Serum AMH Research Articles

Outcome of Endometriosis Treatment In Infertile Patients In A Tertiary Level Hospital

Introduction: Prevalence of endometriosis is 6-10% in reproductive-age females. Around 25-35% of infertile women may be affected by endometriosis. Modalities of treatment for infertile patients depends on the stage of the disease. It starts from ovulation inducing drug to advanced ART. The objective of this study was to assess the outcome of surgical treatment in infertile, endometriosis patients. Materials and Methods: It was an observational study, which was conducted at Reproductive Endocrinology and infertility Unit, Dhaka Medical College. Total 144 patients were included during July 2018 to July 2021, aged 20-40 yrs. All the demographic variables, clinical and sonographic findings, and hormonal assessment were done. Then, staging was done by clinical pelvic assessment, and ultrasonographic findings. Patients who had ovarian endometrioma, more than 4 cm, were selected for laparoscopic surgery. In patients whose endometrioma was less than 4 cm, or had no ovarian endometrioma, were selected for ovulation induction with or without prior GnRH agonist therapy. Further infertility management were planned according to ovarian reserve, tubal patency, and male factor. Result: Mean age of the patients were 28.30±4.95 yrs. 75.0% patients had primary infertility. Dysmenorrhea was the most common symptom (86.96%), followed by chronic pelvic pain (81.16%). Bilaterality of endometrioma was associated with decreased serum AMH. Laparoscopic surgery was the mainstay of treatment, Cystectomy was done in 58% patients. Conservative treatment was done in remaining patients. Fertility enhancing treatment was done by ovulation inducing drug -letrozole, GnRH agonist, followed by controlled ovarian stimulation and followed by IUI. IVF was advised for fertility management in 26patients (18.06%). Conclusion: Endometriosis is not only associated with decreased ovarian reserve but also responsible for diminished response to ovarian stimulation. So, it is a great challenge to obtain successful fertility treatment for this group of patients. J Dhaka Med Coll. 2023; 32(1) : 9-15

Inter-cycle variability of anti-Müllerian hormone: implications for predicting controlled ovarian stimulation cycle outcomes

BackgroundAnti-Müllerian hormone (AMH) is a widely used marker for estimating ovarian reserve, and it may predict response to ovarian stimulation. While AMH is considered a stable, cycle-independent marker, studies have shown it can exhibit significant fluctuations based on factors like age, reproductive stage, and menstrual cycle phase. The fluctuations in AMH levels can make it challenging to predict individual responses accurately, particularly when the AMH is not measured in the COS cycle. The aim of this study was to assess the inter-cycle variability of serum AMH levels in two consecutive menstrual cycles and their correlation with response to controlled ovarian stimulation outcome in the latter.MethodsIn this single-centre retrospective cohort study, data of normal and low responder patients who underwent intracytoplasmic sperm injection following a GnRH antagonist cycle at a university hospital infertility clinic between January 2022 and December 2023 were reviewed. Serum AMH levels were measured in the early follicular phase of two consecutive menstrual cycles with Elecsys-AMH Roche® system (Roche Diagnostics, Meylan, France). Correlations between AMH levels and controlled ovarian stimulation outcomes, including total oocyte and mature oocyte (MII) counts, were assessed. The study included normal and poor responder women to maintain data integrity.ResultsA total of 79 patients were included in the final analyses. Significant cycle-to-cycle variation in serum AMH levels was observed, with a median variation of 44.3%. Normal responders exhibited a mean change of 0.60 ± 0.46 ng/ml, while poor responders had a mean change of 0.28 ± 0.28 ng/ml. Approximately 20% of patients were reclassified between normal and poor responder categories based on the second AMH measurement. The controlled ovarian stimulation cycle AMH levels showed a stronger correlation with both total oocyte count (r = 0.871, P < 0.001) and MII oocyte count (r = 0.820, P < 0.001) compared to preceding cycle AMH levels.ConclusionAMH levels can exhibit significant variations between consecutive cycles, potentially leading to misclassification of patients. Measuring AMH in the early follicular phase of the COS cycle provides a more accurate prediction of the numbers of total and MII oocytes collected. Consistent and repeated AMH measurements can help clinical decision-making.

7349 Identifying the Onset of Puberty in Boys Born Small for Gestational Age (SGA)

Abstract Disclosure: S.M. Suco: None. A.C. Keselman: None. M.G. Ballerini: None. M.E. Rodriguez: None. M.G. Ropelato: None. S. Rosenbrock: None. D. Braslavsky: None. R.A. Rey: None. R.P. Grinspon: None. Introduction: Some children born SGA have an earlier pubertal onset and more rapid progression. Therefore, it is essential to identify the onset of puberty to proceed in a timely and appropriate manner. As it has also been suggested that there may be some gonadal dysfunction, the classic markers of pubertal onset, for example, testicular volume ≥ 4ml, may not be appropriate in these cases. Objective: To describe the clinical and biochemical characteristics of pubertal maturation in boys born SGA and determine parameters that best identify pubertal onset. Methods: We perform a retrospective, descriptive study of a cohort of boys born SGA with longitudinal follow-up, at a tertiary pediatric public hospital in Buenos Aires, Argentina. The subjects were selected from 1997 to 2023. Main outcome measures were serum levels of LH and AMH and testicular volume (TV). Additionally, height velocity, bone age, IGF1 and HOMA-IR were also collected to analyze its association with puberty. Pubertal onset was defined as serum LH ≥ 0.3 U/L and/or a decrease in serum AMH ≥ 30%. Results: The cohort included 25 boys born SGA, 24% were born prematurely and 60% were referred for short stature. In 18 boys (72%) AMH decline occurred with testicular volume &amp;lt; 4ml, at a median age of 9.8 yr (IQR 8.3 – 11 yr), and with median TV of 2ml. In 5 boys, LH was ≥ 0.3 U/L when AMH decline &amp;gt;30%. In 14 boys (56%) TV was &amp;lt;4ml when serum LH was ≥ 0.3 U/L. The median age for LH ≥0.3 was 11.3yr (IQR 10.4 – 12.2 yr), with a median TV of 3ml. In 3 boys the decrease in AMH occurred concomitantly with the increase in LH, while in 6 it occurred before.Alongside with the AMH decline, acceleration of bone age was observed in 35%, increase in growth velocity in 29%, increase in IGF1 concentrations in 24% and an increase in HOMA-IR in 26% of the boys. Concomitantly with an LH ≥0.3 U/L, acceleration of bone age was observed in 19%, increase in growth velocity in 25%, increase in IGF1 concentrations in 30% and an increase in HOMA-IR in 50% of the boys. Conclusion: The increase in testicular volume to 4ml, a classic parameter used as a marker of pubertal onset, may not be appropriate in a subgroup of children born SGA. Probably other parameters such as the increase in serum LH or the decrease in AMH should be considered. Presentation: 6/1/2024

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

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

Hesperidin attenuates radiation-induced ovarian failure in rats: Emphasis on TLR-4/NF-ĸB signaling pathway

Young women suffering from premature ovarian failure after radiotherapy carry a huge burden in the field of cancer therapy including reproductive loss, emotional stress, and physical troubles that reduce their long-term quality of life. Hesperidin (HSP) exhibited antioxidant, anti-inflammatory, and anti-apoptotic properties. HSP enhanced in vitro follicular maturation and preserved in vivo ovarian stockpile. In this research, the role of HSP in radiation-induced POF in rats was investigated besides ascertaining its underlying mechanisms. Female Sprague-Dawley rats were arbitrarily allocated into four groups: control-group, ϒ-irradiated-group (3.2 Gy once on the 7th day), HSP-group (100 mg/kg, orally for 10 days), and HSP/ϒ-irradiated-group (ϒ-radiation was applied one hour after HSP). At the end of experiment, the whole ovaries were collected for histological and biochemical analyses. Administration of HSP preserved the ovarian histoarchitecture and follicular stock, retained ovarian weight, and conserved serum estradiol and AMH levels following radiation exposure. HSP ameliorated the ovarian oxidative damage mediated by radiation through augmenting the activities of glutathione peroxidase, glutathione reductase, and catalase antioxidant enzymes. HSP exhibited remarkable anti-inflammatory activity by downregulating the expression of ovarian TLR-4, NF-ĸB, and TNF-α. Moreover, HSP suppressed the apoptotic machinery triggered by radiation by reducing p53 and Bax while increasing Bcl-2 mRNA expressions alongside diminishing caspase-3 expression. Additionally, HSP regulated estrous cycle disorder of irradiated rats and improved their reproductive capacity reflected by enhancing pregnancy outcomes. Therefore, HSP represents an appealing candidate as an adjunct remedy for female cancer patients during radiotherapy protocols owing to its antioxidant, anti-inflammatory, anti-apoptotic, and hormone-regulatory effects.

Safety and effectiveness of controlled ovarian stimulation and oocyte retrieval during prepubertal and peripubertal period.

Is itsafe and effective to perform controlled ovarian stimulation (COS) and oocyte retrieval (OR) in prepubertal and peripubertal patients? In this retrospective cohort study, data of 20 pre-/peripubertal patients who underwent COS and OR for the purpose of oocyte cryopreservation (OC) between 2008 and 2023 were reviewed.Following COS, all OR procedures were performed transabdominally using a vaginal ultrasound probe. Ovarian reserve was assessed by serum FSH, LH, estradiol, AMH, and antral follicle counts (AFC) in all subjects. All mature oocytes were vitrified. Mean age of the patients was 15.05 ± 1.87, mean AMH was 0.84 ± 0.8ng/ml, mean FSH was 6.39 ± 3.95IU/L, mean estradiol was 61.6 ± 51.9pg/ml, mean LH was 4.69 ± 3.46IU/L, and mean AFC was 5.5 ± 5.82. Among the patients, 12 had regular menstrual cycle, 5 had irregular menstrual cycle, whereas 3 patients still did not have their menarche yet. The indications for OC were as follows: primary ovarian insufficiency (n = 7), ovarian surgery for ovarian tumors (n = 5) or ovarian torsion (n = 1), mosaic Turner syndrome (n = 2), acute lymphoblastic leukemia (n = 1) anaplastic B-cell lymphoma (n = 1), Ewing's sarcoma (n = 1), Noonan syndrome (n = 1), and Thalassemia (n = 1). The mean number of oocytes retrieved, MII oocytes frozen, and maturation rate were 5.11 ± 5.0, 3.92 ± 4.48, and 75.1 ± 25.6%, respectively.Stepwise linear regression analysis demonstrated a positive correlation between AFC and number of total oocytes retrieved and number of MII oocytes. In the case diagnosed with Noonan syndrome, all 7 retrieved oocytes were MI and all frozen at MI phase. No patient had any complication related to COS or OR. Even though number of the enrolled subjects is limited and mean AMH is lower in our cohort, we demonstrated that performing COS and OR is safe in pre-/peripubertal patients. If required, transabdominal route can be performed in this age group for OR. AFC appears as a prognostic factor for stimulation outcome in this age group. Pediatric patients or young adolescents at risk for primary ovarian insufficiency should not bediscouragedfrom utilizing OC.

Predictive model of IVF outcomes for polycystic ovarian morphology and polycystic ovary syndrome in GnRH antagonist protocol using AMH-MoM and ovarian sensitivity index.

To evaluate the relationship between AMH and ovarian response to controlled ovarian hyperstimulation in women with PCOM and PCOS. A retrospective study was conducted on 559 patients who underwent the IVF-ET cycle between January 2018 and December 2022 at Gangnam Cha Hospital. Patients were divided into 3 groups matched for age and BMI: the PCOS group (n = 54), based on the new 2023 PCOS guideline; the PCOM group (n = 53); and the control group (n = 452) with normal ovaries. Serum AMH levels were converted to multiples of the median (MoM) for each corresponding age. The ovarian sensitivity index (OSI) was calculated as the number of retrieved oocytes divided by the total dose of recombinant FSH administered (per 1000 IU). There were significant differences in AMH-MoM value among women with PCOS [2.7 ± 1.3 (95% CI 2.3-3.0)], those with PCOM [2.0 ± 1.0 (95% CI 1.7-2.3)], and controls [0.8 ± 0.7 (95% CI 0.8-0.9)] (p < 0.001). The abortion rates in the normoovulatory, PCOM, and PCOS groups were 18.2%, 21.1%, and 25.0%, respectively. OSI and live birth rate were positively correlated with the AMH-MoM value in normoovulatory women (r = 0.389, p < 0.05, r = 0.122, p < 0.05), while no such correlation was observed in women with PCOM and PCOS. Ovarian response and live birth rate are possibly correlated with the AMH-MoM value in normoovulatory women, but not in women with PCOM and PCOS.

Novel approach for oligospermia (NAPO) - Protocol for a randomized controlled trial

BackgroundInfertility affects millions of couples globally, with up to 40–50 % of cases linked to impaired semen quality. Insemination or in vitro fertilization are used frequently, regardless of the cause of infertility due to the lack of specific medical interventions for male infertility. Denosumab, an antibody blocking RANKL signaling, may enhance semen quality in infertile men. This randomized controlled trial evaluates if denosumab improves spermatogenesis in men with severely impaired semen quality identified by serum AMH levels as a predictive marker. MethodsNAPO is a single-center, sponsor-investigator-initiated, placebo-controlled, double-blinded randomized trial. Subjects will be randomized in a 2:1 fashion to receive either denosumab 60 mg subcutaneously or a placebo. The study will be carried out at the Division of Translational Endocrinology, Copenhagen University Hospital, Herlev, Denmark. The primary outcome of the study is defined as the difference in sperm concentration (millions/mL) at one spermatogenesis (80 days) after inclusion. DiscussionAn important step in addressing infertility is establishing a viable treatment option for male infertility. With this study, we describe the protocol for a planned RCT aimed at evaluating whether treatment with denosumab can improve sperm concentration in men with severely impaired semen quality. The results of this study will provide evidence crucial for future treatment in a patient group where treatment options are minimal at best. Trial registrationClinical Trials: NCT06300229. Registered on March 12, 2024. Clinical Trials Information System (CTIS): 2023-508325-27-00. Approved on December 19, 2023.

Competence of Combined Low Dose of Human Chorionic Gonadotropin (HCG) and Clomiphene Citrate (CC) Versus Continued CC during Ovulation Induction in Women with CC-Resistant Polycystic Ovarian Syndrome: A Randomized Controlled Trial.

Background and Objectives: Polycystic ovarian syndrome (PCOS) is a widespread endocrine disorder affecting 5-18% of females in their childbearing age. The aim of this study is to assess the efficacy of combining a low dosage of human chorionic gonadotropin (HCG) along with clomiphene citrate (CC) for stimulating ovulation in infertile women diagnosed with CC-resistant PCOS. Materials and Methods: A randomized controlled trial was carried out on 300 infertile CC-resistant PCOS women. All participants were assigned to two groups: the CC-HCG group and the CC-Placebo group. Subjects in the CC-HCG group were given CC (150 mg/day for 5 days starting on the 2nd day of the cycle) and HCG (200 IU/day SC starting on the 7th day of the cycle). Subjects in the CC-Placebo group were given CC and a placebo. The number of ovarian follicles > 18 mm, cycle cancellation rate, endometrial thickness, ovulation rate, clinical pregnancy rate, and occurrence of early ovarian hyper-stimulation syndrome were all outcome variables in the primary research. Results: Data from 138 individuals in the CC-HCG group and 131 participants in the CC-Placebo group were subjected to final analysis. In comparison to the CC-Placebo group, the cycle cancellation rate in the CC-HCG group was considerably lower. The CC-HCG group exhibited a substantial increase in ovarian follicles reaching > 18 mm, endometrial thickness, and ovulation rate. The clinical pregnancy rate was higher in the CC-HCG group (7.2% vs. 2.3%; CC-HCG vs. CC-Placebo). Upon adjusting for BMI and age, the findings of our study revealed that individuals in the CC-HCG group who had serum prolactin levels below 20 (ng/mL), secondary infertility, infertility duration less than 4 years, baseline LH/FSH ratios below 1.5, and serum AMH levels more than 4 (ng/mL) had a higher likelihood of achieving pregnancy. In the CC-Placebo group, there was a greater prediction of clinical pregnancy for those with serum AMH (<4), primary infertility, serum prolactin ≤ 20 (ng/mL), baseline LH/FSH < 1.5, and infertility duration < 4 years. Conclusions: The use of a small dose of HCG along with CC appeared to be an effective treatment in reducing cycle cancelation, improving the clinical pregnancy rate and ovulation rate in CC-resistant PCOS patients. The trial was registered with Clinical Trials.gov, identifier NCT02436226.

Factors associated with successful intraoperative oocyte retrieval for fertility preservation during open pelvic surgery for gynecologic indications

ObjectiveThe study investigated factors associated with successful intra-operative oocyte retrieval for fertility preservation during transabdominal gynecologic surgery. Study designA total of 29 patients who underwent intraoperative oocyte retrieval during staging surgery at a single academic hospital from May 2014 to August 2022 were enrolled in this study, and their outcomes were analyzed. ResultsAmong 29 patients who underwent intra-operative oocyte retrieval during staging surgery, oocytes were obtained in 24 patients, representing 82.8 % of the retrieval rate (24/29), and two patients returned to use cryopreserved oocytes (6.9 %). Among 24 women who succeeded in obtaining oocytes, 20 patients succeeded in oocyte cryopreservation, and two patients proceeded to embryo cryopreservation. The cryopreservation rate was 91.7 % (22/24). All patients with failed oocyte retrieval (n = 5) and cryopreservation (n = 7) were diagnosed with malignancy. AMH of those with successful cryopreservation oocytes was higher than those without cryopreservation (4.10 ng/mL vs. 1.18 ng/mL, p = 0.003). A higher portion of the unstimulated cycle was observed in those with failed cryopreservation (8.3 % vs. 40.0 %, p = 0.01). No complications were noted. ConclusionFor women planning to undergo open pelvic surgery, intra-operative oocyte retrieval is a feasible option. High serum AMH and ovarian stimulation before surgery may predict successful oocyte cryopreservation.

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

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

Low Dose hCG Support in Modified Natural Frozen Embryo Transfer Cycles.

What is the effect of a single low-dose recombinant hCG injection after embryo transfer (ET) in letrozole-induced modified natural frozen embryo transfer cycles (mNC-FET)?. An observational study was conducted in the university-affiliated referral clinic between 2022 and 2024. Women aged 18-42 with at least one vitrified blastocyst obtained from the previous cycle(s) were included. Ovulation induction for endometrial preparation was initiated with oral letrozol (5mg/day) for five days. Ovulation was triggered using 6500IU rec hCG sc when the leading follicle > 17mm, endometrial thickness > 7.5mm, and serum progesterone (P) < 1.5ng/ml. All women received 30mg dydrogesterone/day po for additional five-day luteal support. On the 6th day, ET was performed. Based on a quasi-randomized design, a group of women additionally received a half single bolus of (3250IU) rec hCG (sc) on the morning of 3rd day of ET (hCG group). Women who did not receive additional hCG were assigned as controls.One hundred fifty-four women were detected to be eligible for the study among 2150 initiated FET cycles during the period.Demographic data of the groups, including mean women's age, BMI, serum AMH, and infertility etiologies, were comparable in terms of variables. Mean serum progesterone values and the number of transferred embryos were also similar. A significantly higher ongoing pregnancy/started cycle was documented in the hCG group than in controls (46.7% vs 33.6% respectively, p = 0.03*). A single low-dose hCG injection after ET may improve the OPRs of women in letrozole mNC-FET cycles.

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

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

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

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

P-687 High anti-müllerian hormone is associated with lower live birth rate in IVF/ICSI cycle with fresh transfer but not cumulative live birth rate in PCOS women

Abstract Study question Can serum AMH levels affect pregnancy outcomes particularly live birth rate (LBR) and cumulative live birth rate (CLBR) in PCOS women receiving IVF/ICSI treatment? Summary answer Higher serum AMH indicated a decreased LBR and increased miscarriage rate in PCOS women undergoing IVF/ICSI cycle. However, AMH has no association with CLBR. What is known already AMH could reduce follicle sensitivity to FSH and acts as an inhibitor of primordial follicle recruitment, which is essential for follicle growth. Therefore, AMH has widely been suggested to reflect ovarian reserve and predict ovarian response to assisted reproductive technology (ART). Women with PCOS presented AMH level around 2 to 4-fold higher than normal female. The pathological mechanisms of PCOS are complex. Ovarian follicular arrest is regarded as an important pathophysiology of PCOS, which is a consequence of insufficient FSH secretion or inhibition FSH action. Consequently, increased AMH arise might be associated with severity and poor pregnancy outcomes of PCOS. Study design, size, duration This was a retrospective cohort study included 4719 PCOS patients undergoing IVF/ICSI treatment at the Reproductive Center of Peking University Third Hospital from February 2017 to January 2022. Participants/materials, setting, methods Participants were divided into three groups according to the cutoffs defined by the 25th and 75th percentiles of serum baseline AMH level, low-AMH group, n = 1198 (AMH ≤ 4.98 ng/mL); average-AMH group, n = 2346 (4.98 &amp;lt; AMH &amp;lt; 10.65 ng/mL); high-AMH group, n = 1175 (AMH ≥ 10.65 ng/mL). Baseline parameters and pregnancy outcomes including clinical pregnancy rate (CPR), miscarriage rate, LBR and CLBR were compared among three groups. Main results and the role of chance In our cohort, we observed a significant progressively increase in the number of oocytes retrieved and the number of good-quality embryos per cycle from low- to average- to high-AMH group. No statistical significance was observed in fertilization rate (62% vs 60% vs 60%, P = 0.453). In addition, there was no significant difference in CPR among three groups (44.8% vs 42.8% vs 36.8%, P = 0.069). The miscarriage rate was progressively increased from low, average, and high AMH group (11.2% vs 18.5% vs 20.0%, P = 0.023). Importantly, LBR in fresh transfer was progressively decreased from low, average, and high-AMH group (39.6% vs 33.9% vs 29.0%, P = 0.004). However, no statistical difference but an increasing trend was observed in the CLBR among three groups (55.2% vs 56.9% vs 58.1%, P = 0.753). After adjusting by logistic regression analysis, the results indicated that elevated AMH was still strongly associated with decreased LBR in fresh transfer. In addition, BMI, endometrial thickness, and fertilization rate also have correlations with LBR. Nevertheless, the positive relationship between AMH and miscarriage rate remained only in low and average AMH group. Finally, no significant association was shown between AMH and CLBR in logistic regression analysis. Limitations, reasons for caution Firstly, this was a single-center study and might result in bias. Another limitation was due to its retrospective and non-randomized design. Besides, our study indicated an increasing trend in CLBR without statistical significance. Therefore, further large-scale, high-quality prospective cohort studies are still needed to confirm these findings. Wider implications of the findings These findings bring into consideration the potential role of AMH as the guidance in clinical regime. Since high AMH level might act as a biomarker in predicting worse pregnancy outcomes of PCOS women with IVF/ICSI fresh cycle. Trial registration number not applicable

O-322 What is the number of IVF cycles needed to produce at least one euploid blastocyst in patients of all ages with varied AMH levels

Abstract Study question How many cycles are needed to get at least one blastocyst in patients of different AMH levels and varied ages? Summary answer Age and AMH determine the number of cycles, which ranges from 1 cycle in young patients up to 10 cycles in over-44-year-old patients. What is known already AMH secretion by ovarian granulosa cells initiates during the 36th week of gestation in pre-antral and antral follicles. This persists throughout a woman’s reproductive lifespan. AMH serves as a biomarker for assessing ovarian reserve and forecasting the ovarian response to stimulation. AMH is strongly associated with the quantity of antral follicles and the production of oocytes. AMH can be utilised to determine the initial dosage of FSH in an IVF cycle, as well as serving as a quantitative indicator of the number of oocytes produced. Study design, size, duration In this retrospective cohort study, data was collected from 16,417 ICSI cycles with Preimplantation Testing for Aneuploidy (PGT-A) conducted at three referral fertility centers from Jan 2019 to Dec 2023. We excluded cycles without serum AMH, endocrinopathies or recurrent pregnancy loss, males with total sperm count of less than 5 million and total motility less than 30%, and those with parental chromosomal abnormalities. Participants/materials, setting, methods Patients were stratified into three different categories of AMH (ng/ml), low (&amp;lt; 1.1 ng/mL), intermediate (&amp;gt;1.1 to &amp;lt; 3.0 ng/mL) and high (&amp;gt; 3.0 ng/mL). Each category was subdivided into 6 age sub-categories as follow (&amp;lt; 35), (35 to &amp;lt; 38), (38 to &amp;lt; 40), (40 to &amp;lt; 42), (42 to &amp;lt; 44), (&amp;gt; 44). All of the cycles underwent blastocyst stage biopsy and PGT-A utilising next generation sequencing (NGS). Main results and the role of chance Euploidy rate was statistically insignificant for all AMH levels in the same age group. However, euploid embryo numbers vary significantly. Euploid embryos numbers are shown in low, medium, and high AMH by age group. In the (&amp;lt;35) years was 1.9±1.5, 2.9±2.3, and 4.7±3.5, p &amp;lt; 0.0001. In the (35 to &amp;gt; 38) years was 1.3±0.8, 2.1±1.8, and 3.2±2.6, p &amp;lt; 0.0001. In the (38 to &amp;gt; 40) years was 0.9±0.8, 1.7±1.4, and 2.6±1.7, p &amp;lt; 0.0001. In the (40 to &amp;gt; 42) years was 0.6±0.5, 0.9±0.7, and 1.5±1.4, p &amp;lt; 0.0001. In the (42 to &amp;gt; 44) year was 0.26±0.2, 0.49±0.38, and 0.6±53, p &amp;lt; 0.0001. In the (≥44) years was 0.10±0.10, 0.23±0.21, and 0.40±0.37, p = 0.0170. We calculated the number of cycles needed to produce at least one grade BB or higher euploid blastocyst from the mean number of euploid embryos per cycle: The number of cycles is presented in low, medium, and high AMH. In the (&amp;lt;35) and (35 to &amp;gt; 38), 1 cycle is needed. In (38 to &amp;gt; 40) years, 2 cycles, 1 cycle and 1 cycle. In the (40-42) group 2 cycles, 2 cycles and 1 cycle. In the (42 to &amp;lt; 44) group 4 cycles, 3 cycles and 2 cycles. In the (≥44) group 10 cycles, 5 cycles and 3 cycles. Limitations, reasons for caution The retrospective nature of the study is the main limitation. Wider implications of the findings The study offers valuable insights for patient counselling regarding the required number of cycles to achieve euploid embryos, as well as for financial budgeting for both patients and insurance companies. Trial registration number Not applicable

P-598 Novel inactivating homozygous mutation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) and first live birth after in vitro maturation (IVM): a breakthrough

Abstract Study question How can pregnancy and live birth be achieved in patients with inactivating homozygous luteinizing hormone/choriogonadotropin receptor (LHCGR) mutation? Summary answer We report the first live birth after IVM in a patient with a novel homozygous inactivating LHCGR mutation (exon 6,c.470A&amp;gt;G). What is known already LH plays a fundamental role in female reproductive physiology and is responsible for steroidogenesis, oocyte maturation, ovulation and subsequent progesterone production by the corpus luteum. LH binds to the LHCGR located on the membrane of theca cells and mature granulosa cells. Inactivating mutations of the LHCG receptor lead to the impossibility to obtain final oocyte maturation both during natural cycles and after ovarian stimulation for in vitro fertilization purpose. Until now, egg donation represented the only option to treat their infertility. Study design, size, duration A case report. Participants/materials, setting, methods A 35 year-old nulliparous patient was referred to our university hospital for primary infertility. Main results and the role of chance The 35-year-old nulliparous patient presented with primary spaniomenorrhea but timely and spontaneous onset of secondary sexual characteristics. Serum LH levels were high (ranging from 15 to 30 IU/L) and to a lesser extent so were FSH levels. The ovarian reserve was normal for age, as assessed by serum AMH levels and ultrasound. There was no argument for polycystic ovarian syndrome, 21-hydroxylase deficiency, Cushing’s syndrome or hyperprolactinemia. Two previous attempts of controlled ovarian stimulation with gonadotropins and ovulation trigger with hCG and GnRH-agonist trigger had failed, resulting in low estradiol levels despite correct follicular growth on ultrasound and absence of ovulation after trigger. We identified by genetic analysis a novel homozygous inactivating LHCGR mutation (exon 6, c.470A&amp;gt;G) that had never been described previously. IVM was performed. A total of 7 oocytes were obtained after IVM, resulting in 4 Day 3 embryos. All embryos were frozen. Subsequently, 2 Day 3 embryos were replaced after endometrial preparation by hormone replacement therapy. The patient became pregnant and gave birth to a healthy baby. Two Day 3 embryos remain. Limitations, reasons for caution By definition, a case-report requires further studies to confirm our findings. Wider implications of the findings We describe a novel inactivating LHCGR mutation with subsequent live birth after IVM. As a growing number of gonadotropin receptor mutations are identified, this live birth successfully obtained places IVM as the only reliable option for these patients to conceive with their own eggs. Trial registration number not applicable

P-398 Lower ectopic pregnancy prevalence with natural endometrial preparation in single euploid frozen embryo transfers

Abstract Study question Does the endometrial preparation approach for an euploid-frozen embryo transfer have an impact on the incidence of an ectopic pregnancy? Summary answer The natural cycle endometrial preparation approach seems to have a lower incidence of ectopic pregnancies compared to a hormonal replacement therapy cycle. What is known already Ectopic pregnancy (EP) is an uncommon complication of pregnancy and is associated with significant morbidity. IVF pregnancies have been implicated as a risk factor, but this finding is mostly confounded by multiple embryo transfer and complicated medical history of women undergoing IVF treatment (tubal disease, surgery, endometriosis, etc.). Recent studies have suggested that frozen embryo transfer may reduce the risk of EP, but it is not yet known whether embryo ploidy status and different endometrial preparation regimens affect the risk of EP. Study design, size, duration Retrospective cohort of 1517 pregnancies from 2607 single euploid frozen embryo transfers. Comparator estimates were estimated using multiple large cohort studies in the literature including 58,203,239 pregnancies from unselected cohorts and 220,167 pregnancies from IVF-treated women with the transfer of non-tested embryos. Participants/materials, setting, methods The rate of ectopic per pregnancies were compared to ectopic rate derived from multiple cohorts of IVF-treated women and population level reports of unselected pregnancies (natural conception and IVF). Comparator estimates were obtained with proportion meta-analyses using generalized linear mixed models. Factors associated with ectopic pregnancies were investigated with mixed-effects logistic regression analyses. Main results and the role of chance EP rate in our cohort was 10/1000 pregnancies (95% CI: 5 to 16 per 1000) resulting from single euploid embryo transfers (1.1%, 16/1517). The observed prevalence of EP was 12/1000 pregnancies (95% CI: 6.8 to 21 per 1000) in unselected cohorts and 14/1000 pregnancies (95% CI: 13 to 15 per 1000) after IVF-treatment. Ectopic rate in our study was not significantly different than rates reported in the literature from unselected and IVF pregnancies (P = 0.579 and 0.223, respectively). There were no significant differences between women with ectopic pregnancies and those with clinical pregnancies in terms of age (33.6±5.5 vs. 35.1±5.2 years, P = 0.290), BMI (26.7±4.8 vs. 25.8±4.6 kg/m2, P = 0.475) and serum AMH levels (3.3±2.9 vs. 3.4±3.9 ng/mL, P = 0.854), nor between the quality of embryo transferred between top, good, fair and poor (1.8% vs 0.7% vs 1.9% vs 0.9%, p = 0.088, 0.997 and 0.508 respectively). Ectopic rates were also similar between women with history of cesarean section (1.1% vs 1.0%, P = 0.847) or isthmocele (1.0 vs 1.1%, P = 0.857). There were less ectopic pregnancies following transfers with natural endometrial preparation (0.5 vs 1.5%, natural vs programmed) and the effect showed statistical significance in multivariable analyses (OR: 0.28, 95% CI: 0.06 – 0.88, P = 0.049). Limitations, reasons for caution Small sample size as well as infrequent occurrence of the studied event reduces the power of our study to detect small but clinically meaningful effects with statistical significance. Wider implications of the findings We did not observe a lower than reported prevalence of EP among euploid embryo transfer. However, rate of EP was significantly lower in natural endometrial preparation cycles compared to preparation with exogenous hormones, indicating that a natural cycle might have a protective effect against the development of an ectopic pregnancy. Trial registration number Not applicable

P-698 The ULTRA trial: transvaginal ULTRAsound-guided ovarian ablation using May Health System in women with PCOS-related infertility: clinical and endocrine outcomes of first–in-human feasibility trial

Abstract Study question What is the feasibility of transvaginal ULTRAsound (TVUS)-guided ovarian ablation using the May Health System to improve ovulation, pregnancy, and hormonal abnormalities in PCOS-related infertility? Summary answer The feasibility of TVUS-guided ovarian ablation to improve ovulation, pregnancy, and hormonal abnormalities in PCOS-related anovulatory infertility was demonstrated. A pivotal study is underway. What is known already Laparoscopic ovarian drilling (LOD) is widely accepted as an effective second line treatment in PCOS-related infertility. However, laparoscopy is an invasive procedure that requires general anaesthesia and carries significant risks. Furthermore, there is no standardization of the LOD technique among surgeons. In contrast, the May Health System has been designed to deliver a precisely calculated amount of ovarian ablation via a less invasive route without general anaesthesia. This approach therefore transforms an invasive surgical procedure to an office-based technique similar in ovarian access to the well-established oocyte retrieval. Feasibility and safety results of this trial have previously been reported. Study design, size, duration This study included two feasibility, single-arm clinical trials running in parallel in the EU and US assessing the May Health System in performing TVUS-guided ovarian ablation in anovulatory PCOS women resistant to first-line ovulation induction drugs. Sample size was up to 35 participants with post-procedure follow-up (FU) of 24 months in EU and 12 months in US. Endpoints for this study were technical success, ovulation rates, pregnancy rates, and hormonal changes. Participants/materials, setting, methods Seven fertility centres participated in the trials. Participants were clomiphene/letrozole-resistant PCOS women aged 18-40 years. PCOS was diagnosed according to Rotterdam criteria. Participants underwent TVUS-guided ovarian ablation using the May Health System. The initial five participants underwent laparoscopy concurrent with TVUS-ablation. Post-procedure, serum progesterone was measured weekly until confirmation of ovulation or up to 12 weeks. Women were evaluated at 3 and 6 month, and then telephoned at 9- 12- and 24-month (EU sites only). Main results and the role of chance Thirty-one participants (mean±sd age, 31.9±3.3 years; BMI, 29.84.7kg/m2) underwent May Health TVUS-guided ovarian ablation and 25 completed at least six-months FU, with follow-up ongoing. Fourteen (45.2%) ovulated spontaneously within 3-months. Six more participants (19.3%) ovulated between three and nine months (after restarting CC/LTZ) giving a combined ovulation rate, with and without first-line medication restart, of 64.5% (20/31). Of the 31 participants who underwent the procedure, 10 (32%) have conceived to date, with seven live births, two ongoing, and one miscarriage. In 30 cases (97%), the targeted ablation was achieved successfully, while in one case (3%) the procedure was abandoned for the second ovary due to pain (n = 1). The median (IQR) serum AMH concentrations significantly decreased from baseline 76.1 (32.0, 210.7) to 62.5 (21.2, 253.6) pmol/l at 3-month (p = 0.001) and 56.7 (11.5, 126.8) pmol/l at 6-month (p = 0.001) post-procedure (Figure 2). The magnitude of post-ablation AMH decline was significantly (p = 0.047) greater in those who ovulated (responders) (-23.7% (-36.5, 17.7)) versus non-responders (-7.3% (-25.2, -1.6)). Ovarian volume significantly (p = 0.005) decreased from 13.6±5.1 ml at baseline to 10.1±3.7 ml at 6-month FU. There were no statistically significant changes in mean circulating testosterone, LH, or FAI at 3- or 6-month. Limitations, reasons for caution A limitation of this study is the lack of a comparator treatment / placebo arm. However, this was not necessary for this feasibility trial. It is possible to assume that the post-procedure ovulation and pregnancies could be compared for each participant with pre-procedure lack of ovulation and failure to conceive. Wider implications of the findings These data suggest that the investigational May Health System may offer an effective office-based second line ovulation inducing procedure for PCOS. The observed decline in circulating AMH, which was sustained for at least six months, could be the underlying mechanism of ovarian rebalancing that leads to subsequent resumption of ovulation. Trial registration number NCT03760926

P-356 Fertility preservation for patients with breast cancer: altered response to ovarian stimulation and loss of cholesterol homeostasis in ovarian follicles

Abstract Study question Does the presence of breast cancer alter the ovarian response to hormonal stimulation and the cholesterol homeostasis in ovarian follicles? Summary answer The deleterious impact of breast cancer on the ovarian response might be link to an alteration of the cholesterol biosynthesis in cumulus cells. What is known already Breast cancer is the most frequent cancer in reproductive-aged women. The cancer itself seems to exert a deleterious impact on the ovarian functions. Indeed, cancer patients who undergo fertility preservation before cancer therapy initiation show a poorer response to ovarian stimulation than healthy women. Nevertheless, this impact remains controversial, and the mechanisms by which the cancer impairs the ovarian functions are poorly understood. To our knowledge, no study has yet evaluated the impact of breast cancer on the cholesterol biosynthesis pathway in human cumulus cells, a pathway essential for oocyte competence to maturation and fertilization. Study design, size, duration 30 patients with breast cancer (10 triple negative (TNBC), 10 hormone-receptor positive (HR+) and 10 HER2 positive (HER2+)) and 30 women oocytes donors undergoing oocyte cryopreservation will be included from January 2019. We assess ovarian response to stimulation (number, quality of retrieved oocytes; total FSH dose). We quantify the level of enzymes and regulators of the cholesterol biosynthesis pathway in cumulus cells (CC) by RT-qPCR. We plan to quantify cholesterol levels in follicular fluids (FF). Participants/materials, setting, methods Since January 2019, 25 breast cancer patients (9 TNBC, 8 HR+ and 8 HER2+) and 30 oocytes donors (control group) under 37 years old have been included. Ovarian stimulation was performed with antagonist protocol. Following ovarian pick up and denudation, CC and FF were collected. After total RNAs extraction from CC, the expression levels of enzymes and regulators of the cholesterol biosynthesis pathway were quantified by RT-qPCR. Cholesterol levels will be quantified in FF. Main results and the role of chance The clinico-biological characteristics (age, BMI) are comparable between cancer patients and the control group (p &amp;gt; 0.05). Serum AMH levels are lower in the TNBC subgroup (2.3±1.6 ng/mL) than in the control group (4.7±2.8 ng/mL, p = 0.04). A poorer ovarian response to ovarian stimulation is observed in the breast cancer group compared with the control group (number of mature oocytes: 9.4±5.2 vs. 14.5±7.7, p = 0.007). Among the cancer patients group, the TNBC subgroup shows the poorest ovarian response to stimulation (number of mature oocytes: 7.6±4.3 vs. 14.5±7.7 in control group, p = 0.006) despite the highest total administered FSH dose (2480±880 IU vs. 1831±460 IU in control group, p = 0.02). Dysregulation of the cholesterol biosynthesis pathway is observed in the breast cancer group. For TNBC and HR+ cancer patients, we observed an increase in the transcripts levels of CYP51 enzyme (respectively 3.28±1.69 vs. 1.84±2.33, p = 0.0098 and 1.77±1.78 vs. 1.84±2.33, p = 0.03) and SREBP2 activator (respectively 2.04±0.95 vs. 1.27±1.13, p = 0.003 and 1.12±0.47 vs. 1.27±1.13, p = 0.02) of the cholesterol biosynthesis pathway compared to the control group. In HER2+ cancer patients, a significant decrease in the expression levels of SQLE (0.39±0.34 vs 1.81±3.99, p = 0.001) and DHRC7 enzymes (0.33±0.32 vs 1.21±0.88, p = 0.0002) is observed compared to the control group. Limitations, reasons for caution Our preliminary results should be confirmed with the analysis of a larger number of participants. We should confirm that the observed modulations in the expression levels of enzymes and regulators of the cholesterol biosynthesis pathway led to a loss of cholesterol homeostasis by quantifying cholesterol in FF. Wider implications of the findings Our findings strengthen the hypothesis that cancer exerts a deleterious impact on the ovarian functions, as we observed a lower ovarian response in patients with breast cancer. This project will have clinical implications, such as to adapt the fertility preservation approach according to the breast cancer subtype. Trial registration number Not applicable