Influence of in vitro fertilization on maternal and neonatal outcomes in elderly maternally elderly women
Keywords:
Pregnancy, Maternal Age, Morbidity, Pregnancy Outcome, Reproductive Techniques, Fertilization in VitroAbstract
To establish the effect of in vitro fertilization on the frequency of maternal-neonatal complications in pregnant women over the age of 40 years. Methods: Case-control study nested in a cohort, with retrospective data collection and prospective follow-up. Total cohort of 207 pregnant women. Cases or subcohort with in vitro fertilization and control group with spontaneous pregnancy. Parametric and non-parametric tests were performed to determine the potential association between the variables.
Results: The women who achieved pregnancy through in vitro fertilization had a higher mean age (p = 0.03). Primiparity (44.4% vs. 22.2%, p = 0.02), gestational diabetes rate RR = 2.83 (95% CI: 1.19-6.77; p = 0.023) and caesarean section rate (p = 0.05) were more frequent in cases. In spontaneous pregnancies, a higher frequency of spontaneous labor was observed (56.86% vs. 37.03%; p = 0.019). No differences were found in the prevalence of pre-pregnancy diabetes, hypertensive states of pregnancy, prematurity, intrauterine growth restriction, fetal macrosomia, Apgar test, pathological pH, neonatal admissions, and postpartum hemorrhage. The perinatal mortality rate was higher in the group with pregnancy achieved by in vitro fertilization.
Conclusion: In vitro fertilization conception in a pregnant population with advanced maternal age confers an added risk to it in adverse maternal and neonatal outcomes.
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References
Martin JA, Hamilton BE, Osterman MJK. Births in the United States, 2018. NCHS Data Brief [Internet]. 2019 [consultado 10 de febrero de 2020];(346):1-8. Disponible en: https://www.cdc.gov/nchs/data/databriefs/db346-h.pdf
Instituto Nacional de Estadística [Internet]. Madrid: Movimiento natural de la población; 2016 [consultado el 10 de febrero de 2020]. Disponible en: http:// www.ine.es/jaxi/Tabla.htm?path=/t20/e301/provi/l0/&file=01001.px&L=0.
Chambers GM, Wand H, Macaldowie A, Chapman MG, Farquhar CM, Bowman M, et al. Population trends and live birth rates associated with common ART treatment strategies. Hum Reprod. 2016;31(11):2632–2641. DOI: 10.1093/humrep/dew232
Waldenström U, Cnattingius S, Vixner L, Norman M. Advanced maternal age increases the risk of very preterm birth, irrespective of parity: a population-based register study. BJOG. 2017;124(8):1235–1244. DOI: 10.1111/1471-0528.14368
Bayrampour H, Heaman M. Advanced maternal age and the risk of cesarean birth: a systematic review. Birth. 2010;37(3):219–226. DOI: 10.1111/j.1523-536X.2010.00409.x
Frederiksen LE, Ernst A, Brix N, Braskhøj Lauridsen LL, Roos L, HøstRamlau-Hansen C, et al. Risk of Adverse Pregnancy Outcomes at Advanced Maternal Age. Obstet Gynecol. 2018;131(3):457–463. DOI: 10.1097/AOG.0000000000002504
Luque Fernández MA. Trends in the risk of late fetal mortality, prematurity and low birth weight associated with advanced maternal age in Spain [1996-2005]. Gac Sanit. 2008;22:396–403. DOI: 10.1157/13126919
Rivas-Perdomo EE. Asociación entre edad materna avanzada y los resultados perinatals adversos en una clínica universitaria de Cartagena (Colombia), 2012: Estudio de cohorte retrospectiva. Rev Colomb Obstet Ginecol. 2015;66(3):179-185. DOI: https://doi.org/10.18597/rcog.22.
Almeida NK, Almeida RM, Pedreira CE. Adverse perinatal outcomes for advanced maternal age: a cross-sectional study of Brazilian births. J Pediatr (Rio J). 2015;91(5):493–498. DOI: 10.1016/j.jped.2014.12.002
Qin J, Liu X, Sheng X, Wang H, Gao S. Assisted reproductive technology and the risk of pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a meta-analysis of cohort studies. Fertil Steril. 2016;105(1):73–85.e856. DOI: 10.1016/j.fertnstert.2015.09.007
Helmerhorst FM, Perquin DA, Donker D, Keirse MJ. Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ. 2004;328(7434):261. DOI: 10.1136/bmj.37957.560278.EE
Harlev A, Walfisch A, Oran E, Har-Vardi I, Friger M, Lunenfeld E, et al. The effect of fertility treatment on adverse perinatal outcomes in women aged at least 40 years. Int J GynaecolObstet. 2018;140(1):98–104. DOI: 10.1002/ijgo.12345
McDonald SD, Murphy K, Beyene J, Ohlsson A. Perinatal outcomes of singleton pregnancies achieved by in vitro fertilization: a systematic review and meta-analysis. J Obstet Gynaecol Can. 2005;27(5):449–459. DOI: 10.1016/s1701-2163(16)30527-8
Pandey S, Shetty A, Hamilton M, Bhattacharya S, Maheshwari A. Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. Hum Reprod Update. 2012;18(5):485–503. DOI: 10.1093/humupd/dms018
Toshimitsu M, Nagamatsu T, Nagasaka T, Nagasaka T, Iwasawa-Kawai Y, Komatsu A, et al. Increased risk of pregnancy-induced hypertension and operative delivery after conception induced by in vitro fertilization/intracytoplasmic sperm injection in women aged 40 years and older. Fertil Steril. 2014;102(4):1065–1070.e1. DOI: 10.1016/j.fertnstert.2014.07.011
Silberstein T, Levy A, Harlev A, Saphier O, Sheiner E. Perinatal outcome of pregnancies following in vitro fertilization and ovulation induction. J Matern Fetal Neonatal Med. 2014;27(13):1316–1319. DOI: 10.3109/14767058.2013.856415
Farhi J, Ben-Haroush A, Andrawus N, Pinkas H, Sapir O, Fisch B, et al. High serum oestradiol concentrations in IVF cycles increase the risk of pregnancy complications related to abnormal placentation. Reprod Biomed Online. 2010;21:331–337. DOI: 10.1016/j.rbmo.2010.04.022
Levron Y, Dviri M, Segol I, Yerushalmi G, Hourvitz A, Orvieto R, et al. The ‘immunologic theory’ of pre- eclampsia revisited: A lesson from donor oocyte gestations. Am J Obstet Gynecol. 2014;211:383.e381–383.e385. DOI: 10.1016/j.ajog.2014.03.044
Pinborg A, Wennerholm UB, Romundstad LB, Loft A, Aittomaki K, Söderström-Anttila V, et al. Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? Systematic review and meta-analysis. Hum Reprod Update. 2013;19:87-104. DOI: 10.1093/humupd/dms044
Romundstad LB, Romundstad PR, Sunde A, von Düring V, Skjaerven R, Gunnell D, et al. Effects of technology or maternal factors on perinatal outcome after assisted fertilisation: a population-based cohort study. Lancet. 2008;372(9640):737–743. DOI: 10.1016/S0140-6736(08)61041-7
Mao GH, Feng Z, He Y, Huang YR. Comparisons of the effects of long-acting and short-acting GnRH agonists on embryo quality, endometrial thickness and pregnancy rate in human in vitro fertilization. Arch Med Sci. 2014;10(1):161–166. DOI: 10.5114/aoms.2014.40743
Wennberg AL, Opdahl I, Bergh C, Henningsen AK, Gissler M, Romundstad LB, et al. Effect of maternal age on maternal and neonatal outcomes after assisted reproductive technology. Fertil Steril. 2016;106(5):1142–1149.e14. DOI: 10.1016/j.fertnstert.2016.06.021
Jackson S, Hong C, Wang ET, Alexander C, Gregory KD, Pisarska MD. Pregnancy outcomes in very advanced maternal age pregnancies: the impact of assisted reproductive technology. Fertil Steril. 2015;103(1):76–80. DOI: 10.1016/j.fertnstert.2014.09.037
American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice; Committee on Genetics; U.S. Food and Drug Administration. Committee Opinion No 671: Perinatal Risks Associated With Assisted Reproductive Technology. Obstet Gynecol. 2016;128(3):e61-e68. DOI: 10.1097/AOG.0000000000001643.
Heo JS, Lee HJ, Lee MH, Choi CW. Comparison of neonatal outcomes of very low birth weight infants by mode of conception: in vitro fertilization versus natural pregnancy. Fertil Steril. 2019;111(5):962–970. DOI: 10.1016/j.fertnstert.2019.01.014
Zhu JL, Obel C, Hammer Bech B, Olsen J, Basso O. Infertility, infertility treatment, and fetal growth restriction. Obstet Gynecol. 2007;110(6):1326–1334. DOI: 10.1097/01.AOG.0000290330.80256.97
Scott-Pillai R, Spence D, Cardwell CR, Hunter A, Holmes VA. The impact of body mass index on maternal and neonatal outcomes: a retrospective study in a UK obstetric population, 2004-2011. BJOG. 2013;120(8):932–939. DOI: 10.1111/1471-0528.12193
Lisonkova S, Muraca GM, Potts J, Liauw J, Chan WS, Skoll A, et al. Association BetweenPrepregnancy Body Mass Index and Severe Maternal Morbidity. JAMA. 2017;318(18):1777–1786. DOI: 10.1001/jama.2017.16191.
Matalliotakis I, Cakmak H, Sakkas D, Mahutte N, Koumantakis G, Arici A. Impact of body mass index on IVF and ICSI outcome: a retrospective study. Reprod Biomed Online. 2008;16(6):778–783. DOI: 10.1016/s1472-6483(10)60142-3
Maheshwari A, Stofberg L, Bhattacharya S. Effect of overweight and obesity on assisted reproductive technology--a systematic review. Hum Reprod Update. 2007;13(5):433–444. DOI: 10.1093/humupd/dmm017
Wang YA, Nikravan R, Smith HC, Sullivan EA. Higher prevalence of gestational diabetes mellitus following assisted reproduction technology treatment. Hum Reprod. 2013;28(9):2554–2561. DOI: 10.1093/humrep/det270
Jones BJ, Zöllner J, Haynes S, Cheng F, Dornhorst A. In vitro fertilization treatment influences glucose tolerance in multiple pregnancy. Diabet Med. 2013;30(2):252–254. DOI: 10.1111/j.1464-5491.2012.03761.x
Ashrafi M, Gosili R, Hosseini R, Arabipoor A, Ahmadi J, Chehrazi M. Risk of gestational diabetes mellitus in patients undergoing assisted reproductive techniques. Eur J Obstet Gynecol Reprod Biol. 2014;176:149–152. DOI: 10.1016/j.ejogrb.2014.02.009
Wang H, Wang Z, Meng J, Wang X, Liu L, Chen B. History of infertility relates to increased risk of gestational diabetes mellitus: a meta-analysis. Int J Clin Exp Med [Internet]. 2017 [consultado 10 de febrero de 2020];10(2):1909–1916. Disponible en: https://e-century.us/files/ijcem/10/2/ijcem0039483.pdf
Holst S, Kjær SK, Jørgensen ME, Damm P, Jensen A. Fertility problems and risk of gestational diabetes mellitus: a nationwide cohort study. Fertil Steril. 2016;106(2):427–434.e1. DOI: 10.1016/j.fertnstert.2016.03.040
Gao X, Yan Y, Xiang S, Guangyu Z, Shiping L, Tingting S, et al. The mutual effect of pre-pregnancy body mass index, waist circumference and gestational weight gain on obesity-related adverse pregnancy outcomes: A birth cohort study. PLoS One. 2017;12(6):e0177418. DOI: 10.1371/journal.pone.0177418
Most O, Langer O. Gestational diabetes: maternal weight gain in relation to fetal growth, treatment modality, BMI and glycemic control. J Matern Fetal Neonatal Med. 2012;25(11):2458–2463. DOI: 10.3109/14767058.2011.650250
Chen M, Wu L, Zhao J, Wu F, Davies MJ, Wittert GA, et al. Altered glucose metabolism in mouse and humans conceived by IVF. Diabetes. 2014;63(10):3189–3198. DOI: 10.2337/db14-0103
Nunes VA, Portioli-Sanches EP, Rosin MP, da Silva Araújo M, Praxedes-Garcia P, Valle MM, et al. Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism. J Endocrinol. 2014;221(2):273–284. DOI: 10.1530/JOE-13-0202
Ashrafi M, Sheikhan F, Arabipoor A, Hosseini R, Nourbakhsh F, Zolfaghari Z. Gestational diabetes mellitus risk factors in women with polycystic ovary syndrome (PCOS). Eur J Obstet Gynecol Reprod Biol. 2014;181:195–199. DOI: 10.1016/j.ejogrb.2014.07.043
Pan ML, Chen LR, Tsao HM, Chen KH. Relationship between Polycystic Ovarian Syndrome and Subsequent Gestational Diabetes Mellitus: A Nationwide Population-Based Study. PLoS One. 2015;10(10):e0140544. DOI: 10.1371/journal.pone.0140544
De Leo V, Musacchio MC, Cappelli V, Massaro MG, Morgante G, Petraglia F. Genetic, hormonal and metabolic aspects of PCOS: an update. Reprod Biol Endocrinol. 2016;14(1):38. DOI: 10.1186/s12958-016-0173-x
Kouhkan A, Baradaran HR, Hosseini R, Arabipoor A, Moini A, Pirjani R, et al. Assisted conception as a potential prognostic factor predicting insulin therapy in pregnancies complicated by gestational diabetes mellitus. Reprod Biol Endocrinol. 2019;17(1):83. DOI: 10.1186/s12958-019-0525-4
Szymanska M, Horosz E, Szymusik I, Bomba-Opon D, Wielgos M. Gestational diabetes in IVF and spontaneous pregnancies. Neuro Endocrinol Lett [Internet]. 2011 [consultado 10 de febrero de 2020]; 32(6):885–888. Disponible en: https://europepmc.org/article/med/22286793
Luke B, Brown MB. Elevated risks of pregnancy complications and adverse outcomes with increasing maternal age. Hum Reprod. 2007;22(5):1264–1272. DOI: 10.1093/humrep/del522
Tandberg A, Klungsøyr K, Romundstad LB, Skjærven R. Pre-eclampsia and assisted reproductive technologies: consequences of advanced maternal age, interbirth intervals, new partner and smoking habits. BJOG. 2015;122(7):915–922. DOI: 10.1111/1471-0528.13051
Davies MJ, Marino JL, Willson KJ, March WA, Moore VM. Intergenerational associations of chronic disease and polycystic ovary syndrome. PLoS One. 2011;6(10):e25947. DOI: 10.1371/journal.pone.0025947
Bianco A, Stone J, Lynch L, Lapinski R, Berkowitz G, Berkowitz RL. Pregnancy outcome at age 40 and older. Obstet Gynecol. 1996;87(6):917–922. DOI: 10.1016/0029-7844(96)00045-2
Raunig JM, Yamauchi Y, Ward MA, Collier AC. Placental inflammation and oxidative stress in the mouse model of assisted reproduction. Placenta. 2011;32(11):852–858. DOI: 10.1016/j.placenta.2011.08.003
Nelissen EC, Dumoulin JC, Daunay A, Evers JL, Tost J, van Montfoort AP. Placentas from pregnancies conceived by IVF/ICSI have a reduced DNA methylation level at the H19 and MEST differentially methylated regions. Hum Reprod. 2013;28(4):1117–1126. DOI: 10.1093/humrep/des459
McGovern PG, Llorens AJ, Skurnick JH, Weiss G, Goldsmith LT. Increased risk of preterm birth in singleton pregnancies resulting from in vitro fertilization-embryo transfer or gamete intrafallopian transfer: a meta-analysis. Fertil Steril. 2004;82(6):1514–1520. DOI: 10.1016/j.fertnstert.2004.06.038
Koivurova S, Hartikainen AL, Gissler M, Hemminki E, Sovio U, Järvelin MR. Neonatal outcome and congenital malformations in children born after in-vitro fertilization. Hum Reprod. 2002;17(5):1391–1398. DOI: 10.1093/humrep/17.5.1391
Allen C, Bowdin S, Harrison RF, Sutcliffe A, Brueton L, Kirby G, et al. Pregnancy and perinatal outcomes after assisted reproduction: a comparative study. Ir J Med Sci. 2008;177(3):233–241. DOI: 10.1007/s11845-008-0172-9
Xiong X, Dickey RP, Pridjian G, Buekens P. Maternal age and preterm births in singleton and twin pregnancies conceived by in vitro fertilization in the United States. Paediatr Perinat Epidemiol. 2015;29(1):22–30. DOI: 10.1111/ppe.12166
Perri T, Chen R, Yoeli R, Merlob P, Orvieto R, ShalevY, et al. Are singleton assisted reproductive technology pregnancies at risk of prematurity? J Assist Reprod Genet. 2001;18(5):245–249. DOI: 10.1023/a:1016614217411
Szymusik I, Kosinska-Kaczynska K, Krowicka M, Sep M, Marianowski P, Wielgos M. Perinatal outcome of in vitro fertilization singletons - 10 years’ experience of one center. Arch Med Sci. 2019;15(3):666–672. DOI: 10.5114/aoms.2019.82670
McMahon CA, Ungerer JA, Beaurepaire J, Tennant C, Saunders D. Anxiety during pregnancy and fetal attachment after in-vitro fertilization conception. Hum Reprod. 1997;12(1):176–182. DOI: 10.1093/humrep/12.1.176
Johnson MR, Irvine R, Hills F, Bolton V, Abbas A, Brooks A, et al. Superovulation, IGFBP-1 and birth weight. Eur J Obstet Gynecol Reprod Biol. 1995;59(2):193–195. DOI: 10.1016/0028-2243(95)02040-y
Mainigi MA, Olalere D, Burd I, Sapienza C, Bartolomei M, Coutifaris C. Peri-implantation hormonal milieu: elucidating mechanisms of abnormal placentation and fetal growth. Biol Reprod. 2014;90(2):26. DOI: 10.1095/biolreprod.113.110411
Licht P, Neuwinger J, Fischer O, Siebzehnrübl E, Wildt L. VEGF plasma pattern in ovulation induction: evidence for an episodic secretion and lack of immediate effect of hCG. Exp Clin Endocrinol Diabetes. 2002;110(3):130–133. DOI: 10.1055/s-2002-29090
