The goal of the process is for the recipient to have a child using a donor's healthy eggs for in vitro fertilization (IVF).ⁱ The donor eggs may be fertilized with a partner’s sperm or with donor sperm. Donor eggs are available either fresh or frozen. In fresh egg donation, mature eggs are collected from the donor's ovaries, and are used for immediate in-vitro fertilization (fertilizing the eggs with the donor sperm or a partner’s sperm in the lab) to form embryos. A fresh embryo could then be transferred to the intended parent (or surrogate’s) uterus five days after fertilization. The embryos created from fresh donor eggs can also be frozen (cryopreserved) if not selected for a fresh transfer (most commonly at day 5 blastocyst stage). These donor-egg-derived frozen embryos can then be thawed and transferred at a later date.ⁱⁱ In contrast, in frozen egg donation, the mature eggs collected from the donor's ovaries undergo cryopreservation directly after retrieval from the donor and can be thawed later for in vitro fertilization and subsequent embryo transfer.ⁱⁱⁱ

Traditionally, fresh eggs were used for egg donation IVF, but this requires more logistical coordination, such as having the sperm sample available on the day of retrieval, and selection of a donor prior to egg retrieval. Furthermore, if the recipient is electing for a fresh embryo transfer as well, then very specific coordination of cycle timing between donor and recipient is needed.^iv A fresh embryo transfer using donor egg-derived embryos requires that the recipient’s uterine lining is appropriately prepared for embryo transfer approximately 5 days after the egg retrieval.^v As cryopreservation techniques have improved with time, the use of frozen (cryopreserved) eggs has gained popularity.^vi,vii

Fresh donor eggs

Since 1983, fresh donor egg cycles have led to the birth of hundreds of thousands of healthy newborns worldwide, and this had been viewed as the gold standard compared to using frozen eggs.^viii All egg donors need to undergo controlled ovarian hyperstimulation (COH) to induce multiple follicles/eggs to grow and mature. Following an injection to mature the eggs, the eggs are retrieved using the same egg retrieval process undertaken by individuals who use their own eggs for IVF.

Egg donors must undergo testing to prevent potential transmission of infectious diseases.^ix

Fresh eggs can be donated from either a known (directed) donor, such as a family member or friend, or from an anonymous egg donor through an egg donor program. In the latter case, the egg donor agency coordinates with the recipient’s clinic to screen for a suitable donor and synchronize the donor’s ovarian stimulation and egg retrieval process. The fresh donated eggs are fertilized immediately with the patient’s partner’s or donor sperm to create embryos for either a fresh or subsequent frozen embryo transfer.^x Using fresh donor eggs may be recommended in scenarios when synchronization between the donor’s egg retrieval and the recipient’s embryo transfer is feasible so that both parties can undergo their respective procedures simultaneously.^xi This approach is more common for recipients who have a predictable menstrual cycle, allowing for optimal timing of the embryo transfer.^xii

It is also important to note that some individuals who use fresh egg donors may choose to cryopreserve their embryos for a frozen embryo transfer in a subsequent cycle instead of an immediate fresh embryo transfer.^xiii This can be due to the individual's choice but may also be a result of inadequate uterine lining or other factors that preclude fresh embryo transfer.

Conducting a fresh embryo transfer with fresh eggs may not be suitable when the recipient's reproductive cycle is irregular or difficult to predict.^xiv In such cases, doing a frozen embryo transfer or utilizing frozen donor eggs, both of which generally provide more flexibility in timing, may be preferable. Additionally, logistical challenges, donor availability, or medical considerations for either the donor or recipient could influence the choice between fresh and frozen donor eggs.^xv The decision is often made based on individual circumstances and medical recommendations. Some of the rationale for choosing one option over another is summarized below.

What are the pros and cons of fresh donor eggs?

One advantage of using fresh egg donation is that these programs often provide all of the eggs retrieved from a particular IVF cycle to the recipient. In other words, the eggs are not separated into batches and frozen for use by different recipients. However, it is important that recipients clarify with their clinic or provided whether the donor eggs retrieved from one cycle are being shared by more than one recipient or not, since practices vary considerably by location.

Another consideration with fresh eggs is that they avoid a freeze-thaw process prior to fertilization and are fertilized fresh.  Fresh donor cycles do not risk a loss of oocytes in the cryopreservation and thawing step.^xvi This is because fresh donor eggs are available immediately after egg retrieval, eliminating both the need for thawing as well as potential concerns about the survival of frozen eggs. Some evidence suggested that fresh donor eggs may have higher success rates in terms of pregnancy and live births compared to frozen donor eggs (see below).^{xvii,xviii,xix,xx} However, more recent evidence suggests that there may be no significant differences in outcomes when using fresh or frozen donor eggs, if the same number of oocytes are being obtained.^xxi

In some cases, fresh donor eggs are associated with the following challenges:

• Logistics in synchronizing menstrual cycles between donor and recipient If selecting a fresh embryo transfer: Precise coordination between the donor and the recipient`s menstrual cycle often poses a challenge. The donor’s egg retrieval must be synchronized so that eggs are collected, fertilized, and then transferred as embryos within a certain time frame where the recipient`s endometrium is receptive for implantation.^xxii There is no guarantee that the endometrium achieves a receptive state in time to receive a fresh embryo transfer.
• Increased risk of disease transmission: While egg donors are tested for infectious diseases, fresh donor eggs may lack proper quarantine conditions like those used for sperm donation and semen banks.^xxiii Because fresh eggs need to be used immediately if they are not to be frozen, there is no time to allow for a prolonged quarantine period during which the donor can be re-screened for infectious diseases.^xxiv
• Higher cost and reduced availability: Another possible drawback of opting for fresh oocytes is that this process tends to be more costly per donation cycle. In a typical fresh donation cycle, all eggs are usually donated to a single recipient, mainly because of challenges in coordinating multiple recipients.^xxv This can result in longer wait times for fresh donor eggs to become available. Additionally, the quantity of obtainable oocytes can be unpredictable and typically less than the number of frozen oocytes that could be obtained from a single donor over multiple IVF cycles. The availability of donors may be restricted geographically and the availability of donors from specific ethnic groups might be limited depending on the location.^{xxvi,xxvii,xxviii,xxix}

Frozen donor eggs

The practice of using frozen donor eggs is becoming increasingly common, offering more options to individuals or couples planning to use donor eggs. Oocytes are more susceptible to damage from cryopreservation compared to embryos because they are highly vulnerable to the formation of ice within the cells.^xxx However, improvement in the egg freezing technique by ultra-rapid cooling (vitrification), as opposed to slow freezing, is a scientific breakthrough that allows for excellent oocyte survival rates and pregnancy rates similar to using fresh eggs.^xxxi,xxxii

Vitrification is the process of using certain protective substances (cryoprotectants) in a two-step procedure to freeze eggs, allowing the eggs to be stored for an extended period. The eggs are then warmed in multiple steps to remove the cryoprotectants right before fertilization.^xxxiii

There are two types of vitrification protocols: open and closed. In open vitrification, oocytes directly touch liquid nitrogen using small devices. In closed vitrification, oocytes have no direct contact and instead use tubing systems.^xxxiv While the closed system of vitrification offers an aseptic environment, open vitrification has traditionally been the more common approach in fertility clinics.^xxxv While earlier studies showed that open vitrification systems resulted in higher survival rate of oocytes,^xxxvi subsequent studies did not find any differences in oocyte survival, pregnancy, or live birth rates between open and closed vitrification systems.^{xxxvii,xxxviii,xxxix,xl} This is likely due to advances in development of newer closed vitrification systems.^xli

Frozen donor eggs can be purchased from commercial egg banks or from fertility clinics that have an egg donation program. Usually, frozen eggs are sold in batches of at least six or more. In some countries, IVF and/or egg donation might not be permitted, requiring individuals in search of donor eggs to explore international clinics and egg banks.^{xlii,xliii,xliv} Using frozen donor eggs may be recommended in scenarios where timing fresh cycles between the donor and recipient is challenging. It can also be beneficial when a donor is unavailable for a fresh cycle or when the recipient prefers flexibility in the IVF treatment timeline.

What are the pros and cons of frozen donor eggs?

The introduction of frozen eggs into egg donation programs has several advantages, which address challenges associated with fresh donor eggs:

• Logistical simplicity: Frozen eggs do not require synchronized cycles between the donor and recipient. The thawing of donor eggs can be done at any time when the recipient's endometrium is prepared for embryo transfer.^xlv
• Better quality control: Using frozen eggs allows for more rigorous testing of donors for infectious diseases during donor egg quarantine, a similar standard to that utilized for donor sperm.^xlvi
• Increased selection and availability of donor eggs: The practice of oocyte cryopreservation has given rise to donor oocyte banks, enabling recipients to choose from a list of donors and reducing wait times.^xlvii With the ability to rapidly ship frozen eggs over long distances, recipients have the option to undergo treatments locally, eliminating the need for reproductive tourism.^xlviii In addition to cryopreserved oocytes from individual donors, surplus oocytes from couples undergoing IVF can be preserved and later donated, offering a meaningful option, especially in countries where embryo donation is restricted.^xlix
• Lower costs: Frozen donor eggs can be divided among multiple recipients, which typically helps lower the cost per treatment cycle. However, it remains uncertain if the cost per live birth is also reduced.^l
• Guarantees: Many egg banks provide success guarantees for batches of frozen eggs purchased from them. For example, a guarantee of a certain number of blastocysts per egg batch purchased. In the case that the initial batch did not result in any blastocysts following fertilization with normal sperm, they will provide a replacement batch of frozen eggs. Some other banks have more complex policies that cover live births. There are typically many exclusions to these policies that purchasers should be aware of.

While using frozen donor eggs has several advantages, there are some potential drawbacks to consider:

• Variability in egg survival rates: Typically, frozen eggs are sold in batches of at least six or more, but the actual number available for fertilization may vary. The survival of frozen eggs depends on the thawing process, and unfortunately, not all eggs will necessarily successfully survive this defrosting procedure. Freeze-thaw egg survival rates can exceed 90 percent. ^{li,lii,liii,liv,lv,}
• Variability in egg quality and pregnancy success rates: The freezing and thawing process may also affect the quality of frozen eggs, and not all thawed eggs will result in viable embryos or successful pregnancies leading to variations in success rates compared to fresh eggs. Typically, fertilization rates of frozen-thawed eggs are between 70-80 percent and comparable to those of fresh eggs.^{lvi,lvii,lviii,lix,lx,}

Another consideration is that proper storage and handling of frozen eggs requires specific protocols and equipment, potentially adding complexity to the fertility treatment process.^{lxi,lxii,lxiii,lxiv,lxv,lxvi}

There are also various costs considerations: While frozen donor eggs can potentially reduce costs compared to fresh cycles, there may still be financial implications, including storage and shipping fees.^{lxvii,lxviii,lxix,lxx,lxxi,lxxii}

The existence of commercial egg banks and the convenient cross-border transportation of oocytes, often with differing or insufficient regulation, creates ethical concerns.^lxxiii There is currently no way for patients to determine whether a given egg bank is ethical or not. It is the responsibility of IVF clinics to vet the egg banks that they partner with, but this is not required by governing societies, such as ASRM.^lxxiv However, despite any potential ethical concerns, egg banks have improved access to donor eggs.  

Success rates for fresh vs. frozen donor eggs

Blastocyst formation and pregnancy rates achieved using frozen donor eggs are believed to be comparable to those achieved with fresh donor eggs. The guidelines from the American Society for Reproductive Medicine (ASRM) in 2021 suggest there are no notable differences in pregnancy rates between using fresh and frozen donor eggs.^lxxv

One 2011 study comparing outcomes between frozen eggs to fresh eggs obtained from an egg donation program reported that frozen eggs had a survival rate of 89.4 percent after thawing.^lxxvi No statistically significant differences were observed in the fertilization rate (76.1 percent and 87.5 percent), Day 2 cleavage rate (96.3 percent and 98.0 percent), or blastocyst formation rate (41.3 percent and 45.3 percent) between the frozen and fresh donor eggs.^lxxvii This study suggests that embryos created from frozen eggs develop just as well as those from fresh eggs and can form high-quality blastocysts.^lxxviii Furthermore, another study from 2017 examined 504 egg donation cycles (78 fresh and 426 frozen) where all donors were women younger than 30 years of age and donor eggs were fertilized by intracytoplasmic sperm injection (ICSI) (where a single sperm is directly injected into an egg to facilitate fertilization).^lxxix These authors reported similar blastocyst rates (48.8 vs 51.6 percent) and pregnancy rates (60.9 percent vs. 59.0 percent) between the fresh and frozen donor eggs.^lxxx

Additionally, it is important to consider the choice between a fresh embryo transfer or frozen embryo transfer when using fresh donor eggs. A study in 2021 compared live birth rates between fresh and frozen embryo transfers resulting from fresh donor eggs for 33 863 recipients. They reported a higher live birth rate of 56.6 percent with fresh embryo transfers compared to 44.0 percent with frozen embryo transfers.^lxxxi

National Summary data of IVF clinics by the CDC reported over 20 000 donor egg IVF cycles in the United States in 2018.^lxxxii The success rates ranged between 45-55 percent, with slight differences in live birth rates based on whether the oocytes were fresh or frozen (Table I).

Furthermore, a study in 2020 examining 36 925 IVF cycles recorded by the Society for Assisted Reproductive Technology (SART) reported fresh eggs having a better live birth rate of 47.7 percent compared to 39.6 percent for frozen eggs.^lxxxiv  

In 2020, the Canadian Fertility & Andrology Society (CFAS) reported through the Canadian Assisted Reproductive Technologies Register (CARTR Plus) that the rate of ongoing clinical pregnancy rate for frozen donor oocyte cycles was 42.9 percent, which was slightly lower than the 46.5 percent ongoing pregnancy rate of fresh donor oocyte cycles.^lxxxv An additional study in 2021 comparing fresh to frozen donated eggs (egg-sharing donation program) for ICSI cycles also observed better fertilization rates (81.1 percent vs.75.7 percent), high-quality embryos rate on day 2 (70.3 percent vs. 57.8 percent), and blastocyst development rate (62.4 percent vs. 40 percent) for ICSI cycles using fresh donor eggs compared to frozen donor eggs. ^lxxxvi However, the authors did not observe any significant differences between high-quality blastocyst rate, implantation rate, clinical pregnancy rate, and miscarriage rate.^lxxxvii

In the most comprehensive and newest meta-analysis on this topic, the authors concluded that some of the observed superior outcomes for fresh donor eggs (compared to frozen donor eggs) become similar if the number of thawed eggs is equal to the number of fresh retrieved eggs.^lxxxviii In addition, they noted that if recipients obtain at least 8 eggs, the cumulative live birth rates are 2.5 times higher than if they obtain less than 8 eggs regardless of whether the eggs are frozen or fresh.^lxxxix

Conclusion

The decision regarding whether one should use fresh or frozen donor eggs for conception should be carefully discussed between the donor egg recipient and fertility physician to ensure the choice aligns best with the individual patient's specific needs. Each option presents unique considerations, hence informed discussions between recipients and fertility physicians are vital for a personalized approach.