Improve your chances for embryo implantation

Here are the factors that affect embryo implantation:

1. oocyte (egg) quality
Implantation is more likely to occur when a healthy embryo is present, and the best predictor for a healthy embryo is a healthy egg. Egg quality comes from a number of factors.

2. sperm quality
We now know that paternally imprinted DNA is disproportionately expressed in developing placental tissue. In other words, sperm quality matters a lot when it comes to implantation. For a successful pregnancy, sperm should have stable, well balanced DNA.

What you can do:
There are many ways that sperm quality can be maximized. Antioxidant vitamins are a popular intervention.

3. Embryo quality
Embryo quality is a reflection of both egg and sperm.
If you are doing an IVF cycle, embryo quality can be determined by grading systems. The embryos most likely to continue to develop will have 6, 7, or 8 cells by day 3 of development in the lab.

If you are considering a frozen embryo transfer (FET), embryo quality is also a reflection on the laboratory’s freezing-and-thawing success rates. In general, FET cycles have a pregnancy rate of one-quarter to one-half that of fresh cycles, but the rates vary by clinic. Embryos may be frozen with the traditional slow-freeze protocols, or with the new, flash-freeze vitrification methods. There is still some debate as to which is better.

What you can do:
Maximize egg and sperm quality before you start treatments.
Consider a repeat fresh IVF cycle instead of multiple frozen cycles.

4. The number of embryos transferred
There are some suggestions that embryos help each other to implant. In other words, the more embryos that you transfer, the greater the chance that each one will stick

What you can do
Be very careful with this one. The movement in our field is away from multiple-embryo-transfer, not towards it, because the risks associated with multiple pregnancy are very real. Some clinics even advocate for elective single embryo transfer.

But if there are other impediments to implantation -say, embryo quality is a known concern- then our standard of care is to transfer multiple embryos in the hope that one will take.

5. The woman’s overall health
Tests commonly ordered as part of the overall health screen include thyroid function and prolactin levels.

Depending on your situation and family history, you may also be screened for other systemic diseases that can affect implantation. For example, we might look to rule out diabetes, autoimmune conditions such as elevated Natural Killer cells, a pre-disposition to hypercoagulability, markers for celiac disease….and many more.
If you and your immediate family are otherwise healthy, many of these tests are not routinely offered.

What you can do:
Eat well, exercise moderately, don’t smoke, and continue seeing your family doctor for annual checkups even when under active fertility care.

If you have or suspect a specific medical condition, ask your doctor if further testing is warranted.

6. Shape of the uterus and fallopian tubes
Some women have an anterverted uterus, some women have a retroverted uterus. Both are fine: the terms simply refer to which direction your uterus tips. Of more importance, we need to confirm that the uterine cavity is a normal size and shape for implantation to be successful.

To confirm the structure of your uterine cavity, the gold standard of imaging is a 3-dimensional sonohysterogram. Hysteroscopy (surgery) may also be suggested when necessary. Indications for hysteroscopy include fundal polyps, impinging or submucosal fibroids, and/or a uterine septum extends 10mm or more.

The shape of your fallopian tubes should be confirmed by ultrasound, a hysterosalpingram, or (less often) surgery. I also screen for chlamydial antibodies, as a history of this infection can affect tubes. We know that dilated tubes (”hydrosalpinges”) may compromise implantation, and we sometimes suggest that they be surgically removed before IVF.

What you can do:
Make sure that you have had all the imaging tests available to you updated before starting your treatments.
If your doctor suggests uterine surgery, a second opinion may be warranted. But don’t be too hesitant: the surgery is often a day procedure, and the benefits can be profound.

7. Lining of the uterus
We look at the uterine lining itself, to judge whether or not implantation may be expected. The endometrial lining can be assessed in the following ways:

Appearance on transvaginal ultrasound
An ideal lining will be at least 7mm thick on day of ovulation trigger (HCG).
Ideally, it will also have a “triple line” appearance (an ultrasound finding that denotes a good response to estrogen).
After ovulation, the endometrium compresses somewhat, and the triple-line pattern will be less distinct. These are normal findings.
Luteal endometrial biopsy
An endometrial biopsy is not part of every cycle, but it may be done in the luteal phase of a cycle before IVF, in an effort to confirm that the implantation window exists.

This “window” describes the idea that the lining itself is only receptive to embryo implantation for a short period of time. Various markers for this implantation window have been identified, including histologic appearance & grading, specific findings seen only by electron microscopy, and the staining for various markers that are thought to be associated with implantation.

Probably the best tests for the markers of implantation are being run by Dr Harvey Kliman, associated with Yale. He calls his set of tests the “Endometrial Function Test (EFT)”. I offer the EFT through my office in partnership with Dr Kliman.

But even the EFT is less than ideal. We simply do not know what all the markers are for implantation. This causes great frustration for patients and clinicians alike, for sometimes we suspect a small, or even absent, implantation window yet cannot prove it. In the end, the EFT alone cannot predict implantation failure or success with 100% certainty.

What you can do:

When endometrial thickness is concerning low (the lining is never more than 6mm thick), you should talk to your fertility doctor, for management is highly individualized. Many authorities recommend a BMI of >18.5; a healthy lifestyle that involves no smoking and limited caffeine; and ask that you consider red meat to be part of your diet. Supplemental estrogen is regularly used and acupuncture may also be suggested. But as I said: you should really speak with your doctor.

If you have irregular cycles and a tendency towards a thick lining (>12mm), you might benefit from an endometrial biopsy to rule out hyperplasia.

Even if the EFT is limited, the very act of getting an endometrial biopsy may help with implantion. The proper studies have not yet been done to support this statement, but many smaller ones suggest that implantation may be boosted by as much as 20% in some cases. For more, see this Globe & Mail article.

8. Embryo transfer technique during IVF
In an IVF cycle, embryo(s) selected for transfer will be collected into about 0.020cc of fluid and inserted into the womb. The process of insertion is highly physician dependent: this means that it matters who does your embryo transfer. The following issues will be considered by your doctor:

(a) Transfer medications like progesterone, antibiotics, and steroids.
(b) Cervical preparation
(c) Use of a tenaculum
(d) Catheter type
(e) Ultrasound guidance
(f) Post transfer instructions

What you can do:

Work with a doctor, and a clinic that you trust implicitly. Embryo transfer is very important. Some physicians suggest a mock transfer prior to the IVF cycle itself. It has been my experience that the uterus is lying in a slightly different position every time. In other words, the mock transfer did not help as much as I would have hoped for. I now judge the value of a mock transfer on a case-by-base basis.

9. Luteal Support
We support the luteal (post ovulatory) uterine lining with progesterone whenever we are worried about natural progesterone levels. Progesterone may be taken orally, intramuscularly, vaginally, or rectally.

Other medications that you may read about for the luteal phase, and into early pregnancy, include estrogen, ASA, dexamethasone, Fragmin, Lovenox, IVIG, HCG, and others. We are very cautious here: some of these medications have side effects that, in some circumstances, could be of real concern to you 0r your baby.

What you can do:

Talk to your doctor. The medications that you take in the luteal phase, and into pregnancy, must be compatible with bringing a healthy child into this world. That said, the ideal balance will keep your endometrial lining stable. If you find that you consistently have your period before the planned pregnancy test day, your luteal support may need to be re-examined.

10. Lifestyle
You need to minimize caffeine, quit smoking, and avoid alcohol. Intercourse during the “two week wait”? I believe it to be fine, but I would ask your doctor, as everyone has a different opinion on this subject.

Conclusions

To be successful, your clinic must focus on implantation. Many protocols and techniques are well standardized across fertility clinics, but implantation standards are not. Consequently, there remain great differences in implantation rates between clinics, and between doctors.