Oncofertility in adolescent and young adult hereditary cancer: Considerations for genetics professionals

Adolescents and young adults(AYA)with a cancer diagnosis or those at risk for cancer due to hereditary cancer syndromes may benefit from genetic counseling and testing not only to manage personal risk but also to address reproductive concerns,especially fertility.The opportunity for genetic counselors to provide important risk information is relevant to both the newly diagnosed as well as to unaffected carriers and survivors.However,genetic counselors may need additional training in reproductive options related to AYA cancer to provide this valuable counsel.This commentary uses hereditary breast and ovarian cancer syndrome as a model to highlight important considerations when discussing preimplanatation genetic diagnosis and prenatal diagnosis,particularly in the context of expanded testing for hereditary cancer risk including multigene panels or whole exome or whole genome sequencing.Other hereditary cancers are also addressed;however,less is known about the psychosocial and fertility concerns in these AYA populations.Additionally,we provide an overview of the concept of"oncofertility"-the linkage between cancer care and reproductive medicine that aims to expand the reproductive opportunities of cancer patients-and offer support for the expansion of guidelines to include genetic counselors in AYA cancer patients’treatment planning related to reproductive health and fertility.

Oncofertility:Treatment options from bench to bedside

In recent years,there has been continuous improvement in the treatment and diagnosis of cancer,which has led to a significant improvement in the survival rate of cancer patients.Treatments that include chemotherapy,radiotherapy,surgery,or combined therapy have several side effects that may lead to premature ovarian insufficiency in females or substantial male germ cell loss.Reproductive biologists recommend that all patients who are diagnosed with a malignant tumor must undergo a consultation for fertility protection and preservation.In this review,we discuss the background knowledge,methods,and options for fertility preservation and how these new strategies help oncologists,surgeons,pediatricians,and hematologists,conserve fertility and be aware of the concepts,methods,and importance of fertility guards.This review may aid in the advancement of novel personalized methods for fertility preservation according to patients’conditions.

Case Report <i>ex Vivo</i>Oocyte Collection to Maintain Fertility in a Patient with Micropapillary Serous Borderline Ovarian Tumor

Background: Approximately 11% of cancer cases are diagnosed in people of childbearing age. Borderline ovarian tumors (BOTs) make up 10%-15% of all ovarian epithelial malignancies. More than one-third of all BOTs occur in women under 40 years of age. Maintaining the fertility of cured patients is the common goal of both oncologists and reproductologists. Aim: Giving young women diagnosed with a prognostically worse type of BOT and after bilateral adnexectomy the possibility to have their genetically own children by the method of ex vivo oocyte collection. Case Presentation: A 34-year-old nulligravid woman with BOT underwent right laparoscopic salpingo-oophorectomy. Histologically, a serious borderline tumor with a micropapillary pattern and a tumor locus on the ovarian surface were found. Due to histopathology, the oncologist recommended re-staging surgery: laparotomy, left salpingo-oophorectomy, omentectomy and hysterectomy. The patient refused a hysterectomy as she was planning to get pregnant with her partner. To maintain her fertility, controlled hormonal hyperstimulation and ex vivo aspiration of follicles from the ovary after salpingo-oophorectomy was performed. Ex vivo follicle expiration yielded 10 oocytes. 9 mature oocytes were fertilized by ICSI. The 6 embryos of the highest quality were individually frozen by vitrification. Cryoembryotransfer will be scheduled with the consent of the oncologist. Conclusion: This method is suitable for young women with BOT after bilateral salpingo-oophorectomy in whom ex vivo oocyte collection prevents possible leakage of tumor cells into the abdominal cavity, unlike during the conventional in vivo collection prior to surgery.

The effect of different cancer therapies on clinical outcomes of assisted reproductive technology in breast cancer patients

Objective To evaluate the clinical outcomes of assisted reproductive technology(ART)on fertility preservation and infertility treatment in breast cancer patients who had undergone different cancer therapies.Methods 20 infertile females who had undergone breast cancer treatments during 2011–2018 were studied retrospectively.The patients were divided into two groups based on their cancer treatment methods and their needs of fertility preservation:the combined treatment group,who had both breast cancer surgery combining with any of the three treatments(adjuvant endocrine therapy,radiotherapy or chemotherapy),and the surgery only group.A group of infertile females without breast cancer history were used as a control group.An aromatase inhibitor Letrozole-based ovarian micro-stimulation protocol was used in females from the three groups for in vitro fertilization and embryo transfer.The ART clinical outcomes were evaluated by using the parameters of antral follicle count(AFC),the ratio of FSH/LH,oocyte retrieval number,2 pronucleus(2 PN)fertilization rate,high-quality embryo rate,clinical pregnancy rate,and delivery outcome.Results The surgery only group had significantly lower ratio of FSH/LH than the combined treatment group and the control group.No significant difference on the ART clinical outcomes,evaluated by the aforementioned criteria,were found between the three groups.Conclusions Breast cancer surgery with adjuvant therapies,but not surgery alone,may damage ovarian function.The best time-limited window to preserve fertility for breast cancer patients is after surgery but before the initiation of adjuvant therapies.Importantly,the clinical outcomes of aromatase inhibitor-based ovary micro-stimulation in breast cancer patients are similar to that in non-breast cancer controls.