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Reduction of postoperative adhesions by N,O-carboxymethylchitosan (NOCC): a pilot study
O-11
Table 1: Serial E2 (pg/ml) Values (Mean ⫾ S.D.)
Reduction of postoperative adhesions by N,O-carboxymethylchitosan (NOCC): a pilot study. M. P. Diamond, A. Luciano, D. A. Johns, R. Dunn, P. Young, E. Bieber. Detroit, MI, New Britain, CT, Fort Worth, TX, Houston, TX, San Diego, CA, Danville, PA. Oral presentation preferred. Introduction: Studies demonstrated the ability of NOCC to markedly reduce postoperative adhesions in diverse animal models, thus this pilot study was undertaken to examine the safety and efficacy of NOCC in reducing adhesions. Methods: A multi-center, randomized, placebo controlled trial was conducted comparing NOCC and Ringers lactate. Application took place at the conclusion of the initial surgical procedure. Adhesion reduction was assessed by blinded reviewers at a second-look laparoscopy. NOCC was applied as 200 cc of a 1% NOCC gel which was tamped in place followed by 100 cc of 2% NOCC solution. Efficacy was assessed by covariate analysis. Results: 34 subjects were enrolled; 17 in each group were available for safety analysis and 16 for efficacy analysis. There were no differences between the groups in subject age, racial distribution, height, weight or BMI. There were no deaths or serious adverse events attributable to NOCC, and no adverse events related or probably related to NOCC. Adhesion reformation occurred at 61% of sites in control subjects and 37% in NOCC subjects. Subgroup analysis showed an incidence of adhesion reformation in the control subjects of 84% vs. 34% in the NOCC subjects. Thus, adhesion reformation in the control subgroup was 146% above the rate in the NOCC subjects. In these same subgroups, de novo 1a and 1b adhesions occurred more commonly at sites in control than in NOCC subjects (0.14 vs. 0.05 and 0.19 vs. 0.13, respectively). Considering all subjects, adhesion extent and severity at second look were also less in NOCC subjects. Summary: In summary, these findings demonstrate that laparoscopic NOCC gel and solution intraperitoneal use appears to be safe, as assessed by adverse event review, vital signs, physical examination, and serum chemistries. Despite the small sample size, strong trends were identified for reduction of occurrence, extent, and severity of adhesion reformation and de novo adhesion formation. (Sponsored by Chitogenics, Inc, Morristown, NJ.)
Day-6
Day-5
Day-4
Day-2
Day 0ˆ
Antagonist 439 ⫾ 231 772 ⫾ 326 973 ⫾ 328 1736 ⫾ 894 788 ⫾ 248 (N ⫽ 10) Agonist 230 ⫾ 84 654 ⫾ 294 1203 ⫾ 372 2671 ⫾ 1169 1162 ⫾ 545 (N ⫽ 5) * P ⫽ ⬎.05.
ˆDay 0 ⫽ Day of Oocyte Retrieval.
Table 2: Serial P (ng/ml) Values (Mean ⫾ S.D.)
Antagonist (N ⫽ 10) Agonist (N ⫽ 5)
Day-6
Day-5
Day-4
Day-2
Day 0ˆ
0.6 ⫾ .2
0.8 ⫾ .3
0.8 ⫾ .3
1.4 ⫾ .5
10.5 ⫾ 4.2
0.6 ⫾ .3
0.9 ⫾ .3
1.5 ⫾ .8
1.9 ⫾ .8
13.3 ⫾ 8.0
* P ⫽ ⬍.05.
ˆDay 0 ⫽ Day of Oocyte Retrieval.
Table 3: Histological Dating (Post-Ovulatory Day) by Endometrial Biopsy (Mean ⫾ S.D.)
Antagonist (N ⫽ 10) Agonist (N ⫽ 5) * P ⫽ ⬍.05.
Day 0ˆ
Day 7
5.8 ⫾ 2.1 days 5.9 ⫾ 1.3 days
9.5 ⫾ 1.6 10.5 ⫾ 1.9
ˆDay 0 ⫽ Day of Oocyte Retrieval.
Conclusion: All subjects undergoing C.O.H. with GnRH analogs have elevated P levels in the late follicular phase and accelerated endometrial maturation in the subsequent luteal phase. The advanced endometrial histology is most pronounced at the time of oocyte retrieval, but is still present at the time of implantation. There is no significant difference between pre-retrieval serial progesterone values and endometrial histology between cycles utilizing GnRH agonists and antagonists.
O-13 O-12 Accelerated endometrial maturation in the luteal phase of cycles utilizing controlled ovarian hyperstimulation: impact of GnRH agonist vs. antagonist. R. Boostanfar, C. Slater, S. Klumph, P. Saadat, D. Tourgeman, R. J. Paulson. Dept. of OB/GYN, Division of Reproductive Endocrinology and Infertility, University of Southern California Keck School of Medicine, Los Angeles, CA. Background: It has been previously reported that advanced endometrial maturation occurs during the luteal phase of cycles utilizing controlled ovarian hyperstimulation (C.O.H.). GnRH antagonists have been recently used as an alternative to agonists for ovulation suppression during C.O.H. The impact of C.O.H. utilizing GnRH antagonists on endometrial maturation is unknown. Purpose: To prospectively measure ovarian steroid production in the late follicular phase and its effects on endometrial histomorphology during the subsequent luteal phase among subjects undergoing C.O.H. with either a GnRH agonist or antagonist. Methods: Fifteen oocyte donors undergoing standard C.O.H. were enrolled. Subjects were assigned to two study groups. One group (n ⫽ 10) received one of two GnRH antagonists (Cetrotide威 or Antagon威) and the other group (n ⫽ 5) a GnRH agonist (Lupron威). Serum estradiol (E2) and progesterone (P) levels were obtained throughout ovarian stimulation. Endometrial biopsy was obtained at the time of oocyte retrieval and again 7 days later. Results: The following data are standardized to day of aspiration (Day ⫽ 0).
S10
PCRS Abstracts
Ovarian and adrenal androgen profiles in cycles of controlled ovarian hyperstimulation utilizing GnRH antagonists or agonists. E. Mor, P. Saadat, C. Zhang, F. Z. Stanczyk, C. C. Slater, J. Jain, D. Tourgeman, R. J. Paulson. Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, CA. Introduction: Recent reports have suggested trends towards lower pregnancy rates in in vitro fertilization (IVF) cycles utilizing GnRH antagonists, as compared to agonists. One possible explanation may be higher androgen levels reached in cycles using antagonists, which could affect folliculogenesis and endometrial receptivity. The objective of this study was to compare serum androgen levels during COH utilizing either agonists or antagonists. Material/Methods: Fifteen egg donors aged 24 to 31 underwent standard COH utilizing either an agonist, luperolide acetate (LA) (group I, n ⫽ 6), or an antagonist, ganirelix acetate (GA) (group II, n ⫽ 9). All subjects received a 30-g ethinyl estradiol/0.15-mg desogestrel OC starting in early follicular phase. In group I, LA 1.0 mg was given daily for 2 weeks, then decreased to 0.5 mg when recombinant FSH stimulation was initiated. In group II, stimulation was started 4 days after discontinuing OCs. GA 0.25 mg was added when the lead follicle reached 14 mm. HCG was administered when ⱖ2 follicles reached 18 mm. Specific immunoassays were used to measure testosterone (T), androstenedione (A), DHT, 3␣-diol G, DHEAS, and SHBG. Results: All androgen levels increased during COH. Free T, and A levels were significantly higher than baseline during COH for both antagonist and agonist-suppressed cycles. DHEAS was higher than baseline in all cycles, and reached statistical significance in the antagonist group (p ⬍ 0.05). SHBG levels were significantly lower during stimulation than at baseline. There was no significant difference in androgen levels between antagonist and agonist-suppressed cycles, at baseline or any subsequent cycle days.
Vol. 77, No. 4, Suppl. 3, April 2002
Table 1: Serial E2 (pg/ml) Values (Mean ⫾ S.D.)
Reduction of postoperative adhesions by N,O-carboxymethylchitosan (NOCC): a pilot study. M. P. Diamond, A. Luciano, D. A. Johns, R. Dunn, P. Young, E. Bieber. Detroit, MI, New Britain, CT, Fort Worth, TX, Houston, TX, San Diego, CA, Danville, PA. Oral presentation preferred. Introduction: Studies demonstrated the ability of NOCC to markedly reduce postoperative adhesions in diverse animal models, thus this pilot study was undertaken to examine the safety and efficacy of NOCC in reducing adhesions. Methods: A multi-center, randomized, placebo controlled trial was conducted comparing NOCC and Ringers lactate. Application took place at the conclusion of the initial surgical procedure. Adhesion reduction was assessed by blinded reviewers at a second-look laparoscopy. NOCC was applied as 200 cc of a 1% NOCC gel which was tamped in place followed by 100 cc of 2% NOCC solution. Efficacy was assessed by covariate analysis. Results: 34 subjects were enrolled; 17 in each group were available for safety analysis and 16 for efficacy analysis. There were no differences between the groups in subject age, racial distribution, height, weight or BMI. There were no deaths or serious adverse events attributable to NOCC, and no adverse events related or probably related to NOCC. Adhesion reformation occurred at 61% of sites in control subjects and 37% in NOCC subjects. Subgroup analysis showed an incidence of adhesion reformation in the control subjects of 84% vs. 34% in the NOCC subjects. Thus, adhesion reformation in the control subgroup was 146% above the rate in the NOCC subjects. In these same subgroups, de novo 1a and 1b adhesions occurred more commonly at sites in control than in NOCC subjects (0.14 vs. 0.05 and 0.19 vs. 0.13, respectively). Considering all subjects, adhesion extent and severity at second look were also less in NOCC subjects. Summary: In summary, these findings demonstrate that laparoscopic NOCC gel and solution intraperitoneal use appears to be safe, as assessed by adverse event review, vital signs, physical examination, and serum chemistries. Despite the small sample size, strong trends were identified for reduction of occurrence, extent, and severity of adhesion reformation and de novo adhesion formation. (Sponsored by Chitogenics, Inc, Morristown, NJ.)
Day-6
Day-5
Day-4
Day-2
Day 0ˆ
Antagonist 439 ⫾ 231 772 ⫾ 326 973 ⫾ 328 1736 ⫾ 894 788 ⫾ 248 (N ⫽ 10) Agonist 230 ⫾ 84 654 ⫾ 294 1203 ⫾ 372 2671 ⫾ 1169 1162 ⫾ 545 (N ⫽ 5) * P ⫽ ⬎.05.
ˆDay 0 ⫽ Day of Oocyte Retrieval.
Table 2: Serial P (ng/ml) Values (Mean ⫾ S.D.)
Antagonist (N ⫽ 10) Agonist (N ⫽ 5)
Day-6
Day-5
Day-4
Day-2
Day 0ˆ
0.6 ⫾ .2
0.8 ⫾ .3
0.8 ⫾ .3
1.4 ⫾ .5
10.5 ⫾ 4.2
0.6 ⫾ .3
0.9 ⫾ .3
1.5 ⫾ .8
1.9 ⫾ .8
13.3 ⫾ 8.0
* P ⫽ ⬍.05.
ˆDay 0 ⫽ Day of Oocyte Retrieval.
Table 3: Histological Dating (Post-Ovulatory Day) by Endometrial Biopsy (Mean ⫾ S.D.)
Antagonist (N ⫽ 10) Agonist (N ⫽ 5) * P ⫽ ⬍.05.
Day 0ˆ
Day 7
5.8 ⫾ 2.1 days 5.9 ⫾ 1.3 days
9.5 ⫾ 1.6 10.5 ⫾ 1.9
ˆDay 0 ⫽ Day of Oocyte Retrieval.
Conclusion: All subjects undergoing C.O.H. with GnRH analogs have elevated P levels in the late follicular phase and accelerated endometrial maturation in the subsequent luteal phase. The advanced endometrial histology is most pronounced at the time of oocyte retrieval, but is still present at the time of implantation. There is no significant difference between pre-retrieval serial progesterone values and endometrial histology between cycles utilizing GnRH agonists and antagonists.
O-13 O-12 Accelerated endometrial maturation in the luteal phase of cycles utilizing controlled ovarian hyperstimulation: impact of GnRH agonist vs. antagonist. R. Boostanfar, C. Slater, S. Klumph, P. Saadat, D. Tourgeman, R. J. Paulson. Dept. of OB/GYN, Division of Reproductive Endocrinology and Infertility, University of Southern California Keck School of Medicine, Los Angeles, CA. Background: It has been previously reported that advanced endometrial maturation occurs during the luteal phase of cycles utilizing controlled ovarian hyperstimulation (C.O.H.). GnRH antagonists have been recently used as an alternative to agonists for ovulation suppression during C.O.H. The impact of C.O.H. utilizing GnRH antagonists on endometrial maturation is unknown. Purpose: To prospectively measure ovarian steroid production in the late follicular phase and its effects on endometrial histomorphology during the subsequent luteal phase among subjects undergoing C.O.H. with either a GnRH agonist or antagonist. Methods: Fifteen oocyte donors undergoing standard C.O.H. were enrolled. Subjects were assigned to two study groups. One group (n ⫽ 10) received one of two GnRH antagonists (Cetrotide威 or Antagon威) and the other group (n ⫽ 5) a GnRH agonist (Lupron威). Serum estradiol (E2) and progesterone (P) levels were obtained throughout ovarian stimulation. Endometrial biopsy was obtained at the time of oocyte retrieval and again 7 days later. Results: The following data are standardized to day of aspiration (Day ⫽ 0).
S10
PCRS Abstracts
Ovarian and adrenal androgen profiles in cycles of controlled ovarian hyperstimulation utilizing GnRH antagonists or agonists. E. Mor, P. Saadat, C. Zhang, F. Z. Stanczyk, C. C. Slater, J. Jain, D. Tourgeman, R. J. Paulson. Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, CA. Introduction: Recent reports have suggested trends towards lower pregnancy rates in in vitro fertilization (IVF) cycles utilizing GnRH antagonists, as compared to agonists. One possible explanation may be higher androgen levels reached in cycles using antagonists, which could affect folliculogenesis and endometrial receptivity. The objective of this study was to compare serum androgen levels during COH utilizing either agonists or antagonists. Material/Methods: Fifteen egg donors aged 24 to 31 underwent standard COH utilizing either an agonist, luperolide acetate (LA) (group I, n ⫽ 6), or an antagonist, ganirelix acetate (GA) (group II, n ⫽ 9). All subjects received a 30-g ethinyl estradiol/0.15-mg desogestrel OC starting in early follicular phase. In group I, LA 1.0 mg was given daily for 2 weeks, then decreased to 0.5 mg when recombinant FSH stimulation was initiated. In group II, stimulation was started 4 days after discontinuing OCs. GA 0.25 mg was added when the lead follicle reached 14 mm. HCG was administered when ⱖ2 follicles reached 18 mm. Specific immunoassays were used to measure testosterone (T), androstenedione (A), DHT, 3␣-diol G, DHEAS, and SHBG. Results: All androgen levels increased during COH. Free T, and A levels were significantly higher than baseline during COH for both antagonist and agonist-suppressed cycles. DHEAS was higher than baseline in all cycles, and reached statistical significance in the antagonist group (p ⬍ 0.05). SHBG levels were significantly lower during stimulation than at baseline. There was no significant difference in androgen levels between antagonist and agonist-suppressed cycles, at baseline or any subsequent cycle days.
Vol. 77, No. 4, Suppl. 3, April 2002