Metabolomic analysis of follicular fluid from women with Hashimoto thyroiditis.

Hashimoto thyroiditis is an autoimmune disease characterized by hypothyroidism and a high level of anti-thyroid autoantibodies. It has shown to negatively impact female fertility; however, the mechanisms are unclear. Ovarian follicular fluid appears to be the key to understanding how Hashimoto thyroiditis affecst fertility. Thus, we aimed to evaluated the metabolic profile of follicular fluid and antithyroid autoantibody levels in the context of Hashimoto thyroiditis. We collected follicular fluid from 61 patients, namely 38 women with thyroid autoantibody positivity and 23 women as negative controls, undergoing in vitro fertilization treatment. Follicular fluid samples were analyzed using metabolomics, and thyroid autoantibodies were measured. Fifteen metabolites with higher concentrations in the follicular fluid samples from Hashimoto thyroiditis were identified, comprising five possible affected pathways: the glycerophospholipid, arachidonic acid, linoleic acid, alpha-linolenic acid, and sphingolipid metabolism pathways. These pathways are known to regulate ovarian functions. In addition, antithyroglobulin antibody concentrations in both serum and follicular fluid were more than tenfold higher in women with Hashimoto thyroiditis than in controls. Our data showed that the metabolic profile of follicular fluid is altered in women with Hashimoto thyroiditis, suggesting a potential mechanistic explanation for the association of this disease with female infertility.

Estradiol and Progesterone Levels are Related to Redox Status in the Follicular Fluid During in vitro Fertilization.

Studies have reported a possible association between the levels of oxidative stress biomarkers in follicular fluid (FF) and infertility treatment outcomes. FF analysis can provide important information about oocyte quality. This study aimed to evaluate the possible correlation between oxidative stress biomarker and intrafollicular hormone levels and clinical and laboratory parameters in women during controlled ovarian stimulation. These women were undergoing in vitro fertilization with intracytoplasmic sperm injection (ICSI).The FF samples were acquired from September 2012 to February 2014 from women undergoing private fertility treatment in Rio de Janeiro, Brazil. A total of 196 women who were undergoing ICSI and had different infertility diagnoses were recruited. The FF from each patient (average patient age of 36.3 ± 4.3 years) was collected following puncture of just one follicle with the largest diameter. After ruling out blood contamination by spectrophotometry, 163 patient samples were utilized in the study. In the FF, the progesterone levels were negatively correlated with (a) hydrogen peroxide scavenging capacity (HPSC) (r = -0.294, P < 0.0001), (b) total number of follicles (r = -0.246, P < 0.001) and (c) total number of oocytes punctured (r = -0.268, P = 0.0001). The concentration of serum estradiol exhibited a positive correlation with intrafollicular HPSC (r = 0.165, P = 0.037). Our data indicate that the FF levels of estradiol and progesterone are related to the FF redox status, which is closely associated with the number of oocytes obtained during ICSI procedures.

Vitamin D Receptor TaqI Polymorphism Is Associated With Reduced Follicle Number in Women Utilizing Assisted Reproductive Technologies.

PURPOSE: Calcitriol, or 1,25-hydroxycholecalciferol, is the active form of vitamin D. It binds and activates vitamin D receptor (VDR). Infertility and defective folliculogenesis have been observed in female vdr-knockout mice; however, whether VDR polymorphisms affect human ovarian responses to controlled ovarian stimulation (COS) remains unclear. We hypothesized that VDR polymorphisms are associated with infertility and COS responses. Thus, we evaluated the association between the TaqI, BsmI, and FokI VDR polymorphisms and ovarian responses in women undergoing COS. METHODS: In this study, we recruited a control group (n = 121) comprising volunteers with a history of natural conception and a second group of women undergoing COS (n = 70). TaqI, BsmI, and FokI genotyping was performed via restriction fragment length polymorphism analysis or TaqMan qPCR and Sanger sequencing. Intrafollicular 25(OH)D contents were measured in follicular fluid collected from COS patients during oocyte retrieval. Ovarian response parameters were obtained from patient medical records. RESULTS: There were no significant differences in the genotype frequencies of VDR polymorphisms (TaqI, BsmI and FokI) between the control and COS groups. However, the allele frequency of TaqI (C allele) was significantly lower in the COS group than in the control group (p = 0.02). Follicle number but not oocyte number was lower in patients with TaqI polymorphic (TC/CC) genotypes (p = 0.03). Importantly, the ratio between the number of follicles retrieved and intrafollicular estradiol concentrations was higher in patients with the TC/CC TaqI genotypes (p < 0.02). CONCLUSION: We identified an association between the VDR TaqI polymorphism and reduced follicle number in women undergoing COS, suggesting that VDR signaling affects the ovarian response to stimulation via unknown mechanisms.

Lower follicular fluid vitamin D concentration is related to a higher number of large ovarian follicles.

Vitamin D receptor-knockout mice fail to produce mature oocytes, indicating vitamin D is crucial for folliculogenesis in mice. However, the actions of vitamin D during folliculogenesis remain unknown. This prospective study aimed to assess whether follicular fluid (FF) vitamin D (25OHD3) concentrations are related to specific responses to ovarian stimulation. Women undergoing ovarian stimulation for IVF participated in the study. FF 25OHD3 concentrations were assessed in the first follicle aspirate on oocyte retrieval day. Oestradiol and progesterone concentrations were assessed on the trigger day. K-means grouping analysis showed that 25OHD3 FF concentrations clustered into a higher and lower group (mean ± SEM 17.4 ± 6.61 ng/ml and 35.5 ± 7.17 ng/ml, respectively, P < 0.001). The clusters were analysed according to the oestradiol and progesterone concentrations, follicle number and size and resulting oocyte number and maturity. The FF 25OHD3 concentrations were no different among the infertility diagnoses. The lower 25OHD3 group had more follicles (≥16.0 mm, P = 0.009) and higher serum oestradiol concentrations (P < 0.03) on the day of HCG administration. In this study, lower follicular 25OHD3 concentrations predicted a better response to ovarian stimulation shown by a greater production of larger follicles and higher serum oestradiol concentrations.

High Progesterone levels in the beginning of ICSI antagonist cycles and clinical pregnancy: still a concern?

OBJECTIVE: In controlled ovarian hyperstimulation (COH) using antagonist cycles, an incomplete luteolysis could happen after an inefficient previous luteolysis. Since antagonist cycles are frequent today, this study aims to access the impact of serum progesterone in the beginning and at the end of stimulation, and pregnancy outcomes. METHODS: single-center cohort study, 461 fresh embryo transfers in ICSI antagonist cycles. Serum progesterone levels was measured in the beginning of COH (P4i) and on hCG day (P4f) using threshold values of 1.5ng/mL. Four groups were created: Group 1, P4i and P4f ≤ 1.5; Group 2, P4i ≤ 1.5 and P4f > 1.5; Group 3, P4i > 1.5 and P4f ≤ 1.5 and Group 4, P4i and P4f > 1.5. The clinical pregnancy rate (CPR) and live birth rates (LBR) were the primary outcomes. RESULTS: The number of cycles per group was: 393, 51, 6 and 11, respectively. Group 1 was considered the expected normal, while group 4 represented the persistence of higher levels. There was no difference in age, basal FSH and Estradiol, days of stimulation endometrium thickness and total amount of gonadotropins between group 1 versus group 4. However, significant differences occurred in embryological and clinical outcomes between these 2 groups. CONCLUSION: The impact of serum progesterone in the beginning of stimulation and pregnancy outcomes is a matter of concern. Basal elevated levels could help identify patients that will repeat it on hCG day, being probably a marker to define a freeze-all strategy to these cycles.

Body weight and 25-hidroxyvitamin D follicular levels: a prospective study of women submitted to in vitro fertilization.

OBJECTIVE: Vitamin D deficiency has been largely related to infertility in animals. However, data demonstrating a direct association between hypovitaminosis D and infertility in humans are still conflicting. Increased body weight and an elevated body mass index (BMI) are known for their association with infertility. Therefore, this study attempted to verify whether increases in body weight and the BMI were associated with lower 25-hidroxyvitamin D [25(OH)D3] levels in the follicular fluid (FF) of patients treated for infertility with intracytoplasmic sperm injections (ICSI). This study aimed to assess the FF levels of 25(OH)D3 in women submitted to ICSI and correlate these levels with the different body weight and BMI values observed in the enrolled cohort. METHODS: The FF aspirates of 199 patients submitted to ICSI were collected after oocyte aspiration to check whether FF 25(OH)D3 levels were associated with weight regardless of the etiology of infertility. Chemiluminescent assays were used to assess FF 25(OH)D3 levels. The etiology of infertility was defined based on patient clinical history and follow-up. RESULTS: The patients enrolled in the study were divided into three groups according to their FF 25(OH)D3 levels, as follows: a) deficient (n=71; <20 ng/ml); b) insufficient (n=64; 21< 25(OH) D3>29 ng/ml); and c) sufficient (n=56 >30ng/ml) levels. Patients with lower FF 25(OH)D3 levels had a greater mean weight (64.1kg) when compared to patients with higher 25(OH)D3 levels (60.7kg), p<0.01. No differences were observed in terms of age or etiology of infertility. CONCLUSION: The body weight of the individuals with FF 25(OH)D3 deficiency measured in single follicles was significantly higher regardless of the etiology of infertility. Further epidemiologic and molecular studies are required to verify whether the amount of follicular 25(OH)D3 affects the outcome of IVF procedures.

Prediction of metaphase II oocytes according to different serum Anti-Müllerian hormone (AMH) levels in antagonist ICSI cycles.

OBJECTIVE: This paper aims to assess a qualitative aspect of ovarian response in terms of metaphase II oocytes according to different serum Anti-Müllerian hormone levels in antagonist ICSI cycles. A prediction index might contribute to the individualization of care. METHODS: This observational study looked into 287 antagonist ICSI cycles carried out with patients treated in a single center between January of 2012 and January of 2016. Serum AMH and subgroup analyses were performed based on five AMH ranges (≤ 0.3 ng/mL;> 0.3 and ≤ 0.7 ng/mL; > 0.7 and ≤ 1.0 ng/mL; > 1.0 and < 3.0 ng/mL; ≥ 3.0 ng/mL). The variables analyzed included patient age; serum FSH and antral follicle count at the start of the cycle; number of stimulation days and number follicles ≥ 15 mm on hCG day; number of oocytes retrieved and number of metaphase II oocytes. RESULTS: AMH is a better predictor of ovarian response to controlled ovarian stimulation than AFC or serum FSH, while age is an independent marker. AMH levels ≤0.70 (patients with poor prognosis) were observed in 140 patients (48.7%). Patients within this AMH level range accounted for 92% of the 24 failed cycles (cancelled cycles, no oocytes or immature oocytes retrieved). CONCLUSION: AMH predicts the quality of ovarian response to stimulation, regardless of patient age. Women with AMH levels ≥1.0 and ≤3.0 ng/mL are probably normal responders with good prognosis. Clinical application relies on the examination of the data from each individual center and on the establishment of correlations between AMH levels and ovarian response in the form of metaphase II oocytes.

Live Births after Fertility-saving Surgery in Ovarian Borderline Tumor and Oocyte Donation: Case Report.

A left borderline serous ovarian tumor stage I (FIGO) was discovered and treated in a 26-year-old black nulliparous woman, by conservative approach (laparotomy, salpingo- oophorectomy). In a six months interval she had a 7.5 x 7.1 x 5.7cm multilocular contralateral tumor with septa and vegetative areas and in a year interval a CT showed a 8.4 x 7.4 x 7.0 lesion that precluded a follicular aspiration. The authors discuss the multidisciplinary strategy and the approach with the couple: the best option considered would be the resection of the tumor remaining attached to a new study pelvic. If possible uterine conservation should be held for further procedure of oocyte donation. Two years from the first surgery she had the second laparotomy and six months later she had an ICSI with oocyte donation. She became pregnant and delivered two 34 week-pregnancy boys through C-section due to hypertension plus preeclampsia. There happened a post- operative intestinal obstruction that required a new surgical approach to adhesions lysis. There was no report of tumor lesions then. Seven months later, mother and children are doing well. Comments are made about borderline ovarian tumors and fertility-sparing approaches.