Women who delay childbirth may face infertility by the time they are ready to get pregnant as a women’s fertility is strongly influenced by her age. Age-related decline in fertility is primarily from the decline in the quality and quantity of the eggs. As such, a reasonable strategy to preserve fertility in women who wish to delay childbirth is to freeze their eggs.

Egg freezing is an increasingly popular method to preserve fertility but one must carefully consider if it is the right time to undergo this procedure. If it is done too early in life, the preserved eggs may never be used or if done too late, it could be an ineffective procedure.

What are the factors affecting success rates using egg freezing?

Age +Number of Eggs Retrieved

The two most critical factors determining the probability of achieving a child using previously frozen eggs are the woman’s age at the time of egg collection and the total number of egg collected.

The number of eggs naturally decline as the women ages from approximately 200,000 eggs at the onset of puberty to around 1,000 eggs remaining at menopause. After the age of 37, the rate of decline accelerates rapidly.

As the number of eggs progressively decrease, the quality of the eggs also decline and eventually a minimum threshold is reached where pregnancy is no longer possible. It is estimated that after the age of 45, most of the eggs will have abnormal number of chromosomes.

What are the factors to consider for egg freezing?

Age + Estimated Time for Possible Use + Budget

When a woman decides to freeze her eggs, there are several factors she needs to consider. These include 1. the woman’s age at the time of egg freezing, 2. the intended wait time before pursuing pregnancy and 3. the cost-effectiveness of egg freezing.

Several studies found that reproductive aging is primarily related to the age of the egg and is not influenced very much by the age of the uterus. This means that the probability of pregnancy when using previously frozen eggs is determined primarily by the age of the woman when the eggs were collected rather than the age when she gets pregnant.

If egg freezing is undertaken too early, there is an increased chance that the woman will never be required to use the stored eggs to have children. The woman would have also been unnecessarily exposed to the financial burden and risks associated with ovary stimulation and egg collection.

If egg freezing is undertaken at an older age, the chances of pregnancy will be low due to the reduced number of collected eggs and the decreased quality of the eggs.

In a study by Mensen et al., his team found the highest probability of live birth when egg freezing was performed at the ages <34, and little benefit over no action was seen at the ages 25-30 years. If the only consideration is maximizing live birth rates at any cost, egg freezing should be performed before the age of 34 years. However, when attempts to conceive are delayed for a long period of time and cost-effectiveness is considered, egg freezing can be considered at the age of 37 years.

What is the maximum age for egg freezing?

The maximum age for attempting egg freezing may be as high as 45 years, but the success was limited to those patients producing >5 eggs in response to ovarian stimulation according to a study by Spandorfer et al. in 2007. In this study, patients older than 46 could also get pregnant, but none of these pregnancies resulted in a live birth child.

In some countries, there is the age-limit for IVF using donor eggs. In the Netherlands, the age is 45 years and in Belgium, the ages is 47 years. 

Many questions for egg freezing may come from women aged 38-44. Would they benefit from egg freezing? Egg freezing from women at this age group will result in fewer live birth rates and would need to undergo multiple IVF cycles to potentially achieve pregnancy. Women in this age group need to be thoroughly counseled about the low probability of success and the time and resources required to undergo multiple cycles.

Reference

Schattman GL. Cryopreservation of Oocytes. N Engl J Med. 2015;373:1755-1760.

Pellestor F, Andréo B, Arnal F, Humeau C, Demaille J. Maternal aging and chromosomal abnormalities: new data drawn from in vitro unfertilized human oocytes. Hum Genet. 2003;112(2):195.

Mesen TB, Mersereau JE, Kane JB, Steiner AZ. Optimal timing for elective egg freezing. Fertil Steril. 2015;103(6):1551-6.

Spandorfer SD, Bendikson K, Dragisic K, et al. Outcome of in vitro fertilization in women 45 years and older who use autologous oocytes. Fertil Steril. 2007;87:74.

Stoop D. Social oocyte freezing. Facts Views Vis Obgyn. 2010;2(1):31-4.

In the past, women only had the option of freezing an embryo if they wanted to preserve their fertility. This meant that if the woman was single and wanted to preserve her fertility, she had to find a sperm donor to fertilize the egg before it was frozen.

However, after the ASRM (American Society for Reproductive Medicine) lifted the experimental label for oocyte cryopreservation (egg freezing) in 2012, women today can either freeze their eggs or embroyos for fertility preservation. So which is a better option for you?

Understanding the  Fertility Preservation Process

The beginning process of egg freezing and embryo freezing is the same. First, the woman receives hormone medications to stimulate the ovaries to produce multiple mature eggs. The fertility doctor will monitor the maturation of the eggs during this time to determine the timing of the retrieval. Once the eggs are matured, the patient will undergo a minor surgical procedure to retrieve the matured eggs.

After the retrieval of the matured eggs, the process for egg freezing and embryo freezing diverges. In egg freezing, the collected eggs are processed and frozen soon after the retrieval. In embryo freezing, an additional step of fertilizing the egg with sperm is needed before it is frozen. The collected eggs are processed, fertilized with sperm, developed into an embryo before freezing.

The embryos and eggs are typically frozen by a process called vitrification. The frozen eggs or embryos will be stored at deep sub-zero temperatures (-196 degrees Celcius) in liquid nitrogen until they are ready to be thawed for future fertility procedures.

The Differences: Frozen Embryos vs Frozen Eggs 

Embryo freezing

For just freezing embroyos

Frozen embroyos are more stable and less prone to damage during the freezing and thawing processes compared to frozen eggs.  Also, for retrieved embryos you can test for chromosomal abnormalities, which can increase the odds for live births, but you cannot test retrieved eggs. Therfore, using frozen embryos can potentially provide a better pregnancy outcome later in life than using frozen eggs.

For IVF cycling

There are also many other benefits of freezing embryos. In a standard IVF cycling, freezing embryos can minimize the risk of multiple pregnancy by reducing the number of embryos transferred during a fresh cycle, avoid repeating stimulation cycles, and increasing cumulative pregnancy rates. Some studies showed that women who had transfers of fresh and frozen embryos obtained an 8% additional births by using their frozen embryos. Additionally, with the success rates of post thaw embryo transfer nearing those of fresh embryo transfer couple, the use of frozen embryos is now a routine procedure in assisted reproduction technology. Thus, the number of live births in woman undergoing IVF with post thaw embryo doubled from 12% in 1997 to 25% in 2011. 

Egg freezing

Diversity: More patient populations

Egg freezing can offer more options for diverse patients populations in fertility preservation compared to embryo freezing. These include single women who will undergo fertility compromising cancer treatments, women looking to postpone childbirth to pursue educational or career goals, and those who have diminished ovarian reserve and haven’t met their significant other.

Improved technology: Comparable to retrieved fresh eggs

The technology for egg freezing has improved with vitrification and studies have shown signficant improvements in the post thaw survival rates and clinical pregnancy rates compared to the traditional slow freezing method. Freezing with vitrification has been shown in several studies to have high post thaw survival ranging from 79% to 99%. In 2011, Cobo and Diaz conducted a systematic review comparing vitrified and fresh eggs that showed similar fertilization rates and clinical pregnancy rates between the two groups.

Controversies of Embryo and Egg Freezing

The storage of frozen embryos has generated ethical, legal, and religious concerns in some countries due to the concerns on the fate of the surplus frozen embroyos in storagge. Due to this controversy, countries like Italy and the United Arab Emirates have enacted specific laws that prohibit embryo freezing.

Egg freezing is controversial in some countries with conservative family values, therefore its use is strictly controlled. In China, egg freezing is prohibited to single women whereas in Singapore, only women with certain medical needs such as fertility preservation for cancer patients undergoing chemotherapy are allowed.

Safety of egg and embryo freezing

Recent data shows no increase in the number of congenital abnormalities observed in thawed eggs or embryos. Although freezing eggs and embryos are now well-established procedures, caution is advised until there are sufficient data to rule out potential long-term side effects for these children.

Which is better?

Egg and embryo freezing are now an established technology with high success rates and used for a wide range of indications. It just comes down to lifestyle and circumstances. Women who do not have partner or do not wish to store embryos due to ethical and morals considerations are good candidates for egg freezing. While for couples who want to achieve children later, embryos freezing could be a better option than freezing eggs or sperm separately. 

Reference

Wong KM, Mastenbroek S, Repping S. Cryopreservation of human embryos and its contribution to in vitro fertilization success rates. Fertil Steril. 2014;102(1):19-26.

János Konc, Katalin Kanyó, Rita Kriston, Bence Somoskői, Sándor Cseh. Cryopreservation of Embryos and Oocytes in Human Assisted Reproduction. BioMed Research International. 2014. doi:10.1155/2014/307268

Cobo A, Diaz C. Clinical application of oocyte vitrification: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2011;96(2):277-85.