ASRM2021 Edition đŸ—ŒReproduction Reimagined
ASRM2021 Edition đŸ—ŒReproduction Reimagined

There are so many exciting talks at ASRM2021, Reproduction Reimagined! We are super excited about these IVF Lab focused talks as well as quite a few others!


Title Speakers
O-199 – COULD THE EMA ARTIFICIAL NEURAL NETWORK GRADE BLASTOCYSTS AS AN EMBRYOLOGIST?Lorena Bori, Ph.D1., Daniella Gilboa, MSc2, Ron Maor, BSc.2, Thamara Viloria, PhD3, Ilya Kottel, BSc.2, Daniel S Seidman, MD4 and Marcos Meseguer, Ph.D.1, (1)IVIRMA Global; IVI Foundation, Valencia, Spain, (2)AiVF, Tel Aviv, Israel, (3)IVIRMA Global, Valencia, Spain, (4)AiVF; Sackler Faculty of Medicine, Israel
 RTM32 Ready, Set, Go! How to Skyrocket Your ART Lab Professional Career.Liesl Nel-Themaat, Ph.D., HCLD, University of Colorado Anschutz Medical Campus, Aurora, CO
 RTT27 Emerging Bioengineering Technologies in the ART LabsT. Arthur Chang, PhD, HCLD, ELD, University of Texas Health Science Center, San Antonio, TX
RTT28 â€œBe a Scientist, Not a Robot”. Is That a Lost ART?”Mitchel C. Schiewe, MS, PhD, Ovation Fertility, Newport Beach, CA
 RTT29 The Ideal Cryopreservation Storage System – Characteristics and Equipment.Kimball O. Pomeroy, Ph.D., The World Egg Bank, Phoenix, AZ
INT03 To ICSI ALL or NOT to ICSI ALL: That’s the Question!Mitchel C. Schiewe, MS, PhD, Ovation Fertility, Newport Beach, CA, David H McCulloh, PhD, NYU Grossman School of Medicine, New York, NY, Caroline McCaffrey, PhD, NYU Langone School of Medicine, New York, NY, Bill Venier, MSc, ELD (ABB), San Diego Fertility Center, San Diego, CA and Liesl Nel-Themaat, Ph.D., HCLD, Univ of Colorado
RTW21 Looking Past the Hype: Realistic Expectations for AI-Based Embryo Selection.Dean E Morbeck, Ph.D., M.B.A., Fertility Associates, Auckland, New Zealand
RTW22 Lab Disaster Management: Prepare Today be Ready TomorrowSangita K Jindal, Ph.D., Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY
RTW23 New Lab Equipment: Better Outcomes?Anthony R Anderson, D.HSc, EmbryoDirector.com, San Antonio, TX
SYW06 Crises Management: What We Have Learned from Catastrophic EventsRoman Pyrzak, Ph.D.Kimball O. Pomeroy, Ph.D., The World Egg Bank, Phoenix, AZ and Sangita K Jindal, Ph.D., Albert Einstein College of Medicine / Montefiore Medical Center, Hartsdale, NY
SYW07 ON-DEMAND ONLY SESSION: The Environment: It Affects More Than the Ice Caps!Patricia Hunt, Ph.D.1Dean E Morbeck, Ph.D., M.B.A.2 and Linda C Giudice, MD, PhD1, (1)Washington State University(2)Fertility Associates, Auckland, New Zealand
PLE05 Herbert H. Thomas Plenary Lecture: Applications of Nuclear Transplantation in Reproductive MedicineShoukhrat Mitalipov, PhD, Oregon Health & Science University, Portland, OR
PLE06 Past and Future of IVFEli Y Adashi, MD, The Warren Alpert Medical School, Brown University, Providence, RI
INM08 Snap, Tweet, Tok! Reimagining Patient Education with the Use of Social MediaNatalie M Crawford, MD, MSCR, Fora Fertility, Austin, TX, Jasmine Danielle Johnson, MD, IU Health – Indiana University School of Medicine, Carmel, IN and Temeka Zore, MD, Spring Fertility, San Francisco, CA
SYT07 Artificial Intelligence (AI) in the IVF LaboratoryAlan B Copperman, MD, Sema4, Stamford, CT, Richard Slifkin, BA, TS(ABB), CLT(NYS), Reproductive Medicine Associates of New York, New York, NY and Danielle Soltesz, MBA, MPH, RMA of New York, New York, NY
YM04 PGT Yesterday, Today, and TomorrowJames A Grifo, MD, PhD, New York University, New York, NY, Mike Large, Ph.D., CooperSurgical, Houston, TX and Mark Hughes, Ph.D., COOPERGENOMICS
RTM22 What the IVF Doctor Needs to Know about the IVF LaboratoryEric J. Forman, M.D., Columbia University Fertility Center, New York, NY
RTM08 Polygenic Risk Scores and Embryo Selection: Should We?Amber Gamma, MS, CGC, Northwell Health Division of Medical Genetics, Great Neck, NY
 SYM10 SART-CORS Registry: The State of the ARTJennifer F Kawwass, MD, Emory University School of Medicine, Division of Reproductive Endocrinology and Infertility, Atlanta, GA, Stacey A Missmer, Sc.D., College of Human Medicine, Michigan State University, Grand Rapids, MI and Amanda Nicole Kallen, MD, Yale School of Medicine, New Haven, CT
INT02 Chat with Journal Editors: Good Scientific Publication, Manuscript Review, and Editorial ProcessAlexander M. Quaas, MD, PhD, University of California San Diego, San Diego, CA, Richard J Paulson, MD, MS, University of Southern California, Los Angeles, CA, Denny Sakkas, PhD, Boston IVF, Waltham, MA and David F Albertini, PhD, M.S., Bedford Research Foundation, Salisbury, MA
COVID 19 Vaccine and Sterility
COVID 19 Vaccine and Sterility

The COVID-19 vaccine does not cause sterility! Misinformation spread on social media and false reports circulated have raised questions about whether the COVID-19 vaccine causes female sterility. As a result, there has been a concerning increase in vaccine hesitancy in reproductive-age women. Rest assured, these are unfounded claims. New research has proved that the vaccine does not cause female sterility.

Vaccine hesitancy among this group was largely caused by a false report, shared on social media, that said the spike protein on the coronavirus was the same as another spike protein syncytin-1, which is involved in the development and attachment of the placenta during pregnancy. The report claimed that receiving the COVID-19 vaccine would cause the body and immune system to attack the other spike protein (syncytin-1) and harm fertility. These two spike proteins are different. Receiving the COVID-19 vaccine does not affect the fertility of women hoping to conceive, including through in vitro fertilization (IVF).

Further, when Pfizer was testing vaccines, 23 women volunteer participants became pregnant and did not experience issues with fertility because of the vaccine. The only one who tragically suffered a pregnancy loss did not receive the vaccine, instead receiving the placebo.  

Report SARS-CoV-2 spike protein seropositivity from vaccination or infection does not cause sterility published in the American Society for Reproductive Medicine Journal Fertility & Sterility Reports debunks this myth of sterility at the hands of the vaccine.

Randy Morris, M.D. used IVF frozen embryo transfer (FET) to understand the impact of COVID-19 seropositivity (presence of a serological marker for SARS-CoV-2 in the blood) on embryo implantation. He did this by comparing the implantation rates for SARS-CoV-2 vaccine seropositive (received vaccine), infection seropositive (previously infected with COVID-19), and seronegative women. The study found no difference in maternal serum hCG levels after an embryo transfer or sustained implantation rates across the three groups. Serum hCG levels were measured because human chorionic gonadotropin (hCG) is produced by placental syncytiotrophoblasts following embryo implantation and can be used in the early detection of pregnancy.

The research shows that seropositivity to the SARS-CoV-2 spike protein, whether from vaccination or previous infection with COVID-19, did not hinder embryo implantation or the early stages of pregnancy. Neither infection with COVID-19 nor antibodies produced from the vaccine will cause female sterility. Infection with the disease, however, may have an impact on pregnancy and the mother’s health.

“We hope that all reproductive-aged women will be more confident getting the COVID-19 vaccine, given Dr. Morris’s findings that the vaccine does not cause female sterility,” said Hugh Taylor, M.D., president of the American Society for Reproductive Medicine. “This, and other studies of this nature, further reinforce the ASRM COVID Task Force guidance that, no matter where you are in the family-building process, the COVID-19 vaccine is safe and saves lives.”

Sources

https://www.asrm.org/news-and-publications/news-and-research/press-releases-and-bulletins/new-study-reveals-covid-vaccine-does-not-cause-female-sterility/
https://www.sciencedirect.com/science/article/pii/S2666334121000684
https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/covid-19-vaccines-myth-versus-fact
Frozen and Thawed Embryo
Frozen and Thawed Embryo

The importance of the embryologist’s role in embryo freezing, also called cryopreservation, has grown with the rise in pre-implantation genetic testing and “freeze-all” strategies. Embryo cryopreservation and maintenance is considered to be a standalone sub-discipline of reproductive medicine. Embryo cryopreservation allows women undergoing IVF to have just ONE cycle, but continue to have embryos to use in the future. It helps to reduce the risk of Ovarian Hyperstimulation Syndrome (OHS), and allows for the endometrium to fully recover after ovarian stimulation.

History of Cryopreservation

The idea of maintaining the viability of living reproductive cells and tissues of various species and humans for long-term storage has been around for almost 50 years. Dr. Alan Trounson and Linda Mohr achieved the first human pregnancy from a frozen (8 cell) embryo in 1983 and the first live birth, baby Zoe, in 1984. In 2017, Emma Wren Gibson was born from an embryo that had been frozen for nearly 25 years – possibly the longest gap between conception and birth since IVF began.

Overall, embryo cryopreservation has decreased the number of fresh embryo transfers performed, and maximized the effectiveness of IVF cycles.

Vitrification for embryo freezing

Through efforts to constantly improve cryopreservation techniques, we are now able to preserve cells and tissues through a process called vitrification – transforming cells from a liquid state directly to a glass like state. This is done by replacing all the water in cells (dehydration) with a cryopreservation agent, and then by cooling the embryos to extremely low temperatures, such as −195.79°C (the boiling point of the liquid nitrogen). Cooling down biological objects to such degrees prevents any biological activity, including all the biochemical reactions involved in cell death!

Roles & Responsibilities of Embryologists

When cryopreservation methods fail, dreams and families are lost. Several high profile cases of liquid nitrogen storage failures, as well as the selection and transfer of the “wrong” embryo have been nightmare scenarios for the IVF industry. They highlight the embryologist’s important role in cryopreserving and storing embryos. Some of the roles and responsibilities of embryologists are:

Healthy Sperm healthy pregnancy
Healthy Sperm healthy pregnancy. Photo by Laura Garcia on Pexels.com

Sperm Preparation for ART is necessary! When sperm is ejaculated it is surrounded by fluid (seminal 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. 

The density gradient sperm wash is one of the most popular sperm washing methods. This is because it also works to separate dead sperm cells, white blood cells, and other waste products from the sperm. A test tube is filled with multiple layers of liquids of different densities. Semen is then placed on the top layer of liquid and the test tube is spun in a centrifuge. After it is spun, active, healthy sperm will make their way, to the very bottom layer of the liquid in the test tube, while debris and dead sperm will get caught in the top two layers. These layers can be siphoned off, in order to remove the active sperm from the test tube. 

Companies like ZyMot sell specialty devices for sperm preparation and 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.  

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.

Collecting Sperm Samples At Home

Some IVF labs may request that you and your partner collect the semen sample at home. Should patients be worried about the quality of the sample? 
Originally, IVF labs insisted on “on site” collection, due to chain of custody and identification requirements. We want to see your husband/ partner face, match it to their ID, and know that the sample left their body and went straight into our own hands. 
Should you be worried? It depends on the starting quality of the sperm. 99.9% of samples will be absolutely fine. In fact, once the sample makes it into the lab, it’s going to sit and “liquify” anywhere between 20 minutes to an hour or more. If male factor infertility is present, then it’s probably best to be collected in lab. For example, if retrograde ejaculation is suspected, then we need to collect all the urine AFTER the ejaculation event. Sperm are extremely hardy, and in fact they prefer a bit lower temperatures. Room temperature is perfect. Sperm are designed to withstand days in the punishing and selective vagina, cervix, and reproductive tract. The vagina first tries to kill all the sperm with acidic secretions and white blood cells. Then it sets the sperm on a race through a maze (cervix-uterus-fallopian tube), to reach the egg. In the collection cup, the sperm will be protected in the seminal fluid, and nurtured by the sugars present in it. Just follow all the lab instructions, don’t let the cup get too hot or too cold. Deliver it during the right window of time.

Sperm Preparation Techniques for HIV+ Patients

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 from 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 for sperm preparation, 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. 

Male Fertility and Lifestyle Factors

Male Fertility and Lifestyle Factors are present in up to half of couples. The prevalence of male infertility makes semen analysis one of the most important fertility tests, and it should be performed prior to any female therapy. ⁠
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Male infertility means that a man may not deliver the appropriate quantity or quality of sperm to reach and fertilize an egg. Sperm are manufactured in the testicles and travels through the epididymis and the vas deferens when ejaculated. Sperm require three months to develop, which means a semen analysis done today is reflective of the conditions three months earlier. The conditions that originally caused male infertility may no longer be present.⁠ The IVF Lab will gently wash and prepare the sperm for your ART procedure. Each lab has a slightly different method to separate the sperm with the highest motility for use in IVF or ICSI. ⁠

It seems obvious that heavy alcohol drinking can impair sperm production and disrupt hormones in men while in women it can increase the time it takes to conceive. Smoking can damage sperm DNA in men or damage eggs and affect ovulation in women. Fertility specialists often recommend not consuming caffeine and alcohol during fertility treatments. The study “Alcohol and Caffeine Consumption and Decreased Fertility,” published in Fertility and Sterility demonstrates just that. But did you know about these 5 things that can negatively impact male fertility?

1. Did you know drinking soda has been linked with a 20% reduction in the average monthly probability of conception for both men and women? Energy drinks likely have the same effect but require more study (Boston University, Hatch et al.)

2.The following common medications may cause male fertility problems: some antibiotics, spironolactone, cimetidine, nifedipine, sulfasalazine and colchicine.

3. Very common STIs such as chlamydia, gonorrhea, mumps or HIV and other health conditions, such as diabetes, high blood pressure and depression

4. Enlarged veins in the tested (varicocele).

5. Constant exposure to high temperatures, like saunas or hot tubs, laptop computers, or workers exposed to heat stress.

Male Infertility Diagnoses

Sperm Motility
Sperm motility is important in fertility because sperm need to move through the woman’s reproductive tract to reach and fertilize her egg. Poor sperm motility can be a cause of Male Factor Infertility.⁠
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Did you know that infertility due to male factors ranges from 20% to 70% and that the percentage of infertile men ranges from 2·5% to 12% worldwide? Infertility rates are highest in Africa and Central/Eastern Europe. Additionally, according to a variety of sources, rates of male infertility in North America, Australia, and Central and Eastern Europe vary from 4 5-6%, 9%, and 8-12%, respectively.⁠
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The causes of low sperm motility vary, and many cases are unexplained.⁠
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Damage to the testicles, which make and store sperm, can impact the quality of sperm.⁠
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Common causes of testicle damage include:⁠
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infection⁠
testicular cancer⁠
testicular surgery⁠
an issue a man is born with⁠
undescended testicles⁠
injury⁠
The long-term use of anabolic steroids can reduce sperm count and motility. Drugs, such as cannabis and cocaine, as well as some herbal remedies, can also affect semen quality.⁠
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A varicocele is a swelling of the veins that drain the testicle, which can impact sperm quality. ⁠Varicocele has also been associated with low sperm motility.⁠
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Sperm DNA Fragmentation

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.

Sexually transmitted infections

STDs can also cause infertility in men. The process can be similar to how PID damages a woman’s fallopian tubes. The structures of the male reproductive tract, including the epididymis and urethra, can be damaged by infection with an untreated STDs. ⁠Chlamydia and gonorrhea are the first and second most commonly reported notifiable disease in the United States. ⁠
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Sexually transmitted infections (STIs) are common. People who have a STI often have no symptoms. ⁠
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Extremely common STIs like chlamydia, gonorrhea, syphilis, and mycoplasma genitalium can damage the reproductive organs and cause infertility.⁠

Sperm Agglutination

Sperm agglutination refers to the percentage of sperm that stick together. Male infertility is sometimes caused by the male developing antibodies to his own sperm, which increases agglutination in the semen. This usually results after a trauma to the testicles or surgical procedures such as a vasectomy reversal. When present, anti-sperm antibodies can bind to the sperm, essentially interfering with fertilization and motility.⁠
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Ejaculation disorders include premature ejaculation, anejaculation (the failure to ejaculate), and retrograde ejaculation, which is when semen enters the bladder during orgasm instead of coming out the tip of the penis.⁠

Prior vasectomy, inguinal hernia repairs, scrotal or testicular surgeries, prostate surgeries, and large abdominal surgeries performed for testicular and rectal cancers risk, among others.⁠

In some individuals, spermatozoa may not be present in the ejaculate. This condition is called Azoospermia. This can be either due to problems in sperm production itself or due to obstruction to the flow of semen during ejaculation. Reproductive tract obstruction can be acquired – as a result of infection, trauma, and iatrogenic injury which can occur during bladder neck, pelvic, abdominal, or inguinoscrotal surgery.

Congenital anomalies may be relatively uncommon in the general population but can occur in up to 2 percent of infertile men. The best-known condition is the congenital bilateral absence of the vas deferens (CBAVD) which occurs in almost all men with cystic fibrosis.

Two techniques – Epididymal sperm retrieval & micromanipulation have revolutionized treatment of male infertility in the past decade. Men with congenital bilateral absence of the vas defences (CBAVD) or reproductive tract obstruction are now able to achieve pregnancies with use of these advanced techniques.

PESA

PESA or Percutaneous Epididymal Sperm Aspiration (PESA), does not require a surgical incision. A small needle is passed directly into the head of the epididymis through the scrotal skin and fluid is aspirated. The embryologist retrieves the sperm cells from the fluid and prepares them for ICSI.

MESA

Microsurgical Epididymal Sperm Aspiration (MESA) is used in conditions like obstructive azoospermia, involving dissection of the epididymis under the operating microscope and incision of a single tubule. Fluid spills from the Epididymal tubule and pools in the Epididymal bed. This pooled fluid is then aspirated. Because the epididymis is richly vascularized, this technique invariably leads to contamination by blood cells that may affect sperm fertilizing capacity in vitro.

TESA and TESE

TESE or testicular sperm extraction is a surgical biopsy of the testis whereas TESA or testicular sperm aspiration is performed by inserting a needle in the testis and aspirating fluid and tissue with negative pressure. The aspirated tissue is then processed in the embryology laboratory and the sperm cells extracted are used for ICSI.

Cleavage Stage Embryos

Cleavage Stage Embryos, What happens on Day 3 of an IVF Cycle? We take the embryos out of the incubator to feed them (change the media they are growing in) and check on them. We give them grades at this time and update the physician on the status of the cleavage stage embryos. In the IVF Lab, whenever we move eggs, sperm, or embryos to a new dish, the procedure has to be double witnessed. That means, that name, date of birth, and medical record number are confirmed to be the same on the dish they come from, to the cultural dish they are moving to. An electronic witnessing system may create a record of this movement.

By Day 3 of an IVF cycle, we know how many embryos are “cleaving”. We will know if “0PN” and 1PN embryos (see our Embryologist perspective on Day 1: Fertilization Check). have started dividing, or if any of the normally fertilized eggs “arrests” at the 1 cell stage. Cleaving means the cells are dividing symmetrically and exponentially. One cell should become two, and should become 4 and 4 should become 8, 8 should become 16. Day 3 embryo grading systems are based on counting the number of cells. The thought has always been that an even cell number was better than an odd cell number, and that embryos should have between 4 and 8 cells on day 3. Most day 3 embryo grading systems also give a grade for symmetry and fragmentation, and other subjective variables like the the quality and clarity of the cell’s cytoplasm.

Embryo Fragmentation on Day 3

Embryo fragmentation is a fairly common occurrence. It happens when there is an uneven division of the cells of the embryo. These fragments are of no use to the embryo and are considered “junk” pieces of cytoplasm. The higher the degree of fragmentation, the lower the likelihood of pregnancy. However, fragmentation of 0-15 percent is quite normal and those embryos typically do well.

The standard of care in the US is to grow embryos to blastocyst stage and freeze all of them, and prepare the uterus in a separate cycle. Many embryos look good on day 3, but do not go on to become blastocysts. By day 5, you will know what stage they are and that will give you a much better indication of their ability to make a pregnancy. Many clinics in the US have stopped giving day 3 grades to patients because of the stress and anxiety it causes, and the low amount of information contained in those grades.

Embryonic Genome Activation- Why Embryos stop dividing after day 3.

On day 3, something happens called the embryonic genome activation. Up until day 3, the embryo has been nurtured by factors found in the egg cell. By day 3, the name part of the genome has to kick on. This is exactly when we see a “4 cell block” – the embryonic genome often cannot progress. The embryonic genome activation is a process during which the embryonic genome is activated, i.e. when transcription is evident (day 3 of human embryo development, at the 4- to 8-cell stage). Human embryo development begins in relative transcriptional silence with an oocyte to embryo transition that lasts for about 3 days.  

Assisted Hatching on Day 3

Assisted hatching is where an opening is created in the zona pellucida (the outer coating of proteins) of an embryo. Many IVF labs hatch embryos on day 3 in order to create a little opening that some cells of the trophectoderm to grow out of, where they can be snipped off safely and sent out for genetic analysis. Assisted hatching can also be performed on other days and for other reasons.

Mosaicism can start to be detected by day 3, and any chromosomal division that is abnormal at this stage can lead to a significant proportion of cells being abnormal by the blastocyst stage. One blastomere used to be removed at Day 3 for genetic analysis, but tis type of biopsy is no longer common.

ICSI or IVF

IVF and ICSI have many similarities. However, the differences between them are very important. This post is dedicated to defining the differences between IVF and ICSI.

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. There are two techniques used to fertilize eggs during IVF: conventional insemination (simply referred to as IVF) or intra-cytoplasmic sperm injection (ICSI). 

Before a man’s sperm can fertilize a woman’s egg, the head of the sperm must attach to the outside of the egg. Once attached, the sperm pushes through the outer layer to the inside of the egg (cytoplasm), where fertilization takes place.

Sometimes the sperm cannot penetrate the outer layer, for a variety of reasons. The egg’s outer layer may be thick or hard to penetrate or the sperm may be unable to swim. In these cases, a procedure called intracytoplasmic sperm injection (ICSI) can be done along with in vitro fertilization (IVF) to help fertilize the egg. During ICSI, a single sperm is injected directly into the cytoplasm of the egg.

Conventional Insemination:

In this technique, a woman’s eggs are surrounded by sperm in a petri-dish and ultimately one sperm fertilizes the egg. Conventional insemination (IVF) largely recreates the “best sperm wins” dynamic of natural conception. The fear with IVF is that in 10 – 15% of cases, patients experience total fertilization failure (TFF) where none of their eggs fertilize. That seldom happens with ICSI. Performing PGT after IVF is not recommended. Additionally, the embryologist will not know how many eggs were mature at the time of retrieval, or what their quality was.

ICSI:

In this technique an embryologist selects a single sperm from a man’s semen sample and injects it directly into the egg. The chief issue with ICSI is that this microsurgery costs an additional $1,500 – $3,000, can only be performed on “mature eggs” (ruling out ~20% of eggs that are retrieved), 5 – 15% of eggs are damaged in the process, success rates vary by embryologist.

ICSI is used in 90% of IVF cases that involve male factor infertility (issues with the man’s sperm count or motility) and 60% of cases that don’t.

Apart from the way the sperm is introduced to the egg, there are not too many other differences. The egg retrieval and the monitoring of the embryo remain the same. The transfer of the embryo does as well. The success rates for ICSI (50-80%) are higher than IVF without ICSI (50%). This does not however represent the pregnancy rates which are slightly higher for IVF without ICSI (27% vs. 24%). Live birth and birth defect rates have been reported to be quite similar between the methods.

ICSI Vs PICSI

Before a man’s sperm can fertilize a woman’s egg, the head of the sperm must attach to the outside of the egg. Once attached, the sperm pushes through the outer layer to the inside of the egg (cytoplasm), where fertilization takes place.

Sometimes the sperm cannot penetrate the outer layer, for a variety of reasons. The egg’s outer layer may be thick or hard to penetrate or the sperm may be unable to swim. In these cases, a procedure called intracytoplasmic sperm injection (ICSI) can be done along with in vitro fertilization (IVF) to help fertilize the egg. During ICSI, a single sperm is injected directly into the cytoplasm of the egg.

Why would I need ICSI?

ICSI helps to overcome fertility problems, such as:

-The male partner produces too few sperm to do artificial insemination (intrauterine insemination [IUI]) or IVF.

-The sperm may not move in a normal fashion.

-The sperm may have trouble attaching to the egg.

-A blockage in the male reproductive tract may keep sperm from getting out.

-Eggs that did not fertilize by traditional IVF, regardless of the condition of the sperm.

In vitro matured eggs are being used.

-Previously frozen eggs are being used.

Will ICSI work?

ICSI fertilizes 50% to 80% of eggs. But the following problems may occur during or after the ICSI process:

Some or all of the eggs may be damaged.

The egg might not grow into an embryo even after it is injected with sperm.

The embryo may stop growing.

Once fertilization takes place, a couple’s chance of giving birth to a single baby, twins, or triplets is the same if they have IVF with or without ICSI.

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. 

What if your IVF Lab does ICSI, But you want to try conventional IVF? 

It’s in your best interest to do what the clinic does 99% of the time and not try to be one successful person on a procedure they do 1% of the time. Clinics have switched to ICSI for very very good reasons. It increases our patients success rates. It decreases chances of contaminating DNA from sperm during PGT. The embryologist will be able to examine and inject the nicest looking sperm. Think about it this way, you are preparing for the “Olympics” of baby making. We want to do anything in our power to shave 1 second off your timing so you can WIN the gold. A take home baby as quickly as possible. 

Veering from the established standard of care for a lab (any lab) introduces another possibility to the mix; one of them making an error. 

Why are you hesitating? Some people want it to be as natural as possible, but that’s not a good reason. Everything about the lab environment is not natural. Yes, fertilization failures do happen. This is not the thing to leave to chance, as you will get more than enough of that after the embryo is transferred back to your uterus. Allow the lab to do the procedures that give the highest success rates.

Anxiety and Mood Swings

Anxiety and Mood Swings Life’s challenges are part of the human condition and yet none are immune from the ravages of existence. They arise for reasons you cannot comprehend and leave you feeling like a wounded bird, with broken wings.⁠ Is anxiety associated with IVF? Does IVF cause anxiety? Are there certain medications that cause anxiety? ALL those answers can be found in our blog post today!

Anxiety and Mood Swings? Stress, pre-existing depression, and anxiety from not being able to fall pregnant, combined with hormone therapy, invasive time-consuming tests and procedures, and complicated medication schedules all contribute to the stress and anxiety we feel undergoing IVF. While there have been numerous studies documenting the psychological burden of fertility treatment, there have only been a few studies specifically investigating the role of hormones during ovulation induction.

Infertility is often a silent struggle. Patients who are struggling to conceive report feelings of depression, anxiety, isolation, and loss of control. Depression levels in patients with infertility have been compared with patients who have been diagnosed with increased cancer risk. It is estimated that 1 in 8 couples (or 12% of married women) have trouble getting pregnant or sustaining a pregnancy.

Despite the prevalence of infertility, the majority of infertile women do not share their stories with family or friends, thus increasing their psychological vulnerability. The inability to reproduce naturally can cause feelings of shame, guilt, and low self-esteem. These negative feelings may lead to varying degrees of depression, anxiety, distress, and a poor quality of life.⁠ There are science backed ways to improve these feelings, and mindfulness and meditation are proven strategies to help!

Patients who undergo assisted reproductive treatment (ART) are at significant risk of experiencing psychiatric disorders and it is important to recognize, acknowledge, and assist our patients as they cope with their infertility diagnosis and treatment.⁠

Gonadotropin-releasing hormone agonists suppress a woman’s menstrual cycle, effectively causing menopause. GnRH agonists have been associated with depression in women who are taking it to treat endometriosis. A more recent study of the effect of GnRH agonists on mood during its use for ovulation induction did not show an increase in depression. In a study of the effect of clomiphene citrate and human menopausal gonadotropin (stimulates follicle growth), both have been shown to be associated with significant mood symptoms.

Despite many efforts to break the silence on infertility and pregnancy loss, fertility and miscarriage remain taboo subjects.⁠
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Those suffering don’t share their experiences with others. Non-members of the infertility-and-loss club don’t know how to react or what to do when they are told of a friend’s struggle. Some honestly are uncomfortable hearing about it at all.⁠
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The stigma is strong. Why? With 1 in 8 couples experiencing infertility– and up to 25 percent of pregnancies ending in miscarriage – why as a society are we so uncomfortable discussing these relatively common life events?⁠
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Most causes of infertility and miscarriage are not under the direct control of a couple. However, even when a person knows this, the nagging feeling that “this is all my fault” pulls at them.⁠
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Shame can only survive in dark corners.⁠
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It’s time we break the silence on infertility (miscarriage!). It’s time we stop feeling ashamed of medical problems over which we have little control.⁠

De-stress

Take care of yourself to lower stress levels, which appears to increase fertility treatment success.⁠

Most forms of self care focus on a healthier body, which directly translates to a healthier reproductive system.⁠

⁠Focus on what you can do. Live. Right now. Every day. Don’t make this all about the wait. Make it about you. ⁠

Anxiety and Mood Swings, Meditation, and other forms of mindfulness are known to stress relievers, and those who practice mindfulness on a regular basis report being more content, balanced, and physically healthier. ⁠

Scheduling a telehealth appointment with a fertility doctor may be easier than ever before. You may be able to explore some deeper queries that may arise such as donor eggs, sperm, using a gestational surrogate.⁠

Shove the journal articles aside, unplug from the treadmill of infertility and fertility treatment research, tips and information – and enjoy something mindless for a change- magazine or novels!⁠

Take a good walk or hike: Researchers have found spending time outdoors – even just 10 to 15 minutes in a green space or with a view of the trees/landscape immediately decreases stress and anxiety and mood swings, revives dulled minds, and boosts the immune system.⁠

You know that exercising keeps you healthy. It makes you strong and helps you stay in shape. But it also improves your mood and your sleep. It reduces stress and anxiety and mood swings. It helps your brain to function better.⁠

Infertility Warriors, of all people, need a functioning brain. For all the reasons listed above. That’s why you need to move your physical body in this period of waiting. Not too much, not too little. ⁠

If you are following the guidance about things that will put your body in its optimum state to get pregnant — your weight, foods to avoid/eat, cut down/stop drinking alcohol and smoking, cut back on caffeine and take vitamins — you may have a hard time finding ways to treat yourself during your journey. ⁠
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Find some small and special treats that won’t throw off your fertility diet goals- a single macaron, a decadent dark chocolate. ⁠
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Spend time with friends that lift you up and spend time together as a couple.⁠
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Although it may feel like infertility has taken over your life, it doesn’t define you or your achievements in life. You are amazing and strong! ⁠
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⁠Struggling with infertility can be an extremely lonely process. A lot of people struggling don’t tell friends or family, but it is so important to get support from somewhere. Infertility can leave you questioning everything — your future, your relationship, and most crucially your mental health.⁠
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Talking through your thoughts with someone who understands will help validate your feelings and make you feel less alone. It will also help you see more clearly to be able to take positive action to change how you feel and increase your chances of getting pregnant.⁠
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Research has found that feelings of depression and anxiety peak around three years post-infertility diagnosis. However, six years post-diagnosis, couples are feeling stronger, and depression and anxiety symptoms lessen.⁠
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Bromelain to Brazil Nuts- IVF Myths 

IVF Myth No. 1: Eating pineapple core for five days after embryo transfer can up one’s chances of conception.⁠

The fruit contains bromelain, an enzyme with anti-inflammatory, anticoagulant and blood-thinning properties. Much of the bromelain is concentrated in the core. There are a lot of stories about pineapple’s effectiveness, but not a lot of data backing it up. Some fertility doctors prescribe low-dose baby aspirin — also a blood thinner — to help improve blood flow to the uterus, so the idea is that pineapples could mimic that effect. ⁠

IVF myth No. 2: Eating Brazil nuts during the two-week wait can lead to a healthy pregnancy.⁠

Brazil nuts are packed with selenium. One study (published in the journal Metallomics) found that selenium helps promote healthy egg follicles in female cows, and that same study also found that levels of GPX-1 (a protein found in selenium) were much higher in women who got pregnant after a single embryo transfer.⁠

However, too much selenium can be toxic, so stay within the recommended daily allowance typically just 55 micrograms, with the highest maximum amount being 400 micrograms daily. ⁠

Gestational Carriers 

What is a gestational carrier? A gestational carrier (GC), is not the same as a surrogate. A surrogate is someone who donates her egg and then subsequently carries the child; she is genetically linked to that baby. Today, such cases of true surrogacy are very rare. In the case of a gestational carrier, the woman carrying the pregnancy is in no way biologically related to the child she is carrying; the eggs and sperm are derived from the “intended parents” (or possibly an egg or sperm donor), through the process of In Vitro Fertilization (IVF). The egg is fertilized in the lab, and then the embryo (or embryos) is placed into the uterus of the gestational carrier.

– Absent uterus, either congenital, which means you were born with, or from surgery.⁠

– Abnormalities of the uterus such as severe intrauterine scarring from Asherman’s syndrome or multiple benign tumors of the uterus called fibroids ⁠

– If carrying a pregnancy is too risky where the woman or baby’s life would be in danger (Turner’s Syndrome, or pulmonary hypertension, for example). ⁠

Other circumstances to use a GC include a single male, or in the LGBTQ population of a gay male couple, or single transgender female. Lastly, there may be a strong consideration for a GC if the woman has undergone multiple uterine surgeries for example, fibroid tumors, and also cesarean sections, where the uterine muscle may be weakened to result in complications near the end of the pregnancy as well as when recurrent miscarriage is unexplained following a thorough evaluation and multiple treatments.⁠

According to the American Society for Reproductive Medicine, 859 surrogacy and gestational carrier cycles were performed in the United States in 2010.

Natural Cycle FET and Vaginal Progesterone

Once the ovarian follicles have achieved an adequate size and stage of development, a trigger injection is given to induce the final maturation of the eggs. The timing of this injection is very important to the outcomes of your in vitro fertilization (IVF) cycle and needs to be precise. Mini-STIM, Natural Cycle FET, and Vaginal Progesterone. An egg retrieval procedure is then scheduled for 36 hours following this injection.⁠
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When the hCG trigger is administered too early or too late, or too low a dosage of hCG is administered the result can be an increase in the percentage of immature (M-I) or mature M-II (but aneuploid), eggs at retrieval. ⁠

Have you discussed alternate IVF treatments with your reproductive endocrinologist? ⁠

Mini-IVF (also known as micro or minimal stimulation IVF) is similar to conventional IVF in the procedures used during treatment, but mini-IVF uses weaker medications or lower doses of medications to produce only a few eggs. It may also be done without any ovarian stimulating drugs.⁠

Because lower amounts of fertility drugs are used, the cost per cycle is lower, and the risk of ovarian hyperstimulation syndrome (OHSS) is reduced.⁠

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With frozen embryo transfer, it’s crucial that the timing of transfer occur when a woman’s endometrium is receptive, meaning an embryo can implant. The protocols used to prepare the endometrium for embryo transfer vary more than most of us would imagine — there is truly no standardization, and each clinic you visit might approach this in a different way. Patients undergoing FET may not require hormonal supplementation if normal follicular development and ovulation is observed. ⁠

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Mini-STIM, Natural Cycle FET, and Vaginal Progesterone. Doctors usually prescribe progesterone supplementation to start on the day the eggs are harvested. If pregnancy takes place, the doctor may tell you to continue taking progesterone throughout the first trimester. Progesterone can be taken as an intramuscular injection or vaginally (suppositories, gel, or vaginal tablets). There appears to be no difference in the chances of becoming pregnant or continuing a pregnancy if progesterone is given by injection or intravaginally. You should talk to your doctor about which form of progesterone will better fit your needs.â