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Cryopreservation in assisted reproductive technology: new trends.

During the last few years, cryopreservation has become a relevant addition to therapeutic concepts in reproductive medicine. New data and publications have made it difficult to maintain an overview of all of the new developments and their results. The focus of interest more recently, especially with the cryopreservation of human oocytes and human ovarian tissue, has been vitrification as an interesting alternative to slow freezing methods. Even though studies investigating the slow freezing of human mature oocytes have resulted in very different survival rates, it could be an option for donor oocyte programs, in the case of threatened ovarian loss or when there is an objection to embryo freezing. An optimal freezing protocol and later use of thawed human ovarian tissue is still a point of discussion. There are encouraging results regarding different kinds of autotransplantation, and recently the first birth after orthotopic autotransplantation of cryopreserved/thawed human ovarian tissue was described in the literature. Independent of any objections to cryopreservation in general, vitrification is a potential and effective alternative to conventional slow cryopreservation, especially for oocytes and embryos. Vitrification might be also be an option for human ovarian tissue; however this is only in its infancy and requires much additional investigation. Our article discusses new trends and results of actual studies regarding these issues.

Cryopreservation↗

Does assisted reproduction technology, per se, increase the risk of preterm birth?

There is little doubt that all methods of assisted reproduction increase the likelihood of multiple pregnancy and, as a result, increase the likelihood of preterm birth. Data from the East Flanders Prospective Twin Study clearly show that the proportion of spontaneous to iatrogenic twins has changed from 25:1 to 1:1 over the past two decades. Data from the very low birthweight (VLBW) Infant Database of the Israel Neonatal Network showed that 10% of VLBW singletons were a result of assisted reproduction compared with 60% of the VLBW twins and 90% of the VLBW triplets. Irrespective of plurality, an association between preterm birth and assisted reproduction has long been suspected and was related to causes such as iatrogenic preterm birth (in the so-called 'premium' pregnancies), fertility history, past obstetric performance and to underlying medical conditions of the female partner. With more data available, a clearer picture is defined. Two different, recent meta-analyses showed that singleton pregnancies resulting from in vitro fertilisation (IVF) have increased rates of preterm birth at <33 weeks of gestation (OR 2.99; 95% CI 1.54-5.80), at <37 weeks of gestation (OR 1.93; 95% CI 1.36-2.74) and a relative risk of 1.98 (95% CI 1.77-2.22) for preterm birth in singleton pregnancies resulting from in vitro fertilisation embryo transfer/gamete intra fallopian transfer (IVF-ET/GIFT) compared with naturally conceived pregnancies. Since there is no way to predict which pregnant woman is at increased risk of preterm birth, it may be advisable to consider all pregnancies after assisted reproduction as being at risk. In any case, the most appropriate endpoint after assisted reproduction should also include preterm or term birth as measure of success.

Female↗

Use of GnRH antagonists in ovarian stimulation for assisted reproductive technologies compared to the long protocol. Meta-analysis.

The use of GnRH antagonists has revolutionized ovarian stimulation for assisted reproduction. Two GnRH antagonists are clinically available, namely, cetrorelix and ganirelix. Several studies have directly compared these new stimulation protocols against the long GnRH agonist protocol. To evaluate whether there is a reduction in cases of ovarian hyperstimulation syndrome (OHSS) and/or a reduction in pregnancy rates, a meta-analysis was performed. There was a significant reduction of OHSS cases in the cetrorelix studies (odds ratio, OR, 0.23; 95% confidence interval, CI, 0.10-0.54), but no reduction for ganirelix (OR 1.13; 95% CI 0.24-5.31). The incidence of OHSS degree III cases was reduced in the cetrorelix protocols as compared to the long protocol to a nearly significant degree (OR 0.26; 95% CI 0.07-1.01). Ganirelix did not reduce the incidence of OHSS degree III at all (OR 1.08; 95% CI 0.27-4.38). The pregnancy rate per cycle was significantly lower in the ganirelix protocols than in the long protocol (OR 0.76; 95% CI 0.59-0.98). The studies using cetrorelix showed quite similar, not significantly different results for the antagonist and the long protocol groups for the pregnancy rate per cycle (OR 0.91; 95% Cl 0.68-1.22). From the data one can conclude that cetrorelix but not ganirelix will reduce the incidence of cases of OHSS and that cetrorelix but not ganirelix will result in the same pregnancy rates as the long protocol. Several possibilities to explain this phenomenon are discussed.

Chorionic Gonadotropin↗

Cryopreserved oocytes of infertile couples undergoing assisted reproductive technology could be an important source of oocyte donation: a clinical report of successful pregnancies.

BACKGROUND: Surplus oocytes in assisted reproduction treatment cycles could be saved and donated to other couples. ICSI is usually performed for oocytes that have been stored frozen, considering possible exocytosis of cortical granules (CG). The unavoidability of ICSI merits further study. METHODS: We used a slow method to freeze excess oocytes from infertile couples. After thawing, oocytes were fertilized by either IVF or ICSI according to semen parameters. Some oocytes were examined for CG. RESULTS: Twenty-eight infertile couples cryopreserved a proportion of their oocytes and 12 thawed their oocytes. Three couples used their own oocytes, whereas nine donated their oocytes to nine other couples for 12 cycles. The survival rate from thawing was 90% (73/81). The fertilization rate using IVF (83%) was similar to ICSI (82%). Seven pregnancies (47% per cycle) were achieved; one used her own oocytes and six received donated oocytes. Five women delivered six babies including one set of twins. Two pregnancies aborted. The frozen-thawed oocytes (15/15) revealed no exocytosis of CG. CONCLUSIONS: To freeze oocytes of infertile couples undergoing assisted reproduction treatment may help other couples. Our successful experience may facilitate oocyte banks to become a reality. Both IVF and ICSI are valuable for frozen oocytes.

Adult↗