Higher rate of early-onset preeclampsia in pregnancies following oocyte donation according to increasing maternal age

  • Bianca Masturzo
  • Daniela Di Martino
  • Federico Prefumo
  • Paolo Cavoretto
  • Chiara Germano
  • Gianluca Gennarelli
  • Enrica Roletti
  • Elisa Bottazzoli
  • Federica Fusè
  • Enrico Ferrazzi
  • Danila Morano
  • Antonio FarinaEmail author



To assess the influence of maternal age on the incidence of early-onset preeclampsia requiring delivery before 34 weeks of gestation in pregnancies obtained after oocyte donation.


We carried out a prospective cohort analysis of 431 single and twin pregnancies, admitted to 3 Tertiary Referral Hospital in Northern Italy between 2008 and 2017. The rate of early-onset PE was calculated and stratified according to maternal age (from 30 to 49 years). A reference population of 11,197 single pregnancies collected prospectively at the first trimester of pregnancy in the same geographic area of Italy and in same hospitals was used to calculate the expected incidence of early-onset PE.


In women who delivered after 24 weeks of gestation, the rate of early-onset PE was much higher in oocyte-donation pregnancies, reaching 6.7% (29/431), than the expected rate of 0.5% of the cohort of reference. The mean early PE rate was 4.1% (10/242) in singletons and 10.1% (19/189) in twin pregnancies. According to maternal age, the rate of early PE was 1.16% and 3.12% at 30 years, and 4.98% and 13.14% at 49 years in single and twin pregnancies obtained after oocyte donation, respectively.


Pregnancies obtained after oocyte donation delivering after 24 weeks had a higher risk of early-onset PE requiring delivery before 34 weeks of gestation, than the general population. The risk is directly correlated with the increase of maternal age and is also higher in twin pregnancies.


Oocyte-donor pregnancy Early-onset preeclampsia Maternal age-related risk Binary logistic regression 


Author contributions

BM: protocol/project development, data collection, manuscript writing. DDM: protocol/project development. FP: data collection. PC: data collection. CG: protocol/project development, data collection, manuscript writing. GG: Protocol/project development, data collection. ER: protocol/project development, data collection. EB: data collection. FF: data collection. EF: protocol/project development. DM: protocol/project development, manuscript writing. AF: protocol/project development, data collection, manuscript writing, data analysis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The committee for this study is Professor Antonio Farina.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

404_2019_5291_MOESM1_ESM.docx (13 kb)
Supplementary file1 (DOCX 12 kb)


  1. 1.
    Bustillo M, Buster JE, Cohen SW, Hamilton F, Thorneycroft IH, Simon JA et al (1984) Delivery of a healthy infant following nonsurgical ovum transfer. JAMA 251:889CrossRefGoogle Scholar
  2. 2.
    European IVF-Monitoring Consortium (EIM) for the European Society of Human Reproduction, and Embryology (ESHRE), Calhaz-Jorge C, de Geyter C, Kupka MS, de Mouzon J, Erb K, Mocanu E, Motrenko T, Scaravelli G, Wyns C, Goossens V (2017) Assisted reproductive technology in Europe 2013: results generated from European registers by ESHRE. Hum Reprod 2017(32):1957–1973Google Scholar
  3. 3.
    European IVF-Monitoring Consortium (EIM) for the European Society of Human Reproduction, and Embryology (ESHRE), Calhaz-Jorge C, de Geyter C, Kupka MS, de Mouzon J, Erb K, Mocanu E, Motrenko T, Scaravelli G, Wyns C, Goossens V (2016) Assisted reproductive technology in Europe, 2012: results generated from European registers by ESHRE. Hum Reprod 2016(31):1638–1652Google Scholar
  4. 4.
    Ferraretti AP, Goossens V, Kupka M, Bhattacharya S, de Mouzon J, Castilla JA, et al. (2013) European IVF-Monitoring (EIM) Consortium for the European Society of Human Reproduction and Embryology (ESHRE). Assisted reproductive technology in Europe, 2009: results generated from European registers by ESHRE. Hum Reprod 28:2318–2331.Google Scholar
  5. 5.
    Sauer MV, Kavic SM (2006) Oocyte and embryo donation 2006: reviewing two decades of innovation and controversy. Reprod Biomed Online 12:153–162CrossRefGoogle Scholar
  6. 6.
    Letur H, Peigné M, Ohl J, Cédrin-Durnerin I, Mathieu-D'Argent E, Scheffler F et al (2016) Hypertensive pathologies and egg donation pregnancies: Results of a large comparative cohort study. Fertil Steril 106:284–290CrossRefGoogle Scholar
  7. 7.
    Ohel I, Sheiner E (2009) Does oocyte donation equal cesarean delivery? J Matern Fetal Neonatal Med 22(9):776–779CrossRefGoogle Scholar
  8. 8.
    Klatsky PC, Delaney SS, Caughey AB, Tran ND, Schattman GL, Rosenwaks Z (2010) The role of embryonic origin in preeclampsia: a comparison of autologous in vitro fertilization and ovum donor pregnancies. Obstet Gynecol 116:1387–1392CrossRefGoogle Scholar
  9. 9.
    Levron Y, Dviri M, Segol I, Yerushalmi GM, Hourvitz A, Orvieto R et al (2014) The 'immunologic theory' of preeclampsia revisited: a lesson from donor oocyte gestations. Am J Obstet Gynecol 211(383):e381–385Google Scholar
  10. 10.
    van der Hoorn ML, Lashley EE, Bianchi DW, Claas FH, Schonkeren CM, Scherjon SA (2010) Clinical and immunologic aspects of egg donation pregnancies: a systematic review. Hum Reprod Update 16:704–712CrossRefGoogle Scholar
  11. 11.
    Madeja Z, Yadi H, Apps R, Boulenouar S, Roper SJ, Gardner L et al (2011) PaternalMHC expression onmouse trophoblast affects uterine vascularization and fetal growth. Proc Natl Acad Sci U S A 108:4012–4017CrossRefGoogle Scholar
  12. 12.
    Hiby SE, Walker JJ, O'Shaughnessy KM, Redman CW, Carrington M, Trowsdale J et al (2004) Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success. J Exp Med 200:957–965CrossRefGoogle Scholar
  13. 13.
    Le Ray C, Scherier S, Anselem O, Marszalek A, Tsatsaris V, Cabrol D et al (2012) Association between oocyte donation and maternal and perinatal outcomes in women aged 43 years or older. Hum Reprod 27:896–901CrossRefGoogle Scholar
  14. 14.
    Redman CW, Sargent IL (2010) Immunology of pre-eclampsia. Am J Reprod Immunol 63:534–543CrossRefGoogle Scholar
  15. 15.
    Inversetti A, Mandia L, Candiani M, Cetin I, Larcher A, Savasi V et al (2018) Uterine artery Doppler pulsatility index at 11–38 weeks in ICSI pregnancies with egg donation. J Perinat Med 46:21–27CrossRefGoogle Scholar
  16. 16.
    Di Martino D, Masturzo B, Paracchini S et al (2019) Comparison of two "a priori" risk assessment algorithms for preeclampsia in Italy: a prospective multicenter study. Arch Gynecol Obstet 299(6):1587–1596CrossRefGoogle Scholar
  17. 17.
    Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM (2001) The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy 20:IX–XIVCrossRefGoogle Scholar
  18. 18.
    Masoudian P, Nasr A, de Nanassy J, Fung-Kee-Fung K, Bainbridge SA, El Demellawy D (2016) Oocyte donation pregnancies and the risk of preeclampsia or gestational hypertension: a systematic review and metaanalysis. Am J Obstet Gynecol 214:328–339CrossRefGoogle Scholar
  19. 19.
    Schwarze JE, Borda P, Vásquez P, Ortega C, Villa S, Crosby JA et al (2018) Is the risk of preeclampsia higher in donor oocyte pregnancies? A systematic review and meta-analysis. JBRA Assist Reprod 22:15–19Google Scholar
  20. 20.
    Duckitt K, Harrington D (2005) Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ 330:565 (Epub 2005 Mar 2) CrossRefGoogle Scholar
  21. 21.
    Ortiz C, Rondeau NU, Moore LE, Mulla ZD (2018) Parental age and the risk of gestational hypertension and preeclampsia. South Med J 111:544–548CrossRefGoogle Scholar
  22. 22.
    Jacobsson B (2004) Advanced maternal age and adverse perinatal outcome. Obstet Gynecol 104:727–733CrossRefGoogle Scholar
  23. 23.
    Lamminpää R, Vehviläinen-Julkunen K, Gissler M, Heinonen S (2012) Preeclampsia complicated by advanced maternal age: a registry-based study on primiparous women in Finland 1997–2008. BMC Pregnancy Childbirth 47:1–5Google Scholar
  24. 24.
    Ogawa K, Urayama KY, Tanigaki S, Sago H, Sato S, Saito S et al (2017) Association between very advanced maternal age and adverse pregnancy outcomes: a cross sectional Japanese study. BMC Pregnancy Childbirth 17:349CrossRefGoogle Scholar
  25. 25.
    Ananth CV, Keyes KM, Wapner RJ (2013) Pre-eclampsia rates in the United States, 1980–2010: age-period-cohort analysis. BMJ 347:f6564CrossRefGoogle Scholar
  26. 26.
    Hutcheon JA, Lisonkova S, Joseph KS (2011) Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol 25:391–403CrossRefGoogle Scholar
  27. 27.
    Ben-David A, Glasser S, Schiff E, Zahav AS, Boyko V, Lerner-Geva L (2016) Pregnancy and birth outcomes among primiparae at very advanced maternal age: at what price? Matern Child Health J 20:833–842CrossRefGoogle Scholar
  28. 28.
    Kahveci B, Melekoglu R, Evruke IC, Cetin C (2018) The effect of advanced maternal age on perinatal outcomes in nulliparous singleton pregnancies. BMC Pregnancy Childbirth 18:343CrossRefGoogle Scholar
  29. 29.
    Blázquez A, García D, Rodríguez A, Vassena R, Figueras F, Vernaeve V (2016) Is oocyte donation a risk factor for preeclampsia? A systematic review and meta-analysis. J Assist Reprod Genet 33:855–863CrossRefGoogle Scholar
  30. 30.
    Preaubert L, Vincent-Rohfritsch A, Santulli P, Gayet V, Goffinet F, Le Ray C (2018) Outcomes of pregnancies achieved by double gamete donation: A comparison with pregnancies obtained by oocyte donation alone. Eur J Obstet Gynecol Reprod Biol 222:1–6CrossRefGoogle Scholar
  31. 31.
    Stoop D, Baumgarten M, Haentjens P, Polyzos NP, De Vos M, Verheyen G et al (2012) Obstetric outcome in donor oocyte pregnancies: a matched-pair analysis. Reprod Biol Endocrinol 10:42CrossRefGoogle Scholar
  32. 32.
    Boria F, de la Calle M, Cuerva M, Sainz A, Bartha JL (2018) Impact of oocyte donation on obstetric and perinatal complications in twin pregnancies. J Matern Fetal Neonatal Med 21:1–4CrossRefGoogle Scholar
  33. 33.
    Van Dorp W, Rietveld AM, Laven JS, van den Heuvel-Eibrink MM, Hukkelhoven CW, Schipper I (2014) Pregnancy outcome of non-anonymous oocyte donation: a case-control study. Eur J Obstet Gynecol Reprod Biol 182:107–112CrossRefGoogle Scholar
  34. 34.
    Francisco C, Wright D, Benkő Z, Syngelaki A, Nicolaides K (2017) Hidden high rate of preeclampsia in twin compared to singleton pregnancies. Ultrasound Obstet Gynecol 50:88–92CrossRefGoogle Scholar
  35. 35.
    Krotz S, Fajardo J, Ghandi S, Patel A, Keith LG (2002) Hypertensive disease in twin pregnancies: a review. Twin Res 5:8–14CrossRefGoogle Scholar
  36. 36.
    Suzuki S, Igarashi M (2009) Risk factors for preeclampsia in Japanese twin pregnancies: comparison with those in singleton pregnancies. Arch Gynecol Obstet 280:389–393CrossRefGoogle Scholar
  37. 37.
    Sekhon LH, Gerber RS, Rebarber A, Saltzman DH, Klauser CK, Gupta S et al (2014) Effect of oocyte donation on pregnancy outcomes in in vitro fertilization twin gestations. Fertil Steril 101:1326–1330CrossRefGoogle Scholar
  38. 38.
    Blazquez A, García D, Vassena R, Figueras F, Rodriguez A (2018) Risk of pre-eclampsia after fresh or frozen embryo transfer in patients undergoing oocyte donation. Eur J Obstet Gynecol Reprod Biol 227:27–31CrossRefGoogle Scholar
  39. 39.
    Wright D, Syngelaki A, Akolekar R, Poon LC, Nicolaides KH (2015) Competing risks model in screening for preeclampsia by maternal characteristics and medical history. Am J Obstet Gynecol 213(62):e1–10Google Scholar
  40. 40.
    Pados G, Camus M, Van Steirteghem A, Bonduelle M, Devroey P (1994) The evolution and outcome of pregnancies from oocyte donation. Hum Reprod 1994(9):538–542CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Bianca Masturzo
    • 1
  • Daniela Di Martino
    • 2
  • Federico Prefumo
    • 3
  • Paolo Cavoretto
    • 4
  • Chiara Germano
    • 1
  • Gianluca Gennarelli
    • 1
  • Enrica Roletti
    • 5
  • Elisa Bottazzoli
    • 6
  • Federica Fusè
    • 6
  • Enrico Ferrazzi
    • 2
  • Danila Morano
    • 7
  • Antonio Farina
    • 8
    Email author
  1. 1.Department of Surgical Sciences, OIRM S. Anna HospitalUniversity of TurinTurinItaly
  2. 2.Fondazione IRCCS Ca’ Granda, Ospedale Maggiore PoliclinicoMilanItaly
  3. 3.Department of Obstetrics and GynecologyUniversity of BresciaBresciaItaly
  4. 4.Gynecology and Obstetrics Department, IRCCS San Raffaele HospitalVita-Salute UniversityMilanItaly
  5. 5.Gynecology and Obstetrics DepartmentMaggiore University HospitalParmaItaly
  6. 6.Department of Woman, Mother and Neonate, Buzzi Children’s HospitalUniversity of MilanMilanItaly
  7. 7.Department of Obstetrics and GynecologySant’Anna University HospitalFerraraItaly
  8. 8.Division of Obstetrics and Prenatal Medicine, Department of Medicine and Surgery (DIMEC) Sant’Orsola-Malpighi HospitalUniversity of BolognaBolognaItaly

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