Published Manuscripts
Tag: Modern Medicine
Single Euploid Embryo Transfer Outcomes after Uterine Septum Resection
Study Objective: To study pregnancy outcomes after single euploid embryo transfer (SEET) in patients who underwent prior uterine septum resection to those with uteri of normal contour, without M€ullerian anomalies or uterine abnormalities including polyps or fibroids, and without a history of prior uterine surgeries.
Design: Retrospective cohort study.
Setting: Single academic affiliated center.
Patients: 60 cycles of patients with prior hysteroscopic uterine septum resection who underwent an autologous SEET
between 2012 and 2020 were used as the investigational cohort. A 3:1 ratio propensity score matched control cohort of 180 single euploid embryo transfer cycles from patients without a history of uterine septa were used as the control group.Interventions: No interventions administered.
Measurements and Main Results: Pregnancy, clinical pregnancy loss, ongoing clinical pregnancy, and live birth rates in patients with a history of uterine septum resection compared with matched patients without M€ullerian anomalies or uterine surgeries.
Patients with a prior uterine septum had significantly lower rates of chemical pregnancy (58.33% vs 77.2%, p = .004), implantation (41.67% vs 65.6%, p = .001), and live birth (33.33% vs 57.8%, p = .001) per transfer. No statistical difference in clinical pregnancy loss rates was found when comparing septum patients with controls (8.33% vs 7.8%, p = .89).Conclusion: Patients with a history of hysteroscopic resection who undergo in vitro fertilization are more susceptible to suboptimal clinical outcomes compared with patients with normal uteri. Early pregnancy loss rates in patients with a uterine septum are higher than in those without; however, after resection, the rates are comparable. Patients born with septate uteri require assessment of surgical intervention prior to SEET, and to optimize their reproductive outcomes. Journal of Minimally Invasive Gynecology (2024) 00, 1−6. © 2024 AAGL. All rights reserved.
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Correlation of self‑reported racial background to euploidy status and live birth rates in assisted reproductive technology cycles
Purpose To determine whether the embryonic euploidy rate and live birth outcomes following single, euploid embryo
transfer (SEET) difer among women of self-reported racial and ethnic backgrounds.Methods This retrospective cohort study included all infertile patients of diferent self-reported racial backgrounds who underwent In vitro fertilization (IVF) with preimplantation genetic testing for aneuploidy (PGT-A) and an autologous single euploid embryo transfer (SEET) from December 2015 to December 2019 at a single private and academic assisted reproduction technology center. Primary outcome measures included ploidy rates among diferent racial groups. Secondary outcomes included clinical pregnancy, clinical pregnancy loss, and live birth rates.
Results Five thousand fve hundred sixty-two patients who underwent an IVF cycle with ICSI-PGT-A were included. A
total of 24,491 blastocysts were analyzed. White participants had on average more euploid embryos and higher euploidy
rates when compared to their counterparts (p≤0.0001). However, after controlling for confounding factors, there was no
association between race and the odds of having a higher euploidy rate (aOR 1.31; 95% CI 0.63–2.17, p=0.42). A total of
4949 patients underwent SEET. Pregnancy outcomes did not difer among patients of varying self-reported races.Conclusions Euploidy rates and pregnancy outcomes were comparable among patients of diferent racial backgrounds who underwent a SEET.
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Walking the tightrope: Fertility preservation among hereditary breast and ovarian Cancer syndrome Previvors
Introduction: Fertility-related concerns cause significant anxiety among patients with Hereditary Breast and Ovarian Cancer Syndrome (HBOC). The Society of Gynecologic Oncology and the American Society for Reproductive Medicine recommend patients diagnosed with HBOC receive early referral to a reproductive endocrinologist. However, evidence about fertility trends in this patient population are limited and guidelines are scarce. The aim of this study is to compare fertility preservation among patients with HBOC to control patients undergoing fertility treatment without a diagnosis of infertility.
Methods: This retrospective study included patients who presented to a single academic institution for fertility preservation in the setting of diagnosis of HBOC. In this study, HBOC patients are referred to as those who had tested positive for pathogenic mutations in BRCA1, BRCA2 or were at high-risk for HBOC based on a strong family history (defined as >3 family members diagnosed with HBOC) without a genetic mutation. HBOC patients were matched in a 1:1 fashion to a control group undergoing fertility preservation without a diagnosis of infertility or HBOC. All analysis was done using SPSS version 9.4 (SAS Institute, Cary, NC).
Results: Between August 1st, 2016 and August 1st, 2022, 81 patients presented to the study center for consultation in the setting of HBOC. Of those who presented, 48 (59.2%) ultimately underwent oocyte cryopreservation and 33 (40.7%) underwent embryo cryopreservation. Patients who underwent oocyte cryopreservation due to BRCA1 status were more likely to present for fertility consultation at a younger age compared to control patients (32.6 vs. 34.7 years, p = 0.03) and were more likely to undergo oocyte cryopreservation at a younger age (32.1 vs. 34.6 years, p = 0.007). There was no difference in age at initial consultation or age at procedure for patients with BRCA2 or patients with a strong family history compared to control patients (p > 0.05). There was no difference in the mean age of patients with HBOC at presentation for consultation for embryo cryopreservation or the mean age the patient with HBOC underwent embryo cryopreservation compared to control patients (p > 0.05). Patients with BRCA1 or BRCA2 did not have expedited time from consultation to first cycle start (p > 0.05). After adjusting for factors including anti-Müllerian hormone (AMH) level and age, patients considered in the HBOC group due to family history had less time between consultation and oocyte cryopreservation cycle compared to control patients. (179 vs. 317 days, p = 0.045). There was no difference in time from consultation to starting cycle for embryo cryopreservation for patients with HBOC compared to controls (p > 0.05).
Conclusion: Patients with HBOC did not undergo expedited fertility treatment compared to control patients undergoing oocyte and embryo cryopreservation for non-infertility reasons. Patients diagnosed with BRCA1 had more oocytes retrieved compared to the control population which is possibly due to earlier age of presentation in the setting of recommended age of risk reducing surgery being age 35–40. When age matched, cycle outcomes did not differ between HBOC and control patients. Given the known cancer prevention benefit and recommendations for risk-reducing surgery, future studies should focus on guidelines for fertility preservation for patients with HBOC.
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Effect of Postthaw Change in Embryo Score on Single Euploid Embryo Transfer Success Rates
Objective: To assess whether the change in embryo morphology from precryopreservation to postthaw is associated with the embryo transfer success rates in single euploid embryo transfer cycles.
Design: Retrospective cohort study.
Setting: Academic affiliated fertility clinic.
Patient(s): Patients who underwent a single euploid embryo transfer cycle from September 2016 to April 2022 were included. A decision support tool was used to assign each embryo a reproductive potential score on the basis of the day of biopsy, expansion, and grade of trophectoderm and inner cell mass at the time of cryopreservation and after thaw. Embryos were divided into 4 groups: group 1included embryos with the same score after thaw (reference); group 2 included those with a higher score; group 3 included those with a lower score; and group 4 included those that did not re-expand after thaw.
Intervention(s): No interventions administered.
Main Outcome Measure(s): The primary outcome was the live birth rates (LBRs) per embryo transfer. The secondary outcomes included the chemical pregnancy, clinical pregnancy, and clinical pregnancy loss rates. Comparative statistics and univariate analyses were performed using the Kruskal-Wallis and c2 tests. Multivariate logistic regression fitted with generalized estimating equation was performed to compare the odds of live birth between groups.
Result(s): A total of 7,750 embryo transfers performed for 4,613 patients met inclusion criteria: 5,331 in group 1; 486 in group 2; 1,726 in group 3; and 207 in group 4. In the univariate analysis, there was a statistically significant difference in the LBR between groups 1, 2, 3, and 4 (55.8% vs. 51.4%, 47.5%, and 26.6%). Logistic regression controlling for oocyte age, antimullerian hormone, body mass index, € endometrial thickness, year of embryo transfer, time from thaw to final grading, and embryo score before cryopreservation showed significantly lower odds of live birth when the embryo was downgraded (odds ratio [OR], 0.70; confidence interval [CI], 0.62–0.79) or did not re-expand (OR, 0.36; CI, 0.26–0.51) than those with no change in score. When controlling for all variables, there was a significant increase in the odds of live birth between embryos that had a higher score after thaw and those without a change (OR, 1.42; CI, 1.14–1.76). There was no significant difference in the clinical pregnancy loss rate among the 4 groups.
Conclusion(s): The change in the quality of the embryo after thaw is an important factor in embryo transfer success. In an adjusted analysis, the chemical and clinical pregnancy rates and LBR per embryo transfer all significantly decrease in embryos that were downgraded or did not expand on the day of single euploid embryo transfer. Embryos that re-expand and have improved quality after thaw have the highest odds of live birth. (Fertil Steril 2024;-:-–-. 2024 by American Society for Reproductive Medicine.)
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Rescue in vitro maturation using ovarian support cells of human oocytes from conventional stimulation cycles yields oocytes with improved nuclear maturation and transcriptomic resemblance to in vivo matured oocytes
Purpose: Determine if the gene expression profles of ovarian support cells (OSCs) and cumulus-free oocytes are bidirectionally infuenced by co-culture during in vitro maturation (IVM).
Methods: Fertility patients aged 25 to 45 years old undergoing conventional ovarian stimulation donated denuded immature oocytes for research. Oocytes were randomly allocated to either OSC-IVM culture (intervention) or Media-IVM culture (control) for 24–28 h. The OSC-IVM culture condition was composed of 100,000 OSCs in suspension culture with human chorionic gonadotropin (hCG), recombinant follicle stimulating hormone (rFSH), androstenedione, and doxycycline supplementation. The Media-IVM control lacked OSCs and contained the same supplementation. A limited set of in vivo matured
MII: oocytes were donated for comparative evaluation. Endpoints consisted of MII formation rate, morphological and spindle quality assessment, and gene expression analysis compared to in vitro and in vivo controls.
Results: OSC-IVM resulted in a statistically signifcant improvement in MII formation rate compared to the Media-IVM
control, with no apparent efect on morphology or spindle assembly. OSC-IVM MII oocytes displayed a closer transcriptomic maturity signature to IVF-MII controls than Media-IVM control MII oocytes. The gene expression profle of OSCs was modulated in the presence of oocytes, displaying culture- and time-dependent diferential gene expression during IVM.Conclusion: The OSC-IVM platform is a novel tool for rescue maturation of human oocytes, yielding oocytes with improved nuclear maturation and a closer transcriptomic resemblance to in vivo matured oocytes, indicating a potential enhancement in oocyte cytoplasmic maturation. These improvements on oocyte quality after OSC-IVM are possibly occurring through bidirectional crosstalk of cumulus-free oocytes and ovarian support cells.
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Effect of various contraceptives on oocyte yield and maturation in patients undergoing planned oocyte cryopreservation: a retrospective cohort study
Research question: Do the various forms of hormonal and non-hormonal contraceptives have any association with ovarian stimulation outcomes, such as oocyte yield and maturation, in patients undergoing planned oocyte cryopreservation (POC)?
Design: This retrospective cohort study included all patients who underwent POC cycles between 2011 and 2023. The use of types of contraception before a POC cycle was recorded. The study evaluated the median number of cumulusoocyte complexes obtained after vaginal oocyte retrieval and the proportion of metaphase II oocytes that underwent vitrification among all the cohorts.
Results: A total of 4059 oocyte freezing cycles were included in the analysis. Eight types of contraceptive method were recognized in patients undergoing ovarian stimulation: intrauterine device (IUD), copper (n = 84); IUD, levonorgestrel low dose (<52 mg) (n = 37); IUD, levonorgestrel (n = 192); subdermal etonogestrel implant (n = 14); injectable medroxyprogesterone acetate (n = 11); etonogestrel vaginal ring (n = 142); combined oral contraceptive pills (n = 2349); and norelgestromin transdermal patch (n = 10). The control group included patients not using contraceptives or using barrier or calendar methods (n = 1220). Among all the cohorts the median number of cumulusoocyte complexes retrieved during oocyte retrieval was comparable (P = 0.054), and a significant difference in oocyte maturity rate with median number of vitrified oocytes was found (P = 0.03, P < 0.001, respectively). After adjusting for confounders a multivariate analysis found no association between the type of contraceptive and proportion of metaphase II oocytes available for cryopreservation.
Conclusions: Among the various forms of contraception, none was shown to have an adverse association with oocyte yield or maturation rate in patients undergoing POC
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Recent clomiphene citrate exposure does not impact subsequent clinical outcomes in single euploid frozen embryo transfer cycles
Carlos Hernandez-Nieto,, Joseph Lee, Tamar Alkon-Meadows, Luz Soto-Cossio, Benjamin Sandler, Tanmoy …
Read MoreFertility treatment outcomes in transgender men with a history of testosterone therapy
Atoosa Ghofranian, M.D.,Samantha L. Estevez, M.D.,Caroline Gellman, M.D., Dmitry Gounko, B.S., …
Read MoreAssisted Reproductive Technology Treatment Outcomes in Women With Liver Disease
Lee JD, Gounko D, Lee JA, Mukherjee T, Kushner T. Am J Gastroenterol. 2023 Dec 1;118(12):2184-2190. …
Read MoreAssessing the clinical viability of micro 3 pronuclei zygotes
Canon C, Thurman A, Li A, Hernandez-Nieto C, Lee JA, Roth RM, Slifkin R, Briton-Jones C, Stein D, …
Read MoreAn interpretable machine learning model for predicting the optimal day of trigger during ovarian stimulation
Fanton M, Nutting V, Solano F, Maeder-York P, Hariton E, Barash O, Weckstein L, Sakkas D, Copperman …
Read MoreImproving preeclampsia risk prediction by modeling pregnancy trajectories from routinely collected electronic medical record data
Li S, Wang Z, Vieira LA, Zheutlin AB, Ru B, Schadt E, Wang P, Copperman AB, Stone JL, Gross SJ, Kao …
Read MoreIn Vitro Fertilization and Early Pregnancy Outcomes After Coronavirus Disease 2019 {COVID-19} Vaccination
Aharon D, Lederman M, Ghofranian A, Hernandez-Nieto C, Canon C, Hanley W, Gounko D, Lee JA, Stein …
Clinical implementation of algorithm-based embryo selection is associated with improved pregnancy outcomes in single vitrified warmed euploid embryo transfers
Friedenthal J, Hernandez-Nieto C, Roth RM, Slifkin R, Gounko D, Lee JA, Nazem T, Briton-Jones C, …
Read MoreEvaluating in vitro fertilization outcomes of patients with low body mass index following frozen-thawed embryo transfer
Oliva M, Nazem TG, Lee JA, Copperman AB. Int J Gynaecol Obstet. 2021 Oct;155(1):132-137. Epub 2021 …
Read MoreParental chromosomal heteromorphisms are not associated with an increased risk of embryo aneuploidy
Hernandez-Nieto, C., Gayete-Lafuente, S., Alkon-Meadows, T., Lee, J., Luna-Rojas, M., Mukherjee, …
Read MoreRate of Post-Fertilization Mitotic Activity Predicts Embryonic Competence via Next Generation Sequencing: An Analysis of 39,301 Cleavage Stage Embryos
Friedenthal J, Pan S, Gounko D, Briton-Jones C, Lee J, Copperman A. JBRA Assist Reprod. 2021 Oct …
Read MoreA multi-centre international study of salivary hormone oestradiol and progesterone measurements in ART monitoring
Sakkas D, Howles CM, Atkinson L, Borini A, Bosch EA, Bryce C, Cattoli M, Copperman AB, de Bantel …
Read MoreExpanded carrier screening for preconception reproductive risk assessment: Prevalence of carrier status in a Mexican population
Hernandez-Nieto, C., Alkon-Meadows, T., Lee, J., Cacchione, T., Iyune-Cojab, E., Garza-Galvan, M., …
Read MoreEndometrial preparation before the transfer of single, vitrified-warmed, euploid blastocysts: does the duration of estradiol treatment influence clinical outcome?
Sekhon L, Feuerstein J, Pan S, Overbey J, Lee JA, Briton-Jones C, Flisser E, Stein DE, Mukherjee T, …
Read MoreNew insights into human prolactin pathophysiology: genomics and beyond
Chang, S., & Copperman, A. B. (2019). Current Opinion in Obstetrics & Gynecology, 31(4), …
Read MorePaternal contribution to embryonic competence
Stein D, Ukogu C, Ganza A, Gounko D, Lee J, Bar-Chama N, Copperman AB. Cent European J Urol. …
Read MoreWhat is the reproductive potential of day 7 euploid embryos?
Hernandez-Nieto, C., Lee, J. A., Slifkin, R., Sandler, B., Copperman, A. B., & Flisser, E. …
Read MoreBlastocyst Vitrification, Cryostorage and warming does not impact embryo transfer success, infant birthweight or timing of delivery
Lucky Sekhon, MD, Joseph A. Lee, BA, Eric Flisser, MD, Alan B. Copperman, MD, Daniel Stein, MD. …
Read MoreCaring for BRCA Carriers Strategies to Promote Health and Preserve Fertility
Nola S. Herlihy, Lucky Sekhon, Joseph A. Lee, Daniel Stein, Alan B. Copperman, Matthew A. Lederman. …
Read MoreHow time to healthy singleton delivery could affect decision-making during infertility treatment: a Delphi consensus
Bosch, E., Bulletti, C., Copperman, A. B., Fanchin, R., Yarali, H., Petta, C. A., Polyzos, N. P., …
Read MoreOptimal Interval of Time from Operative Hysteroscopy to Embryo Transfer in an In Vitro Fertilization Cycle
Aharon, D., Sekhon, L., Lee, J. A., Ascher-Walsh, C., & Copperman, A. B. (2019). Journal of …
Read MoreThe effect of female body mass index on in vitro fertilization cycle outcomes: a multi-center analysis
Kudesia, R., Wu, H., Hunter Cohn, K., Tan, L., Lee, J. A., Copperman, A. B., & Yurttas Beim, P. …
Read MoreIdentifying at-risk populations: are we simply not doing enough fertility preservation procedures?
Flisser E. (2018). Fertility and Sterility, 110(4), 640–641. June 18, 2018. Download
Read MoreEmbryo aneuploidy is not impacted by selective serotonin reuptake inhibitor exposure
Carlos Hernandez-Nieto, M.D., Joseph Lee, B.A., Taraneh Nazem, M.D., Dmitry Gounko, M.A., Alan …
Read MoreCo-ivf for same-sex female couples
Chloe Getrajdman, BA; Joseph A. Lee, BA; Alan B. Copperman, MD. Semin Reprod Med 2017;00:1–5. …
Read MoreProfound pituitary suppression following oral contraceptive pretreatment in gonadotropin-releasing hormone antagonist cycles does not impact outcome: a retrospective cohort study
Vela G, Ruman J, Luna M, Sandler B, and Copperman AB. JFIV Reprod Med Genet 2017, 5:2. Download
Read MoreFreeze-only versus fresh embryo transfer in a multicenter matched cohort study: contribution of progesterone and maternal age to success rates
Ange Wang, M.D., Anthony Santistevan, M.S., Karen Hunter Cohn, Ph.D., Alan Copperman, M.D., John …
Read MoreReproductive outcome is optimized when an embryo transfer is performed 1 to 3 months after cervical dilation
Jorge Rodriguez-Purata, MD; Robert Pacheco, BA; Lucky Sekhon, MD; Joseph A. Lee, BA; Lawrence …
Read MoreHatching status before embryo transfer is not correlated with implantation rate in chromosomally screened blastocysts
Jorge Rodriguez-Purata, MD; Julian Gingold, MD, PhD; Joseph A. Lee, BA; Michael C. Whitehouse, BA; …
Reproductive outcome is optimized by genomic embryo screening, vitrification and subsequent transfer into a prepared synchronous endometrium
Jorge Rodriguez-Purata, MD; Joseph Lee, BA; Michael Whitehouse, BA; Marlena Duke, MS; Lawrence …
Read MoreMaximum basal FSH predicts reproductive outcome better than cycle-specific basal FSH levels: waiting for a “better” month conveys limited retrieval benefits
Gingold JA, Lee JA, Whitehouse MC, Rodriguez-Purata J, Sandler B, Grunfeld L, Mukherjee T, …
Read MoreIn-vitro maturation of germinal vesicle and metaphase I eggs prior to cryopreservation optimizes reproductive potential in patients undergoing fertility preservation
Lee JA, Sekhon L, Grunfeld L, Copperman AB. Curr Opin Obstet Gynecol. 2014 Jun;26(3):168-73. …
Read MoreBeauty, brains or health: trends in ovum recipient preferences
Flores H, Lee J, Rodriguez-Purata J, Witkin G, Sandler B, Copperman AB. Womens Health (Larchmt). …
Read MoreFemale cystic fibrosis mutation carriers and assisted reproductive technology: does carrier status affect reproductive outcomes?
VanWort TA, Lee JA, Karvir H, Whitehouse MC, Beim PY, Copperman AB. Fertil Steril. 2014 …
Read MoreClinically recognizable error rate after the transfer of comprehensive chromosomal screened euploid embryos is low
Werner MD, Leondires MP, Schoolcraft WB, Miller BT, Copperman AB, Robins ED, Arredondo F, Hickman …
Read MoreOptimizing human oocyte cryopreservation for fertility preservation patients: should we mature then freeze or freeze then mature?
Lee JA, Barritt J, Moschini RM, Slifkin RE, Copperman AB. Fertil Steril. 2013 Apr;99(5):1356-62. …
Read MoreSocial and psychological assessment of women undergoing elective oocyte cryopreservation - A 7-year analysis
Victoria Vallejo, Joseph A. Lee, Lisa Schuman, Georgia Witkin, Enrique Cervantes, Benjamin Sandler, …
Read MoreResults with GnRH antagonist protocols are equivalent to GnRH agonist protocols in comparable patient populations
Luna M, Vela G, McDonald CA, Copperman AB. Results with GnRH antagonist protocols are equivalent to …
Read MoreMedical versus surgical treatment for early pregnancy loss in infertile patients - Which approach facilitates more rapid return to subsequent treatment cycle?
Victoria Vallejo, Hilde I.G. Cotton, Joseph A. Lee, Enrique Cervantes, Benjamin Sandler M.D, Alan B …
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