- Email: [email protected]
Ovulation induction outcomes: analysis of more than 1500 cycles
DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Consecutive patients with moderate to severe OHSS diagnosed between retrieval and embryo transfer from August 2008 until April 2009 were included (N¼6). All embryos were frozen and patients received cabergoline 0.5 mg daily for 7 days and ganirelix 250 mcg daily for 2 days. Day 0 was defined as the date of diagnosis/treatment. Serial weights and days to resolution of symptoms were recorded. The control group included concurrent patients who were diagnosed with late onset moderate to severe OHSS (N¼5). This group was chosen as all early onset OHSS patients were treated with cabergoline and ganirelix. Groups were compared using the Wilcoxon rank sum test. RESULTS: See table below. TABLE 1. Median (25%, 75%) Age BMI FSH utilized (units) Peak E2 (pg/dL) Follicles Weight change day #2 (lbs) Weight change day #4 Weight change day #7 # of unscheduled visits Days to resolution
Treatment
Control
P Value
27.0 (25.3, 33.0) 23.3 (19.9, 24.8) 400.0 (262.2, 581.3) 6430.0 (5065.0, 8970.0) 53.5 (49.3, 55.5) 3.5 (1.9, 4.3) 4.5 (3.5, 4.8) 6.4 (4.8, 6.6) 0.0 (0.0, 0.3) 6.0 (4.0, 7.5)
29.0 (28.0, 36.5) 23.8 (21.2, 34.0) 225.0 (187.5, 262.5) 1886.0 (1748.5, 3041.5) 37 (29.5, 39.5) þ3 (0.3, þ5.6) þ1.9 (0.8, þ6.7) 1.8 (2.8, þ4.9) 3.0 (1.5, 6.5) 20.0 (18.3, 23.3)
0.17 0.52 0.09 0.008* 0.008* 0.008* 0.016* 0.056 0.007* 0.012*
CONCLUSIONS: Treated patients had more rapid weight loss, shorter duration to resolution, and fewer unscheduled visits. This protocol may represent a rapid and cost-effective outpatient therapy for patients diagnosed with moderate to severe OHSS.
P-544 Wednesday, October 21, 2009 ARE PHARMACOKINETIC (PK) PARAMETERS OF FOLLICLE STIMULATING HORMONE (FSH) DIFFERENT IN OBESE IVF PATIENTS? D. H. McCulloh, S. S. Morelli. University Reproductive Associates, Hasbrouck Heights, NJ; Obstetrics, Gynecology and Women’s Health, UMDNJ-New Jersey Medical School, Newark, NJ. OBJECTIVE: Serum FSH in response to FSH injections is seldom monitored during IVF, so PK data for FSH are sparse. Our objective was to determine if PK parameters vary with BMI, weight, height and/ or age. DESIGN: Retrospective analysis of 33 IVF cycles at a University-based outpatient clinic. MATERIALS AND METHODS: Patients underwent controlled ovarian hyperstimulation using leuprolide and gonadotropins. Data included BMI, weight, height, age, daily doses of gonadotropin, and serum FSH levels determined each day of monitoring (Immulite 1000). NJMS IRB approved the study. A numerical model in Microsoft EXCEL mimics serum FSH levels in a patient following FSH injections. Patient data were fitted (in Microsoft BASIC) by the model to obtain 3 PK parameters: two time constants (1) for appearance of FSH in the blood from the injection site (tin), (2) for disappearance of FSH from the blood (tout) and (3) a factor relating serum FSH to IUs injected (Fvol). Fvol, tout, and tin (the shorter of the two t’s) were inserted in the model to determine the rate of rise of peaks after the first injection (tapproachmax) and the ratio of peak values last/first (C38/C1). Patient values were compared by two-tailed Student’s t-tests after grouping by BMI, weight, height, and age. RESULTS: Obese patients (BMI>30) had significantly smaller Fvol (0.023 0.013) and tin (7.6 2.3 hr) than nonobese patients (BMI<30) (0.043 0.003; and 15.8 2.4 hr, respectively) (p ¼ 0.0008 and p ¼ 0.019, respectively). For all other parameters, there was no significant difference (tout ¼ 46.8 7.4 hr; tapproachmax ¼ 46.8 7.0 hr; C38/C1 ¼ 3.2 0.27). There were no significant differences when comparing patients grouped by height (<5’5’’ vs. >5’5’’) or age (<35 vs. >35 years). CONCLUSIONS: PK parameters for FSH varied greatly. Fvol’s decrease with increased BMI (or weight) suggests a dilution effect. Smaller tin with greater weight or BMI suggests that FSH moves more rapidly either into or out of the blood in obese patients. Supported by: No outside support.
FERTILITY & STERILITYÒ
P-545 Wednesday, October 21, 2009 EVALUATING THE LUTEAL ESTRADIOL (E2) PATCH/GNRH ANTAGONIST (E2-PRIME) PROTOCOL FOR PATIENTS WITH EVIDENCE OF DIMINISHED OVARIAN RESERVE. C. M. Mullin, N. Noyes, A. E. Reh, F. Licciardi, L. C. Krey, A. S. Berkeley. NYU Fertility Center, NYU Langone Medical Center, New York, NY. OBJECTIVE: To compare E2-Prime vs. OCP-microdose GnRH agonist (MCD) vs. clomiphene citrate (CC) protocols, all using gonadotropins. DESIGN: Retrospective analysis. MATERIALS AND METHODS: 156 cycles were analyzed according to protocol þ history of retrieved IVF cycle. All patients presented with evidence of diminished ovarian reserve, either a high D2 FSH or poor response to gonadotropin. Comparison of age, cancellation rate (CR), D2 E2/FSH, total gonadotropin dose, # cycle days, peak E2, # eggs retrieved (ER), # mature (MII) eggs, fertilization (FR), implantation (IR), and clinical pregnancy rate (PR) were analyzed according to protocol þ IVF history using c , ANOVA or their nonparametric equivalents as appropriate. RESULTS: MCD achieved a higher PR using less gonadotropin for a shorter duration as compared to E2-prime & CC, regardless of prior IVF history (Table). TABLE 1. Comparison of Clinical Outcomes. Prior Retrieved Cycle
Protocol (n)
No Prior Retrieved Cycle MCD (45)
E2-Prime (33)
CC (12)
MCD (26)
E2-Prime (28)
CC (12)
Mean Age ns/ns 393 404 403 413 394 403 4 8 3 16 18 0 CR (%)c/c c/c 3460 132247 3752 3046 103173 4057 D2E2 c/a 59 35 711 611 47 811 D2FSH 45231413 6298876 54381811 49991533 60801105 56001181 Total c/ns Gonadotropin(IU) #Cycle Daysa/b 92 111 103 102 112 92 21171151 1501658 1761 1050 1536677 12821800 1627701 Peak E2a/b 96 84 74 63 75 62 # ERns/ns 85 64 54 53 64 52 # MIIns/ns ns/ns FR (%) 54 43 53 33 44 32 ns/b 16 7 12 28 20 3 IR (%) ns/b 38 15 17 58 22 8 PR (%)
a¼p<0.05; b¼p<0.005; c¼p<0.0005; ns¼no significance; ANOVA analyses. CONCLUSIONS: Amongst poor prognostic patients with no prior retrieved IVF cycles, MCD is superior to E2-prime and CC. In contrast, patients with prior retrieved cycles responded similarly to the 3 protocols, with the only caveat being that MCD required less drug for fewer days.
P-546 Wednesday, October 21, 2009 OVULATION INDUCTION OUTCOMES: ANALYSIS OF MORE THAN 1500 CYCLES. A. Sarhan, H. A. Baydoun, H. W. Jones, S. Bocca, S. C. Oehninger, L. A. Stadtmauer. Jones Institute for Reproductive Medicine, Norfolk, VA; Epidemiology, Eastern Virginia Medical School, Norfolk, VA. OBJECTIVE: To evaluate the outcomes of a large cohort of patients undergoing ovulation induction cycles. DESIGN: A retrospective cohort study of 1525 ovulation induction cycles performed in 694 patients between August 1998 and December 2008. MATERIALS AND METHODS: Patients underwent ovulation induction cycles with gonadotropins then timed intercourse or intrauterine insemination. Clomiphene citrate or a GnRH antagonist were used in about 10% of the cycles. Strategies used to reduce multiple gestations included low gonadotropin doses, and cancellation in high risk patients for more than three follicles > 16 mm or high estradiol levels. RESULTS: Per cycle pregnancy rate was 12.4% with a per cycle live birth rate of 7.5%. There was a trend towards higher per cycle pregnancy rate and live birth rate in younger patients (P¼.0002). Multiple pregnancy rate was 12.7% with 10.1% twins and 2.6% triplets. Miscarriage rate was 25.8%, after excluding biochemical pregnancies, with a trend towards decreased miscarriages in younger patients (P¼.004). The use of a GnRH antagonist decreased the risk of miscarriage (AOR .26, 95% CI .07-.91). Patients with hypothalamic ovarian dysfunction were associated with the highest per cycle pregnancy rate and live birth rate of
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37.5% (no miscarriages) followed by PCOS. The lowest per cycle live birth rates were in women with diminished ovarian reserve, recurrent miscarriages, and uterine myomas (2%). The birthweight of a singleton from a pregnancy with a vanishing twin (n¼8) was significantly lower than the birthweight of a singleton without a vanishing twin (2882 gm vs 3250gm, P¼.013). CONCLUSIONS: Reducing multiple pregnancy with ovulation induction remains an important and challenging goal although there are no strict universal guidelines. In this cohort of patients, the high order multiple pregnancy rate was limited to 2.6% by using certain strategies. Risks of multiple pregnancy include a lower birthweight of the surviving singleton originating from a twin pregnancy. Supported by: Organon Schering Plough.
P-547 Wednesday, October 21, 2009 HUMAN CHORIONIC GONADOTROPIN (HCG) TYPE DOES NOT EFFECT THE RATE OF EMBRYO DEVELOPMENT. J. W. Catt, K. M. Peters, D. Ezcurra. Embryology Laboratory, Monash IVF, Melbourne, VIC, Australia; Medical Department, Merck Serono Australia, Sydney, NSW, Australia; Medical Department, Merck Serono International SA, Geneva, Switzerland. OBJECTIVE: The aim of this study was to assess two hCG preparations: r-hCG (OvidrelÒ250mcg or 6250IU) and u-hCG (PregnylÒ10,000IU) and the rate of embryo development in clinical practice. DESIGN: Retrospective observational. MATERIALS AND METHODS: 286 ICSI treatment cycles between September 2007 and Dec 2007 were analysed. A GnRH agonist mid-luteal down regulation with 150-450 IU of recombinant FSH (r-FSH) depending on patient aetiology was employed. When at least two follicles had reached 18mm diameter final follicular maturation was induced with 250 mcg r-hCG or 10,000 IU u-hCG. Oocyte retrieval was scheduled 38 hours later. ICSI was performed on Metaphase II oocytes. Syngamy assessed 24 hours post insemination (hpi), day 2 assessment occurred between 42- 44 hpi, day 3 at 64-68 hpi. Blastocyst transfer occurred 5 days post-OPU. A clinical pregnancy was defined as a fetal heart 6 weeks after embryo transfer and implantation rate defined as the number of viable fetal hearts per embryo transferred. ANOVA was used for continous data and Chi Square for categorical data; statistical significance was set at P<0.05. RESULTS: Table 1. TABLE 1.
Age (years) BMI (kg/m^2) Daily gonadotropins IU Number MII oocytes Number 2PN zygotes Day 2 (cell number) Day 3 (cell number) Clinical Pregnancy Implantation rate
r-hCG (250mcg or 6250 IU)
u-hCG (10 000 IU)
P value (*P<0.05)
34.0 þ/ 3.7 24.9 þ/ 5.8 262.3 þ/ 112.6 8.4 þ/ 5.0 5.6 þ/ 3.9 4.1 þ/ 0.03 8.6 þ/ 0.04 37 % 33%
35.3 þ/ 3.6 24.7 þ/ 5.6 267.3 þ/ 111.2 9.1 þ/ 6.1 6.8 þ/ 4.9 4.0 þ/ 0.05 8.7 þ/ 0.05 37% 28%
0.007* 0.78 0.72 0.25 0.01* 0.46 0.13
CONCLUSIONS: We conclude that r-hCG is as effective as u-hCG for inducing final follicular maturation in COS. Even though fertilisation rate is lower in r-hCG group, embryo development occurs as expected and is associated with similar pregnancy rates.
on the rate of apoptosis in cumulus cells and outcomes of cycles of intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: 29 couples, at their first cycle, undergoing ICSI for severe male factor infertility were enrolled. r-hFSH (GONALÒ f , Merck Serono) was administered to 19 patients (Group A) and hMG (MenopurÒ, Ferring) to 10 patients (Group B), using a standard long agonist protocol. Apoptosis of pooled cumulus cells was assessed after treatment with hyaluronidase (Bio-Sage, USA) to remove cells from the oocytes. DNA damage was detected using TUNEL staining. RESULTS: No significant differences were found in median age (363.4 years vs. 402.1 years), serum estradiol concentration at human chorionic gonadotropin administration (1568929 vs. 1624651) or fertilization rates (96% vs. 100%) between Groups A and B. Significantly less gonadotropins FSH units were administered in Group A than Group B (1808754 IU vs. 34991516 IU; p<0.05) and significantly more oocytes were collected (7.13.2 vs. 4.72.9; p<0.05). The rate of cumulus cell apoptosis was significantly lower in Group A than Group B (19.4% vs. 35.3%; p<0.05). Higher rates of pregnancy and implantation were found in Group A (32% and 12%, respectively) than in Group B (10% and 3.8%, respectively) but the difference was not significant (probably due to the low number of patients in Group B). CONCLUSIONS: Compared with hMG, the use of r-hFSH resulted in significantly more oocytes retrieved, less gonadotropins used, and a lower rate of cumulus cell apoptosis. r-hFSH was also associated with better ICSI outcomes, in terms of pregnancy and implantation rates. A larger study is required to confirm these data. P-549 Wednesday, October 21, 2009 USE OF GONADOTROPIN RELEASING HORMONE ANTAGONIST (GNRHANT) TO REDUCE OVARIAN HYPERSTIMULATION SYNDROME (OHSS) IN IVF PATIENTS ON A GONADOTROPIN RELEASING HORMONE AGONIST (GNRHA) SUPPRESSION PROTOCOL. L. N. Weckstein, D. S. Wachs, M. Hinckley, S. Willman, C. Sgarlata, D. Galen. Reproductive Science Center of the Bay Area, San Ramon, CA. OBJECTIVE: Severe OHSS remains a significant complication of IVF treatment. A number of strategies to reduce the incidence of severe OHSS have been used. We evaluated a recently proposed technique adding GnRHAnt to an IVF GnRHa protocol when serum estradiol (E2) levels are high in order to bring the E2 level down prior to Chorioic Gonadotropin alfa (r-hCG) trigger. DESIGN: Retrospective Review. MATERIALS AND METHODS: From 1/1/07 through 12/31/08 all IVF patients with a GnRHa protocol who had an E2 R 5000 pg/ml during stimulation were divided into two groups. GnRHAnt- cycles were triggered with r-hCG with an E2 R 5000 or after 1-2 days of coasting. GnRHAntþ cycles were given 0.25mg GnRHAnt when the E2 was > 5000 pg/ml and it was anticipated that they would be triggered 1-2 days later based on follicle size. GnRHa was stopped and they received 75-150 IU FSH and 75 IU HMG on the day of GnRHAnt administration. Egg donors were included in this study. These groups were retrospectively evaluated for clinical pregnancy rates (CPR) and incidence of severe OHSS as defined as: 1) no embryo transfer (ET) due to OHSS, 2) aspiration of ascites, or 3) hospitalization. RESULTS: There was a higher E2 max in the GnRHAntþ group. There was no significant difference in severe OHSS between groups. There was a trend toward increased clinical pregnancy rates (CPR) in the autologous GnRHAntþ group. TABLE 1. Comparison of GnRHþ and GnRH- cycles.
P-548 Wednesday, October 21, 2009 OVARIAN STIMULATION PROTOCOL INFLUENCES THE APOPTOTIC RATE OF HUMAN CUMULUS CELLS: A COMPARATIVE STUDY BETWEEN RECOMBINANT AND URINARY HUMAN FOLLICLE-STIMULATING HORMONE (FSH). G. Ruvolo, L. Bosco, E. Cittadini. Centro Di Biologia Della Riproduzione, Palermo, Italy; University OF Palermo, Dipartimento di Biologia della Sviluppo, Palermo, Italy; Centro Di Biologia Della Riproduzione, Palermo, Italy. OBJECTIVE: Cumulus cells may affect oocyte quality and, thus, influence the outcomes of in vitro fertilization. We compared the effect of ovarian stimulation using two formulations of FSH. DESIGN: A prospective study to compare the effects of recombinant human (r-h)FSH and urinary-derived human menopausal gonadotropin (hMG)
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Abstracts
Cycles E2 Max CPR Own Eggs CPR Donor Eggs No ET Aspiration Ascites
GnRHAntþ
GnRHAnt
45 6679 153 pg/ml 22/36 (61%) 7/9 (78%) 4/45 (8.9%) 2/45 (4.4%)
130 5623 49 pg/ml 47/98 (48%) 24/32 (75%) 3/130 (2.3%) 3/130 (2.3%)
p < 0.001 p ¼ 0.08 p ¼ 0.9 p ¼ 0.08 p ¼ 0.6
CONCLUSIONS: GnRHAnt does not appear to reduce severe OHSS in GnRHa protocol IVF cycles at risk for OHSS. There is a trend toward increased CPR in autologous GnRHAntþ cycles. This may be due to better egg/embryo quality by avoiding coasting or may be due to an endometrial effect.
Vol. 92., No. 3, Supplement, September 2009
Treatment
Control
P Value
27.0 (25.3, 33.0) 23.3 (19.9, 24.8) 400.0 (262.2, 581.3) 6430.0 (5065.0, 8970.0) 53.5 (49.3, 55.5) 3.5 (1.9, 4.3) 4.5 (3.5, 4.8) 6.4 (4.8, 6.6) 0.0 (0.0, 0.3) 6.0 (4.0, 7.5)
29.0 (28.0, 36.5) 23.8 (21.2, 34.0) 225.0 (187.5, 262.5) 1886.0 (1748.5, 3041.5) 37 (29.5, 39.5) þ3 (0.3, þ5.6) þ1.9 (0.8, þ6.7) 1.8 (2.8, þ4.9) 3.0 (1.5, 6.5) 20.0 (18.3, 23.3)
0.17 0.52 0.09 0.008* 0.008* 0.008* 0.016* 0.056 0.007* 0.012*
CONCLUSIONS: Treated patients had more rapid weight loss, shorter duration to resolution, and fewer unscheduled visits. This protocol may represent a rapid and cost-effective outpatient therapy for patients diagnosed with moderate to severe OHSS.
P-544 Wednesday, October 21, 2009 ARE PHARMACOKINETIC (PK) PARAMETERS OF FOLLICLE STIMULATING HORMONE (FSH) DIFFERENT IN OBESE IVF PATIENTS? D. H. McCulloh, S. S. Morelli. University Reproductive Associates, Hasbrouck Heights, NJ; Obstetrics, Gynecology and Women’s Health, UMDNJ-New Jersey Medical School, Newark, NJ. OBJECTIVE: Serum FSH in response to FSH injections is seldom monitored during IVF, so PK data for FSH are sparse. Our objective was to determine if PK parameters vary with BMI, weight, height and/ or age. DESIGN: Retrospective analysis of 33 IVF cycles at a University-based outpatient clinic. MATERIALS AND METHODS: Patients underwent controlled ovarian hyperstimulation using leuprolide and gonadotropins. Data included BMI, weight, height, age, daily doses of gonadotropin, and serum FSH levels determined each day of monitoring (Immulite 1000). NJMS IRB approved the study. A numerical model in Microsoft EXCEL mimics serum FSH levels in a patient following FSH injections. Patient data were fitted (in Microsoft BASIC) by the model to obtain 3 PK parameters: two time constants (1) for appearance of FSH in the blood from the injection site (tin), (2) for disappearance of FSH from the blood (tout) and (3) a factor relating serum FSH to IUs injected (Fvol). Fvol, tout, and tin (the shorter of the two t’s) were inserted in the model to determine the rate of rise of peaks after the first injection (tapproachmax) and the ratio of peak values last/first (C38/C1). Patient values were compared by two-tailed Student’s t-tests after grouping by BMI, weight, height, and age. RESULTS: Obese patients (BMI>30) had significantly smaller Fvol (0.023 0.013) and tin (7.6 2.3 hr) than nonobese patients (BMI<30) (0.043 0.003; and 15.8 2.4 hr, respectively) (p ¼ 0.0008 and p ¼ 0.019, respectively). For all other parameters, there was no significant difference (tout ¼ 46.8 7.4 hr; tapproachmax ¼ 46.8 7.0 hr; C38/C1 ¼ 3.2 0.27). There were no significant differences when comparing patients grouped by height (<5’5’’ vs. >5’5’’) or age (<35 vs. >35 years). CONCLUSIONS: PK parameters for FSH varied greatly. Fvol’s decrease with increased BMI (or weight) suggests a dilution effect. Smaller tin with greater weight or BMI suggests that FSH moves more rapidly either into or out of the blood in obese patients. Supported by: No outside support.
FERTILITY & STERILITYÒ
P-545 Wednesday, October 21, 2009 EVALUATING THE LUTEAL ESTRADIOL (E2) PATCH/GNRH ANTAGONIST (E2-PRIME) PROTOCOL FOR PATIENTS WITH EVIDENCE OF DIMINISHED OVARIAN RESERVE. C. M. Mullin, N. Noyes, A. E. Reh, F. Licciardi, L. C. Krey, A. S. Berkeley. NYU Fertility Center, NYU Langone Medical Center, New York, NY. OBJECTIVE: To compare E2-Prime vs. OCP-microdose GnRH agonist (MCD) vs. clomiphene citrate (CC) protocols, all using gonadotropins. DESIGN: Retrospective analysis. MATERIALS AND METHODS: 156 cycles were analyzed according to protocol þ history of retrieved IVF cycle. All patients presented with evidence of diminished ovarian reserve, either a high D2 FSH or poor response to gonadotropin. Comparison of age, cancellation rate (CR), D2 E2/FSH, total gonadotropin dose, # cycle days, peak E2, # eggs retrieved (ER), # mature (MII) eggs, fertilization (FR), implantation (IR), and clinical pregnancy rate (PR) were analyzed according to protocol þ IVF history using c , ANOVA or their nonparametric equivalents as appropriate. RESULTS: MCD achieved a higher PR using less gonadotropin for a shorter duration as compared to E2-prime & CC, regardless of prior IVF history (Table). TABLE 1. Comparison of Clinical Outcomes. Prior Retrieved Cycle
Protocol (n)
No Prior Retrieved Cycle MCD (45)
E2-Prime (33)
CC (12)
MCD (26)
E2-Prime (28)
CC (12)
Mean Age ns/ns 393 404 403 413 394 403 4 8 3 16 18 0 CR (%)c/c c/c 3460 132247 3752 3046 103173 4057 D2E2 c/a 59 35 711 611 47 811 D2FSH 45231413 6298876 54381811 49991533 60801105 56001181 Total c/ns Gonadotropin(IU) #Cycle Daysa/b 92 111 103 102 112 92 21171151 1501658 1761 1050 1536677 12821800 1627701 Peak E2a/b 96 84 74 63 75 62 # ERns/ns 85 64 54 53 64 52 # MIIns/ns ns/ns FR (%) 54 43 53 33 44 32 ns/b 16 7 12 28 20 3 IR (%) ns/b 38 15 17 58 22 8 PR (%)
a¼p<0.05; b¼p<0.005; c¼p<0.0005; ns¼no significance; ANOVA analyses. CONCLUSIONS: Amongst poor prognostic patients with no prior retrieved IVF cycles, MCD is superior to E2-prime and CC. In contrast, patients with prior retrieved cycles responded similarly to the 3 protocols, with the only caveat being that MCD required less drug for fewer days.
P-546 Wednesday, October 21, 2009 OVULATION INDUCTION OUTCOMES: ANALYSIS OF MORE THAN 1500 CYCLES. A. Sarhan, H. A. Baydoun, H. W. Jones, S. Bocca, S. C. Oehninger, L. A. Stadtmauer. Jones Institute for Reproductive Medicine, Norfolk, VA; Epidemiology, Eastern Virginia Medical School, Norfolk, VA. OBJECTIVE: To evaluate the outcomes of a large cohort of patients undergoing ovulation induction cycles. DESIGN: A retrospective cohort study of 1525 ovulation induction cycles performed in 694 patients between August 1998 and December 2008. MATERIALS AND METHODS: Patients underwent ovulation induction cycles with gonadotropins then timed intercourse or intrauterine insemination. Clomiphene citrate or a GnRH antagonist were used in about 10% of the cycles. Strategies used to reduce multiple gestations included low gonadotropin doses, and cancellation in high risk patients for more than three follicles > 16 mm or high estradiol levels. RESULTS: Per cycle pregnancy rate was 12.4% with a per cycle live birth rate of 7.5%. There was a trend towards higher per cycle pregnancy rate and live birth rate in younger patients (P¼.0002). Multiple pregnancy rate was 12.7% with 10.1% twins and 2.6% triplets. Miscarriage rate was 25.8%, after excluding biochemical pregnancies, with a trend towards decreased miscarriages in younger patients (P¼.004). The use of a GnRH antagonist decreased the risk of miscarriage (AOR .26, 95% CI .07-.91). Patients with hypothalamic ovarian dysfunction were associated with the highest per cycle pregnancy rate and live birth rate of
S241
37.5% (no miscarriages) followed by PCOS. The lowest per cycle live birth rates were in women with diminished ovarian reserve, recurrent miscarriages, and uterine myomas (2%). The birthweight of a singleton from a pregnancy with a vanishing twin (n¼8) was significantly lower than the birthweight of a singleton without a vanishing twin (2882 gm vs 3250gm, P¼.013). CONCLUSIONS: Reducing multiple pregnancy with ovulation induction remains an important and challenging goal although there are no strict universal guidelines. In this cohort of patients, the high order multiple pregnancy rate was limited to 2.6% by using certain strategies. Risks of multiple pregnancy include a lower birthweight of the surviving singleton originating from a twin pregnancy. Supported by: Organon Schering Plough.
P-547 Wednesday, October 21, 2009 HUMAN CHORIONIC GONADOTROPIN (HCG) TYPE DOES NOT EFFECT THE RATE OF EMBRYO DEVELOPMENT. J. W. Catt, K. M. Peters, D. Ezcurra. Embryology Laboratory, Monash IVF, Melbourne, VIC, Australia; Medical Department, Merck Serono Australia, Sydney, NSW, Australia; Medical Department, Merck Serono International SA, Geneva, Switzerland. OBJECTIVE: The aim of this study was to assess two hCG preparations: r-hCG (OvidrelÒ250mcg or 6250IU) and u-hCG (PregnylÒ10,000IU) and the rate of embryo development in clinical practice. DESIGN: Retrospective observational. MATERIALS AND METHODS: 286 ICSI treatment cycles between September 2007 and Dec 2007 were analysed. A GnRH agonist mid-luteal down regulation with 150-450 IU of recombinant FSH (r-FSH) depending on patient aetiology was employed. When at least two follicles had reached 18mm diameter final follicular maturation was induced with 250 mcg r-hCG or 10,000 IU u-hCG. Oocyte retrieval was scheduled 38 hours later. ICSI was performed on Metaphase II oocytes. Syngamy assessed 24 hours post insemination (hpi), day 2 assessment occurred between 42- 44 hpi, day 3 at 64-68 hpi. Blastocyst transfer occurred 5 days post-OPU. A clinical pregnancy was defined as a fetal heart 6 weeks after embryo transfer and implantation rate defined as the number of viable fetal hearts per embryo transferred. ANOVA was used for continous data and Chi Square for categorical data; statistical significance was set at P<0.05. RESULTS: Table 1. TABLE 1.
Age (years) BMI (kg/m^2) Daily gonadotropins IU Number MII oocytes Number 2PN zygotes Day 2 (cell number) Day 3 (cell number) Clinical Pregnancy Implantation rate
r-hCG (250mcg or 6250 IU)
u-hCG (10 000 IU)
P value (*P<0.05)
34.0 þ/ 3.7 24.9 þ/ 5.8 262.3 þ/ 112.6 8.4 þ/ 5.0 5.6 þ/ 3.9 4.1 þ/ 0.03 8.6 þ/ 0.04 37 % 33%
35.3 þ/ 3.6 24.7 þ/ 5.6 267.3 þ/ 111.2 9.1 þ/ 6.1 6.8 þ/ 4.9 4.0 þ/ 0.05 8.7 þ/ 0.05 37% 28%
0.007* 0.78 0.72 0.25 0.01* 0.46 0.13
CONCLUSIONS: We conclude that r-hCG is as effective as u-hCG for inducing final follicular maturation in COS. Even though fertilisation rate is lower in r-hCG group, embryo development occurs as expected and is associated with similar pregnancy rates.
on the rate of apoptosis in cumulus cells and outcomes of cycles of intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: 29 couples, at their first cycle, undergoing ICSI for severe male factor infertility were enrolled. r-hFSH (GONALÒ f , Merck Serono) was administered to 19 patients (Group A) and hMG (MenopurÒ, Ferring) to 10 patients (Group B), using a standard long agonist protocol. Apoptosis of pooled cumulus cells was assessed after treatment with hyaluronidase (Bio-Sage, USA) to remove cells from the oocytes. DNA damage was detected using TUNEL staining. RESULTS: No significant differences were found in median age (363.4 years vs. 402.1 years), serum estradiol concentration at human chorionic gonadotropin administration (1568929 vs. 1624651) or fertilization rates (96% vs. 100%) between Groups A and B. Significantly less gonadotropins FSH units were administered in Group A than Group B (1808754 IU vs. 34991516 IU; p<0.05) and significantly more oocytes were collected (7.13.2 vs. 4.72.9; p<0.05). The rate of cumulus cell apoptosis was significantly lower in Group A than Group B (19.4% vs. 35.3%; p<0.05). Higher rates of pregnancy and implantation were found in Group A (32% and 12%, respectively) than in Group B (10% and 3.8%, respectively) but the difference was not significant (probably due to the low number of patients in Group B). CONCLUSIONS: Compared with hMG, the use of r-hFSH resulted in significantly more oocytes retrieved, less gonadotropins used, and a lower rate of cumulus cell apoptosis. r-hFSH was also associated with better ICSI outcomes, in terms of pregnancy and implantation rates. A larger study is required to confirm these data. P-549 Wednesday, October 21, 2009 USE OF GONADOTROPIN RELEASING HORMONE ANTAGONIST (GNRHANT) TO REDUCE OVARIAN HYPERSTIMULATION SYNDROME (OHSS) IN IVF PATIENTS ON A GONADOTROPIN RELEASING HORMONE AGONIST (GNRHA) SUPPRESSION PROTOCOL. L. N. Weckstein, D. S. Wachs, M. Hinckley, S. Willman, C. Sgarlata, D. Galen. Reproductive Science Center of the Bay Area, San Ramon, CA. OBJECTIVE: Severe OHSS remains a significant complication of IVF treatment. A number of strategies to reduce the incidence of severe OHSS have been used. We evaluated a recently proposed technique adding GnRHAnt to an IVF GnRHa protocol when serum estradiol (E2) levels are high in order to bring the E2 level down prior to Chorioic Gonadotropin alfa (r-hCG) trigger. DESIGN: Retrospective Review. MATERIALS AND METHODS: From 1/1/07 through 12/31/08 all IVF patients with a GnRHa protocol who had an E2 R 5000 pg/ml during stimulation were divided into two groups. GnRHAnt- cycles were triggered with r-hCG with an E2 R 5000 or after 1-2 days of coasting. GnRHAntþ cycles were given 0.25mg GnRHAnt when the E2 was > 5000 pg/ml and it was anticipated that they would be triggered 1-2 days later based on follicle size. GnRHa was stopped and they received 75-150 IU FSH and 75 IU HMG on the day of GnRHAnt administration. Egg donors were included in this study. These groups were retrospectively evaluated for clinical pregnancy rates (CPR) and incidence of severe OHSS as defined as: 1) no embryo transfer (ET) due to OHSS, 2) aspiration of ascites, or 3) hospitalization. RESULTS: There was a higher E2 max in the GnRHAntþ group. There was no significant difference in severe OHSS between groups. There was a trend toward increased clinical pregnancy rates (CPR) in the autologous GnRHAntþ group. TABLE 1. Comparison of GnRHþ and GnRH- cycles.
P-548 Wednesday, October 21, 2009 OVARIAN STIMULATION PROTOCOL INFLUENCES THE APOPTOTIC RATE OF HUMAN CUMULUS CELLS: A COMPARATIVE STUDY BETWEEN RECOMBINANT AND URINARY HUMAN FOLLICLE-STIMULATING HORMONE (FSH). G. Ruvolo, L. Bosco, E. Cittadini. Centro Di Biologia Della Riproduzione, Palermo, Italy; University OF Palermo, Dipartimento di Biologia della Sviluppo, Palermo, Italy; Centro Di Biologia Della Riproduzione, Palermo, Italy. OBJECTIVE: Cumulus cells may affect oocyte quality and, thus, influence the outcomes of in vitro fertilization. We compared the effect of ovarian stimulation using two formulations of FSH. DESIGN: A prospective study to compare the effects of recombinant human (r-h)FSH and urinary-derived human menopausal gonadotropin (hMG)
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Abstracts
Cycles E2 Max CPR Own Eggs CPR Donor Eggs No ET Aspiration Ascites
GnRHAntþ
GnRHAnt
45 6679 153 pg/ml 22/36 (61%) 7/9 (78%) 4/45 (8.9%) 2/45 (4.4%)
130 5623 49 pg/ml 47/98 (48%) 24/32 (75%) 3/130 (2.3%) 3/130 (2.3%)
p < 0.001 p ¼ 0.08 p ¼ 0.9 p ¼ 0.08 p ¼ 0.6
CONCLUSIONS: GnRHAnt does not appear to reduce severe OHSS in GnRHa protocol IVF cycles at risk for OHSS. There is a trend toward increased CPR in autologous GnRHAntþ cycles. This may be due to better egg/embryo quality by avoiding coasting or may be due to an endometrial effect.
Vol. 92., No. 3, Supplement, September 2009