P–717 Where do cryopreserved embryos end up after a positive pregnancy test?

Study question What is the destination of supernumerary embryos after a positive pregnancy test? Summary answer Half of the surplus cryopreserved embryos in assisted reproduction treatments are not transferred. What is known already Many of the surpernumerary cryopreserved embryos in assisted reproductive technologies are not transferred. This is a constant issue in many fertility centers around the world. Our objective was to report what happens with vitried surplus embryos after IVF in patients with a positive pregnancy test, carrying out an analysis according to age and final evolution of the pregnancy. Study design, size, duration This is a retrospective descriptive study. We analyzed 245 embryo transfer cycles, performed between January 2013 to December 2017, in 235 patients with a positive pregnancy test and who vitrified surplus embryos. Participants/materials, setting, methods All the patients underwent treatment with their own oocytes. The variables studied were: age, miscarriage rate (MR) and live birth rate (LBR). We compared the destination of the cryopreserved embryos according to the patient’s age and pregnancy evolution. Statistical analysis was performed with Fisher’s exact test. Main results and the role of chance 20% of the IVF cycles (n = 49) were performed in women older than 40 years, 42% between 35 and 39 (n = 103) and 38% in women younger than 35 (n = 94). Average age was 35.8 ± 4.1 years. 859 embryos were cryopreserved (3.5 ± 1.9 cryopreserved embryos/patient). Average search time for surplus embryos was 20.5 ± 17.9 months, rising to 36.9 ± 14.9 months after delivery and decreasing to 8.7 ± 7.8 months after miscarriage (P < 0.0001). Up to date there are 118 (48.2%) patients whose cryopreserved embryos have not been transferred yet. Signficant differences were found in the three groups in using the cryopreserved embryos according to whether or not they had delivery. Almost half of the surplus cryopreserved embryos are not transferred. Regardless of the age of the patient, all groups showed the same behavior regarding the utilization of the cryopreserved embryos after delivery. It is essential to advise couples who perform assisted reproductive technologies, with a good probability of success (regardless of the patient’s age), about the responsibility that embryonic cryopreservation entails. Argentine legislation has limitations regarding the availability of cryopreserved surplus embryos. Limitations, reasons for caution This is a retrospective study. Wider implications of the findings: We believe that Public Health policies related to this issue should be re evaluated based on these results. Trial registration number Not applicable

P–157 The pregnancy potential of embryos cryopreserved and thawed twice: A case-control study

Study question What are the pregnancy and perinatal outcomes of twice-cryopreserved embryos compared to once-cryopreserved embryos? Summary answer Transfers of twice-cryopreserved embryos result in similar live birth rates (LBR) and perinatal outcomes compared to transfers of once-cryopreserved embryos. What is known already Repeated cryopreservation of viable surplus embryos in frozen embryo transfer (FET) cycles is a potential method to increase the cumulative pregnancy rate and reduce the risks related to multiple pregnancies. Currently, evidence on the safety and success of repeated cryopreservation is limited. Existing data from a few studies indicate that the vitrification of previously slow-frozen or vitrified embryos does not negatively impact pregnancy outcome, and no long-term health consequences in neonates have been reported. However, due to the limited number of reported pregnancies and children, more studies are needed. Study design, size, duration This retrospective register-based case-control study included FETs (n = 2834) performed at the University Hospital of Turku and the Central Hospital of Central Finland, Finland, between January 2012 and December 2019. The case group consisted of twice-cryopreserved FETs (n = 89), and the control group consisted of once-cryopreserved FETs (n = 304). The matching criteria were embryonic age at transfer and female age category of less or over 35 years. Participants/materials, setting, methods All the FETs in the case group and 86% in the control group were single-embryo transfers (p = <0.001). The first cryopreservation was performed by slow freezing or vitrification (cases 58% vs 42% and controls 40% vs 60%, p = 0.002, respectively). The re-cryopreservation method was vitrification. Mixed effects logistic regression was used to analyse the pregnancy outcomes, and a linear mixed model was used to analyse neonatal weight, adjusting for gestational age, neonatal sex, parity and BMI. Main results and the role of chance The survival rate of the twice-cryopreserved embryos was 92.2% (94/102), and 93.7% (89/95) of the planned FETs could be carried out. FET was performed with D3–4 embryos in 17 cases and 68 controls and with D5–6 embryos in 72 cases and 238 controls. The rates of live birth, clinical pregnancy and miscarriage in the case and the control groups were comparable (27.0% vs 31.9%, p = 0.35; 31.4% vs 36.8%, p = 0.35 and 4.5% vs. 3.9%, p = 0.77, respectively). No difference was seen in the preterm delivery rate (cases 4.2% vs controls 10.3%, p = 0.69). Twenty-five children were born in the case group and 100 in the control group. No differences in birth weights were detected between the groups (3730 g, upper and lower quartiles 3500 g and 4050 g, vs 3490g, upper and lower quartiles 3150 g and 3900 g, p = 0.28), and, in the case group, all the newborns’ birth weights were appropriate for gestational age. There were no congenital malformations among the newborns in the case group. In the control group, there was one pregnancy termination due to aneuploidy, one case of undescended testicles, one child with a hypoplastic aortic valve without stenosis and one child with craniosynostosis. Limitations, reasons for caution This study was retrospective, and the small sample size limits interpretation of the results. FET has been demonstrated to increase the risk for fetal macrosomia and gestational hypertension/pre-eclampsia. Whether repeated cryopreservation enhances these effects or influences neonatal health in the long term needs further investigation. Wider implications of the findings: Acceptable LBR and neonatal outcomes may be expected after transfer of twice-cryopreserved embryos. Also, the survival rate is high. To avoid embryo wastage or transfer of multiple embryos, good quality surplus embryos from FET cycles may be considered for repeated cryopreservation by vitrification. Trial registration number Not applicable

The Effect of Post warming Culture Period Between Thawing and Transfer of Cryopreserved Embryos on Reproductive Outcomes After In Vitro Fertilization (IVF): A Systematic Review and Meta-analysis

Background: The purpose of this study was to evaluate the effect of post warming culture period between thawing and transfer of cryopreserved embryos on reproductive outcomes after in vitro fertilization (IVF). Methods: An extensive literature search was performed using PubMed, EmBase, and the Cochrane library from January 2000 to August 2019. A systematic review and meta–analysis of clinical trials was performed in this manuscript. The trials represented patients with embryo transfers of at least one previously cryopreserved good quality embryo. Main outcome measures of the study included clinical pregnancy rate, live birth rate, miscarriage rate, and ectopic pregnancy rate. Results: A total of 5338 trial/abstracts were identified through a literature search. Totally, five studies were included in the systematic review, and three in the final meta–analysis. The studies included 1717 embryo transfers, 605 after short culture, and 1112 after long culture. The clinical pregnancy rate (CPR) was the most consistent outcome reported. The CPR was slightly better after short time culture with a RR of 1.09 (0.95–1.26, 95%CI) but this difference was not statistically significant. The great heterogenicity in the results reported in the included studies made it impossible to compare all planned outcomes. Conclusion: There are no differences in reproductive outcomes if cryopreserved embryos are transferred after overnight culture or after two hours of culture following thawing. Due to small number and the poor quality of trials reported on this topic, the results of this review should be treated with caution.

Storage Time of Cryopreserved Embryos and Pregnancy Outcomes: A Dose-Response Meta-Analysis

Purpose Cryopreservation techniques have become an essential part of assisted reproduction technology. Embryos may be cryopreserved for several years before transfer, and the safety of long-term cryopreservation needs to be considered. This dose-response meta-analysis was conducted to evaluate whether there were dose-response relationships between the storage time of cryopreserved embryos and pregnancy outcomes such as survival rate, implantation rate, miscarriage rate, clinical pregnancy rate, and congenital malformation rate. Methods After searching the databases PubMed, Embase, MEDLINE, CCRT and related reviews up until June 4, 2020, seven studies were included for analysis. Two reviewers extracted the relevant information and independently assessed the study quality using the Newcastle-Ottawa scale. Potential linear or non-linear dose-response relationships were assessed with a random-effect dose-response meta-analysis. Results No dose-response association was found between duration of embryo cryostorage and survival rate, implantation rate, miscarriage rate, clinical pregnancy rate or congenital malformation rate. Conclusion The interval between the start of embryo cryopreservation and frozen/thawed embryo transfer does not influence pregnancy outcomes.

Psychotherapy of a Relationship Break-Up in the Context of Assisted Reproductive Technologies

The paper is focused on ethical issues of making decisions about cryopreserved embryos in the context of relationship break-up in the framework of the embryo’s legal status and the church’s stand on the matter. All these issues can be viewed as part of a broader problem of intuitive and rational foundations for decision-making when facing difficult situations in life. On the one hand, the stressful context of the situation implies intuitive-driven decision-making; on the other hand, assisted reproductive technologies are largely counter-intuitive. We describe the peculiarities of family psychotherapy with mixed-agenda couples going through a divorce who have joint cryopreserved embryos but disagree on what to do with them. We introduce a protocol for psychotherapeutic work in the situation when one partner wishes to continue with the fertility treatment and have a child while the other partner is determined to utilize joint embryos as unwanted biological material. In addition, we discuss emotional and social complications that may arise (guilt, unfaithfulness of one of the partners, other losses, and grieving).