A retrospective study of ovarian tissue cryopreservation in female patients with hematological diseases for fertility preservation.

PURPOSES: To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases. METHODS: We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized. RESULTS: A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81 years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12 ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24 IU/L in examination before OTC. FSH was greater than 10.0 IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 109/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 109/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 109/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 109/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58 min, and the average blood loss was 32.1 ± 41.6 mL. The maximum blood loss was 200 mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 109/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20 days and began HSCT within 30 days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3 years after HSCT and resumed regular menstruation 6 months after OTT. CONCLUSIONS: Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.

Kuntai capsule for the treatment of diminished ovarian reserve: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Diminished ovarian reserve (DOR) results in reduced fertility. Kuntai capsule, a Chinese patent medicine, which can nourish the heart and kidneys, has shown promising efficacy in its treatment. However, there is no enough clinical evidence to confirm the efficacy and safety of Kuntai capsule. AIM OF THE STUDY: This review aims to evaluate Kuntai capsule's potential benefits and detriments for diminished ovarian reserve. MATERIALS AND METHODS: Databases namely China National Knowledge Infrastructure, WANFANG Database, Chinese Science and Technology Journal Database, Chinese Biomedical Literature Database, PubMed, Cochrane Library, and Embase were searched from their inception to July 2023. We included randomized controlled trials (RCTs) comparing Kuntai capsule to hormone therapy (HT) and Kuntai capsule in combination with HT to HT alone for DOR treatment. The risk of bias was evaluated using RoB 1.0. A Meta-analysis was performed using RevMan 5.4 software. The primary outcomes were antral follicle count (AFC) and serum anti-Müllerian hormone (AMH), secondary outcomes were follicle-stimulating hormone (FSH) and adverse reactions. RESULTS: A Meta-analysis of 12 randomized controlled trials (RCTs), encompassing a total of 905 DOR patients was conducted. The results indicated that the combination of Kuntai capsule with HT exhibited superior efficacy in enhancing AFC (MD = 1.34, 95% CI [0.96,1.72]) and AMH levels (MD = 1.09 (ng/mL) 95% CI[0.80,1.38]), Kuntai capsule demonstrated improvements in AFC (MD = 0.65, 95% CI [0.48,0.83]) in DOR patients compared to HT alone. CONCLUSIONS: Based on the available results, the combination of Kuntai capsule with HT appears to improve the AFC, AMH and FSH levels of DOR patients. Kuntai capsule alone appears to improve the AFC and FSH levels of DOR patients. However, included trials had methodological quality issues, further standardized research is required.

Exposure to heavy metallic and trace essential elements and risk of diminished ovarian reserve in reproductive age women: A case-control study.

The associations between metallic elements and ovarian reserve function have remained uncertain yet. In this case-control study, we involved 149 women with diminished ovarian reserve (DOR) and 151 women with normal ovarian reserve, and assessed the levels of six heavy metallic (Cr, Cd, As, Hg, Pb, and Mn) and seven trace essential (Se, Fe, Zn, Co, Mo, Cu, I) elements in their follicular fluid with inductively coupled plasma mass spectrometry. Associations were examined with logistic regressions and Bayesian kernel machine regression (BKMR). As a result, we found that the medium and the highest tertiles of Pb were significantly associated with an increased likelihood of DOR compared to the lowest tertile, while the medium or/an the highest tertiles of Cu, I, and Fe showed significantly lower likelihoods of DOR compared to the lowest tertiles. Cu and Pb showed significantly non-linear associations with ovarian reserve markers such as follicle-stimulating, anti-mullerian hormone levels, and antral follicle count. With the rising overall concentrations of heavy metals, the likelihood of DOR increased although not significant. There was a trend of a "U-shaped" association across the whole concentration range of trace essential elements and the likelihood of DOR. Our study revealed that avoiding heavy metallic elements and properly supplementing trace essential elements are conducive to ovarian function.

The role of anti-Mullerian hormone and other correlates in patients with polycystic ovary syndrome.

BACKGROUND: Anti-Müllerian hormone (AMH) has recently emerged as a promising biomarker for the detection of polycystic ovarian morphology. In polycystic ovary syndrome (PCOS), an elevated level of AMH has been suggested to add value to the Rotterdam criteria in cases of diagnostic uncertainty. In this study, we evaluated the correlation between AMH and PCOS, and the potential role of AMH in PCOS diagnosis. METHODS: A case-control study was performed on a total of 200 females, 100 of which were diagnosed with PCOS as per Rotterdam revised criteria (2003) and 100 as the control (non-PCOS group). Patient medical records were therefore retrieved for clinical, biochemical and ultrasound markers for PCOS diagnosis. Sensitivity, specificity, area under receiver operating characteristic (AUROC) curve, and multivariate linear regression models were applied to analyze our data. RESULTS: Mean serum levels of LH and AMH, and LH/FSH ratio were significantly different between compared groups. In the PCOS group, the mean serum AMH level was 6.78 ng/mL and LH/FSH ratio was 1.53 while those of controls were 2.73 ng/mL and 0.53, respectively (p < .001). The most suitable compromise between 81% specificity and 79% sensitivity was obtained with a cutoff value of 3.75 ng/mL (26.78 pmol/L) serum AMH concentration for PCOS prediction, with an AUROC curve of 0.9691. CONCLUSION: Serum AMH cutoff level of 3.75 ng/mL was identified as a convenient gauge for the prediction of PCOS and an adjuvant to the Rotterdam criteria.

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.

Low Anti-Mullerian Hormone Levels Are Associated with the Severity of Anxiety Experienced by Healthcare Professionals During the COVID-19 Pandemic.

The objective of this study is to investigate a possible correlation between anxiety status and anti-Mullerian hormone (AMH) levels among healthcare professionals who provide medical care directly to COVID-19-positive patients during the recent pandemic. Fifty-two healthcare professionals (nurses, midwives, and residents) who provide medical care directly to COVID-19-positive patients in inpatient clinics or intensive care units were enrolled in this study. Serum AMH levels were analyzed to reflect ovarian reserve. The Beck Anxiety Inventory (BAI) and the State-Trait Anxiety Inventory (STAI-S and STAI-T, respectively) were completed by participants to assess their anxiety status. A linear regression model with participant age as the constant variable was applied to analyze the relationship between inventory scale scores and AMH levels. P-values less than 0.05 were considered statistically significant. The mean AMH value was significantly lower for the participants in the moderate/severe anxiety group compared to the minimal/mild anxiety group (p = 0.007). A linear regression analysis revealed a significant negative correlation between AMH levels and both BAI (B = -0.030, standard error = 0.010, p = 0.004) and STAI-S and STAI-T scores when age was controlled (both p = 0.003). The severity of anxiety experienced during the recent COVID-19 pandemic among healthcare professionals, who provide medical care directly to COVID-19-positive patients, is found to be related to low AMH levels.

Efficacy and safety of Zi Gui Nv Zhen® capsules used in TCM for fertility preservation in patients with diminished ovarian reserve.

OBJECTIVE: To evaluate for the first time whether Zi Gui Nv Zhen® capsules (ZGNZC), until now used in traditional Chinese medicine (TCM) for menopausal complaints, can increase the fertility of Chinese women with diminished ovarian reserve (DOR). METHODS: Prospective, randomized, open-labeled 3-monthly study; 109 DOR patients (aged 20-40 years) receiving either ZGNZC (experimental group, n = 75) or not (control group, n = 34). Main outcomes: markers for ovarian function, thickness/type of the endometrium during ovulation, and pregnancy rate. Between-group analysis (A) comparing experimental vs. control group and within-group analysis (B) comparing data at baseline and after study in each of both groups. RESULTS: (A) Between-group-analysis: patients with ZGNZC had a higher endometrium thickness (0.75 vs. 0.62; p<.05) and higher anti-Müllerian hormone (AMH, 0.50 vs. 0.40; p<.05) than control group. Pregnancy rates were higher in the experimental than the control group (26.7% vs. 14.7%; n.s.). (B) Within-group-analysis: ZGNZC decreased levels of follicle-stimulating hormone (FSH, 11.42 vs. 8.69), increased estradiol-levels (E2, 56.09 vs. 73.36), and type A endometrium rates (5.3% vs. 39.7%) (all p< .05) and increased antral follicle count (AFC, 2 vs. 3). All hepato-renal biomarkers remained within the norm. The tolerability was good. There were no adverse events. CONCLUSIONS: In women with DOR who wish to conceive, three months' application of ZGNZC can improve ovarian function and oocyte quality by adjusting the neuroendocrine system, can improve endometrial properties and proliferation, necessary for a healthy pregnancy, and increased the clinical pregnancy rate in our prospective randomized observational study.

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.

Effect of samul-tang on female fertility via RAS signaling pathway in ovaries of aged mice.

Samul-tang (SM), a traditional herbal medicine, is used to treat age-related human conditions, such as infertility and menstrual irregularities. The mechanism underlying the role of SM in ovary function needs elucidation. In this study, the influence of SM administration on the ovarian reserve of aged mice was investigated. Female BALB/c mice (8 and 40 weeks-old) were administered with distilled water (young or old group) or SM for 4 weeks. SM administration prevented age-related ovarian follicle loss in mice. Quality of oocytes and blastocysts were enhanced in SM-administrated mice compared to those of non-treated old mice. Further, SM administration increased the pregnancy rate and number of litters. SM triggered changes in aging-related genes that are linked to the RAS-mediated pathway. Thus, we demonstrate that SM can be used to increase the oocyte yield in aged women, potentially improving age-related cognitive decline in the ovarian reserve.

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.

Evaluation of expression and serum concentration of anti-Mullerian hormone as a follicle growth marker following consumption of fennel and flaxseed extract in first-generation mice pups.

BACKGROUND: The aim of the present study was to assess the expression and serum level of AMH in first-generation female mice pups following fennel and flaxseed consumption. METHODS: Twenty pregnant NMRI mice were allocated into four groups including control (CTL), fennel (FV), flaxseed (LU) and FV+ LU. Sixty-four female offsprings after lactation period, received the same regimen as their mothers for 56 and 240 days. The ovarian follicles development, serum concentration of AMH, as well as gene and protein expression of AMH were evaluated in the female offsprings at post-natal day 56 (PND56) and 240 (PND240). RESULTS: The number of total growing follicles were raised in the FV group in compression to the all experimental groups. In contrast, LU group showed a marked decrease in their numbers. The highest level of serum AMH was seen in the FV-diet mice, whereas LU negatively affected it. The expression level of AMH also increased in the FV and FV + LU groups, while a reduction was observed in the LU group. As well, IHC data showed that the number of AMH-positive cells in almost ovarian follicles of FV and FV + LU-treated mice was in compared to those of the LU group. CONCLUSIONS: The overall effect of fennel treatment (alone and in combination with flaxseed) on ovary might be maintain primordial follicle storage through increased expression and serum level of AMH.

Effects of Vitamin D Supplementation on Surrogate Markers of Fertility in PCOS Women: A Randomized Controlled Trial.

Vitamin D (VD) might play an important role in polycystic ovary syndrome (PCOS) and female fertility. However, evidence from randomized controlled trials (RCT) is sparse. We examined VD effects on anti-Müllerian hormone (AMH) and other endocrine markers in PCOS and non-PCOS women. This is a post hoc analysis of a single-center, double-blind RCT conducted between December 2011 and October 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. We included 180 PCOS women and 150 non-PCOS women with serum 25-hydroxyvitamin D (25(OH)D) concentrations <75 nmol/L in the trial. We randomized subjects to receive 20,000 IU of VD3/week (119 PCOS, 99 non-PCOS women) or placebo (61 PCOS, 51 non-PCOS women) for 24 weeks. Outcome measures were AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, dehydroepiandrosterone sulfate, and androstenedione. In PCOS women, we observed a significant treatment effect on FSH (mean treatment effect 0.94, 95% confidence interval [CI] 0.087 to 1.799, p = 0.031) and LH/FSH ratio (mean treatment effect -0.335, 95% CI -0.621 to 0.050, p = 0.022), whereas no significant effect was observed in non-PCOS women. In PCOS women, VD treatment for 24 weeks had a significant effect on FSH and LH/FSH ratio but no effect on AMH levels.

The effect of selenium and vitamin E supplementation on anti-Mullerian hormone and antral follicle count in infertile women with occult premature ovarian insufficiency: A randomized controlled clinical trial.

OBJECTIVE: Increased accumulation of reactive oxygen species (ROS) in the process of oogenesis is one of the most well known causes of ovarian insufficiency and decreased ovarian reserve. Selenium and vitamin E as cofactors of glutathione peroxidase plays an important role in the removal of ROS in the ovary. We evaluated the effects of selenium and vitamin E supplementation on anti-Mullerian hormone (AMH) index and antral follicle count (AFC) (primary outcomes) and mean ovarian volume (MOV) and side effects of these supplements (secondary outcome) in infertile women with occult premature ovarian insufficiency (OPOI). METHODS: 70 patients were allocated into the control and treatment groups through block randomization method. 35 women in the treatment group received 200 ng selenium and 400IU vitamin E and 35 women in the control group received placebo for a total of 90 days. AMH index, AFC and mean ovarian volume (MOV) were investigated in both groups after 12 months of study. RESULT: There was no significant difference between groups before intervention in AMH (Mean difference: -0.08; 95% CI: -0.20 to.08; p=0.33), AFC (-0.71; 95%CI: -1.44 to -0.01; p=0.05) and MOV (-0.55; 95% CI: -0.85 to -0.24; p=0.001). There was a significant increase in AMH (mean difference: 0.59; 95% CI: 0.48 to 0.71; p<0.001), AFC (5.08; 95% CI: 4.36 to 5.08; p<0.001) and MOV (2.17; 95% CI: 1.87 to 2.47; p<0.001) in selenium + vitamin E group compared to placebo group 12 months after intervention. These supplements had no side effects. CONCLUSION: Supplementation with selenium and vitamin E can increase AMH, AFC and MOV in women with OPOI.

Vitamin D and Polycystic Ovary Syndrome: a Narrative Review.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders of reproductive age women and contributes to metabolic dysfunctions including insulin resistance (IR) and dyslipidemia. Vitamin D is a steroid hormone, which is involved in calcium metabolism and bone structure and has a potential role in the prevention of many illnesses, including cancers, autoimmune disorders, hypertension, diabetes, and obesity. Recently, it has been reported that vitamin D deficiency was a common complication of PCOS and vitamin D status was associated with reproductive ability, metabolic alterations, and mental health of PCOS patients. This review summarizes the advances between vitamin D status and the pathophysiological process of PCOS. Vitamin D level was negatively associated with serum androgen level. Vitamin D treatment could reduce serum androgen and anti-MüllerianHormone (AMH) levels, and decrease endometrial thickness, which resulted in improvement of menstrual cycle and folliculogenesis of PCOS patients. Moreover, vitamin D concentrations were negatively correlated with parameters of IR and body fat mass. Vitamin D supplementation has beneficial effects on IR and lipid metabolism. In addition, a positive of vitamin D on mental health of PCOS patients was proposed. Understanding the relationship between vitamin D status and the symptoms of PCOS patients is of great clinical significance to treat and prevent the progression of PCOS.

A comparison of the efficacy and safety of complementary and alternative therapies for premature ovarian insufficiency: A protocol for network meta-analysis.

BACKGROUND: With the increase in the incidence of premature ovarian insufficiency (POI) over the years, the ovarian function has become one of the integral aspects of research in reproductive medicine today. POI seriously affects the physical and mental health of women, especially reproductive health. Studies show both complementary and alternative therapies to be effective in treating POIs. However, consistency in conclusions is still far-fetched. In light of this, we will carry out a study to evaluate the effectiveness and safety of complementary and alternative therapies for POIs. We therefore develop a study protocol for a proposed network meta-analysis (NMA) and systematic review on POI. METHODS: The following electronic bibliographic database will be searched: VIP database, Wanfang database, Chinese National Knowledge Infrastructure (CNKI), The Cochrane Library, PubMed, EMBASE and Web of Science from inception till 31 December 2019. A search at the World Health Organization (WHO) International Clinical Trials Registry Platform will also be done. Subsequently, the searched data will undergo independent screening, retrieving, and risk of bias assessment by 2 reviewers. Analysis will be performed on included studies using the NMA technique. Next, the primary outcomes will be compared using ADDIS 1.16.5 and Stata 15.0. RESULTS: The safety and effectiveness of alternative and complementary therapies used in the treatment of POI will be compared and evaluated. CONCLUSION: This work will provide high-quality evidence for clinicians in the field to build on for best practices in effective interventions (complementary and alternative therapies) for POI. ETHICS AND DISSEMINATION: This NMA is a secondary research which based on some previously published data. Therefore, the ethical approval was not necessary. PROSPERO REGISTRATION NUMBER: CRD42020163873.

The Association between Vitamin D and Anti-Müllerian Hormone: A Systematic Review and Meta-Analysis.

Accumulating evidence from animal and human studies indicates a role for vitamin D in female reproductive physiology, and numerous clinical studies have suggested its potential benefit for various aspects of human reproduction. Anti-Müllerian hormone (AMH) is an ovarian biomarker that plays an important role in folliculogenesis. It is the most sensitive ovarian reserve marker and is widely used clinically in reproductive medicine. While initial studies have suggested that vitamin D may be associated with ovarian reserve markers, including AMH, evidence has been conflicting. Currently, there is considerable debate in the field whether vitamin D has the capacity to influence ovarian reserve, as indicated by the AMH level. The current systematic review aims to evaluate and summarize the available evidence regarding the relationship between vitamin D and AMH. In total, 18 observational studies and 6 interventional studies were included in this systematic review. Cross-sectional studies have reported largely discrepant findings regarding an association between serum vitamin D and AMH levels, which are likely due to the heterogeneity in study populations, as well as the apparently complex relationship that may exist between vitamin D and AMH. However, meta-analysis of interventional studies performed herein that examined the effects of vitamin D supplementation on serum AMH levels indicates a cause-effect relationship between vitamin D and AMH, the direction of which appears to depend on a woman's ovulatory status. Serum AMH was significantly decreased following vitamin D supplementation in polycystic ovarian syndrome (PCOS) women (standardized mean difference (SMD) -0.53, 95% CI -0.91 to -0.15, p < 0.007), while it was significantly increased following vitamin D supplementation in ovulatory women without PCOS (SMD 0.49, 95% CI 0.17 to 0.80, p = 0.003). In conclusion, the results of this systematic review demonstrate that the relationship between vitamin D and AMH is a complex one, and large, randomized trials of vitamin D supplementation focusing on different vitamin D status ranges are necessary to gain more insight into the nature of this relationship and the potential benefit of vitamin D to female reproduction in general.

Investigation of the effects of vitamin D treatment on the ovarian AMH receptors in a polycystic ovary syndrome experimental model: an ultrastructural and immunohistochemical study.

The aim of this study was to demonstrate the effects of vitamin D treatment on ultrastructural changes and AMHR2 expression in the ovary in PCOS rat model. A total of 24 female prepubertal rats were divided into 3 groups. In group 1, sesame oil was injected and used as control group. In group 2, PCOS was created by the injection of 6 mg/kg/day DHEA. In group 3, PCOS was created and 120 ng/100 g 1,25 (OH)2D3 treatment was performed. At the end of the 28th day, the blood samples were collected. The ovarian tissues were obtained for electron microscopic and immunohistochemical examinations. Serum AMH, testosterone, FSH, LH levels and LH/FSH ratios were higher in the PCOS group compared to the control group and decreased in the treatment group compared to the PCOS group. AMHR2 expression was increased in atretic and premature luteinizate antral follicles in the PCOS group compared to the control group, and decreased in the treatment group compared to the PCOS group. PCOS group electron micrographs showed degenerative changes in developing follicles, cystic follicles characterised with granulosa cell layer attenuation and thickening of the theca cell layer, and lipid accumulation in the interstitial cells. Structural changes observed in the PCOS group were improved with vitamin D treatment. As a result, there is an interaction between PCOS, AMH serum levels and AMHR2 in the ovarian follicles. Vitamin D has a positive effect on hormonal and structural changes in the PCOS group. We concluded that vitamin D supplementation may be beneficial in PCOS patients.

Influence of Βeta-Cryptoxanthin Supplementation on Ovarian Reserve and Fertility Status in Aged Wistar Rats.

Previous observational studies have suggested that ß-cryptoxanthin, a micronutrient present in yellow and orange fruit and vegetables, may help delay the onset of menopause. Given the widespread social trend of delaying pregnancy, the possibility that ß-cryptoxanthin supplementation may delay age-related loss of fertility and onset of menopause is of significant interest. In a parallel study, either saline or ß-cryptoxanthin (5 µg/kg rat/day) was delivered to Wistar albino rats via an osmotic pump from 4 to 7 months of age. All control and ß-cryptoxanthin-treated dams were fertile at 7 months of age, with no differences in litter size, sex ratio, or pup viability at the time of mating at 7, 9, 11, and 15 months of age (p ≥ .05 for all). As expected, over time there was a pronounced decrease in litter size and serum anti-Müllerian hormone (AMH), but with no significant differences between the two groups at any time point. Overall, there was a positive correlation between litter size and AMH (r = 0.324, p = .012), confirming a link between this serum marker of ovarian reserve status and fertility potential. At 16 months, bilateral oophorectomies were performed at necropsy, before conducting follicle density assessments of ovarian reserve. The total number and stage of follicle development were similar between the ß-cryptoxanthin and control groups (13.8 ± 3.2 cf 10.2 ± 4.8, respectively, p > .05). ß-cryptoxanthin supplementation for 3 months early in reproductive life was not effective in delaying ovarian senescence or enhancing fertility in rats later in life, contrary to the association suggested by observational studies in humans.

The influence of maternal androgen excess on the male reproductive axis.

Prenatal androgen excess is suspected to contribute to the development of polycystic ovary syndrome (PCOS) in women. Evidence from preclinical female animal models links maternal androgen excess with the development of PCOS-like features and associated alterations in the neuronal network regulating the reproductive axis. There is some evidence suggesting that maternal androgen excess leads to similar reproductive axis disruptions in men, despite the critical role that androgens play in normal sexual differentiation. Here, the specific impact of maternal androgen excess on the male hypothalamic-pituitary-gonadal axis was investigated using a prenatal androgenization protocol in mice shown to model PCOS-like features in females. Reproductive phenotyping of prenatally androgenised male (PNAM) mice revealed no discernible impact of maternal androgen excess at any level of the reproductive axis. Luteinising hormone pulse characteristics, daily sperm production, plasma testosterone and anti-Müllerian hormone levels were not different in the male offspring of dams administered dihydrotestosterone (DHT) during late gestation compared to controls. Androgen receptor expression was quantified through the hypothalamus and identified as unchanged. Confocal imaging of gonadotropin-releasing hormone (GnRH) neurons revealed that in contrast with prenatally androgenised female mice, PNAM mice exhibited no differences in the density of putative GABAergic innervation compared to controls. These data indicate that a maternal androgen environment capable of inducing reproductive dysfunction in female offspring has no evident impact on the reproductive axis of male littermates in adulthood.

The effect of acupuncture on anti-mullerian hormone and assisted reproduction outcome in Polycystic Ovary Syndrome patients undergoing in vitro fertilization.

OBJECTIVES: To evaluate the effect of acupuncture at follicular phase of menstrual cycle on anti-mullerian hormone levels in patients with polycystic ovary syndrome undergoing in-vitro fertilisation and to see its impact on assisted reproduction outcome. METHODS: The prospective, randomised, controlled trial was conducted from March 2011 to July 2012 at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. In the center, the patients randomly chose odd or pair number, the patients with odd numbers classified as an interventional group and the patients with paired numbers as non-interventional group. Infertile polycystic ovary syndrome patients aged 20-40 years were enrolled from the hospital's Assisted Reproduction Centre from March 2011 to July 2012. The patients were randomised into two groups, with one receiving follicular phase acupuncture for 30-40 minutes according to the principles of traditional Chinese medicine, and the other group not getting subjected to acupuncture. Serum and follicular anti-mullerian hormone concentration were determined. RESULTS: Of the 102 patients, 33(32.4%) were in the intervention group, while 69(67.6%) were in the control group. There was no significant effect of acupuncture on serum and follicular fluid anti-mullerian hormone levels in the intervention group compared to the control group (p>0.05). Serum progesterone and estradiol levels on the day of giving human chorionic gonadotrophin, as well as serum progesterone and estradiol levels on the day of oocytes pick-up were significantly lower in the intervention group (p<0.05). Number of embryos transferred, clinical and ongoing pregnancy rates were significantly higher in the intervention group (p<0.05) with a significant decrease of ovarian hyper-stimulation syndrome rate in the intervention group (p<0.05). CONCLUSIONS: Follicular phase acupuncture was found to have a positive effect for polycystic ovary syndrome patients undergoing in-vitro fertilisation, but it had no effect on anti mullerian hormone concentrations.