Aging and Rejuvenation

Areas of Investigation

The consequences of reproductive aging are encountered on a daily basis in the infertility clinic. With this in mind, researchers at IVI RMA Global are working to identify the mechanisms responsible for reproductive aging.

These projects include studies on:

changes in the epigenome associated with aging,
telomere dynamics in gametes and peripheral blood
mitochondrial function in preimplantation embryos.

The scientific team is also focused on devising treatment strategies to activate dormant follicles in patients at advanced stages of reproductive aging. These techniques have produced pregnancies in multiple patients with a diagnosis of primary ovarian insufficiency (also termed premature ovarian failure).

Investigators
working in this area

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Name
Antonio Pellicer , M.D., Ph.D. Chief Executive Officer for IVIRMA Global IVI Rome
Emre Seli, M.D. US Research Director RMA New Jersey
Juan García Velasco, M.D., Ph.D. Chief Scientific Officer for IVIRMA Global IVI Madrid
Sonia Herraiz, Ph.D. Ovarian Rejuvenation and Fertility Preservation Research Group Leader at FIVI. FIVI Valencia
Irene Cervelló, Ph.D. Laboratory Manager & Endometrial Stem Cell and Bioengineering Research Group Leader at the IVI Foundation Research Department FIVI Valencia
Elisa Varela, Ph.D Principal Investigator of the Telomeres in Reproduction at FIVI-IVIRMA IVI Madrid
Carmina Vidal, M.D., Ph.D. Gynecologist and Reproductive Medicine Specialist at IVI Valencia IVI Valencia
Evelin Lara, M.D. Director of the Egg Donation Unit at IVI Barcelona IVI Barcelona
Roberto Matorras, M.D., Ph.D. Coordinator for Research and Education at IVI Bilbao IVI Bilbao
Scott Morin, M.D. Reproductive Endocrinologist at RMA of Northern California RMA Northen California
José Remohí, M.D – Ph.D. Founding Partner IVI-RMA Global IVI Valencia
Richard T Scott, M.D.,H.C.L.D. Founding Partner IVIRMA Global RMA New Jersey
Pilar Alamá, M.D., Ph.D. Director of the Egg Donation Unit IVI Valencia
Cesar Diaz-Garcia Medical Director IVI London

Publications
from this area

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Ovarian reserve parameters and IVF outcomes in 510 women with poor ovarian response (POR) treated with intraovarian injection of autologous platelet rich plasma (PRP). Cakiroglu Y, Yuceturk A, Karaosmanoglu O, Kopuk SY, Korun ZEU, Herlihy N, Scott RT, Tiras B, Seli E Aging (Albany NY). 2022 doi: 10.18632/aging.203972
Follicular activation in women previously diagnosed with poor ovarian response: a randomized, controlled trial César Díaz-García, Sonia Herraiz, Loida Pamplona, Jessica Subirá, María José Soriano, Carlos Simon, Emre Seli, Antonio Pellicer Fertility and Sterility. 2022 doi:
What are the advantages of the DuoStim strategy? María Cerrillo, Gustavo Nardini Cecchino, María Cruz Medicina Reproductiva y Embriología Clínica . 2021 doi:
Disease-inducing potential of two leukemic cell lines in a xenografting model. Manavella DD, Herraiz S, Soares M, Buigues A, Pellicer A, Donnez J, Diaz-Garcia C, Dolmans MM J Assist Reprod Genet. Mar. 2021 doi: 10.1007/s10815-021-02169-2
Stem Cell Paracrine Signaling for Treatment of Premature Ovarian Insufficiency Polonio AM, Garcia-Velasco J A, Herraiz S Front Endocrinol. Mar. 2021 doi: 10.3389/fendo.2020.626322
Vitamin D in Follicular Fluid Correlates With the Euploid Status of Blastocysts in a Vitamin D Deficient Population. Arnanz A, De Munck N, El Khatib I, Bayram A, Abdala A, Melado L, Lawrenz B, Coughlan C, Pacheco A, Garcia-Velasco J A, Fatemi HM Front Endocrinol. Jan. 2021 doi: 10.3389/fendo.2020.609524
Medroxyprogesterone acetate is a useful alternative to a gonadotropin-releasing hormone antagonist in oocyte donation: a randomized, controlled trial Giles J, Alama P, Gamiz P, Vidal C, Badia P, Pellicer A, Bosch E, Fertil Steril. Apr. 2021 doi: 10.1016/j.fertnstert.2021.02.036
Prediction of embryo survival and live birth rates after cryotransfers of vitrified blastocysts Coello A, Nohales M, Meseguer M, de Los Santos M J, Remohi J, Cobo A, Reprod Biomed Online. May. 2021 doi: 10.1016/j.rbmo.2021.02.013
Effects of Hydrosalpinx on Endometrial Implantation Failures: Evaluating Salpingectomy in Women Undergoing in vitro fertilization Palagiano A, Cozzolino M, Ubaldi F M, Palagiano C, Coccia M E, Rev Bras Ginecol Obstet. 18-Feb. 2021 doi: 10.1055/s-0040-1722155
Sigue habiendo indicaciones para el ciclo natural? Castro B, Ortega I, 2017 doi:
Telomeres in aging and reproduction. Varela E, Sanchez de Puerta I, Garcia-Velasco J A, Curr Opinion in Obstetrics and Gynecology. 2017 doi:
Aging is associated with changes in mitochondrial dynamics, function and mtDNA quantity. Babayev E, Wang T, Szigeti-Buck K, Lowther K, Taylor HS, Horvath T, Seli E, Maturitas. 2016 doi:
Exccesive age-related decline in functional ovarian reserve in infertile women: prospective cohort of 15500 women. Iliodromiti S, Iglesias C, Messow CM, Cruz M, Garcia-Velasco J A, Nelson SM, J Clin Endocrinol Metab. 2016 doi:
Excessive Age-Related Decline in Functional Ovarian Reserve in Infertile Women: Prospective Cohort of 15,500 Women. Iliodromiti S, Iglesias C, Messow CM, Cruz M, Garcia-Velasco J A, Nelson SM, J Clin Endocrinol Metab. 2016 doi:
Contribution of different bone marrow-derived cell types in endometrial regeneration using an irradiated murine model Gil-Sanchis C, Cervello I, Khurana S, Faus A, Verfaillie C, Simon C, Fertil Steril. Jun. 2015 doi: 10.1016/j.fertnstert.2015.02.030
Altered Levels of Mitochondrial DNA Are Associated with Female Age, Aneuploidy, and Provide an Independent Measure of Embryonic Implantation Potential. Fragouli E, Spath K, Alfarawati S, Kaper F, Craig A, Michel CE, Kokocinski F, Cohen J, Munne S, Wells D, PLoS Genet. 2015 doi:
Intra-sample heterogeneity of sperm DNA methylation. Jenkins TG, Aston K, Trost C, Farley J, Hotaling J M, Carrell D, Mol Hum Reprod. 2015 doi:
Obstetric and neonatal outcome of pregnancies fathered by males on immunosuppression after solid organ transplantation Morken NH, Diaz-Garcia C, Reisaeter AV, Foss A, Leivestad T, Geiran O, Hervas D, Brännström M, 2015 doi:
Oocyte cryopreservation as a preventive measure for age-related fertility loss. Cil AP, Turkgeldi L, Seli E, Semin Reprod Med. 2015 doi:
Oocyte mitochondrial function and reproduction. Babayev E, Seli E, Curr Opin Obstet Gynecol. 2015 doi:
Ovarian ageing Seli E, Semin Reprod Med. 2015 doi:
Role of oocyte vitrification for fertility preservation programs. Herrero J, Rubio I, Curr Trends Clin Embryol. 2015 doi:
Strategies for controlled ovarian stimulation in the setting of ovarian ageing. Ata B, Seli E, Semin Reprod Med. 2015 doi:
Aneuploidy across individual chromosomes at the embryonic level in trophectoderm biopsies: changes with patient age and chromosome structure. Franasiak J M, Forman EJ, Hong KH, Werner M D, Upham KM, Treff NR, J Assist Reprod Genet. 2014 doi:
Diminished Effect of Maternal Age on Implantation After Preimplantation Genetic Diagnosis With Array Comparative Genomic Hybridization. Harton GL, Munne S, Surrey M, Grifo J, Kaplan B, McCulloh DH, Griffin DK, Wells D, PGD Practitioners Group, Obstet Gynecol Surv. 2014 doi:
Feasibility, acceptance, and efectiveness of an ergonomics training program. Franasiak J M, Craven R, Mosaly P, Gehrig PA, J Soc Laparoendosc Surg. 2014 doi:
Genetic associations with diminished ovarian reserve: a systematic review of the literature. Greene AD, Patounakis G, Segars JH, J Assist Reprod Genet. 2014 doi:
Pregnancy success after hysteroscopic sterilization reversal. Franasiak J M, Monteith C, Berger G, Zerden M, Obstetrics and Gynecology. 2014 doi:
The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Franasiak J M, Forman EJ, Hong KH, Werner M D, Upham KM, Treff NR, Fertil Steril. 2014 doi:
Increased numbers of DNA-damaged spermatozoa in samples presenting an elevated rate of numerical chromosome abnormalities. Enciso M, Alfarawati S, Wells D, Hum Reprod. 2013 doi:
Sildenafil citrate improves perinatal outcome in fetuses from pre-eclamptic rats Herraiz S, Pellicer B, Serra V, Cauli O, Cortijo J, Felipo V, Pellicer A, BJOG. Oct. 2012 doi: 10.1111/j.1471-0528.2012.03430.x
Analysis of diagnostic angiography and angioembolization in the acute management of renal trauma using a national data set. Hotaling J M, Sorensen MD, Smith TG 3rd, Rivara FP, Wessells H, Voelzke BB, J Urol. 2011 doi:
Different telomere-length dynamics at the Inner Cell Mass versus Established Embryonic Stem (ES) cells. Varela E, Schneider RP, Ortega S, Blasco MA, Proc Natl Acad Sci USA. 2011 doi:
Redefining advanced maternal age as an indication for implantation genetic screening. Milan M, Cobo A, Rodrigo L, Mateu E, Mercader A, Buendia P, Peinado V, Delagado A, MIr P, Simon C, Remohi J, RBM Online. 2010 doi:
Swim-up procedure selects spermatozoa with longer telomere length. Santiso R, Tamayo M, Gosalvez J, Meseguer M, Garrido N, Fernandez JL, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2010 doi:
Influence of paternal age on assisted reproduction outcome Bellver J, Garrido N, Remohi J, Pellicer A, Meseguer M, Reprod Biomed Online. Nov. 2008 doi: 10.1016/s1472-6483(10)60305-7
Male age negatively impacts embryo development and reproductive outcome in donor oocyte ART cycles. Scott R T, Elkind-Hirsch KE, Miller BT, Miller KA, Frattarelli JL, Fertil Steril. 2008 doi:
Maternal age-related differential global expression profiles observed in human oocytes. Steuerwald NM, Bermúdez MG, Wells D, Munne S, Cohen J, RBM Online. 2007 doi:
Age and uterine receptiveness: predicting the outcome of oocyte donation cycles Soares S R, Troncoso C, Bosch E, Serra V, Simon C, Remohi J, Pellicer A, J Clin Endocrinol Metab. Jul. 2005 doi: 10.1210/jc.2004-2252
Diminished ovarian reserve and access to care. Scott R T, Fertil Steril. 2004 doi:
Infertility after age 35: Diagnostic strategies. Seifer DB, Scott R T, Buyalos RP, Ob Gyn Management. 1996 doi:
Intraobserver, interobserver variation of sperm critical morphology: comparison of examiner and computer-assisted analysis. Hofmann GE, Santilli BA, Kindig S, Scott R T, Johnson CA, Fertil Steril. 1996 doi:
Repercusión of the hormonal substitute therapy in the antitrombin III. Seara S, Guillen V, Santiago L, Blanco C, Rodriguez R, Morin S J, Garcia JA, Endocrinology. 1996 doi:
Age related decline in Female fertility is not due to diminished capacity of the uterus to sustain embryo implantation. Navot D, Drews MR, Bergh PA, Guzman I, Karstaedt A, Scott R T, Garrisi GJ, Hofmann GE, Fertil Steril. 1994 doi:
Bleeding patterns in postmenopausal women taking continuous combined or sequential regimens of conjugated estrogens with medroxyprogesterone acetate Archer DF, Pickar JH, Bottiglioni F, Menopause Study Group, Obstet Gynecol. 1994 doi:
Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone. Woodruff JD, Pickar JH, Menopause Study Group, Am J Obstet Gynecol. 1994 doi:

Presentations
from this area

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ASRM2020 P-280 CHARACTERIZATION OF TELOMERE STATUS DURING OVARIAN AGING IN THE SAMP8 (SENESCENCE ACCELERATED MOUSE PRONE 8) MODEL. Polonio AM González-García MT Córdova-Oriz I Marta Medrano Chico-Sordo L Garcia-Velasco JA Elisa Varela Presented at 76th American Society of Reproductive Medicine Scientific Congress P-123 FOLLICULAR ACTIVATION BY INTRAOVARIAN INJECTION OF AUTOLOGOUS PLATELET RICH PLASMA (PRP) IN WOMEN WITH PRIMARY OVARIAN INSUFFICIENCY (POI): IMPACT ON OVARIAN RESERVE AND IVF OUTCOME. Cakiroglu Y Saltik A Yuceturk A Karaosmanoglu O Yildirim Kopuk S Scott RT Seli E Presented at 76th American Society of Reproductive Medicine Scientific Congress P-864 OVARIAN RESERVE PARAMETERS AND IVF OUTCOMES IN 510 WOMEN WITH POOR OVARIAN RESPONSE (POR) TREATED WITH INTRAOVARIAN INJECTION OF AUTOLOGOUS PLATELET RICH PLASMA (PRP) Cakiroglu Y Saltik A Yuceturk A Karaosmanoglu O Yildirim Kopuk S Scott RT Seli E Presented at 76th American Society of Reproductive Medicine Scientific Congress P-608 IN YOUNG WOMEN WITH POOR OVARIAN RESPONSE (POR), MICRORNA EXPRESSION IN PERIPHERAL BLOOD MONONUCLEAR (PBMN) CELLS IS ALTERED COMPARED TO NORMO-RESPONDER CONTROLS Cozzolino M Titus S Herraiz S Pellicer A Scott RT Seli E Presented at 76th American Society of Reproductive Medicine Scientific Congress P-355 IMPACT OF ULTRASOUND DIAGNOSIS OF ADENOMYOSIS ON PREGNANCY RATE AND OUTCOME IN IVF CYCLES WITH DONATED OOCYTES: A PROSPECTIVE STUDY Exacoustos C Cosentino M Loiudice L Martire FG Galliano D Pellicer A Presented at 76th American Society of Reproductive Medicine Scientific Congress
ESHRE 2020 O-088 Bone marrow derived stem cells restore ovarian function and fertility in premature ovarian insufficiency women. Interim report of a randomized trial: mobilization versus ovarian injection. Pellicer N Herraiz S Martínez RM Buigues A Gómez-Seguí I Martínez J Pellicer A Presented at the 36th annual meeting of the European Society of Human Reproduction and Embryology
SRI 2020 0-143 G-CSF Mobilized Plasma Regenerate Ovarian Stroma and Restore Ovarian Function. Buigues A Marchante M Martínez J Pellicer A Herraiz S Presented at the 67th Annual Meeting of the Society for Reproductive Investigation T-206 Endometrial Aging Evidence at Transcriptomic Level Devesa-Peiro A Sebastian-Leon P Pellicer A Diaz-Gimeno P Presented at the 67th Annual Meeting of the Society for Reproductive Investigation
ASRM 2019 P-417 Effect of different 6-dimethylaminopurine (6-DMAP) treatments on reversible arresting of mono and tripronuclear embryos at the pronuclear stage Grau Gonzalez-Picazo A Soler N Escribá MJ Vendrell X Viloria T Presented at the 35th annual meeting of the European Society of Human Reproduction and Embryology P-110 Blastocyst grade predicts outcome after frozen euploid transfer in patients with recurrent pregnancy loss Marugappan G Kim G Kort JD Hanson BM Neal SA Tiegs AW Osman EK Scott RT Lathi RB Presented at the 35th annual meeting of the European Society of Human Reproduction and Embryology P-455 Multi-site, blind prospective trial assessing whether semen oxidation reduction potential (SORP) assessment can be used to predict low fertilisation with conventional IVF: interim analysis Pool G Rogers S Mania A Everett G Doshi AM Srikantharajah S Joshi HN Wilding M Bishop S Muriel L Maalouf W Hickman C Presented at the 74th Scientific Congress & Expo of the American Society for Reproductive Medicine
ESHRE 2019 P-134: Protein profile of euploid single embryo transfer reveals differential patterns among them. Meseguer M Bori L Del Gallego R Remohí J Quinonero A Dominguez F Presented at the 74th Scientific Congress & Expo of the American Society for Reproductive Medicine
SRI 2019 Association of Blood Cadmium and Lead Levels with Reproductive Lifespan Among Postmenopausal Women: NHANES 2005-2014. Gonzalez-Martin R Telez-Plaza M Domínguez F Presented at the 34rd annual meeting of the European Society of Human Reproduction and Embryology
ASRM 2018 Ultra-low oxygen (o2) tension after day 3 of in vitro development does not alter blastocyst transcriptome: a comparison of 2% versus 5% o2 tension in extended culture Morin SJ Wang T Tao X Earnhardt M Seli E Scott RT Presented at the 34rd annual meeting of the European Society of Human Reproduction and Embryology Gonadotrophin receptor polymorphisms (fshr n680s and lhcgr n312s) are not of clinical outcome and live birth in ivf cycles Pirtea P Marin D Sun L Hong K Zhan Y Tao X Scott RT Presented at the 65th Annual Meeting of the Society for Reproductive Investigation Abc trial: appraisal of body content. Frozen embryo cycles are not impacted by the negative effects of obesity seen in fresh cycles Kim G Morin SJ Patounakis G Juneau C Neal SA Presented at the 65th Annual Meeting of the Society for Reproductive Investigation Evaluation of sperm mitochondrial dna copy number as a predictor of in vitro fertilization/intracytoplasmic sperm injection (ivf/icsi) cycle outcomes in a large infertile population Tiegs W Tao X Landis J Rajchel J Bedard JL Seli E Wells D Fragouli E Scott RT Presented at the 65th Annual Meeting of the Society for Reproductive Investigation
ESHRE 2018 Functional genomic meta-analysis identifies similarities between endometrial-related subfertilities Devesa A Sebastian-Leon P Garcia-Garcia F Arnau V Pellicer A Diaz-Gimeno P Presented at the 73rd annual meeting of the American Society of Reproductive Medicine
SRI 2018 Stem Cell-Secreted Paracrine Factors in Human Endometrial Regeneration López-Pérez N Santamaría X Díaz-Gimeno P Sebastian-Leon P Faus A Remohí J Pellicer A Simón C Cervelló I Presented at the 33rd annual meeting of the European Society of Human Reproduction and Embryology
ASRM 2017 Estimation of reproductive success according to age, number of oocytes and etiology in elective or oncological fertility preservation (FP) patients Cobo A Meseguer M Coello A Sanchez E Garcia Velasco J Remohí J Pellicer A Presented at the 33rd annual meeting of the European Society of Human Reproduction and Embryology Oocyte dysmorphisms are not associated with post warming survival, fertilization and embryo development in own oocytes vitrification cycles Coello A Sanchez E Campos P Vallejo B Meseguer M Cobo A Presented at the 33rd annual meeting of the European Society of Human Reproduction and Embryology Incidental diagnosis of a parental balanced reciprocal rearrangement in couples undergoing routine aneuploidy screening by targeted next generation sequencing (TNGS) Garnsey HM Eccles JM Iturriaga A Scott RT Zimmerman RS Presented at the 64th Annual Meeting of the Society for Reproductive Investigation Current surgical experience and deficits in reproductive endocrinology and infertility training across fellowships in the United States Goodman L Khan Z Franasiak JM Juneau CR Morin SJ Neal SA Scott RT Goldberg JM Presented at the 64th Annual Meeting of the Society for Reproductive Investigation

Areas of Investigation