The implantation of an embryo in the uterus is a crucial early step in establishing a successful pregnancy.
Here we are talking about the first few steps of life ………
This is a hatching blastocyst, ready to find its implantation site and begin life in its new home for the next 9 months.
You can see how busy this little embryo has been just getting this far by clicking here!
There are some things we know about implantation and much we don’t know – most of the information we do have comes from research done with IVF patients. But of course what applies to implantation of an embryo in an IVF cycle also applies to natural conception.
Some IVF specialists refer to the inside of the uterus as “The hidden frontier”, since once that embryo is transferred to the uterus, all they can do is cross their fingers and hope something happens. But actually there is more we can do ………
Our discussion today could also be called “Where to next for the IVF patient who is NOT getting pregnant”? This frustrating situation might be occurring for the IVF patient who, despite creating good looking embryos like the little guy above, fails to establish a viable pregnancy after they are transferred to the womb.
Women in this situation start to think that there is something wrong with them, something wrong with their body or mind that they won’t accept an embryo. Or something wrong with the inside of their uterus and its lining.
We have heard for a long time from reproductive specialists that implantation is ALL about the embryo (“embryo driven” they say) and further …… ALL about the quality of the egg and its aging (in women over 37) chromosomes. This theory suggested that if you had an embryo that was genetically normal, all would be hunky dory.
But now we know that’s not the case. You might be surprised to hear that in most IVF clinics only about half of the “genetically normal” embryos (determined by pre-implantation genetic diagnosis/screening, PGD or PGS) actually implant and become a viable pregnancy.
So what is going on with the large number of genetically normal embryos which DON’T implant? Can we still blame lack of implantation on the poor embryo? Or the poor eggs?
Perhaps in some cases we can – the eggs might not impart enough “energy” to the embryo to keep it dividing and implanting successfully. There’s certainly things we can do to help that situation – but THAT is another story (stay posted). ☺
But in many cases, the failure might be at the implantation stage, and relate to the all important relationship between the uterine lining and the embryo. So lets look at all the things we know can make a uterine lining (also called the endometrium) more receptive and how we might be able to influence these.
This might be the key to helping all those genetically normal embryos who fail to get a foothold and become a viable pregnancy.……….
The structure of the lining – the tri-laminar appearance
The lining of the womb must be adequately prepared for pregnancy (decidualised) before it can recognise and accept an embryo. On an ultrasound, a more receptive lining has a tri-laminar appearance. The action of oestrogen in the follicular phase leading up to ovulation, stimulates the lining to develop until it shows this 3 layer appearance (ultrasound from Dr Sher, SIRM), which has been associated with better implantation rates in frozen embryo cycles.
How can you encourage your lining to look like this? – see below.
There must not be any structural impediments to implantation, such as uterine abnormalities, polyps, fibroids, retained products from an earlier miscarriage or adenomyosis. For the latter, there is much can be done with Chinese medicine (sorry that’s another story for later, too……) but for the other factors, surgery may be required. Best to get the expert opinion of a reproductive specialist.
The inside lining should look smooth like this (ultrasound from Prof Gadir) …….
Good blood supply to the deeper layers of the endometrium
Blood flow to the uterus, and particularly the endometrial and sub-endometrial regions of the uterus, appears to be advantageous for implantation.
How can this be influenced? See below.
A calm and chilled out uterus
Frequency of uterine contractions increase around the time of ovulation (maybe to help sperm move up into the tubes), and usually calm down by about the time of implantation (under the influence of progesterone) some 5 – 6 days later. However its not unusual for women having an embryo transfer in an IVF cycle, to experience some cramping, which might not be conducive to implantation. The more contractions after embryo transfer the lower the rate of successful implantation. As you can see from this graph (Hum Reprod, vol.13 no.7 pp.1968) when there are more than 5 contractions per min the implantation rate drops to around 10% compared to lower rates of contractions where the implantation rate is 50%.
There are some things we can do to help that situation too, but that’s another story too (stay posted).
Thick and juicy lining.
Studies have shown that the lining needs to be 6 or more millimetres for successful implantation. This requires not only correct tissue structure and the right receptors and likely many other factors we don’t know about yet, but also the right balance of hormones (see “regulating the cycle” below)
Optimal hormone levels
As you’ve seen above, we need good levels of estrogen to prime and stimulate the growth of a receptive lining. We need good levels of progesterone to maintain it and to ease the contractility of the uterus during the implantation window. In some IVF cycles, the levels of these hormones are not ideal and are certainly nothing like the sorts of levels the body experiences in a normal menstrual cycle. This is why some IVF clinics prefer to transfer (defrosted frozen) embryos in a natural cycle into a natural environment.
For women who are trying to conceive naturally, making sure that the ovaries are functioning well will usually ensure that levels of estrogen and progesterone are optimal for creating the uterine lining conditions that promote implantation (see “regulating the cycle” below).
A friendly immune environment
The immune system plays a crucial role in whether an embryo will successfully implant or not. Autoimmune disease, or subtle imbalances in the immune regulation of the uterine environment can have a large impact on an embryo’s attempts to implant. For example elevated uterine levels of certain immune cells called natural killer (NK) cells have been shown to impede successful implantation or establishment of pregnancy, as have activated T lymphocytes. On the other hand the actions of some T cells and NK cells are necessary to promote a favourable environment for implantation. Its getting the balance right ……. This is a complex and fascinating topic much of which, you guessed it, is another story for another day (and see below).
A fresh food diet
You may have heard about how important the diet of the mother is to the development of the embryo, and then the growing fetus in the early days of pregnancy (the Barker hypothesis). Maternal diet at this time can have a big influence on the risk of development of chronic diseases later in the baby’s adult life. Diet can change the pre-implantation environment of the uterus and hence affect the newly arrived embryo – specifically diet has been shown to change the amino acid balance. We know that amino acids play a number of physiological roles in pre-implantation development – they can be an energy source for the blastocyst, or building blocks for new proteins or DNA, or act as antioxidants or cell signalling messengers. In the IVF incubators, amino acids are important components of the medium embryos grow in.
Women who have diets that are based primarily on fresh vegetables and fruit with some fish, have what may be a more favourable amino acid profile in the uterus than women who eat a lot of red meat and dairy. The uterine amino acid profiles of the women who eat more fresh foods and less red meat show a low amino acid environment – and it is thought that this may selectively support the development and implantation of high quality embryos (sometimes called metabolically “quiet” embryos).
And now you need to think about all the tools you have at your disposal to really help make a quality uterine lining that is conducive to embryo implantation.
6 steps you can take now to help create an ideal lining …….
Regulate your menstrual cycle
In traditional TCM texts (dating back many hundreds of years) applying treatment to improve ovary function was called “regulating the cycle”.
Chinese medicine doctors knew way back in the Qing Dynasty, that if their treatments encouraged a regular and problem free menstrual cycle, then fertility would be improved. We know now that this means that the ovaries are producing the right balance of estrogen and progesterone, which helps the uterine lining to develop well and the uterine environment to be ideal for implantation.
(Improving ovary function also has the added benefit of improving pre-menstrual and menstrual symptoms).
Check for any structural impediments inside the uterus.
If necessary ask your reproductive specialist to arrange for the removal of polyps or fibroids affecting the lining or other internal structural impediments.
In the case of adenomyosis (a form of endometriosis in the uterus wall that can affect implantation), a programme of chinese herbs and acupuncture is useful. It may take several months to improve the uterine lining quality, but it is often very effective, if you persist with treatment.
Improve blood flow to the uterus.
Electro-acupuncture has been shown to improve blood flow to the uterus. It has also been shown to significantly improve the appearance of the lining (remember that trilaminar appearance?) and the rate of embryo implantation, and pregnancy.
Fine needles are gently inserted into acupuncture points on the abdomen and legs, or TENS pads are placed on these points, and a mild current is passed through them so a pulse can be felt.
Regulate your immune system
This may seem easier to say than to do, but there are useful things you can do with lifestyle and acupuncture. Research has shown that ratios of certain immune cells that are conducive to implantation can be favourably influenced by acupuncture and some herbal formulas.
We know that stress can affect the immune system, elevating levels of activated T cells in the uterine lining, which can reduce implantation rates of embryos. We also know that high resting levels of cortisol are linked with elevated markers of inflammatory processes in the body which may adversely affect implantation of the embryo.
Fortunately acupuncture has been shown to exert a beneficial modulatory effect on immune imbalances caused by anxiety and stress. In one study the maximum effect on the immune system of women suffering heightened anxiety was measured 72 hours after they received acupuncture and the effects of a course of acupuncture were still evident a month after it was completed. Read more here …..
Improve your diet
You’ve heard it all before, I’m sure…..but did you realise that what you eat actually directly influences the environment of the uterine lining and implantation, and this can be measured? You should emphasise fresh vegetables and fruits, with good quality protein especially from vegetable and fish sources, rather than too much meat. This is the proven best diet for fertility (from the Harvard nurses study) and for providing a beneficial amino acid balance in the uterus.
Take Chinese herbs
Talk to your Chinese medicine doctor about herbs which can help improve the integrity of the lining, and increase implantation rates.
There is a simple and time tested Chinese medicine remedy called Zi Shen Yu Tai Pill which appears to help implantation of embryos in an IVF cycle.
This formula, which has been used for hundreds of years in China for recurrent miscarriage has recently been shown to improve uterine receptivity by up-regulation of certain adhesion molecules and other key factors. We often use this sort of formula with women who are having embryo transfers, either fresh or frozen.