Administration of subcutaneous human chorionic gonadotropin with the lupron trigger (L+SQuhCG): a comparison with intramuscular hCG (uhCG) and recombinant hCG (rhCG) in egg donors

results. The objective of this study was to investigate the impact of serum estradiol levels and estradiol/follicle ratio on trigger day on the pregnancy outcome. DESIGN: Retrospective Study. MATERIALS AND METHODS: Ovarian stimulation was performed with a GnRH analog down regulation utilizing long or micro-flare protocols with recombinant FSH and LH. Follicular development was assessed by transvaginal ultrasound measurement. Ovulation was induced with recombinant hCG when 3 or more follicles were at least 18 mm in diameter. According to serum E2 level on the day of hCG administration, all cycles were divided into 3 groups: <3000 pmol/L, 3000-7000 pmol/L and >7000 pmol/L. IVF pregnancy results were compared among those three groups. Statistical analysis was done by using chi-square test. RESULTS: Results were shown in table 1. The statistical differences in the ratio of E2/follicle among three groups were significant. The clinical pregnancy rate and implantation rate in the high estradiol group (>7000) were significantly higher than that in the low estradiol group (<3000). Table1. Comparison of IVF outcome according to the serum E trigger day.

E2 level No. of cycles Age, years No. of follicles E2/follicle ratio Average embryos transferred Clinical pregnancy rate (%) Implantation rate (%)

<3000 22 35 13.0 165.7a 1.7 4 (18.2)a 4 (11.4)a

3000-7000 33 35 15.2 293.6b 1.9 9 (27.3)ab 13 (20.6)ab

levels on the

2

>7000 24 34 22.1 410.4c 1.9 11 (45.8)b 16 (35.6)b

a,b Values with different superscript letters within the same row are significant different (p<0.05).

CONCLUSION: Our results suggest that higher estradiol levels and higher E2/follicle ratios on the day of hCG administration are associated with higher rates of clinical pregnancy and implantation. P-401 Tuesday, October 15, 2013 HCG DOSE AS LOW AS 500 IU IN COMBINATION WITH GNRH AGONIST TRIGGER CAN BE EFFICACIOUS FOR FRESH EMS. T. Daneshmand,a,b BRYO TRANSFER. B. S. Shapiro,a,b F. C. Garner,a,b M. Aguirre,a C. Hudson.a aFertility Center of Las Vegas, Las Vegas, NV; bDept. of Obstetrics and Gynecology, University of Nevada School of Medicine, Las Vegas, NV. OBJECTIVE: Cycles using GnRH agonist trigger alone are reportedly associated with poor IVF outcomes following fresh transfer, and some centers have therefore combined low-dose hCG with the agonist trigger. The minimum effective hCG dose for this method has not been established. This study compares IVF outcomes for different ranges of hCG dose used in combination with GnRH agonist in fresh autologous embryo transfer in high responders. DESIGN: Retrospective study. MATERIALS AND METHODS: This study included 145 fresh autologous embryo transfers following agonist trigger in combination with hCG dose of 500-1500 IU in patients <38 years of age with at least 20 developing follicles. The hCG dose was adjusted according to patient weight, and dos-

TABLE 1.

hCG dose range (IU) Embryo transfers Age (yr) E2 day of trigger (pg/ml) Follicles >12mm Weight (kg) hCG Dose (IU) Oocytes collected OHSS cases Embryos transferred Fetal hearts Implantation rate (%) Live births (rate, %)

500-799

800-1199

1200-1500 P-value

38 42 65 30.1
5.4 30.3
3.6 31.2
3.9 4881
1947 4049
1533 4485
1493 28.9
6.6 55.5
6.1 632
68 21.2
6.2 1 1.7
0.5 35 53.9 23 (60.5)

FERTILITY & STERILITYÒ

0.2409 0.2574

28.8
5.4 25.8
5.2 0.0009 63.6
14.0 66.5
13.6 <0.0001 968
101 1392
117 <0.0001 19.4
5.9 19.8
6.1 0.2822 0 0 1.8
0.4 1.9
0.3 0.1748 45 55 59.2 45.5 0.1555 25 (59.5) 36 (55.4) 0.8514

ages were gradually decreased over the six-year study period. Luteal support included progesterone and estradiol supplements. RESULTS: The data set was partitioned into three groups according to hCG dose (see Table 1). The three groups differed significantly in weight and hCG dose, but not in age, E2 level, follicle count, oocytes collected, transferred embryos, implantation rate, or live birth rate. There was one case of OHSS. CONCLUSION: These findings suggest that hCG dose as low as 500IU in combination with GnRH agonist trigger can be efficacious for fresh embryo transfer. Prospective randomized studies are needed. P-402 Tuesday, October 15, 2013 REPEATED INJECTION OF GnRH AGONIST FOR TRIGGERING FINAL OOCYTE MATURATION IN PATIENTS AT HIGH RISK OF OHSS IN GnRH ANTAGONIST PROTOCOL: A PROSPECTIVE, COHORT STUDY. S.-L. Chen, X. Chen, D.-S. Ye, Y.-X. He, T. Tao. Center for Reproductive Medicine, Dept.Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. OBJECTIVE: Gonadotropin-releasing hormone (GnRH) agonist is sufficient for triggering final oocyte maturation in GnRH antagonist protocol and can significantly reduce incidence of ovarian hyperstimulation syndrome(OHSS) in high-risk patients. However, lower oocyte yield was reported in patients with lower LH level post trigger with single injection of GnRH agonist, which might be related to the shorter duration and lower amount of LH induced by GnRH agonist. Our aim is to study repeated injection of GnRH agonist for preventing OHSS and maintain clinical outcome in high risk patients who receive controlled ovarian stimulation (COS) in GnRH antagonist protocol. DESIGN: prospective cohort study. MATERIALS AND METHODS: A total of 44 patients at high risk of OHSS undergoing IVF/ICSI-ET were included. Patients were triggered with a single bolus of 0.2 mg triptorelin at night and had second injection of 0.2 mg triptorelin 12 hours later when at least one of the following criteria was reached: (i) serum E2 R3500 pg/ml, (ii) R18 follicles measuring R11 mm. RESULTS: No severe and 2 cases of moderate OHSS were observed in the 44 oocyte retrieval cycle. number of aspirated follicles was 35.3
12.9(2061) and the number of retrieved oocytes was 19.7
6.8(440). Oocyte yield rate (ratio of the total number of collected oocytes to number of follicles measuring R11 mm on the day of oocyte retrieval) and fertilization rate per cycle were 71.5%
26.7% and 66.2%
19.6%. 9 of 44 patients underwent ICSI and the oocyte maturity rate was 70.0%
18.9%. Embryo transfer was cancelled in 6 patients because of thin endometrium. The implantation rate, clinical pregnancy rate and ongoing pregnancy rate per transfer cycle were 26.3%, 39.5% % and 36.8%. CONCLUSION: Repeated injection of GnRH agonist in GnRH antagonist protocol get good oocyte yield, which effectively prevent incidence of OHSS as well as maintain a good clinical outcome, might be a feasible and safe protocol for patients at high risk of OHSS. Supported by: National Natural Science Foundation of China (81170574). P-403 Tuesday, October 15, 2013 ADMINISTRATION OF SUBCUTANEOUS HUMAN CHORIONIC GONADOTROPIN WITH THE LUPRON TRIGGER (L+SQuhCG): A COMPARISON WITH INTRAMUSCULAR HCG (uhCG) AND RECOMBINANT hCG (rhCG) IN EGG DONORS. S. J. Morin,a D. H. McCulloh,b A. Gillan,b F. Licciardi.b aObstetrics and Gynecology, NYU Langone Medical Center, New York, NY; bNYU Fertility Center, New York, NY. OBJECTIVE: To compare outcomes between trigger by Leuprolide Acetate (L) 40 units + subcutaneous (SQ) uhCG 1,000 units, UhCG 10,000 IU intramuscular (IM), and RhCG 500 mg in egg donors(DE). DESIGN: Retrospective cohort. MATERIALS AND METHODS: DE cycles triggered with L+SQuhCG were analyzed between 3/2012 through 12/2012. (1,000 unit vials of uhCG and 40 unit vials of L were prepared for donor SQ injection by the pharmacy.) These were compared to DE cycles triggered with either uhCG (reconstituted and injected IM) or rhCG (injected IM) between 1/2009 and 12/2011. Peak estradiol (E2) levels, egg number, 2PN number, number and grade of transferred embryos, and post-trigger hCG levels were examined. Implantation (IR) and clinical pregnancy rates (CPR) were compared. T-test and X2 were used.

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RESULTS: Post-trigger hCG levels were similar between uhCG and rhCG. Levels were significantly lower but were detected in the L+SQuhCG group. L+uhCG donors were younger and had more advanced blast stages. There was no significant difference in peak E2, egg number, 2PNs, IR or CPR between the groups. TABLE 1.

Donors (n¼252) Age Peak E2 #oocytes retrieved #2PNs Day 1 HCG Recipients (n¼335) #Embryos transferred Mean Blastocyst Stage IR CPR

uHCG (n¼125)

rHCG (n¼58)

L+SQuhCG (n¼69) p-value

28.1 27.0 25.9 p<0.01 3482 2899 2839 NS 21.1 18.8 20.7 NS 14.4 12.6 13.8 NS 218.2 231.7 32.3 p<0.001 uHCG rHCG L+SQuhCG p-value (n¼176) (n¼75) (n¼ 84) 1.93 1.81 1.48 NS 3.2 3.5 3.8 p<0.01 49.3% 57.9% 61.0% p¼0.09 (169/343) (44/76) (36/59) 66.4% 76.1% 70.0% p¼0.07 (117/176) (32/42) (28/40)

CONCLUSION: Administration of L+SQuhCG is an effective triggering mechanism for oocyte donors. Though serum levels are lower, this is predictable given its smaller dosage. Retrieval outcomes and recipient outcomes were no different between egg donors triggered with L+SQuhCG, uhCG, or rhCG. Thus, L+SQuhCG does not compromise outcome when trying to avoid OHSS. The administration of uhCG SQ avoids the necessity to teach patients IM injection techniques and reduces concern over patient error. P-404 Tuesday, October 15, 2013 A COMPARISON OF GONADOTROPIN RELEASING HORMONE AGONIST (GnRHa) AND HUMAN CHORIONIC GONADOTROPIN (hCG) FOR FINAL OOCYTE MATURATION IN AN EGG DONOR POPULATION. S. J. Morin,a D. H. McCulloh,b F. Licciardi.b aObstetrics and Gynecology, NYU Langone Medical Center, New York, NY; bNYU Fertility Center, New York, NY. OBJECTIVE: To compare retrieval and recipient outcomes between GnRHa and hCG triggers in egg donors. DESIGN: Retrospective cohort. MATERIALS AND METHODS: Anonymous donor egg cycles were reviewed from 1/2009 through 12/2011.183 donors were included and categorized based on method of oocyte trigger: hCG (10,000 IU) or GnRHa (40 units). Donor cycles were analyzed for age, peak estradiol (E2) levels, oocyte number and maturity (M2), embryo (2PN) number, and number and grade of embryos transferred. Recipient implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR) were then compared. Statistical analysis was performed using t-test and X2. RESULTS: When compared to hCG, patients in the GnRHa group had more oocytes retrieved, mature oocytes, and fertilized embryos. Mean stage of transferred blastocysts was also significantly higher in the GnRHa group. TABLE 1.

DONORS (n¼183) Age Peak E2 # oocytes retrieved # M2’s # 2PN’s RECIPIENTS (n¼253) # Embryos transferred Mean Blastocyst Stage IR CPR LBR

hCG (n¼125)

GnRHa (n¼59)

p-value

28.1 3482 (+/- 1857) 21.1 (+/- 9.2) 17.8 (+/- 8.2) 14.4 (+/- 7.3) hCG (n¼176) 1.93 3.2 49.3% (169/343) 66.4% (117/176) 60.8% (107/176)

27.0 3564 (+/- 1602) 27.1 (+/- 14) 23.6 (+/- 11.7) 19.5 (+/- 10) GnRHa (n¼77) 1.86 3.6 57.8% (85/147) 77.9% (60/77) 67.5% (52/77)

N.S. N.S. p<0.05 p<0.001 p<001 p-value N.S. p<0.01 p¼0.08 p¼0.07 P¼0.3

GnRHa vs. hCG trigger and outcomes.

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ASRM Abstracts

There was also a trend toward improved IR, CPR, and LBR in the GnRHa group, though this difference did not reach statistical significance. CONCLUSION: The superior yields of oocytes, mature oocytes, and embryos in the GnRHa group likely reflect our tendency to use GnRHa trigger to avoid ovarian hyperstimulation syndrome (OHSS) in high responders. Certainly, there was no detrimental effect apparent following the use of GnRHa as the trigger. We have shown that the outcome of using GnRHa is at least equivalent to hCG as a trigger. We believe that the use of GnRHa provides effective treatment for donors in whom we wish to avoid OHSS. P-405 Tuesday, October 15, 2013 TRIGGER OF OOCYTE MATURATION WITH LOW-DOSE HUMAN CHORIONIC GONADOTROPIN (hCG) REDUCES THE RISK OF OVARIAN HYPERSTIMULATION SYNDROME (OHSS) AND IMPROVES IVF OUTCOME. Y. Ying, J. Mayer, S. Plosker. Department of Obstetrics & Gynecology, University of South Florida, Tampa, FL. OBJECTIVE: 10,000 IU hCG has been routinely used for the induction of oocyte maturation in the IVF treatment, but there is no solid scientific evidence to support whether 10,000 IU hCG is really needed to induce oocyte maturation. In this study, we compared the risk of OHSS development, oocyte maturation rate and IVF success rate in the high-risk patients after 5,000 IU hCG vs 10,000 IU hCG triggers in donor or non-donor IVF cycles. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: All high-risk patients < 40 years old, who were given with 5,000 IU hCG or 10,000 IU hCG with peak estradiol level > 4000 pg/ml during stimulation were included in this study. The data were collected from our IVF data base or from the Allscripts electronic records. Patients who took 5,000 IU hCG with E2 > 4000 pg/ml (52 patients) were compared with control patients who took 10,000 IU hCG with peak E2 > 4000 pg/ml (91 patients). The following parameters were collected and compared between 5,000 and 10,000 IU hCG patients: Patient mean age, number of eggs retrieved, percentage of eggs at MII stage, fertilization rate, number of embryos transferred, percentage of patients with either moderate or severe OHSS, implantation rate and percentage of live birth or ongoing pregnancy. RESULTS: There were no statistical differences between groups with 5,000 IU hCG and 10,000 IU hCG in terms of patient’s age, number of eggs retrieved, percentage of eggs at MII stage, fertilization rate and number of embryos transferred (P > 0.05). 5.8% of patients in the 5,000 IU hCG group developed OHSS, which was significantly lower than 20.6% of patients in the 10,000 IU hCG group (P < 0.05). Implantation rate and percentage of live birth or ongoing pregnancy in the group of 5,000 IU hCG were significantly higher than those of 10,000 IU hCG group (45.0% vs 24.5%, P < 0.001; 64.7% vs 37.9%, P < 0.01). CONCLUSION: The trigger of oocyte maturation with 5,000 IU hCG in high-risk patients reduces the risk of OHSS development and improve IVF outcome. P-406 Tuesday, October 15, 2013 MONITORING CRITERIA TO PREDICT OVARIAN HYPERSTIMULATION SYNDROME IN ICSI/IVF CYCLES. C. Brunet,a M. Picandet,a N. Molinari,b T. Anahory,a A. Gala,c H. Dechaud.a aReproductive Medicine Unit, Montpellier, France; bStatistic Departement, Montpellier, France; cReproductive Biology Unit, Montpellier, France. OBJECTIVE: To define criteria from S8 ovarian ultrasound data for prevention of ovarian hyperstimulation syndrome (OHSS) in ICSI/IVF cycles. DESIGN: Case-control retrospective study. MATERIALS AND METHODS: Study performed between January 2007 and December 2012. The statistical analysis was performed in uni and multivariate logistic regression. Characteristics of high risk of ovarian hyperstimulation population (n¼512) are: oocytes number>18, estradiol level at HCG day>4000 pg/ml or cancelled cycle after coasting. All the other attempted ICSI/IVF in the same period are in the control group (n¼2064). The characteristics analysed are age, BMI, causes of infertility, follicular count, AMH, use of agonist or antagonist protocol, start and total gonadotrophin dose, estradiol level, number of follicles at 10-11 mm, 12-13, 14-15 and >16 mm at day 8 of the ovarian stimulation. RESULTS: The ovulatory anomalies, the AMH level and the start and total dose of gonadotrophin are different in the two groups. After adjustment,

Vol. 100, No. 3, Supplement, September 2013