Hunt-Gibbon SUM 2019

Fertility & Nutrition

A Capstone Project
Jeani Hunt-Gibbon, Graduate Student, MS Nutritional Sciences, University of Washington
Table of Contents
1. Introduction
2.Process & Target Population
○ Survey Results
3. Nutrition Issue of Focus: Nutrition and Fertility
○ Current Guidelines
4.Methods of Investigation
○ Search terms and methods
5. Evidence Analyses Summary: The Nutrition
Care Process for Infertility
6.Executive Summary
7. Dissemination Plan & Next steps

Introduction
Approximately 15% of couples of

reproductive age experience infertility
in the United States (1), and worldwide
the numbers are similar (2). Infertility is
defined as the inability to get pregnant
after 12 months of unprotected sex or
after 6 months for couples where the
woman is over 35 (3). In the United
States, approximately 12% of women
currently have impaired fertility (4).
Additionally, over 25% of infertility
cases are attributable to the male
partner, underscoring the need to include them in assessment and interventions (5).
Infertility is associated with increasing age, gynecologic disorders such as PCOS and
endometriosis as well as modifiable nutrition and lifestyle factors (6, 7).

Nearly 150,000 fertility procedures were performed in 2013 (8), and that number is only
growing. Fertility is at a national low partially due to delayed pregnancy and other
personal choices (8, 9). However, this also means more women will eventually seek
fertility counseling in order to achieve pregnancy at later ages.

While the nuances of how diet and lifestyle directly affect fertility are not completely
known, more and more details are being illuminated through both observational and
experimental studies. Yet, there are very few resources dietitians can access in order to
understand this issue fully. This project was created to formulate a central educational
asset that dietitians can utilize in order to understand evidence-based nutritional and
lifestyle changes that can improve fertility outcomes as well as techniques for working
with clients with infertility. An online lecture is available along with a companion
manual created for RDs and their patients. This is available for free to dietitians and
other healthcare workers through the Women’s Health Dietetic Practice Group website.
This will provide a foundation for RDs to use in order to treat patients with infertility
diagnoses, improving fertility outcomes. With this lecture, RDs can work in conjunction
with fertility doctors and other healthcare practitioners in order to provide
evidence-based diet and lifestyle interventions to these patients
References
1. Thoma, M. E., McLain, A. C., Louis, J. F., King, R. B., Trumble, A. C., Sundaram, R., & Buck Louis, G. M. (2013).
Prevalence of infertility in the United States as estimated by the current duration approach and a traditional
constructed approach. Fertility and Sterility, 99(5), 1324-1331.e1.
https://doi.org/10.1016/j.fertnstert.2012.11.037
2. WHO | Global prevalence of infertility, infecundity and childlessness. (n.d.). Retrieved January 20, 2019, from
https://www.who.int/reproductivehealth/topics/infertility/burden/en/
3. Lindsay, T. J., & Vitrikas, K. R. (2015). Evaluation and treatment of infertility. American Family Physician, 91( 5),
308–314.
4. Infertility | Reproductive Health | CDC. (2018). Retrieved June 5, 2018, from
https://www.cdc.gov/reproductivehealth/infertility/index.htm
5. 38. Salas-Huetos, A., Bulló, M., & Salas-Salvadó, J. (2017). Dietary patterns, foods and nutrients in male
fertility parameters and fecundability: a systematic review of observational studies. Human Reproduction
Update, 23(4), 371–389. https://doi.org/10.1093/humupd/dmx006
6. Thoma, M. E. et al. (2013). Prevalence of infertility in the United States as estimated by the current duration
approach and a traditional constructed approach. Fertility and Sterility, 99(5), 1324-1331.e1.
7. Sharma, R., Biedenharn, K. R., Fedor, J. M., & Agarwal, A. (2013). Lifestyle factors and reproductive health: taking
control of your fertility. Reproductive Biology and Endocrinology: RB&E, 11, 66.
https://doi.org/10.1186/1477-7827-11-66
8. Infertility | Reproductive Health | CDC. (2018). Retrieved June 5, 2018, from
9. Tavernise, S. (2018, May 17). U.S. Fertility Rate Fell to a Record Low, for a Second Straight Year. The New York
Times. Retrieved from https://www.nytimes.com/2018/05/17/us/fertility-rate-decline-united-states.html
Process & Target Audience
This project began as a collaboration with Judy Simon, MS, RDN, CD, CHES, FAND. Judy’s
expertise on the topic of fertility and nutrition is unparalleled in the field. She is sought
after throughout the country. Yet, few dietitians have substantial knowledge of this
subject area. Therefore, we identified a need for an educational tool for other dietitians
to use in order to gain a basic understanding of evidence-based nutrition practices for
fertility. This tool would exist online and be accessible to registered dietitians and other
healthcare workers for free.

The Women’s Health DPG (WHDPG) was identified as a logical partner for this endeavor,
as they have provided a basic webinar on the topic to their members. Their mission is to
“Empower members to be the most valued source of nutrition expertise in women’s
health throughout the lifespan.” In particular, they target stages of life specific to
women, including preconception. This project is directly in line with these goals,
allowing members to provide high quality nutrition expertise on fertility. In addition,
the educational tool will allow for dietitians to get continuing education credit through
the Academy of Nutrition and Dietetics (AND), as it constitutes additional education on
a topic important to many patients.

The Women’s Health DPG requires a project proposal, which outlines the project and
evidence-based information on the topic. This application is available as appendix I.
Once that was approved, a survey was created and went out to the members of the
Women’s Health DPG assessing the need for this educational tool and specific topics
that might be of interest. Results of this survey are included below:

Survey Results:
1: Strongly Agree
5: Strongly Disagree
Please Explain Your Answer (highlights):

“I am an RD working for an MFM/OBGYN practice -- and see women for pre-conception, especially IVF
preconception counselling.”
“ I work with women's with PCOS and am always looking for ways to improve my expertise in the area that
is challenging for this population.”
“There is so much to learn and read, it would be great to have it all in one place”
“This would be a new area of study much needed for RDNs”
1: Strongly Agree
5: Strongly Disagree
68% of responded prefered a powerpoint or lecture based format. 21% had viewed some
sort of fertility and nutrition webinar or continuing education presentation in the past.
Of these, most were from Today’s Dietitian or from the Women’s Health DPG. Given
these results, a video presentation format using Panopto was decided upon. It was also
decided that the presentation would provide specific information about nutrition
interventions for fertility using the nutrition care process as a framework.
Nutrition Issue of Focus
While it is difficult to attribute a particular percentage of infertility cases to lifestyle

factors, diet, exercise and weight, they are widely accepted to contribute to fertility
outcomes and assisted reproduction technology (ART) outcomes (1, 2). Several medical
conditions related to infertility are known to be associated with lifestyle parameters,
including PCOS, endometriosis, obesity and hypothalamic amenorrhea (1). Many studies
(discussed below) have also explored how micronutrients, macronutrients and dietary
patterns contribute to risk for infertility as well as their relationship to conception and
live birth. However, traditional approaches to infertility usually include costly medical
interventions and procedures before lifestyle interventions are considered (3, 4). Yet,
certain conditions are known to merit lifestyle interventions as a first line of defense,
such as PCOS (5).

There is very little information on the nutrition care process for infertility provided by
the Academy of Nutrition and Dietetics (AND) Nutrition Care Manual (NCM). For
conditions such as PCOS, the NCM recommends that patients who are obese follow the
same weight loss recommendations as other obese patients (6). The WHDPG, however,
has provided a webinar on the topic previously. Other than this, there are few
educational resources for dietitians to follow in order to provide medical nutrition
therapy to infertility patients. A need for a more structured nutrition care process for
this common issue is apparent.

The American College of Obstetricians and Gynecologists (ACOG), an association of
physicians specializing in women’s health, provides information for patients who may
have infertility. They recommend visiting an obstetrician-gynecologist, a urologist (if
you’re male), or a reproductive endocrinologist if a specialist is needed (7). The tests
listed below under “Tests of Fertility” are generally administered. ACOG acknowledges
that diet and lifestyle may play a role in infertility. They mention in particular that
overweight, underweight and over exercise can affect female fertility, and alcohol can
affect male fertility on their website. Clearly, there is a role for registered dietitians to
play here. However, they are not mentioned specifically on the ACOG website, but rather
an emphasis is placed on hormonal, surgical and other medical treatments.

Similarly, the American Society for Reproductive Medicine (ASRM), an organization
which was designed to be the leader in information, education and standards for
reproductive medicine, recommends medical treatment through drugs or surgery (4).
Otherwise, they recommend IVF or other ART treatments. However, they have recently
developed a special interest group called NutriSig for members who are interested in
nutrition and fertility. Yet, there are few dietitians involved. This is not surprising given
the focus of their organization, but more collaboration between disciplines and diet and
lifestyle resources are needed for these patients.

References
1. Sharma, R., Biedenharn, K. R., Fedor, J. M., & Agarwal, A. (2013). Lifestyle factors and reproductive health: taking
control of your fertility. Reproductive Biology and Endocrinology, 11( 1), 66.
https://doi.org/10.1186/1477-7827-11-66
2. Homan, G. F., Davies, M., & Norman, R. (2007). The impact of lifestyle factors on reproductive performance in
the general population and those undergoing infertility treatment: a review. Human Reproduction Update,
13(3), 209–223. https://doi.org/10.1093/humupd/dml056
3. Rossi, B. V., Abusief, M., & Missmer, S. A. (2016). Modifiable Risk Factors and Infertility. American Journal of
Lifestyle Medicine, 10(4), 220–231. https://doi.org/10.1177/155982761455802
4. ASRM. Frequently Asked Questions About Infertility. (2017). Retrieved January 31, 2019, from
https://www.reproductivefacts.org/faqs/frequently-asked-questions-about-infertility/?_ga=2.59167721.59523
145.1559265863-1409499754.1559265863&ct=b89a7a26d05b2abb73465a1a9051febaf1ae7eb0e9a13996a74ac67c
e4a441565b50b76edae9b6a21002deb1926123e5c950decca7958838e52c60d1ff524c0d
5. 12. Balen, A. H., et al. (2016). The management of anovulatory infertility in women with polycystic ovary
syndrome: an analysis of the evidence to support the development of global WHO guidance. Human
Reproduction Update, 22(6), 687–708.
6. Polycystic Ovarian Syndrome PCOS - Nutrition Care Manual. (n.d.). Retrieved April 8, 2019, from
https://www-nutritioncaremanual-org.offcampus.lib.washington.edu/topic.cfm?ncm_category_id=1&ncm_to
c_id=28418
7. Treating Infertility - ACOG. (2017). Retrieved Jan 5, 2019, from
https://www.acog.org/Patients/FAQs/Treating-Infertility?IsMobileSet=false
Methods of Investigation
Research was conducted using the PubMed database primarily supplemented with
Google Scholar and some Google searches. Many articles were also provided by
collaborators. Judy simon provided article titles for several of the articles used, as did
Hillary Wright. The ASRM website was used for information on fertility testing and
treatment. The Nutrition Care Manual was used for information on nutrition diagnoses,
monitoring and evaluation. Research was conducted over a period of several months
from July, 2018 to March, 2019. Articles were generally of a high quality (see appendix II
for evidence analyses of three main articles used) and published in peer reviewed
journals. A partnership was formed with the Women’s Health DPG as described above.
They agreed to provide a platform for the presentation and help promote it. See
agreement in appendix III.

Search Terms:
Nutrition:
Fertility and nutrition
Infertility and nutrition
Diet and infertility/fertility
Lifestyle and infertility/fertility
Micronutrients and fertility/infertility
Vitamins and fertility/infertility
Dietary Patterns and fertility/infertility
Dietary patterns and IVF outcomes
Nutrition and IVF outcomes
Mediterranean diet and fertility/infertility
Foods and infertility/fertility
Supplements and infertility/fertility
Macronutrients and infertility/fertility
Dietary fat and infertility/fertility
Dietary protein and infertility/fertility
Carbohydrates and infertility/fertility

Conditions:
Obesity and infertility/fertility
Overweight and infertility/fertility
Age and fertility/infertility
Polycystic Ovary Syndrome and fertility/infertility
Endometriosis and fertility/infertility
Hypothalamic amenorrhea and fertility/infertility
Hypo/hyperthyroidism and infertility/fertility
Menstrual cycle length disorders
Tests of infertility
Treatment of infertility
Diminished ovarian reserve

Reviewers
In order to qualify for continuing education credit, an educational module must be
reviewed by three experts in the field. Judy Simon provided introductions to two
registered dietitians currently practicing fertility nutrition - Rachelle Mallik and Hillary
Wright. Rachelle worked for Weill Cornell Center for Reproductive Medicine and
Infertility and now owns her own fertility focused nutrition business. Hillary Wright is
the Director of Nutrition Counseling for the Domar Center for Mind Body Health and a
Senior Nutritionist at the Dana Faber Cancer Institute. She specializes in women’s
health.

The Women’s Health DPG agreed to provide a third expert reviewer - Lauren Manaker,
who owns her own fertility-focused nutrition practice and has written an e-book on
male fertility. Each reviewer examined the presentation and provided electronic
comments, which were then incorporated into the final presentation before filming it.

A sound room at the University of Washington’s Odegaard Hall was reserved in order to
film the presentation using Panopto software. The video was then made available to the
WHDPG for continuing education for its members.
Evidence Analyses Summary

Nutrition Assessment of Infertility Patients
In order to assess a patient who has been diagnosed with infertility by a reproductive
specialist or other medical provider, medical history must be provided. One must verify
an infertility diagnosis and any attributed causes in order to understand relevant
nutritional interventions. A 24 to 48 hour recall is also a useful tool for assessing diet
quality and adherence to a diet that is conducive to fertility, as outlined in the
intervention section. Labs may also be relevant as discussed under Fertility Tests.
Follicle stimulating hormone, anti-mullerian hormone, androgens, blood glucose and
other labs may be relevant for measuring the severity of the conditions discussed below.
Lastly, physical findings are often useful in assessing fertility-related conditions such
as PCOS, obesity and hypothalamic amenorrhea all discussed below. These items should
be noted and used later for follow-up and as measurements of success. Of course, for
couples with infertility, the ultimate measure of success is viable pregnancy. However,
this is not always achievable only through diet and lifestyle intervention and working
together with a reproductive team is often advisable.

Obesity’s Complex Relationship with Fertility
As with any patient, dietitians will want to assess BMI and physical characteristics.
Obesity can have significant effects on fertility, though this does not mean that obese
couples cannot achieve pregnancy through diet and lifestyle changes with or without
assisted reproductive technology (ART). It has been shown in studies that obese women
are more likely to have irregular menses (1). This is believed to be due to hormonal
changes induced by excess adipose tissue, which causes increases in insulin resistance
and insulin secretion as well as adipose aromatase, which produces excess estrogen (1).
In one cross sectional study of 120 obese women, those over 175% of ideal body weight
were found to be more likely to have menstrual irregularity than women below 150% of
IBW (54% compared to 19%) (2). Women who are obese are also more likely to be
anovulatory and have anovulatory infertility (1). It has been found that women of a BMI
greater than 27 have a relative risk of anovulatory infertility of 3.1 compared to women
with a normal range BMI. In this population, weight loss may help to restore ovulation
and ability to achieve pregnancy (1).

Obese women also require higher doses of medications used to induce ovulation with
generally less successful results (1). However, studies have been contradictory as to
whether BMI affects in vitro fertilization (IVF) and other ART outcomes. Some have
shown no relationship at all (3, 4). However a systematic review from 2011 found that
both overweight and obese women were less likely to achieve clinical pregnancy
through IVF and intracytoplasmic sperm injection (ICSI) and more likely to have a
miscarriage (5). A recent systematic review of weight loss interventions in order to
improve fertility in men and women who are overweight and obese concluded that
certain interventions do improve pregnancy rates (6). Specifically, Best et al. found that
reduced calorie diets and exercise interventions for women were more likely than
control interventions to result in pregnancy with a risk ratio of 1.59 for pregnancy.
However, the confidence interval was 1.01 to 2.50. There are also mixed study results on
obesity and miscarriage (1). Obesity’s effects on fertility are multifactorial and are
related to oocyte quality, follicular recruitment and ovulation as well as fertilization
and embryo development in addition to negative effects on the endometrium (6).
Knowing this, it makes sense to counsel women who are overweight or obese and
experiencing hormonal disturbances or anovulation on weight loss techniques and
physical activity. However, it’s important to take into account that these techniques
have limitations.
Obesity may also affect male fertility. Specifically, men with obesity have an increased
risk of oligozoospermia and asthenozoospermia in some studies (7). Plus, central
adiposity is linked with reduced sperm count, concentration and motility (7). Other
measurements of associations between male fertility and obesity have mixed evidence.
Hormonally, obesity may reduce availability of testosterone and increase androgen
availability, also possibly contributing to lowered fertility. Therefore, it is important to
counsel male patients about diet and lifestyle changes that may reduce BMI as well.

Age & Fertility
( Figure 1: 8)

When working with infertility patients it is important to keep in mind that age is an
independent effector when it comes to fecundity (8). A cohort study of older women
attempting to get pregnant through natural means found that while the median time to
pregnancy for women under 38 was 3 months, that time increased for every year
increase in age, with women 38-39 years of age having an average 4 month time to
pregnancy and women 40-41 having an average 8 months time to pregnancy. In
addition, after 40, the average time to pregnancy was greater than 1 year (8). Reduction
in fecundability began at age 34 with a 14% decreased compared to women age 30-31,
19% decrease age 36-37, 30% decrease in women 38-39 and 53% decrease in women
40-41 (8). This doesn’t mean it’s impossible to get pregnant at ages over 40, but the
likelihood of successful pregnancy does go down, and it can be important to discuss this
with patients, as diet and lifestyle changes can only go so far.
Polycystic Ovarian Syndrome (PCOS) & Fertility

PCOS is a common syndrome, affecting approximately 5-10% of women (9). PCOS is a
variable syndrome that often includes oligo-ovulation or anovulation,
hyperandrogenism and the presence of polycystic ovaries. According to the Rotterdam
criteria, the syndrome must include 2 of the these 3 symptoms (10). These were
reaffirmed in recent guidelines published by Monash University (11). It was also
emphasized that ultrasound is not a necessary diagnostic tool for the syndrome.
Common symptoms include hirsutism, alopecia, acne, menstrual irregularity, insulin
resistance and a greater risk for several chronic diseases (9,10,11).

(Figure 2: 12) Approximately 80% of women with anovulatory infertility also have PCOS
(9). Elevated luteinizing hormone and hyperandrogenism can affect ovulation.
Premature granulosa cell luteinization can occur due to hyperinsulinemia and
hyperandrogenism (13). It is also possible that oocyte maturation is impaired by the
growth factor dysregulation. While women with PCOS are more likely to have infertility,
they are not necessarily less able to have a successful pregnancy, as studies have shown
that over a lifetime, women with PCOS tend to have the same number of successful
parity as women without it (14, 15). However, careful management of the syndrome is
needed in order to achieve pregnancy.

First line treatment of PCOS is lifestyle related. The ASRM recommends a hypocaloric,
low glycemic load diet and increased physical activity (16). Many women with PCOS are
given drug therapy to induce ovulation. Letrozole and Clomiphene citrate are common
interventions that patients may be prescribed in order to induce ovulation (9). Letrozole
works by inhibiting estrogen synthesis. Metformin may also improve ovulation, while
helping with insulin resistance (10). If these do not work, gonadotropins are second line
therapy for ovulation induction (10). Ultimately, IVF may be required to achieve
pregnancy if these other therapies fail for PCOS patients. Specific nutrition
interventions for PCOS are discussed below under “Interventions”.
Endometriosis and Fertility

Endometriosis is another common cause of infertility, affecting somewhere between 20
and 50% of subfertile women (17). It is a condition wherein the endometrial tissue
adheres to areas outside the uterus, such as the pelvic peritoneum. It ranges in severity
and can cause painful periods and infertility as well as inflammation. Diagnosis is done
through laparoscopy and examination of lesions. The main theory behind pathogenesis
is the reverse flow of menstrual flux through the fallopian tubes including endometrial
fragments, which then implants in tissue, causing a chronic inflammatory state (17, 18).
There are many theories as to how this connects to infertility. However, no one
mechanism is agreed upon. In certain cases infertility is caused by actual occlusions,
which prevent sperm implantation, but this is the exception. Other causes are
multifactorial (17).

Treatment can include drug therapy, mostly through hormonal drugs that either
prevent ovulation or stimulate it. Neither of these has proven consistently effective in
eventually inducing fertility. Surgery has also had mixed results (17). However, ART
seems effective in aiding to achieve pregnancy. IUI and IVF can both be effective and
may be considered for a population with endometriosis, though the condition can affect
success rate (19). There are a few specific dietary recommendations for those with
endometriosis that can help to mitigate inflammation discussed below under
“Interventions”.

Hypothalamic Amenorrhea and Infertility
While there are few systematic reviews on the topic, another common cause of
infertility is secondary amenorrhea. The absence of menses after menarche or
secondary amenorrhea can be explained by many different circumstances (20).
However, the majority of cases of secondary amenorrhea are related to PCOS,
hypothalamic amenorrhea, hyperprolactinemia or ovarian failure. Hypothalamic
amenorrhea is the most common form and often occurs in conjunction with
psychological stress, over exercise, undernutrition, lack of available energy or severe
weight changes (20). Long-distance running and other endurance athletes are
particularly vulnerable (21). HOwever, it should be noted that not all patients have
underweight BMIs. This condition causes infertility due to a hormone cascade that leads
to very low estrogen levels, thus causing lack of ovulation and endometrial thickening,
making it impossible to become pregnant (22). Prolongment of this condition can cause
long-term atrophy of the uterus and related organs (22).

There are a few RCTs on the treatment of hypothalamic amenorrhea. Small trials have
also shown the effectiveness of cognitive behavioral therapy in treatment (23).
Hormonal treatments meant to induce ovulation are also used, such as human
menopausal gonadotropin and gonadotropin releasing hormone (22). IVF is a
recommended option for women with this disorder. However, success rates vary. A
recent systematic review of treatment concluded that leptin, dietary interventions and
other non-pharmacological interventions are all effective treatments (24). Specific
dietary and lifestyle recommendations are included below under “Interventions”.
Hypothyroidism & Subclinical Hypothyroidism

Thyroid hormones are an integral part of the process of fertility. Triiodothyronine (T3)
works with FSH to stimulate granulosa proliferation and maintenance (25). Thyroxine
may also play a direct role in oocyte quality, as oocytes have been found to have
receptors for it (26). Thyroid hormones may also affect sperm quality (26). In women,
hyperthyroidism tends to cause hypomenorrhea and polymenorrhea, while
hypothyroidism can be associated oligomenorrhea and amenorrhea (26). It is estimated
that 20% of infertile women have thyroid disease. Hypothyroidism may also be
associated with a thin endometrium (26). The affiliated menstrual irregularities can
affect fertility and should be addressed in patients attempting to get pregnant. If your
patient has thyroid disease, be sure they are seeing an endocrinologist to address these
issues.

There is limited evidence that subclinical hypothyroidism or hypothyroidism that
doesn’t meet the current cut off of 5 mIU/L of thyroid stimulating hormone (TSH), but is
still higher than 2.5 mIU/L may affect fertility outcomes (27). According to an ASRM
systematic review on the topic, some studies have shown an affiliation between
subclinical hypothyroidism and ovulatory dysfunction. However, there is a lack of
consistency in the definition of subclinical hypothyroidism and the methodology of
these studies. Similarly, there is mixed evidence that thyroid antibodies indicating mild
thyroid autoimmunity are associated with infertility. However, some studies show that
treatment with Levothyroxine may improve pregnancy outcomes (28).

Fertility Tests
Tests of biochemical and physiological causes of infertility are indicated after 12 or
more months of regular unprotected intercourse without successful pregnancy (29) or
after 6 months when the female partner is over 35 years old (30). At most stages of
infertility diet and lifestyle changes can be beneficial. However, it is important to work
together with a team of reproductive specialists if patients qualify as infertile.
Test (29) Biological Significance Interpretation/Relevance
Tests of Ovarian Reserve Measure of quality and quantity of Gives information to clinicians to
oocytes ultimately indicating guide counseling of planning for
fecundity pregnancy. Often used by
reproductive clinicians in
deciding which form of ART to
pursue.
Antimullerian Hormone & Glycoprotein hormones produced Direct measures of quantity of
inhibin B by small ovarian follicles. AMH Is number of follicles. Decline with
secreted by primary, preantral and age.
antral follicles. Inhibin B is secreted
by antral preantral follicles.
Follicle Stimulating Hormone A drop in inhibin B causes less Indirect measure of oocyte
(FSH) negative feedback, which increases quantity
FSH secretion
Estradiol Increases in FSH earlier in a Used in conjunction with other

woman’s cycle will accelerate new tests to determine ovarian
follicular growth and increase reserve.
estradiol. This eventually results in
a shorter cycle.
Antral follicle count Number of follicles with 2-10 mm Numbers are indicative of the
diameters. Test done during the size of the follicular pool and
early follicular phase via eggs available for retrieval.
ultrasonographic transvaginal
scan.
Ovarian Volume Ultrasound of size of ovaries Declines with age and can
correspond to ovarian reserve.
Hysterosalpingogram Dye is injected in the uterus and Indicates if there are structural
cervix, while x-ray imagery is taken abnormalities or tubal
of its course through the uterus into occlusions.
the fallopian tubes
Tests of Male Fertility
Tests of Semen Analyses (31)
Semen concentration and Measures of the quantity and Low volume can suggest potential
volume density of sperm retrograde ejactulation,
ejaculatory duct obstruction,
hypogonadism or other
structural issues. Azoospermia
(absence of sperm) or
oligozoospermia (low sperm
concentration) can indicate
retrograde ejaculation when
coupled with the presence of
sperm in post-ejaculatory
urinalysis.
Sperm motility and Measures of sperm structure and Can help diagnose infertility and
morphology movement subfertility in men based on
relative measures in the
population.
Sperm DNA tests and Tests of genetic factors and Can help predict whether ART
anti-sperm antibody tests potential autoimmune factors in will be effective.
sperm
Transrectal Ultrasonography Sonogram of seminal vesicles Can help to diagnose

obstructions.
Ovarian reserve is a test of oocyte quality and or quantity that is measured both through
biochemical tests and an ultrasound of the ovaries (29). The biochemical tests include
measurement of follicle-stimulating hormone (FSH), anti-mullerian hormone (AMH),
estradiol and inhibin B. Inhibin B and AMH are secreted by small ovarian follicles, so
their levels are a direct reflection of the number of ovarian follicles remaining.
Decreased inhibin B will increase the amount of FSH secreted by the pituitary gland,
which will increase estradiol production and ends up shortening the length of a cycle
over time (29). Fertility patients should have had a test of FSH and Estradiol together, as
varying levels of these hormones distinguish between thyroid disorders and ovarian
disorders (30).

Antral follicular count (AFC) and ovarian volume are measures of egg number and
quality and assessed through ultrasound. The AFC is indicative of the overall follicular
reserve and correlates to the number of oocytes that can be retrieved during ART (29).
Ovarian volume decreases with age and can be indicative of ovarian reserve (29).

According to the ASRM, ovarian reserve should be used as a screening test rather than a
definitive diagnosis - giving doctors an idea of which patients are at risk for diminished
ovarian reserve and ultimately are less likely to get pregnant via ART. Of these tests
AMH likely has the most potential to be used for screening for poor ovarian response to
ART, and there is fair evidence that AFC may be useful in this regard as well, but all of
these tests should not be combined as some are highly correlated. Diminished ovarian
reserve is distinct from menopause and only applies to women of reproductive age. It
indicates that a woman will have lower response to ovarian stimulation and is less likely
to conceive naturally or with ART (29). However, it does not mean it will be impossible to
get pregnant.

Another test that may be performed is a hysterosalpingogram. This is a test wherein dye
is injected in the uterus and cervix, while x-ray imagery is taken of its course through
the uterus into the fallopian tubes (29). This helps screen for tubal occlusion and any
structural abnormalities of the uterus (30).
Male Fertility Analysis

Male factors contribute to the majority of infertility cases (31). When a male partner of a
couple with infertility is evaluated, reproductive history, including items such as any
major medical conditions or procedures and any exposure to gonadotoxins is recorded.
Then, a semen analysis is performed, which includes examination of sperm
concentration, motility and morphology (31). These parameters are good indicators of
potential for conception and help to categorize men as either infertile or subfertile (31).
However, these numbers are not a direct reflection of normal sperm parameters in the
general population, as men with semen values outside these ranges may still be fertile
and those within normal parameters can still be infertile. If an initial screening is
abnormal, specialized tests may be used. These include endocrine testing,
post-ejaculatory urinalysis, transrectal ultrasonography or tests on semen such as
leukocytes in semen, antisperm antibodies and sperm DNA tests (31).
Nutrition Diagnosis for Infertility
Common Nutrition Diagnosis for Infertility Patients (32)

Problem Etiology Signs & Symptoms
Excess Carbohydrate Related to PCOS and As evidenced by weight

Intake insulin resistance gain, insulin levels, glucose
levels
Inadequate Caloric Intake Related to hypothalamic As evidenced by energy

amenorrhea deficit, amenorrhea, TSH
levels, failure to meet more
than 75% of needs
Inadequate Protein Intake Related to PCOS or As evidenced by not

hypothalamic amenorrhea meeting more than x% of
protein needs (based on
weight) or low protein diet,
weight loss
Inadequate Iron intake Related to increased needs As evidenced by ferritin

due to desire to become level, fatigue, low iron diet
pregnant
Food and nutrition-related Related to infertility As evidenced by diet not

knowledge deficit conducive to becoming
pregnant (exp: high fast
food intake, low fruit and
vegetable intake)
Inadequate vitamin intake Related to infertility As evidenced by diet low in

(vitamin D, Folate, B12 vitamin or labs related to
Vitamin E or other related vitamin
vitamins)

Evidence-based Nutrition Interventions
Female Partner
There is no one fertility diet. However, recent research shows that certain dietary
patterns may be more conducive to conception either through natural means or
through ART (33). In addition, large cohort studies have shown some specific foods to be
beneficial for lowering time to pregnancy (TTP), risk of infertility and increasing the
likelihood of a successful pregnancy in women.
Mediterranean Diet
Several recent studies have examined specific dietary patterns and fertility. The
Mediterranean diet pattern was associated with lower “difficulty getting pregnant” in a
case control study of 485 women in Spain in which a large cohort was asked, “Have you
consulted a physician because of difficulty getting pregnant?” and those who responded
“yes” were matched with a variable number of controls (34). A food frequency
questionnaire was administered previously to determine adherence to a “Mediterranean
type dietary pattern”. In this study those in the highest quartile of adherence had a 22
to 44% lower risk of having difficulty getting pregnant compared to those in the lowest
quartile of adherence. Specifically, of the 485 cases examined, 94 were in the highest
quartile of adherence, compared with 141 in the lowest quartile (P = .002). Those in the
highest quartile of adherence had a matched odds ratio for seeking infertility help of .56
when adjusted for animal protein, trans fat and fiber intake. The researchers cited
theories that linoleic acid may be an important factor in this diet, as it is a precursor to
necessary prostaglandins in the ovulatory cycle as well as those that play a role in
endometrial thickening. They also hypothesized that the Mediterranean diet may lower
insulin resistance, which could be more conducive to ovulation.

A study in the Netherlands examining 2007 couples undergoing IVF with ICSI also found
a positive association between adherence to a Mediterranean type diet and increased
fertility. Diet was determined through the examination of FFQ data rather than a
verified score (35). However, they compared it with previous Mediterranean diet studies
and found good comparability. Mediterranean diet was defined as “high intakes of
vegetable oils, vegetables, fruits, nuts, fish, and legumes, low dairy intake, and moderate
intake of alcohol,” and high adherence was associated with a 40% increase in
probability of clinical pregnancy as well as an increase in serum and follicular fluid
folate and B6, compared with those with the lowest adherence to this dietary pattern.
These researchers believed that this may have contributed to an increase in fertility due
to their relationship with homocysteine build up, which may be related to poor
outcomes in ART. Importantly, in order to tease apart effects of a Mediterranean diet
and other dietary patterns considered healthful, the researchers in this study also
examined a “health conscious, low-processed” dietary pattern with many of the same
qualities, except that it featured a different fat profile. This diet pattern was not
associated with high intake of linoleic acid or an increase in serum B6 and was not
associated with an increase in clinical pregnancy. The researchers largely attribute the
benefits to these differences.

Another more recent study which examined the Mediterranean Diet using the verified
MedDietScore and IVF outcomes in a cohort of 244 Greek couples with primary
infertility found that those in the highest tertile of adherence to the Med diet, as
measured by the verified MedDietScore, were 65% more likely to achieve clinical
pregnancy and 67% more likely to have a live birth than the lowest tertile of adherence
(36). Fully adjusted risk ratios were .29 for clinical pregnancy for the lowest vs. highest
tertiles of adherence and .25 for live birth for the lowest vs. highest tertiles of adherence
to the MedDietScore. Of those in the highest tertile, 50% achieved clinical pregnancy,
compared with 29.1% of those in the lowest tertile of adherence. Similarly, 48.8% of
those in the highest tertile achieved live birth vs. 26.6% in the lowest tertile of
adherence. When stratified by age, this benefit only held true for those under 35 years
of age.

The CDC pools data from fertility clinics across the United States. For the year 2016
approximately 29% of IVF cycles resulted in live birth (37). This suggests the
Mediterranean diet may represent a significant increase in odds of successful birth
when used in conjunction with IVF.

Previously, one of the largest studies to examine diet and infertility (N = 17,544) - the
Nurse’s Health Study II (38), concluded that a diet higher in monounsaturated fats,
lower in trans fats, higher in plant-based foods and lower in animal proteins as well as
rich in complex carbohydrates, high fat dairy and nonheme iron and multivitamins was
associated with a much lower risk of infertility. In this cohort, they found that women
in the highest quintile of adherence to what they identified as the “fertility diet” pattern
had a relative risk of .34 for ovulatory disorder infertility. The diet was based on
previous studies of this large cohort.

Specific Foods
Seafood
There is further evidence that these foods are conducive to increased fertility in a recent
study that linked consumption of 8 or more servings of seafood per cycle with lower
time to pregnancy and greater sexual activity (39). This was true for both men and
women. Specifically, in a cohort of 501 couples, men who consumed 8 or more servings
of seafood per cycle had 47% greater fecundity (defined as lower time to pregnancy)
than those who consumed 1 or less servings per cycle. Similarly, women who consumed
8 or more servings of seafood per cycle had 60% greater fecundity. When both partners
consumed 8 or more servings of seafood per cycle had 21.9% greater sexual intercourse
frequency compared to couples who consumed less seafood. In this study, seafood was
defined as fish or shellfish.

The researchers wished to address the contradiction that women who are pregnant are
often told to avoid fish due to mercury risk. Yet, there are many proposed benefits to
fish for fertility, such as increased progesterone levels. These numbers meant that for
couples consuming 8 or more servings of seafood per cycle, 81% were pregnant by
month 6, while 64% of those consuming less became pregnant in this time period.
Similarly, 92% of the 8 or more serving group was pregnant by month 12, whereas 79%
of the couples consuming less were. The researchers believed this may have been
attributable to the benefits of omega 3 fatty acids, which had previously been shown to
lower risk of anovulation and increase progesterone.

Fruit & Fast Food
Higher fruit consumption and lower “fast food” or highly processed food consumption
was associated with a shorter TTP and a lower risk of infertility in a retrospective cohort
performed on 5628 nulliparous women in 2018 (40). Here fast food was defined as
burgers, fried chicken, pizza and hot chips from fast food outlets. Specifically, the
researchers found that women consuming greater than or equal to 3 servings of fruit
per day had a median TTP .2 - .6 months shorter than those consuming less, and women
who consumed no fast food had an average .4 to .9 months shorter TTP than those
consuming varying amounts of these foods. In other words, those consuming fruit less
than 3 times per month had a time ratio of 1.19 (or 19% increase in median TTP) for
pregnancy compared with women consuming fruit 3 or more times per week.

The study also found those consuming less than 3 servings of fruit per day had between
a 7 and 29% increase in risk of infertility, and those consuming fast food 4 or more
times per week had between 18 and 41% greater risk of infertility. Though it is not
specifically enumerated, it is likely the fast foods were high in saturated fat, refined
grains, additives and other ingredients associated with poor quality diet. Grieger et al.
mention that the saturated fat, sodium and sugar may be detrimental to the quality of
oocytes by altering the follicular fluid lipoproteins. The researchers proposed that the
antioxidants and phytochemicals in fruit, meanwhile, may impart a benefit on fertility.

Taken together these studies begin to create the foundation of a diet that is conducive to
fertility - one that is high in fruits, vegetables, whole grains and unsaturated fats and
low in highly processed foods. This provides evidence for these specific
recommendations when speaking to fertility patients.

Fatty Acids
To understand this on a macronutrient level, a few studies have examined fatty acid
intake and fertility. Both the Nurses’ Health Study II and a more recent study by Wise et
al. found that trans fats were associated with lowered fertility. In the Nurses’ Health
Study II, trans fats were found to increase risk of ovulatory disorder infertility (38, 41).
Wise et al. examined two cohorts - one in North America and one in Denmark and found
that trans fats were associated with reduced fecundability or a fecundability ratio of .86
for those with the highest quartile of intake as determined by FFQ vs. the lowest quartile
of intake. Fecundability ratio was defined as the ratio of cycle-specific probability of
conception comparing exposed women to unexposed women. However, this was only
true in the North American cohort. This was likely due to the fact that trans fat intake
was very low amongst the Danish cohort, where trans fats have been taken out of the
food system.

Similarly, Wise et al. found that low omega 3 fatty acid intake was associated with lower
fecundability. Women who consumed the highest quartile of omega 3’s had a
fecundability ratio of 1.21 compared to those in the lowest quartile of consumption.
However, there was little association in the Danish cohort, presumably due to the fact
that omega 3 consumption was high across the whole cohort and did not vary as much.
The authors attributed the potential benefits of omega 3’s to their relationship with
prostaglandins. Specifically, omega 3s increase progesterone levels, which in turn
create a higher prostacyclin to thromboxane ratio, which may increase blood flow. At
the same time, trans fats have been associated with inflammation and insulin
resistance, which are negatively associated with ovulatory function (41).

A smaller Australian study of overweight women undergoing IVF found a correlation
with successful pregnancy and polyunsaturated fat intake, specifically the omega-6
fatty acid linoleic acid (42). In addition, a recent cohort study found that women
undergoing ART benefited from higher serum levels of both omega 3 fatty acids and
omega 6 fatty acids (43). In a random sample of 100 women undergoing ART, who were
participants in the EARTH prospective cohort, higher serum levels of omega 3 fatty acids
and omega 6 fatty acids were associated with greater probability of clinical pregnancy
and live birth. Moran et al. proposed this may be due to the fact that higher saturated
fat in follicular fluid has been inversely associated with number of oocytes, while
omega 6 and omega 3 fatty acids have been associated with better embryo morphology.

Whole Grains
Another aspect of a Mediterranean style diet that may be beneficial is consumption of
whole grain products. While not many studies have examined this, a study of 273
women undergoing IVF found an association between both implantation and live birth
and the highest quartile of whole grain intake (44). Women in the highest quartile of
whole grain intake had a 70% implantation rate per cycle, whereas women in the lowest
quartile had a 51% implantation rate. Each serving of whole grains was per day was
associated with a 33% higher odds of implantation. Whole grain intake was also
associated with endometrial thickness. This association was attributed to the
consumption of the bran portion of the grain. The researchers hypothesized that this
was due to antioxidant effects of micronutrients such as phytic acid, vitamin E and
selenium as well as the actions of phytoestrogens present in lignans, which may directly
increase endometrial thickness. In addition, whole grains may contribute to glucose and
insulin regulation, reducing the amount of androgens in the bloodstream.

Micronutrients
A 2017 Harvard review by Gaskins et al. concluded that there is good evidence that
Folate may be beneficial for those seeking to achieve pregnancy by reducing risk of
infertility and pregnancy loss and increasing positive outcomes of ART (45). This same
review found no conclusive evidence for the supplementation of vitamin D, as many
studies are contradictory. However, a possible mediating factor is ethnicity, which
seems to play a role in whether vitamin D is beneficial in ART. Various cohort studies of
vitamin D sufficiency (defined as a serum level over 30 ng/dl) have shown greater
success rates for women with higher serum concentrations (46, 47). However, some
studies have found no relationship (48). This may be mediated through race, as one
study found vitamin D levels to be predictive of IVF success in non-hispanic whites but
not in Asians (49).

There is mixed evidence for most other micronutrients. Vitamin B6 through its work
with Folate in the homocysteine pathway, and vitamin C, through its antioxidant
effects, may contribute to fertility in women (50). More studies are needed. That said, it
is safe and simple to suggest a prenatal vitamin for any patients looking to get pregnant
in order to ensure no underlying deficiencies are affecting fertility. Because these
vitamins do not have any specific standards, a vitamin with the DRI of folic acid, iron,
choline, vitamin D and B6 would be appropriate. The Nurses’ Health Study II showed a
lower risk of infertility with intake of multivitamins (38) with a RR of .88 to .59 for
ovulatory infertility depending on how many vitamins were taken per week compared
to women who didn’t take any vitamins per week. The researchers attributed this at
least in part to the folic acid in the vitamins.

Other Substances
Gaskins et al. concluded that antioxidants are not proven to be beneficial in supplement
form for women. However, in men several studies show some promising results,
particularly with regard to sperm quality, as mentioned below (45). Alcohol and caffeine
have also been studied extensively in relation to fertility. However, these studies have
contradictory conclusions. Most studies have been retrospective and may have been
subject to recall bias. Therefore, evidence for the relationship of these substances with
fertility outcomes remains insufficient. Moderate intake of caffeine (no more than 2
cups per day) and little to no alcohol due to its teratogenic nature are considered best
practices.

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ttps://doi.org/10.1097/GCO.0b013e3283609138

Male Partner
Food & Macronutrients

Evidence of beneficial and detrimental properties of several common foods exists for
men as well. Low fat dairy, fish and fruits and vegetables are in general associated with
better sperm outcomes. Whereas, higher fat dairy, processed meat and sweets have been
associated with poorer sperm outcomes (1). A systematic review by Salas-Huetos et al.
from 2017 found only 35 out of 1940 recent observational studies on nutrition and male
fertility to be of high enough quality to include (1). Thus, it is clear that more high
quality studies are needed on these topics. Of the studies they examined, several had
promising evidence that certain foods are associated with sperm outcomes. In general
food with an antioxidant effect or antiinflammatory effect is associated with better
sperm outcomes, while food that increases inflammation or oxidative stress is
associated with poor sperm outcomes. In addition, foods that are conducive to insulin
sensitivity seem to have positive effects on sperm, while those that cause insulin
resistance (i.e. high glycemic index foods) seem to be detrimental. Slals-Huetos et al.
largely attribute these benefits to the antioxidant effects of the micronutrients in these
foods, such as vitamin C, vitamin E and polyphenols. Antioxidant levels have been
previously associated with the production of reactive oxygen species (ROS) in sperm (2),
and studies have shown ROS has detrimental effects on sperm (3). In addition folate,
which plays an essential role in DNA synthesis is also found in these foods. Similarly,
omega 3 fatty acids may help mitigate oxidative stress in sperm.

For example, a case control study showed that men with infertility consumed less
non-fat milk, shellfish, tomatoes and lettuce and more yogurt, meat products and
potatoes than controls (4). A later study showed infertile men had significantly lower
carbohydrate, fiber, and lycopene intake in addition to higher fat and protein (5). In
another study, those with less motile sperm or asthenozoospermia consumed less fruit
and vegetables, less poultry, non-fat milk and seafood than controls, while consuming
more processed meats, dairy and sweets than controls (6). In a cross-sectional study, low
fat milk was found to be associated with higher sperm concentration and motility (7).
Another study by the same team found fish consumption to be inversely associated with
poor sperm morphology (8). However, processed meats were shown to correspond to
negative sperm morphology. A Dutch study, which compared a traditional dutch diet,
high in meat and potatoes and whole grains and low in sweets with a “health conscious
diet” high in fruits, vegetables and whole grains found that both were positively
associated with measures of sperm quality (9).

Similarly to females, the Mediterranean dietary pattern has been positively correlated
with measures of fertility in men. Higher sperm concentration, total sperm count and
sperm motility were positively correlated with adherence to the Mediterranean diet in a
cross sectional study of 225 men in 2016 (10). Few studies have looked at established
dietary patterns and male fertility, but Gaskins et al. did perform a similar study to their
women’s study above, categorizing men as adherent to a “prudent diet” high in fish,
chicken, fruits, vegetables, legumes and whole grains or a “Western diet” high in
processed meat, refined grains, processed foods, high calorie drinks and sweets. While
they found no association between sperm parameters and the Western diet, they did
find a positive correlation between adherence to the prudent diet and sperm motility
(11).

Fats
Total fat, particularly saturated fat appears to be negatively associated with measures of
sperm quality. Whereas, omega 3’s and other PUFAs have consistently been associated
with higher quality sperm in studies. Sperm with low motility have been associated with
high intake of saturated fats and trans fats as well as higher intake of total fat (6, 12).
Total fat intake has also been negatively associated with sperm count and concentration
(13). In contrast, omega-3 fats and DHA fats appear to have a protective effect against
asthenozoospermia (12). Omega 3’s have also been positively associated with normal
sperm morphology (13).
Micronutrients
There is good evidence that antioxidant consumption may be associated with better
sperm quality in men (1). This appears to be due to the fact that oxidative stress has
detrimental effects on sperm. Vitamin C, vitamin E, vitamin D, zinc, folate and selenium
have been shown to be beneficial for sperm quality (6,14). Vitamin C intake has also
been associated with total sperm count, concentration and motility (15).

Other substances
No major relationship between fecundability and alcohol consumption has been found
in men. However, some compelling evidence has shown that high caffeine consumption
may be negatively associated with fecundability (1). Coenzyme Q10 has been shown in
two trials to be beneficial for sperm quality, and in one trial to be beneficial for eventual
pregnancy (16, 17).

It is worth noting that it is common for patients to question whether they should avoid
inorganic foods or exposure to potential endocrine disruptors such as phthalates and
other plastics. These substances have been investigated in regard to fertility and may be
worth mentioning. Potential resources for dietitians would be the EARTH cohort studies
on bisphenol A and phthalates (18, 19).
Nutrition Interventions for Specific Conditions
PCOS
Of all of the conditions related to fertility, PCOS may require the most specific dietary
recommendations due to its close association with insulin resistance and obesity. If
these are present, a greater emphasis on macronutrient distribution is placed, similarly
to the treatment of type II diabetes. The Mediterranean diet can be a useful guideline
here, due to its emphasis on healthy fats and whole grains. In addition, a recent study
showed that soy may be beneficial as a source of protein for those with PCOS and may
help to lower BMI and increase insulin sensitivity, while decreasing male hormones and
inflammatory markers (20). Therefore, it may be beneficial to recommend whole foods
sources of soy proteins for clients with PCOS.

Endometriosis
For endometriosis, one small trial found that there may be a benefit to a high
antioxidant diet to curb the associated oxidative stress (21). In particular, women who
partook in a diet high in fruits, vegetables, nuts and seeds, providing high amounts of
vitamins A, C and E, had lower oxidative stress blood markers after two months of
adherence to the diet. This provides some evidence that a high antioxidant diet may be
beneficial to recommend to those with endometriosis. There is also evidence that a diet
rich in less inflammatory foods (fruits, vegetables, omega 3 fatty acids) may help to
prevent endometriosis, and more inflammatory foods (red meat, alcohol, trans fats)
may increase risk (22).

Hypothalamic Amenorrhea
In the case of hypothalamic amenorrhea, several small trials have been attempted in
which energy intake was of particular focus. A systematic review by Kyriakidis et al.
found that these showed inconsistent results. Most of these studies increased caloric
intake and decreased athletic training in order to restore energy balance. In most cases,
more of the intervention groups experienced restored menses than controls or at least
had better hormone markers (23). Therefore, dietitians may choose to focus on energy
balance with this clientele. However, it is important to note that it can take up to 6
months or more for menses to be restored.
Monitoring & Evaluation of Infertility Patients

Fertility patients will often require multiple visits to a dietitian in order to continue to
monitor any lifestyle changes that have been implemented and whether they have
achieved the desired effect. At these intervals, it may be beneficial to retake a 24-48
hour recall to assess whether dietary changes have been implemented. If relevant,
continue to track anthropometric measures. Even small amounts of weight loss have
been associated with better outcomes. Some labs such as FSH, TSH and blood glucose
levels and others can be used to measure success of lifestyle programs. Dietitians should
work in conjunction with reproductive specialists to determine the correct goals and
labs to monitor. Lastly, physical findings can also be useful in measuring progress. For
instance, in the case of hypothalamic amenorrhea - return of normal fat deposits may
be a positive sign of decreased physical activity and increased caloric intake.

Notably, many of these interventions take time to implement and have effects. Most of
the studies cited herein have taken place over several months. This may mean meeting
with a patient multiple times in order to reinforce positive dietary changes and
behaviors. During this time, it may be important to work across medical disciplines to
coordinate with a patient’s reproductive team. If pregnancy does result, dietitians can
also play a role in ensuring a healthy pregnancy, along with a patient’s obstetrician.
Ultimately, working with couples struggling with infertility can be very rewarding and
represents a new avenue for dietitians to influence positive outcomes for patients.

References
1. Salas-Huetos, A., Bulló, M., & Salas-Salvadó, J. (2017). Dietary patterns, foods and nutrients in male fertility
parameters and fecundability: a systematic review of observational studies. Human Reproduction Update,
23(4), 371–389. https://doi.org/10.1093/humupd/dmx006
2. Ross, C., Morriss, A., Khairy, M., Khalaf, Y., Braude, P., Coomarasamy, A., & El-Toukhy, T. (2010). A systematic
review of the effect of oral antioxidants on male infertility. Reproductive Biomedicine Online, 20(6), 711–723.
https://doi.org/10.1016/j.rbmo.2010.03.008
3. Aitken, R. J., Gibb, Z., Baker, M. A., Drevet, J., & Gharagozloo, P. (2016). Causes and consequences of oxidative
stress in spermatozoa. Reproduction, Fertility, and Development, 28( 1–2), 1–10. https://doi.org/10.1071/RD15325
4. Mendiola, J., Torres-Cantero, A. M., Moreno-Grau, J. M., Ten, J., Roca, M., Moreno-Grau, S., & Bernabeu, R. (2009).
Food intake and its relationship with semen quality: a case-control study. Fertility and Sterility, 91( 3), 812–818.
5. Mendiola, J., Torres-Cantero, A. M., Vioque, J., Moreno-Grau, J. M., Ten, J., Roca, M., … Bernabeu, R. (2010). A low
intake of antioxidant nutrients is associated with poor semen quality in patients attending fertility clinics.
Fertility and Sterility, 93(4), 1128–1133. h
ttps://doi.org/10.1016/j.fertnstert.2008.10.075
6. Eslamian, G., Amirjannati, N., Rashidkhani, B., Sadeghi, M.-R., & Hekmatdoost, A. (2012). Intake of food
groups and idiopathic asthenozoospermia: a case-control study. Human Reproduction (Oxford, England),
27( 11), 3328–3336. https://doi.org/10.1093/humrep/des311
7. Afeiche, M. C., Bridges, N. D., Williams, P. L., Gaskins, A. J., Tanrikut, C., Petrozza, J. C., … Chavarro, J. E. (2014).
Dairy intake and semen quality among men attending a fertility clinic. Fertility and Sterility, 101( 5), 1280–1287.
8. Afeiche, M. C., Gaskins, A. J., Williams, P. L., Toth, T. L., Wright, D. L., Tanrikut, C., … Chavarro, J. E. (2014).
Processed meat intake is unfavorably and fish intake favorably associated with semen quality indicators
among men attending a fertility clinic. The Journal of Nutrition, 144( 7), 1091–1098.
https://doi.org/10.3945/jn.113.190173
Sterility, 94( 6), 2096–2101. https://doi.org/10.1016/j.fertnstert.2009.12.079
10. Karayiannis, D., Kontogianni, M. D., Mendorou, C., Douka, L., Mastrominas, M., & Yiannakouris, N. (2017).
Association between adherence to the Mediterranean diet and semen quality parameters in male partners
of couples attempting fertility. Human Reproduction (Oxford, England), 32(1), 215–222.
https://doi.org/10.1093/humrep/dew288
11. Gaskins, A. J., Colaci, D. S., Mendiola, J., Swan, S. H., & Chavarro, J. E. (2012). Dietary patterns and semen
quality in young men. Human Reproduction (Oxford, England), 27(10), 2899–2907.
12. Eslamian, G., Amirjannati, N., Rashidkhani, B., Sadeghi, M.-R., Baghestani, A.-R., & Hekmatdoost, A. (2015).
Dietary fatty acid intakes and asthenozoospermia: a case-control study. Fertility and Sterility, 103(1), 190–198.
13. Attaman, J. A., Toth, T. L., Furtado, J., Campos, H., Hauser, R., & Chavarro, J. E. (2012). Dietary fat and semen
quality among men attending a fertility clinic. Human Reproduction (Oxford, England), 27(5), 1466–1474.
14. Eslamian G, Amirjannati N, Rashidkhani B, Sadeghi MR, Hekmatdoost A. Nutrient patterns and
asthenozoospermia: a case-control study. Andrologia 2016. In Press.
15. Eskenazi, B., Kidd, S. A., Marks, A. R., Sloter, E., Block, G., & Wyrobek, A. J. (2005). Antioxidant intake is
associated with semen quality in healthy men. Human Reproduction (Oxford, England), 20(4), 1006–1012.
https://doi.org/10.1093/humrep/deh725
16. Safarinejad, M. R. (2009). Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive
hormones in infertile men. The Journal of Urology, 182( 1), 237–248. https://doi.org/10.1016/j.juro.2009.02.121
17. Giahi, L., Mohammadmoradi, S., Javidan, A., & Sadeghi, M. R. (2016). Nutritional modifications in male
infertility: a systematic review covering 2 decades. Nutrition Reviews, 74(2), 118–130.
https://doi.org/10.1093/nutrit/nuv059
18. Mínguez-Alarcón, L., Gaskins, A. J., Chiu, Y.-H., Williams, P. L., Ehrlich, S., Chavarro, J. E., … EARTH Study Team.
(2015). Urinary bisphenol A concentrations and association with in vitro fertilization outcomes among women
from a fertility clinic. Human Reproduction (Oxford, England), 30(9), 2120–2128.
https://doi.org/10.1093/humrep/dev183
19. Messerlian, C., Souter, I., Gaskins, A. J., Williams, P. L., Ford, J. B., Chiu, Y.-H., … EARTH Study Team. (2016).
Urinary phthalate metabolites and ovarian reserve among women seeking infertility care. Human
Reproduction (Oxford, England), 31(1), 75–83. https://doi.org/10.1093/humrep/dev292
20. Karamali, M., Kashanian, M., Alaeinasab, S., & Asemi, Z. (2018). The effect of dietary soy intake on weight loss,
glycaemic control, lipid profiles and biomarkers of inflammation and oxidative stress in women with polycystic
ovary syndrome: a randomised clinical trial. Journal of Human Nutrition and Dietetics: The Official Journal of
the British Dietetic Association, 31( 4), 533–543. https://doi.org/10.1111/jhn.12545
21. Mier-Cabrera, J., Aburto-Soto, T., Burrola-Méndez, S., Jiménez-Zamudio, L., Tolentino, M. C., Casanueva, E., &
Hernández-Guerrero, C. (2009). Women with endometriosis improved their peripheral antioxidant markers
after the application of a high antioxidant diet. Reproductive Biology and Endocrinology: RB&E, 7,
https://doi.org/10.1186/1477-7827-7-54
22. Jurkiewicz-Przondziono, J., Lemm, M., Kwiatkowska-Pamuła, A., Ziółko, E., & Wójtowicz, M. K. (2017).
Influence of diet on the risk of developing endometriosis. Ginekologia Polska, 8 8( 2), 96–102.
https://doi.org/10.5603/GP.a2017.0017
Executive Summary
Infertility is defined as the inability to become pregnant after 12 months of unprotected
sex or six months if you are over 35 years of age (1). Approximately 15% of couples of
reproductive age have infertility (2). 35% of these cases are attributable to both male and
female partner factors (3). This educational module was created to provide information
on nutrition interventions for men and women with infertility in an online format,
easily accessible by dietitians and other healthcare practitioners. It was sponsored by
the Women’s Health DPG and contains specific recommendations for both men and
women with infertility in the framework of the nutrition care process as included
below:
Fertility Nutrition Assessment
➔ Medical hx & Lab tests related to fertility
➔ Full nutrition hx w/recall & supplements (important to review safety)
➔ Anthropometrics & nutrition focused physical exam
Conditions that Affect Fertility
➔ Obesity (insulin resistance) & Underweight (hypothalamic amenorrhea) (ASRM
#5 & 16 in presi)
➔ Age - time to pregnancy (TTP) increases significantly after age 37 (4)
➔ PCOS - can cause infertility through amenorrhea and insulin resistance (5)
➔ Endometriosis - affects 20% or more of subfertile women (6)
➔ Thyroid Conditions - Affects cycles & can cause subfertility (7,8,9)
➔ Diminished Ovarian Reserve - low response to stimulation (10)
➔ Sperm quality and quantity (11)
Fertility Testing
All fertility tests for women are essentially tests of oocyte quality and quantity (11)
● Anti-mullerian hormone (AMH) - direct measure
● Follicle stimulating hormone (FSH) - indirect measure
● Estrogen - indirect measure
● Antral follicle count - indicates follicular pool
● Ovarian volume - declines with age, corresponds to ovarian reserve
● Hysterosalpingogram (HSG) - visual test for abnormalities or tubal occlusions
Male Fertility Tests are essentially tests of sperm quality and quantity (12)
● Semen concentration and volume
● Sperm motility and morphology
● Sperm DNA and anti-sperm antibody tests
● Transrectal ultrasonography - visual test of functioning
Example Nutrition Diagnosis (13)
Inadequate caloric intake related to amenorrhea as evidenced by weight loss,
amenorrhea, TSH levels, failure to meet more than 75% of needs.
Nutrition Interventions for Infertility
Evidence-based dietary recommendations to improve female fertility outcomes
➔ Mediterranean diet - associated with less difficulty getting pregnant, higher
clinical pregnancy, better IVF outcomes (14, 15, 16)
➔ Nurses Health Study “Fertility Diet” - high monounsaturated fat, low trans fat,
plant-based, complex carbohydrates & full fat dairy (RR = .34 for infertility) (17)
➔ Seafood - lower TTP & greater sexual activity (18)
➔ 3+ servings of fruit/day - lower TTP compared to less (19)
➔ 0 - 2 times per week fast food consumption - 34 - 41% lower risk of infertility
compared to 4+ meals per week (19)
➔ Whole grains - Each serving of whole grain was associated with a 33% higher
odds of implantation (20)
➔ High omega 3 and low trans fats - higher fecundability ratio (21)
➔ Folate, Vitamin B6, Multivitamins - associated with better fertility outcomes (22,
23)
➔ Vitamin D, Alcohol, Caffeine - still some controversy (22)
Evidence-based dietary recommendations to improve male fertility outcomes
➔ Increase intake of fruits & veggies, fiber, PUFAs, poultry, antioxidant rich foods,
low fat dairy and milk (24)
➔ Decrease intake of sweets, total fat, trans-fat, processed meats, full-fat dairy,
caffeine and alcohol (24)
➔ Mediterranean diet & “Dutch Diet” associated with better sperm parameters (25)
➔ Certain antioxidant supplements may increase live birth rate (26)
➔ Some evidence for coenzyme Q10 and L Carnitine as supplements (27)
Condition Specific Recommendations
● PCOS- focus on macronutrient balance, physical activity to mitigate insulin
resistance. Lifestyle is first line of treatment, soy protein can be helpful (28)
● Endometriosis - anti-inflammatory foods may help (29, 30)
● Hypothalamic Amenorrhea - higher kcal & less exercise can restore menses (31)
Monitoring & Evaluation for Infertility
● Reassess nutrition intake, PA, anthropometrics & nutrition focused physical
exam every 4-6 weeks
● Multiple individual consults and group nutrition education can be beneficial
● Labs: FSH, LH, TSH & blood glucose
● Consider HAES, mindful eating approach
● Work with the whole reproductive team

The module is available online for continuing education credit through the Women’s
Health DPG website.
Dissemination, Evaluation & Next Steps

This lecture will primarily be disseminated through the Women’s Health DPG. They have
agreed to place a link on their website and promote it to their membership through their
newsletter and other channels. Because this lecture will live on the web and available to
healthcare professionals and students, we will also promote it by reaching out to the
Academy of Nutrition and Dietetics (AND) and asking them to promote it through their
newsletter and social media channels. In addition, the lecture will be promoted through
the following venues:
- Personal social media & website of both student and preceptor
- Sharing with nutrition students at the University of Washington
- Continuing education websites
- UW public health channels (Right as Rain or other)

The educational module will be evaluated through a follow-up survey that will be linked
to at the end of the presentation. The questions will line up with the survey given to the
women’s health DPG to see before and after changes. The survey will detail whether
viewers believe they have learned basic information about fertility and nutrition and
feel equipped to work with patients in this realm in the future. The survey is attached in
appendix IV. Specifically, it will address the learning objectives outlined in the
presentation:
➢ Identify hormones and conditions related to infertility and recognize their
relevance to the nutrition care process.
➢ Classify clinical fertility tests and their significance to dietitians.
➢ Define and apply evidence-based nutrition assessment, diagnosis, intervention,
monitoring and evaluation techniques for women and their male partners
diagnosed with infertility.
➢ Describe which micronutrients, macronutrients and dietary patterns can
improve fertility outcomes.
➢ Apply specific recommendations for the infertility-related conditions.

In order to remain relevant, this information will need to be updated periodically and
incorporated more into curriculums. Infertility must be treated like other chronic
diseases and included in coursework that addresses common chronic illnesses through
the medical nutrition therapy. In addition, the Nutrition Care Manual currently does
not address fertility extensively. This information should be incorporated into the
manual as a framework for the nutrition care process for infertility, as it was developed
with rigorous evidence review and evaluated by several leading RDs in the field of
nutrition and fertility.

Personally, I plan to incorporate this expertise into my own practice when I become a
registered dietitian. I will specifically seek out patients looking to address these issues
and work through the nutrition care process as outlined in the presentation with them.
If more dietitians are educated in this area, it may eventually be possible to incorporate
diet and lifestyle interventions into healthcare practices specializing in women’s health
and fertility, allowing for a more integrated approach to fertility treatment. This could
represent an alternative form of treatment that allows some couples with infertility to
conceive naturally and others to improve ART outcomes.
References
1. Lindsay, T. J., & Vitrikas, K. R. (2015). Evaluation and treatment of infertility. American Family Physician, 91(5),
308–314.
2. Thoma, M. E. et al. (2013). Prevalence of infertility in the United States as estimated by the current duration
approach and a traditional constructed approach. Fertility and Sterility, 99(5), 1324-1331.e1.
3. Infertility | Reproductive Health | CDC. (2019, January 16). Retrieved April 23, 2019, from
4. Steiner, A. Z. et al. (2016). Impact of female age and nulligravidity on fecundity in an older reproductive
age cohort. Fertility and Sterility, 1 05(6), 1584-1588.e1.
5. Balen, A. H., et al. (2016). The management of anovulatory infertility in women with polycystic ovary
6. Tanbo, T. et al. (2017). Endometriosis-associated infertility: aspects of pathophysiological mechanisms and
treatment options. Acta Obstetricia Et Gynecologica Scandinavica, 96( 6), 659–667.
7. Cho, M. K. (2015). Thyroid dysfunction and subfertility. Clinical and Experimental Reproductive Medicine, 42(4),
131–135. https://doi.org/10.5653/cerm.2015.42.4.131
8. Dittrich, R., Beckmann, M. W., Oppelt, P. G., Hoffmann, I., Lotz, L., Kuwert, T., & Mueller, A. (2011). Thyroid
hormone receptors and reproduction. Journal of Reproductive Immunology, 90(1), 58–66.
https://doi.org/10.1016/j.jri.2011.02.009
the infertile female population: a guideline. Fertility and Sterility, 104(3), 545–553.
10. Practice Committee of the American Society for Reproductive Medicine. (2012). Testing and interpreting
measures of ovarian reserve: a committee opinion. Fertility and Sterility, 98( 6), 1407–1415.
12. Practice Committee of the American Society for Reproductive Medicine. (2015). Diagnostic evaluation of
the infertile male: a committee opinion. Fertility and Sterility, 103( 3), e18-25.
13. Nutrition Diagnosis Snapshot. (2018). Retrieved February 18, 2019, from
https://www.ncpro.org/pubs/2018-idnt-en/category-2
14. Toledo, E., Lopez-del Burgo, C., Ruiz-Zambrana, A., Donazar, M., Navarro-Blasco, I., Martínez-González, M. A., & de
Irala, J. (2011). Dietary patterns and difficulty conceiving: a nested case-control study. Fertility and Sterility,
96(5), 1149–1153. https://doi.org/10.1016/j.fertnstert.2011.08.034
Sterility, 94(6), 2096–2101. https://doi.org/10.1016/j.fertnstert.2009.12.079
16. Karayiannis, D., Kontogianni, M. D., Mendorou, C., Mastrominas, M., & Yiannakouris, N. (2018). Adherence to the
Mediterranean diet and IVF success rate among non-obese women attempting fertility. Human Reproduction
(Oxford, England), 33( 3), 494–502. https://doi.org/10.1093/humrep/dey003
17. Chavarro, J. E., Rich-Edwards, J. W., Rosner, B. A., & Willett, W. C. (2007). Diet and lifestyle in the prevention
of ovulatory disorder infertility. Obstetrics and Gynecology, 110(5), 1050–1058.
https://doi.org/10.1097/01.AOG.0000287293.25465.e1
18. Gaskins, A. J., Sundaram, R., Buck Louis, G. M., & Chavarro, J. E. (2018). Seafood Intake, Sexual Activity, and
Time to Pregnancy. The Journal of Clinical Endocrinology and Metabolism, 103(7), 2680–2688.
https://doi.org/10.1210/jc.2018-00385
19. Grieger, J. A., Grzeskowiak, L. E., Bianco-Miotto, T., Jankovic-Karasoulos, T., Moran, L. J., Wilson, R. L., …
Roberts, C. T. (2018). Pre-pregnancy fast food and fruit intake is associated with time to pregnancy. Human
Reproduction (Oxford, England), 33(6), 1063–1070. https://doi.org/10.1093/humrep/dey079
20. Gaskins, A. J., Chiu, Y.-H., Williams, P. L., Keller, M. G., Toth, T. L., Hauser, R., … EARTH Study. Team. (2016).
Maternal whole grain intake and outcomes of in vitro fertilization. Fertility and Sterility, 105(6),
1503-1510.e4. https://doi.org/10.1016/j.fertnstert.2016.02.015
21. Wise, L. A., Wesselink, A. K., Tucker, K. L., Saklani, S., Mikkelsen, E. M., Cueto, H., … Hatch, E. E. (2018).
22. Dietary Fat Intake and Fecundability in 2 Preconception Cohort Studies. American Journal of Epidemiology,
187(1), 60–74. https://doi.org/10.1093/aje/kwx204
23. Gaskins, A. J., & Chavarro, J. E. (2018). Diet and fertility: a review. American Journal of Obstetrics &
Gynecology, 218( 4), 379–389. https://doi.org/10.1016/j.ajog.2017.08.010
24. Buhling, K. J., & Grajecki, D. (2013). The effect of micronutrient supplements on female fertility. Current
Opinion in Obstetrics and Gynecology, 2 5( 3), 173. h
ttps://doi.org/10.1097/GCO.0b013e3283609138
26. Karayiannis, D., Kontogianni, M. D., Mendorou, C., Douka, L., Mastrominas, M., & Yiannakouris, N. (2017).
Association between adherence to the Mediterranean diet and semen quality parameters in male partners
of couples attempting fertility. Human Reproduction (Oxford, England), 32(1), 215–222.
https://doi.org/10.1093/humrep/dew288
27. Showell, M. G., Mackenzie-Proctor, R., Brown, J., Yazdani, A., Stankiewicz, M. T., & Hart, R. J. (2014). Antioxidants
for male subfertility. The Cochrane Database of Systematic Reviews, (12), CD007411.
https://doi.org/10.1002/14651858.CD007411.pub3
28. Giacone, F., Condorelli, R. A., Mongioì, L. M., Bullara, V., La Vignera, S., & Calogero, A. E. (2017). In vitro effects of
zinc, D-aspartic acid, and coenzyme-Q10 on sperm function. Endocrine, 56( 2), 408–415.
https://doi.org/10.1007/s12020-016-1013-7
29. Karamali, M., Kashanian, M., Alaeinasab, S., & Asemi, Z. (2018). The effect of dietary soy intake on weight loss,
glycaemic control, lipid profiles and biomarkers of inflammation and oxidative stress in women with polycystic
ovary syndrome: a randomised clinical trial. Journal of Human Nutrition and Dietetics: The Official Journal of
the British Dietetic Association, 31(4), 533–543. https://doi.org/10.1111/jhn.12545
30. Mier-Cabrera, J., Aburto-Soto, T., Burrola-Méndez, S., Jiménez-Zamudio, L., Tolentino, M. C., Casanueva, E., &
Hernández-Guerrero, C. (2009). Women with endometriosis improved their peripheral antioxidant markers
after the application of a high antioxidant diet. Reproductive Biology and Endocrinology: RB&E, 7,
https://doi.org/10.1186/1477-7827-7-54
31. Jurkiewicz-Przondziono, J., Lemm, M., Kwiatkowska-Pamuła, A., Ziółko, E., & Wójtowicz, M. K. (2017).
Influence of diet on the risk of developing endometriosis. Ginekologia Polska, 8 8( 2), 96–102.
https://doi.org/10.5603/GP.a2017.0017
Appendix I
WHDPG application
https://docs.google.com/document/d/1j_IPcx_1XU9GwsB-HQ-64oWjkuxRkW-9XhKp
ROxVS0k/edit?usp=sharing
Appendix II
Evidence Analysis Examples
https://drive.google.com/file/d/11zIV0P1NahHLc0SFO75xMU1qYr4_VyNg/view?usp
=sharing
https://docs.google.com/document/d/1wG-WIaWAmaF1KS1eKJUoMcHL5iUeZaCZh5
RqNc0YlIk/edit?usp=sharing
https://docs.google.com/document/d/1swfLGlWbKWPjQOFbJQ10_zMAjyOILqmtCqa
XfzsF05g/edit?usp=sharing
Appendix III
WH DPG Agreement
https://drive.google.com/file/d/1FJp-QOMW6U-B6L81QqhNMzfgBfVDs4sI/view?usp
=sharing
Appendix IV
Post course quiz
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Hunt-Gibbon SUM 2019

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Fertility & Nutrition

Approximately 15% of couples of

Process & Target Audience

Please Explain Your Answer (highlights):

Nutrition Issue of Focus

While it is difficult to attribute a particular percentage of infertility cases to lifestyle

Evidence Analyses Summary

Polycystic Ovarian Syndrome (PCOS) & Fertility

Endometriosis and Fertility

Hypothyroidism & Subclinical Hypothyroidism

Test ​(29) Biological Significance Interpretation/Relevance

Estradiol Increases in FSH earlier in a Used in conjunction with other

Tests of Male Fertility

Tests of Semen Analyses (31)

Transrectal Ultrasonography Sonogram of seminal vesicles Can help to diagnose

Male Fertility Analysis

Nutrition Diagnosis for Infertility

Common Nutrition Diagnosis for Infertility Patients (32)

Excess Carbohydrate Related to PCOS and As evidenced by weight

Inadequate Caloric Intake Related to hypothalamic As evidenced by energy

Inadequate Protein Intake Related to PCOS or As evidenced by not

Inadequate Iron intake Related to increased needs As evidenced by ferritin

Food and nutrition-related Related to infertility As evidenced by diet not

Inadequate vitamin intake Related to infertility As evidenced by diet low in

Evidence-based Nutrition Interventions

Food & Macronutrients

Nutrition Interventions for Specific Conditions

Monitoring & Evaluation of Infertility Patients

Dissemination, Evaluation & Next Steps

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Test (29) Biological Significance Interpretation/Relevance