What is it and why does my IVF Clinic do it

Assisted Hatching: What is it and why does my IVF Clinic do it?

Assisted hatching is a laboratory procedure that is sometimes performed along with in vitro fertilization (IVF) treatment. ⁠Assisted hatching is where an opening is created in the zona pellucida of an embryo. This is the outer coating (shell) of proteins. The embryo naturally breaks out of this shell as it grows. By doing this, it assists the embryo in hatching and attaching to the wall of the uterus for implantation.⁠

The hope is that assisted hatching might give the embryo extra room to expand, less stress escaping the zona to implant in the uterine wall, and finally lead to a pregnancy.⁠ Studies suggest that assisted hatching might help improve pregnancy chances for certain groups of patients. Assisted hatching may help improve pregnancy chances in women who have failed to get pregnant in previous IVF cycles and those with a poor prognosis (who are not likely to conceive).

During assisted hatching, the outer shell of the embryo is artificially weakened by making a small hole in the zona pellucida.⁠

Assisted Hatching: What is it and why does my IVF Clinic do it?

It may help improve pregnancy chances in women who have failed to get pregnant in previous IVF cycles and those with a poor prognosis (who are not likely to conceive).⁠

Reasons to Perform Assisted Hatching

If you had PGT performed on your embryos, then they were hatched before being biopsied. However, they may be hatched again with the laser after the embryo is thawed. ⁠We typically only freeze embryos that we think are destined for success-no matter what their grade is. The grade is simply a snapshot in time, and can change after biopsy/freezing and thawing. A top quality embryo can thaw terribly and vice versa. There is some evidence that assisted hatching helps embryos implant.

Potential Risks

Some people think that IVF in general may increase the risk of having a twin pregnancy. Influencing factors include the oocyte age being < 35 years old, prolonging the embryo culture, micromanipulation of the zona pellucida after procedures such as intracytoplasmic sperm injection (ICSI) or assisted hatching (AH), and after fresh embryo transfer. (Tarlatzis 2002; Jian 2004; Knopman 2014; Kanter 2015).

Infertility Research
Image by Sarah Pflug

Infertility research priorities have been proposed for 2021. Healthcare professionals, people with fertility problems and infertility researchers (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process resulting in an article that was published in Human Reproduction in November 2020 outlining the top future infertility-related research priorities. The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions.

The top 10 infertility research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified. These top ten research priorities in each topic area outline the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, to assist research funding organizations and researchers to develop their future research agenda.

Blog Series: Top Ten IVF Research Priorities

The first of the top ten infertility research priorities for medically assisted reproduction is “What are the causes of implantation failure?” In this post we will dissect the various hypotheses, tests, treatments and potential avenues of research. 

The placental paradox

The riskiest moment in any human pregnancy is when the fertilized egg attaches to the uterine wall and tries to establish a link between embryo and mother. About half of IVF pregnancies fail during this implantation stage, and we all know how many natural pregnancies end at that time as well.

At some stage in the evolution of animals, we went from mammals that lay eggs, like the monotreme family (the platypus and echidna are the living members of), to marsupials or pouch gestating mammals like kangaroos, koalas and possums, to placental mammals like us. But even among placental mammals NOT all placentas are the same.

For example, in cows there are specific spots of attachment between the fetus and the mother called cotyledons, and this is so different than in humans where we have a total attachment between the placenta and the uterus. That is why you do NOT see cows bleeding out form a uterine rupture or suffering from, for example gestational diabetes or high blood pressure. Their blood supply is just not that connected to the developing fetus. We really see that our complex placenta developed evolutionarily to protect the embryo from our own immune system.

There is a kind of paradox that perplexes researchers of infertility, a mother’s inflammatory reaction to the embryo is the biggest threat to pregnancy, it also seems necessary for the pregnancy to be successful.

Implantation Failure 

Implantation failure or RIF is an imprecisely defined clinical disorder characterized by failure to achieve pregnancy after repeated embryo transfers with genetically normal embryos. multicomponent, bidirectional signaling between the embryo and endometrium. A healthy uterus, free from endometriosis, polyps, fibroids, and with a thick lining is one piece of the puzzle, a euploid, or chromosomally normal embryo is another piece, less than 60% of euploid embryos result in pregnancy.

There are 4 main culprits or areas of active infertility research investigations. The 4 are; progesterone resistance, shifted window of receptivity, decreased integrin expression, and immune system disturbances.

Infertility researchers are identifying all of the biological components involved, developing tests to definitively say if that process is in a disease or abnormal state, and then drug treatments that work!

Progesterone resistance and infertility research

Estrogen stimulates endometrial proliferation, estrogen also causes an increase in progesterone receptor expression, enabling the establishment of the “window of receptivity”. Progestogen is directly responsible for the timing – the opening and closing of the window of receptivity. Endometriosis can actually cause progesterone resistance, disrupting the establishment, and opening or closing of the window.

There is a gene called BCL6 and its expression in the endometrium has been correlated in patients with unexplained or endometriosis-associated infertility. There is a test to see what the activity of this gene is called the Receptiva DX test.

Shifted window of receptivity 

The window of receptivity itself has a molecular signature – meaning certain genes are expressing certain proteins- and this can be determined with a test called the ERA test. Implantation itself is actually a tightly controlled inflammatory response that coordinates the embryo “invasion”.

The embryo is essentially a foreign invader. It is half NOT your own DNA but the partner or sperm source. So the uterine lining and muscular wall must allow invasion by this foreign entity, without alerting your immune system to attack, and establish a vascular blood supply that can support pregnancy.

Decreased integrin expression and infertility research

Integrins are cell to cell adhesion molecules. They are the principal receptors on animal cells for binding most extracellular matrix proteins. They are basically a little ladder that crosses the membranes of both cells, in this case the embryo’s and the uterine endometrium.

Endometrial integrins are key molecules that promote embryo attachment. Right now, we have one good drug candidate to increase integrin expression, called letrozole. Letrozole is known as an “aromatase” inhibitor there is another very common mild aromatase inhibitor – Aspirin! Aromatase, is also called estrogen synthetase or estrogen synthase, because it is an enzyme responsible for a key step in the biosynthesis of estrogens.

There are so many features of embryo implantation that are consistent with the hallmarks of cancer and tumor invasion. In fact, it is often noted that “all the tricks cancer knows, were learned from the embryo”. The tricks here being invading tissue, establishing a blood supply for uncontrolled cell growth, and evading detection by the immune system. There are dozens of drug molecules from the cancer treatment world that can inhibit aromatase.  

The immune system and infertility research

Two immune system components cytokines (which are generally associated with inflammation) and uterine natural killer cells have important roles in successful implantation.

Excessive and altered inflammatory signaling has long been suspected in implantation failure and recurrent pregnancy loss. Natural killer (NK) cells are members of a rapidly expanding family of innate lymphoid cells (ILCs). During pregnancy, NK cells are the most abundant lymphocytes in the uterus at the maternal-fetal interface and are involved in placental vascular remodeling. So discovering the complete set of cells and all their functions is still necessary.

We had one good drug molecule called glucocorticoids to investigate – they are a type of corticosteroid hormone that is very effective at reducing inflammation and suppressing the immune system. Glucocorticoids were selected to study, based on the biologic plausibility of restoring a normal immunologic response in the endometrium to promote healthy embryo implantation- however many gold standard clinical trials and meta-analysis of the data have failed to show improvement. For this reason, ASRM guidelines currently recommend against the routine use of glucocorticoids to improve implantation rates. 

But there are dozens of other suspected immune pathways and drug molecules to explore.

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. 

mosaic-embryos

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: 

Detailed investigation into the cytogenetic constitution and pregnancy outcome of replacing mosaic blastocysts detected with the use of high-resolution next-generation sequencing.

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.

Analysis of implantation and ongoing pregnancy rates following the transfer of mosaic diploid-aneuploid blastocysts.

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.

What are the Warning Signs of Low Quality IVF Clinics?

IVF Clinic

IVF clinic quality is so important. How can you spot red flags? How do you choose a fertility clinic? What questions can a lay person ask to begin to understand the quality of an IVF Lab? Quality goes beyond pregnancy success rates to new technologies, inspections and accreditations, staff experience and more!

In the industry, we alway say, START with SART! The federal government requires fertility clinics to report IVF treatment cycle success rates, and you can find those statistics on the SART website. It also has a tool that allows prospective patients to search for fertility clinics by ZIP code, state or region; plus, women can plug in information such as their age, height, weight, and how many prior births they’ve had to predict their chances of success with assisted reproductive technology. 

Most IVF programs are proud of their results and may list them on their website, however, whatever they are advertising should match the number of cycles and the outcomes reported to SART or found in the CDC Assisted Reproductive Technology Fertility Clinic Success Rates Report. 

Verified IVF Lab Accreditation

One way to determine IVF clinic quality is to look for verified lab accreditation on the CDC report or in the actual facility itself, it will usually be posted in plain site. Find out who the inspecting agency is, the College of American Pathologists? The Joint Commission? 

Another possible thing to note is to look at what percentage of their patients are in your age range, or have the same infertility diagnosis as you do. 

Consider how the clinic’s staff talk to you, what they say – how professional does the care feel? Use all of your senses. Is the care personalized and professional enough so you feel comfortable?” An example of dehumanizing behavior: some clinics have an application process to decide if you should be treated there. 

Failed to call in prescriptions to pharmacy

Lost paperwork

Lost appointments

Failed to call with results

Failed to order appropriate test

Look on Indeed, Glassdoor, or other job sites to get an idea of staff turn over and what staff have to say. The embryologist’s perspective is important! Find out how experienced the providers are, how well-trained they are and how long have they been there? As with other fields of medicine, experience matters in reproductive medicine. Providers should be fellowship-trained and board-certified in the field, both of which are the standard. Also inquire how long the medical providers have been at the facility. If there seems to be high staff turnover, there could be leadership and organizational issues at the clinic.

Does your clinic offer the latest treatments?

IVF clinic quality can be influenced by the techniques used. Look for clinics that can offer the latest treatments and protocols. These might include blastocyst transfer, freeze all cycles, mini or low STIM IVF, preimplantation genetic screening of blastocyst stage embryos and single embryo transfer, ERA or endometrial receptivity assay testing. 

The introduction of intracytoplasmic sperm injection (ICSI) resulted in a choice of fertilization methods between conventional in vitro fertilization by insemination (IVF) and fertilization by ICSI. Fertilization by insemination relies on the normal healthy functions of the sperm, and those can be bypassed by injection directly into the oocyte. Severe oligospermia (low sperm concentration), asthenozoospermia (low motility) or teratozoospermia (abnormal morphology) are all good reasons to use ICSI. However, many clinics routinely use 100% ICSI no matter what the diagnosis is. In the case of IVF, unexpected complete fertilization failure (CFF) in an individual cycle is a well-known phenomenon and is a risk to the success of IVF cycles.

A suggestion originated in the early 2000s that the high hormone levels derived from a stimulated IVF cycle would encourage a non-receptive, out-of-phase endometrium. Then, a concept arose that adopting a freeze-all approach would not only minimize the risk of ovarian hyper response syndrome, but maybe even improve pregnancy rates in the general IVF population. Now, the latest clinical “meta-analysis” of fresh vs frozen transfers, (involving 5379 eligible subjects and 11 trials!), found eFET associated with a higher live birth rate only in hyper-responders. There was no outcome difference between fresh and frozen in normal responders, nor in the cumulative live birth rate of the two overall groups. Now, here is where it gets complicated. 

Fresh vs. Frozen Embryo Transfer?

The CDC described the increase in the number of elective FET cycles between 2007 and 2016 as ‘dramatic’. They went from zero to more than 60,000 cycles per year. In its summary of US activity for 2016, the CDC seems unequivocal – at least, based on its observational registry data – that rates of pregnancy and live birth are higher after frozen transfers than after fresh. Yet the (published, peer reviewed or randomized clinical trial) so far has not shown a large difference. It seems to be a case where the clinical trials have not caught up with clinical practice. Because there is clear evidence that for hyper responders outcomes are better, many clinics now rely on a freeze all strategy to reduce this detrimental outcome.   

Financial Aspects: Less may not mean more.

IVF clinic quality is not always tied to cost, but it can be. Experts say not to choose your clinic based solely on insurance coverage. Base your decision on the performance of the individual clinic. Clinics that have higher volumes will naturally have embryologists who get to participate in a lot of procedures. Fertilization rates should be above 70% and 40-50% of fertilized eggs should make it to the blastocyst stage. 

Weigh the cost of the treatments with the CDC success rates. Good clinics with high success rates may cost more up front but may get you pregnant faster and at a lower cost in the long run instead of paying for multiple treatments.

High Tech IVF Clinic Management

Consider inquiring about the technologies the clinic uses. Do they use an EMR? Does it have a patient Portal for easy communication? Is there an electronic consenting process? Does the lab have state of the art cryo-storage monitoring systems? Does the lab use “electronic witnessing”? Quality control and assurance are of utmost importance in an IVF lab.

We hope you found this post helpful!

Reproduction is all about women, right? How could they be forgotten? Like so much of science and medicine, discoveries and accompaniments that should be credited to women have been overlooked. Reproductive health has come a long way. Back in the day, infertility used to puzzle scientists. They simply could not understand why one couple had better chances of conceiving a child than others. This was a time when IVF did not exist and the idea of “test-tube babies” would appall someone.

I’m glad we have come a long way with regards to social stigma and scientific discoveries. But that would not have been possible without the valuable contributions of various women. Unfortunately, most of these women NEVER got the recognition they deserved unlike their male counterparts. So in this blog post, we want to highlight their scientific achievements. Share this post with others so we can help spread the word!

Miriam Menkin– The first in vitro fertilization

This is where it all started! Miriam Menkin was a laboratory technician who worked for a fertility expert named John Rock. You might have heard of Rock because he received a lot of the credit for stumbling across IVF when Menkin didn’t. Menkin was always in charge of introducing the sperm to an egg in a petri dish and monitoring it for a half an hour. This one Friday night however, she was exhausted after caring for her own eight month-old at home. She arrived at the lab to do the routine procedure and dozed off while watching the petri dish. When she woke up, an hour had passed! Unfortunately she lost track of time.

When Menkin took a look at the petri dish she couldn’t believe her eyes. The egg and sperm had fertilized! This was the first ever fertilization that had taken place outside of the body. She called for Rock immediately and once he came, he apparently turned pale. They’d finally done it! To preserve the embryo she had to keep adding droplets of liquid to it. She did this in one hand while eating a sandwich in the other. 

Unfortunately, Menkin did not receive much of the credit. Though this discovery certainly had a serendipitous nature, it should not take away from the fact that it were Menkins actions that had led to it. As a single mother, she continued to balance her work and personal life and when Menkin and Rock were flooded with letters by infertile couples about their recent feat, the both of them went off to co-author 18 papers, 2 of which were on this achievement and were published in the journal Science. 

The lack of recognition for Menkin might arise from a mix of her both being a woman and a lab technician. She did not receive the same praise as her male counterparts who were scientists or doctors. 

She was a scientist, with a scientist’s mind, and a scientist’s precision, and a scientist’s belief in the importance of following protocols” – Margaret Marsh

Jean Purdy– Embryologist to the first IVF baby

If you know a bit about IVF, then you know that the first IVF baby to ever be born was Louise Brown. Jean Purdy was a nurse/embryologist who was the first person to see the first successful division of the embryo! She was outrageously left off the plaque in the hospital which Brown was born in! The people who did make the plaque were Professor Sir Robert Edwards and the surgeon Patrick Steptoe. Edward’s archives reveal that he wrote to Oldham Area Health Authority in 1980 requesting the plaques in the hospital include Purdy’s name.

It never happened.

The reason for this is because she might not have been viewed as important because she was an embryologist and nurse but not a doctor. If there is anything you should know about IVF, it is that it takes a village to raise an embryo.

Madelin Evans, an archivist, said the letters do not reveal an “explicit reason” why Purdy’s name was omitted but that “it probably had quite a bit to do with the fact she was a nurse, an embryologist and a woman I suppose”.

She died at the age of 39 in 1985, her name not on the plaque. But we will not let he be one of the forgotten women of reproduction!

Muriel Harris– IVF Nuring Pioneer

Harris was an operation theater superintendent on the team who was on the team who delivered Louise Brown. Unfortunately, when Harris went on a vacation the doctors decided to move up the birth and perform cesarean section. She missed the birth, but that was not the end of her story.

She might not have been there for that glorified moment, but what she helped do before and after the birth is JUST as important. The team closed down that facility and opened a new facility named Bourn Hall. This was the world’s first IVF clinic! She played a massive role in turning a run down location into a clinic that would grant wishes of many couples struggling with infertility. 

She was not a surgeon or physician and unfortunately that meant she did not get the recognition she deserves. 

Ruth Fowler– Made STIMS possible

Ruth Fowler might not have been directly involved in the first IVF baby’s birther, but she contributed a great deal of research to reproductive medicine in general. She was the grand-daughter of Earnest Rutherford, who himself won the Nobel Prize for chemistry in 1908, for his studies on disintegration of the elements, and the chemistry of radioactive substances. Fowler’ mother died shortly after Ruth was born and her father died when she was 13. She had a rough childhood to say the least but that did not stop her from earning her degree in biology at the University of Edinburgh and then working on her PhD on genetics there as well.

Fowler and her husband Bob Edwards wrote about ways to increase the number of synchronized eggs recoverable from adult female mice through a series of five papers (1957–1961), on the control of ovulation induced by use of exogenous hormones. This feat of hers helped debunk the common misconception that superovulation of adults was not possible.

Fowler had 5 children but she continued the hustle! She still published more papers about the growth of human embryos in the laboratory, the genetics of early human development and on the progesterone, protein composition of the uterine fluids of the rabbit and the importance in understanding the environment experienced by the preimplantation embryo.

If you thought her papers ended there… well you’re wrong! Fowler continued to write with Edwards throughout even the year the first IVF baby was born! At this time her papers focused on the dynamics and endocrinology of follicular development. It’s hard to keep up with how many topics she delved into! She poured her life and soul into discovering new things and helping reproductive medicine evolve. Her husband received the Nobel laureate while she did not. She deserves more. She was, however, called upon to receive the award when her husband was too ill.

What we need to do

Spread the word. The women in science both in history and present day need more recognition and respect for their work especially women of color. We must encourage more women of color to pursue jobs in STEM and medicine and also acknowledge those who currently in the STEM and medicine fields. 

We also must not follow in the path of the popular medical dramas that portray the wrong image of medicine. They ignore the many different people that are crucial in surgeries, procedures, patient care you name it! Healthcare is never a one man job. Nurses, lab technicians and everyone deserve equal respect. In the rapidly evolving space of science, it’s important the names of those who have contributed great amounts are not lost. 

References:

  1. Martin H. Johnson, IVF: The women who helped make it happen, Reproductive Biomedicine & Society Online, Volume 8, 2019, Pages 1-6, ISSN 2405-6618,
  1. “Female nurse who played crucial role in IVF ignored on plaque” by The Guardian https://www.theguardian.com/society/2019/jun/10/jean-purdy-female-nurse-who-played-crucial-role-in-ivf-ignored-on-plaque
  2. “The Female Scientist Who Changes Human Fertility Forever” by BBC Future https://www.bbc.com/future/article/20200103-the-female-scientist-who-changed-human-fertility-forever
  3. “Our History” by Planned Parenthood
Image by Sarah Pflug

We are SO excited to announce that our CEO Dr. Carol Curchoe has appeared as a guest on the podcast Beat infertility! She participated in several different episodes:

These episodes cover a HUGE range of topics and we can’t wait for you to listen to them! 

Each episode starts off with a little background about who Dr. Curchoe is. “Inside the IVF Lab” then delves into what it’s like inside an IVF lab! Some of the topics covered by Dr. Curchoe in this episode include:

“Epigenetics 101” is an awesome crash course in epigenetics! The episode gives you an insightful glimpse into the science behind epigenetics and what it has to do with fertility. The topics covered are:

“Artificial Intelligence in Assisted Reproduction” explains what role AI plays in fertility treatments! It is an exciting episode that shows how the field of assisted reproduction is evolving and adapting to be able to incorporate new ideas and inventions. This episode answered questions such as:

There is a LOT more that is covered but it would take up this entire blog post to get into it!

“Evaluating your IVF Lab” where we discuss the latest advanced technologies for IVF labs.

This is just a fraction of what is discussed and if any of these questions are some of YOUR burning questions, check out these episodes! The Beat Infertility Podcast is hosted by the amazing Heather Huhman, who transforms the episode into a wonderful and insightful learning experience. She is an infertility warrior herself and makes it one of her top priorities to spread knowledge among the community about the science behind infertility, assisted reproduction technology (ART) and lots more! Knowledge is power and Heather’s mission to share information from one infertility warrior to another is an attempt to have each person use that power to take control of their TTC journey.

What is Beat Infertility Podcast?

As we’ve mentioned, Beat Infertility is a podcast about all things infertility. They currently have over 500 episodes, with 270+ EXPERT interviews, and the air “IVF warriors’ stories” every Monday. Some of their recent episodes have been about

Support services

Beat Infertility isn’t only a podcast, they offer support services as well! They have lots of material for you to read through that can help you navigate your TTC journey. They also provide fertility coaching programs at various prices. They offer three different plans and regardless of the plan you choose, you are offered one-on-one time with a fertility coach to help come up with the perfect action plan! Each plan comes with a certain amount of texting support when undergoing IUI, IVF, surrogacy cycles, etc. 

It is also important to note that along with personalized fertility coaching programs, they also host a community of other infertility warriors! It is a network of others who are all navigating their own TTC journeys and understand the struggles of one another. Unfortunately, infertility is often misunderstood by those who have not experienced it. They underestimate the pain that an individual might feel when he or she cannot become a parent. Worst of all, they might even try to take control of your fertility through social stigma! That’s a BIG no. Join the community of infertility warriors to be surrounded by people who do understand you and support your choices and decisions. 

Ask a doctor!

One of the cool things about Beat Infertility is they often broadcast bonus episodes where Dr. Allison Rogers (board certified in both Obstetrics and Gynecology and Reproductive Endocrinology and Infertility) can answer your burning questions! If there is something you really want to know, submit it on their website and your question might be featured in the video!

Our Final Thoughts

Please head on over to Beat Infertility! We were so happy to be able to collaborate with them and share what we can with the TTC tribe! We hope these episodes helped answer any questions you might have always had but didn’t know who to ask. One of the things that makes Beat Infertility so amazing, is that the community, podcast and so many elements of the organization are built by people who are infertility warriors themselves. They have experienced infertility first-hand and will never judge you, underestimate the pain you’ve felt or question your decisions. When you are in need of a support system and your past ones have failed you, we urge you to visit Beat Infertility. 

Find all our collaborations and press links here.

Reference:

Beat Infertility

This is why you need to have ART Compass! Reagents traceability.

reagents

But wait, what is reagents traceability? You’ve come to the right place! Today we’re going to break down what that term means, why ART Compass enhances the ease at which it can be done, and why all of this matters in the first place.

What is reagent traceability?

High school labs were intimidating. There were so many beakers, burettes, and solutions that you’d be afraid of messing something up! An IVF lab is a lot more complicated! With so many solutions and apparatus present, it is crucial to monitor their usage. Some of the information that is important to know by lab directors and staff is:

These data points must be tracked against patient cycles, so that the vessel and/or corresponding patients affected by a defect, manufacturer recall, etc can be discovered in a timely manner. Many electronic witnessing systems give this a cursory effort, but miss the mark by failing to correlate any of these data points with pregnancy outcomes. This is where laboratories are faltering.

Why is it important?

That’s a good question. These quality control measures have been established to ensure that the services a certain IVF lab is providing are of good quality. This is incredibly crucial! A family out there is trusting a specific IVF lab with their baby, and it is the lab’s job to ensure that the environment of the lab supports the growth of the embryo cultures. This is ensured by providing aseptic conditions for the embryos and also maintaining a safe work environment for the lab staff. 

How does ART Compass help?

As we mentioned before many electronic witnessing systems give this a cursory effort, but miss the mark by failing to correlate any of the previously mentioned data points with pregnancy outcomes. ART Compass tracks all of the data points for true insight into patient outcomes. All of this information is in one place on a mobile device for easy access by the lab director and personnel! By forming this correlation, clinics are able to gather more information and really understand how exactly each feature of reagents‘ traceability affects pregnancy outcomes. Do a certain manufacturer’s products seem to be showing better results? Are there any expired reagents that are providing bad outcomes? If so, ART Compass highlights such errors and enables you to make the necessary changes required. Quality control is essential to any business, but in an IVF lab, there are literally lives depending on it. 

A lab without ART Compass?

We’ve talked about what ART Compass can do for you, but let’s highlight what a clinic might be missing out on without the app! Undesirable outcomes when culturing embryos or regarding lab safety are already a hassle to deal with. Not knowing where they originated from? It just makes the whole problem worse! Let me outline some examples:

The manufacturer of a certain solution doesn’t seem to get it quite right. The solution was contaminated during the manufacturing process and has been used in several cultures for embryos. The cultures do not result in success and you would like to know why. However, tracing back the steps of multiple laboratory personnel isn’t only time consuming but almost impossible sometimes! It’s difficult to identify the source of these failed cultures.

A laboratory that does use our app?

Well, the app monitors the usage of all reagents! It then correlates such data to data regarding successful pregnancies. So you can easily trace back the cause of the failed cultures! By doing so you can quickly fix the issue and have things go back to normal. 

As we said, an IVF lab is a complex setting with many moving parts. The ART Compass app can make the job easier for a lab director to have a birds-eye view of everything. All this information on a device at the touch of their fingertips! Lots of couples struggling with infertility heavily depend on IVF labs to be able to successfully carry out an IVF cycle. They trust that their IVF lab will incorporate the utmost precision and accuracy into their work. By making the job of the lab director easier (among other individuals), the ART Compass app hopes to create an environment where embryos can grow safely to eventually become a little bundle of joy for a couple. 

References:

  1. Cutting R, Pritchard J, Clarke H, Martin K. Establishing quality control in the new IVF laboratory. Hum Fertil (Camb). 2004;7(2):119-125. doi:10.1080/14647270410001709188

Our Message on IVF.net About the Digitalization of Quality Control

We’ve got great news! A post by our CEO Dr. Carol Curchoe was featured on IVF.net! She explains EVERYTHING about how ART Compass has changed the realm of cloud-based quality assurance (QA) and quality control (QC) for good and how cloud-based laboratory quality management systems are crucial for the development of IVF! A lot of the processes and data that are required to be recorded in IVF quality control are done on paper. Maybe it’s time to digitize a lot of what we do, and to save time and sanity of embryologists. 

ivf quality control

Image by Matthew Henry

Embryology Competency Assessments for IVF Quality Assurance

Dr. Curchoe delves into how staff competency assessments are available for staff to review their knowledge of embryology on a regular basis. This is important because even with a new and improved digitized path It’s always important to make sure that staff have complete knowledge on how to maintain quality control and quality assurance in the IVF lab. They should be able to tell if everything is up to standard and is in good shape for the lab to be a great home for your embryos! 

“ART Compass is a new paradigm— digitizing staff related competency assessments, training documentation, annual procedure evaluations, and real time “in-cycle” embryologist KPI statistics— for 21st century IVF lab QC/QA in “the cloud”.” -Dr. Curchoe

ART Compass and quality control digitalization

So what exactly can ART Compass do digitally? Well our mobile application and the web-based portal technology allows for quick data collection, real-time analysis, management, and distribution of multimedia files, automated reporting and the ability to use device hardware features, such as; the phone’s camera image editing with a finger and a biometric fingerprint data to enhance security!

Endless possibilities

Now it is time to start thinking about the big picture! What is it that can be implemented alongside ART Compass or any other mobile application out there for maximization of quality of patients’ IVF cycles? Electronic witnessing systems using RFID tags, QR codes, barcodes or other image capture approaches, if implemented alongside ART Compass for complete accuracy, can help eliminate the need to record who has done what in the lab by hand. All these data that are collected can then be tied in with the outcome data of that lab.

This way, you can identify what is improving the results of your lab and what is leading in undesirable outcomes. Another realm of possibility is IoT (Internet of Things) sensors. These can be used for real-time monitoring of room temperature humidity volatile organic compounds, and door open count among others and if this is paired with the clinical outcome data collected by ART Compass, you are able to see how these parameters affect the outcomes.

There’s a lot more that Dr. Curchoe explores in terms of the possibilities when it comes to integrating digitized means of data collection and QC and QA. However we do want to share with you a little more about IVF.net!

What is IVF.net?

Good question! IVF.net is basically an embryologist’s paradise or perhaps even for anyone involved in IVF. You can find everything you need in one spot. You can find out about the latest IVF-related news and announcements to stay up-to-date about new developments! Or you can search for new job positions for careers in the IVF world. If you are thinking of placing a new piece of equipment in your lab or clinic, you can find all of the product reviews on their website in one spot.

You have to make sure you have the best of the best machinery equipped in your lab! If you are looking for some new textbook material or resources in general for scientists on IVF, infertility and reproduction, you’ve got it all on IVF.net. IVF.net can also help you find and discover education and embryology course opportunities to help build that resume of yours and start your journey towards a career in reproductive medicine!

Our final thoughts

So whether you’re looking to find a new job in reproductive medicine and IVF or if you’re trying to develop that resume of yours and take a part-time or full-time course in embryology, stop by IVF.net. As per our CEO’s, post on the website let us know what you think about the digitalization of IVF and these new methods that might possibly change the field of IVF and reproductive medicine for good.

IVF is something that requires the utmost precision and accuracy and that is allowed or enabled when there is the highest degree of quality control and quality assurance in the lab. Any of the tiniest mistakes could possibly lead to an unsuccessful pregnancy or undesirable outcome. And that is simply not acceptable when someone’s embryos are in our hands. The times of scattered paper records and confusing data entry systems is long gone. Now it is the time to revolutionize IVF and to make sure that instead of having embryologists pour their energy into QC and QA, risking burnout (something a mobile app could take care of) they can spend more time taking care of your embryos!


Does Blastocyst Grading Matter?⁠

Blastocyst grading is not an exact science, but it is a tool that providers use in addition to other factors to determine which embryos may be fit for transferring. ⁠Despite forty years of research and clinical application, the average success rate of IVF today has been reported to be as low as 20-40%. Selection of the best embryo is key to the success of IVF cycles.

Blastocysts are embryos that have advanced to the 5 or 6 day stage.

Blastocysts possess an inner cell mass which will become the baby. The outer layer of cells of the blastocyst are called the trophoblast. The trophoblast will become the placenta.This layer surrounds the inner cell mass and a fluid-filled cavity known as the blastocoel. Blastocysts are qualified by their inner cell mass and trophoblast.
⁠
Rating blastocysts follows a three-part system of grading, however there are many systems of grading.

The three parts are always: ⁠
-The degree of the expansion of the embryo’s cavity.⁠
-The inner cell mass (the baby-making part) quality.⁠
-The trophectoderm quality (the cell layer that makes the placenta and the membranes surrounding the baby).⁠
⁠
The number and quality of blastocysts available is a key determinant for a patient’s chance of success with ART, thus blastocyst development rate is an important measure of an IVF clinic’s performance. ⁠ While morphological evaluation is widely accepted and implemented in most IVF clinics worldwide, the exact morphologic parameters used to score embryos are highly variable between clinics, and the assessment process is strikingly subjective even between embryologists at the same clinic. Embryo grading is not the end all and be all though- every embryologist has stories of remarkable transfer outcomes with poor quality embryos!

However, most human embryos do not have the genetic potential to develop normally to the blastocyst stage, hatch from their shells, implant, and continue normal embryonic development in order to result in a live birth.

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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