To compare the outcomes of orthotopic and heterotopic ovarian tissue transplantation (OTT) techniques.
Mixed prospective-retrospective cohort study.
Academic hospital.
A total of 14 recipients of ...autologous OTT.
Of the 14 women, 12 who received orthotopic (n = 6) or heterotopic (n = 6) transplants met the inclusion criteria. All orthotopic transplants and one heterotopic ovarian tissue transplant were performed laparoscopically. Although 5 of the 6 remaining heterotopic transplants were performed subcutaneously under local anesthesia or intravenous sedation, one was performed with robotic assistance. With the exception of one recipient who solely desired restoration of endocrine function, all underwent oocyte retrieval either to cryopreserve oocytes and embryos before the graft function ceased or because they could not otherwise conceive (hysterectomy, radiation damage, and heterotopic transplant).
Primary outcome measures were graft function and longevity, and the number of embryos generated per retrieval.
The mean age at ovarian tissue harvesting and transplantation was lower in patients with orthotopic vs. heterotopic transplants, although the proportion of transplanted ovarian cortex was lower in heterotopic transplant cases. All grafts restored ovarian endocrine function. Fertilization rates, the number of embryos generated per retrieval, and the mean number of nonarrested embryos were significantly lower in heterotopic OTT. However, time to function and graft longevity were similar between the groups. Although 4 of the 6 women conceived and delivered 7 children among orthotopic ovarian tissue recipients, one recipient had 3 spontaneous live births after heterotopic OTT, presumably because of the induction of function in the remaining menopausal ovary.
It appears that orthotopic OTT results in higher gamete and embryo quality. However, the endocrine function restoration rate and longevity are similar between the 2 approaches. When feasible, orthotopic OTT should be preferred for those who intend to conceive, although a less invasive heterotopic OTT can be performed for those who primarily desire ovarian endocrine function.
Ovarian cryopreservation followed by autotransplantation is still considered an experimental strategy for fertility preservation (FP) mainly because the success rates are unknown.
To determine cohort ...epidemiologic characteristics and success rates of autologous ovarian tissue transplantation (OTT) with previously cryopreserved tissue.
Literature review from 1999 to October 1, 2016. Additional cases were retrieved from meeting abstracts and own database. We selected studies that reported autologous OTT with previously banked tissue in humans. We did not include any cases involving fresh ovarian tissue transplantation or those performed to treat idiopathic premature ovarian failure/insufficiency. Both authors reviewed and selected studies for eligibility, which resulted in 59 full-text studies assessed for eligibility. Cases were extracted from original reports and reviews by the junior author, and the senior author reviewed and verified the extracted data.
Nineteen reports were included for qualitative synthesis. In 10 studies, detailed data were available to determine clinical and live birth + ongoing (LB + OG) pregnancy as well as endocrine restoration rates. Three hundred nine OTTs were performed with cryopreserved tissue, resulting in the birth of 84 children and 8 OG pregnancies. The cumulative clinical and LB + OG rates were 57.5% and 37.7%, respectively, and the endocrine restoration rate was 63.9%.
Success rates with cryopreserved OTT have reached promising levels. Given these recent data, ovarian tissue cryopreservation should be considered as a viable option for FP.
Cancer is a major public health problem around the world. Currently, about 5% of women diagnosed with cancer are of reproductive age. These young survivors may face compromised fertility. The effects ...of chemotherapeutic agents on ovarian reserve and its clinical consequences are generally inferred from a variety of surrogate markers of ovarian reserve, all aiming to provide prognostic information on fertility or the likelihood of success of infertility treatment. Until recently, the mechanisms that are responsible for chemotherapy-induced ovarian damage were not fully elucidated. The understanding of these mechanisms may lead to targeted treatments to preserve fertility. In this manuscript, we will review the current knowledge on the mechanism of ovarian damage and clinical impact of chemotherapy agents on fertility.
We reviewed the most recent developments including the safety and effectiveness data and success rates in individualized ovarian stimulation protocols for adult and postpubertal females with cancer.
...In women with breast cancer, aromatase inhibitor- and tamoxifen-supplemented stimulation protocols increase the margin of safety by limiting estrogen exposure. The outcomes of ovarian stimulation appear similar between cancer and noncancer populations, even with the recently developed random-start protocols, which allow initiation of ovarian stimulation anytime during the menstrual cycle. Based on lower anti-Mullerian hormone levels and primordial follicle density, carriers of BRCA pathogenic variants ( BRCApv ) have decreased ovarian reserve in comparison to women without those variants and may lose larger portion of their ovarian reserve post chemotherapy. Oocyte cryopreservation is also emerging as a suitable fertility preservation approach for selected postpubertal girls as young as 12 years of age.
Individualized ovarian stimulation approaches combined with improvements in cryopreservation techniques increased the success and safety margin to preserve fertility with oocyte freezing. Women with BRCApv , on the other hand, may be at disadvantage as they have lower ovarian reserve and may lose larger portion of their ovarian reserve post chemotherapy compared to women who do not carry these variants.
The ovaries are susceptible to damage following treatment with gonadotoxic chemotherapy, pelvic radiotherapy, and/or ovarian surgery. Gonadotoxic treatments have also been used in patients with ...various nonmalignant systemic diseases. Any women of reproductive age with a sufficiently high risk of developing future ovarian failure due to those medical interventions may benefit from embryo cryopreservation though the tools of assessment of such a risk are still not very precise. Furthermore, the risk assessment can be influenced by many other factors such as the delay expected after chemotherapy and the number of children desired in the future. Embryo cryopreservation is an established and most successful method of fertility preservation when there is sufficient time available to perform ovarian stimulation. This publication will review the current state, approach, and indications of embryo cryopreservation for fertility preservation.
Breast cancer is the most common malignancy diagnosed in women in the United States. Many breast cancer survivors are concerned that cancer treatment will compromise their reproductive potential. ...Despite this concern, most women receive limited information addressing preservation of fertility before initiating adjuvant chemotherapy. Historically, the supraphysiologic levels of estrogens associated with ovarian stimulation have precluded the use of assisted reproductive technologies in the presence of breast cancer. In an effort to mitigate the potential effects of elevated estrogen levels during ovulation induction, we developed a novel ovarian stimulation protocol for women with breast cancer, with the use of aromatase inhibitors. Our studies suggest that in the short term, aromatase inhibitors plus gonadotropins are safe and effective agents for ovarian stimulation in fertility preservation cycles. In this review, we outline the data supporting the use of aromatase inhibitors for ovarian hyperstimulation in women with breast cancer before initiating adjuvant chemotherapy.
The loss of fertility and early menopause are common after gonadotoxic therapies and radical pelvic surgery. The strategy of ovarian tissue cryopreservation and auto-transplantation was introduced to ...prevent this significant quality of health issue. Ovarian transplantation with cryopreserved tissue has gone through remarkable evolution in the last 20 years. In this review, we detail the history and evolution of ovarian transplantation with cryopreserved tissue from its origins to the present. Ovarian cryopreservation and transplantation approach was first tested with animal models. The approach was then validated in human ovarian xenografting models before being applied to patients in pioneering clinical studies. The first orthotopic and heterotopic approaches to ovarian transplantation was developed by Oktay et al. who reported the first successful restoration of ovarian function with these approaches beginning in 2000 with first embryo development in 2004. Controversy remains on when the first live birth occurred after orthotopic ovarian transplantation with cryopreserved tissue as the patient was ovulating with elevated progesterone levels in the case reported in 2004; first live birth is likely to be the one reported by Meirow et al. in 2005. Nevertheless, the technique has evolved to reach a level where most recent live birth rates are exceeding 35% and the procedure is no longer considered experimental by many.
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