When you seek the help of a fertility specialist to conceive, your first step is to undergo diagnostic tests to understand your likelihood of success. This is followed by a comprehensive consultation with your doctor to discuss what those test results have revealed. With those answers in hand, you will decide on the best course of treatment together.
If the answer to your fertility challenge is in vitro fertilization (IVF), this next step comes with a whole new set of questions. As a reproductive endocrinologist, the most common question I hear is usually, “How many embryos will I have at the end of this process?” To get to the answer, it’s important to understand the concept of IVF attrition.
What is IVF attrition?
IVF attrition is the rate at which your reproductive material declines or tapers down once it has been retrieved and begun to develop in the embryology lab. In other words, the number of eggs that are retrieved are not likely to result in an equal amount of reproductively viable embryos.
Instead, they will gradually decrease in number as they go from a retrieved egg to a fertilized egg and then through the various stages of embryo development. For example, if 10 eggs are retrieved, but there are only three chromosomally normal embryos at the end of the IVF process, the attrition rate would be 70%.
As hard as this can be to accept, attrition is a completely normal (and expected) biological process. It may feel overwhelming to hear, but this is exactly how conception works in the natural process as well. The vast majority of ovulation cycles do not result in successful pregnancies. With IVF, we simply have the privilege of seeing this natural attrition process happen in real time in the embryology laboratory.
Egg development: menstrual cycle vs. IVF cycle
It all starts with the egg!
In a typical menstrual cycle, several follicles (the fluid-filled sacs that contain the eggs) begin to develop, increase in size and secrete estrogen to begin the maturation process of the egg. One of these follicles becomes dominant and the rest fail to develop (become atretic) and are reabsorbed back into the body. The dominant follicle releases an egg into the fallopian tube during ovulation, which can then be fertilized by sperm.
In an IVF cycle, we stimulate that normal cycle with a special mix of medications which induces the development of multiple dominant follicles in the ovaries (as opposed to just one). After this follicular stimulation phase, we try to maximize the number of viable eggs by “triggering” ovulation at the optimal time, when the highest number of eggs will be mature. The “trigger shot” is the final injection in an IVF cycle before retrieval.
Common medications used to trigger ovulation include Novarel®, Pregnyl®, Ovidrel®, and Lupron®.
The IVF funnel
In the IVF laboratory, the journey from an egg to an embryo with reproductive potential can be viewed as a funnel. The attrition that occurs from eggs to embryos is a natural process. To better understand this concept, let’s break down each stage of an IVF cycle.
Stage 1: Egg retrieval
The first stage of IVF involves stimulating the ovaries with hormones to induce the growth of multiple follicles at the same time. While several follicles may develop, not all will contain mature eggs suitable for fertilization. Each person’s potential to grow many eggs will vary and is known as their ovarian reserve.
After about 10 days of stimulation, the follicular growth phase is complete. Mature follicles measure around 15-25mm in diameter and each one contains a single immature egg. During a minor surgical procedure called egg retrieval, each of these mature follicles are punctured to collect the eggs inside. Each retrieved egg is then sent into the embryology laboratory for assessment.
Some of the retrieved eggs may not be fully developed and therefore unable to receive sperm. This is the first drop-off in the attrition funnel. For example, even if 10 eggs are retrieved, there may only be eight mature. Only mature eggs can successfully fertilize and become a single-celled embryo, known as a zygote.
Stage 2: Fertilization
The retrieved eggs are then exposed to sperm (either a male partner’s or a donor’s) in hopes of fertilization. Fertilization means that the genetic material from the egg and the genetic material from the sperm become one. This new combination of genetic material is the new embryo (zygote).
Fertilization may occur through one of two methods: conventional insemination or intracytoplasmic sperm injection (ICSI). Both methods are very effective and may be used for different reasons:
- Conventional insemination is when the egg is surrounded by thousands of sperm in a small droplet in a petri dish. Hundreds of sperm will then attach to the cells around the egg. Some sperm will reach the outer “shell” of the egg, but only one will merge with the membrane of the egg to deposit its genetic material and complete the fertilization process. This mimics the natural selection process as best we can in a laboratory setting.
- Intracytoplasmic sperm injection (ICSI) is when an embryologist selects a single normally shaped, moving sperm and manually injects it through the shell and membrane of the egg to deliver the sperm’s genetic material and achieve fertilization. ICSI is used for several different reasons, one being male factor infertility.
Either way, we expect that around 80% of mature eggs will fertilize. However, while most mature eggs will fertilize, not all fertilized eggs will develop into viable embryos.
Stage 3: Embryo development
The fertilized eggs, now embryos, are cultured in the IVF laboratory over the next 5-7 days in temperature, humidity, pH-controlled incubators in a solution that provides the necessary nutrients which allow embryos to develop. During this time, they undergo rapid cell division and development. This is another phase where attrition should be expected. After three days, embryos have 6-12 cells. In general, most (if not all) embryos that fertilize will reach this stage.
The greatest attrition occurs between day 3 and days 5 or 7 (the blastocyst stage). However, not all embryos will reach the blastocyst stage, which represents an embryo with the highest likelihood for implantation and a successful pregnancy. A blastocyst is the final stage of embryo growth before we cryopreserve (freeze) them or perform an embryo transfer.
Only 30% to 60% of embryos growing on day 3 will reach the blastocyst stage. A blastocyst is a 100-300 cell embryo that has two cellular groupings—one that will become the placenta and one that will develop into the fetus.
If you’re interested in getting your embryos tested prior to embryo transfer or cryopreservation, a biopsy of the placental grouping will be performed, and the sample will then be sent off for in-depth preimplantation genetic testing (PGT) before the embryos are cryopreserved.
Stage 4: Embryo selection for embryo transfer
After five days of culture in the incubator, an embryologist will carefully assess the developing embryos and select the one(s) that appears to be the most cellularly normal (highest quality) for embryo transfer. Any remaining high-quality embryos not transferred will be cryopreserved for future attempts at pregnancy.
Stage 5: Embryo transfer
Finally, the selected embryo(s) is transferred to the uterus. Even at this stage, not all embryos will implant successfully. Implantation depends on various factors, including embryo quality and uterine receptivity.
Factors affecting attrition
Several factors can influence the degree of attrition in IVF, including:
- Age: Women are born with 1-2 million eggs, but by the time they reach age 30, they only have about 150,000 eggs left. As women age, the quality of those eggs naturally declines, leading to higher rates of attrition typically seen in the embryology laboratory.
- Egg quality: The quality of eggs retrieved plays a significant role in fertilization and embryo development. Certain lifestyle choices can affect egg quality, which means it is important to avoid smoking and other potentially harmful environmental exposure to maximize your reproductive potential.
- Sperm quality: Poor sperm quality can also affect fertilization rates and embryo development. ICSI is used to assist fertilization in these cases, and it is also important for men to work with their doctor to maximize sperm health.
- Embryo quality: Embryos with normal chromosomal makeup (46 chromosomes) have a higher chance of reaching the blastocyst stage and successfully implanting.
- Genetic factors: Chromosomal abnormalities (i.e. having too many or too few chromosomes) can lead to embryonic arrest (when the embryo stops dividing cells or progressing) or failure to implant in the uterus after transfer. There are other factors beyond chromosomes that we do not yet fully understand that relate to the success of any particular embryo.
Chances of pregnancy with IVF
In vitro fertilization (IVF) has come a long way since the first IVF baby was born in the UK in 1978. According to the Society for Assisted Reproductive Technology’s (SART) preliminary 2021 report, women under the age of 35 had an average 54% chance of a live birth per each intended egg retrieval.
In women over the age of 35, that percentage can be lower (around 40.5%), but with advancements in embryo testing and the transfer of a chromosomally normal embryo, the chance of pregnancy is still strong.
To learn more about national averages or compare demographics, visit SART’s website, which also offers an interactive data tool to calculate your cumulative chances of success with IVF.
Managing expectations
IVF attrition may be a difficult concept to grapple with, but the most important thing to know is that this process is natural and expected, regardless of your diagnosis. While it can be disappointing to see the number of eggs and embryos decrease through attrition, focusing on the quality of the remaining embryos is crucial.
Even one embryo at the end of an IVF cycle offers you an excellent chance at a healthy pregnancy, and the sooner you begin your fertility treatment journey, the better your chances are of getting more high-quality embryos.
Always discuss your individual attrition rates with your fertility specialist. Understanding the factors that may be contributing to attrition can help you make informed decisions about treatment options, such as genetic testing, donor eggs or alternative fertility treatments.
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