WHAT THIS EVIDENCE MEANS FOR PRACTICE
Elective single embryo transfer is the only ART embryo transfer strategy that will reduce the twin pregnancy rate. However, it is not a good approach for all patients and must be carefully utilized in selected patients who have a good prognosis.
Vitrification for cryopreservation of embryos appears to be superior to slow freezing
Leibo S, Pool T. The principal variables of cryopreservation: solutions, temperatures, and rate changes. Fertil Steril. 2011;96(2):269–276.
Cobo A, Diaz C. Clinical application of oocyte vitrification: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2011;96(2):277–285.
Cryopreservation is a method by which cells are suspended in a solution of salts and low-molecular-weight organic compound, cooled to subzero temperatures (approximately –196°C) in liquid nitrogen, stored, and then rewarmed. Cryopreservation has become a major component of the practice of assisted reproduction, with more than 37,000 pregnancies produced from cryopreserved embryos from 2005 through 2009 in the United States alone.5,6
Standard (slow) freezing methods for embryo cryopreservation involve suspension of the embryos in a 10% solution of propylene glycol supplemented with 3.4% sucrose, cooling them to –35°C at a rate of 0.3°C/min, submerging them in liquid nitrogen for storage, and rewarming the frozen embryos at a rate of approximately 300°C/min to thaw them.5
A major advance in the science of cryopreservation is the use of vitrification, a method of freezing in which the embryos are equilibrated with a 10% or 15% solution of cryoprotectant and then exposed briefly (30–60 seconds) to a 20% to 40% solution of cryoprotectant to achieve relative cellular dehydration. The embryos are then placed in a storage container and submerged in liquid nitrogen. During vitrification, embryos can be cooled at a rate exceeding 1,000°C/min. Vitrified embryos are stored at approximately –196°C and thawed in ultra-rapid fashion.
The development of vitrification methods has significantly advanced the technology of oocyte cryopreservation, which has been utilized for:
- preservation of fertility in cancer patients
- social reasons (e.g., lack of a partner)
- egg-donation programs
- minimization of the risk of ovarian hyperstimulation syndrome
- storage of surplus eggs when embryo cryopreservation is not feasible.
Cobo and Diaz recently conducted a systematic review and meta-analysis of randomized, controlled trials of oocyte vitrification. They found that the potential for fertilization, embryogenesis, and pregnancy from oocytes that had undergone vitrification and warming was not significantly different from the potential for fresh oocytes and was better than the potential for oocytes that had undergone freezing and thawing from standard freezing cycles.
Although the findings of the meta-analysis were limited by the small number of studies and possible selection bias, an increasing body of evidence supports the use of vitrification for cryopreservation of oocytes. Large-scale controlled trials are needed. Until they are performed, the findings of the meta-analysis should be interpreted with caution.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Newer ultra-rapid freezing of oocytes and embryos using vitrification appears to produce results that are superior to those obtained with traditional slow freezing. Large randomized, controlled trials are needed to confirm the improved efficacy of vitrification.
Anti-Müllerian hormone is an informative test of ovarian reserve—but lacks a nod from the FDA
Buyuk E, Seifer D, Younger J, Grazi R, Lieman H. Random anti-Mullerian hormone (AMH) is a predictor of ovarian response in women with elevated baseline early follicular follicle-stimulating hormone levels. Fertil Steril. 2011;95(7):2369–2372.
Li H, Yeung PW, Lau E, Ho PC, Ng EH. Evaluating the performance of serum anti-Müllerian hormone concentration in predicting the live birth rate of controlled ovarian stimulation and intrauterine insemination. Fertil Steril. 2010;94(6):2177–2181.
Lee J, Kim S, Jee B, Suh C, Kim KC, Moon SY. Anti-Müllerian hormone as a predictor of controlled ovarian hyperstimulation outcome: comparison of two commercial immunoassay kits. Fertil Steril. 2011;95(8):2602–2604.
Although it is well understood that both the quantity and quality of oocytes decline with age, the assessment of ovarian reserve continues to be a clinical challenge. Accurate evaluation can predict a woman’s response to infertility treatment, including IVF, and estimate her chance of conception. Noninvasive tests of ovarian reserve are a critical component of any evaluation of fertility. Although a woman’s age is the single most important historical factor in the assessment of reproductive capacity, there is significant variation in ovarian aging among women.
Historically, age, antral follicle count (AFC), and measurement of cycle day 3 follicle-stimulating hormone (FSH) and estradiol (E2) levels have been the most widely used measures of ovarian reserve, but mounting evidence suggests that assessment of the anti-Müllerian hormone (AMH) level may be even more informative.
AMH, also known as Müllerian-inhibiting substance, is a dimeric glycoprotein. A member of the transforming growth factor–ß family, AMH is closely related to inhibin and activin and is secreted by granulosa cells of preantral and small antral follicles in post-pubertal females.7 AMH aids in the coordination of ovarian follicular development by inhibiting recruitment of additional primordial follicles and decreasing the sensitivity of preantral and small antral follicles to FSH.8,9