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Anti-Müllerian hormone (AMH) serves as an indirect marker for predicting primordial follicles that are representative of ovarian reserve. In this study the possibility of using AMH and age to predict the ovarian reserve in domestic cats. Ovaries and blood were collected from 30 cats undergoing routine ovariohysterectomy. The animals were divided into three age groups: prepubertal (<4 mo, n = 10), adult (1–5 y, n = 10), and senior (>5 y, n = 10). Blood was collected at surgery for serum AMH measurements using the AMH Gen II ELISA kit. The intra-assay coefficient of variation (CV) and inter-assay CV were 3.56 % and 7.68 %, respectively. One side of the ovary was processed to determine AMH localization using immunohistochemistry and for a histological count of follicles, which is the gold standard. The expression of AMH protein was quantified from the contralateral ovary by Western blot analysis. Primordial follicles exhibited the most pronounced inverse relationship with age (rho = −0.779, P < 0.05), followed by a positive association with serum AMH concentration (rho = 0.490, P < 0.05), indicating that both age and AMH are potential markers indicative of primordial follicles. Furthermore, secondary (rho = 0.651, P < 0.05) and small antral follicles (rho = 0.648, P < 0.05) were identified as the major sources of circulating AMH, as indicated by the stronger correlation with serum AMH concentrations compared with primary follicles. However, there was no significant correlation between the expression of AMH protein and other factors, including age, primordial follicles, primary follicles, secondary follicles, small antral follicles, and serum AMH concentration. A model for predicting primordial follicle number using serum AMH concentration (AIC = 672.66, P < 0.05) and age (AIC = 668.93, P < 0.05) was established. In conclusion, both serum AMH concentration and age may serve as comparable markers of ovarian reserve in domestic cats. Moreover, AMH is particularly useful in situations where age information is not available. • Ovarian AMH protein expression for the first time quantified by western blot revealed no differences among age groups. • No correlation between ovarian and serum AMH concentration was found. • A model for predicting ovarian reserve in the cats was developed. [ABSTRACT FROM AUTHOR]

BACKGROUND Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance of ovarian hormone levels, reduced or lost fertility, and an increased risk of early menopause. Previous studies have often focused on the direct effects of chemotherapeutic drugs on ovarian follicles, such as direct DNA damage-mediated apoptotic death and primordial follicle burnout. Emerging evidence has revealed an imbalance in the ovarian microenvironment during chemotherapy. The ovarian microenvironment provides nutritional support and transportation of signals that stimulate the growth and development of follicles, ovulation, and corpus luteum formation. The close interaction between the ovarian microenvironment and follicles can determine ovarian function. Therefore, designing novel and precise strategies to manipulate the ovarian microenvironment may be a new strategy to protect ovarian function during chemotherapy. OBJECTIVE AND RATIONALE This review details the changes that occur in the ovarian microenvironment during chemotherapy and emphasizes the importance of developing new therapeutics that protect ovarian function by targeting the ovarian microenvironment during chemotherapy. SEARCH METHODS A comprehensive review of the literature was performed by searching PubMed up to April 2024. Search terms included 'ovarian microenvironment' (ovarian extracellular matrix, ovarian stromal cells, ovarian interstitial, ovarian blood vessels, ovarian lymphatic vessels, ovarian macrophages, ovarian lymphocytes, ovarian immune cytokines, ovarian oxidative stress, ovarian reactive oxygen species, ovarian senescence cells, ovarian senescence-associated secretory phenotypes, ovarian oogonial stem cells, ovarian stem cells), terms related to ovarian function (reproductive health, fertility, infertility, fecundity, ovarian reserve, ovarian function, menopause, decreased ovarian reserve, premature ovarian insufficiency/failure), and terms related to chemotherapy (cyclophosphamide, lfosfamide, chlormethine, chlorambucil, busulfan, melphalan, procarbazine, cisplatin, doxorubicin, carboplatin, taxane, paclitaxel, docetaxel, 5-fluorouraci, vincristine, methotrexate, dactinomycin, bleomycin, mercaptopurine). OUTCOMES The ovarian microenvironment shows great changes during chemotherapy, inducing extracellular matrix deposition and stromal fibrosis, angiogenesis disorders, immune microenvironment disturbance, oxidative stress imbalances, ovarian stem cell exhaustion, and cell senescence, thereby lowering the quantity and quality of ovarian follicles. Several methods targeting the ovarian microenvironment have been adopted to prevent and treat CAOD, such as stem cell therapy and the use of free radical scavengers, senolytherapies, immunomodulators, and proangiogenic factors. WIDER IMPLICATIONS Ovarian function is determined by its 'seeds' (follicles) and 'soil' (ovarian microenvironment). The ovarian microenvironment has been reported to play a vital role in CAOD and targeting the ovarian microenvironment may present potential therapeutic approaches for CAOD. However, the relation between the ovarian microenvironment, its regulatory networks, and CAOD needs to be further studied. A better understanding of these issues could be helpful in explaining the pathogenesis of CAOD and creating innovative strategies for counteracting the effects exerted on ovarian function. Our aim is that this narrative review of CAOD will stimulate more research in this important field. REGISTRATION NUMBER Not applicable. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does luteal estradiol (E2) pretreatment give a similar number of retrieved oocytes compared to no-pretreatment in advanced-aged women stimulated with corifollitropin alfa in an antagonist protocol? SUMMARY ANSWER Programming antagonist cycles with luteal E2 gave similar number of retrieved oocytes compared to no-pretreatment in women aged 38–42 years. WHAT IS KNOWN ALREADY Programming antagonist cycles with luteal E2 pretreatment is a valuable tool to organize the IVF procedure better and is safe without any known impact on cycle outcome. However, variable effects were observed on the number of retrieved oocytes depending on the treated population. In advanced-age women, recruitable follicles tend to decrease in number and to be more heterogeneous in size but it remains unclear if estradiol pretreatment could change the oocyte yield through its negative feed-back effect on FSH intercycle rise. STUDY DESIGN, SIZE, DURATION This non-blinded randomized controlled non-inferiority trial was conducted between 2016 and 2022 with centrally computerized randomization and concealed allocation. Participants were 324 women aged 38–42 years undergoing IVF treatment. The primary endpoint was the total number of retrieved oocytes. Statistical analysis was performed with one-sided alpha risk of 2.5% and 95% confidence interval (CI) with the non-inferiority of E2 pretreatment proved by a P value <0.025 and a lower delta margin of the CI within two oocytes compared to no pretreatment. Secondary endpoints were duration and total dosage of recombinant FSH, cancellation rate, percentage of oocyte pick-up (OPU) on working days, total number of metaphase II oocytes and obtained embryos, fresh transfer live birth rate, and cumulative live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS This multicentric study enrolled women with regular cycles, weight >50 kg and body mass index <32, IVF cycle 1–2. According to randomization, micronized estradiol 2 mg twice a day was started on days 20–24 and continued until Wednesday beyond the onset of menses followed by administration of corifollitropin alfa on Friday, i.e. stimulation (S)1 or from D1-3 of a natural cycle in unpretreated patients. GnRH antagonist was started at S6 and additional FSH at S8. MAIN RESULTS AND THE ROLE OF CHANCE Basal characteristics were similar in patients randomized in E2 pretreated (n = 164) and non-pretreated (n = 160) groups (intended to treat (ITT) population). A total of 291 patients started treatment (per protocol (PP) population), 147 in E2 pretreated group with a mean number [SD] of pre-treatment days 9.8 [2.6] and 144 in the non-pretreated group. Despite advanced age, oocyte yields ranged from 0 to 29 in both groups with a median number of 6 retrieved oocytes in accordance with a mean anti-Müllerian hormone (AMH) level above 1.2 ng/ml. We demonstrated the non-inferiority of E2 pretreatment with a mean difference of −0.1 oocyte 95% CI [−1.5; 1.3] P  = 0.004 in the PP population and a mean difference of −0.44 oocyte [−1.84; 0.97] P  = 0.014 in the ITT population. Oocyte retrieval was more often on working days in E2 pretreated patients (91.9 versus 74.2%, P  < 0.001). In patients reaching OPU, the duration of stimulation was statistically significantly longer (11.7 [1.7] versus 10.8 [1.8] days, P  < 0.001) and the extra FSH dosage in addition to corifollitropin alfa was statistically significantly higher (1040 [548] versus 778 [504] IU, P  < 0.001) in E2 pretreated than non-pretreated patients. We did not observe any significant differences in the number of retrieved oocytes (8.4 [6.1] versus 9.1 [6.0]), in the number of Metaphase 2 oocytes (7 [5.5] versus 7.3 [5.2]) nor in the number of obtained embryos (5 [4.6] versus 5.2 [4.2]) in E2 pretreated patients compared to non-pretreated patients. The live birth rate after fresh transfer (16.2% versus 18.5%, respectively), and the cumulative live birth rate per patient (17.7% versus 22.9%, respectively) were similar in both groups. Among the PP population, 31.6% of patients fulfilled the criteria for group 4 of Poseïdon classification (AMH <1.2 ng/ml and/or antral follicle count <5). In this sub-group of patients, we observed in contrast a statistically higher number of retrieved oocytes in E2 pretreated patients compared to non-pretreated (5.1 [3.8] versus 3.4 [2.7], respectively, the mean difference of +1.7 oocyte [0.2; 3.2] P  = 0.022) but without significant difference in the cumulative live birth rate per patient (15.7% versus 7.3%, respectively). LIMITATIONS, REASONS FOR CAUTION Our stimulated women older than 38 years obtained a wide range of collected oocytes suggesting very different stages of ovarian aging in both groups. E2 pretreatment is more likely to increase oocyte yield at the stage of ovarian aging characterized by asynchrony of a reduced follicular cohort. Another limitation is the sample size in sub-group analysis of patients with AMH <1.2 ng/ml. Finally, the absence of placebo for pretreatment could also introduce possible bias. WIDER IMPLICATIONS OF THE FINDINGS Programming antagonist cycles with luteal E2 pretreatment seems a useful tool in advanced age women to better schedule oocyte retrievals on working days. However, the potential benefit of the number of collected oocytes remains to be demonstrated in a larger population displaying the characteristics of decreased ovarian reserve encountered in Poseïdon classification. STUDY FUNDING/COMPETING INTEREST(S) Research grant from (MSD) Organon, France. I.C. S.D. B.B. X.M. S.G. and C.J. have no conflict of interest with this study. I.C.D. declares fees as speaker from Merck KGaA, Gedeon Richter, MSD (Organon, France), Ferring, Theramex, and IBSA and participation on advisory board from Merck KGaA. I.C.D. also declares consulting fees, and travel and meeting support from Merck KGaA. N.M. declares grants paid to their institution from MSD (Organon, France); consulting fees from MSD (Organon, France), Ferring, and Merck KGaA; honoraria from Merck KGaA, General Electrics, Genevrier (IBSA Pharma), and Theramex; support for travel and meetings from Theramex, Merck KGaG, and Gedeon Richter; and equipment paid to their institution from Goodlife Pharma. N.C. declares grants from IBSA Pharma, Merck KGaA, Ferring, and Gedeon Richter; support for travel and meetings from IBSA Pharma, Merck KGaG, MSD (Organon, France), Gedeon Richter, and Theramex; and participation on advisory board from Merck KGaA. A.G.L. declares fees as speaker from Merck KGaA, Gedeon Richter, MSD (Organon, France), Ferring, Theramex, and IBSA. TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT02884245. TRIAL REGISTRATION DATE 29 August 2016. DATE OF FIRST PATIENT'S ENROLMENT 4 November 2016. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can pregnancy outcomes following fresh elective single embryo transfer (eSET) in gonadotropin-releasing hormone (GnRH) antagonist protocols increase using a gonadotropin (Gn) step-down approach with cessation of GnRH antagonist on the day of hCG administration (hCG day) in patients with normal ovarian response? SUMMARY ANSWER The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on the hCG day is effective in improving live birth rates (LBRs) per fresh eSET cycle. WHAT IS KNOWN ALREADY Currently, there is no consensus on optimal GnRH antagonist regimens. Studies have shown that fresh GnRH antagonist cycles result in poorer pregnancy outcomes than the long GnRH agonist (GnRHa) protocol. Endometrial receptivity is a key factor that contributes to this phenomenon. STUDY DESIGN, SIZE, DURATION An open label randomized controlled trial (RCT) was performed between November 2021 and August 2022. There were 546 patients allocated to either the modified GnRH antagonist or the conventional antagonist protocol at a 1:1 ratio. PARTICIPANTS/MATERIALS, SETTING, METHODS Both IVF and ICSI cycles were included, and the sperm samples used were either fresh or frozen from the partner, or from frozen donor ejaculates. The primary outcome was the LBRs per fresh SET cycle. Secondary outcomes included rates of implantation, clinical and ongoing pregnancy, miscarriage, and ovarian hyperstimulation syndrome (OHSS), as well as clinical outcomes of ovarian stimulation. MAIN RESULTS AND THE ROLE OF CHANCE Baseline demographic features were not significantly different between the two ovarian stimulation groups. However, in the intention-to-treat (ITT) population, the LBRs in the modified antagonist group were significantly higher than in the conventional group (38.1% [104/273] vs. 27.5% [75/273], relative risk 1.39 [95% CI, 1.09–1.77], P  =   0.008). Using a per-protocol (PP) analysis which included all the patients who received an embryo transfer, the LBRs in the modified antagonist group were also significantly higher than in the conventional group (48.6% [103/212] vs. 36.8% [74/201], relative risk 1.32 [95% CI, 1.05–1.66], P  =   0.016). The modified antagonist group achieved significantly higher implantation rates, and clinical and ongoing pregnancy rates than the conventional group in both the ITT and PP analyses (P  <   0.05). The two groups did not show significant differences between the number of oocytes retrieved or mature oocytes, two-pronuclear zygote (2PN) rates, the number of embryos obtained, blastocyst progression and good-quality embryo rates, early miscarriage rates, or OHSS incidence rates (P  >   0.05). LIMITATIONS, REASONS FOR CAUTION A limitation of our study was that the subjects were not blinded to the treatment allocation in the RCT trial. Only women under 40 years of age who had a good prognosis were included in the analysis. Therefore, use of the modified antagonist protocol in older patients with a low ovarian reserve remains to be investigated. In addition, the sample size for Day 5 elective SET was small, so larger trials will be required to strengthen these findings. WIDER IMPLICATIONS OF THE FINDINGS The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on hCG day improved the LBRs per fresh eSET cycle in normal responders. STUDY FUNDING/COMPETING INTEREST(S) This project was funded by grant 2022YFC2702503 from the National Key Research & Development Program of China and grant 2021140 from the Beijing Health Promotion Association. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER The RCT was registered in the Chinese Clinical Trial Registry; Study Number: ChiCTR2100053453. TRIAL REGISTRATION DATE 21 November 2021. DATE OF FIRST PATIENT'S ENROLLMENT 23 November 2021 [ABSTRACT FROM AUTHOR]

STUDY QUESTION Are markers of epigenetic age acceleration in follicular fluid associated with outcomes of ovarian stimulation? SUMMARY ANSWER Increased epigenetic age acceleration of follicular fluid using the Horvath clock, but not other epigenetic clocks (GrimAge and Granulosa Cell), was associated with lower peak estradiol levels and decreased number of total and mature oocytes. WHAT IS KNOWN ALREADY In granulosa cells, there are inconsistent findings between epigenetic age acceleration and ovarian response outcomes. STUDY DESIGN, SIZE, DURATION Our study included 61 women undergoing IVF at an academic fertility clinic in the New England area who were part of the Environment and Reproductive Health Study (2006–2016). PARTICIPANTS/MATERIALS, SETTING, METHODS Participants provided a follicular fluid sample during oocyte retrieval. DNA methylation of follicular fluid was assessed using a genome-wide methylation screening tool. Three established epigenetic clocks (Horvath, GrimAge, and Granulosa Cell) were used to predict DNA-methylation-based epigenetic age. To calculate the age acceleration, we regressed epigenetic age on chronological age and extracted the residuals. The association between epigenetic age acceleration and ovarian response outcomes (peak estradiol levels, follicle stimulation hormone, number of total, and mature oocytes) was assessed using linear and Poisson regression adjusted for chronological age, three surrogate variables (to account for cellular heterogeneity), race, smoking status, initial infertility diagnosis, and stimulation protocol. MAIN RESULTS AND ROLE OF CHANCE Compared to the median chronological age of our participants (34 years), the Horvath clock predicted, on an average, a younger epigenetic age (median: 24.2 years) while the GrimAge (median: 38.6 years) and Granulosa Cell (median: 39.0 years) clocks predicted, on an average, an older epigenetic age. Age acceleration based on the Horvath clock was associated with lower peak estradiol levels (−819.4 unit decrease in peak estradiol levels per standard deviation increase; 95% CI: −1265.7, −373.1) and fewer total (% change in total oocytes retrieved per standard deviation increase: −21.8%; 95% CI: −37.1%, −2.8%) and mature oocytes retrieved (% change in mature oocytes retrieved per standard deviation increase: −23.8%; 95% CI: −39.9%, −3.4%). The age acceleration based on the two other epigenetic clocks was not associated with markers of ovarian response. LIMITATIONS, REASONS FOR CAUTION Our sample size was small and we did not specifically isolate granulosa cells from follicular fluid samples so our samples could have included mixed cell types. WIDER IMPLICATIONS OF THE FINDINGS Our results highlight that certain epigenetic clocks may be predictive of ovarian stimulation outcomes when applied to follicular fluid; however, the inconsistent findings for specific clocks across studies indicate a need for further research to better understand the clinical utility of epigenetic clocks to improve IVF treatment. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by grants ES009718, ES022955, ES000002, and ES026648 from the National Institute of Environmental Health Sciences (NIEHS) and a pilot grant from the NIEHS-funded HERCULES Center at Emory University (P30 ES019776). RBH was supported by the Emory University NIH Training Grant (T32-ES012870). TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to show that anti-Mullerian hormone (AMH) may be used as a quantitative marker of ovarian reserve in Turkish girls aged 18 years and younger and establish the reference values for AMH in Turkish girls. Material and Methods: This retrospective study included girls between 8-18 years old, without premature ovarian failure or without genetic factors resulting in ovarian dysgenesis. Blood specimens were collected after overnight fasting early in the morning during the early follicular phase. Measurement of serum levels of gonadotropins and AMH was done. Mean serum AMH levels of different age groups and best fitting curve representing AMH percentiles (10th, 25th, 50th, 75th, 90th) were calculated. Results: In total 785 girls with a mean age of 16.16±1.90 years were included, divided into seven age groups. The mean serum AMH level for the total cohort was 5.20±4.19 ng/mL. There was a significant difference between the mean values of AMH in age groups as follows: ≤12 and 17-≤18 (p=0.011). The best fitting curves for AMH percentiles were 4th order polynomial functions. There was a significant correlation between AMH and age and follicle stimulating hormone levels (r=0.148, p<0.001 and r=-0.092, p=0.010). Conclusion: Our results reflect the real-life data for serum AMH values in Turkish girls. Our nomogram may be useful for counseling adolescents about their ovarian reserve and diagnosing other gynecological diseases. A longitudinal study is necessary for improving the predictive value of AMH values in girls aged 18 and younger. [ABSTRACT FROM AUTHOR]

To discover new variants associated with low ovarian reserve after gonadotoxic treatment among adult female childhood cancer survivors using a genome-wide association study approach. Genome-wide association study. Not applicable. A discovery cohort of adult female childhood cancer survivors from the pan-European PanCareLIFE cohort (n = 743; median age: 25.8 years), excluding those who received bilateral ovarian irradiation, bilateral oophorectomy, central nervous system or total body irradiation, or stem cell transplantation. Replication was attempted in the US-based St. Jude Lifetime Cohort (n = 391; median age: 31.3 years). Female childhood cancer survivors are at risk of therapy-related gonadal impairment. Alkylating agents are well-established risk factors, and the interindividual variability in gonadotoxicity may be explained by genetic polymorphisms. Data were collected in real-life conditions, and cyclophosphamide equivalent doses were used to quantify alkylation agent exposure. Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function, and the findings were combined in a meta-analysis. Three genome-wide significant (<5.0 × 10−8) and 16 genome-wide suggestive (<5.0 × 10−6) loci were associated with log-transformed AMH levels, adjusted for cyclophosphamide equivalent dose of alkylating agents, age at diagnosis, and age at study in the PanCareLIFE cohort. On the basis of the effect allele frequency (EAF) (>0.01 if not genome-wide significant), and biologic relevance, 15 single nucleotide polymorphisms were selected for replication. None of the single nucleotide polymorphisms were statistically significantly associated with AMH levels. A meta-analysis indicated that rs78861946 was associated with borderline genome-wide statistical significance (reference/effect allele: C/T; effect allele frequency: 0.04, beta (SE): −0.484 (0.091). This study found no genetic variants associated with a lower ovarian reserve after gonadotoxic treatment because the findings of this genome-wide association study were not statistically significant replicated in the replication cohort. Suggestive evidence for the potential importance of 1 variant is briefly discussed, but the lack of statistical significance calls for larger cohort sizes. Because the population of childhood cancer survivors is increasing, large-scale and systematic research is needed to identify genetic variants that could aid predictive risk models of gonadotoxicity as well as fertility preservation options for childhood cancer survivors. [ABSTRACT FROM AUTHOR]

To evaluate the association between the urinary benzophenone-3 concentrations and measures of ovarian reserve (OR) among women in the Environment and Reproductive Health study seeking fertility treatment at Massachusetts General Hospital (MGH) in Boston, Massachusetts. Prospective cohort study. MGH infertility clinic in Boston, Massachusetts. Women in the Environment and Reproductive Health cohort seeking fertility treatment. Women contributed spot urine samples prior to assessment of OR outcomes that were analyzed for benzophenone-3 concentrations. Antral follicle count (AFC) and day 3 follicle-stimulating hormone (FSH) levels were evaluated as part of standard infertility workups during unstimulated menstrual cycles. Quasi-Poisson and linear regression models were used to evaluate the association of the specific gravity–adjusted urinary benzophenone-3 concentrations with AFC and FSH, with adjustment for age and physical activity. In the secondary analyses, models were stratified by age. This study included 142 women (mean age ± standard deviation, 36.1 ± 4.6 years; range, 22–45 years) enrolled between 2009 and 2017 with both urinary benzophenone-3 and AFC measurements and 57 women with benzophenone-3 and FSH measurements. Most women were White (78%) and highly educated (49% with a graduate degree). Women contributed a mean of 2.7 urine samples (range, 1–10), with 37% contributing ≥2 samples. Benzophenone-3 was detected in 98% of samples. The geometric mean specific gravity–corrected urinary benzophenone-3 concentration was 85.9 μg/L (geometric standard deviation, 6.2). There were no associations of benzophenone-3 with AFC and day 3 FSH in the full cohort. In stratified models, a 1-unit increase in the log geometric mean benzophenone-3 concentration was associated with a 0.91 (95% confidence interval, 0.86–0.97) times lower AFC among women aged ≤35 years and an increase in the FSH concentration of 0.73 (95% confidence interval, 0.12–1.34) IU/L among women aged >35 years. In the main models, urinary benzophenone-3 was not associated with OR. However, younger patients may be vulnerable to the potential effects of benzophenone-3 on AFC. Further research is warranted. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of barbed and conventional sutures on reproductive outcomes and ovarian reserve after laparoscopic treatment for benign non‐endometrioma ovarian cysts. Methods: This retrospective study was conducted at an affiliated women's hospital between May 2017 and December 2019. Patients with benign non‐endometriotic ovarian cysts undergoing laparoscopic cystectomy were included. Results: Patients received barbed sutures (221 patients) or conventional smooth sutures (203 patients) intraoperatively. The two groups had comparable baseline characteristics. The surgical duration and ovarian suturing time were significantly shorter in the barbed suture group than in the conventional smooth suture group (P < 0.001 and P = 0.002, respectively). The rate of postoperative hemoglobin decline and serum anti‐Müllerian hormone decline were similar between the two groups (P > 0.05). A total of 316 (74.53%) patients experienced at least one pregnancy postoperatively: 170 (76.92%) and 146 (71.92%) patients in the barbed suture and conventional smooth suture groups, respectively (χ2 = 1.395, P = 0.238). Multivariate Poisson regression demonstrated that barbed sutures had no significant effect on the overall postoperative pregnancy rate (adjusted incidence rate ratio, 1.10; 95% confidence interval, 0.93–1.36; P = 0.382). Conclusion: In patients with benign non‐endometriotic ovarian cysts undergoing laparoscopic ovarian cystectomy, barbed sutures had a reproductive outcome similar to that of conventional smooth sutures while providing higher surgical efficiency without adverse effects on the postoperative ovarian reserve. Barbed sutures are probably a viable option to conventional smooth sutures. Synopsis: The reproductive outcome of barbed sutures was similar to that of conventional smooth sutures in patients with benign non‐endometriotic ovarian cysts undergoing laparoscopic ovarian cystectomy. [ABSTRACT FROM AUTHOR]

Introduction: It is still unclear whether Crohn's disease (CD) might be associated with diminished ovarian reserve (OvR) and factors influencing anti‐Mullerian hormone (AMH) levels in CD are poorly known. Material and Methods: We conducted a comprehensive literature search of multiple electronic databases from inception to June 2022 to identify all studies reporting AMH levels or factors associated with diminished OvR in patients with CD. Results: Of the 48 studies identified in our search, eight (including 418 patients with CD) were finally included. The mean difference (95% confidence interval [CI]) in the AMH level between pooled CD patients and controls was −0.56 (−1.14 to 0.03) (p = 0.06). A history of CD‐related surgery was not associated with a lower OvR (odds ratio, OR [95% CI] 1.34, [0.66–2.7]; p = 0.4). While disease activity and perianal disease seems associated with a low OvR, disease location (L2 vs. L1, OR [95% CI] = 95% CI [0.47–7.4]; p = 0.4) and L3 vs. L1 (OR [95% CI] = 1.44 [0.67–3.12]; p = 0.3), CD medication, and disease behavior were not. Conclusions: Our systematic review and meta‐analysis did not identify a significantly low OvR in patients with CD. Contrary to CD‐related surgery risk factor, active disease was associated lower AMH levels. [ABSTRACT FROM AUTHOR]

Background & Objective: There is disagreement about the correlation between serum 25-OH vitamin D (25OH-D) concentrations and ovarian reserve. The aim of this study was to evaluate the correlation between serum levels of 25OH-D and ovarian reserve parameters, including Anti-mullerian hormone (AMH), Follicle stimulating hormone (FSH), and Antral follicular count (AFC) in the tropical zone. Materials & Methods: In this cross-sectional study, 148 infertile women were enrolled. On the third day of their cycles, vitamin D3, FSH, and AMH were measured. An ultrasound scan was done for the measurement of the ovaries AFC. Participants were divided into women with normal ovarian reserve (NOR) and women with diminished ovarian reserve (DOR). Then two groups were compared based on the levels of vitamin D. Results: Our findings showed that there were significant differences in vitamin D levels between the DOR and NOR groups (11.52±12.24 and 22.74±12.7, respectively), (P value <0.001). The partial Spearman correlation test depicted an inverse relationship between vitamin D and FSH (rho=-0.21, P =0.009). Also, there was a positive relationship between vitamin D and AMH and AFC, (rho=0.27, P=0.001) and (rho=0.39, P< 0.001) respectively. Conclusion: This study demonstrated that there was an inverse relationship between levels of vitamin D and FSH and a positive relationship with AMH and AFC. It appears that the level of vitamin D is important in DOR. [ABSTRACT FROM AUTHOR]

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Background: Insulin resistance (IR) is related with adverse outcomes of in vitro fertilization (IVF) in women with obesity, but little is known about the relationship between IR and unexpected poor ovarian response (uPOR) in non-obese subjects with sufficient ovarian parameters (classified as POSEIDON group 1). This research aims to explore the association between the homeostasis model assessment of insulin resistance (HOMA-IR) and uPOR in non-obese women with normal biomarkers of ovarian reserve. Methods: The retrospective cohort study was conducted at a fertility center. The main inclusion criteria were age < 35 years, body mass index (BMI) < 28 kg/m2, normal ovarian reserve (anti-Mullerian hormone ≥ 1.2 ng/ml, antral follicle count ≥ 5). Women undergoing the first oocyte retrieval cycle were included consecutively between 2018 until 2023. Patients who have ≤ 9 oocytes retrieved were defined as uPOR. The multivariable logistic model and subgroup analysis were conducted after adjusting confounders. Results: A total of 6977 cycles were included. The adjusted odds ratio was 1.25 (95% confidence interval [CI], 1.12–1.39) for the increment of Ln HOMA-IR which was taken as a continuous variable. Meanwhile, as a sensitivity analysis, elevated tertile of HOMA-IR exhibited an increase in risk of uPOR for the third tertile (≥ 2.75) when compared with the first tertile (< 1.75) with OR of 1.33 (95%CI, 1.15–1.54). In the subgroup analysis, the positive association remained consistent. Conclusion: Elevated HOMA-IR values is significantly associated with increased risk of uPOR in non-obese women classified as POSEIDON group 1. Our study provided evidence for the adverse influence of IR on the ovarian response during IVF and shed light on the importance of IR measurement at the time of pre-stimulation among non-obese women. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress (OS) is one of the major causes of ovarian aging and dysfunction. Indole-3-propionic acid (IPA) is an indole compound derived from tryptophan with free radical scavenging and antioxidant properties, and thus may have potential applications in protecting ovarian function, although the exact mechanisms are unknown. This study aims to preliminarily elucidate the potential mechanisms of IPA that benefit ovarian reserve function through network pharmacology, molecular docking, and experimental verification. Methods: The related protein targets of IPA were searched on SwissTargetPrediction, TargetNet, BATMAN-TCM, and PharmMapper databases. The potential targets of diminished ovarian reserve (DOR) were identified from OMIM, GeneCards, DrugBank, and DisGeNET databases. The common targets were uploaded directly to the STRING database to construct PPI networks. We then performed GO and KEGG enrichment analysis on the targets. Subsequently, molecular docking and molecular dynamics simulation were used to validate the binding conformation of IPA to candidate targets. Furthermore, we carried out in vitro experiments to validate the prediction results of network pharmacology. Results: We identified a total of 61 potential targets for the interaction of IPA with DOR. The PPI network topological parameter analysis yielded 13 hub genes for DOR treatment. The GO biological process enrichment analysis identified 293 entries, mainly enriched in aging, signal transduction, response to hypoxia, negative regulation of apoptotic process, and positive regulation of cell proliferation. The KEGG enrichment analysis mainly included lipid and atherosclerosis, progesterone-mediated oocyte maturation, AGE-RAGE, relaxin, estrogen, and other signaling pathways. The molecular docking further revealed the direct binding of IPA with six hub proteins including NOS3, AKT1, EGFR, PPARA, SRC, and TNF. In vitro experiments showed that IPA pretreatment attenuated H2O2-induced cellular oxidative stress damage, while IPA exerted cytoprotective and antioxidant damage effects by regulating the six hub genes and antioxidant proteins. Conclusion: We systematically illustrated the potential protective effects of IPA against DOR through multiple targets and pathways using network pharmacology, and further verified the cytoprotective effect and antioxidant properties of IPA through in vitro experiments. These findings provide new insights into the targets and molecular mechanisms whereby IPA improves DOR. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate changes in ovarian reserve and quality of life in women treated with ultrasound-guided high-intensity focused ultrasound (USgHIFU) for uterine fibroids. Methods: In this single-center prospective study, a total of 69 patients with uterine fibroids treated with USgHIFU from October 2018 to November 2021 were enrolled. Fibroid volume, anti-Müllerian hormone (AMH) levels, uterine fibroid symptom scores, and uterine fibroid symptoms and quality of life (UFS-QOL) questionnaire scores before and 1, 3, and 6 months after USgHIFU treatment were analyzed. Correlations between AMH levels and age, fibroid type, and fibroid location were assessed. Results: Data from 54 of the 69 patients included in the present study were analyzed. The UFS-QOL scores at baseline and at 1 month and 6 months after USgHIFU treatment were 70 (50.75–87.50), 57 (44.75–80.00), and 52 (40.75–69.00) points, respectively (p < 0.001). The rate of fibroid volume reduction increased significantly at the 3-month follow-up compared with the 1-month follow-up (p < 0.001), and no significant change was observed between the 3-month and 6-month follow-ups (p > 0.99). The median AMH levels before and at 1, 3 and 6 months after treatment were 1.22 (0.16–3.28) ng/ml, 1.12 (0.18–2.52) ng/ml, 1.15 (0.19–2.08) ng/ml and 1.18 (0.36–2.43) ng/ml, respectively (p = 0.2). Multivariate linear regression analyses revealed that age was independently associated with AMH levels. Conclusions: USgHIFU treatment for uterine fibroids can significantly improve quality of life with minimal adverse effects on ovarian function. [ABSTRACT FROM AUTHOR]

Research question: Does luteinizing hormone (LH) levels on human chorionic gonadotropin (HCG) trigger day (LHHCG) affect the clinical outcomes of patients with diminished ovarian reserve (DOR) undergoing gonadotropin-releasing hormone antagonist (GnRH-ant) protocol? Methods: Retrospective analysis fresh embryo transfer cycles of DOR patients who underwent GnRH-ant protocol from August 2019 to June 2023. The participants were divided into different groups according to LHHCG level and age. The clinical data and outcomes were compared between groups. Results: In patients with DOR, the HCG positive rate (59.3% versus 39.8%, P = 0.005), embryo implantation rate (34.5% versus 19.7%, P = 0.002), clinical pregnancy rate (49.2% versus 28.4%, P = 0.003), live birth rate (41.5% versus 22.7%, P = 0.005) in LHHCG < 2.58 IU/L group were significantly higher than LHHCG ≥ 2.58 IU/L group. There was no significant correlation between LHHCG level and clinical pregnancy in POSEIDON group 3. In POSEIDON group 4, the HCG positive rate (52.8% versus 27.0%, P = 0.015), embryo implantation rate (29.2% versus 13.3%, P = 0.023), clinical pregnancy rate (45.3% versus 18.9%, P = 0.010) in LHHCG < 3.14 IU/L group were significantly higher than LHHCG ≥ 3.14 IU/L group. Logistic regression analysis indicated that LHHCG level was an independent influencing factor for clinical pregnancy in POSEIDON group 4 patients (OR = 3.831, 95% CI: 1.379–10.643, P < 0.05). Conclusions: LHHCG level is an independent factor affecting pregnancy outcome of fresh embryo transfer in DOR patients undergoing GnRH-ant protocol, especially for advanced-aged women. LHHCG had a high predictive value for POSEIDON group 4 patients, and LHHCG ≥ 3.14 IU/L predicts poor pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This article explores the impact of chemotherapy on ovarian function in female cancer survivors, emphasizing the importance of preserving fertility alongside cancer treatment. Chemotherapy-induced ovarian failure (CIOF) poses a significant concern, affecting patients' quality of life. The study aims to identify genetic markers predictive of CIOF through a systematic review of existing literature. The review identifies four relevant studies focusing on genetic factors associated with CIOF. Findings suggest potential associations between genetic variations, like CYP3A4*1B and GSTA1, and CIOF risk. Moreover, BRCA mutations may influence ovarian reserve recovery post-chemotherapy. While current assessment methods rely on biochemical tests and ultrasound imaging, genetic testing holds promise for personalized fertility preservation strategies. Integrating genetic markers into clinical practice could revolutionize decision making in fertility preservation for female cancer survivors, enhancing reproductive potential preservation. Background: Recent advances in cancer diagnosis and treatment have significantly improved survival rates among women of reproductive age facing cancer. However, the potential iatrogenic loss of fertility caused by chemotherapeutic agents underscores the need to understand and predict chemotherapy-induced ovarian damage. This study addresses this gap by systematically reviewing the literature to investigate genetic markers associated with chemotherapy-induced ovarian failure (CIOF). Objective: The primary objective is to identify genetic markers linked to CIOF, contributing to a comprehensive understanding of the factors influencing fertility preservation in female cancer survivors. Methods: A systematic review was conducted using PubMed, EMBASE, Web of Science, Scopus, and OVID electronic databases from inception through December 2023. Studies were included if they featured genomic assessments of genes or polymorphisms related to CIOF in women with histologically confirmed tumors. Exclusion criteria comprised in vitro and animal studies, reviews, and pilot studies. The resulting four human-based studies were scrutinized for insights into genetic influences on CIOF. Results: Of the 5179 articles initially identified, four studies met the inclusion criteria, focusing on alkylating agents, particularly cyclophosphamide, and anthracyclines. Su et al. explored CYP3A41B variants, revealing modified associations with CIOF based on age. Charo et al. investigated GSTA1 and CYP2C19 polymorphisms, emphasizing the need to consider age and tamoxifen therapy in assessing associations. Oktay et al. delved into the impact of BRCA mutations on anti-Müllerian hormone (AMH) levels post-chemotherapy, supported by in vitro assays. Van der Perk et al. focused on childhood cancer survivors and revealed significant associations of CYP3A43 and CYP2B6*2 SNPs with AMH levels. Conclusions: This systematic review analyzes evidence regarding genetic markers influencing CIOF, emphasizing the complex interplay of age, specific genetic variants, and chemotherapy regimens. The findings underscore the need for a personalized approach in assessing CIOF risk, integrating genetic markers with traditional ovarian reserve testing. The implications of this study extend to potential advancements in fertility preservation strategies, offering clinicians a comprehensive baseline assessment for tailored interventions based on each patient's unique genetic profile. Further research is essential to validate these findings and establish a robust framework for integrating genetic markers into clinical practice. [ABSTRACT FROM AUTHOR]

DNA damage is a key factor affecting gametogenesis and embryo development. The integrity and stability of DNA are fundamental to a woman's successful conception, embryonic development, pregnancy and the production of healthy offspring. Aging, reactive oxygen species, radiation therapy, and chemotherapy often induce oocyte DNA damage, diminished ovarian reserve, and infertility in women. With the increase of infertility population, there is an increasing need to study the relationship between infertility related diseases and DNA damage and repair. Researchers have tried various methods to reduce DNA damage in oocytes and enhance their DNA repair capabilities in an attempt to protect oocytes. In this review, we summarize recent advances in the DNA damage response mechanisms in infertility diseases such as PCOS, endometriosis, diminished ovarian reserve and hydrosalpinx, which has important implications for fertility preservation. [ABSTRACT FROM AUTHOR]

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. Materials and 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Aim: The use of methotrexate (MTH), a drug commonly prescribed to treat rheumatoid arthritis, cancer, and certain autoimmune diseases, has been linked to early ovarian failure and infertility in women when used in varying amounts and durations. In this study, the possible effects of MTH exposure at different doses on rat ovary were investigated histologically and immunohistochemically. Materials and Methods: A total of 21 female rats, Wistar albino, were utilized in the investigation. The control group (n = 7) was not subjected to any treatment. The 10 mg/kg MTH group (n = 7) and the 20 mg/kg MTH group (n = 7) were given intraperitoneal injections of 10 mg/kg and 20 mg/kg methotrexate, respectively. Five days after injection, the ovarian tissues were taken out of the anesthetized rats and subjected to routine histological tissue processing. The histological evaluation was performed with hematoxylin and eosin (H&E) and Masson's trichrome (MT) on paraffin block sections. Additionally, immunohistochemical staining was performed to determine AMH immunoreactivity. Results: In both MTH groups, histopathological changes were observed, particularly in the 20 mg/kg group, and these included the presence of areas of edema as well as dilated or congested blood vessels. Furthermore, the 20 mg/kg MTH group exhibited increased fibrotic tissue in the ovarian medulla. The number of follicles and AMH immunoreactivity were observed to be reduced in the MTH groups, with the reduction reaching a statistically significant level in the 20 mg/kg MTH group ovary. In terms of AMH immunoreactivity, it is demonstrated that there is no statistical significance between the control and 10 mg/kg MTH groups. Conclusion: The dose of MTH should be considered carefully, as increasing the dose may lead to deterioration of ovarian histopathology and a reduction in the reserve of the ovary. [ABSTRACT FROM AUTHOR]

Diagnosing Hashimoto thyroiditis (HT) relies on thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) titers. The influence of these antibodies on female infertility remains a subject of debate. This study aims to explore the effect and mechanism of HT on female infertility. First, a single-center cross-sectional study was conducted to investigate whether TgAb and TPOAb are the key factors leading to female infertility. Second, bioinformatic analysis was performed to investigate the potential target molecules and pathways. Third, in vivo experiments were performed to explore the effects of elevated TgAb levels on embryo implantation in a mouse model of autoimmune thyroiditis (AIT). Four hundred and five infertile women and 155 healthy controls were enrolled in the cross-sectional study. Results indicated that the TPOAb titer was associated with female infertility, while the TgAb titer showed no significant association. The increased levels of TgAb and TPOAb are not significantly correlated with anti-Mullerian hormone. Bioinformatic analysis indicated that the common target molecules for HT and female infertility include interleukin (IL)-6, IL-10, matrix metalloproteinase 9, and tumor necrosis factor, suggesting potential regulation through multiple signaling pathways such as HIF-1, VEGF, MAPK, and Th17 cell differentiation. A certain dose of porcine thyroglobulin can successfully establish a mouse model of AIT. In this mouse model, embryo implantation and ovarian reserve remain unaffected by elevated TgAb levels. In conclusion, the serum TPOAb titer was associated with infertility due to female factors but the TgAb titer showed no significant association. A simple increase in serum TgAb titer does not affect embryo implantation and ovarian reserve in the AIT model. [ABSTRACT FROM AUTHOR]

Summary: We compared serum anti‐Mullerian hormone (AMH) levels in women with sickle cell disease (SCD) (n = 152) to those of Black comparison women (n = 128) between the ages of 20 and 45 years and evaluated the impact of hydroxyurea (HU) and iron overload on ovarian reserve in those with SCD. SCD treatment was abstracted from medical records. Linear regression models were fit to examine the relationship between log(AMH) and SCD, adjusting for age. The analysis was repeated to account for HU use (current, previous, never) and iron overload (ferritin ≥1000 ng/mL vs. <1000 ng/mL). AMH estimates among women with SCD were lower than those among comparison women (2.23, 95% confidence interval [CI] 1.80–2.76 vs. 4.12, 95% CI 3.11–5.45, respectively). Women with SCD who were currently using HU had 63% lower (95% CI 43–76) AMH values than comparison women; those with SCD with prior or no HU use also had lower AMH estimates than comparison women, but the difference was less pronounced. There were no differences in predicted AMH values among women with SCD for those with and without iron overload. Women with SCD and low AMH may have a shorter reproductive window and may benefit from referral to a reproductive specialist. [ABSTRACT FROM AUTHOR]

Background: Women with diminished ovarian reserve (DOR) have fewer eggs than would be expected at their age. It is estimated that 10% of women seeking fertility treatment are diagnosed with DOR. However, the success rate of medically assisted reproduction (MAR) is significantly lower in women with DOR, thus many seek additional approaches. Aim: To explore the health needs of women with DOR, treatment options and experience of treatment including traditional complementary integrative medicine (TCIM). Methods: Anyone with a diagnosis of DOR, living in Australia or New Zealand, aged over 18 were invited to complete an online survey distributed via fertility support networks and social media platforms from April to December 2021. Results: Data from 67 respondents were included. The main aspects of health that were impacted by DOR were fertility (91.0%) and mental health (52.2%). The main treatment recommended was MAR with most women either currently using MAR (38.8%) or having previously used MAR (37.3%). TCIM was widely used with 88.1% of women utilising supplements, 74.6% consulting with TCIM practitioners, and 65.7% adopting self‐care practices. The main reasons for using TCIM were to improve fertility or support pregnancy, and to support general health and well‐being. Conclusions: Women with DOR have additional health needs apart from infertility, most notably mental health support. The main form of treatment utilised is MAR, despite DOR being challenging for fertility clinicians. TCIM was widely used, and respondents perceived benefits related to improving fertility, supporting pregnancy, or improving well‐being through use of acupuncture, meditation, naturopathy, massage, yoga. [ABSTRACT FROM AUTHOR]

Dynamic mutations in the 5′ untranslated region of FMR1 are associated with infertility. Premutation alleles interfere with prenatal development and increase infertility risks. The number of CGG repeats that causes the highest decrease in ovarian reserves remains unclear. We evaluated the effect of FMR1 CGG repeat lengths on ovarian reserves and in vitro fertilization (IVF) treatment outcomes in 272 women with alleles within the normal range. FMR1 CGG repeat length was investigated via PCR and capillary electrophoresis. Alleles were classified as low-normal, normal, and high-normal. Serum levels of follicle-stimulating hormone and anti-Mullerian hormone (AMH) in the follicular phase of the menstrual cycle were measured, and antral follicles (AFC) were counted. IVF outcomes were collected from medical records. Regarding FMR1 CGG repeat length alleles, 63.2% of women presented at least one low-normal allele. Those carrying low-normal alleles had significantly lower AMH levels than women carrying normal or high-normal alleles. Low-normal/low-normal genotype was the most frequent, followed by low-normal/normal and normal/normal. A comparison of ovarian reserve markers and reproductive outcomes of the three most frequent genotypes revealed that AFC in the low-normal/normal genotype was significantly lower than the low-normal/low-normal genotype. The low number of FMR1 CGG repeats affected AMH levels and AFC but not IVF outcomes per cycle of treatment. [ABSTRACT FROM AUTHOR]

Objective: Multiple sclerosis (MS) has a complex pathobiology, with genetic and environmental factors being crucial players. Understanding the mechanisms underlying heterogeneity in disease activity is crucial for tailored treatment. We explored the impact of DNA methylation, a key mechanism in the genetics‐environment interplay, on disease activity in MS. Methods: Peripheral immune methylome profiling using Illumina Infinium MethylationEPIC BeadChips was conducted on 249 untreated relapsing–remitting MS patients, sampled at the start of disease‐modifying treatment (DMT). A differential methylation analysis compared patients with evidence of disease activity (EDA) to those with no evidence of disease activity (NEDA) over 2 years from DMT start. Utilizing causal inference testing (CIT) and Mendelian randomization (MR), we sought to elucidate the relationships between DNA methylation, gene expression, genetic variation, and disease activity. Results: Four differentially methylated regions (DMRs) were identified between EDA and NEDA. Examining the influence of single nucleotide polymorphisms (SNPs), 923 variants were found to account for the observed differences in the 4 DMRs. Importantly, 3 out of the 923 SNPs, affecting DNA methylation in a DMR linked to the anti‐Mullerian hormone (AMH) gene, were associated with disease activity risk in an independent cohort of 1,408 MS patients. CIT and MR demonstrated that DNA methylation in AMH acts as a mediator for the genetic risk of disease activity. Interpretation: This study uncovered a novel molecular pathway implicating the interaction between DNA methylation and genetic variation in the risk of disease activity in MS, emphasizing the role of sex hormones, particularly the AMH, in MS pathobiology. ANN NEUROL 2024;96:289–301 [ABSTRACT FROM AUTHOR]

To study the relationship between neighborhood deprivation index (NDI) and markers of ovarian reserve and outcomes of controlled ovarian stimulation among young, healthy oocyte donors. Retrospective cohort study. A total of 547 oocyte donors who underwent 905 oocyte retrieval cycles (2008–2020) at a private fertility center in Sandy Springs, Georgia, United States. Neighborhood deprivation index was calculated using principal component analysis applied to census-level measures of poverty, employment, household composition, and public assistance, which was then standardized and linked to donor information on the basis of donor residence. Markers of ovarian reserve, including antral follicle count (AFC) and antimüllerian hormone (AMH) levels, and outcomes of controlled ovarian stimulation including number of total and mature oocytes retrieved and ovarian sensitivity index (OSI) (defined as the number of oocytes retrieved/total gonadotropin dose × 1,000). Multivariable generalized estimating equations with Poisson and normal distribution were used to model the relationship between NDI and outcome measures adjusting for age, body mass index, and year of retrieval. The mean (SD) age of donors was 25.0 (2.8) years and 29% of the donors were racial or ethnic minorities. There were no associations between donor NDI and ovarian reserve markers. For every interquartile range increase in NDI, there was a reduction of −1.5% (95% confidence interval: −5.3% to 2.4%) in total oocytes retrieved although the effect estimate was imprecise. Associations of NDI with a number of mature oocytes retrieved and OSI were in a similar direction. We observed evidence for effect modification of the NDI and OSI association by donor race. There was a suggestive positive association between NDI and OSI in Black donors but no association in White donors. In this cohort of young, healthy, racially diverse oocyte donors, we found little evidence of associations between NDI and markers of ovarian reserve or outcomes of ovarian stimulation. [ABSTRACT FROM AUTHOR]

Objective: The main purpose of this study was to elucidate the anti-apoptotic effects of curculigoside (CUR) on ovarian granulosa cells (GCs) in a mouse model of cyclophosphamide (CTX)-induced premature ovarian failure (POF). Method: Intraperitoneal injection of CTX (100 mg/kg body weight) induced POF in mice. Thirty-six female mice were divided into six groups: blank group; POF model group; low-dose CUR group; medium-dose CUR group; high-dose CUR group; and estradiol benzoate group. Mice were orally administered for 28 consecutive days. Twenty-four hours after the completion of treatment, mice were weighed and euthanized, and blood was collected from the eyeball under anesthesia. The ovaries were surgically separated and weighed, and the ovarian index was calculated. Hematoxylin–eosin (HE) staining was used to observe follicular development and corpus luteum morphology in the ovaries. Serum levels of follicle stimulating hormone (FSH), anti-Müllerian hormone (AMH) and estradiol (E2) were measured. Superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) content and malondialdehyde (MDA) levels in ovarian tissue were determined. The GC apoptosis level was measured. Western blotting was used to detect protein expression levels of Beclin-1, LC3, P62, AKT, p-AKT, mTOR and p-mTOR in the ovaries. Results: The results showed that CUR can improve body weight and ovarian index; promote follicular development and reduce follicular atresia; improve FSH, AMH and E2 levels; downregulate MDA levels and restore antioxidant enzyme activity; inhibit the autophagy level; activate the AKT/mTOR signaling pathway; and alleviate GC apoptosis. Conclusion: CUR improves POF by activating the AKT/mTOR signaling pathway, inhibiting autophagy and alleviating GC apoptosis. [ABSTRACT FROM AUTHOR]

The relationship between premature ovarian insufficiency (FXPOI) and premutation in the FMR1 gene is well established. In recent years, though, a potential relationship between the latter and a low ovarian reserve has been suggested. To explore it, we conducted a retrospective study in an IVF program at a university tertiary referral center in Barcelona (Spain). Data were obtained retrospectively from a total of 385 women referred for FMR1 gene testing at our institution from January 2018 to December 2021. We compared the prevalence of FMR1 gene premutation between 93 of them, younger than 35 years, with a diminished ovarian reserve (DOR), characterized by levels of anti-Mullerian hormone < 1.1 ng/mL and antral follicle count < 5; and 132 egg donors screened by protocol that served as the controls. We found a higher prevalence of FMR1 premutation in the DOR group (seven patients (7.69%)) than in the control group (one patient (1.32%)), Fisher-exact test p-value = 0.012). We concluded that compared with the general population represented by young egg donors, the prevalence of FMR1 gene premutation is higher in young patients with a diminished ovarian reserve. Although these findings warrant further prospective validation in a larger cohort of patients within DOR, they suggest that, in clinical practice, FMR1 premutation should be determined in infertile young patients with DOR in order to give them adequate genetic counselling. [ABSTRACT FROM AUTHOR]

Ovarian aging, a natural process in women and various other female mammals as they age, is characterized by a decline in ovarian function and fertility due to a reduction in oocyte reserve and quality. This phenomenon is believed to result from a combination of genetic, hormonal, and environmental factors. While these factors collectively contribute to the shaping of ovarian aging, the substantial impact and intricate interplay of chronic inflammation in this process have been somewhat overlooked in discussions. Chronic inflammation, a prolonged and sustained inflammatory response persisting over an extended period, can exert detrimental effects on tissues and organs. This review delves into the novel hallmark of aging—chronic inflammation—to further emphasize the primary characteristics of ovarian aging. It endeavors to explore not only the clinical symptoms but also the underlying mechanisms associated with this complex process. By shining a spotlight on chronic inflammation, the aim is to broaden our understanding of the multifaceted aspects of ovarian aging and its potential clinical implications. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether trigger and oocyte collection at a smaller follicle size decreases the risk of premature ovulation while maintaining the reproductive potential of oocytes in women with a severely diminished ovarian reserve undergoing modified natural‐cycle in‐vitro fertilization. Methods: This was a retrospective cohort study including women who had at least one unsuccessful cycle (due to no response) of conventional ovarian stimulation with a high dosage of gonadotropins and subsequently underwent a modified natural cycle with a solitary growing follicle (i.e. only one follicle > 10 mm at the time of trigger). The association between follicle size at trigger and various cycle outcomes was tested using regression analyses. Results: A total of 160 ovarian stimulation cycles from 110 patients were included in the analysis. Oocyte pick‐up (OPU) was performed in 153 cycles and 7 cycles were canceled due to premature ovulation. Patients who received their trigger at smaller follicle sizes (≤ 15 mm) had significantly lower rates of premature ovulation and thus higher rates of OPU (98.9% vs 90.8%; odds ratio, 9.56 (95% CI, 1.58–182.9); P = 0.039) compared with those who received their trigger at larger follicle sizes (> 15 mm). On multivariable analysis, smaller follicle sizes at trigger (> 10 to 13 mm, > 13 to 15 mm, > 15 mm to 17 mm) were not associated significantly with a lower rate of cumulus–oocyte complex (COC) retrieval, metaphase‐II (MII) oocytes or blastulation when compared to the > 17‐mm group. On sensitivity analysis including only the first cycle of each couple, the maturity rate among those with COC retrieval was highest in follicle sizes > 15 to 17 mm (92.3%) and > 13 to 15 mm (91.7%), followed by > 10 to 13 mm (85.7%) and lowest in the > 17‐mm group (58.8%). During the study period, five euploid blastocysts developed from 48 fertilized MII oocytes with follicle sizes of 12 mm (n = 3), 14 mm (n = 1) and 16 mm (n = 1) at trigger. Of those, four were transferred and resulted in two live births, both of which developed from follicles with a size at trigger of 12 mm. Conclusions: The ideal follicle size for triggering oocyte maturation may be smaller in women with a severely diminished ovarian reserve managed on a modified natural cycle when compared to conventional cut‐offs. The risk of OPU cancellation was significantly higher in women triggered at follicle size > 15 mm and the yield of mature oocytes was not adversely affected in women triggered at follicle size > 13 to 15 mm compared with > 15 to 17 mm. Waiting for follicles to reach sizes > 17mm may be detrimental to achieving optimal outcome. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFASs) are a class of anthropogenic organic compounds widely present in the natural and human living environments. These emerging persistent pollutants can enter the human body through multiple channels, posing risks to human health. In particular, exposure to PFASs in women may cause a series of reproductive health hazards and infertility. Based on a review of the existing literature, this study preliminarily summarizes the effects of PFAS exposure on the occurrence and development of female reproductive endocrine diseases, such as polycystic ovary syndrome (PCOS), endometriosis, primary ovarian insufficiency (POI), and diminished ovarian reserve (DOR). Furthermore, we outline the relevant mechanisms through which PFASs interfere with the physiological function of the female ovary and finally highlight the role played by nutrients in reducing the reproductive health hazards caused by PFASs. It is worth noting that the physiological mechanisms of PFASs in the above diseases are still unclear. Therefore, it is necessary to further study the molecular mechanisms of PFASs in female reproductive diseases and the role of nutrients in this process. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion This study aimed to illustrate the copper status of diminished ovarian reserve in Chinese women, especially the effects of copper, ceruloplasmin, non‐ceruloplasmin‐bound copper (NCC) and CuZn superoxide dismutase (SOD1).This case–control, cross‐sectional investigation included women with diminished ovarian reserve (DOR group, n = 35) and matched normal ovarian reserve (NOR group, n = 35). The serum levels of copper, ceruloplasmin, NCC, SOD1, follicle‐stimulating hormone, luteinizing hormone, estradiol, testosterone, and anti‐Müllerian hormone were tested and analyzed.The serum copper concentrations (60.88%), NCC (54.75%) and SOD1 (54.75%) in the DOR group were significantly higher than those in the NOR group (all P < 0.001), and the concentrations of the three markers were higher in most subgroups (P < 0.001). The correlation analysis verified the correlation between copper status and impaired ovarian function. Additionally, linear regression analysis showed that NCC and SOD1 levels were negatively correlated with anti‐Müllerian hormone (P < 0.05 or 0.001).Our exploration found significant increases in copper, NCC and SOD1 levels in DOR and suggests a possible link. Copper status is expected to serve as the predictive marker for DOR. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: This study evaluates the research developments concerning Rehmanniae Radix in ovarian hypofunction diseases. It explores the processing methods of Rehmanniae Radix, the variations in its compounds before and after processing, the mechanism of Rehmanniae Radix and its active compounds in improving ovarian function, and the advancements in clinical applications of traditional Chinese medicine (TCM) compound that include Rehmanniae Radix. Methods: Comprehensive literature search was conducted using databases such as China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, National Science and Technology Library, the Pharmacopoeia of the People's Republic of China, Pubmed, and the Web of Science Database. The search utilized the following Medical Subject Headings (MeSH) and keywords: "Rehmanniae Radix," "Drying Rehmannia Root," "Rehmannia glutinosa," "Rehmanniae Radix Praeparata," "Traditional Chinese Medicine Processing," "Pharmacological Effects," "Ovarian Aging," "Diminished ovarian reserve," "Premature ovarian insufficiency," "Premature Ovarian Failure," "Ovarian hypofunction diseases". Results: The ancient Chinese medical books document various processing techniques for Rehmanniae Radix. Contemporary research has identified changes in its compounds processing and the resultant diverse therapeutic effects. When processed into Rehmanniae Radix Praeparata, it is noted for its ability to invigorate the kidney. TCM compound containing Rehmanniae Radix is frequently used to treat ovarian hypofunction diseases, demonstrating significant clinical effectiveness. The key changes in its compounds processing include cyclic dilute ether terpene glycosides, phenylethanol glycosides, sugars, and 5-hydroxymethylfurfural. Its pharmacological action is primarily linked to the improvement of granulosa cell proliferation, antioxidative and anti-aging properties, and modulation of the immune and inflammatory microenvironment. Furthermore, Rehmanniae Radix also offers therapeutic benefits for cardiovascular and cerebrovascular diseases, osteoporosis and cognitive dysfunction caused by low estrogen levels. Thereby Rehmanniae Radix mitigates both the short-term and long-term health risks associated with ovarian hypofunction diseases. Conclusion: Processed Rehmanniae Radix has shown potential to improve ovarian function, and its compound prescriptions have a definite effect on ovarian dysfunction diseases. Therefore Rehmanniae Radix was garnering interest for both basic and clinical research, with promising application prospects as a future therapeutic agent for ovarian hypofunction diseases. However, further studies on its toxicology and the design of standardized clinical trials are necessary to fully establish its efficacy and safety. [ABSTRACT FROM AUTHOR]

Female fertility depends on the ovarian reserve of follicles, which is determined at birth. Primordial follicle development and oocyte maturation are regulated by multiple factors and pathways and classified into gonadotropin-independent and gonadotropin-dependent phases, according to the response to gonadotropins. Folliculogenesis has always been considered to be gonadotropin-dependent only from the antral stage, but evidence from the literature highlights the role of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) during early folliculogenesis with a potential role in the progression of the pool of primordial follicles. Hormonal and molecular pathway alterations during the very earliest stages of folliculogenesis may be the root cause of anovulation in polycystic ovary syndrome (PCOS) and in PCOS-like phenotypes related to antiepileptic treatment. Excessive induction of primordial follicle activation can also lead to premature ovarian insufficiency (POI), a condition characterized by menopause in women before 40 years of age. Future treatments aiming to suppress initial recruitment or prevent the growth of resting follicles could help in prolonging female fertility, especially in women with PCOS or POI. This review will briefly introduce the impact of gonadotropins on early folliculogenesis. We will discuss the influence of LH on ovarian reserve and its potential role in PCOS and POI infertility. [ABSTRACT FROM AUTHOR]

Objective: To analyse the serum levels of soluble adhesion molecule 1 (sICAM 1), 17 helper T cells (Th17) and system immune inflammation index (SII) and endometriosis cyst degree of adhesion and the relationship between the ovarian reserve function after surgery for. Methods: From January 2020 to October 2023 in our hospital laparoscopic surgical endometriosis cyst removal of 90 cases of ectopic intrauterine membrane cyst patients into the observation group, according to the degree of endometriosis cyst adhesion, divided into severe adhesion group (32 cases) and the severe adhesion (58 cases). Physical examination work in the same period of 90 cases of healthy women in the control group. To detect all patients serum sICAM 1, resistance to seedling le tube hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) levels and peripheral blood levels of Th17, SII. Multiple Logistic regression was used to analyze the relationship between sICAM-1, Th17, SII and adhesion of severe ectopic endometrial cyst. Postoperative serum AMH, FSH, LH and E2 levels were compared between the severe adhesion group and the non-severe adhesion group, SICAM-1, Th17, SII Pearson correlation analysis and the relationship between indicators of ovarian reserve function. Results: The levels of serum sICAM-1 and Th17 in peripheral blood in observation group were higher than those in control group, and SII was higher than those in control group (P<0.05). Serum sICAM-1 and peripheral blood Th17 levels in severe adhesion group were higher than those in non-severe adhesion group, SII was higher than that in non-severe adhesion group(P<0.05). Multiple Logistic regression analysis showed that sICAM-1, Th17 and SII were all independent influencing factors of severe ectopic endometrial cyst adhesion(P<0.05). Postoperative serum AMH and E2 levels were lower than the non-severe group, and FSH and LH levels were higher than the non-severe group (P<0.05). Pearson correlation analysis showed that sICAM-1, Th17 and SII in patients with endometriosis cyst were negatively correlated with postoperative AMH and E2 (P<0.05), and positively correlated with FSH and LH (P<0.05). Conclusion: Serum sICAM-1, Th17 and SII are positively correlated with the adhesion degree of endometriosis cyst, which is helpful to reflect the postoperative ovarian reserve function and worthy of further study and application. [ABSTRACT FROM AUTHOR]

Delayed conceiving is a failure of a female to attain clinical pregnancy within a year without the use of contraception or any precautionary measure. The females of reproductive age (20–49 years) are the sufferers, that is, about 1.5 million or 10% of couples globally are facing this issue. Delayed conception can be caused by several reasons including diet, lifestyle, and genetic and clinical problems. Deficiencies or overconsumption of any nutrient may also cause delayed conception in females. Dietary deficits such as iron, iodine, zinc, folate, and vitamin D reduce the ovarian reserve. Heavy metals such as copper, manganese, lead, and cadmium also have an impact on fertility. Overconsumption of fast foods and nonhome‐made foods increases the likelihood of infertility by 2–3. Smoking, physical activity, age, polycystic ovary syndrome (PCOS), obesity, and depression have all been considered lifestyle and clinical factors. If women have a sedentary lifestyle, too much exercise or obesity both contribute to infertility. In clinical factors, type 1 diabetes, insulin resistance, and hypertension mainly cause infertility. Our focus in this review is on the studies probe that how these variables contributed to delayed conception and how it can be controlled to help combat infertility. Prevention from delayed conception involves consuming a healthy and balanced diet that contains essential nutrients engaging in physical activity and abstaining from smoking, PCOS, and medical issues. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMaterials and methodsResultsConclusions\nSHORT CONDENSATIONThe aim of this article was to discuss all the factors affecting the age at menopause and their correlation with ovarian reserve.A narrative review of original articles was performed using PubMed until December 2023. The following keywords were used to generate the list of citations: ‘menopause’, ‘ovarian reserve’ ‘oocytes quality and quantity’, ‘ovarian ageing’.Menopause is the final step in the process of ovarian ageing and is influenced by the oocyte pool at birth. Conditions that accelerate follicle depletion during the reproductive lifespan lead to premature ovarian insufficiency (POI) and premature ovarian failure (POF), while a higher ovarian reserve is associated with a delayed time to menopause. Reproductive history, sociodemographic, lifestyle and iatrogenic factors may impact ovarian reserve and the age at menopause.Some factors affecting the age at menopause are modifiable and the risks of early menopause may be preventable. We hypothesise that by addressing these modifiable factors we may also preserve ovarian reserve. However, further interventional studies are needed to evaluate the effects of the described strategies on ovarian reserve.The age of menopause is determined by the process of follicle depletion, which leads to a decrease in the quantity and quality of oocytes. Various factors such as demographics, menstrual patterns, reproductive history, family history, genetics, and lifestyle choices appear to influence the age at which natural menopause occurs. Some of these factors can be modified. Considering the relationship between ovarian reserve and the age of natural menopause, is it possible to intervene on these modifiable factors to preserve ovarian reserve? [ABSTRACT FROM AUTHOR]

Objective: This study explored the impact of one session of low-pressure leg blood flow restriction (BFR) during treadmill walking on dual-task performance in older adults using the neurovisceral integration model framework. Methods: Twenty-seven older adults participated in 20-min treadmill sessions, either with BFR (100 mmHg cuff pressure on both thighs) or without it (NBFR). Dual-task performance, measured through light-pod tapping while standing on foam, and heart rate variability during treadmill walking were compared. Results: Following BFR treadmill walking, the reaction time (p = 0.002) and sway area (p = 0.012) of the posture dual-task were significantly reduced. Participants exhibited a lower mean heart rate (p < 0.001) and higher heart rate variability (p = 0.038) during BFR treadmill walking. Notably, BFR also led to band-specific reductions in regional brain activities (theta, alpha, and beta bands, p < 0.05). The topology of the EEG network in the theta and alpha bands became more star-like in the post-test after BFR treadmill walking (p < 0.005). Conclusion: BFR treadmill walking improves dual-task performance in older adults via vagally-mediated network integration with superior neural economy. This approach has the potential to prevent age-related falls by promoting cognitive reserves. [ABSTRACT FROM AUTHOR]

Introduction: Premature ovarian insufficiency (POI) is one of the causes of female infertility. Unexplained POI is increasingly affecting women in their reproductive years. However, the etiology of POI is diverse and remains elusive. We and others have shown that brain-derived neurotrophic factor (BDNF) plays an important role in adult ovarian function. Here, we report on a novel role of BDNF in the Developmental Origins of POI. Methods: Placental BDNF knockout mice were created using CRISPR/CAS9. Homozygous knockout (cKO(HO)) mice didn't survive, while heterozygous knockout (cKO(HE)) mice did. BDNF reduction in cKO(HE) mice was confirmed via immunohistochemistry and Western blots. Ovaries were collected from cKO(HE) mice at various ages, analyzing ovarian metrics, FSH expression, and litter sizes. In one-month-old mice, oocyte numbers were assessed using super-ovulation, and oocyte gene expression was analyzed with smart RNAseq. Ovaries of P7 mice were studied with SEM, and gene expression was confirmed with RT-qPCR. Alkaline phosphatase staining at E11.5 and immunofluorescence for cyclinD1 assessed germ cell number and cell proliferation. Results: cKO(HE) mice had decreased ovarian function and litter size in adulthood. They were insensitive to ovulation induction drugs manifested by lower oocyte release after superovulation in one-month-old cKO(HE) mice. The transcriptome and SEM results indicate that mitochondria-mediated cell death or aging might occur in cKO(HE) ovaries. Decreased placental BDNF led to diminished primordial germ cell proliferation at E11.5 and ovarian reserve which may underlie POI in adulthood. Conclusion: The current results showed decreased placental BDNF diminished primordial germ cell proliferation in female fetuses during pregnancy and POI in adulthood. Our findings can provide insights into understanding the underlying mechanisms of POI. [ABSTRACT FROM AUTHOR]

BACKGROUND: Currently, hormone replacement therapy is the main treatment in Western medicine for patients with decreased ovarian function, but these patients are not sensitive to exogenous hormones, leading to unsatisfactory therapeutic effect. Zishen-Yutai pills can nourish the blood and calm the fetus, tonify the kidney and spleen, invigorate qi and strengthen the body. Studies have confirmed that Zishen-Yutai pill is effective in reducing follicle-stimulating hormone index and improving traditional Chinese medicine symptoms in patients with diminished ovarian reserve. However, few studies have been conducted to improve the implantation rate of patients by improving endometrial receptivity. OBJECTIVE: To evaluate the effect of Zishen-Yutai pills on the clinical outcome of patients with diminished ovarian reserve undergoing frozen-thawed embryo transfer again. METHODS: A total of 300 patients with diminished ovarian reserve who underwent frozen-thawed embryo transfer to assist pregnancy after the first failure in the Center of Reproductive Medicine, Changzhou Maternal and Child Health Care Hospital from January 2019 to December 2021 were selected as the study subjects. Subjects were randomly treated with a placebo or Zishen-Yutai pills in a ratio of 1:2, with 100 cases in the treatment group and 200 cases in the control group. However, 13 patients fell off due to lack of contact, refusal to take medicine or other reasons. Finally, 90 cases in the treatment group and 197 cases in the control group were included in the study. Oral medication was administered 7 days before frozen-thawed embryo transfer transplantation at a dose of 5 g/time, 3 times/day. To investigate whether taking Zishen-Yutai pills could improve the clinical outcome of patients with diminished ovarian reserve after frozen-thawed embryo transfer again, the primary outcome measures included clinical pregnancy rate, implantation rate, abortion rate, live birth rate, offspring birth weight and birth defects. RESULTS AND CONCLUSION: Compared with the control group, the clinical pregnancy rate (P < 0.05) and implantation rate (P=0.009) were significantly increased after the oral administration of Zishen-Yutai pills. Correlation analysis showed that taking the Zishen-Yutai pill was positively correlated with the number of implanted embryos (r=0.200, P=0.001) and clinical pregnancy (r=0.235, P=0.000). There was no correlation between taking Zishen-Yutai pills and indexes of endometrial thickness and blood flow. It is indicated that Zishen-Yutai pills can improve the clinical pregnancy rate and implantation rate of frozen-thawed embryo transfer recurrence in patients with diminished ovarian reserve. [ABSTRACT FROM AUTHOR]

Pathogenic germline variants in the FOXL2 gene are associated with Blepharophimosis, Ptosis, and Epicanthus Inversus syndrome (BPES) in humans, an autosomal dominant condition. Two forms of BPES have emerged: (i) type I (BPES‐I), characterized by ocular signs and primary ovarian failure (POI), and (ii) type II (BPES‐II) with no systemic associations. This study aimed to compare the distribution of FOXL2 variants in idiopathic POI/DOR (diminished ovarian reserve) and both types of BPES, and to determine the involvement of FOXL2 in non‐syndromic forms of POI/DOR. We studied the whole coding region of the FOXL2 gene using next‐generation sequencing in 1282 patients with non‐syndromic POI/DOR. Each identified FOXL2 variant was compared to its frequency in the general population, considering ethnicity. Screening of the entire coding region of the FOXL2 gene allowed us to identify 10 different variants, including nine missense variants. Of the patients with POI/DOR, 14 (1%) carried a FOXL2 variant. Significantly, six out of nine missense variants (67%) were overrepresented in our POI/DOR cohort compared to the general or specific ethnic subgroups. Our findings strongly suggest that five rare missense variants, mainly located in the C‐terminal region of FOXL2 are high‐risk factors for non‐syndromic POI/DOR, though FOXL2 gene implication accounts for approximately 0.54% of non‐syndromic POI/DOR cases. These results support the implementation of routine genetic screening for patients with POI/DOR in clinical settings. [ABSTRACT FROM AUTHOR]

Hemoglobin diseases like sickle cell disease (SCD) and β-thalassemia (BT) present fertility challenges for affected patients. SCD and BT result from abnormal hemoglobin production or structure and pose numerous health concerns. Despite medical advancements improving the quality of life or even providing cures, SCD and BT pose unique fertility concerns for women. Young women with these disorders already contend with reduced ovarian reserve and a narrower fertile window, a situation that is compounded by the gonadotoxic effects of treatments like medications, transfusions, stem cell transplants, and gene therapy. While crucial for disease control, these interventions may lead to reproductive health issues, increasing infertility and early menopause risks. Ovarian tissue cryopreservation (OTC) offers potential for future motherhood to women with hemoglobin disorders facing infertility related to curative treatments. OTC involves surgically removing, preparing, and freezing ovarian tissue containing primordial follicles capable of producing mature oocytes, offering advantages over oocyte cryopreservation alone. However, the application of OTC for patients with hemoglobin disorders presents unique challenges, including special health risks, financial barriers, and access to care. This comprehensive literature review delves into the current state of ovarian tissue cryopreservation for fertility preservation in patients with hemoglobin disorders. Empowering patients with informed reproductive choices in the context of their hemoglobin disorders stands as the ultimate goal. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Germline genome editing of IVF embryos is controversial because it is not directly health or lifesaving but is intended to prevent genetic diseases in yet-unborn future offspring. The following criteria are thus proposed for future clinical trials: (i) Due to medical risks, there should be cautious and judicious application while avoiding any non-essential usage, with rigorous patient counseling. (ii) Genome editing should only be performed on the entire batch of IVF embryos without initial PGT screening if all of them are expected to be affected by genetic disease. (iii) When there is a fair chance that some IVF embryos will not be affected by genetic diseases, initial PGT screening must be performed to identify unaffected embryos for transfer. (iv) IVF embryos with carrier status should not undergo germline genome editing. (v) If patients fail to conceive after the transfer of unaffected embryos, they should undergo another fresh IVF cycle rather than opt for genome editing of their remaining affected embryos. (vi) Only if the patient is unable to produce any more unaffected embryos in a fresh IVF cycle due to advanced maternal age or diminished ovarian reserves, can the genome editing of remaining affected embryos be permitted as a last resort. [ABSTRACT FROM AUTHOR]

Background: Ovarian reserve is one of the most important factors that influences the success of assisted reproductive technology (ART). Recently, the role of anti-müllerian hormone (AMH) in ART has been investigated as a marker for the prediction of ovarian response. We aim to examine this relationship within a large Iranian population. Materials and Methods: In this cross-sectional study, we obtained data from 1000 infertile couples who referred to the Research and Clinical Centre of Yazd Infertility Clinic for in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Serum AMH levels, oocyte count, numbers of fertilised oocytes, endometrial thickness, and percentage of mature oocytes were measured. The relationship between AMH serum levels and the number and quality of oocytes and embryos in ART cycles was analysed. Results: In the linear regression model, the log of the variables total dose of gonadotropin, two pronuclei (2PN), log oestradiol, total embryos, duration of stimulation, number of embryos transferred, protocol, and cause of infertility were significant predictors of log AMH. Conclusion: There appears to be a relationship between serum AMH levels in the early follicular phase and ovarian reserve. Higher serum AMH levels were also associated with shorter ART cycles. [ABSTRACT FROM AUTHOR]

Background: Middle-aged working women represent most patients attending fertility clinics for in vitro fertilization (IVF) treatment. In this study, we aimed to identify the association of women's working status with clinical pregnancy and miscarriage in the first trimester after IVF treatment. Materials and Methods: In this single-centre cross-sectional study at a private clinic in Kazakhstan, we reviewed electronic medical records of all IVF with intracytoplasmic sperm injection (ICSI) and fresh embryo transfer (ET) cycles from January 2018 to December 2019 (n=654). 300 cycles in patients with normal ovarian reserve and registered working status of a female partner in the medical records were selected for the analysis. The study's primary outcome measures were clinical pregnancy rates and clinical miscarriage in the first trimester. Results: 204 women were employed, while 96 were not employed before the start of treatment. The mean age of all patients was 32.2 ± 4.8 years, ranging from 23 to 46 years. Two-thirds of working women had office-based occupations employed as doctors, school and university teachers, accountants, clerks, and managers. One-third of the study participants had manual labor jobs, including service positions and plant workers. There was no association between women's working status and clinical pregnancy rate adjusted for age, antral follicle count, history of pelvic adhesiolysis, and embryo development stage at embryo transfer. However, working women had almost five times the risk of the first trimester miscarriage compared to non-working women [adjusted odds ratio (aOR) 4.56, 95% confidence interval (CI): 0.52 to 4.96] adjusted for age and number of retrieved oocytes. Conclusion: Women who work before commencing IVF treatment can be reassured of having equal chances of conception following the treatment compared to non-working women. The observed risk of first trimester miscarriage in working women necessitates further research before drawing any conclusions from medical and public health points. [ABSTRACT FROM AUTHOR]

BACKGROUND Girls with Turner syndrome (TS) lack a partial or complete sex chromosome, which causes an accelerated decline of their ovarian reserve. Girls have to deal with several dilemmas related to their fertility, while only a limited number of them are referred to a fertility specialist and counselled about options of family planning on time. OBJECTIVE AND RATIONALE This scoping review provides an update of the literature on fertility in girls with TS throughout their lifespan and aims to propose a clinical practice guideline on fertility in TS. SEARCH METHODS Databases of PubMed, Embase, and Web of science were searched using the following key terms: Turner syndrome, fertility, puberty, pregnancy, sex-hormones, karyotype, fertility preservation, assisted reproductive techniques, and counselling, alongside relevant subject headings and synonymous terms. English language articles published since 2007 were critically reviewed. Pregnancies after using donated oocytes and data about girls with TS with Y-chromosomal content were excluded. OUTCOMES This search identified 1269 studies of which 120 were extracted for the review. The prevalence of natural conception ranged from 15% to 48% in women with 45,X/46,XX, 1% to 3% in women with 45,X, and 4% to 9% in women with other TS karyotypes. When assessing a girl's fertility potential, it was crucial to determine the karyotype in two cell lines, because hidden mosaicism may exist. In addition to karyotype, assessment of anti-Müllerian hormone (AMH) played a significant role in estimating ovarian function. Girls with AMH above the detection limit were most likely to experience spontaneous thelarche, menarche, and ongoing ovarian function during the reproductive lifespan. Fertility preservation became more routine practice: vitrification of oocytes was reported in 58 girls with TS and a median of five oocytes were preserved per stimulation. Ovarian tissue cryopreservation has demonstrated the presence of follicles in approximately 30% of girls with TS, mostly in girls with mosaic-TS, spontaneous puberty, and AMH above the detection limit. Although girls and their parents appreciated receiving counselling on fertility in TS, only one in ten girls with TS received specialized counselling. Unfamiliarity with fertility preservation techniques or uncertainties regarding the eligibility of a girl for fertility preservation constituted barriers for healthcare professionals when discussing fertility with girls with TS. WIDER IMPLICATIONS There currently is a high demand for fertility preservation techniques in girls with TS. A reliable prognostic model to determine which girls with TS might benefit from fertility preservation is lacking. Only a minority of these girls received comprehensive fertility counselling on the full spectrum of fertility, including uncertainties of fertility preservation, pregnancy risks, and alternatives, such as adoption. Fertility preservation could be a viable option for girls with TS. However, the question remains whether enough oocytes can be obtained for a realistic prospect of a live birth. It is important that girls and parents are empowered with the necessary information to make a well-informed decision. [ABSTRACT FROM AUTHOR]