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Fertility, IVF and Egg Donation
by Dr. Mohamad Irani on Apr.02, 2019, under Chromosomal Abnormalities in Eggs, Embryo implantation, IVF success rates, Miscarriage, Number of IVF Embryos to Transfer, Preimplantation Genetic Screening, Single Embryo Transfer
It has been an exciting time for the field of Reproductive Medicine, which has witnessed major advances over the last three decades. For instance, the recent evolution in Preimplantation Genetic Testing for aneuploidy (PGT-A, formerly called Preimplantation Genetic Screening [PGS]), has provided an important tool to enhance embryo selection and subsequently elective single embryo transfer (eSET).
Advancements of Preimplantation Genetic Testing for Aneuploidy (PGT-A)
Embryo biopsy on Day 3 has been suggested to adversely affect the implantation potential of the embryo. Hence, the majority of IVF laboratories have switched to blastocyst biopsy on Day 5 or 6. Evidence supports that the improvements in the biopsy technique, and the removal of approximately 4-5 cells from the trophectoderm (precursors to the placenta) on Day 5, when performed by expert embryologists, may not negatively impact the reproductive potential of the embryo.
Furthermore, enhancements to genetic testing, which currently analyzes all chromosomes compared to the initial platform that analyzed only a limited number of chromosomes, have significantly improved the accuracy of the test.
Clinical Benefits of PGT-A
This technology has significantly decreased miscarriage rates and increased the implantation rate per transfer. The high implantation potential of embryos determined to be euploid by PGT-A has contributed to the increased adoption of elective single embryo transfer, (eSET). This has subsequently reduced the incidence of multiple gestations, and all associated maternal and fetal complications.
Despite its critical advantages, PGT-A comes with some risks and may not be the best option for all patients; therefore, personalization of care is key to success. All patients should understand the pros and cons of each procedure in order to make informed decisions.
In my practice, I help patients understand the advanced reproductive technologies that offer them their best chance of achieving a healthy baby.
IVF patients often focus attention on the grading of their embryos at the time of transfer. We do the morphological grading on IVF embryos to assess the rate of development, the number of cells and how healthy the cells look.
However the underlying chromosomal competence or lack of chromosomal competence is far more important than the morphological grade of an embryo. Grading involves shades of gray but chromosomal competence is a black or white issue.
The beautiful looking embryo that is chromosomally abnormal is not going to make a healthy baby and an embryo that does not get a high grade but is chromosomally normal should still have a high implantation potential and be likely to result in the birth of a healthy baby after transfer to the uterus.
As far as embryos go, it’s good to be pretty but much more important to be chromosomally normal. Chromosomal competence can be determined with preimplantation genetic screening (PGS) which should be done at the blastocyst stage of embryo development with trophectoderm biopsy.
Beautiful looking blastocyst,Not as pretty looking blastocyst
The blastocyst embryos shown above look different. The embryo on the left gets a high grade and the one on the right does not. There are far less cells in this embryo and the appearance of those cells results in a lower grade.
However, if the “lower grade” embryo was tested and normal by PGS and the “high grade” one was abnormal then the lower grade embryo would be very likely to result in a healthy baby after transfer and the pretty one would have no chance.
Advancing female age results in changes in the eggs leading to more errors occurring when the egg matures at the time of ovulation. This causes an increased percentage of embryos that are chromosomally abnormal as women get older.
At age 30 the percentage of chromosomally abnormal embryos (called aneuploid) is about 30%. Beyond age 30 the rate of these abnormalities in eggs goes up significantly as shown in the table below.
|Female Age||Percent of Embryos Aneuploid|
With genetic screening of embryos we can eliminate the embryos with chromosomal abnormalities from being transferred back to the uterus. When we get the IVF chromosome screening test results back we hope to have at least one chromosomally normal embryo for transfer.
IVF with PGS success rates are significantly higher in our program than success rates for IVF without PGS for all age groups. The amount of improvement seen in success rates after preimplantation genetic testing increases with female age because of the increasing chance for unscreened embryos to be abnormal.
Avoiding transfer of embryos with chromosomal abnormalities significantly improves embryo implantation. What we are currently seeing with PGS in our center is:
- 63% for live birth if we transfer back one PGS normal embryo
- 80% for live birth if we transfer 2 normal embryos (a lot of twins)
- See our overall IVF success rates
This is independent of female age. It does not matter if we got the eggs from a 30 year old or a 42 year old. After having PGS testing (and found normal) they have the same chance for implantation – at any age.
I believe that the future of IVF will be to do PGS on almost all IVF embryos. The two issues holding us back from using PGS more are the additional costs and the 24 hour turn around for test results.
This 24 hour delay results in the need for a frozen embryo transfer being done a few weeks later instead of a fresh embryo transfer right away. Patients sometimes don’t want to wait any longer to try to get pregnant.
However, some recent studies suggest frozen embryo transfers allow a better uterine environment for embryo implantation and better success rates. Therefore, perhaps frozen transfers will be utilized more in the future even when PGS is not done.
The cost for PGS screening will go down over time as will the time needed to get results back from the genetics lab. This will result in more utilization of this powerful technology by couples having IVF.
Welcome to the
Advanced Fertility Center of Chicago
Richard Sherbahn, MD is a Board Certified Reproductive Endocrinology and Infertility specialist.
Dr. Sherbahn founded the Advanced Fertility Center of Chicago in 1997.
He will post regularly about fertility issues.
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