soy content and phytoestrogens. However, it is worth noting that tofu is considered to have positive effects on fertility, particularly in males, since it possesses antioxidant characteristics that may contribute to enhanced fertility. Fish, which is abundant in omega-3 fatty acids, has been found to have positive effects on reproductive health. However, it is important to exercise caution during pregnancy to prevent excessive exposure to mercury. Deli meats and processed meats, which have been classified as carcinogenic, are generally advised against. The consumption of red meat, particularly when it exceeds the upper quartile of intake, has the potential to have adverse effects on the progression of embryos and the success rates of IVF. According to Dr. Crawford, it is advisable to adopt a diet that prioritizes plant-based foods, exercises moderation in the use of red meat, and pays careful attention to the origin of food in order to account for any variations in environmental consequences. The discourse aims to question the denial surrounding the correlation between dietary preferences, environmental contaminants, and their impact on reproductive well-being [37].

References

37. Kowalska, K., et al., The Change in the Content of Nutrients in Diets Eliminating Products of Animal Origin in Comparison to a Regular Diet from the Area of Middle-Eastern Europe. Nutrients, 2020. 12(10).

29. 02:37:38 Tools: Supplements; Prenatal Vitamins, Omega 3s, Vitamin D, Coenzyme Q10

Dr. Natalie Crawford emphasizes the importance of nutritional supplements, especially for individuals in their reproductive years. A prenatal vitamin containing folic acid is recommended for both men and women, not only during pregnancy but also in preparation, as folate is vital for cell division and follicle growth. Vitamin D deficiency is widespread, impacting reproduction, and a daily intake of 1,000 international units is advised. Omega-3 fatty acids, crucial for anti-inflammatory benefits and fetal brain development, are found in many prenatal, but additional supplements are recommended if absent. Coenzyme Q10 (CoQ10) supports mitochondrial function, benefiting meiosis, cell division, ovulation, and egg and sperm quality. A daily dose of 200 milligrams, three times a day, is suggested, with emphasis on consistent intake regardless of the form (gel capsules or powdered capsules). The podcast addresses dosages, potential benefits, and the role of essential fatty acids in brain health during pregnancy [28].

References

38. Stanhiser, J., et al., Omega-3 fatty acid supplementation and fecundability. Hum Reprod, 2022. 37(5): p. 1037-1046.

30. 02:42:26 L-Carnitine & Male Fertility; PCOS & Myo-inositol; Metformin

Dr. Natalie Crawford proposes a strategy for enhancing male fertility, which involves the administration of a gramme of L-carnitine and a gramme of vitamin C, in conjunction with a multivitamin and CoQ10 supplementation. The present approach has been specifically developed for individuals of the male gender who exhibit atypical sperm parameters. The prescription for women seeking to improve their reproductive health involves the inclusion of supplementary vitamin D in conjunction with a prenatal supplement containing folic acid. Within the realm of Polycystic Ovary Syndrome (PCOS), Dr. Crawford directs attention toward the widely discussed inositol supplement, with specific emphasis on myo-inositol. Myo-inositol has been found to be effective in addressing insulin resistance in individuals with PCOS, leading to enhanced insulin sensitivity and the potential mitigation of inflammatory pathways. Dr. Crawford emphasizes the association between insulin resistance and testosterone synthesis in individuals with PCOS, advising males to exercise caution regarding the potential effects on testosterone levels when using supplements such as metformin. The author highlights the significance of tailored methods for supplementation and underscores the necessity for individuals to evaluate the potential impact of specific supplements on their well-being, taking into account their own health conditions and objectives [39].

Figure 12. Improvement Effect of Metformin on Female and Male Reproduction [40].

References

39. Goyal, M. and A.S. Dawood, Debates Regarding Lean Patients with Polycystic Ovary Syndrome: A Narrative Review. J Hum Reprod Sci, 2017. 10(3): p. 154-161.

40. Shpakov, A. O. (2021). Improvement effect of metformin on female and male reproduction in endocrine pathologies and its mechanisms. Pharmaceuticals, 14(1), 42.

31. 02:47:11 Egg Retrieval, Ovarian Hyperstimulation Syndrome, Minimal Stimulation

Dr. Natalie Crawford discusses the timeline and procedures associated with IVF, emphasizing the importance of lifestyle and behavioral changes leading up to the process. Explaining the 90-day sperm cycle and the vulnerability of eggs during this period, she highlights the significance of adopting healthy habits well in advance. During IVF, patients undergo subcutaneous shots for approximately 12 to 14 days to stimulate egg growth, experiencing pelvic pressure and bloating due to rising estrogen. The egg retrieval procedure, usually done under IV sedation with drugs like propofol and fentanyl, lasts about 20 minutes. Dr. Crawford notes the necessity of avoiding intercourse during this time to prevent complications like ovarian hyper-stimulation syndrome (OHSS) and the potential for unintended pregnancies. OHSS risks are mitigated in modern practices with advanced protocols. Overall, understanding the medication and sedation choices of the fertility clinic is crucial for patients to manage expectations and ensure a comfortable experience [41].

References

41. Namavar Jahromi, B.M., et al., Ovarian Hyperstimulation Syndrome: A Narrative Review of Its Pathophysiology, Risk Factors, Prevention, Classification, and Management. Iran J Med Sci, 2018. 43(3): p. 248-260.

32. 02:57:56 INVOcell

Dr. Natalie Crawford examines the invocell process, which aims to enhance the financial accessibility of IVF for particular patient demographics, including individuals with refractory PCOS or tubal factor infertility. The plastic apparatus has the capacity to accommodate a maximum of ten eggs, facilitating the interaction between sperm and eggs within the vaginal environment. The significance of patient selection for this technique is underscored by Dr. Crawford, who emphasizes its appropriateness for instances of unexplained infertility or difficulties with fertilization. Although invocell provides a three-dimensional environment that closely mimics natural conditions, it has certain limitations in terms of data collecting and the absence of assistance for embryo freezing. The success of a patient is contingent upon various aspects, such as age and diagnosis, hence necessitating a comprehensive evaluation of its relevance on a case-by-case basis. Notwithstanding its inherent limits, the aforementioned approach can prove to be a helpful alternative, particularly for individuals requiring donor sperm or encountering distinctive obstacles in the process of conception [42].

Figure 14. Mini IVF with INVOCELL®: The Newest Technology [43].

References

42. Cunha, A. and A.M. Póvoa, Infertility management in women with polycystic ovary syndrome: a review. Porto Biomed J, 2021. 6(1): p. e116.

43. https://www.fcionline.com/treatments/invocell-mini-ivf/.

33. 03:03:12 Egg Freezing, Intracytoplasmic Sperm Injection (ICSI), Sperm Fragmentation

In her discourse, Dr. Natalie Crawford emphasizes the significance of optimizing egg retrieval in the context of IVF and egg freezing. She specifically highlights the value of tailoring techniques to each individual, taking into account their antral follicle count as a determining factor. The author highlights the importance of removing cumulus cells prior to cryopreserving eggs, which necessitates the use of intracytoplasmic sperm injection (ICSI) during the fertilization process. ICSI is a technique that involves the careful selection of sperm with normal morphology and motility for direct injection into the egg. This method is particularly useful in cases where there is DNA fragmentation present. Dr. Crawford provides insight into the historical backdrop of the reputation of ICSI, as well as its present-day prevalence resulting from its notable success rates. The author explores the underlying reasons for selecting ICSI as a preferred option for individuals seeking fertility treatments, taking into account its cost-effectiveness in comparison to the possibility of undergoing several IVF cycles. Furthermore, the author discusses urological viewpoints, proposing that procedures for sperm extraction could potentially reduce DNA fragmentation and improve overall results [44].

References

44. Antonouli, S., et al., The impact of sperm DNA fragmentation on ICSI outcome in cases of donated oocytes. Arch Gynecol Obstet, 2019. 300(1): p. 207-215.

34. 03:19:47 Hormone Replacement Therapy & Menopause

Dr. Natalie Crawford supports the utilization of hormone replacement therapy (HRT) as a treatment option for women experiencing menopause. She places significant emphasis on the early initiation of HRT in order to maximize its potential benefits. In response to the concerns raised by the Women's Health Initiative study, the author emphasizes the importance of avoiding extended periods of hypoestrogenic states prior to initiating hormone replacement therapy in order to minimize any negative consequences. In the discourse, Dr. Crawford examines diverse alternatives for estrogen replacement therapy, including estradiol oral tablets, vaginal inserts, and transdermal patches, with the objective of emulating the chemical composition of endogenous estradiol. In order to mitigate the potential occurrence of endometrial cancer, the individual emphasizes the importance of utilizing a combination of estrogen and progestin. This can be achieved through several administration techniques, such as daily or cyclic progestin regimens, as well as the utilization of an intrauterine device (IUD). Dr. Crawford espouses the implementation of personalized hormone dosages designed to alleviate symptoms and improve general welfare, thereby addressing the longstanding disregard for women's health post-menopause. The author places significant emphasis on the significance of intervention for women who are facing early ovarian failure. They advocate for the promotion of empowerment and proactive management of menopausal symptoms as a means to achieve improved health outcomes and an extended lifespan [45].

References

45. Hodis, H.N. and W.J. Mack, Menopausal Hormone Replacement Therapy and Reduction of All-Cause Mortality and Cardiovascular Disease: It Is About Time and Timing. Cancer J, 2022. 28(3): p. 208-223.

35. 03:22:25 Early signs of Menopause

Dr. Natalie Crawford provides insight into the perimenopausal phase, underscoring the need to acknowledge alterations in menstruation patterns as indicative of a diminishing ovarian reserve. The author delineates symptoms commonly connected with reduced amounts of estrogen throughout this particular phase, encompassing cognitive impairment, physical weariness, cranial discomfort, sudden episodes of intense heat, decreased sexual desire, and complications pertaining to the vulvar-vaginal region. In the realm of fertility, Dr. Crawford endeavors to debunk prevalent beliefs, with a particular focus on dispelling fallacies surrounding the practice of egg harvesting and its potential ramifications on reproductive capacity [46].

References

46. Santoro, N., C.N. Epperson, and S.B. Mathews, Menopausal Symptoms and Their Management. Endocrinol Metab Clin North Am, 2015. 44(3): p. 497-515.

Preprint

Preprint

Dr. Natalie Crawford: Female Hormone Health, Fertility & Vitality