IVF and ICSI have many similarities. However, the differences between them are very important to note as you make a decision about your treatment path.

What is conventional Insemination (IVF)?

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. 

Fertilization by insemination relies on the normal healthy functions of the sperm as well as for the egg’s outer layer to be optimal. An egg’s outer layer may be thick or hard to penetrate due to egg quality or maternal age related issues.

And let’s face it, if both the sperm and egg were optimal, you may not need the assistance of IVF to conceive in the first place. 

A few other downsides to conventional insemination are:

• 10 – 15% of cases, patients experience total fertilization failure (TFF), when none of their eggs fertilize.
• Performing PGT after conventional IVF is not recommended
• Embryologist will not know how many eggs were mature at the time of retrieval, or what their quality was.

These are all things that are important to know to help diagnose your case and help plan for the next steps in your journey.

What is ICSI?

In this technique an embryologist selects a single sperm from a man’s semen sample and injects it directly into the egg. ICSI is used in 90% of IVF cases that involve male factor infertility 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. 

Another 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.

The success rates for ICSI (50-80%) are higher than IVF without ICSI (50%). Live birth and birth defect rates have been reported to be quite similar between the methods, but ICSI is especially important for couples who want to have their embryos genetically tested.

The downsides to ICSI is:

• This microsurgery costs an additional $1,500 – $3,000. I
• t can only be performed on “mature eggs” (ruling out ~20% of eggs retrieved).
• 5 – 15% of eggs are damaged in the process.
• Success rates vary by embryologist.
• Pregnancy rates are slightly higher for IVF without ICSI (27% vs. 24%). 

Why would I need ICSI?

ICSI helps to overcome fertility problems, such as Male Factor issues where fertilization previously seemed impossible, to now be achieved if…

• 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 that keeps sperm from getting out.

ICSI allows embryologists to look at the eggs and know the quality and maturation right after the egg retrieval, and determine if egg quality issues are present. ICSI helps…

• Eggs that did not fertilize by traditional IVF, regardless of the condition of the sperm.
• History of eggs in previous cycles having low fertilization rates using traditional IVF.
• If in vitro matured eggs are being used.
• If previously frozen eggs are being used.

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

It’s in your best interest to do what your clinic does 99% of the time. Clinics have switched to ICSI for very very good reasons. It increases their patients’ success rates and decreases chances of contaminating DNA from sperm during PGT. The embryologist will be able to examine and inject the nicest looking sperm.  

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

With all of this said, speak to your clinic about their success rates for women or couples with similar age and diagnosis. This will help you get a better understanding at what is best for you.

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A normal embryo (that is euploid) has 23 pairs of chromosomes and has a better chance at leading to a successful live-birth than an 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. ⁠

And then there are mosaic embryos, which consist of both euploid and aneuploid cells. 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. About 10-15% of all embryos are mosaic.⁠

Up to three types of preimplantation genetic testing can be performed on embryos during the IVF process.

• 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

How is PGT performed?

PGT begins with a biopsy of an embryo in the blastocyst stage of development. The biopsy removes 3 to 10 cells from the outer layers of cells that will become the placenta.

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 and results are typically returned in a week to 10 days.

A study by Cimadomo et al. (2018) showed that inconclusive results occur about 1.5-5% of the time. This happens 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.⁠

Do you need PGT?

PGT-A, CCS, or PGS is a diagnostic tool to tell your fertility doctor which embryos are likely to be chromosomally normal and therefore, which to transfer.⁠

As women age, the chance of a chromosomally normal embryo declines. On average, under age 30, roughly half of the embryos will be normal. Over age 40, 1/3 to 1/2 of all women will not find a viable embryo after PGT-A.⁠

Euploid (normal) embryos are most likely to lead to living birth and should be transferred first. Embryos that are mosaic can still lead to living birth, but depending upon the type, do so less often, and carry some risk. Embryos that are aneuploid almost never lead to live birth and if they do, carry a major risk the child will be unhealthy.⁠

PGT typically costs $5,000, but can help to avoid:⁠

• FailedFET (each costs $3,000 to the patient)⁠
• Miscarriages ⁠
• Multiple gestation births from transferring back more than one embryo. 

The current data do not support the universal use of PGT-A for all patients undergoing IVF. Depending on where you live in the world PGT may not be offered as a regular service by your clinic. For example, some countries require that a known genetic issue exist in order for PGT to be carried out. 

If you are someone who produces very few blasts, your clinic may not want to take the risk of PGT or the freezing and thawing process damaging the embryo. They therefore may opt to do a fresh transfer instead. 

As always, discuss your options and concerns based on your specific diagnosis with your practitioner.

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Whether the freeze-all embryo strategy does increase IVF success rates is still up for debate. Over 11 clinical trials and 5000 eligible subjects later, eFET was found to be 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. 

But, 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 Embryos over a Fresh Transfer strategy to reduce this poor outcome. 

Who should consider a “Freeze-all” Embryo Strategy?

According to RBMO, Depending on the clinical setting, IVF deferred frozen embryo transfer could provide significant advantages over fresh embryo transfer for the following reasons: 

If you’re at Risk for OHSS: 

The first obvious candidate based on the above data are women who are at risk for OHSS (ovarian hyperstimulation syndrome). Mild OHSS happens in up to a third of all IVF cycles while more moderate to severe OHSS happens only 3 percent to 8 percent of the time.

OHSS is often seen in women with PCOS or high responders. Women with over 25 eggs retrieved are more likely to suffer from severe OHSS.

If you have known endometrial anomalies:

Thin endometrium, polyps, associated metrorrhagia, submucosal leiomyomas and endometritis, or elevated progesterone levels on the last day of stimulation, a freeze-all should be considered as surgery or a long lupron protocol may be required before transfer.

If you are using PGT:

If you have known genetic issues or are looking to rule them out and increase your implantation success with PGT, you will be required to freeze all embryos as you wait for the test results.  

Endometrial receptivity:

Ovarian stimulation with IVF and intracytoplasmic sperm injection (ICSI) cycles may have a negative effect on endometrial receptivity due to higher estrogen and progesterone levels. If you receptivity is in question, an ERA test may be recommended before you transfer your embryos, and therefore a freeze-all strategy would be implemented.

If you have a day 6 or 7 Blastocyst:

A recent meta-analysis, the transfer of day-5 blastocysts was associated with significantly higher pregnancy rates compared with the transfer of day-6 blastocysts as the intrinsic embryo implantation potential in day-6 blastocysts is impaired (Bourdon et al., 2020a), an asynchrony between the endometrium and day-6 blastocysts is also a possibility, reported significantly lower live birth rates in fresh day-6 compared with fresh day5 blastocyst transfers, whereas this difference was not found with frozen embryo transfer 

If you’ve had a failed Fresh Transfer:

Freeze-all strategy increases the chances of a live birth in women with repeated IVF/ ICSI failures. Women with at least one failed fresh blastocyst transfer have a significantly greater probability of a live birth with the ‘freeze-all’ and subsequent thawed approach than with another fresh cycle 

If you are at high risk of a thromboembolic event:

Fresh transfers are associated with an increased risk of thromboembolic diseases (pulmonary embolism and venous thrombosis), with a doubling of risks during pregnancies than those who conceive naturally or with a FET. That’s because a fresh embryo transfer is preceded by an elevated level of oestradiol and consequently a hypercoagulation state. Therefore, a freeze-all strategy could be the best option to limit the thromboembolic risks induced by ART treatments in women who are at high risk of a thromboembolic event.

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You’ve been so INVOLVED up to this point. Administering shots and going to your checkups made you feel “in control” (even if that is an illusion). But then you arrive at the clinic for retrieval, and it’s all out of your hands. 

It’s even out of your physician’s hands. Your eggs are about to pass through a tiny window, into the hands of an embryologist you have never met. 

You are usually asked to arrive at your clinic two hours ahead of your retrieval. You will be asked to fast for at least 12 hours. Once you get checked in and changed into a not-so-fancy robe, you’ll be asked to empty your bladder before being wheeled into the operating room.

What happens in prep for Egg Retrieval? 

The Embryologist will do a “time out” through the tiny window that leads to the sterile lab. They will confirm your name, date of birth and IVF cycle plan with the physician. Then you will start to go under, as the anesthesiologist puts you “to sleep”. 

After you are comfortably asleep, the nurses, medical assistants and physician will drape all of your exposed skin with soft sterile towels. The vagina is washed and prepped for the ultrasound guided transvaginal oocyte retrieval. The physician positions the gooseneck light, and the OR lights are turned down low for the retrieval to begin!

What happens during Egg Retrieval?

In short, the Embryologist goes hunting for eggs. They look for eggs in every shape and size and depend on eggs being surrounded by a nice “cloud” of fluffy, nurturing cumulus cells. 

In general, your last scan tells your physician and embryologists how many eggs to expect. They make that determination based on the number of follicles over 14 mm. They are also seeing if the “small” follicles did or did not hold a mature egg.

As the tubes of follicular fluid are handed through the window, they are taken into a dark, warm, and humid environment. They then pour the fluid into a petri dish and start examining it closely under a microscope. As an Embryologist finds eggs, they count to your clinical team; One, Two, Three, and so on. 

Mostly, the number of eggs expected are retrieved and sometimes, you get a huge surprise and get more eggs than expected! Occasionally, there are retrievals that yield no eggs. There are several reasons that can occur; something went wrong with the stimulation protocol. Maybe only one egg was expected, but it can’t be found. Perhaps the patient didn’t time the trigger correctly or the surgery started late and the patient ovulated, or the trigger didn’t “absorb” properly. Maybe it’s a rare case of empty follicle syndrome. Whatever the cause, “no egg” retrievals are devastating.

At the same time as your retrieval is happening, the sperm for your egg insemination is being processed. Maybe it is being thawed, or in the case of fresh samples, it is being separated from the semen of the ejaculate and being prepared so the best most “motile” sperm will be available for later use.

What happens in the lab post Egg Retrieval?

After the eggs are collected they are washed, and sometimes they rest in the cumulus cells in an incubator hoping for any last – or slow maturation to happen, before they are processed further. 

In conventional IVF the eggs stay in the cumulus until they are combined with sperm cells. But if ICSI will be performed, then they are “striped” of the cumulus cells, graded, and their quality assessed. 

On average, about 80% of the eggs that are retrieved will be mature enough to fertilize. To assess egg maturity and quality, an embryologist dissolves the cumulus cells from around the eggs with an enzyme. Then gently swish each egg cell up and down in a tiny pipette, about the width of a sharp pencil lead. In the end they only want to see one single, clean cell- THE EGG!

Then only the mature and healthy eggs are then separated for fertilization. Mature eggs are referred to as “MII” ie. “meiosis two” ready oocytes. Besides seeing nice mature MII oocytes, the lab may see slightly immature eggs, called MI (Meiosis I) or very immature eggs called “GV” (ie geminal vessicle). Unfortunately, sometimes we see eggs that have fractured zonas, or are severely compromised due to vacuoles, dented cyctoplasm, or other abnormalities. 

Whether you and your physician opt for ICSI or conventional IVF, or if your lab only offers ICSI, your eggs will be combined with your partner or donor sperm within a few hours of the egg retrieval. This is referred to as “insemination” and it is not the same as fertilization. 

To learn more about insemination and your choices of ICSI or IVF, click here.

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