intrauterine insemination (IUI) therapy

ENDOMETRIUM P-465 Wednesday, October 22, 2014 RATIO OF PROGESTERONE TO NUMBER OF FOLLICLES ON THE DAY OF FINAL OOCYTE MATURATION AS A PROGNOSTIC TOOL IN IN VITRO FERTILIZATION CYCLES. M. Roque,a S. Geber,a M. Sampaio,a F. Guimar~aes,a M. Valle,a M. A. Checa.b aOrigen - Center for Reproductive Medicine, RJ, RJ, Brazil; bDepartment of Obstetrics and Gynecology, Hospital Del Mar, Universitat Autonoma de Barcelona, Barcelona, Catalu~ na, Spain. OBJECTIVE: The main objective of this study was to establish a ratio of progesterone (P) levels to the number of follicles (P/F ratio) on the day of human chorionic gonadotropin (hCG) administration and to evaluate whether this ratio was associated with in vitro fertilization (IVF) outcomes. DESIGN: Prospective observational cohort study. MATERIALS AND METHODS: The study was conducted between January 2012 and June 2013. Accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 145 subjects in each group were necessary to recognize a relative risk (RR) R0.6 as statistically significant. A total of 337 patients submitted to controlled ovarian stimulation with gonadotropin-releasing hormone antagonist protocol and day 3 fresh embryo transfer were included; all had P levels %1.5 ng/mL on hCG day. The P/F ratio was calculated as [P(ng/mL)/number of follicles], measured on the day of final oocyte maturation. The statistical analysis was performed using Student’s t test, the chi-square test, and linear regression models. Receiver operating characteristics (ROC) analysis was conducted to establish the most efficient cut-off value for the P/F ratio to discriminate between successful and unsuccessful IVF outcomes. This value was determined based on an equivalent sensitivity and specificity level, and the highest value of the area under the curve (AUC) was determined. A p value of <0.05 was considered statistically significant. The main outcome measure was ongoing pregnancy rate. RESULTS: Using ROC, we established a cut-off level of 0.075 for the P/F ratio. The sensitivity (71%), specificity (71.1%), and AUC (0.756; 95% CI 0.704–0.807) of the test showed that it was a good prognostic test. Overall results are shown in the table below.

IR, % CPR, n (%) OPR, n (%)

P/F% 0.075 (n¼157)

P/F > 0.075 (n¼178)

RR (95% CI)

p value

32.8 96 (61) 86 (55)

12 34 (19) 32 (18)

0.37 (0.27-0.49) 0.31 (0.23-0.43) 0.33 (0.23-0.46)

<0.001 <0.001 <0.001

CPR: clinical pregnancy rate; IR: implantation rate; OPR: ongoing pregnancy rate; P/F: ratio of progesterone levels to number of follicles CONCLUSION: Even in a selected group of patients without progesterone elevation (P levels %1.5 ng/mL), the P/F ratio is a good prognostic test for IVF outcomes that can correlate the P levels with the ovarian response. It would be better to define a ratio between P levels and ovarian response instead of using a single P level as prognostic tool in IVF cycles. P-466 Wednesday, October 22, 2014 CLINICAL EFFICIENCY OF EMBRYO TRANSFER PERFORMED IN RECEPTIVE VS NON-RECEPTIVE ENDOMETRIUM DIAGNOSED BY THE ENDOMETRIAL RECEPTIVITY ARRAY (ERA) TEST. M Ruiz Alonso,a P. Dıaz-Gimeno,b E. Gomez,a A. Rincon-Bertolın,a Y. Vladimirov,c N. Garrido,b C. Simon.a,b,d aIVIOMICS, Valencia, on Instituto Valenciano de Infertilidad, Valencia University Spain; bFundaci and Instituto Universitario IVI/INCLIVA, Valencia, Spain; cSofia Hospital of Reproductive Medicine, Sofia, Bulgaria; dDepartment of Ob/Gyn, Stanford University School of Medicine, Stanford, CA. OBJECTIVE: To evaluate the clinical efficiency of embryo transfer (ET) performed in receptive (R) vs non-receptive (NR) days by the ERA test [1-3]. DESIGN: Multicenter prospective and retrospective study analyzing the clinical outcome in patients with ET in R vs NR days according to ERA. MATERIALS AND METHODS: We analyzed 2,445 patients with ERA. Embryos were not chromosomally analyzed in these cycles. Clinical

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ASRM Abstracts

outcome was reviewed retrospectively for ET at NR day in the NR group, and prospectively for ET at R day in the R group. We measured implantation rate (IR), pregnancy rate (PR), and ongoing pregnancy rate (OPR). Sensitivity was calculated as the proportion of non-pregnant with ET at NR day, and specificity as pregnancies obtained after ET in R day. Positive and negative predictive values (PPV and NPV) were the ratios of true positives and true negatives respectively. RESULTS: From a total of 2,445 patients analysed, 1877 were R (77%), and 568 were NR (23%). Clinical documented follow-up was possible only in 257 patients (205 R (80%) and 52 NR (20%)). In the R group, PR, OPR and IR were 45%, 60%, and 74% respectively, whereas in the NR group were 13%, 23%, and 0%. Specificity of ERA was 91%, although sensitivity due to the multifactorial condition of the implantation process was 33%. PPV was 0.77 and NPV was 0.60. Clinical outcome and efficiency of ET according ERA diagnosis

Clinical Outcome IR First attempt IR Total attempts PR First attempt PR Total attempts OPR First attempt OPR Total attempts Clinical efficiency True False Sensitivity (TP/TP+FN) Specificity (TN/TN+FP) PPV (TP/TP+FP) NPV (TN/TN+FN)

NR (52)

R (205)

13% (12/90) 10% (17/174) 23% (12/52) 17% (17/100) 0% (0/12) 0% (0/100) Positive (52) 40 12 0.33 0.91 0.77 0.60

45% (161/355) 41% (182/441) 60% (123/205) 55% (140/253) 74% (91/123) 74% (103/140) Negative (205) 123 82

CONCLUSION: Our data demonstrate that embryos transferred in a NR endometrium diagnosed by ERA have lower IR and PR and in this retrospective series never produced a live birth, whereas when a personalized ET is performed in the R endometrium, clinical results were above the standard (45% IR, 60% PR, and 74% OPR). These results highlight the relevance of the endometrial factor and its personalized diagnosis in ART. Supported by: FIVI & IVIOMICS P-467 Wednesday, October 22, 2014 PROGNOSTIC VALUE OF ENDOMETRIALTHICKNESS ON PREGNANCY OUTCOMES OF SUBGROUPS OF INFERTILE WOMEN UNDERGOING LETROZOLE/INTRAUTERINE INSEMINATION (IUI) THERAPY. A. N. Blevins, H. C. L. Bohler, R. K. Hunter. Obstetrics, Gynecology and Women’s Health, University of Louisville School of Medicine, Louisville, KY. OBJECTIVE: To determine whether the incidence and prognostic value of thin endometrium differs among women with different causes of infertility who are undergoing letrozole/IUI therapy. DESIGN: Retrospective cohort. MATERIALS AND METHODS: Infertile women undergoing letrozole/ IUI therapy at our academic medical center between January 01, 2012 and January 31, 2014 were eligible for analysis. Inclusion criteria required performance of a mid-cycle transvaginal ultrasound to assess follicular and endometrial development prior to administration of human chorionic gonadotropin as an ovulation trigger. Exclusion criteria included active smoking status, body mass index greater than 40 kg/m2, use of frozen or donor sperm, and use of in-cycle estrogen supplementation. Charts were retrospectively reviewed, and data regarding patient demographics, medical history, cycle characteristics, and pregnancy outcomes were recorded. Data were analyzed using chi-square, one-sample t-tests, one-way ANOVA, and Mann-Whitney U tests as appropriate, with p values of <0.05 being considered statistically significant. RESULTS: 215 women met criteria for inclusion and were divided into subgroups based on primary diagnoses of polycystic ovarian syndrome (PCOS, 31.1%), male factor (30.2%), unexplained (19.0%), endometriosis (9.3%), diminished ovarian reserve (DOR, 7.4%), or recurrent pregnancy loss (2.8%). The incidence of thin endometrium, defined as less than 7.0mm, was significantly higher in the unexplained group (39.0%) compared to the PCOS (20.8%) and endometriosis (15.0%) groups. Overall pregnancy rates were significantly higher in the PCOS group (25.4%) and lower in the

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DOR group (0.0%). Pregnancy outcomes were not independently predicted by endometrial thickness for any group. Adjusting for lead follicle diameter, women in the unexplained group who became pregnant tended to have thinner endometrial measurements than non-pregnant women from the other groups (p<0.05). CONCLUSION: Thin endometrium is more common among women with unexplained infertility undergoing letrozole/IUI therapy than women with other primary diagnoses. However, endometrial thickness is not a significant predictor of pregnancy outcomes, and women with unexplained infertility and thin endometrial measurements may show improved outcomes compared to other women with similar follicular profiles. P-468 Wednesday, October 22, 2014 IS ENDOMETRIAL THICKNESS ON DAY OF TRANSFER A PREDICTOR OF PREGNANCY RATE IN IVF?. M. Irani,a D. B. Seifer,b K. Melzer,b J. Makarov,b D. Chavkin,b R. V. Grazi.b aOB/Gyn, Maimonides Medical Center, Brooklyn, NY; bOB/Gyn, Division of Reproductive Endocrinology and Infertility, Maimonides Medical Center, Brooklyn, NY. OBJECTIVE: Multiple factors can affect IVF success rate including endometrial receptivity, quality of the embryo and the transfer technique. Some studies have shown that endometrial thickness is a good indicator of endometrial receptivity. The majority of studies have examined the sonographic appearance of the endometrium on the day of hCG administration. The objective of this study was to test the hypothesis that endometrial thickness measured on the day of embryo transfer (EMT-ET) may be more informative of IVF success rates than EMT evaluated on the day of hCG administration (EMT-hCG). DESIGN: A prospective cohort study. MATERIALS AND METHODS: EMT-hCG and EMT-ET were measured by transvaginal sonogram in 101 women (22-48 years old) undergoing IVF between September 2013 and February 2014. Chemical pregnancy, clinical pregnancy, and miscarriage rates were evaluated. T-test and Pearson correlation were used as appropriate. RESULTS: Age was a significant predictor of IVF success rate (p¼0.037). After adjusting for age, fresh cycles were associated with significantly higher clinical pregnancy rates compared to frozen cycles (64.2% versus 41.7%; p¼0.024). The overall rate of miscarriage was 24.5%. There was a trend toward a negative correlation between the rate of miscarriage and EMT-ET (r¼-0.41; p¼0.08) but not with EMT-hCG (p¼0.17). For women younger than 35 years, there was a trend toward a positive correlation between EMT-ET and clinical pregnancy rate (r¼0.71; p¼0.055). In the same age group, EMT-hCG was significantly higher in women who achieved clinical pregnancy (11.1mm+/-0.4 [SEM]) when compared to women who did not (9.5mm+/-0.4; p¼0.02). CONCLUSION: EMT-hCG is a better predictor of clinical pregnancy rate than EMT-ET; however, EMT-ET may be more informative of potential miscarriage than EMT-hCG. P-469 Wednesday, October 22, 2014 BENEFICIAL EFFECT OF LOCAL INJURY TO THE ENDOMETRIUM IN INTRACYTOPLASMIC SPERM INJECTION (ICSI) PATIENTS WITH RECURRENT IMPLANTATION FAILURE. P. J. Buzzi, M. P. Zappacosta, L. Auge, L. Isa, E. Young Obejero, A. Bello. IFER Instituto de Ginecologıa y Fertilidad, Buenos Aires, Argentina. OBJECTIVE: Successful embryo implantation depends on a well-functioning endometrium as well as a normal healthy embryo. Several investigators have suggested that patients with implantation failure (IF) may benefit from mechanical endometrial stimulation performed in the cycle preceding the actual treatment cycle. The aim of this study is to assess the influence of local injury to the endometrium in a selected group of ICSI patients with prior IF. DESIGN: Prospective cohort study. MATERIALS AND METHODS: Patients % 36 years old undergoing IVF between October 2012 –December 2013 with R2 IVF failures and with at least 2 good quality embryos transferred were considered for the analysis. A study group (n¼21) included women who underwent hysteroscopy+biopsy in the cycle preceding the current IVF treatment. Control group (n¼20) underwent a repeat cycle with no intervention. Baseline characteristics of both groups confirmed no different history of IVF-ET failures and a similar performance in the present IVF-ET treatment: mean number of IVF trials 2.2 vs. 2.1 cycles, age 31.8 vs. 31.9 yrs Number of oocytes retrieved: 11.0  6.0 vs 10.4  5.3 Number of good quality Day 3 embryos

FERTILITY & STERILITYÒ

obtained 5.7  3.9 (51.8%) 5.8  4.1 (56.3%).A similar number of good quality Day 3 embryos were transferred into the uterus in the control and in the experimental groups (2.8  1.3 and 2.6  1.3, respectively)T-test and chi square test were used. RESULTS: Hystologycal analysis of the endometrium biopsies showed chronic endometritis in 9.5% (2 /21) of the study population. No other pathologycal findings were reported. . Transfer of embryos in the IVF-ET cycle that immediately followed the endometrium treatment (STUDY GROUP) resulted in a clinical pregnancy rate of 63.2% and a 47.4% ongoing /live birth rate, significantly higher than those obtained in the control group (40% and 25%). CONCLUSION: Local injury to the endometrium prior to controlled ovarian stimulation may considerably improve implantation rates and pregnancy outcomes in patients with implantation failure. P-470 Wednesday, October 22, 2014 THE MIR-16 FAMILY IS HORMONALLY REGULATED IN ENDOMETRIAL STROMAL CELLS AND ALTERED BY SUPEROVULATION IN A MURINE MODEL. S. White P. T. Jimenez. Obstetrics & Gynecology, University of Texas Southwestern Medical Center, Dallas, TX. OBJECTIVE: The purpose of this study was to determine the expression and hormonal regulation of the microRNA (miRNA, miR) -16 family in endometrial stromal cells during embryo implantation. DESIGN: Experimental laboratory study in CD1/ICR mice. MATERIALS AND METHODS: To determine the differential expression of miRNAs before and at the time of implantation, eight week old CD1/ICR female mice were mated with males of known fertility and sacrificed at 0.5 dpc (morning of vaginal plug) or 4.5 dpc. RNA from endometrial stromal cells isolated from the whole uterus at 0.5 dpc and from implantation sites at 4.5 dpc of three mice at each time point underwent microRNA microarray analysis in triplicate. A separate cohort of mice was sacrificed at 0.5, 2.5, 4.5, and 8.5 dpc to confirm the microarray results. To analyze hormonal regulation of the miRNAs, ovariectomized mice were subcutaneously injected with vehicle (sesame oil) or 1 mg estradiol-17b for 48 hr. Another cohort of mice was either injected with 10 IU PMSG followed by 10 IU hCG 48 hrs later to induce superovulation or allowed to ovulate spontaneously. Endometrial stromal cells were isolated. After RNA isolation, RT-qPCR was performed for the three members of the miR-16 family, miR-15a, -15b, and -16, as well as for their predicted targets, Indian Hedgehog (IHH), HOXA10, and PTCH1. GraphPad Prism 5 was used for statistical analysis. P value < 0.05 was considered significant. RESULTS: In the miRNA array, miR-16 was significantly downregulated at 4.5 dpc versus 0.5 dpc; this was confirmed by RT-qPCR. The miR-16 family members, miR-15a and -15b were also decreased at 4.5 dpc. The putative targets of the miR-16 family, IHH, HOXA10 and PTCH1, were significantly, but transiently upregulated at 2.5 dpc. miR-16 family members were increased with estradiol treatment in the ovariectomized mice. On the other hand, IHH and PTCH1 were significantly downregulated following 48 hr of estradiol treatment. Superovulation also increased miR-16 family expression and downregulated the predicted target IHH. CONCLUSION: The miR-16 family is gradually downregulated following ovulation with a maximal decrease at implantation (4.5 dpc). The coordinate increase in the miR-16 targets may serve an important role in embryo implantation. By contrast, superovulation or estradiol treatment caused rapid and profound upregulation of miR-16 family expression. Our findings suggest that aberrant induction of the miR-16 family by estradiol treatment or superovulation may alter the expression of its targets necessary for successful implantation. Supported by: K12 HD000849-25 (PTJ). P-471 Wednesday, October 22, 2014 HOMEOBOX TRANSCRIPTION FACTOR MSX1 IS REDUCED IN HUMAN ENDOMETRIAL BIOPSIES OF WOMEN FROM INFERTILE COUPLES. A. D. Bolnick,a J. M. Bolnick,a B. A. Kilburn,a J. Oakes,a J. Dai,a M. P. Diamond,b S. K. Dey,c D. R. Armant.a aObstetrics and Gynecology, Wayne State University, Detroit, MI; bObstetrics and Gynecology, Georgia Regents University, Augusta, GA; cDivision of Reproductive Sciences, Cincinnati Children’s Hospital, Cincinnati, OH. OBJECTIVE: To evaluate MSX1 protein expression in human endometrial biopsies from fertile and infertile patients across the secretory phase of the menstrual cycle.

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