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10 Things Embryologists Wish You Knew About IVF

As couples navigate through their fertility journey, you will meet with your physician and begin the process for IVF that includes preparation, stimulation, and monitoring.

In the background is the functioning of the IVF laboratory, where what is actually occurring can be a bit of a mystery. It is after all an almost literal black box! A windowless lab that is under strict lock and key and is often a dark, warm humid atmosphere, just like a human fallopian tube which is the site of fertilization inside the body. 

The scientist who combines the sperm and egg and helps the resulting embryos to grow in a controlled environment is called an embryologist. Access to the laboratory or embryologists in most clinics is limited. 

An embryologist is a fertility specialist that helps to create embryos to either be used in IVF right away or to be frozen for later use. Embryologists aren’t MDs, but we are highly trained medical professionals, usually holding a Masters’s degree or a Ph.D. due to the specialized nature of our work. Here are ten things we want you to know about IVF!

  1. What is a blastocyst and why is embryo grading important?

    A blastocyst describes an embryo stage reached usually after about five days of development post-fertilization. It has about 50-150 cells and has started to develop specific regions with different cellular destinies. The blastocyst is working hard; pumping fluids towards its center, creating a fluid-filled center and expanding like a water filled balloon. Embryo grading is when embryologists grade embryos based on their potential to successfully implant and result in a pregnancy. The criteria varies from clinic to clinic but the goal is always the same-transfer the best embryo! Embryologists have lots of training in grading embryos and make the best decision they can for you and your embryos. New technologies like AiVF‘s artificial intelligence system EMA are replacing the subjective human analysis of blastocysts with data-driven decision making, while bringing automation and full transparency to the process, which can make IVF efficient, accurate, and easy.
  2. Why are there so many unknowns about “IVF Add-Ons like EmbryoGlue, PGT-A, Assisted Hatching etc?

    In my opinion, this is the result of thirty years of political turmoil in the US. research on embryos and IVF has largely been driven out of the public sphere and into the private sector, entirely supported by commercial interests and individual clinics.
  3. A lot of embryos look amazing on Day 3, but do not go on to form blastocysts. Why?

    Embryonic gene activation (EGA) is the process by which an embryo begins to transcribe its newly formed genome. Sperm play an essential role in embryonic genome activation and embryonic progression to blastocyst. Embryos often “arrest” at this stage.
  4. Why did I get so many abnormal embryos by PGT?

    Aneuploidy (abnormal or incorrect chromosome number) is common in humans and is the leading cause of all human birth defects as well as miscarriage. For those new to the terminology, PGT is a genetic test that takes place before embryo transfer, designed to tell you if each embryo is chromosomally healthy. An embryo that is euploid (normal) has 23 pairs of chromosomes and has a better chance at leading to a successful live-birth than an abnormal (aneuploid) embryo. Aneuploid embryos have missing or extra chromosomes and will typically fail to implant, result in a miscarriage, or lead to the birth of a child with a chromosomal disease. ⁠Aneuploidy (abnormal or incorrect chromosome number) is common in humans and is the leading cause of all human birth defects as well as miscarriage. ⁠We can perform up to three types of preimplantation genetic testing on embryos during the IVF process. Those include:⁠ ⁠ PGT-A, which screens for an abnormal number of chromosomes.⁠ PGT–M is the test for individual, or monogenic, diseases.⁠ PGT-SR tests for abnormal chromosomal structural rearrangements, like translocation or inversion.⁠ ⁠ ⁠PGT begins with a biopsy of an embryo in the blastocyst stage of development, usually on day 5 or 6 of embryo development. The biopsy removes 3 to 10 cells from the trophectoderm, which is the outer layer of cells that will become the placenta as the embryo develops. The biopsy does not remove any cells from the inner cell mass, which develops into the fetus.⁠ ⁠ After these cells are removed, the blastocyst is frozen and stored in the lab.⁠ ⁠ The biopsied cells are sent for laboratory testing. Results are typically returned in a week to 10 days following the biopsy.⁠ ⁠ Besides the two possible PGT results we’ve already talked about– euploid and aneuploid– there are also two others: mosaic and inconclusive. A mosaic embryo consists of both euploid and aneuploid cells. While mosaicism has existed all along, PGT has only been able to recognize mosaicism in embryos within the past three years, so there is still a lot of research ongoing about their potential. What we know now is that about 10-15% of all embryos are mosaic.⁠ Embryo biopsy can also yield an “inconclusive’ or “No result”. That means that the trophectoderm biopsy sample was insufficient to be used for PGT or that it did not meet the quality control standards for analysis.⁠ ⁠ A study by Cimadomo et al. (2018) showed that inconclusive results occur about 1.5-5% of the time because the cell sample is not loaded properly and the tube is actually empty, or that the sample was degraded. ⁠ ⁠ Inconclusive or no result embryos have a good chance of being “normal”. A large study (Demko et al., 2016) found for women <35 there is about a 60% chance of a blastocyst being euploid (normal) to 30% by age 41. The chance of getting NO euploid (normal) embryos was about 10% for <35 and about 50% by 43.⁠
  5. I am disappointed that I didn’t have more eggs.

    15 is the optimal number of eggs to retrieve without putting you at risk for #OHSS. More eggs often means lower quality and higher estrogen levels, which can impair implantation in fresh IVF Cycles.
  6. IVF has a 100% success rate.

    The success rate of IVF is about 40% in couples below the age of 35. Also, the success rate of IVF depends on factors such as age, cause of #infertility, and biological and hormonal conditions. One of the reasons for this, is that although many blastocysts may LOOK morphologically normal, their behavior can differ in surprising and clinically relevant ways. For example, during development, the blastocyst pushes against the surrounding zona pellucida to expand. Some embryos do this with no trouble, while others struggle and go through a series of contractions and expansions. AiVF’s computer vision analysis of time-lapse videos of embryos has shown that blastocyst pumping events have a high negative predictive value for subsequent failed implantation. AiVF’s AI-based digital embryology management platform was able to shed light on this complex question, by showing that contractions and expansions greater than 8 microns in diameter were associated with poor implantation rates independent of other morphokinetic features.
  7. IVF is the same thing no matter which clinic you go to.

    NOPE! Not all fertility clinics are created equal, so it’s important to do your research to help you make an informed decision. In addition to looking for a clinic with high-qualified #fertilitydoctors, it’s critical to choose a clinic with a superior IVF lab. You can check out a clinic’s success rates at Society of Assisted Reproductive Technology or the Centers for Disease Control and Prevention website.
  8. Infertility is a female problem.

    Most of the practical and emotional infertility support out there is aimed at women. Maybe because we are the ones being stimmed and undergoing the surgeries. But we need to get the men more involved! It’s a common misconception that women are most affected by infertility. In some cultures “male infertility” is literally unheard of, like culturally it does not exist. In fact, men and women are equally affected. In heterosexual couples, 1/3 of infertility cases are attributed to men, 1/3 to women, and 1/3 are unknown. With regard to our healthcare, often we will be the first to approach an infertility doctor, who will then prescribe a standard work up of invasive tests that have become the norm for women who experience problems conceiving: that includes multiple appointments, multiple hormone tests, internal, transvaginal scans to check your womb for fibroids, and an HSG test, where dye is pushed into your fallopian tubes to see if they were blocked. Only then, does the male partner typically obtain a semen analysis. Sometimes, men may need to modify their lifestyle habits quite a bit, but this is often brought up late, if at all. Some providers argue that assessing lifestyle factors and history, or for physical problems like varicocele, is even more important than the traditional semen analysis. Raising awareness male infertility will help us to get more funding, resources, research, and even donations made by male donors.
  9. IVF is only used for individuals/couples struggling with #infertility.

    Families with a history of genetic disorders can do IVF with pre-implantation genetic testing to screen their embryos for single gene disorders and to prevent the genetic condition from being passed onto their children. Even fertile couples use IVF to have more control over their family building, such as being able to chose the order of the sex of their children or for optimal timing for their lives and careers. Also, IVF is used by moms and dads who are single by choice and for LGBTQ couples to build their families.
  10. Eggs, Sperm and Embryo Myths!

    We cannot tell “female” (X- bearing) sperm from male (Y-bearing) sperm. There is a persistent myth that X or Y bearing sperm look different from each other or swim at different rates. These myths are not based on good, solid science! Every egg, sperm and the resulting combination of the two are different. That makes every attempt at IVF using different gametes a different experience. From the embryologist’s point of view, each egg looks different, but we can’t see the DNA with a microscope to select the “good” eggs. Embryologists will care and nurture your gametes, but cannot repair or make an embryo better by culturing it in the laboratory. Some embryos don’t freeze well or survive the thaw, and are just indicators that there is probably something flawed about them or something we don’t yet understand scientifically speaking. Additionally, each embryo is as different as any child resulting from that embryo would be, but we can’t treat each embryo differently. Adhering strictly to IVF lab culture protocols is what elevated assistant reproductive technologies from being an art into being a reproducible science.
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