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P-739
P-737 PROSPECTIVE, RANDOMIZED, CONTROLLED STUDY OF IN VITRO FERTILIZATION-EMBRYO TRANSFER WITH GNRH ANTAGONIST (CETRORELIX) OR A SHORT PROTOCOL OF THE GNRH AGONIST (TRIPTORELIN). C. Ma, J. Qiao, P. Liu. Peking University Third Hospital, Beijing, China. OBJECTIVE: To evaluate the results of the use of GnRH antagonist (GnRHant) and GnRH analog (GnRHa) in three groups of IVF/ICSI patients DESIGN: Single-center randomized, prospective, controlled study MATERIALS AND METHODS: Ninety infertile couples who underwent ovarian stimulation for IVF-ET. Multiple dose of 0.25 mg (Group I) and a single dose of 3 mg (Group II) of cetrorelix(Cetrotide; Serono, Swiss)(60 patients) was administered in the late follicular phase. A depot preparation of triptorelin (Decapeptyl) was chosen as a control agent and a short GnRHa protocol as a control group(30 patients) (Group III) .Ovarian stimulation was conducted with FSH(Gonaf, Serono, Swiss) RESULTS: No LH surge occurred in three groups. The mean number of stimulation days with gonadotropins was (8.33⫾0.96), (8.69⫾0.93 )and ( 8.50⫾1.07) in Groups I , II and III respectively, showing no statistical difference. The median ampules of FSH administered in Group I was (24.30⫾⫾4.37), in Group II ( 26.48⫾4.38), and in Group III (26.67⫾5.0).The median numbers of mature oocytes obtained per patient was (13.47⫾7.60), (18.66⫾8.37) and (15.77⫾10.78) in Groups I, II and III, respectively. The fertilization rate was (78.97⫾18.11) % in Group I , (72.35⫾25.44)% in Group II and (76.80⫾23.10)% in Group III. The clinical pregnancy rates per patient were statistically comparable in the GnRH-a group (30.8%) and in the GnRH antagonist group (37.9% in group I, 28.6% in Group II), as were ongoing pregnancy rates per embryo transfer 31.0%, 25.9% , 30.8% for the cetrorelix I, II and triptorelin groups, respectively. The pregnancy rates were not statistically different. Tolerance of cetrorelix was excellent. No severe or moderate ovarian hyperstimulation syndrome (OHSS) of cetrorelix groups occurred. CONCLUSION: Both cetrorelix single-dose and multidose protocol prevented LH surges in all patients studied. GnRHant and GnRHa provide comparable results in patients, while GnRHant allows a higher flexibility in the treatment. Supported by: peking university third hospital
P-738 367 INTRAUTERINE INSEMINATION CYCLES WITH OR WITHOUT A GNRH ANTAGONIST: A PROSPECTIVE RANDOMIZED STUDY. J. Gomez-Palomares Sr., B. Acevedo-Martin, M. Chavez, M. Manzanares, E. R. Hernandez, E. Ricciarelli. FIV-MADRID, Madrid, Spain. OBJECTIVE: Multifollicular recruitment during controlled ovarian hyperstimulation in intrauterine insemination (COH-IUI) can bring about a sudden increase in E2 serum levels that is enough to induce an LH surge while follicular growth is still in progress. Thus, to avoid the risk of an unexpected follicular luteinization, ovulation is generally induced as soon as the leading follicle has reached the 18 mm boundary. However, this decreases the possibilities for gestation since it changes the IUI cycle from multi- to monofollicular. Suppressing gonadotropin-LH release with a GnRH antagonist will prevent premature LH surges and follicle luteinization, and allow us to postpone ovulation. With this in mind, we thought that if pregnancy rates in IUI were related to the number of mature follicles present on the day HCG was indicated and, if the limiting factor for follicular development was premature luteinization, why couldn’t any unexpected LH surge be controlled with a GnRH antagonist during the COH-UIU cycle? Thus, the objective of this study was to determine whether including a GnRH antagonist in COH-IUI cycles would increase pregnancy rates. DESIGN: Prospective randomized study. MATERIALS AND METHODS: 367 women (19-38 years old) with primary or secondary infertility were included in this prospective randomized study. PCO and endometriosis were excluded. The patients were randomly (by a computer) assigned to controlled ovarian stimulation with rFSH ⫹ the GnRH antagonist (Ganirelix Acetate) initiated when the recruited follicles were ⱖ16mm (n⫽184) or with rFSH alone (n⫽183). Ovulation was induced with HCG 5,000 IU/ i.m. A single insemination was
FERTILITY & STERILITY威
performed, 36-38 hours post-HCG, in both groups. Continuous variables were compared with Student’s t test. The Chi-Squared test and Fisher test were used to compare clinical outcome between the two groups. P 4 follicles ⱖ16 mm), eight in the antagonist group and six in the control group. A non significant increase in the total amount of rFSH (629.5⫾358 vs 698.1⫾310 units) and cycle length (6.9 ⫾3.3 vs 7.8⫾2.3) was seen in the GnRH antagonist group with respect to the control group. The mean number of antagonist ampoules used was 2⫾1.2. The number of mature follicles (2.1⫾1.3 vs. 1.7⫾1.09, p⬍0.05) and pregnancy rates (25% vs. 11%, p⬍0.05) were significantly higher in patients treated with GnRH antagonist than in the control group, respectively. A similar number of twin pregnancies occurred in both groups (two and three, respectively), but the antagonist group also had one triplet gestation. CONCLUSION: Adding GnRH antagonist to COH-IUI cycles significantly increases pregnancy rates. This increase seems to be related with the number of follicles recruited, and thus, first, the use of GnRH antagonist is not recommended in monofollicular IUI cycles and, second, the risk of multiple gestations needs to be carefully evaluated. Supported by: None
P-739 GNRH ANTAGONIST IS A RELIABLE OVARIAN STIMULATION REGIMEN FOR IVF TREATMENTS. J. Zhu, M. J. Hickey, J. Levin. Hinsdale Center for Reproduction, Hinsdale, IL. OBJECTIVE: In the six years since introduction of GnRH antagonists, it has been shown that treatment duration and gonadotropin consumptions have decreased during ART cycles. However, success rates with GnRH-ant use have been questioned (Griesinger et al; 2005). Our objective with this study was to review success rates during a period that our practice used GnRH-antagnist as the primary choice IVF protocol. DESIGN: Retrospective study (11/2001 - 8/2005). MATERIALS AND METHODS: This study was a retrospective chart review including all GnRH-antagonist treatment cycles with fresh embryo transfer from 11/01 through 8/05. Patients were pretreated with approximately three weeks of oral contraceptive pills starting on day 3 of menses. Gonadotropin stimulation was initiated on day 2-4 of their subsequent menses. GnRH-antagonist (Antagon/Ganirelix) initiation was variable based upon follicle diameter (像14), estradiol levels (⬎400), and usually occurred on day 5 or 6 but as early as day 4 of stimulation. GnRH-antagonist dosing usually was 250g SQ, but occasionally 500g SQ, each day through and including the day of hCG (10,000 iu IM) administration. Gonadotropin dosing was variable and hCG was administered when at least three follicles reached a mean diameter of at least 18mm. No gonadotropin was given on the day of hCG. Oocyte retrieval was performed 35-37 hours after hCG. Embryo transfer was performed typically on day 3, but occasionally on day 5 (e.g. when single embryo transfer was desired). Clinical pregnancy was defined as ultrasound evidence of an intrauterine embryonic pole with heartbeat by the 5th week following oocyte retrieval. RESULTS: 94% of GnRH-antagonis cycles triggered with hCG between day 9-11 of GnRH administration. Length of gonadotropin stimulation did not differ with patient’s age. It also did not correlated with either E2 or P4. Clinical pregnancy rates did not very with the length of stimulation days i.e. 41.7%, 50.0%, 38.5% and 33.3% for hCG on day 9, 10, 11 and 12. Clinical pregnancy rates as expected did trend lower with patient’s age although there was no significant difference was found, i.e. 56.5%, 39.3%, 33.3% and 56% for age of ⱕ 34, 35-37, ⱖ38 years old and donor groups respectively. There were no significant difference in E2 and P4 between age groups, except for the donors who had higher P4 on the day of hCG with 1.72 ⫾ 0.22 ng/ml that was significantly higher than patient’s group with age ⱕ 34 (1.24 ⫾ 0.051 ng/ml Pⱕ0.001), 35-37 (1.19 ⫾ 0.057 ng/ml Pⱕ0.001) and 38-40 years old (1.34 ⫾ 0.090 ng/ml Pⱕ0.05) respectively. CONCLUSION: These data suggest that pregnancy rates after GnRHantagonist treatment are acceptable for all age groups and for donor cycles. Also, this review suggests that stimulations with GnRH-antagonist may be expected to trigger, on average, one day sooner comparing to our previous experience with using agonist. Notably, during oocyte donor stimulations, progesterone levels increased, which may be a result of their younger age. Supported by: None
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P-738 367 INTRAUTERINE INSEMINATION CYCLES WITH OR WITHOUT A GNRH ANTAGONIST: A PROSPECTIVE RANDOMIZED STUDY. J. Gomez-Palomares Sr., B. Acevedo-Martin, M. Chavez, M. Manzanares, E. R. Hernandez, E. Ricciarelli. FIV-MADRID, Madrid, Spain. OBJECTIVE: Multifollicular recruitment during controlled ovarian hyperstimulation in intrauterine insemination (COH-IUI) can bring about a sudden increase in E2 serum levels that is enough to induce an LH surge while follicular growth is still in progress. Thus, to avoid the risk of an unexpected follicular luteinization, ovulation is generally induced as soon as the leading follicle has reached the 18 mm boundary. However, this decreases the possibilities for gestation since it changes the IUI cycle from multi- to monofollicular. Suppressing gonadotropin-LH release with a GnRH antagonist will prevent premature LH surges and follicle luteinization, and allow us to postpone ovulation. With this in mind, we thought that if pregnancy rates in IUI were related to the number of mature follicles present on the day HCG was indicated and, if the limiting factor for follicular development was premature luteinization, why couldn’t any unexpected LH surge be controlled with a GnRH antagonist during the COH-UIU cycle? Thus, the objective of this study was to determine whether including a GnRH antagonist in COH-IUI cycles would increase pregnancy rates. DESIGN: Prospective randomized study. MATERIALS AND METHODS: 367 women (19-38 years old) with primary or secondary infertility were included in this prospective randomized study. PCO and endometriosis were excluded. The patients were randomly (by a computer) assigned to controlled ovarian stimulation with rFSH ⫹ the GnRH antagonist (Ganirelix Acetate) initiated when the recruited follicles were ⱖ16mm (n⫽184) or with rFSH alone (n⫽183). Ovulation was induced with HCG 5,000 IU/ i.m. A single insemination was
FERTILITY & STERILITY威
performed, 36-38 hours post-HCG, in both groups. Continuous variables were compared with Student’s t test. The Chi-Squared test and Fisher test were used to compare clinical outcome between the two groups. P 4 follicles ⱖ16 mm), eight in the antagonist group and six in the control group. A non significant increase in the total amount of rFSH (629.5⫾358 vs 698.1⫾310 units) and cycle length (6.9 ⫾3.3 vs 7.8⫾2.3) was seen in the GnRH antagonist group with respect to the control group. The mean number of antagonist ampoules used was 2⫾1.2. The number of mature follicles (2.1⫾1.3 vs. 1.7⫾1.09, p⬍0.05) and pregnancy rates (25% vs. 11%, p⬍0.05) were significantly higher in patients treated with GnRH antagonist than in the control group, respectively. A similar number of twin pregnancies occurred in both groups (two and three, respectively), but the antagonist group also had one triplet gestation. CONCLUSION: Adding GnRH antagonist to COH-IUI cycles significantly increases pregnancy rates. This increase seems to be related with the number of follicles recruited, and thus, first, the use of GnRH antagonist is not recommended in monofollicular IUI cycles and, second, the risk of multiple gestations needs to be carefully evaluated. Supported by: None
P-739 GNRH ANTAGONIST IS A RELIABLE OVARIAN STIMULATION REGIMEN FOR IVF TREATMENTS. J. Zhu, M. J. Hickey, J. Levin. Hinsdale Center for Reproduction, Hinsdale, IL. OBJECTIVE: In the six years since introduction of GnRH antagonists, it has been shown that treatment duration and gonadotropin consumptions have decreased during ART cycles. However, success rates with GnRH-ant use have been questioned (Griesinger et al; 2005). Our objective with this study was to review success rates during a period that our practice used GnRH-antagnist as the primary choice IVF protocol. DESIGN: Retrospective study (11/2001 - 8/2005). MATERIALS AND METHODS: This study was a retrospective chart review including all GnRH-antagonist treatment cycles with fresh embryo transfer from 11/01 through 8/05. Patients were pretreated with approximately three weeks of oral contraceptive pills starting on day 3 of menses. Gonadotropin stimulation was initiated on day 2-4 of their subsequent menses. GnRH-antagonist (Antagon/Ganirelix) initiation was variable based upon follicle diameter (像14), estradiol levels (⬎400), and usually occurred on day 5 or 6 but as early as day 4 of stimulation. GnRH-antagonist dosing usually was 250g SQ, but occasionally 500g SQ, each day through and including the day of hCG (10,000 iu IM) administration. Gonadotropin dosing was variable and hCG was administered when at least three follicles reached a mean diameter of at least 18mm. No gonadotropin was given on the day of hCG. Oocyte retrieval was performed 35-37 hours after hCG. Embryo transfer was performed typically on day 3, but occasionally on day 5 (e.g. when single embryo transfer was desired). Clinical pregnancy was defined as ultrasound evidence of an intrauterine embryonic pole with heartbeat by the 5th week following oocyte retrieval. RESULTS: 94% of GnRH-antagonis cycles triggered with hCG between day 9-11 of GnRH administration. Length of gonadotropin stimulation did not differ with patient’s age. It also did not correlated with either E2 or P4. Clinical pregnancy rates did not very with the length of stimulation days i.e. 41.7%, 50.0%, 38.5% and 33.3% for hCG on day 9, 10, 11 and 12. Clinical pregnancy rates as expected did trend lower with patient’s age although there was no significant difference was found, i.e. 56.5%, 39.3%, 33.3% and 56% for age of ⱕ 34, 35-37, ⱖ38 years old and donor groups respectively. There were no significant difference in E2 and P4 between age groups, except for the donors who had higher P4 on the day of hCG with 1.72 ⫾ 0.22 ng/ml that was significantly higher than patient’s group with age ⱕ 34 (1.24 ⫾ 0.051 ng/ml Pⱕ0.001), 35-37 (1.19 ⫾ 0.057 ng/ml Pⱕ0.001) and 38-40 years old (1.34 ⫾ 0.090 ng/ml Pⱕ0.05) respectively. CONCLUSION: These data suggest that pregnancy rates after GnRHantagonist treatment are acceptable for all age groups and for donor cycles. Also, this review suggests that stimulations with GnRH-antagonist may be expected to trigger, on average, one day sooner comparing to our previous experience with using agonist. Notably, during oocyte donor stimulations, progesterone levels increased, which may be a result of their younger age. Supported by: None
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