At Pacific Fertility Center, we consider very carefully the number of embryos we transfer to each patient. Our goal is to create a healthy singleton pregnancy. We do our best to avoid multiple gestations. Consequently, in many cycles where we think that the chance of pregnancy is extremely high, we transfer only a single embryo. Our outstanding and robust embryo cryopreservation program preserves all embryos that were not transferred in the fresh cycle. Patients who transfer only a single embryo can feel secure in knowing that there are frozen embryo(s) available should they be needed.

Recently, we completed our analysis of the cumulative pregnancy rates per cycle for 2007. This type of report represents the overall pregnancy chance from a single IVF treatment cycle. This data was not available previously as many patients delay their use of frozen embryos. This cumulative analysis looks at the chance of pregnancy from a single IVF cycle when using both fresh embryos and subsequent frozen embryos, if needed.

Table 1 shows the rates for patients that used their own eggs (oocytes).
Table 2 shows pregnancy rates for patients that were the recipients of donor oocytes.

Please note that these are not delivered pregnancy rates. Many of these pregnancies are ongoing. There are also some patients that have not yet achieved pregnancy, but have frozen embryos remaining.

In vitro fertilization (IVF) is perhaps one of the most effective options available for the treatment of infertility. This procedure has been available in the developed world for approximately 30 years, and has been responsible for 1-4% of all conceptions. While IVF was originally developed for the treatment of female tubal factor, it has evolved to include treatment of male factor infertility via intra-cytoplasmic sperm injection (ICSI), as well as oocyte quality factor (Decreased Ovarian Reserve, or DOR). With the development of embryo biopsy techniques, IVF has also grown to incorporate pre-implantation genetic screening of embryos (PGD) to avoid genetic diseases in embryos and to screen for normal chromosomes. In the history of mankind, IVF will undoubtedly remain the greatest development for the treatment of human infertility for the foreseeable future.

Since the introduction of IVF, there has been a directly proportional increase in multiple gestation births. Traditionally IVF centers have measured success as the number of live births, irrespective of outcomes. This increase in multiple births is driven by the clinical incentives for live births, but some may also be driven by patient request. Two studies have shown that 20% of European and US infertile couples wanted a multiple birth^{(1, 2)}. Even after counseling regarding the risks of a multiple gestation, many patients still wanted to transfer 2 embryos. As IVF success rates have increased, and as the embryo freezing technologies have improved, a shift in the philosophy of IVF providers is occurring. Success rates are more likely to be measured as “live birth of a singleton (single baby) pregnancy”—in other words, “one healthy baby at a time”.

As the number of babies born after IVF has grown, there has been increased interest in looking at the pregnancy and birth outcomes in the successful IVF population. While potential complications for mother and babies are increased with any multiple gestation, there may also be an increased risk for complications even with IVF singleton babies. However, it may not be the IVF treatment itself that results in this increased risk for complications. The questions that reproductive endocrinologists and high-risk pregnancy specialists are trying to answer are primarily: 1) Is there a higher risk for a baby of any adverse birth outcome if that baby is conceived in an IVF laboratory? and 2) Is there something inherent about a past diagnosis of infertility which places even a singleton gestation at greater risk of pregnancy and birth complications?

IVF Singletons:

A number of large studies have addressed the question of increased risk to IVF babies ^(3-7). They echo a similar theme concerning birth outcomes, most importantly preterm birth <37 weeks, and low birth weight. One study compares the differences in degree of risk of poor outcomes with IVF babies vs. naturally-conceived babies. There appears to be a 93% increased risk for IVF singletons as compared to naturally conceived singletons, and a 57% increased risk for IVF twins versus naturally conceived twins⁽⁶⁾. Certainly the overall chance of a preterm delivery is much smaller for singletons than twins, and a twin pregnancy carries much greater risks overall.

A review of the US birth registry indicates that the proportion of IVF singleton babies born at full term with low-birth-weight is decreasing, but the proportion of IVF singleton babies born prior to full term with low-birth-weight is stable. In either case, the incidence of low-birth-weight is higher in babies born after IVF when compared with the general population. While outcomes of low-birth-weight babies may be getting better, there are still elevated risks for singleton low-birth-weight babies conceived via IVF.

For most of these studies looking at risks for IVF babies, factors known to influence pregnancy and birth outcomes are taken into consideration in the analysis. These important factors include maternal age and prior birth history. However, other factors may also be important but are not as well accounted for: factors such as previous poor obstetrical outcome, smoking status, socio-economic status, performance of fetal reduction procedure (especially for the analysis of the singleton data), types of ovarian stimulation protocols, media used in the IVF laboratory, and/or use of laboratory techniques (ICSI, etc.).

Infertility per se may itself be a risk factor for poorer pregnancy and birth outcomes. In an attempt to answer this important question, IVF outcomes have been compared with either non-IVF fertility treatments such as ovulation induction (OI) or to spontaneous conception outcomes. Numerous studies ^(8-15) have evaluated this question, and shown a higher risk of preterm birth for both IVF and OI babies as compared to spontaneously conceived singleton pregnancies. When evaluating outcomes for sub-fertile women (infertility for greater than 1 year) who spontaneously conceive, again we see a greater risk of preterm deliveries, obstetrical complications and adverse birth outcomes ^(16-18). These studies strongly suggest that there is an inherent characteristic of infertile patients which place them at greater risk of poorer pregnancy and birth outcomes. Whether this is due to uterine or embryo issues is not yet known.

IVF Twins:

Many studies have compared the outcomes for twins conceived via IVF versus spontaneous conception. These outcomes were summarized and reviewed in a meta-analysis of birth outcomes of IVF twins in studies up to 2003 ⁽¹⁹⁾. The specific findings showed an increase in the chances of a preterm birth (57% increase), admission to the neo-natal intensive care unit (two-fold increase), and Cesarean section delivery (33% increase). No other parameters were significantly different from spontaneously-conceived twins.

These differences between twin gestations conceived via IVF versus spontaneously-conceived twins were similar for cycles of twin gestation conceived via ovulation induction (OI). The rate of prematurity seemed to be higher for the IVF than OI group ⁽²⁰⁾.

In conclusion, when comparing singleton or twin gestations conceived via IVF or spontaneously, the degree of difference in the overall risk is greater for the singleton-baby births than twins. This is especially true with regards to preterm delivery which is increased two-fold in IVF singletons and by 40% (adjusted for age) in twins. While most studies have made adjustment for factors which can affect birth outcomes, such as maternal age, some other potential factors are difficult to measure, such as history of infertility or direct effects of IVF technology itself. It appears as though infertility prior to conception may play a larger role in IVF outcomes, for both singleton and twin gestations.  

1. Thurin A et al. Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization. N Engl J Med 2004; 351:2392-2402.
2. Ryan GL et al. The desire of infertile patients for multiple births. Fertil Steril 2004; 81; 500-504.
3. Jackson RA et al. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol 2004; 103; 551-563.
4. Helmerhorst FM et al. Perinatal outcomes of singletons and twins after assisted conceptions; a systematic review of controlled studies. BMJ 2004; 328; 261.
5. McGovern PG et al. Increased risk of preterm birth in singleton pregnancies resulting from in vitro fertilization-embryo transfer or gamete intrafallopian transfer: a meta-analysis. Fertil Steril 2004; 82; 1514-1520.
6. McDonald SD et al. Perinatal outcomes of singleton pregnancies achieved by in vitro fertilization: a systematic review and meta-analysis. J Ostet Gynaecol Can 2005; 27; 449-459.
7. Bower C et al. Assisted reproductive technologies and birth outcomes: overview of recent systematic reviews. Reprod Fertil Dev 2005; 17; 329-333.
8. French National IVF Registry. Analysis of 1986 to 1990 data. Fertil Steril 1993; 59; 587-95.
9. Frydman R et al. An obstetric assessment of the first 100 births from the in vitro program of Clamart, France. Am J Obstet Gynecol 1986; 154; 550.
10. McFaul P et al. An audit of obstetric outcome of 148 consecutive pregnancies from assisted conception: implication for neonatal services. Br J Obstet Gynecol 1993; 100; 820-5.
11. Tan S et al. Obstetric outcome of In vitro fertilization pregnancies compared with normally conceived pregnancies. Am J Obstet Gynecol 1992; 167; 778-84.
12. Wang JX et al. The obstetric outcome of singleton pregnancies following IVF/GIFT. Hum Reprod 1994; 9; 141-6.
13. Tanbo T et al. Obstetric outcome in singleton pregnancies after assisted reproduction. Obstet Gyncol 1995; 86; 188-92.
14. Rufat P et al. Task force report on the outcome of pregnancies and children conceived by in vitro fertilization (France 1987-1989). Fertil Steril 1994; 154; 550-5.
15. Friedler S et al. Births in Israel resulting from in vitro fertilization/embryo transfer. 1982-1989: National registry of the Israeli association for fertility research. Hum Reprod 1992; 7; 1159-63.
16. Basso O et al. Subfecundity and neonatal mortality: longitudinal study within the Danish national birth cohort. BMJ 2005; 330; 393-394.
17. Basso O et al. Infertility and preterm delivery, birthweight, and Caesarean section: a study within the Danish National Birth Cohort. Hum Reprod 2003; 18; 2478-2484.
18. Pandian Z et al. A review of unexplained infertility and obstetric outcome: a 10 year review. Hum Reprod 2001; 16; 2593-2597.
19. McDonald S et al. Perinatal outcomes of in vitro fertilization twins: a systematic review and meta-analysis. AM J Obstet Gynecol 2005; 193; 141-152.
20. Adler-Levy Y et al. Obstetric outcome of twin pregnancies conceived by in vitro fertilization and ovulation induction compared with those conceived spontaneously. Europ J Obstet Gynecol and Reprod Biol 2007; 133; 173-178.

Many IVF programs routinely schedule frozen embryo transfers (FET) to occur on specific days by putting their patients on estrogen and progesterone to prepare the uterine lining for implantation. This allows for a flexible schedule for the clinic and the patient, i.e. it allows the clinics to group FETs together and avoid weekend transfer procedures. However, the patient must remain on both estrogen and progesterone to support the pregnancy for up to 12 weeks.

More and more, clinics are starting to schedule FETs in natural cycles, timed to natural ovulation with minimal medications. This does mean that a transfer can occur any day of the week. Due to tradition and convenience, some clinics remain hesitant to switch to natural cycle FETs. Part of the problem is that there have been very few studies showing what the success rates were in natural vs. programmed FET cycles. The few studies that have been published have reported on a fairly limited number of cycles.

Pacific Fertility Center has always been a proponent of natural cycle FETs. Because we do about 400 FETs each year, we have been able to gather a large number of cycles to evaluate. Most of our patients we evaluated for this study were in natural cycles but some patients had to do programmed cycles because they did not ovulate regularly or because they had to travel some distance to come to PFC for their FET and needed to have the more precise scheduling that a programmed cycle affords.

In our study, we looked at 1,378 frozen embryo transfers done between 2000-2005. Of these, 934 were done in patients using embryos from their own eggs and 444 were done in patients using embryos from donor eggs. The bottom line is that there were no differences in delivered pregnancy rates within both groups of patients (own eggs and donor eggs) between those patients having a transfer timed to natural ovulation or those patients with estrogen-progesterone uterine preparation.

Because we feel that a natural cycle is less costly, requires no blood tests and (usually) fewer ultrasounds and injections, patients find this a desirable alternative to the more common, programmed FET. In addition to these patient-friendly reasons for choosing natural cycle FETs, we now feel PFC has solid data to justify this approach.

Preliminary results of this study were presented at an oral presentation at the Pacific Coast Reproductive Society meeting in Palm Springs this past April (see sidebar).

This study has just been submitted to Fertility and Sterility, the major reproductive endocrinology journal of the American Society for Reproductive Medicine. We expect full publication after the peer review process is completed.

Carolyn Givens, MD

“Outcomes of Natural Cycles vs. Programmed Cycles for 1378 Frozen Embryo Transfers” Carolyn R. Givens, M.D.a, Leslie C. Markun,b Isabelle P. Ryan, M.D.,a Philip E. Chenette, M.D.,a Carl M. Herbert, M.D.,a and Eldon D. Schriock, M.D.a Submitted July 2007 to Fertility and Sterility.

Pacific Fertility Center Team
Left to Right: Front: Philip Chenette, MD, Isabelle Ryan, MD, Carolyn Givens, MD
Back: Joe Conaghan, PhD, Carl Herbert, MD, Eldon Schriock, MD

2006 IVF Pregnancy Rates
Pacific Fertility Center is pleased to share our in vitro fertilization (IVF) pregnancy rates for 2006. Our outstanding in vitro fertilization pregnancy rates are made possible thanks to our team of ABOG board certified specialists in Reproductive Endocrinology and Infertility and highly trained embryologists.

Pacific Fertility Center’s investment in enhanced methods of embryo culture has improved outcomes with in vitro fertilization. New incubators, culture media, and procedures have increased embryo quality and embryo implantation rates. Each embryo has a higher potential to produce a pregnancy, which allows us to transfer fewer embryos, reducing the risk of higher order multiples.

Our technology offers better pregnancy rates with fewer numbers of embryos transferred. Based on this improvement we are instituting a new emphasis on single embryo transfers and expect to significantly reduce the risk of multiples and achieve our goal of “optimal” pregnancy outcomes.

2006 Highlights:
• Pregnancy Rates with Day 5 (Blastocyst Transfers) – Selecting day 5 (blastocyst) fresh embryo transfers, we achieved a 59% pregnancy rate per transfer for women under age 35 using their own oocytes. As remarkably we achieved a 49% pregnancy rate per transfer for all women under age 43 using their own eggs.

• Outstanding Oocyte Donation Pregnancy Rates – Oocyte donation pregnancy rates are one of the best indicators of an outstanding IVF laboratory. Last year we achieved a 73% pregnancy rate per transfer for fresh day 5 transfers in women using donated oocytes. As not all donor oocyte recipients used a day 5 transfer, the combined pregnancy rate for all Day 3 or Day 5 fresh embryo transfers was an outstanding 66%.

Notes on Pacific Fertility Center statistics:
1. Pacific Fertility Center does not restrict IVF to only those patients most likely to succeed, (a practice which often leads to higher pregnancy rates). Our less restrictive approach is confirmed by our high percentage of Decreased Ovarian Reserve, DOR (a basal FSH level of 10 mIU/mL or higher). As reported by SART/CDC in 2005, 24% of PFC patients were diagnosed with DOR.

2. PFC performs a substantial volume of IVF and oocyte donor cycles. This allows for better statistical accuracy of our data, (the fewer number of patients – the less statistically significant the rates become). We feel it keeps all of us well attuned to the practice of ART.

3. Although we individualize treatment to each patient’s diagnosis and prognosis, our goal is to adhere to ASRM guidelines on the maximum number of embryos to transfer, in order to lower the risk of high order multiples.

Pacific Fertility Center is pleased to provide its final IVF laboratory statistics for 2005. (This is the most recent data from our clinic and has not yet been reported to CDC/SART. This data includes undelivered pregnancies. The pregnancies counted as positive include all pregnancies with a clear gestational sac on ultrasound examination. We urge caution when comparing these statistics to that of another center. Be advised that a comparison of clinic success rates may not be meaningful because patient medical characteristics and treatment approaches may vary from clinic to clinic.)

Comparing IVF programs by published statistics requires some insight into why programs may or may not be different. We have listed some key points to facilitate your understanding of our statistics.

Some factors associated with Pacific Fertility Center statistics:

1. Pacific Fertility Center does not restrict IVF to only those patients most likely to succeed (a practice which often leads to higher pregnancy rates). Our less restrictive approach is confirmed by our high percentage of DOR patients as described in point #2.
2. Over the years, PFC has treated a substantial number of IVF patients diagnosed with Decreased Ovarian Reserve, DOR (a basal FSH level of 10 mIU/mL or higher). As reported by SART/CDC, in 2003 and 2004, 28% and 22% of PFC patients, respectively, were diagnosed with DOR.
3. PFC performs a substantial volume of IVF and ovum donor cycles. This allows for better statistical accuracy of our data, (the fewer number of patients – the less statistically significant the rates become). We feel it keeps all of us well-attuned to the practice of ART.
4. PFC’s non-donor egg success rates with frozen embryo transfers approaches that of fresh embryo transfers. We have had a very strong embryo freezing program for many years and are proud of this. Our patients can avoid high order multiple pregnancies by transferring fewer fresh embryos and successfully freezing the remaining embryos. They may also increase the odds of having more than one pregnancy from a single IVF cycle.

FRESH EMBRYO TRANSFER CYCLES
Table 1: IVF with Own Eggs

Table 2: IVF with Ovum Donor

FROZEN EMBRYO TRANSFER CYCLES
Table 3: IVF with Own Eggs/Frozen Embryo Transfers

Table 4: IVF with Ovum Donor

An individual’s chances for success are based on a variety of factors including age, diagnosis and choice of treatment. We will be happy to discuss any questions you may have and estimate your individual chances of success.

PFC’s 2002 success rate data has just been submitted to the Society of Assisted Reproductive Technology (SART) and the Center for Disease Control (CDC). The data could not be compiled until all the 2002 babies were born (late 2003).

As stated every year in the SART-CDC report, there are important factors to consider when using clinic statistics to compare individual clinics’ success rates. For an example, some clinics will accept all patients and other clinics may be less inclined to perform IVF on patients with lower probabilities of success. Some centers may see older patients, on average, or patients with more difficult infertility problems. Furthermore, some clinics will transfer more embryos to achieve a higher success rate, placing a patient at greater risk of high order multiples (triplets or more). For more information on factors to consider and to view published data from 2001, please refer to the CDC website, http://www.cdc.gov/ART/index.htm.

Key points to consider:

1. Comparing IVF programs by published statistics requires some insight into why programs may or may not be different. For instance, in 2002 at Pacific Fertility Center, 33% of our patients undergoing IVF had a diagnosis of Decreased Ovarian Reserve, DOR, (a basal FSH level of 10 mIU/mL or higher). This percentage of patients with this diagnosis is one of the highest in the United States. (It is the highest in the nation for centers reporting over 300 IVF cycles per year.) This is a most difficult diagnosis to overcome and therefore PFC is proud that we were able to maintain such high levels of delivered pregnancy with one out of 3 patients undergoing IVF with DOR.
   
2. Our high percentage of DOR patients confirms that we do not restrict the patients who pursue IVF to only those patients most likely to succeed. Despite this fact, PFC’s success rates continue to climb every year. We feel this steady improvement is due to continued innovation and strengthening of all aspects of our program.PFC performs a substantial volume of IVF and ovum donor cycles. This allows for better statistical accuracy of our data (strength in numbers) and we feel keeps all of us well-attuned to the practice of ART.
3. PFC’s success rates with frozen embryo transfers approaches that of fresh embryo transfers. We have had a very strong freezing program for many years now and are proud of this. Our patients can avoid high order multiple pregnancies and increase the odds of having more than one child from an IVF cycle.

If you have any questions about this data, please let us know. We’ll be happy to discuss them with you and estimate your individual chances of success.

Q:
If I use an egg donor, how many embryo transfers can I expect?

A:
PFC maintains detailed records of all treatment procedures and outcomes at our world class laboratory. Nevertheless, the answer to this question is not as straight forward as one might expect. Averages can be summarized, but there are wide swings in the first stage of this procedure – how many eggs a donor can produce. Also, the decision on how many fertilized eggs to implant and how many to freeze can be highly subjective according to the patient.

In 2002, each donor recipient received an average of 23 eggs. But one donor that year failed to produce even a single egg, whereas another donor produced a remarkable 52 eggs. Several successful pregnancies resulted from only a three egg retrieval, so remember, it only takes one healthy embryo to establish a pregnancy!

Once the eggs are retrieved, the fertilization rates are a tad bit more predictable, since most of the donors are in their 20s. In 2002, between 65% – 76% of the retrieved eggs from donors successfully fertilized, depending on whether the donated eggs underwent IVF or IVF-ICSI.

In the next step, the implantation stage, PFC transferred on average 2.3 embryos per patient, and froze on average 7.8 from a single donor cycle. (The average number for freezing would have jumped from 7.8 to nearly 10 if this figure had excluded the 20% of women who did not produce enough eggs for freezing.)

In other words, 80% of donor egg recipients had at least some remaining embryos to freeze after the initial implantation.

And the odds were good for those embryos that entered the deep freeze. Last year, 77% of all thawed embryos were transferred, an improvement over previous years.