DNA Fragmentation

DNA Fragmentation

DNA fragmentation is the separation of DNA into strands.  High DNA fragmentation can be a cause for male factor infertility that isn’t always examined.

What causes DNA Fragmentation?

There are a number of possible causes of DNA damage:

  1. Oxidative stress – oxidation is known to cause DNA damage. Antioxidants may help counter oxidation.  Some studies have demonstrated a benefit in supplementing certain antioxidants in men with male factor infertility such as vitamin E, coenzyme Q10, zinc and selenium.
  2. Seasonal variation – One study demonstrated a higher DNA fragmentation index in semen samples collected in the winter, versus those collected in the spring.
  3. Genetic mutations – genetic defects in the genes that code for DNA repair.  XRCC1, XPD6 and XPD23 are the genes that regulate DNA repair.  Significant associations have been found between polymorphisms of these genes and higher DNA fragmentation index (DFI).
  4. Varicocele – a varicose vein in the testicles can cause a high DFI.  Surgical varicocele repair can help improve DFI.

How can naturopathic medicine help improve DNA Fragmentation?

  1. Use of select antioxidants at the correct dose and frequency can help improve DFI.
  2. The herb Uncaria tomentosa as a water extract has been shown to enhance the function of the genes that code for DNA repair.
  3. Probiotics – one study found that probiotic supplementation could help reduce DNA fragmentation in rats.

References

Rubes J1, Rybar R, Prinosilova P, Veznik Z, Chvatalova I, Solansky I, Sram RJ. Genetic polymorphisms influence the susceptibility of men to sperm DNA damage associated with exposure to air pollution. Mutat Res. 2010 Jan 5;683(1-2):9-15. doi: 10.1016/j.mrfmmm.2009.09.010.

Omu AE1, Al-Azemi MK, Kehinde EO, Anim JT, Oriowo MA, Mathew TC. Indications of the mechanisms involved in improved sperm parameters by zinc therapy. Med Princ Pract. 2008;17(2):108-16. doi: 10.1159/000112963. Epub 2008 Feb 19.

Kasimanickam R1, Kasimanickam V, Thatcher CD, Nebel RL, Cassell BG. Relationships among lipid peroxidation, glutathione peroxidase, superoxide dismutase, sperm parameters, and competitive index in dairy bulls. Theriogenology. 2007 Mar 15;67(5):1004-12. Epub 2006 Dec 22.

Khalil AA1, Abou-Gabal AE, Abdellatef AA, Khalid AE. Protective role of probiotic lactic acid bacteria against dietary fumonisin B1-induced toxicity and DNA-fragmentation in sprague-dawley rats. Prep Biochem Biotechnol. 2015 Aug 18;45(6):530-50. doi: 10.1080/10826068.2014.940969.

Transfer One Embryo or Two?

embryo transfer one or two

Embryo Transfer: One or Two?

Should I Transfer One Embryo or Two?

A recently published study has provided new insights into whether it’s more beneficial to transfer one embryo or two. The authors demonstrated that the live birth rate is as good as or better with two single embryo transfer cycles than with one double embryo transfer cycle. In some patients the live birth rate was up to 20% higher. Other studies have shown that when two or more embryos are transferred, the excess embryos have a negative impact on the one viable embryo contributing to a low birth weight, a higher risk of preterm labor, an elevated risk of miscarriage and/or cognitive or developmental impairment.

Source: Barbara Luke, ScD, MPH, Morton B. Brown, PhD, Ethan Wantman, MBA, Judy E. Stern, PhD, Valerie L. Baker, MD, Eric Widra, MD, Charles C. Coddington III, MD, William E. Gibbons, MD, Bradley J. Van Voorhis, MD, G. David Ball, PhD.  Application of a validated prediction model for in vitro fertilization: comparison of live birth rates and multiple birth rates with 1 embryo transferred over 2 cycles vs 2 embryos in 1 cycle. Presented at the 35th annual meeting of the Society for Maternal-Fetal Medicine, San Diego, CA, Feb. 2-7, 2015.

Ectopic Pregnancy and IVF

Ectopic Pregnancy and IVF

Women undergoing IVF are at greater risk of ectopic pregnancy (2-5%) compared to women who conceive naturally (2-3%).    Suffering an ectopic pregnancy can be particularly devastating for these women as fertility is already impaired and an ectopic pregnancy can mean the loss of a fallopian tube.

Recent research suggests that the way to lower ectopic pregnancy rates in women who conceive via IVF, is to split an IVF cycle over two cycles, that is, on one cycle mature the follicles and retrieve the eggs, freeze the day 5 embryo and then do a frozen embryo transfer on the following cycle.  Why do this?  Because the study concluded that the least risk for ectopic pregnancy during IVF was in a day 5 frozen embryo transferred into a more hormonally balanced uterus than a uterus that is still under the influence of higher hormone levels caused by the drugs used to stimulate egg follicle production. The calculated risk for ectopic pregnancy in these patients was less than 1%.

Source: Cong Fang, Ph.D., Rui Huang, Ph.D., Li-Na Wei, Ph.D., Lei Jia, M.M. Frozen-thawed day 5 blastocyst transfer is associated with a lower risk of ectopic pregnancy than day 3 transfer and fresh transfer.  Reproductive Medicine Research Center, Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China. March 2015Volume 103, Issue 3, Pages 655–661.e3

What is MTHFR?

What is MTHFR?

Probably something you’ve never heard of and even something your doctors have never heard of.  It’s an enzyme that is used to convert inactive folic acid into its active form – 5-methyltetrahydrofolate or 5MTHF.

Why is MTHFR Important?

Well we all know how important folic acid is to prevent birth defects.  Every woman who is trying to conceive is advised to take folic acid supplements.  However, not everyone is capable of making MTHFR and converting the folic acid found in supplements into the active form of folic acid.  5MTHF is vital for healthy methylation, an important step in liver detoxification and helps prevent damage to DNA that can lead to birth defects and cancer.  It turns out that the genetic defect that causes an inability to produce enough MTHFR is not uncommon, in fact, depending on the study and the population you look at, this defect occurs in up to 60% of the population.

What are the implications of an MTHFR defect?

  • Inability to detoxify waste, pollutants and even excess hormones
  • Recurrent pregnancy loss or miscarriage
  • Greater predisposition to giving birth to children with birth defects such as cleft palate
  • Greater risk of cancer

What Can Be Done About It?

Every woman in my practice who is trying to conceive is advised to take folic acid in it’s active form, 5MTHF. I never recommend inactive folic acid supplements.  In some women, this is all that’s necessary. Others will have multiple such defects such that just supplying active folic acid makes them feel worse.

Want to Know if You Have the Defect?

You can order a test kit to determine all of your genetic defects here: https://www.23andme.com/en-ca/ (I have no affiliation with this company.  Be aware that there are concerns about how this data is used by this company).  I can also run a test specifically for the MTHFR defect through Gamma Dynacare.

Am I an Expert on MTHFR?

Nope, but I’m working on it.  Dr. Ben Lynch is the most well informed naturopathic doctor regarding MTHFR.

Low AMH?

Low AMH

What is AMH?

AMH stands for Anti-Mullerian Hormone.  It is a substance that is secreted when follicles are developing into eggs in the ovaries.   AMH production is greatest in follicles that are less than 4 mm (preantral and small antral).

Why Measure AMH?

We can use AMH as a guide as to how many follicles are developing.  A normal AMH would indicate that there are a normal number of follicles in the development stage.

What does low AMH mean?

Females are born with follicles in the ovaries that can develop into eggs.  In their resting (primordial) state, follicles don’t secrete AMH, as they develop up to when they reach about 8 mm, they secrete AMH and then once they reach 8 mm, they stop. Research has shown that AMH level can provide a sense of how many resting follicles are left.  However, a low AMH may also mean that there are lots of primordial follicles, but something is suppressing their development.  Removing the impediment to follicle development (often a hormone imbalance), can get eggs developing normally and secreting AMH.  Women with PCOS will have a high AMH because there are lots of follicles stuck in the development stage, but not reaching the size they need to be to get released.  There are also natural ways to balance hormones and get those follicles fully developing so that they can be released as eggs.

Phthalates and Male Infertility

Phthalates and Male Infertility

A recent study found that male children of mothers who were exposed to even low levels of phthalates, particularly diethylhexyl phthalate (DEHP) had significantly shorter anogenital distance (AGD) at birth.  AGD is an indicator of reproductive health.  Phthalates are chemicals used to make plastic more flexible. People are exposed to phthalates by eating and drinking foods that have been in contact with containers and products containing phthalates and women are particularly exposed through personal care products like shampoo, conditioners, soaps and cosmetics.

Limiting exposure to phthalates is important as well as optimizing liver metabolism to break down phthalates into waste that can be excreted in the urine.

Source: Hum. Reprod. (2015)doi: 10.1093/humrep/deu363

3 Hormone Tests Never (or Rarely) Done by Fertility Clinics

Fertility Hormone Tests

Women attending a fertility clinic hoping for investigation into why they are having fertility problems, are often left feeling disappointed by a diagnosis of “unexplained infertility”.  Most fertility clinics will screen for the more obvious hormones estradiol, progesterone, LH, FSH and sometimes prolactin.  Estradiol, progesterone, LH and FSH are the hormones that will be manipulated with fertility drugs, so these are of interest to fertility doctors.

Three Hormone Tests That are Rarely (if ever) Done

There are 3 tests that are almost never run that could be impacting your fertility:

Testosterone

Testosterone is a male hormone that women make, just to a lesser extent in most cases.  Because it is more masculine, if it’s elevated it can interfere with the normal function of the female hormones.  Low levels of testosterone can also be bad news since it is a building block for your ovaries to make into estrogen, if it’s low, estrogen levels can be lower.

DHEAs

DHEAs is a weaker male hormone or androgen.  Similar to testosterone, too much can inhibit egg development and release, too little means poor egg development and quality.  Older women are sometimes given DHEAs and there is some research that in women who are low in it, DHEAs can help ovulation and fertility.  However, in my opinion, it would be best to know where the woman falls before giving this as a treatment.

Androstenedione

Like the above two, androstenedione is more of an androgen and the same holds true for this hormone as the other two – too much or too little can have a negative impact on fertility.

Not Worth it to Do ICSI vs Conventional IVF?

A retrospective analysis looking at the data on fresh IVF and ICSI cycles from 1996-2012 found that while the use of ICSI had doubled between that period, ICSI use was associated with small but statistically significant decreases in implantation, pregnancy, live birth, multiple birth, and low birth weight rates compared with conventional IVF. The use of intracytoplasmic sperm injection (ICSI) was not associated with improved reproductive outcome compared to conventional in vitro fertilization (IVF), researchers reported.

Source: Sheree L. Boulet, DrPH, MPH; Akanksha Mehta, MD; Dmitry M. Kissin, MD, MPH; Lee Warner, PhD; Jennifer F. Kawwass, MD; Denise J. Jamieson, MD, MPH Trends in Use of and Reproductive Outcomes Associated With Intracytoplasmic Sperm Injection JAMA. 2015;313(3):255-263. doi:10.1001/jama.2014.17985.

It is my opinion that forcing a pregnancy is not a healthy thing.  It’s better to improve the health of the respective parents and remove barriers to fertility such as hormone imbalance or inadequacies, oxidative stress and nutrient deficiencies.

 

Signs and Symptoms of Ovulation

Ovulation

Step one if you are hoping to conceive is to know for sure that you are ovulating.  Having a regular period does not guarantee regular ovulation.  Read on to find out how to know if you are ovulating:

  1. Lower abdominal pain or cramping. Some women will feel ovulation, many don’t.  What you feel may be successful ovulation or it may be a vain attempt by your ovaries to release an egg.  Abdominal pain or cramping around midcycle does not guarantee that you ovulated.
  2. Cervical mucous. Cervical mucous is clear, stretchy, gooey, egg white mucous that is typically produced 24-72 hours prior to ovulation.  This mucous helps sperm make its way up the cervix and into the uterus.  It is a sign that your body is gearing up to ovulate, but doesn’t mean that you’ll necessarily succeed.
  3. Breast tenderness. Some women get tender breasts at ovulation, many don’t.  Estrogen peaks at ovulation, progesterone peaks about a week after, so breast tenderness at ovulation can be too much estrogen.  Breast tenderness a week afterward can be an imbalance between estrogen and progesterone.
  4. Basal Body Temperature. Charting basal body temperature carefully can be extremely helpful in monitoring ovulation and fertility.  You want to take your resting body temperature first thing in the morning, as soon as you open your eyes, before you do anything (including going to the washroom or having intercourse) and after you have had at least 4 hours of continuous sleep.  Take it your entire cycle and use an app like Fertility Friend or Kindara to plot the graph.  There will be a small temperature dip of about 0.2 degrees Celsius at ovulation and a subsequent increase in temperatures, about 0.5 degrees Celsius higher than the previous temperatures in the first half of your cycle.
  5. Luteal phase progesterone. If you think you’ve ovulated, and you’re trying to conceive, it would be helpful to have a luteal phase progesterone measurement done.  This is typically measured one week post ovulation.  You want to use your Basal Body Temperature data to pinpoint ovulation and have progesterone measured by a blood test about a week later.  Peak progesterone levels should be nearer the high end of the normal range for luteal phase progesterone.  Our lab’s luteal progesterone range is 5.3 – 86 nmol/L.  Since a week post ovulation is when progesterone is at its highest, we want it to be closer to 86.  For fertility, I prefer 7 day post ovulation progesterone to be above 60 nmol/L.