Outcome of single embryo transfer (SET) on day two with regard to presence or absence of single nucleation of embryo in the four cell stage at transfer

personal reasons (11 were parous and 13 were nulliparous.) The mean age was 34.8 ⫾ 3.2 years. The mean number of zygotes was 11.4 ⫾ 5.0. All patients had embryos to cryopreserve with the mean number of embryos cryopreserved 5.3 ⫾ 3.2. Of the 30 patients, 18 conceived, with one ectopic pregnancy and 2 miscarriges, giving an on-going pregnancy/delivery rate of 50% for the fresh transfer. Of the 15 unsuccessful patients, 6 conceived with an on-going pregnancy on a subsequent frozen transfer, yielding a cumulative on-going pregnancy/delivery rate of 70%. All 15 patients who initially conceived with on-going pregnancies have yet to use their cryopreserved embryos, thus the potential for an even greater cumulative pregnancy rate still remains. CONCLUSION: Many programs, including our own, have recognized the theoretical advantage of SBT through the calculated implantation rates achieved with double blastocyst transfer. However, the practice of SBT remains limited, awaiting more data that could offer assurance to programs and patients about the wisdom of this option. Our fresh transfer success rate of 50% for a patient population in their mid-30’s is indeed encouraging, yet it is the cumulative pregnancy rate of 70% that may facilitate the transition from a double blastocyst transfer to a single blastocyst transfer. Supported by: None

P-194 Neonatal outcome and congenital malformations in cases of multiple births after in vitro fertilization and embryo transfer. K. Sasaki, S. Sasaki, S. Takahashi, Y. Nakajo, K. Kyono. Lady’s Clinic Kyono, Miyagi, Japan. OBJECTIVE: Women who deliver after IVF-ET are averagely older than women who conceive and deliver naturally. A high percentage of IVF users experience greater risks because it is their first pregnancy. We examined whether multiple pregnancies and mother’s age influenced IVF-ET children. DESIGN: Retrospective study. MATERIALS AND METHODS: Between July 1995 and Jan 2003, 551 women were impregnated at our private ART clinic. The patients obtained 720 children after IVF-ET. We carried out a mail survey with parents. Survey parameters were physical development (height and weight) and mental development (development rates of movement and language). The results were examined according to maternal age (Group A was ⬍35 years and Group B was ⱖ35 years). Additionally, each multiple pregnancy was examined (twin, triple). We examined physical growth and mental development in comparison with Japanese Ministry of Health and Welfare standards. RESULTS: We received responses from 640 of the 720 children (rate of answer 88.9%). The average of maternal age (mean ⫾ SD) was 30.7⫾2.5 years old (Group A) and 36.9⫾1.9 years old (Group B). Rate of multiple births were 51.1% (twin 42.3%, triple 7.8%: Group A), and 33.9% (twin 30.4%, triple 3.5%: Group B) When giving birth, the ratio of low weight and preterm infants were high in the cases of multiple births (Table 1). Regardless of maternal age, twin and triplets showed a physical development delay of 6 or more months compared to singletons. Twins were able to catch up to the 50th percentile curve at about 6 months after birth. Triplets catch up to the 50th percentile curve at 1 year after birth. Mental development was the same. There were significant differences in the rate of congenital malformation between singleton and multiple babies. The rate of chromosome abnormality of the Group B was higher than the Group A (Table 1). Table I

children after IVF. We have reported that there is no significant difference in growth patterns between each delivery group of ICSI, C-IVF and FET. Therefore, it is of great importance that multiple pregnancies be reduced in order to ensure the optimum health of babies in ART. Supported by: None

P-195 Selective reduction and following development of dichorionic twins after IVF-ET. Y. Nakajo, A. Yagi, K. Fuchinoue, K. Sasaki, K. Kyono. Lady’s Clinic Kyono, Miyagi, Japan. OBJECTIVE: Multiple pregnancies account for an increasing percentage of low birth weight infants, preterm births, and perinatal mortality. The purpose of this study was to investigate the prenatal factors associated with selective reduction in dichorionic twins. DESIGN: The influence of selective reduction on physical and mental development of dichorionic twins was examined. MATERIALS AND METHODS: We studied a cohort of all twin dichorionic pregnancies in our clinic between October 2000 and March 2004. Selective reduction from three to two was performed in 14 cases (11 cases give birth, two cases are ongoing pregnancies, and one case miscarried). All selective reduction procedures were performed between 7 and 10 weeks, using transvaginal suction under ultrasound guidance. 124 cases were not reduced (81 cases gave birth, 29 cases are ongoing pregnancies, and 13 cases miscarried, 1 case was stillborn). We compared cases of selective reduction and non reduced twins regarding perinatal outcome and development. Furthermore, cases of triple pregnancies were compared with these findings. Univariate analysis was performed by ␹2-test for categorical variables and by two-tailed t-test for numerical variables. RESULTS: Abortion rates didn’t show significant differences between Non reduced twins and Reduced twins (10.5% vs.7.1%). There were 4 cases of infant mortality in the Non reduced twins group. Table 1 showed the pregnancy outcome in the three groups (Non reduced twins, Reduced twins and Non reduced triplets). In reduced twins, the rate of premature birth and low birth weight was significantly higher than non reduced twins, but remained lower than that of triplets. There was no significant difference between Non reduced and Reduced groups in terms of weight at birth. Physical development showed little variation after 6 months and mental development was the same among the three groups from 3 months to 1 year of age.

a Birth weight discordance: 100(A-B)/A. (A and B was the birth weight. A⬎B)

CONCLUSION: This study suggests that selective reduction is a safe and effective method to reduce perinatal risk for mother and fetus caused by multiple pregnancies. However, it is most important that we prevent multiple pregnancies. People who take charge of medical treatment should understand the inherent risk of multiple pregnancies. Moreover, patients who often hope for multiple pregnancies believing it increases their odds of having a healthy baby must be educated about the risks that accompany multiple pregnancies. Supported by: None

P-196 Outcome of single embryo transfer (SET) on day two with regard to presence or absence of single nucleation of embryo in the four cell stage at transfer. P. J. Sundstrom, P. M. Saldeen. IVF kliniken, Malmo¨ , Sweden. CONCLUSION: The findings of this study point out that multiple pregnancies constitute the most serious complication for both mother and

FERTILITY & STERILITY威

OBJECTIVE: In attempt to optimise the chance of pregnancy, single blastocyst transfer has become increasingly popular. We have, since many

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years, selected the embryo/s for transfer by its⬘ appearance on day two or three only. The aim of the study was to compare the outcome after SET on day two with regard to presence or not of a single nucleus in each blastomere of embryo in the four cell stage at transfer. DESIGN: Single center private practice. Retrospective non-randomized. MATERIALS AND METHODS: From August 1st 2002 to March 1st 2004 a total of 1106 fresh ETs after standard IVF or ICSI were carried out, of which SET was performed in 765 (69%) of the treatments. Of these, 590 were day two transfers and of these 514 had a 4 cell embryo (regular, fragmentation 0 ⫺ 20%) transferred. A single nucleus in each of four blastomeres was visualized in 389 of the transfers and 125 had four cell embryo, each with zero to three blastomeres showing a single nucleus, at transfer. RESULTS: The overall clinical pregnancy rate (PR) (at least a fetal sac) was 33%. The clinical PR after SET also was 33%. The clinical PR after SET of a 4 cell embryo with a single nucleus in each blastomere was 41% (160/389) while, if the transferred 4 cell embryo showed zero to three blastomeres with a single nucleus, the clinical PR was 26% (32/125) (P ⬍ 0.003). CONCLUSION: SET of a 4 cell embryo on day two, in which each blastomere showed a single nucleus, resulted in a significantly higher clinical PR and implantation rate (41%) in comparison to SET of a 4 cell embryo on day two with zero to three blastomeres showing a single nucleus (26% PR). Supported by: None

P-197 Prolonged use of OCP’s prior to ART increases cycle cancellation rates in patients with tubal factor, male factor and unexplained infertility. J. D. Parker, A. Y. Armstrong, J. H. Segars, F. W. Larsen. Combined Federal Fellowship in REI, NIH, NICHD, PREB, NNMC, WRAMC, USUHS, Bethesda, MD; Walter Reed Army Medical Center, Washington, DC. OBJECTIVE: Ovarian suppression and patient scheduling are frequently accomplished by placing patients undergoing ART on oral contraceptive pills (OCP). In a previous study we showed that those patients on OCP’s for down regulation prior to ART for ⬎ 42 days had a significantly higher cancellation rate (Fertil. Steril, 80:S3,110, 2003). Further investigation led us to determine if this phenomenon was related to specific infertility diagnoses. The objective of this study was to determine if poor outcome with prolonged OCP use correlated with specific infertility diagnoses. DESIGN: Retrospective Cohort Analysis. MATERIALS AND METHODS: Women undergoing their first ART cycle from April 1999 through 2004 were included for analysis. All were pre-treated with 35 microgram monophasic OCP’s. Ovarian hyperstimulation was with a GnRH-agonist flare (40 mcg SQ BID). All infertility diagnoses, ART cycle types, and stimulation protocols were considered. Cycle cancellation and clinical pregnancy rates (CPR) per cycle start were then compared between ART cycles in which OCP pre-ART cycle was ⱕ 42 days and ⬎ 42 days. Statistical significance was determined by Fisher’s Exact Test, with p ⬍ 0.05 considered significant. RESULTS: 1105 ART cycles met criteria for analysis. OCP pre-treatment of ⱕ 42 days occurred in 485 cycles and ⬎ 42 days occurred in 620 cycles. Patient age and basal FSH were not significantly different between the groups. The cycle cancellation rate overall was 7.2% for patients taking OCP’s ⱕ 42 days vs. 17.6% for those taking OCP’s ⬎ 42 days (p ⬍ 0.001). Categorized by diagnoses the results were as follows:

Pregnancy rates and clinical pregnancy rates per transfer were not significantly different among all groups. CONCLUSION: Prolonged oral contraceptive pill use prior to ART increased cycle cancellation rates among patients with tubal factor, male factor, and unexplained infertility. Cycle cancellation rates were similar in those with endometriosis or anovulation. Although cycle cancellation rates were increased, clinical pregnancy rates did not differ if embryo transfer occurred. Supported by: None.

P-198 A mathematical model for IVF success. J. P. Stassart, G. D. Ball, R. H. Castillo, R. B. Bayless, H. E. Grotjan. RMIA, Woodbury, MN; Serono, Inc., Rockland, MD. OBJECTIVE: Assisted Reproductive Technologies are complex medical procedures that must be performed skillfully to yield the desired outcome ⫺ a single, viable pregnancy. A mathematical model for IVF success is described and used to illustrate the use of the model to determine whether success ⫺ or its converse, failure ⫺ can be attributed to the quality of embryo(s) transferred, transfer technique or uterine environment. The underlying hypothesis is that the distribution of pregnancies among multiples, singletons and failures can be used to identify the more predominate reasons for failures. DESIGN: Materials and Methods. Success is usually defined as the number of infants born (or number of pregnancies or number of embryos that implant) divided by the number of embryos transferred. The Observed Success Rate (SRObs) is a function Embryo Factors (EF; embryo quality) and Non-Embryo Factors (NEF) with NEF including transfer technique and uterine receptivity. Transfer technique and uterine receptivity are considered linked because a failure of either leads to the same outcome ⫺ a failed cycle. EF: Use p and q to denote the probability that an embryo implants or does not implant, respectively, with p ⫹ q ⫽ 1. Assume that the ability of each embryo to establish a pregnancy is an independent event. The probability of distinct events can then be multiplied to calculate the probability of combined events. Accordingly, the distribution of higher order multiple, twin, single and failed pregnancies is given by the equation (p ⫹ q)n where n is number of embryo transferred. NEF: For a single patient, the NEF are treated as a categorical Yes / No variable given values of 1 or 0; if any embryo establishes a pregnancy, the NEF for that patient is assumed to be 1. When a pregnancy is not established, the NEF for that patient may be 0 or may result from the proportion of embryos incapable of establishing a pregnancy (qn). For a group of patients, NEF equals the proportion of patients that have both a receptive endometrium and receive a satisfactory transfer and hence ranges from 0 to 1. SRObs: The SRObs is a the product of EF and NEF: SRObs ⫽ EF ● NEF ⫽ (p ⫹ q)n ● NEF MATERIALS AND METHODS: (See Design) RESULTS: To illustrate how this model can be used, examine the predicted outcomes resulting from the transfer of 2 embryos (n⫽2) under the following conditions:

The above calculations illustrate that, with the transfer of 2 embryos, the ratio of twin to single pregnancies can be used as a starting point to distinguish whether failures primarily result from embryo factors (i.e., poor embryo quality) or non-embryo factors (improper transfer technique or poor uterine receptivity). CONCLUSION: The SRObs in IVF can be described mathematically using reasonably simple concepts and assumptions. Most importantly, the model predicts that the distribution of multiple, singleton and failed pregnancies can be used to distinguish general cause of failed cycles. Supported by: None

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Vol. 82, Suppl. 2, September 2004