Biomarkers Of Ovarian Reserve Research Articles

Anti-Müllerian hormone as a predictor of oocyte yield following controlled ovarian stimulation in the rhesus macaque.

Anti-Müllerian hormone (AMH) is widely used in the clinic as a biomarker for ovarian reserve and to predict ovarian response to gonadotropin stimulation. Patients with higher AMH levels tend to yield more oocytes and have better outcomes from assisted reproductive technology (ART) procedures. The goal of this study is to determine if AMH can be used to predict the outcome of controlled ovarian stimulation in rhesus macaques, which are commonly used in biomedical research, to refine animal use while maximizing oocyte yield. We hypothesized that pre-stimulation AMH values can be used to predict oocyte yield and quality. Regularly cycling adult macaques underwent controlled ovarian stimulation and baseline (pre-stimulation) plasma AMH levels were determined using an AMH-specific enzyme-linked immunoassay. Oocytes were collected by laparoscopic or ultrasound-guided aspiration, then counted and evaluated for quality and stage of meiosis. Sperm from established fertile males were used to inseminate the oocytes in vitro with fertilization success checked 14 - 16 hours later. Females were grouped by oocyte yield: low ≤ 17; mid = 18 - 41; high ≥ 42. We found that high and mid yielders had significantly higher AMH than low yielders (p<0.0001) and the percent of mature oocytes was greater in the high and mid yielders. There were no significant differences in oocyte quality or ova fertilization rate. These data suggest that AMH is a useful measure for controlled ovarian stimulation success in rhesus macaques and can be used to identify suitable animals for oocyte donation before entering them into a stimulation protocol.

Switch to Integrase Strand Transfer Inhibitors during the Menopausal Transition is Associated with Accelerated Body Composition Change in Women with HIV.

Integrase strand transfer inhibitors (INSTIs) and the menopausal transition have separately been associated with body composition changes in women with HIV (WWH), but their interaction is unknown. From 2006-2019, 1131 non-pregnant WWH with viral suppression [(419 who switched to INSTI (INSTI+); 712 who did not switch (INSTI-)] and 887 women without HIV (WWOH) from the Women's Interagency HIV Study were included. Mixed effect models were used to evaluate change in waist circumference (WC) and BMI by menopausal phase defined using anti-Müllerian hormone, a biomarker of ovarian reserve. During premenopause, WWH had increases in WC (INSTI+: 0.01cm per 6 month (mo); 95%CI:-0.29,0.32 and INSTI-: 0.22cm per 6mo;95%CI:-0.01,0.44) that were not statistically significantly different from WWOH; there was also little difference by INSTI status. In late perimenopause, INSTI+ had faster increases in WC (0.37cm per 6mo;95%CI:0.15,0.60) while INSTI- had smaller increases (0.14cm per 6mo;95%CI:-0.06,0.34) compared to WWOH. In menopause, INSTI+ had faster increases peaking at 43mo then declining while INSTI- had smaller increases (0.14cm per 6mo;95%CI:-0.02,0.30). Compared to INSTI-, in late perimenopause, INSTI+ had 0.26 cm per 6mo (95%CI:0.02,0.50) faster linear increases in WC and in menopause, INSTI+ was associated with faster increases peaking at 41mo. BMI trajectories were similar to WC in late peri- and menopausal women. Switching to an INSTI-based regimen during late peri- and menopause is associated with faster increases in WC and BMI when compared to women who did not switch. Menopausal status should be considered when switching to an INSTI.

Ovarian reserve does not influence natural conception: insights from infertile women.

There is several albeit not univocal evidence suggesting that ovarian reserve is not related to the chance of natural pregnancy, provided that the remnant follicular pool is sufficient to ensure regular menstrual cycles. Nevertheless, available studies have some methodological limitations, and the issue cannot be considered definitively ascertained. To further address this issue, we retrospectively selected infertile women whose infertility diagnostic work-up was unremarkable (unexplained infertility-cases) and matched them by age and study period to a group of infertile women who were diagnosed with severe male infertility (controls). If ovarian reserve impacts on natural fertility, one had to expect lower ovarian reserve among women with unexplained infertility. Tested biomarkers included AMH, AFC and day 2-3 serum FSH. The primary aim was the frequency of women with serum AMH < 0.7ng/ml. Two-hundred fifty-two women with unexplained infertility and 252 women with male infertility were included. All biomarkers of ovarian reserve did not differ between the study groups. AMH levels < 0.7ng/mL were observed in 26 (10%) women with unexplained infertility and 35 (14%) women with male infertility (p = 0.28). The adjusted OR was 0.76 (95% CI: 0.44-1.33). Significant differences did not also emerge when repeating this dichotomous analysis using other biomarkers and other thresholds for the definition of low-ovarian reserve. This study confirms that ovarian reserve is unremarkable to natural conception. Physicians and patients should be aware of this concept to avoid inappropriate counseling and undue clinical decisions.

Anti-Müllerian Hormone Serum Levels as Biomarker of Ovarian Reserve in Adult Women with Juvenile Idiopathic Arthritis Treated with csDMARDs and/or bDMARDs: A Pilot Study

Background/Objectives: Juvenile idiopathic arthritis (JIA) is a chronic childhood disease that often persists into the reproductive years. JIA may impact long-term fertility due to the prolonged exposure to immunosuppressive therapies. Methods: A total of 35 adult JIA female patients of childbearing age and 20 age-matched healthy controls were studied to test their anti-Müllerian hormone (AMH) serum levels as a biomarker of ovarian reserve. Demographic characteristics, disease duration, previous and current treatments, disease activity (DAS44), and a health assessment questionnaire (HAQ) were recorded. Results: JIA patients had a mean age of 22.3 ± 2.9 years, a disease duration of 12.3 ± 6.1 years, and a DAS44 of 1.24 ± 0.61. No differences were found in AMH serum levels between JIA and controls (5.78 ± 2.37 ng/mL vs. 6.60 ± 2.68 ng/mL, respectively; p = 0.17). Among the patients, 22 (62.9%) were receiving a stable dose of methotrexate (MTX) and 19 (54.3%) a dose of TNFα inhibitors. No difference in AMH serum levels was observed between JIA patients who were or were not exposed to MTX (p = 0.29) or to TNFα inhibitors (p = 0.50). Conclusions: Ovarian reserve as assessed by AMH serum levels appears to be comparable between those with JIA and age-matched controls and does not appear to be influenced by disease characteristics or prior/concomitant exposure to immunosuppressive drugs.

Association Between Homocysteine Levels and Ovarian Reserve in Subfertile Women.

To evaluate the relationship between homocysteine levels and anti-mullerian hormone (AMH) levels, a biomarker of ovarian reserve, and the effect of high homocysteine levels on ovarian reserve in subfertile women. Observational case-control study. Place and Duration of the Study: Samsun Training and Research Hospital, Samsun, Turkiye, from October to December 2023. Seventy-nine subfertile women and 35 healthy fertile women were included in this study. AMH, homocysteine, thyroid stimulating hormone (TSH), free T3 (fT3), free T4 (fT4), iron, and ferritin levels of subfertile and fertile women were compared. Logistic regression, receiver operating characteristic, and Kaplan-Meier analyses were performed for homocysteine levels. AMH, fT4, iron, and ferritin levels were lower in subfertile women than in fertile women (p <0.001). Homocysteine and TSH levels were higher in subfertile women than in fertile women (p <0.001). The sensitivity for homocysteine levels was 94.90% and the specificity was 94.30%. In the Kaplan-Meier analysis, homocysteine levels of 12.90 μmol/L and above were found to be risky in terms of fertility. Homocysteine levels, AMH, and ferritin levels were negatively correlated and TSH levels were positively correlated in subfertile women (p <0.001). However, these correlations were not observed in fertile women (p >0.05). High homocysteine levels can be considered as a risk factor affecting ovarian reserve in subfertile women. Anti-mullerian hormone, Female subfertility, Homocysteine, Hyperhomocysteinaemia, Ovarian reserve.

P-378 Relation between AMH serum levels and recovered mature oocytes in infertile, healthy, and oncological patients

Abstract Study question Does AMH serum levels correlate with the recovered mature oocytes in similar way among infertile, healthy, and oncological patients? Summary answer AMH serum levels correlated well with the number of mature oocytes in infertile, healthy, and oncological patients What is known already AMH is a protein produced by granulosa cells from pre-antral follicles and uses as biomarker of ovarian reserve. The aim of ovarian stimulation in the IVF setting or fertility preservation is obtaining metaphase II oocytes. The value of serum AMH to predict the number of mature oocytes has not been study in a comparative way among infertile patients vs. healthy and oncological population Study design, size, duration Retrospective study of the AMH serum levels and number of recovered mature oocytes in oocyte vitrification cycles from April 2017 to June 2023. We included 78 patients with cancer, 119 healthy patients and 668 infertile patients undergoing oocyte vitrification for fertility preservation or as accumulation of oocytes strategy Participants/materials, setting, methods This single centre study included Infertile patients ≤ 42 with gynaecological pathology (endometriosis, polycystic ovarian syndrome, low ovarian reserve, and/or tubal factor), any type of cancer and healthy women demanding social fertility preservation. We excluded IVF healthy patients (normal patients with exclusively male factor). AMH serum level was measured before ovarian stimulation. We analysed the probability of obtain ≥ 8 mature oocytes considering as normal AMH (1.2 ng/mL). Ethical approval was obtained for this stud Main results and the role of chance IVF patients were older and had higher body mass index than the other two groups. AMH serum level (ng/mL) was similar among groups; in IVF patients (1.88 [1.67-2.09]); oncological patients (2.25 [1.85-2.65]), and healthy women (2.5 [2.2-2.8]). (p= 0.064). Ovarian stimulation was longer and more FSH units were employed in IVF patients. Oestradiol level at the oocyte maturation triggering was lower in oncological patients. The number of MII oocytes was significantly lower in IVF patients (6.1 [5.9-6.4]) compared with oncological and healthy patients (9.2[8.0-10.5]; 9.9 [9.0-10.8], respectively). AMH level correlated well with the number of recovered mature oocytes and similar among groups. The Odds Ratio to recover ≥ 8 mature oocytes considering as normal AMH (1.2 ng/mL) showed a probability 8.3 times higher in healthy patients, but only 0.3 times in IVF patients and 0.5 times in oncological patients. A OR: 9.1 was observed for obtain ≥ 8 mature oocytes between normal vs low AMH. The area under the curve in the ROC curve for AMH was 0.7191 Limitations, reasons for caution This study had limitations in the sample size and differences in ovarian stimulation protocol as oncological patients in hormone-dependent cancer received letrozole while conventional ovarian stimulation with FSH was performed in IVF and healthy patients. IVF patients’ group was heterogeneous in the aetiology of infertility Wider implications of the findings This study remarks the use of AMH in different conditions: infertility, oncological, and healthy status. Although no differences were found in correlation with the number of mature oocytes, the probability to obtain ≥ 8 mature oocytes with normal AMH was higher in healthy women compared with infertile patients Trial registration number 2306-VGO-128-EM

Association of serum anti-mullerian hormone concentration with fertility status of crossbred (Vrindavani) cows

Anti-Mullerian hormone (AMH) is considered a biomarker of ovarian follicular reserve and fertility in humans and farm animals. A study was carried out to evaluate the peripheral AMH concentration in high and low fertile crossbred cows. Vrindavani crossbred cows (n=60) at the institutional dairy farm were used for the study. The age-specific decline in AMH concentration was evident, with the highest concentration at 4-6 years (134.8±17.74 pg/mL) corresponding to second to third parity. Retrospective assessment of fertility using 217 lactation records in crossbred cows revealed that circulatory AMH was higher by 69 pg/mL in the high fertile cows than those of low fertile cows. It was concluded that the serum AMH concentration was influenced by age and parity. Further, serum AMH concentrations were found to be higher in the group of cows that had superior fertility records in comparison to the group with low-performing animals.

Association between neighborhood poverty and ovarian reserve: the ovarian aging study.

This study aimed to examine the association between neighborhood poverty and ovarian reserve. Among 1,019 healthy premenopausal women in the Ovarian Aging Study, aggregate exposure to neighborhood poverty was examined in relation to biomarkers of ovarian reserve, antimüllerian hormone (AMH) and antral follicle count (AFC). Specifically, the interaction of age-x-neighborhood poverty was assessed cross-sectionally to determine whether AMH and AFC declines across women may be greater in women exposed to more neighborhood poverty. Neighborhood poverty was assessed by geocoding and linking women's residential addresses in adulthood to US Census data. Independent of covariates, a significant interaction term showed the association between age and AMH varied by degree of exposure to neighborhood poverty in adulthood ( b = -0.001, P < 0.05). AMH declines increased progressively across women exposed to low, medium, and high levels of neighborhood poverty. In addition, main effects showed that higher neighborhood poverty was related to higher AMH in the younger women only ( b = 0.022, P < 0.01). Results related to AFC were all nonsignificant ( P > 0.05). Across women, greater aggregate exposure to neighborhood poverty in adulthood was related to lower ovarian reserve, indexed by AMH. In addition, there was a positive association between neighborhood poverty and AMH in younger women that attenuated in the older women. Together, results suggest that neighborhood disadvantage may have detrimental impacts that manifest as initially higher AMH, resulting in greater ovarian follicle loss over time. However, it remains unclear whether these results examining differences across women may replicate when AMH declines by neighborhood poverty are examined longitudinally.

Serum anti-Müllerian hormone around the time of ovulation simulated by exogenous hormones in clouded leopards (Neofelis nebulosa).

Anti-Müllerian hormone (AMH) is produced by granulosa cells of the antral follicles. It serves as a promising biomarker for ovarian reserve and responsiveness to ovarian stimulation in humans and domestic animals. This study aimed to validate the AMH Gen II enzyme-linked immunosorbent assay (ELISA) and correlate ovarian structures with serum AMH concentrations after stimulation treatment in clouded leopards (Neofelis nebulosa). Serum samples were collected from 12 women (age 6.21 ± 3.56 years), and serum AMH concentrations were analysed using AMH Gen II ELISA. The animals were divided into two groups based on ovarian structures [preovulatory follicles (>2 mm) and/or corpora hemorrhagica] along with the presence of uterine tonicity visualized laparoscopically around the time of ovulation. Animals that exhibited these reproductive features were identified as the responder group (n = 9, aged 7.59 ± 2.96 years), whereas those lacking the corresponding features were assigned to the nonresponder group (n = 3, aged 2.06 ± 0.53 years). The intra-assay coefficient of variation (CV) and interassay CV was 3.56% and 7.75%, respectively. The linearity of AMH dilution was confirmed (r2 = .998), and the percentage of recovery ranged from 93% to 115%. The results demonstrated that overall serum AMH concentrations around the time of ovulation were negatively correlated with age (rs = -.692, p = .013). However, serum AMH concentrations were not correlated with the average number of ovarian structures (rs = -.535, p = .074). Thus, AMH Gen II ELISA was validated in clouded leopards. Around the time of ovulation, serum AMH decreased with advancing age and ovarian responsiveness cannot be evaluated using serum AMH.

Oocyte competence is comparable between progestin primed ovarian stimulation with Norethisterone acetate (NETA-PPOS) and GnRH-antagonist protocols: A matched case-control study in PGT-A cycles

ObjectiveTo outline oocyte competence after progestin primed ovarian stimulation with Norethisterone acetate (NETA-PPOS) compared to conventional GnRH-antagonist protocol. Study designRetrospective matched case-control study involving advanced-maternal-age women undergoing ICSI with PGT-A. 89 NETA-PPOS were matched with 178 control patients based on maternal age and ovarian reserve biomarkers. Both groups underwent recombinant-FSH OS with GnRH-agonist ovulation trigger and collected ≥1 MII. In the study group, NETA (10 mg/day) was administered orally starting from day2 of the menstrual cycle. Euploid blastocyst rate per cohort of metaphase-II oocytes (EBR per MII) was the primary outcome. All other embryological and clinical outcomes were reported. Gestational age, birthweight and length were also assessed. ResultsThe EBR per MII was comparable among PPOS and control (13.9 % ± 19.3 % versus 13.3 % ± 17.9 %; the sample size allowed to exclude up to a 10 % difference). Blastocysts morphology and developmental rate were similar. No difference was reported for all clinical outcomes among the 61 and 107 vitrified-warmed euploid single blastocyst transfers respectively conducted. The cumulative live birth delivery rate per concluded cycles was also comparable (24.7 % versus 21.9 %). Neonatal outcomes were analogous. ConclusionsOocyte competence after NETA-PPOS and standard OS is comparable. This evidence is reassuring and, because of its lower cost and possibly higher patients’ compliance, supports PPOS administration whenever the patients are indicated to freeze-all (e.g., fertility preservation, PGT-A, oocyte donation). More data are required about follicle recruitment, oocyte yield, gestational and perinatal outcomes. Randomized-controlled-trials are advisable to confirm our evidence.

#88 : Correlation Between AMH Levels and Aneuploidy Rates in Patients Over 40 Years of Age: A Novel Finding

Background and Aims: AMH is a crucial biomarker of ovarian reserve and predictor of ovarian response to stimulation. Ovarian reserve is inversely proportional to women’s age, consequently lower AMH levels are seen in older women particularly at [Formula: see text]40 yrs of age. A correlation between age and embryo aneuploidy was established but not with AMH level. We hypothesize that older women with good ovarian reserve produce less aneuploid embryos and produce the same blastocyst rate. Method: A retrospective study was undertaken involving 507 IVF cycles in patients aged [Formula: see text]40 years who had ICSI with PGT-A using NGS. The cycles were categorized into three main cohorts based on the patient’s AMH level: low (&lt; 1.1 ng/mL), moderate (&gt;1.1 to [Formula: see text] 3.0 ng/mL) and high (&gt; 3.0 ng/mL). Each cohort was subdivided into 3 age sub-cohorts as follow: (40 to &lt;42), (42 to &lt;44), and (&gt;44). Our primary outcome was aneuploidy rate whereas the secondary outcome was blastulation rate. Results: The results will be mentioned in sequence: low AMH, moderate AMH and, high AMH levels. In the [Formula: see text]40 to &lt; 42 age group, the aneuploidy rates were 78.2%, 72.3% and, 67.2%, respectively (n = 232; p = 0.027). The blastulation rates were 53.8%, 47.7% and, 48.5% respectively (p&gt; 0.05). In the [Formula: see text]42 and &lt;44 age group, the aneuploidy rates were 89.2%, 83.2% and, 81.5% respectively (n = 136 p=0.039). The blastulation rates were 45.2%, 46.2% and, 43.8% respectively p&gt; 0.05. In the [Formula: see text]44 age group, the aneuploidy rates were 93.9%, 91.2% and, 89.4% respectively (n = 139; p = 0.043). The blastulation rates were 41.2%, 39.2% and, 38.8% respectively (p&gt;0.05). Conclusion: The aneuploidy rates rises when AMH levels decreases; whereas the blastulation rates was not associated with AMH levels in the population studied.

Serum miRNA as a predictive biomarker for ovarian reserve after endometrioma-cystectomy

Ovarian endometrioma (OE) is a common gynecological disease that is often treated with surgery and hormonal treatment. However, ovarian cystectomy can impair the ovarian reserve (OR). Previously, we showed that perioperative administration of dienogest (DNG) is an effective option for OR preservation. However, there were differences in the extent of OR preservation among patients following perioperative DNG treatment. In the current study, we performed a global examination of serum microRNAs (miRNAs) to identify accurate biomarkers that predict post-operative restoration of OR following perioperative DNG treatment. We also sought to identify specific miRNAs related to the anti-Müllerian hormone (AMH). miRNA sequencing was performed on serum samples obtained from twenty-seven patients who received perioperative DNG treatment. Candidate miRNAs were selected by comparing patients whose ORs were restored postoperatively (responder group, n = 7) with those whose ORs were not (non-responder group, n = 7). miR-370–3p and miR-1307–3p were significantly upregulated in the responder group, whereas miR-27b-3p was upregulated in the non-responder group. The pretreatment value of each miRNA could predict DNG responsiveness for OR following ovarian cystectomy (area under the curve [AUC] > 0.8). The quantitative polymerase chain reaction (qPCR) revealed only miR-1307–3p was found to be significantly upregulated in the responder group (P < 0.05). In addition, we identified miR-139–3p, miR-140–3p, and miR-629–5p as AMH-associated miRNAs. The transition of AMH showed a correlation with miR-139–3p (P < 0.05, r = −0.76). The miRNAs identified herein represent potential serum biomarkers of clinical value in predicting OR prior to DNG treatment.

Association between ovarian reserve and spontaneous miscarriage and their shared genetic architecture.

Can potential mechanisms involved in the likely concurrence of diminished ovarian reserve (DOR) and miscarriage be identified using genetic data? Concurrence between ovarian reserve and spontaneous miscarriage was observed, and may be attributed to shared genetic risk loci enriched in antigen processing and presentation and autoimmune disease pathways. Previous studies have shown that lower serum anti-Müllerian hormone (AMH) levels are associated with increased risk of embryo aneuploidy and spontaneous miscarriage, although findings have not been consistent across all studies. A recent meta-analysis suggested that the association between DOR and miscarriage may not be causal, but rather a result of shared underlying causes such as clinical conditions or past exposure. Motivated by this hypothesis, we conducted the present analysis to explore the concurrence between DOR and miscarriage, and to investigate potential mechanisms using genetic data. Three data sources were used in the study: the clinical IVF data were retrospectively collected from an academically affiliated Reproductive Medicine Center (17786 cycles included); the epidemiological data from the UK Biobank (UKB), which is a large-scale, population-based, prospective cohort study (35 316 white women included), were analyzed; and individual-level genotype data from the UKB were extracted for further analysis. There were three modules of analysis. First, clinical IVF data were used to test the association between ovarian reserve biomarkers and the subsequent early spontaneous miscarriage risk. Second, the UKB data were used to test the association of spontaneous miscarriage history and early menopause. Third, individual-level genotype data from the UKB were analyzed to identify specific pleiotropic genes which affect the development of miscarriage and menopause. In the analysis of clinical IVF data, the risk of early spontaneous miscarriage was 1.57 times higher in the group with AMH < 1.1 ng/ml group (P < 0.001), 1.62 times for antral follicular count <5 (P < 0.001), and 1.39 times for FSH ≥10 mIU/ml (P < 0.001) in comparison with normal ovarian reserve groups. In the analysis of UKB data, participants with a history of three or more miscarriages had a one-third higher risk of experiencing early menopause (odds ratio: 1.30, 95% CI 1.13-1.49, P < 0.001), compared with participants without spontaneous miscarriage history. We identified 158 shared genetic risk loci that affect both miscarriage and menopause, which enrichment analysis showed were involved in antigen processing and presentation and autoimmune disease pathways. The analyses of the UKB data were restricted to participants of European ancestry, as 94.6% of the cohort were of white ethnicity. Further studies are needed in non-white populations. Additionally, maternal age at the time of spontaneous miscarriage was not available in the UKB cohort, therefore we adjusted for age at baseline assessment in the models instead. It is known that miscarriage rate in IVF is higher compared to natural conception, highlighting a need for caution when generalizing our findings from the IVF cohort to the general population. Our findings have implications for IVF clinicians in terms of patient counseling on the prognosis of IVF treatment, as well as for genetic counseling regarding miscarriage. Our results highlight the importance of further research on the shared genetic architecture and common pathophysiological basis of DOR and miscarriage, which may lead to new therapeutic opportunities. This work was supported by the Hunan Youth Science and Technology Innovation Talent Project (2020RC3060), the International Postdoctoral Exchange Fellowship Program (Talent-Introduction Program, YJ20220220), the fellowship of China Postdoctoral Science Foundation (2022M723564), and the Natural Science Foundation of Hunan Province, China (2023JJ41016). This work has been accepted for poster presentation at the 39th Annual Meeting of ESHRE, Copenhagen, Denmark, 25-28 June 2023 (Poster number: P-477). The authors declare no conflict of interest. N/A.

The Effect of Calcium on Biomarkers of Ovarian Fertility in Premature Ovarian Failure: A Systematic Review

Introduction: Premature ovarian failure (POF) is a condition in which ovarian function decreases or follicles are depleted in women aged less than 40 years. Calcium, along with vitamin D, is a mineral with many benefits for the reproduction system. This review is written to observe the effect of calcium on ovarian fertility biomarkers in premature ovarian failure. Methods: The literatures search was conducted utilizing numerous search engines, namely PubMed, Cochrane, Springer, Science Direct, Nature, and Google Scholar. Article publication year was restricted from 2016 to 2022. Article search keywords included “calcium”, “vitamin D”, “premature ovarian failure”, “premature ovarian insufficiency”, “amenorrhoea”, “ovarian reserve biomarkers”, “estradiol”, “follicle stimulating hormone”, and “luteinizing hormone”. Article selection was performed using the preferred reporting items for systematic review and meta-analysis protocols guidelines (PRISMA-P). The first author’s name, publication year, samples number, age range of subjects, duration of data collection, geographical setting, study design, and conclusions of research results were extracted from the selected paper. Results: 8397 articles were obtained from the six search engines. 13 articles met the inclusion criteria. Research conducted by Iran reported a significant correlation between vitamin D levels and AMH levels (p&lt;0.001). In comparison, the research in Bangladesh showed a significant positive correlation between vitamin D levels and AMH levels (r=0.433; p=0.001) and vitamin D levels and AFC values (r=0.419; r=0.001). However, 11 other researchers reported contradictory results. Conclusion: The calcium and vitamin D effect on reproductive health related to POF occurrence is still inconsistent. Therefore, observational and experimental research is needed to analyze this topic.

P-238 Non-interventional study comparing the effectiveness and safety of r-hFSH:r-hLH versus r-hFSH in women aged 35-42 years with normal ovarian reserve undergoing GnRH antagonist ART treatment

Abstract Study question Is ovarian stimulation (OS) with r-hFSH:r-hLH more effective than OS with r-hFSH alone in women aged 35-42 with normal ovarian reserve treated with ART? Summary answer Compared to r-hFSH alone, OS with r-hFSH:r-hLH for ART treatment was associated with a significant increase in clinical pregnancy and live birth per initiated cycle. What is known already Meta-analyses and secondary analyses of clinical data provide evidence that OS during ART treatment with r-hFSH:r-hLH is associated with improved reproductive outcomes when compared to r-hFSH alone in various patient groups with: a) advanced maternal age , b) low ovarian reserve or , c) hypo response to OS. Other subgroups of patients might also benefit of the use of r-hFSH:r-hLH during OS for ART treatment. We aimed to determine if, in a real-world setting, OS with r-hFSH:r-hLH is associated with improved clinical benefit when compared to r-hFSH alone in patients aged 35-42 years with normal ovarian reserve. Study design, size, duration A non-interventional study including women aged 35-42 years with normal ovarian reserve biomarkers (menstrual cycle day 2 or 3 FSH&amp;lt;12IU/L or 9&amp;lt;AFC&amp;lt;20 with a 2&amp;lt;diameter&amp;lt;10 mm, or AMH ≥1.2ng/ml) undergoing OS for ART treatment (fresh transfer only; GnRH antagonist protocol) in 12 French centers between 1/1/2008 and 31/12/2016, with a follow-up period up to 31/12/2017. The analysis included two cohorts: a) 4,323 OS cycles with r-hFSH alone, and b) 1,070 OS cycles with r-hFSH:r-hLH. Participants/materials, setting, methods Anonymized data were extracted from the Retrospective Multicenter Statistical database, including 12 French centers. A generalized linear model was used to address lack of randomization. The fixed effect part included age, an ovarian reserve estimator and stimulation; the random effect included age, AMH, AFC, FSH, cause of infertility and number of attempts, center and patient effect. Clusters (matched subsets) were built based on the propensity score by using a two-stage algorithm. Main results and the role of chance We included in our analysis 4,472 women receiving ART treatment after OS with r-hFSH (mean age: 37.8 years; 4,323 cycles) or with r-hFSH:r-hLH (mean age: 38.1 years; 1,070 cycles). In the r-hFSH cohort the mean AMH level was 2.81 ng/ml and mean AFC was 12.0, in the r-hFSH:r-hLH cohort they were 2.14 ng/ml and 10.0, respectively. The mean total r-hFSH dose were 2,275 IU (r-hFSH cohort) and 3,002 IU (r-hFSH:r-hLH cohort). Mean ± SD number of oocytes were 8.1 ± 5.7 (r-hFSH cohort) and 6.1 ± 4.3 (r-hFSH:r-hLH cohort); mean ± SD number of embryos were 4.0 ± 3.4 (r-hFSH cohort) and 3.3 ± 3.2 (r-hFSH:r-hLH cohort). The unadjusted ongoing pregnancy rate reached 17.1% in the r-hFSH cohort and 20.4% in the r-hFSH:r-hLH cohort, whilst the unadjusted live birth rate reached 17.0% and 20.2%, respectively. Unadjusted pregnancy failure rate was 6.6% and 3.7%, respectively. After adjusting for confounders, when compared to OS with r-hFSH, OS with rhFSH:rhLH was associated with a higher clinical pregnancy rate (Risk ratio,RR 1.232; 95% CI 1.058 to 1.436; p-value = 0.007) and a higher live birth rate (RR 1.452; 95% CI 1.227-1.1719, p-value &amp;lt;0.001) per initiated cycle. Limitations, reasons for caution Since this was a real-world data study, no random assignment of stimulation was performed, and some residual confounding is possible due to unmeasured confounders. Live births resulting from further transfers of frozen embryos were not included in the analysis. Wider implications of the findings This study demonstrated that OS with r-hFSH:r-hLH improves live birth rate in women &amp;gt; 35 years old with a normal ovarian reserve, compared to r-hFSH only. Sound RWE studies can be combined with RCTs to guide clinical and payer’s decision making, paving the way to precision medicine. Trial registration number Not applicable

P-800 Autologous stem cell ovarian transplant induced long-lasting effects on the plasma proteome of women with premature ovarian insufficiency

Abstract Study question Does autologous stem cell ovarian transplant (ASCOT) induce any long-term modifications in the plasma proteomic profile of women with premature ovarian insufficiency (POI)? Summary answer Stem cell mobilization and infusion into the ovary elicit long-term proteomic changes in peripheral blood plasma composition in women with POI, reverting age-related proteomic changes. What is known already Patients with POI are challenging to treat, with oocyte donation remaining as the only feasible option to achieve pregnancy. Previous attempts to overcome the fertility problems of these patients have mainly been based on ovarian stimulation, and were likely unsuccessful due to the lack of stimulable antral follicles remaining in the ovaries. Our group described that ASCOT in patients with impaired ovarian function improves ovarian reserve biomarkers, follicle and oocyte quantity enabling pregnancy and delivery of healthy babies. Beneficial effects of ASCOT were associated with the presence of different stem-cell secreted factors in apheresis plasma. Study design, size, duration Experimental cohort study with plasma samples of POI women undergoing stem cell mobilization with granulocyte-colony stimulating factor (mobilization arm; N = 3) or stem cell mobilization and infusion into the ovarian artery (ASCOT arm; N = 3). Peripheral plasma samples were collected from all patients at recruitment (Pre), during bone marrow stem cell mobilization and collection by apheresis (Apheresis), and three months after mobilization or ASCOT (Post). Participants/materials, setting, methods Proteins were isolated from plasma samples and quantified by SWATHTM to compare the plasma proteomic profile of the different time points (Pre, Apheresis, Post), using an ElasticNet penalized linear regression method. To determine the biological processes affected by stem cell mobilization and infusion into the ovary, a Gene Ontology Enrichment Analysis for the differentially expressed proteins (DEPs) was performed, considering significantly enriched those GO Biological Processes with a False Discovery Rate &amp;lt;0.05. Main results and the role of chance Discriminant analysis highlighted clear distinctions between the plasma proteome at the three evaluated time points. Both the stem cell mobilization and ASCOT technique induced statistically significant modifications in the plasma composition, reversing some age-related protein expression changes. Specifically, differences between Apheresis and Pre samples were explained by fourteen DEPs, revealing the functional analysis an enrichment in processes related to the complement cascade, immune system, and platelet degranulation. When the link of these proteomic changes with aging was evaluated, we found three proteins that were upregulated in Apheresis [C1QC, LYSC, LYAM1] whose plasma levels decrease with aging, and one downregulated protein [CRP] whose expression rises with age. Regarding Post samples, twenty-four DEPs with respect to Pre condition were found within the mobilization arm, being two of them linked with aging [MMP2 and ALDOC]. These DEPs were related with immune response and platelet degranulation but also with processes associated with responses to oxygen-containing compounds and growth hormones, and blood vessel maturation. Within the ASCOT arm, Pre and Post samples were clearly differentiated by eleven DEPs, although any GO Biological Process were found. Nevertheless, among these DEPs, we found DIAC which increases in plasma with aging and was downregulated after ASCOT. Limitations, reasons for caution Considering the small sample size used in this study, further experimental studies will be needed to validate the results. Moreover, further research will be necessary to determine the extent of the regenerative effects of the identified DEPs within the ovaries, and their direct implications in ovarian aging. Wider implications of the findings Our findings highlight the potential proteins and biological processes that may promote the follicle activation and growth observed after ASCOT. Identifying plasma proteins that regenerate aged or damaged ovaries could lead to more effective, targeted and/or preventive therapies for affected patients. Funding: CIPROM/2021/058, PI21/00170, CP19/00141 and CD20/00116. Trial registration number NCT03535480

The effect of ajwa dates (Phoenix dactylifera L) consumption to anti-Mullerian hormone level of perimenopausal woman

Ageing in the female reproductive system is most clearly seen when entering the perimenopausal period, where there is a decrease in the number and function of oocytes and significant endocrine changes. Inflammation and accumulation of reactive oxygen species (ROS) are considered to be the most responsible factors for the reduction in ovarian reserve. Anti-Mullerian Hormone (AMH) is used as a biomarker of ovarian reserve and clinically as a predictive biomarker of menopause. Ajwa dates contain phytochemicals with antioxidant and anti-inflammatory activities. This study aimed to analyse the effect of consuming ajwa dates on AMH levels in perimenopausal women. This research was a quasi-experimental study with a pre-post control design which was conducted at Sitti Khadijah 1 Muhammadiyah Hospital, Makassar, Indonesia, from May until October 2021. It involved 44 perimenopausal subjects aged 42 - 48 years, which were divided into 2 groups randomly (28 subjects consumed ajwa dates as the intervention group, sixteen as the control group). AMH levels were assessed before and after the 8week intervention period and analysed using the ELISA method. The result showed that AMH levels in the intervention and the control groups after 8 weeks of treatment decreased by 0.37±0.36 ng/mL and 0.55±0.19 ng/mL, respectively. The decrease in AMH levels between the two groups was significantly different (p&lt;0.05) where AMH levels in the intervention group declined less than in the control group. In conclusion, AMH levels in perimenopausal women who consumed ajwa dates decreased less than perimenopausal women who did not consume ajwa dates. The reduction of ovarian reserve in perimenopausal women can be inhibited through the intervention of exogenous antioxidants from ajwa dates which AMH levels were the indicator.

Impact of immune checkpoint inhibition on ovarian reserve in patients with melanoma enrolled in the ECOG-ACRIN E1609 adjuvant trial.

12013 Background: Immunotherapy with immune checkpoint inhibition (ICI) is being widely adopted in the treatment of patients with a wide range of malignancies. However, we have no data on how these therapies influence fertility or ability to undergo fertility treatments after therapy. Within the melanoma community numerous women of childbearing age have been treated with ICI including ipilimumab, nivolumab and pembrolizumab. Anti-mullerian hormone (AMH) is a biomarker of ovarian reserve and a predictor of response to fertility treatments, including in vitro fertilization (IVF). In women under the age of 35 who have no reproductive pathology, AMH should be detectable and remain relatively stable over time. Above the age of 35 AMH decline accelerates as the number of eggs decreases more rapidly due to normal ovarian aging. Methods: Pre and post-treatment samples from women aged 20-35 whose melanoma was treated with 3 mg/kg ipilimumab (57%) or 10 mg/kg ipilimumab (43%) in the adjuvant setting on trial ECOG-ACRIN E1609 were analyzed in collaboration with the BWH Reproductive Endocrine Laboratory. Serum samples were tested for luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, AMH and prolactin. Results: Samples from E1609 were available from 28 female patients with a median age of 28 (min 20, max 35). The median time between samples was 8.0 months (min 0.7, max 16.4). 53% of patients had stage IIIB melanoma, 43% stage IIIC and one patient had M1a disease. AMH, estradiol and LH significantly decreased after treatment (p &lt; 0.001, p = 0.016, p = 0.012, respectively) (Figure 1); there was no significant difference in the level of FSH and prolactin before and after the treatment (p = 0.68, p = 0.12, respectively). The median AMH was 4.24 ng/mL in the pre-treatment group and 3.51 in the post-treatment group. Conclusions: In this study of young women treated with ipilimumab there was a significant decrease in AMH before and after ICI therapy suggesting that ovarian reserve and possibly female fertility may be impacted by immune checkpoint inhibition. Further investigation is needed to look at PD-1 inhibition and combination immunotherapy effects on ovarian reserve and female fertility. In addition, there is a similar need to examine ICI effects on male fertility.

Predictors of success of ovarian drilling or redrilling in polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is defined using the Rotterdam criteria. PCOS affects 5%–15% of females of reproductive age and is the first cause of infertility due to anovulation. The aim of this work was to predict success of laparoscopic ovarian drilling (LOD) or redrilling in PCOS. Methods: This observational study was carried out on 50 female cases in childbearing with BMI range from 18-28Kg/m2, infertility > 3 years, irregular menstrual cycles and aged from 20-35 years old. All cases were subjected to pelvic examination except in virgins, ultrasound examination, determine baseline level of anti-Mullerian hormone (AMH) and 3-dimensional color Doppler. Results: AMH had a significant decline after first and second drilling as compared to before first and second drilling respectively (p <0.001). Follicle count in right ovary had a significant decline after first and second drilling as compared to before first and second drilling respectively (p <0.001). Ovarian volume in right ovary had a significant decline after first and second drilling as compared to before first and second drilling respectively (P = 0.002 and <0.001 respectively). Conclusions: In infertile females with PCOs, laparoscopic ovarian re-electro-cautery increased rate of spontaneous pregnancy and the majority of changes in ovarian reserve biomarkers reported following drilling may be viewed as normalisation of the function of the ovary instead of a decline in ovarian reserve.

Impact of Anti-HER2 Therapy Alone and With Weekly Paclitaxel on the Ovarian Reserve of Young Women With HER2-Positive Breast Cancer.

The potential gonadotoxicity of anti-HER2 agents remains largely unknown, and limited, conflicting evidence exists for taxanes. Antimüllerian hormone (AMH) is an established biomarker of ovarian reserve that may aid in quantifying anticancer treatment-induced gonadotoxicity. The present biomarker analysis of the randomized phase III neoadjuvant NeoALTTO trial included premenopausal women aged ≤45 years at diagnosis of HER2-positive early breast cancer with available frozen serum samples at baseline (ie, before anticancer treatments), at week 2 (ie, the "biological window" of anti-HER2 therapy alone), and/or at the time of surgery (ie, after completing paclitaxel + anti-HER2 therapy, before starting adjuvant chemotherapy). The present analysis included 130 patients with a median age of 38 years (interquartile ratio [IQR], age 33-42 years). AMH values at the 3 time points differed significantly (P<.001). At baseline, median AMH levels were 1.29 ng/mL (IQR, 0.56-2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median, 1.10 ng/mL; IQR, 0.45-2.09 ng/mL; P<.001). At surgery, a larger significant decline in AMH levels was observed (median, 0.01 ng/mL; IQR, 0.01-0.03 ng/mL; P<.001). Although the type of anti-HER2 treatment (trastuzumab and/or lapatinib) did not seem to impact the results, age and pretreatment ovarian reserve had a major influence on treatment-induced gonadotoxicity risk. This NeoALTTO biomarker analysis showed that anti-HER2 therapies alone had limited gonadotoxicity but that the addition of weekly paclitaxel resulted in marked AMH decline with possible negative implications for subsequent ovarian function and fertility.