Endometrial fluid transcriptomics as a new non-invasive diagnostic method of uterine receptivity

of Child Health and Human Development (NICHD) Program. This work is also supported in part by the Burnett Research Fund. REPRODUCTIVE ENDOCRINOLOGY AND GYNECOLOGY O-115 Tuesday, October 31, 2017 11:00 AM ENDOMETRIAL FLUID TRANSCRIPTOMICS AS A NEW NON-INVASIVE DIAGNOSTIC METHOD OF UTERINE RECEPTIVITY. F. Vilella,a D. Bolumar,b D. Blesa,b M. Clemente-Ciscar,b A. Rincon,b D. Valbuena,b C. Simon.c aIgenomix / INCLIVA / Stanford University, Valencia, Spain; b Igenomix, Valencia, Spain; cObs/Gyn Dept., Valencia University/INCLIVA, Igenomix, Ob/Gyn Dept., Stanford University Ob/Gyn Dept., Baylor College of Medicine, Valencia, Spain. OBJECTIVE: The diagnosis of endometrial receptivity is being used as a clinical test to manage the endometrial factor in patients with implantation failure. Yet, this procedure is invasive and it delays personalized embryo transfer (pET) until the next cycle. We aim to develop a non-invasive approach based on the analysis of the transcriptomic signature in the endometrial fluid (EF). DESIGN: Fifty-six patients with implantation failure that underwent Endometrial Receptivity Analysis (ERA) test leading to successful pET, and the transcriptomic signature of their paired EF samples was analyzed blindly to compare receptivity diagnoses. MATERIALS AND METHODS: EF was aspirated immediately before endometrial biopsy using a flexible catheter (Wallace, SMI) inserted into the uterine cavity obtaining 10-20 ml of EF per patient that were snap frozen and stored. RNA was extracted using RNeasy mini-kit (Qiagen) and qualitychecked using Fragment Analyzer (AATI, USA). Gene expression was analysed using Ion AmpliSeq RNA for ERA custom panel in an Ion S5 system (Life Tech, USA) coupled to a computational predictor. RESULTS: Paired samples of EF and endometrial biopsy from the same patients (n¼56) were analysed separately. In 13 EF samples (23.2%) RNA quantity and/or quality were poor (mean: concentration 28.5 ng/ml; RIN 1.75). The remaining 43 EFs (76.8%) with mean concentration of 108.3 ng/ml and RIN of 4.3, generated good-quality libraries for sequencing. These 43 EFs yielded results concordant with their paired endometrial biopsies analysed by ERA: 33 were confirmed receptive (76.7%), 7 pre-receptive (16.3%), and 3 post-receptive (7.0%). EF testing resulted in 100% sensitivity and specificity with no false positive or negatives vs ERA. CONCLUSIONS: Transcriptomic profiling of EF samples gave high sensitivity and specificity vs the invasive test. Technical improvement in the collection and shipment of EF is necessary to avoid RNA degradation. Thus, EF offers a non-invasive alternative to diagnose endometrial receptivity for personalized embryo transfer without a need for endometrial biopsy.

O-116 Tuesday, October 31, 2017 11:15 AM INTERGENERATIONAL EFFECTS OF CHEMOTHERAPY ON FECUNDITY: BOTH MALE AND FEMALE CHILDREN BORN TO WOMEN EXPOSED TO CHEMOTHERAPY HAVE FEWER CHILDREN. B. Patel,a H. Meeks,b Y. Wan,b E. B. Johnstone,a M. Glenn,c K. Smith,b J. M. Hotaling.d aObstetrics & Gynecology, University of Utah, Salt Lake City, UT; bHuntsman Cancer Institute, Salt Lake City, UT; cHematology and Hematologic Malignancies, Huntsman Cancer Institute, Salt Lake City, UT; dUniversity of Utah, Salt Lake City, UT. OBJECTIVE: To determine whether fecundity is decreased in children of women exposed to chemotherapy. DESIGN: This is a retrospective cohort study utilizing the Utah Population database (UPDB), a comprehensive population-based resource that links birth, medical, death and cancer records for individuals in Utah. Three generations were used for analysis. The exposed generation (F0) comprises of women from birth to age 45 with a history of cancer able to produce offspring (F1 generation) after chemotherapy exposure. The number of offspring (F2 generation) born to this F1 generation was compared first to matched, unexposed members of the general population and secondly to unexposed cousins. MATERIALS AND METHODS: Number of live births to the F1 generation was compared with conditional Poisson regression models (regression

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ASRM Abstracts

coefficient, 95% confidence interval, p-value). The unexposed general population was 10:1 matched to exposed F1 children by both F0 and F1 gender and birth year. The unexposed cousins were matched by F1 birth year (+/- 5 years). RESULTS: There were 132 individuals in the exposed F1 generation with 59 females and 73 males. The unexposed general population comprised 1278 subjects with 570 females and 708 males. The unexposed cousins had 146 individuals with 78 females and 68 males. The exposed F1 individuals had 77.2% fewer children (1-exp(-1.48); -2.51 to -0.70; p ¼ 0.001) relative to the unexposed in the general population. F1 males had 86.9% fewer children (1-exp(-2.03); -4.91 to -0.51; p ¼ 0.0045) and F1 females had 70.5% fewer children (1-exp(-1.22); -2.40 to -0.36; p ¼ 0.016). When compared to their unexposed cousins, the F1 generation had 74.3% fewer children (1-exp(1.36); -2.82 to -0.29; p ¼ 0.029). CONCLUSIONS: The sons and daughters (F1 generation) of chemotherapy-exposed women (F0 generation) have fewer live births when compared to both matched, unexposed general population and unexposed cousin comparison groups, an association that may be stronger among male offspring. Chemotherapy given to women may have intergenerational effects on fertility. Further research should evaluate the germ line and gametes of children born to mothers exposed to chemotherapy for genetic and epigenetic changes. O-117 Tuesday, October 31, 2017 11:30 AM PRE-CONCEPTION ALLOSTATIC LOAD IS NOT ASSOCIATED WITH DIMINISHED OVARIAN RESERVE AMONG WOMEN WITH UNEXPLAINED INFERTILITY. W. Vitek,a E. S. Barrett,b O. Mbowe,c S. W. Thurston,c N. Santoro,d M. P. Diamond.e aUniversity of Rochester Medical Center, Rochester, NY; bDepartment of Epidemiology, Rutgers University School of Public Health, Piscataway, NJ; cDepartment of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY; dObstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO; efor the NICHD Cooperative Reproductive Medicine Network, Augusta, GA. OBJECTIVE: Gestational allostatic load (AL), a composite measure of chronic physiological stress in pregnancy, is associated with pregnancy complications. It is unclear if chronic physiological stress impacts ovarian reserve. Our objective is to determine if preconception AL is associated with diminished ovarian reserve. DESIGN: A secondary data analysis based on data from 837 women who participated in AMIGOS, a multi-center, randomized clinical trial of superovulation/insemination for unexplained infertility. MATERIALS AND METHODS: Women with unexplained infertility (ages 18-40) were enrolled and at baseline, biological and anthropometric measures were collected. One- and two-tailed AL scores were calculated as a composite of the following baseline variables: body mass index, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, dehydroepiandrosterone sulfate, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, C-reactive protein, and HOMA score. Participants received clomiphene, letrozole or gonadotropin with IUI for up to four cycles and if they conceived, were followed throughout pregnancy. We fit multi-variable logistic regression models examining AL in relation to day 3 FSH, antimullerian hormone and antral follicle count. RESULTS: Adjusting for age and tobacco, in one-tailed and two tailed analyses, AL was not associated with AMH and AFC, though AL was negatively associated with FSH.

Table. Linear regression models examining allostatic load scores in relation to measures of ovarian reserve in AMIGOS1.

One-tailed allostatic load Two-tailed allostatic load Ovarian reserve measure2 AMH AFC FSH

n

Point estimate (p-value)

Point estimate (p-value)

836 -0.016 (0.26) 826 0.009 (0.35) 837 -0.019 (0.0007)*

1 adjusted for age and smoking status distributed and were log transformed.

0.004 (0.85) 0.003 (0.82) -0.005 (0.55) 2

All measures were non-normally

Vol. 108, No. 3, Supplement, September 2017