Efficacy of ovarian tissue cryopreservation for fertility preservation: lessons learned from 545 cases.

STUDY QUESTION: How effective is ovarian tissue cryopreservation (OTC)? SUMMARY ANSWER: In our cohort of patients who underwent OTC, premature ovarian failure (POF) rates, return rates and pregnancy rates after autotransplantation were 31.5, 4.4 and 33%, respectively. WHAT IS KNOWN ALREADY: OTC for fertility purposes has been performed for >20 years now. With over 86 live births reported worldwide and success rates of ~30% after autotransplantation of frozen-thawed ovarian cortex, the procedure should no longer be considered experimental. However, very few publications report the efficacy of this procedure. STUDY DESIGN, SIZE, DURATION: Cases of ovarian tissue cryobanking for fertility preservation performed between 1997 and 2013 in a single institution were reviewed by analysis of the cryobank database and a prospective questionnaire sent out in March 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 545 patients who underwent OTC during this period. The analysis included indications for OTC, survival rates, ovarian function and spontaneous pregnancies after OTC, come-back rates for ovarian tissue transplantation, pregnancy rates after transplantation, and complication and satisfaction rates. MAIN RESULTS AND THE ROLE OF CHANCE: OTC was performed in this cohort at a mean age of 22.3 ± 8.8 years for oncological indications (79%), benign gynecological pathologies (17.5%) and genetic risks of POF (3.5%). Of the 545 patients, 29% were under 18 years of age at the time of OTC and 15% were prepubertal. While 10% of patients died from their disease, 21 patients (3.9%) underwent autotransplantation, 7 of whom delivered a healthy baby, yielding a post-transplantation live birth rate of 33%. Of 451 patients who were sent the questionnaire, 143 agreed to respond (32%). Nevertheless, ovarian function could not be evaluated in 36% of those who answered. Of 92 evaluable patients, 31.5% were menopausal and 68.5% showed persistent ovarian function. Of 52 women who attempted to conceive naturally, 37 were successful (71%). Among 140 patients who answered the questionnaire, 96% were satisfied with the procedure and only 1 major complication (intra-abdominal hemorrhage) was encountered. Among all the patients, 12% have donated their ovarian cortex for research purposes or have had it destroyed. LIMITATIONS, REASONS FOR CAUTION: The questionnaire participation rate (32%), limited follow-up (mean 7.6 ± 3.5 years) and use of only clinical criteria for evaluation of ovarian function made it difficult to accurately assess the risk of POF and efficiency of OTC. WIDER IMPLICATIONS OF THE FINDINGS: Our findings confirm a 30% pregnancy rate after ovarian cortex autotransplantation but also stress the difficulties of evaluating the real efficacy of OTC. STUDY FUNDING/COMPETING INTEREST(S): No funding was sought for this study and none of the authors have any conflict of interest. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registration ID: CRYOFONOV01.

A series of 3190 laparoscopic hysterectomies for benign disease from 1990 to 2006: evaluation of complications compared with vaginal and abdominal procedures.

OBJECTIVE: The aim of this study was to evaluate the complication rate after laparoscopic total hysterectomy and laparoscopic subtotal hysterectomy (LASH) in case of benign disease. DESIGN: All complications were prospectively recorded at the time of surgery and analysed retrospectively. SETTING: University hospital. POPULATION: Among 4505 hysterectomies performed by the same team using the same techniques between 1990 and 2006, 3190 were performed by laparoscopy, 906 by the vaginal route and 409 by laparotomy. METHODS: Laparoscopic hysterectomies, defined as laparoscopic subtotal hysterectomy (LASH) and total laparoscopic hysterectomy [laparoscopy-assisted vaginal hysterectomy (LAVH) switched to total laparoscopic hysterectomy (TLH) in 2000], were compared with vaginal and abdominal hysterectomies. MAIN OUTCOME MEASURES AND RESULTS: Since the early 1990s, the number of laparoscopic procedures has continued to grow, while the number of abdominal and vaginal procedures has decreased. Both minor complications (fever >38.5 degrees C after 2 days, bladder incision of <2 cm and iatrogenic adenomyosis) and major complications (haemorrhage, vesicoperitoneal fistula, ureteral injury, rectal perforation or fistula) have been observed during the surgical procedure itself and postoperatively. In the LASH group (n = 1613), the minor complication rate was 0.99% (n = 16) and the major complication rate 0.37% (n = 6). In the total laparoscopic hysterectomy (LAVH/TLH) group (n = 1577), the minor complication rate was 1.14% (n = 18) and the major complication rate 0.51% (n = 8). In the vaginal hysterectomy group (n = 906), minor and major complication rates were 0.77% (n = 7) and 0.33% (n = 3), respectively. In the abdominal hysterectomy group (n = 409), minor and major complication rates were 0.73% (n = 3) and 0.49% (n = 2), respectively. CONCLUSION: The results from our series of 4505 women clearly show that, in experienced hands, laparoscopic hysterectomy is not associated with any increase in major complication rates.

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 Hodgkin's 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.

Laparoscopic splenectomy in adults and children: experience with 31 patients.

BACKGROUND: Open surgery is the standard approach for splenectomy in hematologic disorders, but a few cases of successful laparoscopic splenectomy have been reported. METHODS: Thirty-one patients (18 adults, group 1; and 13 children, group 2) underwent laparoscopic splenectomy. Indications for surgery included idiopathic thrombocytopenic purpura (25 patients), congenital spherocytosis (4 patients), and hemolytic anemia (2 patients). In 97% of the patients the diameter of the spleen was less than 15 cm. RESULTS: Laparoscopic splenectomy was successful in 94% of the patients; conversion to open surgery was mainly related to hemorrhage. Accessory spleen was found in 39% in group 1 and 8% in group 2. Two adults received intraoperative autotransfusion. Postoperative morbidity was minimal. The median postoperative stay was 3 days (range, 2 to 12 days) in group 1 and 2 days (range, 2 to 5 days) in group 2. CONCLUSIONS: Laparoscopic splenectomy is safe in both adults and children. Adequate selection of patients (small-size spleen, splenic destruction on preoperative scanning of platelets), appropriate preparation in patients with idiopathic thrombocytopenic purpura (immunoglobulin G), and meticulous surgical technique (with routine opening of the gastrocolic ligament to search for accessory spleen) are key factors in obtaining the same long-term results as with open surgery.

Treatment of postpneumonectomy empyema with or without bronchopleural fistula.

Bronchopleural fistula with empyema is an uncommon but tragic complication after pulmonary resection. The possible therapeutic procedures are discussed. The patient often requires multiple surgical interventions and prolonged hospitalisation. According to the literature, open window thoracostomy (OWT) and even mutilating interventions such as myoplasty or thoracoplasty have to be performed when simple chest-tube drainage and antibiotic therapy do not suffice as illustrated by the present case.

Allograft of ovarian cortex between two genetically non-identical sisters: case report.

Aggressive chemotherapy and radiotherapy generally result in the loss of both endocrine and reproductive functions. In 1990, a woman aged 20 years, presenting with beta-thalassemia major, underwent chemotherapy (busulfan and cyclophosphamide) and total body irradiation (TBI) before bone marrow transplantation (BMT), the donor being her 17-year-old HLA-compatible sister. The treatment resulted in premature ovarian failure. In 2006, after excision of ovarian cortical fragments from the HLA-compatible sister, these fragments were immediately sutured to the ovarian medulla of the patient. Both procedures were performed by laparoscopy. Six months after reimplantation, vaginal ultrasonography and hormone concentrations indicated recovery of ovarian secretion and function. From 6 to 11 months, the patient experienced menstrual bleeding and the development of a follicle concomitant with high estradiol levels. Eleven months after reimplantation, two follicles were detected and punctured under vaginal ultrasonographic control. Two mature oocytes were retrieved and inseminated by ICSI. Two embryos (2- and 3-cell) were obtained. Allotransplantation of fresh ovarian tissue was laparoscopically performed between two genetically non-identical sisters. Restoration of ovarian function was achieved after six months. Oocyte retrieval and embryo development were demonstrated.

Restoration of ovarian function after orthotopic (intraovarian and periovarian) transplantation of cryopreserved ovarian tissue in a woman treated by bone marrow transplantation for sickle cell anaemia: case report.

Ovarian function after orthotopic transplantation of cryopreserved ovarian tissue has been restored in women with malignant disease. Here the techniques are adapted for a non-cancer patient. In 1999, right oophorectomy was performed in a 21 year old woman before chemotherapy, prior to bone marrow transplantation. Ovarian cortex was frozen, according to a strict protocol. After thawing, ovarian cortex was reimplanted into the ovary and in a peritoneal window close to the ovary in 2004. Four-and-a-half months after reimplantation, LH, FSH, 17beta-estradiol and progesterone levels, as well as ultrasonography, demonstrated the presence of an ovulatory cycle. After this cycle, the patient experienced two other ovulatory cycles, evidenced by FSH and 17beta-estradiol concentrations, as well as ultrasound demonstration of a follicle. Follicular development was clearly observed in both the intraovarian site (1st and 2nd cycle) and the peritoneal window (3rd cycle). Restoration of endocrine ovarian function occurred after ovarian cortical strips, biopsied and cryopreserved before chemotherapy, were reimplanted into the ovary itself and a periovarian peritoneal window.

What are the implications of myomas on fertility? A need for a debate?

In order to evaluate the relationship between leiomyomas and infertility, which remains a subject of debate, we have tried to evaluate the impact of myomas on fertility and pregnancy outcome in different conditions where myomas are implicated. Medline research was conducted of publications appearing between January 1988 and August 2001 on the subjects of myomas and myomectomy and their impact on fertility and pregnancy outcome in infertile women. A total of 106 manuscripts were consulted. The incidence of myomas in infertile women without any obvious cause of infertility is estimated to be 1-2.4%. The relationship between leiomyomas and infertility remains a subject of debate. The question is: do myomas influence fertility? We are obliged to conclude that the question remains. The absence of an answer to this crucial question is probably due to the fact that we have not yet conducted the appropriate prospective studies required to obtain any clear results.

Transplantation of cultured explants of human endometrium into nude mice.

The objective of this study was to analyse the histological and immunohistochemical characteristics of cultured explants of human endometrium transplanted into nude mice. Biopsies of eutopic endometrium were taken from six patients during laparoscopic surgery and classified according to the phase of the cycle. All the explants were cultured with oestrogen and progesterone for 24 h before transplantation into 15 mice. Four mice were grafted with explants of menstrual endometrium, four with explants of late proliferative endometrium, and seven with explants of late secretory-premenstrual endometrium. Typical endometrial glands and stroma were observed in 87% of cases 3 weeks after the transplantation. All the grafts revealed histological characteristics of the proliferative phase, even when the endometrial biopsy was taken during the late secretory phase. Immunohistochemical studies revealed that the proliferation index was high, whatever the menstrual phase of the endometrial biopsy. An extensive vascular network developed at the interface between the graft and the surrounding tissue. Vascular endothelial growth factor (VEGF) positive stained cells were observed in all grafts, the VEGF score being significantly higher in epithelial cells than in stromal cells. In conclusion, human endometrial explants, cultured for 24 h, could be successfully transplanted into nude mice. Immunohistochemical studies proved that human cultured endometrial tissue could not only survive in nude mice but could also become very active and develop characteristics different from the tissue of origin. An active vascular network is a necessary condition for the survival of the graft and may be explained by the high VEGF content.

A stratified intraoperative surgical strategy is mandatory during laparoscopic common bile duct exploration for common bile duct stones. Lessons and limits from an initial experience of 92 patients.

BACKGROUND: Open exploration and endoscopic sphincterotomy (ES) remain the preferred treatment of common bile duct stones (CBDS). The recent spread of laparoscopy has worsened the dilemna of choosing between surgical and endoscopic treatment of CBDS. The aim of this study was to critically evaluate the results of our preliminary experience with laparoscopic common bile duct exploration (CBDE) for CBDS. METHODS: Ninety-two consecutive patients were prospectively submitted to laparoscopic CBDE. Surgical strategy included an initial transcystic approach or laparoscopic choledochotomy. Failure of stone clearance was managed by conversion to open CBDE or by postoperative ES. Electrohydraulic lithotripsy and papillary balloon dilatation were selectively used. Stone clearance was assessed by choledochoscopy and control cholangiography. RESULTS: The overall laparoscopic stone clearance in this series was 84% (transcystic route 63% and choledochotomy 93%). Conversion to laparotomy was mandatory in 12% of the patients because of incomplete stone clearance and in 5% because of intraoperative complications. Postoperative ES was required in 4% of the patients, giving an overall surgical success rate of 96%. When indicated (small and limited number of stones located below the cysticocholedochal junction, with a dilated and patent cystic duct) the transcystic route had the lower success rate, the higher complication rate, and the shorter operative time and postoperative hospital stay. When indicated (accessible and dilated common bile duct over 7 mm), laparoscopic choledochotomy had the higher success rate, the lower complication rate, the longer operative time, and the longer postoperative hospital stay, which is related to associated external biliary drainage. The hospital mortality included two high-risk patients (2%) and the complications rate was 15%. CONCLUSIONS: Laparoscopic CBDE is safe in selected patients. A stratified intraoperative surgical strategy is mandatory in deciding between a transcystic route and choledochotomy with specific indications for each approach. When feasible, laparoscopic choledochotomy is more efficient and safe than the transcystic route, but it is associated with a longer postoperative hospital stay, which is due to external biliary drainage.

Laparoscopic treatment of gallbladder duplication. A plea for removal of both gallbladders.

BACKGROUND: Gallbladder duplication is a rare congenital condition, which can now be detected preoperatively by imaging studies. METHODS: We report a case of duplicated gallbladder with symptomatic unilobar gallstones. Appropriate biliary workup (ultrasound, oral cholecystography, and intravenous cholangiography) allowed a correct preoperative diagnosis. RESULTS: Laparoscopic treatment included selective removal of the diseased accessory gallbladder. However, postoperative acute cholecystitis and symptomatic gallstone occurred in the remaining main gallbladder, and laparoscopic reintervention was required 27 months later. CONCLUSIONS: This case illustrates the need for complete removal of both gallbladders during initial surgery. Precise intraoperative recognition of vascular and biliary anatomy-including abnormalities-is highlighted to avoid mistakes during surgery.

Adult polycystic liver disease: is fenestration the most adequate operation for long-term management?

OBJECTIVE: The aim of this study was to evaluate the immediate and long-term results in a retrospective series of patients with highly symptomatic adult polycystic liver disease (APLD) treated by extensive fenestration techniques. A classification of APLD was developed as a stratification scheme to help surgeons conceptualize which operation to offer to patients with APLD. SUMMARY BACKGROUND DATA: Treatment options for APLD remain controversial, with partisans of fenestration techniques or combined liver resection-fenestration. METHODS: Clinical symptoms, performance status, liver volume measurement by computed tomography (CT), and morbidity were recorded before surgery and after surgery. Adult polycystic liver disease was classified according to the number, size, and location of liver cysts and the amount of remaining liver parenchyma. Follow-up was obtained by clinical and CT examinations in all patients. RESULTS: Ten patients with highly symptomatic APLD were operated on using an extensive fenestration technique (by laparotomy in 8 patients and by laparoscopy in 2 patients, 1 of whom conversion to laparotomy was required). The mean preoperative liver volume was 7761 cm3. There was no mortality. Postoperative morbidity occurred in 50%, mainly from biliary complications, requiring reintervention in two cases. Massive intraoperative hemorrhage occurred in one patient. During a mean follow-up time of 71 months (range, 17 to 239 months), all patients were improved clinically according to their estimated performance status. The mean postoperative liver volume was 4596 cm3, which represents a mean liver volume reduction rate of 43%. However, in type III APLD, despite absence of clinical symptoms, a significant increase in liver volume was observed in 40% of the patients. CONCLUSIONS: Extensive fenestration is effective in relieving symptoms in patients with APLD. Hemorrhage and biliary complications are possible consequences of such an aggressive attempt to reduce liver volume. The procedure can be performed laparoscopically in type I APLD. A longer follow-up period is mandatory in type II APLD, to confirm the usefulness of the fenestration procedure. In type III APLD, significant disease progression was observed in 40% of the patients during long-term follow-up. Fenestration may not be the most appropriate operation for long-term management of all types of APLD.