luteal support for art high responders with crinone 8% (90mg) twice daily results in higher...

2
TABLE 2. Treatment outcomes between study (Endometrin vaginal progesterone luteal support) and the control group (intramuscular progesterone luteal support) Endometrin vaginal progesterne Intramuscular progesterne P Value Number of patients 145 399 Pregnancies (positive beta hCG) 84 (58%) 229 (57%) NS Clinical pregnancies 71 (49%) 210 (53%) NS Chemical pregnancies 13 (16%) 19 (8.3%) NS Miscarriage 7 (8%) 22 (10%) NS Data are presented as number (rate), NS ¼ Not statistically significant CONCLUSIONS: In women undergoing IVF-ET with the long protocol, luteal support with the vaginal progesterone, Endometrin Ò , was associated with comparable treatment outcomes to those who used IM-progesterone lu- teal support. Supported by: Ferring Pharmaceuticals research support. P-762 EFFECT OF ESTRADIOL SUPPLEMENT IN A LUTEAL PHASE OF IN VITRO FERTILIZATION AND EMBRYO TRANSFER (IVF-ET); A META-ANALYSIS. S. Chun, B. C. Jee, H. Kim, Y. J. Kim, C. S. Suh, S. H. Kim. Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea; Obstetrics and Gynecology, Seoul National University Bun- dang Hospital, Seongnam, Korea. OBJECTIVE: To clarify the effect of estradiol supplement in a luteal phase of stimulated IVF cycles. DESIGN: A systemic review and meta-analysis of randomized controlled trials (RCTs). MATERIALS AND METHODS: A literature search of the National Li- brary of Medicine and the National Institutes of Health (PubMed), MED- LINE and Cochrane Controlled Trials Register (CENTRAL) (The Cochrane Library) was performed. The last search date was November 2007. A meta-analysis was performed using Review Manager (RevMan ver. 4.2 for Windows, The Nordic Cochrane Centre, Copenhagen, Den- mark). In this meta-analysis, primary outcome was defined as clinical preg- nancy rate (PR) per patient. Secondary outcomes were clinical PR per ET, implantation rate (IR), ongoing PR per patient, clinical abortion rate (AR) and ectopic PR. RESULTS: We found fourteen articles comparing IVF-EToutcomes after administration of estradiol plus progesterone versus progesterone only as a luteal supplementation. Finally, nine studies were reviewed in the meta- analysis. There were no statistically significant differences with regard to clinical PR per patient (RR: 1.27, 95% CI: 0.83-1.96), clinical PR per ET (RR: 1.53, 95% CI: 0.84-2.78), IR (RR: 1.26, 95% CI: 0.41-3.86), ongoing PR per patient (RR: 1.23, 95% CI: 0.73-2.08), clinical AR (RR: 1.02, 95% CI: 0.43-2.38) and ectopic PR (RR: 0.53, 95% CI: 0.07-4.10). When we as- sessed gonadotropin-releasing hormone (GnRH) agonist cycles only sepa- rately from seven studies, no statistical significant differences were observed between two groups with regard to clinical PR per patient (RR: 1.32, 95% CI: 0.79-2.19), clinical PR per ET (RR: 1.83, 95% CI: 0.96- 3.49), IR (RR: 1.20, 95% CI: 0.34-4.21), ongoing PR per patient (RR: 1.34, 95% CI: 0.37-4.82), clinical AR (RR: 1.05, 95% CI: 0.48-2.28) and ec- topic PR (RR: 0.53, 95% CI: 0.07-4.10). When GnRH antagonist cycles only were separately assessed from three studies, clinical PRs per patient from two studies and ongoing PRs per patient from three studies were all similar between two groups (RR: 0.94, 95% CI: 0.62-1.42, and RR: 1.09, 95% CI: 0.79- 1.50). CONCLUSIONS: The currently available evidence in this meta-analysis suggests that the addition of estrogen to progesterone for luteal phase sup- port does not increase the PRs in IVF. However, there is an obvious need for further large, multi-center RCTs with more confidence that will assess the effect of estradiol plus progesterone during the luteal phase on IVF outcomes. Supported by: None. P-763 GnRH-AGONIST ADMINISTRATION IN THE MID-LUTEAL PHASE YIELDS FAVORABLE PREGNANCYAND IMPLANTATION RATES IN STIMULATED IN VITRO FERTILIZATION CYCLES WITH GnRH-ANTAGONIST. Z. R. Hubayter, A. Rettberg, A. Ibrahim, H. Zacur, J. Garcia, S. J. Muasher. Gynecology and Obstetrics, Johns Hop- kins Medical Institution, Baltimore, MD; Muasher Center for Fertility and IVF, Fairfax, VA. OBJECTIVE: Our goal was to assess a novel role for GnRH-agonist as a supplement in luteal phase. GnRH-agonist receptors are present in the en- dometrium and the ovaries. Furthermore, the corpus luteum function may im- prove with GnRH-agonist induced endogenous flare with pituitary hormones. In vitro, GnRH-agonists have improved mouse embryo developement. Re- cent studies have demonstrated improved implantation rate with the use of a single dose GnRH-agonist 6 days after oocyte retreival in an IVF cycle (Te- sarik, Hum Reprod, 2006,21: 2572-9). Our objective was to evaluate the im- pact of a daily GnRH-agonist at the time of implantation (Days 5-7 following retreival) on IVF outcomes in antagonist cycles. DESIGN: Retrospective analysis. MATERIALS AND METHODS: We reviewed 49 consecutive patients, in which the patients underwent controlled ovarian hyperstimulation with go- nadotropins and with GnRH-antagonist (Ganirelix acetate 0.25 mg/day) added on stimulation day 6. In addition to the standard progesterone supple- mentation, patients were given leuprolide acetate 0.5 mg SC on days 5, 6, and 7 of the luteal phase. Age and basal FSH matched historical control group, given the same ovarian stimulation protocol but without GnRH-agonist post retrieval, was used for comparison. Statistical analysis was performed with SAS version 9.0 (Carey, NC). Student-t test was used to compare the two groups, and NPAR1WAY (Kruskal-Wallis test) for nonparametric analysis when necessary. A p value of % 0.05 was considered statistically significant. RESULTS: Table 1 demonstrates the findings. When compared to the matched control, with similar numbers of embryos transfered per cycle (3 vs. 2.8, P¼0.55), significantly higher clinical pregnancy (55% vs. 23%, P < 0.01) and implantation rates (28% vs. 9%, P < 0.01) were observed. TABLE 1. IVF outcome with GnRH-agonist luteal supplementation Parameter Mean (SD) Age (years) 34.7 (4.4) Day 3 FSH (IU/L) 7.9 (2.2) Peak estradiol (pg/ml) 1664 (957) Embryos transferred (n) 3.0 (0.8) Pregnancy rate / transfer 55% Implantation rate 28% Miscarriage rate 11% CONCLUSIONS: Mid luteal phase support with GnRH-agonist, around the days of implantation appears to yield favorable outcomes in IVF cycles using GnRH-antagonists for ovarian stimulation. A large randomized pro- spective controlled trial will need to be conducted in order to confirm these findings. Supported by: None. P-764 LUTEAL SUPPORT FOR ART HIGH RESPONDERS WITH CRIN- ONE 8% (90mg) TWICE DAILY RESULTS IN HIGHER PREG- NANCY RATES THAN INTRAMUSCULAR PROGESTERONE. C.-H. Ho, S.-U. Chen. Obstetricsand Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan. OBJECTIVE: The use of progesterone for luteal support has been demon- strated to be beneficial in assisted reproductive cycles, yet the optimal route of progesterone administration has still not been established. This article compares the luteal progesterone supplementation with vaginal gel or intra- muscular progesterone among high responders of assisted reproductive treat- ment. DESIGN: Prospective randomized study. MATERIALS AND METHODS: After controlled ovarian hyperstimula- tion with long or short gonadotropin releasing hormone agonist protocol, FERTILITY & STERILITY Ò S365

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Page 1: Luteal support for ART high responders with crinone 8% (90mg) twice daily results in higher pregnancy rates than intramuscular progesterone

TABLE 2. Treatment outcomes between study (Endometrin vaginal progesterone

luteal support) and the control group (intramuscular progesterone luteal support)

FERTILITY & STERIL

Endometrinvaginal

progesterne

ITY�

Intramuscularprogesterne

P Value

Number of patients

145 399 Pregnancies

(positive beta hCG)

84 (58%) 229 (57%) NS

Clinical pregnancies

71 (49%) 210 (53%) NS Chemical pregnancies 13 (16%) 19 (8.3%) NS Miscarriage 7 (8%) 22 (10%) NS

Data are presented as number (rate), NS ¼ Not statistically significant

CONCLUSIONS: In women undergoing IVF-ET with the long protocol,luteal support with the vaginal progesterone, Endometrin�, was associatedwith comparable treatment outcomes to those who used IM-progesterone lu-teal support.

Supported by: Ferring Pharmaceuticals research support.

P-762

EFFECT OF ESTRADIOL SUPPLEMENT IN A LUTEAL PHASE OFIN VITRO FERTILIZATION AND EMBRYO TRANSFER (IVF-ET);A META-ANALYSIS. S. Chun, B. C. Jee, H. Kim, Y. J. Kim, C. S. Suh,S. H. Kim. Obstetrics and Gynecology, Seoul National University Hospital,Seoul, Korea; Obstetrics and Gynecology, Seoul National University Bun-dang Hospital, Seongnam, Korea.

OBJECTIVE: To clarify the effect of estradiol supplement in a luteal phaseof stimulated IVF cycles.

DESIGN: A systemic review and meta-analysis of randomized controlledtrials (RCTs).

MATERIALS AND METHODS: A literature search of the National Li-brary of Medicine and the National Institutes of Health (PubMed), MED-LINE and Cochrane Controlled Trials Register (CENTRAL) (TheCochrane Library) was performed. The last search date was November2007. A meta-analysis was performed using Review Manager (RevManver. 4.2 for Windows, The Nordic Cochrane Centre, Copenhagen, Den-mark). In this meta-analysis, primary outcome was defined as clinical preg-nancy rate (PR) per patient. Secondary outcomes were clinical PR per ET,implantation rate (IR), ongoing PR per patient, clinical abortion rate (AR)and ectopic PR.

RESULTS: We found fourteen articles comparing IVF-ET outcomes afteradministration of estradiol plus progesterone versus progesterone only asa luteal supplementation. Finally, nine studies were reviewed in the meta-analysis. There were no statistically significant differences with regard toclinical PR per patient (RR: 1.27, 95% CI: 0.83-1.96), clinical PR per ET(RR: 1.53, 95% CI: 0.84-2.78), IR (RR: 1.26, 95% CI: 0.41-3.86), ongoingPR per patient (RR: 1.23, 95% CI: 0.73-2.08), clinical AR (RR: 1.02, 95%CI: 0.43-2.38) and ectopic PR (RR: 0.53, 95% CI: 0.07-4.10). When we as-sessed gonadotropin-releasing hormone (GnRH) agonist cycles only sepa-rately from seven studies, no statistical significant differences wereobserved between two groups with regard to clinical PR per patient (RR:1.32, 95% CI: 0.79-2.19), clinical PR per ET (RR: 1.83, 95% CI: 0.96-3.49), IR (RR: 1.20, 95% CI: 0.34-4.21), ongoing PR per patient (RR:1.34, 95% CI: 0.37-4.82), clinical AR (RR: 1.05, 95% CI: 0.48-2.28) and ec-topic PR (RR: 0.53, 95% CI: 0.07-4.10). When GnRH antagonist cycles onlywere separately assessed from three studies, clinical PRs per patient fromtwo studies and ongoing PRs per patient from three studies were all similarbetween two groups (RR: 0.94, 95% CI: 0.62-1.42, and RR: 1.09, 95% CI:0.79- 1.50).

CONCLUSIONS: The currently available evidence in this meta-analysissuggests that the addition of estrogen to progesterone for luteal phase sup-port does not increase the PRs in IVF. However, there is an obvious need forfurther large, multi-center RCTs with more confidence that will assess theeffect of estradiol plus progesterone during the luteal phase on IVFoutcomes.

Supported by: None.

P-763

GnRH-AGONIST ADMINISTRATION IN THE MID-LUTEALPHASE YIELDS FAVORABLE PREGNANCYAND IMPLANTATIONRATES IN STIMULATED IN VITRO FERTILIZATION CYCLESWITH GnRH-ANTAGONIST. Z. R. Hubayter, A. Rettberg, A. Ibrahim,H. Zacur, J. Garcia, S. J. Muasher. Gynecology and Obstetrics, Johns Hop-kins Medical Institution, Baltimore, MD; Muasher Center for Fertilityand IVF, Fairfax, VA.

OBJECTIVE: Our goal was to assess a novel role for GnRH-agonist asa supplement in luteal phase. GnRH-agonist receptors are present in the en-dometrium and the ovaries. Furthermore, the corpus luteum function may im-prove with GnRH-agonist induced endogenous flare with pituitary hormones.In vitro, GnRH-agonists have improved mouse embryo developement. Re-cent studies have demonstrated improved implantation rate with the use ofa single dose GnRH-agonist 6 days after oocyte retreival in an IVF cycle (Te-sarik, Hum Reprod, 2006,21: 2572-9). Our objective was to evaluate the im-pact of a daily GnRH-agonist at the time of implantation (Days 5-7 followingretreival) on IVF outcomes in antagonist cycles.

DESIGN: Retrospective analysis.MATERIALS AND METHODS: We reviewed 49 consecutive patients, in

which the patients underwent controlled ovarian hyperstimulation with go-nadotropins and with GnRH-antagonist (Ganirelix acetate 0.25 mg/day)added on stimulation day 6. In addition to the standard progesterone supple-mentation, patients were given leuprolide acetate 0.5 mg SC on days 5, 6, and7 of the luteal phase. Age and basal FSH matched historical control group,given the same ovarian stimulation protocol but without GnRH-agonist postretrieval, was used for comparison. Statistical analysis was performed withSAS version 9.0 (Carey, NC). Student-t test was used to compare the twogroups, and NPAR1WAY (Kruskal-Wallis test) for nonparametric analysiswhen necessary. A p value of % 0.05 was considered statistically significant.

RESULTS: Table 1 demonstrates the findings. When compared to thematched control, with similar numbers of embryos transfered per cycle (3vs. 2.8, P¼0.55), significantly higher clinical pregnancy (55% vs. 23%,P < 0.01) and implantation rates (28% vs. 9%, P < 0.01) were observed.

TABLE 1. IVF outcome with GnRH-agonist luteal supplementation

Parameter

Mean (SD)

Age (years)

34.7 (4.4) Day 3 FSH (IU/L) 7.9 (2.2) Peak estradiol (pg/ml) 1664 (957) Embryos transferred (n) 3.0 (0.8) Pregnancy rate / transfer 55% Implantation rate 28% Miscarriage rate 11%

CONCLUSIONS: Mid luteal phase support with GnRH-agonist, aroundthe days of implantation appears to yield favorable outcomes in IVF cyclesusing GnRH-antagonists for ovarian stimulation. A large randomized pro-spective controlled trial will need to be conducted in order to confirm thesefindings.

Supported by: None.

P-764

LUTEAL SUPPORT FOR ART HIGH RESPONDERS WITH CRIN-ONE 8% (90mg) TWICE DAILY RESULTS IN HIGHER PREG-NANCY RATES THAN INTRAMUSCULAR PROGESTERONE.C.-H. Ho, S.-U. Chen. Obstetrics and Gynecology, Taipei Veterans GeneralHospital, Taipei, Taiwan; Obstetrics and Gynecology, National TaiwanUniversity Hospital, Taipei, Taiwan.

OBJECTIVE: The use of progesterone for luteal support has been demon-strated to be beneficial in assisted reproductive cycles, yet the optimal routeof progesterone administration has still not been established. This articlecompares the luteal progesterone supplementation with vaginal gel or intra-muscular progesterone among high responders of assisted reproductive treat-ment.

DESIGN: Prospective randomized study.MATERIALS AND METHODS: After controlled ovarian hyperstimula-

tion with long or short gonadotropin releasing hormone agonist protocol,

S365

Page 2: Luteal support for ART high responders with crinone 8% (90mg) twice daily results in higher pregnancy rates than intramuscular progesterone

a total of 206 patients with more than 20 follicles or serum estradiol levelsmore than 3,000 pg/mL were randomized into two groups. Two days after oo-cyte retrieval, each patient began luteal supplementation with vaginal gel 90mg twice daily (104 patients) or intramuscular progesterone 50 mg (102 pa-tients) for 14 days.

RESULTS: Both groups had similar mean age, cause of infertility, baselinehormone levels, number of retrieved and fertilized oocytes, and number oftransferred embryos. Vaginal gel group had slightly higher implantationrate (27.4% versus 21.0%, p¼ 0.070) and significantly higher ongoing preg-nancy rate (51.0% versus 37.3%, p¼ 0.048) than intramuscular progesteronegroup. The miscarriage rates in two groups were comparable.

CONCLUSIONS: It is concluded that for high responders, using vaginalprogesterone gel twice daily for luteal support results in better pregnancy out-comes than intramuscular progesterone. A high local progesterone effectfrom vaginal gel might improve endometrial receptivity under high serum es-tradiol levels.

Supported by: None.

P-765

SERUM PROGESTERONE LEVELS WITH ENDOMETRIN COM-PARED TO PROGESTERONE IN OIL AND ASSOCIATED PREG-NANCY OUTCOMES IN A LARGE IVF CENTER. A. Beltsos,A. Robinson, M. K. Martin-Johnston, K. Lederer, K. Sasada, M. Byers. Fer-tility Centers of Illinois, Chicago, IL; Lutheran General Hospital, Park Ridge,IL; Illinois Masonic Medical Center, Chicago, IL; Ferring Pharmaceuticals,Chicago, IL.

OBJECTIVE: To evaluate serum progesterone levels and pregnancy out-comes in IVF cycles with progesterone vaginal inserts compared to proges-terone in oil.

DESIGN: Retrospective analysis in large IVF program.MATERIALS AND METHODS: From April 2007 to December 2007, over

1300 fresh, nondonor IVF cycles were identified using Endometrin (FerringPharmaceuticals) vaginal progesterone or Progesterone in oil (PIO) intramus-cular for luteal phase support. Standard controlled ovarian hyperstimulationand laboratory protocols were followed using either GnRH agonist or antag-onist formularies. Serum progesterone levels (ng/ml) were evaluated on dayof pregnancy test. Statistical significance was evaluated by ANOVA and chisquare. A probability of <0.05 was considered significant.

RESULTS: See Table Below.

TABLE 1. Results

Parameter

S366 Abstracts

Endometrin N¼568

PIO N¼751 p-value

Age

36.4 35.9 NS Total Dose of

Gonadotropin

4509.2 4506.4 NS

Oocytes Retrieved

12.4 12.9 NS Pregnancy Rate per

transfer

42.9% 41.3% NS

Serum Progesterone

47 50 NS Clinical Pregnancy Rates 35.4% 35.1% NS

CONCLUSIONS: In this analysis of pregnant IVF patients the mean initialserum progesterone levels on Endometrin appear to be similar to those onprogesterone in oil. It has been reported that progesterone levels on vaginalproducts might be lower than expected and in these circumstances, it is im-portant to consider the form of progesterone being given. Furthermore, preg-nancy occurrence and outcome appear to be the same as with progesterone inoil as well as being a more patient friendly approach.

Supported by: None.

EMBRYO TRANSFER

P-766

SINGLE EMBRYO TRANSFER VERSUS DOUBLE EMBRYOTRANSFER IN VITRIFIED FROZEN-THAWED BLASTOCYSTTRANSFER CYCLES: RETROSPECTIVE ANALYSIS OF 967 CRYO-PRESERVED CYCLES WITH NO MORE THAN TWO BLASTO-CYSTS. S. J. Chae, C. Y. Hur, W. D. Lee, J. H. Lim. Maria FertilityHospital, Seoul, Korea.

OBJECTIVE: To compare single embryo transfer (SET) with double em-bryo transfer (DET) in the frozen-thawed blastocyst embryo transfer (FBET).

DESIGN: Retrospective analysis.MATERIALS AND METHODS: This study included 967 FBET cycles

with SET or DET in 836 women who had less than 3 FBEs in Maria FertilityHospital from January 2005 to December 2007. All embryos were vitrifiedusing EM grids after artificial shrinkage. Clinical outcomes such as implan-tation rate, clinical pregnancy rate, and multiple pregnancy rate were com-pared between SET and DET using chi-square test.

RESULTS: Mean age of patients (mean�SD) was not different betweenfor SET (33.9�3.7, 256 cycles) and DET (33.4�3.3, 711 cycles). SET andDET showed no significant difference in cause of infertility, previous IVFprotocol, and fertilization method. SET showed similar implantation rate(21.5%) compared to DET (21.4%). Clinical pregnancy rate (23.8% vs.36.4%) and on-going pregnancy rate (19.1% vs. 29.4%) in SET werelower than those in DET (P<0.05). SET had no multiple pregnancies.However, multiple pregnancy rate was 6.3% in DET. In subgroup analysisof good quality embryo transfer, there was no significant differences inimplantation rate (35.7% vs. 26.4%), clinical pregnancy rate (35.7% vs.43.0%), and on-going pregnancy rate (34.3% vs. 37.8%) between SETand DET. However, multiple pregnancies (10.8%) were occurred only inDET (Table 1).

CONCLUSIONS: Good quality SET is comparable to DET with regardto clinical pregnancy and on-going pregnancy in FBET. Good quality SETis more advantageous than DET in avoiding multiple pregnancies inFBET.

TABLE 1. Clinical outcomes in single embryo transfer versus double embryo

transfer in frozen-thawed good quality blastocyst transfer

<35

years old

Vol. 90, S

uppl 1,

R 35

years old

Septem

n (%)

RR 95% CI n (%) RR 95% CI

Implantation rate

Double embryo transfer

116/408

(28.4%)

35/164

(21.3%)

Single embryo transfer

16/ 47

(34.0%)

1.299

0.685-2.465 9/23

(39.1%)

2.369

0.947-5.927

Clinical pregnancy rate

Double embryo transfer

92/204

(45.1%)

31/82

(30.0%)

Single embryo transfer

16/47

(34.0%)

0.628

0.324-1.220 9/23

(39.1%)

1.058

0.409-2.732

On-going pregnancy rate

Double embryo transfer

83/204

(40.7%)

25/82

(30.5%)

Single embryo transfer

15/47

(31.9%)

0.683

0.348-1.341 9/23

(39.1%)

1.466

0.561-3.829

Multiple pregnancy rate

Double embryo transfer

25/204

(12.3%)

5/82

(6.1%)

Single embryo transfer

0 0

All data were assessed using chi-square test.

Supported by: None.

P-767

WHO CAN BENEFIT FROM SINGLE EMBRYO TRANSFER? EX-PANDING THE ASRM/SART CRITERIA FOR SINGLE EMBRYOTRANSFERRED. G. Jeng, M. Macaluso, J. Chang, M. Sunderam. Divisionof Reproductive Health, Centers for Disease Control and Prevention, Atlanta,GA.

OBJECTIVE: In 2004, ASRM/SART recommended that women withgood prognosis (age<35 using fresh non-donor eggs, no prior ART failure,and extra embryos for cryopreservation) consider single embryo transfer(SET). Although a general trend towards fewer embryos transferred follow-ing the guideline have resulted in fewer multiple deliveries, overall, multiplebirths still account for one third of IVF births in the U.S. This may be due to

ber 2008