Pineapple core & embryo implantation – theories and facts

The internet has quite a lot to say about how eating pineapple cores may help fertility by improving the chances of implantation.  We all want to feel that there is something special we can do to help us at crucial times, and rituals bring comfort. But does this one work? The theories and arguments include… that pineapple enables a shift in the immune system, that it increases blood flow to the uterus, and that it has long been used in traditional Chinese medicine to help fertility…

The immune theory – Th1 and Th2 helper cells and implantation – and what we now know about Treg cells

The theory is that pineapple core contains bromelain which is known to have an anti-inflammatory effect, and that an anti-inflammatory immune response may assist implantation. The immune system includes helper cells and 2 types of these are Th1 and Th2 cells. They each produce different proteins known as cytokines…

The shift from Th1 to Th2 dominance during implantation

• Th1 cells produce more defensive and pro-inflammatory cytokines – this is thought to be beneficial before and after ovulation

• Th2 cells produce more tolerant and anti-inflammatory cytokines – this is thought to help implantation and pregnancy

• There is a natural shift from Th1 to Th2 dominance in the second part of the menstrual cycle – progesterone levels and sexual activity both help this shift

• High Th1 levels have been linked to implantation failure and miscarriage  (though this is unsurprising as it suggests there may be underlying inflammation in the uterus which needs treating)

So does Bromelain help with Th2 dominance? Perhaps not… 12 men taking high dose Bromelain of 3,000units showed increases in both Th1 and Th2 activity.   The increases were only seen at high doses and a pineapple slice will contain considerably less than this.

Treg cells are now known to be important for implantation

The Th1 Th2 theory has been questioned in recent years and is now thought to be an oversimplification. Implantation is now known to be helped by immune regulatory cells known as Treg cells which depend on progesterone and oestrogen levels and are supported by the right levels of Vitamin D, fatty acids and probiotics The bromelain in pineapple is known to have an immune modulating effect but no studies have focused on its effect on Treg cells yet. 

The increased blood flow theory - Bromelain may help blood flow to the uterus – but reduced blood flow is needed during implantation

The theory is that by acting as a blood thinner the bromelain in the pineapple core ‘drives’ blood flow to the uterus

• Blood flow to the uterus is important during the first part of the cycle while you are growing follicles and your uterine lining.

• Blood flow is high at the time of ovulation BUT then reduces in preparation for implantation.

• Some people do need help with blood flow

  • Bromelain is thought to have blood thinning properties similar effect to aspirin, and there is evidence that anticoagulants can improve blood flow to the uterus  

  • Some people will benefit from taking blood thinners because they have clotting disorders, uterine artery impedance, antiphospholipid antibodies or an autoimmune condition like Lupus – they may need to take their anticoagulant while preparing to conceive or during their IVF cycle

• Taking something to thin the blood only at the time of implantation is unlikely to be helpful

Pineapple isn’t one of the foods stated to help fertility in Traditional Chinese Medicine (TCM)

A number of sites suggest that pineapple has a long history of use in treating infertility in TCM. Foods are regarded as having energetic or medicinal properties in TCM and some foods are considered to assist fertility but pineapple hasn’t been one of them historically. It is used in TCM to calm stomach upsets and intestinal inflammation and Western research supports this showing that Bromelain calms intestinal inflammation and spasm. TCM nutritional prescriptions are tailored to each person just as herbal prescriptions are - so pineapple may suit some people but not everyone.

should you take the pineapple before or during implantation?

Websites vary in the advice they give about timing but the usual recommendation is to eat pineapple for 5 days starting the day after ovulation, the day of IUI or the day of embryo transfer. Implantation takes place from day 7 to day 10 after fertilisation, so this means that…

• if you are trying to conceive naturally you would be taking the pineapple before implantation has started (day 1 to 5 after fertilisation)

• most IVF cycles are transferred on day 5 so you would be taking the pineapple during implantation (day 5 to 10 after fertilisation)

Summary

• there isn’t any research or traditional medicine history to support taking pineapple to assist implantation

• pineapple has a known anti-inflammatory effect and so may be useful for women with endometriosis and auto-immune disorders

• preparation is important - your pre-conception diet and supplements are more likely to influence the immune system favourably toward implantation than 5 days of pineapple

• if you are already on aspirin or clexhane check with your doctor before taking pineapple as too many blood thinners at once may affect success

• if you do decide to take it during an IVF cycle it may be more logical to start from the day after egg collection

Folic Acid & Fertility - 7 things you need to know

You’re taking your Folic Acid supplements regularly so you don’t need to worry about getting Folate from your diet.  Right?   Well… the availability of the right form of Folate may affect hormone balance, implantation, mood, miscarriage, pre-eclampsia and pre-term birth risk in some people.

Here’s what you need to know.

1.     We need Methylfolate - which is the active form our body can use

• Folic Acid is the synthetic form which is in most supplements

• Folate is the natural form found in food

• Both Folic Acid and Folate are converted to Methylfolate in the body

• Some people have less of the active enzyme needed for the conversion – this is because of a genetic variation called the MTHFR variant (scroll down for the technical bit)

• We can get Methylfolate from food

2.     Methylfolate levels may affect fertility

PCOS – A methylfolate supplement combination showed more improvement in menstrual cycle regularity, BMI reduction, testosterone and homocysteine reduction and insulin sensitivity.  The recent Italian study compared treatment with combined myo-inositol, gymnemic acid and methylfolate to treatment with myo-inositol plus folic acid in women with PCOS.

The MTHFR variant - Approximately 10% of the UK have a genetic variation called homozygous C677T which means they can’t make methylfolate so efficiently.  This has been associated with recurrent implantation failure, low mood, higher homocysteine which may affect DNA quality, higher miscarriage risk and pre-eclampsia.

• Recurrent implantation failure rates were higher in women with the variant in a Korean review study

• High homocysteine - Last year a French study found that infertile couples with the variant had higher homocysteine levels - but this reduced with 600mcg methylfolate supplements daily – the study suggests that people with the variant should be treated with methylfolate instead of high dose folic acid

  • In May the same researchers published a case history of a woman who’s homocysteine increased to 17.2 micromol/L on high dose folic acid 5mg, and decreased to 8.2 micromol/L when switched to 500mcg methylfolate.

Methylfolate may also affect mood while trying to conceive and during pregnancy - In February a study found that a prenatal supplement containing methyfolate offered some protective effect against depression in women who had a previous diagnosis of depression.

3.     Methylfolate levels may affect pregnancy and miscarriage risk

Miscarriage – 16 women with MTHFR variations and a history of 3 or more miscarriages were given high dose Methylfolate 5mg daily plus B6 50mg daily and B12 1mg weekly resulting in reduced homocysteine levels and 7 live births

Pre-term birth - Recent reviews have found an association between the C677T variant and preterm birth and low birth weight (Wu et al. 2017) (Fang et al. 2018) though not all previous studies demonstrate this.

4.     Food contains both folate and methylfolate

‘eating the rainbow’ helps methylfolate levels - rich sources include

• green leafy vegetables, spinach, kale, cabbage, broccoli, cauliflower, asparagus, lettuce, peas - vegetables are best lightly cooked or raw

• strawberries, blueberries and other berries - including frozen

• oranges, grapefruits and citrus fruits - including juices

beans and pulses are rich sources of folate but this is not in the methylfolate form unless they are sprouted

5.     Folic acid is important! - and expert opinions vary on the best form of folate

Folic acid is the most cost effective and available way of reducing birth defects. It protects against neural tube defects and supplementing is an important part of prenatal care.  For most people it is the cheapest way of providing essential folate supplementation during pre-conception and pregnancy. 

The UK government is currently consulting on fortifying bread and flour with folic acid to help prevent neural tube defects and confer other health benefits.  A 2015 study estimates that 2000 fewer neural tube defect pregnancies would have occurred since 1998 if the UK had adopted the same policy as the USA in fortifying flour with folic acid.

• Red blood cell folate was below the protective level for birth defects in 91% of women of childbearing age in a National Diet and Nutrition Survey

• Start taking extra folate before trying to conceive - 3 months is ideal

Not everyone agrees that methylfolate may be a better treatment

• Professor Anne Molloy states that maintaining good levels of folate with Folic Acid supplements helps people with the MTFHR variant and that MTHFR testing is not necessary

• A study published in May found that when infertile men with the MTHFR variant took 800mcg of folic acid for 3 months their sperm quality, DNA fragmentation and pregnancy outcome improved

6.     You need vitamins B12 B6 and B2 to help your body use folate

Taking folate as part of a prenatal that contains other B vitamins is better than taking it on its own.  The other B vitamins help you utilise folate and help keep homocysteine low

• B12 is needed to help methylfolate work

• B12 deficiency and high homocysteine have been associated with miscarriage in women with the C677T variant

• High homocysteine can be caused by deficiency in folate, B12 and B6 as well as by the MTHFR variant

• taking a supplement with at least 2.5mcg vitamin B12 daily is recommended with your folate

7.     The MTHFR variant – how to get tested

If you have a history of recurrent miscarriage or a diagnosis of unexplained infertility it may be worth getting tested, though maintaining a good intake of folate and other B vitamins through both diet and supplements is the first essential.

• Your GP can do blood tests for folate levels and homocysteine levels – if they are normal then even if you have the variant it isn’t affecting you adversely

• Saliva tests are available online to check for the MTHFR variant. Prices start at £80.

  • The test will tell you if you have any MTHFR variants – only the homozygous C677T variant has been shown to have implications for fertility, the heterozygous form is common and shouldn’t be a cause for concern.

summary - key points for helping fertility with folate

• Preparation is key – start changing your diet and taking a preconception supplement before trying to conceive

• Folic Acid as part of a prenatal will be adequate as a supplement for most women

• Eating leafy green vegetables, berries and citrus fruit daily will supply Methylfolate

• If you have had recurrent miscarriages or IVF failures consider switching to a prenatal containing L-Methylfolate

• Don’t take folic acid on it’s own - choose a preconception or prenatal multivitamin with at least 2.5mcg B12

• Men need folate for their fertility too

The technical bit

The terminology can get confusing…

• MTHF is methylfolate (L-5-methyltetrahydrofolate) also known as L-methylfolate

• MTHFR is the enzyme needed to produce methylfolate

• MTHFR variant is the genetic variation

• Homocysteine is an amino acid

how genetics affect the MTHFR enzyme

The enzyme needed to convert folic acid or folate into a usable form is called 5-MTHF reductase (MTHFR) – it allows recycling of the amino acid homocysteine to methionine.

• If MTHFR levels are low then homocysteine levels can build up and this has been linked to infertility, miscarriage, birth defects, mental health problems and heart disease

• High homocysteine causes oxidative stress and can affect DNA

Some people have a genetic variation called the MTHFR variant

• There are about 30 types of variant

• Each variant may be heterozygous or homozygous

  • Homozygous means that both of the gene pair are affected by the variant - so it’s effects are more severe

• A variant called C677T is the one that has been studied most

• Homozygous C677T is linked to lower folate and higher homocysteine levels

• Appoximately 10% of the UK population has the homozygous C677T variant and the incidence is higher in people of Mediterranean decent

Non-invasive embryo testing is becoming a reality – but we’re not there yet

Until now genetic screening of embryos for chromosomal abnormalities has required taking a few cells from the embryo.  The disadvantages of this are a small risk of damage to the embryo and the cost involved in the procedure

The new test looks at the fluid that the embryo has been growing in.  This contains traces of DNA from the embryo.

How non-invasive embryo testing is developing globally

US company PerkinElmer showcased their new niPGT-A testing kit at a scientific congress in Philadelphia this month. They’ve collected data from 15 laboratories worldwide comparing biopsy result with culture medium results and have found more than 90% correlation between the two.  Not perfect but a very good start.

In Australia Monash IVF began offering non-invasive testing in all it’s clinics in May and they report 95% concordance between biopsy and culture medium results.  The test is available for $495 (£263) per embryo.

Where is the DNA being released from?

The procedure remains controversial  – genetic consultant Dr Antonio Capalbo presenting at an ESHRE meeting in September stated that more questions need answering before the test is ready for clinical use.

A concern is that we don’t yet know exactly where the DNA in the culture medium is coming from.  It’s not certain that it’s coming from the inner cell mass of the embryo, or may come from cells surrounding the embryo. Contamination with other DNA could affect results.

In the UK a case study at IVF clinic CRGH combined both invasive and non-invasive testing on two embryos resulting in ongoing pregnancy.  The study states non-invasive testing to be an addition to diagnosis rather than a replacement for embryo biopsy.  At least until we know more.

Advantages of non-invasive embryo screening

• increased accessibility

• lower cost

• no need to wait until the embryo has hatched, so information is more easily obtained about each embryo

• it is possible that the fluid may show a more complete picture of the embryo’s genetic health than taking a few cells with biopsy – research is ongoing with this

Disadvantages of non-invasive embryo screening

• can only be used on embryos which have been fertilised by ICSI - this is to avoid picking up the sperm’s DNA instead of the embryo’s DNA

• embryos need to be cultured until day 6 - getting sufficient DNA into the culture medium takes time

• a small percentage of embryos may not release enough DNA into the culture medium