Carriers of cystic fibrosis among sperm donors: complete CFTR gene analysis versus CFTR genotyping.

OBJECTIVE: To determine the frequency of cystic fibrosis (CF) carriers among sperm donors in Spain studied through a complete analysis of the CFTR gene and to compare the results with those that would have been obtained by the 4 genotyping panels of the CFTR gene most commonly used as a carrier test in the context of assisted reproduction in our country. DESIGN: Descriptive observational study. SETTING: Private center. PATIENTS: Nine hundred thirty-five sperm donors, from January 2014 to June 2019. INTERVENTION: None. MAIN OUTCOME MEASURE: Presence of pathogenic variants in the CFTR gene. RESULTS: 17% of the donors were carriers of at least 1 pathogenic variant in CFTR, with 39 different pathogenic variants detected. Only 4 of these 39 variants (10.27%) would have been detected by the 4 genotyping tests considered, and 22 variants (56.41%) would not have been detected by any of the genotyping tests. The pathogenic variants of the CFTR gene included in the different genotyping tests analyzed vary widely, and <50% are common to all of them. CONCLUSIONS: Although the was not based in the general population, these results show that the use of genotyping tests is associated with a high reproductive risk, because the rate of detection of CF carriers was lower when these panels were applied, in comparison with the complete study of the CFTR gene. We recommend that complete sequencing of the CFTR gene by next-generation sequencing be performed as a screening method for CF in sperm donors.

Obstetric and neo-natal outcomes of ICSI cycles using pentoxifylline to identify viable spermatozoa in patients with immotile spermatozoa.

Pentoxifylline (PF) represents an effective tool in stimulating motility and identifying viable spermatozoa in intracytoplasmic sperm injection (ICSI) patients presenting exclusively with immotile spermatozoa. However, its use is not universally accepted for its possible detrimental effects on oocytes, embryos or newborns. To evaluate whether PF use may affect obstetrical/neo-natal outcomes, 102 patients achieving a clinical pregnancy after a PF-ICSI in four IVF units in Spain and Italy were followed up after delivery. Neo-natal malformations were classified according to the World Health Organization International Classification of Diseases (ICD-10, range Q00-Q99). Malformation rate was compared with data published by other groups regarding children conceived by conventional IVF or ICSI reporting a 5.3% and 4.4% frequency of ICD-10 codes, respectively. Of 134 clinical pregnancies, 122 babies (82 singletons and 40 twins) were registered. Among singletons, the rates of low birthweight (≤2500 g) and preterm birth (<37 weeks) were 6.1% and12%, respectively. Regarding malformation rate per live births, 4/122 (3.3%, 95% confidence interval: 0.9-8.2%) babies with ICD-10 malformations were recorded. This is the first report on neo-natal outcomes deriving from PF-ICSI. Although based on a limited cohort, results do not suggest an increase of adverse outcomes, including malformation rates, following this procedure.

Maximum number of children per sperm donor based on false paternity rate.

PURPOSE: The aim of this study is to estimate the weight of each relevant factor in such unions of inadvertent consanguinity and to determine a "reasonable" limit for the number of children per donor, matching the probability of inadvertent consanguinity arising from the use of sperm donor in assisted reproduction with that of such a union arising from false paternity. METHODS: In this study, we applied to Spanish data a mathematical model of consanguineous unions, taking into account the following factors: maximum number of live births/donor, fertility rate, average number of births per donor in a pregnancy, donor success rate, matings per phenotype, number of newborns/year, and number of donors needed in the population/year and births by false paternity. RESULTS: In Spain, the number of inadvertent unions between descendants of the same donor in Spain has been estimated at 0.4/year (one every two and a half years), although this frequency decreases as the reference population increases. On the other hand, the frequency of unions between family members due to false paternity has been estimated at 6.1/year. Thus, only 6% of such unions are due to the use of donor sperm. CONCLUSION: A total of 25 children per sperm donor are needed to align the probability of inadvertant consanguinity arising from the use of assisted reproduction with that due to false paternity. Therefore, we consider this number to be the maximum "reasonable" number of children born per donor in Spain.

Effect of Monotherapy with Darunavir/Ritonavir on Viral Load in Seminal Fluid, and Quality Parameters of Semen in HIV-1-Positive Patients.

Patients with human immunodeficiency virus type 1 (HIV-1) who receive antiretroviral therapy (ART) often achieve increased survival and improved quality of life. In this respect, monotherapy with darunavir/ritonavir (mDRV/r) can be a useful treatment strategy. This prospective study analyses the effect of mDRV/r on sperm quality and viral load in a group of 28 patients who had previously been given conventional ART and who had recorded a viral load <20 copies/mL for at least six months. These patients were given mDRV/r at a dose of 800/100 mg for 48 weeks. At baseline (V0), CD4, CD8, FSH, LH and testosterone levels were measured, together with HIV-1 viral load in plasma and semen. In addition, seminal fluid quality was studied before mDRV/r treatment was prescribed. At week 48 (V1), HIV-1 viral load in plasma and semen and the quality of the seminal fluid were again measured. The results obtained indicate that at V0, 10% of the patients with ART had a positive viral load in seminal fluid (>20 copies/ml), and that at V1, after mDRV/r treatment, this figure had fallen to 3%. The quality of seminal fluid was close to normal in 57% of patients at V0 and in 62% at V1. We conclude that, similar to ART, mDRV/r maintains HIV-1 viral load in most patients, and that there is no worsening in seminal fluid quality.