In-Vitro Fertilization

• Guarantee of success
• Choosing an IVF clinic
• ACFS Success rates
• Grading of embryos
• The truth about money back guarantees

ACFS Guarantee of Success

We are confident enough in our IVF program and committed to the success of our patients, that if you are not successful with two fresh attempts at IVF, including the use of your frozen embryos, we will do a third cycle of standard IVF, using your own eggs, at no charge. The third cycle would have to be done within a year so the laboratory testing would not be too old, and would not include anesthesia if needed for TVA, ICSI, AH, PGD, blastocyst transfer, embryo freezing and medications.

If you have any questions about our ACFS Guarantee of Success,
please feel free to contact the office at 480-860-4792.

Choosing an IVF Clinic

Important Factors to Consider when Comparing IVF- Assisted Reproductive Technology (ART) Data between clinics

Patients considering IVF, with or without ICSI will want to find the clinic in their area with the highest success rates. Many will search the internet to find the clinic with the best statistics. According to our Society, comparisons between clinics must be made with caution. Many times you may not be comparing apples to apples. Some clinics may be more willing than others to accept patients with low chances of success or may specialize in various ART treatments that attract particular types of patients. No reported success rate is absolute. A clinic's success rates will vary year to year even if all determining factors are the same. As an extreme example, if a clinic reports only one IVF cycle in a given category, the clinic's success rate will either be 0% or 100%. Some clinics see more than the average number of patients with difficult infertility problems. Some clinics are willing to offer IVF to most potential users, even those who have a low probability of success. Others discourage such patients or encourage them to use donor eggs, a practice that results in higher success rates among older women. Clinics that accept a higher percentage of women who previously have had multiple unsuccessful IVF cycles will generally have lower success rates. In contrast, clinics that offer IVF procedures to patients who might have become pregnant with less technologically advanced treatment will have higher success rates.

Many programs are very aware of the fact that patients will search web sites to find a clinic, in their area, with the highest success rates, and knowing this, may "pad" their reported success rates by refusing to do "certain" patients who may not be the "best statistical candidates". Therefore, a patient who has been unsuccessful several times, has decreased response rates with follicle numbers, the couple with decreased fertilization rates, decreased number of embryos, decreased quality of embryos on a fresh or frozen cycle, an elevated FSH level or increased maternal age may be "talked out of trying" with her own eggs and only offered donor eggs. By these women not doing IVF using their own eggs, they would not negatively affect the clinic's success rates and statistics. Although, Arizona Center for Fertility Studies prides itself on its high success rates with IVF, we are never motivated by our statistics, and feel very strongly that a patient should always have the choice as to whether or not she wants to use her own eggs; no matter if she is not "the ideal candidate". The use of donor eggs, at ACFS, is a choice, never the only option; and we deeply respect a woman's right to choose.

A related issue is that success rates are presented in terms of cycles, as required by law, rather than in terms of women. As a result, women who had more than one ART cycle in 2007 are represented in multiple cycles. If a woman who underwent several ART cycles at a given clinic either never had a successful cycle or had a successful cycle only after numerous attempts, the clinic's success rates would also would be lowered.

Cancellation rates affect a clinic's success rates. Success rates for unstimulated (or "natural") cycles are included with those for stimulated cycles. Success rates are calculated per cycle rather than per patient. Therefore, for patients who undergo both fresh and frozen cycles, success rates are calculated separately for each cycle. Clinics that have very good live birth rates with frozen embryos would have higher ART success rates if these births were included as successes from the original stimulated cycle. Patients should look at both rates when assessing a clinic's success rates.

The number of embryos transferred varies from clinic to clinic. In 2007 the average number of embryos that a clinic transferred to women younger than age 35 ranged from one to five, although guidelines recommend only two. Some programs will transfer more embryos to try to improve their success rates. The American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology discourage the transfer of a large number of embryos because it increases the likelihood of multiple gestations. Multiple gestations in turn, increase both the probability of premature birth and its related problems and the need for multifetal pregnancy reduction.

Arizona Center for Fertility Studies follows the guidelines set forth by our society but reserves the right to occasionally go outside those guidelines, by one embryo, if it is medically indicated and fully discussed with the couple as to the reason why and all possible complications.

At ACFS, we are confident in our experience, as well as the expertise of our embryology lab, and we encourage patients to look at other program's statistics, but to make sure that they are "comparing apples to apples" and they ask those tough questions and be sure that the clinic is more interested in the patient's wishes than their own statistics. The greater the differences between how ACFS does IVF compared to the way another clinic had done IVF that was unsuccessful, the greater the chance that IVF at ACFS can be successful. The other clinic definitely did it "the right way" but it was their way. If ACFS did it exactly the same way, you could not blame a couple for not trying again if they wanted to use their own eggs. Although, donor eggs is always an option for repeated unsuccessful attempts at IVF, the greater the differences in how ACFS does your IVF based on their experience, the greater the chance the couple can be successful in doing IVF again. Although IVF offers important options for the treatment of infertility, the decision to use ART involves many factors in addition to success rates. Going through repeated ART cycles requires substantial commitments of time, effort, money, and emotional energy. Therefore, couples should carefully examine all related financial, psychological, and medical issues before beginning treatment. Location and selection of the clinic is not nearly as important as the women's right to choose, commitment of the entire staff to the overall well being of the patient and a proven record of excellence and high success rates.

IVF is preformed in the following fashion with informed consent:

1. Administration of fertility drugs to stimulate maturation of follicles (eggs) on the ovary(s).
2. Monitoring the growth and development of the follicle(s) in the ovary by ultrasound imaging.
3. Administration of hCG to complete the maturation of the eggs and allow timing of egg retrieval prior to ovulation, known as the "trigger" shot.
4. Ultrasound guided transvaginal aspiration of eggs. In rare cases laparoscopy may be used for egg retrieval.
5. Transfer of the eggs to the laboratory for microscopic examination and evaluation.
6. Addition of prepared sperm cells from a partner or a donor, to fertilize the eggs. In some cases ICSI (intra-cytoplasmic sperm injection) will be performed prior to incubation. If elected, assisted hatching will be done or preimplantation genetic diagnosis prior to uterine transfer.
7. If fertilization is successful, a pre-determined number of embryos will be transferred into the uterus by a small catheter inserted through the cervix.
8. Prior to and after embryo transfer a woman may be put on low dose prednisone, oral antibiotics and baby aspirin which has been shown to improve implantation and subsequent pregnancy rates.

Patients have been informed of the following procedures, risks and limitations and will have the opportunity to discuss them with Dr. Nemiro.

1. Fertility medications and ovulation inducing drugs may result in over stimulation of the ovary(s), which may cause pain, abdominal swelling, or other discomfort.
2. Follicle development will be monitored by vaginal ultrasound. This is considered non-invasive and not associated with any known risk.
3. Transvaginal egg retrieval is an out patient procedure using MD anesthesia or RN-IV sedation. There is a very small risk of injury to surrounding organs or tissues. If this should occur, repair will be made at the time of injury, and is usually a small bleeder in the vaginal wall from the aspirating needle.
4. Transferring the embryos into the uterus may cause slight discomfort, cramping, spotting, or infection. There is a slight possibility of ectopic pregnancy (less than 5%) with any attempt at pregnancy. This would require treatment by MTX (methotrexate) or surgery to remove the ectopic pregnancy.
5. The transfer of multiple embryos may result in multiple gestation. The risks of prematurity and other complications have been explained.

Patients are advised that any of the following may occur to prevent pregnancy.

1. The time of ovulation may be misjudged (is rare to non-existent with the use of hCG trigger), may be unpredictable (again rare with the use of hCG trigger), may occur prior to retrieval (only if retrieving on a natural cycle), or may not occur in the monitored cycle (only if there is no follicular response), precluding any attempt to obtain an egg(s).
2. Pelvic adhesions may prevent access to the ovary(s), but fortunately is very uncommon.
3. Medical emergencies may make an operating room and/or anesthesia unavailable (would have to be a natural disaster but ACFS has back-up power supply to adequately run the entire ART and cryo labs).
4. Withdrawing an egg may be unsuccessful (generally because there was no egg in the follicle).
5. The egg(s) may be of poor quality. This may or may not be visible or known to the embryologist or physician at the time of recovery.
6. The partner may be unable to obtain a semen specimen (if this is anticipated than ACFS will get a sperm sample in advance and freeze it, or in extreme cases, schedule back-up MESA/TESA.
7. The sperm sample may be of poor quality (this is generally eliminated by doing ICSI.)
8. Fertilization may not occur; performing ICSI (intra-cytoplasmic sperm injection) does not guarantee fertilization (generally an egg quality issue).
9. Cleavage or cell division of the fertilized egg(s) may not occur (again, generally an egg quality issue).
10. The embryo(s) may not develop normally and would not be transferred.
11. Implantation may not occur.
12. A laboratory accident may result in loss or damage to the egg, sperm, or embryo (very rare).
13. Transfer of the embryo(s) may not be successful (by doing a mock transfer first, this should never happen).

At ACFS, all embryology laboratory equipment, incubators and ancillary ART equipment has back-up electrical power in case of a power outage.

Fertilization occurs in 4-6 hours in humans but there are no visible signs until approximately 17-18 hours later. The first signs that fertilization have occurred visibly in the development of two round bodies in the center of the egg. The slightly smaller body is the female pronucleus and contains 23 chromosomes that the egg contributes to the embryo; the other round body is the male pronucleus and contains the contribution of 23 chromosomes from the sperm. It is critical that the egg is checked at this point in time for fertilization, because over the next 6 hours or so, the two pronuclei come together in a process known as syngamy, where the two pronuclei join chromosomes, forming one nucleus of 46 chromosomes. Within the next 6 hours (30 hours from fertilization) the, now "fertilized egg" will divide producing a 2-cell embryo. Further division or "cleavage" takes place every 10-12 hours, producing a 4- cell embryo on day 2, an 8-cell embryo on day 3, a morula or ball of, too many cells to count, on day 4, and a blastocyst on day 5.

After fertilization, if the embryo is looked at too late in this process, than "abnormal" fertilization can be overlooked and the embryo will "appear normal". This "abnormal" embryo can divide and even implant but will not produce a viable pregnancy and is only destined to abort, resulting in a miscarriage and disappointment.

Arizona Center For Fertility Studies - Phoenix and Scottsdale IVF Success Rates

Success Rates 1/08 Through 12/09

Pregnancy Rates Per Fresh Embryo Transfer With ICSI/IVF

	<35 years	35-37 years	38-40 years	41+
Positive HCG	78%(29/37)	68% (17/25)	55% (12/22)	32% (6/19)
Gestational Sac on Ultrasound	73% (27/37)	60% (15/25)	45% (10/22)	26% (5/19)

Pregnancy Rate Per Embryo Transfer With Frozen Embryos

	<35 years	35-37 years	38-40 years	41+
Positive HCG	62% (16/26)	43% (3/7)	31% (4/13)	50% (2/4)
Gestational Sac on Ultrasound	46% (12/26)	43% (3/7)	23% (3/13)	50% (2/4)

Pregnancy Rate Per Transfer Using Donor Oocytes

	All Patients
Positive HCG	56% (22/39)
Gestational Sac on Ultrasound	51% (20/39)

Pregnancy Rate Per Transfer Using Frozen Donor Oocytes/Embryos

	All Patients
Positive HCG	47% (14/30)
Gestational Sac on Ultrasound	43% (13/30)

Note that a comparison of clinic success rates may not be meaningful because patient medical characteristics and treatment approaches may vary from clinic to clinic.

Grading of Embryos

There are many embryo grading systems that embryologists use to evaluate embryos for transfer. The ASRM (American Society of Reproductive Medicine) has attempted to establish a standard grading system, so when a patient or previous clinic is talking about "the quality of the embryos", it can be interpreted and understood by the clinic she is now at, which is important in trying to understand why her cycle of IVF was unsuccessful and what "changes" can be made to result in a successful outcome. Even with standardized grading systems, which is still not universally used, evaluation and scoring of any stage of embryo development, from fertilization to a hatching blastocyst is critical to the experience and expertise of the embryologist.

After oocyte (egg recovery), the eggs are placed in the incubator for a number of hours before they are checked for maturity. At that time, the embryologist will remove the cells surrounding each egg (cumulus cells) and check the egg for maturity. Each mature egg will undergo ICSI, and be placed back in the incubator. The following day the embryo will be checked for fertilization but is not graded. The embryos will not be checked again until day 3, 4, or 5 (blastocyst) depending on when the transfer was planned. At that point in time, the embryologist will check each embryo and "grade" it, picking the best for transfer, and he will determine if the remaining ones are suitable for cryopreservation.

Grading of a day 3 embryo is based on the number of cells that make up the embryo, the amount of fragmentation, and the symmetry of each of the embryo's cells (blastomeres).

1. An embryo should be between 7-9 cells on day 3, with an ideal embryo being 8 cells. However, a 7-cell or 9-cell embryo can be perfectly fine and result in a successful pregnancy. In ACFS experience, embryos that are 5-cells or less, have a significantly lower chance of achieving a successful pregnancy. A 6- cell embryo may be okay, and should be considered for transfer if there are not embryos of higher cell number. At ACFS, we have had successful pregnancies from the transfer of 6-cell embryos, however, they are statistically lower than if the cell number was higher.
2. Fragmentation is when parts of an individual cell(s) in the embryo break apart or "fragment" and appear as small fragments or "blebs" within the embryo. In ACFS experience, the degree of fragmentation is directly related to the overall quality of the embryo. If an embryo has no fragmentation it is scored an A, if the embryo has less than or equal to 10% fragmentation it is scored a B. Embryos with a greater percentage of fragmentation are scored C or D. Generally, when embryo fragmentation is scored A or B, it is considered to be a very good embryo and suitable for transfer. C scored embryos can be transferred but statistically result in lower pregnancy rates. At ACFS, if an embryo is scored with D fragmentation, it is not recommended for transfer or cryopreservation. It is put back in culture (as ACFS always does), and experience shows that these embryos begin to degenerate over the next day or so.
3. Symmetry is assessing the cells in the embryo is see if they are all the same size, or symmetrical. If all the cells in the embryo are the same size, the embryo is rated G (good). If a few of the embryo's cells are different sizes it is scored F (fair); and if most of the blastomeres are of all different sizes, it is scored a P (poor). Embryos that are scored G or F are suitable for transfer, and along with the other scoring criteria, help to predict success. Embryos scored D, are not recommended for transfer or cryo, and almost always are associated with decreased cell numbers and increased fragmentation. Again, they are placed back in the incubator, and within 1-2 days undergo significant degeneration. In ACFS experience, symmetry, or lack of perfect symmetry, is not as significant as cell numbers and fragmentation. Many times, embryos with less than perfect symmetry, have resulted in successful pregnancies.
4. Other factors that go into evaluating an embryo for transfer but are not part of the scoring system is appearance of the zona pellucida (does it appear "hardened" (see assisted hatching link), whether or not the cytoplasm of the embryo is homogenous or granular (or grainy) and the presence of vacuoles inside the cytoplasm of individual cells. Vacuoles are the walled off areas of waste material produced by the embryo. A large number of vacuoles within an embryo, statistically, is indicative of a lesser quality embryo but, as an isolated factor, may not necessarily indicate that the embryo would not result in a successful pregnancy. It is only when increased vacuolization and/or increased cytoplasm granularity, along with decreased cell numbers, fragmentation and asymmetry, does it predict decreased success rates with embryo transfer.

In summary, a "perfect" day 3 embryo should be 8AG - eight cells, no fragmentation and all the cells are equal and symmetrical. Human embryos are so variable, and although scoring is very important in helping to decide which embryos to recommend for embryo transfer and which to freeze, embryo quality as evaluated under the microscope, even by very experienced embryologists, ultimately is only a reasonable "estimate" of predicting the chances for a successful pregnancy. Any good embryologist will tell you that "even though an embryo(s) looks good, it doesn't mean that it is good" and visa versa.

Scoring of blastocysts are similar but have a completely different set of scoring criteria. Blastocyst quality is determined by evaluating the outer ring of cells, known as the trophectoderm or trophoblastic cells, that will eventually form the placenta; the inner cell mass or ICM, which is made up of the stem cells, that the baby will develop from; and finally, the degree of expansion of the blastocyst cavity and whether or not it has started to "hatch" or break out of its zona pellucida or "shell". Again, scoring of a blastocyst depends on the experience and expertise of the embryologist. Like day 3 embryos, scoring of even blastocysts is an imperfect science, and some very nice looking blastocysts do not produce a pregnancy; whereas, less than optimum ones do. However, the basic rule of thumb is "that the best of the best embryos" make it to the blastocyst stage, and a very nice blastocyst has a greater chance statistically of producing an ongoing pregnancy than a lesser quality one.

Since there are many other contributing factors involved that we cannot see or identify, embryo scores are, at best, generalizations about "quality" and are often inaccurate. Many times, ACFS has seen cycles fail after transferring 2-3 "perfect" looking embryos; and many times see successful ongoing pregnancies after transferring only one "decreased quality" embryo. The actual "potential" of the embryo to implant and continue normal development is impossible to accurately measure and predict with current technology. Although some clinics will cancel the embryo transfer if there is only one embryo or several embryos of "poor quality"; for the above reason and based on extensive experience, ACFS will always recommend transferring one embryo, even if it did not get the "best" scoring. "Bad embryos" do not cause "bad babies", they cause no babies. Therefore, as long as there is even the slightest chance of success, ACFS recommends the transfer of "less than optimum" embryos.

One additional thing that is very important is the embryo transfer. A traumatic and/or bloody difficult transfer can result in decreased pregnancy rates probably by disrupting the endometrial lining, introducing blood into the uterine cavity, triggering an inflammatory reaction, or by just having the embryos exposed to the outside environment, as opposed to the incubator environment, for too long. At ACFS, several months before an embryo transfer, a mock transfer is done to measure the depth of the uterine cavity, the degree of angulation and direction of the cervical canal and the ease or difficulty of eventual embryo transfer. At the time of the actual embryo transfer there should be no surprises. At ACFS, embryo transfers take less than 30 seconds from the time the embryos are removed from the culture environment of the incubator to being loaded in the transfer catheter.

Ultimately, the true test of embryo quality is whether it results in a successful pregnancy and live birth. IVF is not an exact science, and when nothing has been overlooked, the woman has a reasonable FSH level and she is at a clinic with proven high success rates, than a successful ongoing pregnancy, is for the most part, with a few exceptions of very poor sperm quality even with ICSI, determined by the overall genetic quality of the egg. A thousand things can effect that, most of which we can not determine and/or correct. With controlled ovarian stimulation, ACFS tries to get as many eggs as genetically predetermined in each individual woman. The more eggs you get (balancing avoiding OHSS) the more possible embryos a woman has, the greater the percentage that the embryologist can find "good quality" embryos to transfer and enough to freeze. However, there are plenty of women that are "low responders"; they do not make a lot of eggs/embryos, but the ones they make are "excellent" and result in a successful pregnancy. But successful IVF may take more than one attempt. Each stimulation cycle is an independent cycle and is usually different than the previous one. If the first IVF cycle is not successful, ACFS has learned a tremendous amount of information about the woman and can change things with the next attempt. Thousands of previous cycles have "told" us what to do on that initial attempt, but every woman is unique and you can only conclude "generalizations" about what is the best protocol for any particular woman or age group.

The Truth About Money Back Guarantees

At Arizona Center for Fertility Studies, we do not offer a money back guarantee. This is for several reasons:

1. We believe that a money back guarantee is mostly a "marketing tool". Most patients will not qualify. Even if they qualify and are not successful, they will only get a portion of the money back. Generally, these "guarantees" are for the standard services of IVF and do not include the anesthesia, medications, lab tests, ICSI, AH, PGD and freezing fees that are associated with the procedure. Clinics will only qualify patients that have the "best chance" of success.
2. It does not feel ethically right to us at ACFS to have a couple qualify and pay $30,000 plus dollars for a money back guarantee and get pregnant on the first attempt. Normally that one cycle would cost around $10,000, including ICSI and freezing; and they would then be out $20,000 plus dollars. We believe in a fair price for each cycle, where, if the couple needs to do IVF more than once, it is affordable.
3. We are confident in our experience and the expertise of our embryology lab that couples should have a good success with one or two attempts, either using their fresh or frozen embryos.