The effect of levothyroxine and prednisolone treatment on pregnancy in in vitro fertilization patients with positive thyroid autoantibodies.

AIM: To investigate the effects of levothyroxine and prednisolone treatment, or in combination, on positive thyroid autoantibodies in infertile patients undergoing in vitro fertilization (IVF) therapy. METHODS: This retrospective study included a total of 190 patients with positive thyroid autoantibodies (anti-T and anti-TPO) who underwent IVF treatment between January 2008 and March 2016. Patients were divided into four groups: group 1-levothyroxine group (n = 50), group 2-prednisolone group (n = 50), group 3-levothyroxine and prednisolone combination (n = 25), group 4-control group (n = 65). Anti-T and anti-TPO levels before IVF and at the time of embryo transfer (ET), b-hcg positivity, clinical and biochemical pregnancy, miscarriage rate, and live birth rate were compared among groups. RESULTS: In levothyroxine-treated group, mean anti-TPO levels significantly decreased at the time of ET compared to before IVF treatment levels (p = 0.036). In group 3, mean anti-T and anti-TPO levels significantly decreased at the time of ET compared to levels before IVF treatment (p < 0.05). Patients who became pregnant in group 1, mean anti-T anti-TPO levels significantly decreased compared to before IVF treatment levels (p < 0.05). The biochemical pregnancy rate was significantly higher in group 2 (p = 0.03). Abortion rates were the highest in group 3, but no significant difference was found among groups. The group treated with levothyroxine had a significantly increased rate of live birth compared to the control group (p = 0.02). CONCLUSIONS: Levothyroxine addition during IVF treatment of patients with positive thyroid antibodies in subclinical hypothyroidism increases the take-home baby pregnancy rate. Whether subclinical hypothyroidism or not in IVF treatment, levothyroxine is more effective than low-dose corticosteroids.

Impact of 5'-AMP-activated protein kinase (AMPK) on Epithelial Sodium Channels (ENaCs) in human sperm.

Hyperpolarization is associated with decreased intracellular Na+ concentration through the closure of the epithelial Na+ channels (ENaCs) during capacitation. 5'-AMP-activated protein kinase (AMPK) is involved in the regulation of Na+ transport by reducing ENaC-ß abundance in the plasma membrane in somatic cells. However, it is not known whether AMPK acts on ENaCs in sperm. The aim of the present study was to analyze the role of AMPK activation in the regulation of ENaC and to examine its relationship with capacitation-associated hyperpolarization of human sperm. Human sperm were treated with AICAR (AMPK activator) in non-capacitating and capacitating conditions. AMPK activity and ENaC-ß concentration were evaluated by ELISA. Flow cytometry was used to measure tyrosine phosphorylation, hyperpolarization, intracellular Na+ concentration and acrosome reaction. Immunofluorescence staining was carried out to analyze the distribution of ENaC-ß and CD46 in sperm. We found that induction of capacitation triggered AMPK phosphorylation. AMPK activation by AICAR increased tyrosine phosphorylation. AICAR decreased ENaC-ß levels, mainly localized at the principal-piece of the flagellum, resulting in lower intracellular Na+ concentration and increased hyperpolarization of the plasma membrane. Altogether, these data provide evidence that AMPK activation is involved in capacitation-associated hyperpolarization by reducing ENaC abundance in human sperm.

Further delineation of familial polycystic ovary syndrome (PCOS) via whole-exome sequencing: PCOS-related rare FBN3 and FN1 gene variants are identified.

AIM: To identify pathogenic rare coding Mendelian/high-effect size variant(s) by whole-exome sequencing in familial polycystic ovary syndrome (PCOS) patients to elucidate PCOS-related pathways. METHODS: Twenty women and their affected available relatives diagnosed with PCOS according to Rotterdam criteria were recruited. Whole-exome sequencing on germ-line DNA from 31 PCOS probands and their affected relatives was performed. Whole-exome sequencing data were further evaluated by pathway and chemogenomics analyses. In-slico analysis of candidate variants were done by VarCards for functional predictions and VarSite for impact on three-dimensional (3D) structures in the candidate proteins. RESULTS: Two heterozygous rare FBN3 missense variants in three patients, and one FN1 missense variant in one patient from three different PCOS families were identified. CONCLUSION: We identified three novel FBN3 and FN1 variants for the first time in the literature and linked with PCOS. Further functional studies may identify causality of these newly discovered PCOS-related variants, and their role yet remains to be investigated. Our findings may improve our understanding of the biological pathways affected and identify new drug targets.

Assessment of a Novel Fixation Method of a Frameless Intrauterine Contraceptive Device Inserted during Cesarean Delivery as a Means of Preventing Displacements and Expulsions: A Prospective Observational Study.

The primary objective of this study was to assess the novel fixation method of a frameless copper-releasing intrauterine device inserted following placental delivery during cesarean section and analyze its impact in reducing device displacement and expulsion during and after uterine involution. We hypothesized that the dual-anchoring technique could reduce the risk of intrauterine device displacement and expulsion during and after the uterine involution. The study was conducted at the Gazi University Medicine Faculty Hospital in Ankara, Turkey. Twenty-one pregnant women were enrolled. Insertion was performed following placental removal. To confirm the proper placement and good retention of the device, the distance between the fundal serosa (S) and device anchor knot (A) was measured (S-A) during follow-ups, by ultrasound. There were significant differences in the S-A, as observed by ultrasound at discharge and at 6 weeks post-delivery, which is consistent with the tissue contractions associated with uterine involution. Notwithstanding the uterine involution, no device displacements or expulsions occurred, which indicated a good retention of the frameless device. This innovative retention method of the frameless intrauterine device ensures a well-tolerated, long-term contraception, allowing for immediate contraception and proper pregnancy spacing for cesarean scar healing, and overcomes the issue of expulsion encountered with conventional intrauterine systems.

Investigation of oxidative stress status in cumulus cells in patients with in vitro fertilization

Background/aim: The negative impact of oxidative stress on oocytes obtained from in vitro fertilization (IVF) patients is a challenge for the optimization of live birth rates. In this study, it is aimed to investigate whether oxidant/antioxidant parameters have a predictive value in terms of determining the count and quality of oocytes. Materials and methods: Catalase (CAT), glutathione-S-transferase (GST), arylesterase (ARE) enzyme activities, and malondialdehyde (MDA) levels were analysed in cumulus cells of poor responder (n = 28, oocyte count ≤ 4), normo responder (n = 48, 5 ≤ oocyte count ≤ 14), and high responder (n = 26, oocyte count ≥ 15) patient groups continuing IVF treatment. Results: The cumulus cell GST enzyme activity were statistically significantly increased in the high responders group compared to the poor responder and the normo responder's groups (p < 0.001 and p = 0.002, respectively). The cumulus cell MDA levels were significantly decreased in the high responder group compared to the poor responder group (p = 0.008). The cumulus cell CAT (p = 0.175) and ARE (p = 0.124) enzyme activities were examined but no statistically significant difference found between the groups. Conclusion: The significant increase in GST enzyme activity and significant decrease in MDA levels in the high responder group indicate that oxidative stress has an effect oocyte status and quality.

Considerations on a new, frameless copper-releasing intrauterine system for intracesarean insertion and its future clinical significance: A review.

Family planning is a system for attaining the desired number of children and enabling a desired spacing between pregnancies. Family planning can be achieved through both the use of contraceptive methods and the treatment of infertility. A woman's ability to limit her pregnancy has a significant effect on her health.While family planning reduces the rate of unintented pregnancies, it also reduces the number of unsafe abortions. Contraception is an important component of family planning and reproductive health. Among various contraceptive methods, intrauterine devices (IUDs) are very popular because of some of the features of IUDs including being affordable, simplicity of insertion, long duration of action and reversibility. Modern, frameless, copper IUDs contain more copper and their copper content is contained in the solid tubular sleeves rather than in the wire which increases efficacy and lifespan. Immediate postpartum intrauterine device insertion (IPPI) during cesarean section can be considered in women who desire long acting, reversible contraception. Fertility returns instantly after removal of the device and pregnancy rate is not affected. IPPI is a very attractive method, especially for women who have undergone cesarean and require an interval of contraception before getting pregnant again. However, IPPI needs more clinical attention due to many aspects. The advantages remain including the prevention of unintended short interval pregnancies and, by providing an optimal timeframe for post-cesarean uterine recover, can reduce the incidence of the next cesarean delivery. With the publication of international IPPI studies, it will take a place in the range of globally available contraceptive methods, which in this author's opinion, it deserves.

Maternal serum alpha-fetoprotein levels are normal in Fanconi anemia: Can it be a lack of postnatal inhibition of AFP gene resulting in the elevation?

We investigated the feasibility of using serum alpha-fetoprotein (AFP) levels as a screening test for prenatal diagnosis of Fanconi anemia (FA). Serial measurements in maternal serum were recorded. Parents, both heterozygous for FA, had declined prenatal molecular testing. The infant was born with no somatic abnormalities, and FA was confirmed by postnatal molecular analysis. Maternal serum AFP levels during each trimester of pregnancy were normal indicating that these levels cannot be used as a screening test in prenatal diagnosis. Three-year follow-up after birth showed constantly elevated serum levels in the patient from the start, suggesting a lack of postnatal inhibition on AFP gene.