Cross border donation of oocytes: a solution to the problem?

In vitro fertilization (IVF) with donor oocytes is an increasingly widespread therapeutic option for women who cannot make use of their own oocytes. In this procedure, the donor of the oocyte undergoes controlled ovarian hyperstimulation in conventional IVF and, after oocyte retrieval, her oocytes (fresh or warmed after vitrification) are inseminated in vitro with the sperm of the recipient’s partner (sperm of male donor can also be used). The fertilized oocytes are then transferred to the hormonally synchronized endometrium of the recipient. This approach has progressively become ethically and legally accepted in the majority of countries. In Europe for example, among the 39 countries offering assisted reproductive technology (ART), a total of 56,516 egg donation cycles were reported in 2014. As the number of potential recipients is continuously increasing, the major difficulty in establishing a donor oocyte program is the limited availability of donor subjects.

Until recently, IVF treatments have been technologically confined in terms of location and duration. Fertilization had to be done quickly following stimulation of ovaries and extraction of oocytes, and transfer of the oocytes was usually done at the same facility, with transfer to other facilities being possible only over short distances. Reproductive health was therefore a fertile ground for so called “reproductive tourism”, or “Cross-border reproductive care”. These terms refer to patients traveling from their home country to another one in order to get fertility treatment through ART. In countries in which donors’ availability is insufficient to cover the therapeutic demands, patients could resort to traveling abroad for treatment. Other drivers for fertility tourism are legal regulations, or lower price and higher success reported in foreign countries when compared to the home country.

The development of cryobanks along with improvements in cryopreservation techniques, like oocyte and embryo vitrification, have led to the design of stimulation-retrieval-transfer procedures that permit cross border transfer of oocytes, and enable oocyte donation. Until a few years ago, the most used freezing technique, called slow freezing, provided disappointing results for oocyte cryopreservation and had a low yield for embryo freezing, giving an average survival rate of around 52%. Then vitrification techniques became widespread throughout the early 2000s, following the first birth from oocyte vitrification was reported in 1999, and represented a real breakthrough in reproductive biology and medicine. They in fact enabled oocyte cryopreservation to be achieved with excellent survival rates and pregnancy chances similar to those with fresh transfers. 

Oocyte vitrification has radically changed donation programs, practically uncoupling the donation from the reception both from a spatial and a temporal point of view. This has led to the development of cryobanks of donated oocytes, with several recipient programs completely based on the providing vitrified donor oocytes, thus creating donor egg banks (i.e., no fresh extraction of oocytes for a specific recipient). Usually, donor oocyte cryobanks provide sets of mature vitrified oocytes per recipient (usually six), claiming results similar to those obtained with the use of fresh oocytes. Studies report comparable success rates when using vitrified and fresh oocytes, but the live birth rate (when the same number of oocytes are used) still needs to be investigated. Donor egg banking provides relative benefits in terms of treatment, such as scheduling flexibility, and can allow for better phenotypical matching between recipient and donor, especially in small programs. Most importantly, donor oocyte banking has also made it possible to transfer oocytes across borders.

A serious consideration is the mode and method of oocyte transport. Although commercial transport websites imply that moving embryos is relatively risk free, recent studies report that methods of shipment and types of transportation matter. Liquid nitrogen vapor containers or “dry shippers” (i.e., cryotanks filled with liquid nitrogen that is absorbed into porous interior packing material) are commonly preferred for air transport, whereas liquid nitrogen-filled tanks are more often seen in shorter, land-based travel because of the specific requirements and risks of each mode of transport. Damage to vitrified oocytes has been reported from factors such as vibration/movement, increased temperature, air pressure, and horizontal tank positioning during transport. Furthermore, loss of survival of vitrified oocytes was reportedly lessened with the use of a road courier as opposed to air transport. 

Recommendations for the safe transport of oocytes must include full compliance with all applicable state and national laws and regulations. It is also essential to consider the regulations that may be applied by the receiving jurisdiction and any other jurisdiction that the material may pass through on the way to its final destination. These regulations include packaging and labeling of cryoshipped specimens, restrictions on sending oocytes to an unlicensed clinic, and even a requirement for written agreements if third-party carriers are used. European Union (EU) transport is fairly easy among the EU countries, requiring, among specific packaging guidelines, a written confirmation of acceptance from the receiving clinic as well as documentation of infectious disease testing compliance. Oocytes coming into the United States may need to meet US Food and Drug Administration tissue guidelines and are subject to United States customs inspections (which has caused some problems in the past as a result of delays in processing). A commercial invoice describing the contents and value of cryopreserved material is also required. Importing and exporting patient specimens in and out of the US may also trigger compliance with some of the regulations of the International Air Transport Association and the Federal Department of Transportation. Other countries may require the receiving clinic to have certain certification (import/export certificates that prove the authorization to receive the shipment) or the courier to be certified or approved. Finally, before moving oocytes, it is important to ascertain whether the receiving jurisdiction has any restrictions on the importation/exportation of gametes or whether it even allows for cryostorage of specific reproductive material. Some countries ban cryostorage of certain reproductive material, and shipped specimens may be refused when they reach the intended destination.

In conclusion, transportation of eggs between different international laboratories has permitted an increased accessibility to oocyte donation in countries with low availability of donors. This accessibility has manifested itself in an increased number of pregnancies from IVF. Importantly, in order to benefit from donated oocytes from across the world, a qualified shipping and delivery service must be utilized.  ׳

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