OBJECTIVE: To compare the ovarian reserve and the results of infertility treatment, as well as to investigate the relapse rate in the first year after the assisted reproductive technology (ART) cycle in patients with multiple sclerosis (MS) referred to Royan Institute.
METHODS: This retrospective study was carried out to evaluate all women diagnosed with MS and referred to Royan Institute for assessment and treatment of possible infertility between 2011 and 2022. The control group consisted of randomly selected healthy women with tubal factor infertility who were referred for treatment during the same time period and matched in terms of age. A comparison was made between groups in terms of ovarian reserve and infertility treatment outcomes. Additionally, patients with MS who met the criteria were monitored via telephone to evaluate the symptoms, disability and relapse rate both pre- and post-ART.
RESULTS: Over the course of a decade, the database documented a total of 60 cases diagnosed with MS. Upon examination of the records, it was found that in 27 patients only admission was done without any hormonal assessment or infertility treatment cycle and 5 patients proceeded with the intrauterine insemination cycle. Eventually, 28 women with MS underwent the ART cycle and all of them were treated with interferon beta, glatiramer acetate, or some oral disease modifying therapies. No statistically significant difference in terms of the basal levels of luteinizing hormone, follicle-stimulating hormone and anti-Müllerian hormone was found between the MS and control groups (P > 0.05). Two groups were comparable in terms of menstrual status. The study revealed that both groups exhibited similarities in terms of the controlled ovarian stimulation protocol and duration, the dosage of gonadotropin administered, as well as the ovarian response type, clinical pregnancy rate, and live birth rate (P > 0.05). After follow up, only 2 patients (9.5%) reported relapse of symptoms within one year after ART.
CONCLUSIONS: The ovarian reserve and ovarian stimulation cycle and pregnancy outcomes following the ART cycle in MS patients were similar to the age-matched control group. The relapse rate of multiple sclerosis did not show a significant increase within a year following the ART cycle.

UNASSIGNED: To quantitatively evaluate the effect of coenzyme Q10 (CoQ10) pretreatment on outcomes of IVF or ICSI in women with diminished ovarian reserve (DOR) based on the existing randomized controlled trials (RCTs).
UNASSIGNED: Nine databases were comprehensively searched from database inception to November 01, 2023, to identify eligible RCTs. Reproductive outcomes of interest consisted of three primary outcomes and six secondary outcomes. The sensitivity analysis was adopted to verify the robustness of pooled results.
UNASSIGNED: There were six RCTs in total, which collectively involved 1529 participants with DOR receiving infertility treatment with IVF/ICSI. The review of available evidence suggested that CoQ10 pretreatment was significantly correlated with elevated clinical pregnancy rate (OR = 1.84, 95%CI [1.33, 2.53], p = 0.0002), number of optimal embryos (OR = 0.59, 95%CI [0.21, 0.96], p = 0.002), number of oocytes retrieved (MD = 1.30, 95%CI [1.21, 1.40], p < 0.00001), and E2 levels on the day of hCG (SMD = 0.37, 95%CI [0.07, 0.66], p = 0.01), along with a reduction in cycle cancellation rate (OR = 0.60, 95%CI [0.44, 0.83], p = 0.002), miscarriage rate (OR = 0.38, 95%CI [0.15, 0.98], p = 0.05), total days of Gn applied (MD = -0.89, 95%CI [-1.37, -0.41], p = 0.0003), and total dose of Gn used (MD = -330.44, 95%CI [-373.93, -286.96], p < 0.00001). The sensitivity analysis indicated that our pooled results were robust.
UNASSIGNED: These findings suggested that CoQ10 pretreatment is an effective intervention in improving IVF/ICSI outcomes for women with DOR. Still, this meta-analysis included relatively limited sample sizes with poor descriptions of their methodologies. Rigorously conducted trials are needed in the future.

UNASSIGNED: In women, exposure to endocrine disrupting chemicals might accelerate the depletion of the ovarian reserve and might be associated with accelerative reproductive aging and fertility. We examined the longitudinal associations of exposure to bisphenols and phthalates with anti-Müllerian hormone concentrations.
UNASSIGNED: Pregnant women of 18 years or older that resided in Rotterdam between 2002 and 2006 were eligible for participation in this longitudinal prospective cohort study. We measured urinary bisphenol and phthalate concentration at three time-points in pregnancy among 1405 women, of whom 1322 women had serum Anti-Müllerian Hormone (AMH) measurements 6 and/or 9 years postpartum. We performed linear regression models to assess the association of urinary bisphenol and phthalate metabolites with AMH after 6 and 9 years, and linear mixed-effect model to assess the association with AMH over time. Models were adjusted for sociodemographic and lifestyle factors.
UNASSIGNED: In our multivariable linear regression models we observed associations of higher urinary pregnancy-averaged mono-isobutyl phthalate (mIBP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and monobenzyl phthalate (mBzBP) with lower serum AMH after both 6 and 9 years. However, these associations did not remain after adjustment for multiple testing. No significant associations of bisphenol A with AMH were present in our study sample. In our linear mixed-effects models, higher mIBP, mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mEOHP, and mBzBP were associated with lower overall AMH levels (differences -0.07 (95% CI -0.13, -0.02), -0.09 (-0.15, -0.02), -0.08 (95% CI -0.14, -0.02), and -0.08 (-0.13, -0.03) μg/L per doubling in mIBP, mEHHP, mEOHP, and mBzBP respectively) (all False Discovery Rate adjusted p-values < 0.05).
UNASSIGNED: We identify decreases in indices of ovarian reserve in relationship to prenatal phthalate exposures. Studies are needed replicating our results among large multi-ethnic non-pregnant populations and assessing transgenerational effects of exposure on ovarian reserve.
UNASSIGNED: This study was supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organisation for Health Research and Development, the European Research Council, the Dutch Heart Foundation, the Dutch Diabetes Foundation, the European Union\'s Horizon 2020 Research and Innovation Program, the National Institutes of Health, Ansh Labs Webster, and the Royal Netherlands Academy of Arts and Sciences.

The COVID-19 pandemic caused by SARS-CoV-2 has presented numerous health challenges, including long-term COVID, which affects female reproductive health. This review consolidates the current research on the impact of SARS-CoV-2 on the menstrual cycle, ovarian function, fertility, and overall gynecological health. This study emphasizes the role of angiotensin-converting enzyme receptors in viral entry and the subsequent tissue-specific pathological effects. It also explores the potential influence of long COVID on hormonal balance and immune responses, contributing to menstrual irregularities and impaired ovarian function. The findings indicate a higher prevalence of long-term COVID-19 among women, highlighting the substantial implications for reproductive health and the need for sex-sensitive longitudinal studies. Enhanced surveillance and targeted research are essential to develop effective interventions that prioritize women\'s reproductive well-being following SARS-CoV-2 infection. This review advocates for a sex-informed approach to ongoing COVID-19 research and healthcare strategies, aiming to provide up-to-date and pertinent data for healthcare providers and the general public, ultimately improving outcomes for females affected by long COVID.

Reproductive aging not only affects the fertility and physical and mental health of women but also accelerates the aging process of other organs. There is an urgent need newfor novel mechanisms, targets, and drugs to break the vicious cycle of mitochondrial dysfunction, redox imbalance, and germ cell apoptosis associated with ovarian aging. Autophagy, recognized as a longevity mechanism, has recently become a focal point in anti-aging research. Although mitophagy is a type of autophagy, its role and regulatory mechanisms in ovarian aging, particularly in age-related ovarian function decline, remain unclear. Nerve growth factor inducible gene B (Nur77) is an early response gene that can be stimulated by oxidative stress, DNA damage, metabolism, and inflammation. Recent evidence recommends that decreased expression of Nur77 is associated with age-related myocardial fibrosis, renal dysfunction, and Parkinson\'s disease; however, its association with ovarian aging has not been studied yet. We herein identified Nur77 as a regulator of germ cell senescence, apoptosis, and mitophagy and found that overexpression of Nur77 can activate mitophagy, improve oxidative stress, reduce apoptosis, and ultimately enhance ovarian reserve in aged mice ovaries. Furthermore, we discovered an association between Nur77 and the AKT pathway through String and molecular docking analyses. Experimental confirmation revealed that the AKT/mTOR signaling pathway is involved in the regulation of Nur77 in ovarian function. In conclusion, our results suggest Nur77 as a promising target for preventing and treating ovarian function decline related to reproductive aging.

Diminished ovarian reserve (DOR) is associated with reduced fertility and poor reproductive outcomes. The association between dietary patterns and DOR was not well studied. The purpose of this study was to evaluate the relationship between adhering to the healthy eating index (HEI-2015) and the risk of DOR. In this case-control study, 370 Iranian women (120 with DOR and 250 age- and BMI-matched controls) were examined. A reliable semi-quantitative food frequency questionnaire was used to collect diet-related data. We analyzed the HEI-2015 and their dietary intake data to determine major dietary patterns. The multivariable logistic regression was used in order to analyze the association between HEI-2015 and risk of DOR. We found no significant association between HEI-2015 score and risk of DOR in the unadjusted model (OR 0.78; 95%CI 0.59, 1.03). After controlling for physical activity and energy intake, we observed that women in the highest quartile of the HEI-2015 score had 31% decreased odds of DOR (OR 0.69; 95%CI 0.46, 0.93). This association remained significant even after adjusting for all potential confounders. Overall, increased adherence to HEI may lead to a significant reduction in the odds ratio of DOR. Clinical trials and prospective studies are needed to confirm this association.

UNASSIGNED: To evaluate the efficacy of peri-trigger female reproductive hormones (FRHs) in the prediction of oocyte maturation in normal ovarian reserve patients during the in vitro fertilization-embryo transfer (IVF-ET) procedure.
UNASSIGNED: A hospital database was used to extract data on IVF-ET cases from January 2020 to September 2021. The levels of female reproductive hormones, including estradiol (E2), luteinizing hormone (LH), progesterone (P), and follicle-stimulating hormone (FSH), were initially evaluated at baseline, the day of the trigger, the day after the trigger, and the day of oocyte retrieval. The relative change in E2, LH, P, FSH between time point 1 (the day of trigger and baseline) and time point 2 (the day after the trigger and day on the trigger) was defined as E2_RoV1/2, LH_RoV1/2, P_RoV1/2, and FSH_RoV1/2, respectively. Univariable and multivariable regression were performed to screen the peri-trigger FRHs for the prediction of oocyte maturation.
UNASSIGNED: A total of 118 patients were enrolled in our study. Univariable analysis revealed significant associations between E2_RoV1 and the rate of MII oocytes in the GnRH-agonist protocol group (p < 0.05), but not in the GnRH-antagonist protocol group. Conversely, P_RoV2 emerged as a potential predictor for the rate of MII oocytes in both protocol groups (p < 0.05). Multivariable analysis confirmed the significance of P_RoV2 in predicting oocyte maturation rate in both groups (p < 0.05), while the association of E2_RoV1 was not significant in either group. However, within the subgroup of high P_RoV2 in the GnRH-agonist protocol group, association was not observed to be significant. The C-index was 0.83 (95% CI [0.73-0.92]) for the GnRH-agonist protocol group and 0.77 (95% CI [0.63-0.90]) for the GnRH-antagonist protocol group. The ROC curve analysis further supported the satisfactory performance of the models, with area under the curve (AUC) values of 0.79 for the GnRH-agonist protocol group and 0.81 for the GnRH-antagonist protocol group.
UNASSIGNED: P_RoV2 showed significant predictive value for oocyte maturation in both GnRH-agonist and GnRH-antagonist protocol groups, which enhances the understanding of evaluating oocyte maturation and inform individualized treatment protocols in controlled ovarian hyperstimulation during IVF-ET for normal ovarian reserve patients.

The aim of this study is to evaluate the effects of obesity on clinical outcomes in diminished ovarian reserve (DOR) patients undergoing intracytoplasmic sperm injection cycles. In this retrospective observational cross-sectional study, women admitted to current clinic with DOR undergoing intracytoplasmic sperm injection were divided into 2 groups according to the obesity. Patient age, body mass index, anti-mullerian hormone, baseline follicle stimulating hormone and baseline estradiol levels, antral follicle count, total gonadotropin dose, day of stimulation, number of mature (MII) oocytes, and clinical pregnancy were evaluated. There were no statistically significant differences between groups in terms of age, anti-mullerian hormone, baseline follicle stimulating hormone, baseline estradiol levels, antral follicle count, and clinical pregnancy (P > .05). Total gonadotropin dose, the days of ovarian stimulation were higher and number of MII oocyte were less in the obese group (P < .05). Logistic regression analyses also revealed that the days of ovarian stimulation and number of MII oocyte were significant factors in the study group. ROC curve analysis showed obesity is a negatively affecting factor in DOR patients. Obesity causes more gonadotropin dose longer days of stimulation, and less number of MII oocyte. However clinical pregnancy rate is not negatively affected by obesity according to the current study.

The aim of this study is to evaluate the risk factors for empty follicle syndrome (EFS) in patients with diminished ovarian reserve (DOR) undergoing an intracytoplasmic sperm injection cycle. In this retrospective study, patients with DOR were divided into 2 groups according to the presence of empty follicles on the day of oocyte retrieval. Patient age, body mass index (BMI), anti-Müllerian hormone (AMH), baseline follicle stimulating hormone (FSH) and estradiol (E2) levels, basal antral follicle count (AFC), total gonadotropin dose, and day of stimulation were recorded as risk factors. The association between EFS and these variables was assessed using the logistic regression method and ROC curve analysis. Increased BMI, low AMH, higher baseline FSH, low baseline AFC, higher gonadotropin dose, and longer day of ovulation induction were independent risk factors for EFS in patients with DOR. ROC curve analysis showed that BMI, AMH, baseline FSH, baseline AFC, higher gonadotropin dose, and longer ovulation induction days were predictive parameters in this group. According to the current study, higher BMI, lower AMH, higher baseline FSH, lower baseline AFC, higher gonadotropin dose and longer ovulation induction days were independent risk factors for EFS in patients with reduced ovarian reserve.

We aimed to conduct a systematic review of the data in the literature on ovarian reserve and ovarian hormone following laparoscopic ovarian drilling (LOD). The PubMed, ScienceDirect, and ProQuest databases were comprehensively searched using a combination of keywords such as \"ovarian reserve\", \"laparoscopic ovarian drilling\", \"luteinizing hormone\", \"follicle-stimulating hormone\", \"inhibin\", \"LH/FSH ratio\", \"ovulation\", and \"testosterone\". All studies involving females of reproductive age who were officially diagnosed with polycystic ovarian syndrome (PCOS) and had undergone LOD with reported data concerning at least one of the following parameters were considered for inclusion: ovarian reserve, anti-Mullerian hormone (AMH), inhibin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, and testosterone. All the included studies were evaluated by the GRADE scale for bias and their findings were synthesized by four independent coauthors. A total of 38 studies involving 3118 female patients were included. Based on our findings, a significant number of participants experienced spontaneous ovulation along with a significant decrease in ovarian reserve, and a significant decrease in AMH, LH, and testosterone, with no significant changes in FSH and inhibin B. With the end goal of LOD being to improve fertility and pregnancy rates among females with PCOS, it is important to look at the first few steps that enable this. As expected, there was a significant improvement in ovulation while the ovarian reserve decreased. Along with the decrease in ovarian reserve, there was a significant normalization in AMH, LH, and testosterone levels. LOD may exert its main effects through the manipulation of the ovarian reserves.