Reproductive outcomes of dual trigger therapy with GnRH agonist and hCG versus hCG trigger in women with diminished ovarian reserve: a retrospective study.

BACKGROUND: Diminished ovarian reserve (DOR) is one of the obstacles affecting the reproductive outcomes of patients receiving assisted reproductive therapy. The purpose of this study was to investigate whether dual trigger, including gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG), can improve pregnancy outcomes in patients with DOR undergoing in vitro fertilization (IVF) cycles using mild stimulation protocols. METHODS: A total of 734 patients with DOR were included in this retrospective study. Patients were divided into a recombinant hCG trigger group and a dual trigger group (hCG combined with GnRHa) according to the different trigger drugs used. The main outcome measures included the number of oocytes retrieved, the fertilization rate, the number of transferable embryos, the implantation rate, the clinical pregnancy rate, the miscarriage rate, the live birth rate (LBR), and the cumulative live birth rate (CLBR). Generalized linear model and logistic regression analyses were performed for confounding factors. RESULTS: There were 337 cycles with a single hCG trigger and 397 cycles with dual trigger. The dual trigger group demonstrated significantly higher numbers of retrieved oocytes [3.60 vs. 2.39, adjusted ß = 0.538 (0.221-0.855)], fertilized oocytes [2.55 vs. 1.94, adjusted ß = 0.277 (0.031-0.523)] and transferable embryos [1.22 vs. 0.95, adjusted ß = 0.162 (-0.005-0.329)] than did the hCG trigger group, whereas no significant difference in the fertilization rate was observed between the two groups. Moreover, the embryo transfer cancellation rate (35.5% vs. 43.9%) was obviously lower in the dual trigger group. Among the fresh embryo transfer cycles, the implantation rate, clinical pregnancy rate, miscarriage rate and live birth rate were similar between the two groups. After controlling for potential confounding variables, the trigger method was identified as an independent factor affecting the number of oocytes retrieved but had no significant impact on the CLBR. CONCLUSIONS: Dual triggering of final oocyte maturation with hCG combined with GnRHa can significantly increase the number of oocytes retrieved in patients with DOR but has no improvement effect on the implantation rate, clinical pregnancy rate or LBR of fresh cycles or on the CLBR.

Effect of LH level on HCG trigger day on clinical outcomes in patients with diminished ovarian reserve undergoing GnRH-antagonist protocol.

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.

Dietary acid load and risk of diminished ovarian reserve: a case-control study.

BACKGROUND: The epidemiologic evidence on the association between acid load potential of diet and the risk of diminished ovarian reserve (DOR) is scarce. We aim to explore the possible relationship between dietary acid load (DAL), markers of ovarian reserve and DOR risk in a case-control study. METHODS: 370 women (120 women with DOR and 250 women with normal ovarian reserve as controls), matched by age and BMI, were recruited. Dietary intake was obtained using a validated 80-item semi-quantitative food frequency questionnaire (FFQ). The DAL scores including the potential renal acid load (PRAL) and net endogenous acid production (NEAP) were calculated based on nutrients intake. NEAP and PRAL scores were categorized by quartiles based on the distribution of controls. Antral follicle count (AFC), serum antimullerian hormone (AMH) and anthropometric indices were measured. Logistic regression models were used to estimate multivariable odds ratio (OR) of DOR across quartiles of NEAP and PRAL scores. RESULTS: Following increase in PRAL and NEAP scores, serum AMH significantly decreased in women with DOR. Also, AFC count had a significant decrease following increase in PRAL score (P = 0.045). After adjustment for multiple confounding variables, participants in the top quartile of PRAL had increased OR for DOR (OR: 1.26; 95%CI: 1.08-1.42, P = 0.254). CONCLUSION: Diets with high acid-forming potential may negatively affect ovarian reserve in women with DOR. Also, high DAL may increase the risk of DOR. The association between DAL and markers of ovarian reserve should be explored in prospective studies and clinical trials.

Effectiveness of naturopathy for pregnancy in women with diminished ovarian reserve: feasibility randomized controlled trial.

RESEARCH QUESTION: Is conducting a randomized control trial (RCT) to assess the effectiveness of whole-system naturopathy in improving pregnancy rates among women with diminished ovarian reserve (DOR) feasible? DESIGN: A two-arm, parallel group, assessor-blinded feasibility RCT was conducted. Women with DOR, trying to conceive naturally or by ART, were randomly assigned to naturopathy plus usual care, or usual care alone for 16 weeks. Primary outcomes were feasibility (recruitment, adherence, retention rates), acceptability and safety. Secondary outcomes included ongoing pregnancy rates, live birth rates and health-related outcomes (mental health, quality of life, diet, exercise, sleep and weight). Statistical significance of the differences between the two groups (P-values) were exploratory. RESULTS: One hundred and fifteen women completed the screening survey between March and November 2022. Of these, 66 women were assessed for eligibility and 41 (62%) consented. Recruitment resulted in seven enrolments each month. All 41 participants (100%) adhered to the intervention, 38 (93%) completed end-point questionnaires, 32 (78%) found study participation to be acceptable and 18 out of 21 (86%) from the intervention group would recommend a naturopathic intervention to other women with DOR. The naturopathic treatment was associated with only mild and temporary adverse events. No between-group differences were observed for pregnancy and live birth rates. CONCLUSION: The evaluation of whole-system naturopathy through a RCT was feasible and the treatment was acceptable and well tolerated according to women with DOR. Outcomes from this study will help inform sample size calculations powered for fertility outcomes for future RCTs on this topic.

Metabolic signature of follicular fluid in infertility-related diseases: a narrative review.

Metabolomics offers new methods to identify biomarkers for oocyte and embryo quality, and for a better understanding of the physiopathology of infertility. This review investigated the latest findings regarding metabolome-derived biomarkers in follicular fluid of women with the most common types of infertility, and the potential impact on reproductive medicine outcomes. PubMed was searched for publications on metabolomics and human follicular fluid, and key biomarkers, kinetics and relationships with infertility diseases were identified. A reduced concentration of glucose and increased concentrations of lactate and pyruvate were found in follicular fluid of patients with endometriosis and diminished ovarian reserve, and the opposite was found in patients with polycystic ovary syndrome. These signatures may lead to the hypothesis of changed metabolite concentrations in patients with endometriosis and diminished ovarian reserve, and a metabolic pathway alteration with decreased aerobic glycolysis in patients with polycystic ovary syndrome. However, the pattern found in patients with endometriosis and low responders may also be expected in follicular fluid of fertile women. Larger studies are needed to confirm the results. An international database may help to highlight follicular fluid biomarkers in order to improve the selection of cryopreserved oocytes, and to enrich culture medium to restore normal metabolism and improve reproductive treatment outcomes.

Do women with severely diminished ovarian reserve undergoing modified natural-cycle in-vitro fertilization benefit from earlier trigger at smaller follicle size?

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.

Chitosan alleviates ovarian aging by enhancing macrophage phagocyte-mediated tissue homeostasis.

BACKGROUND: Age-related changes in the ovarian microenvironment are linked to impaired fertility in women. Macrophages play important roles in ovarian tissue homeostasis and immune surveillance. However, the impact of aging on ovarian macrophage function and ovarian homeostasis remains poorly understood. METHODS: Senescence-associated beta-galactosidase staining, immunohistochemistry, and TUNEL staining were used to assess senescence and apoptosis, respectively. Flow cytometry was employed to evaluate mitochondrial membrane potential (MMP) and apoptosis in granulosa cells lines (KGN), and macrophages phagocytosis. After a 2-month treatment with low molecular weight Chitosan (LMWC), ovarian tissues from mice were collected for comprehensive analysis. RESULTS: Compared with the liver and uterus, the ovary displayed accelerated aging in an age-dependent manner, which was accompanied by elevated levels of inflammatory factors and apoptotic cells, and impaired macrophage phagocytic activity. The aged KGN cells exhibited elevated reactive oxygen species (ROS) and apoptotic levels alongside decreased MMP. H2O2-induced aging macrophages showed reduced phagocytosis function. Moreover, there were excessive aging macrophages with impaired phagocytosis in the follicular fluid of patients with diminished ovarian reserve (DOR). Notably, LMWC administration alleviated ovarian aging by enhancing macrophage phagocytosis and promoting tissue homeostasis. CONCLUSIONS: Aging ovarian is characterized by an accumulation of aging and apoptotic granulosa cells, an inflammatory response and macrophage phagocytosis dysfunction. In turn, impaired phagocytosis of macrophage contributes to insufficient clearance of aging and apoptotic granulosa cells and the increased risk of DOR. Additionally, LMWC emerges as a potential therapeutic strategy for age-related ovarian dysfunction.

Effect of diminished ovarian reserve on the outcome of fresh embryo transfer in IVF/ICSI cycles among young women: A retrospective cohort study.

OBJECTIVE: This study aims to investigate the effect of diminished ovarian reserve (DOR) on the clinical outcomes and maternal and infant safety of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) procedures in young women aged ≤ 35 years. METHODS: A retrospective cohort study was performed to analyze the clinical data of 4,203 infertile women aged ≤ 35 years who underwent fresh embryo transfer (ET) in IVF/ICSI cycles. The data were collected from their initial visits to Fujian Maternity and Child Health Hospital between January 2015 and January 2022. Based on their ovarian reserve, the participants were categorized into two groups: DOR group (n = 1,027) and non-DOR group (n = 3,176). A propensity score matching (PSM) method was employed to ensure a relatively balanced distribution of covariates. The primary outcome assessed in this study was the live birth rate, while the secondary observation indicators included rates of high-quality embryo development, blastocyst formation, clinical pregnancy, and miscarriage, along with perinatal complications, neonatal birth weight, and the incidence of low birth weight (LBW). RESULTS: The DOR group showed notably lowered rates of blastocyst formation (59.8% vs. 64.1%), embryo implantation (29.8% vs.33.3%), clinical pregnancy (47.9% vs. 53.6%), and live birth (40.6% vs. 45.7%) compared to the non-DOR group (all P < 0.05). However, no statistically significant differences were observed in the high-quality embryo rate, miscarriage rate, perinatal complications, neonatal birth weight, or LBW incidence in infants between both groups (all P > 0.05). CONCLUSION: DOR has been found to reduce both clinical pregnancy and live birth rates in young females undergoing fresh ET in IVF/ICSI cycles. However, this reduction does not increase the risk of perinatal complications or LBW of infants through live birth cycles.

Health needs, treatment decisions and experience of traditional complementary and integrative medicine use by women with diminished ovarian reserve: A cross-sectional survey.

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.

The Protective Role of Magnoliae Flos in Preventing Ovotoxicity and Managing Ovarian Function: An In Vitro and In Vivo Study.

Magnoliae Flos (MF) is a medicinal herb widely employed in traditional medicine for relieving sinusitis, allergic rhinitis, headaches, and toothaches. Here, we investigated the potential preventive effects of MF extract (MFE) against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity in ovarian cells and a mouse model of premature ovarian insufficiency (POI). The cytoprotective effects of MFE were assessed using CHO-K1 or COV434 cells. In vivo, B6C3F1 female mice were intraperitoneally injected with VCD for two weeks to induce POI, while MFE was orally administered for four weeks, beginning one week before VCD administration. VCD led to a significant decline in the viabilities of CHO-K1 and COV434 cells and triggered excessive reactive oxygen species (ROS) production and apoptosis specifically in CHO-K1 cells. However, pretreatment with MFE effectively prevented VCD-induced cell death and ROS generation, while also activating the Akt signaling pathway. In vivo, MFE increased relative ovary weights, follicle numbers, and serum estradiol and anti-Müllerian hormone levels versus controls under conditions of ovary failure. Collectively, our results demonstrate that MFE has a preventive effect on VCD-induced ovotoxicity through Akt activation. These results suggest that MFE may have the potential to prevent and manage conditions such as POI and diminished ovarian reserve.

Diagnostic Value of Autoantibodies against Steroidogenic Enzymes and Hormones in Infertile Women with Premature Ovarian Insufficiency.

The objective of the study was to evaluate the profile and diagnostic significance of serum autoantibodies in infertile patients with premature ovarian insufficiency (POI). The pilot study included 26 patients of reproductive age with POI and diminished ovarian reserve who received complex treatment using new surgical technologies (Group 1) and 18 patients without POI (Group 2). The profile of serum autoantibodies, including anti-ovarian antibodies, antibodies against thyroid peroxidase (TPO), steroidogenic enzymes, and steroid and gonadotropic hormones, was studied using modified ELISAs and human recombinant steroidogenic enzymes (CYP11A1, CYP19A1, CYP21A2). Patients in Group 1 had higher levels of IgG autoantibodies against steroidogenic enzymes, estradiol, progesterone, and TPO than those in Group 2. Tests for IgG antibodies against CYP11A1, CYP19A1, and CYP21A2 exhibited high sensitivity (65.4-76.9%), specificity (83.3-89.9%), and AUC values (0.842-0.910) for POI, the highest in the first test. Three-antibodies panel screening showed higher diagnostic accuracy (84.1% versus 75-79.6%). The levels of these antibodies correlated with menstrual irregularities and a decrease in the antral follicle count. Thus, antibodies against CYP11A1, CYP19A1, and CYP21A2 have a high diagnostic value for POI. Three-antibody panel screening may improve the accuracy of POI diagnosis and be useful for identifying high-risk groups, early stages of the disease, and predicting POI progression.

Benefit from luteal phase progestin-primed ovarian stimulation with clomiphene citrate supplementation in young women with diminished ovarian reserve: a retrospective study. / åµæ³¡æœŸå’Œé»„ä½“æœŸé«˜å­•æ¿€ç´ çŠ¶æ€ä¿ƒæŽ’åµæ–¹æ¡ˆåœ¨å¹´è½»åµå·¢å‚¨å¤‡åŠŸèƒ½å‡é€€å¥³æ€§ä¸­çš„åº”ç”¨.

OBJECTIVES: To compare the pregnant outcomes of luteal phase progestin-primed ovarian stimulation (PPOS) protocol with clomiphene citrate supplementation (LPPOS+CC) and follicular phase PPOS+CC protocol (FPPOS+CC) in young women with diminished ovarian reserve (DOR). METHODS: A total of 483 women aged ≤35 years with DOR, who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)/embryo transfer (ET) with controlled ovarian stimulation using LPPOS+CC (n=257) or FPPOS+CC (n=226) protocols during June 2018 and December 2021 at the First Affiliated Hospital of Wenzhou Medical University, were included in this retrospective study. The baseline characteristics, ovarian stimulation, endocrinological indicators, clinical outcomes between the two groups, and pregnancy outcomes of women achieved at least one high-quality cleavage-stage embryo or good-morphology blastocyst between the two groups were compared. RESULTS: No statistically significant differences were identified between the groups with respect to number of oocytes retrieved, oocyte maturation rate, high-quality cleavage-stage embryo cycle rate, the percentage of women with profound pituitary suppression, preterm birth rate, and live birth rate (P>0.05). Compared to FPPOS+CC group, the duration of stimulation [11.0 (9.0,12.0) vs. 9.0 (8.0,11.0) d, P<0.01] was significantly longer in the LPPOS+CC group. The LH levels on the day of trigger [4.0 (2.7,5.3) vs. 5.1 (3.2,7.2) IU/L, P<0.01], the percentage of women with LH levels of >10 IU/L on the trigger day (3.13% vs. 10.67%, P<0.01), and the two pronucleate (2PN) rate of ICSI oocytes (72.16% vs. 79.56%, P<0.05) were significantly lower in the LPPOS+CC group than those in the FPPOS+CC group. The consumption of total gonadotropin [2213 (1650,2700) vs. 2000 (1575,2325) IU, P<0.01], the progesterone levels on the day of trigger [1.3 (0.8,2.9) vs. 0.9 (0.6,1.2) ng/mL, P<0.01], the clinical pregnancy rate [61.88% vs. 46.84%, P<0.01], and implantation rate [42.20% vs. 31.07%, P<0.01] in the LPPOS+CC group were significantly higher than those in the FPPOS+CC group. CONCLUSIONS: Compared to FPPOS+CC, the LPPOS+CC protocol appears to have better pregnancy outcomes for young women with DOR undergoing IVF-ICSI-ET.

Paeoniflorin Alleviates Cisplatin-Induced Diminished Ovarian Reserve by Restoring the Function of Ovarian Granulosa Cells via Activating FSHR/cAMP/PKA/CREB Signaling Pathway.

Paeoniflorin (PAE) is the main active compound of Radix Paeoniae Rubra (a valuable traditional Chinese medicine and a dietary supplement) and exerts beneficial effects on female reproductive function. However, the actions of PAE on diminished ovarian reserve (DOR, a very common ovarian function disorder) are still unclear. Herein, our study investigated the effect and potential mechanism of PAE on DOR by using cisplatin-induced DOR mice and functional impairment of estradiol (E2) synthesis of ovarian granulosa-like KGN cells. Our data show that PAE improved the estrous cycle, ovarian index, and serum hormones levels, including E2, and the number of antral follicles and corpora lutea in DOR mice. Further mechanism results reveal that PAE promoted aromatase expression (the key rate-limiting enzyme for E2 synthesis) and upregulated the FSHR/cAMP/PKA/CREB signaling pathway in the ovaries. Subsequently, PAE improved the levels of E2 and aromatase and activated the FSHR/cAMP/PKA/CREB signaling pathway in KGN cells, while these improving actions were inhibited by the siRNA-FSHR and FSHR antagonist treatments. In sum, PAE restored the function of E2 synthesis in ovarian granulosa cells to improve DOR by activating the FSHR/cAMP/PKA/CREB signaling pathway, which exhibited a new clue for the development of effective therapeutic agents for the treatment of DOR.

Metabolomic Analysis Reveals Association between Decreased Ovarian Reserve and In Vitro Fertilization Outcomes.

In vitro fertilization (IVF) is a highly effective treatment for infertility; however, it poses challenges for women with decreased ovarian reserve (DOR). Despite the importance of understanding the impact of DOR on IVF outcomes, limited research has explored this relationship, particularly using omics approaches. Hence, we conducted a study to investigate the association between DOR and IVF outcomes, employing a metabolomic approach. We analyzed serum samples from 207 women undergoing IVF treatment, including 89 with DOR and 118 with normal ovarian reserve (NOR). Our findings revealed that DOR was significantly associated with unfavorable IVF outcomes, characterized by a reduced oocyte count, lower embryo quality, and decreased rates of pregnancy and live births. Furthermore, we identified 82 metabolites that displayed significant alterations in DOR patients, impacting diverse metabolic pathways. Notably, a distinct panel of metabolites, including palmitic acid, stearic acid, LysoPC(9:0(CHO)/0:0), PC(18:0/9:0(CHO)), and PC(16:0/9:0(CHO)), exhibited discriminatory power between the DOR and NOR groups, showcasing a strong correlation with IVF outcomes. These findings emphasize the crucial role of metabolomic disruptions in influencing IVF outcomes among women with DOR.

Intriguing connection between diminished ovarian reserve and childhood traumatic experiences, a prospective case-control study.

INTRODUCTION: Diminished ovarian reserve (DOR) presents a complex challenge in the field of infertility, with factors like age and genetics traditionally under scrutiny. However, the potential influence of adverse childhood experiences on ovarian reserve remains a relatively unexplored area. This research aims to contribute novel insights to the understanding of diminished ovarian reserve etiology, shedding light on previously unexplored risk factors and their potential implications. DESIGN: This case-control study was conducted at an Assisted Reproductive Technology (ART) Center of a university hospital. Infertile patients admitted to the ART center were enrolled in the study. The case group consisted of 102 infertile women diagnosed with diminished ovarian reserve, and the control group consisted of 103 healthy women with male factor infertility. An interview lasting approximately 30 min was held in a separate room with those who volunteered to participate in the study. Due to the sensitivity of the research subject, the data was collected anonymously. The Childhood Trauma Questionnaire was used to measure adverse childhood experiences, and the Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depression in the study. The results were compared between the case and the control groups. RESULTS: Overall, the total score of the Childhood Trauma Questionnaire and all subscale scores were higher in the case group (38.28 ± 9.86) than in the control group (35.10 ± 9.52). According to HADS, the total score was 15.92 ± 7.98 in the case group and 14.22 ± 6.87 in the control group. CONCLUSIONS: Our pioneering study is designed to investigate a previously unexplored risk factor in low ovarian reserve. Considering our data and other studies in the literature examining childhood traumas as a risk, it makes us think that the issue is worth examining.

Predictive Factors for the Formation of Viable Embryos in Subfertile Patients with Diminished Ovarian Reserve: A Clinical Prediction Study.

This study aims to construct and validate a nomogram for predicting blastocyst formation in patients with diminished ovarian reserve (DOR) during in vitro fertilization (IVF) procedures. A retrospective analysis was conducted on 445 DOR patients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) at the Reproductive Center of Yulin Maternal and Child Health Hospital from January 2019 to January 2023. A total of 1016 embryos were cultured for blastocyst formation, of which 487 were usable blastocysts and 529 did not form usable blastocysts. The embryos were randomly divided into a training set (711 embryos) and a validation set (305 embryos). Relevant factors were initially identified through univariate logistic regression analysis based on the training set, followed by multivariate logistic regression analysis to establish a nomogram model. The prediction model was then calibrated and validated. Multivariate stepwise forward logistic regression analysis showed that female age, normal fertilization status, embryo grade on D2, and embryo grade on D3 were independent predictors of blastocyst formation in DOR patients. The Hosmer-Lemeshow test indicated no statistical difference between the predicted probabilities of blastocyst formation and actual blastocyst formation (P > 0.05). These results suggest that female age, normal fertilization status, embryo grade on D2, and embryo grade on D3 are independent predictors of blastocyst formation in DOR patients. The clinical prediction nomogram constructed from these factors has good predictive value and clinical utility and can provide a basis for clinical prognosis, intervention, and the formulation of individualized medical plans.

Healthy eating index and risk of diminished ovarian reserve: a case-control study.

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.

Maximizing ovarian function and fertility following chemotherapy in premenopausal patients: Is there a role for ovarian suppression?

As more premenopausal patients undergo fertility preserving cancer treatments, there is an increased need for fertility counseling and ovarian sparing strategies. Many patients receive gonadotoxic chemotherapeutic agents which can put them at risk of primary ovarian insufficiency or profoundly diminished ovarian reserve. Traditionally, estradiol and follicle stimulating hormone (FSH) values have been used to evaluate ovarian function but more recently, reproductive endocrinologists have been proponents of anti-mullerian hormone (AMH) as a validated measure of ovarian potential. While the gold standard for fertility preservation remains oocyte cryopreservation, data suggest there may be additional interventions that can mitigate the gonadotoxic effects of chemotherapeutic agents. The main objectives of this focused review were to quantify the risk of primary ovarian failure associated with the most common chemotherapies used in treatment of gynecologic cancers and to evaluate and recommend potential interventions to mitigate toxic effects on ovarian function. Chemotherapeutic agents can cause direct loss of oocytes and primordial follicles as well as stromal and vascular atrophy and the extent is dependent upon mechanism of action and age of the patient. The risk of ovarian failure is the highest with alkylating agents (42.2 %), anthracyclines (<10-34 % in patients under 40 years versus 98 % in patients aged 40-49), taxanes (57.1 %) and platinum agents (50 %). Multiple trials demonstrate that gonadotropin releasing hormone (GnRH) agonists, when administered concurrently with chemotherapy, may have protective effects, with more patients experiencing resumption of a regular menstruation pattern and recovering ovarian function more quickly post-treatment. Premenopausal patients receiving chemotherapy for the treatment of gynecologic cancers should receive adequate counseling on the potential adverse effects on their fertility. Although oocyte cryopreservation remains the gold standard for fertility preservation, there is some evidence to suggest that GNRH agonists could help maintain and preserve ovarian function and should be considered.

Comparison of progestin-primed ovarian stimulation regimen and antagonist regimen in women aged 35 years or older with diminished ovarian reserve: A propensity score-matched study.

OBJECTIVE: Diminished ovarian reserve (DOR) has been a major challenge in infertility treatment. The present study aimed to compare the efficacy of progestin-primed ovarian stimulation (PPOS) regimen and antagonist regimen in infertile patients aged 35 years or older with DOR. METHODS: A retrospective study of 289 in vitro fertilization (IVF) cycles from April 2016 to June 2022 was performed. Propensity score matching (PSM) was used to balance the baseline characteristics between the two groups at a ratio of 1:1. RESULTS: After matching, there were 87 cycles in the PPOS group and 87 cycles in the antagonist group. The primary outcome measures included the incidence of premature LH surge, the number of retrieved oocytes, and the number of mature oocytes, which were comparable between the two groups (all P values >0.05). There were no significant differences in laboratory indicators and final clinical outcomes between the two groups (all P values >0.05). CONCLUSIONS: For DOR patients aged 35 years or older, the number of retrieved oocytes and the number of mature oocytes were comparable between the PPOS and antagonist groups. Moreover, the two regimens showed no difference in the inhibition of premature LH surge.

Mitochondrial Morphology and Function Abnormality in Ovarian Granulosa Cells of Patients with Diminished Ovarian Reserve.

In this study, we examined the changes in the mitochondrial structure and function in cumulus granulosa cells of patients with diminished ovarian reserve (DOR) to explore the causes and mechanisms of decreased mitochondrial quality. The mitochondrial ultrastructure was observed by transmission electron microscope, and the function was determined by detecting the ATP content, reactive oxygen species (ROS) levels, the number of mitochondria, and the mitochondrial membrane potential. The expression of ATP synthases in relation to mitochondrial function was analyzed. Additionally, protein immunoblotting was used to compare the expression levels of mitochondrial kinetic protein, the related channel protein in the two groups. Patients with DOR had abnormal granulosa cell morphology, increased mitochondrial abnormalities, decreased mitochondrial function, and disturbed mitochondrial dynamics. Additionally, the silent information regulator 1 (SIRT1)/phospho-AMP-activated protein kinase (P-AMPK)-peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) pathway expression was decreased, which was speculated to be associated with the decreased mitochondrial mass in the DOR group. The mitochondrial mass was decreased in granulosa cells of patients in the DOR group. The mitochondrial dysfunction observed in granulosa cells of patients in the DOR group may be associated with dysregulation of the SIRT1/P-AMPK-PGC-1α-mitochondrial transcription factor A (TFAM) pathway.