What exactly is egg freezing?

Planned oocyte cryopreservation (OC), also known as oocyte cryopreservation for anticipated gamete exhaustion (OCAG) or planned egg freezing — is a fertility preservation method where multiple eggs are removed from the ovaries and stored for future use.ⁱ A woman who wishes to or needs to delay a future pregnancy, or who is donating eggs for future use, may opt to freeze oocytes. Planned egg freezing was considered experimental until 2013, when the American Society of Reproductive Medicine (ASRM) published guidelines stating that pregnancy rates and safety data from studies supported planned oocyte cryopreservation.ⁱⁱ‍

The process of oocyte cryopreservation (egg freezing) refers to the harvesting of unfertilized eggs which are then frozen for later use for in vitro fertilization (IVF). This is different from embryo cryopreservation, which refers to freezing fertilized eggs, also called embryos.ⁱⁱⁱ

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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 uterus; with egg freezing, the eggs are not fertilized with sperm before they are frozen.^iv  

The first step is for the patient to be screened to make sure they are suitable candidates for egg freezing. Blood tests are performed 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 which have reached a size between 2-10mm; 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.^v Finally, doctors will also screen for conditions such as human immunodeficiency virus (HIV) and hepatitis B and C as well as for hormone imbalances that can affect fertility such as hypo- or hyperthyroidism and hyperprolactinemia.

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 may 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 medications to encourage the ovaries to produce multiple mature eggs which can then be harvested. The fertility drugs and medications used for ovarian stimulation vary depending on individual factors and are usually self-injected at home.  

OS continues until about 36 hours prior to egg harvest, 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. Then, before the patient ovulates, the mature eggs will be retrieved in an outpatient procedure called oocyte retrieval or follicular aspiration.^vi This is when 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?

During retrieval, doctors will remove as many eggs as possible in order to increase the chances of a successful pregnancy and live birth in the future.^vii In one recent study with 231 patients, there was an average of 10 mature eggs obtained per retrieval with a 68.8 percent oocyte fertilization rate amongst those oocytes which were thawed and used for IVF.^viii 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 The eggs are inspected by the embryologist to determine if they are mature, as in most cases only mature eggs have the potential to be fertilized in the future.  

Once eggs are harvested, they are then stored in liquid nitrogen at -190°C in a process known as vitrification.^x  Clinics used to freeze eggs using “slow-freezing,” but now almost all eggs are flash-frozen through vitrification, a method that is up to 1 000 times faster.^xi Through vitrification, eggs survive at a higher rate and are more likely to be successfully fertilized, implanted, and lead to a successful pregnancy.^xii  

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Who is a good candidate for egg freezing?

Women might consider egg freezing if they are about to undergo a medical procedure or treatment that will negatively affect their fertility, such as radiation or chemotherapy for cancer, or surgery that could damage their ovaries.^xiii Others might have a medical condition that is known to cause pregnancy complications such as sickle cell anemia or lupus, in which case 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. Additionally, patients undergoing female to male gender transition may wish to egg freeze prior to starting hormone replacement therapy or undergoing affirmation surgery which can lead to sterility.

Those with a family or personal medical history that affects fertility such as early or premature menopause (menopause occurring before 40 years of age), Turner syndrome (a chromosomal abnormality that can cause ovarian failure) or known genetic conditions that may lead to primary ovarian insufficiency might also benefit from egg freezing.^xiv  

Finally, women who are not ready to start a family and are concerned about the age-related decline in fertility might choose to freeze their eggs to later attempt pregnancy.

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How are eggs thawed?

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

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

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What are the success rates of egg freezing?

Most frozen eggs survive the 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, both because women in these age groups have more eggs remaining in their ovaries and because those eggs are less likely to have chromosomal abnormalities.^xvii  

One study including 128 IVF treatment cycles and 1 283 vitrified oocytes analyzed live birth efficiency per warmed oocyte and stratified this by age. Women <30 years of age had a live birth efficiency of 7.4 percent per vitrified/thawed oocyte compared to 5.2 percent for women >38 years of age.^xviii This suggests that more harvested eggs would be required amongst women >38 years of age to achieve a live birth. The authors further estimated based on their data that to achieve a 70 percent chance of live birth, women between 30-34 would need to freeze 14 mature oocytes, compared to 15 oocytes for those 35-37 years old and 26 for those 38-40 years old.^xix In addition, a 2017 study that presents a mathematical model for success with frozen eggs found that an individual who is 34 with 20 mature frozen oocytes has a 90 percent chance of having at least one live birth.^xx This live birth rate drops to 75 percent and 37 percent respectively for people ages 37 and 42. Outcomes may also be affected by factors such as body mass index and hormone levels, but more research is needed to know how much these characteristics change outcomes.  

The ASRM’s most recent guidelines suggest that women be counseled that live birth rates for embryo transfer are better when oocyte cryopreservation is performed in younger vs older women; 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 women.^xxi

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What is the difference between egg freezing and embryo freezing?

Egg freezing involves the cryopreservation of mature oocytes. In comparison, in embryo freezing, a mature oocyte is harvested and then fertilized with sperm to make an embryo which is then cryopreserved. Women may opt for egg freezing as compared to embryo freezing if they do not have an intended sperm donor or sperm-providing partner at the time of their cryopreservation. This gives the woman freezing her eggs the option to use the sperm of a future partner or a donor she can select at the time of her desired pregnancy. Furthermore, this 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 these embryos are used to achieve pregnancy.  

One advantage of embryo freezing compared to oocyte freezing is that embryo freezing enables fertility specialists to better assess the quality of the eggs upfront by evaluating how many of the eggs successfully fertilize. This may help patients have a better understanding of how many oocytes and cycles might be needed to achieve pregnancy in the future. As oocytes frozen in egg freezing are not fertilized, predictions about the number of oocytes that might be 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.

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What are the risks of egg freezing?

Most of the risks and side effects of egg freezing are similar to those of IVF. Side effects relate to the hormones used during ovarian stimulation, and can include fatigue, nausea, headaches, breast tenderness, bloating, and mood swings.^xxii  Similar to 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, in which case patients experience pelvic or abdominal pain, abdominal bloating, nausea and vomiting. In less than two 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  

In general, the egg retrieval process can cause mild pelvic and abdominal pain for a day or two, and while other complications are rare, other possible risks include bleeding, infection, or damage to the bowel, bladder, or blood vessels.^xxv  

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

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How are frozen eggs stored?

While not true for all countries, in the U.S. there is currently 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 upon with a clinic in advance of the procedure.

Those who decide not to use their frozen eggs may ask that the clinic dispose of them at any point. Some clinics will return the eggs to their owners if desired. Other people choose to donate unused eggs to someone they know, or to other anonymous individuals through the fertility clinic or a donor agency.^xxix Finally, some people choose to donate unused or excess eggs for scientific purposes, such as for stem cell research.

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Conclusion

Egg freezing does not always result in a live birth later; however, it remains a valid option for women who are about to have their fertility affected due to medical constraints or for those who are not ready to have a child yet. Women who are interested in using egg freezing to preserve their fertility should speak to a physician regarding their options, and then use that information to make an informed decision related to their fertility.

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