TUBB8 mutations as a cause of oocyte maturation abnormalities: presentation of oocyte and embryo profiles and novel mutations.

RESEARCH QUESTION: What are the embryonic profiles and oocyte maturation dynamics in patients with tubulin beta eight class VIII (TUBB8) mutations leading to oocyte maturation abnormalities (OMAS), and are pregnancies possible in this population? DESIGN: A prospective cohort study was undertaken in a private fertility clinic between January 2019 and December 2022. Whole-exome genomic studies (WES) were performed to detect mutation types. In-vitro maturation (IVM) was compared in 18 subjects: nine with TUBB8 mutations, and nine without TUBB8 mutations to act as the control group. The distributions of oocyte maturation and embryonic development profiles were recorded. IVF and IVM outcomes of the 18 cases were evaluated. The primary outcomes were the embryonic profiles and maturation dynamics of oocytes derived from IVF or IVM in women as related to TUBB8 mutations. RESULTS: Mutations were detected in 52 of 89 (58.4%) women who underwent WES analysis. Twelve TUBB8 mutations were detected in nine women (10.1%) with OMAS. Seven novel TUBB8 mutations were noted. Two pregnancies were obtained in women with c.535 G>A TUBB8 mutations. When comparing IVM outcomes between women with and without TUBB8 mutations, there were no differences in oocyte, embryo or pregnancy parameters (P>0.05 in all cases). CONCLUSIONS: It is clear that further TUBB8 mutations which cause oocyte or embryonic arrest will be detected in future. Although biochemical or ectopic pregnancies may be possible in some of these women, no live births or ongoing pregnancies have been reported to date.

Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal.

Myometrium cells are an important reproductive niche in which cyclic mechanical forces of a pico-newton range are produced continuously at millisecond and second intervals. Overproduction and/or underproduction of micro-forces, due to point or epigenetic mutation, aberrant methylation, and abnormal response to hypoxia, may lead to the transformation of fibroid stem cells into fibroid-initiating stem cells. Fibroids are tumors with a high modulus of stiffness disturbing the critical homeostasis of the myometrium and they may cause unfavorable and strong mechanical forces. Micro-mechanical forces and soluble-chemical signals play a critical role in transcriptional and translational processes' maintenance, by regulating communication between the cell nucleus and its organelles. Signals coming from the external environment can stimulate cells in the format of both soluble biochemical signals and mechanical ones. The shape of the cell and the plasma membrane have a significant character in sensing electro-chemical signals, through specialized receptors and generating responses, accordingly. In order for mechanical signals to be perceived by the cell, they must be converted into biological stimuli, through a process called mechanotransduction. Transmission of fibroid-derived mechanical signals to the endometrium and their effects on receptivity modulators are mediated through a pathway known as solid-state signaling. It is not sufficiently clear which type of receptors and mechanical signals impair endometrial receptivity. However, it is known that biomechanical signals reaching the endometrium affect epithelial sodium channels, lysophosphatidic acid receptors or Rho GTPases, leading to conformational changes in endometrial proteins. Translational changes in receptivity modulators may disrupt the selectivity and receptivity functions of the endometrium, resulting in failed implantation or early pregnancy loss. By hypermethylation of the receptivity genes, micro-forces can also negatively affect decidualization and implantation. The purpose of this narrative review is to summarize the state of the art of the biomechanical forces which can determine fibroid stem cell transformation and, thus, affect the receptivity status of the endometrium with regard to fertilization and pregnancy.

Perinatal Outcomes In Monozygotic Pregnancies Resulting From Assisted Reproductive Technology Procedures: A Single-Center 6-Year Experience Based On A Large Cohort Of Pregnancies.

OBJECTIVE: Monozygotic twin (MZT) pregnancies increase the risk of maternal and infant mortality and include many complications. The present study describes our assisted reproductive technology (ART) procedures from the viewpoint of perinatal outcomes in MZT pregnancies. METHODS: In this retrospective clinical cross-sectional study, 1159 in vitro fertilization (IVF) cycles performed between October 2014 and December 2019 were reviewed and perinatal outcomes and general clinical conditions analyzed. RESULTS: Sixteen MZT pregnancies were observed, resulting in an incidence of 1.38%. The MZT pregnancy incidence for patients aged ≤35 and >35 years were 0.2% and 1.1%, respectively. Eight MZT pregnancies resulted in live births, while five ended in miscarriage. A significant positive correlation was found between the number of attempts and the age of female (r:0.674; p=0.004) and male (r:0.657; p=0.006) partners. Cumulus-Oocytes Complexes (COC) (r:0.635; p=0.008), Metaphase II Oocyte (MIIO) (r:0.627; p=0.009), Pronucleus Oocyte (PO) (r:0.585; p=0.017) were correlated with serum AMH levels. The number of MZT was positively correlated with male partner age (r:0.527; p=0.036) and negatively correlated with embryo transfer day (ETd) (r:-0.548; p=0.028). CONCLUSIONS: The incidence of MZT pregnancies observed in this study was similar to the incidence reported in the literature, although risk was more pronounced among women aged >35 years. Due to potential risks for mothers and fetuses, MZT pregnancies may become a problem as the number of individuals seeking IVF continues to increase.

Comparison of complication rates after transvaginal ultrasound-guided oocyte pick-up procedures with respect to ovarian response.

OBJECTIVE: The aim of this study was to compare the complication rates of oocyte pick-up (OPU) procedures via transvaginal ultrasonography in patients with different levels of ovarian reserve. METHODS: In total, 789 patients who underwent OPU procedures for in vitro fertilization (IVF) were included in the study. RESULTS: Individuals with normal ovarian reserve had a 2.947-fold higher risk of complications in OPU procedures than individuals with low ovarian reserve, and individuals with high ovarian reserve had a 7.448-fold higher risk of complications than individuals with low ovarian reserve. In addition, a higher number of IVF trials was associated with an increased risk of complications. CONCLUSION: The results of this study show that OPU has a higher risk of complications, particularly severe pain, in patients with high ovarian reserve. It is thought that complications can be reduced by preferring mild stimulation in patients with high ovarian reserve. Collecting fewer oocytes is also associated with a lower risk of complications from OPU. Even if a patient's reserve is very good, fewer and higher-quality oocytes should be targeted with the use of the lowest possible dose of drugs.

First trimester glycosylated hemoglobin for gestational diabetes mellitus screening.

OBJECTIVE: Our aim in this study is to evaluate the efficacy of HbA1c in screening for GDM during the first trimester of pregnancy. MATERIALS AND METHODS: In this retrospective cohort study, we evaluated the first trimester HbA1c (ft-HbA1c) levels of 195 pregnant women who attended our university hospital's obstetrics clinic. Blood samples were drawn from patients during 11-14 weeks of gestation. After that, all patients were screened using standardized one-step 75gr OGTT between 24 and 28 weeks of pregnancy. RESULTS: In this study, 195 pregnant women were included. Thirty-two (16.4%) of the women included in this study were diagnosed with GDM. The mean ft-HbA1c level was 5.52% in those who developed GDM and 5.21% in those who did not develop GDM (p = 0.000). Only seven (3.6%) of the women included in this study had an ft-HbA1c level above the prediabetes limit of 5.7%. All these women with prediabetes developed GDM. The cut-off value for ft-HbA1c to distinguish GDM was 5,33%. For this cut-off value, the sensitivity was 71.9%, and the specificity was 82.8%. CONCLUSION: The findings suggest that ft-HbA1c level is a promising biomarker for GDM screening. Especially, patients with ft-HbA1c level ≥5.33% are at increased risk for developing GDM.

Surgical Removal of Hydrosalpinx Improves Endometrium Receptivity by Decreasing Nuclear Factor-Kappa B Expression.

Although physiologic amount of inflammation is necessary for successful implantation, pathological inflammation inhibits the expression of receptivity molecules and genes. Because hydrosalpinges is an inflammatory disease, adverse effects of hydrosalpinges on implantation may be in part mediated by disturbed endometrial expression of nuclear factor-kappa B (NF-κB), a dimer implicated in inflammation. We examined the expression of NF-κB p65 (Rel A) during the window of implantation in the endometrium of infertile women (n = 14) with uni or bilateral hydrosalpinges prior to and following salpingectomy and of fertile controls (n = 14) by immunohistochemistry. We assessed the influence of salpingectomy on NF-κB p65 expression by comparing pre- and post-operative endometrial samples. To evaluate the intensity of endometrial NF-κB p65 (Rel A) immunoreactivity, H-score method was used. We showed a decrease in NF-κB p65 expression in 13 out of the 14 post-salpingectomy endometrial samples. The mean NF-κB p65 level was significantly higher in the endometrium of women with hydrosalpinges before salpingectomy compared with control cases without hydrosalpinges (3.94 ± 6.2 vs 2.18 ± 0.7, p < .02). Salpingectomy decreased the mean endometrial NF-κB p65 levels in both unilateral and bilateral hydrosalpinges (2.87 ± 1.1). When we compared the endometrial NF-κB p65 levels of the post-salpingectomy samples with their age-matched fertile controls, we did not observe any significant difference. After salpingectomy, the mean H-score of endometrial NF-κB p65 expression significantly decreased to a level similar to that of the fertile group (2.87 ± 1.1 vs 2.18 ± 0.7, p > .64). NF-κB p65 expression was detected in cytoplasmic and membranous parts of luminal and glandular epithelial cells of endometrium obtained before salpingectomy. Both epithelial and stromal components of the endometrium showed decreased staining for NF-κB p65 compared with the pre- and post-salpingectomy samples. The decreased NF-κB p65 (Rel A) immunoreactivity was predominantly localized to luminal and glandular epithelial cells. Uni or bilateral hydrosalpinges causes pathological endometrial inflammation. Improvement in pathological inflammation following salpingectomy in women with hydrosalpinges may be in part mediated by the downregulation of endometrial NF-κB p65 (Rel A) expression.