Prediction of a reciprocal translocation by preimplantation genetic screening (PGS)

POSTER PRESENTATIONS P-1 PREDICTION OF A RECIPROCAL TRANSLOCATION BY PREIMPLANTATION GENETIC SCREENING (PGS). Alyssa Snider, Refik Kayali, Cengiz Cinnioglu, Tristan Darvin, Gary Harton. BACKGROUND: An estimated 1/500 individuals carry a balanced chromosome rearrangement, and this frequency may be as high as 1/100 in the IVF patient population. Balanced translocations typically have no impact on an individual’s health; however, the transmission of unbalanced translocations can cause infertility and miscarriage. Karyotyping is routinely performed for a patient with a history of multiple pregnancy losses, but is not part of the standard workup for the unselected infertility patient. We hypothesize that patterns of segmental aneuploidies found in PGS results can predict a maternal or paternal balanced translocation. OBJECTIVE: The objective of the study is to determine the ability of PGS to predict a previously unknown balanced translocation in one member of the reproductive couple through pattern detection in a cohort of embryos tested. MATERIALS AND METHODS: Translocation patterns were identified by observing two or more similar terminal deletions or duplications, with or without complete aneuploidy of that chromosome, in the cohort of embryos tested, using either aCGH or NGS. PGS is unable to predict a translocation when the size of terminal segments is below the resolution of PGS and when the number of embryos tested is too small to allow observable patterns to emerge. Inversion and Robertsonian translocation predictions were not included in this study. We notified the IVF center of the suspected translocation and recommended chromosome analysis. We requested clinical follow up to know if the suspected balanced translocation was confirmed by karyotype. RESULT(S): Fourteen PGS cases over a two-year span had patterns predictive of a reciprocal maternal or paternal balanced translocation. The average cohort size in which a pattern was detected was 7.7 embryos, and the smallest cohort size was 3. Of the fourteen cases, six had karyotyping that confirmed the suspected translocation in one member of the reproductive couple. One patient declined karyotyping, and five patients were lost to follow up. The remaining two cases were recently identified, and outcomes are pending. Therefore, in all cases in which the recommended karyotyping was performed, the suspected balanced translocation was confirmed. CONCLUSION(S): Our results show that PGS patterns of terminal segmental aneuploidy are highly predictive of a maternal or paternal reciprocal translocation. Future studies will develop criteria to also identify patterns predictive of Robertsonian translocations and inversions. We will standardize prediction criteria across each of our national and international laboratories and evaluate the frequency of chromosome rearrangement predictions in PGS cases. Confirming a maternal or paternal chromosome rearrangement can shed light on the cause of infertility and/or previous miscarriages. In addition, a newly identified translocation may have implications for past PGS cycles, would alter the estimated aneuploidy rate in future PGS cycles, and may affect the decision to use a gamete donor. Balanced translocations can be inherited and therefore may impact other family members in their reproductive years. Our data underscore the importance of follow up testing and counseling by a licensed genetic counselor when PGS predicts a balanced translocation. FINANCIAL SUPPORT: None. All authors are employees of Igenomix USA. References: None.

to embryo transfer show decreased implantation rates. Furthermore, the clinical pregnancy rate following assisted reproductive technology is significantly lower among patients with fluid in the endometrial cavity. Often clinicians identify fluid in the cavity just prior to initiation of progesterone in frozen embryo transfers (FETs). Given the concern over this finding, these cycles are either canceled or allowed to progress and reevaluated before transfer. There are currently no data examining this unique group of patients. OBJECTIVE: This study seeks to determine if fluid present in the endometrial cavity that resolves with progesterone administration still impacts pregnancy outcomes. MATERIALS AND METHODS: FETs from 2001-2016 at a single IVF center were retrospectively reviewed. Blastocyst transfers that demonstrated presence of fluid in the endometrial cavity were evaluated. All patients underwent serial transvaginal ultrasounds and presence of fluid was recorded at 2 time points: just before progesterone administration and after progesterone administration prior to transfer. Those transfers in which the fluid resolved after progesterone administration were compared to transfers without any fluid in the cavity recorded at any time point in the FET. Patient demographics, prior surgical history, and use of preimplantation genetic screening were recorded. Statistical analysis was performed using a chi-squared test of proportions and student’s t-test. RESULTS: 393 blastocyst transfers demonstrated fluid prior to progesterone initiation that resolved after progesterone administration and was not present at time of transfer. These transfers were compared to 8449 blastocyst transfers without fluid. The live birth rate was found to be significantly lower in the transfers that demonstrated fluid prior to progesterone start even when it resolved before transfer (31.8% v. 43.7%, p<0.0001). The difference may be even greater as these groups did not account for age or use of preimplantation genetic screening. Among the patients with fluid present, prior uterine surgery including cesarean delivery, septum resection, and myomectomy were recorded and the probability of having had surgery was equivalent between those patients who achieved a live birth and those who did not (p¼0.1949). There was also no statistical difference in endometrial thickness between patients who achieved a live birth and those who did not (9.36  2.38 mm v. 8.96  2.28 mm, p¼0.1127). CONCLUSIONS: When fluid is present in the endometrial cavity during the proliferative phase, this impacts pregnancy rates even if the fluid resolves and is not present at the time of transfer. The presence of fluid in the cavity is likely multifactorial and may be benign in origin versus a true pathology that explains the diminution in live birth rate. SUPPORT: None. References: 1. Shan L, Lin S, Juanzi S. ‘‘Impact of endometrial cavity fluid on assisted reproductive technology outcomes.’’ Int J Gynaecol Obstet. 2016 Mar; 132(3):278-83. 2. Chien LW, Au HK, Xiao J, Tzeng CR. ‘‘Fluid accumulation within the uterine cavity reduces pregnancy rates in women undergoing IVF.’’ Hum Reprod. 2002 Feb;17(2):351-6. 3. He RH, Gao HJ, Li YQ, Zhu XM. ‘‘The associated factors to endometrial cavity fluid and the relevant impact on the IVF-ET outcome.’’ Reprod Biol Endocrinol. 2010 May 14. _ et al. ‘‘Transient intrauterine 4. Polat, M., Boynukalin, F.K., Yarali, I. fluid accumulation not due to hydrosalpinx or any identifiable pelvic pathology is not detrimental to IVF outcome’’ Arch Gynecol Obstet 2014. 5. Akman MA1, Erden HF, Bahceci M. ‘‘Endometrial fluid visualized through ultrasonography during ovarian stimulation in IVF cycles impairs the outcome in tubal factor, but not PCOS, patients.’’ Hum Reprod. 2005 Apr;20(4):906-9.

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PERSISTENT FLUID IN THE ENDOMETRIAL CAVITY THAT RESOLVES AFTER PROGESTERONE ADMINISTRATION PRIOR TO TRANSFER DOES IMPACT LIVE BIRTH RATE. R. Chattopadhyay,a C. R. Juneau,b,c J. Landis,b S. J. Morin,b,c S. A. Neal,b,c R. T. Scott.a,b,c aRutgers, Robert Wood Johnson Medical School, New Brunswick, NJ, USA; b Reproductive Medicine Associates of New Jersey, Basking Ridge, NJ, USA; cSidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.

FEWER THAN 9 DAYS OF ESTROGEN EXPOSURE PRIOR TO PROGESTERONE INITIATION RESULTS IN LOWER PREGNANCY RATES IN PROGRAMMED FROZEN EMBRYO TRANSFER CYCLES. Michael P. Dougherty, MD,a Scott J. Morin, MD,b,c Caroline R. Juneau, MD,b,c Shelby A. Neal, MD,b,c Richard T. Scott, MD, HCLD.b,c aRutgers-Robert Wood Johnson Medical School, New Brunswick, NJ; bSidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA; cReproductive Medicine Associates of New Jersey, Basking Ridge, NJ.

BACKGROUND: Outcomes in IVF are dependent upon a successful embryo transfer within a receptive uterus. Optimization includes assessment of fluid within the endometrial cavity. Studies examining presence of fluid prior

FERTILITY & STERILITYÒ

BACKGROUND: Programmed frozen embryo transfer (FET) cycles allow greater scheduling flexibility to clinics and patients and reduce the

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