Ovarian Reserve Tests Research Articles

Surgical techniques for ovarian endometriosis

Key content: All patients with ovarian endometriosis should be offered an individualised, shared decision‐making approach informed by clinical history, symptoms and fertility status. Surgical management of ovarian endometriosis can be effective in treating endometriosis‐associated pelvic pain and infertility, but there is no current evidence that surgery for ovarian endometriosis increases the success of in vitro fertilisation (IVF) treatment. Ovarian reserve tests should be considered before any ovarian surgery and can help guide the patient towards the optimal treatment. The Endometriosis Fertility Index should be incorporated into pre‐operative consultations as a validated tool that estimates the likelihood of spontaneous conception following surgical intervention. Surgeons should be trained in different surgical techniques, types of diathermy and haemostatic agents that can minimise the risk of inadvertent injury to normal ovarian cortex. Learning objectives: To facilitate informed decision‐making regarding the treatment of ovarian endometriosis. To gain insight into the possible surgical techniques available to manage ovarian endometriosis and the evidence behind them. To understand the impact of each technique on endometriosis‐associated pain, fertility outcomes and recurrence rates. Ethical considerations: Should fertility preservation be offered to all women of reproductive age with fertility aspirations and a diagnosis of endometriomas? Should integrated care boards (ICBs) devise specific criteria to offer funding for fertility preservation as an option before surgery for ovarian endometriosis?

Dehydroepiandrosterone supplementation improves diminished ovarian reserve clinical and in silico studies

The therapeutic role of dehydroepiandrosterone (DHEA) supplementation among infertile women with diminished ovarian reserve (DOR) is still unclear. Objective evaluation of different ovarian reserve tests (ORTs) such as serum anti-Mullerian hormone (AMH), serum follicle stimulating hormone (FSH), and antral follicle count (AFC) in women with diminished ovarian reserve is required. This is a cross-sectional study performed in Mosul city, Iraq, with 122 infertile women who had been diagnosed with DOR. The enrolled women’s age ranged from 18 to 45 years old (mean age of 29.46 ± 2.64 years). The ages of the enrolled women ranged from 18 to 45 years (mean age of 29.46 ± 2.64 years). To assess the influence of DHEA supplements (25 mg, three times/day for 12 weeks) across different age groups, the women were initially divided into three groups (18 to 27 years old, 28 to 37 years old, and ≥ 38 years old). Significant differences were noticed in AMH, FSH, level and AFC before and after DHEA supplementation. (AMH: 0.64 ± 0.82 vs. 1.98 ± 1.32, AFC: 2.86 ± 0.64 vs. 5.82 ± 2.42, and FSH: 12.44 ± 3.85 vs. 8.12 ± 4.64), statistically obvious significant differences regarding the results of AMH (p < 0.001), AFC (p < 0.001), and FSH (p < 0.001). DHEA supplementations improved the ovarian reserve of the enrolled women, which was more evident in younger women (<38 years old) than older women (≥38 years old). The AMH serum levels and AFC value can be considered the best, most reliable and significant OR parameters. However, large randomized multicenter studies are required to confirm the available results and data.

Molecular Factors Predicting Ovarian Chemotoxicity in Fertile Women: A Systematic Review.

Background: Recent advances in cancer diagnosis and treatment have significantly improved survival rates among women of reproductive age facing cancer. However, the potential iatrogenic loss of fertility caused by chemotherapeutic agents underscores the need to understand and predict chemotherapy-induced ovarian damage. This study addresses this gap by systematically reviewing the literature to investigate genetic markers associated with chemotherapy-induced ovarian failure (CIOF). Objective: The primary objective is to identify genetic markers linked to CIOF, contributing to a comprehensive understanding of the factors influencing fertility preservation in female cancer survivors. Methods: A systematic review was conducted using PubMed, EMBASE, Web of Science, Scopus, and OVID electronic databases from inception through December 2023. Studies were included if they featured genomic assessments of genes or polymorphisms related to CIOF in women with histologically confirmed tumors. Exclusion criteria comprised in vitro and animal studies, reviews, and pilot studies. The resulting four human-based studies were scrutinized for insights into genetic influences on CIOF. Results: Of the 5179 articles initially identified, four studies met the inclusion criteria, focusing on alkylating agents, particularly cyclophosphamide, and anthracyclines. Su et al. explored CYP3A41B variants, revealing modified associations with CIOF based on age. Charo et al. investigated GSTA1 and CYP2C19 polymorphisms, emphasizing the need to consider age and tamoxifen therapy in assessing associations. Oktay et al. delved into the impact of BRCA mutations on anti-Müllerian hormone (AMH) levels post-chemotherapy, supported by in vitro assays. Van der Perk et al. focused on childhood cancer survivors and revealed significant associations of CYP3A43 and CYP2B6*2 SNPs with AMH levels. Conclusions: This systematic review analyzes evidence regarding genetic markers influencing CIOF, emphasizing the complex interplay of age, specific genetic variants, and chemotherapy regimens. The findings underscore the need for a personalized approach in assessing CIOF risk, integrating genetic markers with traditional ovarian reserve testing. The implications of this study extend to potential advancements in fertility preservation strategies, offering clinicians a comprehensive baseline assessment for tailored interventions based on each patient's unique genetic profile. Further research is essential to validate these findings and establish a robust framework for integrating genetic markers into clinical practice.

Update on Assessment of Ovarian Reserve Testing.

Women are increasingly postponing pregnancy to achieve specific goals, and as it is known, the ovarian reserve (OR) declines with age, especially after the 30s. Assessing the OR helps in managing the care of women seeking pregnancy. Several OR tests (ORTs) have been advocated for assessing OR. This review aims to discuss the different ORTs and the consequences of their use. For each topic, a PubMed search was conducted using MeSH terms. The following terms were used: ovarian reserve, ovarian reserve tests, anti-Müllerian hormone, antral follicle count, and diminished ovarian reserve. The search for further references was complemented by manual search, review, synthesis, and summarization of retrieved articles. In this review, we clarified the concept of OR and the different ORTs and provided a guide for the ultrasound to assess OR. In addition, the clinical value of ORTs was highlighted to explain the implications of the results of these tests and how they can aid in patient counseling. A number of ORTs are available to the clinician. Anti-Müllerian hormone and antral follicle count are the most valuable, but as with all ORTs, they are best used as screening, not diagnostic tests for OR. Screening for OR is most helpful when applied to specific groups.

Correlation of Follicle-stimulating Hormone, Anti-Mullerian Hormone, and Antral Follicle Count with Age in Ovarian Reserve Testing.

Ovarian reserve and hence ovarian response has a key role in assisted reproductive technology and predicting response to gonadotrophins in controlled ovarian hyperstimulation. Various tools, namely follicle-stimulating hormone (FSH), anti-Mullerian hormone (AMH), antral follicle count (AFC), estradiol, etc., have been studied to discover the best determinant of ovarian reserve. The aim of our study is to correlate different reproductive hormones with age of women to estimate ovarian reserve and to evaluate reliable marker for aiding infertility treatment. It is an observational study performed for 6 months, with 88 women (aged 21-39 years) having a complaint of infertility, enrolled in the infertility clinic of a tertiary care hospital. Baseline scan for AFC was done for every patient and their blood was sent for serum FSH, AMH analysis. Statistical procedures were employed to determine the association between age and reproductive hormones (i.e. FSH and AMH) as independent variables and AFC as a dependent variable. A strong negative correlation was noted between FSH and AMH and between age and AMH (r = -0.492 and r = -0.498, respectively). A weak negative correlation was seen between AMH and total AFC (r = -0.241). A moderate positive correlation was seen on comparing age and FSH (r = 0.331), whereas no correlation was seen on comparing FSH with AFC and AMH with AFC. The presence of ovarian cyst did not affect AMH or AFC but reduced FSH values significantly. In the quest to determine a panel test for ovarian reserve testing we conclude, FSH and AFC should perform fairly in poor resource and low socioeconomic setting. The combination of FSH with AMH and AFC might aid in better determination of ovarian reserve in tertiary centers with available resources.

Impact of uterine artery embolization on ovarian function and pregnancy outcome after uterine-fibroids treatment: A prospective study.

Uterine fibroids are benign tumors that originate from smooth muscle cells of the uterus. It is the most common gynecological disorder, affecting up to 80% of women of reproductive age. Uterine fibroids can cause various symptoms such as abnormal uterine bleeding, pelvic pain, infertility, and pregnancy complications. The treatment options for uterine fibroids include medical therapy, surgical intervention, and minimally invasive techniques. To compare ovarian function of women with uterine fibroids who did or did not undergo uterine artery embolization (UAE). This prospective cohort study enrolled 87 women with symptomatic uterine fibroids who underwent UAE, and 87 women with the same symptoms who did not undergo UAE but received conservative management or other treatments. The two groups were matched for age, body mass index, parity, and baseline characteristics of uterine fibroids. The primary outcome was ovarian function that was evaluated by serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH), as well as ovarian reserve tests, such as antral follicle count (AFC) and ovarian volume (OV). The secondary outcome was fertility that was evaluated based on the menstrual cycle, ovulation, conception, pregnancy, and delivery. The participants were followed-up for 36 months and assessed at 1, 3, 6, 12, 24, and 36 months after treatment. The study found that the most common minor complication of UAE was postembolization syndrome in 73.6% of women, resolving within a week. No significant differences were observed between the UAE group and the control group in serum levels of reproductive hormones (FSH, LH, E2, AMH) and ovarian reserve indicators (AFC, OV) at any point up to 36 months post-treatment. Additionally, there were no significant differences in conception, pregnancy, or delivery rates, with the average time to conception and gestational age at delivery being similar between the two groups. Birth weights were also comparable. Finally, there was no significant correlation between ovarian function, fertility indicators, and the type or amount of embolic agent used or the change in fibroids post-treatment. UAE resulted in significantly positive pregnancy outcomes, no adverse events post-treatment, and is a safe and effective treatment for uterine fibroids that preserves ovarian function and fertility.

Effect of intraovarian platelet-rich plasma injection on IVF outcomes in women with poor ovarian response: the PROVA randomized controlled trial.

Does intraovarian platelet-rich plasma (PRP) injection increase the number of mature oocytes obtained after controlled ovarian stimulation (COS) in young women with poor ovarian response (POR) undergoing IVF? Intraovarian PRP injection procedure does not improve mature oocyte yield after COS in women less than 38 years old with an established IVF history of POR. POR is frequently encountered among the infertile population and the number of women seeking infertility treatment related to POR is increasing. Effective treatment options for this patient population to conceive with autologous oocytes are lacking. Case series and cohort studies suggest that intraovarian PRP injection may improve follicular recruitment in women with premature ovarian insufficiency (POI) and POR, yet robust randomized studies have not been performed to date to determine the clinical utility of this intervention. This was a multi-center randomized controlled trial (RCT) conducted at university-affiliated reproductive centers in the USA and Turkey, between January 2020 and November 2022. Patients who met inclusion criteria (<38 years old, two or more prior cycles with <3 oocytes retrieved; and without single gene disorders, prior ovarian surgery, endometriomas, BMI >35 kg/m2, or severe male factor infertility) were randomized to either the PRP or control group. Patients in both groups subsequently underwent COS, oocyte retrieval, ICSI, preimplantation genetic testing for aneuploidy (PGT-A), and single euploid embryo transfer. Number of metaphase II (MII) oocytes obtained was the primary outcome. Secondary outcomes included ovarian reserve tests (antral follicle count [AFC] and anti-Müllerian hormone [AMH]), blastocyst and euploid blastocyst yields, and sustained implantation. The study was powered to detect a difference of one mature oocyte obtained at oocyte retrieval. In total, 83 patients met inclusion criteria and were randomized to receive autologous intraovarian PRP injection (n = 41) or to no intervention (n = 42). No significant differences were observed in number of MII oocytes retrieved per cycle (2.8 ± 2.4 vs 3.1 ± 3.3 in PRP vs control, respectively; P = 0.9), blastocysts (1.0 ± 1.3 vs 1.3 ± 2.1, P = 0.8), or euploid blastocysts (0.8 ± 1.1 vs 0.9 ± 1.6; P = 0.5). Similarly, no differences were observed in the likelihood of obtaining at least one euploid blastocyst (45% vs 37%, P = 0.4; relative risk [RR], 95% CI = 0.9, 0.6-1.2) or the rate of sustained implantation (31% vs 29%, P = 0.9; RR 1.0, 0.7-1.3). Posttreatment AFC (7.9 ± 4.5 vs 6.8 ± 4.8, P = 0.3) and AMH (0.99 ± 0.98 vs 0.7 ± 0.6, P = 0.2) were also not different between the groups. Results from this RCT may not be generalizable to other PRP preparations owing to heterogeneity and lack of standardization. The control groups did not undergo a sham ovarian injection, which would have been relevant had the results shown benefit of PRP injection. Only patients with POR were included in this study, and these results may not be generalizable to more severe diminution of ovarian reserve, as seen with POI. The intraovarian PRP injection procedure does not improve mature oocyte yield or other parameters of IVF outcome in women less than 38 years old with an established IVF history of POR. The results from this study do not support the use of intraovarian PRP injection in this population. Departmental funds were used and no external funding was requested for this study. ES is a consultant for and receives grant funding from the Foundation for Embryonic Competence. All other authors have no conflict of interest to declare. Clinicaltrials.gov Registry Identifier: NCT04163640. 15 November 2019. 24 February 2020.

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

'Age specific variations in ovarian reserves in healthy fertile and infertile women: A cross sectional study.

Ovarian reserve tests are valuable for evaluation of female fertility, and to formulate appropriate treatment strategies for infertile women. Antral follicle count (AFC) and Anti-Mullerian hormone (AMH) are most reliable markers of ovarian reserve which are related inversely to age. There are many factors that affect ovarian reserve like race, ethnicity, fertility status, BMI or any chronic illness. We conducted this study to find outage specific nomograms for AMH and AFC among fertile and Infertile Indian women, to find out any variations between fertile and Infertile ovarian reserves at various centiles, to define the age cut-off of decline in AMH and AFC among fertile and Infertile Indian women and to find correlation between AMH and AFC. It was a prospective cross sectional single centre study conducted at a tertiary hospital of northern India from March 2017 to February 2022. Fertile healthy women were recruited from family planning clinic, oocyte donors and subfertile women from Gynaecology and ART clinic. AMH was done using ELISA, Beckmann Coulter Gen II assay and AFC was done using TVS with high frequency probe (9.0 MHZ, Voluson,S-6, GE Healthcare, USA) by trained personnel. R Statistical Programming Language was used for statistical modelling and visualization. Age-specific AFC centile chart and AMH centile chart were generated using GAMLSS (Generalized Additive Models for Location Scale and Shape) package available in R Statistical Computing Language. A Non-linear decline in ovarian reserves among fertile, while linear among infertile women was seen. Centiles defined for both groups with a faster decline in infertile women. Age cut off for decline in AMH and AFC in fertile women approximately 31 years using ROC analysis and Age cut off for decline in AMH and AFC in infertile women is approximately 34 years. There seems to be a good correlation between AFC and AMH. We need to counsel women to consider child bearing well before ovarian reserves decline (31-34 years).

Evaluation of ovarian reserve in unexplained ınfertile cases: a case-controlled study

BackgroundThe aim of this study was to evaluate the effectiveness of current ovarian reserve tests in unexplained infertile cases.Material and methodsThis case–control study was conducted on 70 unexplained infertile women who were included in a tertiary university hospital. Both groups of basal FSH, estradiol, antimullerian hormone (AMH), inhibin B, ovarian volume, total antral follicle count (AFC), ovarian volume, and ovarian stromal blood flow (peak systolic velocity (PSV), S/D (systole and diastole ratio), resistance index (RI), and pulsatility index (PI)) values were compared.ResultsThe mean AMH, inhibin B, PSV, and stromal blood flow values of the control group patients were higher than those in the unexplained infertility group. However, the values of the means of RI and PI of the cases in the control group were lower than those in the infertility group. When PI’s value was ≥ 2.00, its sensitivity was 65.7%, and its specificity was 64.3%. In the case of the RI, its value was ≥ 0.745, its sensitivity was 65.7%, and its specificity was 62.9%. In order to show ovarian reserve in unexplained infertile cases, the sensitivity values can be sorted from high to low as follows: PI > RI > estradiol > FSH > ovarian volume > AFC > inhibin B > stromal blood flow > PSV > S/D.ConclusionIn the unexplained infertile patient group with normal ovarian reserve test results, basal estradiol, decreased PI, and RI values may be used as good ovarian reserve predictors.

Anti-Müllerian hormone beyond an ovarian reserve marker: the relationship with the physiology and pathology in the life-long follicle development.

Anti-Müllerian hormone (AMH), an indirect indicator of the number of remaining follicles, is clinically used as a test for ovarian reserve. Typically, a decline suggests a decrease in the number of remaining follicles in relation to ovarian toxicity caused by interventions, which may implicate fertility. In contrast, serum AMH levels are elevated in patients with polycystic ovary syndrome. AMH is produced primarily in the granulosa cells of the preantral and small antral follicles. Thus it varies in association with folliculogenesis and the establishment and shrinking of the follicle cohort. Ovarian activity during the female half-life, from the embryonic period to menopause, is based on folliculogenesis and maintenance of the follicle cohort, which is influenced by developmental processes, life events, and interventions. AMH trends over a woman's lifetime are associated with in vivo follicular cohort transitions that cannot be observed directly.

The effect of letrozole as an adjunct in GnRH-antagonist protocol on IVF/ICSI outcome in women with endometriosis: a randomized clinical trial

BackgroundTo evaluate the effect of adding letrozole to the antagonist ovarian stimulation protocol (COS) on in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcome in endometriosis patients.MethodsThis randomized clinical trial was carried out in the department of infertility treatment at Arash Women’s Hospital from May 2019 to May 2021. The eligible women with normal ovarian reserve tests who had endometriosis diagnosis and underwent IVF/ICSI cycles were evaluated. A flexible regimen of GnRH-antagonist protocol was used for COS. In the experimental (n = 34), the patients received 5 mg letrozole daily for the first 5 days in combination with 150 IU of recombinant follicle-stimulating hormone (rFSH). In the control group (n = 30), the patients received only the same dose of rFSH. The treatment cycle was compared between groups.ResultsAnalysis of demographic characteristics, severity of endometriosis, and baseline hormonal tests of patients showed that the two groups were similar and comparable. The means of total used gonadotropins ampoules and serum E2 level on oocyte trigger day in the letrozole group were significantly lower than those of in the control group (P = 0.03 and P = 0.004, respectively). No statistically significant difference in terms of the total number of retrieved and MII oocytes as well as the total numbers of obtained and top-quality embryos, and cryopreserved embryos was found.ConclusionThe co-treatment of letrozole with gonadotropins during the antagonist protocol was associated with a reduction in the total dose of gonadotropins, although it had no effect on the oocyte or embryo yield in patients with endometriosis.Trial registrationThe study was registered in the Iranian Registry of Clinical Trials on 2018 -07-13 (IRCT20150310021420N4 at www.irct.ir, registered while recruiting).

Luteinizing Hormone/Human Chorionic Gonadotropin Receptor N312S Single-Nucleotide Polymorphism and Its Impact on Clinical and Reproductive Outcomes in Assisted Reproductive Technology: A Prospective Cohort Study.

Objective The aim of this study was to determine the genotypic distribution of luteinizing hormone/human chorionic gonadotropin receptor (LHCGR) N312S single-nucleotide polymorphism (SNP) and to investigate its impact on clinical and reproductive outcomes in infertile Indian women undergoing assisted reproductive technology (ART). Study design and settings This was a prospective cohort study conducted at a tertiary care university hospital. Subjects and methods Infertile women aged between 21 and 40 years undergoing ART with an antagonist protocol were enrolled in this study. A 2-ml sample of peripheral venous blood was collected from each woman and genotyped for the LHCGR N312S SNP. Participants were divided into three groups based on their SNP: NN, NS, and SS. All subjects underwent controlled ovarian hyperstimulation (COH) through a gonadotropin-releasing hormone (GnRH) antagonist protocol and intracytoplasmic sperm injection (ICSI). Of the 140 women recruited based on selection criteria, 128 underwent embryo transfer. We compared the genotypic distribution of the LHCGR N312S SNP, baseline characteristics, clinical outcomes, and reproductive outcomes in ART among the three groups. Data were analyzed using IBM SPSS Statistics for Windows, Version 29 (Released 2022; IBM Corp., Armonk, New York, United States). The chi-square test and Fisher-Irwin test were employed to evaluate significant differences among the qualitative categorical variables. A p-value of less than 0.05 was considered statistically significant. Results Among the test subjects, 19.3% were homozygous for the LHCGR N312 SNP (NN group), 38.6% were heterozygous (NS group), and 42.1% were homozygous for the LHCGR S312 SNP (SS group). Baseline characteristics were similar among the three groups. In terms of ovarian reserve tests, significantly lower anti-Müllerian hormone (AMH) levels were observed in the SS group compared to the NS and NN groups (2.8 ± 2.1 vs. 3.2 ± 2.5 vs. 4.3 ± 3.3; p=0.03). No significant differences were observed in COH outcomes such as duration of stimulation, total gonadotropin requirement, oocyte yield, or the number of good-quality embryos among the three groups. The cumulative pregnancy rate (82.9% vs. 50.0% vs. 38.2%, p=0.0005), cumulative clinical pregnancy rate (78.8% vs. 44.7% vs. 34.5%, p = 0.0005), and cumulative live birth rate (50.0% vs. 20.2% vs. 20.0%, p=0.005) were significantly higher in the NN group than in the NS and SS groups. Conclusion The study's findings suggest that LHCGR N312 may help predict reproductive outcomes in ART, which may aid in providing better counseling to infertile couples. We need more studies on individualized/personalized COH using pharmacogenomics for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) supplementation based on combined FSH and LH receptor SNP and to assess their effects on ART outcomes.

Perceived and Objective Fertility Risk Among Female Survivors of Adolescent and Young Adult Cancer

Fertility is important to many survivors of adolescent and young adult (AYA) cancer, yet data on this population's fertility perceptions and their alignment with objective infertility risk are scant. To assess whether estimated treatment gonadotoxicity and posttreatment menstrual pattern are associated with higher infertility risk perception. This retrospective cohort study included female young adult survivors of cancer diagnosed between ages 15 and 39 years were recruited between March 25, 2015, and September 24, 2018, from 2 state cancer registries, social media, and clinician referrals to participate in a study of posttreatment ovarian function. Data analysis occurred between March 1 and September 1, 2022. Participants reported their menstrual pattern. Estimated treatment gonadotoxicity was ascertained through medical record review. Participants reported infertility risk perception and were categorized as increased risk (feeling less fertile or unable to become pregnant) or no increased risk (feeling more or as fertile) compared with female individuals their age. Objective infertility risk was determined by estimated gonadotoxicity, menstrual pattern, and ovarian reserve testing of self-collected dried blood spots. Multivariable logistic regression identified factors associated with perceived infertility and underestimation or overestimation of infertility risk. This study included 785 female participants with a mean (SD) age of 33.2 (4.8) years at enrollment and 25.9 (5.7) years at diagnosis. Most participants self-identified their race and ethnicity as White (585 [74.5%]) and non-Hispanic (628 [78.7%]). Most participants (483 [61.5%]) perceived a higher risk of infertility compared with female participants their age. Prior exposure to moderate- or high-gonadotoxicity treatments was associated with higher odds of perceiving increased infertility risk compared with exposure to low-gonadotoxicity treatments (adjusted odds ratio [AOR], 2.73 [95% CI, 1.87-3.97] and 15.39 [95% CI, 5.52-42.96], respectively). Amenorrhea and irregular cycles were associated with higher odds of perceiving increased infertility risk (AOR, 3.98 [95% CI, 2.13-7.41] and 1.69 [95% CI, 1.19-2.40], respectively). Perceived infertility risk had minimal agreement with objective risk (κ = 0.19). Multiparity (AOR, 4.17 [95% CI, 2.61-6.64]) was associated with increased odds of underestimation, while older age (AOR, 0.94 [95% CI, 0.89-0.98]), endocrine comorbidity (AOR, 0.35 [95% CI, 0.18-0.69]), and prior infertility (AOR, 0.16 [95% CI, 0.07-0.38]) were associated with lower odds of underestimation. Multiparity (AOR, 0.48 [95% CI, 0.27-0.86]), breast cancer (AOR, 0.38 [95% CI, 0.20-0.73]), and skin cancer (AOR, 0.24 [95% CI, 0.11-0.51]) were associated with lower odds of overestimation. In this cohort study, survivors of AYA cancer had high rates of perceiving increased infertility risk but frequently overestimated or underestimated their risk. These findings suggest that counseling on infertility risk throughout survivorship may reduce misalignment between perceptions and actual risk, decrease fertility-related psychological distress, and inform family planning decisions.

Age-related change in AMH in women seeking fertility – a hospital-based study across India

Objective The emergence of Anti-Mullerian Hormone (AMH) as a reliable biomarker for evaluating ovarian reserve in females indirectly predicting fertility potentials. Related studies contribute to the importance of AMH level tests for ovarian reserve, but limited studies are there to contribute to the geographical distribution of AMH levels in PAN India. This study assessed the age-related change in AMH in the Indian scenario. Design and Setting This is a retrospective hospital-based study. Patient(s) The study included 1,71,595 Indian infertile females visiting different clinics of Indira IVF Hospital Private Limited during the year August 2015 –August 2022 in the age group of 21-50 years. Intervention(s) NA Result(s) The average AMH included in the study was 2.66±1.89 ng/mL. The maximum number of females younger than 30 years had AMH levels of 3.86 ±3.12 ng/mL, and those in older age (31-50 years) group had AMH levels of 2.86 ± 2.7ng/mL. The analysis revealed that AMH levels were negatively correlated with age in all four zones (South, West, East, and North). The correlation coefficients ranged from -0.394 to -0.423, indicating a moderate negative relationship between age and AMH levels. The median AMH levels in the different zones ranged from 1.76 to 2.24 ng/dl. In contrast, the mean AMH levels varied between 2.54±2.75 and 3.03±2.94 ng/dl, indicating some variability in the distribution of AMH levels across the regions. Conclusion(s) The result shows a moderate correlation between females and AMH where r = -0.418 across India. The AMH value shows a sharp fall around 27 years of age.

Disease-Free Survival Does Not Differ According to Fertility Preservation Technique for Young Women With Breast Cancer

ABSTRACT Approximately 5% of breast cancer cases occur in women younger than 40 years, and the 5-year overall survival for women between the ages of 15 and 44 years is 90%. As the childbearing age increases, so too does the proportion of women who wish to achieve pregnancy after breast cancer. The conception rate among these women is 40% lower than the general population, as a result of advanced age and the gonadal toxicity of chemotherapy. Fertility preservation (FP) techniques enable young patients to freeze gametes before treatment; however, the most recommended method of FP is oocyte or embryo vitrification after controlled ovarian hyperstimulation (COH), which has limited safety data in breast cancer patients. This retrospective cohort study aimed to evaluate disease-free survival (DFS) in a large cohort of women with breast cancer who underwent FP techniques with or without COH. Patients with breast cancer between 18 and 43 years old referred for FP to 2 university hospitals between July 2013 and July 2019 were included. Women not included in the FP program after oncofertility counseling, those with stage 4 disease at diagnosis or history of other invasive cancer, or those with gonadotoxic treatment have been excluded. Patients were split into 2 groups, with the STIM group receiving at least 1 COH protocol using a gonadotropin-releasing hormone antagonist with or without an aromatase inhibitor and the no STIM group not undergoing ovarian stimulation. Patient characteristics, obstetric variables, and oncology characteristics were collected from medical records. Disease-free survival and overall survival were estimated using Kaplan-Meier plots and compared between the 2 groups by log-rank test. A total of 740 women (76.7%) who attended oncofertility consultations for breast cancer were included. Of these, 328 (44.3%) underwent at least 1 ovarian stimulation cycle, and 412 (55.7%) had an FP technique without exogenous FSH administration. The STIM group was significantly older and had lower values in ovarian reserve tests, and more women in the no STIM group underwent a mastectomy and neoadjuvant chemotherapy. The proportion of patients with hormone receptor-positive tumors was equal in both groups. Letrozole was coadministered with exogenous gonadotropin in 39.3% of women in the STIM group (Let-COH). Overall, 16.8% of patients had a tumor still present on oocyte retrieval after COH, of which 55% received a Let-COH protocol. Follow-up data were available for 80.9% (559/740) of patients. Cancer recurrence was documented in 87 patients (27 in STIM, 60 in no STIM), and DFS was not statistically different between the groups (log-rank test P = 0.09). Neither difference in DFS nor overall survival was observed in the Let-COH group compared with those undergoing COH after breast surgery. Kaplan-Meier estimates of overall survival at 4 years were 97.6% in the STIM and 93.6% in the no STIM groups, and after adjusting for prognostic parameters, the risk of death remained significantly lower in the STIM group (hazards ratio, 0.55 [0.35–0.85]). The results of this large retrospective cohort study demonstrate that the use of COH for FP patients with breast cancer before or after breast tumor surgery is safe; however, a longer duration of follow-up will provide a more definite safety profile.

RegEMR: a natural language processing system to automatically identify premature ovarian decline from Chinese electronic medical records

BackgroundThe ovarian reserve is a reservoir for reproductive potential. In clinical practice, early detection and treatment of premature ovarian decline characterized by abnormal ovarian reserve tests is regarded as a critical measure to prevent infertility. However, the relevant data are typically stored in an unstructured format in a hospital’s electronic medical record (EMR) system, and their retrieval requires tedious manual abstraction by domain experts. Computational tools are therefore needed to reduce the workload.MethodsWe presented RegEMR, an artificial intelligence tool composed of a rule-based natural language processing (NLP) extractor and a knowledge-based disease scoring model, to automatize the screening procedure of premature ovarian decline using Chinese reproductive EMRs. We used regular expressions (REs) as a text mining method and explored whether REs automatically synthesized by the genetic programming-based online platform RegexGenerator + + could be as effective as manually formulated REs. We also investigated how the representativeness of the learning corpus affected the performance of machine-generated REs. Additionally, we translated the clinical diagnostic criteria into a programmable disease diagnostic model for disease scoring and risk stratification. Four hundred outpatient medical records were collected from a Chinese fertility center. Manual review served as the gold standard, and fivefold cross-validation was used for evaluation.ResultsThe overall F-score of manually built REs was 0.9444 (95% CI 0.9373 to 0.9515), with no significant difference (paired t test p > 0.05) compared with machine-generated REs that could be affected by training set sizes and annotation portions. The extractor performed effectively in automatically tracing the dynamic changes in hormone levels (F-score 0.9518–0.9884) and ultrasonographic measures (F-score 0.9472–0.9822). Applying the extracted information to the proposed diagnostic model, the program obtained an accuracy of 0.98 and a sensitivity of 0.93 in risk screening. For each specific disease, the automatic diagnosis in 76% of patients was consistent with that of the clinical diagnosis, and the kappa coefficient was 0.63.ConclusionA Chinese NLP system named RegEMR was developed to automatically identify high risk of early ovarian aging and diagnose related diseases from Chinese reproductive EMRs. We hope that this system can aid EMR-based data collection and clinical decision support in fertility centers.

O-065 A multi-center randomized controlled trial of intraovarian injection of platelet rich plasma for women with poor ovarian response

Abstract Study question Does intraovarian injection of autologous platelet-rich plasma (PRP) improve oocyte yield in young patients with poor ovarian response (POR)? Summary answer Intra-ovarian PRP injection did not result in increased number of oocytes retrieved or improvement of any other relevant measured outcomes. What is known already POR is one of the major hurdles to overcome in patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Several methods have recently emerged to attempt follicular reactivation in these patients with a poor prognosis. One of them, the intra-ovarian injection of autologous PRP, demonstrated promising results in retrospective and prospective cohort studies. Study design, size, duration This was a multi-center, randomized controlled trial (RCT) to evaluate the efficacy of PRP in improving IVF outcomes in women with POR. Patients who met inclusion criteria (&amp;lt;38 years, two or more prior cycles with &amp;lt; 3 oocytes retrieved, and without single gene disorders, prior ovarian surgery, endometriomas, BMI &amp;gt;35, or severe male factor infertility) were randomized to either receive an autologous intra-ovarian PRP injection (PRP group) or no intervention (control group) prior to COH. Participants/materials, setting, methods A total of 83 patients were randomized to PRP group (n = 41) or control group (n = 42). After treatment, patients underwent COH, oocyte retrieval, intracytoplasmic sperm injection (ICSI), preimplantation genetic testing for aneuploidy (PGT-A), and single frozen euploid embryo transfer. Number of MII oocytes obtained was the primary outcome. Secondary outcomes included ovarian reserve tests (antral follicle count [AFC] and anti-Mullerian hormone [AMH]), blastocyst and euploid blastocyst yields, and sustained implantation. Main results and the role of chance No significant differences were observed in number of MII oocytes retrieved (3.1 ± 3.3 vs 2.8 ± 2.4 in PRP vs control, respectively; p = 0.9), blastocysts (1.3 ± 2.1 vs 1.0 ± 1.3, p = 0.8), or euploid blastocysts (0.9 ± 1.6 vs 0.8 ± 1.1; p = 0.5) per cycle. Similarly, no differences were observed in the likelihood of obtaining at least one euploid blastocyst (37 vs 45%, p = 0.4; relative risk [RR], 95% confidence interval [CI] 0.9, 0.6-1.2) or the rate of sustained implantation (29 vs 31%, p = 0.9; RR 1.0, 0.7-1.3). Pre- and post-treatment AFC in both groups (PRP: from 5.2 ± 3.2 to 7.9 ± 4.5, p &amp;lt; 0.0001; control: from 5.6 ± 3.3 to 6.8 ± 4.8, p = 0.02) were statistically significantly different, whereas AMH was different in the PRP group only (PRP: 0.73 ± 0.46 to 0.99 ± 0.98, p = 0.02; control: 0.70 ± 0.59 to 0.73 ± 0.57, p = 0.59). Limitations, reasons for caution Oocyte retrieval took place the cycle immediately following treatment; therefore, we could not evaluate long-term effects of PRP on ovarian reserve or response. Lack of a placebo group would limit interpretability had a difference between groups been observed. The effect of PRP on patients &amp;gt;38 years old was not studied. Wider implications of the findings Intra-ovarian PRP injection did not improve reproductive outcomes by any relevant measure. Our findings do not support wide utilization of PRP to improve IVF outcomes in women with POR. Trial registration number NCT04163640

P-409 Oocyte cryopreservation following ovarian stimulation for fertility preservation in transgender men: a French case series

Abstract Study question To evaluate the feasibility and results of a fertility preservation program for transgender men. Summary answer Ovarian stimulation outcomes are similar between transgender men and oocyte donation candidates, leading to a satisfactory mean number of cryopreserved oocytes. What is known already The reproductive potential of transgender people may be impaired by gender-affirming hormone treatment (GAHT) and is obviously suppressed in case of gender-affirming surgery involving bilateral ovariectomy and/or hysterectomy. The evolution of medical support for transgender people has made fertility preservation strategies possible. Fertility preservation in transgender men mainly relies on oocyte cryopreservation following controlled ovarian stimulation. However, few data are available to date on the subject, concerning small sample sizes, so no reliable conclusions can be drawn about the feasibility and efficiency of fertility preservation procedures in trans men. Study design, size, duration This retrospective study reports the results of fertility preservation counselling in 118 transgender men referred to our fertility centre from September 2018 to December 2022. Among them, 16 benefited from oocyte cryopreservation. Ovarian stimulation outcomes were compared with those of cisgender oocyte donors. Participants/materials, setting, methods Sixteen transgender men benefited from oocyte cryopreservation following ovarian stimulation and were matched 1:1 to cisgender oocyte donors according to age and body mass index. Antral follicle count and serum AMH levels were systematically measured. Primary outcomes included duration of the stimulation, total FSH dose, peak serum estradiol, oocyte yield, number of mature oocytes, and maturity rate (mature oocytes/total oocytes collected). Results were compared using Fisher’s exact or Wilcoxon’s rank sum tests. Main results and the role of chance One hundred and eighteen transgender men were referred in our centre for fertility preservation counselling. Among them, 95 asked for a medical consultation, and 86 came to the appointment. Following the consultation, only 16 (18.6%) finally decided to benefit from oocyte cryopreservation following ovarian stimulation, including 2 that had already started testosterone therapy. Sixteen presumably fertile oocyte donors were matched based on age and BMI. Mean age of trans’ men was 23.9 ± 5.0. Basal ovarian reserve tests showed satisfactory results in trans’ men and oocyte donors, with similar AMH (4.5 ± 2.3 vs. 4.4 ± 3.2, respectively, NS) but lower AFC in trans’men than in oocyte donors (13.8 ± 11.0 vs. 26.7 ± 10.1, p = 0.033). This result may be explained by a more frequent use of the abdominal approach to assess AFC in the transgender group. Ovarian stimulation outcomes were comparable, with no differences in the duration of stimulation, total FSH dose and peak estradiol levels, leading to a comparable mean number of mature oocyte (15.4 ± 9.9 vs. 17.2 ± 10.6, respectively, NS). Thirteen out 16 transgender men had 10 or more cryopreserved mature oocyte following a single procedure. Limitations, reasons for caution Only a low percentage of trans men that were referred to our centre finally chose to perform oocyte cryopreservation, leading to a small sample size. The majority of them had not started any GAHT, preventing us to evaluate the potential consequences of these treatments on ovarian stimulation outcomes. Wider implications of the findings While parenthood strategies for transgender people have long been ignored, fertility preservation is an important issue to consider, especially because medical treatments and surgeries may be undertaken in very young adults. Oocyte cryopreservation seems to represent a feasible way for trans men to preserve their fertility for future biological parenting. Trial registration number N/A

P-298 Women undergoing IVF-ICSI cycles after mild Covid-19 infection do not show a poor ovarian response: A prospective randomized controlled study

Abstract Study question Does mild COVID-19 infection in women undergoing IVF-ICSI cycles affect their ovarian reserve ? Summary answer A recent past mild COVID-19 infection does not seem to alter the ovarian reserve testing and ovarian response to stimulation in women undergoing IVF-ICSI cycles. What is known already Since December 2019, the world has been facing a COVID-19 pandemic. Besides its effect on mortality, COVID-19 infection raises questions about short and longterm effects on general health. Clinical manifestations are highly heterogeneous and involve many different organs. The SARS-CoV-2 virus penetrates human cells by directly binding with angiotensin-converting enzyme 2 (ACE2) receptors present on the cell surface.The ACE2 receptors are present in testes and in ovarian tissue. In the ovary, ACE2 plays a role in the response to gonadotrophins, steroidogenesis regulation, and in follicle development, angiogenesis and degeneration and therefore, SARS-CoV-2 could be responsible for adversely affecting ovarian reserve. Study design, size, duration A prospective randomized controlled study was conducted between June 2020 and December 2021. Women with primary or secondary infertility undergoing IVF-ICSI between the age of 25-40 years were included. All the women underwent a COVID testing by RT-PCR and were subsequently tested for ovrian reserve by assessing their AMH and AFC (USG). Participants/materials, setting, methods The study population consisted of 128 women, 22% of whom were COVID RT-PCR positive. None of the tested women presented with a history of severe COVID-19 infection. They were randomized into two groups depending on whether they were positive for past COVID-19 infection or negative. These women were then subjected to AMH testing and estimation of AFC by transvaginal ultrasonography. Main results and the role of chance The difference between the initial AMH concentration and AMH concentration tested during ART treatment was not significantly different between the COVID RDT positive group and COVID RDT negative group (–1.24 ng/ml [–0.35 to –1.61) versus –0.56ng/ml [–0.15 to –1.11], P = 0.22). Similarly the AFC (Antral Follicle Count) was also not significantly different between the two groups of patients. The results of this prospective study showed that, based on AMH concentrations, mild COVID-19 infection did not affect ovarian reserve in our population of asymptomatic women who underwent an ART protocol susequently. Limitations, reasons for caution First, it has been shown that the AMH concentration is modified during ART treatment as this hormone is secreted by granulosa cells of small growing follicles thus reflecting the granulosa cell activity. Second, a relatively small number of women were included in the analysis and larger study groups are required. Wider implications of the findings The wider implication of our study is that AMH concentrations were tested in the same women at different time points and could, therefore, analyse any potential modification of the ovarian reserve after COVID-19 infection. This information can be used to reassure the population who have been afflicted by COVID-19 infection. Trial registration number not applicable