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1. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Author

Rahmioglu, Nilufer, Mortlock, Sally, Ghiasi, Marzieh, Møller, Peter L., Stefansdottir, Lilja, Galarneau, Geneviève, Turman, Constance, Danning, Rebecca, Law, Matthew H., Sapkota, Yadav, Christofidou, Paraskevi, Skarp, Sini, Giri, Ayush, Banasik, Karina, Krassowski, Michal, Lepamets, Maarja, Marciniak, Błażej, Nõukas, Margit, Perro, Danielle, Sliz, Eeva, Sobalska-Kwapis, Marta, Thorleifsson, Gudmar, Topbas-Selcuki, Nura F., Vitonis, Allison, Westergaard, David, Arnadottir, Ragnheidur, Burgdorf, Kristoffer S., Campbell, Archie, Cheuk, Cecilia S. K., Clementi, Caterina, Cook, James, De Vivo, Immaculata, DiVasta, Amy, Dorien, O., Donoghue, Jacqueline F., Edwards, Todd, Fontanillas, Pierre, Fung, Jenny N., Geirsson, Reynir T., Girling, Jane E., Harkki, Paivi, Harris, Holly R., Healey, Martin, Heikinheimo, Oskari, Holdsworth-Carson, Sarah, Hostettler, Isabel C., Houlden, Henry, Houshdaran, Sahar, Irwin, Juan C., Jarvelin, Marjo-Riitta, Kamatani, Yoichiro, Kennedy, Stephen H., Kepka, Ewa, Kettunen, Johannes, Kubo, Michiaki, Kulig, Bartosz, Kurra, Venla, Laivuori, Hannele, Laufer, Marc R., Lindgren, Cecilia M., MacGregor, Stuart, Mangino, Massimo, Martin, Nicholas G., Matalliotaki, Charoula, Matalliotakis, Michail, Murray, Alison D., Ndungu, Anne, Nezhat, Camran, Olsen, Catherine M., Opoku-Anane, Jessica, Padmanabhan, Sandosh, Paranjpe, Manish, Peters, Maire, Polak, Grzegorz, Porteous, David J., Rabban, Joseph, Rexrode, Kathyrn M., Romanowicz, Hanna, Saare, Merli, Saavalainen, Liisu, Schork, Andrew J., Sen, Sushmita, Shafrir, Amy L., Siewierska-Górska, Anna, Słomka, Marcin, Smith, Blair H., Smolarz, Beata, Szaflik, Tomasz, Szyłło, Krzysztof, Takahashi, Atsushi, Terry, Kathryn L., Tomassetti, Carla, Treloar, Susan A., Vanhie, Arne, Vincent, Katy, Vo, Kim C., Werring, David J., Zeggini, Eleftheria, Zervou, Maria I., Adachi, Sosuke, Buring, Julie E., Ridker, Paul M., D’Hooghe, Thomas, Goulielmos, George N., Hapangama, Dharani K., Hayward, Caroline, Horne, Andrew W., Low, Siew-Kee, Martikainen, Hannu, Chasman, Daniel I., Rogers, Peter A. W., Saunders, Philippa T., Sirota, Marina, Spector, Tim, Strapagiel, Dominik, Tung, Joyce Y., Whiteman, David C., Giudice, Linda C., Velez-Edwards, Digna R., Uimari, Outi, Kraft, Peter, Salumets, Andres, Nyholt, Dale R., Mägi, Reedik, Stefansson, Kari, Becker, Christian M., Yurttas-Beim, Piraye, Steinthorsdottir, Valgerdur, Nyegaard, Mette, Missmer, Stacey A., Montgomery, Grant W., Morris, Andrew P., and Zondervan, Krina T.

Published
2023
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3. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Author

Rahmioglu, N, Mortlock, S, Ghiasi, M, Moller, PL, Stefansdottir, L, Galarneau, G, Turman, C, Danning, R, Law, MH, Sapkota, Y, Christofidou, P, Skarp, S, Giri, A, Banasik, K, Krassowski, M, Lepamets, M, Marciniak, B, Noukas, M, Perro, D, Sliz, E, Sobalska-Kwapis, M, Thorleifsson, G, Topbas-Selcuki, NF, Vitonis, A, Westergaard, D, Arnadottir, R, Burgdorf, KS, Campbell, A, Cheuk, CSK, Clementi, C, Cook, J, De Vivo, I, DiVasta, A, Dorien, O, Donoghue, JF, Edwards, T, Fontanillas, P, Fung, JN, Geirsson, RT, Girling, JE, Harkki, P, Harris, HR, Healey, M, Heikinheimo, O, Holdsworth-Carson, S, Hostettler, IC, Houlden, H, Houshdaran, S, Irwin, JC, Jarvelin, M-R, Kamatani, Y, Kennedy, SH, Kepka, E, Kettunen, J, Kubo, M, Kulig, B, Kurra, V, Laivuori, H, Laufer, MR, Lindgren, CM, MacGregor, S, Mangino, M, Martin, NG, Matalliotaki, C, Matalliotakis, M, Murray, AD, Ndungu, A, Nezhat, C, Olsen, CM, Opoku-Anane, J, Padmanabhan, S, Paranjpe, M, Peters, M, Polak, G, Porteous, DJ, Rabban, J, Rexrode, KM, Romanowicz, H, Saare, M, Saavalainen, L, Schork, AJ, Sen, S, Shafrir, AL, Siewierska-Gorska, A, Slomka, M, Smith, BH, Smolarz, B, Szaflik, T, Szyllo, K, Takahashi, A, Terry, KL, Tomassetti, C, Treloar, SA, Vanhie, A, Vincent, K, Vo, KC, Werring, DJ, Zeggini, E, Zervou, M, Stefansson, K, Nyegaard, M, Uimari, O, Yurttas-Beim, P, Tung, JY, Adachi, S, Buring, JE, Ridker, PM, D'Hooghe, T, Goulielmos, GN, Hapangama, DK, Hayward, C, Horne, AW, Low, S-K, Martikainen, H, Chasman, D, Rogers, PAW, Saunders, PT, Sirota, M, Spector, T, Strapagiel, D, Whiteman, DC, Giudice, LC, Velez-Edwards, DR, Kraft, P, Salumets, A, Nyholt, DR, Magi, R, Becker, CM, Steinthorsdottir, V, Missmer, SA, Montgomery, GW, Morris, AP, Zondervan, KT, Rahmioglu, N, Mortlock, S, Ghiasi, M, Moller, PL, Stefansdottir, L, Galarneau, G, Turman, C, Danning, R, Law, MH, Sapkota, Y, Christofidou, P, Skarp, S, Giri, A, Banasik, K, Krassowski, M, Lepamets, M, Marciniak, B, Noukas, M, Perro, D, Sliz, E, Sobalska-Kwapis, M, Thorleifsson, G, Topbas-Selcuki, NF, Vitonis, A, Westergaard, D, Arnadottir, R, Burgdorf, KS, Campbell, A, Cheuk, CSK, Clementi, C, Cook, J, De Vivo, I, DiVasta, A, Dorien, O, Donoghue, JF, Edwards, T, Fontanillas, P, Fung, JN, Geirsson, RT, Girling, JE, Harkki, P, Harris, HR, Healey, M, Heikinheimo, O, Holdsworth-Carson, S, Hostettler, IC, Houlden, H, Houshdaran, S, Irwin, JC, Jarvelin, M-R, Kamatani, Y, Kennedy, SH, Kepka, E, Kettunen, J, Kubo, M, Kulig, B, Kurra, V, Laivuori, H, Laufer, MR, Lindgren, CM, MacGregor, S, Mangino, M, Martin, NG, Matalliotaki, C, Matalliotakis, M, Murray, AD, Ndungu, A, Nezhat, C, Olsen, CM, Opoku-Anane, J, Padmanabhan, S, Paranjpe, M, Peters, M, Polak, G, Porteous, DJ, Rabban, J, Rexrode, KM, Romanowicz, H, Saare, M, Saavalainen, L, Schork, AJ, Sen, S, Shafrir, AL, Siewierska-Gorska, A, Slomka, M, Smith, BH, Smolarz, B, Szaflik, T, Szyllo, K, Takahashi, A, Terry, KL, Tomassetti, C, Treloar, SA, Vanhie, A, Vincent, K, Vo, KC, Werring, DJ, Zeggini, E, Zervou, M, Stefansson, K, Nyegaard, M, Uimari, O, Yurttas-Beim, P, Tung, JY, Adachi, S, Buring, JE, Ridker, PM, D'Hooghe, T, Goulielmos, GN, Hapangama, DK, Hayward, C, Horne, AW, Low, S-K, Martikainen, H, Chasman, D, Rogers, PAW, Saunders, PT, Sirota, M, Spector, T, Strapagiel, D, Whiteman, DC, Giudice, LC, Velez-Edwards, DR, Kraft, P, Salumets, A, Nyholt, DR, Magi, R, Becker, CM, Steinthorsdottir, V, Missmer, SA, Montgomery, GW, Morris, AP, and Zondervan, KT

Abstract

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.

Published
2023

11. Successive single embryo transfer cycles lead to reduced risk without compromising success rates in women under 38

Author

Hunter Cohn, K., primary, Wu, H., additional, Schnorr, J., additional, Arredondo, F., additional, Miller, B., additional, Leondires, M.P., additional, Gutmann, J., additional, Weckstein, L., additional, Nulsen, J., additional, Katz, S.E., additional, Lin, P.C., additional, Copperman, A.B., additional, Widra, E.A., additional, and Yurttas Beim, P., additional

Published
2016
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13. Development of personalized predictive models for non-IVF and IVF procedures in lesbian and single women sheds light on applicability of infertility biomarkers to women of unknown fertility status

Author

Santistevan, A., primary, Hunter Cohn, K., additional, Schnorr, J., additional, Arredondo, F., additional, Miller, B., additional, Leondires, M.P., additional, Gutmann, J., additional, Weckstein, L., additional, Katz, S.E., additional, Nulsen, J., additional, Lin, P.C., additional, Copperman, A.B., additional, Widra, E.A., additional, and Yurttas Beim, P., additional

Published
2016
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16. Pregancy loss is a major risk for premature IVF treatment discontinuation

Author

B.T. Miller, Alan B. Copperman, J.N. Gutmann, H. Karvir, Yurttas Beim P, Hunter Cohn K, F. Arredondo, and M.P. Leondires

Subjects
Ivf treatment, medicine.medical_specialty, Reproductive Medicine, business.industry, Obstetrics, Obstetrics and Gynecology, Medicine, business, Discontinuation
Published
2016

35. A clinical research integration special program (CRISP) for young women with primary ovarian insufficiency

Author

Falorni A, Minarelli V, Cm, Eads, Cm, Joachim, Persani L, Rossetti R, Yurttas Beim P, Va, Pellegrini, Pf, Schnatz, Rafique S, Kissell K, Ka, Calis, Popat V, and Lawrence M Nelson

Subjects
Adult, Biomedical Research, Insufficienza ovarica primitiva, autoimmunità ovarica, terapia ormonale, Primary Ovarian Insufficiency, Article, Pregnancy, Humans, Female, Genetic Predisposition to Disease, Disease Susceptibility, Program Development
Abstract

Large-scale medical sequencing provides a focal point around which to reorganize health care and health care research. Mobile health (mHealth) is also currently undergoing explosive growth and could be another innovation that will change the face of future health care. We are employing primary ovarian insufficiency (POI) as a model rare condition to explore the intersection of these potentials. As both sequencing capabilities and our ability to intepret this information improve, sequencing for medical purposes will play an increasing role in health care beyond basic research: it will help guide the delivery of care to patients. POI is a serious chronic disorder and syndrome characterized by hypergonadotrophic hypogonadism before the age of 40 years and most commonly presents with amenorrhea. It may have adverse health effects that become fully evident years after the initial diagnosis. The condition is most commonly viewed as one of infertility, however, it may also be associated with adverse long-term outcomes related to inadequate bone mineral density, increased risk of cardiovascular disease, adrenal insufficiency, hypothyroidism and, if pregnancy ensues, having a child with Fragile X Syndrome. There may also be adverse outcomes related to increased rates of anxiety and depression. POI is also a rare disease, and accordingly, presents special challenges. Too often advances in research are not effectively integrated into community care at the point of service for those with rare diseases. There is a need to connect community health providers in real time with investigators who have the requisite knowledge and expertise to help manage the rare disease and to conduct ongoing research. Here we review the pathophysiology and management of POI and propose the development of an international Clinical Research Integration Special Program (CRISP) for the condition.

37. Freeze-only versus fresh embryo transfer in a multicenter matched cohort study: contribution of progesterone and maternal age to success rates.

Author

Wang A, Santistevan A, Hunter Cohn K, Copperman A, Nulsen J, Miller BT, Widra E, Westphal LM, and Yurttas Beim P

Subjects
Adult, Age Distribution, Biomarkers blood, Cohort Studies, Female, Fertilization in Vitro statistics & numerical data, Humans, Infertility, Female blood, Middle Aged, Ovulation Induction statistics & numerical data, Pregnancy, Retrospective Studies, United States epidemiology, Young Adult, Cryopreservation statistics & numerical data, Embryo Transfer statistics & numerical data, Infertility, Female epidemiology, Infertility, Female therapy, Maternal Age, Pregnancy Rate, Progesterone blood
Abstract

Objective: To compare implantation and ongoing pregnancy rates in freeze-only versus fresh transfer cycles., Design: Retrospective matched cohort study., Setting: Not applicable., Patient(s): Women selected using a matching algorithm for similar distributions of clinical characteristics for a total of 2,910 cycles (1,455 fresh cohort and 1,455 freeze-only cohort)., Intervention(s): None., Main Outcome Measure(s): Implantation and ongoing pregnancy rates., Result(s): Implantation and ongoing pregnancy rates were statistically significantly higher in the freeze-only transfer cohort than in the matched fresh transfer cohort: ongoing pregnancy rate for freeze-only was 52.0% (95% confidence interval [CI], 49.4-54.6) and for fresh was 45.3% (95% CI, 42.7-47.9), odds ratio (OR) 1.31 (95% CI, 1.13-1.51). In a stratified analysis, the odds of ongoing pregnancy after freeze-only transfer were statistically significantly higher for women both above and below age 35 with progesterone concentration >1.0 ng/mL (age ≤35: OR 1.38 [1.11-1.71]; age >35: OR 1.73 [1.34-2.24]). For women with progesterone concentration ≤1.0 ng/mL, no statistically significant difference in freeze-only odds of ongoing pregnancy was observed in either age group. The sensitivity analysis revealed that increasing maternal age alone (regardless of progesterone) trended toward a more beneficial effect of freeze-only cycles. A lower progesterone concentration was associated with statistically significantly higher ongoing pregnancy odds for fresh but not freeze-only cycles., Conclusion(s): Freeze-only transfer protocols are associated with statistically significantly higher ongoing implantation and pregnancy rates compared with fresh transfer cycles. This effect is most pronounced for cycles with progesterone >1.0 ng/mL at trigger and may also be stronger for older patients., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Published
2017
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38. A clinical research integration special program (CRISP) for young women with primary ovarian insufficiency.

Author

Falorni A, Minarelli V, Eads CM, Joachim CM, Persani L, Rossetti R, Yurttas Beim P, Pellegrini VA, Schnatz PF, Rafique S, Kissell K, Calis KA, Popat V, and Nelson LM

Subjects
Adult, Disease Susceptibility immunology, Female, Genetic Predisposition to Disease, Humans, Pregnancy, Primary Ovarian Insufficiency etiology, Primary Ovarian Insufficiency physiopathology, Program Development, Biomedical Research organization & administration, Primary Ovarian Insufficiency therapy
Abstract

Large-scale medical sequencing provides a focal point around which to reorganize health care and health care research. Mobile health (mHealth) is also currently undergoing explosive growth and could be another innovation that will change the face of future health care. We are employing primary ovarian insufficiency (POI) as a model rare condition to explore the intersection of these potentials. As both sequencing capabilities and our ability to intepret this information improve, sequencing for medical purposes will play an increasing role in health care beyond basic research: it will help guide the delivery of care to patients. POI is a serious chronic disorder and syndrome characterized by hypergonadotrophic hypogonadism before the age of 40 years and most commonly presents with amenorrhea. It may have adverse health effects that become fully evident years after the initial diagnosis. The condition is most commonly viewed as one of infertility, however, it may also be associated with adverse long-term outcomes related to inadequate bone mineral density, increased risk of cardiovascular disease, adrenal insufficiency, hypothyroidism and, if pregnancy ensues, having a child with Fragile X Syndrome. There may also be adverse outcomes related to increased rates of anxiety and depression. POI is also a rare disease, and accordingly, presents special challenges. Too often advances in research are not effectively integrated into community care at the point of service for those with rare diseases. There is a need to connect community health providers in real time with investigators who have the requisite knowledge and expertise to help manage the rare disease and to conduct ongoing research. Here we review the pathophysiology and management of POI and propose the development of an international Clinical Research Integration Special Program (CRISP) for the condition.

Published
2014

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