recurrent miscarriage Archives - Fertility Fact Checker

Your anti-müllerian hormone (AMH) is checked, you can tell to the hour when you are ovulating and you are pretty sure you’re the only one of your friends who uses acronyms such BFP, DPO and CD* in their every day life. You are just about ready to go for your next IVF cycle.

But here are 5 tests that may significantly impact on your fertility and IVF success.

As always though, don’t just start supplementing and self treating these things without medical advice as if your levels are already spot and you start self-prescribing, supplementation could do more harm than good. But they are definitely worth chatting to your fertility specialist about if you are concerned or have had recurrent failures.

Vitamin D

Like everything in fertility the research is mixed, but low levels of Vitamin D has been associated with endometriosis, the development of insulin resistance in women with PCOS and uterine fibroids¹. When the vitamin D in follicular fluid (the fluid surrounding each of your eggs) was measured in a group of women doing IVF, it was found that when women were deficient in vitamin D, for every one unit increase in vitamin D there was a 6% increase in the chances of an ongoing pregnancy rate². I’d take that.

Speak to your fertility specialist to see what your levels are (when you are pregnant they will test you for it anyway) and in the meantime focus on absorbing vitamin D from the sun – in a completely sunsmart way of course.

Thyroid function

That pesky thyroid has a big role to play and if it isn’t working properly can impact pretty much everything you can think of to do with reproducing life. This includes impaired ovulation, fertilization, implantation, miscarriage, and late pregnancy complications³. The acceptable levels of thyroid hormones can vary and there is some debate whether or not things like thyroid autoimmunity even matters enough to need to be tested³; though a recent meta-analysis suggests that although it does not impact number of eggs retrieved, fertilisation, implantation or clinical pregnancy rate thyroid autoimmunity may be implicated in miscarriage rates (this is still overwhelmingly unlikely to happen though and certainly not something to add to your worries – I have high thyroid antibodies and still got a take home baby. Two, infact.)⁴. What it does highlight though is that completing thyroid testing is a worthwhile activity, especially because depending on your medical history thyroid problems can often be treated.

Immunology issues

The role of autoimmunity in fertility is becoming more accepted and many doctors may test for immunology issues as standard when you start treatment. Some autoimmune tests include anti-nuclear antibodies, anti-DNA/ histone antibodies, antiphospholipid antibodies, antisperm antibodies, natural killer assay and cardiolipin antibodies. That is a lot of antibodies and only the tip of the iceberg.

Not all these markers are always a direct reason for infertility and some women can have them and oops! just happen to fall pregnant accidentally. They all are implicated in infertility though and it is certainly worth another blood test or two to ensure that they aren’t a hiding passenger on your fertility journey. Again, if something is found, depending on your circumstances, your fertility specialist may have a suitable treatment.

Melatonin

Melatonin is a powerful antioxidant and may benefit fertility by helping to keep oxidative stress in ovaries and eggs to a minimum which in turn improves egg quality. Several studies have been conducted investigating melatonin as a supplement for women undergoing IVF and found that when the optimal level of melatonin was reached that it was associated with a higher number and quality of mature eggs at harvest⁵. It has also been found to support the production of progesterone in women with luteal phase defect (though don’t even think about stopping those progesterone suppositories if you doctor has prescribed them; although a significant difference was found the impact on actual progesterone levels was still relatively small)⁵.

As always, do not go self-medicating, as although melatonin has not been found to be poisonous, supplementation is not always recommended in women undergoing IVF for a number of reasons. Supplements can sometimes interact with the prescribed medications taken and in women with autoimmune conditions melatonin supplements can have immune-stimulatory capabilities. Speak to your doctor before starting any supplements and in the meantime try to balance your melatonin levels by ensuring you get adequate sleep and natural daylight.

Sperm fragmentation

This isn’t a blood test but rather a sperm test for the men. Ideally it should be done as part of your initial work up at your clinic but it can easily get overlooked – particularly if you and your partner already have an obvious reason for your difficulty with fertility. In fact one study suggests that for couples with unexplained infertility, 80% of these couples later had their reason ‘explained’ as being due to sperm defragmentation when the appropriate tests were done⁶. That does seem a little amazing…

After a sperm sample is provided, in a sperm fragmentation test, the sperm is looked at to see if the DNA is healthy and intact. If DNA fragmentation is high this means that a high percentage of sperm is damaged. The treatment options are limited, though Menevit supplements may be of assistance (your doctor may have recommended this anyway), and it may mean that ICSI will have a greater chance of success for you than standard IVF.

Please note that this list is not exhaustive. They are just a few points designed to open up the conversation with your fertility specialist. Iron, zinc and magnesium levels are just a few others you might want to discuss.

*If you’re not quite there with the acronym thing BFP means big fat positive, DPO is days post ovulation and CD is cycle day.

Vanni, V., Vigano, P., Somigliana, E. , Papaleo, E., Paffoni, A., Pagliardini, L. & Candiani, M. 2014 Vitamin D and assisted reproduction technologies: current concepts. Reproductive Biological Endocrinology. 2014; 12: 47. Published online 2014 May 31. doi: 1186/1477-7827-12-47
Ozkan, S., Jindal, S., Greenseid, K., Shu, J., Zeitlian, G., Hickmon, C. & Pal, L. (2010) Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertility and Sterility. Vol 94 (4) 1314–1319.
Unuane, D., Velkeniers, B., Deridder, S., Branvenboer, B., Tournaye, H. and De Brucker, M. (2016) Impact of thyroid autoimmunity on cumulative delivery rates in in vitro fertilization/intracytoplasmic sperm injection patients. Fertility and Sterility. 106 (1) 144 – 150.
Busnelli, A., Paffoni, A., Fedele, L. &, Somigliana, E.(2016). The impact of thyroid autoimmunity on IVF/ICSI outcome: a systematic review and meta-analysis. Human Reproduction Update. 22(6) 775-790.
Fernando, S. & Rombauts, L. (2014) Melatonin: shedding light on infertility? – a review of the recent literature. Journal of Ovarian Research 7 98
Lewis, S. (2013) The place of sperm DNA fragmentation testing in current day fertility management. Middle East Fertility Society Journal. 18 (2) 78 -82

Tin hat thinking is when you do something which you can see might be worth a try even though the hard scientific backing isn’t necessarily there. Things that can’t hurt to try and there seems to be loads of qualitative evidence on the internet though the quantitative evidence seems a bit lacking. You know the general sort of things – eating organic, not wearing perfume or cosmetics and perhaps eliminating dairy. They might be things that your naturopath prescribes, but what your fertility specialist doctor might say makes no difference. I realize this sounds quite dismissive to naturopaths and it is really not meant to. The more and more I research into fertility treatments the more and more I can see that sometimes some of the answers are in the way we live our lives rather than being solely dependent on how many units of Gonal F we are injecting into our stomach.

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For me, eating a gluten free diet was one of those tin hat thinking moments. After several failed cycles I felt the need to attempt to take some control back and try something different. So amongst a couple of other things I tried eating gluten free diet starting from cycle day one. I did happen to get a BFP on the cycle I went gluten free, though I was also on some additional medication which also would have made an impact. Saying that though, I also know of others who have also experienced a BFP when eating gluten free (and there is that qualitative evidence again). But was it just coincidence and would it have been ‘our time’ regardless? Who knows. For a significant number of people though, particularly those with unexplained infertility, eating a gluten free diet may be much more than tin hat thinking and might just well be the real underlying cause of their infertility.

Celiac Disease

Celiac disease occurs in up to 1% of the population, but only 20- 50% of those may experience symptoms. As you are probably aware, traditionally people who have celiac disease are required to eat a gluten free diet. This is because celiac disease is an autoimmune condition which is triggered by gluten which is the protein fraction of wheat, barley and rye. There is a bit of a complex biochemistry reaction but essentially the gluten causes a number of chain reactions which results in an inflammatory response in the body and the production of some specific antibodies. It is perhaps the presence of these antibodies that may contribute to difficulty conceiving, recurrent miscarriages and once you are finally pregnant with one that sticks, intrauterine growth restriction, which can result in your baby being born with a significantly lower birth weight and other difficulties.

The evidence for associating gluten with infertility

There has been a bit of research around celiac disease and just last year a meta-analyisis was completed investigating the association between celiac disease and issues of the reproductive system in women (Tersigni, 2014). The meta-analysis included 24 studies that had been completed on this area and here are what I consider the five essential things to know:

1. Women with unexplained infertility or recurrent miscarriage have a 5 or 6 fold, respectively, increased risk of being affected from celiac disease compared with the general population.

2. Classic celiac symptoms are often absent, or at most the symptom may be the very general fatigue associated with iron deficiency anaemia. This means that it can be a significant length of time before diagnosis, and hence treatment is initiated.

3. Before and after studies have been done on women with celiac disease and the number of children they were able to have before and after diagnosis. Before diagnosis women with celiac disease were found to have less numbers of children than women without celiac disease. After diagnosis and treatment this number returned to similar numbers. This indicates that treatment of celiac disease and eating a gluten free diet is beneficial to aiding fertility in women with celiac disease and seemingly reverses the destructive mechanisms.

4. There are two suggested mechanisms by which celiac disease limits fertility: firstly causing malabsorption and nutrient deficiency and secondly, the accompanying automimmune reactions.

It is believed by preventing the absorption of nutrients an imbalance in the reproductive hormones such as luteinising hormone and follicle stimulating hormone is experienced. This in turn prevents normal ovarian functioning and hence causes infertility. Deficiency of nutrients such as folic acid also ultimately leads destruction of the rapidly growing embryo as it needs this acid to develop neurons and develop normally.

The second mechanism being autoimmune factors effects fertility in two ways. One possible way is that the antibodies produced by women with celiac disease destroy the outer layer of the blastocyst. This prevents the embryo from implantation and forming the placenta as it is this outer layer of the blastocyst that gives rise to the developing placenta. Another possible way is that the antibodies prevent the endometrium from growing new blood vessels, again preventing implantation resulting in a BFN once again.

5. Women with celiac disease also show an increased risk of miscarriage, intra-uterine growth restriction, low birth weight and preterm delivery. This indicates that the implications for having celiac disease go far beyond difficulties at conception and that a long term gluten free is essential in women with celiac disease who achieve preganancy.

Take action!

Especially if you have ‘unexplained’ infertility or recurrent miscarriage, at your next appointment ask your doctor if you have been screened for a sensitivity to gluten. The symptoms are not always the typical responses and can easily be missed. One of the first screens to do is to test for endomysial and anti-TG antibodies (Tersigni, 2014)

Check out the possibility of eating a gluten free diet. Although on the one hand it has never been easier to knowingly eat gluten free – there is pretty much a gluten free substitute for EVERYTHING these days, on the other hand it is nearly impossible to cut out all the hidden gluten – it sometimes seems gluten is everywhere… there is wheat syrup and hence gluten in that Cadbury’s chocolate bar you have just eaten!

If you are just starting out to eat gluten free the big things to avoid are foods containing wheat. That includes pretty much all cereals, baked goods, bread, cakes, pastry, noodles and pasta. Vegetables, fruit and meat are fine as is rice and some other non-wheat grains. Like I said though, the ‘hidden’ gluten is in a lot of things including salad dressings, soups and beer. If you are serious about going gluten free it is therefore essential to check the back of the pack before eating.

As for me, although I did decide to stop eating gluten I have not yet been tested for the specific antibodies that often present with a gluten sensitivity. I will request these at my next appointment but in the mean time I found it ‘worthwhile’ eating gluten free if for no other reason than knowing that I had given things my ‘best shot’. Anyway, as previously discussed, for a significant number of women with infertility the idea of eating a gluten free diet is perhaps based in science and not so ‘tin hat’ as what I first thought.

Reference

Tersigni, C., Castellani, R., deWaure, C., Fattorossi, A., De Spirito, M., Gasbarrini, A., Scambia, G. & Di Simone, N. (2014) Celiac disease and reproductive disorders: meta-analysis of epidemiologic associations and potential pathogenic mechanisms. Human Reproduction Update. 20 (4) 582–593

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