What exactly is egg freezing?

Planned egg freezing — also known as planned oocyte cryopreservation (OC) or oocyte cryopreservation for anticipated gamete exhaustion (OCAG) — is a fertility preservation method where multiple unfertilized eggs are removed from the ovaries, then cryopreserved and stored for future use.ⁱ It is different from embryo cryopreservation, which refers to freezing fertilized eggs.ⁱⁱ Eventually, the unfertilized eggs (also called oocytes) will be used for in vitro fertilization (IVF).

Planned egg freezing was considered experimental until 2013, when the American Society for Reproductive Medicine (ASRM) published guidelines stating that pregnancy rates and safety data from studies supported planned oocyte cryopreservation.ⁱⁱⁱ It is one route used by females who wish or need to delay a pregnancy, or who are donating eggs for future use.

Who might opt for egg freezing?

There are several instances where an individual might consider egg freezing:

• Before undergoing a fertility-impacting procedure: Certain medical procedures and treatments can negatively affect fertility, such as radiation or chemotherapy for cancer. Some surgeries can also damage the ovaries.^iv
• ^‍When there is a medical condition affecting pregnancy: Medical conditions such as sickle cell anemia or lupus are known to cause pregnancy complications. In those cases, eggs may be frozen for future use with a gestational carrier, or for the patient to use when their condition stabilizes or improves, or to increase the likelihood of successful pregnancy.
• ‍Before a female-to-male gender transition: Patients may wish to freeze eggs prior to starting hormone replacement therapy or undergoing affirmation surgery, which can lead to sterility.
• ‍When family or personal medical history may affect fertility: Individuals who suspect they may experience early or premature menopause (menopause occurring before 40 years of age), or have Turner syndrome (a chromosomal abnormality that can cause ovarian failure), or a known genetic condition that may lead to primary ovarian insufficiency might benefit from egg freezing.^v
• ^‍To protect pregnancy options in the future: People who are not ready to start a family but are concerned about an age-related decline in fertility might choose egg freezing, then attempt pregnancy at a later date.

What is involved in the egg freezing process?

The process for freezing eggs is the same as the early steps of IVF, though the paths diverge after eggs are retrieved from the ovaries. The eggs will not be fertilized with sperm before being frozen.^vi

Screening

First, the patient needs to be screened to make sure they are a suitable candidate for egg freezing. Blood tests are used to estimate ovarian reserve, or the total number of eggs and follicles that remain in the patient’s ovaries. Some tests that might be performed include follicle-stimulating hormone (FSH) and/or anti-Müllerian hormone (AMH), which can estimate the number of remaining eggs in the ovaries. A transvaginal ultrasound can also be used to identify and count the number of follicles that have reached a size between 2 to 10mm; this is known as an antral follicle count (AFC) and will help determine how well a patient may respond to ovarian stimulation medication used in the egg freezing process.^vii Finally, the physician will screen for conditions such as human immunodeficiency virus (HIV) and hepatitis B and C, and for hormone imbalances that can affect fertility such as hypo- or hyperthyroidism and hyperprolactinemia.

Ovarian stimulation

Once ovarian reserve has been assessed and the initial screening tests have been performed, patients will undergo the stimulation process to facilitate egg retrieval. Sometimes, fertility physicians recommend a priming protocol prior to ovarian stimulation.

Ovarian stimulation (OS), also known as controlled ovarian stimulation (COS), involves giving an individual a series of fertility medications to encourage the ovaries to produce multiple mature eggs that can then be retrieved. The fertility drugs and medications used for ovarian stimulation vary depending on individual factors and are usually self-injected at home.

Triggering

OS continues until about 36 hours prior to egg retrieval, when the final maturation of eggs is induced with one last injection referred to as the “trigger.” The trigger prompts the eggs to prepare for ovulation in a carefully timed sequence.

Egg retrieval

Then, before the patient ovulates, the mature eggs are retrieved in an outpatient procedure called oocyte retrieval or follicular aspiration.^viii During this procedure, eggs are removed by a doctor using a hollow needle that is inserted through the vagina, guided by a transvaginal ultrasound, while the patient is under local anesthetic or mildly sedated. The egg retrieval process itself takes half an hour or less.

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How many eggs are retrieved for egg freezing?

There is limited data as to the optimal number of eggs that should be obtained. Accordingly, the most recent ASRM guidelines do not specify a target number of eggs that should be retrieved.^ix

During egg retrieval, doctors remove as many mature eggs as possible to increase the chances of a successful pregnancy and live birth in the future.^x The eggs are inspected by the embryologist to determine if they are mature, because in most cases only mature eggs have the potential to be fertilized in the future.

Once eggs are retrieved, they are stored in liquid nitrogen at -190°C in a flash-freezing process known as vitrification.^xi It is up to 1,000 times faster than “slow freezing,” the process that used to be preferred by clinics.^xii Through vitrification, eggs survive at a higher rate and are more likely to be successfully fertilized and implanted, then lead to a successful pregnancy.^xiii

In one recent study with 231 patients, there was an average of 10 mature eggs obtained per retrieval. Among the oocytes that were thawed and used for IVF, there was a 68.8 percent fertilization rate.^xiv

For more information, read “What are the success rates of egg freezing?” below.

What happens after eggs are thawed?

When it is time to use the eggs, they are warmed up before being fertilized with sperm. Intracytoplasmic sperm injection (ICSI), where a single sperm is injected directly into an egg to increase the chance of fertilization, is recommended for previously cryopreserved eggs.^xv The sperm can come from a partner or from a sperm donor.

Eggs that are fertilized become embryos and are typically cultured for three to five days into a more advanced developmental stage before being transferred into the uterine cavity.

What are the success rates of egg freezing?

Most frozen eggs survive the egg thawing process; freezing with liquid nitrogen offers a thaw survival rate of about 90 percent.^xvi Rates vary by clinic and most clinics track their data.

The younger the egg-freezing patient is, the more likely each frozen egg will result in a live birth. Outcomes are best with donors in their 20s or early 30s for two reasons: females in these age groups have more eggs remaining in their ovaries, and their eggs are less likely to have chromosomal abnormalities.^xvii

One study, which included 128 IVF treatment cycles and 1,283 vitrified oocytes, analyzed live birth efficiency per warmed oocyte and stratified it by age. Females under 30 years of age had a live birth efficiency of 7.4 percent per vitrified/thawed oocyte compared to 5.2 percent for females older than 38 years of age.^xviii These numbers suggest that more harvested eggs would be required amongst females older than 38 years of age to achieve a live birth.

The authors further estimated how many mature oocytes would need to be frozen to achieve a 70 percent chance of live birth:^xx

• Females aged 30 to 34 would need to freeze 14 mature oocytes
• Females aged 35 to 37 would need to freeze 15 mature oocytes
• Females aged 38 to 40 would need to freeze 26 mature oocytes

The ASRM’s most recent guidelines suggest that individuals should be counseled that live birth rates for embryo transfer are better when oocyte cryopreservation is performed in younger versus older females; however, there is not enough data to suggest an optimal age for planned cryopreservation. Some centers may place stricter age-related limits on egg cryopreservation, while others may offer egg freezing to older patients.^xxi

What is the difference between egg freezing and embryo freezing?

Egg freezing involves the cryopreservation of mature oocytes. Embryo freezing, on the other hand, cryopreserves embryos (mature oocytes that have been retrieved and then fertilized with sperm).

Females may opt for egg freezing instead of embryo freezing if they do not have a sperm-providing partner or sperm donor at the time of their cryopreservation. In the future when they desire a pregnancy, they can choose to use the sperm of a partner or donor. Egg freezing also allows the patient to have complete control over the planned use of their eggs, as compared to embryo freezing where both parties providing genetic material may have opinions about if and how the embryos are used to achieve pregnancy.

One advantage of embryo freezing is that it enables fertility specialists to better assess the quality of the eggs upfront by evaluating how many of them successfully fertilize. This analysis may help patients have a better idea of how many oocytes and cycles might be needed to achieve pregnancy in the future. As the oocytes used in egg freezing are not fertilized, any predictions about the number of oocytes needed to achieve a pregnancy are based only on available data related to a patient’s age, not on the actual fertilization rate of an individual’s eggs.

What are the risks of egg freezing?

Most of the risks and side effects of egg freezing are similar to those experienced during IVF. Side effects relating to the hormones used during ovarian stimulation can include fatigue, nausea, headaches, breast tenderness, bloating, and mood swings.^xxii

Like a full IVF cycle, there is also a risk of developing ovarian hyperstimulation syndrome (OHSS), where the ovaries enlarge significantly, and fluid can leak into the abdominal cavity.^xxiii Most cases are mild or moderate, and patients experience pelvic or abdominal pain, abdominal bloating, nausea, and vomiting. In less than 2 percent of cases, OHSS can become acute and can lead to severe abdominal pain, rapid weight gain and abdominal distention, kidney failure, blood clots, shortness of breath, and, in very rare cases, death.^xxiv

The egg retrieval process itself can cause mild pelvic and abdominal pain for a day or two. Other complications are rare but may include bleeding, infection, or damage to the bowel, bladder, or blood vessels.^xxv

Some patients with a history of estrogen-sensitive cancers (certain breast or endometrial cancers, for example) may be given different ovarian stimulation medications because standard protocols may increase risk for cancer recurrence. Data suggests that stimulation with these alternate regimens is safe,^xxvi but the research in this area is limited.^xxvii

How are frozen eggs stored?

While regulations vary by country, the U.S. currently has no limit on how long eggs or embryos can be frozen or stored. The annual cost for storing frozen eggs starts at approximately $600.^xxviii Frozen egg storage fees should be agreed with a clinic before the procedure.

What happens to unused eggs?

If an individual decides not to use their frozen eggs, or has excess eggs, they have a few options:^xxix

• They can ask the clinic to dispose of the eggs at any point.
• They can donate the unused eggs to someone they know, or to anonymous individuals through the fertility clinic or a donor agency.
• They can donate unused or excess eggs for scientific purposes, such as for stem cell research.

Some clinics will return the eggs to their owners if desired.

Conclusion

Egg freezing does not always result in an eventual live birth; however, it remains a valid option for many people including females undergoing fertility-impacting medical treatments and females who are not yet ready to have a child. Individuals interested in using egg freezing to preserve fertility should speak to a physician about their options, and then use that information to make an informed decision.