Medical research and reproductive medicine in an ethical context: a critical commentary on the paper dealing with uterine lavage published by Munné et al.

A recent study published in Human Reproduction claimed that uterine lavage offers a non-surgical, minimally invasive strategy for the recovery of human embryos from fertile women who do not want or need IVF for medical reasons but who desire preimplantation genetic testing (PGT) for embryos. To prove this hypothesis, the researchers recruited dozens of young Mexican women. The prospective oocyte donors underwent ovarian stimulation to induce the production of multiple mature oocytes. Subsequently, these women were inseminated by donor semen. A few days later, the developing embryos were collected by uterine lavage (uterine flushing) and subjected to genetic testing for aneuploidies (PGT-A). Oocyte donors with persistently elevated hCG levels, indicating the implantation of one or more embryos after uterine lavage, had to undergo uterine curettage and/or treatment with methotrexate. A critical opinion paper discussing the aforementioned study was published by De Santis and colleagues and has raised critical issues that are largely technical in nature. However, this opinion paper neglects-from our point of view-critical issues of the Mexican study regarding ethical principles and moral standards in human research. These aspects are summarized below.

Use of dimethylxanthine theophylline (SpermMobil®) does not affect clinical, obstetric or perinatal outcomes.

PURPOSE: To evaluate whether the use of a commercially available dimethylxanthine theophylline compound (SpermMobil®) for artificial sperm activation would negatively affect clinical, obstetric and perinatal outcomes. METHODS: Artificial sperm activation (ASA) was used when sperm motility after preparation was low or absent in our clinical standard procedure practice. ICSI cycles using either testicular or ejaculated sperm with concentration smaller than 5 million/ml from August 2012 to January 2018 were retrospectively analyzed (n = 815) and divided into two groups, a control group where no ASA was needed and the SpermMobil® group with ASA. RESULTS: The fertilization rate was significantly higher in the control group, but pregnancy and implantation rates did not differ significantly. Number of embryos transferred, good quality embryos for ET and number of frozen blastocysts were similar in both groups. Clinical pregnancy loss was significantly reduced in the SpermMobil® group, which was reflected in slightly better live birth rates than in the control group. Furthermore, there were no significant differences regarding gestational age, weight, height and z score for singletons or multiples in the SpermMobil® (n = 27 and n = 10) or control (n = 144 and n = 67) groups. There were no reports of malformation, perinatal mortality or intensive therapy in the SpermMobil® group, whereas in the control group, 12 babies needed intensive care, besides one intrauterine death. CONCLUSION: The use of SpermMobil® in samples with mostly immotile sperm not only facilitates the embryologists work but also optimizes the treatment outcomes for those patients with a bad prognosis. This is the first report of obstetric and perinatal outcomes after applying a theophylline derivative in human clinical use.