SCIENCE PULSE    Grading of Blastocysts

For patients having their embryos transferred at the blastocyst stage, the grading procedure used to assess the embryos can seem complicated. However, we simply look to see that the embryos are developing normally, are not slowing down, and are preparing for implantation in the uterus.

In the 2 days following fertilization, embryos go through 3 rounds of cell division. The fertilized oocyte divides in 2, these cells each divide again to give 4, and then these divide to give 8. In the resulting 8-cell embryo, each cell should be 1/8 the size of the original oocyte since there is no growth in size, and each cell should be intact and symmetrical. When we assess embryos at this stage, we first count the number of cells and we then assign a grade based on how good the embryo looks. Embryos that have disintegrating or asymmetrical cells are assigned a lower grade.

At this early stage, the individual cells stay together because they are contained within a shell called the zona pellucida. However, as the embryo progresses past the 8-cell stage, dividing to 16 and then 32, the cells attach to each other and cooperate to form a tight ball called a morula. At the morula stage, the cells are pressed so tightly together that individual cells cannot easily be identified or counted. Once the attachments between cells are formed, the cells begin to pump fluid into the center of the ball, giving rise to a tiny fluid filled cavity or cyst. As long as the junctions between cells hold, no fluid can escape from the cyst, and the cyst grows larger as more fluid is pumped in.

These are critical days for the embryo. In addition to forming the central cyst, the embryo is also busy organizing its cells into two distinct populations. As the embryo moves beyond the 8-cell stage, some cells stay on the outside of the ball and some are pushed to the inside. In the typical 16-cell embryo, there are 12 outer and 4 inner cells. At the 32-cell stage, 22 of the cells are outer cells and 10 are inner cells. Creating more outer cells is deliberate, because these cells are needed to maintain the integrity of the cavity as it becomes larger. More importantly however, these cells will become the placenta, and having enough cells to establish the placenta is critical to successful implantation in the uterus. Once the placenta is established, it can feed the inner cells which become the developing fetus.

The appearance of the cyst at the center of the morula marks the next embryo stage, the blastocyst. In assessing the blastocyst, we look at the size of the cyst and the integrity of the outer and inner cells. Depending on the size of the cyst, the blastocyst is referred to as early, expanding or fully expanded. If the cyst has become large enough to cause the embryo to burst through its shell, we call it a hatching blastocyst. Occasionally, we even see fully hatched blastocysts. Hatching is a natural process that frees the embryo from its shell to allow implantation to occur. The more expanded the cyst has become, the more we favor the embryo for transfer.

In addition to looking at cyst expansion, the grade of the blastocyst is further determined by the integrity of the inner and outer cells. Embryos with more cells are better, and the best blastocysts are well expanded with distinct inner and outer cell populations. In poor quality blastocysts, there can be few cells in one or both populations, and/or the cavity can be small. And sometimes, even in embryos with beautiful outer cells, we cannot see any inner cells at all. These embryos are destined to fail since a full blastocyst with 32 cells is incapable of making inner cells if they do not already exist.

The embryos that are most difficult to assess are those where the cavity has just begun to open up, but has not expanded sufficiently to allow us to see inside. These early blastocysts are usually assigned lesser grades as we are unable to determine whether any inner cells are present. We often look at these embryos again several hours later to see if further expansion has revealed the presence of those critical inner cells. We would then re-grade the embryo, if appropriate.

All of this development, from fertilization to blastocyst expansion and hatching, normally follows a tight timeline that is independent of cell number. The embryo attempts to hatch from its shell approximately 5 or 6 days post fertilization, regardless of the number of cells it contains. If development is slow, and cell number is consequently low, the outer cells stretch to enclose the cyst and expansion continues. This is important, as the uterus waits only a few days for the embryo to implant. If the embryo takes too long to make the “right” number of cells for expansion and hatching, it may miss the implantation window. The practical result of this is that we still get high implantation rates even if only early blastocysts are available for transfer.

The above phenomenon is relevant to frozen embryo transfer cycles too, because many embryos lose one or more cells as a result of freezing and thawing. Such embryos still try to form blastocysts according to their original timeline, even though they may have less than the ideal number of cells. The consequences of arriving with plenty of cells but too late for the uterus are worse than having a chance to implant even with fewer cells. As a result, frozen-thawed embryos that have lost a cell or two are not assigned a lower grade since we still consider them to have high implantation potential.  Joe Conaghan, Ph.D., HCLD

ASK THE EXPERT    Choosing an Egg Donor, Part 2

In the June 2008 issue of the Fertility Flash, Dr. Isabelle Ryan answered a question on how to choose an egg donor from a medical perspective. This month I’ll focus on the psychological aspects of choosing an agency egg donor. As the Marriage and Family Therapist at Pacific Fertility Center, this is a question I address regularly. All PFC patients considering ovum donation will have a complimentary meeting with me

Choosing an egg donor may seem like a daunting and foreign process. You are undertaking an unfamiliar task that you probably never planned on. But now that you are here, it may help to remember that the gene pool is huge. No matter whose gametes create your offspring; your children will be a magical and unique blend of nature and nurture. DNA is not destiny. Your love, your values, your womb, all have an impact on the person your child will become.

I find the following to be helpful reminders as you move forward with choosing a donor:

• The experience of attachment to a child, the feeling of being in love with him or her, happens regardless of whether one or both parents share the child’s DNA.



• Mothers and fathers are the ones that raise and love a child. Donors are the ones that donated or helped.



• Most donors donate for a complex blend of altruistic and monetary reasons.



• Each of our PFC agency donors has a psychological interview with me. In addition they take a psychological test (PAI); this test assists me in assessing not only their personality, but also their honesty and reliability.



• The more stringent your criteria for choosing a donor, the longer it will take to find her.

So, how in the world do you choose a donor?

I think there is a relatively simple answer to this seemingly complex question.

Choose the donor that jumps off the page at you. Choose the donor whom you like best, resonate with, feel a connection to, are impressed by.

That donor may or may not look exactly like you, but she will be someone you might have chosen as a friend or you could imagine as your daughter.

I believe the goal in choosing an egg donor is to be able to look at your child and either say or think to yourself, “we couldn’t use my DNA, but we chose someone we thought was lovely, interesting, attractive, smart, motivated (add the adjectives of your choice) to be our child’s donor. “

Practically speaking, if you have a partner, it may work best to look at donor profiles separately from him or her. After each of you note your favorites, you should then come together and choose from the selections that you both indicated. This process helps assure you both were able to choose without pressure from your partner.

Finally, please remember there is no “perfect donor,” but that does not mean you won’t be blessed with the “perfect child.” Peggy Orlin, MS, MFT

A PATIENT ODYSSEY    Marni & Jean

As a lesbian couple, we were aware that getting pregnant might be a challenge and might require medical intervention, but decided to try at home anyway.  Since Jean is older it made sense for her to carry first.  In 2002, we began the process of trying to conceive with our known donor.  We had a few challenges to overcome. Our donor was from out of state and we had to use a shipping kit designed by University of Chicago Andrology Lab to maintain the viability of the sperm.  We hired a midwife to come to our home, clean the semen sample and do the insemination.  In 2004, after two years of trying and many dollars spent, it became apparent that we were not going to be successful on our own. 

We spoke to our OB/GYN who recommended that we work with a fertility specialist.  On a recommendation from a Pacific Fertility Center staff counselor, Peggy Orlin, we contacted Dr. Eldon Schriock at PFC.  Though the initial paperwork and set up seemed daunting, we were able to complete the required items quickly and were ready to start fertility treatment with Dr. Schriock in March 2005.  Jean was set to do the “Clomid challenge” test on our first attempt.  With new FDA regulations looming in May 2005, we felt we had limited time to get Jean pregnant with our current donor so the pressure was on.  Although the PFC staff was not initially familiar with our shipping kit, they were more than willing to work with it and help us with the logistics.  Jean had a fortunate experience with Clomid and on April 15, 2005 with 3 good follicles we completed our first IUI with PFC.  Two weeks and 3 positive pregnancy tests later, we confirmed that we were in fact going to have a baby.  It was hard to believe that after so many years and tries it was actually happening.  Now 3 years later we have a beautiful and fun two year old girl named Logan. 

When Logan was 5 months old, there was an accident in my family that gave us pause.  We realized life is short and you never know what is in store for you around the next corner .We decided to begin the process of trying to get Marni pregnant. In May 2006 we made the decision that we would begin the process at home, but needless to say, we were unsuccessful. After 6 months we would again meet with Dr. Schriock and his fabulous team of nurses and doctors.    Because of our history with PFC, we were able to quickly begin the process and get started trying to achieve pregnancy at PFC. 

With the new FDA regulations now in place we had a host of new hoops to jump through. Once we cleared the list of hurdles, we began our attempt to get Marni pregnant.  After many different fertility treatments (Clomid, Letrazole, and Follistim), three different PFC doctors (Dr. Schriock, Dr. Ryan and Dr. Givens) all suggested that if we were committed to our donor then we should seriously think about IVF as an option because of the quality of his frozen/thawed sperm.  In October 2007 we began the IVF process.  Though there was a lot to manage and keep track of (when to give shots, appointments, blood tests, etc.) we never felt alone.  The PFC doctors, nurses and staff were always available for a phone conference to answer any questions or concerns.  In late November 2007 we completed IVF - the egg retrieval and embryo transfer process.  Four embryos were implanted out of the seven that fertilized.  In December 2007, two weeks later, we received the positive blood test result and were ecstatic.  Unfortunately, within days of the positive pregnancy result it became clear that this was not going to be a viable pregnancy.  Marni had apparently been pregnant with twins. She miscarried the first embryo and had to undergo not only the abortion pill, but a subsequent D&C to remove the second gestational sac.  Dr. Schriock and all of the staff, nurses and other doctors were available for emotional support and medical guidance throughout the process. 

We completed our second egg retrieval and awaited the fertilization results.  Our hopes were high but we were realistic and knew that anything could happen. As it turned out, Marni’s second round of IVF was unsuccessful. Though the quality of embryos was better than in the first cycle, she did not get pregnant.  We had a few conversations with Dr. Schriock and determined that if she were to continue trying to get pregnant, it would take an ovum donor and a lot of money.  We decided to have Jean try again, because we wanted to be pragmatic and realistic and keep the goal of adding to our family in mind.  Jean is currently under Dr. Schriock's care and last week she completed a course of Clomid and an IUI.  We are now in the waiting period and are hopeful for a positive result. 

ur experience with PFC, Dr. Schriock and all the other staff has been great.  We had a few bumps along the way but the doctors, nurses, office manager and staff responded quickly and effectively.  We always felt at ease to express concerns and ask questions.  Everyone we encountered at PFC has a good understanding of how emotional this process can be and has always been empathetic in their dealings with us.  We never felt uncomfortable as a lesbian couple.  We would absolutely recommend PFC for their cutting edge technology, knowledge and exceptional care during this highly emotional event.

Best Regards,
Marni & Jean

CRITICAL REVIEW    Top 10 Fertility Myths

1. A healthy woman in her late 30’s or even in her 40’s, will have the fertility of a younger woman.

Although it is always better to be healthy, especially when it comes to carrying a pregnancy, the likelihood of conception is tied to the age of a woman’s eggs and is not closely related to her general health.

2. You should have sex every other day during the fertile window.

For most men, sperm recovery is very rapid. Sometimes when an IVF cycle is done and there are many eggs to fertilize, we ask for a second semen sample. We are often amazed when the second sample, collected just 2 hours after the first sample, has even better numbers. So, rather than attempting to “save up good sperm” by having less frequent intercourse during the most fertile time period, we recommend more frequent intercourse. A home ovulation predictor kit is useful to time sex to ovulation. When using the ovulation predictor kit, we recommend sex on the first day of the LH surge and the next day too.

3. Fertility medications are associated with a higher risk of cancer.

In the early 1990’s, some concerns were raised that taking fertility medications might be associated with a higher lifetime risk of ovarian cancer. Since then, several studies have been published that did not find this to be true. Because of this thorough and extensive research we feel comfortable using these medications not only on patients, but our egg donors as well.

4. Fertility medications (especially injectable fertility medications) cause women to be emotional wrecks.

Although Clomid (clomiphene citrate) has well-known side effects related to its anti-estrogen effects, the injectable fertility medications do not tend to cause the same negative mood alterations. These drugs increase estrogen levels, a hormone which tends to have positive affects on mood.

5. Using fertility drugs and getting multiple eggs might use up my future eggs and cause me to go into menopause earlier than expected.

Humans usually only ovulate one mature egg each month. This egg is contained in the dominant follicle and grows in one ovary or the other. For each dominant follicle that develops in any particular cycle, there are several other follicles/potential eggs available that are also trying to become that dominant follicle. The number of these other “antral” follicles varies from woman to woman and to lesser degree, from cycle to cycle. In general, the number of antral follicles declines with female age. Once the dominant follicle has been selected and the egg ovulated, the menstrual period or a pregnancy begin, and the other antral follicles, undergo programmed cell death, called atresia. The use of fertility medications rescues this group of antral follicles from atresia. For this reason creating multiple mature follicles and obtaining multiple eggs in any one cycle does not use up future eggs. We are simply rescuing eggs that would have otherwise died that month.

6. Having a miscarriage is a good sign that a woman is fertile.

Approximately 70% of miscarriages are due to abnormal chromosomes (DNA) in the embryo. As a woman ages, more and more of her eggs become abnormal In fact, at age 40, only 1 in 10 eggs on average has normal chromosomes; so a woman at that age may only ovulate one normal egg per year. While a miscarriage may indicate that fertilization and implantation can occur, it doesn’t necessarily mean that overall egg quality is good. Egg quality is the best indicator of the ability to produce a viable pregnancy.

7. Stress is a major cause of infertility.

There is enough circumstantial evidence to indict stress as a collaborator when it comes to fertility; however, there is very little evidence to convict stress as a major perpetrator. Usually there is some other underlying cause to the problem, even if it is just age-related sub-fertility (decline in fertility due to female age and therefore higher numbers of abnormal eggs). Stress, however, can compound the problem and possibly negatively impact egg quality and uterine lining quality. Look for a new addition to our website, the Domar Fertility Stress Questionnaire, to assess your stress levels.

8. In Vitro Fertilization can help women in their late 40’s and even 50’s to conceive with their own eggs.

Despite the number of celebrities having babies in their mid-forties and beyond, these babies may not necessarily have been the result of an in vitro fertilization process using their own eggs. While we respect a woman’s right to privacy and their decision not to divulge this little detail, the perception left with the public is that fertility treatments can extend one’s reproductive life. Unfortunately, this simply is not true. There is a very, very low probability of improving one’s success of conceiving after age 43 by using assisted reproduction, unless the woman considers using donor eggs.

9. In Vitro Fertilization success rates are low.

Across the United States, including patients of all ages, the delivered success rates for in vitro fertilization have risen from about 20% in the mid-1990s to about 35% in the mid-2000s. During this same period, fewer embryos were being transferred to the uterus per cycle and the triplet and higher-multiple pregnancy rates dropped dramatically. Though it may take more than one attempt to conceive, the majority of patients are successful.

10. Very few people ever experience infertility.

Many fertility patients feel they are the only ones in their circle of friends and acquaintances suffering from infertility. At times, it seems as though everyone else is having a baby. Actually, one in six couples is having trouble with conception, they just may not talk about it. Since they are not pushing a stroller, there is no outward visible sign of their fertility status. When couples decide to share the story of their fertility quest, they often find there are many of their peers experiencing similar difficulties. They discover friends who can not only relate but also provide valuable support. Carolyn Givens, M.D.

MOVIE REVIEW    Baby Mama

In the movie Baby Mama, a successful, single businesswoman who dreams of having a baby discovers she is infertile and hires a working class woman to be her unlikely surrogate. If you are considering using a gestational carrier (GC), and want a better understanding of the role she will play in your family, do NOT go see this movie!!

Every patient’s nightmare occurs in this movie—events that would never happen in real life!!

Unlike the movie, you should expect the following things when using a GC:

• She will not move into your home



• She will not smoke or drink alcohol



• She will eat well throughout the pregnancy—including regularly taking her prenatal vitamins.



• You will know from your clinic if the GC has achieved a pregnancy or not. The GC will not be able to “fake” a pregnancy



• If pregnant, she will be carrying your embryos. A skilled clinic can assure you that it is not possible for the GC to be pregnant with her own eggs in your treatment cycle



• Your GC will already have her own children. She will not be doing a treatment cycle with you, while also attempting to conceive with her own eggs



• Your GC will not be poor and uneducated



• Your GC will not be asking for $100K from you.

It is critical that you choose your GC wisely. At PFC we do not recommend choosing a GC via the internet. If a GC candidate is not registered with an agency, there may be a reason for this—be cautious. It is in the interest of all involved parties—yourself and the GC, to use and work with an agency who recruits and represents the GC. The agency should be your advocate as well and act as a go-between between you and the GC. It is important to choose your GC agency wisely.

There is no regulatory body for either egg donor or gestational carrier agencies—so you must do your own research. Some questions to consider are: how long has the agency been in operation, what is their reputation (among clients and also among fertility clinics), how many GCs do they have available and which states do the GC candidates reside in, how many overall cases does the agency manage per year, how large is their staff, can they respond to your questions/needs in a timely manner, and will they take care of all involved parties.

The agency will require an administrative fee, and this fee should include some of the following services. A thorough preliminary screening process should be performed. This would include an evaluation of the candidate GC’s personal, psychological and medical background. Any potential candidate with a personality or medical issue, or social instability should be screened out by a thorough process. All GCs should have an obstetrical history consistent with ease of conceiving, as well as uncomplicated gestation and deliveries. All should have finished their personal childbearing. All should have a stable home life, and intact personal support systems.

Once your GC is in treatment, your fertility clinic will hormonally manipulate the GC’s menstrual cycle to ASSURE that if she achieves a pregnancy, it will be from your designated embryos. She will have close monitoring by the fertility clinic staff, and they will provide you direct and thorough communication about how your GC is doing. This includes being directly informed about whether or not she has achieved a pregnancy in that treatment cycle. You will always be the first to know!!

Most GCs will have some form of education. While they are paid for their services, they truly are doing this because they enjoy being pregnant, they love their children, and want to pass that gift on to another person(s). The GC will not be “negotiating” a fee as the pregnancy occurs and develops—all fees and legal contracts are established prior to the start of any medical treatment. This will be arranged by your agency.

If you need the help of a GC to start or expand your family, rest assured that it will not be the chaotic scene portrayed in “Baby Mama”. However, you do need to do your research and choose wisely when dealing with an agency that is locating GCs and drafting contracts. PFC recommends that before you sign any contract, the medical records for your chosen candidate be reviewed by your fertility physician. Ultimately it is your PHYSISICIAN who makes the recommendation as to the medical eligibility of your potential GC.

Using a GC can be very rewarding. Being prepared upfront is the best way to maximize that wonderful overall experience. Isabelle Ryan, MD

Free Seminar Overcoming Infertility: The Next Step to Parenthood Ask • Meet • Learn Led by PFC’s Infertility Specialists Dates: August 20, 2008 September 17, 2008 Location: Pacific Fertility Center 55 Francisco Street, 5th Floor San Francisco, CA 94133 Contact: Please call for reservations, directions and parking information: 888-834-3095

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