Unexplained Infertility

Unexplained Infertility

Unexplained infertility is probably the most frustrating of fertility diagnoses because it leaves couples wondering why they can’t conceive. There are certain fertility tests that fertility clinics don’t do and other aspects of fertility that can’t necessarily be measured.  For the former, patients often seek naturopathic care. For the latter, as a naturopathic doctor, I would treat them as if these issues were a problem since we can’t test to confirm whether they are or aren’t and there is no harm in treating “as if”.

Factors that may Cause Unexplained Infertility

1. Endometriosis – The only definitive test for endometriosis is laparoscopic surgery. Most women with infertility have never had a laparoscopy done, a number of women with unexplained infertility may have undiagnosed endometriosis. Conservative estimates put the incidence of undiagnosed endometriosis at 11% of the population.
2. Undetected hormone imbalance – Did you know that most fertility clinics do not test ALL of your hormones? The standard tests run by fertility clinics include LH, FSH, estradiol, progesterone and prolactin.  Some of my patients haven’t even had something as basic as a 7-day post ovulation progesterone level tested.  Additional tests that may be relevant to your fertility include: DHEAs, testosterone, DHT, androstenedione, repeated prolactin measurements, 7-day post ovulation progesterone, and thyroid hormone tests (TSH, free T3, free T4, anti-TPO and anti-thyroglobulin antibodies).
3. Implantation failure – Implantation requires the right hormonal mix, as well as normal nitric oxide levels. Nitric oxide plays an important role in endometrial functions such as endometrial receptivity, implantation and menstruation.
4. Undiagnosed Celiac disease – In one recent study, patients with unexplained infertility, recurrent miscarriage or intrauterine growth restriction (IUGR) were found to have a significantly higher risk of celiac disease than the general population.
5. Oxidative stress – oxidative stress may be a mediator for conception.  There may be a threshold for reactive oxygen species, above which conception may not occur.
6. Genetics – undetected genetic defects such as MTHFR mutation may contribute to infertility through undermethylation (detoxification) and/or impaired DNA synthesis.
7. Sperm DNA Fragmentation – a DNA Fragmentation Index (DFI) of greater than 20 is considered to cause a reduced chance of natural pregnancy, where a DFI greater than 30 is associated with very low chance for achieving pregnancy by natural conception or by insemination.  A DNA fragmentation test may or may not have been performed as part of the male partner’s sperm count.
8. Pelvic Inflammatory Disease – Having a history of pelvic inflammatory disease has been associated with a higher incidence of infertility.

Naturopathic Treatment for Unexplained Infertility

First, we would need to determine the root cause.  In some instances, this involves requesting additional tests either through your family doctor or fertility clinic or through me. These may include more detailed hormone testing, extensive thyroid testing, testing for celiac disease, DNA fragmentation testing (for the male partner), and possibly laparoscopic surgery (or treatment as if the problem is endometriosis).  There are natural means of addressing oxidative stress (antioxidants), restoring healthy nitric oxide levels, treating endometriosis, and balancing hormones. Testing can be done for the MTHFR mutation, as well as a number of other genetic defects that may impact fertility through 23andme.com.  For me, the diagnosis of “unexplained infertility”, just means having to dig deeper to find the root cause. Only then can you address that cause and restore normal fertility.

References:

Tersigni C, Castellani R, de Waure C, Fattorossi A, De Spirito M, Gasbarrini A, Scambia G, Di Simone N. Celiac disease and reproductive disorders: a 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.

Karatas A, Eroz R, Bahadır A, Keskin F, Ozlu T, Ozyalvaclı ME. Endothelial nitric oxide synthase gene polymorphisms (promoter -786T/C, exon 894 G/T, and intron G10T) in unexplained female infertility. Gynecol Obstet Invest. 2014;77(2):89-93. doi: 10.1159/000357442. Epub 2014 Feb 5.

Oleszczuk K, Augustinsson L, Bayat N, Giwercman A, Bungum M. Prevalence of high DNA fragmentation index in male partners of unexplained infertile couples. Andrology. 2013 May;1(3):357-60. doi: 10.1111/j.2047-2927.2012.00041.x. Epub 2012 Dec 14.

Chwalisz K1, Garfield RE. Role of nitric oxide in implantation and menstruation. Hum Reprod. 2000 Aug;15 Suppl 3:96-111.

Elizabeth H. Ruder,a Terryl J. Hartman,b and Marlene B. Goldmanc. Impact of oxidative stress on female fertility. Curr Opin Obstet Gynecol. 2009 Jun; 21(3): 219–222.

Lalouschek W, Aull S, Serles W, Wolfsberger M, Deecke L, Pabinger-Fasching I, Mannhalter C. The relation between erythrocyte volume and folate levels is influenced by a common mutation in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T). J Investig Med. 2000 Jan;48(1):14-20.

Buck Louis GM, Hediger ML, Peterson CM, Croughan M, Sundaram R, Stanford J, Chen Z, Fujimoto VY, Varner MW, Trumble A, Giudice LC; ENDO Study Working Group. Incidence of endometriosis by study population and diagnostic method: the ENDO study. Fertil Steril. 2011 Aug;96(2):360-5. doi: 10.1016/j.fertnstert.2011.05.087. Epub 2011 Jun 29.

In a study involving women diagnosed with infertility from 200-2013, it was found that those with pelvic inflammatory had significantly higher rates of infertility than controls. Females with obesity, thyroid problems, ovarian abscesses, and bacterial infections also had higher rates of infertility.  Source: Relationships between female infertility and female genital infections and pelvic inflammatory disease: a population-based nested controlled study. 2018. Clinics, 73.