Median Antral Follicle Count Research Articles

An age-related nomogram for antral follicle count: an observational study of 3821 women

Research questionTo investigate the relationship between antral follicle count (AFC) and chronological age and establish expected values for AFC. DesignThis is a retrospective cohort study at a specialist gynaecological ultrasound centre in London. Women presenting to a gynaecology diagnostic unit for investigation of symptoms or routine check-up, and undergoing transvaginal ultrasound examinations, between the 1st of January 2017 and 22nd of September 2022. ResultsWe analysed 8821 data entries from 7573 women. We estimated the relationship between AFC and age to develop an AFC nomogram independent of the stage in the menstrual cycle. The AFC corresponding to the 10th, 25th, 50th, 75th and 90th centiles for each patient and age group have been calculated. Both nomogram and condition specific populations displayed a gaussian relationship between AFC and age. For the nomogram population, a peak median AFC of 30, was observed between the age groups of 21 -23. The AFC distribution of the previous cystectomy group was found to be statistically different in comparison to the nomogram population(P<0.0001). However, the same did not hold true for those on hormonal contraception (P=0.43). ConclusionsWe provide an AFC nomogram reporting median and interquartile values for AFC by chronological age across the reproductive years. This is a useful tool for providing counselling for those undergoing ovarian reserve assessments taken any time in the menstrual cycle including for those on hormonal contraceptives or previous cystectomy.

Effect of breast cancer prognostic factors on ovarian reserve and response in fertility preservation

Research questionDo breast cancer prognostic factors influence ovarian reserve and response to ovarian stimulation in the context of fertility preservation? DesignObservational, bicentric retrospective study of 352 women with breast cancer who underwent ovarian stimulation using a random start gonadotrophin releasing hormone antagonist protocol and vitrified oocytes between November 2015 and August 2022. Serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) were measured. The number of oocytes recovered, maturation rate and follicular output rate (FORT) were analysed according to patients’ characteristics and breast cancer prognostic factors. ResultsMedian age was 34 years (31.1–37.1). Median AFC and serum AMH level were 17 (12–26) follicles and 2 (1.2–3.4) ng/ml, respectively. After ovarian stimulation, 10.5 (6.0–16.0) oocytes were recovered, with eight (4–13) being mature. Mean oocyte maturation rate was 79% (62–92). Antral follicle count (>12) significantly affected the risk of recovering fewer than eight mature oocytes (P < 0.0001, multivariate analysis). Follicular responsiveness to FSH, assessed by the follicular output rate (FORT index) and number of oocytes recovered, were 31% (21–50) and 10.5% (6.0–16.0), respectively. FORT index and ovarian stimulation outcomes were not influenced by breast cancer prognostic factors. ConclusionBreast cancer prognostic factors do not influence ovarian reserve markers or response to ovarian stimulation in fertility preservation. Therefore, tumour grade, triple-negative status, HER2 overexpression and high Ki67 should not alter the fertility-preservation strategy when considering ovarian stimulation for oocyte vitrification.

Evaluation of ovarian reserve in women with thyroid autoimmunity.

To compare the ovarian reserve of women of reproductive age with and without thyroid autoimmunity (TAI). We performed a retrospective analysis of medical records from an assisted reproduction clinic from February 2017 to December 2021. Women aged between18 and 47 years with data on antithyroperoxidase and antithyroglobulin (anti-Tg) antibodies and assessment of ovarian reserve by anti-müllerian hormone (AMH) and antral follicle count (AFC) were included. Among the 188 participants included, 63 were diagnosed with TAI, and 125 had both antibodies negative. AMH and AFC were compared between groups. Subanalysis based on age, types of antibodies, and thyroid function markers were performed. In addition, bivariate analysis and regression models were used. Overall, there was no difference in the median levels of AMH or AFC between the two groups. However, in the subgroup analysis by age, we observed a trend towards lower median levels of AMH in women over 39 years with TAI (0.9 ng/mL vs. 1.5 ng/mL, p=0.08). In a subanalysis according to antibodies, we found a significantly lower median AFC in the group with anti-Tg than in the group without this antibody (8.0 follicles vs. 11.5 follicles, p=0.036). We also found a significantly higher prevalence of anti-Tg in patients with low ovarian reserve compared to those with normal reserve (60.7% vs. 39.3%, p=0.038). The ovarian reserve of women with TAI appears to be insidiously compromised over the years, with a decreased ovarian reserve in women with anti-Tg.

P-263 Clinical factors influencing the incidence of tripronuclear zygotes in IVF

Abstract Study question Is the incidence of tripronuclear zygotes (3PN) in IVF cycles influenced by clinical, patient and treatment parameters? Summary answer Tripronuclear zygotes incidence in IVF cycles was influenced by Antral Follicle Count, number of oocytes retrieved, sperm progressive motility, and the use of fresh semen. What is known already Tripronuclear zygotes are indicative of abnormal fertilisation and are not routinely considered suitable for transfer. It is therefore important to optimise their detection and minimise their occurrence. Tripronuclear zygotes can originate as a result of the combination of one maternal and two paternal sets of chromosomes (fertilisation of a haploid oocyte by two haploid spermatozoa or by one diploid spermatozoon) or the combination of one paternal and two maternal sets of chromosomes (fertilisation of a diploid oocyte by one haploid spermatozoon) (1). Study design, size, duration This is a retrospective study of 550 IVF cycles performed between April 2018- April 2021, in a single UK clinic. IVF cycles either within (group 1) or exceeding (group 2) the key performance indicator (KPI) for the incidence of 3PN (&amp;lt;6%) (2), were assessed for associations with quantitative cycle variables. Proportion of 3PN per cycle was assessed for associations with qualitative variables. Cycles using donor oocytes (n = 73) were excluded for analyses assessing patient (maternal) parameters. Participants/materials, setting, methods Continuous variables including age, body mass index, Antral Follicle Count (AFC), anti-Mullerian hormone (AMH), oocytes recovered, timing from sperm production to insemination or oocyte recovery to insemination, sperm concentration, progressive motility and morphology were analysed by Mann-Whitney U Test. Qualitative variables including patient ethnicity, own/donor oocyte source, fresh/frozen sperm, stimulation regimen and oocyte recovery needle were analysed by logistic regression assuming binomial errors. Significance was assumed at p &amp;lt; 0.05. Main results and the role of chance There was no difference between groups where 3PN incidence exceeded or fell within the KPI when procedure timings and clinical parameters were assessed. There was also no relationship between patient characteristics (age, body mass index, AMH levels, ethnicity, oocyte source (own/donor)), semen concentration or semen morphology and the proportion of 3PN per cycle. However, number of oocytes retrieved in group 2 was significantly higher than group 1 (group 1, n cycles = 307, median oocytes retrieved = 8; group 2, n cycles = 170, median oocytes retrieved = 12 [95% CI -4, -1]) (p &amp;lt; 0.001). Similarly, AFC was significantly increased in group 2 (group 1, n cycles = 254, median AFC = 11; group 2, cycles n = 150, median AFC = 13 [95% CI -4, -1]) (p = 0.009). Likewise, the mean sperm motility parameters were higher for cycles exceeding the 6% 3PN KPI, with 64.6 ± 0.91% vs 68.8 ± 1.11% total motility (p = 0.004), and 57.1 ± 0.97% vs 61.7 ± 1.2% progressive motility (p = 0.003) for group 1 and 2 respectively. Proportion of 3PN per cycle was also significantly higher with fresh semen compared to frozen (6.6 ± 0.39% vs 4.7 ± 0.51%) (p = 0.006). Limitations, reasons for caution This is a retrospective study of a single UK clinic. Further analysis, expanding sample size, are required to confirm these findings. Wider implications of the findings Our finding that number of oocytes recovered influences 3PN incidence is in agreement with previous studies (3, 4). Fresh and high progressively motile sperm may be more capable of zona pellucida penetration leading to polyspermy and 3PN. Adjustment of sperm concentration at insemination could be considered in higher risk circumstances. Trial registration number na

P-647 Intake of soy foods and soy isoflavones in relation to ovarian reserve among women presenting to a fertility center

Abstract Study question Are soy food and isoflavone intakes associated with ovarian reserve as measured by antral follicle count (AFC)? Summary answer Within the observed range of intake, soy food or isoflavone consumptions are not associated with AFC. What is known already Phytoestrogens are structurally similar to 17β-estradiol, and bind to ER-α and ER-β in vitro resulting in weak estrogenic activity. Previous work in ruminants, felines and rodents has shown that exposure to phytoestrogens can have major adverse impacts on reproduction. However, findings of studies in humans suggest that soy foods and soy phytoestrogens may not have major deleterious impacts on reproductive hormone levels or reproductive outcomes, and could even be beneficial in couples undergoing infertility treatment. Study design, size, duration Women presenting to a large academic fertility center between April 2007 and December 2019 were invited to participate in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study. Intake of 15 soy-based foods during the previous three months was obtained at baseline and intake of soy phytoestrogens was estimated from these reports. AFC was assessed with transvaginal ultrasound performed as part of diagnostic evaluation for infertility. Participants/materials, setting, methods We included 667 women who reported their soy food intake and had an AFC assessment. Women were divided in groups of increasing soy food and soy isoflavone intake with women who reported not consuming soy-based foods serving as the reference group. We evaluated the association of soy foods and soy isoflavones intake with AFC using Poisson regression models adjusting for confounders. Analyses were also stratified by age, BMI, and smoking status. Main results and the role of chance Women had median baseline age of 35.0 years and BMI of 23.4 kg/m2. Mean (range) intake of soy foods was 0.1 (0-7.4) servings/day, and mean (range) intake of isoflavones was 6 (0-166) mg/day, which is comparable to that of women in the general population of the USA. Intakes of soy foods or isoflavones were not related to AFC. The median (IQR) AFC for women who did not consume soy foods and women in the highest category of soy intake (&amp;gt;0.45 servings/day, median 0.88 servings/day) were 12 (9, 18) and 13 (9, 19). After adjustment for potential confounders, the mean difference in AFC between women in the highest category of soy intake and women who did not consume soy was -0.5% (-6.6%, 6.1%). Soy food intake remained unrelated to AFC when intake was categorized using different cutoff values when intake was modeled as a continuous variable when departures from a linear association were considered, and when we excluded from analysis 76 women whose AFC ultrasound scan was performed before they completed the diet assessment. Soy intake was also unrelated to AFC within categories of age, BMI and smoking status. Findings for soy isoflavones mirrored those for soy-food intake. Limitations, reasons for caution Self-reported soy intake may have resulted in measurement error leading to attenuation of observed relations towards the null. Also, all participants were women presenting to a fertility center and therefore, findings may not be generalizable to women in the general population. Wider implications of the findings Our findings suggest soy food and isoflavone intakes within the ranges observed among women in the general population of the USA is unlikely to influence ovarian reserve in any meaningful way. Trial registration number Not applicable

Placental histology following assisted hatching in fresh transfer cycles.

To assess placental histological findings following assisted hatching in fresh transfer in vitro fertilization cycles. Evaluation of a historic cohort of live singleton deliveries after fresh embryo transfer (ET) at a single university medical center between 2009 and 2017. We compared perinatal outcomes and placental histology in cases where assisted hatching was performed prior to ET (AH group) and cases with no AH (no AH group). Overall, 166 deliveries following AH were compared to 494 deliveries with no AH. Patients' demographics were similar between the groups. Median antral follicle count was significantly lower in the AH group, median 11 (range 1-50) vs. 16 (range 1-80), p < 0.001, and the primary indication for infertility treatment significantly more often diminished ovarian reserve (p < 0.001). Cycle characteristics in the AH group included a higher gonadotropin dose employed, and a lower rate of single and blastocyte transfer. Pregnancies following AH were associated with less low-lying placentas, 0.6% vs. 6.2%, p = 0.001, and comparable for other perinatal outcomes. After adjusting for confounders, the rate of bilobated placentas was higher following AH, aOR 7.10, 95% CI 1.50-33.51. The rate of perivillous depositions was higher with AH, aOR, 95% CI 3.18, 1.46-6.93, and the rate of chorangiosis lower in this group, aOR, 95% CI 0.32, 0.11-0.93. The overall rate of vascular lesions was similar between the groups. Pregnancies following AH are notable for a lower rate of placenta previa, yet a higher rate of bilobated placentas and perivillous depositions and less chorangiosis, warranting further investigation.

Beverage intake and ovarian reserve among women from a fertility center

To evaluate the associations of caffeinated, alcoholic, and sweetened beverage intakes with antral follicle count (AFC), a well-accepted biomarker of ovarian reserve. Observational prospective cohort study. Fertility center at an academic hospital. This study includes 567 women seeking fertility care at the Massachusetts General Hospital who participated in the Environment and Reproductive Health Study. None. Women self-reported consumption of caffeinated (coffee, tea, soda), alcoholic (wine, beer, liquor), sugar-sweetened, and artificially sweetened beverages using a validated food-frequency questionnaire. Antral follicle count was assessed using a transvaginal ultrasound performed on the 3rd day of an unstimulated menstrual cycle or on the 3rd day of a progesterone withdrawal bleed. Median (interquartile range) age and AFC were 35.0 (32.0-38.0) years and 13.0 (9.0-18.0), respectively. Median (range) intake of caffeinated, alcoholic, sugar-sweetened, and artificially sweetened beverages in servings/day were 1.08 (0-7.08), 0.35 (0-3.84), 0.04 (0-4.80), and 0.04 (0-7.50), respectively. All examined beverages were unrelated to AFC. The multivariable adjusted mean AFC (95% confidence interval) for women in the top and bottom quartiles of intake were 13.8 (13.0-14.7) and 13.8 (12.9-14.7) for caffeinated beverages; 13.8 (13.0-14.7) and 13.8 (13.0-14.6) for alcoholic beverages; 13.5 (12.6-14.4) and 13.3 (12.4-14.2) for sugar-sweetened beverages; and 13.2 (12.4-14.1) and 13.4 (12.6-14.3) for artificially sweetened beverages. Low-to-moderate intakes of caffeinated, alcoholic, sugar-sweetened, and artificially sweetened beverages were unrelated to ovarian reserve, as measured by AFC, in a cohort of women seeking fertility care.

The Impact of BRCA1- and BRCA2 Mutations on Ovarian Reserve Status

This study aimed to investigate whether female BRCA1- and BRCA2 mutation carriers have a reduced ovarian reserve status, based on serum anti-Mullerian hormone (AMH) levels, antral follicle count (AFC) and ovarian response to ovarian hyperstimulation. A prospective, multinational cohort study was performed between October 2014 and December 2019. Normo-ovulatory women, aged 18–41 years old, applying for their first PGT-cycle for reason of a BRCA mutation (cases) or other genetic diseases unrelated to ovarian reserve (controls), were asked to participate. All participants underwent a ICSI-PGT cycle with a long-agonist protocol for controlled ovarian hyperstimulation. Linear and logistic regression models were used to compare AMH, AFC and ovarian response in cases and controls. Sensitivity analyses were conducted on BRCA1- and BRCA2 mutation carrier subgroups. Thirty-six BRCA mutation carriers (18 BRCA1- and 18 BRCA2 mutation carriers) and 126 controls, with mean female age 30.4 years, were included in the primary analysis. Unadjusted median AMH serum levels (IQR) were 2.40 (1.80–3.00) ng/ml in BRCA mutation carriers and 2.15 (1.30–3.40) ng/ml in controls (p = 0.45), median AFC (IQR) was 15.0 (10.8–20.3) and 14.5 (9.0–20.0), p = 0.54, respectively. Low response rate was 22.6% among BRCA mutation carriers and 9.3% among controls, p = 0.06. Median number of retrieved oocytes was 9 (6–14) in carriers and 10 (7–13) in controls, p = 0.36. No substantial differences were observed between BRCA1- and BRCA2 mutation carriers. Based on several biomarkers, no meaningful differences in ovarian reserve status were observed in female BRCA mutation carriers compared to controls in the context of ICSI-PGT treatment.

Female parental consanguinity is associated with a reduced ovarian reserve

Research questionIs parental consanguinity associated with a reduced ovarian reserve in women from the Arabian Peninsula, comparing anti-Müllerian hormone (AMH) and antral follicle count (AFC)? DesignRetrospective large-scale observational study including 2482 women from the Arabian Peninsula, aged 19–49 years, who had their serum AMH and AFC measured as part of their fertility assessment, from May 2015 to November 2019. Consanguinity was defined as women whose parents were first-degree or second-degree cousins. Serum AMH was measured for all participants. ResultsA total of 2198 women were included: 605 in the consanguine group (27.53%), 1593 (72.47%) in the non-consanguine group. There were no significant differences between groups in terms of body mass index, years of infertility or smoking status. Women from the consanguine group were significantly younger (mean age 33.74 ± 6.64 years) compared with the non-consanguine group (mean age 34.78 ± 6.64 years, P < 0.0001). Median AMH and AFC for the consanguine group were 1.90 ng/ml (min–max: 0.01–23.8) and 11 (0–80), respectively, and for the non-consanguine group 1.84 ng/ml (min–max: 0.01–23.0) and 11 (0–60), respectively. AMH and AFC exhibit an age-dependent decline. As both parameters are age-dependent, the multivariate analysis showed that women from the consanguine group presented significantly lower AMH (coefficient of variation [CV] –0.07 ± 0.03, P = 0.036) and AFC (CV –0.16 ± 0.06, P = 0.003) compared with non-consanguine women, and the highest differences were found for women below 35 years of age (AMH median [min–max]: 2.82 ng/ml (0.01–23.80) versus 2.92 ng/ml (0.01–23.00); P = 0.035; AFC median [min–max]: 15 (0–80) versus 14 (0–80); P = 0.001). ConclusionThe adjusted analysis by age indicates that female parental consanguinity is associated with reduced ovarian reserve in the studied population. Clinical evaluation should include extensive family history and subsequent counselling of the affected couples.

Ethnic and Sociocultural Differences in Ovarian Reserve: Age-Specific Anti-Müllerian Hormone Values and Antral Follicle Count for Women of the Arabian Peninsula.

BackgroundAnti-Müllerian hormone (AMH) and antral follicle count (AFC) age-specific reference values form the basis of infertility treatments, yet they were based upon studies performed primarily on Caucasian populations. However, they may vary across different age-matched ethnic populations. This study aimed to describe age-specific serum AMH and AFC for women native to the Arabian Peninsula.MethodsA retrospective large-scale study was performed including 2,495 women, aged 19 to 50 years, native to the Arabian Peninsula. AMH and AFC were measured as part of their fertility assessment at tertiary-care fertility centres. Age-specific values and nomograms were calculated.Results2,495 women were evaluated. Mean, standard deviation and median values were calculated for AMH and AFC by 1-year and 5-years intervals. Median age was 34.81 years, median AMH was 1.76ng/ml and median AFC was 11. From the total group, 40.60% presented with AMH levels below 1.3ng/mL. For women <45 years old, the decrease in AFC was between -0.6/-0.8 per year. Up to 36 years old, the decrease of AMH was 0.1ng/ml. However, from 36 to 40 years old, an accelerated decline of 0.23ng/ml yearly was noted. In keeping with local customs, 71.23% of women wore the hijab and 25.76% the niqab. AMH and AFC were significantly lower for niqab group compared with hijab group (p=0.02 and p=0.04, respectively).ConclusionThis is to-date the largest data set on age-specific AMH and AFC values in women from the Arabian Peninsula aiming to increase clinical awareness of the ovarian reserve in this population.

P–432 Do stage and grade of malignancy impact fertility preservation in breast cancer patients?

Abstract Study question Do stage and grade of breast cancer impact the number of retrieved mature oocytes during controlled ovarian stimulation for fertility preservation? Summary answer Stage and grade of breast cancer do not impact the number of retrieved mature oocytes. Higher grade breast cancer requires higher gonadotropin doses during stimulation. What is known already Cancer can impair ovarian response by unknown mechanisms. Some authors suggest that it could be detrimental on fertility because it elicits a catabolic state, increasing stress hormone levels. Some studies have also shown that ovarian response to controlled ovarian stimulation (COS) is, in some way, compromised in oncological patients. Little is known about the impact of different types of cancer on ovarian reserve, and specifically whether higher stage and grade could compromise egg retrieval during fertility preservation (FP) techniques. Study design, size, duration: Retrospective cohort study evaluating data of FP treatment cycles among women with breast cancer at the Oncofertility Unit of San Raffaele Hospital, Milan in the period from 2011 to 2019. Participants/materials, setting, methods Inclusion criteria were: breast cancer diagnosis; age 22–41; oocyte cryopreservation after stimulation with a random start GnRH-antagonist protocol. Patients receiving chemotherapy before FP were excluded. We compared outcomes between low-stage (stage I) and high-stage (stage II-III) patients and low-grade (G1-G2) and high-grade (G3) patients. Main study outcome was the total number of retrieved mature oocytes. Univariate analysis was performed by Mann-Whitney test, Kruskal-Wallis test and Fisher’s exact test. Multivariate analysis was performed by logistic regression. Main results and the role of chance 101 stimulation cycles were included. High-stage disease patients were significantly younger than low-stage. Median antral follicle count (AFC) was 12 in low-stage and 10 in high-stage (age-adjusted p = 0.92) and median anti-mullerian hormone (AMH) levels were 1.9 ug/L in low-stage and 1.8 ug/L in high-stage (age-adjusted p = 0.22). No significant difference in stimulation protocols and follicle-stimulating hormone (FSH) start and total dose could be detected between the 2 groups. Median number of vitrified oocytes was 7 in both groups (p = 0.75). No significant difference could be observed in median AFC (13 vs 10, p = 0.14) and AMH levels (2.1 vs 1.5, p = 0.88) between low-grade and high-grade disease patients. When adjusting for age, AFC was found to be significantly lower in high-grade disease patients (p = 0.03). Patients with high-grade tumors were stimulated with higher doses of FSH (age-adjusted p-value=0.03). Median number of vitrified oocytes was 6 in low-grade patients and 7 in high-grade (p = 0.35). In a multivariate model including age, cancer stage, cancer grade and molecular classification, the only significant factor found to be inversely associated with AFC was cancer grade (OR 3.6; 95% CI 0.7 – 6.5, p = 0.01), while only age was significantly associated with oocyte retrieval (OR 0.4; 95% CI 0.01 – 0.9, p = 0.04). Limitations, reasons for caution The main limitations of our study are its retrospective design and the small sample size. Wider implications of the findings: Fertility preservation counselling and ovarian stimulation protocols of breast cancer patients could be implemented with cancer grade. Trial registration number Not applicable

Age-Specific Distribution of Serum Anti-Mullerian Hormone and Antral Follicle Count in Indian Infertile Women.

Background:Ovarian reserve declines with age. However, there are considerable ethnic differences in the decline of ovarian reserve between individuals.Aim:This study aimed to make age-specific percentile charts of anti-Mullerian hormone (AMH) and antral follicle count (AFC) in Indian infertile women and to find the proportion of young women with low ovarian reserve.Setting and Design:This was a retrospective data analysis of AMH and AFC of 5525 infertile women from August 2015 to December 2018.Materials and Methods:Infertile women aged 20– 44 years, with body mass index 18–32 kg/m2 and having both ovaries were included in the study. Women with pituitary/adrenal disorders, malignancy, total AFC >40, tuberculosis, endometriosis, autoimmune disorders, smoking, chemotherapy, radiotherapy and recent ovarian surgery were excluded from the study.Statistical Analysis:Comparison between groups was done by Chi-square test.Results:About 14.5% of women <35 years and 50.5% of women >35 years had low AMH values (<1.1 ng/ml). In addition, 5.6% of women <35 years and 23.6% of women >35 years had a low AFC of ≤5. In this study, 55.7% of women who had low AMH and 50.7% who had low AFC were <35 years of age. The median AMH values were 4.23 ng/mL in 20–25 years’ age group, 3.48 ng/mL in women aged 26–30 years, 2.43 ng/mL in women aged 31–35 years, 1.28 ng/mL in women aged 36–40 years and0.52 ng/mL in 40–44 years’ age group. The median AFCs were 20, 18, 14, 10 and 6 for each of the age groups, respectively.Conclusion:This study suggests that approximately more than half of the infertile women who were tested to have low ovarian reserve were <35 years of age.

Hydroxyurea Is a Potential Risk Factor for Diminished Ovarian Reserve in Young Adults with Sickle Cell Anemia

Introduction: Females are born with a set number of ovarian follicles. Ovarian reserve, defined by the number of primordial follicles, decreases with age. Diminished ovarian reserve (DOR) is a risk factor for shortened reproductive lifespan, infertility and poor assisted reproductive technology outcomes. Young women with sickle cell anemia (SCA) are at risk for DOR1,2. Whether hydroxyurea (HU) use contributes to this risk is not established. Antimullerian hormone (AMH), a biomarker of the ovarian follicle pool, is used with antral follicle count (AFC) and follicle stimulating hormone (FSH), to estimate ovarian reserve. The extent to which AMH corresponds with visualized AFC in SCA, and thus serves as a reasonable surrogate biomarker, is unknown. The purpose of this study was to test the hypothesis that young women with SCA have lower AMH than age and race matched controls and that HU exposure is a risk for DOR. Methods: Subjects from our Adult Sickle Cell Center had ovarian reserve measured on day 3-5 of the menstrual cycle or at any time if on menses-suppressing contraception. We measured serum AMH, FSH, estradiol and AFC by ultrasound. Subjects' demographic, reproductive and SCA treatment history were obtained. HU exposure variables included (1) age at first exposure, (2) use at time of study visit, (3) markers of adherence (MCV and ANC), and (4) refill data. Ferritin was used to assess iron overload. We compared AMH levels in subjects ages 19-25 and 26-31 years to AMH levels in age-matched African American women controls with tubal factor infertility and no chemotherapy exposure, and age-matched levels from the historic Multicenter Study of Hydroxyurea (MSH) cohort2. We then compared subject characteristics by the presence of DOR (AMH &amp;lt;1.1ng/mL ± FSH &amp;gt; 10 - 40IU) or primary ovarian insufficiency (POI), (AMH &amp;lt; 1.1ng/mL and FSH ≧ 40IU). The chi-squared and Mann Whitney U test was used for categorical and continuous variables, respectively, to determine associations with DOR. Results: Sixteen women with SCA participated with a median age of 25.5 years (IQR 21,29), hemoglobin 8.8g/dL (IQR 8,9.2), MCV 96.9fL (IQR 88.6, 101.1), ANC 5.7K/mcl (IQR 3.4, 8.4), and ferritin 857ng/mL (IQR 246, 1957). All had prior HU exposure. The median age at first HU exposure was 17.5 years (IQR 14.5, 21), median months of HU exposure was 23 (IQR 2.8, 38.5). Twelve subjects were taking HU at the study visit and, by refills, 7 took continuous HU in the previous 6-months, median dose 1715mg (IQR 1000, 2000). Lower AMH and AFC was observed in older subjects as expected. AMH was lower in study subjects compared to controls in both age groups: 19 - 25 years [2.48ng/mL (IQR 1.7, 3.4) vs 7.45ng/mL (IQR 6.5, 10.7), p&amp;lt;.001], 26- 31 years [1.34ng/mL (IQR 0.87,2.2) vs 2.04ng/mL (IQR 1.7,3.2), p=0.08]. The JHU and MSH cohorts had no difference in AMH (p&amp;gt;0.05)1. Younger women (19-25yo) had higher median AFC than older women (26-31yo), a difference that was not statistically significant (14(IQR 8, 35) vs 9(IQR 7,12) follicles). Four of 16 subjects had DOR; all four were taking HU and &amp;gt;25yo. In those with or without DOR, there was no difference in median BMI (21.1(20.7, 22.4) vs 24.7 (IQR 20.8, 26.2), hemoglobin (8.7 (IQR 8.4, 8.9) vs 8.8 (7.9, 9.8) g/dL), or ferritin (602 (IQR 131, 1529) vs 875 (IQR 303, 1975). DOR was associated with a lower median AFC (5.5(IQR 4, 7) vs 12 (IQR 9,24) oocytes p=0.04) and higher MCV (112 vs 92fL, p=0.02). Table 1 compares DOR and HU exposure our cohort, the MSH2 and a pediatric cohort1. In all cohorts, some young women exposed to HU have DOR. Conclusions In this pilot study of ovarian reserve in young adult women with SCA, AMH is significantly lower in age- and race-matched controls and levels are similar to an historic SCA cohort. AMH and AFC were both lower in older subjects, suggesting that AMH is a reasonable ovarian reserve marker in SCA. No women had POI. DOR was associated with lower AFC and higher MCV. In young adult women of reproductive age with SCA, taking HU may be a risk for DOR. This data forms the basis for ongoing research on the pathobiological mechanisms and clinical significance of DOR in women with SCA. References 1Pecker, LH et al. Hydroxycarbamide and ovarian reserve in the Multicenter Study of Hydroxycarbamide. British Journal of Haematology. 2020. 2Elchuri, SV et al. The effects of hydroxyurea and bone marrow transplant on AMH levels in females with SCA. Blood Cells Mol Dis. 2015. Disclosures Pecker: Forma Therapeutics: Consultancy. Lanzkron:GBT: Research Funding; HRSA: Research Funding; Ironwood: Research Funding; NHLBI: Research Funding; PCORI: Research Funding; Pfizer: Research Funding; Pharmacy Times Continuing Education: Honoraria; Prolong: Research Funding.

Association of the functional ovarian reserve with serum metabolomic profiling by nuclear magnetic resonance spectroscopy: a cross-sectional study of ~\u2009400 women

BackgroundWomen with diminished ovarian reserve are known to have increased cardiovascular risk, whether there is a continuous association between the ovarian reserve biomarkers; anti-Müllerian hormone (AMH), antral follicle count (AFC) and cardio-metabolic risk factors are unknown.MethodsA cross-sectional study of 398 women intending to undergo IVF with pre-treatment early follicular AMH and AFC measurements. Serum lipids, lipoprotein subclasses and low-molecular-weight metabolites were quantified by NMR spectroscopy (155 metabolic measures). Associations were analysed using multivariable regression.ResultsParticipants were mean 35.5 (SD 4.43) years old and had a median AMH of 16 pmol/l (IQR 8.8, 28.0 pmol/l) and a median AFC of 12 (IQR 7.16). AMH showed positive associations with HDL, omega-6 and polyunsaturated fatty acids and the amino acids isoleucine, leucine and tyrosine, with effects ranging from 0.11 (95%CI 0.004 to 0.21) for total lipids in small HDL to 0.16 (0.06 to 0.26) for isoleucine, for a mean difference of one SD of metabolite per one SD increment in AMH, and negatively with acetate: − 0.31(− 0.22, − 0.004) SD per 1 SD AMH. AFC was positively associated with alanine, glutamine and glycine. Results were consistent, though less precisely estimated, when restricted to those women who were preparing for treatment because of their partner’s infertility.ConclusionsIn women intending to have IVF, AMH and AFC were not associated with traditional lipid measured but were associated with a number of novel cardiovascular risk factors. Prospective studies will be required for replication, determination of causality and confirmation that ovarian reserve is impacting on metabolism rather than variation in metabolism is influencing ovarian reserve.

Ovarian reserve markers and endocrine profile during oral contraception: Is there a link between the degree of ovarian suppression and AMH?

The ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) are suppressed in varying degree during the use of combined oral contraceptives (COC). Further, long-term use of COC can mask a condition of premature ovarian insufficiency. A desirable clinical tool that could distinguish true low ovarian reserve markers from COC-induced low levels during use of COC is warranted. The aim of this multicenter study including 235 COC users was to assess whether low age-adjusted AMH levels during COC use were linked to concomitant low levels of LH, FSH, estradiol and androgens – as a potential future tool to differentiate between ‘false’, COC-induced low AMH levels vs. true low AMH. Study population and methods: In total, 235 COC users from the general population aged 19–40 years were included. AMH, AFC and a reproductive hormonal profile were measured during COC intake. Age-adjusted AMH levels (Z-scores) were calculated from a comparison group of 983 non-users of COC. Differences in hormonal profile were tested between women with low versus high age-adjusted AMH-quartiles based on non-parametric Wilcoxon rank sum tests. The outcomes of interest were levels of gonadotropins, estradiol and androgens according to the four the age-adjusted AMH quartiles to find out if women with low age-adjusted AMH levels had a stronger gonadotropin suppression compared with women with higher age-adjusted AMH levels. Mean age of COC users was 30.2 years (SD 3.8), median AMH 14 pmol/l (inter-quartile range (IQR) 8.7–23)), median AFC 16 (IQR 11–25). We found no significant differences across the age-adjusted AMH quartiles in either the levels of gonadotropins, estrogens or androgens, respectively. Thus, the degree of suppression of FSH, LH, androgens and estradiol are unlikely to be a useful tool to differentiate between false low and true low ovarian reserve markers during COC use. Presently, there seems to be no alternative to withdrawal of the COC and to re-test the ovarian reserve after 2–3 months. Trial registration Trial no. NCT02785809 (www.clinicaltrials.gov)

Endometrioma-related reduction in ovarian reserve (ERROR): a prospective longitudinal study

To evaluate whether endometrioma is associated with a progressive decline in ovarian reserve, and to compare the rate of decline with natural decline in ovarian reserve. Prospective, observational study. Tertiary university hospital, endometriosis clinic. Forty women with endometrioma and 40 age-matched healthy controls. Women with endometriomas who did not need hormonal/surgical treatment at the time of recruitment and were expectantly managed. Controls were age-matched, healthy women. All participants underwent serum antimüllerian hormone (AMH) testing twice, 6months apart. Sexually active patients with endometrioma also underwent antral follicle count. Change in serum AMH levels. Median (25th-75th percentile) serum AMH level at recruitment was 2.83 (0.70-4.96) ng/mL in the endometrioma group and 4.42 (2.26-5.57) ng/mL in the control group. The median percent decline in serum AMH level was 26.4% (11.36%-55.41%) in the endometrioma group and 7.4% (-11.98%, 29.33%) in the control groups. Twenty-two women with endometrioma who had antral follicle count (AFC) had median AFC of 10 (8-12) at recruitment and 8 (6.3-10) at 6months. Women with endometrioma experience a progressive decline in serum AMH levels, which is faster than that in healthy women. NCT02438735.

Reproductive Outcomes of Segmented In Vitro Fertilization in Patients Diagnosed with Endometriomas

Study ObjectiveTo assess the impact of ovarian endometriomas on endometrial receptivity in frozen embryo transfer (FET) of segmented in vitro fertilization (IVF) cycles. DesignRetrospective, matched-control study (Canadian Task Force classification II-2). SettingA single, private assisted-reproduction technology center. PatientsThirty patients diagnosed with unilateral or bilateral endometriomas were compared with 60 patients without endometriomas in a population of 1894 patients who underwent segmented IVF treatment between September 2014 and September 2016. InterventionIntracytoplasmic sperm injection with blastocyst freeze-all and FET. Measurements and Main ResultsThe primary endpoint of the study was a viable pregnancy (>14 weeks). The mean diameter of diagnosed endometriomas was 25.7 ± 10.6 mm. The median antral follicle count was significantly lower in the endometrioma group compared with the entire study population (11.5; interquartile range [IQR], 6.0–17.0 vs 14.0; IQR, 9.0–22.0; p = .042). The median number of mature ovarian follicles (≥14 mm) per antral follicle that developed during controlled ovarian stimulation was not significantly different between the groups (11.0 [IQR, 5.8–14.3] vs 10.0 [IQR, 6.0–15.8]; p = .908); however, the median number of oocytes retrieved was lower in the endometrioma group (11.5 [IQR, 6.0–21.5] vs 13.5 [IQR, 9.0–20.8]; p = .373). The biochemical pregnancy, implantation, and ongoing pregnancy rates were not significantly different between the endometrioma and control groups. ConclusionAlthough ovarian endometriomas result in reduced ovarian reserve and oocyte retrieval, their impact on reproductive outcome is limited with FET.

Urinary triclosan concentrations and diminished ovarian reserve among women undergoing treatment in a fertility clinic

To investigate the association between urinary triclosan concentrations and antral follicle count (AFC), a well-accepted marker of ovarian reserve, among women from a fertility center. Prospective cohort study. Hospital fertility center. A total of 109 women. Urinary triclosan concentrations quantified by online solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry. AFC through transvaginal ultrasonography on the third day of an unstimulated menstrual cycle or on the third day of a progesterone withdrawal bleed. The geometric mean of the specific gravity-adjusted urinary triclosan concentrations for the 225 samples provided by the 109 women was 13.0μg/L (95% confidence interval [CI], 8.9, 19.1). Women had median (with interquartile range) AFC of 13 (8, 18). The specific gravity-adjusted urinary triclosan concentrations were inversely associated with AFC (-4%; 95% CI, -7%, -1%). Women with triclosan concentrations above the median had lower AFC compared with those whose triclosan concentrations were equal to or below the median, with an adjusted difference of -3.2 (95% CI, -3.9, -1.6) among those with a body mass index <25kg/m2 and -1.8 (95% CI, -3.2, -0.3) among those who were <35years old. Specific gravity-adjusted urinary triclosan concentrations were inversely associated with AFC in women seeking care at a fertility center. This association was modified by age and body mass index, with the younger and leaner women showing larger decreases in AFC.

EP11.03: Influence of insulin resistance level on ultrasound imaging of the ovaries in women with polycystic ovary syndrome: preliminary study

Polycystic ovary syndrome (PCOS) is a common disorder of premenopausal women characterised by hyperandrogenism and chronic anovulation. The polycystic ovary morphology (POM) is consistent with, but not essential, for the diagnosis of the syndrome. POM are defined on ultrasound by the increase ovaries volume than 10 cm3 and presence of 8 or more subcapsular follicular cysts ≤10 mm and increased ovarian stroma. Since the report by Bergen in 1980 that PCOS was associated with hyperinsulinemia, it has become clear that the syndrome has major metabolic as well as reproductive morbidities. Now it is known, that PCOS is often associated with insulin resistance (IR).The aim of this study was to assess ovarian volume, antral follicles volume and antral follicle count (AFC), depending on the IR level, in patients with PCOS. 31 patients with diagnosed PCOS and insulin resistance were included in the study. For each patient fasting glucose and fasting insulin levels were measured and IR index (HOMA IR) was calculated. For each patients AFC, ovarian and antral follicles volume were measured by three dimensional ultrasound in Vocal and 5D Follicle technique (Samsung Medison UGEO WS80A Elite). Spearman's correlation coefficient (Spearman's Rho) was calculated. Median ovarian volume was 10.7 cm3 (range 7.88–23.9 cm3), median antral follicles volume was 44 mm3 (range 17–128 mm3), while median AFC was 15 (range 8–26). Median HOMA IR was 2.02 (range 0.95–7.3). Spearman's Rho for ovarian volume and HOMA IR was 0.54, for antral follicle volume and HOMA IR was 0.75, for AFC and HOMA IR was −0.77. The association between all variables were statistically significant (P < 0.01). The study showed a strong positive correlation between IR level and ovarian volume, antral follicles volume. We have also observed a strong negative correlation between AFC and IR. The ultrasound imaging of the ovaries may be a promising tool for predicting IR level in patients with PCOS.

Is parental consanguinity associated with reduced ovarian reserve?

This observational study assessed whether women descending from consanguineous unions have reduced ovarian reserve compared with daughters of non-consanguine couples. Two hundred and ninety-one women (≤39 years) were treated in a tertiary care centre in Kuwait. Women underwent a complete anamnesis, including an evaluation of the possible presence of parental consanguinity, transvaginal ultrasound on day 2/3 of the cycle to obtain the antral follicle count (AFC), determination of serum concentrations of FSH, LH, oestradiol and in case of low ovarian reserve (AFC < 9) anti-Müllerian hormone (AMH). The median AFC of non-consanguineous daughters was 11, while daughters from consanguineous parents displayed a significantly lower median AFC (7; P < 0⋅0001). FSH was slightly higher in the consanguineous patients, while LH and oestradiol concentrations did not vary between groups. In total, 29.9% of consanguineous patients had an AFC ≥ 9, compared with 63.9% of non-consanguineous patients. Consanguineous patients did not exhibit an age-dependent AFC-decline and displayed reduced AFC and AMH concentrations. The multivariate analysis revealed female consanguinity, as well as surgical history in non-consanguineous women, as strong positive predictors of low ovarian reserve. Parental consanguinity is strongly associated with reduced ovarian reserve. Future studies should evaluate a possible association between parental consanguinity and infertility.