Sordia-Hernández, Luis Humberto

We assessed the available evidence regarding adverse effects on surrogate and patient-important health outcomes of third- and fourth-generation combined oral contraceptives among premenopausal women. We performed a systematic review and meta-analysis including randomized controlled trials and observational studies comparing third- and fourth-generation combined oral contraceptives with other generation contraceptives or placebo. Studies that enrolled women aged 15 to 50 years, with at least three cycles of intervention and 6 months of follow-up were included. A total of 33 studies comprising 629,783 women were included. Low-density lipoprotein cholesterol levels were significantly lower in fourth-generation oral contraceptives (mean differences (MD): −0.24 mmol/L; [95% CI −0.39 to −0.08]), while total cholesterol was significantly increased in levonorgestrel users when compared to third-generation oral contraceptives (MD: 0.27 mmol/L; [95% CI 0.04 to 0.50]). A decreased arterial thrombosis incidence was shown in fourth-generation oral contraceptive users, as compared to levonorgestrel (incidence rate ratio (IRR): 0.41; [95% CI 0.19 to 0.86]). No difference was found in the occurrence of deep venous thrombosis between fourth-generation oral contraceptives and levonorgestrel users (IRR: 0.91; [95% CI 0.66 to 1.27]; p = 0.60; I 2 = 0%). Regarding the remaining outcomes, data were heterogeneous and showed no clear difference. In premenopausal women, the use of third- and fourth-generation oral contraceptives is associated with an improved lipid profile and lower risk of arterial thrombosis. Data were inconclusive regarding the rest of outcomes assessed. This review was registered in PROSPERO with CRD42020211133.

Abstract Study question Does the selection of blastocysts for single embryo transfer, through the diagnosis of aneuploidy, improves the live birth rate in patients undergoing in vitro fertilization? Summary answer There seems to be no statistical difference in live birth rates between embryos with preimplantational genetic diagnosis (PGD) and those without. What is known already: Initial reports indicate that reproductive results improve after the selection of embryos to be transfer after performing a biopsy of the blastomeres, or trophectoderm cells, with the subsequent comprehensive analysis of the chromosomes. However, these results are now questioned. Reports in the literature are contrasting, so the real utility of selecting all embryos through comprehensive chromosome analysis calls for a more careful analysis that compares the risks, costs, and benefits of these techniques and their actual utility in reproductive results of patients treated with in vitro fertilization. Specifically results related to live birth rate. Study design, size, duration A systematic review of prospective studies evaluating live birth rate after embryo transfer of embryos selected by blastocyst biopsy for aneuploidy analysis compared with reproductive outcomes in embryo transfers of embryos selected morphologically, without biopsy nor screening for aneuploidies. Participants/materials, setting, methods A literature search was performed in PubMed, EmBase, and the Cochrane library (from January 2000 to december 2019). A cumulative meta-analysis and evaluation of heterogeneity was performed for the clinical pregnancy rate. The quality of the included studies was assessed using Cochrane’s Risk of Bias tool and ROBINS I for observational studies Main results and the role of chance Seven studies were included, three were randomized controlled trials and four were non-randomized studies of intervention (NRSI). The included studies were published between 2013 and 2019. For the preimplantational genetic diagnosis, three studies used array comparative genomic hybridization, three studies used next generation sequencing and only one study used qPCR. A total of 1638 patients were included, only two studies excluded patients with advanced maternal age (>35 years), two studies studied patients with recurrent implantation failure and three studies patients with recurrent pregnancy loss. Regarding the assisted reproduction techniques (ART), only studies where embryos where biopsied after day five for the genetic diagnosis where considered, most used ICSI and performed frozen-thawed transfer of up to two embryos, only one study allowed patients to be transferred with more than two embryos per cycle. Reproductive outcomes (live birth rate, miscarriage rate, clinical pregnancy) were extracted considering the events per embryo transfer and calculating the pooled odds ratios (OR) with 95% confidence intervals (95%CI) as our main outcome, sensitivity analyses will be performed using the events per cycles to assess the robustness of the effect estimate. Preliminary meta-analyses resulted in a pooled OR of 1.45 (95%CI 0.24–8.78) for NRSI and 1.34 (95%CI 0.85–2.11) for RCT. Limitations, reasons for caution The main limitation was the quantity of studies with acceptable methodology. This generated heterogeneity, hindering the evaluation of the true impact of PGD in ART outcomes. The use of events per embryo transfer as a main outcome could bias the results favoring PGD as less embryos are usually transferred. Wider implications of the findings: Our results show that there are too few studies with adequate methodology to generate a conclusion about the true benefit of PGD. However, a slight tendency favoring the reproductive outcomes of PGD was found. Trial registration number PROSPERO CRD42020198866