**8. Conclusion**

202 Current Frontiers in Cryobiology

with choanal atresia and the other with Rubenstein-Taybi syndrome (Borini et al., 2007). Chian et al. analyzed rates of malformations in their 2008 cohort of 200 babies born after vitrification. Overall, only 5 birth defects were noted, for a malformation rate of 2.5% (Chian et al., 2008b). This rate is consistent with that seen in spontaneously conceived pregnancies and those following fresh IVF (Tan et al., 1992). In the Chian study, 2 ventricular septal defects (VSD), 1 case of biliary atresia, 1 club foot and 1 skin hemangioma were described in neonates. In their systematic review of the literature, Wennerholm et al. found that children who underwent karyotype analysis after oocyte cryopreservation were all within normal

The largest study to date of congenital anomalies following oocyte cryopreservation was published in 2009 by Noyes, Porcu and Borini. In this literature review, the authors identified 936 infants born after oocyte cryopreservation. In this worldwide population of infants, only 12 of 936 had either a major or minor congenital anomaly, for a malformation rate of 1.3% (Noyes et al., 2009). Defects seen included 3 VSD, 3 clubfoot, 1 choanal atresia, 1 biliary atresia, 1 Rubenstein-Taybi syndrome, 1 Arnold-Chiari syndrome, 1 cleft palate, and 1 skin hemangioma; some of these defects have already been discussed from earlier studies (Borini et al., 2007; Chian et al., 2008b). No difference in rates of major or minor congenital anomalies was found when compared to the United States birth outcome data from the Centers for Disease Control and Prevention (CDC). The CDC reports major structural or genetic birth defects occurring in 3% of live births (CDC, 2011); the number of malformations seen after oocyte cryopreservation is, in fact, lower than this national average. Importantly, the birth defects amassed in this group mirror those seen most commonly in the general population. Additionally, the authors stratified the infants between those born after slow freeze versus vitrification protocols. There was no major difference in the rate of anomalies found after these methods of oocyte cryopreservation (1.1% versus 1.5%, respectively). No epigenetic syndromes were found in this international group of infants born after oocyte cryopreservation, though these have been reported for

Ovarian tissue cryopreservation, which has been less studied and is not as widely used as oocyte cryopreservation, has also resulted in successful pregnancies. The first birth after ovarian tissue cryopreservation and autotransplantation was documented in 2004 (Donnez et al., 2004). To date, there have been 13 infants born to 10 women after ovarian tissue cryopreservation (Donnez et al., 2011). Two of these women conceived and delivered two healthy infants in subsequent pregnancies from thawed, transplanted ovarian tissue. These 10 case-reports suggest that ovarian function may be restored anywhere from 2 to 5 years post-transplant of cryopreserved tissue. Women who received chemotherapy before taking measures to preserve ovarian tissue all had significantly decreased length of graft function, compared to those who cryopreserved ovarian tissue before initiating a chemotherapy regimen. All singleton gestations delivered at term, after 37 weeks' gestational age. Additionally, all of the infants born after this method of fertility preservation are alive and healthy, without any known congenital anomalies or perinatal morbidity (Donnez et al.,

Studies of pregnancy outcome and neonatal well-being are extremely important with any new reproductive technology. Perhaps more crucial, however, is the ability to track and register pregnancies that arise out of oocyte cryopreservation cycles. The Human Oocyte

limits (Wennerholm et al., 2009).

other types of ART.

2011).

A variety of ART strategies have been introduced over the past few decades without being deemed "experimental" or requiring IRB approval. Moreover, new procedures in ART have not historically been required to demonstrate improved efficacy over established protocols before being introduced into clinical practice (Noyes et al., 2010). One example is the introduction of ICSI in the 1990s (Palermo et al., 1995). Though ICSI is more invasive than conventional IVF, it was quickly embraced in the field and used widely for couples with severe male factor infertility after extensive informed consent. Other ART techniques, such as frozen embryo storage, prenatal genetic diagnosis (PGD), laser assisted hatching, and even human chorionic gonadotropin (hCG) agonist triggering of ovulation have not required implementation under the "auspices of an IRB." Instead, informed consent documents highlight risks and benefits of these procedures and infertility centers are expected to honestly present data regarding success rates and outcomes. In light of these inconsistencies, it seems incongruous to require such stringent, IRB-approved regulations for oocyte cryopreservation, which has been shown to produce high survival rates. Clinics should be transparent about their experience, their site-specific pregnancy rates, and the associated perinatal outcomes.

Though oocyte cryopreservation was first introduced more than three decades ago, the past several years have yielded significant enhancement of techniques and documentation of efficacy. Current and future advancements have the potential to preserve reproductive potential for young women with cancer prior to gonadotoxic treatments as well as for those seeking elective preservation of their fertility. As stimulation techniques are simplified, costs are contained, safety and efficacy are documented, and more wide-spread awareness of the reproductive aging process is achieved, it is likely that the number of women who are able to benefit from this new technology will continue to increase.
