Heterotopic Ovarian Transplantation Research Articles

Heterotopic ovarian transplantation instead hormonal replacement therapy after radical hysterectomy for cervical cancer: case report and review of literature.

Only a few case reports have described heterotopic ovarian tissue transplantation (OTT) with the only objective of restoring ovarian function. Case report and review of the literature forreporting cases of heterotopic OTT with the only aim of restoring ovarian endocrine function. In a cancer survivor woman with a history of hysterectomy and bilateral oophorectomy for cervical cancer and because she poorly tolerated hormone replacement therapy (HRT), we performed a heterotopic OTT in a pelvic subcutaneous "pocket" after an OT cryostorage of 17years. A cyclic ovarian endocrine function started 3months after OTT with an immediate patient self-described improvement of her quality of life. A second OTT was performed 19months after, due to hot flushes recurrence and FSH increase. Despite a cyclic endocrine function, progesterone levels have always been low, resulting in a relative hyperoestrogenism state. In the future, the indications of heterotopic OTT could be spread in alternative to HRT. However, our data suggest that the heterotopic graft environment is less favorable to corpus luteum development, and further studies are needed to assay the best site of heterotopic graft, the optimal number of ovarian cortexfragmentsto graft, and the potential risk of relapse in case of malignant residual disease.

Comparison of orthotopic and heterotopic autologous ovarian tissue transplantation outcomes

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.

Effects of resveratrol on HIF-1α/VEGF pathway and apoptosis in vitrified duck ovary transplantation

Preservation of ovarian tissues is an effective way to ensure genetic diversity of susceptible natural bird populations that are in danger of extinction. We examined whether the addition of the plant phenol resveratrol to vitrification solutions ameliorates the damaging effects of tissue hypoxia and reperfusion injury when the tissues are transplanted. Duck ovary tissues were frozen in the presence of varying concentrations of resveratrol in cryopreservation solutions and then transplanted under the renal capsules of 2-day-old Shelducks. Samples of the transplanted tissues were examined on days 3- and 9- post transplantation for activation of hypoxia-, antioxidant- and apoptosis-related gene expression and apoptosis. Resveratrol significantly increased expression of VEGF, HIF-1α, Nrf2, CAT and Bcl-2 mRNA and decreased BAX and Caspase-3 mRNA and reduced numbers of TUNEL-positive cells after vitrification and heterotopic ovarian transplantation. Resveratrol improved the antioxidant capacity, reduced apoptosis and activated the HIF-1α/VEGF pathway to promote angiogenesis 3- and 9-days following transplantation. These results indicated that the addition of resveratrol to vitrification solutions intended for long-term cryopreservation of ovary tissues improves survival in storage and the grafts following transplantation. This study provides a theoretical basis for the successful transplantation of avian ovarian tissue after vitrification.

P53 Plays an Important Role in the Early Stage of Autologous Heterotopic Transplantation of Ovaries into the Backs of Mice

BackgroundSubcutaneous ovarian transplantation has recently begun receiving increased attention. Fourteen days after transplantation is used as an important time point for assessing the recovery of ovarian function. The goal of this study is to determine the expression of apoptotic genes in the ovary at this time. MethodsThis study investigated follicle development and the expression of 3 apoptosis genes (Bax, Bcl2, and P53) after mouse ovaries were transplanted. Seven-week-old mouse ovaries were autologously transplanted into back muscle. The ovaries were harvested on day 14, morphology was observed by hematoxylin and eosin staining, and the distribution of 3 proteins was observed by immunohistochemistry. TUNEL staining showed where apoptosis occurred in the ovary. Finally, RT-PCR/Western blotting was used to analyze the differential expression of mRNA/proteins between the transplantation group and the control group. ResultsThe results revealed follicles at different stages at the edge of the grafts. In immunohistochemical experiments, BAX, BCL2, and P53 were found to be extensively expressed in the transplant group and the control group. P53 was strongly expressed in the medulla of transplanted ovaries. Bax was strongly expressed in the antral follicles of both groups. The results were consistent with the results of the TUNEL experiments.Three genes (Bax, Bcl2, and P53) were downregulated in the transplanted groups. The results showed that significant differences were detected in Bax and P53 mRNA expression levels between the transplanted groups and the control group (P < .01). Bcl2 expression was not significantly different, but the Bax/Bcl2 ratio increased. The results of the protein experiments were the same. ConclusionP53 may downregulate Bax in the early stage of transplantation. Follicle growth and atresia were regulated through modulation of Bcl2- and Bax-mediated apoptotic pathways in heterotopic ovarian transplantation.

A Systematic Study on Reproductive Endocrine Function Recovery From Subcutaneous Ovarian Autotransplantation in Mice After 2 Weeks

BackgroundHeterotopic ovarian transplantation can not only restore the reproductive and endocrine function of animals but can also be studied with a specialized animal model. The aim of the study was to determine whether the reproductive endocrine function of the subcutaneously transplanted ovary was restored after 2 weeks. MethodsThe ovaries of 7-week-old mice were autologously transplanted into the back muscle. Fourteen days later, the ovarian structure was examined by hematoxylin and eosin staining. We continuously observed vaginal smears for changes in the estrous cycle. Estrogen and androgen concentrations were detected on the 14th day. The oocytes were collected and then used for in vitro maturation (IVM) and in vitro fertilization (IVF). ResultsThe cyclical estrous cycle changes were similar to those of the control group. There were no differences in the serum androgen and estrogen levels between the graft and control groups. The oocytes were able to develop into blastocysts after IVM and IVF. These results indicated that ovarian endocrine and reproductive function were restored within 2 weeks. ConclusionOur studies have shown that this ovarian heterotopic autotransplantation technique is able to restore steroidogenic and gametogenic functions at day 14 after transplantation. So far, the 14th day after transplantation is a landmark during the recovery from autologous heterotopic ovarian transplantation in the back of the mouse. This time point is the appropriate window to study heterotopic ovarian transplantation in mice.

A case report and follow-up of the first live birth after heterotopic transplantation of cryopreserved ovarian tissue in Eastern Europe

BackgroundOvarian insufficiency is a major concern for long-term cancer survivors. Although semen freezing is well established to preserve male fertility, the possibilities to secure post-cancer female fertility are mostly limited to oocyte or embryo freezing. These methods require time-consuming ovarian stimulation with or without in vitro fertilization (IVF) that evidently delays cancer therapy. Ovarian tissue cryopreservation and subsequent thawed tissue autotransplantation are considered the most promising alternative strategy for restoring the fertility of oncology patients, which has not yet received the full clinical acceptance. Therefore, all successful cases are needed to prove its reliability and safety.Case presentationHere we report a single case in Estonia, where a 28-year-old woman with malignant breast neoplasm had ovarian cortex cryopreserved before commencing gonadotoxic chemo- and radiotherapy. Two years after cancer therapy, the patient underwent heterotopic ovarian tissue transplantation into the lateral pelvic wall. The folliculogenesis was stimulated in the transplanted tissue by exogenous follicle-stimulating hormone and oocytes were collected under ultrasound guidance for IVF and embryo transfer. The healthy boy was born after full-term gestation in 2014, first in Eastern Europe.ConclusionDespite many countries have reported the first implementation of the ovarian tissue freezing and transplantation protocols, the data is still limited on the effectiveness of heterotopic ovarian transplant techniques. Thus, all case reports of heterotopic ovarian tissue transplantation and long-term follow-ups to describe the children’s health are valuable source of clinical experience.

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

To demonstrate the technical advances since the time we reported the first successful case in 2000 and our modern approach to autologous transplantation of frozen-thawed human ovarian tissue. A step-by-step video demonstration of three surgical approaches was created by editing the surgical footage obtained during ovarian transplantation procedures. Academic. Three patients who previously underwent ovarian tissue harvesting and cryopreservation before gonadotoxic cancer treatments or radical cancer surgery are presented. The illustrated techniques include robot-assisted orthotopic (technique 1) and heterotopic (technique 2) approaches using the da Vinci Xi (Intuitive Surgical) robotic system and a decellularized human extracellular tissue matrix (Alloderm; LifeCell Corp.) as a tissue scaffold, as well as a percutaneous autotransplantation approach (technique 3). Successful completion of procedures without complications and ovarian graft function with demonstration of E2 production and follicle development. All cases were completed without complications. Ovarian graft function was confirmed by E2 production, follicle growth by 10-14weeks after transplantation, and later embryo development. Since our first report of successful restoration of ovarian function after orthotopic transplantation of frozen-banked ovarian tissue in 2000 (1), followed by our first reports of subcutaneous heterotopic transplantation techniques (2, 3), ovarian tissue cryopreservation followed by subsequent transplantation has become a promising fertility preservation option for young women with cancer who do not have sufficient time to undergo oocyte or embryo cryopreservation and for prepubertal girls (4, 5). The same approach also has the advantage of restoring ovarian endocrine function and fertility without a need for assisted reproduction (6, 7). In the very first successful procedure that we reported in 2000, we used conventional laparoscopy, and the tissues were reconstructed and mounted on a polycellulose scaffold (Surgicel) (1, 7). Since then, we have made significant modifications in our surgical approach with potential improvements in outcomes. Here we illustrate three main techniques of ovarian tissue transplantation resulting in the restoration of ovarian function in all cases. In the first two cases, we illustrated the robot-assisted orthotopic and heterotopic approaches using Alloderm. Robotic ovarian transplantation may increase precision, provide more delicate graft handling, and reduce the time from tissue thawing to transplantation (6, 8). Alloderm is regenerated de-epithelized human cadaver skin, which consists of several extracellular matrix components. It has been safely used in the surgery and dentistry fields for enhancing tissue regeneration and vascularization (9, 10). Furthermore, our earlier laboratory work indicated the critical role of extracellular matrix in primordial follicle growth initiation and preantral follicle growth (11, 12). Prior to our use of Alloderm as part of ovarian transplant procedures, we tested it in human ovarian xenograft models and found Alloderm to incorporate well with ovarian tissue (8). Only after that test did we adopt it for use in ovarian transplants. The utility of the extracellular tissue matrix may thus enhance our ovarian autotransplantation techniques by facilitating ovarian reconstruction and potentially improving neovascularization. In fact, we have seen improved follicle growth and response to ovarian stimulation with the use of Alloderm in our first cases (8). We use heterotopic ovarian transplantation when the pelvis is not suitable for autotransplantation due to past radiation or scarring or when there are other medical contraindications for transplantation in the pelvis. The third technique we illustrated was percutaneous heterotopic ovarian autotransplantation. This is a simple approach that can be used in surgically high-risk patients, as it is done with local anesthesia or IV sedation and without entering abdominal cavity. Additionally, same approach can be utilized when there is heightened concern that the ovarian tissue may harbor a disease that can recur, requiring close surveillance and easier removal of the ovarian graft. While ovarian endocrine function and follicle growth are restored with efficiency using the percutaneous ovarian transplants, our initial experience suggests that oocyte quality may be impaired in SC locations (2, 3, 13). Hence that technique may be more suitable when the only purpose is restoration of ovarian endocrine function. However, we have encountered recurrent live births from spontaneous conceptions following SC ovarian transplants, prompting the question of whether the grafted tissue can augment the function of in situ menopausal ovary (13, 14). While ovarian cryopreservation and transplantation may no longer be considered experimental, there are many exciting questions remaining to be answered on the full potential of this procedure.

Robot-assisted orthotopic and heterotopic ovarian tissue transplantation techniques

Robot-assisted orthotopic and heterotopic ovarian tissue transplantation techniques

Genetic and Pharmacological Modulation of Akt1 for Improving Ovarian Graft Revascularization in a Mouse Model.

Ovarian tissue cryopreservation and transplantation is one of a few available treatments for fertility preservation in women diagnosed with cancer. Rapid revascularization is essential for reducing hypoxic damage after grafting and protecting the primordial follicles reserve. Using a mouse model of heterotopic ovarian graft transplantation, we have delineated the role of endothelial Akt1 expression using longitudinal magnetic resonance imaging follow-up to quantify angiogenic response. Endothelial Akt1 activation in ovarian grafts promoted angiogenesis to support the graft during posttransplantation hypoxic period. Similarly, simvastatin therapy activated Akt1 at the transplantation site and improved the revascularization and vascular support of ovarian grafts. These results serve as an important first step toward pharmacological intervention to improve revascularization of ovarian grafts and restoration of fertility in cancer survivors. The pro-angiogenic effects reported here may extend beyond improving ovarian graft reception in fertility preservation and could potentially be used for different organ or tissue transplantation.

Revisiting the role of heterotopic ovarian transplantation: futility or fertility

Scepticism hovers over the future of heterotopic transplantation of cryopreserved human ovarian tissue, as its clinical efficacy and practicability for fertility preservation is still debatable. Despite its limitations, the potential advantages and roles of heterotopic transplantation should not be ignored. Indeed, restoration of ovarian function after heterotopic transplantation of cryopreserved ovarian tissue has been consistently demonstrated in humans. There are many unknowns with this technology, such as the optimal heterotopic site, environmental factors and oocyte quality. Hence, it will require further investigations before making a final verdict. Until then, rather than being considered prematurely as a futile technology, heterotopic ovarian transplantation should be viewed positively, with potential roles for restoration of ovarian function and fertility.

Assessment of long term endocrine function after transplantation of frozen-thawed human ovarian tissue to the heterotopic site: 10 year longitudinal follow-up study

To assess the longevity of ovarian grafts in five cancer patients who underwent heterotopic autotransplantation of frozen-thawed ovarian tissue. Five cancer survivors underwent heterotopic ovarian transplantation between 2001 and 2011. Stored ovarian tissue (for 1-10 years) was rapidly thawed and transplanted into the space between the rectus sheath and the rectus muscle (8-20 cortical sections per patient). Endocrine function was assessed by monthly blood tests (FSH, LH, E2, progesterone and testosterone) and ultrasound after transplantation. The monitoring was continued until the cessation of endocrine function by consecutive blood tests (E2 < 20 pg/ml; FSH ≥ 35 IU/L). Endocrine function was restored in all patients between 12-20 weeks after transplantation. Four patients required the second transplantation one to two years after the first transplantation. The duration of endocrine function after the second transplantation was much longer (9 months-84 months). The longest duration of endocrine function was seen in a woman who underwent ovarian transplantation in 2003 and 2004 after radiotherapy for cervical cancer. Even more than seven years after transplantation, endocrine function has not ceased (FSH 9.5, E2 108, on July 1, 2011). Of note, this patient underwent three IVF cycles in 2004 which resulted in four embryos. Long-term endocrine function lasting for seven years can be established with heterotopic transplantation of cryobanked human ovarian tissue. Re-establishment of long-term endocrine function after ovarian transplantation will benefit young cancer survivors with premature ovarian failure.

Four spontaneous pregnancies and three live births following subcutaneous transplantation of frozen banked ovarian tissue: What is the explanation?

To report the long-term follow-up of an experimental heterotopic ovarian transplantation with frozen-thawed ovarian tissue. Long-term follow-up of an experimental surgery; case report. Academic reproductive medicine center. A 28-year-old cancer survivor with previous Hodgkin disease and relapse. Laparoscopic oophorectomy for ovarian cryopreservation before preconditioning chemotherapy for hematologic stem cell transplantation. Ovarian tissue thawing and subcutaneous heterotopic ovarian transplantation in the lower abdominal wall 2½ years after the hematologic stem cell transplantation. Resumption of ovarian function after transplantation, recovery of fertility, and pregnancy outcome. Follicle development was observed in the graft 2 months after transplantation, and a P value of 14 ng/mL indicated ovulation. The patient conceived spontaneously four times within 5 years and delivered three children. The in situ ovary remained atrophic but showed occasional follicle activity contemporaneously with the graft. The mechanism behind spontaneous restoration of fertility with consecutive viable pregnancies after a heterotopic ovarian transplantation needs to be explored. Further laboratory and clinical research will be needed to explore the true origin of pregnancies after ovarian transplantations.

Orthotopic and heterotopic ovarian tissue transplantation

BACKGROUNDTransplantation of ovarian tissue is, at present, the only clinical option available to restore fertility using cryopreserved ovarian tissue. More than 30 transplantations of cryopreserved tissue have been reported, and six babies have been born, worldwide, following this procedure. Despite these encouraging results, it is essential to optimize the procedure by improving the follicular survival, confirming safety and developing alternatives. Here, we review the different factors affecting follicular survival and growth after grafting.METHODSRelevant studies were identified by searching Pubmed up to January 2009 with English language limitation. The following key words were used: (ovarian tissue or whole ovary) AND (transplantation) AND (cryopreservation or pregnancy). Using the literature and personal experience, we examined relevant data on the different exogenous and clinical factors affecting follicular development after grafting.RESULTSClinical factors such as the patient's age and the transplantation sites influenced the lifespan of the graft. A heterotopic transplantation site is not optimal but offers some advantages and it may also promote the hormonal environment after a combined heterotopic and orthotopic transplantation. Exogenous factors such as antioxidants, growth factors or hormones were tested to improve follicular survival; however, their efficiency regarding further follicular development and fertility potential remains to be established.CONCLUSIONAdditional evidence is required to define optimal conditions for ovarian tissue transplantation. Alternatives such as whole ovary or isolated follicles transplantations require further investigation but are likely to be successful in humans in the future.

O-11: Embryo development from oocytes retrieved from cryopreserved human ovarian tissue after heterotopic autotransplantation

Ovarian cryopreservation and transplantation has been recognized as a valuable strategy for fertility preservation in cancer patients. Several cases of successful ovarian transplantation, either orthotopic or heterotopic, have been reported. Nevertheless, it is still experimental. To date, only two babies were born after orthotopic transplantation of ovarian tissue, but none with heterotopic transplantation. The purpose of this study was to demonstrate the feasibility of obtaining viable embryos necessary to establish a pregnancy after heterotopic transplantation of cryopreserved human ovarian tissue. Clinical prospective study The study was approved by the institutional review board. A 28-year-old woman with cervical cancer consented for ovarian tissue cryopreservation in 2002 before chemotherapy and radiotherapy. Two years later, the patient requested ovarian tissue transplantation to restore her fertility. Eighteen sections of stored ovarian tissue (5x5x1 mm) were thawed rapidly in a warm water bath (30°C), rehydrated in a stepwise manner, and transplanted into the space between the rectus sheath and the rectus muscle. After transplantation, ovarian function was monitored with serial blood tests (FSH, LH, E2, P4) and ultrasound. Once restoration of the normal ovarian function was established, hormone profiles were obtained weekly, and the ovarian grafts were stimulated with rFSH. When a dominant follicle size reached at 14mm in diameter, 250μg of rhGC was administered, and 36 hours later oocytes were retrieved under ultrasound-guidance. Retrieved oocytes were matured in vitro for 24 hours before fertilization by intracytoplasmic sperm injection (ICSI) technique. Embryos were cultured for 3 days and cryopreserved while waiting for a surrogacy. Restored ovarian function was evidenced by hormonal profiles (FSH 13.5, E2 227.6) about 4 months after transplantation and has remained for more than 2 years. At the same time, a sonogram revealed growing follicles in the graft. The first oocyte retrieval was performed 9 months after transplantation, and the second retrieval was done 5 months after the first one. Total of five oocytes were collected (four MI oocytes and one MII oocyte). Three out of four MI oocytes were developed to full maturity in vitro. All four MII oocytes (1+3) were successfully fertilized by ICSI. Two embryos were cultured in vitro for 3 days before cryopreservation (one 6-cell embryo, one 3-cell embryo). Other two were cryopreserved on day 2, as the embryo quality appeared to be somewhat poor. This study demonstrated that long term ovarian function can be restored by heterotopic ovarian transplantation, and that oocytes retrieved from the ovarian graft can be successfully fertilized. Furthermore, the normal developmental potential of the fertilized oocytes originated from frozen-thawed ovarian grafts was confirmed by 3-day in vitro culture for the first time. Although heterotopic autotransplantation of cryopreserved ovarian tissue can be a viable strategy to restore fertility in cancer patients, the efficacy and safety of this technique should be further investigated before full clinical applications.

Optimizing the Outcome of Grafted Ovarian Tissue: Exogenous Gonadotropins to Increase Microvessel Density and Follicular Survival

Background: Fertility preservation by ovarian cryopreservation and heterotopic ovarian transplant is hampered by ischemic damage of the transplanted graft and poor oocyte viability. Design: Two longitudinal experiments were done - phase A: to evaluate if the administration of gonadotrophins (hMG) or vascular endothelial growth factor (VEGF) increases follicular survival after heterotopic autologous ovarian transplantation, and phase B: to determine if the administration of hMG enhanced neovascularization by increase in microvessel density in the heterotopic xenologous ovarian transplant. Methods: A: In three sheep, ovaries were removed and immediately transplanted into the abdominal wall. In one sheep, VEGF was administered at the transplantation site during surgery, the second was treated with hMG after transplantation for 2 weeks, and the third sheep served as control. B: The ovaries from two other sheep were removed, prepared in tissue pieces, and immediately grafted into the subcutaneous space of several combined immunodeficient (SCID-)mice (n=20). Following the transplantation, 10 of these mice (group 1) were treated with hMG until they were sacrificed, the other 10 untreated mice (group 2) served as controls. In each group, two mice were sacrificed at intervals of 2,4,6,10, and 14 days after grafting to permit histologic examination of the grafted tissue. Results: A: Whereas VEGF had no effect on follicular survival after transplantation (12.0% vs. 7.4%.),the administration of hMG increased follicular survival (12.0% vs. 29.0%). B: The use of hMG resulted in significantly higher numbers of microvessels per mm 2 (mean) at all of the time points studied - at 2 days 22 vs. 13 (p < 0.001), 4 days 22 vs. 13 (p < 0.001), 6 days 17 vs. 13 (p = 0.006), 10 days 28 vs. 12 (p < 0.001), and 14 days 35 vs. 16 (p<0.001), respectively. Conclusion: The improved follicular survival and increase in microvessel density in heterotopic ovarian transplants associated with the use of hMG suggests that neovascularization may be an important mechanism by which hMG improves the survival of ovarian transplants.

Spontaneous conceptions and live birth after heterotopic ovarian transplantation: is there a germline stem cell connection?

Ovarian cryopreservation and transplantation is an emerging technology to preserve fertility in women and children undergoing cancer treatment. Recent reports of live births after orthotopic transplantation raised hopes for the future success of this procedure. However, doubts remained whether the reported pregnancies were as a result of resumed function in the remaining ovary. We recently performed an autologous heterotopic ovarian transplantation in a 32-year-old Hodgkin lymphoma survivor who was menopausal for 2.5 years as a result of a preconditioning chemotherapy given before a hematopoietic stem cell transplant. Subsequent to the transplantation, the patient conceived twice within 3 months and delivered a healthy female child at 40 weeks of gestation. The occurrence of spontaneous pregnancies after heterotopic ovarian transplantation highlights the need for caution when interpreting the source of pregnancies in recipients with intact ovaries. On the other hand, the temporal relationship between the ovarian transplant and the spontaneous resumption of ovarian function and pregnancies in previously menopausal women is intriguing, especially in the light of recent reports of germ cell renewal and migration from the bone marrow to the ovary in rodents.

A technique for transplantation of ovarian cortical strips to the forearm

Objective To describe a forearm heterotopic ovarian transplantation technique. Design Case study. Setting Academic medical center. Patient(s) One patient with stage IIIB squamous cell cervical carcinoma and one patient with recurrent benign ovarian cysts. Intervention(s) Preparation of thin ovarian cortical slices and transplantation under the skin of the forearm. Main outcome measure(s) Follicular development and oocyte retrieval; cyclical estradiol (E 2) and progesterone (P 4) production; restoration of serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels to reproductive age range. Result(s) Both patients were menopausal immediately after oophorectomy. The first patient developed a dominant follicle 10 weeks after transplantation, and her gonadotropin levels decreased to nonmenopausal levels. Percutaneous aspiration of ovarian follicles yielded a metaphase I (M-I) oocyte that was matured to metaphase II (M-II). The first patient’s graft was functional for at least 21 months. In the second patient, ovarian follicle development was detected 6 months after transplantation, and periodic menstruation occurred thereafter. Spontaneous ovulation was confirmed by a midluteal increase in her P 4 levels. Menstruation and follicle development continued for more than 2 years after the transplant. Conclusion(s) Heterotopic transplantation of ovarian tissue to the forearm is a simple and promising technique to restore ovarian function in women who become menopausal due to chemotherapy, surgery, or radiation.

Resumption of ovarian function in a patient with premature ovarian failure (pof) after human fresh, heterologous, heterotopic ovarian transplantation

Objective: The recent advances in gonadal tissue cryobiology and transplantation enable physicians to offer preservation of gonadal function and prevention of fertility problems. Not only before chemo or radiotherapy but also in women at risk of POF. Most of the studies were performed with animals, xenografting and human autologous models, but a close hormonal follow up was not reported. To the best of our knowledge, this is the first case of a fresh, heterologous hystocompatible human ovarian tissue transplantation in an heterotopic location to a POF patient.

Heterotopic ovarian transplantation without vascular pedicle in syngeneic Lewis rats: long-term evaluation of effects on ovarian structure and function

Objective: To assess the long-term efficacy of intraperitoneal (IP) and subcutaneous (SC) ovarian autotransplantation in rats. Design: Experimental animal study. Setting: Unit of Experimental Research, Barcelona University School of Medicine. Animal(s): Female syngeneic Lewis rats aged 14 weeks. Intervention(s): Group A, control group undergoing ovariectomy (n = 15); group B, undergoing ovariectomy and IP autologous heterotopic transplant (n = 15); and group C, ovariectomized with SC autologous heterotopic transplant (n = 15). In groups B and C, five animals were killed and their ovaries removed for morphometric analysis at 30 days after transplantation; five additional animals were killed at 180 days, and the remaining five animals were killed at 360 days. Main Outcome Measure(s): Ovarian morphometric analysis and serial measurement of E 2 and FSH serum levels. Result(s): The mean number of antral follicles in the control group A was significantly higher than that observed in the ovarian grafts collected and examined 30 days after grafting in rats from groups B and C, but the mean granulosa cell area was significantly higher in both transplantation groups than in controls because of ovarian follicular hyperplasia. Histological examination of ovaries removed at 6 and 12 months after grafting in groups B and C showed increasing degrees of fibrosis, loss of primordial follicles, and the presence of epithelial cysts. In groups B and C, from day 30 after surgery onward, serum E 2 was significantly higher and FSH significantly lower, respectively, than in group A. E 2 and FSH patterns in groups B and C were similar throughout the study period. Conclusion(s): Heterotopic ovarian transplantation without vascular pedicle in rats is characterized by follicular hyperplasia endocrinologically functional, followed by progressive loss of follicles in heterotopic ovarian autografts.