Publications by authors named "Isabelle Demeestere"

52 Publications

Pregnancy After Breast Cancer: A Systematic Review and Meta-Analysis.

J Clin Oncol 2021 Jul 1:JCO2100535. Epub 2021 Jul 1.

Fertility and Procreation Unit, Gynecologic Oncology Department, European Institute of Oncology IRCCS, Milan, Italy.

Purpose: Many patients and physicians remain concerned about the potential detrimental effects of pregnancy after breast cancer (BC) in terms of reproductive outcomes and maternal safety. This systematic review and meta-analysis aimed at providing updated evidence on these topics.

Methods: A systematic literature review was conducted to identify studies including patients with a pregnancy after BC (PROSPERO number CRD42020158324). Likelihood of pregnancy after BC, their reproductive outcomes, and maternal safety were assessed. Pooled relative risks, odds ratios (ORs), and hazard ratios (HRs) with 95% CIs were calculated using random effects models.

Results: Of 6,462 identified records, 39 were included involving 8,093,401 women from the general population and 112,840 patients with BC of whom 7,505 had a pregnancy after diagnosis. BC survivors were significantly less likely to have a subsequent pregnancy compared with the general population (relative risk, 0.40; 95% CI, 0.32 to 0.49). Risks of caesarean section (OR, 1.14; 95% CI, 1.04 to 1.25), low birth weight (OR, 1.50; 95% CI, 1.31 to 1.73), preterm birth (OR, 1.45; 95% CI, 1.11 to 1.88), and small for gestational age (OR, 1.16; 95% CI, 1.01 to 1.33) were significantly higher in BC survivors, particularly in those with previous chemotherapy exposure, compared with the general population. No significantly increased risk of congenital abnormalities or other reproductive complications were observed. Compared to patients with BC without subsequent pregnancy, those with a pregnancy had better disease-free survival (HR, 0.66; 95% CI, 0.49 to 0.89) and overall survival (HR, 0.56; 95% CI, 0.45 to 0.68). Similar results were observed after correcting for potential confounders and irrespective of patient, tumor, and treatment characteristics, pregnancy outcome, and timing of pregnancy.

Conclusion: These results provide reassuring evidence on the safety of conceiving in BC survivors. Patients' pregnancy desire should be considered a crucial component of their survivorship care plan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.21.00535DOI Listing
July 2021

Gonadal Function Recovery in Patients With Advanced Hodgkin Lymphoma Treated With a PET-Adapted Regimen: Prospective Analysis of a Randomized Phase III Trial (AHL2011).

J Clin Oncol 2021 Jun 22:JCO2100068. Epub 2021 Jun 22.

Department of Haematology, University Hospital F Mitterrand and Inserm UMR1231, Dijon, France.

Purpose: The prospective, randomized AHL2011 trial demonstrated that the use of the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (ABVD) after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) in early responders on the basis of a positron emission tomography (PET)-driven strategy was safe and minimized toxicity compared with standard 6 BEACOPP cycles. This substudy investigated the benefit of this strategy in gonadal function and fertility in patients under 45 years old.

Methods: Ovarian function was assessed by serum measurement of follicle-stimulating hormone (FSH), estradiol, and anti-müllerian hormone in women, and semen analysis, FSH, and testosterone levels were used to evaluate testicular function in men at baseline, end of treatment, and during 5 years of follow-up.

Results: A total of 145 women and 424 men, enrolled between May 19, 2011, and April 29, 2014, were included. The risk of premature ovarian insufficiency (FSH > 24 IU/L) and of having a low ovarian reserve (anti-müllerian hormone < 0.5 ng/mL) was reduced after treatment in the PET-driven group (odds ratio [OR], 0.20; 95% CI, 0.08 to 0.50; = .001 and OR, 0.15; 95% CI, 0.04 to 0.56, = .005, respectively). Both parameters were correlated with age and dose of alkylating agents. However, no significant differences were observed in terms of pregnancy rates. Men in the PET-driven group had a higher recovery rate of sperm parameters after treatment compared with the standard BEACOPP group, as well as a lower risk of severe testicular damage (OR, 0.26; 95% CI, 0.13 to 0.5; < .0001) and a higher likelihood of achieving pregnancy (OR, 3.7; 95% CI, 1.4 to 9.3; = .004).

Conclusion: Although both treatments affected ovarian reserve and spermatogenesis, the PET-driven strategy decreased the risk of gonadal dysfunction and infertility in advanced Hodgkin lymphoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.21.00068DOI Listing
June 2021

Association of Germline BRCA Pathogenic Variants With Diminished Ovarian Reserve: A Meta-Analysis of Individual Patient-Level Data.

J Clin Oncol 2021 Jun 23;39(18):2016-2024. Epub 2021 Apr 23.

Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT.

Purpose: To determine whether germline (g) pathogenic variants are associated with decreased ovarian reserve.

Materials And Methods: An individual patient-level data meta-analysis was performed using five data sets on 828 evaluable women who were tested for g. Of those, 250 carried g, whereas 578 had tested negative and served as controls. Of the women with g four centers studied those affected with breast cancer (n = 161) and one studied unaffected individuals (n = 89). The data were adjusted for the center, age, body mass index, smoking, and oral contraceptive pill use before the final analysis. Anti-Müllerian hormone (AMH) levels in affected women were drawn before presystemic therapy.

Results: The mean age of women with versus without g (34.1 ± 4.9 34.3 ± 4.8 years; = .48) and with g versus g (33.7 ± 4.9 34.6 ± 4.8 years; = .16) was similar. After the adjustments, women with g had significantly lower AMH levels compared with controls (23% lower; 95% CI, 4 to 38; = .02). When the adjusted analysis was limited to affected women (157 with g 524 without, after exclusions), the difference persisted (25% lower; 95% CI, 9 to 38; = .003). The serum AMH levels were lower in women with g (33% lower; 95% CI, 12 to 49; = .004) but not g compared with controls (7% lower; 95% CI, 31% lower to 26% higher; = .64).

Conclusion: Young women with g pathogenic variants, particularly those affected and with g, have lower serum AMH levels compared with controls. They may need to be preferentially counseled about the possibility of shortened reproductive lifespan because of diminished ovarian reserve.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.20.02880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260903PMC
June 2021

Fertility preservation for female patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Lancet Oncol 2021 02;22(2):e45-e56

Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Pediatric Oncology, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Female patients with childhood, adolescent, and young adult cancer are at increased risk for fertility impairment when treatment adversely affects the function of reproductive organs. Patients and their families desire biological children but substantial variations in clinical practice guidelines reduce consistent and timely implementation of effective interventions for fertility preservation across institutions. As part of the PanCareLIFE Consortium, and in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in female patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. This clinical practice guideline leverages existing evidence and international expertise to develop transparent recommendations that are easy to use to facilitate the care of female patients with childhood, adolescent, and young adult cancer who are at high risk for fertility impairment. A complete review of the existing evidence, including a quality assessment, transparent reporting of the guideline panel's decisions, and achievement of global interdisciplinary consensus, is an important result of this intensive collaboration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(20)30594-5DOI Listing
February 2021

Ovarian tissue cryopreservation and transplantation in patients with central nervous system tumours.

Hum Reprod 2021 04;36(5):1296-1309

Pôle de Gynécologie, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.

Study Question: Is there a possibility of reseeding cancer cells potentially present in frozen ovarian tissue from patients with central nervous system (CNS) tumours?

Summary Answer: Malignancy reseeding in cryopreserved ovarian tissue from 20 patients with CNS tumours was not detected by histology, immunohistochemistry (IHC), molecular biology or xenotransplantation.

What Is Known Already: Ovarian metastasis potential has been documented in patients with leukaemia, borderline ovarian tumours, advanced breast cancer and Ewing sarcoma. However, data on the safety of transplanting frozen-thawed ovarian tissue from cancer patients with CNS tumours are still lacking.

Study Design, Size, Duration: This prospective experimental study was conducted in an academic gynaecology research laboratory using cryopreserved ovarian cortex from 20 patients suffering from CNS tumours. Long-term (5 months) xenografting was performed in immunodeficient mice.

Participants/materials, Setting, Methods: Subjects enrolled in the study were suffering from one of six types of CNS tumours including medulloblastoma, ependymoma, primitive neuroectodermal tumours, astrocytoma, glioblastoma and germinoma. The presence of malignant cells was investigated with disease-specific markers for each patient in cryopreserved and xenografted ovarian tissue by histology, IHC via expression of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) for quantification of GFAP and ENO2 gene amplification.

Main Results And The Role Of Chance: Serial sections of cryopreserved and xenografted ovarian tissue from 20 patients showed no malignant cells by histology. All samples were negative for NSE and GFAP, although these neural markers were expressed extensively in the patients' primary tumours. Analysis by RT-ddPCR revealed no cancer cells detected in cryopreserved and xenografted ovarian fragments from subjects with astrocytoma, ependymoma, glioblastoma or medulloblastoma. Taken together, the study found no evidence of malignancy seeding in frozen-thawed and xenotransplanted ovarian tissue from patients affected by CNS cancers.

Limitations, Reasons For Caution: This analysis cannot guarantee complete elimination of disseminated disease from all cryopreserved ovarian cortex, since we are unable to examine the fragments used for transplantation.

Wider Implications Of The Findings: This is the first study to be conducted in patients with CNS cancers undergoing ovarian tissue cryopreservation and transplantation, and clearly demonstrates no tumour seeding in their frozen-thawed and xenografted tissue. This information is vital for doctors to provide patients with meaningful and accurate advice on the possibilities and risks of ovarian tissue reimplantation.

Study Funding/competing Interest(s): This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique-the Excellence of Science (FNRS-EOS), number 30443682 awarded to M.-M.D. and T.Y.T.N., FNRS grant number 5/4/150/5 and FNRS-PDR Convention grant number T.0077.14 awarded to M.-M.D., grant 2018-042 from the Foundation Against Cancer awarded to A.C., and private donations (Ferrero, de Spoelberch). The authors declare no competing financial interests.

Trial Registration Number: N/A.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/humrep/deaa353DOI Listing
April 2021

Cancer survivorship: Reproductive health outcomes should be included in standard toxicity assessments.

Eur J Cancer 2021 Feb 29;144:310-316. Epub 2020 Dec 29.

Edinburgh University Cancer Centre, Edinburgh, UK.

It is well established that cancer and its treatment, whether by chemotherapy, radiotherapy, hormone therapy, or surgery, can adversely impact reproductive function in both women and men. The effects of cancer treatment on reproductive function in both sexes may lead to loss of fertility, sexual desire and function, and hormone deficiency, which results in additional long-term morbidity in more than a third of patients. Given the importance of reproductive function to most people, and the often devastating effect of cancer treatment on it, we propose that proactive assessment of the functional and endocrinological impact of treatment be made a vital component of the assessment of modern cancer treatment, and should be a routine part of discussions with patients before and after treatment, both in trials and in routine care. Reproductive counselling should be proactive and encouraged, as implementation of such counselling has been shown to be beneficial to patient mental health, quality of life, and adherence to treatment. Similarly, efforts should be made to provide more adequate and accurate information to patients, as well as to offer appropriate fertility preservation approaches, which may potentially influence their treatment decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2020.11.032DOI Listing
February 2021

ESHRE guideline: female fertility preservation.

Hum Reprod Open 2020 14;2020(4):hoaa052. Epub 2020 Nov 14.

European Society of Human Reproduction and Embryology, Central Office, Grimbergen, Belgium.

Study Question: What is the recommended management for women and transgender men with regards to fertility preservation (FP), based on the best available evidence in the literature?

Summary Answer: The ESHRE Guideline on Female Fertility Preservation makes 78 recommendations on organization of care, information provision and support, pre-FP assessment, FP interventions and after treatment care. Ongoing developments in FP are also discussed.

What Is Known Already: The field of FP has grown hugely in the last two decades, driven by the increasing recognition of the importance of potential loss of fertility as a significant effect of the treatment of cancer and other serious diseases, and the development of the enabling technologies of oocyte vitrification and ovarian tissue cryopreservation (OTC) for subsequent autografting. This has led to the widespread, though uneven, provision of FP for young women.

Study Design Size Duration: The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 November 2019 and written in English were included in the review.

Participants/materials Setting Methods: Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee.

Main Results And The Role Of Chance: This guideline aims to help providers meet a growing demand for FP options by diverse groups of patients, including those diagnosed with cancer undergoing gonadotoxic treatments, with benign diseases undergoing gonadotoxic treatments or those with a genetic condition predisposing to premature ovarian insufficiency, transgender men (assigned female at birth), and women requesting oocyte cryopreservation for age-related fertility loss.The guideline makes 78 recommendations on information provision and support, pre-FP assessment, FP interventions and after treatment care, including 50 evidence-based recommendations-of which 31 were formulated as strong recommendations and 19 as weak-25 good practice points and 3 research only recommendations. Of the evidence-based recommendations, 1 was supported by high-quality evidence, 3 by moderate-quality evidence, 17 by low-quality evidence and 29 by very low-quality evidence. To support future research in the field of female FP, a list of research recommendations is provided.

Limitations Reasons For Caution: Most interventions included are not well studied in FP patients. As some interventions, e.g. oocyte and embryo cryopreservation, are well established for treatment of infertility, technical aspects, feasibility and outcomes can be extrapolated. For other interventions, such as OTC and IVM, more evidence is required, specifically pregnancy outcomes after applying these techniques for FP patients. Such future studies may require the current recommendations to be revised.

Wider Implications Of The Findings: The guideline provides clinicians with clear advice on best practice in female FP, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in FP.

Study Funding/competing Interests: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. R.A.A. reports personal fees and non-financial support from Roche Diagnostics, personal fees from Ferring Pharmaceuticals, IBSA and Merck Serono, outside the submitted work; D.B. reports grants from Merck Serono and Goodlife, outside the submitted work; I.D. reports consulting fees from Roche and speaker's fees from Novartis; M.L. reports personal fees from Roche, Novartis, Pfizer, Lilly, Takeda, and Theramex, outside the submitted work. The other authors have no conflicts of interest to declare.

Disclaimer: . .  www.eshre.eu/guidelines. ESHRE Pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hropen/hoaa052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666361PMC
November 2020

Efficacy and Safety of Controlled Ovarian Stimulation With or Without Letrozole Co-administration for Fertility Preservation: A Systematic Review and Meta-Analysis.

Front Oncol 2020 7;10:574669. Epub 2020 Oct 7.

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.

The co-administration of letrozole during controlled ovarian stimulation (COS) with gonadotropins is used to limit the potentially harmful effects of a supra-physiological rise in estrogen levels on hormone-sensitive cancers. However, the efficacy and safety of adding letrozole to COS remain debated. This is a systematic review and meta-analysis of published studies that compared the efficacy and safety of COS with co-administration of letrozole vs. COS without letrozole in all patient populations. A secondary analysis was done including only the studies in breast cancer patients. The primary efficacy endpoint was the number of retrieved mature Metaphase II (MII) oocytes. Secondary efficacy and safety endpoints were total number of oocytes, maturation rate, fertilization rate, number of cryopreserved embryos, peak estradiol levels, progesterone levels, and total gonadotropin dose. Data for each endpoint were reported and analyzed thorough mean ratio (MR) with 95% confidence interval (CI). A total of 11 records were selected including 2,121 patients (990 patients underwent COS with letrozole and 1,131 COS without letrozole). The addition of letrozole to COS did not have any negative effect on the number of mature oocytes collected (MR = 1.00, 95% CI = 0.87-1.16; = 0.967) and the other efficacy endpoints. COS with letrozole was associated with significantly decreased peak estradiol levels (MR = 0.28, 95% CI = 0.24-0.32; < 0.001). Similar results were observed in the secondary analysis including only breast cancer patients. These findings are reassuring on the efficacy and safety of COS with gonadotropins and letrozole and are particularly important for fertility preservation in women with hormone-sensitive cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.574669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575927PMC
October 2020

Implications of Nonphysiological Ovarian Primordial Follicle Activation for Fertility Preservation.

Endocr Rev 2020 12;41(6)

Research Laboratory in Human Reproduction, Université Libre de Bruxelles, Brussels, Belgium.

In recent years, ovarian tissue cryopreservation has rapidly developed as a successful method for preserving the fertility of girls and young women with cancer or benign conditions requiring gonadotoxic therapy, and is now becoming widely recognized as an effective alternative to oocyte and embryo freezing when not feasible. Primordial follicles are the most abundant population of follicles in the ovary, and their relatively quiescent metabolism makes them more resistant to cryoinjury. This dormant pool represents a key target for fertility preservation strategies as a resource for generating high-quality oocytes. However, development of mature, competent oocytes derived from primordial follicles is challenging, particularly in larger mammals. One of the main barriers is the substantial knowledge gap regarding the regulation of the balance between dormancy and activation of primordial follicles to initiate their growing phase. In addition, experimental and clinical factors also affect dormant follicle demise, while the mechanisms involved remain largely to be elucidated. Moreover, most of our basic knowledge of these processes comes from rodent studies and should be extrapolated to humans with caution, considering the differences between species in the reproductive field. Overcoming these obstacles is essential to improving both the quantity and the quality of mature oocytes available for further fertilization, and may have valuable biological and clinical applications, especially in fertility preservation procedures. This review provides an update on current knowledge of mammalian primordial follicle activation under both physiological and nonphysiological conditions, and discusses implications for fertility preservation and priorities for future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/endrev/bnaa020DOI Listing
December 2020

Fertility preservation counselling for childhood cancer survivors.

Lancet Oncol 2020 03 14;21(3):329-330. Epub 2020 Feb 14.

Haematology Oncology Unit, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(20)30065-6DOI Listing
March 2020

Interaction between PI3K/AKT and Hippo pathways during in vitro follicular activation and response to fragmentation and chemotherapy exposure using a mouse immature ovary model.

Biol Reprod 2020 03;102(3):717-729

Research Laboratory on Human Reproduction, Université Libre de Bruxelles, Brussels, Belgium.

Understanding and control of the massive and accelerated follicular growth that occurs during in vitro culture of ovarian tissue is a crucial step toward the development of efficient culture systems that offer an attractive alternative to ovarian tissue transplantation for fertility restoration in cancer survivors. One outstanding question focuses on processes that occur prior to cryopreservation, such as tissue sectioning or chemotherapeutic treatment, might exacerbate this follicular activation. Although the PI3K/AKT/mTOR pathway is well known as a major trigger of physiological and chemotherapy-induced follicular activation, studies have shown that disruption of Hippo pathway due to ovarian fragmentation acts as an additional stimulator. This study aimed to characterize the possible interactions between these pathways using post-natal day 3 mouse ovaries cultured for 4 or 48 h. Morphology, gene transcription, and protein levels were assessed to investigate the impact of sectioning or chemotherapy exposure (4-hydroperoxycyclophosphamide [4HC], 3 and 20 μM). The effect of an mTORC1 inhibitor, Everolimus, alone or as a 4HC co-treatment to prevent follicle activation was evaluated. The results showed that organ removal from its physiological environment was as effective as sectioning for disruption of Hippo pathway and induction of follicle activation. Both PI3K/AKT/mTOR and Hippo pathways were involved in chemotherapy-induced follicular activation and responded to fragmentation. Surprisingly, Everolimus was able to prevent the activation of both pathways during chemotherapy exposure, suggesting cross-talk between them. This study underscores the major involvement of PI3K/AKT/mTOR and Hippo pathways in in vitro follicle activation and provides evidence that both can be regulated using mTORC1 inhibitor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/biolre/ioz215DOI Listing
March 2020

Oncofertility: Pharmacological Protection and Immature Testicular Tissue (ITT)-Based Strategies for Prepubertal and Adolescent Male Cancer Patients.

Int J Mol Sci 2019 Oct 21;20(20). Epub 2019 Oct 21.

Research Laboratory in Human Reproduction, Faculty of Medicine, Université Libre de Bruxelles (ULB), B-1070 Brussels, Belgium.

While the incidence of cancer in children and adolescents has significantly increased over the last decades, improvements made in the field of cancer therapy have led to an increased life expectancy for childhood cancer survivors. However, the gonadotoxic effect of the treatments may lead to infertility. Although semen cryopreservation represents the most efficient and safe fertility preservation method for males producing sperm, it is not feasible for prepubertal boys. The development of an effective strategy based on the pharmacological protection of the germ cells and testicular function during gonadotoxic exposure is a non-invasive preventive approach that prepubertal boys could benefit from. However, the progress in this field is slow. Currently, cryopreservation of immature testicular tissue (ITT) containing spermatogonial stem cells is offered to prepubertal boys as an experimental fertility preservation strategy by a number of medical centers. Several in vitro and in vivo fertility restoration approaches based on the use of ITT have been developed so far with autotransplantation of ITT appearing more promising. In this review, we discuss the pharmacological approaches for fertility protection in prepubertal and adolescent boys and the fertility restoration approaches developed on the utilization of ITT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20205223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834329PMC
October 2019

Answer to Controversy: miR-10a Replacement Approaches Do Not Offer Protection against Chemotherapy-Induced Gonadotoxicity in Mouse Model.

Int J Mol Sci 2019 Oct 8;20(19). Epub 2019 Oct 8.

Research Laboratory on Human Reproduction, Université Libre de Bruxelles (ULB), 808 Route de Lennik, 1070 Brussels, Belgium.

It is well known that chemotherapeutic agents may lead to premature ovarian failure and infertility. Therefore, fertility preservation is highly recommended for female cancer survivors. Despite the currently available techniques, new, non-invasive methods need to be developed to protect the ovarian follicles during oncological treatments. MicroRNAs can be effective tools in this field, as they alter their expression during chemotherapy exposure, and hence they can be useful to minimize the off-target toxicity. Previously, we identified several miRNAs with an important role in newborn mouse ovaries exposed to chemotherapy; among them, the miR-10a was one of the most downregulated miRNAs. Given the controversial role of miR-10a in the ovarian function, we decided to investigate its implication in chemotherapy-induced gonadotoxicity. The downregulated levels of miR-10a were restored by a liposome system conjugated with a mimic miR-10a, and the overexpressed miR-10a prevented the upregulation of the targeted gene, phosphatase and tensin homolog (). The apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) Assay and expression quantification, while histological studies were also performed to evaluate the follicle count and development. Our results showed that the miR-10a replacement could not protect the ovaries from chemotherapy-induced apoptosis, whereas the targeting of may affect the follicle activation via the phosphoinositide 3-kinase (PI3K)/PTEN/protein kinase B (AKT) pathway. Consequently, the application of miR-10a in fertility preservation is not recommended, and the role of miR-10a needs to be further elucidated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20194958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801898PMC
October 2019

Impact of Taxanes, Endocrine Therapy, and Deleterious Germline Mutations on Anti-müllerian Hormone Levels in Early Breast Cancer Patients Treated With Anthracycline- and Cyclophosphamide-Based Chemotherapy.

Front Oncol 2019 12;9:575. Epub 2019 Jul 12.

Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.

Limited evidence exists on the impact of adding a taxane, using endocrine therapy and carrying a deleterious germline mutation on ovarian reserve measured by anti-müllerian hormone (AMH) levels of young breast cancer patients receiving (neo)adjuvant cyclophosphamide- and anthracycline-based chemotherapy. This is a biomarker analysis including young (≤ 40 years) early breast cancer patients with known germline mutational status and available prospectively collected frozen plasma samples before and after chemotherapy. Chemotherapy consisted of either six cycles of FEC (5 fluorouracil 500 mg/m, epirubicin 100 mg/m, cyclophosphamide 500 mg/m) or three cycles of FEC followed by three cycles of docetaxel (D, 100 mg/m). Endocrine therapy consisted of tamoxifen (±GnRH agonists). AMH levels at baseline, 1 and 3 years after diagnosis were compared according to type of chemotherapy (FEC only vs. FEC-D), use of endocrine therapy (yes vs. no) and deleterious germline mutations (mutated vs. negative). Out of 148 included patients, 127 (86%) received D following FEC chemotherapy, 90 (61%) underwent endocrine therapy, and 35 (24%) had deleterious germline mutations. In the whole cohort, AMH levels drastically dropped 1 year after diagnosis ( < 0.0001) with a slight but significant recovery at 3 years ( < 0.0001). One year after diagnosis, patients treated with FEC only had higher median AMH levels than those who received FEC-D (0.22 vs. 0.04 μg/L, = 0.0006); no difference was observed at 3 years (0.06 and 0.18 μg/L, = 0.47). Patients under endocrine therapy had significantly higher AMH levels than those who did not receive this treatment 1 year after diagnosis (0.12 vs. 0.02 μg/L; = 0.008), with no difference at 3 years (0.11 and 0.20 μg/L, = 0.22). AMH levels were similar between -mutated and -negative patients at baseline (1.94 vs. 1.66 μg/L, = 0.53), 1 year (0.09 vs. 0.06 μg/L, = 0.39) and 3 years (0.25 vs. 0.16 μg/L; = 0.43) after diagnosis. In breast cancer patients receiving FEC chemotherapy, adding D appeared to negatively impact on their ovarian reserve in the short-term; no further detrimental effect was observed for endocrine therapy use and presence of a deleterious germline mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.00575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640206PMC
July 2019

Knowledge, attitudes and practice of physicians towards fertility and pregnancy-related issues in youngBRCA-mutated breast cancer patients.

Reprod Biomed Online 2019 May 10;38(5):835-844. Epub 2019 Jan 10.

Fertility Clinic, Research Laboratory on Human Reproduction, CUB-Erasme and Université Libre de Bruxelles, Brussels, Belgium.

Research Question: This study explored the knowledge, attitudes and practice of physicians towards fertility and pregnancy-related issues in young BRCA-mutated breast cancer patients.

Design: Physicians attending two international breast cancer conferences completed a 26-item questionnaire exploring fertility preservation, pregnancy during (BCP) or after breast cancer. A statistical comparison was carried out of the responses exploring the same issues in young breast cancer patients overall or specifically in those with BRCA mutations.

Results: The survey was completed by 273 physicians. Ovarian tissue cryopreservation (33% versus 40%; P = 0.009) and gonadotrophin-releasing hormone analogues during chemotherapy (74% versus 81%; P = 0.001) were less commonly suggested in BRCA-mutated patients than in the overall breast cancer population. 42% of respondents agreed or were neutral on the statement that ovarian stimulation should not be considered safe in BRCA-mutated breast cancer patients. 45% and 30% agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence in BRCA-mutated patients or in the overall breast cancer population, respectively (P < 0.001). 15% and 3% disagreed that transplanting the cryopreserved ovarian tissue can be considered safe in BRCA-mutated patients or in the overall breast cancer population, respectively (P < 0.001). 33.3% were against the addition of platinum agents as neoadjuvant chemotherapy in BRCA-mutated patients with BCP.

Conclusions: Several misconceptions on fertility preservation and pregnancy-related issues in breast cancer patients persist even among physicians directly involved in breast cancer care. Focused research efforts to address these issues in BRCA-mutated breast cancer patients and education to improve physicians' knowledge and adherence to available guidelines are urgently needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2018.11.031DOI Listing
May 2019

Fertility, sexuality and cancer in young adult women.

Curr Opin Oncol 2019 07;31(4):259-267

Fertility Clinic for a Sexual Health Program, Center for Cancer Prevention and Genetics, Dana-Farber Cancer Institute.

Purpose Of Review: To provide an up-to-date overview on indications, efficacy and safety of the existing fertility preservation strategies as well as on the features and management of sexual dysfunction in young adult women with newly diagnosed cancer.

Recent Findings: Because of the improved life expectancy of cancer survivors, a growing attention should be given to the side effects of anticancer treatments. Among young cancer patients, risk of infertility and sexual dysfunction are of great concern.

Summary: As advocated by guidelines, patients need to be thoroughly informed of potential side effects of treatment before starting them. On this regard, efforts should be made to improve the counseling of young adult patients around fertility and sexuality. Fertility preservation strategies should be properly and extensively explained to all young patients, weighting the pros and cons to choose the more appropriate options for each situation. In addition, discussing sexual dysfunction and delivering sexual rehabilitation for cancer survivors not only allows for renewal of sexual function but can also promote increased quality of life and help women create a new and satisfying chapter in their life for many years after cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCO.0000000000000540DOI Listing
July 2019

Oncofertility counselling in premenopausal women with HER2-positive breast cancer.

Oncotarget 2019 Jan 29;10(9):926-929. Epub 2019 Jan 29.

Department of Medical Oncology, Institut Jules Bordet and Université Libre de Bruxelles, Brussels, Belgium.

A complete oncofertility counselling should be offered to all premenopausal patients before the administration of anticancer treatments. This important discussion is a crucial step for allowing them to take fully informed decisions about the proposed therapy and its potential long-term consequences as well as on their need and interest of accessing the available strategies for ovarian function and/or fertility preservation. In premenopausal women with HER2-positive early breast cancer, limited evidence exists to counsel them about the potential added gonadotoxicity of targeted agents beyond the damage already caused by chemotherapy. In addition, the prognostic role of treatment-induced amenorrhea in this setting was unknown. In our exploratory analysis within the ALTTO (BIG 2-06) trial, we have recently described the rates of treatment-induced amenorrhea after chemotherapy plus trastuzumab and/or lapatinib and the prognostic value of developing this side effect according to the hormone receptor status of their tumours. We observed similar rates of treatment-induced amenorrhea in the four anti-HER2 treatment arms. The lack of an increased rate of treatment-induced amenorrhea in the dual anti-HER2 blockade arm suggests the possible gonadal safety of these agents. In addition, women with HER2-positive/hormone receptor-positive tumours showed significantly better survival outcomes if they developed treatment-induced amenorrhea, while no difference was observed for those with HER2-positive/hormone receptor-negative disease. Future research efforts are needed to address the gonadotoxicity of the new available targeted agents as well as to elucidate which is the best adjuvant endocrine therapy in premenopausal women with HER2-positive/hormone receptor-positive disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.26565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398182PMC
January 2019

Fertility and hormone preservation and restoration for female children and adolescents receiving gonadotoxic cancer treatments: A systematic review.

J Pediatr Surg 2019 Nov 22;54(11):2200-2209. Epub 2019 Jan 22.

Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Division of Pediatric Surgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. Electronic address:

Background/purpose: The purpose of this systematic review by the American Pediatric Surgical Cancer Committee was to summarize evidence from the current medical literature regarding fertility restoration and hormone replacement for female children and adolescents treated with gonadotoxic treatments.

Methods: Using PRISMA guidelines, questions were addressed by searching Medline, Cochrane, Embase Central and National clearing house databases using relevant search terms. Eligible studies included those that addressed ovarian tissue cryopreservation (OTC), oocyte harvest, ovarian transposition, and ovarian tissue auto-transplantation for females under the age of 20. Four reviewers independently screened studies for eligibility, extracted data and assessed the risk of bias. Study outcomes were summarized in a narrative synthesis.

Results: Two thousand two hundred seventy-six studies were identified by database search and manual review and 2185 were eliminated based on defined exclusion criteria. Ninety-one studies served as the basis for the systematic review. There were 1019 patients who underwent OTC with ages ranging from 0.4 to 20.4 years old, with 298 under the age of 13. Twenty patients aged 13-20 years old underwent successful oocyte harvest. Thirty-seven children underwent ovarian transposition as a means of fertility preservation. Eighteen patients underwent auto-transplantation of thawed ovarian cortical tissue that was harvested before the age of 21 years resulting in 10 live births.

Conclusions: Clinically accepted and experimental fertility preservation options such as OTC, oocyte cryopreservation, and ovarian transposition are available to females aged 20 years and younger who are at risk for premature ovarian insufficiency and infertility due to gonadotoxic treatments. There is a large cohort of pediatric-aged patients, with a wide variety of diagnoses and treatments, who have undergone fertility preservation. Currently, fertility and hormone restoration experience for patients who were 20- years of age or younger at the time of fertility preservation remains limited.

Level Of Evidence: IV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpedsurg.2018.12.021DOI Listing
November 2019

Challenges of fertility preservation in non-oncological diseases.

Acta Obstet Gynecol Scand 2019 05 12;98(5):638-646. Epub 2019 Mar 12.

Research Laboratory on Human Reproduction and Fertility Clinic, CUB-Erasme, Université Libre de Bruxelles, Brussels, Belgium.

Clinicians should provide fertility counseling to all patients receiving gonadotoxic treatment. International scientific societies have mainly focused on oncological patients, and fewer efforts have been made to apply these recommendations to women diagnosed with benign disease (eg benign hematological diseases, autoimmune diseases, and gynecological or genetic disorders). However, these indications account for 8%-13% of the demand for fertility preservation. The risk of premature ovarian failure due to treatment, or to the disease itself, can be considered fairly high for many young women. Counseling and adequate management of these women require particular attention due to the severe health conditions that are associated with some of these diseases. In this review, we address specific issues related to providing adequate fertility counseling and management for women who have been diagnosed with the major non-oncological indications, based on the literature and on our clinical experience.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aogs.13577DOI Listing
May 2019

Letrozole-associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients: assessment of oocyte quality related biomarkers.

Reprod Biol Endocrinol 2019 Jan 3;17(1). Epub 2019 Jan 3.

Fertility Clinic, Department of Obstetrics and Gynecology, CUB-Hôpital Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, Brussels, Belgium.

Background: Fertility preservation (FP) protocols in case of breast cancer (BC) include mature oocyte cryopreservation following letrozole associated controlled ovarian hyperstimulation (Let-COH). To date, the impact of Let-COH on the follicular microenvironment has been poorly investigated, although a high androgen/estrogen ratio was previously associated with low oocyte quality.

Methods: In this prospective study, follicular fluid (FF) steroid levels (estradiol, testosterone, progesterone) and cumulus cell (CC) gene expression related to oocyte quality (HAS2, PTGS2, GREM1) were compared between 23 BC patients undergoing Let-COH for FP and 24 infertile patients undergoing conventional COH without letrozole. All patients underwent an antagonist COH cycle, and ovulation was triggered with hCG or GnRHa in both groups.

Results: FF estradiol levels were significantly lower while testosterone levels were significantly higher in the study group compared to controls irrespective of the trigger method. However, estradiol levels increased significantly with GnRHa triggering compared to hCG in the study group (median = 194.5 (95.4-438) vs 64.4 (43.8-152.4) ng/ml, respectively, p < 0.001), but not in the control group (median = 335.5 (177.5-466.7) vs 354 (179-511) ng/ml, respectively). After hCG trigger, Cumulus cell (CC) gene expression was lower in the study group compared to the control group, and difference was significant for PTGS2. Conversely, CC gene expression of PTGS2 and GREM1 was significantly higher in the study group compared to controls when ovulation was triggered with GnRHa.

Conclusions: Let-COH triggered with hCG may negatively impact oocyte quality. However, ovulation triggering with GnRHa may improve the oocyte microenvironment and cumulus cell genes expression in Let-COH, suggesting a positive impact on oocyte quality in breast cancer patients.

Trial Registration: Clinicaltrials.gov - NCT02661932 , registered 25 January 2016, retrospectively registered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12958-018-0443-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318989PMC
January 2019

Ovarian protection with gonadotropin-releasing hormone agonists during chemotherapy in cancer patients: From biological evidence to clinical application.

Cancer Treat Rev 2019 Jan 1;72:65-77. Epub 2018 Dec 1.

Fertility Clinic, CUB-Hôpital Erasme and Research Laboratory on Human Reproduction, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.

Survivorship issues are an area of crucial importance to be addressed as early as possible by all health care providers dealing with cancer patients. In women diagnosed during their reproductive years, the possible occurrence of chemotherapy-induced premature ovarian insufficiency (POI) is of particular concern being associated with important menopause-related symptoms, psychosocial issues as well as infertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy has been studied to reduce the gonadotoxic impact of chemotherapy thus diminishing the chance of developing POI. Despite more than 30 years of research in both preclinical and clinical settings, the performance of this strategy has remained highly debated until recently. In particular, the potential mechanisms of action for the protective effects of GnRHa during chemotherapy are still not clearly identified. Nevertheless, important novel research efforts in the field have better elucidated the role of this option that is now endorsed for clinical use by several guidelines. This manuscript aims at providing an extensive overview of the literature on the use of temporary ovarian suppression with GnRHa during chemotherapy in cancer patients by addressing its biological rationale, the available preclinical and clinical evidence as well as the still existing grey zones in this field that future research efforts should address.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctrv.2018.11.006DOI Listing
January 2019

Another step towards improving oncofertility counselling of young women with Hodgkin's lymphoma.

Lancet Oncol 2018 10 13;19(10):1264-1266. Epub 2018 Sep 13.

Research Laboratory on Human Reproduction, Fertility Clinic, CUB-Hôpital Erasme, Université Libre de Bruxelles, Brussels 1000, Belgium.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(18)30562-XDOI Listing
October 2018

The BCY3/BCC 2017 survey on physicians' knowledge, attitudes and practice towards fertility and pregnancy-related issues in young breast cancer patients.

Breast 2018 Dec 22;42:41-49. Epub 2018 Aug 22.

Fertility and Procreation Unit, Gynecologic Oncology Department, IRCCS European Institute of Oncology, European School of Oncology (ESO), Milan, Italy.

Background: Fertility and pregnancy-related issues are major concerns for young breast cancer patients. Limited data are available on physicians' knowledge, attitudes and practice in these fields.

Methods: A 26-item questionnaire exploring 3 different topics (fertility preservation, pregnancy after breast cancer and breast cancer during pregnancy) was sent by email to physicians attending the 2016 3rd European School of Oncology (ESO) - European Society for Medical Oncology (ESMO) Breast Cancer in Young Women Conference (BCY3) and the 15th St. Gallen International Breast Cancer Conference 2017 (BCC 2017). Given the selected sample, survey respondents were expected to have a higher than average interest in the management of breast cancer patients. Descriptive analyses were performed.

Results: A total of 273 physicians (105 at BCY3 and 168 at BCC 2017) completed the survey; 37.0%, 46.9% and 34.8% reported never having consulted the available international guidelines on fertility preservation, pregnancy after breast cancer and management of breast cancer during pregnancy, respectively. Up to 18.3% of respondents did not know if the different fertility preservation options were available in their country; 22.3% suggested that controlled ovarian stimulation should not be considered safe in patients with hormone receptor-positive disease. A total of 30.4% of respondents agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence. Regarding breast cancer during pregnancy, 23.8% and 38.1% disagreed or were neutral on the statements that endocrine therapy and anti-HER2 agents should be avoided during pregnancy, respectively.

Conclusions: Further educational initiatives are needed to improve physicians' knowledge and adherence to available guidelines when addressing fertility and pregnancy-related issues in young breast cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.breast.2018.08.099DOI Listing
December 2018

Fertility and pregnancy issues in BRCA-mutated breast cancer patients.

Cancer Treat Rev 2017 Sep 14;59:61-70. Epub 2017 Jul 14.

Fertility Clinic, Research Laboratory on Human Reproduction, CUB-Erasme, and Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.

Fertility and pregnancy-related issues represent one of the main areas of concerns for young women with breast cancer. Carrying a germline deleterious BRCA mutation adds additional burden on this regard due to the specific issues that should be considered during the oncofertility counseling of this special patient group. Despite the availability of a growing amount of data in the general breast cancer population on the feasibility and safety of fertility preservation and pregnancy after diagnosis, numerous challenges remain for BRCA-mutated breast cancer patients in whom very limited studies have been performed so far. Therefore, studies aiming to address the specific issues of these patients, including the impact of the mutation on their fertility potential, the safety and efficacy of the different strategies for fertility preservation, and the feasibility of having a pregnancy after diagnosis, should be considered a research priority. The aim of the present manuscript is to perform an in depth overview on the role of BRCA mutations in breast cancer with a specific focus on their impact on reproductive potential, and to discuss the fertility and pregnancy issues faced by BRCA-mutated breast cancer patients. The final goal of this manuscript is to highlight current and upcoming knowledge in this field for trying to help physicians dealing with these patients during oncofertility counseling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctrv.2017.07.001DOI Listing
September 2017

Controversies about fertility and pregnancy issues in young breast cancer patients: current state of the art.

Curr Opin Oncol 2017 Jul;29(4):243-252

aMedical Oncology Clinic bBreast Cancer Translational Research Laboratory, Institut Jules Bordet, l'Université Libre de Bruxelles (U.L.B.) cFertility Clinic, Research Laboratory on Human Reproduction Erasme, and l'Université Libre de Bruxelles (U.L.B.), Brussels, Belgium dMedical Oncology and IRON/U1245, Centre Henri Becquerel, Rouen, France.

Purpose Of Review: For trying to help physicians in counseling their young patients with breast cancer interested in fertility preservation and future reproductive plans, this manuscript aims to perform an overview of the main available data on 10 controversies in this field.

Recent Findings: Thanks to the improvement in patients' prognosis, a growing attention towards fertility and pregnancy issues has been given over the past years and is currently provided to young breast cancer patients. However, several grey zones persist in many domains of this field and some physicians are still uncomfortable to deal with these issues.

Summary: Despite the great number of breast cancer patients experiencing fertility and pregnancy concerns at the time of diagnosis, the pursuit of fertility preserving strategies is realized only for a small proportion of them. The lack of adequate oncofertility counseling at the time of anticancer treatment decisions and the high costs of fertility preserving procedures can be considered the main explanations for these findings. The several ongoing registries and prospective studies investigating fertility and pregnancy issues in young breast cancer patients are crucial to acquire more robust data and try to address and solve the still unmet controversies in this field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCO.0000000000000380DOI Listing
July 2017

Viable Options for Fertility Preservation in Breast Cancer Patients: A Focus on Latin America.

Rev Invest Clin 2017 Mar-Apr;69(2):103-113

Breast Cancer Centre, Zambrano Hellion Hospital, Tecnologico de Monterrey, Monterrey, NL, Mexico.

Thanks to the improved survival outcomes observed in recent years, a growing attention has been given to the quality of life issues faced by young women with breast cancer such as fertility preservation and concerns related to future pregnancies. However, several challenges remain for young women with breast cancer considering undergoing fertility preservation strategies. Further specific issues on this regard should be taken into account in Latin America, where patients and physicians face particular barriers that hinder the routine adoption of this practice. Hence, further efforts are needed to overcome these deficiencies and improve the correct referral of breast cancer patients to fertility preservation strategies. The aim of the present review is to focus on the risk of anticancer treatment-related premature ovarian failure and infertility in young breast cancer patients, to summarize the current knowledge on the available options for fertility preservation, and to discuss the safety issues of pregnancy in breast cancer survivors. Furthermore, this review aims to highlight the specific clinical challenges in this field encountered by healthcare providers and young breast cancer patients from Latin American countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.24875/ric.17002179DOI Listing
December 2017

Outcomes of immature oocytes collected from ovarian tissue for cryopreservation in adult and prepubertal patients.

Reprod Biomed Online 2017 Jun 20;34(6):575-582. Epub 2017 Mar 20.

Research Laboratory on Human Reproduction, Campus Erasme, Université Libre de Bruxelles (ULB), Belgium; Fertility Clinic, Department of Obstetrics and Gynecology, CUB-Erasme Hospital, Université Libre de Bruxelles (ULB), Belgium.

The efficiency of oocyte in-vitro maturation (IVM) and vitrification procedures after ex-vivo collection from ovarian tissue were assessed according to patient age, number of retrieved oocytes and tissue transport conditions. The combined procedure was performed in 136 patients: 130 adults (mean 27.6 ± 5.6 years) and six prepubertal girls (mean 8.7 ± 2.3 years). A higher mean number of oocytes were collected in girls compared with adults (11.5 ± 8.0 versus 3.8 ± 4.2, respectively, P < 0.001) but the percentage of degenerated oocytes was significantly higher in girls (35.5% versus 17.1%, respectively, P < 0.001). IVM rates were significantly lower in prepubertal than postpubertal population (10.3% versus 28.1%, P = 0.002). In adults, a negative correlation was observed between number of retrieved oocytes and age (P = 0.002; r = -0.271); the correlation was positive between anti-Müllerian hormone (AMH) and number of collected oocytes (P = 0.002; r = 0.264). IVM rates were not correlated with AMH levels (r = 0.06) or age (r = -0.033). At present, nine oocytes and one embryo have been warmed in four patients and one biochemical pregnancy obtained. This suggests the combined procedure could be an additional option for fertility preservation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2017.03.007DOI Listing
June 2017

Reply to M. Lambertini et al.

J Clin Oncol 2017 03 28;35(7):805-806. Epub 2016 Nov 28.

Isabelle Demeestere, Research Laboratory on Human Reproduction, Université Libre de Bruxelles, Brussels, Belgium; Pauline Brice, St Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Fedro A. Peccatori, European Institute of Oncology, Milan, Italy; Alain Kentos, Jolimont Hospital, Haine-Saint-Paul, Belgium; Jehan Dupuis, Henri Mondor Hospital, Paris, France; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerp, Belgium; Rene-Olivier Casasnovas, Centre Hospitalier Universitaire Dijon, Dijon, France; Eric Van Den Neste, Cliniques Universitaires Université Catholique de Louvain Saint-Luc, Brussels, Belgium; Julie Dechene, Research Laboratory on Human Reproduction, Université Libre de Bruxelles, Brussels, Belgium; Viviane De Maertelaer, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Belgium; Dominique Bron, J. Bordet Institute, Brussels, Belgium; and Yvon Englert, Research Laboratory on Human Reproduction, Université Libre de Bruxelles, and Erasme Hospital, Brussels, Belgium.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2016.70.6093DOI Listing
March 2017

Does oocyte donation compared with autologous oocyte IVF pregnancies have a higher risk of preeclampsia?

Reprod Biomed Online 2017 Jan 14;34(1):11-18. Epub 2016 Oct 14.

Fertility Clinic, Department of Obstetrics and Gynecology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.

The aim of this study was to evaluate whether pregnancies resulting from oocyte donation have a higher risk of preeclampsia compared with pregnancies after IVF using autologous oocytes. Propensity score matching on maternal age and parity was carried out on a one to one basis, and a total of 144 singleton pregnancies resulting in delivery beyond 22 gestational weeks, achieved by oocyte donation, were compared with 144 pregnancies achieved through IVF and intracytoplasmic sperm injection with the use of autologous oocytes. All pregnancies were achieved after fresh embryo transfer. Obstetric and neonatal outcomes were compared for each pregnancy. Singleton pregnancies after oocyte donation were associated with a significantly higher risk for preeclampsia (OR 2.4, CI 1.02 to 5.8; P = 0.046), as well as for pregnancy-induced hypertension (OR 5.3, CI 1.1 to 25.2; P = 0.036), and caesarean delivery (OR 2.3, CI 1.4 to 3.7; P = 0.001) compared with pregnancies using autologous oocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2016.10.002DOI Listing
January 2017

Assessment of ovarian reserve and fertility preservation strategies in children treated for cancer.

Minerva Ginecol 2017 Feb 27;69(1):57-67. Epub 2016 Oct 27.

Research Laboratory on Human Reproduction, Université Libre de Bruxelles, Brussels, Belgium -

Introduction: The survival rate of chemotherapy treatments of malignant cancer or non-malignant conditions are continuously improving. As a result, there is an increased number of patients who received a gonadotoxic treatment during childhood and who later face fertility issues. Depending on the extent of the damage to the ovaries, acute or late complications may occur. Acute ovarian failure is defined by permanent amenorrhea after a high-risk treatment. When the drugs used are less gonadotoxic, ovarian insufficiency might appear later. This literature review will review both the current solutions for management of high-risk patients and the care options for low and medium risk patients.

Evidence Acquisition: For each patient the risk of premature ovarian insufficiency should be evaluated individually before treatment. Guidelines clearly recommend to preserve fertility of high-risk group before treatment, but questions remain about the future counselling of patients with low or moderate risk.

Evidence Synthesis: Demand for fertility preservation methods has greatly increased. In this context, studies focusing on the best fertility preservation methods for patients, either before chemotherapy for the high-risk group or during the follow-up for the others, are essential. For the high-risk group, ovarian tissue cryopreservation is the only option for prepubertal girls. For postpubertal girls, oocytes vitrification could also be offered.

Conclusions: The risk of premature ovarian failure must be evaluated for each patient treated with gonadotoxic therapies. Fertility preservation must be offered in high-risk patients and appropriate follow-up should be proposed to anticipate later fertility issue in low and medium risk patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0026-4784.16.03992-7DOI Listing
February 2017