Pascale Jadoul

Livebirth after orthotopic transplantation of cryopreserved ovarian tissue

BACKGROUND The lifesaving treatment endured by cancer patients leads, in many women, to early menopause and subsequent infertility. In clinical situations for which chemotherapy needs to be started, ovarian tissue cryopreservation looks to be a promising option to restore fertility. In 1997, biopsy samples of ovarian cortex were taken from a woman with stage IV Hodgkins lymphoma and cryopreserved before chemotherapy was initiated. After her cancer treatment, the patient had premature ovarian failure. METHODS In 2003, after freeze-thawing, orthotopic autotransplantation of ovarian cortical tissue was done by laparoscopy. FINDINGS 5 months after reimplantation, basal body temperature, menstrual cycles, vaginal ultrasonography, and hormone concentrations indicated recovery of regular ovulatory cycles. Laparoscopy at 5 months confirmed the ultrasonographic data and showed the presence of a follicle at the site of reimplantation, clearly situated outside the ovaries, both of which appeared atrophic. From 5 to 9 months, the patient had menstrual bleeding and development of a follicle or corpus luteum with every cycle. 11 months after reimplantation, human chorionic gonadotrophin concentrations and vaginal echography confirmed a viable intrauterine pregnancy, which has resulted in a livebirth. INTERPRETATION We have described a livebirth after orthotopic autotransplantation of cryopreserved ovarian tissue. Our findings suggest that cryopreservation of ovarian tissue should be offered to all young women diagnosed with cancer.

Fertility preservation in girls during childhood: is it feasible, efficient and safe and to whom should it be proposed?

BACKGROUND In prepubertal and adolescent girls, fertility may be impaired by gonadotoxic treatments, repeat ovarian surgery or genetic disorders. Cryopreservation of ovarian cortex is an existing option to preserve fertility in these young girls at risk of premature ovarian failure (POF). The efficacy, feasibility and risks of ovarian cryopreservation in children must be assessed in order to validate the technique. METHODS Here, we conducted a review of ovarian cryopreservation in adults and, more specifically, in children using the PubMed databases. In addition, our own experience with ovarian cryopreservation in children was evaluated and compared with the literature. RESULTS Analysis of the literature and six published series on ovarian cryopreservation in children, as well as our own series of 58 cases, show that there is no reason to doubt its efficacy in this young population. However, no consensus has yet been reached on the indications for the technique. Indeed, with existing models, the real risk of POF may be over- or underestimated. CONCLUSION Our review suggests that ovarian cortex cryopreservation is feasible and as safe as comparable operative procedures in children. Although no births have yet resulted from freeze-thawing of prepubertal ovarian cortex, the results of this approach in adults are encouraging. However, the absence of consensus on the indications for fertility preservation, as well as the optimal timing and quantity of ovarian cortex for cryopreservation, should be taken into consideration when discussing fertility issues with girls at risk of POF and their parents.

Laparoscopic management of endometriomas using a combined technique of excisional (cystectomy) and ablative surgery

OBJECTIVE To describe and evaluate a new technique of laparoscopic treatment of endometriomas that combines excisional and ablative surgery. DESIGN Descriptive and prospective study. SETTING Gynecology research unit in a university hospital. PATIENT(S) Fifty-two women under 35 years of age presenting for infertility and/or pelvic pain with endometriomas larger than 3 cm were included in the study. None had undergone any surgery for endometriosis. INTERVENTION(S) A large part of the endometrioma wall was first excised according to the cystectomy technique. After this first step, CO(2) laser was used to vaporize the remaining 10%-20% of the endometrioma wall close to the hilus. MAIN OUTCOME MEASURE(S) The feasibility of this new technique was assessed. Ovarian volume and antral follicle count (AFC) were compared between operated ovaries and nonoperated ovaries of patients with endometriosis and controls (women with male factor infertility). RESULT(S) The combined technique was possible in all cases. The volume of the ovary after the combined technique was similar to that of the contralateral normal ovary, as well as to that observed in infertile women without endometriosis presenting for male factor infertility. The AFC on day 2-5 showed the same number of antral follicles in all subgroups. Histopathology of the excised part of the endometrioma revealed the presence of follicles in only one case (2%). The pregnancy rate was 41% at a mean follow-up of 8.3 months. Recurrence of a small endometrioma was observed in only one case (2%). CONCLUSION(S) The combined technique (stripping and ablation) has proved not to be deleterious to the ovary.

Live birth after transplantation of frozen-thawed ovarian tissue after bilateral oophorectomy for benign disease.

OBJECTIVE To report the restoration of ovarian function and pregnancy in a woman after bilateral oophorectomy for benign disease after autotransplantation of cryopreserved ovarian cortex. DESIGN Case report. SETTING Gynecology research unit in a university hospital. PATIENT(S) A 28-year-old woman who underwent bilateral adnexectomy for ovarian abscesses at the age of 18 years. INTERVENTION(S) We performed ovarian cortex autotransplantation to a peritoneal pocket in the broad ligament. MAIN OUTCOME MEASURE(S) Restoration of ovarian activity and pregnancy. RESULT(S) Restoration of ovarian function began at 20 weeks and was achieved 24 weeks after transplantation. After the fifth stimulation attempt, two mature oocytes were obtained and microinjected. One embryo (seven cells) was obtained and transferred, leading to a normal pregnancy. The patient delivered a healthy baby boy weighing 2,370 g at 38 weeks of gestation. CONCLUSION(S) Ovarian cortex cryopreservation can be performed at the time of surgery for benign diseases when fertility is impaired. We report the first pregnancy to occur after ovarian tissue cryopreservation for benign ovarian pathology after bilateral oophorectomy.

Conservative treatment may be beneficial for young women with atypical endometrial hyperplasia or endometrial adenocarcinoma

OBJECTIVE To evaluate whether an alternative treatment to radical hysterectomy exists for young women with endometrial adenocarcinoma. DESIGN A review of the literature (70 articles) plus personal results. SETTING University hospital. PATIENT(S) Women with atypical endometrial hyperplasia or adenocarcinoma. MAIN OUTCOME MEASURE(S) The recurrence rate and the pregnancy rate after conservative therapy. CONCLUSION(S) Conservative treatment of well-differentiated stage I endometrial adenocarcinoma can be considered in young patients, with close surveillance to diagnose any possible recurrence.

Ovarian tissue cryopreservation and transplantation in cancer patients

Advances in the diagnosis and treatment of childhood, adolescent and adult cancer have greatly increased the life expectancy of premenopausal women with cancer. The ovaries are very sensitive to cytotoxic treatment, especially to alkylating agents. The only established method of fertility preservation is embryo cryopreservation according to the Ethics Committee of the American Society for Reproductive Medicine (2005), but this option requires the patient to be of pubertal age, have a partner or use donor sperm and be able to undergo a cycle of ovarian stimulation, which is not possible when the chemotherapy has to be initiated immediately or when stimulation is contraindicated, according to the type of cancer. For patients who need immediate chemotherapy, cryopreservation of ovarian tissue is the only possible alternative. This article reports the techniques and results of orthotopic transplantation of cryopreserved ovarian tissue. Among almost 30 cases reported in the literature, six live births have been achieved to date.

Restoration of ovarian function in orthotopically transplanted cryopreserved ovarian tissue: a pilot experience.

Cryopreservation of ovarian tissue is currently proposed to young cancer patients before chemo- or radiotherapy to preserve their fertility. In this study, ovarian cortex was removed by laparoscopy from five women and cryopreserved before chemotherapy. After chemotherapy, they all experienced amenorrhoea due to premature ovarian failure and requested reimplantation of their cryopreserved ovarian tissue several years later. Thawed fragments were then grafted to an orthotopic site in all five women. Two of them underwent a second reimplantation. Ovarian function recovery was evaluated by hormone concentration measurement, follicular development on ultrasound and menstruation recovery. The first signs of ovarian function restoration (oestradiol peak, decrease in FSH, ultrasound showing follicular development) occurred between 16 and 26 weeks after reimplantation. Elevated FSH concentrations were sometimes observed between series of consecutive ovulatory cycles, demonstrating the presence of a relatively low ovarian reserve. There were no signs of disease recurrence in any patients with malignant disease. In conclusion, restoration of ovarian function was observed in all cases. Grafts remained functional in all the women. Transplantation of cryopreserved ovarian tissue to an orthotopic site appears to restore ovarian endocrine function, without any signs of disease recurrence.

Pregnancy and live birth after autotransplantation of frozen-thawed ovarian tissue in a patient with metastatic disease undergoing chemotherapy and hematopoietic stem cell transplantation

OBJECTIVE To report a live birth after orthotopic transplantation of cryopreserved ovarian tissue. DESIGN Case report. SETTING Department of Gynecology, Cliniques Universitaires Saint-Luc, Brussels. PATIENT(S) Woman with metastatic cancer who had her ovarian tissue cryopreserved in 2001 before undergoing chemotherapy and hematopoietic stem cell transplantation, resulting in premature ovarian failure. INTERVENTION(S) Orthotopic reimplantation of ovarian cortex performed 7 years after cryopreservation. MAIN OUTCOME MEASURE(S) Restoration of ovarian activity. RESULT(S) Restoration of ovarian activity was observed 3.5 months after reimplantantation, and ongoing pregnancy was diagnosed 9 months after grafting. The patient delivered a healthy baby weighing 2.830 kg. CONCLUSION(S) Our patient represents the thirteenth live birth to occur after orthotopic reimplantation of cryopreserved tissue, but the first in a woman treated for metastatic disease.

Current Thinking on the Pathogenesis of Endometriosis

This manuscript is a review of new ideas regarding the pathogenesis of peritoneal endometriosis, ovarian endometriosis, and retroperitoneal adenomyosis. Peritoneal endometriosis, the different aspects of which (black, red and white) represent distinctive steps in the evolutionary process, can be explained by the transplantation theory. Red lesions are the most active and most highly vascularized lesions and are considered to be the first stage of peritoneal endometriosis. The retroperitoneal nodule is an adenomyotic nodule whose histopathogenesis is not related to the implantation of regurgitated endometrial cells but to metaplasia of Müllerian remnants located in the rectovaginal septum. Metaplastic changes of Müllerian rests into adenomyotic glands involving the rectovaginal septum and the retroperitoneal space are responsible for the striking proliferation of the smooth muscle, creating an adenomyomatous appearance similar to that of adenomyosis in the endometrium.

Clinical and biologic evaluation of ovarian function in women treated by bone marrow transplantation for various indications during childhood or adolescence

OBJECTIVE To evaluate which factors determine premature ovarian failure after bone marrow transplantation (BMT) during childhood and adolescence. DESIGN Cross-sectional study. SETTING Academic teaching hospital. PATIENT(S) Thirty-five women with previous allogeneic (n = 19) or autologous (n = 16) BMT for benign (n = 12) or malignant disease (n = 23). Mean age at BMT was 9.8 ± 5.2 years. Eighteen patients had received total body irradiation (TBI). Twenty-three (66%) were premenarchal at the time of BMT. INTERVENTION(S) Evaluation of ovarian function. MAIN OUTCOME MEASURE(S) Retrospective analysis of gynecologic history and hormone measurements (FSH, E(2), and antimüllerian hormone [AMH]) in relation to initial pathology, treatment protocols, age, and menarchal status at the time of BMT and time elapsed since BMT. RESULT(S) Clinical evidence of persistent ovarian function after BMT was found in 46% of patients (16/35), but low AMH concentrations (<1.2 μg/L) were observed in 85% of patients, including a large subset (2/3) of clinically eugonadal subjects. Age ≤10 years at the time of BMT and absence of TBI were significantly and independently associated with higher rates of clinically proven persistent ovarian function at the time of evaluation. CONCLUSION(S) After BMT, ovarian function is impaired in the majority of women, even without clinical signs of premature ovarian failure. This impairment is mostly related to older age at the time of treatment and conditioning treatment with TBI.