adminart, Author at Art Compass IO

Oocyte Maturation

In Vitro Maturation (IVM) was developed as an alternative to traditional IVF due to the adverse outcomes of ovarian hyperstimulation syndrome and the costs

associated with the administration of FSH. The treatment also has the potential to overcome other causes of infertility such as male factor, gamete donation and poor response to stimulation, and also has profound benefits for women undergoing oocyte or embryo cryopreservation with an estrogen-sensitive tumor or with a prothrombotic medical condition. IVM consists of collecting immature (ie. Geminal Vesicle or GV) oocytes and applying FSH and HCG in the culture media.

In vitro maturation of immature oocytes from an unstimulated cycle is an emerging technology. One of the safest ways to prevent OHSS is to not stimulate the ovaries. During an in vitro maturation of oocytes cycle, the immature eggs are retrieved from ovaries that are barely stimulated or completely unstimulated. The eggs are maturated in defined culture media for 24 to 48 hours and fertilized through IVF or ICSI. 4 IVM is an experimental technique that consists of the in vitro conversion of oocytes at the GV stage to oocytes at the metaphase II stage. This technology must include nuclear and cytoplasmic maturation of the oocyte and give rise to embryos that have a developmental potential that is similar to embryos obtained from standard IVF or from spontaneously in vivo matured oocytes. A few IVM practitioners advocated for “rescue IVM” in IVF conventional settings to prevent severe OHSS. “Rescue IVM” is when the physician has come to the conclusion that a safe conventional IVF cycle cannot be done so they change the treatment direction to an IVM protocol to the cycle instead. If the aspiration happens prior to the follicle selection, then OHSS risk can be eliminated.

Though IVM shows promising results, it is not a mainstream for fertility treatment. Mainly because there are difficulties retrieving eggs from immature ovaries that are not stimulated, and a lower chance of live births compared to conventional IVF, and there is an increased rate of abnormalities in meiotic spindles and chromosomes from immature eggs.

Sperm Preparation for ART

When sperm is ejaculated it is surrounded by fluid. A typical ejaculate contains cells, debris, dead and damaged sperm, and healthy, motile sperm. Healthy sperm is critical to the success of ART procedures and so we use sperm preparation techniques to separate functional spermatozoa for IUI, IVF, and ART and for cryopreservation. In the IVF lab there are essentially 4 techniques we use commonly; Swim-up, Swim-down, Sucrose and Ficoll-400 density gradient techniques. Each lab finds that one of these techniques will yield more motile, live and normal looking sperm for their procedures.

Companies like ZyMot sell specialty devices for sperm separation that can be very expensive. The idea is that they simulate the cervical and uterine pathways that sperm must navigate to naturally fertilize an egg. By mimicking this natural selection method, sperm can be isolated without the use of chemicals or centrifugation that may damage the sperm. Instead they use microfluidic technology to isolate healthy sperm by laminar flow, which creates gradients through channels. These devices have been tested in randomized controlled trials, which is the gold standard of medical research.

Data shows that up to 25% of semen specimens from men with an undetectable burden of viral RNA (HIV particles in their blood) are HIV positive. Each semen sample must be tested because those results are not consistent. HIV is detected in some samples and not others form the same man, even when HIV is not detected in the blood. SPAR stands for special program of assisted reproduction. They have developed highly sensitive techniques to detect the viral load in semen samples viruses like HIV, CMV, and Hepatitis C, and special procedures to wash the semen samples. This allows the sperm to be used for IVF to decrease or virtually eliminate the risk of transmitting the infection. These specimens can only be used for IVF, they are not appropriate for intrauterine insemination.

ICSI was developed for men with poor sperm quality and quantity. Low sperm count, sperm motility, and abnormal morphology can be indications for ICSI. Abnormal morphology (shape of sperm) has been linked to poor fertilization. Fertilization can now be achieved for men where it previously seemed impossible. It is now used exclusively in some clinics, and it is especially important for couples who want to have their embryos genetically tested. One of the reasons why it is so widely used now, is so that the embryologists can look at the eggs and know the quality and maturation right after the egg retrieval. In conventional IVF, the egg quality and maturity is essentially a mystery because the eggs are surrounded by cells until the day after the fertilization. Fertilization rates are generally higher after ICSI compared to conventional IVF. The more embryos you have the better the chance of pregnancy!

One variation of ICSI is called “PICSI” which stands for physiological ICSI, and uses a specialized dish coated in a substance called hyaluronan. Healthy sperm are attracted to that enzyme and stick to it, they are later used to inject the egg with.

Sperm DNA Fragmentation Testing

DNA fragmentation can be caused by a variety of factors such as infection, chemotherapy, radiotherapy, smoking, drug use, or advanced age. SDF is linked to impaired fertilization, poor embryo quality, increased spontaneous abortion rates and reduced pregnancy rates after assisted reproduction. Currently, there seems to be insufficient evidence to support the routine use of SDF in male factor evaluation nevertheless the importance of DNA fragmentation in spermatozoa has been acknowledged in the latest American Urological Association (AUA) and European Association of Urology (EAU) guidelines on male infertility. Several strategies have been proposed to minimize the influence of abnormal chromatin integrity on ART outcomes. Obesity, smoking, toxins, pollutants, and Bisphenol A (BPA). They include: intake of oral antioxidants, varicocele ligation, frequent ejaculation and sperm sorting.

In vitro gametogenesis (IVG)

A new process called in vitro gametogenesis (IVG) is currently being developed, and if successful, it will completely transform the way humans think about reproduction.

The process of IVG creates sperm and egg cells in a lab from just about any adult cell. IVG uses skin or blood cells to reverse engineer a special type of cells called induced pluripotent stem cells (iPSCs). Essentially, iPSCs are adult cells that have been genetically reprogrammed into an embryonic state, meaning they have the potential to transform into any type of cell: kidney cells, muscle tissue, sperm, or eggs.

IPSCs can be used to create the necessary components for reproduction: eggs and sperm. They’re also at the forefront of all sorts of important research, including disease treatment, transplant science, and cutting-edge drug development.

In the hypothetical human IVG process, an individual would provide a skin biopsy. A lab would then reprogram those skin cells to create induced pluripotent stem cells, which would then be used to create eggs or sperm.

Today, we still need a man and a woman to make a baby. Reproduction still requires testes to make sperm and ovaries to produce eggs.

In 2016, a team of scientists at Tokyo University of Agriculture in Japan helped a female mouse successfully give birth to 26 pups, using eggs created from skin cells.

In 2018, Japanese scientists were able to generate immature human eggs, using induced pluripotent stem cells derived from human blood cells. These incomplete eggs would not be viable for fertilization, but they do represent a major step toward the development of a successful human IVG process.

Oocyte Activation

A small percentage of individuals continue to face repeated fertilization failure, even with normal sperm parameters and a good ovarian response and multiple ICSIs. Normally, when the sperm binds an egg a cascade of events occurs that results in oscillating waves of calcium ions in the egg. This is called egg activation! If this is missing or deficient in a patient it results in zygotes that arrest and cleavage stage defects. Calcium ionophores are the molecules that increase the concentration of calcium ions, and when artificially applied to an egg can activate the egg so that fertilization can occur.

A meta-analysis by Murugesu et al. (2017) included fourteen studies, and found activation with calcium ionophore increased fertilization, embryo cleavage, blastocyst and implantation rates, as well as overall clinical pregnancy rate per embryo transfer (OR=3.48) and live birth rate (OR=3.44). Calcium ionophore treatment may be especially helpful for patients with specific conditions, such as a condition called globozoospermia, which is when the sperm lacks a feature called the acrosome, or if previous, unexplained failed fertilization occurred.

https://www.fertstert.org/article/S0015-0282(17)30488-0/pdf

DHEA – de hydro epi andro sterone.

One of the hottest topics in IVF right now is the use of DHEA to rejuvenate ovarian function, because currently up to 1 in 4 IVF cycles are characterized by poor ovarian response. “Poor responders” suffer from Diminished Ovarian Reserve (DOR) resulting in fewer oocytes and decreased rates of pregnancy. Some studies claim that use of DHEA supplementation improves pregnancy chances in women with Diminished Ovarian Reserve by reducing aneuploidy—chromosome number abnormalities in embryos. DHEA, according to some reports, has been very successful in increasing the number and quality of eggs, reducing the risks of miscarriages and shortening the time to pregnancy.

Endometrial Receptivity Assays

The Endometrium must be prepared with progesterone for the embryo to implant. The typical metric is to look for a think “triple line” pattern. ERA testing determines if the endometrium is “genetically” receptive or not at the time of sampling, by analyzing a few hundred genes that get turned on or off and are known to be important for true endometrial receptivity. When your lining looks ready after but is not expressing the right genes and therefore the right proteins, your “window of implantation” is displaced. ERA testing can find your personalized window of implantation in case of displacement, and will allow a personalized timing for embryo transfer. 3 in every 10 patients have a displaced window of implantation. Use of the ERA test in one study, resulted in a 73% pregnancy rate in patients with previous implantation failure.

https://www.researchgate.net/scientific-contributions/2068756675_M_Ruiz-Alonso

Millions of babies have been born through Assisted Reproductive Technologies (ART), however, only 30% of IVF cycles succeed in a clinical pregnancy. Aside from increasing the success rate, there are other goals for continued improvement across the IVF industry; to simply get patients pregnant faster, reduce treatment dropout, or to reduce embryo wastage. Innovations in Artificial Intelligence (AI) will drive ART that is more reproducible, standardized, efficient, and less costly. Artificial intelligence and big data: Companies are using “big data” and predictive analytics to help fertility doctors recommend the best course of treatment based on what’s worked for patients with similar demographics. Others are using artificial intelligence to predict which embryo will create a viable pregnancy, instead of relying on scientist’s (occasionally) subjective judgment.⁠

Nanotechnology helps sperm swim: Male Infertility issues contribute to about half of all cases of infertility. One major cause is low sperm motility, or the sperm’s inability to swim to the egg. Nano-tech motors can slip over a sperm’s tail to propel it next to an egg.⁠

Creating “Three-person” embryos: The goal of so-called three-person IVF is to create embryos that have nuclear DNA from a woman and her partner but with healthy mitochondrial DNA from an egg donor. Three-person embryos have been created for two reasons, to correct inherited mitochondrial disorders or as an attempt to reverse the biological clock of older women. ⁠

Freeze all Vs. Fresh Transfer

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, the 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.

The latest clinical meta-analysis of fresh vs frozen transfers, now 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.

The CDC described the increase in the number of elective FET cycles between 2007 and 2016 as ‘dramatic’, rising steeply from almost 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, and because there is clear evidence that for hyper responders outcomes are better, many clinics are now relying on a freeze all strategy to reduce this poor outcome.

Devroey P, Polyzos NP, Blockeel C. An OHSS-free clinic by segmentation of IVF treatment. Hum Reprod 2011; 26: 2593–2597.
Wong KM, Van Wely M, Mol F, et al. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2017 Mar 28;3:CD011184. doi: 10.1002/14651858.CD011184.pub2.
Roque M, Haahr T, Geber S. Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes. Hum Reprod Update 2019; 25: 2-14.
CDC. Assisted Reproductive Technology: National Summary Report. 2016.

Embryo Retained in Catheter

Thaw Biopsy Revit

Personalized Genomic Medicine

Anticoagulants; Asprin, Lovenox, Heparin

C4M2 mutation is found on the Annexin 5 which keeps the blood thin enough for pregnancy to progress successfully. When mutated, the gene fails to work adequately causing blood clotting, which eventually leads the body to abort the fetus.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by production of antibodies – antiphospholipid antibodies (aPL) – that “attack” the person’s own body, resulting in blood clots and/or pregnancy complications.

For APS patients with a history of pregnancy complications only:

oral low-dose aspirin (LDA), which prevents clots by blocking platelet aggregation.

subcutaneous injections of prophylactic, low-dose heparin (an anticoagulant drug that prevents the clotting ability of the blood).

Prevents the formation of blood clots in the embryo and placenta
Increases the production of cellular substances important to successful embryo implantation in the uterine lining
Increases insulin-like growth at the site of the embryo’s implantation
Increases production of protein assisting in binding the early embryo in the uterine lining
Effects suppression on the immunologic cause of recurrent miscarriage
https://www.ebiomedicine.com/article/S2352-3964(16)30280-8/fulltext

MTHFR

People differ in how much folate or folic acid they need for their health – based on the activity of “the MTHFR gene”. A mutation in this gene causes very low activity of the MTHFR protein in the body. This results into a highly reduced ability of the body to convert folic acid into a usable form and can lead to accumulation of the amino acid homocysteine – which is toxic to the body.

The biggest reason why knowing your MTHFR gene result is because it is involved in creating healthy DNA for both you and your future child. Active folate is directly involved in the synthesis of new DNA. And while we have a constant demand for the production of new and healthy DNA, you can imagine that demand for this hugely increases during pregnancy, when you are growing a new life!

Issues with not enough healthy DNA available for both mother and growing child can result in issues with pregnancy, fetal growth, and general childhood development.

It is also used by the body to prevent levels of a substance in the body called homocysteine from climbing too high, which can be related to blood clots and increased risk of blot clot formation during pregnancy.

It is also important to create molecules called ‘methyl groups’, which act as instruction manuals for your DNA and cells, telling them the correct way to ‘behave’, so they do not do anything unwanted (e.g. cause disease or dysfunction within the body). We need healthy levels of these methyl groups to methylate/instruct your DNA, and without it cells are uncontrolled and can start to cause problems.

Formation of red blood cells, white blood cells, and platelets, which are all vital for both the health of the mother during pregnancy and also for the health of the child during pregnancy and after birth as they begin to rapidly grow and come into contact with bacteria and pathogens to strengthen their immune system.

As you can see, addressing and supporting your MTHFR genes during your preconception phase is the best way to healthily support both your body once you fall pregnant, and the growth and development of your new baby.

Knowing your MTHFR gene result and supporting your folate levels where needed is a key step in preconception, and both should not be undervalued!

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 degree or a PhD due to the specialized nature of our work. Here are ten things we want you to know about IVF!

What is a blastocyst and why is embryo grading relevant?

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 embaby! But it’s always possible that things might actually not go as planned. Sometimes an embryo with a lower grade implants successfully and vice versa! Even though science is very logical and precise, that doesn’t mean that there can’t be some surprising ups and downs.

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.

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.

All About PGT?

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.⁠

⁠You have to make a LOT of eggs to have a good cycle.

15 is the optimal number of eggs to retrieve without putting you at risk for OHSS. More eggs often means they are lower quality and higher estrogen levels, which can impair implantation in fresh IVF Cycles.

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.

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 highly-qualified fertility doctors, 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.

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.

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.

EGG, 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.

Don’t 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.

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”?

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! Find out what to ask.

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.

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?

A possible thing to note could be 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. 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.

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 embryos and single embryo transfer, ERA or endometrial receptivity assay testing.

The introduction of intracytoplasmic sperm injection (ICSI) has 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.

In the ever-evolving world of IVF lab accreditation and quality management, there are numerous standards and frameworks to choose from, such as from ASRM and ESHRE. However, there’s one accreditation agency that stands out as the optimal choice – the College of American Pathologists (CAP). If you’ve just stumbled upon CAP Accreditation, don’t fret; this comprehensive guide will walk you through the ins and outs, helping you determine if CAP Accreditation is right for your lab and, if so, how to embark on the journey toward excellence.

What is CAP IVF Lab Accreditation?

The CAP Checklist for IVF lab accreditation is a remarkable publication brought to you by the College of American Pathologists. It is more than just a checklist; it’s a meticulously detailed roadmap designed to ensure and enhance quality management in clinical embryology, andrology, and endocrinology labs. Specifically, these standards are meticulously crafted to align with and uphold the USA federal CLIA88 guidelines for clinical laboratories.

Who Needs CAP Accreditation?

CLIA88 isn’t just a suggestion; it’s a legally mandated framework. By law, every clinical laboratory must be in strict compliance with CLIA 88. But what sets CAP Accreditation apart is its capacity to not only meet but exceed these standards. So, whether you’re running an established IVF lab or venturing into this cutting-edge field for the first time, CAP Accreditation is your key to unlocking a world of quality, precision, and excellence.

Staying Ahead of the Curve with CAP Checklist Updates

The College of American Pathologists understands the importance of maintaining consistency and stability in their checklists. While the world of IVF lab accreditation is dynamic, CAP strives not to make major changes to the checklists. This dedication to stability allows IVF labs to maintain their focus on quality assurance without the constant disruption of adapting to significant updates.

For IVF labs, this commitment to minimizing major changes in the checklists is a relief. It allows you to build a strong foundation of quality practices and focus on continuous improvement rather than navigating extensive checklist revisions.

To help you stay informed and up-to-date, we’ve still analyzed the minor changes in recent CAP Checklist updates and compiled them into a convenient reference table for your convenience.

CAP Checklist Update Key Changes & Updates

As a reminder, if you’re looking for a “Turn Key” set of IVF lab Standard Operating Procedures (SOPs), you can find them within the ART Compass IVF Lab Management platform. These SOPs are designed to seamlessly integrate with the latest CAP Checklist updates, making your journey toward CAP Accreditation smoother and more efficient.

Stay with us as we continue to unravel the secrets of CAP IVF Lab Accreditation, equipping you with the knowledge and insights needed to not only meet industry standards but to stand out as a beacon of excellence in the field of IVF.

In the USA, The IVF industry is experiencing a pressing, double-edged problem: it struggles to fill new embryologist positions, an estimated 5% of the existing workforce is already beyond retirement age (65-67 years old)—and an estimated additional 20-40% will reach retirement age within the next 7 years. Embryologists are the core of the IVF supply chain, and a shocking “grey” rhino (an obvious yet ignored threat) is in the room. We cannot make more embryos without more embryologists. By all predictions, the IVF industry is on track to grow astoundingly in the next ten years as millennials who have put off childbearing for career begin to seek age-related infertility care. We are so focused on growing good embryos, but how do we grow (attract) new embryologists?

An ASRM practice document [1]“Minimum standards for practices offering assisted reproductive technologies: a committee opinion” states that:

“There should be a contingency plan in place for all personnel essential to a program in case of illness, absence, or departure of an individual from the program. The purpose of the contingency plan is to ensure that critical operations within the laboratory and practice are covered without interruption.”

Our entire field is in dire need of a contingency plan.

40% of our current workforce is attributed to the “Baby Boomer” generation. The oldest Baby Boomers are 75 years old, and the youngest are now 58. I would wager to guess that the vast majority of 67-75 year olds have already retired. Just think of the IVF lab directors and embryologists you know who will retire in the next 5-7 years (i.e. the 58-65 year olds). Each one likely directs numerous offsite laboratories. And new IVF laboratories open every day. Are enough new HCLD certificates being granted to ensure that IVF labs can continue to function at high levels of patient care and quality after this looming tsunami of retirements?

As a result of this human capital conundrum, it has become even more important that IVF clinics ensure knowledge transfer, retention, and upskilling occur.

Knowledge Transfer

Campbell et al. note in “The in vitro fertilization laboratory: teamwork and teaming”[2] that “Knowledge sharing is vital among an IVF laboratory team to build on the knowledge base and enable succession and development. Clinical case review, journal-based learning, and research opportunities all facilitate such sharing and knowledge building.” Embryologists who are struggling to simply complete the expected clinical laboratory work of the day may not be able to fulfill these ideals, as well as train and supervise junior team members.

The model of meeting for scientific congresses, where this type of knowledge transfer typically occurs, was briefly derailed during the global coronavirus pandemic. Scientific congresses can only serve a fraction of embryologists. The long overdue International IVF Initiative (I3) rose, modernizing the age-old practice of knowledge transfer with the added benefit of democratizing access for embryologists worldwide. Alternate approaches to further modernize the concept of “knowledge transfer” in embryology and the ARTs are so important. Chocair et al [3] proposed a robust roadmap to modernize knowledge transfer that includes multiple digital methods; online self-assessment programs, digital technology integration through blogs, podcasts, and influential videos, an online platform education management platform to report training logbooks, including a “knowledge assessment passport” among other action items. The Y and Z generations of workers are digital natives (digital “junkies” even..) they cannot live without their mobile devices. Investment in and support for “digital first” knowledge transfer technologies is essential. (Full disclosure, I am the inventor of one such unsupported technology, the ART Compass mobile app, so it goes without saying, these opinions are biased).

Embryologist Retention

There is a childcare crisis in the USA. The majority of embryologists are women of childbearing years. These two things are essentially incompatible.

Embryologist schedules are unpredictable (consider the odd 100 egg retrieval or 6 hour TESE) and can start well before a school day begins and stretch until well after a school day ends. Additional childcare considerations must be made for holidays and weekend shifts. That doesn’t even take into consideration the mental anguish of missing significant family related events or milestones. An added consideration is that families rarely reside in multi-generational households (or even in the same city) and Baby Boomers are no longer retiring in a timely fashion due to a combination of economic fragility brought on by multiple successive economic failures and longer life-spans. Even when they do retire, they don’t necessarily want to watch little ones. They have already raised their own children and are ready for travel, adventure, and leisure. Many embryologists are confronted with a very simple calculus: “Do I make enough in one hour to cover one hour of childcare?” With the skyrocketing cost of childcare as well as the scarcity of available childcare providers, too often that answer is “no”.

One action item for the field at large is to train more male embryologists. Diversifying the workforce will have numerous benefits; including, greater insulation from multiple maternity leaves of absence. However, an even more pressing need is to fix the culture of IVF practices to be less rigid, less demanding, and more flexible for those with families or even without, recognizing that work life balance will drive the decisions of Gen Z and Gen Y. And to do that, we must support the elevation of our female embryologists to the highest ranks (PhD/HCLD). It stands to reason that if 80% of embryologists are female, 80% of lab directors should also be female. However, we see the opposite is true. It is clear that when men do become embryologists, they quickly ascend the ranks to become lab directors, or presumptuously, I think they must leave the field because they won’t stand for the intense hours/ low pay/ holidays and weekends. So modulating the intense, unpredictable “culture” of IVF labs should have the impact of retaining both genders equally.

Upskilling

In the USA, we have few formal “embryologist” education, training, or placement programs. The bulk of all new embryologist training falls to the senior embryologists. This dearth, coupled with high embryologist demand has led to the rise of a number of commercialized and privatized training programs to fill the void. Currently, these programs have stellar reputations. But what is to stop predatory programs from also springing up? Generally, consumers of education programs have some level of assurance and transparency because there is oversite and regulation of higher education. Results are measurable and formally assessed and documented, sources of capital and cash flow are understood, the quality of training and/or placement is guaranteed. One action item for the field could be a standardized and digital education management platform to report training logbooks, that includes the “knowledge assessment passport” mentioned above. One example, and in response to the COVID-19 pandemic, the American Center for Reproductive Medicine (ACRM) transitioned its annual training to a fully online modules included manual semen analysis, sperm morphology and ancillary semen tests (testing for leukocytospermia, sperm vitality, and anti-sperm antibody screening)[4].

Conclusion

Within higher education, abundant models exist for hands on biotech training at the “associate degree” open enrollment level, but grow scarcer at the BS / BA level. Advocacy associations for the ART industry might focus lobbying efforts at State legislature levels that acknowledge that without an appropriately skilled workforce, it is impossible to grow this highly-regulated industry. Local ART education programs should eliminate barriers to ART careers by providing access to expensive equipment, space, and real-life education through hands-on learning opportunities, learning FDA, CLIA and other regulatory requirements that result in highly employable, and valuable technical careers in ART. An intriguing new study, Clinical Laboratory Workforce: Understanding the Challenges to Meeting Current and Future Needs [5] suggests further innovative ways to improve workforce recruitment and retention, including; financial incentives to encourage professional development and job satisfaction; and flexible schedules, benefits, tuition incentives, and sign-on bonuses.

Acknowledgment

Unpublished Online survey by the educational platform International IVF Initiative.

Palmer GA, Tully B, Angle M, Sadruddin S, Howles C, Nagy ZP, et al. Occupational Demand & Resultant Stress of reproductive scientists: Outcomes from an International survey.

References

Practice Committee of the American Society for Reproductive Medicine, P.C.o.t.S.f.A.R.T., B. Practice Committee of the Society of Reproductive, and a.a.o. Technologists. Electronic address, Minimum standards for practices offering assisted reproductive technologies: a committee opinion. Fertil Steril, 2021. 115(3): p. 578-582.
Campbell, A., et al., The in vitro fertilization laboratory: teamwork and teaming. Fertil Steril, 2022. 117(1): p. 27-32.
Choucair, F., N. Younis, and A. Hourani, The value of the modern embryologist to a successful IVF system: revisiting an age-old question. Middle East Fertility Society Journal, 2021. 26(1): p. 15.
Agarwal, A., et al., A Web-Based Global Educational Model for Training in Semen Analysis during the COVID-19 Pandemic. World J Mens Health, 2021. 39(4): p. 804-817.
Edna C. Garcia, M., M. Iman Kundu, and P. and Melissa A. Kelly, Clinical Laboratory Workforce: Understanding the Challenges to Meeting Current and Future Needs. . 2021.

Preventing errors in the IVF Lab is the top priority of every embryologist. But how do they happen, and what can we do about them?

Have you ever driven home, but didn’t know how you got there? That’s your brain on autopilot mode. Brain scans have revealed that when your mind wanders, it switches into this mode to enable you to carry on doing tasks quickly and reasonably accurately, but without conscious thought.

“Autopilot mode” one of the most dangerous times for an embryologist. Reasonable accuracy is not acceptable in what we do. Yet, as human beings, we all make errors. Sometimes, your brain and eyes just don’t see what’s right there in front of you.

Part of embryologist training is not just learning the technical procedures, but training your brain to not take “shortcuts.” We do this by implementing a set of tricks to constantly kick the grey matter from autopilot mode back into full consciousness on a regular basis. Each embryologist must develop their own magic set of tricks to ensure nearly 100% accuracy, always. The eyes of a junior embryologist must be trained to actually SEE what is in front of them, and to not accept what our brain wants us to see, or what one THINK they should be seeing (i.e. seeing an empty dish when there are really embryos in it!). Even “seniors” can be lulled I into complacency by many years without an error, until and unexpected are truly horrific mistake happens out of the blue.

The unique nature of IVF and fertility care demands an incredibly high standard to avoid errors. This makes embryology a medical professions with one of the highest rates of stress and burnout. You can never just “put it on autopilot” or lose concentration, even for a second. The consequences can be catastrophic for both patients and the clinic.

While mistakes may occasionally be due to system failures, malfunctioning equipment, or a break in the chain of custody, the hardest type to deal with, especially in the lab, is simple human error.

Here are 4 tips to prevent human error in the IVF lab.

Declutter work spaces and always clean the entire space, including discarding pipette tips between handling patient specimens.
Take breaks in between similar procedures. Practice the last “pause” before any tissue leaves your hand.
Eliminate the “hand off” so that an embryologist finishes each procedure from start to finish.
Say each patient’s name out loud (or embryo number) when moving between embryos or patients.

In fertility care, any instance in which gametes or embryos are lost, degraded, or misdirected constitutes an adverse event – a medical error. The comprehensive training and accreditation of an embryologist is designed to minimize any potential impact on patient samples.

Fortunately, IVF errors are rare. A study published recently found that in a 10-year period (2009 to 2019), 133 errors occurred that resulted in lawsuits out of approximately 2.5 million IVF procedures in the U.S. A 2018 study of non-conformance with standards from the International Organization for Standardization found that 99.96% of procedures (36,654 IVF treatment cycles) in one clinic network had zero violations.

I’ve had both my best day and my worst day as an embryologist. While research on the unconscious mind has shown that the brain makes judgments and decisions quickly and automatically, I look forward to an AI-enabled lab, where repetitive and mundane tasks are automated and intelligent, AI-enabled tools monitor and control safety with precision and ease.

Do you have story to share when an error occurred in the lab and you were able to correct it?

Spring is a season of new life, renewal, and growth. It’s a time when the earth awakens from its winter sleep and bursts forth with vibrant colors and new beginnings. For those struggling with infertility, spring can symbolize hope and the possibility of new life.

If you’re waiting to get pregnant, the journey can be long and difficult. It’s easy to become overwhelmed with the daily routine of charting cycles, taking medications, and undergoing fertility treatments. But as the days get longer and warmer, it’s important to take a step back and appreciate the beauty of the season and the hope it brings.

Just as the earth goes through cycles of growth and renewal, so do our bodies. Infertility can be a frustrating and emotional rollercoaster, but it’s important to remember that every cycle is a new beginning. With each new cycle, there’s the possibility of new life, and the hope that this time will be the one.

Oocytes, or eggs, undergo a complex process of maturation before they can be fertilized. This process takes several months, and is influenced by a variety of factors, including age, genetics, and lifestyle choices. There are steps that individuals can take to support the maturation process and increase their chances of conception. One of the most effective ways is to make lifestyle changes and incorporate certain supplements into the daily routine.

For example, studies have shown that maintaining a healthy weight, exercising regularly, and reducing stress levels can all positively impact oocyte maturation and improve fertility. In addition, taking supplements such as folic acid, vitamin D, and omega-3 fatty acids can also support the maturation process and improve overall reproductive health.

Spring is also a time for self-care and renewal. Take some time to pamper yourself, whether it’s with a relaxing bubble bath, a massage, or a day out in nature. Focus on activities that bring you joy and relaxation, and don’t forget to connect with loved ones for support.

The season of renewal also provides an opportunity to reflect on your fertility journey and set new goals. Take some time to reassess your priorities, and consider any lifestyle changes that might improve your chances of conceiving. This could mean adjusting your diet, exercise routine, getting enough high quality sleep, or reducing stress levels.

Remember, you’re not alone on this journey. Seek out support from friends, family, or a professional counselor if you’re feeling overwhelmed. Spring is a season of new beginnings, and with each new cycle, there’s the possibility of new life and hope.

So, as you embrace the season of spring, remember that your journey towards parenthood is also a journey of growth and renewal. Take a deep breath, appreciate the beauty around you, and have faith that your new beginning is just around the corner