Engineering strategies and challenges in building the follicular microenvironment for a bioprosthetic ovary.

Fertility preservation in girls with Turner syndrome: limitations, current success and future prospects

In vitro maturation of oocytes: uncommon indications

Robot-assisted orthotopic and heterotopic ovarian tissue transplantation techniques: surgical advances since our first success in 2000

Ovarian tissue and follicle transplantation as an option for fertility preservation

Fertility preservation in men and women: Where are we in 2021? Are we rising to the challenge?

Thawing fertility: a view of ovarian tissue cryopreservation processes and review of ovarian transplant research

Complete follicular development and recovery of ovarian function of frozen-thawed, autotransplanted caprine ovarian cortex

Histologic and ultrastructural features of cryopreserved ovine ovarian tissue: deleterious effect of 1,2-propanediol applying different thawing protocols

How efficacious is transplantation of ovarian cortex previously exposed to chemotherapy? Prior exposure to chemotherapy did not disrupt the function of cryopreserved ovarian tissue after transplantation. Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) is an efficacious technique for restoration of female fertility. At least 130 children have been born following this procedure. To date, little is known about the efficacy of OTT in patients exposed to cancer chemotherapy prior to OTC. This study evaluates the recovery of ovarian function and fertility in 31 consecutive patients who had received OTT, between 2005 and 2015. Thirty one patients, wanting children, were transplanted with autologous ovarian cortex, among which 22 patients (71%) had been exposed to chemotherapy before OTC. Recovery of ovarian function was considered total once menstruation occurred. Ovarian function recovery (OFR), ovarian graft survival, and incidence of pregnancy were related to previous chemotherapy exposure, type of chemotherapy and graft characteristics (number of grafted fragments and follicular density). The amount of ovarian tissue collected was the only parameter to show any significant change between patients with versus without previous chemotherapy. At 1year after OTT, the cumulative incidence of OFR was 83% (93% in patients exposed to chemotherapy and 67% in others (P = 0.14)). A low follicular density (<0.3foll/mm2) in the transplant and a low number of grafted fragments (<16) were significantly associated with a delayed OFR. Graft survival at 2years after OTT was 77%. It was significantly lower in patients exposed to bifunctional alkylating agents before ovarian cryopreservation and in patients with a low follicular density. The proportion of women who succeeded in having at least one live birth was 23% in the total population, 0% (0/9) in the group 'no previous chemotherapy', and 32% (7/22) in the group 'previous chemotherapy'. The cumulative incidence of pregnancy (Kaplan-Meier) at 3years after OTT was 36% overall and 49% in case of previous chemotherapy, with no difference related to previous chemotherapy exposure. In total there were 13 pregnancies and 8 births in 7 patients. The pathology in the two groups of patients was not comparable. In the group of patients who had chemotherapy before OTC, there were 95% of hematological malignancies. In the group of patients who did not have chemotherapy before OTC only 1 out of 9 patients had a malignant hematological disease while 44% had some pathology affecting the ovaries. Few women are available for study and only large changes are likely to have statistical significance. These results suggest that prior cancer chemotherapy should no longer be considered a limitation to cryopreservation of ovarian tissue and current recommendations in this regard should be revised. This study was supported by the Agence de la Biomédecine (France's biomedical office). There are no competing interests to report. NCT02184806.

In the late 1990s, ovarian tissue cryopreservation was first employed clinically to preserve fertility in female children, adolescents, and young adults with cancer in Europe and the United States. In 2004, Donnez reported the first live birth after ovarian tissue cryopreservation and transplantation. Ovarian tissue cryopreservation can be employed when ova cannot be collected by intravaginal procedures, when induction of ovulation is impossible in girls before menarche, and when cancer therapy must be initiated promptly and there is insufficient time to induce ovulation. In patients with some cancers (e.g., ovarian cancer and leukemia), tumor cells can potentially infiltrate the ovaries and could be transferred by transplanting thawed ovarian tissue so ovarian tissue cryopreservation is contraindicated. Recently, live birth has been achieved up to 30% of women undergoing transplantation of cryopreserved and thawed ovarian tissue. If ovarian tissue contains more primordial follicles (as in children/adolescents), the likelihood of live birth after transplantation is higher. Therefore, the patient's age should also be considered. However, even a woman who underwent ovarian tissue cryopreservation in her late 30s has achieved live birth. Since initial clinical application of ovarian tissue cryopreservation and transplantation in 1997, approximately 100 live births have been reported, including 3 in Japan. This article reviews the current status of ovarian tissue cryopreservation and transplantation of thawed ovarian cortex for fertility preservation.

Safety of ovarian cryopreservation and transplantation in patients with acute leukemia: a case series

Twins born after transplantation of ovarian cortical tissue and oocyte vitrification

Modeling delay of age at natural menopause with planned tissue cryopreservation and autologous transplantation

Worldwide, >130 babies have been born from ovarian tissue cryopreservation (OTC) and ovarian tissue transplantation (OTT). Ovarian tissue cryopreservation can improve quality of life among young female cancer survivors. Here, we assessed the feasibility of OTC and subsequent OTT in Hong Kong via xenografts in nude mice. This pilot study was conducted in a university-affiliated tertiary hospital. Fifty-two ovarian tissues were collected from 12 patients aged 29 to 41 years during ovarian surgery, then engrafted into 34 nude mice. The efficacies of slow freezing and vitrification were directly compared. In Phase I, non-ovariectomised nude mice underwent ovarian tissue engraftment. In Phase II, ovariectomised nude mice underwent ovarian tissue engraftment, followed by gonadotrophin administration to promote folliculogenesis. Ovarian tissue viability was assessed by gross anatomical, histological, and immunohistochemical examinations before and after OTC. Follicular density and morphological integrity were also assessed. After OTC and OTT, grafted ovarian tissues remained viable in nude mice. Primordial follicles were observed in thawed and grafted ovarian tissues, indicating that the cryopreservation and transplantation protocols were both effective. The results were unaffected by gonadotrophin stimulation. This study demonstrated the feasibility of OTC in Hong Kong as well as primordial follicle viability after OTC and OTT in nude mice. Ovarian tissue cryopreservation is ideal for patients who cannot undergo the ovarian stimulation necessary for oocyte or embryo freezing as well as prepubertal girls (all ineligible for oocyte freezing). Our findings support the clinical implementation of OTC and subsequent OTT in Hong Kong.

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