- Email: [email protected]
Luteal GnRH-Antagonist Suppression Prior to Gonadotropin Stimulation: A Promising Novel Method for Patients with Persistent Elevation in the Serum Levels of Follicle Stimulating Hormone (FSH)
IVF-ET. In patients having multiple prior surgeries for severe pelvic endometriosis, additional surgeries prior to IVF-ET may add significant risks and cost. Objective: The purpose of this study is to evaluate whether TVS-A/S of large or multiple OE prior to COH for IVF-ET may be used safely to improve pregnancy outcomes. Materials and Methods: This retrospective study evaluated patients diagnosed with recurrent OE following 1-4 (mean 2.68) surgeries for Stage IV endometriosis from 2/05-7/08. TVS-A/S was performed in the clinic setting under conscious sedation using a 14g Cook echotip needle. Following aspiration, Erythromycin 500 mg (Doxycycline in cases of allergy) in D5W containing 1% lidocaine was used for sclerosis of OE. OE size, number, patient tolerability, side effects, and subsequent COH and IVF-ET outcomes were compared for each patient using Student’s t-tests. Results: 20 patients, age 25-44 (mean 37.8 yrs.) with 1-3 (mean 2.4) OE measuring 13-68 mm. (mean 38 mm.) underwent TVS-A/S. 13 patients underwent COH for IVF-ET using luteal phase GnRHa and 225u of HMG b.i.d. until HCG administered for >3 follicles >17 mm 53.8% of patients had endometriosis noted at follicular aspiration, with OE of 10-24 mm for an average reduction size of OE of 32.6 mm (P<.001). 3-14 (mean 7.46) oocytes were retrieved with an overall fertilization rate of 59.6% (range 0%100%). 12/13 cases resulted in ET of 2-4 (mean 3.5) embryos for an overall clinical pregnancy rate of 50%. 3 cases yielded sufficient embryos for cryopreservation. No patient experienced major complications from TVS-A/S or IVF-ET, however 3 patients (15%) required a return clinic visit for additional analgesia within 24 hours of TVS-A/S. Conclusions: TVS-A/S of OE appears to be safe and effective in reducing OE volume prior to IVF-ET and may maintain pregnancy rates in poor prognosis patients while avoiding the risks of further surgical intervention.
P-16 Luteal GnRH-Antagonist Suppression Prior to Gonadotropin Stimulation: A Promising Novel Method for Patients with Persistent Elevation in the Serum Levels of Follicle Stimulating Hormone (FSH). Z.R. Hubayter, H. Zacur, L. Kolp, J. Garcia. Department of Gynecology and Obstetrics, The Howard and Georgeana Jones Service, The Johns Hopkins Medical Institutions, Baltimore, MD. Background: Patients with repetitive elevation in baseline FSH (>10 mIU/ mL) are unlikely to conceive with in vitro fertilization (IVF) if performed during that cycle. These women are typically refused treatment in many fertility centers or are referred to egg donation. Objective: To determine the IVF outcomes in a novel approach for luteal suppression in women with persistently elevated baseline FSH. Materials and Methods: Retrospective review revealed 54 patients with persistently elevated FSH and who underwent 78 IVF cycles from 2004 through 2008 using this novel approach. Persistent elevation of the FSH was defined as FSH > 10 mIU/mL on at least two separate occasions on cycle day (CD) 2. These patients were pretreated with a single dose of Cetrorelix acetate (3 mg SC) ten days after ovulation for luteal suppression. Upon onset of menses, ovarian stimulation was initiated with gonadotropins. Ganirelix acetate was added on stimulated CD6. The IVF outcomes were collected and compared to historical controls (17 cycles with elevated baseline FSH, similar stimulation protocol, but No GnRH-antagonist luteal suppression). Statistical analysis was performed using SAS version 9.0 (Cary, NC). Pearson coefficient was used for correlation analysis. P<0.05 was considered statistically significant. Results: The mean age of participants was 37.6 3.5 years. The mean CD2 FSH was 13.7 3.7 IU/L (FSHmax ¼ 30 IU/L). Following luteal GnRH-antagonist administration, mean FSH dropped to 6.6 2.5 IU/L. The mean number of total oocytes and embryos obtained were 5.5 3.6 and 3.2 2.7, respectively. Patients had a mean of 12 stimulation days and required an average of 46 and 23 ampoules of rFSH and urinary menotropins, respectively. The pregnancy rate was 23.1% with an average embryo transfer of 2 per cycle. The ongoing pregnancy rate was 14.1% while the implantation rate was 9.2%. These values were higher than the rates observed in the historical control group (No pregnancies in 17 cycles). Patients whose embryos were obtained through ICSI appeared to have a better pregnancy outcome with this protocol (r¼0.3, P¼.0.008). Prior IVF outcomes did not correlate with future successes with this method. Conclusions: GnRH-antagonist administered in the late luteal phase prior to ovarian stimulation yields a favorable outcome in women with persistent elevation of baseline FSH. Poor responders defined by baseline FSH > 10 mIU/mL and who would frequently be denied access to treatment with IVF, may benefit from this novel method.
FERTILITY & STERILITYÒ
P-17 Follicular Phase Serum Hormone Concentrations in Cryopreserved Embryo Transfer Cycles: Is There a Minimum Threshold Level for a Successful Pregnancy?. Z. Hubayter, N. Evangelopoulos, J. Garcia, L. Kolp. Johns Hopkins Medical Institution, Lutherville, MD. Background: Cryopreservation of supernumerary embryos has been successful for almost three decades. Thawed embryos can be transferred in subsequent artificial or natural cycle. In a study by Venners et al, higher follicular phase estrogen metabolites concentration was associated with higher probability of achieving a clinical pregnancy in normally cycling women (Venners, Hum Reprod, 2006; 2272-2280). This interesting finding may apply to cryopreserved embryo transfer cycles since the follicular phase in such cycles is relatively similar to the follicular phase in normal menstrual cycles. Objective: Our objective is to assess whether follicular phase serum hormonal concentrations are correlated with pregnancy outcomes in cryopreserved cycles. Materials and Methods: Retrospective analysis in a university affiliated academic institution. We reviewed all patients undergoing cryopreserved embryo transfers between January 2005 and January 2007. We evaluated the serum estradiol, luteal hormone, and progesterone concentration prior to ovulation. In Venners’ study, higher follicular estradiol was more predictive of favorable pregnancy outcome. As such, we recorded the maximum estradiol concentration achieved in these cycles, during the 3 days preceding ovulation. Furthermore, we recorded the endometrial thickness with transvaginal sonogram. Statistical analysis was performed with SAS version 9.0 (Cary, NC). Student-t test and the Pearson Correlation analysis were performed. Results: A total of 126 frozen embryo cycles were evaluated. The clinical pregnancy rates were similar among the different groups of cryopreserved embryo transfers (natural (31%) vs. stimulated with estradiol (27%)). Furthermore there was no correlation between the pre-ovulatory estradiol concentration and pregnancy outcome. The mean maximum follicular estradiol level reached was 221 pg/ml in women who ultimately conceived (vs. 237 in non-pregnant, P¼0.6). Furthermore, women with the maximum follicular estradiol level as low as 61 pg/ml or as high as 433 pg/ml were able to achieve a successful pregnancy. Similarly, pre-ovulatory follicular serum Progesterone and LH concentrations were not predictive of outcomes. Estradiol levels were not correlated to the endometrial thickness. Moreover, the latter did not correlate with pregnancy outcomes. Conclusions: Our data demonstrate that neither supraphysiologic nor low estradiol level is correlated with outcomes in cryopreserved embryo transfer cycles. The measurements of serum hormonal concentrations in such cycles are not warranted to determine the probability of a successful outcome, and should not be relied upon to defer embryo transfer to a subsequent cycle.
P-18 Zygote Intrafallopian Transfer (ZIFT): A Viable Option for Women of Advanced Maternal Age. J.K. Jain, L. Meng. Santa Monica Fertility Specialists, Santa Monica, CA. Background: Recurrent implantation failure and spontaneous abortion are more prevalent in women of advanced maternal age (AMA) primarily due to increased rates of gamete and embryonic aneuploidy. Murine models demonstrate lower live birth rates from in-vitro cultured embryos versus those developed in-vivo. It follows that in-vitro culture may contribute to abnormal human embryonic development leading to implantation failure. Zygote Intrafallopian Transfer (ZIFT) may improve implantation rates by providing optimal conditions for early embryonic development. Objective: To determine whether ZIFT improves implantation rate in patients of AMA who previously failed traditional in-vitro fertilizationembryo transfer (IVF-ET). Materials and Methods: All patients R36 years of age at the time of their first IVF-ET, who failed to achieve a clinical pregnancy and subsequently underwent a ZIFT procedure over a four year period from 2004-2008 were included. Cycles involving egg donation and frozen embryos were excluded. The primary endpoint of the study was implantation rate. Results: Seven patients who underwent 10 IVF-ET cycles (mean 1.4 failed IVF-ET cycles) and nine ZIFT cycles were included in the analysis. The mean age at the time of the first IVF-ET was 39.0 1.2 (36-43) and at the time of the first ZIFT 39.7 1.1 (36-43) (P>0.05). A total of 39 embryos (mean 3.9 0.5 embryos per ET, range 1-6) were transferred in the IVF-ET group versus 43 zygotes (mean 4.8 0.3) zygotes per ZIFT, range 3-6) in the
S15
P-16 Luteal GnRH-Antagonist Suppression Prior to Gonadotropin Stimulation: A Promising Novel Method for Patients with Persistent Elevation in the Serum Levels of Follicle Stimulating Hormone (FSH). Z.R. Hubayter, H. Zacur, L. Kolp, J. Garcia. Department of Gynecology and Obstetrics, The Howard and Georgeana Jones Service, The Johns Hopkins Medical Institutions, Baltimore, MD. Background: Patients with repetitive elevation in baseline FSH (>10 mIU/ mL) are unlikely to conceive with in vitro fertilization (IVF) if performed during that cycle. These women are typically refused treatment in many fertility centers or are referred to egg donation. Objective: To determine the IVF outcomes in a novel approach for luteal suppression in women with persistently elevated baseline FSH. Materials and Methods: Retrospective review revealed 54 patients with persistently elevated FSH and who underwent 78 IVF cycles from 2004 through 2008 using this novel approach. Persistent elevation of the FSH was defined as FSH > 10 mIU/mL on at least two separate occasions on cycle day (CD) 2. These patients were pretreated with a single dose of Cetrorelix acetate (3 mg SC) ten days after ovulation for luteal suppression. Upon onset of menses, ovarian stimulation was initiated with gonadotropins. Ganirelix acetate was added on stimulated CD6. The IVF outcomes were collected and compared to historical controls (17 cycles with elevated baseline FSH, similar stimulation protocol, but No GnRH-antagonist luteal suppression). Statistical analysis was performed using SAS version 9.0 (Cary, NC). Pearson coefficient was used for correlation analysis. P<0.05 was considered statistically significant. Results: The mean age of participants was 37.6 3.5 years. The mean CD2 FSH was 13.7 3.7 IU/L (FSHmax ¼ 30 IU/L). Following luteal GnRH-antagonist administration, mean FSH dropped to 6.6 2.5 IU/L. The mean number of total oocytes and embryos obtained were 5.5 3.6 and 3.2 2.7, respectively. Patients had a mean of 12 stimulation days and required an average of 46 and 23 ampoules of rFSH and urinary menotropins, respectively. The pregnancy rate was 23.1% with an average embryo transfer of 2 per cycle. The ongoing pregnancy rate was 14.1% while the implantation rate was 9.2%. These values were higher than the rates observed in the historical control group (No pregnancies in 17 cycles). Patients whose embryos were obtained through ICSI appeared to have a better pregnancy outcome with this protocol (r¼0.3, P¼.0.008). Prior IVF outcomes did not correlate with future successes with this method. Conclusions: GnRH-antagonist administered in the late luteal phase prior to ovarian stimulation yields a favorable outcome in women with persistent elevation of baseline FSH. Poor responders defined by baseline FSH > 10 mIU/mL and who would frequently be denied access to treatment with IVF, may benefit from this novel method.
FERTILITY & STERILITYÒ
P-17 Follicular Phase Serum Hormone Concentrations in Cryopreserved Embryo Transfer Cycles: Is There a Minimum Threshold Level for a Successful Pregnancy?. Z. Hubayter, N. Evangelopoulos, J. Garcia, L. Kolp. Johns Hopkins Medical Institution, Lutherville, MD. Background: Cryopreservation of supernumerary embryos has been successful for almost three decades. Thawed embryos can be transferred in subsequent artificial or natural cycle. In a study by Venners et al, higher follicular phase estrogen metabolites concentration was associated with higher probability of achieving a clinical pregnancy in normally cycling women (Venners, Hum Reprod, 2006; 2272-2280). This interesting finding may apply to cryopreserved embryo transfer cycles since the follicular phase in such cycles is relatively similar to the follicular phase in normal menstrual cycles. Objective: Our objective is to assess whether follicular phase serum hormonal concentrations are correlated with pregnancy outcomes in cryopreserved cycles. Materials and Methods: Retrospective analysis in a university affiliated academic institution. We reviewed all patients undergoing cryopreserved embryo transfers between January 2005 and January 2007. We evaluated the serum estradiol, luteal hormone, and progesterone concentration prior to ovulation. In Venners’ study, higher follicular estradiol was more predictive of favorable pregnancy outcome. As such, we recorded the maximum estradiol concentration achieved in these cycles, during the 3 days preceding ovulation. Furthermore, we recorded the endometrial thickness with transvaginal sonogram. Statistical analysis was performed with SAS version 9.0 (Cary, NC). Student-t test and the Pearson Correlation analysis were performed. Results: A total of 126 frozen embryo cycles were evaluated. The clinical pregnancy rates were similar among the different groups of cryopreserved embryo transfers (natural (31%) vs. stimulated with estradiol (27%)). Furthermore there was no correlation between the pre-ovulatory estradiol concentration and pregnancy outcome. The mean maximum follicular estradiol level reached was 221 pg/ml in women who ultimately conceived (vs. 237 in non-pregnant, P¼0.6). Furthermore, women with the maximum follicular estradiol level as low as 61 pg/ml or as high as 433 pg/ml were able to achieve a successful pregnancy. Similarly, pre-ovulatory follicular serum Progesterone and LH concentrations were not predictive of outcomes. Estradiol levels were not correlated to the endometrial thickness. Moreover, the latter did not correlate with pregnancy outcomes. Conclusions: Our data demonstrate that neither supraphysiologic nor low estradiol level is correlated with outcomes in cryopreserved embryo transfer cycles. The measurements of serum hormonal concentrations in such cycles are not warranted to determine the probability of a successful outcome, and should not be relied upon to defer embryo transfer to a subsequent cycle.
P-18 Zygote Intrafallopian Transfer (ZIFT): A Viable Option for Women of Advanced Maternal Age. J.K. Jain, L. Meng. Santa Monica Fertility Specialists, Santa Monica, CA. Background: Recurrent implantation failure and spontaneous abortion are more prevalent in women of advanced maternal age (AMA) primarily due to increased rates of gamete and embryonic aneuploidy. Murine models demonstrate lower live birth rates from in-vitro cultured embryos versus those developed in-vivo. It follows that in-vitro culture may contribute to abnormal human embryonic development leading to implantation failure. Zygote Intrafallopian Transfer (ZIFT) may improve implantation rates by providing optimal conditions for early embryonic development. Objective: To determine whether ZIFT improves implantation rate in patients of AMA who previously failed traditional in-vitro fertilizationembryo transfer (IVF-ET). Materials and Methods: All patients R36 years of age at the time of their first IVF-ET, who failed to achieve a clinical pregnancy and subsequently underwent a ZIFT procedure over a four year period from 2004-2008 were included. Cycles involving egg donation and frozen embryos were excluded. The primary endpoint of the study was implantation rate. Results: Seven patients who underwent 10 IVF-ET cycles (mean 1.4 failed IVF-ET cycles) and nine ZIFT cycles were included in the analysis. The mean age at the time of the first IVF-ET was 39.0 1.2 (36-43) and at the time of the first ZIFT 39.7 1.1 (36-43) (P>0.05). A total of 39 embryos (mean 3.9 0.5 embryos per ET, range 1-6) were transferred in the IVF-ET group versus 43 zygotes (mean 4.8 0.3) zygotes per ZIFT, range 3-6) in the
S15