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O-2 Minimal stimulation IVF using clomiphene citrate (CC) and oral contraceptive pill (OC) pretreatment for LH suppression
ORAL
PRESENTATIONS
o-1 A Randomized Trial Comparing Clomiphen Citrate With Tamoxifen for Ovulation Induction in Obese Anovulatory Women. R. Boostanfar, J.K, Jain, R.J. Paulson, D.R. Mishell, Jr., Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, CA. Introduction: Tamoxifen (TMX) has been shown to be efficacious for the induction of ovulation in anovulatory women who had previously failed to ovulate with clomiphen citrate (CC) To date, there have been no studies to investigate the use of TMX in obese anovulatory women. Purpose: To evaluate the rates of ovulation and pregnancy in a cohort of obese anovulatory women with infertility in a prospective randomized trial. Methods: From August 1997 to October 1998, 47 obese anovulatory women with no other causes of infertility, a mean of 3.54 ? 2.56 years of infertility, a mean age of 25.7 (2 4.38) years, and no prior use of ovulation induction medication were enrolled. The BMI of the CC group was 3 1.44 -C 6.80 and the BMI of the TMX group was 29.99 ? 5.47 (P>.O5). Subjects were randomized to receive either 50 mg of CC or 20 mg of TMX 5-9 days after the onset of a progesterone induced withdrawal bleed. Subjects were monitored for ovulation by obtaining serum progesterone on cycle day 23 and were monitored for pregnancy by measurement of HCG. If ovulation, as defined by a mid-luteal progesterone level >3.0 ng/mL, failed to occur with the initial dose of either drug, then the dose of that drug was sequentially increased. The daily dose of CC was increased to 100 mg and then 150 mg, and the dose of TMX was increased to 40 mg and then 60 mg. A total of 59 evaluable TMX cycles and 53 CC cycles were available for interpretation. Results: The overall presumptive rate of ovulation in the TMX group was 28159 (47.5%) and in the CC group and was 22153 (41.5%) in the CC group. The ovulatory rate per cycle in subjects who received 20 mg of TMX was 43.2% and in subjects who received 50 mg of CC was 46.7%. Ovulatory rates per cycle with 40 mg of TMX and 100 mg of CC were 26.7% and 26.4%. With the use of 60 mg of TMX or 150 mg of CC, the ovulatory rate was 28.6% in each group. Four subjects (16.7%) who received TMX failed to ovulate with 60 mg, and 5 (21.7%) subjects who received CC did not ovulate with 150 mg. There were 3 pregnancies in the TMX group and 2 pregnancies in the CC group. The cumulative TMX pregnancy rate was 10.7% per ovulatory cycle, and the cumulative CC pregnancy rate per ovulatory cycle was 11 .O%. Conclusions: In a cohort of obese anovulatory women, the ovulation and pregnancy rates are similar with CC and TMX and are lower than those previously reported in nonobese patients. PI1 SOOl5-0282(99)00020-5
o-2 Minimal Stimulation IVF Using Clomiphene Oral Contraceptive Pill (OC) Pretreatment sion. E.F. Branigan, M.A. Estes. Bellingham WA.
Citrate (CC) and for LH SuppresIVF, Bellingham,
Controlled ovarian hyperstimulation is used in most IVF cycles to increase the number of oocytes and embryos available and to achieve the highest pregnancy rates (PR). Cycle costs, multiple gestation, and ovarian hyperstimulation syndrome risks are also FERTILITY
& STERILITY@
increased. Unstimulated IVF offers a lower cost and lower risk alternative. However, PRs are significantly lower and cycles are difficult to monitor because the LH surge is not suppressed. The ob,jective of this study was to determine if OC suppression of the ovarian axis prior to minimal (CC) ovarian stimulation IVF would make the procedure easier to perform by preventing the LH surge and result in increased oocytes, embryos, and PR compared to unstimulated IVF. Thirty-six women under the age of 40 with partners who did not have male factor problems were placed on OCs for 35-42 days before starting CC 100 mg for 7 days. Daily ultrasound, estradiols, and twice-daily serum LH levels were performed after 5 days of stimulation. HCG was given when at least two follicles had mean diameters of 18 mm and sonographic follicle aspiration was performed 34 hours later. The 36 women underwent 71 cycles with 7 canceled for a single dominant follicle (10%). There were no LH surges recorded and mean LH levels were 3.5 i: 1.5. Sixty-four cycles had follicle aspiration with a mean 3.2 + 1.1 mature oocytes (M-II) retrieved and a range of l-8. Fertilization rale was 90% and a mean of 2.8 ? 0.6 embryos were transferred per relrieval. Twenty-one of the 64 cycles resulted in a clinical pregnancy (fetal heartbeat at 7 week gestation ultrasound) for a 32.8% PR per retrieval. There were two other biochemical pregnancies and 3 twin gestations. We conclude that OC pre-treatment effectively suppresses LH surges that allows multiple mature oocyte development with CC ovarian stimulation. This results in a multiple embryo transfer that markedly improves PR compared to unstimulated IVF. It provides a lower cost and lower risk alternative to controlled ovarian hyperstimulation IVF without sacrificing pregnancy rate. PI1 SOOl5-0282(99)00021-7
o-3 Single Sperm Freezing in Evacuated Mouse Zona Pellucidae: Comparative Trial on Zona Preparation and Sperm Isolation Procedures. M.C. Schiewe, Y. Han, R.P. Marrs. California Fertility Associates/Institute for Fertility Research, Santa Monica, CA. The experimental aim of this project was to address several technical questions involved in single sperm freezing to optimize future clinical application. In a preliminary study, we determined that both an ICSI-type or laser zona drilling-type procedure could be used to evacuate the cellular contents of freshly collected mouse eggs/zygotes, however the ICSI-type approach was more effective at retaining injected sperm due to the random loss of highly motile sperm through the ZP hole post-laser zona drilling (LZD). In Study 1, using a 3x2 factorial arrangement of treatments, we evaluated the efficiency of inserting different numbers of sperm/ZP (1-3sp, 4-6sp, 7- 1Osp; in 10% PVP solution) and recovering motile sperm by ICSI pipette extraction or LZD swim-out. The LZD procedure involved the use of a 1.48 nm laser diode attached to an IVF workstation (Cell Robotics, Albuquerque, NM) to drill a 1Opm diameter oblong hole in individual mouse ZP containing fresh, motile sperm. All ZPs were maintained in an ICSI dish (FalconTM 1006) in microdroplets of mHTF + 10% SSS under oil and assessed for sperm viability and recovery of motile sperm external to the ZP. In Study 2. after injecting normal motile sperm (1, 3 or 5/ZP) in mHTF with 10% PVP or no PVP, we assessed the sperm motility and structural morphology (normal, bent neck, damaged tail) post-injection and recovery (3x2 factorial design). In Study 1, no difference in sperm loss during injection occurred when injecting 1-3s~ (O/32), 4-6s~ (4/82), or 7-10s~ (12/148)/ZP. There was no difference in the recovery of motile sperm (100%) using ICSI or LZD treatments after injecting 1-3s~. Sperm survival and recovery decreased (P
PRESENTATIONS
o-1 A Randomized Trial Comparing Clomiphen Citrate With Tamoxifen for Ovulation Induction in Obese Anovulatory Women. R. Boostanfar, J.K, Jain, R.J. Paulson, D.R. Mishell, Jr., Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, CA. Introduction: Tamoxifen (TMX) has been shown to be efficacious for the induction of ovulation in anovulatory women who had previously failed to ovulate with clomiphen citrate (CC) To date, there have been no studies to investigate the use of TMX in obese anovulatory women. Purpose: To evaluate the rates of ovulation and pregnancy in a cohort of obese anovulatory women with infertility in a prospective randomized trial. Methods: From August 1997 to October 1998, 47 obese anovulatory women with no other causes of infertility, a mean of 3.54 ? 2.56 years of infertility, a mean age of 25.7 (2 4.38) years, and no prior use of ovulation induction medication were enrolled. The BMI of the CC group was 3 1.44 -C 6.80 and the BMI of the TMX group was 29.99 ? 5.47 (P>.O5). Subjects were randomized to receive either 50 mg of CC or 20 mg of TMX 5-9 days after the onset of a progesterone induced withdrawal bleed. Subjects were monitored for ovulation by obtaining serum progesterone on cycle day 23 and were monitored for pregnancy by measurement of HCG. If ovulation, as defined by a mid-luteal progesterone level >3.0 ng/mL, failed to occur with the initial dose of either drug, then the dose of that drug was sequentially increased. The daily dose of CC was increased to 100 mg and then 150 mg, and the dose of TMX was increased to 40 mg and then 60 mg. A total of 59 evaluable TMX cycles and 53 CC cycles were available for interpretation. Results: The overall presumptive rate of ovulation in the TMX group was 28159 (47.5%) and in the CC group and was 22153 (41.5%) in the CC group. The ovulatory rate per cycle in subjects who received 20 mg of TMX was 43.2% and in subjects who received 50 mg of CC was 46.7%. Ovulatory rates per cycle with 40 mg of TMX and 100 mg of CC were 26.7% and 26.4%. With the use of 60 mg of TMX or 150 mg of CC, the ovulatory rate was 28.6% in each group. Four subjects (16.7%) who received TMX failed to ovulate with 60 mg, and 5 (21.7%) subjects who received CC did not ovulate with 150 mg. There were 3 pregnancies in the TMX group and 2 pregnancies in the CC group. The cumulative TMX pregnancy rate was 10.7% per ovulatory cycle, and the cumulative CC pregnancy rate per ovulatory cycle was 11 .O%. Conclusions: In a cohort of obese anovulatory women, the ovulation and pregnancy rates are similar with CC and TMX and are lower than those previously reported in nonobese patients. PI1 SOOl5-0282(99)00020-5
o-2 Minimal Stimulation IVF Using Clomiphene Oral Contraceptive Pill (OC) Pretreatment sion. E.F. Branigan, M.A. Estes. Bellingham WA.
Citrate (CC) and for LH SuppresIVF, Bellingham,
Controlled ovarian hyperstimulation is used in most IVF cycles to increase the number of oocytes and embryos available and to achieve the highest pregnancy rates (PR). Cycle costs, multiple gestation, and ovarian hyperstimulation syndrome risks are also FERTILITY
& STERILITY@
increased. Unstimulated IVF offers a lower cost and lower risk alternative. However, PRs are significantly lower and cycles are difficult to monitor because the LH surge is not suppressed. The ob,jective of this study was to determine if OC suppression of the ovarian axis prior to minimal (CC) ovarian stimulation IVF would make the procedure easier to perform by preventing the LH surge and result in increased oocytes, embryos, and PR compared to unstimulated IVF. Thirty-six women under the age of 40 with partners who did not have male factor problems were placed on OCs for 35-42 days before starting CC 100 mg for 7 days. Daily ultrasound, estradiols, and twice-daily serum LH levels were performed after 5 days of stimulation. HCG was given when at least two follicles had mean diameters of 18 mm and sonographic follicle aspiration was performed 34 hours later. The 36 women underwent 71 cycles with 7 canceled for a single dominant follicle (10%). There were no LH surges recorded and mean LH levels were 3.5 i: 1.5. Sixty-four cycles had follicle aspiration with a mean 3.2 + 1.1 mature oocytes (M-II) retrieved and a range of l-8. Fertilization rale was 90% and a mean of 2.8 ? 0.6 embryos were transferred per relrieval. Twenty-one of the 64 cycles resulted in a clinical pregnancy (fetal heartbeat at 7 week gestation ultrasound) for a 32.8% PR per retrieval. There were two other biochemical pregnancies and 3 twin gestations. We conclude that OC pre-treatment effectively suppresses LH surges that allows multiple mature oocyte development with CC ovarian stimulation. This results in a multiple embryo transfer that markedly improves PR compared to unstimulated IVF. It provides a lower cost and lower risk alternative to controlled ovarian hyperstimulation IVF without sacrificing pregnancy rate. PI1 SOOl5-0282(99)00021-7
o-3 Single Sperm Freezing in Evacuated Mouse Zona Pellucidae: Comparative Trial on Zona Preparation and Sperm Isolation Procedures. M.C. Schiewe, Y. Han, R.P. Marrs. California Fertility Associates/Institute for Fertility Research, Santa Monica, CA. The experimental aim of this project was to address several technical questions involved in single sperm freezing to optimize future clinical application. In a preliminary study, we determined that both an ICSI-type or laser zona drilling-type procedure could be used to evacuate the cellular contents of freshly collected mouse eggs/zygotes, however the ICSI-type approach was more effective at retaining injected sperm due to the random loss of highly motile sperm through the ZP hole post-laser zona drilling (LZD). In Study 1, using a 3x2 factorial arrangement of treatments, we evaluated the efficiency of inserting different numbers of sperm/ZP (1-3sp, 4-6sp, 7- 1Osp; in 10% PVP solution) and recovering motile sperm by ICSI pipette extraction or LZD swim-out. The LZD procedure involved the use of a 1.48 nm laser diode attached to an IVF workstation (Cell Robotics, Albuquerque, NM) to drill a 1Opm diameter oblong hole in individual mouse ZP containing fresh, motile sperm. All ZPs were maintained in an ICSI dish (FalconTM 1006) in microdroplets of mHTF + 10% SSS under oil and assessed for sperm viability and recovery of motile sperm external to the ZP. In Study 2. after injecting normal motile sperm (1, 3 or 5/ZP) in mHTF with 10% PVP or no PVP, we assessed the sperm motility and structural morphology (normal, bent neck, damaged tail) post-injection and recovery (3x2 factorial design). In Study 1, no difference in sperm loss during injection occurred when injecting 1-3s~ (O/32), 4-6s~ (4/82), or 7-10s~ (12/148)/ZP. There was no difference in the recovery of motile sperm (100%) using ICSI or LZD treatments after injecting 1-3s~. Sperm survival and recovery decreased (P