Marker Of Ovarian Reserve Research Articles

Air Pollutants and Ovarian Reserve: A Systematic Review of the Evidence

Abstract Background Growing evidence points to an association between ambient air pollution and decreased human reproductive potential. The aim of this study was to systematically review the association between air pollutants and female ovarian reserve. Methods The literature was searched in six electronic databases through August 2023. Screening of the 75 articles retrieved for inclusion criteria resulted in the selection of 12 human observational studies that evaluated the effect of environmental pollutants on markers of female ovarian reserve. The study protocol was registered on PROSPERO (registration code CRD42023474218). Results The study design of selected studies was found to be cross-sectional (2 of 10), retrospective cohort (7 of 10), prospective cohort (2 of 10), and case-control (1 of 10). The study population was equally distributed between Asians (60%) and Americans (50%) with an Italian minority (10%). The main findings showed a higher body of evidence for the environmental pollutants PM2.5, PM10, and NO2, while a low body of evidence for PM1, O3, SO2, and a very low body of evidence for benzene, formaldehyde, and benzo(a)pyrene, yet consistently showing significant inverse association data. The overall methodological quality of the selected studies was rated moderated across the 14 domains of the NIH toolkit. Conclusions Increased exposure to air pollutants seems to be associated with reduced female ovarian reserve with evidence being strongest for pollutants such as PM2.5, PM10, and NO2. More evidence is needed to draw conclusions about causality. Key messages • Increased exposure to air pollutants seems to be associated with reduced female ovarian reserve with evidence being strongest for pollutants such as PM2.5, PM10, and NO2. • Global environmental policy programs are urgently needed to reduce the risks associated with reduced fertility such as reduced birth rates or the use of assisted reproductive technologies.

Key predictors of fertility: Exploring the role of Vitamin-D

Background & Objectives: The relationship of Vitamin-D (VD) with Luteinizing Hormone (LH), Follicle stimulating Hormone (FSH) and Anti Mullerian Hormone (AMH) is recognized. This study was conducted to determine whether VD is a predictor of fertility and investigate its relationship with female reproductive hormones and markers of ovarian reserve in female population of Karachi. Methods: A cross-sectional study was performed from July 2020 to June 2022 at the Aga Khan University Hospital (AKUH) with recruitment of 135 fertile and infertile subjects. VD, AMH, FSH and LH levels were estimated by ‘Enzyme Linked Immunosorbent assay (ELISA)’. By applying binary logistic regression, variables with p-value < 0.25 in univariate analysis were used for multivariate regression model and adjusted odds ratios were computed. In multivariate analysis, significance was p-value ≤ 0.05. Results: VD deficiency was observed in all infertile female subjects. In univariate regression analysis, FSH, LH, LH/FSH ratio and VD levels turned out to be significant. The Multivariate analysis represented that for every one ng/mL increase in VD level, the odds of fertility were expected to be 50.154 times higher with p-value < 0.001. The positive correlation of VD with FSH was significant. Conclusion: VD deficiency was prevalent in all infertile female subjects. VD levels were strong predictor of fertility in the study population. The significant association of VD with FSH explained the indirect effect of VD on follicular development and ovarian functions however no relationship of VD with ovarian reserve was exhibited. Note: AI assisted technologies were used in the preparation of the manuscripts, to improve readability and language. doi: https://doi.org/10.12669/pjms.40.10.9774 How to cite this: Salahuddin H, Zaki S, Ashraf M, Rehana Rehman4. Key predictors of fertility: Exploring the role of Vitamin-D. Pak J Med Sci. 2024;40(10):2363-2367. doi: https://doi.org/10.12669/pjms.40.10.9774 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Intraovarian injection of autologous platelet-rich-plasma: myth or reality?

The diminished ovarian reserve (DOR) relates to a condition in which the ovary experiences a decline in its typical reproductive capacity. Despite notable advancements in understanding the pathophysiology of reduced ovarian reserve in recent years, significant unresolved challenges remain, particularly concerning the optimal therapeutic approaches for this complex condition. The main aim of this study was to investigate the potential of platelet-rich plasma (PRP) in enhancing ovarian follicle numbers by assessing changes in ovarian reserve markers. A comprehensive literature search was conducted on the following databases: PubMed/MEDLINE, SCOPUS, The Cochrane Library, Science Direct and Web of Science. All the relevant studies published till October 2023 were screened. After removing duplicates, and full-text evaluation, 9 articles were eventually included in the present review. The pregnancy rate (PR) among patients with poor ovarian reserve (POR) ranged from 13% to 40%, indicating the potential effectiveness of PRP as a rejuvenating treatment. The live birth rate (LBR) ranged from 13% to 20%, comparable to or not lower than the LBR of a matched healthy population aged between 38 and 42 years. Furthermore, the data presented thus far support the notion that PRP may lead to an average clinical PR of 10% in women affected by premature ovarian insufficiency (POI) and perimenopause. PRP can not be regarded as a gamete replacement therapy, but rather as an 'additional' therapeutic tool in the management of women with DOR or POR, as well as in peri-menopausal women. Additional qualitative studies are required to validate the existing evidence, as the literature currently lacks randomized controlled trials (RCTs) in this regard.

Air pollutants and ovarian reserve: a systematic review of the evidence.

Growing evidence indicates an association between ambient air pollution and decreased human reproductive potential. This study aims to systematically review the association between air pollutants and female ovarian reserve. The literature was searched in six electronic databases through June 2024. Screening the 136 articles retrieved for inclusion criteria resulted in the selection of 15 human observational studies that evaluated the effect of environmental pollutants on ovarian reserve markers. The study protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO, registration code: CRD42023474218). The study design of the selected studies was found to be cross-sectional (2 of 15), retrospective cohort (10 of 15), prospective cohort (2 of 15), and case-control (1 of 15). The study population was distributed as follows: Asians (53%, eight studies), Americans (33%, five studies), and Europeans (14%, two studies). The main findings showed a higher body of evidence for the environmental pollutants PM2.5, PM10, and NO2, while a low body of evidence for PM1, O3, SO2, and a very low body of evidence for benzene, formaldehyde, and benzo(a)pyrene, yet consistently showing significant inverse association data. The overall methodological quality of the selected studies was rated moderated across the 14 domains of the National Institutes of Health (NIH) toolkit. The data suggest that increased exposure to air pollutants seems to be associated with reduced ovarian reserve, with the most substantial evidence for pollutants such as PM2.5, PM10, and NO2. However, more evidence is needed to draw conclusions about causality.

Anti-Müllerian hormone: biology and role in endocrinology and cancers.

Anti-Müllerian hormone (AMH) is a peptide belonging to the transforming growth factor beta superfamily and acts exclusively through its receptor type 2 (AMHR2). From the 8th week of pregnancy, AMH is produced by Sertoli cells, and from the 23rd week of gestation, it is produced by granulosa cells of the ovary. AMH plays a critical role in regulating gonadotropin secretion, ovarian tissue responsiveness to pituitary hormones, and the pathogenesis of polycystic ovarian syndrome. It inhibits the transition from primordial to primary follicles and is considered the best marker of ovarian reserve. Therefore, measuring AMH concentration of the hormone is valuable in managing assisted reproductive technologies. AMH was initially discovered through its role in the degeneration of Müllerian ducts in male fetuses. However, due to its ability to inhibit the cell cycle and induce apoptosis, it has also garnered interest in oncology. For example, antibodies targeting AMHR2 are being investigated for their potential in diagnosing and treating various cancers. Additionally, AMH is present in motor neurons and functions as a protective and growth factor. Consequently, it is involved in learning and memory processes and may support the treatment of Alzheimer's disease. This review aims to provide a comprehensive overview of the biology of AMH and its role in both endocrinology and oncology.

Intraovarian Platelet-Rich Plasma Administration for Anovulatory Infertility: Preliminary Findings of a Prospective Cohort Study.

Background/Objectives: Infertility constitutes a significant challenge for couples around the world. Ovarian dysfunction, a major cause of infertility, can manifest with anovulatory cycles, elevated follicle-stimulating hormone levels, and diminished ovarian reserve markers such as anti-Müllerian hormone (AMH) levels or the Antral Follicle Count (AFC). Blood-derived therapies including platelet-rich plasma (PRP) have been used in fertility treatments in women with low ovarian reserve or premature ovarian insufficiency. This prospective clinical cohort study aims to assess the effects of intraovarian PRP therapy on ovarian function in women diagnosed with anovulatory cycles. Methods: The preliminary findings of this prospective cohort study are based on the first 32 patients enrolled. In this study, patients over 40 years old with anovulatory infertility were included. Venous blood samples were collected from each participant for the preparation of autologous platelet-rich plasma (PRP). Each participant received two courses of intraovarian PRP injections using a transvaginal ultrasound-guided approach. Serum levels of reproductive hormones before and after PRP intervention were measured. Results: This study's results demonstrate a significant improvement in ovarian physiology following transvaginal ultrasound-guided PRP infusion. A 75% increase in Antral Follicle Count (AFC) was observed, which was statistically significant. Furthermore, statistically significant reductions in follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels were observed. Serum Vitamin D 1-25 levels were substantially increased after the injection. Conclusions: These findings highlight the beneficial impact of intraovarian PRP injection in optimizing ovarian function and other metabolic parameters. However, the published literature on this subject is limited and further clinical studies should be conducted to confirm the role of intraovarian PRP in fertility treatments.

Female fertility preservation for family planning: a position statement of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR).

This position statement by the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) aims to establish an optimal framework for fertility preservation outside the standard before oncological therapies. Key topics include the role of fertility units in comprehensive fertility assessment, factors impacting ovarian potential, available preservation methods, and appropriate criteria for offering such interventions. The SIFES-MR writing group comprises Italian reproductive physicians, embryologists, and scientists. The consensus emerged after a six-month period of meetings, including extensive literature review, dialogue among authors and input from society members. Final approval was granted by the SIFES-MR governing council. Fertility counselling transitions from urgent to long-term care, emphasizing family planning. Age, along with ovarian reserve markers, is the primary predictor of female fertility. Various factors, including gynecological conditions, autoimmune disorders, and prior gonadotoxic therapies, may impact ovarian reserve. Oocyte cryopreservation should be the preferred method. Women 30-34 years old and 35-39 years old, without known pathologies impacting the ovarian reserve, should cryopreserve at least 12-13 and 15-20 oocytes to achieve the same chance of a spontaneous live birth they would have if they tried to conceive at the age of cryopreservation (63% and 52%, respectively in the two age groups). Optimal fertility counselling necessitates a long-term approach, that nurtures an understanding of fertility, facilitates timely evaluation of factors that may affect fertility, and explores fertility preservation choices at opportune intervals.

Serum anti-Mullerian hormone levels in Turkish girls aged 18 and younger for ovarian reserve determination

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. 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. 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). 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.

Risk factors for diminished ovarian reserve in women: Current state of the problem

Ovarian reserve is the basis of female fertility. The main markers of ovarian reserve are the level of anti-Mullerian hormone and the number of antral follicles. In addition to the natural age-related loss of follicles, many women experience a premature diminished ovarian reserve associated with a number of factors. This can be caused by both various diseases and environmental factors, lifestyle, and social aspects.The aim of this review was to examine the influence of external factors on the ovarian reserve and women fertility. A systematic analysis of data from modern scientific literature, domestic and foreign sources was carried out. The search involved such resources as PubMed, MEDLINE, Science Direct, eLibrary, Scopus, Cyberleninka. A detailed analysis of the influence of environmental pollution, lifestyle (sleep, nutrition, physical activity), previous surgeries, bad habits, obesity, psychological and social factors on the ovarian reserve and reproductive function of women was carried out. Significantly diminished ovarian reserve was noted with low sleep quality, excessive physical activity, and an unbalanced diet poor with animal proteins. Regular consumption of alcohol, smoking and exposure to certain chemical environmental pollutants cause premature follicle apoptosis and the onset of menopause. Circadian dysrhythmia, chronic stress and obesity can lead to the ovarian menstrual cycle disorders and the development of infertility in women. Previous parovarium surgeries are a significant risk factor for diminished ovarian reserve. Further population-based studies are needed to determine the precise mechanisms of influence of various factors on female fertility.

Reduced anti-Müllerian hormone levels in males with inherited bone marrow failure syndromes.

Fanconi anemia (FA), dyskeratosis congenita-related telomere biology disorders (DC/TBD), and Diamond-Blackfan anemia (DBA) are inherited bone marrow failure syndromes (IBMFS) with high risks of bone marrow failure, leukemia, and solid tumors. Individuals with FA have reduced fertility. Previously, we showed low levels of anti-Müllerian hormone (AMH), a circulating marker of ovarian reserve, in females with IBMFS. In males, AMH may be a direct marker of Sertoli cell function and an indirect marker of spermatogenesis. In this study, we assessed serum AMH levels in pubertal and postpubertal males with FA, DC/TBD, or DBA and compared this with their unaffected male relatives and unrelated healthy male volunteers. Males with FA had significantly lower levels of AMH (median: 5 ng/mL, range: 1.18-6.75) compared with unaffected male relatives (median: 7.31 ng/mL, range: 3.46-18.82, P = 0.03) or healthy male volunteers (median: 7.66 ng/mL, range: 3.3-14.67, P = 0.008). Males with DC/TBD had lower levels of AMH (median: 3.76 ng/mL, range: 0-8.9) compared with unaffected relatives (median: 5.31 ng/mL, range: 1.2-17.77, P = 0.01) or healthy volunteers (median: 5.995 ng/mL, range: 1.57-14.67, P < 0.001). Males with DBA had similar levels of AMH (median: 3.46 ng/mL, range: 2.32-11.85) as unaffected relatives (median: 4.66 ng/mL, range: 0.09-13.51, P = 0.56) and healthy volunteers (median: 5.81 ng/mL, range: 1.57-14.67, P = 0.10). Our findings suggest a defect in the production of AMH in postpubertal males with FA and DC/TBD, similar to that observed in females. These findings warrant confirmation in larger prospective studies.

Anti-Müllerian hormone does not predict cumulative pregnancy rate in non-infertile women following four IUI cycles with donor sperm.

To evaluate the predictive value of serum AMH for clinical pregnancy in non-infertile population undergoing intrauterine insemination with donor sperm (ds-IUI). This multicenter prospective study (ClinicalTrials.gov ID: NCT06263192) recruited all non-infertile women undergoing ds-IUI from June 2020 to December 2022 in three different fertility clinics in Spain and Chile. Indications for ds-IUI included severe oligoasthenoteratozoospermia, female partner, or single status. Clinical pregnancy rates were compared between women with AMH ≥ 1.1 and < 1.1ng/mL. The main outcome measure was the cumulative clinical pregnancy rate after up to 4 ds-IUI cycles. A total of 458 ds-IUI cycles were performed among 245 patients, of whom 108 (44.08%) achieved clinical pregnancy within 4 cycles, 60.2% of these occurring in the first attempt and 84.2% after two attempts. We found no significant differences in AMH levels or other parameters (such as age, BMI, FSH, AFC) between women who became pregnant and those who did not. Cumulative pregnancy rates and logistic regression analysis revealed that AMH ≥ 1.1ng/mL was not predictive of ds-IUI success. While a high positive correlation was observed between AFC and AMH (r = 0.67, p < 0.001), ROC curve analyses indicated that neither of these ovarian reserve markers accurately forecasts cumulative ds-IUI outcomes in non-infertile women. The findings of this multicenter study suggest that AMH is not a reliable predictor of pregnancy in non-infertile women undergoing ds-IUI. Even women with low AMH levels can achieve successful pregnancy outcomes, supporting the notion that diminished ovarian reserve should not restrict access to ds-IUI treatments in eligible non-infertile women.

P-697 The effect of smoking and vaping on hormonal ovarian reserve markers in women of reproductive age in the United Kingdom

Abstract Study question What impact do smoking and vaping have on ovarian reserve markers Anti-Mullerian Hormone (AMH) and Follicle-Stimulating Hormone (FSH)? Summary answer Smoking and vaping negatively affect AMH and FSH levels in women, with significant age-related differences in ovarian reserve markers observed. What is known already Previous studies have established a link between smoking and accelerated ovarian follicular depletion, evidenced by lower serum AMH levels and reduced antral follicle count (AFC). Smoking is known to increase FSH levels indirectly by affecting pituitary function. However, the impact of vaping, a growing trend especially among younger individuals, on ovarian reserve markers like AMH and FSH remains under-researched and requires comprehensive investigation to understand its full implications on reproductive health. Study design, size, duration This cross-sectional study analysed medical history and serum AMH and FSH concentrations from capillary blood samples of 8,340 women aged 21-45. Participants were stratified by 5-year age intervals and excluded if they had reproductive health conditions or used hormonal contraception. Samples were analysed from individuals using an at-home hormone testing service, with statistical analysis including unpaired t-tests and Cohen’s d for effect size, focusing on smokers/vapers versus non-smokers/non-vapers. Participants/materials, setting, methods The study included UK women aged 21-45 providing capillary blood samples for serum AMH and FSH measurement using an at-home testing service. Exclusions applied to those with reproductive conditions or on hormonal contraception. Smoking and vaping status were self-reported through an online health assessment. AMH and FSH concentration differences were analysed via unpaired t-test; a p-value of &amp;lt; 0.05 was considered statistically significant and mean values±SD were reported. Main results and the role of chance Among 8,340 participants, 312 smoked and 653 vaped. Lower serum AMH values were observed in smokers and vapers in all age groups, with significant differences at ages 31-35 for smokers (20.73±16.23 vs 25.37±19.80 pmol/L in smokers and non-smokers respectively; p = 0.003) and 36-40 for vapers (13.65±13.34 vs 16.88±14.32 pmol/L in vapers and non-vapers respectively; p = 0.01). No significant differences in serum FSH concentration were found among vapers, however, FSH levels were higher in smokers across all ages. This was significant in individuals aged 21-25 (8.01±2.52 vs 6.87±3.33 IU/L in smokers and non-smokers respectively; p = 0.02) and 31-35 (8.33±3.31 vs 7.70±3.51 IU/L smokers and in non-smokers respectively; p = 0.04). These results suggest a detrimental effect of smoking and vaping on ovarian reserve markers, with statistical significance indicating the role of chance is minimal in the observed differences. Limitations, reasons for caution Self-reported smoking/vaping status may introduce bias. The study does not report the duration or frequency of participants’ smoking and vaping habits. The study’s cross-sectional design limits causality inference, however it provides a valuable insight for future longitudinal research to explore these relationships over time and explore underlying mechanisms. Wider implications of the findings These findings highlight the potential risks of smoking and vaping on women’s reproductive health, emphasising the need for awareness and preventive measures, especially among younger populations and the increased use of vaping. Trial registration number not applicable

P-664 Insulin-like peptide 3 as a potential biomarker in predicting IVF success and ovarian reserve in women with unexplained infertility and diminishing ovarian reserve

Abstract Study question Could insulin-like peptide 3 (INSL3) predict ovarian reserve and in vitro fertilization (IVF) success in women with unexplained infertility (UI) and diminishing ovarian reserve (DOR)? Summary answer In women with DOR, reduced intrafollicular and serum INSL3 levels correspond with low AMH and high FSH levels, similar to established ovarian reserve markers. What is known already INSL3, belonging to the insulin-like peptide family, is produced by theca interna cells within antral follicles and the corpora lutea. It is hypothesized that INSL3 is integral to the initial development and function of antral follicles, specifically through its regulatory effect on androgen biosynthesis in the thecal cells of these follicles. Moreover, INSL3 is implicated in the modulation of the ovarian microenvironment, which is essential for facilitating the maturation of oocytes. Study design, size, duration This research was carried out at the IVF centers of two tertiary university hospitals, assessing 49 infertile women with either UI (n = 24) or DOR (n = 25) during IVF treatment. A control group (n = 26) comprised women with normal ovarian reserve undergoing IVF due to male or tubal factors. Outcome parameters are ovarian reserve markers (serum FSH, estradiol, AMH, INSL3 concentration and antral follicle count [AFC]), positive pregnancy rate and live birth rate (LBR) (gestational age ≥28 weeks). Participants/materials, setting, methods Women aged between 20-40 with a body mass index (BMI)&amp;lt;30 kg/m² were included. Serum FSH, estradiol, AMH, INSL3 levels and AFC were evaluated on menstrual cycle days 2 or 3, and INSL3 in follicular fluid from dominant follicles (&amp;gt;14 mm) were evaluated during oocyte retrieval. Exclusions included endocrine abnormalities (e.g., polycystic ovary syndrome, hyperprolactinemia, hypo and hyperthyroidism) cycle cancellation due to lack of a viable embryo, uncorrected Mullerian anomalies, recurrent miscarriage history and hydrosalpinx presence. Main results and the role of chance The mean age in the study groups was 28.41±3.5 (UI), 32.40±4.21 (DOR), and 29.65±3.91 (control). In the DOR group, female age (p = 0.001), BMI (p = 0.049), duration of infertility (p = 0.006), previous IVF attempts (p &amp;lt; 0.001), basal FSH (p &amp;lt; 0.001), and basal estradiol (p &amp;lt; 0.001) were higher, while AMH (p &amp;lt; 0.001), AFC (p &amp;lt; 0.001), and follicular fluid INSL3 (p &amp;lt; 0.001) were lower. Serum INSL3 in DOR was lower but not statistically significant. No correlation was found between serum INLS, follicular fluid INSL3, ovarian reserve markers, positive pregnancy rates, miscarriage, and LBR. DOR group had longer stimulation durations (p = 0.017), but lower max estradiol (p &amp;lt; 0.001), fewer oocytes (p &amp;lt; 0.001), mature follicles (p &amp;lt; 0.001), and PN (p &amp;lt; 0.001). Pregnancy rates were 54.1% (UI), 24% (DOR), and 53.84% (control); LBRs were 54.1% (UI), 20% (DOR), and 42.3% (control), with significant differences in pregnancy tests (p = 0.04) and LBR (p = 0.03), both lower in DOR. Univariate analysis identified duration of infertility (p = 0.019) and basal FSH (p = 0.009) as significant LBR predictors. Multivariable analysis confirmed basal FSH (p = 0.033) as significant, with increased duration of infertility and basal FSH level reducing LBR probability. Limitations, reasons for caution The limited sample size of our study potentially undermines the robustness of circulating INSL3 as a predictive biomarker for DOR, evidenced by the non-significant decrease in serum INSL3 levels in the DOR group. Moreover, the lack of INSL3 level assessment during oocyte retrieval further constrains our findings. Wider implications of the findings Our research explored INSL3 as a viable biomarker for predicting ovarian reserve and IVF success in UI and DOR cases. Reduced INSL3 levels in circulation and follicular fluid in DOR patients could be beneficial in clinical practice. Trial registration number not applicable

O-226 Effects of preventive uterine artery occlusion during laparoscopic myomectomy on ovarian reserve markers: a randomized controlled trial

Abstract Study question Does definitive occlusion of uterine arteries have a short or long term impact on anti-Müllerian hormone (AMH) levels in reproductive age women undergoing laparoscopic myomectomy? Summary answer Preventive uterine artery occlusion during laparoscopic myomectomy does not impact AMH levels in reproductive age women. What is known already Uterine leiomyoma are the most common benign tumours in women of reproductive age. For symptomatic women willing to retain their uterus, especially for a future pregnancy, the current gold standard is the myomectomy for subserous/intramural leiomyoma. Temporary or definitive occlusion of uterine arteries can be performed to control bleeding during surgery but its impact on ovarian reserve markers is still unknown. A single randomized trial with a one-year follow-up demonstrated that temporary bilateral uterine artery occlusion during laparoscopic myomectomy slightly decreased AMH levels at day-2 after surgery but has no impact thereafter 3, 6 and 12 months postoperatively. Study design, size, duration We conducted a randomized controlled trial with a two-year follow-up evaluating the effect of definitive occlusion of uterine arteries on ovarian reserve via sequential measures of anti-Müllerian hormone (AMH) levels. Fifty-eight women with symptomatic leiomyoma type FIGO 3-6 scheduled for laparoscopic myomectomy at were included between July 2015 and October 2021. Participants/materials, setting, methods Patients were randomized into: the intervention group (laparoscopic myomectomy with preventive occlusion of uterine arteries) and the control group (laparoscopic myomectomy without occlusion of uterine arteries) ). AMH evaluated at T0 and followed at 1 month (T1), 3 months (T3), 6 months (T6), 12 months (T12) and 24 months (T24) after surgery. Intraoperative blood loss, leiomyoma recurrence and adenomyosis occurrence were also evaluated comparing pre- and post-operative findings. Finally, pregnancies and live births were monitored. Main results and the role of chance Women in both groups did not differ in their baseline characteristics in terms of age, body mass index, ethnicity, parity, wish to become pregnant, hormonal treatment, leiomyoma number and size, baseline haemoglobin levels, bleeding symptoms baseline AMH levels and antral follicular count (AFC). The mean operative time was similar in between both groups. Mean blood loss during surgery was on average 138 (±104)ml in the intervention group versus 436 (±498)ml in controls (p &amp;lt; 0.001). The difference in haemoglobin between before and after surgery was significantly higher in the control group 21.8 (±12.7)g/l compared with the intervention group 14.8 (±8.9)g/l (p = 0.02). Regarding clinical symptoms, most patients had decreased menstrual flow at the last follow-up visit (24 months) compared to baseline in both group improvement of dysmenorrhea followed the same trend with a reduction in pain levels in both groups. Risk of leiomyoma recurrence was found similar between both groups. Most importantly, AMH levels were similar between groups at all times (T1, T3, T6, T12 and T24) and non-inferiority of preventive occlusion was demonstrated with a non-inferiority margin of -3.5pmol/L (0.5 ng/ml). The pregnancy rate was not different between groups. Limitations, reasons for caution Our sample size was calculated to detect a clinically relevant difference of at least two-third of the standard deviation in AMH levels, but we cannot exclude a smaller impact on AMH with a different sample size. Wider implications of the findings Preventive uterine artery occlusion during laparoscopic myomectomy does not impact ovarian reserve markers and can be safely used to control perioperative bleeding. Trial registration number NCT02563392

P-051 Results of Intrauterine Insemination (IUI) with donor semen in women with poor ovarian reserve

Abstract Study question If we have a woman with a poor ovarian reserve, will she have a lower chance of pregnancy after a cycle of IUI? Summary answer A woman with a poor ovarian reserve has a lower chance of pregnancy, although in donor IUI we have an acceptable rate of pregnancy. What is known already Actually, the better predictor to define a poor ovarian reserve is a low antimullerian hormone (AMH). AMH is a well-known predictor of ovarian reserve, which allow to predict a response after an in vitro fecundation (IVF) cycle. Nevertheless, we also know that a low AMH does not mean to be not able to get pregnant. Few studies have compared different markers of ovarian reserve as predictors of pregnancy after an IUI cycle, and those which have done it have conflictive results. Maternal age seems to be strongly linked with the chance of pregnancy. Study design, size, duration We designed a retrospective cohort study with longitudinal follow-up upon the patients who undergo an IUI cycle in a public hospital of third level (Hospital Virgen del Rocio, Seville, Spain). We included 1059 cycles of IUI (383 with conjugal and 676 with donor semen) between 2015 and 2021. These cycles belong to 390 patients (64 with poor ovarian reserve and 326 with normal ovarian reserve). Participants/materials, setting, methods We collected data from clinical history which is completed during the visit of the patients. Cohort was stratified between patients with a low AMH (&amp;lt;1.1 ng/ml) and normal AMH (&amp;gt;1.1 ng/ml). We used this cut point following the definition of our regional guideline that includes when we can practice fertility treatments. Our main variable was pregnancy rate, defining pregnancy as an echography at 7 weeks with at least one embryo with cardiac activity. Main results and the role of chance When we compared pregnancy rate between normal ovarian reserve against poor ovarian reserve, we did not find statistically significant results in conjugal IUI independently that we compared by cycle (11.2% in normal ovarian reserve vs 3.8% in poor reserve (p = 0.2)) or by couple (27.97% in normal ovarian reserve vs 8.3% in poor ovarian reserve (p = 0.1)). We found differences with the same comparison in donor IUI by cycle (20.2% normal reserve vs 6.8% in poor reserve (p = 0.001)) and by couple (56.83% in normal ovarian reserve vs 21.15% in poor reserve (p = 0.001)). Nevertheless, pregnancy rate in IUI was similar to what we will get with an IVF cycle with only one oocyte. We compared pregnancy rate between normal ovarian reserve patients who undergo a conjugal IUI cycle, with low reserve patients who undergo a donor IUI cycle. When we compared by cycle normal ovarian reserve patients had 11.2% pregnancy rate, while poor ovarian reserve patients had a 6.8% (p = 0.1). When we compared by couple normal ovarian reserve patients had a pregnancy rate of 27.97% while poor ovarian reserve patients had a 21.15% (p = 0.3). Actually, our regional guide excludes poor ovarian reserve woman of an IVF cycle in the public system. Limitations, reasons for caution We had the proper limitations of an observational retrospective study. As we are a public center, we must follow our regional guide which defines whether we can do a treatment or not. Wider implications of the findings Patients with a poor ovarian reserve have a lower pregnancy rate during IUI with donor semen. Nevertheless, this rate could be acceptable especially when we cannot offer them an IVF cycle in public healthcare. Trial registration number Not applicable

O-244 AMH levels in infertile women in APAC region - prospective study in multiple countries, ethnicities and centres

Abstract Secretary General, Asia Pacific Initiative on Reproductive (ASPIRE) President, Taiwan Endometriosis Society Founder &amp; CEO, Taipei Fertility Center AMH is produced by granulosa cells of small growing follicles in the ovary and serum AMH levels strongly correlate with the number of growing follicles, AMH has been used clinically as a marker for ovarian reserve. Despite being of similar ages, with similar AMH levels, durations of ovarian stimulation, and gonadotropin doses, Asian women have been documented as having decreased AFCs and lower yields of total and mature oocytes after ovarian stimulation compared to their Caucasian counter- parts. These earlier data suggested that the effect of ethnicity was as an independent marker of ovarian reserve and potentially subsequent reproductive outcomes. We conducted the first multi-nation, multi-centre, and multi-ethnicity prospective cohort study from January 2020 to May 2021 to investigate serum AMH profiles among infertile Asian women. A total of 4613 women who visited fertility clinics at 12 IVF centres in 11 regions throughout Asia were recruited from Taiwan, China, Hong Kong SAR, India, Indonesia, Japan, Korea, Malaysia (2 centres), Thailand, Vietnam, and Singapore. The inclusion criteria were female partners aged 20–43years and naive to any ovarian stimulation cycle. The AMH measurement was performed using an AMH automated assay on a clinically validated platform. Among the 12 centres that joined the study, most demonstrated racial homogeneity except for Singapore and Malaysia which presented a highly diverse ethnic profile, while others were supposedly monoethnic communities. Unexplained or male infertility is the most common infertility cause in most countries, except for China with a notably high incidence of tubal disease. Age, ethnicity, obesity, and PCOS are significantly associated with ovarian reserve. The highest rates of PCOS were found in Indians (18.6%), Malays (18.9%), and Vietnamese (17.7%), yet remarkably lean with lower obesity rate was found in Vietnamese. Serum AMH levels are not affected by smoking or GnRHa and OCPs pretreatment but are affected by endometrioma surgery. Moreover, the assay can be conveniently conducted on any day of the menstrual cycle and is not influenced by the use of fresh or frozen samples. The rate of decline in ovarian reserve increases with age in Asian women, at 0.13ng/ml/year at 25–33years old and 0.31ng/ ml/year at 33–43 years old. We also found that a cut-off at 4.0 ng/ml could be considered for PCOS diagnosis in the Asian region. Despite limitations, the results can help guide clinicians for personalized infertility treatment, and call for further investigation into the effects of genetic, environmental and lifestyle factors on ovarian reserve.

P-371 It’s worth the freeze: outcomes from thawing electively cryopreserved oocytes are comparable in patients with reduced vs normal ovarian reserve at the time of cryopreservation

Abstract Study question For patients coming back to use oocytes derived from elective cryopreservation, does their initial ovarian reserve predict thaw survival, embryos’ developmental milestones and pregnancy success? Summary answer Thaw survival, fertilization rate, embryo development and pregnancy success rates do not vary significantly according to AMH level at initial cryopreservation. What is known already Increasing numbers of patients are electing to cryopreserve oocytes for future use. AMH (Anti Mullerian Hormone) is an ovarian reserve marker often assessed prior to initiation of treatment that predicts response to fertility treatment and the resulting oocyte yield. However, it is not known whether oocytes derived from a patient with compromised ovarian reserve (perhaps over multiple treatment cycles) will fare as well as that of a patient with normal ovarian reserve and a higher per cycle oocyte yield. Our study seeks to shed light on whether a lower initial AMH level negatively impacts the prognosis of the thawed oocytes. Study design, size, duration We included in our retrospective study all oocyte thaw cycles resulting from electively cryopreserved oocytes since 1996 at a single academically affiliated fertility center. 325 patients completed a total of 510 thaw cycles. 315 cycles were excluded from analysis for no AMH information. 6376 oocyte cryopreservation cycles were performed over that timeframe. The primary outcomes were laboratory statistics including oocyte survival, fertilization and embryo blastulation rates, while the secondary outcome was cumulative live birth rates. Participants/materials, setting, methods AMH categories of &amp;lt; 1, 1-2 and &amp;gt; 2 were selected to stratify reduced, low-normal, and normal ovarian reserves, respectively. 70.7% inseminated oocytes with partner sperm while the remaining 29.3% used donor sperm. Mean age at time of oocyte cryopreservation was 36.5 (range 27.5 to 46.2) while mean age at time of oocyte thaw was 39.2 (range 27.7 to 47.5). The statistical analysis was performed using ANOVA for mean comparisons and chi-squared for pregnancy data. Main results and the role of chance Average oocyte yield per cryopreservation cycle was significantly different across AMH groups (7.7 oocytes in AMH &amp;lt; 1, 10.5 oocytes in AMH 1-2, and 17.2 oocytes in AMH &amp;gt; 2, p &amp;lt; 0.01). The number of treatment cycles completed was highest in patients with AMH &amp;lt; 1 at 1.26 cycles. Oocyte survival (mean 89.0%), fertilization rate (mean 75.3%), and blastocyst conversion rate (mean 62.4%) did not vary significantly across AMH groups. Time to oocyte use was not significantly impacted by AMH at the time of initial testing. Those with reduced AMH &amp;lt; 1 came back earlier to utilize the oocytes (787 days), vs 1141 days for patients with AMH 1-2 and 1021 days for patients with AMH &amp;gt; 2. However, this difference was not statistically significant, p = 0.4. The rate of PGT-A euploid embryos did not vary between groups (38.8% in AMH &amp;lt; 1, 45.3% in AMH 1-2, 53.0% in AMH &amp;gt; 2, p = 0.07). Clinical pregnancy, miscarriage rate, and live birth rate in the first transfer cycle was not impacted by AMH. Total cumulative live birth rate was not correlated with AMH (31.6% in AMH &amp;lt; 1, 44.4% in AMH 1-2, 47.8% in AMH &amp;gt; 2, p = 0.48). Limitations, reasons for caution This data was collected at a single fertility center and thus has limited generalizability. 8.0% of patients came back to utilize their oocytes, which varies widely across the published literature. 60.6% of patients did not have AMH assessed as part of their pre-treatment testing and were excluded from analysis. Wider implications of the findings Although reduced ovarian reserve impacts oocyte yield, many studies find no impact on resulting oocyte quality, embryo development and pregnancy success rates. Those with compromised AMH have comparable oocyte thaw outcomes to those with normal ovarian reserve, though more oocyte cryopreservation cycles may be needed to achieve a successful outcome. Trial registration number N/A

P-428 Identifying key factors for achieving biochemical pregnancy in first autologous IVF cycles: an artificial intelligence-assisted approach

Abstract Study question What key factors determine a positive biochemical pregnancy outcome in first autologous IVF cycles, as identified by machine learning (ML) algorithms? Summary answer Maternal age, AMH, BMI, number of day 3 embryos and total embryos transferred emerged as top predictors for biochemical pregnancy across several ML methods. What is known already ML methods are powerful tools that discern patterns from multiple features to predict outcomes. Beyond their clear predictive capabilities, ML algorithms also offer valuable clinical insights by uncovering underlying data trends. These insights come from understanding the algorithms’ decision-making processes, revealing the rationale behind their predictions. While maternal age is known to influence IVF success, other pre-treatment and in-cycle factors also play a significant role. Understanding these factors can enhance patient management and guide clinical advice and interventions. Study design, size, duration This multicenter retrospective study included data from 9,945 cycles performed between January 2010 and July 2021. Only first autologous cycles using fresh oocytes and donor or patient sperm (fresh or frozen) were included. Preimplantation genetic testing (PGT) cycles were excluded. Both pre-treatment and in-cycle variables were considered, with treatment outcome expressed as cumulative biochemical pregnancy. Cases and variables deemed to have poor data quality were excluded. The final dataset comprised 80 variables and 7350 cycles. Participants/materials, setting, methods Five ML classifier algorithms were applied to predict cumulative biochemical pregnancy using pre-treatment and in-cycle variables. The models tested included logistic regression, support vector machine, random forests, gradient boosting and multilayer perceptron. Shapley values analysis was performed to explain the decision-making structures of all the algorithms tested, quantifying the impact of each included feature on outcome prediction. Main results and the role of chance Within our cohort, mean maternal age was 37.3±4.7 years, mean serum AMH was 2.4±2.1 ng/ml, mean BMI was 23.7±4.0 and mean antral follicle count (AFC) was 11.6± 7.6. Notably, 40.1% of cycles used donor sperm, while 33.8% of male patients were normozoospermic. The majority of cycles (90.8%) used antagonist stimulation protocols, yielding an average of 7.8±5.5 oocytes per patient. Fertilization rate was 70.6%, with a mean of 2.7±1.8 usable embryos obtained per cycle. Fresh embryo transfers accounted for 73% of cases, with an average of 1.5±0.9 transfers performed per cycle. The embryo utilization rate was 64.6% and 48.1% of cycles resulted in a biochemical pregnancy. Among the evaluated algorithms, the gradient boosting model demonstrated superior performance, with an accuracy of 70.6±1.4% and AUC of 77.3±1.7%. Shapley values across all five algorithms consistently revealed the negative correlation between maternal age and biochemical pregnancy rates. Among pre-treatment variables, AMH levels had a positive influence on outcomes, followed by BMI, AFC, and parity status. Regarding in-cycle variables, the number of embryos available at day 3 and the total number of embryos transferred, positively affected the chances of pregnancy. The number of mature oocytes was also an important in-cycle predictive feature. Limitations, reasons for caution his retrospective study spans an extended timeframe, suggesting potential variations in clinical and laboratory practices over the years. Therefore, caution is advised in generalizing the results to other patient populations or to contemporary data gathered using newer and enhanced clinical protocols. Wider implications of the findings The consistent identification of maternal age, ovarian reserve markers, and embryo quantity as primary predictors of pregnancy by the five AI models corroborates existing clinical understanding. This consistency emphasizes the strength and dependability of AI to reinforce and complement clinical knowledge with data-driven evidence. Trial registration number not applicable

P-605 Effectiveness of follitropin delta in patients with potential poor response: A post hoc analysis from the ESTHER-1 trial

Abstract Study question What is the effectiveness of individualised follitropin delta dosing compared to conventional follitropin alfa dosing in patients with potential poor response undergoing ovarian stimulation? Summary answer Individualised follitropin delta dosing provides a favourable efficacy and safety balance and is as good as follitropin alfa in patients with potential poor ovarian response. What is known already Poor ovarian response to controlled ovarian stimulation constitutes a challenge in in-vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment. The dosing algorithm of follitropin delta incorporates the prediction of ovarian response based on anti-Müllerian hormone (AMH), an accurate marker of ovarian reserve, and body weight, for an individualised dosing. In the general IVF/ICSI population and potential high responders, individualised follitropin delta reduces the risk of ovarian hyperstimulation syndrome (OHSS) and/or preventive interventions for OHSS, with sustained efficacy compared to conventional follitropin alfa. However, the performance of follitropin delta in the subpopulation of patients with potential poor response has not been evaluated. Study design, size, duration Post hoc analysis of 332 patients with potential poor response from the ESTHER-1 trial (determined by AMH level at screening &amp;lt;9 pmol/L). Patients received the maximum daily dose of 12 µg follitropin delta (fixed dosing throughout stimulation) as stipulated by the dosing algorithm for patients with AMH &amp;lt;15 pmol/l, or follitropin alfa at a starting dose of 150 IU, with potential dose adjustments from stimulation day 6 and onwards (maximum daily dose of 450 IU). Participants/materials, setting, methods Participants were women, 18–40 years, undergoing their first IVF/ICSI cycle in a GnRH antagonist protocol, including triggering with human chorionic gonadotrophin, IVF/ICSI insemination, and single or double blastocyst transfer on Day 5. Ultrasound was performed 10–11 weeks after transfer to confirm ongoing pregnancy. All pregnancies were followed until birth. Study outcomes include number of oocytes retrieved and number of good quality blastocysts, ongoing pregnancy and live birth rates, cycle cancellation and OHSS rates. Main results and the role of chance A total of 332 patients (25.0% of the overall ESTHER-1 population) had serum AMH at screening of &amp;lt; 9 pmol/l and were included in the analysis: 168 were treated with follitropin delta and 164 were treated with follitropin alfa. Baseline characteristics were similar between the treatment groups, with a mean age of 34.8 years, a median AMH of 5.7 pmol/l and a mean weight of 64.5 kg. With follitropin delta, the mean daily dose was 12.0 µg and with follitropin alfa 12.4 µg, resulting in mean total doses of 104.6 µg and 112.3 µg, respectively. The mean number of oocytes retrieved was 5.8 ± 3.5 with follitropin delta and 5.5 ± 3.6 with follitropin alfa and the mean number of good-quality blastocysts was 1.2 ± 1.4 with both treatments. The ongoing pregnancy rate was 29.8% with follitropin delta and 29.3% with follitropin alfa and the live birth rates were 29.2% and 28.7%, respectively. Thirteen patients (7.7%) treated with follitropin delta and 14 (8.5%) treated with follitropin alfa had their cycles cancelled due to poor response. One case of OHSS (0.6%) was observed in the follitropin delta group, and 3 cases (1.8%) were observed in the follitropin alfa group. Limitations, reasons for caution The main limitation of the study is its post hoc nature. Furthermore, the study is based on a relatively small number of patients. Wider implications of the findings This subgroup analysis, alongside the normoresponder and the potential hyperresponder subgroup of the ESTHER-1 trial, adds evidence for the effectiveness of follitropin delta across all ovarian reserve subgroups of the infertile population. Trial registration number NCT01956110

P-684 Anti-müllerian hormone predictive value for cumulative pregnancy rate in non-infertile women following four intrauterine insemination with donor sperm

Abstract Study question Are anti-Müllerian hormone (AMH) levels predictive of cumulative pregnancy rate in non-infertile women undergoing intrauterine insemination with donor sperm (ds-IUI)? Summary answer AMH has limited predictive value for clinical pregnancy after 4 cycles of ds-IUI in non-infertile women. Decreased AMH concentration does not necessarily reduce pregnancy rates. What is known already Physiologically, pregnancy rates decline due to oocyte quality deterioration upon advancing maternal age. AMH is a widely-used marker of ovarian reserve and follicular response but not an infertility test, despite being sometimes referred to as such. This misconception can lead to unnecessary complex ART treatments only based on low AMH. Indeed, the predictive value of AMH for natural conception and IUI remains uncertain and highly controversial in the literature. Study design, size, duration This multicenter prospective observational study evaluated the correlation between AMH levels and pregnancy rates in 182 non-infertile women undergoing ds-IUI. Participants were recruited from June 2020 to December 2022 from three centers: Hospital del Mar in Barcelona (Spain), Fertty Clinic in Barcelona (Spain) and Clinica de la Mujer in Viña del Mar (Chile). Participants/materials, setting, methods The study included women aged 25-39 years, normal BMI, regular periods, and without ovarian pathology or endometriosis, who were undergoing ds-IUI for severe oligoasthenoteratozoospermia, female partner, or single status. Baseline AMH and antral follicle count (AFC) by TVUS was registered. Reproductive outcomes were compared between women with AMH &amp;gt;1.1 and AMH ≤1.1 ng/mL. The main outcome was the cumulative clinical pregnancy rate after up to 4 ds-IUIs in a 3-year frame. Main results and the role of chance Kaplan Meier’s analysis did not show cumulative pregnancy rate superiority in women with AMH &amp;gt;1.1 ng/mL vs &amp;lt; 1.1 ng/mL (log rank Mentel Cox 1,502; p-value 0.46; ROC curve analysis predictor for clinical pregnancy, AUC=0.586). AMH and AFC were found to be significantly correlated (Pearson’s coefficient r = 0.632, p-value &amp;lt;0.001). Additionally, women who achieved pregnancy were found to be significantly younger (p-value &amp;lt;0.05) versus women who did not. However, no differences in AMH levels were found between them (p-value 0.33). Limitations, reasons for caution Limitations of the study include interpretation of results in extreme concentrations of AMH, potential impact of polycystic ovary syndrome (PCOS) in women with high AMH values, lower representation of patients with low AMH levels, and variability in ovulation induction regimens prior to ds-IUI (exposure to different rFSH dosages). Wider implications of the findings AMH is not a reliable predictor for pregnancy in ds-IUI. Even women with extremely low AMH levels can achieve successful outcomes, which are associated with age. The results of this multicenter study support that low AMH should not be used as an exclusion criterion for non-infertile women seeking ds-IUI. Trial registration number IRB Protocol ID 2020/9445