GIVF Achieves First Birth From Egg Freezing Technology

By: Jennifer Machovina, RN, BSN, Director, Donor Egg Program and Andrew Dorfmann, MS, ELD (ABB), Director, Embryology Laboratory

When we met Stacy in June 2007, it would have been hard to imagine all the twists and turns that lay ahead for her, and how in the end, GIVF would use an exciting new embryology technique for cryopreserving oocytes to help her and her husband to complete their family.

Like so many couples who come to GIVF for help starting a family, she and her husband had wanted to have a baby for a long time. They had used In Vitro Fertilization (IVF) to have their first child and were overjoyed when they succeeded on their very first try and Stacy gave birth to a beautiful little girl. Unfortunately, when it came time to try again they didn't have the same luck.

Stacy and her husband were at a difficult crossroad, so they decided to look into other options. During a consultation on future treatment options, we discussed our donor egg program with her. As it happened, GIVF was studying the feasibility of oocyte cryopreservation (often called "freezing") using a new method called vitrification. This new method has the potential for great flexibility and efficiency in the donor egg process and is also a way for certain women to preserve their fertility in the face of cancer or increasing age. As part of a clinical trial, GIVF was offering several cycles of vitrified donor oocytes to pioneering recipient couples who qualified for the study. Stacy and her husband were perfect for the trial and decided to become participants.

When their treatment cycle began, two embryos were transferred into Stacy's uterus. After waiting through eleven anxious days before she could have a pregnancy test, we were able to give her the great news that her test was positive! She had overcome her first hurdle, but there was still a long way to go. Her next pregnancy test showed a great rise in her pregnancy level. Therefore, we tentatively scheduled an ultrasound for her sixth week of pregnancy.

We walked into the office that day full of nervous excitement. We had not yet achieved a pregnancy through oocyte vitrification at GIVF, but were very hopeful about this case. Would this be the day we'd be able to hear an incredible sound and the proof of all our hard work, patience and perseverance? Standing in the hall outside the procedure room, we heard all of the normal sounds of a gestational ultrasound: the sonographer clicking buttons on the ultrasound machine and the physician chatting away while putting on his gloves. Then, there was a seemingly endless silence, until we heard the wondrous sound of a heartbeat. When we understood what had happened, tears instantly welled up and we were speechless. We were able to help Stacy and her husband create a miracle. Now, Stacy and her husband are enjoying a beautiful baby girl. For them, it is a dream come true. It is also a dream realized for the GIVF staff. The nurses and physician, Dr. Stephen Lincoln, the donor coordinators and the innovative professionals in the Embryology Lab all know that we accomplished something significant and meaningful for Stacy and for future patients. Stacy's pregnancy was the culmination of extensive research at GIVF on how to cryopreserve eggs so that, when warmed, they will fertilize and create a healthy pregnancy. We realize that GIVF achieved yet another milestone in our quest for new ways to help our patients. But most importantly, we were able to help this incredible couple fulfill their dream of having another child to love. We wish them great health and happiness in the years to come and we look forward to helping many other couples with the same innovative technology.

Can A "Kiss" Restore Fertility?

A study presented at the annual meeting for the Society for Endocrinology reported on a potential fertility therapy for women with low sex hormone levels. The small study included ten women who were not menstruating due to a hormone imbalance. The researchers gave half of the women injections of a hormone called kisspeptin. Kisspeptin, the small hormone that is associated with the initiation of puberty, also plays a vital role in the brain to trigger ovulation. The signaling between kisspeptin and its cell receptor GPR54 is essential to activate gonadotrophin-releasing hormone (GnRH) neurons, the nerve cells involved in the initiation of ovulation. The women who received kisspeptin had a 48-fold increase in LH and a 16-fold increase in FSH compared to the women in the control group. Study author Dr. Waljit Dhillo stated, "This is a very exciting result and suggests that kisspeptin treatment could restore reproductive function in women with low sex hormone levels. Our future research will focus on determining the best protocol for repeated kisspeptin administration with the hope of developing a new therapy for infertility."

And it is just a coincidence that the name kisspeptin is associated with fertility. Scientists in Hershey, PA discovered the gene and named it after the popular candy Hershey's Kisses.

Study Shows Fertility Drugs Do Not Increase Risk of Ovarian Cancer

A study published in the British Medical Journal found that the use of fertility drugs does not increase a women's risk of ovarian cancer. Previous studies have produced conflicting results. This is the largest study (over 50,000 women) ever performed on the topic and was conducted by the Danish Cancer Society. The women were all patients at Danish fertility clinics between 1963 and 1998. The researchers looked at the effects of four groups of fertility drugs over an average period of sixteen years. They found no increased risk of ovarian cancer after use of any fertility drug. There was also no increased risk among those women who completed ten or more cycles or those women who did not become pregnant. The researchers do note that many of the study participants have not reached the peak age for ovarian cancer and they will continue to monitor the risk.

Biomechanical Processes in Embryo Implantation

A Tel Aviv University reseacher recently published an article in the journal Fertility and Sterility on the biomechanical processes of embryo implantation in an IVF cycle. Professor Elad has been studying the biomechanical engineering of pregnancy for over 15 years. He is currently studying how the uterus contracts before the embryo implants itself into the uterine wall. He explains “Uterine contractions push the fluid inside a woman’s womb in a peristaltic fashion, which helps sperm reach the ovum in the fallopian tube. And after fertilization, this same peristalsis propels the embryo to its implantation site in the uterine wall. It’s a fluid mechanics issue." He believes the physical positioning of the women and the shape and size of her uterus affect the implantation process. By studying this mechanical process he hopes to predict the optimal time and site for implantation during an IVF cycle.

Professor Elad is developing a computer simulation program which will model how and when IVF embryos should be transferred to the uterus. He states “There is no such thing as a standard uterus. Our research offers best practices for women of all shapes and sizes.” It is hoped this research can improve IVF success rates; and at the same time reduce the number of embryos transferred and avoid the risk of multiple births.

The Top 10 Top Ten Infertility Lists

1. Top Ten tips for coping with infertility problems

2. Top Ten infertility questions to ask your doctor

3. Top Ten ways to boost your fertility

4. Top Ten fertility challenges

5. Top Ten things NOT to say

6. Top Ten infertility myths

7. Top Ten factors which can affect male fertility

8. Top Ten foods for fertility

9. Top Ten monthly fertility mistakes women make

10. Top Ten infertility books

Teens 'Clueless' About Infertility

Canadian researchers conducted a survey of teens which highlighted a lack of knowledge about infertility. Of the 608 teens surveyed (average age 17.5), only 6% understood the link between sexually transmitted diseases (STD's) and higher rates of infertility. The scientists also found that low income students were among the least informed of the participants, being the least aware of the links between infertility and STD's. About 25 percent thought fertility problems only occurred among women 40 years or older. On a positive note, more than 1/2 the teens were open to being screened for STD's as a means of protecting their fertility. Also most responded that their fertility was important to them. The researchers suggested that education programs should target teens to increase infertility awareness. They noted that it is important to educate young people about modifiable risk factors for infertility; such as body fat, smoking, caffeine consumption, excessive exercise, drug use, and sexually transmitted infections.

Women's History Month

A woman's fingerprints on the fingerprints of life　

In 1962, James Watson, Francis Crick and Maurice Wilkins received the Nobel Prize in Physiology and Medicine for the work all three performed in nucleic acid research, but primarily for the discovery of the double helix structure of DNA by Watson and Crick. In popular culture Watson and Crick are often referred to as the men who discovered DNA, the genetic code that carries the "instructions" for the development and functioning of cells and organisms. Popular history is deficient, however, by leaving out a fourth name, that of Rosalind Franklin, whose contribution to the discovery of the double helix was equal to, and possibly greater than, that of Watson, Crick or Wilkins, although Watson and Crick were instrumental in identifying the operation of base pairs in DNA.

Rosalind Franklin, born in 1920 in London, graduated from Newnham College, Cambridge in 1941, but was granted a titular degree, as at that time women were not granted full degrees by Cambridge. During World War II Franklin performed cutting edge research on coal and high strength carbon fibers in support of the war effort. In 1945 she was awarded her PhD in physical chemistry from Kings College, Cambridge and joined the faculty, where she became a member of a group working on DNA research. There she encountered Maurice Wilkins, who subsequently was assigned the work on the B form of DNA while Franklin directed the effort on the A form of DNA. Drs. Wilkins and Franklin had very different personalities. Some professional antipathy developed between the two of them.

Dr. Franklin did significant work with x-ray defraction. She took many photographs using this technology that essentially verified the double helix structure of DNA (there had been alternative theories, such as one developed by Linus Pauling, who thought that DNA must be a triple helix). One of the great controversies in modern science is centered on these photos. Photo 51, described as, "amongst the most beautiful x-ray photographs of any substance ever taken," was shown by Wilkins to James Watson without Franklin's knowledge or consent. Max Perutz, Crick's thesis advisor, showed Crick a report containing calculations by Franklin, also without her knowledge or consent. On one hand, Dr. Franklin was in the process of moving from Kings College to another university, while her research belonged to Kings College. On the other hand, the crucial role played by Franklin's research is undeniable. "The instant I saw the picture," Watson was to write many years later, "my mouth fell open and my pulse began to race..."

In a tale reminiscent of Alexander Graham Bell and Elisha Gray both filing patent applications for the telephone on the exact same day in 1876, Dr. Franklin submitted two papers on the general structure of DNA on March 6, 1953 to a major scientific journal in Denmark, just one day before Watson and Crick completed their model. Watson and Crick published a full description of their model in Nature on April 23, 1953. In many respects, Dr. Franklin was a victim of her own meticulous nature. She felt that more research was required to confirm the data, which lead to one heated exchange between Watson and Franklin in which he told her that she did not know how to interpret her own data. In 1953, Franklin went on with her plans to leave Cambridge and went on to work on the tobacco mosaic and on polio viruses and other path breaking work that laid the foundation of structural virology before her untimely death in 1958. Since the Nobel Prize cannot be given posthumously, we will never know whether she would have been recognized with the Nobel prize along with Watson, Wilkins and Crick in 1962, but it appears doubtful since she stopped working on DNA after she left Cambridge.

In 1998, the National Portrait Gallery placed a portrait of Franklin along side those of Drs. Watson, Crick and Wilkins. In 2002, the U.S. National Institutes of Health's National Cancer Institute created the "Rosalind E. Franklin Award for Women in Science" and in 2008 Columbia University posthumously granted her the Horowitz Prize in honor of her "seminal contribution to the structure of DNA." Numerous buildings and gardens have been named for Dr. Franklin around the world, but her greatest legacy remains her groundbreaking scientific work.

Real Time Sperm Testing Takes Step Forward

Scientists have created a new method for testing sperm quality before it is used in IVF cycles. Currently, the results of testing the quality of sperm DNA can be used to make inferences about the sperm in a specimen or about the sperm that a particular male produces, not about a particular sperm itself. This is because current sperm DNA tests are destructive tests, which means that the sperm is rendered useless as a result of the testing and therefore cannot be used in fertilization. Unlike existing tests this new test is not destructive to the sperm and the "best" sperm can be chosen for fertilization.

As discussed in this article, researchers at the University of Edinburgh figured out how to chemically fingerprint a sperm to determine its quality. Laser light is used to trap an individual sperm and the sperm's DNA properties are identified by the patterm of the vibrations they emit in a process known as Raman spectroscopy.

Dr Alistair Elfick, lead scientist on the project, said: "In natural conception the fittest and healthiest sperm are positively selected by the arduous journey they make to the egg. What our technology does is to replace natural selection with a DNA based 'quality score'." It should be noted that a sperm's job it two-fold: to contain a package of DNA that is of sufficient quality to create an embryo and support its normal development. The sperm also needs to be able to successfully deliver that DNA package to the egg. Dr. Elfick's work addresses only the DNA quality aspects of the sperm's job description and not the delivery aspects. Unfortunately, no data are available currently to determine the effectiveness of this procedure, but given what we know about the relationship between sperm quality and successful fertilization, it sounds like a promising approach. If proven successful during clinical trial this technology could be available in the next five to ten years.

Common Chemicals Linked to Infertility

A recent study in the journal Human Reproduction links exposure to common household chemicals to an increased risk for infertility. The study included over 1,200 women in early pregnancy who were questioned regarding how long it took them to become pregnant. Two types of PFCs were measured in the blood samples of the women. The first was perfluorooctane sulfonate (PFOS), which is found in some cloth and paper products, and the second was perfluorooctanoate (PFOA), that is commonly used in carpets and personal care products. Researchers found that the higher the concentration of PFCs in a women's blood, the greater the likelihood it will take more than one year for her to become pregnant. According to representatives of manufacturers who use PFCs, the results of the study show only an association and not a cause and effect. However, the major manufacturers of items containing these chemicals have agreed to a voluntary phase-out of their usage.

What is Egg Vitrification?

I've been hearing a lot about egg freezing and vitrification lately. Would you explain a little bit about that?

Answered By: Andrew Dorfmann, M.S., Director of the GIVF Embryology Laboratory

In the last several years, significant advances have been made in the ability to cryopreserve (freeze) oocytes (eggs). While we have been freezing embryos successfully for more than 20 years, freezing oocytes had proven to be a more difficult technique for embryologists. Over the past several years, however, thanks to the advent of Intracytoplasmic Sperm Injection (ICSI) and some refinements in freezing techniques, we have been able to successfully freeze and thaw oocytes with rates of success that are similar to the success we achieve freezing embryos. These efforts were pioneered in Japan and in some European countries such as Italy, where laws governing the freezing of embryos have become quite restrictive.

One of the methods that has been used successfully around the world, including right here at the Genetics & IVF Institute, is vitrification. Vitrification is actually an older method for rapidly freezing cells which has been recently revived to great advantage in the IVF laboratory. Most recent data points to vitrification as the preferred method for freezing both oocytes and blastocyst stage embryos. GIVF now has two ongoing pregnancies from oocyte vitrification and we have adopted vitrification for freezing blastocysts.

The question we are often asked is: why freeze oocytes? There are three fundamental reasons: 1) fertility preservation; 2) donor oocyte banking; and 3) certain potential ethical advantages. Fertility preservation may be attempted for one of two reasons, either for a patient with cancer or another disease who wants to preserve oocytes, or in some cases ovarian tissue, prior to receiving treatment, or for younger women who want to freeze and store oocytes for use later in their lives when they are ready to begin their families. Freezing donor oocytes has the potential to make the process of donor egg IVF considerably easier. It will obviate the need to synchronize donor and recipient cycles, and has the potential to make the process much more efficient for everyone involved and for making donor oocyte treatment more available.

A few advanced infertility practices such as GIVF are investigating the possibilities for donor egg banking. In the future, we probably will see oocyte banking become a reality, just like sperm banking. A GIVF donor egg bank will be initiated soon. More information about this new and exciting program is available in this edition of eNews and on our website.

Freezing oocytes rather than embryos may ease decisionmaking for patients concerned about the disposition of "extra" embryos after IVF cycles. While freezing oocytes is still not an appropriate alternative for most couples, it may become a viable option in the future. Just like embryo freezing, ICSI and countless other new techniques before it, oocyte freezing has a bright future and the potential to revolutionize the practice of IVF.