How do I improve my chances for embryo implantation?

Embryo implantation is complicated, as you can imagine! But here’s a breakdown of some of the key elements that can help you maximize your chances:

1. Oocyte (egg) quality

Implantation is more likely to happen when a healthy embryo is present, and the best predictor for a healthy embryo is a healthy egg. Egg quality is based on 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. We have more on sperm here and here.

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 of the laboratory’s freezing-and-thawing success rates. In some labs, FET cycles have a pregnancy rate of one-quarter to one-half that of fresh cycles, but the rates vary by clinic and many of us are now seeing the same (and even higher) success rates with FET. Embryos may be frozen with the traditional slow-freeze protocols, but with the flash-freeze vitrification methods we are seeing better success rates.

Here’s 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.

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.

We also find we have more success with blastocyst embryos transferred at day 5 rather than morula embryos transferred at day 3.

5. The woman’s overall health

An overall health screen tests many things, and usually includes 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.

Here’s what you can do:

Eat well, exercise moderately, don’t smoke, and continue seeing your family doctor for annual check ups 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 check the structure of your uterine cavity, the gold standard of imaging is a 3-dimensional sonohysterogram. Hysteroscopy (surgery) is used when necessary for things like 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. We also screen for chlamydial antibodies, because a history of this infection can affect tubes. We know that dilated tubes (”hydrosalpinges”) may compromise implantation, and sometimes suggest that they’re surgically removed before IVF.

Here’s what you can do:

Make sure that you have all the imaging tests available to you updated before starting your treatments. If your doctor suggests uterine surgery, you may want to get a second opinion. 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 the transvaginal ultrasound

An ideal lining will be at least 7mm thick on day of ovulation trigger (the day your HCG spikes). Ideally, it will also have a “triple line” appearance (an ultrasound finding that shows 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. Various markers for this implantation window have been identified, including histologic appearance and grading, specific findings seen only by electron microscopy, and the staining for various markers that are thought to be associated with implantation.

There are several tests which analyze endometrial biopsy further looking for markers of implantation. This is controversial, as it does not work as well as we would like, but some tests include Harvey Kliman’s Endometrial Function Test, the “E-tegreity Assay” for beta-3 integrin, and sending a biopsy specimen off for culture (this is most useful when intrauterine fluid is collecting and worries about infection persist).

We offer the EFT through our office in partnership with Dr. Kliman.

Here’s what you can do:

When endometrial thickness is 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 again: 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 implantation. 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.

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

Here’s what you can do:

Work with a doctor and clinic that you really trust. Embryo transfer is very important. Some physicians even suggest doing a mock transfer prior to the IVF cycle itself. It has been our 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 we would have hoped for. We 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 or your baby.

Here’s what you can do:

Definitely 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”? We think it’s 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. Because of this, there are great differences in implantation success rates across both clinics and doctors. We hope this article will help shed light on some of the complications and what you can do to help achieve a successful implantation.