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Research Question: Do breast cancer prognostic factors influence ovarian reserve and response to ovarian stimulation in the context of fertility preservation?, Design: Observational, bicentric retrospective study of 352 women with breast cancer who underwent ovarian stimulation using a random start gonadotrophin releasing hormone antagonist protocol and vitrified oocytes between November 2015 and August 2022. Serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) were measured. The number of oocytes recovered, maturation rate and follicular output rate (FORT) were analysed according to patients' characteristics and breast cancer prognostic factors., Results: Median age was 34 years (31.1-37.1). Median AFC and serum AMH level were 17 (12-26) follicles and 2 (1.2-3.4) ng/ml, respectively. After ovarian stimulation, 10.5 (6.0-16.0) oocytes were recovered, with eight (4-13) being mature. Mean oocyte maturation rate was 79% (62-92). Antral follicle count (>12) significantly affected the risk of recovering fewer than eight mature oocytes (P < 0.0001, multivariate analysis). Follicular responsiveness to FSH, assessed by the follicular output rate (FORT index) and number of oocytes recovered, were 31% (21-50) and 10.5% (6.0-16.0), respectively. FORT index and ovarian stimulation outcomes were not influenced by breast cancer prognostic factors., Conclusion: Breast cancer prognostic factors do not influence ovarian reserve markers or response to ovarian stimulation in fertility preservation. Therefore, tumour grade, triple-negative status, HER2 overexpression and high Ki67 should not alter the fertility-preservation strategy when considering ovarian stimulation for oocyte vitrification., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Anti-Müllerian hormone (AMH), known for its role during sexual differentiation, is a dimeric glycoprotein that belongs to the transforming growth factor-β (TGF-β) family. AMH has recently been identified as a reliable marker of ovarian reserve that can help predict early ovarian follicle loss and menopause onset. AMH levels also reflect the effects of damaging gynecologic surgeries or gonadotoxic treatments such as chemotherapy on ovarian reserve. Furthermore, AMH participates in the diagnosis of certain diseases such as granulosa cell tumors or Polycystic Ovary Syndrome (PCOS). Currently used to establish patient profiles and predict ovarian response to stimulation, its role in ART techniques is crucial. Nevertheless, AMH appears to be a weak independent predictor of qualitative outcomes such as implantation, pregnancy, and live birth. As the reliability and reproducibility of AMH dosage have raised many doubts due to different existing standards and thresholds, an international consensus is still expected to improve AMH measurement and interpretation., (Copyright © 2018. Published by Elsevier Masson SAS.)

STUDY QUESTION Is serum anti-Müllerian hormone (AMH) level predictive of cumulative live birth (CLB) rate after ART or in women trying to conceive naturally? SUMMARY ANSWER Serum AMH level is linked to CLB after IVF/ICSI but data are lacking after IUI or in women trying to conceive without ART. WHAT IS KNOWN ALREADY Serum AMH level is a marker of ovarian reserve and a good predictor of ovarian response after controlled ovarian stimulation. It is unclear whether AMH measurement can predict CLB in spontaneous or assisted conception. STUDY DESIGN, SIZE, DURATION A systematic review and meta-analysis was undertaken to assess whether serum AMH level may predict chances of CLB in infertile women undergoing IVF/ICSI or IUI and/or chances of live birth in women having conceived naturally. PARTICIPANTS/MATERIALS, SETTING, METHODS A systematic review and meta-analysis was performed using the following keywords: 'AMH', 'anti-mullerian hormone', 'live-birth', 'cumulative live birth'. Searches were conducted from January 2004 to April 2021 on PubMed and Embase. Two independent reviewers carried out study selection, quality, and risk of bias assessment as well as data extraction. Odds ratios were estimated using a random-effect model. Pre-specified sensitivity analyses and subgroup analyses were performed. The primary outcome was CLB. MAIN RESULTS AND THE ROLE OF CHANCE A total of 32 studies were included in the meta-analysis. Overall, 27 articles were included in the meta-analysis of the relation between AMH and CLB or AMH and LB after IVF/ICSI. A non-linear positive relation was found in both cases. A polynomial fraction was the best model to describe it but no discriminant AMH threshold was shown, especially no serum AMH level threshold below which live birth could not be achieved after IVF/ICSI. After IVF–ICSI, only four studies reported CLB rate according to AMH level. No statistically significant differences in mean serum AMH levels were shown between patients with and without CLB, but with a high heterogeneity. After exclusion of two studies with high risks of bias, there was no more heterogeneity [ I 2 = 0%] and the mean AMH level was statistically significantly higher in women with CLB. There were not enough articles/data to assess the ability of AMH to predict CLB rate or find an AMH threshold after IUI or in women without history of infertility trying to conceive without ART. LIMITATIONS, REASONS FOR CAUTION The systematic review and meta-analysis had some limitations owing to the limits and bias of the studies included. In the present meta-analysis, heterogeneity may have been caused by different baseline characteristics in study participants, different stimulating protocols for ART, different serum AMH level thresholds used and the use of various assays for serum AMH. This could explain, in part, the absence of a discriminating AMH threshold found in this analysis. WIDER IMPLICATIONS OF THE FINDINGS Serum AMH level is linked to CLB rate after IVF/ICSI but no discriminating threshold can be established, therefore low serum AMH level should not be used as the sole criterion for rejecting IVF treatment, especially in young patients. Data are lacking concerning its predictive value after IUI or in women trying to conceive without ART. Our findings may be helpful to counsel candidate couples to IVF-ICSI. STUDY FUNDING/COMPETING INTERESTS No external funding was obtained for this study. There are no conflicts of interest. REGISTRATION NUMBER PROSPERO CRD42021269332. [ABSTRACT FROM AUTHOR]

BRCA 1 and 2 genes play a critical role in the safeguarding of DNA integrity. It is now well established that BRCA1 and BRCA2-mutated women are at increased risk of breast and ovarian cancers. However, several lines of evidence indicate that this genetic status may also be associated with ovarian dysfunction, in particular a reduced ovarian reserve. Considering the gonadal toxicity of cancer treatments and the recommendation of prophylactic bilateral salpingo-oophorectomy around 40 years, young BRCA mutation carriers are confronted with difficult family planning decisions. Recent development in fertility preservation offers new possibilities for these women, not only before a potential cancer treatment, but also in healthy carriers. If the pregnancy seems to be safe in this population, oocyte vitrification following ovarian stimulation might help BRCA-mutated patients to conceive after cancer treatment or to undergo prenatal genetic diagnosis in order to avoid the risk of transmitting the genetic abnormality to their offspring. The present article aims to extensively discuss the fertility issues related to BRCA gene mutations and the questions raised by the possibility of fertility in this population. [ABSTRACT FROM AUTHOR]

Study Question: Are the maturation rates of oocytes recovered from small antral follicles different between breast cancer patients presenting with or without a BRCA 1/2 gene mutation?Summary Answer: BRCA 1/2 gene mutations do not affect the capacity of oocytes from breast cancer candidates for fertility preservation to mature in vitro.What Is Known Already: Mutations in the BRCA1 and BRCA2 genes are associated with an increased risk for developing breast and ovarian cancer. Controversy exists about fertility and ovarian reserve in BRCA mutation carriers. Studies suggest that these patients may have low ovarian reserve and poor response to ovarian stimulation. The impaired ability of the mutated BRCA gene to repair double-strand breaks in DNA may prompt oocyte aging, apoptosis and meiotic errors. IVM of oocytes retrieved at germinal vesicle stage, followed by vitrification of metaphase II (MII) oocytes has recently emerged as an option for young women seeking fertility preservation, when ovarian stimulation is unfeasible.Study Design, Size, Duration: Retrospective cohort study involving 329 breast cancer candidates for fertility preservation using IVM between January 2014 and December 2017.Participants/materials, Setting, Methods: Inclusion criteria were: age 18-40 years; two ovaries present; no history of chemotherapy; test for BRCA 1/2 mutations performed. Before immature oocyte retrieval, all follicles measuring 2-9 mm in diameter were precisely counted on both ovaries and serum anti-Müllerian hormone (AMH) was measured irrespective of the phase of the cycle. Number of cumulus oocyte complexes (COC) retrieved, maturation rate and number of MII oocytes cryopreserved were compared according to BRCA mutation status.Main Results and the Role Of Chance: Overall, BRCA-mutated women (n = 52) and BRCA-negative women (n = 277) were comparable in terms of age (31.7 ± 3.9 versus 32.3 ± 3.8 years, respectively, P = 0.3), BMI (23.4 ± 4.7 versus 22.6 ± 3.7 kg/m2, respectively, P = 0.3) and ovarian reserve tests (antral follicle count: 20.5 ± 11.4 versus 21.7 ± 12.1 follicles, P = 0.5; serum AMH levels: 3.6 ± 2.9 versus 4.1 ± 3.6 ng/ml, P = 0.3, respectively). The number of COCs retrieved did not differ significantly between both groups (8.9 ± 6.9 versus 9.9 ± 8.1 oocytes, P = 0.5). After similar IVM rates (67 ± 24 versus 62 ± 23%, P = 0.2), the number of MII oocytes cryopreserved was similar in patients presenting BRCA mutation or not (5.1 ± 3.8 versus 6.1 ± 5.1, P = 0.1, respectively).Limitations, Reasons For Caution: Given the low incidence of the mutation, these preliminary findings should be confirmed by further multi-center studies.Wider Implications Of the Findings: Although BRCA mutations are known to alter DNA repair mechanism, it does not seem to impair oocyte capacity to mature in vitro.Study Funding/competing Interest(s): None. [ABSTRACT FROM AUTHOR]

Cancer treatment, such as chemotherapy, induces early ovarian follicular depletion and subsequent infertility. In order to protect gametes from the gonadotoxic effects of chemotherapy, several fertility preservation techniques—such as oocyte or embryo cryopreservation with or without ovarian stimulation, or cryopreservation of the ovarian cortex—should be considered. However, these methods may be difficult to perform, and the future use of cryopreserved germ cells remains uncertain. Therefore, improving the methods currently available and developing new strategies to preserve fertility represent major challenges in the area of oncofertility. Animal and ovarian culture models have been used to decipher the effects of different cytotoxic agents on ovarian function and several theories regarding chemotherapy gonadotoxicity have been raised. For example, cytotoxic agents might (i) have a direct detrimental effect on the DNA of primordial follicles constituting the ovarian reserve and induce apoptosis; (ii) induce a massive growth of dormant follicles, which are then destroyed; or (ii) induce vascular ovarian damage. Thanks to improvements in the understanding of the mechanisms involved, a large number of studies have been carried out to develop molecules limiting the negative impact of chemotherapy on the ovaries. [ABSTRACT FROM AUTHOR]

Objective: To assess whether serum antimüllerian hormone (AMH) levels and antral follicle count (AFC) can predict primordial follicle density within ovarian cortex and the number of oocytes cryopreserved after in vitro maturation (IVM).Design: Retrospective analysis of a case series of patients.Setting: University hospital.Patient(s): Fifty-four women, 18 to 35 years of age, with breast cancer who were candidates for fertility preservation (FP) using ovarian tissue cryopreservation (OTC) associated with oocyte vitrification after unstimulated IVM between July 2013 and December 2016.Intervention(s): Serum AMH levels and transvaginal AFC evaluated before FP, cumulus-oocyte complexes (COC) recovered under ultrasound guidance and incubated for IVM, and ovarian tissue laparoscopically harvested and cryopreserved.Main Outcome Measure(s): Univariate and multivariate analysis between ovarian reserve tests, number of recovered and in vitro matured oocytes, and primordial follicle density histologically obtained within ovarian cortex.Result(s): Univariate analysis showed a statistically significant correlation between AMH or AFC and primordial follicle density. Multivariate analysis showed a predominant statistically significant correlation of serum AMH with density. Antimüllerian hormone also correlated with the number of COC and in vitro matured oocytes.Conclusion(s): Serum AMH levels may reflect the primordial follicle stockpile and may predict outcomes of IVM and OTC when performed for FP. Further analyses are required to evaluate the relevance of performing such procedures in young women who have low values on ovarian reserve tests. [ABSTRACT FROM AUTHOR]