by Dr. Pamela Frank, BSc(Hons), ND
Thorough lab testing for infertility must be done. The majority of essential testing can be done through your medical doctor and therefore would be covered under OHIP. There are also a number of more sophisticated and/or naturopathic medical tests that may be helpful to unearth all the factors that impact your fertility and get at the root cause of the problem. We guarantee you that these can directly impact fertility and are vitally important to know in challenging infertility cases. These include:
Food Allergy/Intolerance Blood Tests
Almost everyone has mild food allergies or food intolerances. These provoke abnormal antibody production that can lead to immune related fertility disorders. Our blood test checks for IgG antibodies to either 95 different foods ($259), or 190 different foods ($469). There is also a panel that can check for IgG and IgA antibodies to 95 foods for $475.
Reference: Physicians should investigate women with unexplained infertility, recurrent miscarriage or IUGR for undiagnosed CD: Tersigni C, Castellani R, de Waure C, Fattorossi A, De Spirito M, Gasbarrini A, Scambia G, Di Simone N. Celiac disease and reproductive disorders: meta-analysis of epidemiologic associations and potential pathogenic mechanisms. Hum Reprod Update. 2014 Jul-Aug;20(4):582-93. doi: 10.1093/humupd/dmu007. Epub 2014 Mar 11.
Adrenal Stress Profile
The adrenal glands facilitate the function of the ovaries. Poor adrenal gland function is common and can lead to low estrogen levels, poor egg development, premature ovarian failure and early menopause. Relevant blood tests: Cortisol a.m. and p.m., DHEAs, testosterone – free and total, androstenedione. Urine test: 24 hour urine catecholamines.
Reference: In women, ovary and adrenal gland produce androgens. Androgens are essential drivers of the primordial to antral follicle development, prior to serving as substrate for estrogen production in the later stages of folliculogenesis: Lebbe M, Woodruff TK. Involvement of androgens in ovarian health and disease. Mol Hum Reprod. 2013 Dec;19(12):828-37. doi: 10.1093/molehr/gat065. Epub 2013 Sep 10.
Heavy metals like mercury, cadmium and nickel have been associated with infertility in men and women. Testing may include 24 urine heavy metal testing.
Reference: A significant difference in endometrial cadmium concentration was found between women with unexplained infertility and fertile women: Tanrıkut E1, Karaer A2, Celik O1, Celik E1, Otlu B1, Yilmaz E1, Ozgul O1. Role of endometrial concentrations of heavy metals (cadmium, lead, mercury and arsenic) in the aetiology of unexplained infertility. Eur J Obstet Gynecol Reprod Biol. 2014 Aug;179:187-90. doi: 10.1016/j.ejogrb.2014.05.039. Epub 2014 Jun 5.
Comprehensive Thyroid Testing
TSH, free T3, free T4. TSH should fall between 0.35-2.50. If it’s greater than 2.50, your thyroid is sub-optimal for fertility and requires treatment. Your doctor may tell you that your thyroid is fine until it is greater than 5.00, this is not acceptable for infertility. Even in the presence of normal TSH, free T3 and free T4, there can be thyroid antibodies – anti-TPO and anti-thyroglobulin antibodies should be tested to see if Hashimoto’s disease is contributing to infertility.
Reference: Subclinical hypothyroidism has been associated with an increased risk of pregnancy loss and neurocognitive deficits in children, especially when diagnosed before or during early pregnancy: Chan S, Boelaert K. Optimal management of hypothyroidism, hypothyroxinaemia and euthyroid TPO antibody positivity preconception and in pregnancy. Clin Endocrinol (Oxf). 2015 Mar;82(3):313-26. doi: 10.1111/cen.12605. Epub 2014 Oct 28.
Vitamin D affects the function of the ovaries and has been found to be low in women with PCOS and endometriosis. Blood test: 25 hydroxyvitamin D
Reference: In human granulosa cells, Vitamin D alters AMH signaling, FSH sensitivity, and progesterone production and release, indicating a possible physiologic role for VD in ovarian follicular development and luteinization: Irani M, Merhi Z. Fertil Steril.Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review. 2014 Aug;102(2):460-468.e3. doi: 10.1016/j.fertnstert.2014.04.046. Epub 2014 Jun 3.
Reference: In women with PCOS, vit D3 might exert a protective effect against the inflammatory action of AGEs by increasing circulating sRAGE. The normalization in serum AMH induced by vit D3 replacement suggests an improvement in folliculogenesis: Irani M, Minkoff H, Seifer DB, Merhi Z.Vitamin D increases serum levels of the soluble receptor for advanced glycation end products in women with PCOS. J Clin Endocrinol Metab. 2014 May;99(5):E886-90. doi: 10.1210/jc.2013-4374. Epub 2014 Feb 27.
Reference: Accumulating evidence suggests that the metabolic pathways of this vitamin may play a key role in the developing of gynaecological/obstetric diseases. VDR-mediated signalling pathways and vitamin D levels seem to (deeply) affect the risk of several gynaecological diseases, such as polycystic ovary syndrome (PCOS), endometriosis, and ovarian and even breast cancer: Colonese F, Laganà AS, Colonese E, Sofo V, Salmeri FM, Granese R, Triolo O.The Pleiotropic Effects of Vitamin D in Gynaecological and Obstetric Diseases: An Overview on a Hot Topic. Biomed Res Int. 2015;2015:986281. Epub 2015 Apr 27.
Gluten Allergy/Celiac disease
Gluten intolerance and celiac disease have been linked to infertility and recurrent miscarriage. Blood tests: IgG, IgA antibodies to gluten and gliadin, tissue transglutaminase and endomyselial antibodies.
Reference: Incidence rate of gluten sensitive celiac disease (GSCD) in women with reproductive dysfunction (RD) is 4.1%. Gluten free diet in GSCD women with RD contributes to reproductive function recovery and normal outcome of pregnancy: Prevalence of gluten-sensitive celiac disease in women with reproductive dysfunction. Ter Arkh. 2012;84(2):31-6.
Conventional Medical and Hormone Blood Tests
FSH (day 3), LH (day 3), estradiol (day 3), progesterone (day 21), testosterone – free and total, DHEAs, Androstenedione, Prolactin, DHT, TSH, free T3, free T4, thyroid antibodies (anti-TPO and anti-thyroglobulin), fasting blood sugar, fasting insulin, HbA1c, 2 hour glucose tolerance test with insulin measurements, 25-hydroxyvitamin D, cortisol a.m. and p.m., MTHFR, CBC, electrolytes, hsCRP, ESR. Any or all of these tests might be appropriate. Most of them will be covered by OHIP if ordered by a conventional medical doctor. I can run these tests for you as well, however, OHIP will not cover the cost of the tests if done through our clinic. Although we only charge what the lab charges us for them tests, the cost can be substantial (~$400).
Anti-phospholipid antibodies may be increased in women who have an immune reaction to their partner’s sperm. Research is inconclusive as to what impact these antibodies may have on female infertility.
Reference: Chighizola CB, de Jesus GR.Antiphospholipid antibodies and infertility. Lupus. 2014 Oct;23(12):1232-8. doi: 10.1177/0961203314529171.
Natural Killer (NK) Cell Activity Assay
Further research is needed before NK cell assessment can be recommended as a diagnostic tool in the context of female infertility or recurrent miscarriage.
Reference: Seshadri S, Sunkara SK.Natural killer cells in female infertility and recurrent miscarriage: a systematic review and meta-analysis. Hum Reprod Update. 2014 May-Jun;20(3):429-38. doi: 10.1093/humupd/dmt056. Epub 2013 Nov 27.
Th1/Th2 Cytokine Ratio
Overstimulation of T helper 1 (Th1) or Th2 cytokines in systemic and local environments, alterations of the prevalence of IL17 and regulatory T cell (Treg) cytokines have been suggested to contribute to the pathogenesis of implantation failure.
Reference: Decreased suppressor activity of the immune system may play a role in implantation failure: Ozkan ZS, Deveci D, Kumbak B, Simsek M, Ilhan F, Sekercioglu S, Sapmaz E. What is the impact of Th1/Th2 ratio, SOCS3, IL17, and IL35 levels in unexplained infertility? J Reprod Immunol. 2014 Jun;103:53-8. doi: 10.1016/j.jri.2013.11.002. Epub 2013 Dec 8.