[Impact of geographical origin on IVF results: A monocentric observational French cohort study comparing 3 populations: Europe, Maghreb and Sub-Saharan Africa]. / Impact de l'origine géographique sur les résultats en FIV : Une étude de cohorte française observationnelle monocentrique comparant 3 populations : Europe, Maghreb et Afrique Subsaharienne.

OBJECTIVE: Many studies in the literature have found an association between geographic origin and poorer IVF outcomes in African American and Asian minority populations compared with Caucasian populations. The limitations of these studies are multiple (inconsistencies in the characterization of ethnic groups, mostly multicenter studies with large variability in success rates between centers, minorities having more limited and delayed access to care). Thus, socioeconomic status may have been an important bias in judging environmental or "genetic" factors. The objective of our study is to determine whether geographic origin would influence IVF response and outcomes in a French university hospital center with equal access to care. MATERIAL AND METHODS: This was a retrospective single-center observational study from January 2013 to January 2020 comparing IVF response in 3 populations of similar size at our Medically Assisted Reproduction center, with all charges covered by Medicare. The primary objective was ovarian response to IVF, and the secondary objectives were clinical pregnancy rate and live birth rate per cycle started. RESULTS: We analyzed 1669 cycles of first IVF attempt in women from Europe (525), Sub-Saharan Africa (649) and Maghreb (495). The SSA and Maghrebi women had a higher BMI. SSA women were more often affected by tubal or uterine infertility, HIV or HBV infection, and were less often nulliparous. The indication of male infertility was more frequent in Maghrebi women with a higher ICSI rate. There was no significant difference in the duration of stimulation, endometrial thickness at induction, number of oocytes collected, fertilization rate, number of embryos transferred and frozen. Nevertheless, the cancellation rate was higher in SSA and Maghrebi women and the total dose of gonadotropins was higher in SSA. No significant difference was found between Maghrebi and European women on IVF outcomes except for a lower number of total embryos in Maghrebi women (3.33 vs. 4.13 on average, P<0.001). The SSA had a lower rate of mature oocytes per puncture (66 % vs. 73 %, P<0.001), a lower number of total embryos per puncture (3.56 vs. 4.13 on average, P<0.016), a lower rate of clinical pregnancies per cycle (11.7% vs. 20.4%, P<0.001), a lower rate of live births per cycle (6.9% vs. 15.2%, P<0.001). CONCLUSION: There was no significant difference between European and Maghrebi women at the end of IVF, but the results were lower for those from SSA.

Early embryo development anomalies identified by time-lapse system: prevalence and impacting factors.

RESEARCH QUESTION: What is the prevalence of embryo abnormal early cleavage (ACL) identified by time lapse and factors related to patients and treatment that explain ACL occurrence? DESIGN: A single-centre, retrospective cohort study. Data were collected on all IVF cycles for which embryos were observed in the EmbryoScope® between December 2015 and August 2017. Only diploid zygotes cleaved on day 2 were included. The study included 318 cycles (250 couples and 1343 embryos). Embryo videos were retrospectively analysed for ACL. The prevalence of each type of ACL was recorded. The influence of clinical factors (whether they were intrinsic to patients or specific to IVF treatment) on ACL occurrence was analysed in multivariate multilevel mixed-effect logistic regression analysis. RESULTS: A high prevalence of ACL was observed: 37.6% (505/1343) of embryos presented at least one ACL, 22.8% (306/1343) a trichotomous mitosis, 25.8% (347/1343) a rapid cleavage, 6.7% (90/1343) a cell fusion and two or more ACL (16.1%). Part of the variation (12-25%) in ACL occurrence could be explained by embryo origin. Trichotomous mitosis and two or more ACL phenotypes were less likely to occur in women with endometriosis or tubal pathology and tubal pathology alone, respectively. No factor related to IVF cycles was found to be statistically associated with ACL occurrence. CONCLUSIONS: Our findings emphasize the importance of considering embryo origin when interpreting studies focusing on embryo characteristics and factors that could affect their quality. The present study is limited by a small sample size of known embryo implantations and monocentric criterion.

A missense mutation in IFT74, encoding for an essential component for intraflagellar transport of Tubulin, causes asthenozoospermia and male infertility without clinical signs of Bardet-Biedl syndrome.

Cilia and flagella are formed around an evolutionary conserved microtubule-based axoneme and are required for fluid and mucus clearance, tissue homeostasis, cell differentiation and movement. The formation and maintenance of cilia and flagella require bidirectional transit of proteins along the axonemal microtubules, a process called intraflagellar transport (IFT). In humans, IFT defects contribute to a large group of systemic diseases, called ciliopathies, which often display overlapping phenotypes. By performing exome sequencing of a cohort of 167 non-syndromic infertile men displaying multiple morphological abnormalities of the sperm flagellum (MMAF) we identified two unrelated patients carrying a homozygous missense variant adjacent to a splice donor consensus site of IFT74 (c.256G > A;p.Gly86Ser). IFT74 encodes for a core component of the IFT machinery that is essential for the anterograde transport of tubulin. We demonstrate that this missense variant affects IFT74 mRNA splicing and induces the production of at least two distinct mutant proteins with abnormal subcellular localization along the sperm flagellum. Importantly, while IFT74 deficiency was previously implicated in two cases of Bardet-Biedl syndrome, a pleiotropic ciliopathy with variable expressivity, our data indicate that this missense mutation only results in primary male infertility due to MMAF, with no other clinical features. Taken together, our data indicate that the nature of the mutation adds a level of complexity to the clinical manifestations of ciliary dysfunction, thus contributing to the expanding phenotypical spectrum of ciliopathies.

Timing of intermittent seminal HIV-1 RNA shedding in patients with undetectable plasma viral load under combination antiretroviral therapy.

It was demonstrated that combination antiretroviral therapy (cART) reduces the HIV-1 viral load (VL) in the blood and the seminal compartment. Some studies have reported that the seminal HIV-1 VL is undetectable in individuals with an undetectable blood plasma viral load (bpVL) under cART. However, some recent studies have demonstrated that seminal HIV-1 RNA may still be detected, and potentially infectious, even in the case of an undetectable bpVL. The aim of this retrospective study was to determine the detection rate of a seminal VL and whether shedding could be intermittent over a very short time. From January 2006 to December 2011, 88 HIV-1 infected men, enrolled in an Assisted Reproduction program, provided 306 semen samples, corresponding to 177 frozen sperm samples (two samples delivered at a one-hour interval (n = 129) or one sample (n = 48)). All enrolled men were under cART, with an undetectable bpVL for more than 6 months. HIV-1 RNA was quantified in seminal plasma using a Roche COBAS Ampliprep COBAS TaqMan HIV-1 test. Seminal HIV-1 RNA was detected in 23 samples (7.5%) from 17 patients (19.3%). This detection rate was stable over years. With regards to the freezing of two samples delivered at a one-hour interval, the proportion of discordance between the first and second samples was 9.3% (12/129). Our results confirm the intermittent shedding of HIV-1 in semen. While this finding has been shown by studies examining longer time intervals, to our knowledge, this has never been demonstrated over such a short time interval.