Assisted Reproduction: What factors interfere in the professional's decisions? Are single women an issue?

<p>Abstract</p> <p>Background</p> <p>With the development of medical technology, many countries around the world have been implementing ethical guidelines and laws regarding Medically Assisted Reproduction (MAR). A physician's reproductive decisions are not solely based on technical criteria but are also influenced by society values. Therefore, the aim of this study was to analyze the factors prioritized by MAR professionals when deciding on whether to accept to perform assisted reproduction and to show any existing cultural differences.</p> <p>Methods</p> <p>Cross-sectional study involving 224 healthcare professionals working with assisted reproduction in Brazil, Italy, Germany and Greece. Instrument used for data collection: a questionnaire, followed by the description of four special MAR cases (a single woman, a lesbian couple, an HIV discordant couple and gender selection) which included case-specific questions regarding the professionals' decision on whether to perform the requested procedure as well as the following factors: socio-demographic variables, moral and legal values as well as the technical aspects which influence decision-making.</p> <p>Results</p> <p>Only the case involving a single woman who wishes to have a child (without the intention of having a partner in the future) demonstrated significant differences. Therefore, the study was driven towards the results of this case specifically. The analyses we performed demonstrated that professionals holding a Master's Degree, those younger in age, female professionals, those having worked for less time in reproduction, those in private clinics and Brazilian health professionals all had a greater tendency to perform the procedure in that case. A multivariate analysis demonstrated that the reasons for the professional's decision to perform the procedure were the woman's right to gestate and the duty of MAR professionals to help her. The professionals who decided not to perform the procedure identified the woman's marital status and the child's right to a father as the reason to withhold treatment.</p> <p>Conclusion</p> <p>The study indicates differences among countries in the evaluation of the single woman case. It also discloses the undervaluation of bioethics committees and the need for a greater participation of healthcare professionals in debates on assisted reproduction laws.</p

Impact of GnRH analogues on oocyte/embryo quality and embryo development in in vitro fertilization/intracytoplasmic sperm injection cycles: a case control study

<p>Abstract</p> <p>Background</p> <p>Despite the clinical outcomes of ovarian stimulation with either GnRH-agonist or GnRH-antagonist analogues for in vitro fertilization (IVF) being well analysed, the effect of analogues on oocyte/embryo quality and embryo development is still not known in detail. The aim of this case-control study was to compare the efficacy of a multiple-dose GnRH antagonist protocol with that of the GnRH agonist long protocol with a view to oocyte and embryo quality, embryo development and IVF treatment outcome.</p> <p>Methods</p> <p>Between October 2001 and December 2008, 100 patients were stimulated with human menopausal gonadotrophin (HMG) and GnRH antagonist in their first treatment cycle for IVF or intracytoplasmic sperm injection (ICSI). One hundred combined GnRH agonist + HMG (long protocol) cycles were matched to the GnRH antagonist + HMG cycles by age, BMI, baseline FSH levels and by cause of infertility. We determined the number and quality of retrieved oocytes, the rate of early-cleavage embryos, the morphology and development of embryos, as well as clinical pregnancy rates. Statistical analysis was performed using Wilcoxon's matched pairs rank sum test and McNemar's chi-square test. P < 0.05 was considered statistically significant.</p> <p>Results</p> <p>The rate of cytoplasmic abnormalities in retrieved oocytes was significantly higher with the use of GnRH antagonist than in GnRH agonist cycles (62.1% vs. 49.9%; P < 0.01). We observed lower rate of zygotes showing normal pronuclear morphology (49.3% vs. 58.0%; P < 0.01), and higher cell-number of preembryos on day 2 after fertilization (4.28 vs. 4.03; P < 0.01) with the use of GnRH antagonist analogues. The rate of mature oocytes, rate of presence of multinucleated blastomers, amount of fragmentation in embryos and rate of early-cleaved embryos was similar in the two groups. Clinical pregnancy rate per embryo transfer was lower in the antagonist group than in the agonist group (30.8% vs. 40.4%) although this difference did not reach statistical significance (P = 0.17).</p> <p>Conclusion</p> <p>Antagonist seemed to influence favourably some parameters of early embryo development dynamics, while other morphological parameters seemed not to be altered according to GnRH analogue used for ovarian stimulation in IVF cycles.</p

The SUMO Isopeptidase Ulp2p Is Required to Prevent Recombination-Induced Chromosome Segregation Lethality following DNA Replication Stress

SUMO conjugation is a key regulator of the cellular response to DNA replication stress, acting in part to control recombination at stalled DNA replication forks. Here we examine recombination-related phenotypes in yeast mutants defective for the SUMO de-conjugating/chain-editing enzyme Ulp2p. We find that spontaneous recombination is elevated in ulp2 strains and that recombination DNA repair is essential for ulp2 survival. In contrast to other SUMO pathway mutants, however, the frequency of spontaneous chromosome rearrangements is markedly reduced in ulp2 strains, and some types of rearrangements arising through recombination can apparently not be tolerated. In investigating the basis for this, we find DNA repair foci do not disassemble in ulp2 cells during recovery from the replication fork-blocking drug methyl methanesulfonate (MMS), corresponding with an accumulation of X-shaped recombination intermediates. ulp2 cells satisfy the DNA damage checkpoint during MMS recovery and commit to chromosome segregation with similar kinetics to wild-type cells. However, sister chromatids fail to disjoin, resulting in abortive chromosome segregation and cell lethality. This chromosome segregation defect can be rescued by overproducing the anti-recombinase Srs2p, indicating that recombination plays an underlying causal role in blocking chromatid separation. Overall, our results are consistent with a role for Ulp2p in preventing the formation of DNA lesions that must be repaired through recombination. At the same time, Ulp2p is also required to either suppress or resolve recombination-induced attachments between sister chromatids. These opposing defects may synergize to greatly increase the toxicity of DNA replication stress

Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: analysis of individual data from 94,638 patients treated in 55 breast cancer centers

Neoadjuvant chemotherapy (NACT) is frequently used in patients with early breast cancer. Randomized controlled trials have demonstrated similar survival after NACT or adjuvant chemotherapy (ACT). However, certain subtypes may benefit more when NACT contains regimes leading to high rates of pathologic complete response (pCR) rates. In this study we analyzed data using the OncoBox research from 94,638 patients treated in 55 breast cancer centers to describe the current clinical practice of and outcomes after NACT under routine conditions. These data were compared to patients treated with ACT. 40% of all patients received chemotherapy. The use of NACT increased over time from 5% in 2007 up to 17.3% in 2016. The proportion of patients receiving NACT varied by subtype. It was low in patients with HR-positive/HER2-negative breast cancer (5.8%). However, 31.8% of patients with triple-negative, 31.9% with HR-negative/HER2-positive, and 26.5% with HR-positive/HER2-positive breast cancer received NACT. The rates of pCR were higher in patients with HR-positive/HER2-positive, HR negative/HER2-positive and triple-negative tumors (36, 53 and 38%) compared to HR-positive/HER2-negative tumors (12%). PCR was achieved more often in HER2-positive and triple-negative tumors over time. This is the largest study on use and effects of NACT in German breast cancer centers. It demonstrates the increased use of NACT based on recommendations in current clinical guidelines. An improvement of pCR was shown in particular in HER2-positive and triple-negative breast cancer, which is consistent with data from randomized controlled trails

Sensor-Controlled Scalp Cooling to Prevent Chemotherapy-Induced Alopecia in Female Cancer Patients

Background: Scalp cooling has been used since the 1970s to prevent chemotherapy-induced alopecia, one of the most common and psychologically troubling side effects of chemotherapy. Currently available scalp cOf the 55 patients, 78% underwent scalp cooling untilooling systems demonstrate varying results in terms of effectiveness and tolerability. Methods: For the present prospective study, 55 women receiving neoadjuvant, adjuvant, or palliative chemotherapy were enrolled. The aim was to assess the effectiveness of a sensor-controlled scalp cooling system (DigniCap: Sysmex Europe GmbH, Norderstedt, Germany) to prevent chemotherapy-induced alopecia in breast or gynecologic cancer patients receiving 1 of 7 regimens. Clinical assessments, satisfaction questionnaires, and alopecia evaluations [World Health Organization (WHO) grading for toxicity] were completed at baseline, at each cycle, and at completion of chemotherapy. Results: Of the 55 patients, 78% underwent scalp cooling until completion of chemotherapy. In multivariate analysis, younger women and those receiving paclitaxel weekly or paclitaxel–carboplatin experienced less alopecia. The compound successful outcome (“no head covering” plus “WHO grade 0/1”) was observed in all patients 50 years of age and younger receiving 4 cycles of docetaxel–cyclophosphamide or 6 cycles of paclitaxel–carboplatin. Conversely, alopecia was experienced by all women receiving triplet polychemotherapy (6 cycles of docetaxel–doxorubicin–cyclophosphamide). For women receiving sequential polychemotherapy regimens (3 cycles of fluorouracil–epirubicin–cyclophosphamide followed by 3 cycles of docetaxel or 4 cycles of doxorubicin–cyclophosphamide followed by 4 cycles of docetaxel), the subgroup 50 years of age and younger experienced a 43% success rate compared with a 10% rate for the subgroup pf older women receiving the same regimens. Conclusions: The ability of scalp cooling to prevent chemotherapy-induced alopecia varies with the chemotherapy regimen and the age of the patient. Use of a compound endpoint with subjective and objective measures provides insightful and practical information when counselling patients