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Impact of obesity on medically assisted reproductive treatments

Published online by Cambridge University Press:  16 March 2022

Romualdo Sciorio Open the ORCID record for Romualdo Sciorio [Opens in a new window] ,
Serena Bellaminutti ,
Luca Tramontano  and
Sandro C. Esteves
Romualdo Sciorio*
Affiliation:
Edinburgh Assisted Conception Programme, EFREC, Royal Infirmary of Edinburgh, UK
Serena Bellaminutti
Affiliation:
Department of Women, Infants and Adolescents, Division of Obstetrics, Geneva University Hospitals, Boulevard de la Cluse 30, 1211 Genève 14, Switzerland
Luca Tramontano
Affiliation:
Department of Women, Infants and Adolescents, Division of Obstetrics, Geneva University Hospitals, Boulevard de la Cluse 30, 1211 Genève 14, Switzerland
Sandro C. Esteves
Affiliation:
ANDROFERT, Andrology and Human Reproduction Clinic, Campinas, Brazil Department of Surgery (Division of Urology), University of Campinas (Brazil) Faculty of Health, Aarhus University, Aarhus, Denmark
*
Author for correspondence: Romualdo Sciorio. Edinburgh Assisted Conception Programme, EFREC, Royal Infirmary of Edinburgh, UK. E-mail: [email protected]
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Summary

Increasing evidence has demonstrated that obesity impairs female fertility and negatively affects human reproductive outcome following medically assisted reproduction (MAR) treatment. In the United States, 36.5% of women of reproductive age are obese. Obesity results not only in metabolic disorders including type II diabetes and cardiovascular disease, but might also be responsible for chronic inflammation and oxidative stress. Several studies have demonstrated that inflammation and reactive oxygen species (ROS) in the ovary modify steroidogenesis and might induce anovulation, as well as affecting oocyte meiotic maturation, leading to impaired oocyte quality and embryo developmental competence. Although the adverse effect of female obesity on human reproduction has been an object of debate in the past, there is growing evidence showing a link between female obesity and increased risk of infertility. However, further studies need to clarify some gaps in knowledge. We reviewed the recent evidence on the association between female obesity and infertility. In particular, we highlight the association between fat distribution and reproductive outcome, and how the inflammation and oxidative stress mechanisms might reduce ovarian function and oocyte quality. Finally, we evaluate the connection between female obesity and endometrial receptivity.

Keywords

Embryo competenceIn vitro embryo developmentInfertilityObesityOocyte qualityReproductive health
Type
Review Article
Information
Zygote , Volume 30 , Issue 4 , August 2022 , pp. 431 - 439
Copyright
© The Author(s), 2022. Published by Cambridge University Press

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References

Aydogan Mathyk, B and Quaas, AM (2021). Obesity and IVF: Weighing in on the evidence. J Assist Reprod Genet 38, 343–5. doi: 10.1007/s10815-021-02068-6 CrossRefGoogle Scholar
Babayev, E and Seli, E (2015). Oocyte mitochondrial function and reproduction. Curr Opin Obstet Gynecol 27, 175–81. doi: 10.1097/GCO.0000000000000164 CrossRefGoogle ScholarPubMed
Belizário, JE, Belizário, JE and Napolitano, M (2015). Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches. Front Microbiol 6, 1050. doi: 10.3389/fmicb.2015.01050 CrossRefGoogle ScholarPubMed
Bellver, J (2008). Impact of body weight and lifestyle on IVF outcome. Exp Rev Obstet Gynecol 3, 607–25. doi: 10.1586/17474108.3.5.607 CrossRefGoogle Scholar
Bellver, J, Rossal, LP, Bosch, E, Zúñiga, A, Corona, JT, Meléndez, F, Gómez, E, Simón, C, Remohí, J and Pellicer, A (2003). Obesity and the risk of spontaneous abortion after oocyte donation. Fertil Steril 79, 1136–40. doi: 10.1016/s0015-028200176-6 CrossRefGoogle ScholarPubMed
Bellver, J, Busso, C, Pellicer, A, Remohí, J and Simón, C (2006). Obesity and assisted reproduction technology outcomes. Reprod Biomed Online 12, 562–8. doi: 10.1016/s1472-648361181-9 CrossRefGoogle Scholar
Bellver, J, Melo, MA, Bosch, E, Serra, V, Remohí, J and Pellicer, A (2007). Obesity and poor reproductive outcome: The potential role of the endometrium. Fertil Steril 88, 446–51. doi: 10.1016/j.fertnstert.2006.11.162 CrossRefGoogle ScholarPubMed
Bellver, J, Martínez-Conejero, JA, Labarta, E, Alamà, P, Melo, MA, Remohí, J, Pellicer, A and Horcajadas, JA (2011). Endometrial gene expression in the window of implantation is altered in obese women especially in association with polycystic ovary syndrome. Fertil Steril 95, 2335–41, 2341.e1. doi: 10.1016/j.fertnstert.2011.03.021 CrossRefGoogle ScholarPubMed
Bellver, J, Pellicer, A, García-Velasco, JA, Ballesteros, A, Remohí, J and Meseguer, M (2013). Obesity reduces uterine receptivity: Clinical experience from 9,587 first cycles of ovum donation with normal weight donors. Fertil Steril 100, 1050–8. doi: 10.1016/j.fertnstert.2013.06.001 CrossRefGoogle ScholarPubMed
Berg, AH and Scherer, PE (2005). Adipose tissue, inflammation, and cardiovascular disease. Circ Res 96, 939–49. doi: 10.1161/01.RES.0000163635.62927.34 CrossRefGoogle Scholar
Boots, C and Stephenson, MD (2011). Does obesity increase the risk of miscarriage in spontaneous conception: A systematic review. Semin Reprod Med 29, 507–13. doi: 10.1055/s-0031-1293204 CrossRefGoogle ScholarPubMed
Borradaile, NM, Han, X, Harp, JD, Gale, SE, Ory, DS and Schaffer, JE (2006). Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death. J Lipid Res 47, 2726–37. doi: 10.1194/jlr.M600299-JLR200 CrossRefGoogle ScholarPubMed
Brännström, M and Enskog, A (2002). Leukocyte networks and ovulation. J Reprod Immunol 57(1–2), 47–60. doi: 10.1016/s0165-037800009-8 CrossRefGoogle ScholarPubMed
Broughton, DE and Moley, KH (2017). Obesity and female infertility: Potential mediators of obesity’s impact. Fertil Steril 107, 840–7. doi: 10.1016/j.fertnstert.2017.01.017 CrossRefGoogle ScholarPubMed
Buccione, R, Schroeder, AC and Eppig, JJ (1990). Interactions between somatic cells and germ cells throughout mammalian oogenesis. Biol Reprod 43, 543–7. doi: 10.1095/biolreprod43.4.543 CrossRefGoogle ScholarPubMed
Cani, PD, Amar, J, Iglesias, MA, Poggi, M, Knauf, C, Bastelica, D, Neyrinck, AMFAVA Fava, F, Tuohy, KM, Chabo, C, Waget, A, Delmée, E, Cousin, B, Sulpice, T, Chamontin, B, Ferrières, J, Tanti, JF, Gibson, GR, Casteilla, L, Delzenne, NM, Alessi, MC and Burcelin, R (2007). Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 1761–72. doi: 10.2337/db06-1491 CrossRefGoogle ScholarPubMed
Canipari, R, Cellini, V and Cecconi, S (2012). The ovary feels fine when paracrine and autocrine networks cooperate with gonadotropins in the regulation of folliculogenesis. Curr Pharmaceut Design 18, 245–55. doi: 10.2174/138161212799040411 Google ScholarPubMed
Chaffin, CL, Latham, KE, Mtango, NR, Midic, U and VandeVoort, CA (2014). Dietary sugar in healthy female primates perturbs oocyte maturation and in vitro preimplantation embryo development. Endocrinology 155, 2688–95. doi: 10.1210/en.2014-1104 CrossRefGoogle ScholarPubMed
Cho, I and Blaser, MJ (2012). The human microbiome: At the interface of health and disease. Nat Rev Genet 13, 260–70. doi: 10.1038/nrg3182 CrossRefGoogle ScholarPubMed
Cinti, S, Mitchell, G, Barbatelli, G, Murano, I, Ceresi, E, Faloia, E, Wang, S, Fortier, M, Greenberg, AS and Obin, MS (2005). Adipocyte death and macrophages localisation and function in adipose tissue of obese mice and humans. J Lipid Res 46, 2347–55. doi: 10.1194/jlr.M500294-JLR200 CrossRefGoogle Scholar
Comstock, IA, Diaz-Gimeno, P, Cabanillas, S, Bellver, J, Sebastian-Leon, P, Shah, M, Schutt, A, Valdes, CT, Ruiz-Alonso, M, Valbuena, D, Simon, C and Lathi, RB (2017). Does an increased body mass index affect endometrial gene expression patterns in infertile patients? A functional genomics analysis. Fertil Steril 107, 740–8.e2. doi: 10.1016/j.fertnstert.2016.11.009 CrossRefGoogle ScholarPubMed
Cox, LM and Blaser, MJ (2013). Pathways in microbe-induced obesity. Cell Metab 17, 883–94. doi: 10.1016/j.cmet.2013.05.004 CrossRefGoogle ScholarPubMed
Cozzolino, M, García-Velasco, JA, Meseguer, M, Pellicer, A and Bellver, J (2021). Female obesity increases the risk of miscarriage of euploid embryos. Fertil Steril 115, 1495–502. doi: 10.1016/j.fertnstert.2020.09.139 CrossRefGoogle ScholarPubMed
De Araújo, JFP, Podratz, PL, Sena, GC, Merlo, E, Freitas-Lima, LC, Ayub, JGM, Pereira, AFZ, Santos-Silva, AP, Miranda-Alves, L, Silva, IV and Graceli, JB (2018). The obesogen tributyltin induces abnormal ovarian adipogenesis in adult female rats. Toxicol Lett 295, 99–114. doi: 10.1016/j.toxlet.2018.06.1068 CrossRefGoogle ScholarPubMed
Dessolle, L, Daraï, E, Cornet, D, Rouzier, R, Coutant, C, Mandelbaum, J and Antoine, JM (2009). Determinants of pregnancy rate in the donor oocyte model: A multivariate analysis of 450 frozen–thawed embryo transfers. Hum Reprod 24, 3082–9. doi: 10.1093/humrep/dep303 CrossRefGoogle ScholarPubMed
DeUgarte, DA, DeUgarte, CM and Sahakian, V (2010). Surrogate obesity negatively impacts pregnancy rates in third-party reproduction. Fertil Steril 93, 1008–10. doi: 10.1016/j.fertnstert.2009.07.1005 CrossRefGoogle ScholarPubMed
Douchi, T, Kuwahata, R, Yamamoto, S, Oki, T, Yamasaki, H and Nagata, Y (2002). Relationship of upper body obesity to menstrual disorders. Acta Obstet Gynecol Scand 81, 147–50. doi: 10.1034/j.1600-0412.2002.810210.x CrossRefGoogle ScholarPubMed
Edson, MA, Nagaraja, AK and Matzuk, MM (2009). The mammalian ovary from genesis to revelation. Endocr Rev 30, 624–712. doi: 10.1210/er.2009-0012 CrossRefGoogle ScholarPubMed
Einarsson, S, Bergh, C, Friberg, B, Pinborg, A, Klajnbard, A, Karlström, PO, Kluge, L, Larsson, I, Loft, A, Mikkelsen-Englund, AL, Stenlöf, K, Wistrand, A and Thurin-Kjellberg, A (2017). Weight reduction intervention for obese infertile women prior to IVF: A randomized controlled trial. Hum Reprod 32, 1621–30. doi: 10.1093/humrep/dex235 CrossRefGoogle ScholarPubMed
Elgart, M, Stern, S, Salton, O, Gnainsky, Y, Heifetz, Y and Soen, Y (2016). Impact of gut microbiota on the fly’s germ line. Nat Commun 7, 11280. doi: 10.1038/ncomms11280 CrossRefGoogle ScholarPubMed
Engin, A (2017). Fat cell and fatty acid turnover in obesity. Adv Exp Med Biol 960, 135–60. doi: 10.1007/978-3-319-48382-5_6 CrossRefGoogle ScholarPubMed
Eppig, JJ (1985). Oocyte-somatic cell interactions during oocyte growth and maturation in the mammal. Dev Biol 1, 313–47. doi: 10.1007/978-1-4615-6814-8_7 Google ScholarPubMed
Field, SL, Dasgupta, T, Cummings, M and Orsi, NM (2014). Cytokines in ovarian folliculogenesis, oocyte maturation and luteinisation. Mol Reprod Dev 81, 284–314. doi: 10.1002/mrd.22285 CrossRefGoogle ScholarPubMed
Finkelstein, EA, Khavjou, OA, Thompson, H, Trogdon, JG, Pan, L, Sherry, B and Dietz, W (2012). Obesity and severe obesity forecasts through 2030. Am J Prev Med 42, 563–70. doi: 10.1016/j.amepre.2011.10.026 CrossRefGoogle ScholarPubMed
Flegal, KM, Kit, BK, Orpana, H and Graubard, BI (2013). Association of all-cause mortality with overweight and obesity using standard body mass index categories: A systematic review and meta-analysis. JAMA 309, 71–82. doi: 10.1001/jama.2012.113905 CrossRefGoogle ScholarPubMed
Garn, H, Bahn, S, Baune, BT, Binder, EB, Bisgaard, H, Chatila, TA, Chavakis, T, Culmsee, C, Dannlowski, U, Gay, S, Gern, J, Haahtela, T, Kircher, T, Müller-Ladner, U, Neurath, MF, Preissner, KT, Reinhardt, C, Rook, G, Russell, S, Schmeck, B, Stappenbeck, T, Steinhoff, U, van Os, J, Weiss, S, Zemlin, M and Renz, H (2016). Current concepts in chronic inflammatory diseases: Interactions between microbes, cellular metabolism, and inflammation. J Allergy Clin Immunol 138, 47–56. doi: 10.1016/j.jaci.2016.02.046 CrossRefGoogle ScholarPubMed
Gilchrist, RB, Rowe, DB, Ritter, LJ, Robertson, SA, Norman, RJ and Armstrong, DT (2000). Effect of granulocyte–macrophage colony-stimulating factor deficiency on ovarian follicular cell function. J Reprod Fertil 120, 283–92. doi: 10.1530/jrf.0.1200283 CrossRefGoogle ScholarPubMed
Hales, CM, Carroll, MD, Fryar, CD and Ogden, CL (2017). Prevalence of obesity among adults and youth: United States, 2015–2016. NCHS Data Brief. Natl Cent Health Stat 288, 1–8.Google Scholar
Hotamisligil, GS (2006). Inflammation and metabolic disorders. Nature 444(7121), 860–7. doi: 10.1038/nature05485 CrossRefGoogle ScholarPubMed
Hou, YJ, Zhu, CC, Duan, X, Liu, HL, Wang, Q and Sun, SC (2016). Both diet and gene mutation induced obesity affect oocyte quality in mice. Sci Rep 6, 18858. doi: 10.1038/srep18858 CrossRefGoogle ScholarPubMed
Hunt, PA and Hassold, TJ (2008). Human female meiosis: What makes a good egg go bad? Trends Genet 24, 86–93. doi: 10.1016/j.tig.2007.11.010 CrossRefGoogle ScholarPubMed
Hunter, N (2015). Meiotic recombination: The essence of heredity. Cold Spring Harb Perspect Biol 7, a016618. doi: 10.1101/cshperspect.a016618 CrossRefGoogle ScholarPubMed
Igosheva, N, Abramov, AY, Poston, L, Eckert, JJ, Fleming, TP, Duchen, MR and McConnell, J (2010). Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes. PLoS One 5, e10074. doi: 10.1371/journal.pone.0010074 CrossRefGoogle ScholarPubMed
Insenser, M, Murri, M, Del Campo, R, Martínez-García, MÁ, Fernández-Durán, E and Escobar-Morreale, HF (2018). Gut microbiota and the polycystic ovary syndrome: Influence of sex, sex hormones, and obesity. J Clin Endocrinol Metab 103, 2552–62. doi: 10.1210/jc.2017-02799 CrossRefGoogle ScholarPubMed
Jang, YJ, Park, JI, Moon, WJ, Dam, PT, Cho, MK and Chun, SY (2015). Cumulus cell-expressed type I interferons induce cumulus expansion in mice. Biol Reprod 92, 20. doi: 10.1095/biolreprod.114.122770 CrossRefGoogle ScholarPubMed
Jasper, MJ, Robertson, SA, Van der Hoek, KH, Bonello, N, Brännström, M and Norman, RJ (2000). Characterisation of ovarian function in granulocyte–macrophage colony-stimulating factor-deficient mice. Biol Reprod 62, 704–13. doi: 10.1095/biolreprod62.3.704 CrossRefGoogle Scholar
Jungheim, ES, Schoeller, EL, Marquard, KL, Louden, ED, Schaffer, JE and Moley, KH (2010). Diet-induced obesity model: Abnormal oocytes and persistent growth abnormalities in the offspring. Endocrinology 151, 4039–46. doi: 10.1210/en.2010-0098 CrossRefGoogle ScholarPubMed
Kawwass, JF, Kulkarni, AD, Hipp, HS, Crawford, S, Kissin, DM and Jamieson, DJ (2016). Extremities of body mass index and their association with pregnancy outcomes in women undergoing in vitro fertilization in the United States. Fertil Steril 106, 1742–50. doi: 10.1016/j.fertnstert.2016.08.028 CrossRefGoogle ScholarPubMed
Kluge, L, Bergh, C, Einarsson, S, Pinborg, A, Mikkelsen Englund, AL and Thurin-Kjellberg, A (2019). Cumulative live birth rates after weight reduction in obese women scheduled for IVF: Follow-up of a randomized controlled trial. Hum Reprod Open, hoz030. doi: 10.1093/hropen/hoz030 CrossRefGoogle Scholar
Kumbak, B, Oral, E and Bukulmez, O (2012). Female obesity and assisted reproductive technologies. Semin Reprod Med 30, 507–16. doi: 10.1055/s-0032-1328879 CrossRefGoogle ScholarPubMed
Kuroda, M and Sakaue, H (2017). Adipocyte death and chronic inflammation in obesity. J Med Invest 64, 193–6. doi: 10.2152/jmi.64.193 CrossRefGoogle ScholarPubMed
Levens, ED and Skarulis, MC (2008). Assessing the role of endometrial alteration among obese patients undergoing assisted reproduction. Fertil Steril 89, 1606–8. doi: 10.1016/j.fertnstert.2007.03.079 CrossRefGoogle ScholarPubMed
Ley, RE, Bäckhed, F, Turnbaugh, P, Lozupone, CA, Knight, RD and Gordon, JI (2005). Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102, 11070–5. doi: 10.1073/pnas.0504978102 CrossRefGoogle ScholarPubMed
Lindheim, L, Bashir, M, Münzker, J, Trummer, C, Zachhuber, V, Leber, B, Horvath, A, Pieber, TR, Gorkiewicz, G, Stadlbauer, V and Obermayer-Pietsch, B (2017). Alterations in gut microbiome composition and barrier function are associated with reproductive and metabolic defects in women with polycystic ovary syndrome (PCOS): A pilot study. PLoS One 12, e0168390. doi: 10.1371/journal.pone.0168390 CrossRefGoogle ScholarPubMed
Liu, R, Zhang, C, Shi, Y, Zhang, F, Li, L, Wang, X, Ling, Y, Fu, H, Dong, W, Shen, J, Reeves, A, Greenberg, AS, Zhao, L, Peng, Y and Ding, X (2017). Dysbiosis of gut microbiota associated with clinical parameters in polycystic ovary syndrome. Front Microbiol 8, 324. doi: 10.3389/fmicb.2017.00324 Google ScholarPubMed
Liu, YX, Zhang, Y, Li, YY, Liu, XM, Wang, XX, Zhang, CL, Hao, CF and Deng, SL (2019). Regulation of follicular development and differentiation by intra-ovarian factors and endocrine hormones. Front Biosci 24, 983–93. doi: 10.2741/4763 CrossRefGoogle ScholarPubMed
Luzzo, KM, Wang, Q, Purcell, SH, Chi, M, Jimenez, PT, Grindler, N, Schedl, T and Moley, KH (2012). High fat diet induced developmental defects in the mouse: oocyte meiotic aneuploidy and fetal growth retardation/brain defects. PLoS One 7, e49217. doi: 10.1371/journal.pone.0049217 CrossRefGoogle ScholarPubMed
Mackenna, A, Schwarze, JE, Crosby, JA and Zegers-Hochschild, F (2017). Outcome of assisted reproductive technology in overweight and obese women. JBRA Assist Reprod 21, 79–83. doi: 10.5935/1518-0557.20170020 CrossRefGoogle ScholarPubMed
Magata, F and Shimizu, T (2017). Effect of lipopolysaccharide on developmental competence of oocytes. Reprod Toxicol 71, 1–7. doi: 10.1016/j.reprotox.2017.04.001 CrossRefGoogle ScholarPubMed
Maheshwari, A, Stofberg, L and Bhattacharya, S (2007). Effect of overweight and obesity on assisted reproductive technology—A systematic review. Hum Reprod Update 13, 433–44. doi: 10.1093/humupd/dmm017 CrossRefGoogle ScholarPubMed
Malhotra, JD and Kaufman, RJ (2007). Endoplasmic reticulum stress and oxidative stress: A vicious cycle or a double-edged sword? Antioxid Redox Signal 9, 2277–93. doi: 10.1089/ars.2007.1782 CrossRefGoogle ScholarPubMed
Mao, L, Lou, H, Lou, Y, Wang, N and Jin, F (2014). Behaviour of cytoplasmic organelles and cytoskeleton during oocyte maturation. Reprod Biomed Online 28, 284–99. doi: 10.1016/j.rbmo.2013.10.016 CrossRefGoogle ScholarPubMed
McClamrock, HD (2008). The great weight debate: Do elevations in body mass index (BMI) exert a negative extraovarian effect on in vitro fertilization outcome? Fertil Steril 89, 1609–10. doi: 10.1016/j.fertnstert.2007.04.004 CrossRefGoogle ScholarPubMed
McLaughlin, EA and McIver, SC (2009). Awakening the oocyte: Controlling primordial follicle development. Reproduction 137, 1–11. doi: 10.1530/REP-08-0118 CrossRefGoogle ScholarPubMed
Meng, F, Guo, F, Abulimiti, B, Zhao, K, Dong, Y, Ma, X, Fu, Z and Ma, Y (2021). Body mass index and all-cause mortality in patients with cardiogenic shock: A systematic review and meta-analysis. Am J Emerg Med 43, 97–102. doi: 10.1016/j.ajem.2021.01.003 CrossRefGoogle ScholarPubMed
Metwally, M, Cutting, R, Tipton, A, Skull, J, Ledger, WL and Li, TC (2007). Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reprod Biomed Online 15, 532–8. doi: 10.1016/s1472-648360385-9 CrossRefGoogle ScholarPubMed
Metwally, M, Ong, KJ, Ledger, WL and Li, TC (2008). Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence. Fertil Steril 90, 714–26. doi: 10.1016/j.fertnstert.2007.07.1290 CrossRefGoogle Scholar
Metwally, M, Preece, R, Thomas, J, Ledger, WL and Li, TC (2014). A proteomic analysis of the endometrium in obese and overweight women with recurrent miscarriage: Preliminary evidence for an endometrial defect. Reprod Biol Endocrinol 12, 75. doi: 10.1186/1477-7827-12-75 CrossRefGoogle ScholarPubMed
Minge, CE, Bennett, BD, Norman, RJ, Norman, RL and Robker, RL (2008). Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reverses the adverse effects of diet-induced obesity on oocyte quality. Endocrinology 149, 2646–56. doi: 10.1210/en.2007-1570 CrossRefGoogle ScholarPubMed
Nilsson, EE and Skinner, MK (2004). Kit ligand and basic fibroblast growth factor interactions in the induction of ovarian primordial to primary follicle transition. Mol Cell Endocrinol 214(1–2), 19–25. doi: 10.1016/j.mce.2003.12.001 CrossRefGoogle ScholarPubMed
Norman, RJ, Noakes, M, Wu, R, Davies, MJ, Moran, L and Wang, JX (2004). Improving reproductive performance in overweight/obese women with effective weight management. Hum Reprod Update 10, 267–80. doi: 10.1093/humupd/dmh018 CrossRefGoogle ScholarPubMed
Norman, RJ, Chura, LR and Robker, RL (2008). Effects of obesity on assisted reproductive technology outcomes. Fertil Steril 89, 1611–2. doi: 10.1016/j.fertnstert.2007.02.065 CrossRefGoogle ScholarPubMed
O’Gorman, A, Wallace, M, Cottell, E, Gibney, MJ, McAuliffe, FM, Wingfield, M and Brennan, L (2013). Metabolic profiling of human follicular fluid identifies potential biomarkers of oocyte developmental competence. Reproduction 146, 389–95. doi: 10.1530/REP-13-0184 CrossRefGoogle ScholarPubMed
Oktay, K, Karlikaya, G, Akman, O, Ojakian, GK and Oktay, M (2000). Interaction of extracellular matrix and activin-A in the initiation of follicle growth in the mouse ovary. Biol Reprod 63, 457–61. doi: 10.1095/biolreprod63.2.457 CrossRefGoogle ScholarPubMed
Ouchi, N, Parker, JL, Lugus, JJ and Walsh, K (2011). Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11, 85–97. doi: 10.1038/nri2921 CrossRefGoogle ScholarPubMed
Ozcan, L and Tabas, I (2012). Role of endoplasmic reticulum stress in metabolic disease and other disorders. Ann Rev Med 63, 317–28. doi: 10.1146/annurev-med-043010-144749 CrossRefGoogle ScholarPubMed
Pasquali, R and Gambineri, A (2006). Metabolic effects of obesity on reproduction. Reprod Biomed Online 12, 542–51. doi: 10.1016/s1472-648361179-0 CrossRefGoogle ScholarPubMed
Piya, MK, McTernan, PG and Kumar, S (2013). Adipokine inflammation and insulin resistance: The role of glucose, lipids and endotoxin. J Endocrinol 216, T1–15. doi: 10.1530/JOE-12-0498 CrossRefGoogle ScholarPubMed
Pohlmeier, WE, Xie, F, Kurz, SG, Lu, N and Wood, JR (2014). Progressive obesity alters the steroidogenic response to ovulatory stimulation a increases the abundance of mRNAs stored in the ovulated oocyte. Mol Reprod Dev 81, 735–47. doi: 10.1002/mrd.22342 CrossRefGoogle ScholarPubMed
Połeć, A, Ráki, M, Åbyholm, T, Tanbo, TG and Fedorcsák, P (2011). Interaction between granulosa-lutein cells and monocytes regulates secretion of angiogenic factors in vitro. Hum Reprod 26, 2819–29. doi: 10.1093/humrep/der216 CrossRefGoogle ScholarPubMed
Rajkovic, A and Pangas, S (2017). Ovary as a biomarker of health and longevity: Insights from genetics. Semin Reprod Med 35, 231–40. doi: 10.1055/s-0037-1603571 Google ScholarPubMed
Ramlau-Hansen, CH, Thulstrup, AM, Nohr, EA, Bonde, JP, Sørensen, TIA and Olsen, J (2007). Subfecundity in overweight and obese couples. Hum Reprod 22, 1634–7. doi: 10.1093/humrep/dem035 CrossRefGoogle ScholarPubMed
Rich-Edwards, JW, Goldman, MB, Willett, WC, Hunter, DJ, Stampfer, MJ, Colditz, GA and Manson, JE (1994). Adolescent body mass index and infertility caused by ovulatory disorder. Am J Obstet Gynecol 171, 171–7. doi: 10.1016/0002-937890465-0 CrossRefGoogle ScholarPubMed
Richards, JS and Hedin, L (1988). Molecular aspects of hormone action in ovarian follicular development, ovulation, and luteinization. Ann Rev Physiol 50, 441–63. doi: 10.1146/annurev.ph.50.030188.002301 CrossRefGoogle ScholarPubMed
Rienzi, L, Vajta, G and Ubaldi, F (2011). Predictive value of oocyte morphology in human IVF: A systematic review of the literature. Hum Reprod Update 17, 34–45. doi: 10.1093/humupd/dmq029 CrossRefGoogle ScholarPubMed
Rimessi, A, Previati, M, Nigro, F, Wieckowski, MR and Pinton, P (2016). Mitochondrial reactive oxygen species and inflammation: Molecular mechanisms, diseases and promising therapies. Int J Biochem Cell Biol 81(B), 281–93. doi: 10.1016/j.biocel.2016.06.015 CrossRefGoogle ScholarPubMed
Rittenberg, V, Seshadri, S, Sunkara, SK, Sobaleva, S, Oteng-Ntim, E and El-Toukhy, T (2011). Effect of body mass index on IVF treatment outcome: An updated systematic review and meta-analysis. Reprod Biomed Online 23, 421–39. doi: 10.1016/j.rbmo.2011.06.018 CrossRefGoogle ScholarPubMed
Riva, A, Borgo, F, Lassandro, C, Verduci, E, Morace, G, Borghi, E and Berry, D (2017). Pediatric obesity is associated with an altered gut microbiota and discordant shifts in Firmicutes populations. Environ Microbiol 19, 95–105. doi: 10.1111/1462-2920.13463 CrossRefGoogle ScholarPubMed
Robker, RL, Akison, LK, Bennett, BD, Thrupp, PN, Chura, LR, Russell, DL, Lane, M and Norman, RJ (2009). Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women. J Clin Endocrinol Metab 94, 1533–40. doi: 10.1210/jc.2008-2648 CrossRefGoogle ScholarPubMed
Rondanelli, M, Perna, S, Faliva, M, Monteferrario, F, Repaci, E and Allieri, F (2014). Focus on metabolic and nutritional correlates of polycystic ovary syndrome and update on nutritional management of these critical phenomena. Arch Gynecol Obstet 290, 1079–92. doi: 10.1007/s00404-014-3433-z CrossRefGoogle ScholarPubMed
Saad, MJ, Santos, A and Prada, PO (2016). Linking gut microbiota and inflammation to obesity and insulin resistance. Physiology 31, 283–93. doi: 10.1152/physiol.00041.2015 CrossRefGoogle ScholarPubMed
Salmassi, A, Mettler, L, Jonat, W, Buck, S, Koch, K and Schmutzler, AG (2010). Circulating level of macrophage colony-stimulating factor can be predictive for human in vitro fertilization outcome. Fertil Steril 93, 116–23. doi: 10.1016/j.fertnstert.2008.09.083 CrossRefGoogle ScholarPubMed
Shimizu, T, Kaji, A, Murayama, C, Magata, F, Shirasuna, K, Wakamiya, K, Okuda, K and Miyamoto, A (2011). Effects of interleukin-8 on estradiol and progesterone production by bovine granulosa cells from large follicles and progesterone production by luteinizing granulosa cells in culture. Cytokine 57, 175–81.CrossRefGoogle ScholarPubMed
Shimizu, T, Imamura, E, Magata, F, Murayama, C and Miyamoto, A (2013). Interleukin-8 stimulates progesterone production via the MEK pathway in ovarian theca cells. Mol Cell Biochem 374(1–2), 157–61. doi: 10.1007/s11010-012-1515-4 CrossRefGoogle ScholarPubMed
Snider, AP and Wood, JR (2019). Obesity induces ovarian inflammation and reduces oocyte quality. Reproduction 158, R79–90. doi: 10.1530/REP-18-0583 CrossRefGoogle ScholarPubMed
Sobaleva, S and El-Toukhy, T (2011). The impact of raised BMI on the outcome of assisted reproduction: Current concepts. J Obstet Gynaecol 31, 561–5. doi: 10.3109/01443615.2011.602138 CrossRefGoogle ScholarPubMed
Styne-Gross, A, Elkind-Hirsch, K and Scott, RT (2005). Obesity does not impact implantation rates or pregnancy outcome in women attempting conception through oocyte donation. Fertil Steril 83, 1629–34. doi: 10.1016/j.fertnstert.2005.01.099 CrossRefGoogle ScholarPubMed
Turnbaugh, PJ, Ley, RE, Mahowald, MA, Magrini, V, Mardis, ER and Gordon, JI (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444(7122), 1027–31. doi: 10.1038/nature05414 CrossRefGoogle ScholarPubMed
Turner, N and Robker, RL (2015). Developmental programming of obesity and insulin resistance: Does mitochondrial dysfunction in oocytes play a role? Mol Hum Reprod 21, 23–30. doi: 10.1093/molehr/gau042 CrossRefGoogle ScholarPubMed
Valckx, SDM, Arias-Alvarez, M, De Pauw, I, Fievez, V, Vlaeminck, B, Fransen, E, Bols, PEJ and Leroy, JLMR (2014). Fatty acid composition of the follicular fluid of normal weight, overweight and obese women undergoing assisted reproductive treatment: A descriptive cross-sectional study. Reprod Biol Endocrinol 12, 13. doi: 10.1186/1477-7827-12-13 CrossRefGoogle ScholarPubMed
Van Blerkom, J (2011). Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion 11, 797–813. doi: 10.1016/j.mito.2010.09.012 CrossRefGoogle ScholarPubMed
Vannuvel, K, Renard, P, Raes, M and Arnould, T (2013). Functional and morphological impact of ER stress on mitochondria. J Cell Physiol 228, 1802–18. doi: 10.1002/jcp.24360 CrossRefGoogle ScholarPubMed
Wang, H, Cheng, Q, Li, X, Hu, F, Han, L, Zhang, H, Li, L, Ge, J, Ying, X, Guo, X and Wang, Q (2018). Loss of TIGAR induces oxidative stress and meiotic defects in oocytes from obese mice. Mol Cell Proteom 17, 1354–64. doi: 10.1074/mcp.RA118.000620 CrossRefGoogle ScholarPubMed
Wang, J and Roy, SK (2004). Growth differentiation factor-9 and stem cell factor promote primordial follicle formation in the hamster: Modulation by follicle-stimulating hormone. Biol Reprod 70, 577–85. doi: 10.1095/biolreprod.103.023234 CrossRefGoogle ScholarPubMed
Wang, JX, Davies, MJ and Norman, RJ (2002). Obesity increases the risk of spontaneous abortion during infertility treatment. Obes Res 10, 551–4. doi: 10.1038/oby.2002.74 CrossRefGoogle ScholarPubMed
Wang, N, Luo, LL, Xu, JJ, Xu, MY, Zhang, XM, Zhou, XL, Liu, WJ and Fu, YC (2014). Obesity accelerates ovarian follicle development and follicle loss in rats. Metab Clin Exp 63, 94–103. doi: 10.1016/j.metabol.2013.09.001 CrossRefGoogle ScholarPubMed
Wang, S, Liu, Y, Shang, Y, Zhai, B, Yang, X, Kleckner, N and Zhang, L (2019). Crossover interference, crossover maturation, and human aneuploidy. BioEssays 41, e1800221. doi: 10.1002/bies.201800221 CrossRefGoogle ScholarPubMed
Wang, S, Liu, Y, Shang, Y, Liu, Y Zhai, B, Yang, X and Zhang, L (2021). Crossover patterns under meiotic chromosome. Asian J Androl 23, 1–2 CrossRefGoogle ScholarPubMed
Wang, Y and Huang, F (2015). N-3 polyunsaturated fatty acids and inflammation in obesity: Local effect and systemic benefit. BioMed Res Int 2015, 581469. doi: 10.1155/2015/581469 Google ScholarPubMed
Wang, YC, McPherson, K, Marsh, T, Gortmaker, SL and Brown, M (2011). Health and economic burden of the projected obesity trends in the USA and the UK. Lancet 378(9793), 815–25. doi: 10.1016/S0140-673660814-3 CrossRefGoogle ScholarPubMed
Wang, Z, Zhao, J, Ma, X, Sun, Y, Hao, G, Yang, A, Ren, W, Jin, L, Lu, Q, Wu, G, Ling, X, Hao, C, Zhang, B, Liu, X, Yang, D, Zhu, Y, Li, J, Bao, H, Wang, A, Liu, J, Chen, Z-J, Tan, J and Shi, Y (2021). Effect of orlistat on live birth rate in overweight or obese women undergoing IVF-ET: Randomized clinical trial. J Clin Endocrinol Metab 106, e3533–45. doi: 10.1210/clinem/dgab340 CrossRefGoogle ScholarPubMed
Wattanakumtornkul, S, Damario, MA, Stevens Hall, SA, Thornhill, AR and Tummon, IS (2003). Body mass index and uterine receptivity in the oocyte donation model. Fertil Steril 80, 336–40. doi: 10.1016/s0015-028200595-8 CrossRefGoogle ScholarPubMed
Wu, R, Fujii, S, Sini, I, Van der Hoek, KH, Jasper, MJ, Ryan, NK, Robker, RL, Robertson, SA and Norman, RJ (2006). Ovarian leukocyte distribution and cytokine/chemokine mRNA expression in follicular fluid cells in women with polycystic ovary syndrome. Hum Reprod 22, 527–35.CrossRefGoogle ScholarPubMed
Wu, LL, Dunning, KR, Yang, X, Russell, DL, Lane, M, Norman, RJ and Robker, RL (2010). High-fat diet causes lipotoxicity responses in cumulus–oocyte complexes and decreased fertilization rates. Endocrinology 151, 5438–45. doi: 10.1210/en.2010-0551 CrossRefGoogle ScholarPubMed
Wu, LL, Russell, DL, Wong, SL, Chen, M, Tsai, TS, St John, JC, Norman, RJ, Febbraio, MA, Carroll, J and Robker, RL (2015). Mitochondrial dysfunction in oocytes of obese mothers: Transmission to offspring and reversal by pharmacological endoplasmic reticulum stress inhibitors. Development 142, 681–91. doi: 10.1242/dev.114850 CrossRefGoogle ScholarPubMed
Xie, F, Anderson, CL, Timme, KR, Kurz, SG, Fernando, SC and Wood, JR (2016). Obesity-dependent increases in oocyte mRNAs are associated with increases in proinflammatory signaling and gut microbial abundance of Lachnospiraceae in female mice. Endocrinology 157, 1630–43. doi: 10.1210/en.2015-1851 CrossRefGoogle ScholarPubMed
Xu, H, Barnes, GT, Yang, Q, Tan, G, Yang, D, Chou, CJ, Sole, J, Nichols, A, Ross, JS, Tartaglia, LA and Chen, H (2003). Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112, 1821–30. doi: 10.1172/JCI19451 CrossRefGoogle Scholar
Yanagi, K, Makinoda, S, Fujii, R, Miyazaki, S, Fujita, S, Tomizawa, H, Yoshida, K, Iura, T, Takegami, T and Nojima, T (2002). Cyclic changes of granulocyte colony-stimulating factor (G-CSF) mRNA in the human follicle during the normal menstrual cycle and immunolocalization of G-CSF protein. Hum Reprod 17, 3046–52. doi: 10.1093/humrep/17.12.3046 CrossRefGoogle ScholarPubMed
Zhang, Z, Fang, Q and Wang, J (2008). Involvement of macrophage colony-stimulating factor (M-CSF) in the function of follicular granulosa cells. Fertil Steril 90, 749–54. doi: 10.1016/j.fertnstert.2007.06.098 CrossRefGoogle ScholarPubMed
Zhang, L, Han, L, Ma, R, Hou, X, Yu, Y, Sun, S, Xu, Y, Schedl, T, Moley, KH and Wang, Q (2015). Sirt3 prevents maternal obesity-associated oxidative stress and meiotic defects in mouse oocytes. Cell Cycle 14, 2959–68. doi: 10.1080/15384101.2015.1026517 CrossRefGoogle ScholarPubMed