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A Holistic Approach to Female Infertility

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Abstract

Fertility issues are common, and potential causes of female infertility can be multifactorial. A thorough history and physical examination and laboratory and imaging tests can provide information regarding ovarian reserve, structural abnormalities, and ovarian and hormonal dysfunctions that can be factors. A holistic approach to infertility treatment is one that is person-centered and considers the individual’s overall health rather than focusing only on the disease. This approach can help women improve their fertility before or in tandem with assisted reproductive technologies. This article provides the nurse practitioner with an overview of holistic lifestyle choices that can potentially improve fertility.


Birth rates for women over 35 have increased steadily from 1972 to the present as women choose delayed childbearing to seek higher education, participate in the workforce, and consider financial and relationship issues and societal values.1 This has also resulted in higher rates of infertility as women try for their first pregnancy later in life.1 It is estimated that 8.5%, or 2.4 million, of women aged 15–49 years were infertile in the United States from 2015 to 2019.2 Approximately 12% of all women aged 15–49 years sought infertility services during this period.2

Infertility is defined as the inability to conceive after 12 months of unprotected intercourse.3 For women over age 35, the period shortens to 6 months.3 Most patients experiencing infertility are referred to fertility specialists for consideration of assisted reproductive technologies (ART). Before referral, visiting a women’s health nurse practitioner in a primary health care setting has benefits. Using a holistic approach, the nurse practitioner can provide an initial assessment that includes looking at behavior and lifestyle factors. In this article, the author describes a holistic approach to care for women with infertility issues before and in tandem with referrals to fertility specialty care. Current evidence for behavior and lifestyle changes that may influence infertility is provided.



Female Infertility Causes and Initial Evaluation

There are several potential causes of infertility in couples. This article focuses on female infertility while recognizing that male factors account for approximately 20%–30% of infertility cases and contribute to 50% of all cases.4 Physical impediments include blocked fallopian tubes due to scarring, surgical removal of fallopian tubes, or uterine anomalies such as fibroids or uterine malformations.3 Hormonal impediments include anovulation due to thyroid disease, polycystic ovary syndrome (PCOS), diminished ovarian reserve, hyperprolactinemia, or other hormonal abnormalities.3 Estrogen-dominant conditions like endometriosis and elevated cortisol due to stress can affect menstrual cycles and ovulation.3 Endocrine and metabolic diseases, including pituitary disease, adrenal disease, eating disorders, diabetes, and autoimmune disorders, also contribute to infertility.3 Other studied potential factors for infertility are the genital tract microbiome, endometrial receptivity, obesity, and genetic disorders.3,5–7

After a thorough history and physical examination, laboratory and imaging tests can provide information regarding ovarian reserve, structural abnormalities, and ovulatory and hormonal function.8 Laboratory tests may include measurement of anti-Müllerian hormone, follicle-stimulating hormone (FSH), estradiol, progesterone, prolactin, and thyroid hormone levels. Testosterone levels and glucose tolerance testing may be considered when PCOS is suspected. Imaging tests, such as hysterosalpingogram, transvaginal ultrasound, or sonohysterography, may be necessary to investigate any uterine or tubal anomalies. Ultrasound can also be done to measure antral follicle count when evaluating ovarian reserve.3,8


Holistic Approach

A holistic approach to infertility treatment is person-centered and considers the individual’s overall health rather than focusing only on the disease. Behavior and lifestyle are essential to consider, including attention to nutrition, avoidance of toxins and pollutants, physical activity, sleep hygiene, stress management, and sexual health.

Education about fertility is another essential component of holistic care for the individual experiencing infertility. Studies show that women’s understanding of the fertile time window is low, fertility awareness practices need to be utilized sufficiently, and women want more information to understand their fertility.9 Fertility awareness methods can improve conception rates by using cervical mucus observation, basal body temperature charting, calendar observations, and ovulatory predictor kits to measure increase in luteinizing hormone (LH).9 Period tracker applications are being used to determine fertility windows and are now Food and Drug Administration-approved for contraception.10 More research is needed on the use of period tracker applications for fertility.10,11

The nurse practitioner needs to understand the evidence behind using behavior and lifestyle changes to improve fertility. Person-centered care with a holistic approach requires sharing this information with women and couples so they can make informed decisions and feel supported.


Diet and Fertility

There is a growing interest in investigating specific diets and any association with fertility. Among the diets that are receiving attention are the Mediterranean diet (MeD), the typical Western-style diet, and more specific diets for individuals seeking ART. The MeD has been well-researched concerning mental and physical health.12 The MeD, which includes whole grains, legumes, low-fat dairy, poultry, fish, olive oil, vegetables, fruits, and red wine, with avoidance of red meat and sugars, has been shown in multiple studies to reduce insulin resistance and obesity.12,13 A systematic review with a meta-analysis of 11 cohort studies evaluated infertile men and women following a diet that contained all of the main food groups of the MeD compared with those with low adherence to the MeD. Clinical pregnancy was analyzed in five studies, with a greater chance of becoming pregnant found with moderate and high adherence to the MeD. The meta-analysis did not confirm that high adherence to the MeD increased the chance of live births, corroborating the results of other studies.12

In contrast to the MeD, the Western-style diet includes simple refined carbohydrates, processed foods, and decreased intake of fruits and vegetables.12 In one cohort study of 5,628 women at their first pregnancy visit, a retrospective look at diet found modest increases in time to pregnancy and infertility for participants with lower intakes of fruit and higher intakes of fast food.14 More direct studies on fast food, lower fruit intake, high glycemic foods, and high fat in the Western-style diet are needed to understand the association with infertility and delayed time in achieving pregnancy.

A profertility diet that included supplemental folic acid, vitamin B12 vitamin D, low-pesticide fruits and vegetables, whole grains, seafood, dairy, and soy foods was shown in one observational study to result in higher pregnancy rates for women undergoing ART.15 However, there are no randomized controlled studies confirming this association.12


Micronutrients

Micronutrients are essential to cellular function, and studies show relationships with fertility. Fertility may be affected by folic acid, vitamin B12 and vitamin B6 in relation to homocysteine metabolism.12 Vitamin B12 and B6 deficiencies cause a buildup of homocysteine.12 Hyperhomocysteinemia affects the vascularity of the chorion, decreases gonadotropin levels, increases endothelial inflammation via cytokine release, and increases oxidative stress, thereby decreasing fertility.12

Vitamin D has a key role in reproductive hormonal function, with vitamin D receptors found in multiple organs including the ovaries, endometrium, placenta, pituitary gland, and hypothalamus.12 There needs to be more clarity on the impact of vitamin D on healthy individuals and their fertility.12 Vitamin D deficiency disrupts calcium balance, escalates proinflammatory cytokines, stimulates insulin levels, and affects glucose metabolism.12 Vitamin D deficiency has been associated with PCOS and endometriosis, both affecting fertility outcomes.16,17

A common finding in PCOS is an elevated LH/FSH level that results in anovulation. In a study that examined the effects of vitamin D on the endocrine and metabolic parameters of PCOS, participants with PCOS who received vitamin D supplementation had improvements in FSH level, LH to FSH ratio, and glucose levels.16 The researchers noted that given the high prevalence of vitamin D deficiency in women with PCOS and the significant decrease in fertility, further investigation with large randomized controlled studies including women with and without PCOS is needed.16

Vitamin D receptors are known for immune modulation, and their presence in reproductive tissues is potentially associated with endometriosis.12,17 Animal studies show that vitamin D can reduce endometriosis development, but clinical studies have been inconsistent and more needs to be done to understand this relationship.12

Minerals may play a role in fertility as deficiencies in calcium, iodine, iron, selenium, and magnesium can affect oocyte quality, embryo fertilization, maturation, and implantation.12 There are no studies to elucidate the influence of calcium on fertility or pregnancy complications. Iron, iodine, and selenium impact thyroid function, and their deficiencies are linked to fertility and pregnancy delay.12 Magnesium is vital to glucose metabolism and is probably associated with insulin sensitivity, impacting hormonal balance.12 Usually, a balanced diet is sufficient to maintain adequate mineral requirements of the body. Still, supplementation may be necessary, and further research is needed on minerals and their connection to fertility.


Antioxidants

The role of antioxidants in fertility continues to be explored in studies. Free radicals damage DNA in the sperm and oocyte through lipid peroxidation in the membranes.13 Free radicals are related to epigenetic factors such as a highly processed diet, alcohol use, obesity, smoking, stress and anxiety, radiation, endocrine-disrupting toxins, infections, and inflammatory conditions.13 Free radicals increase insulin resistance and inflammation and exacerbate conditions such as PCOS and endometriosis associated with infertility.13

Antioxidants neutralize free radicals, potentially increasing blood circulation, impacting sex hormone levels, and increasing insulin sensitivity, thereby improving fertility.12,13 A diet rich in antioxidants is not enough to boost fertility and supplementation may be necessary.13 Studies on antioxidants show L-carnitine, N-acetylcysteine, and alpha-lipoic acid heightened pregnancy probabilities in the over-35 age group.13 L-carnitine is beneficial to women with PCOS, endometriosis, and amenorrhea by balancing hormones, decreasing inflammatory cytokines, and combating oxidative stress.12,18

Vitamins A, C, and E are potent antioxidants. Women with endometriosis and PCOS often have lower levels of these vitamins, and supplementation can reduce oxidative stress.12,19


Probiotics and the Reproductive Microbiome

Extensive research on the gastrointestinal microbiome shows that probiotics positively affect multiple body systems while causing minimal side effects.20 The positive effects and minimal side effects create an appeal for these products.20

Lactobacilli, the predominant microbial species in the vagina, are recognized as a critical player in a healthy reproductive microbiome.20 Lactobacilli prevent the overgrowth of pathogens, improving the endometrial lining and implantation and subsequent pregnancy rates.20,21 Pathogens such as Chlamydia trachomatis, Gardnerella vaginalis, Ureaplasma species, and Gram-negative microorganisms in coexistence with a lack of Lactobacillus may affect fertility.21 Vaginal and oral probiotics have been used in treating and preventing the recurrence of bacterial vaginosis (BV).20 There is speculation that BV could contribute to subfertility.20 Randomized controlled trials on the direct relationship between the reproductive microbiome, probiotics, fertility, and ART outcomes are needed.20,21


Role of Toxins in Fertility

Alcohol and tobacco have been associated with fertility issues and poor pregnancy outcomes.12,22 Heavy alcohol consumption impacts fertility with the development of disordered menstrual cycles.12 It is hypothesized that alcohol directly affects hormones, ovulation, egg maturation, blastocyst development, and implantation.12,22 Tobacco diminishes ovarian reserves, causing delays in conception, increased spontaneous miscarriage, and decreased successful ART outcomes.22 Research has shown a relationship between high caffeine use, a delay in achieving pregnancy, and an increased risk of spontaneous miscarriage.12,23 Caffeine is found in coffee, tea, soda, and cocoa.12


Environmental Pollutants

Over 80,000 registered chemicals in the United States contaminate air, soil, water, consumer products, food, and household dust.24 Nearly 100% of pregnant women have evidence of toxins such as phthalates and pesticides in their system.24 Extensive exposure to toxins can potentially affect conception and cause harm to the embryo and fetus during pregnancy and beyond.24 Endocrine-disrupting chemicals (EDCs), plasticizers, pesticides, and heavy metals such as mercury, lead, and cadmium are prevalent, with adverse effects on reproductive health.24

Mercury accumulates in fish after being released into the environment from incineration, coal burning, and industrial release.24–26 Consuming large fish such as shark, tuna, and swordfish can lead to mercury exposure, affecting estrogen levels and fertility.24,25 Lead exposure can lead to multiple adverse outcomes, including congenital disabilities and miscarriage, but there are no data on fertility.24,26 Cadmium is a heavy metal found in rechargeable batteries, sewage, plastics, and paint. It affects the placenta, causes oxidative stress, and acts as an endocrine disruptor.24,26 Exposure to pesticides can lead to poor reproductive outcomes.24,26 EDCs, including bisphenol A, phthalates, and polybrominated diethyl ethers, mimic or block hormones, affecting fertility.24,26 It is recommended that women reduce exposure to EDCs found in foods, household and personal products, cosmetics, cans, and plastics.24 Air pollution has been associated with miscarriage, and studies show couples who live near major highways have decreased fertility.24,27


Physical Activity

A systematic review found inconclusive results on the association between physical activity, sedentary behavior, and female fertility.28 High levels of physical activity could be a stressor to the body, affecting LH and FSH release and thereby affecting estrogen and progesterone levels necessary for ovulation.28 Alternatively, moderate exercise could be significant in maintaining hormonal balance and improving the ovulatory cycle, especially in specific populations such as women with PCOS or obesity.28


Sleep

Humans will spend a third of their lives asleep, and many complain about poor sleep quality and insomnia.29 With linkages between sleep and chronic, metabolic, and mental health diseases, it is relevant to consider the relationship between sleep and fertility.29 A recent systematic review contributes to our knowledge about the potential impacts of sleep on reproductive function.29 Circadian rhythms and short sleep affect reproductive hormones and menstrual cycles and influence ovarian function and natural fertility. Those who work evening and night shifts show longer times to conception than daytime workers. Short sleep has also been linked to sexual dysfunction, menstrual irregularities, and metabolic disease, impacting fertility. Chronotypes classify the type of sleeper, those who sleep early, sleep late, or intermediate types, and are related to melatonin levels. Melatonin is a hormone that captures free radicals, protects the ovaries from oxidative stress, and impacts fertility.


Stress and Mental Health

The results of studies on how stress can affect fertility are mixed.30,31 Stress can lead to high cortisol levels, which can have an immunosuppressant effect.30 Chronic stress can also lead to low cortisol levels and cause changes in the hypothalamic–pituitary–adrenal axis.31 Hypercortisolism contributes to inflammatory conditions such as rheumatoid arthritis, chronic fatigue syndrome, metabolic disorders, and mental health issues.31 How cortisol interfaces with the reproductive hormones is complex and not completely understood. Cortisol does interfere with the release of gonadotropin-releasing hormone, which guides the menstrual cycle and ovulation.30 High cortisol levels inhibit the normal release of LH and FSH, crucial to ovulation. Some women may be more resilient than others to the effects of cortisol on ovulation. Aging may also affect the relationship between cortisol and reproductive hormones.30

A holistic approach to stress can address the emotional, mental, psychosocial, and spiritual needs of infertile women and reduce infertility-related stress, anxiety, and depression.32 Potential strategies include cognitive behavioral therapy, mind–body interventions, stress management skills, and educational interventions.32,33 In a meta-analysis, psychosocial interventions that improve mental health and stress are positively associated with pregnancy rates.34


Sexual Function

Sexual dysfunction can contribute to infertility or can be an outcome of psychological stress on the couple experiencing infertility.35 Issues with sexual function affect 40%–45% of adult women and 10%–60% of infertile couples.35 Women experiencing infertility face physical and psychological changes during infertility treatment, the burden of costly treatments, and social stigma, which can contribute to sexual dysfunction.35 Approximately 5% of infertility cases are affected by preexisting conditions such as vaginismus, dyspareunia, and hypoactive sexual desire disorder.35 Addressing female responses to the sexual phases of arousal, desire, orgasm, and resolution can help elucidate areas of concern regarding sexual function.35 It is recommended that patients are referred to sex therapy or sexual health clinicians.35


Implications for Practice

A holistic approach to care that is evidence-based is essential for women facing infertility before and in tandem with referrals for ART. Women’s health nurse practitioners in primary care settings can perform a comprehensive medical history and physical examination, order laboratory markers, and interpret initial findings. They can assess understanding of menstrual cycles, fertile windows, and fertility awareness methods, and provide education in these areas.

The nurse practitioner can thoroughly assess behaviors and lifestyle factors that can affect fertility and provide appropriate education, counseling, and referrals. Lifestyle interventions can include dietary changes, nutrient and probiotic supplementation, exercise, toxin and substance use avoidance, mindfulness and mental health practices, stress reduction, and attention to sexual health. Referrals to specialists, including dietitians, physical trainers, pelvic floor therapists, sexual and mental health therapists, and others, can optimize health. Helping women make informed choices regarding their health and fertility can improve outcomes. Nurse practitioners can create an environment within the clinical setting to communicate and deliver care that offers personalization, sensitivity, and continuity.36


Disclosure

The author has no relevant financial interest or affiliations with any commercial interests related to the subjects discussed within this article.


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