Birth after low-level +20 Aneuploid Mosaic Embryo Transfer: A Case Report.

OBJECTIVE: Recently, it has been discussed whether or not mosaic embryo transfers should be performed since they might result in viable pregnancies, although they often end up being discarded. We report a case of successful pregnancy, after a mosaic embryo transfer from an in vitro matured egg and frozen PESA sperm. CASE DESCRIPTION: Tests performed on a female aged 40 years and a male aged 37 years seeking fertility treatment found she had an adequate ovarian reserve and patent fallopian tubes. He had a history of cryptorchidism and inguinal hernia repair. The spermogram showed azoospermia, and testicular ultrasound showed an atrophic left testicle and a normal right testis. The vas deferens was palpated during physical examination. Intracytoplasmic sperm injection with percutaneous epididymal sperm aspiration (PESA) was indicated. Two cycles of IVF after controlled ovarian stimulation with follitropin delta was performed. In the first cycle, seven mature eggs were inseminated, two fertilized normally, resulting in one blastocyst biopsied and analyzed by NGS with complex aneuploid results. In the second cycle, frozen sperm from PESA was used. Three eggs were inseminated on the day of the procedure (resulting in 2 blastocysts), and three in vitro matured eggs were inseminated after 24 hours (resulting in 1 blastocyst). NGS analysis showed two complex aneuploid embryos and one 40% low-level trisomy 20 aneuploid mosaicism (+20) for the post 24-hour embryo. A mosaic embryo transfer was performed, resulting in clinical pregnancy and birth of a healthy baby girl with a normal blood karyotype. DISCUSSION: Mosaic embryo transfer is a topic for discussion. Certain levels of mosaicism do not seem to pose risks to the development of the fetus.

A sharing oocyte donation program: a 15-year cohort stud.

OBJECTIVE: To evaluate clinical and laboratory outcomes of oocyte donation cycles and compare the results from donors and recipients. METHODS: A retrospective cohort study was conducted at a reproductive medicine center. A 586 first fresh oocyte donation cycles, performed from 01/2002 to 12/2017 were included. The outcomes of 290 cycles from donors and 296 from recipients, resulting in 473 fresh embryo transfers, were analyzed. The oocyte division was equally made, whereas, at an odd amount, the donor always had a preference. The data were collected from an electronic database, and analyzed using Chi-square test, Fisher's exact test, Mann-Whitney U-test or Student t-test depending on the data distribution, and multivariate logistic regression, considering p<0.05. RESULTS: The main results comparing donor and recipient, were, respectively: fertilization rate (72.0±21.4 vs. 74.6±24.2, p<0.001), implantation rate (46.2% vs. 48.5%, p=0.67); clinical pregnancy rate (41.9% vs. 37.7%, p=0.39), live birth rates by transfer (33.3 vs. 37.7, p=0.54). CONCLUSIONS: Oocyte donation is often the way donors can access in vitro fertilization, and for recipients seems to be a good option for pregnancy. Demographic and clinical characteristics have a secondary role in oocyte donors under 35 years and patient without comorbidities under 50 years and were not associated with pregnancy outcomes, emphasizing the power of oocyte quality on the success of intracytoplasmic sperm injection treatment. An oocyte-sharing program that offers good and comparable results is fair and worth being encouraged.

The impact of body mass index on laboratory, clinical outcomes and treatment costs in assisted reproduction: a retrospective cohort study.

BACKGROUND: The aim of this study was to evaluate the influence of the body mass index (BMI) on laboratory, clinical outcomes and treatment costs of assisted reproduction, as there are still controversial and inconclusive studies on this subject. METHODS: This research was retrospective cohort study, including women undergoing assisted reproduction in a Reproductive Medicine Center between 2013 and 2020. The participants were divided into groups according to BMI (kg/m2): Group 1 < 25; Group 2, 25-29.9 and Group 3, ≥ 30. A total of 1753 in vitro fertilization (IVF) fresh embryo transfer (ET) cycles were included for assisted reproduction outcomes analysis and 1869 IVF-ET plus frozen embryo transfer (FET) for cumulative pregnancy analysis. RESULTS: As higher the BMI, higher was the proportion of canceled IVF cycles (G1 (6.9%) vs. G2 (7.8%) vs. G3 (10.4%), p = 0.002) and gonadotropin's total dose (IU) and treatment costs (G1 (1685 ± 595, U$ 683,02) vs. G2 (1779 ± 610, U$ 721,13) vs. G3 (1805 ± 563, U$ 764,09), p = 0.001). A greater number of mature oocytes was observed in G1 and G2 (6 [6.4-7.0] vs. 6 [5.6-6.6] vs. 4 [4.6-6.7], p = 0.011), which was not found in oocyte maturity rate (p = 0.877). A significant linear tendency (p = 0.042) was found in cumulative pregnancy rates, pointing to worse clinical outcomes in overweight and obese patients. CONCLUSION: These findings highlight the importance of considering the higher treatment costs for these patients, beyond all the well-known risks regarding weight excess, fertility, and pregnancy, before starting IVF treatments.

Influence of overweight and obesity on perinatal outcomes in assisted reproduction: a retrospective cohort study.

BACKGROUND: In spontaneous pregnancies, maternal weight and gestational diabetes are independent risk factors for macrosomia and large-for-gestational-age newborns. Furthermore, maternal body mass index (BMI) of ≥25 kg/m2 is associated with worse neonatal vitality, classified as an Apgar score of < 7 at the fifth minute of life. However, few studies have evaluated the influence of BMI on perinatal outcomes in pregnancies resulting from assisted reproduction. Therefore, this study aimed to analyze whether the perinatal outcomes of assisted reproduction are influenced by BMI. METHODS: This was a retrospective cohort study performed at a reproductive medicine center. Patients undergoing assisted reproduction (2013-2020) were divided into three groups according to their BMI (kg/m2): group 1, < 25; group 2, 25-29.9, and group 3, ≥30. In total, 1753 in vitro fertilization embryo transfer cycles were analyzed. Data were expressed as mean ± standard deviation or frequency (%). The analysis of variance and chi-square test were performed for comparison. To determine the participants and number of cycles for these analyses, generalized estimating equations were used, considering p < 0.05. RESULTS: In groups 1, 2, and 3, the rates of live birth were 33.5, 32.3, and 29.9% (p = 0.668); preeclampsia were 2.9, 6.1, and 6.3% (p = 0.268); small-for-gestational-age newborns were 23, 23.2, and 21.7% (p = 0.965); macrosomia were 1.9, 0.9, and 2.7% (p = 0.708); Apgar score > 7 at the fifth minute were 97.6, 98.2, and 100% (p = 0.616); and preterm birth were 29.6, 30.1, and 35.1% (p = 0.970), respectively. CONCLUSIONS: In conclusion, although the three groups had similar perinatal outcomes in this study, the study population was too small for conclusive results. The higher the BMI, the lower the chances of clinically relevant LBR and the higher the chances of premature labor and preeclampsia.

Tubal factor, cleavage stage and more than one embryo transferred were risk factors associated with ectopic pregnancy after assisted reproductive treatment.

OBJECTIVE: Ectopic pregnancy is a well-known complication following in vitro fertilization with embryo transfer; studies have questioned, however, whether there are risk factors that could be identified before the procedure. The objective of this study was to investigate the possible risk factors involved in ectopic pregnancy following in vitro fertilization. METHODS: Retrospective case-control study performed at an assisted reproduction clinic in Brazil. To select the control group, we used a 1:4 ratio. The study included 499 patients submitted to in vitro fertilization with clinical pregnancy. We collected the data from electronic records, between 2000-2019 and divided into: Group 1, ectopic pregnancy (n=90) and Group 2, intrauterine pregnancies (n=409). RESULTS: When comparing groups, the results observed were: Tubal factor infertility (35.6% vs. 21.1%, p=.005) (OR 2.0 [1.2-3.4], p=.004); Previous miscarriage history (15.1% vs. 7.1%, p<.05) (OR 2.0 [1.02-4.29], p=.044); Number of cleavage-stage embryo transfers (69.2% vs. 54.0 p=.028) (OR 1.9 [1.08-3.33], p=.025); Two or more embryos transferred (OR 2.5 [1.12-5.70], p=.025), all associated with greater ectopic pregnancy risk. Oocyte recipient patients were excluded from this analysis, but when included a difference was found when comparing the groups (9.4% (10/106) vs. 3.0% (13/434), p=.007), (OR 3.3 [1.41-7.98] p=.005); this result should be interpreted with caution because of the sample size. CONCLUSIONS: In high-risk patients, a single blastocyst transfer seems to be a reasonable approach to decrease the ectopic pregnancy risk.

Is there a better evolutionary outcome in a 4-cell tetrahedron embryo?

With the growing understanding of in vitro fertilization and reproductive technology, the magnitude of studies related to embryonic evolution has also increased. The optimization of embryo selection is crucial to minimize the risk of multiple pregnancies and to guarantee successful implantation and pregnancy. On the second day of culture, the four-cell embryo can be shaped into different arrangements, such as tetrahedral and planar. Previous studies have shown that mammalian embryos have a tetrahedral shape and that any deviation from this ideal configuration can negatively affect blastocyst development. A few studies have also found that planar embryos would be linked to negative predictors of success for reaching the blastocyst stage and its good quality. Therefore, it seems that tetrahedral should be preferred over planar-shaped embryos for embryonic transfers, but there is still little understanding and evidence about this subject. Thus, the objective of the present paper was to review the available literature on study tendencies to compare tetrahedral and planar-shaped embryos considering their effect on implantation and pregnancy results.

Iron chelator deferiprone rescues memory deficits, hippocampal BDNF levels and antioxidant defenses in an experimental model of memory impairment.

Brain-derived neurotrophic factor (BDNF) plays a key role in neural development and physiology, as well as in pathological states. Post-mortem studies demonstrate that BDNF is reduced in the brains of patients affected by neurodegenerative diseases. Iron accumulation has also been associated to the pathogenesis of neurodegenerative diseases. In rats, iron overload induces persistent memory deficits, increases oxidative stress and apoptotic markers, and decreases the expression of the synaptic marker, synaptophysin. Deferiprone (DFP) is an oral iron chelator used for the treatment of systemic iron overload disorders, and has recently been tested for Parkinson's disease. Here, we investigated the effects of iron overload on BDNF levels and on mRNA expression of genes encoding TrkB, p75NTR, catalase (CAT) and NQO1. We also aimed at investigating the effects of DFP on iron-induced impairments. Rats received iron or vehicle at postnatal days 12-14 and when adults, received chronic DFP or water (vehicle). Recognition memory was tested 19 days after the beginning of chelation therapy. BDNF measurements and expression analyses in the hippocampus were performed 24 h after the last day of DFP treatment. DFP restored memory and increased hippocampal BDNF levels, ameliorating iron-induced effects. Iron overload in the neonatal period reduced, while treatment with DFP was able to rescue, the expression of antioxidant enzymes CAT and NQO1.

Novel insights into mitochondrial molecular targets of iron-induced neurodegeneration: Reversal by cannabidiol.

Evidence has demonstrated iron accumulation in specific brain regions of patients suffering from neurodegenerative disorders, and this metal has been recognized as a contributing factor for neurodegeneration. Using an experimental model of brain iron accumulation, we have shown that iron induces severe memory deficits that are accompanied by oxidative stress, increased apoptotic markers, and decreased synaptophysin in the hippocampus of rats. The present study aims to characterize iron loading effects as well as to determine the molecular targets of cannabidiol (CBD), the main non-psychomimetic compound of Cannabis sativa, on mitochondria. Rats received iron in the neonatal period and CBD for 14 days in adulthood. Iron induced mitochondrial DNA (mtDNA) deletions, decreased epigenetic modulation of mtDNA, mitochondrial ferritin levels, and succinate dehydrogenase activity. CBD rescued mitochondrial ferritin and epigenetic modulation of mtDNA, and restored succinate dehydrogenase activity in iron-treated rats. These findings provide new insights into molecular targets of iron neurotoxicity and give support for the use of CBD as a disease modifying agent in the treatment of neurodegenerative diseases.

Por onde anda a histeria? / Where is the hysteria?

O termo histeria foi suprimido das classificações diagnósticas vigentes. Este artigo cita e descreve os diagnósticos que estão agora abrigados no guarda-chuva da histeria, além de discutir algumas implicações sobre essa mudança.

The term hysteria was suppressed from the current diagnostic classifications. This article cites and describes the diagnoses that are now housed under the umbrella of hysteria, in addition to discussing some implications on this change.