Prilocaine Cream

Subjects reported being counseled by a range of health care professionals including assisted reproduction (ART) specialist physicians (53%), ART physicians and nurses (13%), ART nurses only (4%), and genetic counselors (16%). Several subjects reported that more than one health care professional counseled them while 14% reported having no formal counseling/education session prior to using PGD. While the majority of subjects had difficulty comprehending the technical specifics of fluorescence in situ hybridization (FISH), they did understand that using PGD with FISH does not eliminate the possibility of having a child with a chromosome disorder (90%), and that this procedure can detect disorders such as Down syndrome (94%). In addition, the majority of subjects were informed that PGD using FISH does not eliminate the chance that a child could have a condition such as cystic fibrosis (71%) or epilepsy (90%). Of note is that only 41% of subjects appeared to understand chromosomal mosaicism. A significant proportion of patients do not clearly comprehend the specific types of inherited disorders that can be detected by the procedures used in their treatment or how PGD applies to their reproductive goals. Study subjects indicated that being informed about PGD is important to their decision-making to use this technology and the majority of patients report that they are using Internet resources for additional information about PGD. CONCLUSION: The findings suggest that there are both strengths and weaknesses in patient knowledge regarding basic genetics and procedures associated with PGD. Many patients who have undergone PGD treatment do not appear to fully comprehend the risks and limitations associated with this technology. It is important for patients to comprehend the risks and limitations of PGD so that they can have realistic expectations of the procedure and therefore give appropriate informed consent. Genetic counseling strategies for PGD therefore need to be improved in order to protect both patients and fertility clinics. Since 80% of subjects believe that understanding both the procedural information and basic genetics is important in their decision making, it is clear that future studies are necessary to identify which counseling strategies are most effective for counseling patients about PGD. Information gathered from this study indicate that personalized genetic counseling sessions supported by multi-media educational resources may be optimal for educating prospective patients so that they can fully comprehend the risks, benefits, and limitations of PGD. Supported by: None

CLINICAL FEMALE INFERTILITY AND GYNECOLOGY Wednesday, October 19, 2005 3:00 p.m. O-311 The Role of Cabergoline in Hyperprolactinemic Patients Undergoing IVF/ICSI Cycles. G. N. Allahbadia, K. S. Kadam, Y. P. Mhatre, S. Arora, K. Kaur. Rotunda - The Center For Human Reproduction, Mumbai, India. OBJECTIVE: Bromocriptine has been used since a number of years for the treatment of hyperprolactinemic patients. However, patient compliance and side-effects led doctors to search for a better alternative. A recently launched long acting dopaminergic drug, cabergoline, has been reported to be highly effective in these patients. A better patient compliance and fewer side effects was reported by patients on cabergoline. In this prospective study, an attempt was made to study the role of Cabergoline in hyperprolactinemic patients undergoing IVF/ICSI cycles. DESIGN: Prospective , randomized, comparative study. MATERIALS AND METHODS: A comparative, randomized, singlecentre trial was done on patients with hyperprolactinemia undergoing IVF/ ICSI cycles. The patients were divided into two groups, Group A (cabergoline group, n⫽28) and Group B(bromocriptine group, n⫽30) . A dose of cabergoline 0.5mg twice a week (Caberlin, Sun Pharma, India) and bromocriptine 1.25mg twice a day (Sicryptin, Serum Institute, India) was administered to the patients in Group A and Group B respectively. The response was evaluated at 4 weeks and 8 weeks subsequently from the start of the treatment. The efficacy and safety was evaluated on the basis of normalization of prolactin levels, normalization of menstrual cycle, disappearance of galactorrhoea and adverse effects with each of these medications. The clinical pregnancy rate in the both the arms of the study was also evaluated. RESULTS: Normoprolactinemia was achieved in 4 weeks in 26/28patients (92.86%) on cabergoline whilst only 23/30 ( 76.67%) patients on

FERTILITY & STERILITY威

bromocriptine had normal prolactin levels by the 4th week. 25/28 patients (89.57%) had disappearance of galactorrhoea in Group A while only 22/30 (73.33%) patients in Group B reported disappearance of galactorrhoea. Normalization of menses was observed in 22/28(78.57%) and 20/30 (66.67%) in Group A and Group B respectively. There were very few adverse effects recorded in cabergoline group (8/28,28.57%) as compared to the bromocriptine group(21/30, 70%). The clinical pregnancy rate per cycle was 35.71% and 26.6% in the cabergoline and bromocriptine group respectively. Six patients who were previously on bromocriptine therapy before coming to our Center were put on cabergoline during the study and of those four conceived. CONCLUSION: Cabergoline is a very effective drug for lowering of prolactin levels in hyperprolactinemic patients and is very efficacious , better tolerated and much more safe drug than the reference compound, bromocriptine. Supported by: None

Wednesday, October 19, 2005 3:15 p.m. O-312 Adjunctive Use of an Oral Contraceptive (OC) and a Reduced Dose of a GnRH Antagonist for COH/IUI. D. R. Meldrum, A. L. Wisot, B. Yee, G. F. Rosen, D. L. Cassidenti, G. Garzo. Reproductive Partners Medical Group, Redondo Beach, CA; Reproductive Partners Medical Group, La Jolla, CA. OBJECTIVE: In preparation for IVF, a long GnRH agonist protocol provides for scheduling of procedures, synchronization of follicles, prevention of premature luteinization (PL), and prevention of premature ovulation of mature follicles. Although COH/IUI cycles are commonly started day 2 of the cycle, selection of the dominant follicle may already be underway. Pretreatment with an OC synchronizes follicles and has been shown to block the occurrence of an LH surge in a subsequent COH cycle (Gonen Y, Fertil Steril 1990). A study with COH/IUI (Manzi DL, Fertil Steril 1995) has shown that about one-third of cycles demonstrate PL, with a very low success rate and a high rate of miscarriage and improved RESULTS with use of a GnRH agonist in the next cycle. We therefore chose to evaluate COH/IUI following OC, with half of the usual dose of the GnRH antagonist, ganirelix (G) to prevent PL and premature release of follicles. DESIGN: Pilot trial. MATERIALS AND METHODS: Thirteen women (mean age and body weight 34.5 and 136.5) with unexplained infertility or male factor with weight between 110 and 180 pounds and a day 3 FSH less than 10 IU/ml. having their first COH/IUI cycle took OC for 14 to 21 days. Beginning on the fourth day after OC, rFSH (follitropin beta), 75-225 IU was selfadministered daily using a multidose pen. G, 0.125 mg, was administered each morning starting at a lead follicle mean diameter of 14 mm. HCG was given in the evening when there were at least two follicles of 17 mm mean diameter or greater, and IUI was done on the following two mornings. RESULTS: The mean starting dose of rFSH was 161.5 IU. G was given for a mean of 3.5 days. HCG was given after 10.1 days of stimulation with 5.9 follicles over 12 mm. Five women have ongoing pregnancies (38.5%). UTZ showed two sacs in three women, with one of those evolving to one viable fetus. Serum LH levels will be assessed. CONCLUSION: A high rate of ongoing pregnancy was achieved in this small ongoing study with COH preceded by OC and with adjunctive use of a GnRH antagonist. The high number of follicles and twin implantations are consistent with a synchronizing effect of OC and excellent oocyte quality. Based on this initial experience, we have reduced the starting dose to 75-100 IU. The low dose of FSH should offset the additional cost of G. The use of OC is also helpful in scheduling procedures around career activities. A large prospective randomized trial will be necessary to demonstrate a better clinical outcome compared with COH alone. Supported by: Organon USA, Inc.

Wednesday, October 19, 2005 3:30 p.m. O-313 Pain Relief of Hysterosalpingography by Prior Uterine Cervical Application of Lidocaine/Prilocaine Cream. G. Liberty, M. Gal, E. Mazaki, T.

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Eldar-Geva, E. Vatashsky, E. J. Margalioth. Saarezedek Medical Center, Jerusalem, Israel; Shaare-Zedek Medical Center, Jerusalem, Israel. OBJECTIVE: Hysterosalpingography (HSG) is commonly a painful procedure. We sought to evaluate whether application of the local anesthetic lidocaine 25 mg, prilocaine 25 mg/G cream (EMLA® 5%) on the uterine cervix before performing HSG, relieves the pain associated with this procedure. DESIGN: A prospective cohort study to compare the perception of pain during HSG with no analgesia to the perception of pain following preoperative application of EMLA® 5% to the uterine cervix. MATERIALS AND METHODS: During a 1 yr study-period, 79 consecutive patients underwent HSG as part of infertility investigation. All patients were evaluated for the pain related to the procedure by a zero [⫽no pain] to ten [⫽worst pain imaginable] visual analogue scale (VAS). Pain was scored at five predefined steps: speculum application as baseline, at the cervical instrumentation by the tenaculum/canula, at the end of uterine filling, at the end of tubal spillage, and immediately following removal of instruments. In addition, on the next day, the patient was asked to score retrospectively the pain of the entire HSG procedure. The pain scoring method was designed by a ratio to the pain associated with that perceived during speculum application. In the first study period, 38 women underwent HSG without any analgesic treatment (control group). In the following period, 41 women were treated by topical application of 3 mL of EMLA® 5% cream on the uterine cervix using a cervical cup, 30 min before performing the HSG. The student’s t test was used to compare the pain scores at each step in the untreated-control group and the EMLA®-treated group, a P⬍0.05 was considered statistically significant. RESULTS: There was no difference in the baseline speculum application-pain in both study’s groups. Initial analysis of the procedure pain, enables us to define only two significant steps: 1.cervical instrumentation. 2.The following steps of HSG performance (uterine filling, tubal spillage and instruments removal). The cervical instrumentation was found to be more painful then the following steps, in both study groups (P⬍0.001). At this step the EMLA®-treated patients reported significantly less pain then the control group: 1.9 and 2.7 times the baseline pain, respectively (P⫽0.01). The score given retrospectively by the patient on the day after the HSG, correlated with the less painful step in the EMLA®-treated group (r⫽0.8, P⫽0.01) while in the untreated-control group it correlated with the more painful step (r⫽0.8, P⫽0.01). CONCLUSION: Topical application of EMLA® 5% cream on the cervix before HSG performance significantly reduces the pain associated with this procedure. Supported by: None.

Wednesday, October 19, 2005 3:45 p.m. O-314 Impact of GnRH Agonist Versus GnRH Antagonist During Controlled Ovarian Hyperstimulation (COH) on Oocyte Maturity and Aneuploidy: A Pilot Study. S. Ghadir, S. Sarajari, A. Kumar, D. Hill, M. Surrey, A. H. DeCherney. UCLA, Los Angeles, CA; ART, Beverly Hills, CA. OBJECTIVE: It is unclear at this time if existing methods used to prevent the premature LH surge, either by the use of GnRH-agonists or antagonists has implications on the resulting oocyte. In women older than 35 years of age, this could potentially have significant importance as such patients often have a limited number of available mature oocytes and an increased risk for aneuploidy in resulting embryos. The objective of this study was to test the hypothesis that the mechanism of pituitary suppression during COH in IVF cycles, (antagonist vs. agonist) influences rates of oocyte maturity and aneuploidy. DESIGN: Prospective randomized study MATERIALS AND METHODS: Thirty-seven patients between the ages of 35 to 42 years, undergoing IVF, and with day 3 FSH measurements ⱕ12 mIU, were recruited for the study. Patients were randomized to undergo, COH for IVF using a GnRHa (Lupron®, Tap Pharmaceuticals) (n⫽20) or a GnRH antagonist (Ganirelix Acetate, Organon Pharmaceuticals USA, Inc.) (n⫽17) for pituitary suppression. Following OCP therapy, all patients received rFSH (Follistim®, Organon Pharmaceuticals USA, Inc.). Under the agonist protocol, patients began leuprolide acetate 40 ␮g bid on the 3rd

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pill-free day and 150 IU rFSH bid on the 5th pill-free day. Under the antagonist protocol, patients began 150 IU rFSH bid on the 3rd pill-free day and 250 ␮g of ganirelix acetate daily when the lead follicle had reached 14 mm in size. Subsequently, the rFSH dosage was individualized depending on the response. Preimplantation genetic diagnosis (PGD) was performed to assess chromosomes 13, 18, 21, X, and Y on all embryos amenable to biopsy for aneuploidy screening. Parameters assessed included age, FSH, days of stimulation, and total Follistim® dosage. Outcome measures were number of oocytes retrieved, oocyte fertilization rates, embryo aneuploidy rates, and pregnancy outcome. RESULTS: Mean ages were 39.6 ⫾ 2.3 yrs. and 39.2 ⫾ 2.1 yrs. for the ganirelix acetate and leuprolide acetate groups, respectively. The mean baseline FSH, mean total days of stimulation, and the total FSH dosage used during the cycle were 8.5 ⫾ 2.5 IU/L, 11.7 ⫾ 1.5 days, 3881 ⫾ 1077 IU and 8.1 ⫾ 1.9 IU/L, 10.1 ⫾ 1.9 days, 3095 ⫾ 866 IU, for the ganirelix acetate and leuprolide acetate groups, respectively. In the ganirelix acetate arm, the mean number of oocytes retrieved was 7.3, while the mean number of oocytes fertilized and mean number of embryos analyzed by PGD were 4.7 (64.4%) oocytes and 4.9 embryos, respectively. In the leuprolide acetate arm, the mean number of oocytes retrieved was 8.0, while the mean number of oocytes fertilized and mean number of embryos analyzed by PGD were 4.8 (60.0%) oocytes and 4.6 embryos, respectively (p⫽NS). Both groups yielded similar rates of aneuploidy, 53.1% and 50.0% for Ganirelix and leuprolide, respectively (p⫽NS). On average there were 1.4 embryos available for transfer in the ganirelix group and 2.2 embryos available for transfer in the leuprolide group (p⫽NS). The clinical pregnancy rate was 41.7% in the ganirelix group and 15.8% in the leuprolide (p⫽NS). CONCLUSION: In this pilot study, the mechanism of pituitary suppression does not show an affect on the number of mature oocytes retrieved or the genomic quality of resulting embryos as measured by PGD. Furthermore, the trend in pregnancy rates reveals at, at minimum, the antagonist suppression is equivalent to agonist downregulation. Supported by: This study has been supported by an unrestricted educational grant from Organon Pharmaceuticals, USA.

Wednesday, October 19, 2005 4:00 p.m. O-315 Efficacy of a New Agonist-Antagonist Protocol Compared To Microdose Flare-up in Poor Responder IVF Patients. H. F. Erden, M. A. Akman, N. Bayazit, M. Bahceci. German Hospital, Istanbul, Turkey. OBJECTIVE: Poor response in IVF treatment still remains to be a challenge in IVF practice. With the entry of GnRH antagonists into the clinical practice, there are few more protocols which might be a chance for these poor responder patients. The aim of this study was to compare the GnRH agonist-antagonist and microdose flare-up protocols in poor responder IVF patients. DESIGN: Retrospective study MATERIALS AND METHODS: We evaluated the cycles of poor responder patients who underwent IVF between June 2003 and December 2004. The poor responders were the ones who had ⬎10 mIU/mL level on day 3 or had peak estradiol level less than 1000 pg/mL on previous attempts despite the highest gonadotropin dosages. The study included two groups; in Group I there were 484 patients in which microdose flare-up protocol administered. In this group, after a 21 days of oral contraceptive pretreatment 80 mcg leuprolide acetate was administered on day 2 till the day of hCG, later on day 3 gonadotropins of 600 IU of p-FSH were administered. In group II, there were 518 patients in which without previous oral contraceptive pretreatment, again the same dosage of GnRH agonist administered on day 2, later on day 3 gonadotropins were added. Once the leading follicle reached 14 mm in size, GnRH agonist discontinued and daily dosage of 0.25 mg cetrorelix acetate added till the day of hCG. RESULTS: In GnRH agonist-antagonist protocol (group II) there were higher peak estradiol levels, more mature and fertilized oocytes and higher clinical pregnancy. See table I. CONCLUSION: In poor responder IVF patients a new protocol of GnRH agonist-antagonist regimen without previous OC pretreatment yielded

Vol. 84, Suppl 1, September 2005