Diminished Ovarian Reserve

Diminished Ovarian Reserve (DOR) is an important cause of female infertility and is associated with poor ovarian response and lower pregnancy rates during In Vitro Fertilization (IVF). The molecular mechanisms underlying impaired follicular development in DOR remain incompletely understood. Increasing evidence suggests that non-coding RNAs and components of the Hippo signaling pathway play important roles in granulosa cell proliferation, apoptosis, and follicular development. This prospective observational cohort study aims to investigate the expression of the long non-coding RNA (lncRNA) Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), microRNA (miRNA)-181a-5p, Hippo pathway components including Yes-Associated Protein 1 (YAP1) and Connective Tissue Growth Factor (CTGF), and Insulin-Like Growth Factor 1 (IGF1) in follicular fluid-derived cells from women with DOR undergoing IVF compared with women with normal ovarian reserve. The study will also evaluate relationships among these molecular markers and IVF outcomes, including oocyte quality, number of retrieved oocytes, and embryo developmental potential.

The purpose of this clinical trial is to evaluate the efficacy and safety of Bushen Yiqi formula combined with dehydroepiandrosterone (DHEA) in the treatment of women with diminished ovarian reserve (DOR). The study also aims to assess the safety profile of this combined therapy. The main questions this study aims to answer include: 1. Can the Bushen Yiqi formula combined with DHEA improve ovarian reserve in women with DOR? 2. Does the combined treatment improve hormone levels, ovarian follicle parameters, and clinical symptoms? 3. What safety issues may occur during treatment with the Bushen Yiqi formula combined with DHEA? Researchers will compare the Bushen Yiqi formula combined with DHEA to DHEA plus placebo to determine whether the combined therapy is more effective in treating diminished ovarian reserve. Participants will: 1. Be randomly assigned to either the treatment group or the control group 2. Receive DHEA combined with the Bushen Yiqi formula or DHEA combined with placebo for 12 weeks 3. Undergo regular clinical assessments during the study period 4. Have ovarian reserve markers (including AMH and antral follicle count), sex hormone levels (FSH, LH, E2, and testosterone), traditional Chinese medicine symptom scores, Kupperman menopausal index scores, inflammatory markers (CRP and IL-6), and safety indicators evaluated before and after treatment

Female fertility decline has become an important public health issue in China, with a substantial proportion of women of reproductive age experiencing reduced ovarian reserve. However, effective tools for early identification and large-scale prevention of fertility impairment in the general population are still lacking. This study aims to develop and evaluate a precision prevention strategy for early female fertility decline based on the OvaRePred-Plus model, which integrates ovarian reserve markers, lifestyle factors, and reproductive health indicators. A multicenter, cluster randomized controlled trial will be conducted across six medical centers in China, enrolling women aged 20-40 years identified as having early signs of fertility decline. Participants will be allocated to either an intervention group receiving a comprehensive health management program (including dietary optimization, nutritional supplementation, physical activity, and sleep improvement) or a control group receiving routine clinical care. The intervention will last for 12 weeks. The primary outcome is the change in fertility score assessed by the OvaRePred-Plus model. Secondary outcomes include changes in ovarian reserve markers (e.g., AMH), menstrual status, ultrasound parameters, and reproductive outcomes. This study is expected to provide evidence for a scalable and cost-effective strategy for early prevention and management of female fertility decline.

One of the barriers in patients with diminished ovarian reserve (DOR) is the significantly reduced number of oocytes resulting in fewer oocytes collected and embryos formed. Many ovarian stimulation strategies have been proposed to improve oocyte or embryo quantity which is oocyte accumulation could be a potential option with a comparable success rate and reasonable cost. Progestin-primed ovarian stimulation (PPOS) protocol could be suggested as an alternative method of premature Luteinizing hormone (LH) prevention in IVF. It favors segment Assisted Reproductive Technology (ART) cycles such as frozen embryo transfer (FET), oocyte donor, fertility preservation, and oocyte accumulation set. The protocol is more patient-friendly and affordable than the GnRH antagonist regimen regarding LH suppression during ovarian stimulation. Many PPOS protocols have been proposed in which the three most common agents include Dydrogesterone (DYG), Micronised Progesterone (MIP), and Medroxyprogesterone acetate (MPA). Indeed, DYG seems to have some advantages, including oral administration and safety which has been used in the treatment of threatened abortion. Initial evidence of PPOS protocol suggests that oocyte quantity and quality are comparable with other ovarian stimulation regimens. However, data related to the PPOS protocol has not been well documented, including Dydrogesteron-primed ovarian stimulation (DPOS). There has not been an RCT with a large sample size and well-designed to provide more substantial evidence. A randomized trial to compare the effectiveness of PPOS and GnRH antagonist protocol in IVF is urgently needed.

The goal of this observational study is to investigate the distinct tongue manifestation characteristics in patients with diminished ovarian reserve (DOR) compared to healthy individuals, and to clarify the features of tongue coating microbiota, gut microbiota, and their interrelationships in DOR patients. The main question it aims to answer is: Whether there are significant differences in tongue manifestations, tongue coating microbiota, and gut microbiota characteristics between DOR patients and healthy populations; Whether associations exist between tongue coating microbiota and gut microbiota in DOR patients; Whether the pathogenesis of DOR may influence estrogen metabolism through alterations in oral and gut microbiota.

In the context of the accelerating aging population and the continuous decline in birth rates nationwide, delaying reproductive aging in women and protecting the fertility of women of childbearing age have become urgent issues and key demands that need to be addressed in the field of maternal and child health in China. The ovaries have reproductive and hormone secretion functions and are crucial throughout the female reproductive lifecycle. Women of childbearing age in China face a serious problem of diminished ovarian reserve (DOR), which can lead to infertility, failed in vitro fertilization (IVF) treatments, miscarriage, and other adverse pregnancy outcomes, severely affecting the safety of women and their offspring. For DOR patients who desire to conceive, failure to intervene and treat promptly can result in irreversible losses and impose a significant psychological burden on them. However, there are currently no clear and reliable interventions that can improve ovarian function and enhance fertility in women with DOR. Therefore, exploring new, safe, and patient-acceptable intervention strategies is urgently needed, as it may bring hope and light to women with DOR. Nutrient supplementation, especially vitamin supplementation, has received increasing attention in disease treatment due to its safety, bioavailability, and effectiveness. Previous studies have shown that vitamin C may play an important role in treating diminished ovarian reserve. However, its effects on ovarian function need to be validated in the population. Based on the above research background, this project will conduct a randomized, placebo-controlled, double-blind, multicenter trial. The study subjects will be DOR infertility patients undergoing IVF/ICSI treatment. The intervention group will receive oral vitamin C supplementation at a dosage of 500 mg per dose, twice a day; the control group will receive a placebo with the same dosage and method for at least three months. Patients will be followed up until delivery outcomes, comparing the IVF/ICSI treatment results between the vitamin C supplementation group and the placebo group. The primary endpoint of this clinical trial is the live birth rate of the IVF/ICSI treatment cycle. Secondary endpoints include indicators of improved ovarian reserve function, ovarian aging molecular clocks, IVF-embryo culture indicators, pregnancy rates, pregnancy complications, and neonatal conditions, thereby providing new clues and theoretical basis for clinical treatment plans for DOR patients.

This prospective double-blinded randomized placebo control study aims to determine if In Vitro Fertilization (IVF) outcomes are improved by ovarian platelet-rich plasma injections (oPRP) for women diagnosed with diminished ovarian reserve (DOR). Women with DOR notoriously have the lowest chance of pregnancy and live birth compared to age-matched peers with a normal or robust ovarian reserve.

The goal of this observational study is to find differences in serum biomarkers between ovarian function and normal individuals.

The purpose of the study is to understand the effect of nicotinamide mononucleotide (NMN) on patients with diminished ovarian reserve and the outcomes of IVF/ICSI-ET.