Serum uric acid did not affect embryonic and pregnancy outcomes in women without PCOS during IVF procedures.

Objectives: Serum uric acid (UA) levels are associated with many systemic diseases. A previous study confirmed the association between high serum uric acid levels and poor prognosis of in vitro fertilization (IVF) treatment in polycystic ovary syndrome (PCOS) patients. This study aimed to explore the correlation between serum uric acid levels and reproductive outcomes in patients without PCOS. Methods: A retrospective study that included 1057 patients who underwent pre-implantation genetic testing for monogenic disorders (PGT-M) treatment from January 2013 to December 2020 was conducted. The study population was further divided into 3 groups according to serum UA levels: the ≤250 µmol/L group, the 251-360 µmol/L group, and the >360 µmol/L group. The controlled ovarian hyperstimulation (COH) treatment outcomes, embryonic treatment outcomes and pregnancy outcomes of the first frozen embryo transfer (FET) cycle were compared among groups. Multivariable linear regression and binary regression were applied to detect the association between IVF outcomes and serum uric acid levels. Results: The number of retrieved oocytes, fertilization rate, viable embryo rate, blastocyst formation rate and euploid rate were not associated with serum uric acid levels. The mature oocyte rate was negatively correlated with serum uric acid levels. The pregnancy outcomes of the first FET cycle were also not associated with serum uric acid levels. After adjustment for BMI, the perinatal outcomes were not associated with serum uric acid levels. Conclusion: IVF treatment outcomes were not associated with serum uric acid levels in patients without PCOS.

The Ratio of Peripheral Blood Natural Killer Cells is not a Solid Surrogate Immune Index in Unexplained Recurrent Miscarriage.

Background: Immunotherapies targeting peripheral natural killer (pbNK) cells in unexplained recurrent miscarriage (uRM) remain controversial. We hypothesized that the change in pbNK cell count might be a result of innate immune responses rather than a cause. Objective: To explore whether the pbNK count is significantly different in women testing positive than those testing negative for commonly studied autoimmune markers. Methods: Peripheral blood samples were collected from 302 eligible patients with uRM for the antinuclear antibody (ANA) testing determined by the enzyme-linked immunosorbent assay (ELISA), anti-thyroid peroxidase antibody (TPO-Ab) testing and anti-thyroglobulin antibody (Tg-Ab) testing determined by the chemiluminescent immunoassay, and pbNK cell testing determined by flow cytometry. The patients were divided into two groups according to the pbNK normal range, and the comparative analysis entailed an examination of the prevalence rates of autoantibodies within the high pbNK group and the normal pbNK group, followed by a comprehensive investigation into the potential correlations between autoantibodies and pbNK cells. Results: There was a positive association between TPO-Ab positivity and high pbNK cells (p=0.016, OR=5.097, 95% CI 1.356-19.159), while there was a negative association between ANA positivity and high pbNK cells (p=0.013, OR=0.293, 95% CI 0.111-0.773). TPO-Ab-positive patients had a higher pbNK cell count compared with TPO-Ab-negative patients, while ANA-positive patients had a lower pbNK cell count compared with ANA-negative patients. Conclusion: The change in pbNK cell count may be a consequence of immune responses, and there should be careful consideration in applying it as an immunotherapeutic index.

Decrease in peripheral natural killer cell level during early pregnancy predicts live birth among women with unexplained recurrent pregnancy loss: a prospective cohort study.

BACKGROUND: Previous studies have suggested that trophoblast cells inhibit the proliferation of peripheral natural killer cells and that the level of peripheral natural killer cells decrease in the middle and late pregnancy stage among healthy women. The change in peripheral natural killer cell level during early pregnancy and the relationship between the change in peripheral natural killer cell level and pregnancy outcomes among women with unexplained recurrent pregnancy loss have not been sufficiently explored. OBJECTIVE: This study aimed to characterize the level of prepregnancy peripheral natural killer cells in comparison with those in early pregnancy among women with unexplained recurrent pregnancy loss and to determine if the change in the level of peripheral natural killer cells from prepregnancy to early pregnancy can predict pregnancy outcomes. STUDY DESIGN: In this prospective cohort study, 1758 women with recurrent pregnancy loss were recruited between January 2017 and December 2021 among whom 252 women with unexplained recurrent pregnancy loss had prepregnancy and early pregnancy (4-6 weeks gestation) peripheral natural killer cell measurements. These 252 women were divided into 2 groups, namely those with a lower gestational peripheral natural killer cell level (group 1) when compared with prepregnancy levels and those who did not (group 2). The respective outcomes of these groups in terms of live birth and pregnancy loss were comparatively analyzed using chi-square and Student's t tests. Candidate factors that could influence live birth were selected using the Akaike information criterion. The participates were then randomly divided into training and testing groups. A multivariable logistic regression analysis was performed and a nomogram was created to assess the possibility of live birth. The predictive accuracy was determined by the area under the receiver operating characteristic curve and validated by plotting the predicted probabilities and the observed probabilities. A Hosmer-Lemeshow test was used to assess the goodness of fit. RESULTS: When early gestational peripheral natural killer cell levels were compared with prepregnancy peripheral natural killer cell levels, 61.5% (154) of women had a comparatively lower early-gestational peripheral natural killer cell level and 38.9% (98) of women had an increase or no change in the peripheral natural killer cell level. The live birth rate in group 1 was 89.0% (137/154), which was significantly higher than the rate of 49.0% (48/98) in group 2 (P<.001). A decrease in the peripheral natural killer cell level (odds ratio, 1.36; 95% confidence interval, 1.22-1.55; P<.001) and the anti-Muellerian hormone level (odds ratio, 1.41; 95% confidence interval, 1.14-1.81; P=.003) were important predicting factors for a higher live birth rate. Female body mass index (odds ratio, 0.97; 95% confidence interval, 0.82-1.15; P=.763) and parity (odds ratio, 1.61; 95% confidence interval, 0.71-4.12; P=.287) also were predicting factors. Furthermore, the area under the receiver operating characteristic curve of the model to diagnose of live birth was 0.853 with a sensitivity of 81.6% and a specificity of 78.0% using the training data set. And the Hosmer-Lemeshow test showed that the model was a good fit (p=6.068). CONCLUSION: We report a comparative decrease in the peripheral natural killer cell levels in early gestation when compared with prepregnancy cell levels in more than 60% of women with unexplained recurrent pregnancy loss at 4 to 6 weeks of gestation. When compared with prepregnancy peripheral natural killer cell levels, a decrease in the peripheral natural killer cell level during early pregnancy might be a useful predictor of the live birth rate among women with unexplained recurrent pregnancy loss.

Ovarian endometrioma increases the embryo aneuploid rate: an analysis of 7092 biopsied blastocysts from fertile monogenetic disease carriers.

BACKGROUND: Endometriosis affects many reproductive aged patients with fertility decline and poor outcomes of assisted reproductive treatments, mainly by decreased ovarian reserve and lower fertilization and implantation rates. In recent decade, altered oocyte microenvironments and abnormal spindle organization have been reported to be critical to oocyte chromosomal segregation, organization and aneuploid formation. However, clinical evidences are still limited on whether endometriosis influences oocyte and embryo development. We aimed to figure out the impact of endometrioma on embryo aneuploid formation. METHOD: This retrospective cohort study included 1,021 patients (7,092 biopsied embryos) from January 2012 to December 2020. Fertile patients without a history of miscarriage who underwent PGT-M treatment with aneuploid screening were included. Patients with ovarian endometrioma were defined as the study group, while patients without endometriosis were defined as the control group. All demographic, controlled ovarian stimulation treatment and aneuploid screening data were recorded and compared. RESULTS: The incidence of endometrioma in our study population was 6.5%. There were 7,092 embryos biopsied in total, with 308 embryos in the study group and 6,784 embryos in the control groups. The demographic characteristics were comparable between the two groups except the basal FSH level (6.02 IU/L vs. 5.52 IU/L, p = 0.012). The euploid rate of the study group was significantly lower than that of the control group (52.6% vs. 61.8%, p = 0.012), while the oocyte maturation, fertilization, usable embryo and blastocyst formation rates were comparable. Adjusted for basal FSH level, starting stimulating gonadotropin dosage, total gonadotropin dosage and FSH level on hCG day, euploid rate was still negatively related to endometrioma status. CONCLUSIONS: Endometrioma status disturbs oocyte and embryo development. For infertile patients with endometrioma who require assisted reproductive treatment, pre-treatment is necessary to improve treatment outcomes. TRIAL REGISTRATION: Not applicable.

Decreased Ovarian Reserves With an Increasing Number of Previous Early Miscarriages: A Retrospective Analysis.

The fact of ovarian reserve (OR) decreased in women with recurrent miscarriage has been well known. However, Whether OR would decrease with increasing numbers of previous miscarriages (PMs) is still unclear. To address this, OR parameters of following four groups' patients were evaluated: 99 women with one previous miscarriage (PM1), 46 women with two previous miscarriages (PM2) and 35 women with three or more previous miscarriages (PM3). The control group included 213 women without a history of miscarriage (PM0). The correlation of OR parameters and the proportion of diminished ovarian reserve (DOR) patients between the four groups were analyzed using Kendall's Tau-B coefficients. The results showed the median anti-Müllerian hormone (AMH) levels were 4.04, 3.40, 3.14 and 2.55 respectively in the PM0, PM1, PM2 and PM3 groups, respectively (H=15.99, P = 0.001); the median antral follicle counts (AFCs) were 10, 8, 8 and 6, respectively (H=24.53, P < 0.001); and the proportions of DOR patients were 10.8%, 15.2%, 23.9% and 31.4% (χ2 = 13.01, P = 0.005). In addition, AMH level and AFC correlated negatively with the number of PMs (correlation coefficients -0.154, P < 0.001; -0.205, P < 0.001 respectively), the proportion of DOR patients correlated positively with the number of PMs (correlation coefficients 0.156, P = 0.001). After stratification by age, AMH and AFC levels were still significantly lower in the PM3 group than the PM0 group (P < 0.05). The proportion of DOR patients between the PM0 and PM3 groups was statistically significant (P < 0.001). This study showed that AMH levels and AFCs decreased as well as the proportion of DOR patients increased significantly as the number of PMs increased. In conclusion, our study indicates decreased AMH levels and AFCs might be one of the factors contributing to early miscarriage.