SCIENCE PULSE    Day 3 vs. Day 5 Transfer

The field of assisted reproduction is continually changing and this is a good thing because, for the most part, these changes have been for the better. Better medications, improved treatment strategies and a better understanding of laboratory techniques are resulting in constantly improving embryo implantation rates. This will allow us to transfer fewer embryos, reducing the risks for twins or triplets, which will result in better obstetrical outcomes for our patients. Our goal in assisted reproduction is to do all we can to ensure that chromosomally normal embryos have the opportunity to result in a healthy pregnancy.

More and more, Pacific Fertility Center is utilizing the day-5 embryo transfer procedure. The benefits of this are to 1) improve implantation and pregnancy rates and 2) lower the number of embryos transferred*. Allowing embryos to remain in the laboratory for 5 days after egg retrieval (as opposed to the more standard 3 days) gives us an opportunity to choose those embryos most likely to carry normal chromosomes and those most likely to keep developing in the womb after embryo transfer. PFC utilizes low oxygen incubators* almost exclusively. As such, we are seeing an improvement in the percentage of embryos that are developing well in the lab environment, as evidenced by their continued progression from a cleavage stage embryo to a blastocyst stage embryo.

Although Day-5 embryo transfer has been around for a while, we have been hesitant to use it exclusively for our patients. Clinical data suggests that unless a woman has a good number of nice looking embryos on day 3, the risks of having no well developed embryos on day 5 is fairly high. Therefore, the patient choosing to attempt a day-5 transfer might end up with virtually no embryos to transfer. One argument asserts that this is what would probably occur within the uterine lining anyway. However, there are studies suggesting that pregnancy rates in women with less than three or four nice 8-cell embryos on day 3 will have a higher chance of pregnancy with a day-3 transfer as compared to women with less than three or four nice 8-cell embryos who have a day-5 transfer. We are noticing that, with the use of our new low oxygen incubators, we are getting better developed embryos on day 3. These embryos, in turn, have a greater chance of being a nice embryo on day 5.

We are also seeing a small but growing number of couples interested in the transfer of only one embryo because they wish to avoid the risks of having a twin pregnancy. Although the over-whelming majority of babies born as a twin do well, there is a measurable increase in the incidence of perinatal death and cerebral palsy in twins as compared to babies born as a singleton. Also, we have many patients returning to us for baby #2 or #3 and they would like to avoid a multiple gestation. This has been particularly true for our patients using donor egg-derived embryos. Last year, we saw a 50% pregnancy rate in women electively transferring one embryo in the donor egg program. We will definitely support any patient that wishes to transfer only one embryo at a time, and we will likely encourage day-5 transfers to better select the one embryo most likely to implant.

One potential downside of attempting day-5 transfer is the question of whether or not we will increase the number of pregnancies in the fresh IVF cycle at the expense of additional attempts with frozen embryos. This is because embryos frozen at a cleavage stage [day 3] have historically done better with freezing and thawing as compared to day-5 embryos.

Pacific Fertility Center has always had a strong freezing program with excellent success rates with frozen embryo transfers, mostly at the day-3 stage of freezing and thawing. Many patients have asked us why we do not freeze some embryos at day 3 and culture some to day 5. One reason is that when we freeze some embryos at day 3, we are taking them out of contention for fresh embryo transfer and therefore, we may be losing some of the selective advantage of doing a day-5 transfer. With patients that have a very large number of embryos on day 3 that look good (say 15 or more), this may still be a viable strategy. Most patients don’t have many good quality cleavage stage embryos, however. So when we are planning to attempt a day-5 transfer, we will usually plan to culture all embryos to day 5 and select the best one or two for transfer and freeze the remainder as a day-5 embryo. As a result, we are now seeing a larger number of our patients returning for frozen embryo transfer with their day-5 frozen embryos. Our laboratory director, Dr. Joe Conaghan is currently reviewing the data on implantation rates from frozen-thawed day-5 embryos from 2005.

Listed below are some of the situations for which we are more likely to recommend a day 5 transfer. These include:

   1. Any woman undergoing transfer with donor egg-derived embryos (anonymous donors)
   2. Any woman less than 40 with a large number of eggs/embryos/good quality day 3 embryos
   3. Any woman that has had poor success with freezing and thawing on day 3 in prior ART cycles
   4. Any patient considering transferring only one embryo
   5. Any patient with a history of multiple ectopic pregnancies (one recent abstract from the ASRM
       meeting suggested a decrease in the ectopic rate after IVF with a day 5 vs. day 3 embryo transfer).
   6. Any woman with unexplained IVF implantation failures with day-3 transfer.

* For other articles from Fertility Flash related to this subject please click on the following links:
Low O2 Incubators
Stages of Embryo Development
From Egg to Blastocyst

CONCEPTION HEALTH    Exercise and Infertility

In addition to physical benefits, gentle to moderate exercise is a healthy way to control the stress related to dealing with infertility diagnosis and treatment, but not all exercise is beneficial.

Level of Exercise
Everyone has a different level of exercise at which point it interferes with fertility. There is risk that the biological stress associated with exercise may induce ovulation problems and can, at times, increase the risks associated with fertility treatment. Maintaining or initiating a well balanced diet is important. This includes diverse nutrients (complex carbohydrates, balanced protein, low fat), a vitamin supplement and adequate hydration, especially during periods of exercise. Weight should be monitored: if weight loss occurs, intake should be increased; if weight gain occurs, intake should be evaluated and revised accordingly. Rapid weight gain or loss is not recommended.

Extreme exercise may affect fertility in both men and women. Serious athletes may have to add more calories to ward off fertility problems. Individual evaluation by a physician is recommended for those who are in a rigorous exercise program and concerned about their fertility.

If a woman has an established exercise program prior to treatment, that level of activity may be maintained and continued with some minor modifications and reasonable precautions.

If a woman has not begun an exercise program prior to treatment, a gentle start is advised such as walking or swimming 15 to 30 minutes, three days a week. A slow and steady increase in duration and frequency can be accomplished over a period of several weeks. A good guideline to follow is if it is difficult to carry on a conversation, slow down. For those starting a new program and can afford the luxury of a professional trainer, working with one who has expertise in exercise during pregnancy is a great way to begin.

Heavy exercise spurts followed by long periods of no activity is not recommended. Gentle to moderate, regular exercise is best.

Modifications to Exercise During Infertility Care
Generally, it is safe to assume that if an activity is uncomfortable, don’t do it, especially when considering discomfort in the region of the ovaries. Near the end of an IVF cycle and for a month after, avoid jostling tender ovaries and activities where even slight injury to the abdomen may occur. Ovaries are enlarged and may be uncomfortable when being jostled. Aside from causing discomfort, there is an increased risk of ovarian torsion, particularly after 5-7 days of gonadotropins. Bouncing exercises to avoid include vigorous step aerobics and running. Less traumatic, low impact exercises, such as walking, yoga, Pilates, swimming, are preferred.

A general rule of thumb is to aim for a target heart rate of 120-130 from stimulation day 8 to one week post transfer.

Contact sports or other activities that may increase the chance of bumping or hitting the abdomen or increase the risk of a fall such as horseback riding, vigorous racquet sports and downhill skiing should be avoided.

Avoid overheating especially during exercise; this includes hot tubs, hot yoga and exercising during very hot days.

Avoid conditions that limit oxygen availability especially during aerobic exercise; hiking up to a 6000 feet altitude is an acceptable limit.

Scuba diving is absolutely not recommended.

These are general guidelines, however, everyone’s level of comfort and physical condition is unique. It is always recommended patients discuss their exercise regimen with their physician.

PHOTO GALLERY    Day 3 vs. Day 5 Embryos

The sequence shown below shows an 8-cell embryo on day 3 (#1) in which the cells are beginning to press up against one another (see 2 cells flattening against each other). After about 16 hours, the cells have divided again to produce a 16-cell embryo (#2) and they have compacted together even more. By day 4 of life (#3) the embryo is completely compacted to the point that individual cells can no longer be seen. At this stage the embryo is called a morula from the Latin for mulberry. The compaction process results in a fluid tight seal between cells and the embryo can now pump fluid into the center of the ball of cells. The cavitating morula (#4) also allocates cells to the inside and outside (#5) of the growing cavity or cyst. The outer cells will form the placenta of the implanting embryo and the inner cells will form the embryo proper or fetus, as well as some of the extraembryonic membranes such as the yolk sac. When the cyst is formed and cells have been allocated, the embryo is called a blastocyst (#6). The quality of a blastocyst is determined by the number of cells in the outer and inner populations as well as the degree of expansion of the cyst.

ASK THE EXPERTS    Insurance Coverage

Answer:
The package of insurance coverage for infertility treatment is not up to the insurance company, per se. It is typically up to an employer to determine the scope of coverage that is offered by its insurance company, and whether that package includes compensation simply for diagnosis of infertility, or whether it also covers treatment.

Moreover, one cannot assume that coverage will be the same from one employer to another even if that company uses the same insurer. For instance, an employee of Bank of America with Kaiser coverage might have a completely different insurance package for infertility as compared to an employee of Wells Fargo who also has Kaiser insurance. Through negotiation, an employer may choose an insurance plan with more or less infertility coverage than the average plan.

Another caveat has to do with state regulations. A total of 12 states in the United States have passed laws mandating infertility insurance coverage. However much of this regulation is considered a “soft mandate” meaning the insurers only have to offer it to employers who can choose to take it or leave it. California has a soft mandate so companies here are not legally obligated to purchase coverage for its employees.

A more forceful “hard mandate” requires a company to actually provide it, not just offer it. Massachusetts and Illinois are two states that have this hard mandate.

An exception to this is when a company is self-insured and is not legally required to follow state mandates. Because the majority of people with employer-sponsored health insurance policies are "self-insured", the mandates do not apply to the majority of people, even in states with mandates.

Obviously, people who are self-employed and therefore pay for their own insurance might have a greater motivation to research those insurance companies that might have more comprehensive infertility coverage. Watch for subsequent articles in Fertility Flash that address this question for people who purchase insurance directly from insurance companies. In addition, the financial consultants at Pacific Fertility Center are available to work with our patients so they receive the benefits their insurance company provides. Click here for more Insurance Information.

PATIENT ODYSSEY:    Egg Donor’s Journey

  I was a culinary student looking on the Internet for a part time job to help pay for tuition when I stumbled on the possibility of donating my eggs. I liked the idea of being able to help someone else while helping myself. The center was conveniently located and I could still work during the process. It seemed like a win-win situation.

It took me a while to think it through. I came to realize that there were a lot of people who needed this kind of help. After a while, I talked it through with some of my friends and discussed it with my mother. She was very supportive and helped me fill in the family medical history part of the application.

My first experience with Pacific Fertility Center was positive. I was struck by how welcoming they were. I was very curious to discover more about the whole process and they were happy to answer all my questions and to be sure I understood what I was agreeing to do.

Once I was selected as a donor, I learned how to give myself shots. It wasn’t as difficult as I thought it might be. (That part never really bothered me.) The doctors and the nurses were always ready to answer questions as they came up. After donating a few times, I think I met every one of them.

The actual cycles were easy for me except for occasional periods of grumpiness. I was able to maintain my work/class schedule. They really tried to work around my schedule and make it as easy as possible for me. I loved how friendly everyone was. I became friends with the nurses. We were on a first name basis. They were always asking me about my work and if I ran into them outside of work, we would stop and talk.

The best part of being a donor was receiving the thank you notes and flowers. You realize how important your contribution is for people who can’t get pregnant using their own eggs. It felt great to discover that 5 out of 6 got pregnant with my eggs. I really feel like I was able to make a difference in someone’s life. I would definitely recommend becoming an egg donor to others.

After donating the maximum number of cycles, I have now “graduated” from Pacific Fertility Center’s Egg Donor Agency. I miss the friends I made at the center, but am happy to report I am pregnant and starting a family of my own.

FROM US TO YOU:   PFC Receives 5-Star Rating in "Babies By The Bay"

We are pleased to announce that Pacific Fertility Center (PFC) received a 5-Star rating and an informational listing in the 2005 parenting publication, Babies by the Bay, 2nd edition by Michelle L. Keene and Stephanie S. Lamarre. This comprehensive parenting resource delves into numerous aspects of pregnancy and parenting, including health care resources, pre- and post-natal fitness, maternity clothes, and parenting organizations, to name a few. Most of the parenting resources included are based in the San Francisco-Bay Area. Nevertheless, the book does provide a framework for identifying available parenting resources…regardless of the locale.

PFC is profiled in the Infertility chapter. (PFC’s 5-star rating is the highest rating an organization can receive.) The profile lists PFC’s physicians and provides center contact information.

Additionally, Babies by the Bay highlights worthwhile infertility support groups such as RESOLVE and SOREI. Valuable background information on infertility is provided as well. For instance, there is a section dedicated to the prevalence of infertility as well as steps for identifying proper treatments—from speaking with an OB/GYN, to assessing doctor credentials, to evaluating infertility clinic success rates.

Babies by the Bay provides tremendous flexibility for the reader. Chapters are organized intuitively, coinciding with the different stages of parenthood. Sections on childbirth are located in the beginning, and are followed by sections on schools, and after school activities.

Given its breadth of information, Babies by the Bay makes a valuable addition to the library of any prospective or new parent in the Bay Area.

  Left to right: Front Row: Carl Herbert, MD, Isabelle Ryan, MD Back Row: Joe Conaghan, PhD, Eldon Schriock, MD, Carolyn Givens, MD, Philip Chenette, MD

The physicians at Pacific Fertility Center are internationally recognized specialists in reproductive endocrinology and infertility. They have completed top-level medical education, published groundbreaking professional papers, and held positions on the faculty of leading research universities. They continue to participate in reproductive research. All MDs are Board Certified by ABOG as Reproductive Endocrinology and Infertility Specialists. Our state-of-the-art laboratory has one of the most highly trained teams in the country with every embryologist board certified and licensed in their specialty.

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-- Best regards from all of us at Pacific Fertility Center.