Association between Age and Miscarriage in an Assisted Reproductive Technology Population: A 10-Year Cohort Study
-
Doudou Zhao
,
Jie Chen
,
Xiayang Li
,
Zhaofang Li
,
Jingchen Zhang
,
Caixia Gao
,
Wenbo Hong
,
Danmeng Liu
,
Wenhao Shi
,
Juanzi Shi
,
Pengfei Qu
Abstract
Background: Advanced maternal age decreased success of pregnancy rate in the assisted reproductive technology (ART) treatment. We aimed to investigate the association between age and miscarriages in women who required ART for conception.
Methods: A cohort study was conducted using a 10-year sample of 14,898 pregnancy cycles with ART treatment in Xi’an, China. The effects of women’s age on miscarriage were assessed using Poisson regression models. The threshold effect between age and miscarriage was explored through curve fitting.
Results: Compared with lower than 30 years, the risks of early miscarriage and miscarriage were higher in the older age groups (early miscarriage: [35-37 years: RR=1.48, 95% confidence interval (CI): 1.26 to 1.74; ≥38 years: RR=2.25, 95% CI: 1.87 to 2.72]; miscarriage: [35-37 years: RR=1.45, 95%CI: 1.24 to 1.69; ≥38 years: RR=2.17, 95%CI: 1.82 to 2.60]). The nonlinear relationship between age and early miscarriage and miscarriages were observed. The risk of early miscarriage and miscarriage rapidly increased with age after the turning point (age=33 years) (<33 years: [early miscarriage: RR=1.02, 95% CI: 1.00 to 1.04; miscarriage: RR=1.02, 95% CI: 1.00 to 1.03]; ≥33 years: [early miscarriage: RR=1.11, 95% CI: 1.08 to 1.13; miscarriage: RR=1.10, 95% CI: 1.07 to 1.13]).
Conclusion: Among pregnancy cycles undergoing ART, advanced age is associated with higher risk of early miscarriage and miscarriage, and nonlinear relationship between age and early miscarriage and miscarriage were found. More attention should be paid to the risk of pregnant women with older than 33 years in ART treatment.
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8. Wilson EE (2005). Assisted reproductive technologies and multiple gestations. Clin Perinatol, 32(2): 315-328.
9. Xie M, Lao T T, Du M, et al (2019). Risk for Cesarean section in women of advanced maternal age under the changed reproductive policy in China: A cohort study in a tertiary hospital in southwestern China. J Obstet Gynaecol Res, 45(9): 1866-1875.
10. Nybo Andersen AM, Wohlfahrt J, Christens P, et al (2000). Maternal age and fetal loss: population based register linkage study. BMJ, 320(7251): 1708-1712.
11. Grande M, Borrell A, Garcia-Posada R, et al (2012). The effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage. Hum Reprod, 27(10): 3109-3117.
12. Pinheiro R L, Areia A L, Mota Pinto A, et al (2019). Advanced Maternal Age: Adverse Outcomes of Pregnancy, A Meta-Analysis. Acta Med Port, 32(3): 219-226.
13. Kahveci B, Melekoglu R, Evruke I C, et al (2018). The effect of advanced maternal age on perinatal outcomes in nulliparous singleton pregnancies. BMC Pregnancy Childbirth, 18(1): 343.
14. Hsieh H C, Su J Y, Wang S, et al (2020). Age effect on in vitro fertilization pregnancy mediated by anti-Mullerian hormone (AMH) and modified by follicle stimulating hormone (FSH). BMC Pregnancy Childbirth, 20(1): 209.
15. Nelson S M, Lawlor D A (2011). Predicting live birth, preterm delivery, and low birth weight in infants born from in vitro fertilisation: a prospective study of 144,018 treatment cycles. PLoS Med, 8(1): e1000386.
16. Munne S, Mills E, Hill D, et al (2013). Implantation and ongoing pregnancy rate with euploid embryo transfer is independent of maternal age. Fertil Steril, 100(3): S131.
17. Irani M, Zaninovic N, Rosenwaks Z, et al (2019). Does maternal age at retrieval influence the implantation potential of euploid blastocysts? Am J Obstet Gynecol, 220(4): 379.e1-379.e7.
18. Vitagliano A, Paffoni A, Viganò P (2023). Does maternal age affect assisted reproduction technology success rates after euploid embryo transfer? A systematic review and meta-analysis. Fertil Steril, 120(2): 251-265.
19. Reig A, Franasiak J, Scott RT Jr, et al (2020). The impact of age beyond ploidy: outcome data from 8175 euploid single embryo transfers. J Assist Reprod Genet, 37(3): 595-602.
20. Assefa N, Berhane Y, Worku A (2013). Pregnancy rates and pregnancy loss in Eastern Ethiopia. Acta Obstet Gynecol Scand, 92(6): 642-647.
21. Rossen L M, Ahrens K A, Branum A M (2018). Trends in Risk of Pregnancy Loss Among US Women, 1990-2011. Paediatr Perinat Epidemiol, 32(1): 19-29.
22. Farr S L, Schieve L A, Jamieson D J (2007). Pregnancy loss among pregnancies conceived through assisted reproductive technology, United States, 1999-2002. Am J Epidemiol, 165(12): 1380-8.
23. Khalil A, Syngelaki A, Maiz N, et al (2013). Maternal age and adverse pregnancy outcome: a cohort study. Ultrasound Obstet Gynecol, 42(6): 634-643.
24. Spandorfer S D, Davis O K, Barmat L I, et al (2004). Relationship between maternal age and aneuploidy in in vitro fertilization pregnancy loss. Fertil Steril, 81(5): 1265-1269.
25. Dai R, Li L, Zhu H, et al (2018). Effect of maternal age on spontaneous abortion during the first trimester in Northeast China. J Matern Fetal Neonatal Med, 31(14): 1824-1829.
26. Hu L, Du J, Lv H, et al (2018). Influencing factors of pregnancy loss and survival probability of clinical pregnancies conceived through assisted reproductive technology. Reprod Biol Endocrinol,16(1):74.
27. Yan J, Wu K, Tang R, et al (2012). Effect of maternal age on the outcomes of in vitro fertilization and embryo transfer (IVF-ET). Sci China Life Sci, 55(8): 694-8.
28. Norbert G, Vitaly AK, David FA, et al (2016). Improvements in IVF in women of advanced age. J Endocrinol, 230(1): F1-6.
29. Baird D T, Collins J, Egozcue J, et al (2005). Fertility and ageing. Hum Reprod Update, 11(3): 261-76.
30. Franasiak J M, Forman E J, Hong K H, et al (2014). The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Fertil Steril, 101(3): 656-663.e1.
31. Ziebe S, Loft A, Petersen J H, et al (2001). Embryo quality and developmental potential is compromised by age. Acta Obstet Gynecol Scand, 80(2): 169-174.
32. McCallie B R, Parks J C, Trahan G D, et al (2019). Compromised global embryonic transcriptome associated with advanced maternal age. J Assist Reprod Genet, 36(5): 915-924.
33. Ozawa N, Ogawa K, Sasaki A, et al (2019). Maternal age, history of miscarriage, and embryonic/fetal size are associated with cytogenetic results of spontaneous early miscarriages. J Assist Reprod Genet, 36(4): 749-757.
34. Jia C W, Wang L, Lan Y L, et al (2015). Aneuploidy in Early Miscarriage and its Related Factors. Chin Med J (Engl), 128(20): 2772-6.
2. Crawford G E, Ledger W L (2019). In vitro fertilisation/intracytoplasmic sperm injection beyond 2020. BJOG, 126(2): 237-243.
3. European Society of Human Reproduction and Embryology (2020). ART Fact Sheet. Available at: https://www.eshre.eu/Press-Room/Resources (Accessed 27/01/2021).
4. Yang X, Li Y, Li C, et al (2014). Current overview of pregnancy complications and live-birth outcome of assisted reproductive technology in mainland China. Fertil Steril, 101(2): 385-391.
5. Dunietz G L, Holzman C, McKane P, et al (2015). Assisted reproductive technology and the risk of preterm birth among primiparas. Fertil Steril, 103(4): 974-979.e1.
6. Sha T, Wang X, Cheng W, et al (2019). A meta-analysis of pregnancy-related outcomes and complications in women with polycystic ovary syndrome undergoing IVF. Reprod Biomed Online, 39(2): 281-293.
7. Wen J, Jiang J, Ding C, et al (2012). Birth defects in children conceived by in vitro fertilization and intracytoplasmic sperm injection: a meta-analysis. Fertil Steril, 97(6): 1331-1337.e1-4.
8. Wilson EE (2005). Assisted reproductive technologies and multiple gestations. Clin Perinatol, 32(2): 315-328.
9. Xie M, Lao T T, Du M, et al (2019). Risk for Cesarean section in women of advanced maternal age under the changed reproductive policy in China: A cohort study in a tertiary hospital in southwestern China. J Obstet Gynaecol Res, 45(9): 1866-1875.
10. Nybo Andersen AM, Wohlfahrt J, Christens P, et al (2000). Maternal age and fetal loss: population based register linkage study. BMJ, 320(7251): 1708-1712.
11. Grande M, Borrell A, Garcia-Posada R, et al (2012). The effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage. Hum Reprod, 27(10): 3109-3117.
12. Pinheiro R L, Areia A L, Mota Pinto A, et al (2019). Advanced Maternal Age: Adverse Outcomes of Pregnancy, A Meta-Analysis. Acta Med Port, 32(3): 219-226.
13. Kahveci B, Melekoglu R, Evruke I C, et al (2018). The effect of advanced maternal age on perinatal outcomes in nulliparous singleton pregnancies. BMC Pregnancy Childbirth, 18(1): 343.
14. Hsieh H C, Su J Y, Wang S, et al (2020). Age effect on in vitro fertilization pregnancy mediated by anti-Mullerian hormone (AMH) and modified by follicle stimulating hormone (FSH). BMC Pregnancy Childbirth, 20(1): 209.
15. Nelson S M, Lawlor D A (2011). Predicting live birth, preterm delivery, and low birth weight in infants born from in vitro fertilisation: a prospective study of 144,018 treatment cycles. PLoS Med, 8(1): e1000386.
16. Munne S, Mills E, Hill D, et al (2013). Implantation and ongoing pregnancy rate with euploid embryo transfer is independent of maternal age. Fertil Steril, 100(3): S131.
17. Irani M, Zaninovic N, Rosenwaks Z, et al (2019). Does maternal age at retrieval influence the implantation potential of euploid blastocysts? Am J Obstet Gynecol, 220(4): 379.e1-379.e7.
18. Vitagliano A, Paffoni A, Viganò P (2023). Does maternal age affect assisted reproduction technology success rates after euploid embryo transfer? A systematic review and meta-analysis. Fertil Steril, 120(2): 251-265.
19. Reig A, Franasiak J, Scott RT Jr, et al (2020). The impact of age beyond ploidy: outcome data from 8175 euploid single embryo transfers. J Assist Reprod Genet, 37(3): 595-602.
20. Assefa N, Berhane Y, Worku A (2013). Pregnancy rates and pregnancy loss in Eastern Ethiopia. Acta Obstet Gynecol Scand, 92(6): 642-647.
21. Rossen L M, Ahrens K A, Branum A M (2018). Trends in Risk of Pregnancy Loss Among US Women, 1990-2011. Paediatr Perinat Epidemiol, 32(1): 19-29.
22. Farr S L, Schieve L A, Jamieson D J (2007). Pregnancy loss among pregnancies conceived through assisted reproductive technology, United States, 1999-2002. Am J Epidemiol, 165(12): 1380-8.
23. Khalil A, Syngelaki A, Maiz N, et al (2013). Maternal age and adverse pregnancy outcome: a cohort study. Ultrasound Obstet Gynecol, 42(6): 634-643.
24. Spandorfer S D, Davis O K, Barmat L I, et al (2004). Relationship between maternal age and aneuploidy in in vitro fertilization pregnancy loss. Fertil Steril, 81(5): 1265-1269.
25. Dai R, Li L, Zhu H, et al (2018). Effect of maternal age on spontaneous abortion during the first trimester in Northeast China. J Matern Fetal Neonatal Med, 31(14): 1824-1829.
26. Hu L, Du J, Lv H, et al (2018). Influencing factors of pregnancy loss and survival probability of clinical pregnancies conceived through assisted reproductive technology. Reprod Biol Endocrinol,16(1):74.
27. Yan J, Wu K, Tang R, et al (2012). Effect of maternal age on the outcomes of in vitro fertilization and embryo transfer (IVF-ET). Sci China Life Sci, 55(8): 694-8.
28. Norbert G, Vitaly AK, David FA, et al (2016). Improvements in IVF in women of advanced age. J Endocrinol, 230(1): F1-6.
29. Baird D T, Collins J, Egozcue J, et al (2005). Fertility and ageing. Hum Reprod Update, 11(3): 261-76.
30. Franasiak J M, Forman E J, Hong K H, et al (2014). The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Fertil Steril, 101(3): 656-663.e1.
31. Ziebe S, Loft A, Petersen J H, et al (2001). Embryo quality and developmental potential is compromised by age. Acta Obstet Gynecol Scand, 80(2): 169-174.
32. McCallie B R, Parks J C, Trahan G D, et al (2019). Compromised global embryonic transcriptome associated with advanced maternal age. J Assist Reprod Genet, 36(5): 915-924.
33. Ozawa N, Ogawa K, Sasaki A, et al (2019). Maternal age, history of miscarriage, and embryonic/fetal size are associated with cytogenetic results of spontaneous early miscarriages. J Assist Reprod Genet, 36(4): 749-757.
34. Jia C W, Wang L, Lan Y L, et al (2015). Aneuploidy in Early Miscarriage and its Related Factors. Chin Med J (Engl), 128(20): 2772-6.
| Files | ||
| Issue | Vol 53 No 9 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v53i9.16456 | |
| Keywords | ||
| Advanced age Miscarriage Assisted reproductive technology Cohort study Chinese population | ||
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How to Cite
1.
Zhao D, Chen J, Li X, Li Z, Zhang J, Gao C, Hong W, Liu D, Shi W, Shi J, Qu P. Association between Age and Miscarriage in an Assisted Reproductive Technology Population: A 10-Year Cohort Study. Iran J Public Health. 2024;53(9):2030-2039.
