A newer approach for ovarian stimulation in poor responders undergoing IVF

A newer approach for ovarian stimulation in poor responders undergoing IVF

MATERIALS AND METHODS: Patients who underwent the 3 protocols from 1/2004-10/2009 were included. All patients applied 0.1mg E2 patch every alternate d...

55KB Sizes 0 Downloads 91 Views

MATERIALS AND METHODS: Patients who underwent the 3 protocols from 1/2004-10/2009 were included. All patients applied 0.1mg E2 patch every alternate day, starting 10 days post-LH surge. On 2nd dy of E2 patch, patients started Ant for 3 days. CF protocol entailed administering 1mg leuprolide acetate (LA) from cycle day (CD) 2 to 4 and decreasing to 0.5mg on CD5. High dose gonadotropins (FSH/HMG) started on CD3. MDL protocol involved starting 80ug MDL on CD2 followed by FSH/ HMG administration on CD4. Ant protocol involved starting FSH/HMG on CD2. Ant was started when leading follicle reached 13mm or E2 measured 300pg/ml. HCG was given when 2 follicles attained 17 mm. Retrieval occurred 35 hours later. The main outcome measures were: no-start rate, days of stimulation, and cancellation and clinical pregnancy rates. Statistical analyses included c2 test and Mann-Whitney test. P<0.05 was deemed statistically significant. RESULTS: 89 CF, 56 MDL, and 2125 Ant cycles were identified. The baseline characteristics were comparable. The no-start rates were low in all 3 groups. Compared to E2/Ant/Ant group, the E2/Ant/MDL group had a significantly higher cancellation rate (36.4% vs. 18.3%), required more days of stimulation (12.6  2.1 vs. 10.8  2.2) and higher dose of FSH/ HMG (6534.1  1517.6IU vs. 5754.9  1459.8IU). The clinical pregnancy rates per cycle started were comparable in 3 groups (16.3% vs. 20.0% vs. 22.7% respectively). CONCLUSION: Combinations of luteal E2 patch/Ant pretreatment with CF and MDL protocols yielded similar clinical pregnancy rates compared to E2 patch/Ant/Ant protocol and represent viable treatment options for poor responders. Supported by: Institutional.

OBJECTIVE: OHSS remains a significant risk for oocyte donors. The use of Cetrotide Acetate to prevent OHSS was investigated in this patient population. DESIGN: Prospective pilot study. MATERIALS AND METHODS: To date, 11 oocyte donors completed the study. All donors received one 3 mg Cetrotide Acetate injection immediately after oocyte retrieval. All donors were seen on days 1, 2, 5, and 7 after oocyte retrieval. Symptoms, weight, abdominal circumference, ultrasound examination (ovarian volumes, ascites in anterior and posterior cul-de-sacs [CDS]), CBC, comprehensive metabolic profile, FSH, LH, estradiol, prolactin and progesterone levels were recorded at each visit. One way ANOVA was used to detect differences among the 4 visits. RESULTS: None of the 11 donors developed moderate or severe OHSS. Significant differences were found between the 4 visits in estradiol (P < 0.001), Hb (P¼0.028), Hct (P¼0.035), Ca (P¼0.023), ALT (P¼0.026), AST (P¼0.004), and total protein (P¼0.020), with values increasing significantly on days 2 and 5 compared to day 1, and most values returning to baseline day 1 values (or below) 7 days after oocyte retrieval. All the other variables studied were not different between the 4 visits. LH levels became undetectable by day 1 and remained significantly suppressed by day 7 after retrieval, FSH levels were also significantly suppressed, though not to the extent of LH levels. Ovarian volumes and both anterior and posterior CDS ascites increased between days 2 and 5 but returned to baseline by day 7. CONCLUSION: Cetrotide Acetate may represent a novel therapy for OHSS prevention in oocyte donors. Future multi-center, randomized, placebo-controlled trials are needed to evaluate further this novel use of GnRH antagonists in oocyte donors. The current study is ongoing. Supported by: EMD Serono.

P-247 Tuesday, October 26, 2010 LUTEINIZED UNRUPTURED FOLLICLE SYNDROME: CLINICAL SYNDROME OF LACK OF hCG ADMINISTRATION AT OOCYTE RETRIEVAL? K. A. Reynolds, C. Godby, P. Warikoo, M. Abdallah, G. Hofmann. Obstetrics and Gynecology, Bethesda Hospital, Cincinnati, OH. OBJECTIVE: To determine serum hCG levels immediately prior to ovum retrieval after IM or SQ delivery in women undergoing ovum retrieval for IVF, with correlation of serum hCG levels with BMI and IVF outcome parameters. This study was prompted by failed oocyte recovery in a repeat ovum donor whose serum hCG level at the time of ovum retrieval was undetectable. DESIGN: Prospective collection of serum immediately prior to oocyte retrieval from women receiving either IM or SQ hCG injections to trigger ovulation for IVF. MATERIALS AND METHODS: Serum was collected 36 hours after hCG administration in 66 IVF women receiving 10,000 IU hCG (IM) and from 29 ovum donors receiving 250 mcg hCG (SQ). Serum was stored frozen and hCG levels were assayed in batch by immunoassay. Serum hCG levels between the IM and SQ groups were compared by t-test, and compared to BMI, peak estradiol (E2), the number of oocytes and mature oocytes retrieved, fertilization rates, and the number of high quality embryos available for transfer, by regression analysis. RESULTS: Serum hCG levels were higher in the IM group (Mean 183+91, range 45-385 mIU/mL) compared to the SQ group (104+55, range 29-210 mIU/mL) (P¼0.0001). BMIs were also higher in the IM group (Mean IM: 26.6+6.4 vs SQ: 22.8+3.3; P¼0.0001). In the IM group only, the BMI was negatively correlated with serum hCG levels (P¼0.001). Serum hCG levels were not correlated with the serum peak E2, number of total or mature oocytes retrieved, fertilization rates, or number of high quality embryos available for transfer in either, group (P > 0.05). CONCLUSION: The failure to retrieve oocytes from this donor was due to lack of hCG administration. Current pre-ovulatory doses of IM or SQ hCG are adequate to allow appropriate maturation of oocytes for IVF by either administration method, independent of BMI, allowing excellent oocyte quality and IVF outcome. The serum levels described here will allow practitioners to have baseline levels in the event that no, or fewer than expected, oocytes are retrieved.

P-248 Tuesday, October 26, 2010 A NOVEL USE OF CETROTIDE ACETATE IN THE PREVENTION OF OHSS IN OOCYTE DONORS: A PILOT STUDY. F. I. Sharara. Virginia Center for Reproductive Medicine, Reston, VA; Dept of OB/GYN, George Washington University, Washington, DC.

FERTILITY & STERILITYÒ

P-249 Tuesday, October 26, 2010 A NEWER APPROACH FOR OVARIAN STIMULATION IN POOR RESPONDERS UNDERGOING IVF. K. D. E. V. Nayar, A. Agarwal, S. Ved. Akanksha IVF Centre, Mata Chanan Devi Hospital, New Delhi, India; Akanksha IVF Centre, Mata Chanan Devi Hospital, New Delhi, India; Akanksha IVF Centre, Mata Chanan Devi Hospital, New Delhi, India. OBJECTIVE: To evaluate the effect of a combination of step up doses of Letrozole and Gonadotropins in poor responders undergoing IVF. DESIGN: Prospective study from August 2008 to Febuary 2010. MATERIALS AND METHODS: Fifty patients defined as poor responders (< 3 mature follicles and/or E2 < 500 pg/ml) in conventional IVF cycle were included in the study. In next IVF cycle, these patients were administered GnRH agonist for flare effect on CD1-2,followed by Letrozole in step-up doses i.e.2.5 mg tablet given as 1-2-3-4 tabs per day from CD3 to CD6.Inj. FSH/HMG (HP) 300450 IU was started from CD5 and Inj. Cetrorelix from CD7. Variables were compared between previous conventional protocol (control)and new protocol (study). RESULTS: Pregnancy rate was 8% (4/50) in control cycle vs.16% (8/50) in study cycle. Cancellation rate was 5/50 in conventional protocol compared to 2/50 in new protocol. Number of mature follicles were 3.5+ 3 vs. 5.7+2.3. Total FSH/HMG dose required was 4620+1014 IU in control cycle vs. 3946+1160 IU in study cycle.

POOR RESPONDERS–OUTCOME IN CONVENTIONAL IVF PROTOCOL Vs.NEW PROTOCOL

VARIABLE

Pregnancy Rate Cycles cancelled No. of Mature follicles Serum E2 on day of hCG (pgms/ml) Total dose of Gonadotropin(IU)

CONVENTIONAL PROTOCOL

NEW PROTOCOL

(N ¼ 50)

(N¼50)

4/50 (8%) 5/50 3.5  3 824  616

8/50(16%) 2/50 5.7  2.3 786  412

4620  1014

3946  1160

p VALUE

0.178 0.216

S165

CONCLUSION: During early follicular development, rising levels of endogenous gonadotropins stimulate granulosa cells and aromatase enzyme leading to breakthrough estrogen production. Prolonged suppression of aromatase can be accomplished by increasing the dose of aromatase inhibitor in a step up protocol. Along with Gonadotropins, it prolongs the FSH window & in poor responders may decrease cycle cancellation rates and improve pregnancy rates. However larger randomized controlled trials are needed to confirm this. P-250 Tuesday, October 26, 2010 THE EFFECTS OF GnRH ANTAGONIST SINGLE DOSE (0.25MG) ON THE PREVENTION OF OVARIAN HYPERSTIMULATION SYNDROME (OHSS) IN PATIENTS WITH HIGH E2 LEVELS BY COH IN A STANDARD GnRH AGONIST LONG PROTOCOL. Y. Y. Kim, Y. H. Jung, M. H. Kim, J. D. Cho. Obstetrics & Gynecology, Ellemedi Infertility Clinic, Changwon, Gyoung Nam, Republic of Korea. OBJECTIVE: In GnRH antagonist protocol, we have no cases of severe OHSS in GnRH agonist trigger cycles despite very high E2 levels. However, in a standard GnRH agonist long protocol, we have to cancel or coasting for the patient’s safety. The purpose of this study was to confirm the efficient prevention of OHSS by using 0.25mg GnRH antagonist single dose in patients with high E2 levels in a GnRH agonist long protocol. DESIGN: Prospective clinical study. MATERIALS AND METHODS: Patients undergoing IVF-ET with the long GnRH agonist protocol who were identified as high responders based on the peak serum E2 level R 3000pg/ml. 44 patients were in the risk category. Patients who were detected were treated with a GnRH antagonist 0.25mg (Cetrotide) on the day hCG administration or the day before. Recombinant hCG(Ovidrel) 250 mcg was given when following a drop in serum E2 levels. Maximum E2, decreased E2 values and cycle outcome was evaluated. RESULTS: The results are summarized in the table.

P-252 Tuesday, October 26, 2010

TABLE 1. Results

No cycles Age FSH units hMG units Maximum E2 level(pg/ml) Decreased E2 level(pg/ml) E2 decline(%) No. oocytes MII oocytes Endometrium thickness(mm) Clinical PR(%) No. miscarriages(%) Incidence of mild OHSS(%) Incidence of severe OHSS(%)

44 32  4 1276.7  323.9 312.5  277.5 4498.0  606.9* 1556.1  735.3* 65.4  14.7(%) 16.7  7.5 3.6  2.2 10.9  2.2 25/44 (56.0%) 1/25 (4.0%) 1/44(2.0%) 0/44(0.0%)

* P<0.05. Estradiol levels were decreased significantly(65.4  14.7%). However, the number of oocytes retrieval, mature oocytes, endometrium thickness, clinical pregnancy rates were not affected by a fall in serum E2 levels. Mild OHSS appeared in only one patient, we could not detect any OHSS from the rest of the patients. CONCLUSION: We were able to effectively prevent OHSS by only one 0.25mg GnRH antagonist using on the day hCG administration or the day before, while maintaining high pregnancy rates in patients with high E2 levels in a GnRH agonist long protocol.

ART-GENERAL P-251 Tuesday, October 26, 2010 FERTILIZATION RATE AND GOOD QUALITY EMBRYOS WERE SIGNIFICANTLY REDUCED IN IVM-MII (IN VITRO MATURED METAPHASE II) OOCYTES COMPARED WITH SIBLING IN VIVO MATURED MII OOCYTES. E. S. Kim, J. S. Kim, S. H. Lee, Y. S. Ahn, E. H. Kang, I. W. Oh. International Reproduction Center, Seoul Women’s Hospital, Juan 4-dong, Namgu, Inchon, Korea.

S166

Abstracts

OBJECTIVE: Some of the aspirated oocytes from controlled ovarian hyperstimulation are metaphase I (MI) stage. These oocytes could extrude the first polar body within a few hours and could be used for fertilization in intracytoplasmic sperm injection (ICSI) cycles. The aim of the present study was to investigate the fertilization and developmental potential of IVM-MII oocytes. DESIGN: A retrospective study. MATERIALS AND METHODS: 22 ICSI cycles with at least one metaphase I (MI) oocyte were involved in the present study and total 246 oocytes (MII oocyte; 149, MI ooctye; 97) were injected. After ovarian hyperstimulation, oocytes were retrieved and cumulus cells removed immediately. MI oocytes were separated from the sibling in vivo matured MII oocytes and cultured to mature until ICSI. IVM-MII oocytes and sibling in vivo matured MII oocytes were injected between 4 to 6 hrs after oocytes collection. Fertilization rate, cleavage rate, blastomere number of day 3 embryos, and the percentage of good quality embryos were evaluated and compared in both group. Statistical analyses were performed by using Student’s t-test. RESULTS: The fertilization rate of IVM-MII oocytes was significantly lower than that of sibling in vivo matured MII oocytes (63% vs. 89%, P<0.001). Embryo cleavage rates (95% vs. 95%, NS) and the blastomere number of day 3 embryos (6.2  1.3 vs. 6.8  0.9, NS) were similar in two group but the proportion of R8 cell embryos (29% vs. 49%, P<0.05) and the percentage of good quality embryos of day 3 (28% vs. 38%, P<0.05) in IVM-MII oocytes were lower than in vivo matured MII oocytes. CONCLUSION: The significantly reduced fertilization rate and good quality embryos in IVM-MII oocytes suggests that the use of IVM-MII oocytes might be ineffective when enough in vivo matured MII oocytes were obtained, but it might be effective in increasing the number of embryos when few MII oocytes were retrieved.

NATURAL CYCLES YIELD BETTER OUTCOMES THAN HORMONALLY MANIPULATED ARTIFICIAL CYCLES AFTER TRANSFER OF VITRIFIED/WARMED BLASTOCYSTS. E. Chang, M. Kim, J. Han, H. Won, W. Lee, T. Yoon. Fertility Center of CHA Gangnam Medical Center, Department of Obstetrics and Gynecology, CHA University, Seoul, Korea. OBJECTIVE: We aimed to compare the outcomes of transfer cycles involving vitrified/warmed blastocysts and three different endometrial preparation methods. DESIGN: Retrospective study. MATERIALS AND METHODS: In all, 611 women with regular menstruation and normal ovarian function and who underwent vitrified/warmed blastocyst transfer cycles (648 cycles) between January 2007 and December 2009 were recruited. Based on the endometrial preparation method used, transfer cycles were divided into: group 1, natural cycle without human chorionic gonadotropin (hCG) (n ¼ 310); group 2, natural cycle with hCG (n ¼ 134); and group 3, artificial cycle with estrogen and progesterone supplementation (n ¼ 204). RESULTS: Patients in three groups were similar in terms of demographic characteristics and reproductive history. The cycles leading to surplus embryo freezing were also found to be statistically comparable. Implantation rate, clinical pregnancy rates and ongoing pregnancy rates were significantly higher in group 1 than in group 3 (34.9% vs 24.2%: P ¼0.003, 41.9% vs 30.4%: p ¼ 0.008 and 38.1% vs 27.5%: p ¼0.013 ,respectively). However, result between group 1and group 2 were comparable (34.9% vs 33.3%: p ¼ NS, 41.9% vs 41.7%: p ¼ NS, 38.0% vs 38.0%: p ¼ NS, respectively). There were no significant difference between groups in the means of miscarriage rate (group 1: 8.0% vs group 2: 5.2% vs group 3: 6.4%). Other variables found to significantly affect the ongoing pregnancy rate upon multivariate analysis were age at transfer (OR: 0.938, 95% CI: 0.890–0.988, P ¼ 0.016), number of embryos transferred (OR: 1.905, 95% CI: 1.348–2.692, P < 0.001), grade of transferred embryos (OR: 0.572, 95% CI: 0.391– 0.839, P ¼ 0.004), and maximal endometrial thickness (OR: 1.254, 95% CI: 1.143–1.376, P < 0.001). CONCLUSION: The present result suggest that natural cycles with or without hCG yield better outcomes than hormonally manipulated artificial cycles after the transfer of vitrified/warmed blastocysts.

Vol. 94., No. 4, Supplement, September 2010