Oocyte donation has its origins in the clandestine use of donated sperm more than 140 years ago. Since first described in 1983, oocyte donation has resulted in more than 50,000 births in the United States alone and today now accounts for more than 10% of all IVF cycles performed yearly in the United States. The use of donated oocytes has changed the human reproductive landscape, challenging the traditional norms of conception and parenthood. Oocyte donation has also provided a unique scientific model that separates the egg from the uterus, allowing the independent study of each in normal physiologic and pathological conditions and providing insights into the fundamental aspects of reproduction, cell biology, and genetics. This Views and Reviews takes us through the historical development of oocyte donation, its scientific insights, and its application to daily practice and management, as well as insights into what the future may hold for this field.

One could argue that the first case of third-party reproduction was described in Genesis 16 with the story of Abraham, Sarah, Hagar, and Ishmael. After Abraham and Sarah married, they wandered the Middle East and ended up in the city of Hebron, where he complained to God that he was still childless, after God had promised him offspring. As a result, Sarah offered him her “assistant,” Hagar, who was never asked to consent to bearing a child. Here it was said, “It may be that I may obtain children from her.” In a sense, Sarah “borrowed” Hagar’s eggs to give Abraham an heir when she failed to do so herself. Notwithstanding, this arrangement caused Sarah, Hagar, and Abraham, and the resulting child, Ishmael, enormous emotional trauma. These same emotional issues exist today, where third-party reproduction challenges long-held beliefs and requires a new examination of the existing definitions of “family” and “mother.”

Assisted reproduction, as we know, has taken quite some time to evolve since the days of Genesis, and it has undergone an enormous metamorphosis. It wasn’t until 1891 that procedures using rabbit embryos and transfers were first reported. These procedures continued to advance, resulting in the first birth of newborn rabbits from IVF by George Pincus in the 1930s followed by birth of Louise Brown in July 1978 by Robert Edwards and Patrick Steptoe and the birth of Elizabeth Carr by Drs. Howard and Georgeanna Jones in December 1981.

Involvement of oocyte donors took IVF on an unexpected turn. While the advent of assisted reproductive technology came about through the clandestine use of donated sperm more than 140 years ago, where even the woman being inseminated wasn’t told that the sperm was from a donor, the use of donated oocytes to establish pregnancy was first described in a patient with primary ovarian failure in 1983. The landmark efforts of the groups at Monash University and the University of California, Los Angeles, changed the human reproductive landscape forever. With the successful application of these technologies to women after the age of 50, which revealed that women of any age could theoretically become pregnant, the field challenged the traditional norms of conception and parenthood. Now more than 30 years later, donated oocytes have been used to treat a number of clinical situations including ovarian failure, diminished ovarian function, or genetic conditions where one might face the risk of passing an inheritable disorder to a child. Since its inception, oocyte donation has resulted in more than 50,000 births in the United States alone, accounting for almost 14% of all IVF cycles in the United States as reported in the 2012 Society for Assisted Reproductive Technology and Centers for Disease Control and Prevention ART/CDC registry. As the involvement of donors has gained increasing acceptance, the initial public debate, sensational commentaries, and moral concerns for donors have somewhat subsided, and currently most people feel that human oocyte donation is ethically and socially acceptable.

This month’s Views and Reviews focuses on the full circle that egg donation has come, from initially using uterine lavage, which fell out of favor for standard IVF techniques, to its possible current applications and the relevance of oocyte donation as a scientific model that separates the egg from the uterus. Given that it is not possible, due to obvious ethical reasons, to separate the influence and effect of the oocyte from the local uterine milieu on the normal and abnormal development of the early embryo, oocyte donation provides an ideal opportunity to study the contribution of each of these two variables independently from each other when studying implantation/pregnancy rates and obstetrical outcomes. This allows us to uniquely study women with normal physiologic and pathological conditions including endometriosis, polycystic ovarian syndrome, uterine leiomyoma, and obesity as well as women of advanced reproductive age conceiving with their own gametes as we seek to understand how one impacts the other. The successes and milestones of our pioneers among the many including Drs. Sauer, Trounson, and Rosenwaks represent years of research, trial and error, and discovery into the fundamental aspects of reproduction, cell biology, and genetics.

In the first paper in this Views and Reviews, Dr. Mark Sauer, an innovator in the field who developed and applied oocyte donation to American patients, provides his insights and perspectives on the history and development of oocyte donation, as well as his significant foresight into where the field is going. Through the intricate interweaving of scientific insight and clinical experience, Dr. Sauer shares his overview of the history and development of oocyte donation since its inception.

Dr. Zev Rosenwaks, a leading researcher and clinician in oocyte donation over the past three decades, along with Dr. Alexis Melnick, discusses the scientific insights gleaned and challenging clinical scenarios we have learned from in the practice of oocyte donation and its associated techniques. Through their review of the science and practice of oocyte donation they highlight the advances in knowledge related to embryo implantation, frozen ET, oocyte maturation, and fertility preservation that have been derived from oocyte donation research. These insights are also discussed as they are applicable to daily practice and management.

Lastly, Drs. Mindy Christianson and José Bellver review the complexities of implantation of an embryo in the human uterus including development, synchronization, and signaling between the embryo and endometrium where there is a coordinated system of “cross-talk” molecular signaling between the endometrium and blastocyst for these events to occur. They review scientific elements of donor egg cycles including optimal stimulation protocols and endometrial receptivity that have contributed to optimizing and maximizing outcomes in third-party reproduction.

We are honored to have some of the older generation pioneers and newer generation innovators contribute to this Views and Reviews. The pioneers who have forged the way and worked in the trenches to develop the science and apply it to practice and the newer generation innovators who are deepening our understanding of the success and outcomes both contribute to providing a thorough and thought-provoking review of this field. Together these reviews provide a summary of the history, lessons, and future of where we are and where we may be going as the field of third-party reproduction continues to challenge the fundamental concepts of mother, family, and kinship. It is our hope that the first of these two Views and Reviews will provide the scientific and clinical basis of the practice of oocyte donation. In the second part of this Views and Reviews, presented next month, the psychological, social, and legal aspects of oocyte donation will be discussed. We hope that readers will come away with a comprehensive understanding of the profound scientific and clinical impact of oocyte donation on assisted reproduction.

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