Lifestyle and Nutrition for Female Fertility and Reproductive Health

There are many factors that lead to a successful conception and pregnancy, however this article will focus on two primary aspects of this complex biological process, in women specifically; one being the production and release of eggs (ovulation), and the second being the quality of these eggs. The term quality tends to be used to describe the chromosomal contents of the egg and its subsequent ability to develop into a healthy embryo.

We will explore various lifestyle, dietary, and supplementation interventions in relation to these elements of female fertility, and how effective these have been proven to be.

Ovulation and General Health

Ovulatory dysfunction in women is known to be one of the leading causes of subfertility [22]. It can be characterised by the body releasing an egg at a sub-optimal time during the menstrual cycle, ovulation not occurring at all (aka “anovulation”), or ovulation not happening regularly (regularly being once a month).

In addition to being a crucial requirement for pregnancy, ovulation is an important indicator of general health for example it plays a key role in maintaining bone mineral density (BMD) due to the protective qualities of progesterone, which only rises following ovulation. One study found that women who have at least one anovulatory cycle or one short luteal phase across 12 months had significant decreases in BMD compared to women with normal regular cycles [1]. It’s quite well documented that oestrogen is important for bone mineral density [1,2] but some studies have also shown that progesterone plays a key role [1,3,4].

There are many conditions and environmental impacts that can lead to ovulatory dysfunction, some of which also impact egg quality, including but not limited to:

1. PCOS

PCOS is characterised by insulin resistance, anovulatory cycles, androgen dominance (e.g. testosterone), elevated leutenizing hormone (LH), and sometimes decreased follicle stimulating hormone (FSH) [5]. There is some research to suggest a link between insulin sensitivity and ovulation, and various studies have found use of Metformin (a drug widely used to increase insulin sensitivity) may be effective in treating PCOS related anovulation by decreasing androgen dominance [6,7] however it seems there is no conclusive evidence of its impact on live birth rates and further research is needed to understand the role of glucose and the effects of insulin on egg maturation [8].

Although Metformin is traditionally used as a treatment for PCOS, it can cause gastro intestinal issues so some studies have explored whether Myoinositol or Berberine could be used instead:

• The results of one study on PCOS patients showed that Myoinositol was better than Metformin at increasing insulin sensitivity with a similar impact on improving androgen balance and cardiovascular markers [6], however another meta analysis of 17 randomised controlled trials showed no significant improvement in BMI, fasting insulin, testosterone levels, and other markers in PCOS patients following treatment with Myoinositol [16].
• Berberine was similar to Metformin in terms of improving insulin sensitivity, but was better at improving androgen balance and cardiovascular markers compared to both Myoinositol and Metformin. It also showed promising signs of improving body composition compared to no intervention or placebo [6]. In terms of fertility, a meta analysis found that in women with PCOS, used in isolation, Berberine has an insignificant impact on live birth rates, however when combined with lifestyle and other treatments, it improved pregnancy rates, compared with using the other treatments alone [9].
  

Eating a low-carb diet (less than 45% of calories from carbohydrates) has been linked to higher ovulation rates [5], and shown to be effective in increasing insulin sensitivity and FSH, as well as reducing BMI, Testosterone, and LDL cholesterol in PCOS patients [10]. These are similar effects to using Metformin, Berberine, and Myoinositol, however using diet alone can reduce the risk of ovarian hyperstimulation syndrome in women with a higher egg reserve [10].

Omega 3 has been associated with various health benefits including reducing systemic inflammation [12,15] and improved perinatal outcomes [11], and could have particular relevance for women with PCOS [13]. According to some studies, oxidative stress and inflammation cooperate with insulin resistance and androgen dominance to impact ovulatory function [14]. One study shows that taking 1000-3500mg of Omega 3 per day for 6-12 weeks reduces testosterone levels and inflammation [14] which could be beneficial to those with PCOS but it looks like further research is required in this area.

2. Diet, Weight, and BMI

Over 2000 years ago the impact of diet on fertility was commented on by Hippocrates who noted that hard-working, slim servant women were more fertile than their overfed, sedentary Roman employers [8]. Modern science has since begun to explore this hypothesis, finding that extremes of body weight can influence the regulation of ovulation and egg quality [5,17,18]. For example one study found that underweight women have a four fold longer time to pregnancy and, in addition, being under-fuelled or over-exercising can have similar negative impacts on fertility [18].

A prospective cohort Nurses Health Study II conducted on 17,544 women trying to conceive found that women adhering to a traditional “Mediterranean diet” compared to a traditional “western diet” (with less trans fats, more monounsaturated fats, higher plant protein, higher iron, high-fat milk products, and carbohydrates with low-glycaemic index) were at 66% lower risk of anovulatory infertility [5]. Another study found use of a low carb diet was associated with a higher ovulation rate [5]. However, a different review of 7 randomised controlled trials found that “preconception lifestyle advice” based on alcohol abstinence, cessation of smoking, and eating more vegetables among other things resulted in little to no difference in the number of live births. This review acknowledged that the evidence was of very low quality [19] so we definitely need more studies on this subject.

3. Hormonal dysfunction

There are many things that can impact our hormones including:

• Chemicals – multiple studies have found a correlation between endocrine disrupting chemicals (such as BPA, phthalates, and pesticides) and hormone production as well as endometriosis [20] although it should be noted that most of these were in-vitro or animal studies.
• Sleep – sleep deprivation in young women during their follicular phase has been observed to significantly increase Thyroid Stimulating Hormone (TSH) which may have a negative flow-on impact to other hormones such as Gonadotropin Releasing Hormone (GnRH), FSH and LH that are essential for ovulation and egg quality [21, 22]. Further, oestradiol levels in reproductive age women with variable sleep schedules was shown to be higher than compared to those with regular sleep schedules [21].
• Exercise – impacts specific mechanisms leading to ovulation via the hypothalamic-pituitary-gonadal axis, by increasing hypothalamic-pituitary-adrenal (HPA) axis activity. It has been found that in overweight and obese women, exercise contributed to lower insulin and free androgen levels leading to the restoration of HPA regulation of ovulation [17].
  

From a supplementation perspective, Vitex Chaste Tree Berry extract is widely used to support the symptoms of pre-menstrual syndrome (PMS) and infertility [23,25]. It is thought that Vitex can help to regulate ovulation by reducing prolactin levels, thereby having an impact on FSH and other hormones [23,24]. A double blind placebo controlled study found a multi-vitamin pre-natal supplement containing Vitex among other things was effective on women who had experienced infertility for 6-36 months [38]. Although there are lots of studies available supporting Vitex’s use for PMS, theories around its direct impact on ovulation appear to be derived more from either anecdotal evidence or its inclusion with other compounds, and it has been difficult to find study data supporting this.

4. Mitochondrial function

Mitochondrial function is an important aspect of egg quality as it impacts the egg maturation process and subsequent embryo development. A woman’s age and BMI can be a factor here [26,27] but it is also documented that nutrition can play a role. A systematic review found various adverse effects of unbalanced diets, such as high fat/ high sugar, on the Mitochondria of animals [27]. Interestingly within one study the adverse effects were able to be reversed in female mice when administering Co-Enzyme Q10 (an anti-oxidant) which reduced oxidative stress around the egg and saw chromosomal alignment re-established [27].

If oxidative stress is a key contributor to subfertility then it makes sense that we may introduce anti-oxidants to combat this. Although there is limited evidence in the use of anti-oxidants for fertility, Co-Enzyme Q10 is regarded as one of the most promising [28,29] with studies showing an increase in ovulation in women with PCOS [30], a positive impact on inflammation [32], and animal studies resulting in increased egg quality [31]. However, although a meta-analysis showed Co-Enzyme Q10 increasing clinical pregnancy rates, it also found that minimal studies have been undertaken to assess the impact on live birth rates and miscarriage rates [30].

L-carnitine is another popular anti-oxidant which works by transporting medium and long chain fatty acids into the mitochondria and preventing DNA damage from free radicals [33]. It has been shown in many studies to have a positive impact on women with reproductive disorders such as PCOS and endometriosis [34]. Particularly, in endometriosis patients it can modify the localised immune system dysfunction i.e. reduce the production of cytokines which are thought to play a role in inflammation, lesion growth, and have a negative impact on egg maturation, fertilisation, and implantation [33,35,36,37].

5. Endometriosis

As well as causing pain and inflammation, Endometriosis has been associated with infertility. The mechanisms that impact fertility haven’t yet been confirmed [40]. Some think that the lesions themselves are the issue as surgical removal of these can nearly double subsequent pregnancy rates however this appears to be related to structural factors rather than egg production or quality [26].

Another school of thought is the impact of this disease on egg quality, for example the quality of eggs from endometriosis donors vs non-endometriosis donors has been shown to be much lower [39,40]. As mentioned above, the immune system dysfunction in people with Endometriosis appears to play a role in both egg quality and growth of lesions and although some research has been undertaken in-vitro on substances such as Co-Enzyme Q10 [43], more is needed to uncover the impact of antioxidants on this element of the disease.

There’s potential that Omega 3 supplementation’s impact on systemic inflammation could be useful in a similar way and some animal studies have reported a decrease in the growth of lesions when adding fish oils to the diet [12]. Vitamin C and E supplementation has been associated with reduced oxidative stress in women with endometriosis, but no change in pregnancy rates [41], and vitamin D supplementation shows a positive impact on pelvic pain, antioxidant capacity, and inflammatory markers [42] but more studies are needed to understand whether pregnancy rates are affected.

Conclusion

It could be said that reproductive health is a marker of overall health and, vice versa, overall health has a flow-on impact to fertility. Many of the interventions we’ve discussed simply aim to enable the body to operate in its natural efficient state and thus contribute to both fertility and total health:

• Maintaining a healthy BMI can contribute to healthy ovulation.
• Various supplements can be trialled by individuals as appropriate, but omega 3 seems to be the most well researched in terms of contributing to overall health.
• Berberine may be a good alternative to Metformin to improve PCOS symptoms and fertility rates when combined with other lifestyle interventions.
• Sleep and exercise appear to be significant for hormonal health and subsequent ovulation.
  

Although more research is needed on specific reproductive conditions such as Endometriosis and PCOS, using lifestyle and diet interventions to manage weight and overall wellbeing are a low cost/low risk way of balancing hormones and contributing to mitochondrial health, which ultimately can lead to quality, regular egg production.

If you’re planning on making any dietary changes or introducing supplements, it’s absolutely essential that you consult a health professional, especially if you have any underlying health conditions – at best you might waste your money and energy on poor quality supplements or a diet that doesn’t help, and at worst you could cause harm to your body! Always consult and fact-check!

References

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