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Edison, N.; Blakemore, J. K.; Goldman, K. N.; Hodes-Wertz, B.; Grifo, J. A.
ISSN: 0015-0282
CID: 3493692


Druckenmiller, S; Labella, P; DeVore, S; Grifo, J; Hodes-Wertz, B; Noyes, N
ISSN: 1556-5653
CID: 2713712

Erratum: Comment on: Gleicher N et al.,2016. Reprod biol endocrinol Sep5;14(1):54[Reprod Biol Endocrinol (2017),17,15(24)] DOI:10.1186/s12958-017-0240-y [Correction]

Tiegs, A W; Grifo, J A; Munne, S; McCulloh, D H; Hodes-Wertz, B
ISSN: 1477-7827
CID: 2551272

Erratum to: Comment on: Gleicher N et al.,2016. Reprod biol endocrinol Sep 5;14(1):54 [Correction]

Tiegs, Ashley W; Grifo, James A; Munne, Santiago; McCulloh, David H; Hodes-Wertz, Brooke
PMID: 28395662
ISSN: 1477-7827
CID: 2527742

Response to comment on: Gleicher N et al., 2016. Reprod biol endocrinol Sep 5;14(1):54 [Editorial]

Tiegs, Ashley W; Grifo, James A; Munne, Santiago; McCulloh, David H; Hodes-Wertz, Brooke
PMID: 28376830
ISSN: 1477-7827
CID: 2519472

Why do euploid embryos miscarry? A case-control study comparing the rate of aneuploidy within presumed euploid embryos that resulted in miscarriage or live birth using next-generation sequencing

Maxwell, Susan M; Colls, Pere; Hodes-Wertz, Brooke; McCulloh, David H; McCaffrey, Caroline; Wells, Dagan; Munne, Santiago; Grifo, James A
OBJECTIVE: To determine whether undetected aneuploidy contributes to pregnancy loss after transfer of euploid embryos that have undergone array comparative genomic hybridization (aCGH). DESIGN: Case-control study. SETTING: University-based fertility center. PATIENT(S): Cases included 38 patients who underwent frozen euploid ET as determined by aCGH, resulting in miscarriage. Controls included 38 patients who underwent frozen euploid ET as determined by aCGH, resulting in a live birth. INTERVENTION(S): Next-generation sequencing (NGS) protocols were internally validated. Saved amplified DNA samples from the blastocyst trophectoderm biopsies previously diagnosed as euploid by aCGH were reanalyzed using NGS. Cytogenetic reports of the products of conception for 20 of the pregnancies resulting in miscarriage were available for comparison. MAIN OUTCOME MEASURE(S): The incidence of aneuploidy and mosaicism using NGS within embryos resulting in miscarriage and live birth. RESULT(S): Of euploid embryos analyzed by aCGH resulting in miscarriage, 31.6% were mosaic and 5.2% were polyploid by NGS. The rate of chromosomal abnormalities was significantly higher in embryos resulting in miscarriage (36.8%) than in those resulting in live births (15.8%). The rate of mosaicism was twice as high among embryos resulting in miscarriage than those resulting in live birth, but this was not statistically significant. Next-generation sequencing detected more cases of mosaicism than cytogenetic analysis of products of conception. CONCLUSION(S): Undetected aneuploidy may increase the risk of first trimester pregnancy loss. Next-generation sequencing may detect mosaicism and triploidy more frequently than aCGH, which could help to identify embryos at high risk of miscarriage. Mosaic embryos, however, should not be discarded as some can result in live births.
PMID: 27692437
ISSN: 1556-5653
CID: 2273802

Are the biggest losing? analyzing the effect of body mass index (BMI) on pregnancy rates in euploid frozen embyro transfer (FET) cycles [Meeting Abstract]

Smith, M B; Hodes-Wertz, B; Grifo, J; Goldman, K N
OBJECTIVE: The impact of obesity on poor reproductive outcomes, especially miscarriage, is well documented. Our group previously reported that obesity does not increase embryonic aneuploidy, suggesting other factors may be involved in obesity-related subfertility, infertility, and miscarriage. We sought to determine if BMI affects pregnancy rates in patients undergoing euploid FET . DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Patients who underwent in vitro fertilization with pre-implantation genetic screening by trophectoderm biopsy and array comparative genomic hybridization were identified. Height/weight were recorded upon oocyte retrieval. Those who underwent euploid FET within 6 months of retrieval were analyzed. Patients were grouped by BMI according to WHO class. Pertinent parameters from controlled ovarian hyper- stimulation (COH) and FET cycles were collected including day 2 FSH/E2, endometrial thickness/E2 prior to FET, and no. of the following: oocytes retrieved, M2, 2PN, embryos biopsied, euploid embryos, percentage euploid embryos, and embryos transferred. Demographics and pregnancy outcomes were collected. Implantation rate (IR) was defined by gestational sac(s) per embryo(s) transferred, and clinical pregnancy rate (CPR) by fetal cardiac activity (FCA). Miscarriage (SAB) was defined by pregnancy loss following FCA. Data analysis was performed using the Shapiro-Wilk test for normality, the Kruskal-Wallis test to compare means, and Fisher's exact test for dichotomous variables (mean +/- SD, p<0.05, GraphPad Prism). For dichotomous variables, each BMI cohort was compared to the normal weight reference group. RESULTS: 291 patients met inclusion criteria. There were no differences between groups when comparing COH and FET cycle parameters, although underweight group was younger (p=0.005). Following euploid FET, there were no differences in IR, CPR, or live birth rate (LBR) between groups. The miscarriage rate was > 2-fold higher in the obese group compared to normal-weight (18.2% vs. 7.4%) and to all other BMI cohorts, but this did not reach statistical significance. CONCLUSIONS: The miscarriage rate was more than 2-fold higher in the obese group following euploid FET compared to the normal-weight group, although this finding did not reach significance. The trends in our findings support further study into the relationship between obesity, the intrauterine milieu, and pregnancy loss, particularly after the transfer of a highly-competent euploid embryo
ISSN: 1556-5653
CID: 2294392

Beating biology and buying time: An update survey of womens' experiences after oocyte cropreservation (OC) for deferred reproduction [Meeting Abstract]

Hodes-Wertz, B; Druckenmiller, S; Smith, M; Kramer, Y G; Noyes, N
OBJECTIVE: To further understanding of how women who pursue OC for deferred reproduction think and act relative to reproduction and dating. DESIGN: 2016 anonymous 39-question survey with comparison to our prior OC patient survey completed in 2012. MATERIALS AND METHODS: From 2005-15, 1817 women underwent >1 OC treatment cycle at our facility; 866 (48%) agreed to post-treatment contact, and our survey was distributed to these patients. RESULTS: There were 224 survey responses (rate: 26%). From 2012 to 2016, the percentage of women that froze at 33-35y increased (13 to 24%) while those 39-41y decreased (39 to 23%); 44% froze between 36-38y consistent with our clinical data also demonstrating a decrease in age at time of OC. 53% underwent OC in the last 2 years. As in 2012, 80% of respondents were Caucasian, and >70% were never married, reported lack of partner as the no. 1 reason for not yet having children and wished they had undergone OC earlier. The majority now feel the ideal age for egg freezing is 29-34y, with only 16% choosing >35y and <1% choosing >38y. Of note, more (25 vs. 16%) were in a relationship at time of OC with 1/2stating the relationship was <1y. 77% reported difficulty finding someone with whom to co-parent at the time of OC. >80% currently report a desire to have children while <20% remain unsure as to whether they definitely want children in the future. Cost was the greatest obstacle to pursuing OC. 1/3 received financial support, mostly from family, with parents being the most common source. After OC, 30% admitted an attitude change toward parenting, mostly in a positive way (i.e. made it a priority or increased openness to alternative family-creating options). >60% also felt lessening of biological-clock pressure when dating and were more open to using donor sperm if still lacking a suitable partner by age 43 (average; range 35-50y). 1/4 said OC changed their dating habits: feeling more relaxed, focused, less desperate and with more time to find the right partner. >60% admitted discussing OC while dating and 90% with family/friends. They were most often met with positive/ supportive reception. 96% would recommend OC to another. After undergoing OC, 22% got pregnant or had children without resorting to their frozen eggs (2/3 naturally; 1/3 ART; 4% adoption). 13% of respondents thawed eggs resulting in a 32% live birth rate. Of those not yet thawing, 1/2 cited lacking a suitable co-parent as the obstacle; 90% reported future intent to thaw. CONCLUSIONS: Women are pursuing OC at younger ages, with the primary indication being lack of a suitable co-parenting partner; the latter was also the most common reason cited for not returning to use eggs sooner. Cost was prohibitive for many, with some relying on family finances. Most reported OC as a positive experience, improving views of parenting, inciting healthier dating practices, enhancing hope for future family and expanding acceptable options for achieving that goal
ISSN: 1556-5653
CID: 2300282

Discrepant diagnosis rate of array comparative genomic hybridization in thawed euploid blastocysts

Tiegs, Ashley W; Hodes-Wertz, Brooke; McCulloh, David H; Munne, Santiago; Grifo, James A
PURPOSE: Preimplantation genetic screening (PGS) and diagnosis (PGD) with euploid embryo transfer is associated with improved implantation and live birth rates as compared to routine in vitro fertilization. However, misdiagnosis of the embryo is a potential risk. The purpose of this study was to investigate the clinical discrepant diagnosis rate associated with transfer of trophectoderm-biopsied blastocysts deemed to be euploid via array comparative genomic hybridization (aCGH). METHODS: This is a retrospective cohort study including cycles utilizing PGS or PGD with trophectoderm biopsy, aCGH, and euploid embryo transfer at a large university-based fertility center with known birth outcomes from November 2010 through July 2014 (n = 520). RESULTS: There were 520 embryo transfers of 579 euploid embryos as designated by aCGH. Five discrepant diagnoses were identified. Error rate per embryo transfer cycle was 1.0 %, 0.9 % per embryo transferred, and 1.5 % per pregnancy with a sac. The live birth (LB) error rate was 0.7 % (both sex chromosome errors), and the spontaneous abortion (SAB) error rate was 17.6 % (3/17 products of conception tested, but could range from 3/42 to 7/42). No single gene disorders were mistakenly selected for in any known cases. CONCLUSIONS: Although aCGH has been shown to be a highly sensitive method of comprehensive chromosome screening, several possible sources of error still exist. While the overall error rate is low, these findings have implications for counseling couples that are contemplating PGS and PGD with aCGH.
PMID: 26984233
ISSN: 1573-7330
CID: 2032032

Why do euploid embryos miscarry? A retrospective study comparing aneuploidy rates within presumed euploid embryos resulting in miscarriage or live birth using next-generation sequencing (NGS) [Meeting Abstract]

Maxwell, S; Coates, A; Colls, P; Hodes-Wertz, B; McCulloh, D H; McCaffrey, C; Capaldi, R; Gouw, F; Liu, E; Ribustello, L; Munne, S; Grifo, J; Tormasi, S
Study question: Does undetected aneuploidy or mosaicism contribute to pregnancy loss after transfer of euploid embryos by array comparative genomic hybridization (aCGH)? Summary answer: NGS detects more cases of mosaicism and triploidy than aCGH, and mosaicism rates are significantly higher among pregnancies resulting in miscarriage than live birth. What is known already: Array CGH is widely used for pre-implantation genetic screening (PGS). NGS is capable of detecting more cases of mosaicism and triploidy (69XXY), which may assist in reducing the incidence of spontaneous abortion and increase ongoing pregnancy rates. Study design, size, duration: Retrospective study of 183 patients undergoing PGS by aCGH between 8/2012 and 5/2015 at New York University Fertility Center and Oregon Reproductive Medicine. Participants/materials, setting, methods: Saved amplified DNA samples from the 183 blastocyst trophectoderm (TE) biopsies previously diagnosed as euploid by aCGH were re-analyzed using the miSeq NGS platform (Illumina, USA) and VeriSeq NGS technology (Illumina, USA). 44 embryos resulting in a biochemical pregnancy, 62 resulting in miscarriage, and 77 resulting in live birth were available for re-analysis. Main results and the role of chance: 25% (11/44) of embryos resulting in biochemical pregnancies were mosaic, and one embryo was found to be triploid (69, XXY) by NGS. 33.9% (21/62) and 3.2% (2/62) of embryos resulting in miscarriage were mosaic and triploid by NGS, respectively. In contrast, the mosaicism rate among embryos resulting in live birth was only 13% (10/77), which was significantly lower than the rate of mosaicism among miscarriages (p = 0.0062, RR 1.78 with 95% CI 1.23-2.5). Limitations, reasons for caution: This study was limited by its retrospective design. Up to 10% of DNA samples that were undergoing re-analysis were excluded due to degraded DNA, although the frequency was similar in all three groups. Wider implications of the findings: Undetected mosaicism may increase the risk of first trimester pregnancy loss. NGS is more sensitive at picking up mosaicism and triploidy than aCGH. Mosaic embryos can be considered for transfer after genetic counseling and informed consent, but they have a higher miscarriage rate as well as unknown post-natal genetic effects
ISSN: 1460-2350
CID: 2533752