This study compared fetal response to musical stimuli applied intravaginally (intravaginal music [IVM]) with application via emitters placed on the mother’s abdomen (abdominal music [ABM]). Responses were quantified by recording facial movements identified on 3D/4D ultrasound. One hundred and six normal pregnancies between 14 and 39 weeks of gestation were randomized to 3D/4D ultrasound with: (a) ABM with standard headphones (flute monody at 98.6 dB); (b) IVM with a specially designed device emitting the same monody at 53.7 dB; or (c) intravaginal vibration (IVV; 125 Hz) at 68 dB with the same device. Facial movements were quantified at baseline, during stimulation, and for 5 minutes after stimulation was discontinued. In fetuses at a gestational age of >16 weeks, IVM-elicited mouthing (MT) and tongue expulsion (TE) in 86.7% and 46.6% of fetuses, respectively, with significant differences when compared with ABM and IVV (p = 0.002 and p = 0.004, respectively). There were no changes from baseline in ABM and IVV. TE occurred ≥5 times in 5 minutes in 13.3% with IVM. IVM was related with higher occurrence of MT (odds ratio = 10.980; 95% confidence interval = 3.105–47.546) and TE (odds ratio = 10.943; 95% confidence interval = 2.568–77.037). The frequency of TE with IVM increased significantly with gestational age (p = 0.024). Fetuses at 16–39 weeks of gestation respond to intravaginally emitted music with repetitive MT and TE movements not observed with ABM or IVV. Our findings suggest that neural pathways participating in the auditory–motor system are developed as early as gestational week 16. These findings might contribute to diagnostic methods for prenatal hearing screening, and research into fetal neurological stimulation.

Several concerns exist regarding the impact of anticancer treatments on fertility and pregnancy outcome. The detrimental effects of both chemotherapy and radiotherapy on the ovaries are well reported in the available literature. Fewer data are focused on the importance of a functioning uterus to conceive and carry on a healthy pregnancy. The aim of this paper is to provide a narrative review of the current literature to assess the role of uterine irradiation as a potential determinant of infertility and poor obstetrical outcomes. This review addresses the need for multidisciplinary counselling in order to face the poor reproductive and obstetrical outcomes of women who had uterine radiation, according to the different backgrounds (radiotherapy during adulthood versus childhood; total body irradiation versus pituitary, spinal and/or abdominal-pelvic irradiation).

There has been progress in the identification of factors that confer important risk for the development of breast cancer. The factors include: heritable mutations in susceptibility genes; exposure to therapeutic radiation during breast development (as for Hodgkin's disease survivors who received therapeutic radiation to the chest); and histologic lesions, including LCIS and atypical hyperplasias. Testing for mutations in the BRCA1 and BRCA2 breast ovarian cancer susceptibility genes has become part of the established care of breast cancer patients. Genetic information from BRCA1/2 testing is used to help healthy at-risk women to avoid breast and/or ovarian cancer, and ultimately to avoid death from those cancers. Data accumulated over the past decade have provided evidence that breast cancer surveillance can be improved with the addition of breast MRI, that prophylactic oophorectomy substantially reduces the risk of ovarian cancer and, when performed before menopause, can reduce the risk of breast cancer as well, and that prophylactic mastectomy reduces the risk of breast cancer by more than 90%. It has been observed that approximately 80% of BRCA1-associated breast cancers are negative for ER, PR and HER2 (so-called triple negative) and cluster with basal-like breast cancers by DNA microarray, while 80% of BRCA2-associated breast cancers are ER + and PR + , but HER2 negative, and luminal. These data are surprising given the close relationships between these genes in their DNA repair activities, and raise some concern that hormonal interventions will not successfully reduce the risk of BRCA1-associated breast cancers. Other strategies may be necessary to reduce breast cancer risk for this group. Genetic information has been shown to have important implications for women with breast cancer as well. Women with strong family histories of breast and/or ovarian cancer, and women diagnosed before age 40 may consider testing at the time of breast cancer diagnosis if they would use the information to make treatment decisions. Some women choose bilateral mastectomies over breast-conserving treatment if they learn that their risk of second primary breast cancer exceeds 50%, and if their prognosis from the original breast cancer is good. Some women opt for oophorectomy as part of the management of their ER + breast cancer if they are premenopausal mutation carriers (and could participate in TEXT).Recently, novel agents, the PARP inhibitors, have been shown to be effective in the phase II trials in women with BRCA1 or BRCA2 mutations and metastatic ovarian or breast cancer. These drugs target DNA repair pathways that are particularly vulnerable in women with BRCA1/2 mutations. The agents may also be effective in women with sporadic breast cancer, and are currently in trials in Europe and the United States alone and in combination with cytotoxic agents. S2 Magnetic resonance imaging for diagnosis, staging, and follow-up M Morrow Memorial Sloan-Kettering Cancer Center, New York, NY, USA Breast Cancer Research 2009, 11(Suppl 1...

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Study question Could the exclusion of multinucleated cells from an embryo be a mechanism to dispose of cells with aberrant genetic content? Summary answer Exclusion of multinucleated cells could be a self-correction mechanism that would allow some embryos to exclude aneuploid cells. What is known already Multinucleation represents a poor prognosis morphologic trait related to low blastocyst formation rates and implantation rates. Moreover, it has been correlated with an increased rate of aneuploidies and chromosomal abnormalities, thus increasing misscarriage rates. Traditional morphokinetics ensure that excluding blastomeres during the compaction, the embryo could reduce its potential to achieve an euploid blastocyst. According to our previous studies multinucleated embryos excluding multinucleated cells during the blastocyst formation increase their reproductive potential. These studies assessed the clinical outcomes based on the morphokinetics of multinucleated blastomeres, without taking into account the chromosomal status of these embryos. Study design, size, duration Retrospective cohort study involving data from 157 PGT-cycles, performed between 2017 and 2019, with at least one multinucleated embryo. This trial included 678 embryos cultured until blastocyst stage using one-step culture media in time-lapse incubators (Embryoscope, Vitrolife) up to D + 5/6 when PGT-A was performed by trophectoderm biopsy using the NGS analysis technique in good quality embryos (≥3BB) according to the Gardner Score. Chi-square test for a contingency table was performed to compare all groups. Participants/materials, setting, methods Two main groups were considered: Control Group (CG; n = 474), embryos without multinucleation and Multinucleation Group (MNC; n = 204), embryos with at least one blastomere multinucleated on D + 2/3. Multinucleation Group was subdivided in three groups according to the multinucleation cell location using time-lapse technology to track them. MNC-1 (N = 87), no cells excluded; MNC-2 (N = 31), mononucleated cells excluded; MNC-3 (N = 41), multinucleated cells excluded. We had to exclude from the study 45 embryos that could not be follow up. Main results and the role of chance We observed multinucleation in the 20.33% of the embryos. MNC-3 (43.9%) achieved the higher euploidy rate, equivalent to the CG (43.9%); p = 0.998. MNC-1 (26.4%) and MNC-2 (22.6%) had lower euploidy rates than Groups MNC-3 and GC; p < 0.05. Regarding to the aneuploidy rates, MNC-2 (77.4%) showed a higher rate than of the other groups (MNC-1=52.9%; MNC-3=41.5%; CG = 42.0%), being significant compared to the CG and MNC-3; p < 0.05. The mosaicism rate of the MNC-1 (20.7%) is significantly higher than that of the CG (14.0%); p < 0.05. Limitations, reasons for caution Limitations include the retrospective analysis of data, the wide difference on sample size between MNC and CG groups and the amount of embryos excluded due to the impossibility to be monitored. Wider implications of the findings These results prove that embryos excluding multinucleated cells reach equivalent euploidy values than embryos without multinucleation. This outcome, together with previous studies, suggest a self-correction capacity that would allow some embryos to detect and expel cells with aneuploid genetic content, thus improving the global chromosomal status of the embryo. Trial registration number not applicable

Study question Does Assisted hatching (AH) improve success rates when applied to frozen embryo transfers? Summary answer AH does not improve implantation, ongoing pregnancy or live birth rates when applied to thawed embryos. What is known already Vitrification has been proven to be the most efficient technique to preserve human embryos. However, vitrification has some consequences for the embryos, zona pellucida (ZP) hardening being one of them. Multiple studies suggest the need to apply laser Assisted hatching or ZP thinning to thawed embryos in order to improve success rates. Still, there is not enough evidence to ensure the utility of AH, and considering the great variation in design between studies more evidence is needed. Study design, size, duration Study performed from October 2019 and January 2020. Disregarding embryos with natural Hatching and PGT-A. Embryos that, immediately after thawing, were completely expanded (trophectoderm in contact with ZP) were also excluded from the study. We applied a randomization to choose in which embryos we had to perform AH. Neither the gynecologist nor the embryologist performing the embryo transfer knew whether the embryo had AH performed or not. Participants/materials, setting, methods 353 frozen embryo transfers of one blastocist were considered for the study, 71 excluded for expansion after thawing, 65 excluded because of PGT-A, 103 in which we performed AH (AH+) and 114 without AH (AH-). In the AH+ group we performed laser-AH of 1/3 of the ZP, avoiding to damage the trophectoderm and performing the laser shots as far away to the ICM as possible. We used Chi-square testing to assess the effects of AH. Main results and the role of chance We assessed all relevant clinical data parameters. No statistical differences were found in egg age, maternal age, embryo quality, nor endometrial thickness between groups. Implantation and miscarriage rates were equivalent between AH+ group (40.9%; 20.5%) and AH- group (47.4%; 18.5%). The main outcome of this study was live birth rates. No statistical differences were found between groups (AH-= 38.6%; AH + = 30.1%; p = 03221) proving that making it easier to get out of the ZP does not affect success rates. Analyzing the data from the excluded embryos we found no improvement on live birth rates when embryos were expanded just after thawing (38.0%; p = 0.457). As expected, PGT-A embryos yielded higher live birth rates (52.3%; p < 0,05) Limitations, reasons for caution Preliminary study with a small data set. Wider implications of the findings: This study suggest that thawed embryos have the capacity to get out of the ZP regardless if AH was performed or not. Having no positive effects, AH seems to be unnecessary in this scenario. Trial registration number Not applicable

Study question Can all patients decide on the destination of their frozen embryos? Summary answer Patients that don’t have the legal right to donate their surplus embryos, still have the opportunity to ship them to centres in Spain What is known already In most European countries the laws do not allow patients to decide on the destination of their surplus vitrified embryos. In Spain, however, all possible options are allowed but certain requirements must be met for each of them: donation, research and destruction. Even though, most couples do not decide on any of them and do not reply to the documents they receive from the Centre. The reasons for this behaviour are not due to an irresponsible attitude but to the fact that it presents them with a difficult situation, which triggers emotional conflicts. Study design, size, duration The goal of this study is to communicate that since 2018 we have received embryo shipment requests from people who have stored their surplus embryos in other countries, where they cannot donate them. We have evaluated 47 cases and accepted 17 from Italy, Belgium, Ireland and Greece. We evaluated the survival rate after thawing and pregnancy rates, and compared them with the results of surplus embryos that have been donated in our Centre. Participants/materials, setting, methods We received applications from patients from different countries. Given the legal difficulties, we only evaluated those from European Community countries. In order to accept the transfer, we require that they meet all the requirements to be “donation eligible”: clinical history and phenotypic features of parents and siblings born from that cycle, serology results prior to treatment, age under 35 years, good embryo morphology score, and all the information from the embryology laboratory of the Centre. Main results and the role of chance According to our Centre's data, only 3% of patients choose to donate their surplus vitrified embryos to others. In a retrospective review of the informed consents of a total of 5,605 IVF cases in which the patients had frozen supernumerary embryos we found that there are no significant differences in this percentage according to the biological origin of the embryos, neither if a couple or a single woman carried out the treatment. Differences are observed between patients from European countries that are close to each other and which are evidence of the idiosyncrasies of each culture. Donation is chosen by 3% of patients from Spain and the UK, 4% from France, 5.5% from Italy, 6% from Germany, 7% from Ireland. We surveyed patients about their reasons for choosing the destination of their embryos: the main reason why they rejected the possibility of donating embryos was the fear that in the future, their children might meet their biological siblings. In these 17 cases that have been shipped from other countries, blastocyst survival rate after thawing was 90% (compared to 97% in donated embryos in our Centre) and pregancy rate was 56% (compared to 59% in our Centre). Limitations, reasons for caution We don’t know the percentage of patients that would agree to donate their cross-border embryos, and most of them are not even aware of this possibility. They concur in a high socio-economic-cultural level that allows them to be informed and if they are accepted, they must pay the shipment fees. Wider implications of the findings We wonder whether all european patients that are interested in donating their embryos and that won’t resign to abandon them should be informed of this possibility. So far, we have had exquisite cooperation from the centres where they remain vitrified. May globalisation allow them to exercise their generosity! Trial registration number Not applicable