Optimizing Fertility Using Functional Medicine

Functional Fertility:
Optimizing Fertility Using the Functional Medicine Model
KALEA WATTLES, ND, IFMCP
Hormone Advanced Practice Module

July 2021
Disclosure
Kalea Wattles, ND disclosed no financial relationships with any

commercial interests
©2021 The Institute for Functional Medicine
Evidence Icons: Key
Upper-Right Icons: Lower-Right Icons:
• Association, not causation • Animal study

• Lab test • In vitro study
(Labs not generally accepted in conventional care)
• Conflict of interest
• Clinical experience
(Intervention warranted by historical clinical experience of
educator and/or functional medicine community of
• n of 1, or single-case study
practitioners in the context of evidentiary paucity)
• Clinical judgment
(Intervention warranted by clinical judgment of educator
and/or functional medicine community of practitioners in
• In silico (Computerized molecular modeling)
the context of evidentiary paucity)
Malabsorption Chronic inflammation
Dysbiosis Autoimmunity
Intestinal permeability Endometriosis
Structural abnormalities
Maternal DES
Skeletal misalignment PCOS
Visceral placement ovarian aging
Cell membranes egg/sperm quality
fertilization
Surgery implantation
Infection
Hormone imbalance Env. exposures
Thyroid disease Hormone metabolism
Low DHEA Circulatory dysfunction
Poor cervical fluid Metabolic/Vascular disease
SAD
Occupational exposures
Circadian disruption Sedentarism Low antioxidants Emotional Performance pressure

Poor/inadequate sleep Lack of blood flow High AGE’s Physical Isolation
Mental
Financial
Unexplained Infertility? Or….
Nutritional Altered
Poor Gut Toxic
Insufficiencies/ Immune
Health deficiencies Exposures
Activity
LPD/ Thyroid Oxidative Inflamm- Adrenal

Low P Issues Stress ation dysfunction
The Path to Conception
Egg
Egg is
High travels Egg implants Adequate
fertilized
quality through into a progesterone
by high
egg is patent receptive maintains
quality
ovulated Fallopian endometrium endometrium

sperm
tube
Folliculogenesis
The Window of Opportunity
120 days
290 Days (roughly 10 menstrual cycles)

1. Williams CJ, Erickson GF. Morphology and Physiology of the Ovary. [Updated 2012 Jan 30]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK278951/
2. McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocr Rev. 2000 Apr;21(2):200-14. doi: 10.1210/edrv.21.2.0394.
Egg Quality vs Egg Health
Egg health describes the

Egg quality describes modifiable features that
whether an oocyte is contribute to the likelihood that
genetically normal. an egg will fertilize and become
a viable embryo.
AKA it either has 23 • Mitochondrial function

chromosomes or it • Oxidative Stress
doesn’t. • Inflammaging
Maternal DES
PCOS
Skeletal misalignment
ovarian aging
Visceral placement
egg/sperm quality
Cell membranes
fertilization
Infection
Hormone imbalance Env. Exposures
SAD

Mental
Financial
Getting cholesterol to the inner membrane of the mitochondria
is the rate-limiting step in steroid hormone synthesis.
Image created using Biorender.com
Fritz MA, Speroff L. Chapter 2: Hormone biosynthesis, metabolism, and mechanism of action. In: Clinical Gynecologic Endocrinology and Infertility. 8th ed. Lippincott Williams & Wilkins, 2011: p. 39.
Oocytes have the highest concentration of
mitochondrial DNA content in the human body
Latorre-Pellicer A, Lechuga-Vieco AV, Johnston IG, et al. Regulation of Mother-to-Offspring Transmission of mtDNA Heteroplasmy. Cell Metab. 2019;30(6):1120-1130.e5. doi:10.1016/j.cmet.2019.09.007
Mitochondria and Conception
Egg Health
Fertilization Ovulatory
function
Implantation Ovarian
aging
The first several days of embryo
development are powered by cellular
energy produced by maternal mitochondria
Chappel S. The role of mitochondria from mature oocyte to viable blastocyst. Obstet Gynecol Int. 2013;2013:183024. doi: 10.1155/2013/183024. Epub 2013 May 16.
Oocytes and DNA Repair Genes
1. Menezo Y Jr, Russo G, Tosti E, El Mouatassim S, Benkhalifa M. Expression profile of genes coding for DNA repair in human oocytes using pangenomic microarrays, with a special focus on ROS linked decays. J Assist Reprod Genet. 2007 Nov;24(11):513-20. doi: 10.1007/s10815-
007-9167-0.
2. Jaroudi S, Kakourou G, Cawood S, Doshi A, Ranieri DM, Serhal P, Harper JC, SenGupta SB. Expression profiling of DNA repair genes in human oocytes and blastocysts using microarrays. Hum Reprod. 2009 Oct;24(10):2649-55. doi: 10.1093/humrep/dep224.
Low antioxidants
AGEs
Trans fats
Reprinted from Reproductive BioMedicine Online, Vol. 34, Roychoudhury, S., Agarwal, A., Virk, G., & Cho, C.-L., Potential role of green tea catechins in the management of oxidative stress-associated
infertility, Pages 487-498, Copyright 2017, with permission from Reproductive Healthcare Ltd.
Damaged fats
Damaged DNA
Mitochondrial Support for Fertility
• The Mito Food Plan: AKA the OVARY POWER FOOD PLAN
• Supplements:
• ETC support: CoQ10, riboflavin
• Antioxidants: resveratrol, alpha-lipoic acid, melatonin, N-
acetylcysteine
• Other options: L-carnitine, magnesium, curcumin, quercetin, and

green tea
• GLUTATHIONE: oral or intravenous
• Regular, moderate intensity exercise
See References: Mitochondrial Support

References: Mitochondrial Support
1. Ben-Meir A, Burstein E, Borrego-Alvarez A, et al. Coenzyme Q10 restores oocyte mitochondrial function and fertility during
reproductive aging. Aging Cell. 2015;14(5):887-895. doi:10.1111/acel.12368
2. Lee HJ, Park MJ, Joo BS, Joo JK, Kim YH, Yang SW, Kim CW, Kim KH. Effects of coenzyme Q10 on ovarian surface epithelium-derived
ovarian stem cells and ovarian function in a 4-vinylcyclohexene diepoxide-induced murine model of ovarian failure. Reprod Biol
Endocrinol. 2021 Apr 22;19(1):59. doi: 10.1186/s12958-021-00736-x.
3. Xing X, Zhang J, Zhang J, Wang Y, Wang J, Kang J, Quan F, Su J, Zhang Y. Coenzyme Q10 supplement rescues postovulatory oocyte
aging by regulating SIRT4 expression. Curr Mol Pharmacol. 2021 Apr 19. doi: 10.2174/1874467214666210420112819.
4. Ungvari Z, Sonntag WE, de Cabo R, Baur JA, Csiszar A. Mitochondrial protection by resveratrol. Exerc Sport Sci Rev.
2011;39(3):128-132. doi:10.1097/JES.0b013e3182141f80
5. Grive KJ, Sauerbrun-Cutler MT. Resveratrol improves granulosa cell activity through mitochondrial biogenesis. Fertil Steril. 2021
Apr;115(4):909-910. doi: 10.1016/j.fertnstert.2021.02.011.
6. Shaum KM, Polotsky AJ. Nutrition and reproduction: is there evidence to support a "Fertility Diet" to improve mitochondrial
function?. Maturitas. 2013;74(4):309-312. doi:10.1016/j.maturitas.2013.01.011
Maternal DES
PCOS
ovarian aging
Visceral placement
egg/sperm quality
Cell membranes
fertilization
Infection
SAD

Mental
Financial
Summary: Drivers of Hormonal Imbalance
Pattern Description Drivers to Consider
Obesity, BMI, WHR, Inflammation, Aromatase Activity,

Estrogen Dominance ↑Estrogen relative to
Endocrine Disruptors, POPs, Caffeine, Alcohol, Gut
Imbalance ↓Progesterone
Dysbiosis
↓Progesterone, shorter luteal Psychogenic and physiologic Stress, low fat/fat

Luteal Phase
phase <11 days, or <5 ng/mL deficient diet, ”energy deficit” via low calorie diets,
Dysfunction maximum serum progesterone excessive exercise, PCOS
Perimenopause, psychogenic and physiologic stress,

Fluctuations in Changes in hormone levels causes
“sensitivity” to changes in hormone levels through
Hormone Levels signs and symptoms
normal menstrual cycle, e.g. PMS, PMDD
Hormonal Relative or absolute hormone Aging, menopause, premature ovarian failure,

Insufficiency insufficiency nutritional deficiencies
Sub-optimal Hormone SNPs (e.g. for COMT, GST, CYP enzymes), poor diet,
Sub-optimal 2, 4, 16-OH-estrogen
Metabolism Alcohol, HRT, Endocrine Disruptors, PCOS
Supporting Progesterone
summary
Nutrition Rx
• Adequate dietary fat and calories • Utilize Rx progesterone as
needed – will need to ensure
• Vitamin C, E, B6 you are dosing AFTER ovulation
Lifestyle
• Stress support
• Avoid overexercising
• Ensure healthy mitochondria
See References: Supporting progesterone

References: Supporting progesterone
1. Meenakumari KJ, Agarwal S, Krishna A, Pandey LK. Effects of metformin

treatment on luteal phase progesterone concentration in polycystic ovary
syndrome. Braz J Med Biol Res. 2004 Nov;37(11):1637-44.
2. Hermann AC, Nafziger AN, Victory J, et al. Over-the-counter progesterone
cream produces significant drug exposure compared to a Food and Drug
Administration approved oral progesterone product. J Clin Pharmacol .
2005;45(6):614-619
3. Lindner C, Braendle W, Lichtenberg V, Bispink L, Bettendorf G. [GnRH

agonist/hMG stimulation in gamete intrafallopian transfer (GIFT)].
Geburtshilfe Frauenheilkd. 1989 Feb;49 Suppl 1:91-5. German.
4. Hernández García IA, Gutiérrez Gutiérrez AM, Gallardo Lozano E. [Effect of
weight reduction on the clinical and hormonal condition of obese
anovulatory women]. Ginecol Obstet Mex. 1999 Sep;67:433-7. Spanish.
DHEA and Ovarian Response
• DHEA appears to play a role in folliculogenesis/follicle maturation

• In patients with DOR, adequate DHEA may help to decrease
ovarian atresia
• Increases follicular pool by increasing the number of follicles that
are responsive to gonadotropins
1. Hassa H, Aydin Y, Ozatik O, Erol K, Ozatik Y. Effects of dehydroepiandrosterone (DHEA) on follicular dynamics in a diminished ovarian reserve in vivo model. Syst Biol Reprod Med. 2015
Jun;61(3):117-21. doi: 10.3109/19396368.2015.1011353.
2. Gleicher N, Weghofer A, Barad DH. The role of androgens in follicle maturation and ovulation induction: friend or foe of infertility treatment?. Reprod Biol Endocrinol. 2011;9:116. Published 2011
Aug 17. doi:10.1186/1477-7827-9-116
Low Thyroid Function and Fertility
Disrupts
GnRH
Ovarian
reserve
Prevents
activation
of
granulosa
cells
Pregnancy
Elevates complications
prolactin
See References Thyroid Health and Fertility

References: Thyroid Health and Fertility
1. Priya DM, Akhtar N, Ahmad J. Prevalence of hypothyroidism in infertile women and evaluation of
response of treatment for hypothyroidism on infertility. Indian J Endocrinol Metab.
2015;19(4):504‐506. doi:10.4103/2230-8210.159058
2. Verma I, Sood R, Juneja S, Kaur S. Prevalence of hypothyroidism in infertile women and
evaluation of response of treatment for hypothyroidism on infertility. Int J Appl Basic Med Res.
2012;2(1):17‐19. doi:10.4103/2229-516X.96795
3. Acharya N, Acharya S, Shukla S, Inamdar SA, Khatri M, Mahajan SN. Gonadotropin levels in
hypothyroid women of reproductive age group. J Obstet Gynaecol India. 2011;61(5):550‐553.
doi:10.1007/s13224-011-0079-7
4. Weghofer A, Himaya E, Kushnir VA, Barad DH, Gleicher N. The impact of thyroid function and
thyroid autoimmunity on embryo quality in women with low functional ovarian reserve: a case-
control study. Reprod Biol Endocrinol. 2015;13:43. Published 2015 May 15. doi:10.1186/s12958-
015-0041-0
5. Weghofer A, Barad DH, Darmon S, Kushnir VA, Gleicher N. What affects functional ovarian
reserve, thyroid function or thyroid autoimmunity?. Reprod Biol Endocrinol. 2016;14(1):26.
Published 2016 May 10. doi:10.1186/s12958-016-0162-0
Vitamin D and Fertility
• Research exists linking vitamin D deficiency to a number of female
reproductive issues, including gestational diabetes, endometriosis,
PCOS, uterine myomas, premature labor, preeclampsia.
• Women who with sufficient levels of vitamins D (25-OH vitamin D >

30ng/ml) more likely to achieve a positive pregnancy test, clinical
pregnancy and live birth with IVF
• Vitamin D is associated with levels of anti-mullerian hormone,

suggesting that it may play a role in maintaining ovarian reserve
1. Pilz S, Zittermann A, Obeid R, et al. The Role of Vitamin D in Fertility and during Pregnancy and Lactation: A Review of Clinical Data. Int J Environ Res Public Health. 2018;15(10):2241. Published 2018 Oct 12. doi:10.3390/ijerph15102241
2. Dennis NA, Houghton LA, Pankhurst MW, Harper MJ, McLennan IS. Acute Supplementation with High Dose Vitamin D3 Increases Serum Anti-Müllerian Hormone in Young Women. Nutrients. 2017;9(7):719. Published 2017 Jul 8. doi:10.3390/nu9070719
3. Paffoni A, Ferrari S, Viganò P, Pagliardini L, Papaleo E, Candiani M, Tirelli A, Fedele L, Somigliana E. Vitamin D deficiency and infertility: insights from in vitro fertilization cycles. J Clin Endocrinol Metab. 2014 Nov;99(11):E2372-6. doi: 10.1210/jc.2014-1802.
Maternal DES
PCOS
ovarian aging
Visceral placement
egg/sperm quality
Cell membranes
fertilization
Infection
SAD

Mental
Financial
Created with BioRender.com

Supporting Transport Capabilities
1. Acupuncture
2. Physical therapy/abdominal massage
3. Yoga
1. Stener-Victorin E, Kobayashi R, Kurosawa M. Ovarian blood flow responses to electro-acupuncture stimulation at different frequencies and intensities in anaesthetized rats. Auton Neurosci. 2003
Oct 31;108(1-2):50-6. doi: 10.1016/j.autneu.2003.08.006.
2. Robinson RS, Woad KJ, Hammond AJ, Laird M, Hunter MG, Mann GE. Angiogenesis and vascular function in the ovary. Reproduction. 2009 Dec;138(6):869-81. doi: 10.1530/REP-09-0283.
Cervical fluid – an important consideration!
The cervix produces 20-60 mg of cervical fluid DAILY, but might
make as much as 700 mg at ovulation time
“Fertile-quality cervical fluid”

• Signals that ovulation is imminent
• Should be “egg white” consistency

• Serves several important roles for fertility
Martyn F, McAuliffe FM, Wingfield M. The role of the cervix in fertility: is it time for a reappraisal? Hum Reprod. 2014 Oct 10;29(10):2092-8. doi: 10.1093/humrep/deu195.
Cervical fluid – an important consideration!
Cervical fluid has many important roles:
• Protects sperm from an acidic vaginal environment
• Filters abnormal sperm
• Sperm food
• Stores the sperm for later release
• Maintains opening of the cervical canal
Martyn F, McAuliffe FM, Wingfield M. The role of the cervix in fertility: is it time for a reappraisal? Hum Reprod. 2014 Oct 10;29(10):2092-8. doi: 10.1093/humrep/deu195.
5 Tips for Increasing Cervical Fluid Production
1 Hydration!
2 N-acetyl-
cysteine 3 Omega 3s
4 Evening
5
Primrose Oil Acupuncture
1. Mokhtari V, Afsharian P, Shahhoseini M, Kalantar SM, Moini A. A Review on Various Uses of N-Acetyl Cysteine. Cell J. 2017;19(1):11-17. doi:10.22074/cellj.2016.4872
Maternal DES
PCOS
ovarian aging
Visceral placement
egg/sperm quality
Cell membranes
fertilization
Infection
SAD

Mental
Financial
Microbiome and Fertility
• The uterus, once thought to be sterile, appears to have an active microbiota.
• Women being treated for infertility have been shown to host a different
microbial composition in their vagina, cervix, and uterus when compared to
women without infertility.
• IVF outcomes are better in women colonized with a Lactobacillus-dominant

microbiome
• Infection with H. pylori may result in decreased reproductive potential
Tomaiuolo R, Veneruso I, Cariati F, D'Argenio V. Microbiota and Human Reproduction: The Case of Female Infertility. High Throughput. 2020;9(2):E12. Published 2020 May 3. doi:10.3390/ht9020012
Iron, ovulation, and fertility
• Low levels of iron can impair follicle

development
• Adequate iron intake associated with lower
levels of anovulation
• Red blood cells deliver oxygen to ovaries
and uterus → iron deficiency may cause

egg cells to weaken over time and become
unviable.
1. Buhling KJ, Grajecki D. The effect of micronutrient supplements on female fertility. Curr Opin Obstet Gynecol. 2013 Jun;25(3):173-80. doi: 10.1097/GCO.0b013e3283609138.
2. Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Iron intake and risk of ovulatory infertility. Obstet Gynecol. 2006 Nov;108(5):1145-52. doi: 10.1097/01.AOG.0000238333.37423.ab.
Intestinal Barrier Function and Fertility
The loss of intestinal barrier function may result in:

- Ovarian and endometrial inflammation
- Impaired progesterone production
- Negative impact on implantation and placental

development
1. Reid G, Brigidi P, Burton JP, Contractor N, Duncan S, Fargier E, Hill C, Lebeer S, Martín R, McBain AJ, Mor G, O'Neill C, Rodríguez JM, Swann J, van Hemert S, Ansell J. Microbes central to human reproduction. Am J Reprod Immunol. 2015
Jan;73(1):1-11. doi: 10.1111/aji.12319.
2. Silva MSB, Giacobini P. Don't Trust Your Gut: When Gut Microbiota Disrupt Fertility. Cell Metab. 2019 Oct 1;30(4):616-618. doi: 10.1016/j.cmet.2019.09.005.
3. Sirota I, Zarek SM, Segars JH. Potential influence of the microbiome on infertility and assisted reproductive technology. Semin Reprod Med. 2014 Jan;32(1):35-42. doi: 10.1055/s-0033-1361821.
Maternal DES
PCOS
ovarian aging
Visceral placement
egg/sperm quality
Cell membranes
fertilization
Infection
SAD

Mental
Financial
Structure = Function
• Organs
• Skeleton
• Vasculature
Don’t forget about cell membrane health
Important nutrients to support cell membrane health:

• Vitamin C
• Vitamin E
• Inositol
• Choline
• Omega 3 fatty acids

Maternal DES
PCOS
ovarian aging
Visceral placement
egg/sperm quality
Cell membranes
fertilization
Infection
SAD

Mental
Financial
Inflamm-aging and Fertility
• Env. pollutants
• Resveratrol
• Oxidative Stress
• Ginseng
• Aging
• NF-kB inhibitors
• AGEs
• IL-6, TNF-a, NF-kB
Huang Y, Hu C, Ye H, et al. Inflamm-Aging: A New Mechanism Affecting Premature Ovarian Insufficiency. J Immunol Res. 2019;2019:8069898. Published 2019 Jan 2. doi:10.1155/2019/8069898
NF-kB Inhibitors
• Resveratrol • Vitamin B-6 • Ginger
• Pycnogenol • Folate • Dark chocolate
• Curcumin • Grape seed extract • DHEA
• Green tea • Avena sativa • Bilberry extract
• Co-enzyme Q-10 • Stinging nettle
• Vitamin C
• EPA • Glucosamine
• Sulforaphane
• DHA • Benfotiamine
• Boswellia
• Carnosine • Acetyl-l-carnitine
• Allicin
• Lycopene • Potassium
• Alpha-lipoic acid • Magnesium • Vitamin B-12
• Ashwaganda • Melatonin • Pantothenic acid
• Astragalus • Quercetin
• Vitamin E • Blueberries
• Vitamin D-3
Hayden MS, Ghosh S. Shared Principles in NF-κB Signaling. Cell. 2008;132(3):344-362.
Advanced Glycation End Products
• AGEs accumulate in the ovarian follicle and likely play a role
in early ovarian aging.
• AGEs contribute to protein damage, increase inflammation,
and increase oxidative stress. More oxidative stress = worse
egg quality.
• Some research has shown that AGEs cause reduced glucose
uptake by granulosa cells, potentially altering follicular

growth.
• AGEs in the follicular fluid of women undergoing IVF
correlated with poor follicular and embryonic development
1. Diamanti-Kandarakis E, Chatzigeorgiou A, Papageorgiou E, Koundouras D, Koutsilieris M. Advanced glycation end-products and insulin signaling in granulosa cells. Exp Biol Med (Maywood). 2016;241(13):1438-1445.
2. Garg D, Merhi Z. Relationship between Advanced Glycation End Products and Steroidogenesis in PCOS. Reprod Biol Endocrinol. 2016;14(1):71. Published 2016 Oct 21. doi:10.1186/s12958-016-0205-6 doi:10.1177/1535370215584937
3. Uribarri J, Woodruff S, Goodman S, et al. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010;110(6):911-16.e12. doi:10.1016/j.jada.2010.03.018
4. Pertynska-Marczewska M, Diamanti-Kandarakis E. Aging ovary and the role for advanced glycation end products. Menopause. 2017;24(3):345-351. doi:10.1097/GME.0000000000000755
Combating AGEs for Ovarian Health
• Minimize fried/BBQ/high
temp cooking and foods that
have been browned
• Use culinary herbs liberally
• Eat a diet rich in
antioxidants
• Enjoy some green tea
• Consider supplementation
with N-acetyl-cysteine
Yang CT, Meng FH, Chen L, Li X, Cen LJ, Wen YH, Li CC, Zhang H. Inhibition of Methylglyoxal-Induced AGEs/RAGE Expression Contributes to Dermal Protection by N-Acetyl-L-Cysteine. Cell Physiol Biochem. 2017;41(2):742-754. doi: 10.1159/000458734.
Maternal DES
PCOS
ovarian aging
Visceral placement
egg/sperm quality
Cell membranes
fertilization
Infection
SAD

Mental
Financial
Environmental Toxin Exposure
Reproductive Impact
Environmental toxic exposures contribute to infertility in

several ways:
• Contribute to PCOS and blood glucose dysregulation
• Reduce LH secretion
• Altered semen parameters
• Increase rates of miscarriage

Common Environmental Exposures
Several environmental toxins interfere with human reproduction
• Organophosphate pesticides
• PCBs
• Cadmium
•
Mercury
• Benzene
• Phthalates
1. Curtis KM, Savitz DA, Weinberg CR, Arbuckle TE. The effect of pesticide exposure on time to pregnancy [published correction appears in Epidemiology 1999 Jul;10(4):470]. Epidemiology. 1999;10(2):112‐117.
2. Axmon A, Rylander L, Strömberg U, Hagmar L. Time to pregnancy and infertility among women with a high intake of fish contaminated with persistent organochlorine compounds. Scand J Work Environ Health. 2000;26(3):199‐206. doi:10.5271/sjweh.532
3. Buck Louis GM, Sundaram R, Schisterman EF, et al. Heavy metals and couple fecundity, the LIFE Study. Chemosphere. 2012;87(11):1201‐1207. doi:10.1016/j.chemosphere.2012.01.017
4. Burch JB, Wagner Robb S, Puett R, et al. Mercury in fish and adverse reproductive outcomes: results from South Carolina. Int J Health Geogr. 2014;13:30. Published 2014 Aug 15. doi:10.1186/1476-072X-13-30
5. Alviggi C, Guadagni R, Conforti A, et al. Association between intrafollicular concentration of benzene and outcome of controlled ovarian stimulation in IVF/ICSI cycles: a pilot study. J Ovarian Res. 2014;7:67. Published 2014 Jun 18. doi:10.1186/1757-2215-7-67
Toxin Exposure
Questionnaire (TEQ)
In your IFM Toolkit

Folliculogenesis
The Window of Opportunity
120 days
290 Days (roughly 10 menstrual cycles)

1. Williams CJ, Erickson GF. Morphology and Physiology of the Ovary. [Updated 2012 Jan 30]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK278951/
2. McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocr Rev. 2000 Apr;21(2):200-14. doi: 10.1210/edrv.21.2.0394.
Focus on
fiber, protein,
crucifers,
phytonutrients
Ensure pathways of elimination are

open: adequate hydration, daily bowel
movement, regular sweating
Remove sources of exposure: personal care

products, household cleaners, occupational
exposures, mercury amalgams
In your
Toolkit!
Join us for the EDC challenge!
During this interactive post-course experiential activity, we will assess
our own endocrine disrupting chemical exposures and explore
strategies to reduce them.
Week 1: EDCs in our food supply

Week 2: EDCs in cleaning products
Week 3: EDCs in personal care products

Sleep is Essential
• Reproductive hormones released from the brain are released in a
pulsatile manner, which is largely influenced by circadian rhythm
• In addition to hormone production, sexual function is also guided

by circadian rhythm. In humans, peak sexual function occurs in
the late night, with a secondary peak occurring in the very early
morning.
• The maternal circadian system influences the development of her

growing baby. Regular disruptions of the light–dark cycle can
throw off the maternal circadian clock, suppressing the melatonin
increase that normally happens at night.
Evans MC, Anderson GM. Integration of Circadian and Metabolic Control of Reproductive Function. Endocrinology. 2018;159(11):3661-3673. doi:10.1210/en.2018-00691
Stress Management is KEY
STRESS
SUBFERTILITY
Kalantaridou SN, Makrigiannakis A, Zoumakis E, Chrousos GP. Stress and the female reproductive system. J Reprod Immunol. 2004;62(1-2):61‐68. doi:10.1016/j.jri.2003.09.004
Rooney KL, Domar AD. The relationship between stress and infertility. Dialogues Clin Neurosci. 2018;20(1):41-47. doi:10.31887/DCNS.2018.20.1/klrooney
Domar AD, Zuttermeister PC, Friedman R. The psychological impact of infertility: a comparison with patients with other medical conditions. J Psychosom Obstet Gynaecol. 1993;14 Suppl:45-52.
The Mediterranean Diet for Fertility
A Mediterranean style diet is often recommended for couples who
want to optimize their fertility.
This really means:

1. Emphasis on fruits and vegetables
2. Higher content of omega 3 fatty acids

3. Rich sources of vitamin B6 and folate
4. Adequate dietary fiber from vegetables and whole grains
Karayiannis D, Kontogianni MD, Mendorou C, Mastrominas M, Yiannakouris N. Adherence to the Mediterranean diet and IVF success rate among non-obese women attempting fertility. Hum Reprod. 2018 Mar 1;33(3):494-502. doi: 10.1093/humrep/dey003.
The Mito Food Plan
Fiber-rich
veggies and
grains
Emphasis on
vegetables and
fruits
Healthy fat
sources
Maternal DES
PCOS
ovarian aging
Visceral placement
egg/sperm quality
Cell membranes
fertilization
Infection
SAD

Mental
Financial
Egg
Egg is
fertilized
by high
quality

sperm
tubes
Egg
Egg is
fertilized
by high
quality

sperm
tubes
Smoking Chronic infection Stress
Age Infection Nutrition
Etoh Immune factors
Smoking Pelvic trauma Mitochondrial health
Obesity Vitamin D status
ROS
EDCs Adequate hormones
Antioxidants
Medications Blood Supply
Sedentarism Intestinal barrier function
Preconception Labs
DAY 3: DAY 21 Advanced testing as needed:

• LH/FSH • Serum progesterone • Stool analysis
• Estradiol • Adrenal stress index
• Testosterone • Micronutrient testing
• DHEA-S • Oxidative stress assessment
• Prolactin • Toxicity assessment
• Anti-Mullerian Hormone
• TSH, Free T4, Free T3,
Anti-TPO Ab
• CBC, ferritin, iron + TIBC
• CMP
• Hemoglobin A1c
• Fasting insulin
• Hs-CRP
• Homocysteine
Practical Pregnancy Planning
Refer to
reproductive
endocrinology
Consider imaging:
transvaginal ultrasound,
hysterosalpingogram
Advanced testing as needed
Do the standard labs
Teach your patient how to identify her fertile window

Foundational Preconception Supplements
For most women: As needed:

• Prenatal Vitamin • Melatonin
• Fatty Acids • Resveratrol
• Curcumin
• Probiotic
• Inositol
• CoQ10
• NAC/glutathione
• ACES + Zinc
• Iron
Start from a place of

fullness
Thank you!
KALEA WATTLES, ND, IFMCP
Hormone Advanced Practice Module

July 2021

Optimizing Fertility Using Functional Medicine

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Optimizing Fertility Using Functional Medicine

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Functional Fertility:

Optimizing Fertility Using the Functional Medicine Model

KALEA WATTLES, ND, IFMCP

Hormone Advanced Practice Module

Kalea Wattles, ND disclosed no financial relationships with any

• Association, not causation • Animal study

Circadian disruption Sedentarism Low antioxidants Emotional Performance pressure

LPD/ Thyroid Oxidative Inflamm- Adrenal

ovulated Fallopian endometrium endometrium

290 Days (roughly 10 menstrual cycles)

Egg health describes the

AKA it either has 23 • Mitochondrial function

Circadian disruption Sedentarism Low antioxidants Emotional Performance pressure

Image created using Biorender.com

• Other options: L-carnitine, magnesium, curcumin, quercetin, and

See References: Mitochondrial Support

Circadian disruption Sedentarism Low antioxidants Emotional Performance pressure

Obesity, BMI, WHR, Inflammation, Aromatase Activity,

↓Progesterone, shorter luteal Psychogenic and physiologic Stress, low fat/fat

Perimenopause, psychogenic and physiologic stress,

Hormonal Relative or absolute hormone Aging, menopause, premature ovarian failure,

See References: Supporting progesterone

1. Meenakumari KJ, Agarwal S, Krishna A, Pandey LK. Effects of metformin

3. Lindner C, Braendle W, Lichtenberg V, Bispink L, Bettendorf G. [GnRH

• DHEA appears to play a role in folliculogenesis/follicle maturation

are responsive to gonadotropins

See References Thyroid Health and Fertility

• Women who with sufficient levels of vitamins D (25-OH vitamin D >

• Vitamin D is associated with levels of anti-mullerian hormone,

Circadian disruption Sedentarism Low antioxidants Emotional Performance pressure

Created with BioRender.com

“Fertile-quality cervical fluid”

• Should be “egg white” consistency

• Maintains opening of the cervical canal

Primrose Oil Acupuncture

Circadian disruption Sedentarism Low antioxidants Emotional Performance pressure

• The uterus, once thought to be sterile, appears to have an active microbiota.

• IVF outcomes are better in women colonized with a Lactobacillus-dominant

• Infection with H. pylori may result in decreased reproductive potential

• Low levels of iron can impair follicle

and uterus → iron deficiency may cause

The loss of intestinal barrier function may result in:

- Negative impact on implantation and placental

Circadian disruption Sedentarism Low antioxidants Emotional Performance pressure

Important nutrients to support cell membrane health:

• Omega 3 fatty acids

Circadian disruption Sedentarism Low antioxidants Emotional Performance pressure

uptake by granulosa cells, potentially altering follicular

Circadian disruption Sedentarism Low antioxidants Emotional Performance pressure

Environmental toxic exposures contribute to infertility in

• Increase rates of miscarriage

In your IFM Toolkit

290 Days (roughly 10 menstrual cycles)

Ensure pathways of elimination are

movement, regular sweating

Remove sources of exposure: personal care

Week 1: EDCs in our food supply

Week 2: EDCs in cleaning products

Week 3: EDCs in personal care products

• In addition to hormone production, sexual function is also guided

• The maternal circadian system influences the development of her

This really means:

2. Higher content of omega 3 fatty acids