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Preliminary study on the use of gonadotropin releasing hormone (GnRH) antagonist for premature LH surges in GnRH agonist downregulated IVF cycles.
Objective: To determine if reflux of culture media during cervical irrigation at the time of embryo transfer (ET) in patients undergoing in vitro fertilization (IVF) has any effect on pregnancy rates. Design: Prospective, comparative. Materials/Methods: Patients undergoing IVF who were ⬍40 years of age and underwent an ET on either Day 3 or Day 5 were studied. Preparation involved irrigation of the endocervical canal with culture media. The outer sheath of a coaxial transfer catheter was placed at the endocervical canal and connected to a 5 cc syringe. The canal was irrigated using gentle thumb pressure. Upon withdrawing the catheter, excess media and cervical mucus was aspirated. During irrigation, the intrauterine cavity was observed with transabdominal ultrasound to assess if there was reflux of media into the cavity. After irrigation, ET was performed placing the outer sheath of the catheter 1 cm into the cervical canal and passing the inner sheath to a distance 1.5 cm from the fundal region. The location of the catheter tip was identified using 2-dimensional transvesical, transabdominal ultrasound imaging. Patients were categorized as having reflux (Group I) or not (Group II). Clinical pregnancy rates (PR) were compared by chi-square analysis. Age, estradiol, and number of embryos transferred were compared by analysis of variance. Results: Eighty-five patients were studied. Reflux was observed in 48 patients; no reflux was observed in 37 patients. PR were significantly higher in Group I than Group II (60% vs 25%). There was no difference in age (33.1 ⫾ 2.1 vs 34.7 ⫾ 1.7), estradiol (2815 pg/ml ⫾ 1172 vs 2776 ⫾ 1311), number of embryos transferred (2.0 on Day 5 for Groups I and II and 3.1 vs 3.2 in Groups I and II). Conclusions: These data suggest that reflux during cervical irrigation at ET is a frequent event and may enhance the likelihood of pregnancy. Possible factors include a self-selection process of easier transfers more likely to have reflux, facilitation of catheter passage by the media in the cervical canal and lower uterine segment and the possibility that media in the cavity creates a favorable environment for implantation.
Table 1. Serum level day antagonist started Patients Number 1 2 3 4 5 6 7 Average
Patients Number 1 2 3 4 5 6 7 Average
Diagnosis PCO PCO PCO PCO unexplained unexplained endometriosis
Serum level day of HCG
LH (IU/ml)
Progesterone (ng/ml)
LH (IU/ml)
Progesterone (ng/ml)
5.0 5.5 5.7 5.2 5.9 4.0 4.5 5.07 ⫾ 0.70
2.1 1.6 1.0 0.9 1.1 0.8 1.6 1.30 ⫾ 0.48
1.2 1.3 0.9 0.1 0.3 0.1 4.2 1.16 ⫾ 1.4
2.0 1.6 0.8 1.2 0.8 0.8 2.5 1.39 ⫾ 0.6
Diagnosis
Number of days of GnRH antagonist treatment
Pregnancy outcome
PCO PCO PCO PCO unexplained unexplained endometriosis
3 3 6 3 5 2 4
positive positive positive positive negative negative positive
Conclusions: The use of GnRH antagonist can be a valuable tool in rescuing cycles from a premature LH surge. Progesterone levels did not rise significantly enough to have any adverse effect on oocyte quality. The subgroup of PCO patients may benefit the most from this treatment.
P-335 Preliminary study on the use of gonadotropin releasing hormone (GnRH) antagonist for premature LH surges in GnRH agonist downregulated IVF cycles. M. Fakih, I. Gill, Z. Nassar, N. Shamma. IVF Michigan, Rochester Hills, MI. Objective: GnRH agonists are commonly used for pituitary desensitization in IVF cycles. In a small number of cases, patients will breakthrough the desensitization and begin a premature LH surge, and subsequently have their cycles cancelled. The aim of this study is to assess the efficacy of using a GnRH antagonist in patients who have already been downregulated using a GnRH agonist, in order to block the premature LH surge. Design: Prospective clinical study. Materials/Methods: A total of 168 IVF patients were evaluated from October 2000 to January 2001. Of these, 7 patients were found to have premature LH elevations greater than or equal to 4 IU/ml. Ages of patients ranged from 28 to 39. Infertility was secondary to polycystic ovary syndrome (PCO), endometriosis, and unexplained infertility. All patients received late luteal phase downregulation using 1.25 mg Leuprolide acetate as a depot injection. On day 3 of the menstrual cycle, patients had baseline ultrasound and bloodwork consisting of Estradiol, LH, and Progesterone, after which gonadotropin injections were started. Repeat ultrasound and bloodwork were done after 5 days of treatment and then every other day until human chorionic gonadotropin (hCG) administration. All 7 patients were started on a GnRH antagonist (.25 mg/day, sc) starting the day of rise in LH and continued until day of hCG administration. When 3 follicles were observed to be ⬎17 mm, 10,000 units of hCG (Profasi), was given. Progesterone supplementation was given for luteal phase support. Data were analyzed using a paired T-test. Results: The decrease in the average serum LH levels between the start of GnRH antagonists and the day of hCG was statistically significant (p ⬍ .001). There was no difference in the progesterone level between the start of the GnRH antagonist and the day of hCG (p ⫽ .597). All the patients with
S222
PCO who were treated with GnRH antagonist were able to achieve a clinical pregnancy. See Table 1 for data.
Abstracts
P-336 Comparable outcomes for pregnancy and implantation rates with day 3 and day 5 transfer using a transfer day crossover protocol for patients who repeated IVF cycles. M. Abae, W. K. Firisin, M. H. Majercik. Ctr for Advanced Reproductive Endocrinology, Plantation, FL. Objective: To evaluate the clinical outcome of transferring at an alternative stage of embryo development (Day 3 vs. Day 5) in patients who repeat IVF after failing to conceive in their first IVF attempt. Design: Retrospective analysis of Day 3 (D3) vs. Day 5 (D5) with subsequent crossover of transfer day. Materials/Methods: All patients ⬍40 years of age, with normal uterine cavity and ovarian reserve, undergoing their first IVF cycle in our center from Oct. 1998 – Feb. 2001, were divided into 2 groups. Group A consisted of 38 patients who had ET on D5, of whom 7 underwent a second IVF attempt with ET on D3. Group B consisted of 71 patients who had ET on D3, of whom 9 underwent a second IVF attempt with ET on D5. Additionally, 5 patients from Group B underwent a second IVF attempt with another ET on D3, which was determined by our internal criteria for patient candidacy of culturing embryos to D5 (Fertil. Steril., Vol. 74, No. 3S, p. S97). There were no significant differences in mean patient ages, etiology or duration of infertility among the groups. Controlled ovarian stimulation, oocyte retrieval, and embryo culture were performed using standard protocols in all patients. Embryos were cultured in IVF Science media (IVF-20, S1/G1, S2/G2). ICSI was performed when indicated for male factor infertility. ASRM guidelines for number of embryos transferred were followed. All transfers were performed under ultrasound guidance. Pregnancy and implantation rates are expressed per fetal heartbeat. Results: There were no significant differences noted in number of embryos transferred, pregnancy, or implantation rates among the groups. Detailed results are presented in the table below.
Vol. 76, No. 3, Suppl. 1, September 2001
Table 1. Serum level day antagonist started Patients Number 1 2 3 4 5 6 7 Average
Patients Number 1 2 3 4 5 6 7 Average
Diagnosis PCO PCO PCO PCO unexplained unexplained endometriosis
Serum level day of HCG
LH (IU/ml)
Progesterone (ng/ml)
LH (IU/ml)
Progesterone (ng/ml)
5.0 5.5 5.7 5.2 5.9 4.0 4.5 5.07 ⫾ 0.70
2.1 1.6 1.0 0.9 1.1 0.8 1.6 1.30 ⫾ 0.48
1.2 1.3 0.9 0.1 0.3 0.1 4.2 1.16 ⫾ 1.4
2.0 1.6 0.8 1.2 0.8 0.8 2.5 1.39 ⫾ 0.6
Diagnosis
Number of days of GnRH antagonist treatment
Pregnancy outcome
PCO PCO PCO PCO unexplained unexplained endometriosis
3 3 6 3 5 2 4
positive positive positive positive negative negative positive
Conclusions: The use of GnRH antagonist can be a valuable tool in rescuing cycles from a premature LH surge. Progesterone levels did not rise significantly enough to have any adverse effect on oocyte quality. The subgroup of PCO patients may benefit the most from this treatment.
P-335 Preliminary study on the use of gonadotropin releasing hormone (GnRH) antagonist for premature LH surges in GnRH agonist downregulated IVF cycles. M. Fakih, I. Gill, Z. Nassar, N. Shamma. IVF Michigan, Rochester Hills, MI. Objective: GnRH agonists are commonly used for pituitary desensitization in IVF cycles. In a small number of cases, patients will breakthrough the desensitization and begin a premature LH surge, and subsequently have their cycles cancelled. The aim of this study is to assess the efficacy of using a GnRH antagonist in patients who have already been downregulated using a GnRH agonist, in order to block the premature LH surge. Design: Prospective clinical study. Materials/Methods: A total of 168 IVF patients were evaluated from October 2000 to January 2001. Of these, 7 patients were found to have premature LH elevations greater than or equal to 4 IU/ml. Ages of patients ranged from 28 to 39. Infertility was secondary to polycystic ovary syndrome (PCO), endometriosis, and unexplained infertility. All patients received late luteal phase downregulation using 1.25 mg Leuprolide acetate as a depot injection. On day 3 of the menstrual cycle, patients had baseline ultrasound and bloodwork consisting of Estradiol, LH, and Progesterone, after which gonadotropin injections were started. Repeat ultrasound and bloodwork were done after 5 days of treatment and then every other day until human chorionic gonadotropin (hCG) administration. All 7 patients were started on a GnRH antagonist (.25 mg/day, sc) starting the day of rise in LH and continued until day of hCG administration. When 3 follicles were observed to be ⬎17 mm, 10,000 units of hCG (Profasi), was given. Progesterone supplementation was given for luteal phase support. Data were analyzed using a paired T-test. Results: The decrease in the average serum LH levels between the start of GnRH antagonists and the day of hCG was statistically significant (p ⬍ .001). There was no difference in the progesterone level between the start of the GnRH antagonist and the day of hCG (p ⫽ .597). All the patients with
S222
PCO who were treated with GnRH antagonist were able to achieve a clinical pregnancy. See Table 1 for data.
Abstracts
P-336 Comparable outcomes for pregnancy and implantation rates with day 3 and day 5 transfer using a transfer day crossover protocol for patients who repeated IVF cycles. M. Abae, W. K. Firisin, M. H. Majercik. Ctr for Advanced Reproductive Endocrinology, Plantation, FL. Objective: To evaluate the clinical outcome of transferring at an alternative stage of embryo development (Day 3 vs. Day 5) in patients who repeat IVF after failing to conceive in their first IVF attempt. Design: Retrospective analysis of Day 3 (D3) vs. Day 5 (D5) with subsequent crossover of transfer day. Materials/Methods: All patients ⬍40 years of age, with normal uterine cavity and ovarian reserve, undergoing their first IVF cycle in our center from Oct. 1998 – Feb. 2001, were divided into 2 groups. Group A consisted of 38 patients who had ET on D5, of whom 7 underwent a second IVF attempt with ET on D3. Group B consisted of 71 patients who had ET on D3, of whom 9 underwent a second IVF attempt with ET on D5. Additionally, 5 patients from Group B underwent a second IVF attempt with another ET on D3, which was determined by our internal criteria for patient candidacy of culturing embryos to D5 (Fertil. Steril., Vol. 74, No. 3S, p. S97). There were no significant differences in mean patient ages, etiology or duration of infertility among the groups. Controlled ovarian stimulation, oocyte retrieval, and embryo culture were performed using standard protocols in all patients. Embryos were cultured in IVF Science media (IVF-20, S1/G1, S2/G2). ICSI was performed when indicated for male factor infertility. ASRM guidelines for number of embryos transferred were followed. All transfers were performed under ultrasound guidance. Pregnancy and implantation rates are expressed per fetal heartbeat. Results: There were no significant differences noted in number of embryos transferred, pregnancy, or implantation rates among the groups. Detailed results are presented in the table below.
Vol. 76, No. 3, Suppl. 1, September 2001