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.

[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.

Dextran-Based Hydrogel as a New Tool for BALB/c 3T3 Cell Cryopreservation Without Dimethyl Sulfoxide.

INTRODUCTION: Cryopreservation provides an efficient way to preserve cells for a broad range of medical applications, including cell therapy. In clinical practice, cells are frozen in solutions containing dimethyl sulfoxide (DMSO) cryoprotectant agents (CPAs) to reduce their damage during the cooling process. In the current cell preservation methods, polysaccharides such as dextran, a nonpenetrating CPA, are used. However, the cell viability decreases when the solution concentration in polysaccharides increases. MATERIALS AND METHODS: To overcome this limitation, we have developed a dextran-based hydrogel (PSH) as a new CPA. Three molecular weight PSHs (PSH40, PSH70, and PSH500) were synthesized. The physicochemical characteristics of PSHs were studied. Then, their biocompatibility properties were studied in vitro in BALB/c 3T3 cells according to ISO standard 10993-5/12. Crystallization temperature (Tc), that is, ice-crystal formation, was determined using the thermocouple method. Finally, PSHs were used as CPAs in a slow freezing procedure of BALB/c 3T3 cells with Voluven® (Fresenius Kabi, Sèvres, France), and were compared with the DMSO procedure. RESULTS: Our results showed that PSHs were biocompatible and did not modify the osmolality of the Voluven cryopreservation solution. PSHs decreased the Tc when compared with the DMSO procedure. Furthermore, without adding DMSO, PSH500 cryopreserved the viability of BALB/c 3T3 cells, and the result was similar to that of the control conditions. CONCLUSION: PSH500 could represent an alternative to DMSO. It could be used as a new medical device while avoiding DMSO side effects on patients.

Higher live birth rate with stimulated rather than artificial cycle for frozen-thawed embryo transfer.

OBJECTIVE: To study which endometrial preparation allows a better ongoing pregnancy rates (OPR) and live birth rate (LBR) after frozen-thawed embryo transfer (FET) between mild gonadotropin ovarian stimulation (OS) and artificial cycles (AC). STUDY DESIGN: Retrospective follow-up study including all FET performed in one fertility center from 2013 to 2016. In the OS group, gonadotropins were followed by r-hCG triggering. Vaginal micronized progesterone (200 mg/day) was given systematically. In the AC group, estradiol (E2) was started on Day 1. Vaginal micronized progesterone (600 mg/d) was added to E2 for 12 weeks. Data were analyzed using a multiple regression model. RESULTS: Among 1021 FETs, 35% underwent OS preparation, 65% had an AC. As expected, patients in the AC group suffered more from endometriosis (18.5% vs. 12.9%; p = .021) and polycystic ovarian syndrome (21.7% vs. 10.9%; p < .0001) than patients in the OS group. There was no difference between groups with respect to endometrial thickness, number of embryos transferred, development stage at FET, cryopreservation technique. Despite a similar clinical pregnancy rate (CPR) (24.4% vs. 20.8%; p = .189), the OPR was significantly higher in the OS than in the AC group (17.9% vs. 11%; p = .002), leading to an increased LBR (17.1% vs. 9.8%; p < .001). After adjusting for parameters usually linked to early pregnancy losses or potential bias (patient age at freezing, smoking status, PCOS, endometriosis, rank of transfer and previous miscarriages), the results remained significant. CONCLUSION: Despite a similar CPR, LBR was significantly higher with mild OS than with the AC preparation, even after adjusting for potential confounders. In light of these results, the first-line endometrial preparation could be OS instead of an AC. In an AC, a potential defect of the luteal phase may exist, treatment could be optimized to avoid pregnancy losses. A randomized controlled trial should be undertaken to assess the role of OS and ACs in FET.

Various Genital and Reproductive Phenotypes in 46,XX/46,XY Chimeras.

Tetragametic chimeras are due to the fusion of 2 different zygotes after fertilization. When occurring between embryos of different chromosomal sex, the phenotype ranges from fertile individuals to infertile patients and even to patients with variations in sex development. Here, we report 3 new cases of XX/XY chimeras, one in a young boy carrying an abnormal gonad which turned out to be an ovary and 2 in phenotypically normal infertile men, one of whom had been diagnosed previously as a XX-SRY negative male. These cases highlight the importance of combining several cytogenetic and molecular techniques on different tissues for a proper diagnosis and an appropriate prognosis.

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.