Restrictive law regulating art in Italy significantly reduced delivery rate in infertile patients art cycles

P-594 Wednesday, October 27, 2010 CIRCULATING ANTI-MULLERIAN HORMONE LEVELS MAY PREDICT BLASTOCYST FORMATION RATES IN DONOR IVF CYCLES. J. H. Gilbert, J. C. Settle, J. E. Nichols, T. H. Taylor, J. D. Wininger, W. E. Roudebush. Piedmont Reproductive Endocrinology Group, Greenville, SC; Main Line Fertility, Bryn Mawr, PA; Premier Fertility Center, High Point, NC; Biology, Charleston Southern University, Charleston, SC. OBJECTIVE: Anti-Mullerian Hormone (AMH) is a glycoprotein dimer composed of two 72kDa monomers linked by disulfide bridges and is a member of the transforming growth factor-b super family. AMH is produced in small amounts by ovarian granulosa cells after birth until menopause, and then becomes undetectable. AMH performs various physiological functions, e.g. controlling antral follicle development. AMH is routinely used clinically to help determine ovarian reserve status and subsequently, gonadotropin stimulation protocols. Whereas, AMH values can help predict the quantity of oocytes obtained during retrieval, little to no information is available regarding AMH levels on embryo formation rates. To determine if circulating anti-mullerian hormone (AMH) levels relate to blastocyst formation rates following ovarian stimulation in donor IVF. DESIGN: Retrospective analysis of donor cycles. AMH levels were measured and correlated with blastocyst (Grade A or B) formation rates during the IVF cycle. MATERIALS AND METHODS: Circulating AMH levels were measured in donors by a commercially available assay. ART cycles were normalized to control for ovarian stimulation protocol (antagonist) and gonadotropin dose, no male factor, number of stimulation days (10-12 days) and day 5 transfers. Data were analyzed by regression analysis. RESULTS: A total of 18 donor ART cycles were included in this study. The overall blastocyst formation rate was 28.93% (80/342). The mean (+s.e.) AMH level in the donors was 3.941 (+0.459) ng/mL. AMH levels ranged from a low of 1.27 ng/mL to a high of 8.25 ng/mL. Regression analysis revealed a statistically significant binomial correlation between circulating AMH levels in oocyte donors and blastocyst formation rates (P<0.05). CONCLUSION: The data demonstrates a significant and positive correlation between circulating AMH levels in oocyte donors and blastocyst formation rates. This is the first report demonstrating a significant relationship between AMH and blastocyst formation rates.

P-595 Wednesday, October 27, 2010 THE RELATIONSHIP BETWEEN THE CHANGE IN SERUM HIGH SENSITIVITY C-REACTIVE PROTEIN LEVELS AND IVF SUCCESS. B. Seckin, G. Ozaksit, S. Batioglu, M. Ozel, M. Aydogan, B. Senturk. Zekai Tahir Burak Women’s Health Research and Education Hospital, Ankara, Turkey. OBJECTIVE: Levels of C-reactive protein (CRP) have been shown to increase during controlled ovarian hyperstimulation in IVF cycles. There are few studies investigating the role of CRP in the process of implantation. The aim of this study was to assess whether the extent of change in serum high sensitivity CRP (hs-CRP) levels correlate with IVF success. DESIGN: Prospective study. MATERIALS AND METHODS: A total of 69 IVF cycles using long luteal GnRH agonist protocol performed at our institution were studied. Women who had infectious diseases and BMI R 30 kg/m2 were excluded. The serum levels of hs-CRP were measured on the day of initiation of gonadotrophin stimulation and 7 days after embryo transfer, which is the presumed implantation period. CRP ratio was defined as serum level of hs-CRP on day 7 of transfer/ day of initiation of ovarian stimulation. Cycle characteristics and pregnancy rates were examined. Chi-square,Student’s t and paired sample t-tests were used. RESULTS: Patient and cycle characteristics were comparable between pregnant and non-pregnant women. The mean serum concentrations of hs-CRP were not significantly different on the day of commencement of gonadotrophin administration and 7th day after embryo transfer among pregnant and non-pregnant patients(3.61  2.86 mg/L versus 3.24  2.68 mg/L; p¼0.58 and 10.5  11.3 mg/L versus 9.1  11.3 mg/L; p¼0.59,respectively). Serum hs-CRP levels were significantly higher on day 7 after transfer than on day of initiation of gonadotrophin stimulation in conception and non-conception groups. The mean CRP ra-

FERTILITY & STERILITYÒ

tio was not different between the groups (3.71  4.68 versus 3.86  7.24; p¼0.91, respectively). CONCLUSION: We observed significant increase in serum hs-CRP levels during IVF treatment as it is confirmed by previous studies. But this extent of the increment in hs-CRP levels may not play a role in establishing endometrial receptivity. It seems that serum hs-CRP levels can not be a prognostic marker of IVF success.

P-596 Wednesday, October 27, 2010 ELECTIVE SINGLE EMBRYO TRANSFER (eSET) ON DAY 3: WHEN ONE IS PLANNED, BUT TWO MAY BE APPROPRIATE. N. Acevedo, S. C. Pang, J. C. Patel, K. J. Go. Reproductive Science Center of New England, Lexington, MA. OBJECTIVE: To determine whether embryo morphology on Day 3 postretrieval (D3) correlates with implantation potential following Single Embryo Transfer (SET) in IVF patients <35 years of age using autologous oocytes, and whether embryo morphology on D3 can be used to determine the appropriate application of elective SET to maximize implantation potential while minimizing the risk of multiple gestation. DESIGN: Retrospective analysis of data over a consecutive 24 month period from patients under the age of 35 years undergoing autologous IVF treatment at a private IVF clinic. MATERIALS AND METHODS: The morphologies of single embryos transferred at D3 (n¼354) in a continuous 2-year interval (Jan 2008 to Dec 2009) were grouped and each assessed for implantation rate (IR). Embryos were grouped by cell number (<6, 7, 8 or R9) and percent fragmentation (A¼0-9, B¼10-25, C¼>25). The groups were MG1¼ %6C, MG2¼7C or 8C; MG3¼6A/B; MG4¼8A/B; MG5¼ R 9B. IR for the groups were compared to each other and to IR for all D3 ET (SET and multiple embryo ET) by Fisher’s Exact Test; significant differences were identified at P<0.05. RESULTS: The IR of all D3 embryos transferred (SET plus multiple ET) in the study period was 35% (n¼1860). Embryos with higher embryo quality resulted in higher IR from SET. IR of MG1, MG2 and MG3 embryos were significantly different from IR of MG4 embryos (18%, 27%, 33% and 50%, respectively). The difference in IR between MG4 and MG5 embryos (41%) was not statistically significant. CONCLUSION: Our results show that in patients < 35 years of age, SET of embryos with MG4 or MG5 resulted in a significantly higher IR compared to SET of embryos with MG1, MG2, MG3, or the global D3 ET cohort. These findings suggest that a paradigm for prescribing SET may be constructed using embryo morphology to optimize the incidence of implantation, as well as to indicate when a second embryo could reasonably be recommended for transfer if the best embryo available for transfer does not meet this threshold morphology.

P-597 Wednesday, October 27, 2010 RESTRICTIVE LAW REGULATING ART IN ITALY SIGNIFICANTLY REDUCED DELIVERY RATE IN INFERTILE PATIENTS ART CYCLES. P. E. Levi Setti, E. Morenghi, C. Sonia, S. Galliera, V. Arfuso, F. Menduni. Gynecology and Reproductive Medicine, IRCCS Istituto Clinico Humanitas, Rozzano (Mi), Italy; Unita` di Biostatistica, IRCCS - Istituto Clinico Humanitas, Rozzano (Mi), Italy. OBJECTIVE: Aim of this study was to investigate the birth rate for started cycle in our Department before and after the introduction of the law regulating ART in Italy until the Constitutional Court cancelled most of this restrictions. DESIGN: Retrospective study 1996-2009 May of all IVF/ICSI started cycles.MATERIALS AND METHODS: 10708 started cycles were extracted from our database, 3808 performed before the law introduction in March 2004 and 6900 cycles after Law restrictions until May 2009. An intention to treat statistical analysis was performed to detect the delivery rate (pregnancies R 24 weeks) per started cycle in the general population and in patients with a female age less than 36 years and high or equal to 36 years. RESULTS: Our results showed an odd ratio of 1.31 (95% CI 1.19 - 1.45) with a relative risk 125% (95% CI 115% - 136%) with a number needed to treat of -25.

S265

TABLE 1

Cycles Deliveries Cycles < 36 years Deliveries Cycles R 36 years Deliveries

Population

Pre Law

Post Law

10708 1864 (17.4%) 4830 1151 (23.8%) 5878 713 (17.3%)

3808 761 (20.0%) 2106 518 (24.6%) 1702 243 (14.3%)

6900 1103 (16.0%) 2724 633 (23.2%) 4176 470 (11.3%)

P

< 0.001 0.272 0.001

CONCLUSION: Even with all the biases related to retrospective studies, our results demonstrate a significant reduction in birth rate in the overall population that affected principally the older patients, that represents today the majority of our infertile population. Even with a yearly progressive growth of infertile patient age, all International Registers show a clear over the time tendency to higher success rate with the improvement of ART knowledge. This clinical goal was lost in our country with a long period of 3 oocytes only technique. Our results are a relevant clinical information for countries debating restrictive limitations of ART. Supported by: This investigation has been supported by a finalized grant from Lombardy County, Italy (DGR 7255, July 3, 2008).

P-598 Wednesday, October 27, 2010 PREDICTORS OF SPONTANEOUS REDUCTION (SR) IN ART CYCLES? Y. E. Su¨ku¨r, T. Altun, L. Pal. Ankara University, Ankara, Turkey; Obstetrics and Gynecology, Kazan Government Hospital, Ankara, Turkey; Obstetrics, Gynecology and Reproductive Sciences, Yale University, New Haven, CT. OBJECTIVE: To identify patient & cycle parameters that relate to SR in multiple pregnancies (MP) following assisted reproduction (ART). DESIGN: Retrospective cohort study, single center analysis of ART cycles between January 2007-June 2008. MATERIALS AND METHODS: 1st trimester sonography at 6-7 weeks identified 69 clinical MP’s with # gestational sacs ranging between 2-4. Repeat sonography exams undertaken in late 1st & in 2nd trimester assessed ongoing MP’s & SR rate (ongoing MP#/ initial MP# x 100) was calculated. Patient & cycle parameters were compared between those achieving SR of one or more implanted gestations (n¼26) and those proceeding uneventfully (n¼43). RESULTS: The overall SR rate in ART cycles was 26/69 (37.6%). The SR rates were 19/55 (34.5%) in twins, 5/12 (41.6%) & 2/2 (100%) in higher-order pregnancies. Other than endometrial thickness (ET) achieved on the day of hCG administration (higher in ongoing MP, p¼0.017), and patient’s age (higher in SR group, p¼0.047), the remainder of patient & cycle parameters were comparable between the two groups. Each mm increase in ET reduced Odds for SR by 35% after adjusting for age & # embryos transferred (p¼0.029). Significantly increased risk of SR in MP was observed in cycles when ET was < 10 mm (p¼0.032). CONCLUSION: Endometrial thickness<10mm is identified as a risk for SR in multiple pregnancies achieved through ART, an association not previously described. P-599 Wednesday, October 27, 2010 SINGLE EMBRYO TRANSFER (SET) USING GRADUATED EMBRYO SCORE (GES) AND SOLUBLE HUMAN LEUKOCYTE ANTIGEN-G (HLA-G): AN UPDATE. J. D. Fisch. Sher Institute for Reproductive Medicine, Las Vegas, NV. OBJECTIVE: We presented preliminary SET data in 2007 showing a 65% delivery rate from single blastocyst transfer in a small group of patients with a GES and HLA-G+ embryo. This work updates our on-going experience with single embryo transfer among a larger group of patients. DESIGN: Retrospective. MATERIALS AND METHODS: From 2004-2009 a single physician performed 1679 embryo transfers into 806 different patients. All embryos were scored using GES, which uses early developmental milestones to generate a score on day 3 of culture. Embryos scoring 70+ were considered positive. Since 2005, discarded media droplets on day 2 were evaluated for HLA-G secretion in patients not doing PGD with more than 5 embryos. An OD in the range of 0.148-0.210 was considered positive. Main outcome measures: delivery, multiple gestation rates. RESULTS: In all, 248 (15%) embryo transfers were SET. Of these 169 (68%) were GES+ and 79 were GES negative. Of the GES+ SET, 103 (61%) were day

S266

Abstracts

5 ET and 66 (39%) were day 3 ET. The overall delivery rate from SET was 24% (60/248). Among GES+ SET the delivery rate was 31% (52/169), compared to 10% (8/79) if GES negative. Of the GES+ SET, delivery rates were 42% (43/ 103) from day 5 ET and 14% (9/66) from day 3ET. Of the 103 GES+ day 5 SET, HLA-G data was available for 65 (63%). Among GES+ HLA-G+ day 5 SET the delivery rate was 57% (29/51) compared to 21% (3/14) among GES+ HLA-G negative day 5 SET. There was 1 set of monozygotic twins. CONCLUSION: In this update, we reconfirm the benefits of GES and HLA-G for evaluating embryos. Because SET has been difficult for our patients to accept, only a small portion of the total embryos transferred in this period were SET. However, these data show SET does achieve high success rates without significant risk of multiple gestations and the number of patients choosing SET will certainly rise over time. Since 2006 SET has routinely been recommended to our patients if the embryos meet GES/ HLA-G criteria. Increasing confidence with SET has led to increased acceptance. P-600 Wednesday, October 27, 2010 CAN THE NUMBER OF ANTRAL FOLLICLES BEFORE THE START OF GONADOTROPIN STIMULATION PREDICT THE NUMBER OF PREOVULATION FOLLICLES AND TOTAL OOCYTES IN IVF CYCLES? R. P. Dickey, S. N. Taylor, P. Y. Lu, B. M. Sartor, H. E. Dunaway, Jr. The Fertility Institute of New Orleans, Mandeville, LA; Obstetrics and Gynecology, Louisiana State University, New Orleans, LA. OBJECTIVE: To determine if the number of antral follicles at the start of gonadotropin stimulation could predict the number of preovulation follicles and oocytes in IVF cycles. DESIGN: Retrospective analysis of IVF database. MATERIALS AND METHODS: Patients in their first IVF cycle were grouped by method of LH suppression. Group I N ¼ 501 took oral contracptives (OC) and GnRH agonist; Group II N ¼ 193 took OCs and started GnRH antagonist day 5 of stimulation. Antral (AN) follicle count at FSH start was compared with number of preovulatory (PO) follicles the day of hCG and number of total and Metaphase II (M II) oocytes. RESULTS: The average number of AN follicles, PO follicles and oocytes were greater in Group I. Differences between Group I and II decreased with age and were significant only for AN follicles at age 25-29. The ratio of AN follicles to PO follicles > 14mm and total oocytes approximated 1:1 at all ages. Despite this approximation, the number of AN follicles was unrelated to total oocytes (Group I r¼.30 Group II r¼.37), and M II oocytes (Group I r¼.29 Group II r¼.39). The number of AN follicles was better related to total PO follicles (Group I r¼.61, Group II r¼.52) than to follicles >10mm to >16mm. TABLE: Average Follicle and Oocyte Number

Age Antral follicles Group I Group II Preov. follicles: Total Group I Group II Preov. follicles: >10 mm Group I Group II Preov. follicles: >12 mm Group I Group II Preov. follicles: >14 mm Group I Group II Preov. follicles: >16 mm Group I Group II Total Oocytes Group I GroupII Metaphase II Oocytes Group I Group II

25-29

30-34

35-39

40-44

13.9 8.4

10.4 9.5

9.3 7.3

7.0 6.4

24.8 19.6

21.8 18.7

17.5 15.6

12.0 10.8

22.6 17.7

19.8 17.1

16.0 14.5

11.0 9.5

18.8 15.2

16.5 14.6

13.2 12.6

9.7 8.0

13.3 12.0

12.0 10.7

10.1 9.9

7.6 6.1

8.3 7.8

7.5 7.2

6.7 6.5

5.4 4.3

13.6 12.5

12.8 11.6

11.0 9.0

8.6 6.9

11.7 9.6

11.0 9.8

9.7 7.8

7.1 6.1

CONCLUSION: Antral follicles may predict number of preovulatory follicles but not number of oocytes.

Vol. 94., No. 4, Supplement, September 2010