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From the Townsend Letter
April 2013

Integrative Approaches to Infertility for Women
by Jaclyn Chasse, ND 
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Increasing Difficulty in Obtaining Pregnancy
The more you learn about what goes into conception, the more amazing it seems that anyone gets pregnant. The process of conception starts with the transformation of germ cells into gametes (egg and sperm) and ends with the complex signaling processes that allow a embryo to properly implant into the endometrium, altering a woman's normal hormonal cycle and creating an environment to nourish and maintain that pregnancy. From a physiological perspective, pregnancy depends on proper functioning of nearly every underlying process that integrative practitioners consider: balanced inflammatory pathways, angiogenesis, oxidative stress, hormonal balance, detoxification, proper nutrient status, and the list goes on. And so, it's not necessarily surprising that we have seen a decline in fertility over the last few decades along with the declining health reported overall in Americans.

According to the CDC report Fertility, Family Planning, and Reproductive Health of US Women: Data from the 2002 National Survey of Family Growth, more and more women in every age group have had a more difficult time getting pregnant. Between 1982 and 2002, rates of reported impaired fecundity (inability to carry a pregnancy to term) have risen as high as 15% for women aged 35 to 44, or 1 in 8 couples. Even among women with the highest fertility, aged 15 to 24, impaired fecundity rates have nearly doubled from 4% to 7% over the 20-year span.1

Fertility has been declining in men as well. A review of 61 papers published between 1940 and 1990 reported trends in semen analysis results for 14,947 men. Over the half-century, the participants' average sperm concentration decreased from 113 million/mL to 66 million/mL. In addition, the average seminal volume per ejaculation decreased from 3.4 to 2.74 mL.2 This means that the average sperm count (per ejaculation) had dropped from 384.2 million to 181.5 million, a 52.8% decrease.

We are aware of several factors that negatively affect fertility, including nutrient deficiency, environmental exposures, and stress. Thankfully, there may be opportunities to positively affect fertility of couples by decreasing exposure to harmful substances and supporting a healthful environment for both mother and father.

A study conducted by the Forsight Group, a UK-based nonprofit dedicated to promoting preconception care, followed 367 couples ranging in age from 22 to 59. Many couples in the study had a previous history of infertility (37% of couples), miscarriage (38%), therapeutic abortion (11%), still birth (3%), low-birth-weight babies (15%), malformations (2%), and SIDS (1%). All couples received basic preconception care including nutritional counseling and a prenatal multivitamin for both partners. After 2 years, 89% of the couples had achieved live births. Of those with previously diagnosed infertility, 81% achieved live births, suggesting that lifestyle modification may positively affect fertility. Also of note is that within this treatment group, there were no reported miscarriages, perinatal deaths, or malformations, and that most children were born full term and of a healthful weight.3

Starting at the Beginning
Several lifestyle factors have been identified that can promote optimal fertility, including dietary behaviors, stress management, and maintenance of a healthful weight. In addition, adequate nutrient status can influence not only the ability to get pregnant, but the health of the egg and sperm, and thus the health of the child born to those parents. The following interventions can greatly influence fertility, and it is recommended that all couples trying to conceive consider these interventions, whether they have trouble with fertility or not.

Addressing Obesity
Obesity poses a significant threat to fertility as well as for the offspring born to obese parents. In obese men, there is increased aromatase activity, which irreversibly converts testosterone to estradiol, resulting in decreased testosterone and increased estrogen levels.4 It is likely that this plays a role in the lower sperm counts, lower sperm concentration, and poor sperm morphology seen in men with increased BMI and central adiposity. Obese men also have fewer motile sperm and lower testosterone levels, as mentioned above.5,6

It's not only men who experience decreased fertility as their weight creeps up; women are also affected. Obese women have lower pregnancy rates (20.8% versus 28.3% successful cycles, p = 0.04) when they undergo vitro fertilization (IVF) and obese women are more likely to experience preterm births after IVF.7-9 Although this study represents women undergoing IVF, similar fertility trends exist in women trying to conceive naturally.10 Together, obese couples experience higher rates of miscarriage in both spontaneous conception and assisted reproduction.11 In addition to the hormonal changes noted for men, this decreased fertility may be due to increased levels of inflammation which affect ovarian response and the uterine/endometrial environment.

Obesity poses such a hindrance to fecundity that many fertility clinics place a BMI limit for candidacy for the procedure. Addressing obesity for patients is essential to support a healthy conception and pregnancy, and maintenance of a healthful weight should be a first goal for couples wishing to get pregnant. If a weight-loss plan is implemented, it is strongly recommended that clinicians encourage a modified Mediterranean diet, as this diet also has fertility-promoting effects.

Mediterranean Diet
The Mediterranean diet is a recommendation based on the traditional dietary patterns of Crete and the rest of Greece, southern Italy, and southern France.12 It emphasizes an abundance of plant foods, especially fruits and vegetables, and a low intake of red meat. Generally, fat makes up 25% to 35% of total calories, with low intake of saturated fats and high intake of monounsaturated fats such as those in olive oil and omega-3 fats such as in fish. The primary fat consumed in this diet comes from fish, poultry, and olive oil. The diet is high in legumes and whole grains and suggests low to moderate consumption of dairy products and red wine.

The Mediterranean diet has, of course, been studied for its positive effects on cardiovascular disease and overall mortality.13 It has been researched for its effects on diabetes, depression, cognitive function, cancer, weight loss, and much more.14 Of note for this article is the diet's effect on fertility. Observation of 2154 Spanish women aged 20 to 45 years showed that those women with the greatest adherence to a Mediterranean diet pattern (versus Western diet) showed the lowest difficulty of getting pregnant.15 Additionally, a 2010 study of 161 Dutch couples undergoing IVF or IVF with intracytoplasmic sperm injection (ICSI) found that Mediterranean diet adherence increased the probability of pregnancy (odds ratio 1.4).16 Mediterranean diet adherence was also associated with higher folate and vitamin B6 levels in red blood cells and in follicular fluid in the same study.

Stress Management
Stress has a documented impact on fertility. Studies have confirmed that stress inhibits the hypothalamic-pituitary-gonadal (HPG) axis.17 The stress hormones cortisol, epinephrine, and norepinephrine and the hypothalamic-pituitary-adrenal (HPA) axis directly interact with several other hormones, including hormones that regulate the menstrual cycle and gamete maturation (Table 1). Stress can directly modify levels of FSH (follicle stimulating hormone) and LH (luteinizing hormone), which directly affect synthesis of estrogen and progesterone, and dictate follicular maturation and ovulation in women and spermatogenesis and testosterone production in men. Elevated cortisol and ACTH in men can also inhibit the conversion of androstenedione into testosterone in Leydig cells.18 Higher follicular cortisol/cortisone ratios are associated with higher rates of infertility in women.19 It has been noted that men with increased stress have a decrease in glutathione and free sulfhydryl content of semen, both compounds important to combat oxidative stress and toxic exposure.20,21

Table 1: Hormones Directly Affected by the HPA Axis

Gonadotropin releasing hormone (GnRH)
Luteinizing hormone (LH)
Follicle stimulating hormone (FSH)
Endogenous opioids

Interestingly, the link between stress and female fertility goes beyond an increase in stress hormone levels and their downstream effects. Hans Selye observed ovarian atrophy in response to stress in rats.22 It is important to acknowledge that stress mediators can be protective, not just damaging, but high levels can lead to allosteric overload, where there is a high likelihood of changes to the physiological systems that affect fertility.23

It seems as though various methods of stress management and counseling may be successful for couples trying to conceive. A group mind/body intervention increased IVF pregnancy rates from 43% to 52% in women under age 40 about to start their first IVF cycle at a Massachusetts fertility clinic.24 Additionally, "letting go" counseling, focused around releasing control of the process of conception, has also shown benefit. This type of counseling nearly doubled pregnancy rates in the treatment group.25 Many other interventions have showed benefit for both men and women, including standard psychotherapy.

It is essential for practitioners to work with patients to develop a stress-management protocol that will work for each couple, and to be sensitive to the fact that a robust treatment plan may create an increased focus on infertility and therefore, an increased stress in and of itself.

Basic Preconception Supplementation
In this author's opinion, every couple trying to conceive should be put on a basic preconception regimen. Specific nutrients, such as folic acid, have been shown not only to be beneficial to prevent serious birth defects such as spina bifida, but also to negate deleterious epigenetic effects to the offspring of toxic exposures, poor nutrition, and elevated stress levels in the parents.26 No couple lives in a perfect world, and these extra precautions may not only promote fertility but also significantly affect the offspring's adult health status. The most simple preconception program would include a good multivitamin and fish oil for both partners.

A prenatal multivitamin provides key nutrients necessary for both mother and baby throughout fetal development. These include iron, calcium, folate, and zinc. Studies have demonstrated significantly improved pregnancy rates in women on multiple micronutrient supplements compared with folic acid alone (66.7% versus 39.3% achieved conception after 3 menstrual cycles, 60% versus 25% ongoing pregnancy rate).27 Consumption of a prenatal multivitamin has also been associated with significantly improved birth outcomes compared with consumption of folic acid and iron alone, including more healthful birth weight of babies, and decreased rate of stillbirth and miscarriage. A nonsignificant trend of decrease in neonatal deaths has also been observed.28 The same study also reported, not surprisingly, that mothers who took a prenatal vitamin had better micronutrient status postpartum.

Fish oil is another key supplement to include in a preconception protocol for every couple who is contemplating pregnancy in the next 6 months. It has been observed that fertile men tend to have higher blood and spermatozoan levels of omega-3 fatty acids as well as lower serum ratios of omega-6 to omega-3 compared with infertile men.29 For men with oligoasthenoteratospermia (OAT), the worst semen parameters possible, supplementation with omega-3s significantly improved semen parameters including increasing sperm count from 38.7 to 61.7 million and increasing sperm concentration from 15.6 to 28.7 million/mL.30 It is clinically useful to understand that a sperm concentration greater than 20 million/mL is associated with a much higher rate of clinical pregnancy than below 20 million/mL, where the likelihood of natural conception is considered to be approximately zero.31 This fact further emphasizes the benefit of fish oil supplementation. Fish oil supplementation has also been correlated with increased superoxide dismutase (SOD)-like and catalase-like activity, which both demonstrate an increased ability to withstand oxidative stress, as well as positive nonsignificant improvements in sperm motility and morphology.32

While there are not as many studies to validate the benefit of omega-3 supplementation in women, it is fair to assume that the significant benefits to gamete production in men would have some correlation to the analogous structure in a woman, the egg. Increased dietary intake of omega-3 fatty acids in women, especially alpha-linolenic and docosahexaenoic acids (DHA), have been correlated with an improvement in embryo morphology in couples undergoing IVF with ICSI.33

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