Impact of oxygen tension during in vitro maturation: a sibling-oocyte prospective double-blinded study.

OBJECTIVE: To determine whether oxygen (O2) tension (20% vs. 5%) has an impact on oocyte maturation rates and morphology during in vitro maturation (IVM). DESIGN: A prospective, observational, monocentric, sibling-oocyte study. SETTING: University Hospital. PATIENTS: A total of 143 patients who underwent IVM for fertility preservation purposes from November 2016 to April 2021 were analyzed. Patients were included when ≥2 cumulus-oocyte complexes (COCs) were retrieved. The cohort of COCs obtained for each patient was randomly split into two groups: group 20% O2 and group 5% O2. INTERVENTION: Cumulus-oocyte complexes were incubated for 48 hours either under 5% O2 or 20% O2. After 24 and 48 hours of culture, every oocyte was assessed for maturity and morphology, to estimate oocyte quality. Morphology was evaluated considering six parameters (shape, size, ooplasm, perivitelline space, zona pellucida, and polar body characteristics), giving a total oocyte score ranging from -6 to +6. MAIN OUTCOME MEASURES: Maturation rates and total oocyte scores were compared using paired-sample analysis between group 20% O2 and group 5% O2. RESULTS: Patient median age was 31.4 [28.1-35.2] years-old. The mean serum antimüllerian hormone levels and antral follicle count were 3.2 ± 2.3 ng/mL and 27.2 ± 16.0 follicles, respectively. A mean of 10.7 COCs per cycle were retrieved, leading to 6.1 ± 2.4 metaphase II oocytes vitrified (total maturation rate = 57.3%; 991 metaphase II oocytes/1,728 COCs). A total of 864 COCs were included in each group. Oocyte maturation rates were not different between the two groups (group 20% O2: 56.82% vs. group 5% O2: 57.87%, respectively). Regarding oocyte morphology, the mean total oocyte score was significantly higher in group 5% O2 compared with group 20% O2 (3.44 ± 1.26 vs. 3.16 ± 1.32, P=.014). CONCLUSION: As culture under low O2 tension (5% O2) improves oocyte morphology IVM, our results suggest that culture under hypoxia should be standardized. Additional studies are warranted to assess the impact of O2 tension on oocyte maturation and the benefit of IVM under low O2 tension for embryo culture after utilization of frozen material.

Predictive factors for pregnancy after controlled ovarian stimulation and intrauterine insemination: A retrospective analysis of 4146 cycles.

BACKGROUND: The variability in indications and low rate of pregnancy compared to IVF have led many authors to dismiss IUI and offer IVF first-line instead. OBJECTIVES: To determine what are the predictive factors for clinical pregnancy (CP) and live birth (LB) in intrauterine insemination (IUI) cycles following controlled ovarian stimulation (COS). METHODS: Retrospective unicentric study, between January 2009 and December 2016. Patients aged 18 to <43 years who had an IUI following COS with gonadotropins. Statistical analysis was performed using Chi square and logistic regression. RESULTS: 4146 cycles (1312 couples) included. Mean age was 34.7 +/- 4years. LBR per couple was 39% for anovulatory infertility compared to (p < 0.05) unex-plained infertility (28.6%), mixed (23.4%), male factor (20.1%), unilateral tubal (14.2%), low ovarian reserve (13.2%), and endometriosis (stage I and II) (11.1%). Multivariate analysis showed the following factors were associated with CP: Cycle rank ≤3 (Odds ratio (OR) = 1.5, 95% CI: 1.2-1.9, p < 0.001), age <38 years (OR = 1.5, 95% CI: 1.2-2, p < 0.001), ≥2 preovulatory follicles (OR = 1.4, 95% CI: 1.1-1.8, p = 0.004), TMSC ≥ 5 millions (OR = 1.8, 95% CI: 1.3-2.4, p < 0.001). Endometriosis, low ovarian reserve, unilateral tubal and male factor had a negative impact on CPR (OR = 0.3, 95% CI: 0.1-0.5, p < 0.001; OR = 0.4, 95% CI: 0.3-0.7, p < 0.001; OR = 0.5 95% CI: 0.3-0.9, p = 0.01; OR = 0.6, 95% CI: 0.4-0.8, p = 0.002 respectively) compared to anovulatory infertility. CONCLUSION: We confirm that IUI can be an efficient treatment in selected indications. Young patients with anovulatory infertility seem to be the ideal candidates, with a 39% LBR per couple.

Toxoplasma gondii exposure may modulate the influence of TLR2 genetic variation on bipolar disorder: a gene-environment interaction study.

BACKGROUND: Genetic vulnerability to environmental stressors is yet to be clarified in bipolar disorder (BD), a complex multisystem disorder in which immune dysfunction and infectious insults seem to play a major role in the pathophysiology. Association between pattern-recognition receptor coding genes and BD had been previously reported. However, potential interactions with history of pathogen exposure are yet to be explored. METHODS: 138 BD patients and 167 healthy controls were tested for serostatus of Toxoplasma gondii, CMV, HSV-1 and HSV-2 and genotyped for TLR2 (rs4696480 and rs3804099), TLR4 (rs1927914 and rs11536891) and NOD2 (rs2066842) polymorphisms (SNPs). Both the pathogen-specific seroprevalence and the TLR/NOD2 genetic profiles were compared between patients and controls followed by modelling of interactions between these genes and environmental infectious factors in a regression analysis. RESULTS: First, here again we observed an association between BD and Toxoplasma gondii (p = 0.045; OR = 1.77; 95 % CI 1.01-3.10) extending the previously published data on a cohort of a relatively small number of patients (also included in the present sample). Second, we found a trend for an interaction between the TLR2 rs3804099 SNP and Toxoplasma gondii seropositivity in conferring BD risk (p = 0.017, uncorrected). CONCLUSIONS: Pathogen exposure may modulate the influence of the immunogenetic background on BD. A much larger sample size and information on period of pathogen exposure are needed in future gene-environment interaction studies.