Efficacy of clomiphene citrate supplementation to conventional GnRH antagonist protocols in poor responders undergoing assisted reproductive technology - a prospective randomized trial

DESIGN: A pilot study was performed in university-affiliated hospital. MATERIALS AND METHODS: 38 women were collected according to Bologna criteria. Mild ovarian stimulation was initiated with letrozole, clomiphene and a low dose of hMG. After the first ovum pick-up (OPU), hMG and letrozole were administrated to stimulate follicle development,second OPU was performed when dominant follicles matured. All viable embryos were extracted and cryopreserved for later transfer.The primary outcome measured was the number of oocytes retrieved. RESULTS: The results showed that the number of oocytes retrieved was 1.7
1.0 in stage one and 3.5
3.2 in stage two (P<0.05).

The cycle characteristics in double stimulations in patients with POR

cycle characteristics

first OPU (N¼38)

Second OPU (n¼30)

Stimulation duration (days) 10.2
2.4 10.8
3.1 no of follicles >10 mm 1.9
0.9 4.3
2.8 on trigger dat no of follicles >14 mm 1.5
0.6 3.5
2.0 on trigger day no of oocytes retrieved 1.7
1.0 3.5
3.2 no of MII oocytes 1.4
1.0 2.7
2.7 no of fertilized oocytes 1.0
1.0 2.1
2.5 no of cleaved embryos 1.0
1.0 2.0v2.4 no of top-quality embryos 0.7
1.0 1.2
1.5 no of viable embryos 0.9
1.0 1.3
1.4 mature oocyte rate (%) 85.5%(53/62) 78.1%(82/105) fertilization rate (%) 69.8%(37/53) 75.6%(62/82) cancel rate (%) 52.6%(20/38) 43.3%(13/30)

P VALUE 0.265 <0.001

Reproductive outcome in poor responders undergoing IVF/ ICSI in GnRH antagonist protocol

Group I Group II (N¼34) r-LH (N¼30) + r-FSH hp-HMG No. of oocyte 3.32
1.27 retrieved (Mean
SD) Implantation Rate(%) 13.5(10/74) Clinical Pregnancy 26.5 (9/34) Rate (%) Ongoing Pregnancy 17.6 (6/34) Rate (%)

Group III (N¼62) r-FSH

3.17
1.46 3.85
1.38

P Value 0.057

22.6(14/62) 15.0(21/140) 0.303 26.7 (8/30) 30.6 (19/62) 0.879 20.0 (6/30) 24.2 (15/62)

0.738

<0.001 0.001 0.008 0.019 0.045 0.155 0.171 0.167 0.292 0.303

Out of double stimulation, a total of 167oocytes were collected and 68.4% (26/38) succeeded in producing 1-6 viable embryos cryopreserved for later transfer. 21 women underwent 23 FETs, resulting13clinical pregnancies. The implantation rate per transfer was 36.6% (15/41). CONCLUSION: The study Supported that double ovarian stimulations in a same menstrual cycle provided more opportunities to retrieve oocytes in poor responders. The stimulation can start at the luteal phase and get more oocytes in a short period of time, which will be a new hope for POR and newly diagnosed cancer patients needing fertility preservation. Supported by: This study is funded by National Nature Science Foundation of China (grant numbers: 31071275, 81270749 and 31101070) and Natural Science Foundation of Shanghai (grant number. 11411950105). O-189 Tuesday, October 21, 2014 04:45 PM DOES EXOGENOUS LH SUPPLEMENTATION IMPROVE REPRODUCTIVE OUTCOME IN POOR RESPONDER WOMEN UNDERGOING IVF/ICSI IN GNRH ANTAGONIST PROTOCOL. K. D. E. V. Nayar, S. Jain, G. Jain, S. Chulet, G. Kant. Akanksha IVF Centre, New Delhi, India. OBJECTIVE: To compare the efficacy of supplementing r-LH with r-FSH or only highly purified HMG or r-FSH alone in GnRH antagonist protocol, in improving the ovarian response and pregnancy rate in poor responder women undergoing IVF/ICSI. DESIGN: A prospective observational study from October 2012 to September 2013. MATERIALS AND METHODS: 126 poor responder women were included according to Bologna criteria (ESHRE 2010).These women received ovarian stimulation in a standard GnRH antagonist protocol and divided into three groups: Group I (n¼34) received r-LH (75 IU/day) from the start of stimulation along with r-FSH (225 IU/day), group II (n¼30) was stimulated with hp- HMG (300 IU/day) and group III (n¼62) received r-FSH (300 IU/day). Primary outcome measure was clinical pregnancy rate. Secondary outcome was number of oocytes retrieved, implantation rate and ongoing pregnancy rate. Statistical analysis was performed using ANOVA for comparing continuous variables and Chi Square test for categorical variables. The statistical significance was evaluated by calculating the P value. A two-sided P-value < 0.05 was considered significant. RESULTS: There were no demographic or clinical differences between the groups. Mean number of oocytes retrieved were higher in group III,

FERTILITY & STERILITYÒ

though not significant. The difference between clinical pregnancy rate, implantation rate and ongoing pregnancy rate was not statistically significant

CONCLUSION: Our study and the available evidence so far do not demonstrate any beneficial effect of exogenous LH supplementation to the standard GnRH antagonist stimulation protocol in poor responder women undergoing IVF/ICSI. We have compared three different stimulation protocols but number of subjects was insufficient to demonstrate any significant difference. Further larger RCTs are required. O-190 Tuesday, October 21, 2014 05:00 PM EFFICACY OF CLOMIPHENE CITRATE SUPPLEMENTATION TO CONVENTIONAL GNRH ANTAGONIST PROTOCOLS IN POOR RESPONDERS UNDERGOING ASSISTED REPRODUCTIVE TECHNOLOGY - A PROSPECTIVE RANDOMIZED TRIAL. A. Fujimoto,a M. Harada,b T. Hirata,b Y. Osuga,b T. Fujii.b a Obstetrics and Gynecology, Sanraku Hospital, Chiyoda-ku, Tokyo, Japan; b Obstetrics and Gynecology, University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan. OBJECTIVE: To evaluate the effect of clomiphene citrate addition to gonadotropin releasing hormone (GnRH) antagonist protocols in poor responders undergoing assisted reproductive technology (ART). DESIGN: A prospective randomized controlled study was conducted on poor responders undergoing ART treatment in IVF Center of University of Tokyo Hospital. This study was approved by the Intutional Review Board. MATERIALS AND METHODS: Among the patients who visited IVF Center of University of Tokyo Hospital for the purpose of ART, those who fitted at least one of the following inclusion criteria and who fitted no exclusion criteria were eligible for this study. Inclusion criteria: 1. elevated basal serum FSH levels (>10mIU/ml) 2. antral follicle counts <7 in early follicular phase 3. previous poor response to ART treatment (<5 retrieved oocytes) Exclusion criteria: 1.over the age of 45 2. those who underwent oocyte retrieval cycles more than 3 times The patients who gave a written informed consent form were allocated into two groups. In group 1 (n¼44), controlled ovarian stimulation was initiated on day3 with 5 days of clomiphene citrate (2 tabs daily), followed by human menopausal gonadotropin (hMG) administration. After leading follicle diameter reached 14mm, GnRH antagonist Ganirelix was administered in addtion to hMG. In group 2 (n¼45), hMG administration was started on day3, followed by combination with Ganirelix in the same way. RESULTS: There were no significant differences in estradiol levels on day of hCG, number of growing follicles, number of retrieved oocytes and fertilization rate between the two groups. In group 1, total hMG dose and cost for controlled ovarian stimulation were significantly less than those in group 2. Embryo transfer cancellation rate per oocyte retrieval was significantly higher in group 1 (28.6% vs. 2.5%), which was mainly due to inadequate endometrial preparation. However, live-birth rate per fresh embryo transfer and cumulative live-birth rate per patient in the two groups were comparable (9.1% vs. 11.1% and 20.5% vs. 17.8%, respectively). CONCLUSION: The addition of clomiphene citrate in GnRH antagonist protocols could not improve clinical outcomes of ART in poor responders, but it could reduce hMG dose and cost for controlled ovarian stimulation.

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