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Monthly Archives

June 2018

How the Right Diagnosis Can Prevent Miscarriage: The Top 10 Causes

By | Fertility | No Comments

If I had to choose an area of fertility medicine that I love most, it’s working with pregnancy loss. I’m fascinated by each of my unique patients, the vast possibilities, and the ever-changing research. There’s just so much that we don’t know about what it takes to carry a baby to term. If you’re working with a fertility clinic you’ll notice there’s a whole lot of observation during the first two weeks of your cycle, and once you’ve ovulated (or post embryo transfer) there’s not much monitoring after that! Rest assured, this article isn’t about what we don’t know but rather what we do! Fifty percent of miscarriages may not have an identifiable cause, but that means 50% of them do.

 

Let’s go over the stats here for a moment.

 

Recurrent miscarriage is considered two or more consecutive miscarriages, however diagnosis and treatment is often not suggested until three consecutive miscarriages have occurred. Not because you should have to suffer, or because your doctor doesn’t care, but because there’s a 15-25% chance of any pregnancy ending in miscarriage. The most common cause of miscarriage is fetal chromosome abnormality, which is about 60% of the time. While we’re going over the terminology, a “chemical pregnancy” is considered a miscarriage before 5 weeks, however it’s still a miscarriage to me.

 

Factors to consider in miscarriage:

  1. Did you have an early loss in the first trimester, or a late loss in the second or even third? Different diagnoses are more likely in late pregnancy versus early pregnancy.
  2. Do you already have a child, and in trying to conceive again have a miscarriage? Having a baby already can rule out some causes of miscarriage.
  3. Do you have a family history of autoimmune, hormonal, or blood disorders? That makes some of the diagnoses more likely.

 

Factors NOT to consider in miscarriage:

  1. You haven’t “stressed” yourself to the point of miscarriage. I promise!
  2. Exercise is always healthy! You don’t need to avoid physical activity
  3. Progesterone, in any form, is not always the answer. A 2008 Cochrane review found prophylactic progesterone to have no effect on preventing miscarriage, more on this soon.

 

In my practice I don’t wait the “3-loss” rule to begin treatment and diagnosis, if you’ve experienced a loss and you want support, you deserve that support right away.

 

Now let’s get into my Top 10 Most Common Causes of Miscarriage. The majority of the list can be diagnosed with blood work or imaging. The entirety of the list can be treated!

 

  1. Anti-phospholipid syndrome (and other causes of poor placental perfusion)

    This is a syndrome where antibodies attack components of your blood vessels. Anti-phospholipid antibodies include: lupus anticoagulant, anticardiolipin antibody, and anti-B2 glycoprotein. These antibodies interfere with uterine blood flow, more specifically the development of the trophoblast, which are the cells that form the placenta.

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  2. PCOS

    The foundation of PCOS is insulin resistance, which interferes with ovulation, follicle maturation, and maintaining a pregnancy. Insulin resistance, and the corresponding hormonal imbalances, cause poor egg quality, pelvic inflammation, and progesterone deficiency – all which contribute to miscarriage. I will add that metformin has not been found to be beneficial in preventing miscarriage in PCOS, but there are many naturopathic therapies that have!

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  3. Chromosome translocation (it’s not all about the woman!)

    This genetic condition can occur in men or women. If you have a chromosome translocation you won’t have any signs or symptoms, but some of the gametes you produce (i.e. egg or sperm) will also have the translocation. Unfortunately, if you’re conceiving naturally it’s a game of chance as to whether or not you will produce a viable embryo. IVF with PGS (pre-implantation genetic screening) can determine whether your embryo has a viable number of chromosomes.

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  4. Hypothyroidism & thyroid antibodies

    TSH greater than 4.0 during pregnancy is associated with miscarriage, preterm birth, premature rupture of membranes, and placental detachment. Thyroid peroxidase antibody, found in Hashimoto’s thyroiditis, causes similar outcomes.

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  5. Anatomical causes: fibroids, polyps, uterine malformations, cervix incompetence

    Anatomical issues are more commonly at play during second trimester losses, and the outcome depends greatly on the location of the finding. I won’t go into the details here as they are easily diagnosed, and quite obvious, through imaging and pelvic exam.

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  6. Poor quality sperm (it’s not all about the woman!)

    The best test for measuring sperm quality is called sperm DNA fragmentation. Greater than 25% fragmented DNA indicates poor quality. In my experience, beyond lifestyle factors like diet and recreational drug use, medications are the most common culprit of increased DNA fragmentation. Anti-depressant medication, specifically SSRIs, cause statistically significant increases in DNA fragmentation as well as miscarriage.

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  7. Poor quality egg

    If only we had a test for egg quality like we do sperm quality! Age is the number one predictor for egg quality, steadily declining after age 35 – lucky us! But don’t worry, there’s lots that can be done!

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  8. Vitamin D deficiency

    One prospective cohort study identified vitamin D deficiency as a risk factor for miscarriage, preterm birth, and low birth weight. Adequate vitamin D levels, hard to come by in gloomy Canada, are extremely important when it comes to reproductive health. 1 nmol increase in serum vitamin D levels decreases miscarriage rate by 1%. Testing is clearly imperative!

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  9. Inflammation & oxidative stress

    Conditions like PCOS, listed above, and endometriosis cause increased uterine inflammation and oxidative stress. Inflammation can also be elevated in the presence of other autoimmune diseases during pregnancy. However, there is significant research on specific anti-inflammatories and antioxidants increasing live birth rate and preventing miscarriage in these scenarios!

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  10. Progesterone deficiency & hyperprolactinemia

    As I’ve already suggested in this article, progesterone supplementation only appears to be helpful when there is a progesterone deficiency. High dose progesterone supplementation is all too common and I often see the extremely uncomfortable side effects in my patients. It may be indicated in cases of recurrent miscarriage. I’ll also mention hyperprolactinemia here as elevated prolactin levels can suppress progesterone production and lead to deficiency.

 

Honorable mentions:

 

  1. MTHFR deficiency & elevated homocysteine

    MTHFR deficiency refers to a mutation in the gene “MTHFR”, responsible for metabolizing folate (a vitamin found in your prenatal supplement to prevent spina bifida). When folate is not metabolized properly, a build up of an amino acid called homocysteine results. Elevated homocysteine can cause blood clotting and inhibit uterine and placental blood flow.

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  2. Immunological cause

    I’m going to throw out some pretty fancy terms here: HLA incompatibility, anti-paternal antibodies, and natural killer cells. They’re all terms for potential immunological conditions that cause miscarriage, meaning the woman’s immune system is attacking the embryo. Currently there’s insignificant research to suggest any of the above cause miscarriage, and the treatment is theoretical as well.

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  3. Vaginal infection

    I’ve noticed many fertility clinics test for ureaplasma and mycoplasma, and treat both partners with antibiotics if present. There is no clear data that these infections cause miscarriage. I have mixed feelings about the results, as there are often comorbidities present in my patients who have been treated for these infections. However, untreated bacterial vaginosis can indeed cause early miscarriage.

As I mentioned previously, I wouldn’t provide you with this information if there were not ways to diagnose and treat the possibilities. You have options! Just book an appointment with me and let’s get started.

 

References
Iqbal, S., Ghani, F., & Qureshi, R. (2016). Frequency of Thyroid Peroxidase Antibody and its Association with Miscarriages Among Pregnant Women. Journal of the College of Physicians and Surgeons Pakistan26(10), 831-834.
Sundermann, A. C., Edwards, D. R. V., Bray, M. J., Jones, S. H., Latham, S. M., & Hartmann, K. E. (2017). Leiomyomas in pregnancy and spontaneous abortion: A systematic review and meta-analysis. Obstetrics & Gynecology130(5), 1065-1072.
Bärebring, L., Bullarbo, M., Glantz, A., Hulthén, L., Ellis, J., Jagner, Å., … & Augustin, H. (2018). Trajectory of vitamin D status during pregnancy in relation to neonatal birth size and fetal survival: a prospective cohort study. BMC pregnancy and childbirth18(1), 51.
Loss, E. P. PRACTICE BULLETIN.
EVALUATE, W. (2012). Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertility and Sterility98(5).
El Hachem, H., Crepaux, V., May-Panloup, P., Descamps, P., Legendre, G., & Bouet, P.-E. (2017). Recurrent pregnancy loss: current perspectives. International Journal of Women’s Health9, 331–345. http://doi.org/10.2147/IJWH.S100817
No, G. T. G. (2011). The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. April 2011.
Haas, D. M., & Ramsey, P. S. (2008). Progestogen for preventing miscarriage. Cochrane Database Syst Rev2.

The Top 10 Questions to Ask Before Starting IVF

By | Fertility | No Comments

IVF is a big step, physically and financially, and you likely have questions before you commit but you just don’t know what to ask. Of course, how do you know what you don’t know?! The purpose of this blog is to inform you about the IVF process and provide you with some preliminary questions to ask your Reproductive Endocrinologist (RE). It’s important that you feel empowered and in-control when it comes to the decision of IVF. Don’t be afraid to ask questions and advocate for yourself, you always deserve to be in the know!

 

  1. What testing has been completed that makes IVF a necessary procedure for me?

    IVF is not typically the first option when it comes to Assisted Reproductive Technology (ART). You may have already gone through several unsuccessful IUIs, or you/your partner may have a specific circumstance that requires IVF. When it comes to female blood work, a low AMH level and/or high FSH level is an indicator of low ovarian reserve and IVF may improve you ovarian response. For men, if there is hypospermatogenesis, IVF with ICSI (injecting the sperm directly into the egg cytoplasm) may be the best option for you. Do make sure your RE walks you through the evidence that supports the need for IVF in your particular case.

  2. What does IVF involve?

    Ask your RE to go over the procedure with you, including how the medications are administered, the function of each medication (I get asked this one the most!), and how many appointments you will need. You or someone you know will need to be comfortable with the injections! You may also need to adjust your work schedule for the frequent cycle monitoring appointments. The egg retrieval procedure is indeed minor surgery so you should be advised as to how to prepare beforehand.

  3. How much does IVF cost? Do you have funding available?

    This one I’m sure is the most obvious question to ask, IVF is expensive! The funding gets confusing though. In Ontario, one IVF treatment cycle per female patient is funded. However, you are at the liberty of the waitlist at your fertility clinic. Depending on the fertility clinic, you may wait from 6 months to 2 years for your funding. The funding is based on a first come, first serve basis. In order to be eligible you (the woman) must be under the age of 43. The funding does not cover the medications, but it does cover the cost of ALL of your embryo transfers. For example: if you produce 3 viable embryos from your IVF cycle, each embryo will be transferred one at a time; each of these transfers is covered by the funding.

  4. What are the side effects?

    You’ll want to ask about the side effects of the specific medications you are taking as well as the risk of ovarian hyperstimulation syndrome (OHSS) and egg retrieval. Long-term side effects are largely unknown (from my understanding), but you’ll want to know what to expect while taking the medications so you don’t have to resort to “Dr. Google” along the way.

  5. What is the success rate of IVF?

    The success is going to depend on your unique case, as well as your partner’s/donor’s, and both of your ages. The greater the number of high quality embryos produced, the greater your chances for a healthy live birth. The CDC has an amazing tool, based on their compiled data, to calculate your potential success rate. For example, the chance of live birth per embryo transfer between ages 38-40 is 27%. The chance of live birth per egg retrieval procedure between ages 38-40 is 19%.

  6. Based on my lab work how many embryos do you think will be produced?

    This is important for developing realistic expectations for the IVF process. Your RE should be able to predict this for you. To give you a real world example of a female age < 35 using stimulating medications: 10 follicles were retrieved, of these 10 follicles only 7 were mature and viable, of the 7 follicles 5 were fertilized, of these 5 embryos only 3 survived until day 5. That’s a total of 3, day 5 embryos to be transferred.

  7. Do you advise day 3 or day 5 embryo transfer?

    A 5-day-old embryo has more cells than a 3-day-old embryo; it is referred to as a blastocyst. Blastocysts are commonly higher quality embryos than embryos in the cleavage stage (day 3). They’ve survived an extra 2 days on their own! It is worth discussing which practice your RE uses.

  8. Will the embryo transfer be fresh or frozen?

    Frozen embryo transfers are now more common practice, as it gives your body a chance to rest before the transfer. This means you’ll wait until your next cycle to transfer the embryo, rather than right after egg retrieval. The research on live birth rates when comparing fresh and frozen embryos seems to show similar outcomes.

  9. Do you offer PGS (pre-implantation genetic screening)?

    This screening is completed on frozen (and then thawed) day 5 embryos. It is a test to determine whether embryos have an abnormal number of chromosomes. It can be used to prevent miscarriage or lack of embryo implantation. If an embryo has an abnormal number of chromosomes it will not be transferred. Not all clinics offer this technology, and it is an additional cost.

  10. Do you welcome the support of acupuncture and naturopathic medicine during IVF?

    Finally, the most important question of all! Choose an RE who supports a multidisciplinary approach to fertility. It can take a village to make a healthy baby and you deserve access to all tools in that village. Acupuncture and naturopathic medicine have been highly researched for fertility support. We can also help you navigate the IVF process and answer questions your RE may not have the time to answer. You should feel supported every step of the way. Book your appointment here! 

    References
    Hatırnaz Ş, Kanat Pektaş M. Day 3 embryo transfer versus day 5 blastocyst transfers: A prospective randomized controlled trial. Turkish Journal of Obstetrics and Gynecology. 2017;14(2):82-88. doi:10.4274/tjod.99076.
    Aflatoonian A, Karimzadeh Maybodi MA, Aflatoonian N, et al. Perinatal outcome in fresh versus frozen embryo transfer in ART cycles. International Journal of Reproductive Biomedicine. 2016;14(3):167-172.
    Wong, K. M., van Wely, M., Van der Veen, F., Repping, S., & Mastenbroek, S. (2017). Fresh versus frozen embryo transfers for assisted reproduction. The Cochrane Library.
    Mastenbroek, S., Twisk, M., van der Veen, F., & Repping, S. (2011). Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Human reproduction update17(4), 454-466.