Oocyte cryopreservation review: outcomes of medical oocyte cryopreservation and planned oocyte cryopreservation.

BACKGROUND: The utilization of oocyte cryopreservation (OC) has become popularized with increasing numbers of reproductive-aged patients desiring to maintain fertility for future family building. OC was initially used for fertility preservation in postmenarchal patients prior to gonadotoxic therapies; however, it is now available to patients to circumvent age-related infertility and other diagnoses associated with early loss of ovarian reserve. The primary aim of this paper is to provide a narrative review of the most recent and robust data on the utilization and outcomes of OC in both patient populations. OC results in similar oocyte yield in patients facing gonadotoxic therapies and patients undergoing planned OC. Available data are insufficient to predict the live birth rates or the number of oocytes needed to result in live birth. However, oocyte yield and live birth rates are best among patients < 37.5 years old or with anti-mullerian hormone levels > 1.995 ng/dL, at the time of oocyte retrieval. There is a high 'no use' rate (58.9%) in patients using planned OC with 62.5% returning to use frozen oocytes with a spouse. The utilization rate in medical OC patients is < 10%. There is currently no data on the effects of BMI, smoking, or ethnicity on planned OC outcomes. CONCLUSION: It is too early to draw any final conclusions on outcomes of OC in medical OC and planned OC; however, preliminary data supports that utilization of OC in both groups result in preservation of fertility and subsequent live births in patients who return to use their cryopreserved eggs. Higher oocyte yield, with fewer ovarian stimulation cycles, and higher live birth rates are seen in patients who seek OC at younger ages, reinforcing the importance of age on fertility preservation. More studies are needed in medical OC and planned OC to help guide counseling and decision-making in patients seeking these services.

Informative predictors of pregnancy after first IVF cycle using eIVF practice highway electronic health records.

The aim of this study is to determine the most informative pre- and in-cycle variables for predicting success for a first autologous oocyte in-vitro fertilization (IVF) cycle. This is a retrospective study using 22,413 first autologous oocyte IVF cycles from 2001 to 2018. Models were developed to predict pregnancy following an IVF cycle with a fresh embryo transfer. The importance of each variable was determined by its coefficient in a logistic regression model and the prediction accuracy based on different variable sets was reported. The area under the receiver operating characteristic curve (AUC) on a validation patient cohort was the metric for prediction accuracy. Three factors were found to be of importance when predicting IVF success: age in three groups (38-40, 41-42, and above 42 years old), number of transferred embryos, and number of cryopreserved embryos. For predicting first-cycle IVF pregnancy using all available variables, the predictive model achieved an AUC of 68% + /- 0.01%. A parsimonious predictive model utilizing age (38-40, 41-42, and above 42 years old), number of transferred embryos, and number of cryopreserved embryos achieved an AUC of 65% + /- 0.01%. The proposed models accurately predict a single IVF cycle pregnancy outcome and identify important predictive variables associated with the outcome. These models are limited to predicting pregnancy immediately after the IVF cycle and not live birth. These models do not include indicators of multiple gestation and are not intended for clinical application.

Retrospective comparison of pregnancy outcomes of fresh and frozen-warmed single blastocyst transfer: a 5-year single-center experience.

PURPOSE: To assess whether live birth rates (LBR) and maternal/neonatal complications differed following single fresh and frozen-warmed blastocyst transfer. METHODS: The present retrospective observational study analyzed 4,613 single embryo transfers (SET) (646 fresh and 3,967 frozen) from January 1, 2014, to December 31, 2018. Fresh embryo transfer at blastocyst stage was considered according to the age of the patient and her prognosis. In case of the risk of ovarian hyperstimulation syndrome, premature progesterone rise, non-optimal endometrial growth, or supernumerary embryos, cryopreservation with subsequent frozen embryo transfer (FET) was indicated. RESULTS: No differences in LBR were recorded. Fresh embryo transfers yielded an increase both in neonatal complications OR 2.15 (95% CI 1.20-3.86, p 0.010), with a higher prevalence of singletons weighting below the 5th percentile (p 0.013) and of intrauterine growth retardation (p 0.015), as well as maternal complications, with a higher placenta previa occurrence OR 3.58 (95% CI 1.54-8.28, p 0.003), compared to FET. CONCLUSION: LBR appears not to be affected by the transfer procedure preferred. Fresh embryo transfer is associated with higher risk of neonatal complications (specifically a higher prevalence of singletons weighting below the 5th percentile and of intrauterine growth retardation) and placenta previa. Reflecting on the increased practice of ART procedures, it is imperative to understand whether a transfer procedure yields less complications than the other and if it is time to switch to a "freeze-all" procedure as standard practice. TRIAL REGISTRATION: Clinical Trial Registration Number: NCT04310761. Date of registration: March 17, 2020, retrospectively registered.

Racial disparities in frozen embryo transfer success.

PURPOSE: To compare pregnancy and birth outcomes after frozen embryo transfers (FETs) among White, Black, and Asian women and evaluate the effect of patient, protocol, and cycle characteristics on success. METHODS: A retrospective chart review identified women who underwent an autologous FET at an academic fertility center between January 2013 and March 2020. RESULTS: White, Black, and Asian women completed 1,181 (71.7%), 230 (14.0%), and 235 (14.3%) cycles, respectively. Black women were significantly less likely to achieve a positive hCG level (AOR 0.66, 95% CI 0.49-0.90), clinical pregnancy (AOR 0.71, 95% CI 0.53-0.97), and live birth (AOR 0.65, 95% CI 0.47-0.89) compared to White women after adjusting for possible confounders. There were no differences in the aforementioned outcomes when looking at cycles completed by Asian versus White women. When comparing outcomes by endometrial preparation protocol, significant differences were seen amongst the three groups for live birth rates following natural cycle FETs (52.36%, 25.81%, and 44.19% for White, Black, and Asian women, respectively, p = 0.02), a difference not appreciated after programmed FETs. CONCLUSION: Black race is associated with significantly worse pregnancy and live birth rates following FET when compared to White race. Additionally, significant differences in live birth rates among White, Black, and Asian women exist following natural cycle FET versus programmed FET. These disparities in success are not only important for patient counseling, but also when determining management strategies to improve fertility rates among minority women.

The Impact of Embryo Storage Time on Pregnancy and Perinatal Outcomes and the Time Limit of Vitrification: A Retrospective Cohort Study.

Background: The technique of embryo cryopreservation has been increasingly applied in clinical settings. However, there has been a concern about the safety and efficacy of long-term freezing of embryos. Therefore, the aim of this study was to evaluate whether storage time of vitrification had any effects on pregnancy as well as perinatal outcomes, further, to explore the appropriate time limit of vitrification. Methods: The study included women who underwent at least one frozen-thawed cycle with single embryo transfer between January 1st, 2016 and September 30th, 2019. Patients were assigned into 3 groups according to the storage time (<3 months, 3-12 months and >12 months) to evaluate the impact of embryo storage time on pregnancy and perinatal outcomes. To further investigate the time limit of vitrification, propensity score matching was used to compare the primary outcomes of patients with storage time of 1-3 years, 3-5 years, and >5 years to those stored for ≤1 year. Results: A total of 9806 frozen-thawed embryo transfer cycles were included in our study. After adjustment for confounding variables, no significant differences were found in pregnancy outcomes among groups. However, postponement of transfer increased the risks of large for gestational age and placenta previa. In addition, after propensity score matching, 171 cycles with storage time >5 years were matched with those ≤1 year, both the clinical pregnancy rate and live birth rate decreased significantly when the storage time exceeded 5 years. Conclusions: The duration of vitrification did not significantly affect the pregnancy outcomes within 5 years period. However, the clinical pregnancy rate and live birth rate both decreased significantly when the duration of vitrification exceeded 5 years. It is worth noting that the conclusion was drawn from a small sample study after propensity score matching and should be treated with caution. In addition, the cycles were from different time periods, which could have an impact on the results.

Prolonged Cryopreservation Negatively Affects Embryo Transfer Outcomes Following the Elective Freeze-All Strategy: A Multicenter Retrospective Study.

Background: With the development of embryo freezing and warming technology, frozen-thawed embryo transfer (FET) has been widely utilized. However, studies investigating the association between cryopreservation duration and FET outcomes are limited and controversial, and previous studies did not conduct stratification analyses based on demographic or clinical characteristics. Methods: This multicenter retrospective study included 17,826 women who underwent their first FET following the freeze-all strategy during the period from January 2014 to December 2018. Duration of cryopreservation was categorized into five groups: 3-8 weeks, 8-12 weeks, 12-26 weeks, 26-52 weeks, and >52 weeks. Modified Poisson regression and multivariate logistic regression were used to assess the association between cryostorage time of vitrified embryos and transfer outcomes. Moreover, further stratification analyses were performed according to variables with p <0.05 in multivariate models. Results: In this large multicenter study, we observed that storage duration was inversely associated with the possibility of pregnancy and live birth (p <0.001), but not with the risk of ectopic pregnancy and miscarriage. Stratification analyses based on maternal age, the number of oocytes retrieved, and condition of embryo transferred indicated that the inverse correlation was significant in the subpopulation with characteristics: (1) less than 40 years old, (2) more than 3 oocytes retrieved, and (3) only high-quality blastocysts transferred. Conclusion: The results of this large, multicenter, retrospective study suggested that prolonged cryopreservation was inversely associated with the probability of pregnancy and live birth. Therefore, for patients who adopt a freeze-all strategy, early FET might achieve a better outcome.

Clinical outcomes and utilization from over a decade of planned oocyte cryopreservation.

RESEARCH QUESTION: What is the clinical experience of patients who have undergone planned oocyte cryopreservation and oocyte thawing and warming? DESIGN: Retrospective observational cohort study. All women who completed planned oocyte cryopreservation at a single large university-affiliated fertility centre between June 2006 and October 2020 were identified, including the subset who returned to use their oocytes. Patients who underwent oocyte cryopreservation for medical reasons were excluded. Baseline demographics, oocyte cryopreservation and thawing-warming cycle parameters, and clinical outcomes, were extracted from the electronic medical record. The primary outcome was cumulative live birth rate (LBR), and secondary outcomes were cumulative clinical pregnancy rate (CPR), and CPR and LBR per transfer. Results were stratified by age at time of cryopreservation (<38 and ≥38 years). RESULTS: Of 921 patients who underwent planned oocyte cryopreservation, 68 (7.4%) returned to use their oocytes. Forty-six patients (67.6%) completed at least one embryo transfer. The CPR per transfer was 47.5% and LBR was 39.3%. The cumulative LBR per patient who initiated thawing-warming was 32.4%. Cycle outcomes were not significantly different in patients aged younger than 38 years and those aged 38 years or over. No patient aged 40 years or older (n = 6) was successful with their cryopreserved oocytes. Ten patients (14.7%) who were unsuccessful with their cryopreserved oocytes achieved a live birth using donor oocytes, with most (7/10) of these patients aged 38 years and older. CONCLUSION: Only a small percentage of patients returned to use their oocytes, and 32% of those were able to achieve a live birth.

Childhood growth of term singletons born after frozen compared with fresh embryo transfer.

RESEARCH QUESTION: Is the growth of term singletons born after frozen embryo transfer (FET) comparable to those born after fresh embryo transfer and natural conception up to 5 years of age? DESIGN: Observational cohort study in an academic medical centre and municipal child health clinics with repeated measurements carried out by medical professionals. Term singletons born after FET (n = 110) and fresh embryo transfer (n = 181) and their matched natural conception controls (n = 543) born in Oulu, Northern Finland, were included. Mean weights, lengths, heights and head circumferences at the ages of 4, 8 and 18 months and 3 and 5 years were compared. At 3 and 5 years, body mass indices were compared. RESULTS: Childhood growth did not differ between term singletons born after FET, fresh embryo transfer and natural conception, correcting for exact age at measurement and adjusting for maternal body mass index and paternal height. CONCLUSIONS: Similar growth between children born after FET, fresh embryo transfer and natural conception offers reassurance of the safety and feasibility of the steadily increasing use of embryo cryopreservation in assisted reproduction.

Effects of immediate versus delayed frozen embryo transfer in high responder patients undergoing freeze-all cycles.

BACKGROUND: Frozen embryo transfer (FET) can greatly improve the pregnancy outcomes for high responder patients. However, it is not known whether the timing of FET is a risk factor on pregnancy outcomes in high responder patients undergoing freeze-all cycles. METHODS: A retrospective cohort study to compare the pregnancy outcomes of the immediate and delayed FET groups in high responder patients undergoing freeze-all cycles. The two groups were defined as that FET took place either within the first menstrual cycle following oocyte retrieval or afterwards. Propensity score matching was used to make the potential risk factors of the two groups comparable. Multivariable regression analysis was used to study the effect of the timing of FET on pregnancy outcomes in the entire cohort and propensity score-matched cohort, even in different controlled ovarian hyperstimulation protocol cohorts as subgroup analysis. RESULTS: We obtained 1130 patients in immediate FET group and 998 patients in delayed FET group, and the average age of the two groups were 30.30 and 30.63. We showed that the immediate FET group were equivalent to delayed FET group in the entire cohort [clinical pregnancy rate (CPR), 61.0% versus 63.4%, adjusted odd ratio (OR), 0.939, 95% confidence interval (CI), 0.781-1.129; spontaneous abortion rate (SAR), 10.1% versus 12.6%, adjusted OR, 0.831, 95% Cl (0.628-1.098); live birth rate (LBR), 49.9% versus 49.2%, adjusted OR, 1.056, 95% Cl (0.883-1.263)]. The same results were obtained by χ2 test in the propensity score-matched cohort (CPR, 60.5% versus 63.5%; SAR, 11.6% versus 12.3%; LBR, 48% versus 49.3%) (P > 0.05). Subgroup analysis indicated that pregnancy outcomes of immediate FET were no difference to delayed FET in gonadotropin-releasing hormone agonist (GnRH-a) protocol (P > 0.05). The SAR of the immediate FET group were lower than that of the delayed FET group in GnRH antagonist protocol (adjusted OR, 0.645, 95% CI, 0.430-0.966) (P < 0.05), no differences were observed in CPR and LBR (P > 0.05). CONCLUSIONS: The pregnancy outcomes of immediate FET were no difference to delayed FET in high responder population undergoing freeze-all cycles.

Endometrial preparation for frozen-thawed embryo transfer cycles: a systematic review and network meta-analysis.

PURPOSE: To compare the effects of different endometrial preparation protocols for frozen-thawed embryo transfer (FET) cycles and present treatment hierarchy. METHODS: Systematic review with meta-analysis was performed by electronic searching of MEDLINE, the Cochrane Library, Embase, ClinicalTrials.gov and Google Scholar up to Dec 26, 2020. Randomised controlled trials (RCTs) or observational studies comparing 7 treatment options (natural cycle with or without human chorionic gonadotrophin trigger (mNC or tNC), artificial cycle with or without gonadotropin-releasing hormone agonist suppression (AC+GnRH or AC), aromatase inhibitor, clomiphene citrate, gonadotropin or follicle stimulating hormone) in FET cycles were included. Meta-analyses were performed within random effects models. Primary outcome was live birth presented as odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: Twenty-six RCTs and 113 cohort studies were included in the meta-analyses. In a network meta-analysis, AC ranked last in effectiveness, with lower live birth rates when compared with other endometrial preparation protocols. In pairwise meta-analyses of observational studies, AC was associated with significant lower live birth rates compared with tNC (OR 0.81, 0.70 to 0.93) and mNC (OR 0.85, 0.77 to 0.93). Women who achieved pregnancy after AC were at an increased risk of pregnancy-induced hypertension (OR 1.82, 1.37 to 2.38), postpartum haemorrhage (OR 2.08, 1.61 to 2.78) and very preterm birth (OR 2.08, 1.45 to 2.94) compared with those after tNC. CONCLUSION: Natural cycle treatment has a higher chance of live birth and lower risks of PIH, PPH and VPTB than AC for endometrial preparation in women receiving FET cycles.

The outcome of IVF/ICSI cycles in male cancer patients: retrospective analysis of procedures from 2004 to 2018.

INTRODUCTION: Fertility preservation is an important aspect of quality of life in oncological patients, and in men is achieved by semen cryopreservation prior to treatment. Results of in vitro fertilization (IVF) procedures in healthy infertile couples are comparable, regardless of whether fresh or cryopreserved semen is used, but are scarce in male oncological patients. PATIENTS AND METHODS: We performed a retrospective analysis of IVF/intracytoplasmic sperm injection (IVF/ICSI) procedures in infertile couples where men had been treated for cancer in the past. We additionally compared the results of IVF/ICSI procedures with respect to the type of semen used (fresh, cryopreserved). RESULTS: We compared the success rates of 214 IVF/ICSI cycles performed in the years 2004-2018. Pregnancy (30.0% vs. 21.4%; p = 0.12) and live-birth rates (22.3% vs. 17.9%; p = 0.43) per oocyte aspiration were similar between the groups in fresh cycles; however embryo utilization (48.9% vs. 40.0%; p = 0.006) and embryo cryopreservation rates (17.3% vs. 12.7%; p = 0.048) were significantly higher in the cryopreserved semen group. The cumulative pregnancy rate (60.6% vs. 37.7%; p = 0.012) was significantly higher, and the live-birth rate (45.1% vs. 34.0%; p = 0.21) non-significantly higher, in the cryopreserved semen group. CONCLUSIONS: The success of IVF/ICSI procedures in couples where the male partner was treated for cancer in the past are the same in terms of pregnancies and live-births in fresh cycles regardless of the type of semen used. However, embryo utilization and embryo cryopreservation rates are significantly higher when cryopreserved semen is used, leading to a significantly higher cumulative number of couples who achieved at least one pregnancy.

Risk of small for gestational age is reduced after frozen compared with fresh embryo transfer in endometriosis.

RESEARCH QUESTION: What are the perinatal outcomes and especially the risk of small for gestational age (SGA) babies born after frozen versus fresh embryo transfer in mothers affected by endometriosis undergoing treatment with assisted reproductive technology (ART)? DESIGN: A cohort study conducted between November 2012 and October 2017, in which infertile women with endometriosis undergoing ART and achieving singleton pregnancies that lasted beyond 12 weeks of gestation were included. Pregnancies obtained after a frozen embryo transfer (FET) were compared with those obtained after a fresh embryo transfer. A total of 339 pregnant women were included: 112 patients in the fresh embryo transfer group and 227 in the FET group. The main outcome was the rate of SGA. Secondary analyses were performed for adverse pregnancy outcomes and perinatal complications. RESULTS: Of the included women, 109/112 (97.3%) and 222/227 (97.8%) delivered a live child after at least 24 weeks of gestation in the fresh and in the frozen embryo transfer groups, respectively (P = 0.53). The risk of SGA decreased after a FET compared with a fresh embryo transfer (odds ratio [OR] 0.49 [0.25-0.98], P = 0.04) after multivariable analysis. The mean birthweight and the gestational age at delivery were not significantly different between the two study groups. Other pregnancy and perinatal complications were not statistically different between the two study populations. CONCLUSIONS: The present study of endometriosis-affected women found a significantly lower risk of SGA in patients undergoing frozen, mainly blastocyst, embryo transfer compared with patients undergoing fresh, mainly cleavage stage, embryo transfer.

Sperm cryopreservation during the SARS-CoV-2 pandemic.

PURPOSE: Sperm cryopreservation is fundamental in the management of patients undergoing gonadotoxic treatments. Concerns have risen in relation to SARS-CoV-2 and its potential for testicular involvement, since SARS-CoV-2-positive cryopreserved samples may have unknown effects on fertilization and embryo safety. This study therefore aimed to analyze the safety of sperm cryopreservation for cancer patients after the onset of the pandemic in Italy, through assessment of the risk of SARS-CoV-2 exposure and viral RNA testing of semen samples. METHODS: We recruited 10 cancer patients (mean age 30.5 ± 9.6 years) referred to our Sperm Bank during the Italian lockdown (from March 11th to May 4th 2020) who had not undergone a nasopharyngeal swab for SARS-CoV-2 testing. Patients were administered a questionnaire on their exposure to COVID-19, and semen samples were taken. Before cryopreservation, SARS-CoV-2 RNA was extracted from a 150 µl aliquot of seminal fluid in toto using QIAamp viral RNA kit (Qiagen) and amplified by a real time RT PCR system (RealStar SARS-CoV2 RT PCR, Altona Diagnostics) targeting the E and S genes. RESULTS: The questionnaire and medical interview revealed that all patients were asymptomatic and had had no previous contact with COVID-19 infected patients. All semen samples were negative for SARS-CoV-2 RNA. CONCLUSION: This preliminary assessment suggests that a thorough evaluation (especially in the setting of a multidisciplinary team) and molecular confirmation of the absence of SARS-CoV-2 in seminal fluid from asymptomatic cancer patients may assist in ensuring the safety of sperm cryopreservation.

Higher estradiol levels are associated with lower neonatal birthweight after fresh and frozen embryo transfers. A cohort study of 3631 singleton IVF pregnancies.

AIM: To assess the birthweight of neonates conceived after fresh and frozen embryo transfers (FET) and, if different, to investigate whether estradiol levels during the late follicular phase were associated with the observed difference. METHODS: Singleton pregnancies from fresh and FET transfers between January 1990 and December 2013 were compared retrospectively. A total of 2885 singleton pregnancies after fresh embryo transfer and 746 after FET were analyzed. Obstetric and neonatal outcomes were compared between fresh and FET cycles. RESULTS: The singletons born after FET were found to have a significantly higher birth weight (3313 g), compared to those born after fresh embryo transfer (3143 g); p < .001. The main predictor of this difference was found to be estradiol levels at the end of the follicular phase. The difference in birthweight was inversely correlated to estradiol levels considering all cycles together but also considering fresh and frozen cycles separately. CONCLUSIONS: Our study demonstrates a link between high estradiol levels and low birth weight of singletons after IVF both in fresh and frozen-thawed embryo transfer cycles. It provides additional support to the involvement of hyperestrogenemia in the process of implantation and on the subsequent fetal development.

Repeated cryopreservation process impairs embryo implantation potential but does not affect neonatal outcomes.

RESEARCH QUESTION: Does repeated cryopreservation process affect embryo implantation potential and neonatal outcomes of human embryos? DESIGN: This retrospective cohort study was conducted in the Reproductive Medicine Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. All assisted reproductive technology (ART) cycles were carried out between January 2014 and December 2018. Preferentially matched participants were divided into three groups according to the times of embryo cryopreservation: the fresh group (n = 249), the cryopreservation group (n = 244) and the re-cryopreservation group (n = 216). Embryo implantation rate, live birth rate, miscarriage rate and neonatal complication rate were compared among these three groups. RESULTS: The embryo implantation rate, clinical pregnancy rate and live birth rate in the re-cryopreservation group were significantly lower, and the miscarriage rate also slightly increased. Logistic regression analysis indicated that embryos with repeated cryopreservation and lower trophectoderm scores were at higher risk of embryo implantation failure in single embryo transfer cycles (OR 1.79 and 1.56, respectively). No significant differences were observed in gender, gestational age, birthweight, neonatal abnormality and neonatal complications among the groups. CONCLUSIONS: Our findings demonstrate the adverse effect of repeated cryopreservation on embryo implantation potential. The study offers embryologists and reproductive clinicians a warning of detrimental role of repeated cryopreservation. If unnecessary, it is strongly recommended to avoid repeated practice of vitrification and warming on embryos.

Long-term (35 years) cryopreservation of Echinococcus multilocularis metacestodes.

The metacestode of Echinococcus multilocularis is the etiological agent of alveolar echinococcosis. The metacestode stage used for research is maintained in rodents by serial passages. In order to determine whether cryopreservation of E. multilocularis metacestodes would be suitable for long-term maintenance and replace serial passages, isolates of different geographic origin were cryopreserved in 1984-1986. The aim of the current study was to test the viability of cryopreserved isolates following long-term cryopreservation (up to 35 years) and to determine the phylogenetic clades these isolates belonged to. Cryopreserved isolates were tested for viability in vitro and in vivo in gerbils. In vitro results of 5 isolates indicated protoscolex survival in 13 of 17 experiments (76%) and metacestode survival in 5 of 12 (42%) in vivo experiments. In vivo results showed 'abortive lesions' in 13 of the 36 animals, 15 were negative and 8 harboured proliferating metacestode tissue containing protoscoleces. Genetic analysis confirmed the isolates belonged to European, Asian and North-American clades. In conclusion, the results of the current study indicate that metacestodes of E. multilocularis are able to survive long-term cryopreservation. Therefore, cryopreservation is a suitable method for long-term storage of E. multilocularis metacestode isolates and reduces the number of experimental animals.

[Access to fertility preservation for adolescents and young adults aged 15 to 24 years with cancers in Auvergne, France]. / Accès à la préservation de la fertilité des adolescents et jeunes adultes de 15 à 24 ans atteints de cancers en Auvergne, France.

INTRODUCTION: Cancers of adolescents and young adults have particular epidemiological specificities. The improvement in their survival should be accompanied by an increased consideration of the treatments' side effects, among which the potential decrease in fertility. The objective of the study was to describe the access to fertility preservation of these patients at the University Hospital of Clermont-Ferrand over a period of 3 years. METHODS: During this retrospective descriptive study, various socio-demographic and clinical data were collected. RESULTS: One hundred and fifty new cases of cancers were diagnosed in patients aged 15 to 24 years. Forty-four percent received at least one fertility consultation, 29 % for girls and 58 % for boys (P<0.001). The number of cases that did not result in fertility preservation was significantly higher for girls than boys (P=0.005). Fertility preservation was mainly achieved by cryopreservation of ovarian tissue in female adolescents, ovocytes in young women and sperm in boys. DISCUSSION: We observed sex disparities in access to fertility preservation. Despite the existence of recommendations, progress remains to be made. The establishment of clinico-biological platforms should allow a better awareness of patients and professionals, and thus promote access to fertility preservation techniques for young patients with cancer.

Hematopoietic cell infusion-related adverse events in pediatric/small recipients in a prospective/multicenter study.

BACKGROUND: Hematopoietic cell infusion-related adverse events (HCI-AEs) in hematopoietic stem cell transplantations (HSCTs) have been largely attributed to toxicity of dimethyl sulfoxide (DMSO) for cryopreservation, but HSC products also contain various cells and plasma components. Our recent prospective study of 1125 HSCT recipients revealed the highest overall HCI-AE rate in bone marrow transplantation (BMT) using fresh/noncryopreserved products, although products of peripheral blood stem cell transplantation and cord blood transplantation (CBT) are generally cryopreserved with DMSO containing smaller plasma volumes. We aimed to clarify if product volume and component effects are more substantial in small recipients including children. STUDY DESIGN AND METHODS: We performed subgroup analysis on 219 recipients of 45 kg or less body weight (whole small recipients), including 90 children (pediatric recipients), from the original cohort (general recipients). RESULTS: Whereas overall HCI-AE rates did not differ among hematopoietic stem cell sources in the general recipients, bradycardia most often occurred after CBT in whole small recipients. Conversely, whole small and general recipients shared the same trend of having the highest rate of hypertension in BMT. The overall HCI-AE rate was higher in allogeneic HSCT compared with autologous HSCT. Notably, pediatric recipients showed a 10-fold higher incidence of nausea and vomiting in allogeneic HSCT compared with autologous HSCT, suggesting a possible role of allogeneic antigens. Multivariate analysis identified a relatively large infusion volume per body weight as a significant factor correlating with HCI-AE in whole small recipients. CONCLUSIONS: We should be aware of product volume and specific HCI-AEs such as nausea and vomiting in small patients including children.

Is Embryo Cryopreservation Causing Macrosomia-and What Else?

The number of embryos transferred during an IVF cycle is directly related to the high incidence of multiple births, which is the culprit of perinatal morbidity. Therefore, single fresh embryo transfer (ET) strategy, or freeze-all, followed by a single frozen-thawed embryo transfer (FET) cycle, may dramatically reduce the rate of multiple births, without compromising the cumulative live birth rates (LBRs). A literature review was conducted for all available evidences assessing obstetrics and perinatal outcomes associated with FET compared to fresh ET and natural conception. While studies comparing fresh and FET cycles in normal responders have yielded conflicting results for pregnancy rate, FET was associated with lower risk of prematurity and low birth weight and increased risk of large for gestational age (LGA) and/or macrosomic in singletons, when compared with fresh ET. Macrosomic/LGA births have a higher risk of fetal hypoxia, stillbirth, shoulder dystocia, perineal lacerations, cesarean section, postpartum hemorrhage and neonatal metabolic disturbances at birth. Nonetheless, it seems that other than higher risk of fetal macrosomia, there are additional obstetric complications associated with FET. The relative risk of hypertensive disorders in pregnancy, as well as perinatal mortality were also demonstrated to be increased in FET compared with singletons from fresh ET and natural conception. Therefore, when considering elective freeze-all policy, in addition to LBR and the risk of ovarian hyperstimulation syndrome, physicians should consider the aforementioned increased FET cycles' pregnancy complications, including LGA/ macrosomia, hypertensive disorders of pregnancy, as well as perinatal mortality.