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The American Fertility Association’s Monthly Newsletter

November 29, 2007

David Ryley, MD

The State Of The Science: Egg Freezing
By David Ryley, MD

The increased sophistication of the Artificial Reproductive Technologies has revolutionized the treatment of infertile couples over the last 30 years. Our improved understanding and manipulation of the brain-ovarian relationship, oocytes (egg) stimulation and fertilization, and embryo development has resulted in soaring IVF success rates. ART pregnancy and live birth rates approach levels that, not so long ago, were unimaginable. This clinical application of medical research, from bench to bedside, is a triumph that has changed the lives of millions of men and women in their quest to have a family.

As we approach the fourth decade of mastering human IVF, we’re now focusing on the basic element of female fertility-- the egg and its cryopreservation (freezing). Once again, we find ourselves at a critical juncture of providing women with the means to preserve fertility despite obstacles such as age, disease, or certain medical treatments that once seemed insurmountable, This new phase of infertility therapies is filled with great promise and high expectations.

Twenty-one years have passed since the birth of the first infant resulting from the fertilization of a previously frozen egg. It’s estimated that 200-300 children have been successfully delivered after the transfer of embryos created from this process. It’s a relativey small number that indicates how the application of this science has been hampered by reportedly low egg thaw-survival rates, low pregnancy rates, and concerns regarding developmental abnormalities in the skeletal architecture of the frozen mature egg. However, increased patient demand coupled with improved freezing and fertilization techniques has generated a surge of interest and activity in the science of egg freezing.

Indeed, the power of oocyte cryopreservaton, at the moment, lies in the possibility of preserving the fertility of women facing potentially egg damaging chemotherapy or radiation therapy. Improvements in the treatment of cancer have enabled many young women to survive and focus on the potential of having a family. Malignancies striking young people, particularly breast, lymphoma, and leukemia have five-year survival rates in the 85-95% range. Ten to twenty per cent of women diagnosed with breast cancer, the most common malignancy affecting young women, are of child-bearing age. Present estimates suggest that 1/1000 adults are survivors of childhood cancers, this increased survival in no small part due to the successful application of therapies that are toxic to the eggs within the ovaries.

Embryo freezing, a technique with well established and proven success, is presently accepted by both the American Society of Reproductive Medicine and the American Society of Clinical Oncology for the preservation of fertility in women affected by malignancies. However, recognizing that embryo freezing may not be a practical option for young women or women without a life-partner, these professional organizations agree that egg freezing, despite its limitations compared to embryo freezing, can be offered with appropriate institutional review board/independent ethics committee approval and oversight.

Additional candidates for fertility preservation through the freezing of eggs and sperm include couples undergoing IVF who are concerned with the ethics of freezing surplus embryos due to religious or personal concerns.
Women with medical conditions such as endometriosis or certain genetic disorders (BRAC mutations), which result in removal of the ovaries are also potential egg freezing beneficiaries. Increasingly, as we see more women deferring childbearing due to economic and social circumstances, clinicians recognize that the option of egg freezing is an attractive means to preserve fertility. And, as witnessed in the emergence of commercial egg banks, egg freezing would allow donor egg programs to quarantine eggs until appropriate infectious disease screening is performed on the donor, similar to the regulations applied to donor sperm banks.

As the science of egg freezing progresses, so too does the effectiveness of this approach to fertility preservation. The egg, with its large water content, is prone to the damaging effects of ice crystal formation that results from freezing. It’s this structural change has made the process of egg freezing and thawing inefficient, with pregnancy rates as low as 1-5% per thawed egg.

Encouragingly, with improved freezing procedures, particularly the proficient use of cryoprotectants (propanediol, glycerol, ehthylene glycol, DMSO, sucrose) and vitrification (rapid-freezing), enhanced survival of thawed eggs has been reported. When combined with ICSI, which appears to overcome the structural alterations within the zona pellucida, fertilization rates of 60-90% and embryo cleavage rates approaching 90% are seen. Further research is required to assess if these improved outcomes translate into acceptable pregnancy and live birth rates.

We’ve also discovered that the maturational stage of the retrieved egg is a significant factor in its capacity to survive freezing and thawing. As the science of maturing eggs in the laboratory-- In -vitro maturation or IVM-- improves, so too will the eventual yield of eggs that are amenable to ICSI. Recent research has combined the freezing of both mature and immature eggs, the latter undergoing IVM so as to maximize the potential for fertilizable eggs. Women with PCOS, and women with cancers that preclude the use of ovarian would be the beneficiaries of the retrieval of eggs from unstimulated ovaries.

Recent research in cancer patients indicates that combining the freezing of both ovarian tissue and immature eggs subjected to IVM represents a sophisticated combined approache to fertility preservation.

Given the increasing promise of a science with enormous potential, egg freezing should be offered to women with those conditions as a means to preserve their fertility. As clinicians and scientists, we are morally obligated to advance this research in a way that allows a thorough understanding of its risks, benefits, and overall effectiveness. Initial studies, though limited in number, suggest that there is no increase in aneuploidy, birth defects, or developmental delays in the embryos and children derived from frozen eggs. However, a rigorous application of sound statistical analyses applied to well designed studies will be required to determine the overall safety of this research.

Commercial donor egg ventures dedicated to the preservation of female fertility can utilize cutting edge science and IRB-approved protocols that are integral to the advancement of this field. Working under the guidelines of the American Society of Reproductive Medicine, these companies are well served to partner themselves with infertility centers motivated to enhance the care of women requiring fertility preservation. Physicians, recognizing that patients may be susceptible to the promises of an unproven yet promising science, can advise their patients to consider these services in a way that is both clinically justified and ethically appropriate. Informed decisions can be made. The patient’s interests can be protected, and the technology will advance to the benefit of all parties when evidence-based science is strictly employed.

We have mastered the science of IVF, and witnessed its evolution from an experimental technique to the standard of care for the treatment of infertility. Egg freezing holds similar promise for the preservation of fertility, and we are privileged to participate in this emerging field.

Dr. David Ryley is a reproductive endocrinologst at Boston IVF. After graduating from the Tufts University School of Medicine, he completed a fellowship in Reproducitve Endocrinology and Infertility at Harvard Medical School/Beth Israel Deaconess medical Center in 2005. His areas of expertise encompasses ovulatory dysfunction, recurrent miscarriage and reproductive genetics. His research interests include the genetic control of oocyte maturation, IVF outcomes in patients with decreased response to ovulation induction, and the effects of body mass index on female fertility.

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Carolyn Berger, LCSW

Adopting Through Foster Care: Dawn Cooper’s Story
By Carolyn Berger, LCSW

Ask 39-year-old Dawn Cooper about adopting her four teenage daughters through foster care and the first thing you notice is her unbridled enthusiasm. Not only does she make sure she gets dates, ages, and circumstances right, she wants you to get it right, too. Because if you do, you might just consider taking the same foster care path she took to become a parent.

Dawn, an administrative assistant at an Indiana gas and electric company, always knew she wanted to adopt. She was intrigued by “The Josephine Baker Story,” a movie about the African-American performer who, through multiple marriages and a career of extreme highs and lows, managed to adopt twelve children—known as the “Rainbow Tribe.”

About seven years ago, Dawn contacted the Indiana Department of Social Services to tell them she had always gotten along well with teenagers, and wanted to adopt 11 or 12-year-old girls. She liked the idea of adopting older kids, envisioning herself raising them and then becoming a young grandmother still spry enough to be able to play with her grandkids one day. She also reasoned that by adopting older kids she would have a better idea of what a child’s strengths, interests and issues were, and whether they were likely to be compatible with her. Soon after getting certified by the state and undergoing the required parent training, Dawn learned of a sibling set of two girls, ages12 and 13 and in need of a permanent home. Dawn realized was ready and willing to become their single mother by choice.

Dawn Cooper & daughters
Dawn Cooper & her adopted daughters

Tonia, now 19, and Maranda, now 18, had been living with a foster family for six years. They were placed in care after living in abandoned sbuildings with a father on drugs and a mother who couldn’t leave him even after a judge told her she couldn’t keep the girls unless she did. Unfortunately, Tonia and Maranda’s foster parents picked up where their biological parents left off, neglecting them as well. When the girls came to live with Dawn they were clearly suffering from a lack of care-- their teeth were in such bad shape that the dentist Dawn took them to had to administer painkillers after cleaning them.

Unfortunately, Tonia and Maranda’s foster parents did little to help the girls transition into their new life with Dawn. As a result, the girls believed that accepting her as their new mother was an act of betrayal. For a long time they refused to call Dawn “Mom.”

“It was wild when they first came home. These children can certainly be challenging. But they’re not the monsters some people make them out to be, for goodness sake,” Dawn said. She steadfastly treated the girls as her own children and slowly she won them over.

She provided lots of structure and clear-cut expectations. There was no TV during the week and Dawn monitored what they watched on weekends. On Sundays the family attended church. Dawn was very clear about her desire for the girls to get good grades in school as well as follow the rules at home. When Tonia started 7th grade after Dawn adopted her, she hadn’t yet learned her multiplication tables. She is now a college student majoring in elementary education.

Eighteen months after Tonia and Maranda joined her family, Dawn adopted DeLisa, who was then 8. DeLisa, now 13, had been diagnosed with RAD, or reactive attachment disorder. RAD is described in The DSM-IV (a guide for psychiatric diagnosis) as “developmentally inappropriate relatedness,” which is caused by deficient caretaking situations or grossly inadequate parenting. Clearly, DeLisa had not been nurtured as a baby or as a young child. And, although RAD does respond positively to nurturing and adequate care, there are no guarantees. Because DeLisa suffered from RAD, she had no trouble calling Dawn “Mom” from the very beginning. Not to be outdone, Tonia and Maranda then decided they would call Dawn “Mom,” too. Over time DeLisa has been able to develop a loving relationship with Dawn, but still has issues around trust.

Three years after DeLisa joined Dawn’s family, Samantha, now 15, came to the family after surviving a disrupted adoption. Samantha knew that she wanted a permanent family and is making strides now that she has the security of knowing Dawn and her sisters are all in this together—forever.

Dawn admits that raising her girls as a single mom is challenging. Despite all her preparatory reading and learning, she readily admits that she was unprepared for the reality of raising children who had been neglected. She has learned a great deal along the way, much of it through trial and error.

She co-founded a support group for other parents who had adopted through foster care in Indiana, and serves as an Indiana Representative of NACAC (The North American Council on Adoptable Children).

Dawn wants people to know that raising her daughters has been the most gratifying experience of her life. She hopes to continue building her family and adds that she can envision adopting up to ten girls through foster care.

“Adopting older children has its advantages. You know who they are. Their good points and their weaknesses. When you give birth to a baby you have no idea who that baby is or what he or she might become. Everyone has issues,” Dawn said. “But with an older child, you can find someone who is compatible with you, who might share you passions – like basketball or music.”

Carolyn Berger, LCSW, is AFA’s Adoption Coordinator. She is the mother of two sons, one biological and one adopted. Next month’s adoption article will focus on the how to’s of adopting through foster care.

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