IVF Is Safe over 50 If It Is Not Fatal

In vitro fertilization (IVF) and other assisted reproductive techniques have become more popular and accessible and in turn the number of IVF cycles has increased—in the United Kingdom in 2010, over 57,652 cycles of IVF or intracystoplasmic sperm injection were performed in 45,264 women.[1] A third of women used donor eggs and 1.9% of women were over the age of 45.

The proportion of women wishing to conceive outside the reproductive age range is set to increase further in the future. It is important that women have information to decide whether IVF is safe to pursue.

A recent case series of 101 women over the age of 50 using donor egg IVF to conceive concluded they were at high risk of maternal complications of pregnancy including hypertensive disorders and cesarean section but only drew a comparison of similar risk to singleton pregnancies in younger women using donor egg IVF.[2]

The authors claim that the one maternal death likely due to a myocardial infarction in a 49-year-old woman who was a heavy smoker[2] was unrelated to the pregnancy, but this death would have been classified as an indirect death by the United Kingdom Confidential Enquiry into maternal deaths, which has a similar classification system as the World Health Organization—“resulting from previous existing disease, or disease that developed during pregnancy and which was not the result of direct obstetric causes, but which was aggravated by the physiological effect of pregnancy.”[3] [4] Thus, the maternal mortality rate (MMR) of egg donor IVF pregnancy would be equivalent to 990 per 100,000 maternities (95% confidence interval −0.009 to 0.029). This is more than 20 times higher than the MMR reported in the largest retrospective study to date of mortality from IVF treatment and IVF pregnancies.[5]

A healthy patient effect has been ascribed to women undergoing IVF where only women who are medically fit are selected for treatment.[6] However, it is important that even these “fit” women are still given adequate prepregnancy counseling and advice regarding the risks.[7] It is well known that advanced maternal age is a risk factor in itself for various obstetric complications. In relation to older women requiring egg donation IVF, studies have found an increased risk of pregnancy-induced hypertension, preeclampsia, preterm birth, low birth weight, twin pregnancy, and prolonged labor requiring cesarean section compared with IVF controls.[8] [9] [10] [11]

Figures of adverse outcomes from IVF and egg donation IVF pregnancies may also be underreported. Many women may seek treatment overseas, withhold the IVF information from the obstetrician providing antenatal care, or have different medical providers, therefore outcomes may not reported as a result of the IVF. For example, in one case, a 49-year-old woman underwent IVF abroad resulting in a twin pregnancy. Although antenatal care in her home country was uneventful, postdelivery at term the mother died as a result of cerebral hemorrhage secondary to HELLP syndrome (hemolysis, elevated liver enzymes, low platelets).[12]

Postmenopausal women must be counseled regarding all the risks of IVF and subsequent pregnancy. Whatever the dictates of “informed consent,” there must remain a question of what death rate would make it unethical for doctors to perform an elective request procedure.

• References

• 1 Human Fertilisation and Embryology Authority. Fertility treatment in 2010: trends and figures. Available at: http://www/hfea.gov.uk/docs/2011-11-16_-_Annual_Register_Figures_Report_final.pdf . Accessed April 22, 2012
• 2 Kort DH, Gosselin J, Choi JM, Thornton MH, Cleary-Goldman J, Sauer MV. Pregnancy after age 50: defining risks for mother and child. Am J Perinatol 2012; 29: 245-250
• 3 Cantwell R, Clutton-Brock T, Cooper G , et al; Centre for Maternal and Child Enquiries (CMACE). Saving mothers' lives: reviewing maternal deaths to make motherhood safer: 2006–2008. The Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom. BJOG 2011; 118 (Suppl. 01) 1-203
• 4 World Health Organization. The WHO Application of ICD-10 to deaths during pregnancy, childbirth and the puerperium: ICD MM. 2012. Available at: http://apps.who.int/iris/britstream/10665/70929/1/9789241548458_eng.pdf . Accessed August 13, 2012
• 5 Braat DDM, Schutte JM, Bernardus RE, Mooij TM, van Leeuwen FE. Maternal death related to IVF in the Netherlands 1984–2008. Hum Reprod 2010; 25: 1782-1786
• 6 Venn A, Hemminki E, Watson L, Bruinsma F, Healy D. Mortality in a cohort of IVF patients. Hum Reprod 2001; 16: 2691-2696
• 7 Bewley S, Foo L, Braude P. Adverse outcomes from IVF. BMJ 2011; 342: d436
• 8 Wiggins DA, Main E. Outcomes of pregnancies achieved by donor egg in vitro fertilization—a comparison with standard in vitro fertilization pregnancies. Am J Obstet Gynecol 2005; 192: 2002-2006 ; discussion 2006–2008
• 9 Henne MB, Zhang M, Paroski S, Kelshikar B, Westphal LM. Comparison of obstetric outcomes in recipients of donor oocytes vs. women of advanced maternal age with autologous oocytes. J Reprod Med 2007; 52: 585-590
• 10 Nelson SM, Lawlor DA. 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 2011; 8: e1000386
• 11 Le Ray C, Scherier S, Anselem O , et al. Association between oocyte donation and maternal and perinatal outcomes in women aged 43 years or older. Hum Reprod 2012; 27: 896-901
• 12 Schutte JM, Schuitemaker NW, Steegers EAP, van Roosmalen J ; Dutch Maternal Mortality Committee . Maternal death after oocyte donation at high maternal age: case report. Reprod Health 2008; 5: 12

• References

• 1 Paulson RJ, Boostanfar R, Saadat P , et al. Pregnancy in the sixth decade of life: obstetric outcomes in women of advanced reproductive age. JAMA 2002; 288: 2320-2323
• 2 Salihu HM, Shumpert MN, Slay M, Kirby RS, Alexander GR. Childbearing beyond maternal age 50 and fetal outcomes in the United States. Obstet Gynecol 2003; 102 (5 Pt 1) 1006-1014
• 3 Simchen MJ, Yinon Y, Moran O, Schiff E, Sivan E. Pregnancy outcome after age 50. Obstet Gynecol 2006; 108: 1084-1088
• 4 Antinori S, Versaci C, Gholami GH, Panci C, Caffa B. Oocyte donation in menopausal women. Hum Reprod 1993; 8: 1487-1490
• 5 Kort DH, Gosselin J, Choi JM, Thornton MH, Cleary-Goldman J, Sauer MV. Pregnancy after age 50: defining risks for mother and child. Am J Perinatol 2012; 29: 245-250
• 6 Braat DDM, Schutte JM, Bernardus RE, Mooij TM, van Leeuwen FE. Maternal death related to IVF in the Netherlands 1984–2008. Hum Reprod 2010; 25: 1782-1786