The review covers current options for ovarian tissue cryopreservation and transplantation and provides a systematic review of the existing literature from the last 10 years, taking into account all previously published reviews on the subject. The different cryopreservation options available for fertility preservation in cancer patients are embryo cryopreservation, oocyte cryopreservation and ovarian tissue cryopreservation. The choice depends on various parameters: the type and timing of chemotherapy, the type of cancer, the patient's age and the partner status. The different options and their results are discussed, as well as their putative indications and efficacy. The review concludes that advances in reproductive technology have made fertility preservation techniques a real possibility for patients whose gonadal function is threatened by premature menopause, or by treatments such as radiotherapy, chemotherapy or surgical castration.

For patients who are planning to have chemotherapy, radiotherapy or to undergo bilateral oophorectomy, loss of ovarian function will result in premature ovarian menopause and loss of fertility. For these women, although there is no successful method for the cryopreservation of human oocytes, ovarian tissue cryobanking is proposed with a view to its autotransplantation at a later date or the isolation and in-vitro maturation of oocytes. Embryo preservation is indeed not an option for single women and even for married women because delaying treatment for at least 2 months of in-vitro fertilization cycles is inappropriate and life-threatening. Following the success of animal experiments, there have been reports of ovarian cryopreservation for women having to receive chemotherapy and/or radiotherapy. We present four case reports of ovarian tissue cryobanking and review the consequences of chemotherapy and radiotherapy on gonadal function, as well as the indications for freezing ovarian tissue.

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Study question Is once-daily linzagolix treatment for women with moderate to severe endometriosis-associated pain (EAP) safe for use for up to 6 months of treatment? Summary answer Both doses of linzagolix were well-tolerated with minimal BMD decrease and few TEAEs >5% in either linzagolix arm. What is known already Linzagolix (LGX) is an investigational once-daily oral GnRH receptor antagonist that reduces serum estradiol in a dose-dependent manner and is being developed in two dosages for the treatment of endometriosis-associated pain (EAP): 75 mg, and 200 mg dose with hormonal add-back therapy (ABT).  Study design, size, duration EDELWEISS 3 is a randomized, double-blind, placebo-controlled, multicenter Phase 3 trial of linzagolix in women with moderate to severe EAP. The trial includes 3 treatment arms: 75 mg LGX, 200 mg LGX with ABT (E2 1 mg/ NETA 0.5 mg), or placebo. Here we present safety results up to 6 months (24 weeks) of treatment. Participants/materials, setting, methods Eligible reproductive-aged women with moderate-to-severe EAP were randomized and treated (n = 484) for 6 months with 75 mg LGX, 200 mg LGX with ABT (E2 1 mg/ NETA 0.5 mg), or placebo. Safety and tolerability objectives reported here include 6-month results for treatment emergent adverse events (TEAEs), assessment of mean percent change from baseline (CfB) in lumbar spine (LS) bone mineral density (BMD) and Z-scores. The safety analysis set included 484 subjects across the 3 treatment groups. Main results and the role of chance The overall incidence of TEAEs was similar between the placebo and LGX 75 mg group (46.9%) and slightly higher (56.8%) in the LGX 200 mg + ABT group. There were few (3) serious TEAEs, and none were related to LGX. TEAEs that occurred in over 5% of patients in either active treatment arm included headache (10.5%, 8.1%, and 8.0%), hot flush (6.8%, 7.5%, and 2.5%), and fatigue (6.8%, 3.8%, and 2.5%) for the 200 mg LGX with ABT, 75 mg LGX, and placebo groups, respectively. Mean percent CfB (95% CI) in LS BMD was -0.79% (-1.15,  -0.43%), -0.89% (-1.31, -0.47%), and +0.78% (0.41, 1.15%) for the 200 mg LGX with ABT, 75 mg LGX, and placebo groups, respectively. Z-scores at 6 months remained within the same range as baseline in all groups. Limitations, reasons for caution Additional efficacy and safety results from the trial's 24 weeks (6 mo) extension phase are pending. (Edelweiss 6 protocol: NCT04335591) Wider implications of the findings These results support further development of ABT and non-ABT doses of linzagolix that have potential to provide flexibility and choice for women seeking treatment for EAP. A non-ABT option is important for women who have a contraindication to, are at increased risk for complications, or prefer not to use ABT. Trial registration number ClinicalTrials.gov: NCT02778399

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