In vitro fertilization (IVF) has resulted in the birth of more than 8 million babies since the first “test tube baby,” Louise Brown, was born in 1978. But despite years of ongoing research and progressively increasing success rates, unfortunately IVF doesn’t guarantee a healthy pregnancy and live birth. In fact, many people/couples often spend thousands of dollars completing multiple unsuccessful IVF cycles in hopes of bringing home at least one healthy baby.

But why does IVF sometimes fail? To answer this question, we need to learn more about the “IVF funnel,” which illustrates the average drop-off rate at each stage of an IVF cycle. Keep in mind that these are average rates, and many factors must be considered when calculating your unique chances of success at each step of the IVF process. Now let’s get started…

Stage 1: The Egg Retrieval (⬇ 20-30%)

After you administer ovarian stimulation medications for a few days to grow the follicles, you’ll be instructed to administer a medication that triggers ovulation. Your egg retrieval will be scheduled 35-36 hours after that. The goal of these meds is to cause multiple eggs to mature inside the follicles (fluid-filled sacs) in your ovaries so multiple mature eggs can be retrieved for IVF.

It is possible to predict how many eggs will be retrieved based on:

  • The estradiol (E2) level on the day the trigger medication is administered (though certain medications can alter this level)
  • The number of follicles that are >16mm in diameter on the day of trigger
  • Your age and AFC (antral follicle count, which is the number of follicle seen on ultrasound at the beginning of your cycle)

However, these values cannot definitively guarantee how many eggs will be retrieved. For example, roughly 20% of large follicles will not contain an egg at retrieval (these are known as empty follicles). However, the number of eggs retrieved is not what truly matters, but rather the number of retrieved eggs that are mature.

An egg is considered mature if it’s progressed to a stage of development that allows it to be fertilized by a sperm. Eggs that are not mature cannot be fertilized. On average, only 70-80% of eggs that are retrieved are mature.

It’s important to remember that only one egg typically matures in a menstrual cycle, so it’s not unexpected that a small percentage of eggs will not properly develop even under the influence of IVF medications.

Eggs maturity is evaluated prior to egg freezing or intracytoplasmic sperm injection (ICSI), but not conventional insemination.


Stage 2: Insemination (⬇ 20-50%)

Eggs are inseminated on the same day that they’re retrieved or thawed. As I explained, eggs must reach a certain level of development (be mature) in order to be fertilized by sperm.

There are two types of insemination that can be performed in IVF:

  • Conventional insemination: Eggs and sperm are placed into a drop of culture medium (fluid) overnight. The hope is that one sperm will fertilize each mature egg in a process similar to natural conception. Eggs are not graded based on their maturity prior to conventional insemination. On average, conventional insemination has a 50% fertilization rate. However, it’s not recommended in cases of male factor infertility or previous fertilization failure. There is also a higher chance of fertilization failure (having no eggs fertilize) with conventional insemination versus ICSI.
  • Intracytoplasmic sperm injection (ICSI): One single sperm is injected into each mature egg to force insemination to occur. ICSI is only performed on mature eggs and has an average fertilization rate of 50-80%. ICSI is currently the most common method of insemination in most IVF labs.

It’s important to note that not all inseminated eggs will fertilize normally with either method of insemination, hence the drop-off rate of 20-50% at this stage. 


Stage 3: Embryo Development (⬇ 50-70%)

Quick science lesson: fertilized eggs consist of one cell, but that single cell undergoes a process known as mitosis, or cell division, by day 2 of development (2 days after insemination). During this process, the cell will replicate its DNA (genetic material) and divide into two cells with identical DNA. These two cells then undergo mitosis to create four cells, and so on.

By day 3, an embryo is expected to have 6-12 symmetrical cells (8+ is ideal) with less than 20% fragmentation. Embryos that display abnormal development often do not continue developing properly. On average, around 60-80% of fertilized eggs will still be developing by day 3.

While some labs observe and transfer embryos on day 3, many labs wait until day 5. At this point, the embryo should enter the blastocyst stage of development. If an embryo is still developing on day 5 but requires more time to develop further, it can be cultured for another day or two (depending on your lab’s protocol). If an embryo has not developed by this point, it’s considered arrested or non-viable. 

On average, only around 30-50% of embryos that were developing on day 3 will continue developing into usable blastocysts by the end of the IVF cycle. These embryos can be transferred into the uterus, biopsied for PGT, and/or frozen (cryopreserved).

There are many reasons why embryos do not develop properly, including:

  • Genetic abnormalities within the egg, sperm, and/or embryo
  • Egg and/or sperm quality issues
  • Intrinsic issues inside of the embryo, such as impaired mitochondrial function
  • Suboptimal culture conditions (in the lab)

Stage 4: Preimplantation Genetic Testing for Aneuploidy (PGT-A) (⬇ 45-90%)

Embryos that reach the proper stages of development and have normal appearances can be biopsied for PGT. The most common type of PGT is PGT-A, which determines the percentage of an embryo’s cells that have the right number of chromosomes (the right amount of DNA).

Typical PGT-A results are as follows:

  • Aneuploid are embryos that have a high percentage of cells with the wrong amount of DNA 
  • Euploid are embryos with a high percentage of cells with the right amount of DNA
  • Mosaic embryos consist of a combination of cells with the correct and incorrect amount of DNA 

Aneuploid embryos often result in failed implantation, early miscarriage, and other pregnancy complications or birth defects, and aren’t recommended for transfer. The likelihood of aneuploidy increases as the age of the mother (or egg donor) increases, but sperm quality, embryo morphology (appearance), and an embryo’s rate of development also play a role in embryo aneuploidy.

A large retrospective study calculated the chances of having at least one euploid embryo in an IVF cycle based on maternal age and found that:

Age at retrieval (years)

% of cycles with at least one euploid embryo

35

85

40

75

45

45



The same study examined the average number of euploid day 5 embryos obtained per one IVF cycle based on maternal age. These results found:


Age at retrieval (years)

Avg # of embryos sent for PGT testing per cycle

Avg. # of day 5 euploid embryos per IVF cycle

35

5

3

40

4

2

42

4

1

45

< 3

0.5



Finally, this study showed that:


Age at retrieval (years)

% of embryos expected to be euploid

30-35

~60

40

~40

42

~30

45

~10


As these studies show, in general, the younger a woman is at the time of her egg retrieval, the more likely her embryos are to be genetically normal. 

Stage 5: Embryo Transfer and Pregnancy Rates (⬇ 51-77%)

The final stage of an IVF cycle is an embryo transfer, which involves transferring an embryo from a culture (petri) dish into yours or your surrogate’s uterus.

There are many factors that contribute to the success of an embryo transfer, including:

  • The quality of the embryo(s) being transferred, as well as its genetic makeup (euploidy) and rate of development
  • The uterine environment
  • Other systemic factors (blood clotting disorders, immunologic issues)

It’s hard to estimate your personal chance of success following an embryo transfer. The 2020 Society for Assisted Reproductive Technology (SART) National Summary Report calculated the following transfer rates based on maternal age (the woman’s age at the time of retrieval). This did not take into account the embryos’ grades, genetic makeup, rate of development, etc.


Age at retrieval (years)

Implantation rate (%)

Live birth rate 

Mean # of embryos transferred 

<35

51.5

54.5

1.2

35-37

45.4

39.8

1.2

38-40

36.2

26.1

1.4

41-42

21.9

12.7

1.7

>42

8.3

3.9

2.0



This 2021 data from the CDC calculated the percentage of transfers that resulted in a live birth:


Age at retrieval (years)

% of embryo transfers that resulted in a live birth

<35

49.1

35-37

44.8

38-40

40.2

>40

24.4


Some factors that increase transfer success rates are:

  • Transferring a good quality embryo
  • Transferring into an optimal uterine environment
  • A history of successful pregnancies 
  • Maternal age at the time of egg retrieval

Final thoughts about the IVF funnel

As you know now, completing an IVF cycle does not guarantee a healthy live birth, but don’t be discouraged because all of these attrition rates are averages. It’s very possible for someone with few retrieved eggs to still have a successful cycle, just as it is possible for someone with many eggs retrieved to not have a successful cycle. Success rates depend on a lot of factors, so I always recommend asking your doctor what your particular success rate is at your IVF clinic.

Also, it’s possible to have one failed IVF cycle and a subsequent successful cycle, so don’t get discouraged if your first cycle doesn’t work. There are sometimes changes that can be made to medications and other factors that can potentially change outcomes in future cycles.

It takes an average of 2.5 IVF cycles to achieve a pregnancy, so it’s important to set realistic expectations. Though many people find success with IVF, not everyone does. Try not to compare your results to others since everyone’s bodies, medical histories, and journeys are very different.

Again, there are no guarantees in IVF, but if you’re looking for ways to improve your success rates, lifestyle modifications are the most evidence-based approaches, such as:

  • Maintain a healthy diet
  • Drink plenty of water
  • Get plenty of sleep
  • Try to avoid stress
  • Talk with your doctor about supplements that may help improve egg and/or sperm quality
  • Make sure that you have had a workup done to rule out any conditions such as PCOS, uterine polyps or fibroids, as well as abnormal sperm production in the male partner
  • Keep up with your overall health so your hormones are balanced
  • Maintain an exercise routine and a healthy weight

And perhaps most importantly: Do your research! Learn about fertility and reproduction from reputable sources (like Dandi!) and ask your doctor questions about whatever you don’t understand. Good luck!


References:

IVF: Conventional insemination or ICSI? FertilityIQ. Retrieved from https://www.fertilityiq.com/fertilityiq/ivf-in-vitro-fertilization/conventional-insemination-or-icsi

Preimplantation Genetic Testing. The American College of Obstetricians and Gynecologists. (2020). Retrieved from https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/03/preimplantation-genetic-testing#:~:text=The%20main%20purpose%20of%20preimplantation,embryos%20for%20whole%20chromosome%20abnormalities.

Demko Z., Simon A., McCoy R., et al. Effects of maternal age on euploidy rates in a large cohort of embryos analyzed with 24-chromosome single-nucleotide polymorphism–based preimplantation genetic screening (2016). https://linkinghub.elsevier.com/retrieve/pii/S0015028216000662 Retrieved from https://www.fertstert.org/article/S0015-0282(16)00066-2/fulltext

Robles, A. Follicles: What Are They & What Is A Good Number For IVF? (2023). Retrieved from https://alexroblesmd.com/follicles-for-ivf/

Greco, E., Greco, P. F., Listorti, I., et al. (2024). The mosaic embryo: what it means for the doctor and the patient. Minerva obstetrics and gynecology, 76(1), 89–101. https://doi.org/10.23736/S2724-606X.23.05281-8. Retrieved from https://pubmed.ncbi.nlm.nih.gov/37427860/

Society for Assisted Reproductive Technology (SART). Final National Summary Report: Live births per intended embryo transfer (2020). Retrieved from https://sartcorsonline.com/Csr/Public?ClinicPKID=0&reportingYear=2020&newReport=True

 U.S. Department of Health & Human Services. Fact Sheet: In Vitro Fertilization (IVF) Use Across the United States (2024). Retrieved from

https://www.hhs.gov/about/news/2024/03/13/fact-sheet-in-vitro-fertilization-ivf-use-across-united-states.html

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