Fertility preserving options for women of advancing age
- Karine Chung, MD, MSCE
Karine Chung, MD, MSCE
- Assistant Professor of Obstetrics and Gynecology
- Division of Reproductive Endocrinology and Infertility
- USC Keck School of Medicine
- Richard Paulson, MD
Richard Paulson, MD
- Professor and Vice-Chair, Department of Obstetrics & Gynecology
- Chief, Division of Reproductive Endocrinology and Infertility
- University of Southern California
- Keck School of Medicine
Population-based birth statistics demonstrate a consistent increase in the proportion of women choosing to delay childbearing until later in their reproductive years . This trend has largely been attributed to the increase in women pursuing postgraduate educational degrees and higher levels of professional achievement, activities whose demands for time and energy compete with those of starting a family .
Because the ability to conceive is strongly influenced by a woman's age, many women who delay childbearing may face infertility by the time they are ready to become pregnant. The prevalence of infertility increases significantly after age 35 year, and by age 45 years, as many as 99 percent of women are infertile . (See "Effect of advanced age on fertility and pregnancy in women".)
As the trend to delay childbearing continues, and as awareness of the age-related decline in fertility increases, interest in the emerging technologies of fertility preservation has grown. Although these procedures are commonly considered for women undergoing sterilizing treatments (eg, chemotherapy, radiation therapy, ovarian resection), elective use of fertility preservation techniques among women of advancing reproductive age remains controversial [4-8].
Fertility preservation options that may be applied to women of advancing reproductive age will be discussed here. Preservation of fertility in patients undergoing sterilizing therapies is reviewed separately. (See "Fertility preservation in patients undergoing gonadotoxic treatment or gonadal resection".)
AGE-RELATED DECLINE IN FEMALE FERTILITY
The influence of female age on fertility has been clearly established by a number of observational studies, which have consistently demonstrated a decline in pregnancy rates with advancing maternal age. Furthermore, cycles that result in pregnancy are less likely to progress to live births because of higher rates of miscarriage among older women. These relationships are best illustrated by outcome data from clinics performing in vitro fertilization (table 1). (See "Effect of advanced age on fertility and pregnancy in women".)
- National Center for Health Statistics. Birth rate for women age 15-44. www.cdc.gov/nchs/pressroom/04facts/birthrates.htm (Accessed on October 29, 2008).
- Mathews, TJ, Ventura, SJ. National Vital Statistics Report. Birth and Fertility Rates by Educational Attainment: United States, 1994. www.cdc.gov/nchs/pressroom/97facts/edu2birt.htm. (Accessed on November 07, 2008).
- Menken J, Trussell J, Larsen U. Age and infertility. Science 1986; 233:1389.
- ESHRE Task Force on Ethics and Law, Dondorp W, de Wert G, et al. Oocyte cryopreservation for age-related fertility loss. Hum Reprod 2012; 27:1231.
- Hirshfeld-Cytron J, Grobman WA, Milad MP. Fertility preservation for social indications: a cost-based decision analysis. Fertil Steril 2012; 97:665.
- Lockwood GM. Social egg freezing: the prospect of reproductive 'immortality' or a dangerous delusion? Reprod Biomed Online 2011; 23:334.
- Mertes H, Pennings G. Elective oocyte cryopreservation: who should pay? Hum Reprod 2012; 27:9.
- Mertes H, Pennings G. Social egg freezing: for better, not for worse. Reprod Biomed Online 2011; 23:824.
- Rao GD, Chian RC, Son WS, et al. Fertility preservation in women undergoing cancer treatment. Lancet 2004; 363:1829.
- Faddy MJ, Gosden RG, Gougeon A, et al. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod 1992; 7:1342.
- Volarcik K, Sheean L, Goldfarb J, et al. The meiotic competence of in-vitro matured human oocytes is influenced by donor age: evidence that folliculogenesis is compromised in the reproductively aged ovary. Hum Reprod 1998; 13:154.
- Pellestor F, Andréo B, Arnal F, et al. Maternal aging and chromosomal abnormalities: new data drawn from in vitro unfertilized human oocytes. Hum Genet 2003; 112:195.
- Stolwijk AM, Zielhuis GA, Sauer MV, et al. The impact of the woman's age on the success of standard and donor in vitro fertilization. Fertil Steril 1997; 67:702.
- Sauer MV, Paulson RJ, Lobo RA. Reversing the natural decline in human fertility. An extended clinical trial of oocyte donation to women of advanced reproductive age. JAMA 1992; 268:1275.
- Paulson RJ, Hatch IE, Lobo RA, Sauer MV. Cumulative conception and live birth rates after oocyte donation: implications regarding endometrial receptivity. Hum Reprod 1997; 12:835.
- Pickering SJ, Braude PR, Johnson MH. Cryoprotection of human oocytes: inappropriate exposure to DMSO reduces fertilization rates. Hum Reprod 1991; 6:142.
- Society for Assisted Reproductive Technology, American Society for Reproductive Medicine. Assisted reproductive technology success rates. National summary and fertility clinic reports. www.cdc.gov/ART/ART2003. (Accessed on October 29, 2008).
- Wilson C, Check JH, Summers-Chase D, Swenson K. Successful pregnancies from embryos cryopreserved more than ten years: two case reports. Clin Exp Obstet Gynecol 2006; 33:79.
- Aytoz A, Van den Abbeel E, Bonduelle M, et al. Obstetric outcome of pregnancies after the transfer of cryopreserved and fresh embryos obtained by conventional in-vitro fertilization and intracytoplasmic sperm injection. Hum Reprod 1999; 14:2619.
- Shih W, Rushford DD, Bourne H, et al. Factors affecting low birthweight after assisted reproduction technology: difference between transfer of fresh and cryopreserved embryos suggests an adverse effect of oocyte collection. Hum Reprod 2008; 23:1644.
- Practice Committees of American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. Mature oocyte cryopreservation: a guideline. Fertil Steril 2013; 99:37.
- ACOG: Committee Opinion No. 584: oocyte cryopreservation. Obstet Gynecol 2014; 123:221.
- Practice Committee of the Society for Assisted Reproductive Technology, Practice Committee of the American Society for Reproductive Medicine. Essential elements of informed consent for elective oocyte cryopreservation: a Practice Committee opinion. Fertil Steril 2007; 88:1495.
- Chen C. Pregnancy after human oocyte cryopreservation. Lancet 1986; 1:884.
- Jain JK, Paulson RJ. Oocyte cryopreservation. Fertil Steril 2006; 86:1037.
- Gardner DK, Sheehan CB, Rienzi L, et al. Analysis of oocyte physiology to improve cryopreservation procedures. Theriogenology 2007; 67:64.
- Ghetler Y, Skutelsky E, Ben Nun I, et al. Human oocyte cryopreservation and the fate of cortical granules. Fertil Steril 2006; 86:210.
- Wortzman GB, Evans JP. Membrane and cortical abnormalities in post-ovulatory aged eggs: analysis of fertilizability and establishment of the membrane block to polyspermy. Mol Hum Reprod 2005; 11:1.
- Schalkoff ME, Oskowitz SP, Powers RD. Ultrastructural observations of human and mouse oocytes treated with cryopreservatives. Biol Reprod 1989; 40:379.
- Kazem R, Thompson LA, Srikantharajah A, et al. Cryopreservation of human oocytes and fertilization by two techniques: in-vitro fertilization and intracytoplasmic sperm injection. Hum Reprod 1995; 10:2650.
- Porcu E, Fabbri R, Seracchioli R, et al. Birth of a healthy female after intracytoplasmic sperm injection of cryopreserved human oocytes. Fertil Steril 1997; 68:724.
- Mazur P. Limits to life at low temperatures and at reduced water contents and water activities. Orig Life 1980; 10:137.
- Fabbri R, Porcu E, Marsella T, et al. Human oocyte cryopreservation: new perspectives regarding oocyte survival. Hum Reprod 2001; 16:411.
- Oktay K, Cil AP, Bang H. Efficiency of oocyte cryopreservation: a meta-analysis. Fertil Steril 2006; 86:70.
- Kuleshova L, Gianaroli L, Magli C, et al. Birth following vitrification of a small number of human oocytes: case report. Hum Reprod 1999; 14:3077.
- Cobo A, García-Velasco JA, Coello A, et al. Oocyte vitrification as an efficient option for elective fertility preservation. Fertil Steril 2016; 105:755.
- Kuwayama M, Vajta G, Ieda S, Kato O. Comparison of open and closed methods for vitrification of human embryos and the elimination of potential contamination. Reprod Biomed Online 2005; 11:608.
- Cobo A, Diaz C. Clinical application of oocyte vitrification: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril 2011; 96:277.
- Donnez J, Dolmans MM, Pellicer A, et al. Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue: a review of 60 cases of reimplantation. Fertil Steril 2013; 99:1503.
- Practice Committee of American Society for Reproductive Medicine. Ovarian tissue cryopreservation: a committee opinion. Fertil Steril 2014; 101:1237.
- Bianchi V, Lappi M, Bonu MA, Borini A. Oocyte slow freezing using a 0.2-0.3 M sucrose concentration protocol: is it really the time to trash the cryopreservation machine? Fertil Steril 2012; 97:1101.
- Ubaldi F, Anniballo R, Romano S, et al. Cumulative ongoing pregnancy rate achieved with oocyte vitrification and cleavage stage transfer without embryo selection in a standard infertility program. Hum Reprod 2010; 25:1199.
- Spandorfer SD, Bendikson K, Dragisic K, et al. Outcome of in vitro fertilization in women 45 years and older who use autologous oocytes. Fertil Steril 2007; 87:74.
- Quintans CJ, Donaldson MJ, Bertolino MV, Pasqualini RS. Birth of two babies using oocytes that were cryopreserved in a choline-based freezing medium. Hum Reprod 2002; 17:3149.
- Boldt J, Tidswell N, Sayers A, et al. Human oocyte cryopreservation: 5-year experience with a sodium-depleted slow freezing method. Reprod Biomed Online 2006; 13:96.
- Levi Setti PE, Albani E, Novara PV, et al. Cryopreservation of supernumerary oocytes in IVF/ICSI cycles. Hum Reprod 2006; 21:370.
- Sathananthan AH, Trounson A, Freemann L, Brady T. The effects of cooling human oocytes. Hum Reprod 1988; 3:968.
- Pickering SJ, Braude PR, Johnson MH, et al. Transient cooling to room temperature can cause irreversible disruption of the meiotic spindle in the human oocyte. Fertil Steril 1990; 54:102.
- Rienzi L, Martinez F, Ubaldi F, et al. Polscope analysis of meiotic spindle changes in living metaphase II human oocytes during the freezing and thawing procedures. Hum Reprod 2004; 19:655.
- Cobo A, Pérez S, De los Santos MJ, et al. Effect of different cryopreservation protocols on the metaphase II spindle in human oocytes. Reprod Biomed Online 2008; 17:350.
- Gook DA, Osborn SM, Bourne H, Johnston WI. Fertilization of human oocytes following cryopreservation; normal karyotypes and absence of stray chromosomes. Hum Reprod 1994; 9:684.
- Cobo A, Rubio C, Gerli S, et al. Use of fluorescence in situ hybridization to assess the chromosomal status of embryos obtained from cryopreserved oocytes. Fertil Steril 2001; 75:354.
- Noyes N, Porcu E, Borini A. Over 900 oocyte cryopreservation babies born with no apparent increase in congenital anomalies. Reprod Biomed Online 2009; 18:769.
- Winslow, KL, Yang, D, Blohm, PL, Brown, SE, Jossim, P, Nguyen, K. Oocyte cryopreservation: a three year follow-up of sixteen births. Fertil Steril 2001; 76:S120.
- Porcu E, Fabbri R, Damiano G, et al. Clinical experience and applications of oocyte cryopreservation. Mol Cell Endocrinol 2000; 169:33.
- Chian RC, Huang JY, Tan SL, et al. Obstetric and perinatal outcome in 200 infants conceived from vitrified oocytes. Reprod Biomed Online 2008; 16:608.
- AGE-RELATED DECLINE IN FEMALE FERTILITY
- OPTIONS FOR FERTILITY PRESERVATION
- EMBRYO CRYOPRESERVATION
- CRYOPRESERVATION OF OOCYTES
- Mature oocytes
- - Procedure
- Intracytoplasmic sperm injection (ICSI) for zona pellucida hardening
- Use of cryoprotectants to avoid intracellular ice crystal formation
- Methods to limit toxicity of cryoprotectants and solutes
- - Slow freeze
- - Vitrification
- - Slow freeze versus vitrification
- Ovarian tissue
- Age at the time of the procedure
- Maximum age for oocyte cryopreservation
- Planned age of childbearing
- Risk of miscarriage
- Risk to offspring
- - Aneuploidy
- - Congenital anomalies
- LOGISTICS AND COST
- SUMMARY AND RECOMMENDATIONS