Using gonadotropins with hCG activity improves controlled response in PCOS patients undergoing IVF compared to cycles using FSH alone

subsequent transfer in a frozen embryo transfer (FET) cycle (Group A) were matched to their controls with respect to age, peak estradiol, FSH and number of oocytes retrieved (Group B). Pregnancy and implantation rates per transfer were compared. Data were analyzed using the independent t-test and chisquared test. Significance was considered at P<0.05. RESULTS: 68 patients considered at risk of OHSS were matched in two groups. The study included 34 patients in Group A and 34 patients in Group B. Mean patient ages were 33.8  4.1 and 33.7  3.8 for Group A and Group B respectively (P¼0.92). Mean cycle day 3 FSH was 5.3  1.8 mIU/ml for Group A and 6.0  1.5 mIU/ml for Group B (P¼0.14). Mean peak estradiol measured on the day of HCG administration was 5940.9  1870 pg/ml for Group A and 5037.5  1202.2 pg/ml for Group B (P<0.05). The mean number of eggs retrieved in Group A (30.1  14.7) was slightly higher than Group B (24.2  12.8), however not statistically different (P¼0.07). There were no significant differences observed in the age of the patients, FSH, or number of eggs retrieved. Implantation rates per embryo transferred were lower in Group A than in Group B, 35.1% (33/84) vs 39.3% (39/111), but not significantly different (P¼0.46). Clinical pregnancy rates per embryo transfer were 68% (27/40) and 65% (22/34) for Groups A and B respectively (P¼0.50). The clinical pregnancy rates per transfer did not show significant differences. CONCLUSIONS: It is not uncommon for patients to be concerned about the risk of lower pregnancy rates with deferring embryo transfer to a future cycle. Our results show that when embryo transfer was delayed to a subsequent FET cycle pregnancy rates were slightly higher, although not statistically significant, when compared to those cases where a fresh embryo transfer had occurred. Complications from OHSS can be reduced in severity and duration by deferring embryo transfer without adversely affecting overall clinical pregnancy rates. Supported by: None. P-63 INFLUENCE OF THE OVARIAN HYPERSTIMULATION SYNDROME (OHSS) IN EMBRYO QUALITY AND IN IMPLANTATION AND PREGNANCY RATES. C. M. Andraus, S. Abdelmassih, C. C. Rocha, C. Carizza, V. Abdelmassih, R. Abdelmassih. ART, Roger Abdelmassih Human Reprod. Clin. and Res. Ctr., Sa˜o Paulo, Brazil; Roger Abdelmassih Human Reprod. Clin. and Res. Ctr., Sa˜o Paulo, Brazil. OBJECTIVE: Some studies suggest that ovarian hyperstimulation can compromise implantation rates in assisted fertilization treatment cycles. Other studies believe that OHSS does not affect implantation rates or the quality of both oocytes and embryo. The purpose of this study was to evaluate embryonic quality, the implantation and pregnancy rates of patients with OHSS by comparing them to a control group without OHSS. DESIGN: Retrospective. MATERIALS AND METHODS: The study included 1905 patients with an indication for Intracytoplasmic sperm injection (ICSI) of which 156 patients had OHSS and 1749 did not (control group). Both the short and the long protocols were used. HCG was administered when at least 3 follicles had reached 19 mm in diameter. M2 eggs were injected 4 hours after oocyte retrieval. Fertilization and embryo development were assessed at 20h, 44h and 68h after ICSI. Embryo transfer was performed on day 2 or 3. Patients were divided into six groups, namely G1 (patients % 35 years and with mild OHSS), G2 (patients % 35 years and moderate or severe OHSS), G3 (patients between 36 to 40 years and mild OHSS), G4 (patients between 36 and 40 years and moderate to severe OHSS), G5 (patients % 35 years without OHSS) and G6 (patients between 36 and 40 without OHSS). Statistical analyses used one-Way ANOVA or the Fisher’s exact tests at the level of P<0.05. RESULTS: With respect to embryo quality, there was no statistically significance between the total of obtained embryos and the transferred embryos. The percentage of good morphology embryos (AþB) were: 75%, 82%, 73%, 88%, 78% and 78% for G1, G2, G3, G4, G5 and G6 respectively, and transferred embryos were: 95.5%, 100%, 98.5%, 100%, 98% and 97% for G1, G2, G3, G4, G5 and G6, respectively. Implantation rates were: 23% (G1), 56% (G2), 25% (G3), 45% (G4), 21% (G5) and 13.5% (G6). Hence, it was verified an increased implantation rate in G2 and G4 i.e., patients with a moderate or severe OHSS, as well as in the pregnancy rates, which were: 52% (G1), 72% (G2), 44% (G3), 71% (G4), 46% (G5), 47% (G6). CONCLUSIONS: Since no difference between the various groups was identified, our results do corroborate the opinion of certain authors who believe that embryo quality is not affected by OHSS. However, an increase

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Abstracts

in implantation and pregnancy rates was observed in both groups with moderate to severe OHSS i.e., G2 and G4 (% 35 years and 36-40 years, respectively). Supported by: None.

P-64 OOCYTE QUALITY AND EMBRYO QUALITY OF INFERTILE WOMEN WITH POLYCYSTIC OVARIAN SYNDROME. S. Chen, J. Song. OB/GYN, Nanfang Hospital, Southern University, Guangzhou, Guangdong, China; Nanfang Hospital, Southern University, Guangzhou, China. OBJECTIVE: To investigate the oocyte and embryo quality of infertile women with polycystic ovarian syndrome (PCOS), isolated polycystic ovaries morphology (PCO-only) or matched control group undergoing IVF-ET. DESIGN: A retrospective case-control study. MATERIALS AND METHODS: 486 IVF/ ICSI cycles were performed from January 2003 to January 2008. The diagnosis of PCOS was based on Rotterdam criteria. Three study groups were identified: PCOS group (202 cycles), PCO-only group (PCO-only morphology, 134 cycles) and control group (normal ovarian response and age-matched,150 cycles). Oocyte and embryo morphorlogy, including perivitelline space, polar body, granular cytoplasm, smooth endoplasmic reticulum incidence, vacuolization and abnormal zona pellucida, were recorded. Pregnancy outcome were analyzed. RESULTS: Compared with control group, lower maturity rate of oocytes, lower fertilization rate, and fewer number of high-grade embryos were attained in PCOS and PCO-only groups, although more oocytes were retrieved and lower total dose of gonadotropin were administrated (P<0.01). The percentage of transferred two high-quality embryo and total embryo score were lower in PCOS and PCO-only group compared to control group (P<0.05). There were no significant differences of the rate of abnormal perivitelline space, abnormal polar body, abnormal granular cytoplasm, smooth endoplasmic reticulum incidence, vacuolization and abnormal zona pellucida among the three groups in ICSI cycles (P>0.05). But total rate of MII oocyte morphology abnormality was significantly higher in PCOS and PCO-only group compared with control group (P<0.05). Clinical pregnancy were 51.0%, 53.0% and 46.0% in PCOS, PCO-only and control groups, respectively. No significant differences were noted in the implantation and pregnancy rates among the three groups. However the clinical miscarriage rate was significantly higher in women with PCOS group (15.4%) than that in the PCO-only morphology group (5.5%) and control group(5.8%) (P < 0.05). CONCLUSIONS: Infertile women with PCOS have shown to have similar characteristics to women with PCO-only in terms of ovarian response to Gn stimulation, oocyte and embryo quality and pregnancy rates. Oocyte morphology abnormality and embryo quality may be associated with early miscarriage rates in PCOS. It suggested that factors related to oocyte and embryo morphology present in PCOS patients may be instrumental in adverse reproductive outcomes in these women. Supported by: National key basic research development plan of China(2007CB948104).

P-65 USING GONADOTROPINS WITH HCG ACTIVITY IMPROVES CONTROLLED RESPONSE IN PCOS PATIENTS UNDERGOING IVF COMPARED TO CYCLES USING FSH ALONE. C. S. Sipe, M. A. Hilse, M. L. Uhler, M. Martin-Johnson, K. Sasada, A. N. Beltsos. Fertility Centers of Illinois, Glenview, IL; Department of OB/Gyn, Illinois Masonic Medical Center, Chicago, IL. OBJECTIVE: To determine if the addition of LH activity to FSH only protocols in GnRH agonist IVF cycles can improve response in PCOS patients. DESIGN: Retrospective cohort study of women diagnosed with PCOS undergoing IVF at a large urban private practice. MATERIALS AND METHODS: Women ages 21-39 years with polycystic ovary syndrome were recruited to participate in an IVF study in 2007 and 2008. Sixty-four participants had FSH <12, E2 levels < 80 and BMI < 39, < 2 prior IVF cycles for canceled for poor response, and no diabetes. All subjects were prescribed metformin during the study. A long luteal phase agonist protocol was used with Menopur (hMG) with or without

Vol. 90, Suppl 1, September 2008

follicle stimulating hormone. Control subjects were women with PCOS from 2004-2008 who underwent IVF receiving FSH only. An individual’s responses determined dose adjustment and oocyte retrieval was performed 36 hours after hCG trigger. Standard laboratory protocols were followed, including ICSI, assisted hatching and extended culture for blastocyst transfer. Ultrasound guided embryo transfer was performed, and all patients received luteal progesterone support. On-going pregnancy was defined as the presence of a fetal cardiac activity on ultrasound. Statistical significance was determined by t-test. RESULTS: There was no difference in BMI or antral follicle count, but the hMG subjects were younger than the FSH group. Patients receiving hMG medication had shorter stimulations but used more gonadotropins (LH þ FSH). Patients in the FSH only group had significantly more cycles cancelled for over-stimulation than the study population. There was no difference in estradiol, oocytes retrieved, embryos transferred or pregnancy rates between the two groups. CONCLUSIONS: Concerns that patients with PCOS should be stimulated with FSH alone because of their high endogenous LH levels may not be accurate. This study demonstrates that stimulation with hCG activity are shorter, use more total gonadotropins, but most importantly have a lower cancellation rate due to over-response than stimulations using only FSH. TABLE 1. Gonadotropins in PCOS patients undergoing IVF

Parameter

hMG and FSH (N¼64)

FSH alone (N¼46)

30.8 26.5 11.3 2421 2766 14.2 3.6% 1.35 39.6%

32.4* 25.9 12.6* 1730* 1730 14.4 20.0%* 1.69 30.4%

Age BMI Days of stimulation Total dose of gonadotropins Peak Estradiol Oocytes retrieved Cycles cancelled for OHSS Embryos tranferred Ongoing Pregnancy * P< 0.05.

Supported by: In part by an unrestricted educational grant by Ferring Pharmaceuticals, Parsippany, NJ, USA. P-66 EARLY ENDOCRINE, METABOLIC CHARACTERISTICS OF POLYCYSTIC OVARY SYNDROME (PCOS): COMPARISON BETWEEN LEAN AND OVERWEIGHTADOLESCENTS IN SOUTHERN-CHINA. X. Chen, D. Yang, L. Li, Y. Li, Q. Zhang, W. Wang. The 2nd Affiliated Hospital Sun Yat-Sen University, Guangzhou, China. OBJECTIVE: The aims of this study were to further characterize early endocrine and metabolic alterations in adolescents with PCOS and to determine whether differences between lean and overweight women with PCOS are present early in its course. DESIGN: Twenty-two lean and fourteen overweight adolescents with PCOS and Twenty-seven adolescent lean controls were evaluated. MATERIALS AND METHODS: Basal levels of glucose (G0), insulin (I0), sex hormone-binding globulin (SHBG), testosterone(T), free testosterone(FT), LH, and FSH were measured. All patients underwent oral glucose tolerance tests (OGTTs) with blood samples taken at 0, 1 and 2 h. RESULTS: The prevalence of overweight PCOS was 38.89%. The mean LH level was higher in the lean PCOS group than that in overweight PCOS. There was no significant difference in FSH, FAI (Free androgen index) and SHBG levels between lean and overweight PCOS groups. Higher levels of LH and androgens, including total and free testosterone, and FAI were found in the lean PCOS group compared with the lean controls. Fasting glucose(FG) were similar in the three study groups. Fasting insulin(FINS), one-hour insulin (1-h INS), 2-h INS and AUCins were significantly increased in the overweight PCOS compared with the lean PCOS subjects. Plasma insulin levels were similar in the lean PCOS group and lean control group. The fasting glucose to insulin ratio (FGIR) and quantitative insulin sensitivity check index (QUICKI) were significantly reduced in overweight group compared with the lean PCOS group, while homeostasis model assessment (HOMA) was significantly increased in these two groups. No statistically significant differences in the measures of insulin sensitivity were detected between the two lean groups.

FERTILITY & STERILITYÒ

CONCLUSIONS: Adolescents with PCOS manifested clinical, metabolic, and endocrine features similar to those of adult women, and differences between lean and overweight women with PCOS may be detected early in adolescence. Overweight PCOS seemed to be in more severe insulin resistance state. Fasting glucose level failed to detect the glucose tolerance, we recommended to undergo OGTT in adolescent PCOS patients. Supported by: 1) Key Projects in the National Science Technology Pillar Program in the Eleventh Five-year Plan Period. (Grant No. 2007BA104B00) 2) The Medical Science Research Foundation of Guangdong Province. (Grant No.B2007053). P-67 ELECTRO-ACUPUNCTURE AND PHYSICAL EXERCISE REDUCE MESENTERIC ADIPOSE TISSUE GENE EXPRESSION OF SYMPATHETIC MARKERS IN RATS WITH POLYCYSTIC OVARY SYNDROME. L. Mannera˚s, M. Lo¨nn, E. Stener-Victorin. Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, Gothenburg, Sweden; Wallenberg Laboratory, Institute of Medicine, Gothenburg, Sweden. OBJECTIVE: Altered activity of the sympathetic nervous system has been suggested as a potential actor in polycystic ovary syndrome (PCOS) etiology. Electro-acupuncture (EA) and physical exercise has the potential to decrease high activity in sympathetic nervous system via stimulation of ergoreceptors and somatic afferents in the muscles. The aim of this study was to study sympathetic activity in adipose tissue by measuring mesenteric adipose tissue gene expression of sympathetic markers (b3-adrenergic receptor [b3-AR], nerve growth factor [NGF], low affinity p75 neurotrophin receptor [p75NTR] and neuropeptide Y [NPY]) in PCOS rats. Moreover, the effect of low-frequency EA and exercise on gene expression of these markers were evaluated. DESIGN: Female rats were given vehicle (control) or a continuous dose of dihydrotestosterone (PCOS groups), starting prepubertally (21 d). At 69 d of age, the PCOS group was sub-divided into three groups: physical exercise, low-frequency EA, and untreated PCOS. MATERIALS AND METHODS: EA was given to conscious rats every second weekday for 4-5 wk and the rats in the PCOS exercise group had free access to a wheel for 4-5 wk. Gene expression analysis was carried out with real time-RT-PCR using TaqMan low density arrays. RESULTS: Mesenteric adipose tissue gene expression of b3-AR, NGF and NPY were up-regulated in untreated PCOS rats compared with controls. Both low-frequency EA and exercise down-regulated the expression of NGF and NPY, and EA also down-regulated the expression of b3-AR, compared with untreated PCOS rats. Gene expression of p75NTR was not influenced. CONCLUSIONS: Our observations give support to the theory that an increased sympathetic activity may be involved in the development and maintenance of PCOS, and that non-pharmacological treatment may be useful. Supported by: None. P-68 COULD OXIDATIVE STRESS BE RESPONSIBLE FOR POOR OOCYTE COMPETENCE IN WOMEN WITH POLYCYSTIC OVARY SYNDROME? J. Samanta, A. Sanyal, R. Chattopadhyay, S. K. Goswami, S. Sharma, B. N. Chakravarty. ART, Institute of Reproductive Medicine, Kolkata, India; Institute of Reproductive Medicine, Kolkata, India. OBJECTIVE: Circulating reactive oxygen species (ROS) have been reported to induce insulin resistance and hyperandrogenism in women with polycystic ovary syndrome (PCOS). Animal experiments have shown that oxidative stress (OS), induced in vitro, disturbs spindle organization during oocyte meiosis. This study aims to evaluate the effects of follicular fluid (FF) OS on meiotic spindle (MS) formation in oocytes and outcome of in vitro fertilization in PCOS women. DESIGN: Prospective randomized-controlled study at Institute of Reproductive Medicine. MATERIALS AND METHODS: 301 oocytes retrieved from 28 PCOS (Group-A) women and 218 oocytes from 32 age-matched non-PCOS (Group-B) women were analyzed. Long-protocol ovarian stimulation was undertaken and urinary human chorionic gonadotrophin (10,000IU) was used for final oocyte maturation. FF was collected from all follicles above 14mm. 217 FF samples of both groups containing mature oocytes were analyzed for ROS by chemiluminescence (luminometer). All mature oocytes were denuded and observed under Polscope to visualize MS. FF samples of Gr-A were classified as Gr-A1 (oocyte with MS) and Gr-A2 (oocyte without MS). Intracytoplasmic Sperm Injection was performed in all oocytes.

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