prognostic value of endometrial thickness on pregnancy outcomes of subgroups of infertile women...

ENDOMETRIUM

P-465 Wednesday, October 22, 2014

RATIO OF PROGESTERONE TO NUMBER OF FOLLICLES ONTHE DAYOF FINAL OOCYTEMATURATION AS A PROGNOSTICTOOL 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 Obstet-rics 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 ofprogesterone (P) levels to the number of follicles (P/F ratio) on the day of hu-man chorionic gonadotropin (hCG) administration and to evaluate whetherthis 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 betarisk of 0.2 in a two-sided test, 145 subjects in each group were necessaryto recognize a relative risk (RR) R0.6 as statistically significant. A total of337 patients submitted to controlled ovarian stimulation with gonado-tropin-releasing hormone antagonist protocol and day 3 fresh embryo trans-fer were included; all had P levels %1.5 ng/mL on hCG day. The P/F ratiowas calculated as [P(ng/mL)/number of follicles], measured on the day offinal oocyte maturation. The statistical analysis was performed using Stu-dent’s t test, the chi-square test, and linear regression models. Receiver oper-ating characteristics (ROC) analysis was conducted to establish the mostefficient cut-off value for the P/F ratio to discriminate between successfuland unsuccessful IVF outcomes. This value was determined based on anequivalent sensitivity and specificity level, and the highest value of thearea under the curve (AUC) was determined. A p value of<0.05 was consid-ered statistically significant. The main outcome measure was ongoing preg-nancy rate.

RESULTS: Using ROC, we established a cut-off level of 0.075 for the P/Fratio. The sensitivity (71%), specificity (71.1%), and AUC (0.756; 95% CI0.704–0.807) of the test showed that it was a good prognostic test. Overallresults are shown in the table below.

P/F% 0.075 P/F > 0.075 RR

e
292 ASR
(n¼157)

M Abstracts

(n¼178)
(95% CI) p value
IR, %
32.8 12 0.37 (0.27-0.49) <0.001 CPR, n (%) 96 (61) 34 (19) 0.31 (0.23-0.43) <0.001 OPR, n (%) 86 (55) 32 (18) 0.33 (0.23-0.46) <0.001
CPR: clinical pregnancy rate; IR: implantation rate; OPR: ongoing preg-nancy rate; P/F: ratio of progesterone levels to number of follicles

CONCLUSION: Even in a selected group of patients without progesteroneelevation (P levels %1.5 ng/mL), the P/F ratio is a good prognostic test forIVF outcomes that can correlate the P levels with the ovarian response. Itwould be better to define a ratio between P levels and ovarian responseinstead of using a single P level as prognostic tool in IVF cycles.


CLINICAL EFFICIENCY OF EMBRYO TRANSFER PERFORMEDIN RECEPTIVE VS NON-RECEPTIVE ENDOMETRIUM DIAG-NOSED BY THE ENDOMETRIAL RECEPTIVITY ARRAY (ERA)TEST. M Ruiz Alonso,a P. D�ıaz-Gimeno,b E. G�omez,a A. Rinc�on-Ber-tol�ın,a Y. Vladimirov,c N. Garrido,b C. Sim�on.a,b,d aIVIOMICS, Valencia,Spain; bFundaci�on Instituto Valenciano de Infertilidad, Valencia Universityand Instituto Universitario IVI/INCLIVA, Valencia, Spain; cSofia Hospitalof Reproductive Medicine, Sofia, Bulgaria; dDepartment of Ob/Gyn, Stan-ford 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 theclinical 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

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 implantationrate (IR), pregnancy rate (PR), and ongoing pregnancy rate (OPR). Sensi-tivity 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 nega-tive predictive values (PPV and NPV) were the ratios of true positives andtrue 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 possibleonly 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 groupwere 13%, 23%, and 0%. Specificity of ERAwas 91%, although sensitivitydue to the multifactorial condition of the implantation process was 33%. PPVwas 0.77 and NPV was 0.60.

Clinical outcome and efficiency of ET according ERA diagnosis

Clinical Outcome NR (52) R (205)

Vol. 102, N
o. 3, Supplement,
IR First attempt
13% (12/90) 45% (161/355) IR Total attempts 10% (17/174) 41% (182/441) PR First attempt 23% (12/52) 60% (123/205) PR Total attempts 17% (17/100) 55% (140/253) OPR First attempt 0% (0/12) 74% (91/123) OPR Total attempts 0% (0/100) 74% (103/140) Clinical efficiency Positive (52) Negative (205) True 40 123 False 12 82 Sensitivity (TP/TP+FN) 0.33 Specificity (TN/TN+FP) 0.91 PPV (TP/TP+FP) 0.77 NPV (TN/TN+FN) 0.60
CONCLUSION: Our data demonstrate that embryos transferred in a NRendometrium diagnosed by ERA have lower IR and PR and in this retrospec-tive series never produced a live birth, whereas when a personalized ET isperformed in the R endometrium, clinical results were above the standard(45% IR, 60% PR, and 74% OPR). These results highlight the relevance ofthe endometrial factor and its personalized diagnosis in ART.Supported by: FIVI & IVIOMICS


PROGNOSTICVALUEOFENDOMETRIALTHICKNESSONPREG-NANCY OUTCOMES OF SUBGROUPS OF INFERTILE WOMENUNDERGOING LETROZOLE/INTRAUTERINE INSEMINATION(IUI) THERAPY. A. N. Blevins, H. C. L. Bohler, R. K. Hunter. Obstet-rics, Gynecology and Women’s Health, University of Louisville School ofMedicine, Louisville, KY.

OBJECTIVE: To determinewhether the incidence and prognostic value ofthin endometrium differs among women with different causes of infertilitywho 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 andJanuary 31, 2014 were eligible for analysis. Inclusion criteria required per-formance of a mid-cycle transvaginal ultrasound to assess follicular andendometrial development prior to administration of human chorionic gonad-otropin as an ovulation trigger. Exclusion criteria included active smokingstatus, body mass index greater than 40 kg/m2, use of frozen or donor sperm,and use of in-cycle estrogen supplementation. Charts were retrospectively re-viewed, and data regarding patient demographics, medical history, cyclecharacteristics, and pregnancy outcomes were recorded. Data were analyzedusing chi-square, one-sample t-tests, one-way ANOVA, and Mann-WhitneyU tests as appropriate, with p values of <0.05 being considered statisticallysignificant.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 pregnancyloss (2.8%). The incidence of thin endometrium, defined as less than7.0mm, was significantly higher in the unexplained group (39.0%) comparedto the PCOS (20.8%) and endometriosis (15.0%) groups. Overall pregnancyrates were significantly higher in the PCOS group (25.4%) and lower in the

September 2014

DOR group (0.0%). Pregnancy outcomes were not independently predictedby endometrial thickness for any group. Adjusting for lead follicle diameter,women in the unexplained group who became pregnant tended to havethinner endometrial measurements than non-pregnant women from the othergroups (p<0.05).

CONCLUSION: Thin endometrium is more common among women withunexplained infertility undergoing letrozole/IUI therapy than women withother primary diagnoses. However, endometrial thickness is not a significantpredictor of pregnancy outcomes, and women with unexplained infertilityand thin endometrial measurements may show improved outcomes comparedto other women with similar follicular profiles.


IS ENDOMETRIAL THICKNESS ON DAY OF TRANSFER A PRE-DICTOR 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, MaimonidesMedical Center, Brooklyn, NY; bOB/Gyn, Division of Reproductive Endocri-nology and Infertility, Maimonides Medical Center, Brooklyn, NY.

OBJECTIVE: Multiple factors can affect IVF success rate including endo-metrial receptivity, quality of the embryo and the transfer technique. Somestudies have shown that endometrial thickness is a good indicator of endome-trial receptivity. The majority of studies have examined the sonographicappearance of the endometrium on the day of hCG administration. The objec-tive of this study was to test the hypothesis that endometrial thicknessmeasured on the day of embryo transfer (EMT-ET) may be more informativeof IVF success rates than EMT evaluated on the day of hCG administration(EMT-hCG).

DESIGN: A prospective cohort study.MATERIALS ANDMETHODS: EMT-hCG and EMT-ETwere measured

by transvaginal sonogram in 101 women (22-48 years old) undergoing IVFbetween September 2013 and February 2014. Chemical pregnancy, clinicalpregnancy, and miscarriage rates were evaluated. T-test and Pearson correla-tion 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 higherclinical 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 to-ward 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 youngerthan 35 years, there was a trend toward a positive correlation betweenEMT-ET and clinical pregnancy rate (r¼0.71; p¼0.055). In the same agegroup, EMT-hCG was significantly higher in women who achieved clinicalpregnancy (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 ratethan EMT-ET; however, EMT-ET may be more informative of potentialmiscarriage than EMT-hCG.


BENEFICIALEFFECTOFLOCALINJURYTOTHEENDOMETRIUMIN INTRACYTOPLASMIC SPERM INJECTION (ICSI) PATIENTSWITH RECURRENT IMPLANTATION FAILURE. P. J. Buzzi,M. P. Zappacosta, L. Auge, L. Isa, E. Young Obejero, A. Bello. IFER Institutode Ginecolog�ıa y Fertilidad, Buenos Aires, Argentina.

OBJECTIVE: Successful embryo implantation depends on a well-func-tioning endometrium as well as a normal healthy embryo. Several investiga-tors have suggested that patients with implantation failure (IF) may benefitfrom mechanical endometrial stimulation performed in the cycle precedingthe actual treatment cycle. The aim of this study is to assess the influenceof local injury to the endometrium in a selected group of ICSI patientswith prior IF.

DESIGN: Prospective cohort study.MATERIALS ANDMETHODS: Patients% 36 years old undergoing IVF

between October 2012 –December 2013 with R2 IVF failures and with atleast 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 characteris-tics of both groups confirmed no different history of IVF-ET failures and asimilar performance in the present IVF-ET treatment: mean number ofIVF trials 2.2 vs. 2.1 cycles, age 31.8 vs. 31.9 yrs Number of oocytesretrieved: 11.0 � 6.0 vs 10.4 � 5.3 Number of good quality Day 3 embryos

FERTILITY & STERILITY�

obtained 5.7 � 3.9 (51.8%) 5.8 � 4.1 (56.3%).A similar number of goodquality Day 3 embryos were transferred into the uterus in the control andin the experimental groups (2.8 � 1.3 and 2.6 � 1.3, respectively)T-testand 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 path-ologycal findings were reported. . Transfer of embryos in the IVF-ET cyclethat immediately followed the endometrium treatment (STUDYGROUP) re-sulted in a clinical pregnancy rate of 63.2% and a 47.4% ongoing /live birthrate, significantly higher than those obtained in the control group (40% and25%).CONCLUSION: Local injury to the endometrium prior to controlled

ovarian stimulation may considerably improve implantation rates and preg-nancy outcomes in patients with implantation failure.


THE MIR-16 FAMILY IS HORMONALLY REGULATED IN ENDO-METRIAL STROMAL CELLS AND ALTERED BY SUPEROVULA-TION 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 expressionand hormonal regulation of the microRNA (miRNA, miR) -16 family inendometrial stromal cells during embryo implantation.DESIGN: Experimental laboratory study in CD1/ICR mice.MATERIALS ANDMETHODS: To determine the differential expression

of miRNAs before and at the time of implantation, eight week old CD1/ICRfemale mice were mated with males of known fertility and sacrificed at 0.5dpc (morning of vaginal plug) or 4.5 dpc. RNA from endometrial stromalcells isolated from the whole uterus at 0.5 dpc and from implantation sitesat 4.5 dpc of three mice at each time point underwent microRNA microarrayanalysis 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 regula-tion of the miRNAs, ovariectomized mice were subcutaneously injectedwith vehicle (sesame oil) or 1 mg estradiol-17b for 48 hr. Another cohortof mice was either injected with 10 IU PMSG followed by 10 IU hCG 48hrs later to induce superovulation or allowed to ovulate spontaneously. Endo-metrial stromal cells were isolated. After RNA isolation, RT-qPCR was per-formed 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, andPTCH1. GraphPad Prism 5 was used for statistical analysis. P value < 0.05was 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 fam-ily members, miR-15a and -15b were also decreased at 4.5 dpc. The putativetargets of the miR-16 family, IHH, HOXA10 and PTCH1, were significantly,but transiently upregulated at 2.5 dpc. miR-16 family members wereincreased with estradiol treatment in the ovariectomized mice. On the otherhand, IHH and PTCH1 were significantly downregulated following 48 hr ofestradiol treatment. Superovulation also increased miR-16 family expressionand 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 rolein embryo implantation. By contrast, superovulation or estradiol treatmentcaused rapid and profound upregulation of miR-16 family expression. Ourfindings suggest that aberrant induction of the miR-16 family by estradioltreatment or superovulation may alter the expression of its targets necessaryfor successful implantation.Supported by: K12 HD000849-25 (PTJ).


HOMEOBOX TRANSCRIPTION FACTOR MSX1 IS REDUCED INHUMAN ENDOMETRIAL BIOPSIES OF WOMEN FROM INFER-TILE 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 aObstetricsand Gynecology, Wayne State University, Detroit, MI; bObstetrics and Gyne-cology, Georgia Regents University, Augusta, GA; cDivision of ReproductiveSciences, Cincinnati Children’s Hospital, Cincinnati, OH.

OBJECTIVE: To evaluate MSX1 protein expression in human endome-trial biopsies from fertile and infertile patients across the secretory phaseof the menstrual cycle.

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prognostic value of endometrial thickness on pregnancy outcomes of subgroups of infertile women...

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