Effects of vitamin D supplementation on ovarian reserve markers in infertile women with diminished ovarian reserve.

ABSTRACT: The purpose of this study was to evaluate the effects of vitamin D supplementation on ovarian reserve markers, including serum anti-Mullerian hormone (AMH) level, follicle-stimulating hormone (FSH) level, and antral follicle count (AFC), in infertile women with diminished ovarian reserve and vitamin D deficiency.A prospective, nonrandomized, cross-sectional study was conducted. Women aged 18 to 41 years who were unable to become pregnant after 12 months of sexual intercourse and had normal tubal patency, partners with normal semen analysis, diminished ovarian reserve, and 25-hydroxyvitamin D [25(OH)D] deficiency were included. Eligible patients' AFC and serum levels of AMH, FSH, 25(OH)D, 1,25-dihydroxyvitamin D [1,25(OH)D], calcium, phosphate, alkaline phosphatase, and parathormone were assessed before and after administration of 300,000 IU of vitamin D ampules. Changes in the parameter values after vitamin D supplementation were compared with the initial levels.The study was conducted in 62 of the 142 participants. The AFC and AMH, 25(OH)D, 1,25(OH)D, phosphate (P < .01), and calcium levels (P < .05) were statistically significantly increased after vitamin D supplementation. Statistically significant decreases in FSH (P < .01) and alkaline phosphatase levels (P < .05) were observed after vitamin D supplementation. No statistically significant correlations were found between 25(OH)D level and AFC, 1,25(OH)D level, AMH level, and FSH level before and after supplementation (P > .05).As improvements in the ovarian reserve markers were obtained with vitamin D supplementation, vitamin D might be considered as a fertility treatment for patients with diminished ovarian reserve and vitamin D deficiency.

Folate Levels and Pregnancy Rate in Women Undergoing Assisted Reproductive Techniques: a Systematic Review and Meta-analysis.

Maternal nutrition is believed to be closely related to reproductive success and the importance of folate in the reproductive process and its involvement in fundamental biological systems are well known. The present systematic review and meta-analysis will focus on two main aspects: level of folate in women undergoing infertility treatments and association between folate status and success rate in assisted reproductive techniques. Although the importance of folate in the preconceptional phase is known, available data regarding the levels of folate in women who undergo infertility treatments are scarce. Referring to the threshold values generally used for the general population or for supplement users, the concentration of folate in the serum and erythrocytes of infertile women is adequate in the majority of the population with differences related to the geographic origin of the study populations. However, using the red blood cells folate threshold specifically indicated to prevent neural tube defects, the majority of available studies do not offer sufficient data to conclude on the real folate situation. As for the probability of success of ART treatments based on folate levels, our review did not reveal a significant effect.

Metabolomic Profiling of Poor Ovarian Response Identifies Potential Predictive Biomarkers.

Objective: To characterize the serum metabolomic profile and its role in the prediction of poor ovarian response (POR). Patients: Twenty-five women with normal ovarian reserve (24-33 years, antral follicle count [AFC] ≥5, anti-Müllerian hormone [AMH] ≥1.2 ng/ml) as the control group and another twenty-five women with POR (19-35 years, AFC <5, AMH < 1.2 ng/ml) as the study group were collected in our study. The serum levels of the women in both groups were determined from their whole blood by untargeted liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical analysis and cell signal pathways analysis were used to reveal the results. Results: A total of 538 different metabolites were finally identified in the two groups. Tetracosanoic acid, 2-arachidonoylglycerol, lidocaine, cortexolone, prostaglandin H2,1-naphthylamine, 5-hydroxymethyl-2-furancarboxaldehyde, 2,4-dinitrophenol, and D-erythrulose1-phosphate in POR were significantly different from control as were most important metabolites in support vector machines (p <0.05). Metabolomic profiling, together with support vector machines and pathway analysis found that the nicotinate and nicotinamide metabolism pathway, including L-aspartic acid, 6-hydroxynicotinate, maleic acid, and succinic acid semialdehyde, was identified to have significant differences in POR women compared to control women, which may be associated with ovarian reserve. Conclusion: This study indicated that LC-MS-based untargeted metabolomics analysis of serum provided biological markers for women with POR. The nicotinate and nicotinamide metabolism pathway may offer new insight into the complementary prediction and therapeutic potential of POR. The functional associations of these metabolites need further investigation.

Decline in anti-Müllerian hormone concentrations following radioactive iodine treatment in women with differentiated thyroid cancer: A systematic review and meta-analysis.

AIM: Radioactive iodine (RAI) is frequently used as adjuvant therapy in patients with differentiated thyroid cancer (DTC). However, its effect on ovarian reserve has not been fully elucidated, with studies yielding inconsistent results. The aim of this study was to systematically review and meta-analyze the best available evidence regarding the effect of RAI on ovarian reserve in premenopausal women with DTC. METHODS: A comprehensive literature search was conducted in PubMed, Cochrane and Scopus, through to December 6th, 2020. Data were expressed as weighted mean difference (WMD) with a 95% confidence interval (CI). The I2 index was used to assess heterogeneity. RESULTS: Four prospective studies were included in the qualitative and quantitative analysis. Anti-Müllerian hormone (AMH) concentrations decreased at three (WMD -1.66 ng/ml, 95% CI -2.42 to -0.91, p<0.0001; I2 0%), six (WMD -1.58, 95% CI -2.63 to -0.52, p=0.003; I2 54.7%) and 12 months (WMD -1.62 ng/ml, 95% CI -2.02 to -1.22, p<0.0001; I2 15.5%) following a single RAI dose compared with baseline (three studies; n=104). With respect to follicle-stimulating hormone (FSH) concentrations, no difference was observed at six (WMD +3.29 IU/l, 95% CI -1.12 to 7.70, p=0.14; I2 96.8%) and 12 months (WMD +0.13 IU/l, 95% CI -1.06 to 1.32, p=0.83; I2 55.2%) post-RAI compared with baseline (two studies; n=83). No data were available for antral follicle count. CONCLUSIONS: AMH concentrations are decreased at three months and remain low at 6 and 12 months following RAI treatment in women with DTC. No difference in FSH concentrations post-RAI is observed.

Glucocorticoid supplementation improves reproductive outcomes in infertile women with antithyroid autoimmunity undergoing ART: A meta-analysis.

BACKGROUND: Thyroid autoimmune disease (TAI) has been verified to be related to multiple adverse pregnancy outcomes. A growing number of evidences highlight the protective roles of glucocorticoid on the treatments of TAI. This meta-analysis aimed to study whether it is beneficial to add glucocorticoid treatment in infertile women with TAI when they are undergoing assisted reproductive technology (ART). METHODS: We conducted a systematic search in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang database, Weipu China Science and Technology Journal Databases (VIP database) up to September 10, 2020. The Revman 5.3 software was utilized for data statistics. We used a random-effects model to analyze data and the odds ratio (OR) combining with 95% confidence interval (95% CI) were employed to reveal the results. RESULTS: Three publications with 237 antithyroid antibody (ATA)-positive and 384 ATA-negative women were included in the final analysis. Overall, glucocorticoid therapy showed satisfying effects on improving clinical pregnancy rate (OR = 4.63, 95% CI [2.23, 9.58], I2 = 0.0%, P < .0001) and live birth rate (OR = 3.19, 95% CI [1.13, 9.04], I2 = 0.0%, P = .03) of ATA-positive women compared with control group. However, it seems that glucocorticoid showed no significant difference in the abortion rate (OR = 0.62, 95% CI [0.09, 4.32], I2 = 35%, P = .64) and oocyte recovery (OR = 2.26, 95% CI [-1.46, 5.99], I2 = 79%, P < .0001) between the 2 groups. CONCLUSIONS: Glucocorticoid may improve the pregnancy outcomes of ART women with ATA positive, but there is no significant reduction in the risk of miscarriage. Due to the limited enrolled references, glucocorticoid adjuvant therapy should be applied after more randomized controlled trials.

Effects of Periconceptional Multivitamin Supplementation on Folate and Homocysteine Levels Depending on Genetic Variants of Methyltetrahydrofolate Reductase in Infertile Japanese Women.

Methylenetetrahydrofolate reductase (MTHFR) has various polymorphisms, and the effects of periconceptional folic acid supplementation for decreasing neural tube defects (NTDs) risk differ depending on the genotypes. This study analyzed the effectiveness of multivitamin supplementation on folate insufficiency and hyperhomocysteinemia, depending on MTHFR polymorphisms. Of 205 women, 72 (35.1%), 100 (48.8%) and 33 (16.1%) had MTHFR CC, CT and TT, respectively. Serum folate and homocysteine levels in women with homozygous mutant TT were significantly lower and higher, respectively, than those in women with CC and CT. In 54 women (26.3% of all women) with a risk of NTDs, multivitamin supplementation containing folic acid and vitamin D for one month increased folate level (5.8 ± 0.9 to 19.2 ± 4.0 ng/mL, p < 0.0001) and decreased the homocysteine level (8.2 ± 3.1 to 5.8 ± 0.8 nmol/mL, p < 0.0001) to minimize the risk of NTDs in all women, regardless of MTHFR genotype. Regardless of MTHFR genotype, multivitamin supplements could control folate and homocysteine levels. Tests for folate and homocysteine levels and optimal multivitamin supplementation in women with risk of NTDs one month or more before pregnancy should be recommended to women who are planning a pregnancy.

Roles of kisspeptin in IVF/ICSI-treated infertile women and in human granulosa cells.

Kisspeptin, a crucial central regulator of reproduction, has been used as a trigger in in vitro fertilization (IVF) treatment. This study aimed to investigate the roles of kisspeptin in IVF treatment in infertile females (n = 30); and in steroidogenesis in human granulosa-like tumor cell line (KGN). In the human study, blood was collected at three time points including (1) the beginning of gonadotropin stimulation (Phase I), (2) around eight days after gonadotropin stimulation (Phase II), and (3) on the day of ovum pick-up (Phase III). Follicular fluid (FF) was collected at Phase III. Serum human chorionic gonadotropin (hCG) was measured 15 days after embryo transfer and fetal heart beats were determined around 42 days of menstrual cycle to classify the subjects into successful and unsuccessful groups. FF kisspeptin levels were higher in successful compared with unsuccessful subjects (P < 0.01). Kisspeptin levels were significantly higher in FF than in serum in successful subjects (P < 0.05) but were comparable in unsuccessful subjects. Serum kisspeptin was comparable among three phases in the successful group but its levels in Phase III were significantly lower compared with Phase I in the unsuccessful group (P < 0.01). Serum kisspeptin in Phase II/III had positive correlations with serum E2 in Phases II and III and the outcomes of IVF/intracytoplasmic sperm injection (ICSI) treatment including serum hCG levels. For the cell experiment (n = 3), kisspeptin treatment in the presence of FSH together with IGF-1 enhanced CYP19A1 (aromatase) mRNA expression compared with control. FSH alone increased aromatase concentrations in the supernatant compared with control and kisspeptin at the dose of 10-2 mmol/L with FSH enhanced aromatase concentrations in the supernatant compared with FSH alone (P < 0.001 all). In conclusion, kisspeptin enhanced aromatase expression and secretion and was associated with positive outcomes of IVF/ICSI treatment. Further studies regarding supplementation of kisspeptin could reveal its beneficial effects on IVF/ICSI treatment.

Efficacy and safety of Dingkun pill for female infertility patients with low prognosis undergoing in vitro fertilization-embryo transfer: study protocol for a multicenter, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Approximately 15% of couples in the reproductive age are affected by infertility. Women with diminished ovarian reserves (DOR) or with a poor ovarian response (POR) are required to undergo in vitro fertilization and embryo transfer (IVF-ET) to achieve pregnancy. However, studies indicate that poor response to gonadotropin stimulation has been reported in women undergoing IVF-ET. Results from two recent clinical studies in China suggest that traditional Chinese medicine (TCM) formula Dingkun pill (DKP) showed a curative effect by improving the clinical pregnancy rate in women with DOR and POR. However, the heterogeneity of the studies does not allow one to draw a definitive conclusion on the therapeutic effect of DKP. Therefore, the purpose of this study was to investigate the effect of DKP on improving the clinical outcome of pregnancy of IVF-ET in women with low prognosis. METHODS: A multicenter, double-blinded, randomized placebo-controlled trial was conducted. A total of 460 infertile patients undergoing IVF or intracytoplasmic sperm injection (ICSI) were recruited from 12 public hospitals in China. Participants were randomly divided into the experimental group (DKP formula) or the placebo group (control) at a ratio of 1:1. All patients were treated with GnRH antagonist protocol and ovarian stimulation performed for 5 weeks (from the 5th day of the previous menstrual cycle to the day of oocyte retrieval). The patients were followed up for 6 months to record their conception outcome. The primary outcome is to compare the pregnancy outcome to those under placebo treatment. Secondary outcomes included the total count of the retrieved oocyte, embryo quality, endometrial thickness on ET day, implantation rate, and early miscarriage rate. DISCUSSION: Currently, no multicenter, double-blind, randomized, placebo-controlled trials have been performed on the use of the DKP formula to improve on the clinical outcome of the conception of IVF-ET in women with low prognosis. DKP might provide a good clinical solution for females with low prognosis and undergoing IVF. There is no contemporary Western medicine to improve on the clinical outcome of conception in IVF-ET in women with low prognosis. Therefore, it is important to undertake a well-designed randomized trial to determine the effect of DKP in improving the clinical outcome of the conception of IVF-ET in women with low prognosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR). TRIAL REGISTRATION NUMBER: ChiCTR1900026614. Registered on 16 October 2019.

The use of autologous platelet-rich plasma (PRP) versus no intervention in women with low ovarian reserve undergoing fertility treatment: a non-randomized interventional study.

PURPOSE: To investigate the impact of a 3-month course of intracortical injections of autologous platelet-rich plasma (PRP) upon ovarian reserve markers versus no intervention in women with low ovarian reserve prior to undergoing assisted reproductive technology (ART). METHODS: Prospective controlled, non-randomized comparative study conducted in a private fertility clinic, in Venezuela. Women with abnormal ovarian reserve markers (FSH, AMH and AFC) who declined oocyte donation were allocated to one of the following groups according to patient choice: monthly intracortical ovarian PRP injections for three cycles, or no intervention. Primary outcomes were the change in FSH, AMH and AFC pre- and post-treatment. Secondary outcomes included the number of oocytes collected and fertilized, biochemical/clinical pregnancy rates and miscarriage and live birth rates. RESULTS: Eighty-three women were included, of which 46 received PRP treatment and 37 underwent no intervention. Overall median age was 41 years (IQR 39-44). There were no demographic differences between the study groups. At the 3-month follow-up, women treated with PRP experienced a significant improvement in FSH, AMH and AFC, whereas there was no change in the control group. Furthermore, overall rates of biochemical (26.1% versus 5.4%, P = 0.02) and clinical pregnancy (23.9% versus 5.4%, P = 0.03) were higher in the PRP group, while there was no difference in the rates of first trimester miscarriage and live birth between groups. CONCLUSION: PRP injections are effective and safe to improve markers of low ovarian reserve prior to ART, although further evidence is required to evaluate the impact of PRP on pregnancy outcomes.

Cell-free nucleic acids and melatonin levels in human follicular fluid predict embryo quality in patients undergoing in-vitro fertilization treatment.

Despite many advances in assisted reproductive technology (ART), the most viable embryo selection remains a challenge for infertility treatment. This study was designed to investigate whether intra-follicular circulating cell-free DNA (cfDNA) fragments and Melatonin levels predict embryo quality in patients undergoing IVF treatment. A total of eight hundred and ninety-five follicular fluid (ff) samples were collected from 325 infertile patients undergoing IVF treatment. Patients were enrolled from August 2017 to December 2018 in the infertility center of a tertiary care hospital. A clear non-hematic follicular fluid was aspirated after the removal of eggs from the dominant follicles (>18mm) of each patient. Melatonin and E2 levels in each follicular sample were estimated by immune-chemiluminescence using commercially available kits. ALU-qPCR evaluated cfDNA levels in individual follicular fluid samples. Our study presented a significant and negative relationship between intra-follicular cfDNA and melatonin concentration (-0.541: P<0.001). Each individual follicle contains measurable copy number of cfDNA [mean: 1.85±2.98ng/µl (median; 1.86ng/µl (95% Cl: 0.96-2.87)]. In pregnant women cfDNA copy number was significantly decreased in follicular fluid samples(ff) aspirated from matured oocytes than in immature ones [p<0.01; ß = -0.42±0.49; median; 1.45ng/ml (95% Cl: 0.36-2.97) vs. 3.57ng/µl (95% Cl: 0.37-4.01) respectively. While melatonin concentration in ff samples corresponding to mature oocytes was significantly higher than in ff samples related to immature oocytes (p<0.001). Moreover, in pregnant women cfDNA level was significantly lower in ff samples related to oocytes which produces top-quality embryos versus low quality embryos [p<0.001; ß=1.81±0.91; median; 1.25ng/µl (95% Cl: 0.35-1.97)] vs. [(median; 3.65ng/ml (95% Cl: 1.23-6.36)] respectively. Likewise, in non-pregnant women melatonin levels were significantly decreased in ff samples related to embryos with high fragmentation rate (≥25%) than embryos with low fragmentation rate (<25%; p<0.001). Conclusively, this study indicates that Intra-follicular cfDNA and melatonin concentration possibly a new supplemental tool that supports to establish an advanced non-invasive early prognostic test for the patients undergoing IVF/ICSI procedure.

Poor ovarian response is associated with serum vitamin D levels and pro-inflammatory immune responses in women undergoing in-vitro fertilization.

Poor ovarian response (POR1) limits the success of infertility treatment modality. In this study, we aim to investigate if POR is associated with serum 25(OH) vitamin D (VD2) levels and pro-inflammatory immune responses in infertile women with a history of in-vitro fertilization and embryo transfer failures. A retrospective cross-sectional study included 157 women with IVF failures. Study patients were divided into four groups based on serum 25(OH)VD level and ovarian responses during the most recent IVF cycle; low VD (LVD3) with POR, LVD with normal ovarian response (NOR4), normal VD (NVD5) with POR, and NVD with NOR. Serum 25(OH)VD level, cellular- and auto-immunity, and metabolic parameters, including homocysteine and plasminogen activator inhibitor-1 were investigated. Peripheral blood CD56+ NK cell levels (%) and NK cytotoxicity were significantly higher in POR-LVD when compared to the other groups (P < 0.05, respectively). CD19 + B and CD19+/5+ B-1 cell levels were significantly higher in women with POR-LVD as compared with those of NOR-LVD and POR-NVD (P < 0.05, respectively). TNF-α/IL-10 producing Th1/Th2 cell ratio of POR-LVD was significantly higher than those of POR-NVD and NOR-NVD (P < 0.05 respectively). Peripheral blood homocysteine level of POR-LVD was significantly higher than those of NOR-LVD and POR-NVD (P < 0.05 respectively). We conclude that assessment of cellular and autoimmune abnormalities and metabolic factors, such as homocysteine should be considered in women with POR and LVD. VD and folic acid supplementation may be explored further as a possible therapeutic option for POR with immune and metabolic etiologies.

Ulmus minor bark hydro-alcoholic extract ameliorates histological parameters and testosterone level in an experimental model of PCOS rats.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common and multifactorial disease associated with female factor infertility. Ulmus minor bark (UMB) is one of the medicinal plants used in Persian folklore as a fertility enhancer. In the current study, we aimed to elucidate the effect of UMB hydro-alcoholic extract on histological parameters and testosterone condition in an experimental model of PCOS rats. METHODS: Thirty female rats were randomly divided into five groups: (1) control, (2) vehicle, (3) PCOS/50 mg [6 mg/kg dehydroepiandrosterone (DHEA) + 50 mg/kg UMB hydro-alcoholic extract], (4) PCOS/150 mg (6 mg/kg DHEA + 150 mg/kg UMB hydro-alcoholic extract), and (5) PCOS (6 mg/kg DHEA). All interventions were performed for 21 days. Afterwards, stereological analysis was done for determination of ovarian volume and follicle number. The serum level of testosterone was measured by ELISA kit. RESULTS: UMB hydro-alcoholic extract improved the total number of the corpus luteum in the treatment groups when compared to the PCOS group (p<0.05). PCOS/150 mg and PCOS/50 mg groups showed significantly lower total number of the primordial, primary, and secondary follicles as well as testosterone level compared to the PCOS group (p<0.05). The total number of antral follicles and volume of ovary did not differ significantly between groups. CONCLUSION: UMB extract may be an effective and good alternative in improving PCOS histo-logical and testosterone disturbances although further studies are warranted to confirm the safety of UMB plant in human.

Maternal Selenium, Copper and Zinc Concentrations in Early Pregnancy, and the Association with Fertility.

Trace elements such as zinc, copper, and selenium are essential for reproductive health, but there is limited work examining how circulating trace elements may associate with fertility in humans. The aim of this study was to determine the association between maternal plasma concentrations of zinc, copper, and selenium, and time to pregnancy and subfertility. Australian women (n = 1060) who participated in the multi-centre prospective Screening for Pregnancy Endpoints study were included. Maternal plasma concentrations of copper, zinc and selenium were assessed at 15 ± 1 weeks' gestation. Estimates of retrospectively reported time to pregnancy were documented as number of months to conceive; subfertility was defined as taking more than 12 months to conceive. A range of maternal and paternal adjustments were included. Women who had lower zinc (time ratio, 1.20 (0.99-1.44)) or who had lower selenium concentrations (1.19 (1.01-1.40)) had a longer time to pregnancy, equivalent to a median difference in time to pregnancy of around 0.6 months. Women with low selenium concentrations were also at a 1.46 (1.06-2.03) greater relative risk for subfertility compared to women with higher selenium concentrations. There were no associations between copper and time to pregnancy or subfertility. Lower selenium and zinc trace element concentrations, which likely reflect lower dietary intakes, associate with a longer time to pregnancy. Further research supporting our work is required, which may inform recommendations to increase maternal trace element intake in women planning a pregnancy.

Vitamin D and Obesity: Two Interacting Players in the Field of Infertility.

Obesity plays an important role in human fertility in both genders. The same is true for vitamin D, for which accumulating evidence from observational human studies suggests a key role for both male and female fertility. In the latter case, however, robust data from relevant interventional studies are currently lacking. It is also not clear whether obesity and vitamin D deficiency, besides their independent effect on human infertility, act in synergy. Several pathogenetic mechanisms may be proposed as a linkage between vitamin D deficiency and obesity, with respect to infertility. In any case, the independent contribution of vitamin D deficiency in obese infertile states needs to be proven in interventional studies focusing on either vitamin D supplementation in obese or weight loss strategies in vitamin D-deficient infertile patients.

Can Panax Ginseng protect against fertility disorders in hypothyroid female albino rats?

Hypothyroidism is an endocrine disorder due to decreased thyroid hormone production. This endocrine disorder significantly affects the menstrual cycle and fertility. The aim of this present study was to assess the efficacy of Panax ginseng, one of traditional Chinese medicine, in ameliorating the gonadal hormonal dysfunction and lowering oxidative stress accompanied with hypothyroidism in adult female albino rats. After confirming regularity of the oestrus cycle in the female rats in this study, hypothyroidism was induced by using daily 5.0 mg kg-1 oral dose of Neo-mercazole. The hypothyroid rats were randomly grouped into two groups; hypothyroid group (H): did not received any treatment, group II (H+G) was treated with Panax ginseng extract for one months after hypothyroidism induction. Another two groups were included in the study, a negative control group (Euthyroid group) and a positive control group; received Panax ginseng extract only. Hypothyroidism resulted in irregularity of oestrus cycle accompanied with decrease in luteinizing hormone (LH), follicular stimulating hormone (FSH) and estradiol (E2), while prolactin (PRL), progesterone (P) and testosterone (T) hormone were significantly elevated. Hypothyroidism elevated capsae-3 and 8OH-deoxy guanosine expression and increased secretion of corticosterone and ERK1/2. This study showed that Panax ginseng improved hypothyroid-induced deterioration in trophic and gonadal hormones through free radicals' scavenger.

Vitamin D Regulates Maternal T-Helper Cytokine Production in Infertile Women.

Vitamin D (VD) deficiency is associated with reproductive failure. However, the relationship between VD and maternal immunity remains unclear. We investigated the clinical efficacy of VD in maternal T-helper (Th) cytokines in 276 infertile women and examined for Th1 and Th2 cells based on the deficient, insufficient, and sufficient serum 25-hydroxyvitamin D3 (25[OH]VD) levels (<12, 12⁻30, and >30 ng/mL, respectively). Most infertile women had a low-level of VD (87.3%). Immunological tests of pre-/post-VD supplementation were performed in patients who were deficient and insufficient in VD. Of 23 patients, 11 (47.8%) exhibited sufficient VD levels after supplementation. Th1/Th2 cell ratio in patients with insufficient VD was significantly decreased after supplementation (p = 0.004). After supplementation, serum 25(OH)VD levels of the patients: 11 in the sufficient group showed significant decreases in Th1 cell level and Th1/Th2 cell ratio (p = 0.032 and 0.010, respectively), whereas no significant differences in Th1/Th2 cell ratio were recognized in the insufficient group. Furthermore, mid-luteal endometrial biopsies (n = 18) were processed for primary cultures and measured interferon [IFN]-γ and interleukin [IL]-4 in condition media. Decidualizing cultures with 1,25-dihydroxvitamin D3 (1,25[OH]2VD) decreased IFN-γ. Sufficient VD supplementation in women with insufficient VD may optimize maternal T-helper cytokines during pregnancy via rebalancing the Th1/Th2 cell ratio.

Content of fatty acids in a diet and the homocysteine levels in women with fertility disorders.

OBJECTIVES: Assessment of the effects of consumption of fatty acids on the homocysteine levels in women with fertility disorders. METHODS AND RESULTS: The study included 286 women at the age between 23 and 46 years (the mean 33.13±4.21 years) with a fertility disorders. We measured: levels of homocysteine [µmol/L] (n=171), body weight and height (n=286). Body mass index (BMI) was calculated. A diet was assessed by 3-day dietary food records method including one day of the weekend. The mean homocysteine (Hcy) levels were 10.02±2.98 µmol/L. Body weight excess was observed in 29.3% of subjects. The percentage of fatty acids in the total energy [%E] it was demonstrated that the mean rate of MUFAs and PUFAs was statistically significantly lower in diets of women with the homocysteine levels >15 µmol/L compared to the group with the Hcy <10 µmol/L. Based on the results of a correlation between the homocysteine levels and consumption of n-6 fatty acids and n-3 fatty acids it is possible to conclude that there are negative correlations observed indicating that higher consumption of these acids is associated with lower levels of homocysteine. CONCLUSION: Increased consumption of PUFAs, including α-linoleic acid, in a diet seems to be an important factor preventing from hyperhomocysteinemia.

Effect of serum vitamin D level on endometrial thickness and parameters of follicle growth in infertile women undergoing induction of ovulation.

In this paper, 153 infertile women undergoing induction of ovulation at an academic tertiary care centre were included in a cross-sectional study. Serum Vitamin D level was measured and the rate of clinical pregnancy (defined as a sonographic presence of FHR of an intrauterine gestational sac) and patient and cycle parameters were determined. The results showed that a correlation exists between endometrial thickness as well as the number of antral follicles and replete level of Vitamin D. Interestingly, the median level of these two parameters was of upmost level in the most replete tertile of serum Vitamin D level. There was no correlation between the serum level of Vitamin D and pregnancy rate. Vitamin D status was associated with endometrial thickness and number of antral follicles, but this study did not find a pivotal effect of serum Vitamin D level on pregnancy rate. Impact statement What is already known on this subject? Literature reviews have indicated that a Vitamin D deficiency is directly responsible for a reduced fertility and reproduction capacity. Women with higher level of Vitamin D in serum and follicular fluid are more likely to become pregnant. What do the results of this study add? This study, assessing the effect of serum level of Vitamin D on endometrial thickness and parameters of follicle growth in infertile women undergoing induction of ovulation showed that a correlation exists between endometrial thickness as well as the number of antral follicles and replete level of Vitamin D. It can be concluded that a replete Vitamin D status is associated with a better state of endometrial thickness and a number of antral follicles, but this study did not find a pivotal effect of serum Vitamin D level on the pregnancy rate. What are the implications of these findings for clinical practice and further research? If a relationship would be proved between Vitamin D deficiency and endometrial thickness and parameters of follicle growth it is possible that with prescribing supplemental Vitamin D as a relatively inexpensive and safe way along with the other more complex and costly infertility treatments, achieving the pregnancy would be easier.

Efficacy and safety of Ding-Kun-Dan for female infertility patients with predicted poor ovarian response undergoing in vitro fertilization/intracytoplasmic sperm injection: study protocol for a randomized controlled trial.

BACKGROUND: Women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) who have a predicted poor ovarian response (POR) present a challenge for reproductive medicine specialists. Traditional Chinese medicine (TCM) is commonly used in China for such patients, in the belief that it will improve the ovarian response and ultimately increase pregnancy rates. However, there is a lack of high-quality evidence about the effect of TCM on improving ovarian response in such patients. The purpose of this study is to evaluate ongoing viable pregnancy rate at 12 weeks' gestation and related indicators of ovarian response in fertile women who have a predicted poor ovarian response having immediate versus delayed IVF/ICSI after 3 months of Ding-Kun-Dan (DKD) pre-treatment. METHODS/DESIGN: This study is a multicenter, randomized controlled, parallel-group, phase III, superiority clinical trial. Two hundred and seventy-eight eligible female infertility patients with POR will be included in the study and randomly allocated into an immediate treatment group and a DKD group in a 1:1 ratio. Both groups will receive IVF or ICSI as a standard treatment while in the DKD group, a commercially available Chinese medicine, DKD, will be administrated for 3 months before the IVF/ICSI cycle starts. The primary outcome of the study is the ongoing pregnancy rate at 12 weeks' gestation. The secondary outcomes include total gonadotropin dosage, duration of stimulation, estradiol (E2) and progesterone (P) levels on human chorionic gonadotropin (hCG) trigger day, cycle cancellation rate, number of oocytes retrieved, high-quality embryo rate, biochemical pregnancy rate, the change of serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and E2 levels and all side effects, safety outcomes, and any adverse events. The protocol was approved by the Ethics Committee of the First Teaching Hospital of Tianjin university of TCM (approval no. TYLL2017[K] 004). DISCUSSION: IVF/ICSI is increasingly used to treat couples desiring a baby. Many of these women will have poor ovarian function. In China, DKD is commonly used for these patients prior to undergoing IVF/ICSI. There is no effective treatment for poor ovarian response in Western medicine currently. It is important, therefore, to undertake this randomized control trial to determine whether DKD is effective or not. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-IOR-17011697 . Registered on 19 June 2017.

Evaluating the effects of administration of 25-hydroxyvitamin D supplement on serum anti-mullerian hormone (AMH) levels in infertile women.

The aim of the study was to evaluate the effects of administration of 25-hydroxyvitamin D [25(OH) D] on serum antimullerian hormone (AMH) levels in infertile women. The study was performed as a non-randomized clinical trial on 30 infertile women who had low serum level of both 25(OH) D and anti-mullerian hormone. Vitamin D was prescribed 50,000 IU weekly for up to three months for all eligible participants. Serum levels of both 25(OH) D and AMH have increased significantly after treatment with 25(OH) D. There was a significant correlation between serum levels of 25(OH) D after treatment with AMH (p = .029, OR = 2.9, CI 95% = 2.7-5.5). Mean AMH level after treatment was higher in women with sufficient 25(OH) D, than women with insufficient 25(OH) D (1.048 ± 0.644 vs. 0.513 ± 0.284 ng/ml), which shows a significant difference (p = .043). Also, after treatment, in women with mean AMH level of >0.7 ng/ml (19 women), mean level of 25(OH) D was higher than in women with mean AMH level of <0.7 ng/ml (11 women) (59.332 ± 21.751 vs. 38.881 ± 17.281 ng/ml, p = .013). This means that higher levels of 25(OH) D are accompanied with higher levels of AMH. In conclusions with administration and increasing the amount of vitamin D serum levels, the serum levels of AMH have increased.