Fertility: Overcoming Inhibitory Factors
A survey published in 2012 suggested that, at the time, the prevalence of infertility among Canadian couples with the women between 18 and 44 years of age was 11.5%. Based on our observations in clinical practice, it seems that increasingly younger couples are undergoing assisted reproductive technology including in vitro fertilization (IVF) techniques. Clearly, infertility—or perhaps more aptly, subfertility—is becoming a silent epidemic, and one with considerable personal and social impact with respect to emotional cost, financial burden, and health effects, both maternal and child-related.
Among women, the most common cause of infertility is ovulatory dysfunction and associated hormonal imbalances, while among men, diminished sperm counts and motility are most common. This article discusses some of the factors that may contribute to hormonal imbalances and infertility. In addition to identifying and removing, if possible, the underlying factors contributing to these problems, various natural health products (NHPs) have been shown to help boost fertility.
Endocrine disruptors are chemicals that interfere with normal hormone production and/or signaling by mimicking the hormone, usually estrogen. These chemicals are also often referred to as xenoestrogens or, literally, “foreign estrogens.” Per a 2016 review, endocrine-disrupting chemicals (EDCs) have been demonstrated to interfere with the estrogen-receptor or the androgen-receptor signaling, and can interfere with hormone synthesis, secretion, transport, and metabolism. Endocrine disruptors include chemicals such as bisphenol‑A (BPA) and related chemicals such as bisphenol‑B, dioxins, phthalates, perfluorinated chemicals (PFCs), and organophosphate compounds that occur in plastics, canned foods, pesticides, and some cleaners and personal-care products. Emerging data draws a closer link between exposure to these chemicals and a host of reproductive problems.
A recent study found that among 50 couples undergoing in vitro fertilization (IVF), there was an inverse association between male concentrations of phthalate metabolites and blastocyst quality, meaning that higher phthalate levels are linked with lower embryo quality. Another study found that a subgroup of low-chlorinated PCBs, considered to be estrogenic, were significantly higher among anovulatory (not ovulating) women. A study evaluating the effects of BPA found that seminal BPA was inversely associated with sperm counts and quality. In addition, the total amount of PCBs was negatively associated with hormone parameters including total testosterone, free testosterone, the free androgen index, and dihydrotestosterone (DHT) in the blood. An association between phthalate metabolites and lower numbers of antral follicles (antral follicle count, AFC), a marker of decreased ovarian reserve, has also been found among women seeking fertility treatment. These studies are only the most recent, and a wealth of data on this topic has been published in medical research.
In addition to avoiding potential sources of endocrine-disrupting chemicals, maintaining efficient detoxification pathways is important in minimizing their influence on fertility. Supporting optimal digestive, liver, lymphatic, and kidney function through diet strategies and targeted supplementation appears justified. Supplements that may help include probiotics, N‑acetylcysteine (NAC), and milk thistle, to name a few.
There is growing awareness among women that hormonal contraception, such as the birth-control pill, is not really good for them. There is a long list of side effects, but equally important is that most women don’t know how the pill actually works. By introducing additional estrogens and progestins into the body, the pill works by suppressing your own body’s natural hormonal signaling and ovulation. In medical terminology, the pill shuts down signaling from the hypothalamus and pituitary gland to the ovaries. It is simply assumed that after years of suppressing ovulation, the body will simply bounce back after discontinuing the pill. While this may be true for some, it does not appear to be true for all, and many now suspect a link between long-term use of the birth-control pill and subsequent ovulatory disorders such as polycystic ovary syndrome (PCOS).
Overweight, Underweight, and Insulin
Having a body weight on either end of the spectrum appears to be bad for fertility. Being over- or underweight leads to imbalances in estrogen, insulin, and testosterone, which converge by inhibiting ovulation and sperm production. Using the body-mass index (BMI) definition, underweight is considered under 18.5, while overweight is considered over 25. Since adipose or fat tissue produces estrogen, being overweight is associated with estrogen excess as well as insulin resistance. Classically, polycystic ovary syndrome (PCOS) has been associated with being overweight and the presence of insulin resistance. Conversely, being underweight may be associated with symptoms of estrogen deficiency. Oddly enough, insulin resistance or reactive hypoglycemia, a different kind of blood-sugar problem, may be found in these women; newer research has identified a “thin phenotype” PCOS. In men, being overweight has been associated with worse sperm parameters.
Several of the medications and NHPs that have been shown to help with PCOS and promote ovulation do so by reducing insulin resistance. These include inositol, N-acetylcysteine (NAC), and chromium. Herbs that help to balance estrogen and progesterone—such as chaste tree berry, black cohosh, licorice, and peony—may also be helpful in these women.
In men, herbs and nutrients that have been shown to help improve sperm counts and quality include ashwagandha, acetyl-l-carnitine, N‑acetylcysteine (NAC), and selenium.
The Stress Response
The hypothalamic-pituitary-adrenal (HPA) axis plays an important, yet often underestimated role in fertility. Under conditions of stress, the hypothalamus and pituitary gland signal the adrenals to produce cortisol, popularly known as the “stress hormone.” High cortisol levels have an inhibitory effect on reproduction. In addition, the adrenal glands also produce other hormones called androgens, such as DHEAS, which have testosterone-like effects, in addition to testosterone, in women. In women with PCOS, adrenal overresponsiveness to stress (HPA-axis activation) may be a significant source of excess androgens. In one study of women with PCOS, stimulation of the adrenals by the hormone ACTH resulted in adrenal overresponsiveness, demonstrated by excess production of DHEAS, 17 hydroxyprogestersone, and androstenedione. In addition, among women undergoing IVF, higher cortisol levels have been associated with lower chance of pregnancy.
NHPs that may help regulate adrenal function and dampen the stress response include ashwagandha and rhodiola, as well as B vitamins.
- Bushnik, T., et al. “Estimating the prevalence of infertility in Canada.” Human Reproduction. Vol. 27, No. 3 (2012): 738–746.
- Fontana, R., and S. Della Torre. “The deep correlation between energy metabolism and reproduction: A view on the effects of nutrition for women fertility.” Nutrients. Vol. 8, No. 2 (2016): 87.
- Environmental Working Group (EWG). Dirty dozen endocrine disruptors. · http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors · Updated 2013‑10‑28 · Accessed 2017‑04‑02.
- Wu, H., et al. “Parental contributions to early embryo development: Influences of urinary phthalate and phthalate alternatives among couples undergoing IVF treatment.” Human Reproduction. Vol. 32, No. 1 (2017): 65–75.
- Gallo, M.V., et al. “Endocrine disrupting chemicals and ovulation: Is there a relationship?” Environmental Research. Vol. 151 (2016): 410–418.
- Vitku, J., et al. “Associations of bisphenol A and polychlorinated biphenyls with spermatogenesis and steroidogenesis in two biological fluids from men attending an infertility clinic.” Environment International. Vol. 89–90 (2016): 166–173.
- Messerlian, C., et al.; Earth Study Team. “Urinary phthalate metabolites and ovarian reserve among women seeking infertility care.” Human Reproduction. Vol. 31, No. 1 (2016): 75–83.
- Little, J. “Why I think doctors are overprescribing the Pill.” Verily. · http://verilymag.com/2016/07/side-effects-of-the-pill-hormonal-contraceptives-birth-control-womens-health-fertility-awareness · Updated 2016‑07‑20 · Accessed 2017‑03‑31.
- Rupersburg, N. “Why I stopped taking birth control pills.” Cosmopolitan. · http://www.cosmopolitan.com/health-fitness/a44969/i-stopped-taking-my-birth-control-pills/ · Updated 2015‑09‑01 · Accessed 2017‑03‑31.
- Grigg-Spall, H. Sweetening the Pill: or How we got hooked on hormonal birth control. Hants: Zero Books, 2013, ISBN 978‑1780996073, 208 p.
- Marshall, J.C., and A. Dunaif. “Should all women with PCOS be treated for insulin resistance?” Fertility and Sterility. Vol. 97, No. 1 (2012): 18–22.
- Altuntas, Y., et al. “Reactive hypoglycemia in lean young women with PCOS and correlations with insulin sensitivity and with beta cell function.” European Journal of Obstetrics, Gynecology, and Reproductive Biology. Vol. 119, No. 2 (2005): 198–205.
- Bieniek, J.M., et al. “Influence of increasing body mass index on semen and reproductive hormonal parameters in a multi-institutional cohort of subfertile men.” Fertility and Sterility. Vol. 106, No. 5 (2016): 1070–1075.
- Emekçi Özay, Ö., et al. “myo-Inositol administration positively effects ovulation induction and intrauterine insemination in patients with polycystic ovary syndrome: A prospective, controlled, randomized trial.” Gynecological Endocrinology. (2017): 1–5. [Epub ahead of print]
- Thakker, D., et al. “N‑Acetylcysteine for polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled clinical trials.” Obstetrics and Gynecology International. Vol. 2015 (2015): 817849.
- Ashoush, S., et al. “Chromium picolinate reduces insulin resistance in polycystic ovary syndrome: Randomized controlled trial.” The Journal of Obstetrics and Gynaecology Research.” Vol. 42, No. 3 (2016): 279–285.
- Arentz, S., et al. “Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; A review of the laboratory evidence for effects with corroborative clinical findings.” BMC Complementary and Alternative Medicine. Vol. 14 (2014): 511.
- Ahmad, M.K., et al. “Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males.” Fertility and Sterility. Vol. 94, No. 3 (2010): 989–996.
- Balercia, G., et al. “Placebo-controlled double-blind randomized trial on the use of ʟ‑carnitine, ʟ‑acetylcarnitine, or combined ʟ‑carnitine and ʟ‑acetylcarnitine in men with idiopathic asthenozoospermia.” Fertility and Sterility. Vol. 84, No. 3 (2005): 662–671.
- Safarinejad, M.R., and S. Safarinejad. “Efficacy of selenium and/or N‑acetyl-cysteine for improving semen parameters in infertile men: A double-blind, placebo controlled, randomized study.” The Journal of Urology. Vol. 181, No. 2 (2009): 741–751.
- Luque-Ramírez, M., and H.F. Escobar-Morreale. “Adrenal hyperandrogenism and polycystic ovary syndrome.” Current Pharmaceutical Design. Vol. 22, No. 36 (2016): 5588–5602.
- Maas, K.H., et al. “Androgen responses to adrenocorticotropic hormone infusion among individual women with polycystic ovary syndrome.” Fertility and Sterility. Vol. 106, No. 5 (2016): 1252–1257.
- Massey, A.J., et al. “Relationship between hair and salivary cortisol and pregnancy in women undergoing IVF.” Psychoneuroendocrinology. Vol. 74 (2016): 397–405.