Management of infertility and pregnancy in women of advanced age
- Ruth C Fretts, MD, MPH
Ruth C Fretts, MD, MPH
- Assistant Professor of Obstetrics & Gynecology
- Harvard Medical School
All women of reproductive age should receive preconception counseling since many pregnancies are unplanned and thus may occur under less than optimal conditions (eg, poorly controlled diabetes, exposure to teratogens). (See "The preconception office visit".)
Women who delay childbearing are at increased risk of infertility and certain pregnancy complications. Providing information to all patients of child-bearing age about the obstetrical risks of advanced maternal age can help them make informed decisions about the timing of child-bearing.
Women should know that the probability of achieving a pregnancy begins to decline significantly at about age 32 and that coexisting medical disease and pregnancy complications become more common with advancing age. These complications include ectopic pregnancy, spontaneous abortion, fetal chromosomal abnormalities, some congenital anomalies, placenta previa, gestational diabetes, preeclampsia, and cesarean delivery. Such complications may, in turn, result in preterm birth. There is also an increased risk of perinatal mortality. (See "Effect of advanced age on fertility and pregnancy in women".)
These risks should be balanced against career and other personal issues that might favor delaying pregnancy. There are, however, a few advantages to delayed childbearing. As an example, older couples tend to be more emotionally mature and financially stable than when they were younger.
EVALUATION OF FERTILITY
Many experts suggest initiating a fertility evaluation after six months of unprotected intercourse without conception in women 35 to 40 years of age, and immediate evaluation in women over 40 years of age [1,2]. Evaluation is also initiated sooner than six months if the female partner has a history of oligomenorrhea/amenorrhea, pelvic infection, pelvic surgery, chemotherapy, radiation therapy, or endometriosis. (See "Evaluation of female infertility".)
- Practice Committee of the American Society for Reproductive Medicine. Aging and infertility in women: a committee opinion. Fertil Steril 2002; 78:215.
- American College of Obstetricians and Gynecologists. ACOG Committee Opinion. Age-related fertility decline. Obstet Gynecol 2008; 112:409.
- Leridon H. Can assisted reproduction technology compensate for the natural decline in fertility with age? A model assessment. Hum Reprod 2004; 19:1548.
- Corsan G, Trias A, Trout S, Kemmann E. Ovulation induction combined with intrauterine insemination in women 40 years of age and older: is it worthwhile? Hum Reprod 1996; 11:1109.
- Stovall DW, Toma SK, Hammond MG, Talbert LM. The effect of age on female fecundity. Obstet Gynecol 1991; 77:33.
- SART. National Data Summary Report. www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0 (Accessed on May 11, 2012).
- Toner JP, Grainger DA, Frazier LM. Clinical outcomes among recipients of donated eggs: an analysis of the U.S. national experience, 1996-1998. Fertil Steril 2002; 78:1038.
- American Society for Reproductive Medicine a Practice Committee Report A Committee Opinion Aging and Infertility in Women. January 2002.
- Krieg SA, Henne MB, Westphal LM. Obstetric outcomes in donor oocyte pregnancies compared with advanced maternal age in in vitro fertilization pregnancies. Fertil Steril 2008; 90:65.
- Yeh JS, Steward RG, Dude AM, et al. Pregnancy outcomes decline in recipients over age 44: an analysis of 27,959 fresh donor oocyte in vitro fertilization cycles from the Society for Assisted Reproductive Technology. Fertil Steril 2014; 101:1331.
- Kushnir VA, Barad DH, Albertini DF, et al. Outcomes of Fresh and Cryopreserved Oocyte Donation. JAMA 2015; 314:623.
- Quaas AM, Melamed A, Chung K, et al. Egg banking in the United States: current status of commercially available cryopreserved oocytes. Fertil Steril 2013; 99:827.
- Ethics Committee of the American Society for Reproductive Medicine. Electronic address: ASRM@asrm.org, Ethics Committee of the American Society for Reproductive Medicine. Oocyte or embryo donation to women of advanced reproductive age: an Ethics Committee opinion. Fertil Steril 2016; 106:e3.
- Mesen TB, Mersereau JE, Kane JB, Steiner AZ. Optimal timing for elective egg freezing. Fertil Steril 2015; 103:1551.
- Fitzpatrick KE, Tuffnell D, Kurinczuk JJ, Knight M. Pregnancy at very advanced maternal age: a UK population-based cohort study. BJOG 2016.
- 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 2016.
- Haslinger C, Stoiber B, Capanna F, et al. Postponed pregnancies and risks of very advanced maternal age. Swiss Med Wkly 2016; 146:w14330.
- Mathews TJ, Hamilton BE. Mean age of mother, 1970-2000. Natl Vital Stat Rep 2002; 51:1.
- Hamilton BE, Martin JA, Osterman MJ, et al. Births: Final Data for 2014. Natl Vital Stat Rep 2015; 64:1.
- Bacak SJ, Callaghan WM, Dietz PM, Crouse C. Pregnancy-associated hospitalizations in the United States, 1999-2000. Am J Obstet Gynecol 2005; 192:592.
- Nybo Andersen AM, Wohlfahrt J, Christens P, et al. Maternal age and fetal loss: population based register linkage study. BMJ 2000; 320:1708.
- Khalil A, Syngelaki A, Maiz N, et al. Maternal age and adverse pregnancy outcome: a cohort study. Ultrasound Obstet Gynecol 2013; 42:634.
- Solomon CG, Willett WC, Carey VJ, et al. A prospective study of pregravid determinants of gestational diabetes mellitus. JAMA 1997; 278:1078.
- Savva GM, Walker K, Morris JK. The maternal age-specific live birth prevalence of trisomies 13 and 18 compared to trisomy 21 (Down syndrome). Prenat Diagn 2010; 30:57.
- Pettit KE, Hull AD, Korty L, et al. Noninvasive prenatal testing: a replacement for chorionic villus sampling and amniocentesis for advanced maternal age? Obstet Gynecol 2014; 123 Suppl 1:165S.
- Jacobsson B, Ladfors L, Milsom I. Advanced maternal age and adverse perinatal outcome. Obstet Gynecol 2004; 104:727.
- Joseph KS, Allen AC, Dodds L, et al. The perinatal effects of delayed childbearing. Obstet Gynecol 2005; 105:1410.
- Centre for maternal and child enquiries (CMACE) perinatal mortality 2009. CMACE, London, 2011.
- Reddy UM, Laughon SK, Sun L, et al. Prepregnancy risk factors for antepartum stillbirth in the United States. Obstet Gynecol 2010; 116:1119.
- Fox NS, Rebarber A, Silverstein M, et al. The effectiveness of antepartum surveillance in reducing the risk of stillbirth in patients with advanced maternal age. Eur J Obstet Gynecol Reprod Biol 2013; 170:387.
- Dhanjal MK, Kenyon A. Induction of Labour at Term in Older Mothers. Scientific Impact Paper No. 34, Royal College of Obstetricians and Gynaecologists; London, UK, 2013.
- Page JM, Snowden JM, Cheng YW, et al. The risk of stillbirth and infant death by each additional week of expectant management stratified by maternal age. Am J Obstet Gynecol 2013; 209:375.e1.
- Reddy UM, Ko CW, Willinger M. Maternal age and the risk of stillbirth throughout pregnancy in the United States. Am J Obstet Gynecol 2006; 195:764.
- Hedegaard M, Lidegaard Ø, Skovlund CW, et al. Reduction in stillbirths at term after new birth induction paradigm: results of a national intervention. BMJ Open 2014; 4:e005785.
- Smith GC. Life-table analysis of the risk of perinatal death at term and post term in singleton pregnancies. Am J Obstet Gynecol 2001; 184:489.
- Walker KF, Bugg GJ, Macpherson M, et al. Randomized Trial of Labor Induction in Women 35 Years of Age or Older. N Engl J Med 2016; 374:813.
- American College of Obstetricians and Gynecologists. ACOG committee opinion no. 561: Nonmedically indicated early-term deliveries. Obstet Gynecol 2013; 121:911.
- Gülmezoglu AM, Crowther CA, Middleton P, Heatley E. Induction of labour for improving birth outcomes for women at or beyond term. Cochrane Database Syst Rev 2012; :CD004945.
- Walker KF, Malin G, Wilson P, Thornton JG. Induction of labour versus expectant management at term by subgroups of maternal age: an individual patient data meta-analysis. Eur J Obstet Gynecol Reprod Biol 2016; 197:1.
- Nicholson JM, Kellar LC, Kellar GM. The impact of the interaction between increasing gestational age and obstetrical risk on birth outcomes: evidence of a varying optimal time of delivery. J Perinatol 2006; 26:392.
- EVALUATION OF FERTILITY
- OPTIONS FOR TREATMENT OF INFERTILITY
- Our approach
- Controlled ovarian stimulation and intrauterine insemination
- In vitro fertilization
- Oocyte or embryo donation
- PREGNANCY AND MANAGEMENT
- Definition of advanced maternal age pregnancy
- Very advanced maternal age and implications
- Incidence of births to older women
- Risk of miscarriage
- Specific prenatal care issues
- - First and second trimester
- - Third trimester
- Risks of stillbirth versus delivery
- - Induction of labor
- SUMMARY AND RECOMMENDATIONS