Frozen Embryo Transfers- Can the embryo fall out?
After the embryo “fall out” has been transferred and inserted between the uterine walls, it’s not possible for the embryo to fall out as it is deep within the uterus and therefore you can safely continue with your normal routine after having an embryo transfer.
The transfer itself is a fairly simple procedure with very little discomfort. A thin, soft catheter is threaded through the cervix under ultrasound guidance, to be very exact in the embryo placement location, generally 1 to 2 cm from the top of the uterine cavity. After cleansing the cervix with solution, the fertility doctor will place an empty transfer catheter through the cervix into position inside the uterine cavity. Then the embryologist will bring the catheter containing the embryo(s) from the lab a few feet away, so we can minimize the time that the embryos are exposed.
Once we have the embryo(s), we feed the catheter with the embryo(s) fall out through the empty catheter that is in place. On the ultrasound screen, the patient will be able to watch the bubble of air and fluid the embryo is contained in getting placed gently into the uterine cavity. After placement of the embryo(s), the embryologist checks the catheter under the microscope to make sure that the embryo(s) is transferred properly. Then the patient can get up and go straight to the bathroom if needed.
After that, the embryos “fall out” have to implant into the uterine lining on their own over the next few days, with the goal of developing into a successful pregnancy.
But Shouldn’t I Go on Bed Rest?
Several recent studies have confirmed that immediate bed rest after embryo transfer is completely unnecessary. It may seem counter-intuitive, but, in fact, a study published in a well-respected peer-review journal, Fertility, and Sterility (Fertil Steril 2013; 100: 729-35), demonstrated better pregnancy rates with the immediate resumption of normal activities (including the bathroom) compared to bed rest right after the embryo transfer.
What is a Pessary??
Pessaries. A very messy and unpleasant part of many IVF cycles. What is a progesterone pessary? It’s a sort of wax-coated hormone delivery device that can be inserted into the vagina and or anus. The wax coating melts with your body heat to release the hormone you need.
When the wax coating melts, some of it will inevitably drop out. Vaginal insertion will likely be easier, but messier. Anal insertion will likely be a bit more awkward but overall less messy. In both scenarios irritation can occur- either of the cervix or bowels, causing you to have to switch routes.
The Preggars Kitchen has a wonderful and lighthearted essay on this topic. “Pessaries are the enemy of pants!”
Alright, I know what you’re thinking. What in the world is a mosaic embryo?!
The best way to explain it is by picturing a soccer ball. An embryo is also essentially a ball of cells. A soccer ball is mostly made of white pentagons with some black pentagons here and there. Imagine that the white pentagons are the healthy cells and the black pentagons are the unhealthy or abnormal cells. A mosaic embryo is an embryo with some abnormal cells scattered throughout it.
Does this affect a chance at a successful pregnancy?
The answer is very inconclusive. Recently, the American Society for Reproductive Medicine provided guidelines for the clinical management of mosaic embryos. There have been cases observed where mosaic embryos develop into perfectly healthy fetuses and other cases where the chromosomal abnormalities result in conditions such as Down Syndrome. They also have lower implantation and clinical pregnancy rates. Their developmental potential is approximately 40%, and 40% of mosaic embryos result in pregnancy.
Keep in mind, however, that this largely depends on how many abnormal cells are present in the embryo and the percentage of chromosomes affected. If there are normal embryos available (also called euploid embryos) then those should be given first priority and transferred first as they do have the lowest risk of a miscarriage. It may be easy to avoid using a mosaic embryo if there are other embryos that look like they possess much better potential. However, in the cases where there aren’t many embryos left, or the remaining embryos do not look promising, a mosaic embryo might be what an embryologist thinks is the best chance. Then there are “cutoff mosaic embryos.” These are borderline mosaic and shouldn’t have too much of a problem resulting in successful implantation.
It is often suggested to avoid the transfer of mosaic chromosomes X, Y, 13, 18, 21 and uniparental disomy (UPD) of 7, 14 and 15 as well as, IUGR chromosome 16 because these are often viewed to be risky in the “pure aneuploid (abnormal embryo) form.” However, there is currently no published relationship between embryo pre- implantation mosaicism and detection of mosaicism during prenatal diagnosis.
Image by Andrew Apperley
How can a mosaic embryo result in a successful pregnancy?
Good question! An embryo is constantly growing and that means it’s constantly changing! Those abnormal cells might separate themselves to a part of the tissue that doesn’t really affect the chromosomal development of the embryo and hence not cause any health conditions in the fetus.
What causes a mosaic embryo in the first place?
Mosaicism has been linked to culture conditions, technician effect, and company “threshold”. Age surprisingly does not seem to influence mosaicism. Many infertility issues are often linked to age but mosaicism is not one of them. Even egg donors often provide eggs and lead to mosaic embryos up to 30% of the time.
Are the patients notified of a mosaic embryo?
Yes! There is a step in IVF called the embryo biopsy. It’s when a little sample (a clump of cells) is extracted from the embryo and sent for pre-implantation genetic testing (PGT). This test identifies any genetic abnormalities in the cells of the embryo. If there are abnormal cells identified, then the patients are informed. PGT testing can also provide other information about the embryo that might also help the patients and providers come to a decision about which embryo to transfer.
Interestingly, sometimes PGT provides so much information that it makes it a little harder to decide if the embryo should be transferred or not! What I mean by that is sometimes the samples from one embryo might not agree with each other. There is a part of the embryo called the trophectoderm which is the outer layer. There is then the inner cell mass which is quite self-explanatory: the inner part of the embryo.
Agreement of mosaicism between the two samples is only seen 55% of the time. That means that nearly half of the time, one of those two cell regions demonstrated abnormality while the other doesn’t. Additionally, some PGT labs define mosaicism using a broad range of percentages of cells affected. This range is often 20-80% of cells. If there is ever any noise in the data, this broad range might actually be counterproductive and lead to false-negative and positive results. That simply put-is not good.
Is there a “cut-off” for deeming an embryo a mosaic embryo?
When DNA is sent to a PGT lab, the DNA must be amplified. This means a large number of copies of the sample of DNA are produced. This creates a library of data. When the DNA sequences are being read, there is going to be a minimum placed on reliability of the reading. If the quality of the samples are high, then then the lowest limit of reliability is 20% variance. If the quality of the sample isn’t as high, that limit might go up to 30% variance. With the limit being so low, the process is stricter. For example, if the limit is 20%, and a sample has only 22% variance, it is a mosaic embryo. With lower limits, more embryos are considered mosaic and this process is hence stricter. This limit changes from company to company.
Wrapping it up
To sum it all up, mosaic embryos do tend to have less potential to result in successful pregnancies. Does that mean there is a zero percent chance? No, of course not! We’ve explained earlier how mosaic embryos can result in successful pregnancies. IVF is filled with ups and downs and unexpected surprises! But all in all, if you are told one of your embryos is mosaic, consult with your physician on what you think is the best route to take from there. An IVF cycle requires making many tough decisions, but always remember you are not on your own! Your fertility clinic and physician are rooting for you and will help you make the best decision possible!
Quick Facts:
- A considerable number of embryos are being classified as clinically unusable- i.e. “Abnormal.” And have previously been recommended to be discarded. The thought is shifting in the field, that mosaic embryos should be classified as a third category and deprioritized for transfer after euploid embryos.
- Mosaicism is related to culture conditions, technician effect, and company “threshold” (Ovation reports abnormal above 50%, Igenomix reports Abnormal about 75%)
- PGT provides additional information about each embryo, so that patients and providers can determine the optimal transfer order to maximize the chance of a successful pregnancy and to reduce miscarriage rates.
- Depending on the distribution of cells a biopsy can contain all euploid, all aneuploid or a mixture of cells.
- Concordance between TE and ICM has only been demonstrated 55% of the time (in a small study 232 samples, obtained from 58 embryos). 31.3% of embryos with a mosaic aberration reported in the original TE biopsy revealed a euploid profile in the ICM and all three TE samples.
- Some PGT labs use a broad range (20-80% mosaic). Noise in the data mimics low- level mosaicism, therefore using a broad range results in false negatives and positives.
- Only the highest quality DNA samples are reliable down to 20%. Ovation and Igenomix use 30% as a lower limit.
- Mosaic embryos have a reduced but residual developmental potential- up to 40%
- One study found no difference in implantation rates between trisomic, monosomic, or segmental mosaics. *complex mosaics were found to have very little implantation potential.
- Mosaicism does not appear to be age related (even egg donors display 30% mosaicism).
- A recommendation exists to avoid transfer of mosaic chromosomes X, Y, 13, 18, 21 and UPD of 7, 14 and 15 and IUGR chromosome 16, are based on these being incompatible with life in the “pure aneuploid form.” However, there is currently no published link between embryo preimplantation mosaicism and detection of mosaicism during prenatal diagnosis.
- 40% of mosaic embryos result in pregnancy. 40% of mosaic embryos have euploid ICMs and fully abnormal non-mosaic embryos had no normal ICMs.
Munné S, Blazek J, Large M, Martinez-Ortiz PA, Nisson H, Liu E, Tarozzi N, Borini A, Becker A, Zhang J, Maxwell S, Grifo J, Babariya D, Wells D, Fragouli E.
Fertil Steril. 2017 Jul;108(1):62-71.e8. doi: 10.1016/j.fertnstert.2017.05.002. Epub 2017 Jun 1.
Fragouli E, Alfarawati S, Spath K, Babariya D, Tarozzi N, Borini A, Wells D.
Hum Genet. 2017 Jul;136(7):805-819. doi: 10.1007/s00439-017-1797-4. Epub 2017 Apr 9.
Healthy Babies after Intrauterine Transfer of Mosaic Aneuploid Blastocysts.
Greco E, Minasi MG, Fiorentino F.N Engl J Med. 2015 Nov 19;373(21):2089-90. doi: 10.1056/NEJMc1500421. No abstract available.