Ovarian Reserve Tests Research Articles

The consequences of cesarean section and vaginal delivery on ovarian reserve in infertile women

According to the data of the World Health Organization (WHO), although the rate of cesarean section is increasing worldwide, one out of every five births is performed by cesarean section. Cesarean section is life saving for both mother and baby depending on the situation. However, it also brings some complications. Its effect on fertility also raises concerns. The aim of the present study was to investigate the consequences of cesarean section on ovarian reserve. Anti-Mullerian hormone, Follicle-Stimulating Hormone, Luteinizing Hormone, Estradiol, antral follicle count, ovarian volume, and ovarian elastography results of 120 patients under the age of 30 who were not obese and were compatible with the criteria for unexplained infertility of the American Society for Reproductive Medicine were analyzed in both pre-pregnancy and postpartum period. There were 57 patients with vaginal delivery and 63 patients with cesarean section. Differences between the groups according to the mode of delivery and between the pre-pregnancy and postpartum groups were investigated. There was no statistically significant difference for the vaginal birth group in terms of AFC, AMH, FSH, LH, E2, SWE and ovarian volumes between pre-pregnancy and postpartum. In the cesarean section group, AFC, AMH and ovarian volumes were found to be significantly lower in the postpartum period than before pregnancy. As a result, cesarean delivery may have negative consequences for ovarian reserve tests.

Gonadotropin releasing hormone (GnRH) antagonist administration to decrease the risk of ovarian hyperstimulation syndrome in GNRH agonist cycles triggered with human chorionic gonadotropin.

In Gonadotropin releasing hormone(GnRH) agonist IVF, after administration of human chorionic gonadotropin(HCG) triggering, there is a risk of ovarian hyperstimulation syndrome(OHSS). Few methods exist to prevent OHSS in these cases. Therefore, we investigated the use of a GnRH antagonist to decrease the risk of OHSS, due to its ability to decrease VEGF production and function. A retrospective cohort study of 171-IVF patients at risk for developing OHSS after a GnRH agonist cycle with HCG trigger was performed from 2011 to 2019. The patient population consisted of women with an unexpected exuberant response to stimulation based on ovarian reserve testing and were triggered with hCG. Women were converted to a freeze-all cycle and received either cabergoline 0.5mg orally alone for 7days from the collection(Group 1, n = 123) or received cabergoline 0.5mg orally and ganirelix, 250 mcg SC for 7-10days(Group 2, n = 48). Group 1 had more cases of moderate and severe OHSS than group 2-(25% vs. 10% p = 0.03, and 52% vs. 25% p = 0.001 respectively). Group 1 reported more abdominal discomfort and bloating than group 2(91% vs. 65% p < 0.001) and the presence of free fluid was more frequent in group 1 than group 2(74% vs. 35% p < 0.001). Hemoconcentration and electrolyte disturbances were less severe in group 2 than in group 1 (p < 0.001 all cases). In patients at high risk for developing OHSS after hCG trigger in a GnRH agonist cycle, the addition of GnRH antagonists in the luteal phase may reduce the risk of developing moderate and severe OHSS. The GnRH antagonist likely leads to more rapid luteolysis and down regulation of VEGF production and receptor response, thereby decreasing the hallmark increased vascular permeability.

Melatonin prevents cyclophosphamide-induced primordial follicle loss by inhibiting ovarian granulosa cell apoptosis and maintaining AMH expression.

Cyclophosphaty -45mide (Cyc) chemotherapy in young female cancer patients is associated with an increased risk of premature ovarian insufficiency (POI). This study was designed to investigate the protective role of melatonin (Mel) as an adjuvant against Cyc-induced POI. Female mice received a single intraperitoneal (i.p.) dose of Cyc (75 mg/kg). Mel protection was achieved in mice after i.p. injection of melatonin (50 mg/kg) every 24 h for four consecutive days prior to chemotherapy initiation and for 14 additional days. Ovarian reserve testing, hormonal assays for follicle-stimulating hormone, luteinizing hormone, and anti-Müllerian hormone (AMH), assessment of the oxidative stress status, and measurement of the relative expression of genes in PTEN/AKT/FOXO3a and mitochondrial apoptosis pathways were performed. The results showed that treatment with 50 mg/kg Mel significantly prevented Cyc-induced over-activation of primordial follicles by maintaining the plasma level of AMH and subsequently preventing litter size reduction in mice treated with Cyc chemotherapy. Importantly, Mel treatment significantly prevented ovarian granulosa cell loss by inhibiting the mitochondrial apoptotic pathway. Identifying the protective actions of Mel against Cyc-induced primordial follicle loss has important implications for fertility maintenance in young cancer patients undergoing chemotherapy.

Age-related fertility decline and elective oocyte cryopreservation: Knowledge, attitudes and practices in a pilot study of general practitioners.

Increasing numbers of women are experiencing age-related infertility. General practitioners (GPs) are ideally placed to provide initial age-related fertility counselling and fertility specialist referral. The aim of this pilot study was to document doctors' knowledge, attitudes and practices relating to proactive fertility counselling, ovarian reserve testing and oocyte cryopreservation. Seventy-two GPs and general practice registrars were recruited through social media and completed an online survey. Knowledge gaps were shown relating toage-related female fertility decline, ovarian reserve testing and elective oocyte cryopreservation. GPs were more likely to discuss reproductive planning with women aged 35-44 years, compared with younger women. The majority of participants agreed fertility counselling should be provided by GPs; however, barriers identified include limited time, knowledge and concern for causing patient distress. Providing GPs with fertility-focused education and resources may enable sensitive, accurate and timely counselling to improve reproductive outcomes.

P-673 GnRH Agonist Early Follicular Challenge Test as a Predictor of Ovarian Response in Short Antagonist Cycles for Fertility Preservation

Abstract Study question Does the response to GnRH agonist can be used to predict ovarian function in short GnRH antagonist cycles in women undergoing oocyte cryopreservation IVF cycles? Summary answer Response to a single GnRH agonist dose at the beginning of stimulation during short antagonist cycle can predict the outcome of the fertility preservation cycle What is known already There is a need for a reliable test for ovarian reserve. Gonadotrophin agonist stimulation test (GAST) is considered a valid marker for ovarian reserve but the test was never validated for short antagonist protocol. The reported dose for this test was 0.1 mg, however, from the vast experience with GnRH agonist triggering, it is now agreed that the optimal dose for GnRH agonist flare effect is 0.2 mg. Study design, size, duration A prospective observational study of fertility preservation cycles patient in an academic hospital setting. Seventy-four Short GnRH antagonist cycles that underwent an oocyte retrieval between 1 December 2020 and 1 January 2022. Participants/materials, setting, methods On day 2, blood was sampled for basal FSH, LH, and E2 measurements, followed by a subcutaneous injection of 0.2mg GnRH agonist as part of the initial ovarian stimulation. Twelve hours later blood sampling was repeated. E2 response was used as test parameter. The major outcome was the number of cryopreserved oocytes. Main results and the role of chance Participants were divided to groups according to Day 3 E2 to Day 2 E2 response (E3/E2 ratio) to lower and upper third percentiles (&amp;lt;3.32, n = 24 and &amp;gt;5.41, n = 25). Age (32.68 vs. 32.79, p = 0.965), total gonadotropin dose injected 3216.67 vs. 2773.42 IU p = 0.16) and day 3 FSH levels (7.39 vs. 7.16, p = 0.768) were not significantly different between groups. Ovarian response as measured by E2 levels on ovulation trigger (7879.72 vs. 17572.54 pmol/ml, p = 0.001) and number of M2 oocytes retrieved were significantly different (17.92 vs. 6.24, p &amp;lt; 0.001). Linear correlation between E3/E2 ratio and number of M2 oocytes was calculated (R = 0.48, p &amp;lt; 0.001). ROC curve analysis of E3/E2 ratio for more than fifteen M2 oocytes indicate AUC value of 0.82 (cutoff value of 4.22, p &amp;lt; 0.001, 84.6% sensitivity, 70.8% specificity) and for less than five M2 oocytes AUC value of 0.84 (cutoff value of 3.34, p &amp;lt; 0.001, 76.3% sensitivity, 73.3% specificity). The results suggest that the testing response to 0.2mg GnRH agonist positively correlates with treatment outcome of the current cycle. Limitations, reasons for caution Although all patients were tested for FSH levels for ovarian reserve, they were not tested for AMH levels. Wider implications of the findings The response to single GnRH agonist dose during short antagonist cycle can be used as another biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict accurately the outcome of the specific cycle, and potentially used to adjust the treatment dose. Trial registration number NCT04973969

Are antral follicle count and serum anti-Mullerian hormone level, as reliable markers of ovarian reserve, affected by UV radiation?

Objective We aimed to assess whether ovarian reserve test including serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Mullerian hormone (AMH) levels, and antral follicle count (AFC) which are ovarian reserve markers are affected by ultraviolet (UV) radiation or not. Methods Women between the ages of 25 and 40 who served as flight crew constituted the study population in this prospective case-control study. Age-matched women having no risk factor for low ovarian reserve were selected as control group. Participants were compared according to age, duration in profession, and ovarian reserve markers. Results A total of 134 patients were included: 66 participants in study group and 68 participants in control group. Serum AMH levels and AFC were found to be significantly lower while serum FSH and E2 levels were significantly higher in the study group. This difference was found to be more significant, especially in the advanced age group. When the participants were classified according to their working time, lower ovarian reserve was observed in women with longer working time. Discussion Working for a while in the air and being closer to the sun have negative effects on ovarian functions. Preventive measures may be taken earlier in flight crew than those in the normal population to prevent the decline of ovarian functions and possible conceiving problems.

EROSS study: effect of ovarian reserve on sexual satisfaction

The population of this multicenter prospective cohort study comprised 180 women. Women who were admitted to the gynaecology department with any symptoms aged 18–40 years, whose ovarian reserve was tested, were prospectively enrolled in the study. The Female Sexual Function Index (FSFI) survey was administered to all patients. Demographic parameters (age, body mass index), ovarian reserve tests and FSFI scores were analysed. FSFI scores were compared between the patients with diminished ovarian reserve (DOR) and normal ovarian reserve (NOR). Mean women age was 30.8 ± 5.1 years. Median (with quartiles) AFC was 15 (10–20) and anti-mullerian hormone (AMH) was 2.6 (1.3–4.3) ng/mL. Mean FSFI score was 27 ± 4.7. The FSFI score was positively correlated with AMH and AFC and negatively correlated with women age. FSFI score depending on ovarian reserve were; 24.7 ± 5.2 vs. 27.4 ± 4.3, p < .01 (Respectively; DOR group (n = 43) vs. NOR group (n = 132)). Threshold value for AMH to predict sexual hypofunction was 2.32 with 67% sensitivity – 62% specificity (AUC: 0.68 p < .01) and for AFC to predict sexual hypofunction was 15 with 65% sensitivity – 60% specificity (AUC: 0.67 p < .01). In conclusion, the ovarian reserve should be considered in reproductive aged women while assessing the exact aetiology of female sexual dysfunction. IMPACT STATEMENT What is already known on this subject? Sexual dysfunction is a common disorder and negatively affects the life quality of women. Its estimated prevalence is 40% in women worldwide. There are still unknown aetiologies for sexual dysfunction. What do the results of this study add? The female sexual function index is positively correlated with ovarian reserve. Decreasing sexual functions is related to decreased ovarian reserve. Lower AMH than 2.32 ng/dl and lower antral follicle count than 15 are associated with sexual hypofunction. What are the implications of these findings for clinical practice and/or further research? This pilot study showed the relationship between sexual functions and ovarian reserve. In daily practice, the ovarian reserve should be considered in reproductive-aged women while assessing the exact aetiology of the sexual dysfunction. TRIAL REGISTRATION NUMBER NCT04776902 Clinical Trials

Increased versus standard gonadotrophin dosing in predicted poor responders of IVF: an open-label randomized controlled trial.

Does an increased dosing of FSH improve the live birth rate as compared to standard FSH dosing in expected poor responders who undergo IVF? In this trial, women with an expected poor response allocated to increased FSH dosing did not have a statistically significant increase in cumulative live births as compared to a standard FSH dose. Poor ovarian reserve leads to worse IVF outcomes owing to the low number and quality of oocytes. Clinicians often individualize the FSH dose using ovarian reserve tests, including antral follicle count (AFC), and basal plasma FSH or anti-Müllerian hormone level. However, the evidence that increased FSH dosing improves fertility outcomes in women with an expected poor response is lacking. We performed a parallel, open-label randomized controlled trial between March 2019 and October 2021 in an assisted reproduction centre. Women <43 years of age with AFC <10 referred for their first IVF cycle were randomized for increased or standard FSH dosing. In participants allocated to increased FSH dosing, women with AFC 1-6 started with 300 IU/day, while women with AFC 7-9 started with 225 IU/day. In participants allocated to the standard care, women started with 150 IU/day. The primary outcome was cumulative live birth attributable to the first IVF cycle including fresh and subsequent frozen-thawed cycles within 18 months of randomization. Live birth was defined as the delivery of one or more living infants ≥24 weeks' gestation. This trial was powered to detect an 11% difference in live birth attributable to the first IVF cycle. Outcomes were evaluated from an intention-to-treat perspective. We randomized 661 women to start FSH at increased dosing (n = 328) or standard dosing (n = 333). The primary outcome cumulative live birth occurred in 162/328 (49.4%) women in the increased group versus 141/333 (42.3%) women in the standard group [risk ratio (RR) 1.17 (95% CI, 0.99-1.38), risk difference 0.07 (95% CI, -0.005, 0.15), P = 0.070]. The live birth rate after the first embryo transfer in the increased versus standard group was 125/328 (38.1%) versus 117/333 (35.1%), respectively [RR 1.08 (95% CI, 0.83-1.33), P = 0.428]. Cumulative clinical pregnancy rates were 59.1% versus 57.1% [RR 1.04 (95% CI, 0.91-1.18), P = 0.586] with miscarriage rates of 9.8% versus 14.4% [RR 0.68 (95% CI, 0.44-1.03), P = 0.069] in the increased versus standard group, respectively. Other secondary outcomes, including biochemical pregnancy, ongoing pregnancy, multiple pregnancy and ectopic pregnancy, were not significantly different between the two groups both from the first and cumulative embryo transfer. As this study is open-label, potential selective cancelling and small dose adjustments could have influenced the results. In women with predicted poor response, we did not find evidence that increased FSH dosing improves live birth rates. A standard dose of 150 IU/day is recommended at the start of IVF in these women to reduce potential adverse effects and costs. This study was funded by the General Projects of Social Development in Shaanxi Province (No. 2022SF-565). B.W.M. is supported by NHMRC (GNT1176437). B.W.M. reports personal fees from ObsEva, and funding from Merck and Ferring outside the submitted work. Registered at Chinese clinical trial registry (www.chictr.org.cn). Registration number ChiCTR1900021944. 17 March 2019. 20 March 2019.

Evaluation of Female Fertility-AMH and Ovarian Reserve Testing.

Evaluation of the infertile female requires an understanding of ovulation and biomarkers of ovarian reserve. Antimüllerian hormone (AMH) correlates with growing follicles in a menstrual cycle. Increasingly, AMH has been used as a "fertility test." This narrative review describes how to integrate the use of AMH into diagnosis and treatment. A PubMed search was conducted to find recent literature on measurements and use of serum AMH as a marker of ovarian reserve and in treatment of infertility. Serum AMH estimates ovarian reserve, helps determine dosing in ovarian stimulation, and predicts stimulation response. As such, AMH is a good marker of oocyte quantity but does not reflect oocyte health or chances for pregnancy. Screening of AMH before fertility treatment should be used to estimate expected response and not to withhold treatment. Low AMH levels may suggest a shortened reproductive window. AMH levels must be interpreted in the context of the endogenous endocrine environment where low follicle-stimulating hormone, due to hypogonadotropic hypogonadism or hormonal contraceptive use, may lower AMH without being a true reflection of ovarian reserve. In addition, there is an inverse correlation between body mass index and AMH that does not reflect ovarian response. AMH is a useful marker of ovarian reserve in reproductive-aged women. Increased screening of noninfertile women requires a thorough knowledge of situations that may affect AMH levels. In no situation does AMH reflect oocyte health or chances for conception. Age is still the strongest driver in determining success rates with fertility treatments.

Correlation of Anti Mullerian Hormone and Antral Follicular Count in Ovarian Reserve Testing

Background: Ovarian reserve defines a woman’s reproductive ability and the number and quality of oocytes she possesses. It is a complex clinical state dependent on age, genetics, and environmental issues. It can reflect women’s endocrine function and fertility which may gradually decrease with increasing age.

Prediction of poor ovarian response during In vitro fertilization in Nigerian women: A comparison of basal antral follicle count and follicle-stimulating hormone

Background: Poor ovarian reserve has been shown to be associated with poor outcomes of in-vitro fertilization (IVF) treatment. Women who can be reliably identified as expected poor responders can be advised on chances of poor outcomes that may dissuade them from wasting resources on IVF using their own eggs; and offered donor eggs, especially in a resource-poor country like Nigeria. Many centres routinely perform basal follicle-stimulating hormone (FSH) assay before IVF; however, basal antral follicle count (AFC) has emerged as a more reliable test of ovarian reserve that can be provided at a reduced cost compared to FSH in an IVF clinic setting. The determined predictive values of basal AFC compared to FSH in Nigerian women can be used to predict poor ovarian response during IVF treatment; and also to influence local clinical practice in IVF by offering a more reliable and affordable test, thereby avoiding wastage due to duplicate and unnecessary investigations. Aim: The aim is to determine the diagnostic accuracy of basal AFC compared to basal FSH for the prediction of ovarian response during the IVF cycle in Nigerian women. Patients, Materials and Methods: This was a hospital-based prospective comparative study in two private fertility centres in Abuja. Consecutive 166 women that underwent IVF treatment cycles who met the inclusion criteria were recruited. On day 2 to day 4 of a normal cycle, FSH assay and AFC using the Broekmans’ systematic process were done. They had controlled ovarian hyperstimulation by antagonist or agonist and occasionally long protocols. The poor response was defined as <4 follicles of >17 mm on the day of human chorionic gonadotropin trigger or ≤3 oocytes retrieved. Receiver operating characteristics (ROC) analysis was done to determine the level of the area under the curve (AUC) and optimum cut-off values of FSH and AFC in predicting poor ovarian response. Results: Twenty-eight (16.9%) had poor responses. ROC analysis demonstrated that AFC had the largest (AUC = 0.707, P = 0.001) relative to FSH (AUC = 0.591, P = 0.128). The ROC analysis showed that the optimum cut-off value for the prediction of poor response for AFC was ≤10, which had a higher accuracy of 67.5%, while for FSH was ≥8.15 mIU/ml with a lower accuracy of 61.5%. They both had the same sensitivity of 60.7%; however, AFC had better specificity, negative and positive predictive value, and higher odds ratio for the prediction of poor ovarian response. The positive and negative likelihood ratios of both cut-off values suggest that they may not be useful as diagnostic tests. Conclusion: ROC analysis estimated that AFC more accurately predicts poor ovarian response by its larger and more significant AUC compared to FSH in our population of women.

Higher blastocyst implantation in frozen versus fresh embryo transfers in good prognosis patients.

There is emerging evidence that frozen embryo transfers provide a more favorable environment for implantation as compared to fresh embryo transfers. Our objective was to determine if there is a clinical benefit to frozen versus fresh blastocyst transfers in good prognosis patients. Subjects undergoing their first or second IVF/ICSI cycle <38 years of age in an OCP pretreated GnRH antagonist stimulation protocol with supernumerary embryos available for blastocyst cryopreservation were eligible for analysis. Primary transfer was exclusively blastocyst transfer. Exclusion criteria consisted of rescue ICSI, preimplantation genetic testing, donor oocytes, and surrogacy. The cohort was divided into two groups based on whether they underwent a fresh vs. frozen primary transfer. The implantation rates were compared using mixed-effects logistic regression. The clinical pregnancy and live birth rates were compared using logistic regression adjusted for number of oocytes retrieved and number of embryos transferred. All models included age, reason for treatment, and number of prior births as covariates. A total of 615 subjects were included in the study. There were no differences in the two groups with respect to age, BMI, baseline ovarian reserve testing, total gonadotropin dosage, and duration of stimulation. The implantation rate was higher in the frozen-embryo group as compared to the fresh-embryo group (59% and 48% respectively; OR 1.58; 95% CI 1.02-2.44). There was a trend towards higher clinical pregnancy and live birth rates in the frozen-embryo group. These differences persisted in the adjusted analysis. Among good prognosis patients undergoing IVF, frozen embryo transfer was associated with improved implantation rates. Consideration should be given to primary frozen blastocyst transfer in this population.

What is the threshold of mature oocytes to obtain at least one healthy transferable cleavage-stage embryo after preimplantation genetic testing for fragile X syndrome?

What are the chances of obtaining a healthy transferable cleavage-stage embryo according to the number of mature oocytes in fragile X mental retardation 1 (FMR1)-mutated or premutated females undergoing preimplantation genetic testing (PGT)? In our population, a cycle with seven or more mature oocytes has an 83% chance of obtaining one or more healthy embryos. PGT may be an option to achieve a pregnancy with a healthy baby for FMR1 mutation carriers. In addition, FMR1 premutation is associated with a higher risk of diminished ovarian reserve and premature ovarian failure. The number of metaphase II (MII) oocytes needed to allow the transfer of a healthy embryo following PGT has never been investigated. The study is a monocentric retrospective observational study carried out from January 2006 to January 2020 that is associated with a case-control study and that analyzes 38 FMR1 mutation female carriers who are candidates for PGT; 16 carried the FMR1 premutation and 22 had the full FMR1 mutation. A total of 95 controlled ovarian stimulation (COS) cycles for PGT for fragile X syndrome were analyzed, 49 in premutated patients and 46 in fully mutated women. Only patients aged ≤38 years with anti-Müllerian hormone (AMH) >1 ng/ml and antral follicle count (AFC) >10 follicles were eligible for the PGT procedure. Each COS cycle of the FMR1-PGT group was matched with the COS cycles of partners of males carrying any type of translocation (ratio 1:3). Conditional logistic regression was performed to compare the COS outcomes. We then estimated the number of mature oocytes needed to obtain at least one healthy embryo after PGT using receiver operating characteristic curve analysis. Overall, in the FMR1-PGT group, the median number of retrieved and mature oocytes per cycle was 11 (interquartile range 7-15) and 9 (6-12), respectively. The COS outcomes of FMR1 premutation or full mutation female carriers were not altered compared with the matched COS cycles in partners of males carrying a balanced translocation in their karyotype. Among the 6 (4-10) Day 3 embryos obtained in the FMR1-PGT group, a median number of 3 (1-6) embryos were morphologically eligible for biopsy, leading to 1 (1-3) healthy embryo. A cutoff value of seven MII oocytes yielded a sensitivity of 82% and a specificity of 61% of having at least one healthy embryo, whereas a cutoff value of 10 MII oocytes led to a specificity of 85% and improved positive predictive value. This study is retrospective, analyzing a limited number of cycles. Moreover, the patients who were included in a fresh PGT cycle were selected on ovarian reserve parameters and show high values in ovarian reserve tests. This information could influence our conclusion. The results relate only to the target population of this study, with a correct ovarian reserve of AMH >1 and AFC >10. However, the information provided herein extends knowledge about the current state of COS for FMR1 mutation carriers in order to provide patients with proper counseling regarding the optimal number of oocytes needed to have a chance of transferring an unaffected embryo following PGT. None. N/A.

UTILIZATION AND PERCEIVED UTILITY OF HOME FERTILITY TESTING AMONG INFERTILITY PATIENTS AT A SINGLE ACADEMIC FERTILITY CENTER

To characterize utilization and perceived utility of home fertility tests among patients presenting to an academic fertility clinic. New patients visiting the Duke Fertility Center for the diagnosis and management of infertility (based on ICD 10 codes) between December 2020 and February 2021 were eligible for study participation. Patients were sent an electronic invitation via MyChart. Exclusion criteria were: <18 years of age, patient or partner with history of surgical sterilization, or same-sex relationship. The electronic survey included questions to assess pregnancy and infertility history, experience with home fertility tests, demographic characteristics, and insurance status. Home fertility testing was defined as services that were not ordered or performed by their physician or at their physician’s office. Utility scores were assessed by asking participants how likely they were to recommend a given test for a similar patient in their situation. Survey invitations were sent to 326 individuals, 143 surveys were initiated (43.5% response rate), and 108 surveys were completed after excluding participants not meeting inclusion criteria. Utilization and perceived utility scores of home fertility testing technologies are reported in the table below.Tabled 1Home Fertility TestUtilization (N, %)Mean Utility Score (0-10)Calendar methods of ovulation prediction95 (88.0%)7.2Urinary ovulation prediction kits88 (81.5%)7.6Basal body temperature monitoring29 (26.9%)4.9Other methods of ovulation prediction (e.g. Cervical mucus)28 (25.9%)6.4Ovarian reserve testing (e.g. AMH)11 (10.2%)8.8Other hormone analysis (e.g. FSH, TSH, testosterone)15 (13.9%)8.6Home or send-out semen analysis10 (9.3%)6.4Genetic testing (e.g. 23andMe)6 (5.6%)4.7 Open table in a new tab Calendar methods of ovulation prediction and urinary ovulation prediction kits had the highest utilization among new patients presenting for the diagnosis and management of infertility. Send-out ovarian reserve testing and other hormone analysis had the highest degree of discordance between utilization and utility; these tests had the highest utility scores but fewer than 15% of participants reported use.

WHO IS FREEZING EGGS, Y’ALL? DESCRIPTIVE CHARACTERISTICS OF WOMEN UNDERGOING OOCYTE CRYOPRESERVATION AT TWO URBAN FERTILITY CLINICS IN THE SOUTH, WITH A FOCUS ON RACE/ETHNICITY

To describe trends and characteristics of oocyte cryopreservation (OC) cycles at two fertility clinics in an urban, diverse city in the South, and to compare the racial/ethnic backgrounds of women pursuing OC compared to the racial demographic of this city. Retrospective chart review of all OC cycles from 2014-2019 from two Atlanta fertility clinics (one academic and one private). Patient demographics and cycle characteristics were compared between the two clinics using chi-squared analyses for categorical variables and student’s t-tests for continuous variables. A total of 592 patients undergoing OC were included (668 total OC cycles). The majority of patients underwent 1 cycle (n=529, 89.4%), whereas 51 patients did 2 cycles (8.6%), 11 patients did 3 cycles (1.8%), and 1 patient did 5 cycles (0.2%); there was no statistical difference in the number of cycles performed per patient based on the clinic type. The total number of OC cycles increased annually at both clinics; the largest increase in OC use was seen between 2016 to 2018. Mean ovarian reserve testing parameters (AMH, antral follicle count) was similar between clinics. The average age at cryopreservation was 34.8 (private) and 34.0 (academic), with a majority of cycles occurring in women under age 35 (46.8%). The average BMI was similar between clinics (academic 26.5 kg/m2, private 25.2 kg/m2). There was an overall low utilization of frozen oocytes at both clinics; a total of 34 embryo transfer attempts using thawed autologous oocytes were performed. Atlanta is unique in its racial and ethnic diversity and has been used as a model for investigating issues surrounding access to care. Atlanta’s resident census data from 2019 is as follows: 48% black, 39% white, 5% Asian, 5% Hispanic. When compared against the background demographic of Atlanta, OC cycles at both clinics were disproportionately seen in white patients (60.3%), whereas 20.8% of OC cycles were in black patients. OC use among other ethnic groups made up a small percentage of overall cycles, including those in Asian patients (8.3%) and Hispanic patients (3.0%), however this proportion paralleled the racial demographic of Atlanta for these minority residents. When the demographics of Atlanta OC cycles were compared to nationally reported OC trends, the proportion of minorities undergoing OC in Atlanta was greater than the proportion in the national cohort. OC patient demographics were similar at each the private and academic clinics with respect to age, number of OC cycles, race/ethnicity, ovarian reserve testing and BMI. National SART data for race/ethnicity is not available for 47% of OC cycles as previously reported (1), which makes the accuracy of our data unique. Despite the increasing number of OC cycles at both clinics from 2014-2019, there was a disproportionate use of OC among Atlanta’s minority ethnic groups when compared to white patients.

FACTORS ASSOCIATED WITH LOW OR HIGH ANEUPLOIDY RATES AT THE EXTREMES OF AGE

Evaluating patients who are outliers in their rate of embryonic aneuploidy may improve our understanding of drivers of success and failure in assisted reproduction. Our study assesses young patients who produce a high percentage of aneuploid embryos and older patients with low percentages of aneuploid embryos. We aim to identify factors associated with aneuploidy rates above or below age-expected values. This study included patients who underwent controlled ovarian stimulation cycles with preimplantation genetic testing for aneuploidy (PGT-A) from September 2016-December 2019 who had ≥3 embryos biopsied. The mean aneuploidy rates (AR) and distribution among patients <35 years old (yo) and in those >40yo were determined. In patients <35yo, those with AR greater than the 90th percentile were compared to those with AR below the 90th percentile. Among patients >40yo, those with AR <10th percentile were compared to those with AR above the 10th percentile. Baseline demographics and cycle characteristics were compared among the groups using Chi-square, Student’s t-test, and multivariable logistic regression. A total of 1298 cycles in patients <35yo and 562 cycles in patients >40yo were identified and included in the study. In the <35yo cohort, the mean AR was 34.9%, and >90%ile corresponded to a rate of 66.7% and included 86 patients. The mean AR in the >40yo cohort was 33.3%. The <10%ile corresponded to a rate of 70.2% and included 74 patients. In patients <35yo, those with >90%ile AR were similar in age to patients <90%ile (32.2±3.5 vs. 31.9±2.6, p=.19) but had a significantly lower serum AMH (3.22±2.40 vs. 4.80±4.81, p=.008). BMI, BAFC, day 3 FSH, male partner age, male factor diagnosis, and gravidity were similar between the groups, while patients >90%ile had lower parity (0.11±0.36 vs. 0.27±0.66, p=.048). Cycle characteristics including stimulation protocol and duration and estradiol and progesterone at surge were similar. Patients with >90%ile AR had fewer eggs (17.4±7.4 vs. 20.5±9.9, p=.008) and mature oocytes (MII) (12.9±6.1 vs. 16.1±8.0, p<.0001) retrieved but similar MII/oocyte ratio (0.76±0.17 vs. 0.80±0.14, p=.08). Controlling for age, BMI, parity, and eggs retrieved revealed that lower AMH was significantly associated with AR >90%ile (aOR=1.23, 95% CI 1.02-1.25, p=.02). Among women >40yo, those <10%ile AR were significantly younger than those >10%ile (41.0±0.9 vs. 41.8±1.4, p<.0001). No differences were seen in any of the other variables assessed. Young patients with lower AMH levels demonstrated an increased AR, suggesting evidence of both quantitative and qualitative aging in this population. However, even those <35yo with elevated AR consisted of good prognosis patients in terms of ovarian reserve testing and cycle outcome. In patients >40yo, aneuploidy rate is related to age alone, most likely due to the high incidence of meiotic errors in older women.

Evaluation of Ovarian Reserve Tests and Age in the Prediction of Poor Ovarian Response to Controlled Ovarian Stimulation-A Real-World Data Analysis of 89,002 Patients.

AimsThis study aimed to explore the value of ovarian reserve tests (ORTs) for predicting poor ovary response (POR) and whether an age cutoff could improve this forecasting, so as to facilitate clinical decision-making for women undergoing in vitro fertilization (IVF).MethodsA retrospective cohort study was conducted on poor ovary response (POR) patients using real-world data from five reproductive centers of university-affiliated hospitals or large academic hospitals in China. A total of 89,002 women with infertility undergoing their first traditional ovarian stimulation cycle for in vitro fertilization from January 2013 to December 2019 were included. The receiver operating characteristic (ROC) curve was performed to estimate the prediction value of POR by the following ORTs: anti-Mullerian hormone (AMH), antral follicle count (AFC), basal FSH (bFSH), as well as patient age.ResultsIn this retrospective cohort, the frequency of POR in the first IVF cycle was 14.8%. Age, AFC, AMH, and bFSH were used as predicting factors for POR, of which AMH and AFC were the best indicators when using a single factor for prediction (AUC 0.862 and 0.842, respectively). The predictive values of the multivariate model included age and AMH (AUC 0.865), age and AFC (AUC 0.850), age and all three ORTs (AUC 0.873). Compared with using a single factor alone, the combinations of ORTs and female age can increase the predictive value of POR. Adding age to single AMH model improved the prediction accuracy compared with AMH alone (AUC 0.865 vs. 0.862), but the improvement was not significant. The AFC with age model significantly improved the prediction accuracy of the single AFC model (AUC 0.846 vs. 0.837). To reach 90% specificity for POR prediction, the cutoff point for age was 38 years old with a sensitivity of 40.7%, 5 for AFC with a sensitivity of 55.9%, and 1.18 ng/ml for AMH with a sensitivity of 63.3%.ConclusionAFC and AMH demonstrated a high accuracy when using ROC regression to predict POR. When testing is reliable, AMH can be used alone to forecast POR. When AFC is used as a prediction parameter, age is suggested to be considered as well. Based on the results of the cutoff threshold analysis, AFC ≤ 5 and AMH ≤ 1.18 ng/ml should be recommended to predict POR more accurately in IVF/ICSI patients.

P–697 screening for adrenocortical and thyroid peroxidase antibodies to look for underlying autoimmune etiologies in women under 35 with idiopathic diminished ovarian reserve

Abstract Study question Investigate whether screening for autoimmune etiologies is necessary in women with diminished ovarian reserve (DOR) as recommended in the evaluation of premature ovarian insufficiency (POI). Summary answer Adrenocortical antibodies (ACA) screening can be performed in the evaluation of women with idiopathic DOR, especially those with a family history of autoimmune disease. What is known already Autoimmune disorders are more common in POI than in the general population. The most important association is with autoimmune Addison’s disease. Measurement of ACA and / or 21 OH-A is recommended in every POI patients as they appear to be the marker with the highest diagnostic sensitivity for autoimmune POI. Also thyroid peroxidase autoantibodies (TPO-Ab) should be assayed due to the common association between thyroid disease and POI. The underlying etiologies of DOR in young women can be expected to be similar to the etiology of POI since they represent a continuum in the phenotypic expression of premature ovarian aging. Study design, size, duration This pilot case-control study was conducted between January 2019 and April 2020. The study group consisted of patients under the age of 35, who was diagnosed with idiopathic DOR by ovarian reserve tests during infertility work up. Controls were patients of the same age range who diagnosed with isolated tubal factor or male infertility and had normal ovarian reserve test results during infertility work up. Participants/materials, setting, methods Patients with a history of ovarian surgery, cancer, genetic or autoimmune disease were excluded. Abnormal ovarian reserve tests are defined as antral follicle count &amp;lt; 5 and AMH &amp;lt; 1.2 ng/dl corresponding to group 3 according to POSEIDON criteria. In total, 35 DOR patients and 35 controls were included in the study. ACA and TPO-Ab screening were performed in serum samples using indirect immunofluorescence method. Demographics and family history of autoimmune diseases were also evaluated. Main results and the role of chance A higher rate of ACA positivity was detected in the DOR group (34.3%) compare to controls (17.1%), although it was not found to be statistically significant (p = 0.101). The incidence of family history of autoimmune diseases in first degree relatives was positively correlated with ACA positivity (p = 0.006). In DOR group, autoimmune disease history in the family was significantly higher in ACA (+) patients compared to ACA (-) individuals (p = 0.03). TPO-Ab positivity rates were similar between 2 groups (17.1% vs%20, p = 0.75). Limitations, reasons for caution Since this is an observational study and also due to the small sample size, a causal conclusion cannot be reached. Wider implications of the findings: Even if there is no specific treatment option yet for autoimmune ovarian damage, screening for ACA or 21 OH-A may be considered in young women with idiopathic DOR based on knowledge that identification of women with autoimmune POI is clinically important for the identification of subclinical autoimmune Addison’s cases. Trial registration number non applicable

P–715 Nomogram for anti-Mullerian hormone (AMH) and follicle-stimulating hormone (FSH) in healthy infertile women according to the cause of subfertility

Abstract Study question Does the cause of subfertility affect any age-related changes observed in anti-Mullerian hormone (AMH) and follicle-stimulating hormone (FSH)? Summary answer There was no significant effect of the cause of subfertility on AMH and FSH, however women with unexplained subfertility were significantly older than controls. What is known already Ovarian reserve and consequently female fecundity irreversibly diminish with age. Subfertility is an increasingly prevalent clinical presentation with a multitude of underlying pathologies. Ovarian reserve testing, including biomarkers, plays a crucial role in the management of subfertility, particularly in predicting ovarian response during in-vitro fertilisation (IVF) treatment. For some couples, no cause can be identified and their subfertility remains unexplained thus making prognosis and treatment challenging. It has been proposed that these couples may have an ovarian reserve at the extreme lower end of normal. Study design, size, duration: This clinical audit retrospectively investigated 864 subfertile healthy women who had undergone investigation at the Royal Derby Hospital fertility clinic. Data were collected in Excel including age, serum AMH, serum FSH if available, and subfertility diagnosis. The data were collected from a pre-existing database produced by a group of researchers pre–2016 at the Royal Derby Hospital. The researchers had access to pathology lab reports and computerised hospital records containing clinical details. Participants/materials, setting, methods: Subfertility diagnoses were categorised by cause: male factor and tubal factor were combined and served as a control group, oligo-anovulatory factor, endometriosis factor, and unexplained subfertility. If multiple factors were present, oligo-anovulation was taken as the presiding factor. One-way ANOVA using Minitab was used for statistical analysis to assess the effect of cause of subfertility on age, on AMH, and on FSH. For AMH and FSH, age was incorporated as a covariate. Main results and the role of chance AMH significantly decreased with age (p &amp;lt; 0.001) and FSH significantly increased with age (p &amp;lt; 0.05). The age-related change in AMH was more pronounced than in FSH. The cause of subfertility had a statistically significant effect on age. The nature of this was that the unexplained group was significantly older than the control group and the oligo-anovulatory group (p &amp;lt; 0.001). Compared to the control group, AMH was lower in the unexplained and endometriosis groups and higher in the oligo-anovulatory group. However, after adjusting for age, the effect of cause of subfertility on AMH was not significant (R2(adj)=24.91%, p &amp;gt; 0.05). Compared to the control group, FSH was lower in the unexplained, oligo-anovulatory, and endometriosis groups. However, after adjusting for age, the effect of cause of subfertility on FSH was not significant (R2(adj)=2.05%), p &amp;gt; 0.05). Limitations, reasons for caution The previous group of researchers may have exhibited selection bias and clinical interpretation during data collection. The study population was unevenly distributed across the different causes of subfertility. Only the effect of age was accounted for despite many factors being known to affect female fertility. Wider implications of the findings: Respective nomograms for AMH and FSH according to cause of subfertility provide a reference point for clinicians, especially to predict ovarian response during IVF treatment. Although AMH was not significantly lower in the unexplained group compared to the control group, the women were significantly older implying a lower ovarian reserve. Trial registration number Not applicable

P–198 Higher rate of direct uneven cleavage (DUC) embryos in women exhibiting high ovarian response

Abstract Study question Does high ovarian response to controlled ovarian stimulation (COS) have a negative effect on oocyte quality? Summary answer High ovarian response is associated with reduced oocyte quality manifested as higher fraction of immature oocytes and higher rate of direct uneven cleavage (DUC) embryos. What is known already The literature regarding the effect of ovarian hyperstimulation on oocyte quality is limited and controversial. Results from several studies suggest that hyper response to controlled ovarian stimulation has a detrimental effect on oocyte and embryo quality, while others failed to confirm the existence of a direct toxic effect on oocyte and embryo quality. The association between temporal embryonal milestones and implantation rate has been previously demonstrated ,offering an additive tool by which oocyte quality, represented by embryo dynamics, can be evaluated. None of the aforementioned studies, however, used time lapse monitoring (TLM) system to evaluate oocyte and embryo quality. Study design, size, duration This study included a retrospective assessment of morphokinetic parameters performed by TLM from three university affiliated medical centers between January 2014 and December 2019. The developmental process and kinetics of 1863 embryos obtained from the study group, referred as the “ high ovarian response” (HOR) group, was compared to 4907 embryos from the control group - the “normal ovarian response” (NOR) group. Participants/materials, setting, methods The study included patients younger than 38 years who underwent COS with consecutive aspiration of either more than 15 oocytes (the HOR group) or 6–15 oocytes (the NOR group). A comparison was made between the groups regarding morphokinetic parameters, including the rate of embryos manifesting direct uneven cleavage (DUC) at first cleavage (DUC–1), as well as implantation and pregnancy rates. Logistic regression was conducted to assess the association between patients’ characteristics and implantation rate. Main results and the role of chance Oocyte maturation rate was significantly lower, and the DUC–1 embryos rate was significantly higher in the high ovarian response group compared to the normal ovarian response group (56.5% Vs 90.0%, p &amp;lt; 0.001 and 16.2% Vs 12.0%, p = &amp;lt;0.001; respectively). Following the exclusion of DUC–1 embryos, embryos from the HOR and the NOR groups reached the consecutive morphokinetic milestones at a similar rate and demonstrated similar implantation and clinical pregnancy rates. In a multivariate analysis preformed, only maternal age was found to be predictive for implantation. Limitations, reasons for caution The groups were not homogenous in their basic characteristics. Important information regarding the maximal dose of GT obtained, previous IVF response and ovarian reserve testing was lacking Wider implications of the findings: Higher oocyte quantity might have an effect on oocyte quality manifested as higher fraction of incompetent oocytes and higher rate of DUC–1 embryos. Once beyond the preliminary developmental stages, embryos from both groups reach the morphokinetic milestones at a similar rate and display similar implantation and pregnancy rates. Trial registration number Not applicable