Jean-Luc Squifflet

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.

Complications, pregnancy and recurrence in a prospective series of 500 patients operated on by the shaving technique for deep rectovaginal endometriotic nodules

BACKGROUND The debate continues between advocates of the shaving technique and supporters of bowel resection in case of deep endometriosis with rectal muscularis involvement, despite little evidence for better improvement with bowel resection. METHODS We analyzed complication, pregnancy and recurrence rates after deep endometriotic nodule excision by shaving surgery. This is a prospective analysis of 500 cases (<40 years old) of deep endometriotic nodules. RESULTS Laparoscopic nodule resection was performed successfully in all cases. Major complications included: (i) rectal perforation in seven cases (1.4%); (ii) ureteral injury in four cases (0.8%); (iii) blood loss >300 ml in one case (0.2%); and (iv) urinary retention in four cases (0.8%). The median follow-up duration was 3.1 years (range 2-6 years). In our prospective series of 500 women, 388 wished to conceive. Of this number, 221 (57%) became pregnant naturally and 107 by means of IVF. In total, 328 women (84%) conceived. The recurrence rate was 8% among these 500 women, and it was significantly lower (P < 0.05) in women who became pregnant (3.6%) than in those who did not (15%). In women who failed to conceive, or were not interested in conceiving, severe pelvic pain recurred in 16-20% of patients. CONCLUSION In young women, conservative surgery using the shaving technique preserves organs, nerves and the vascular blood supply, yielding a high pregnancy rate and low complication and recurrence rates. There is a need, however, for further strong and energetic debate to weigh up the benefits of shaving (debulking surgery) versus rectal resection (radical surgery).

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.

Surgical treatment of ovarian endometriomas: state of the art?

To define the role of surgery in the treatment of endometriomas, we review the literature available via PubMed and cross-reference the published data. We analyze the arguments in favor of and against surgical treatment of endometriomas and compare surgical techniques. Pain relief and pregnancy rates of more than 50% after surgery are the most important arguments in favor of surgery. Histologic and biologic markers of ovarian reserve show a risk of decreased ovarian reserve that should be taken into consideration, especially in cases of repeated surgery. Considerable surgical expertise is required, and the lack of comparative studies yields no conclusions on the best surgical technique. Despite the risk of decreased ovarian reserve due to the surgical procedure, surgery has an important role in the treatment of ovarian endometriomas, and more studies are required to define the most appropriate surgical technique.

Restoration of ovarian function after allografting of ovarian cortex between genetically non-identical sisters

BACKGROUND Aggressive chemotherapy generally results in the loss of both endocrine and reproductive functions. For some women, however, oocyte, embryo or ovarian tissue cryopreservation were not proposed at the time. For three such women, orthotopic allotransplantation of fresh ovarian tissue from their genetically non-identical sister was performed. METHODS Three women, aged 20, 15 and 12 years, respectively, underwent chemotherapy and total body irradiation before bone marrow transplantation (BMT), the donor in each case being their HLA-compatible sister. Years later, HLA group analysis revealed complete chimerism, and ovarian allografting was performed, with the ovarian tissue donor being the sister who had already donated bone marrow. No immunosuppressive therapy was administered. No sign of rejection was observed. RESULTS Restoration of ovarian function occurred in all three cases, respectively, 6, 3.5 and 3.5 months after transplantation. The timing of the first estradiol peaks and the persistence of ovarian function were probably related to the primordial follicle density of donor ovarian tissue. CONCLUSIONS Even in the absence of immunosuppressive therapy, ovarian allografting between genetically non-identical sisters allowed restoration of ovarian function in cases where previous BMT from the HLA-compatible sister resulted in full chimerism, avoiding the threat of rejection.

Is the baboon model appropriate for endometriosis studies

OBJECTIVE To determinethe prevalence of spontaneous endometriosis andthe incidence of induced endometriosis after endocervical canal resection in baboons. DESIGN Induction and follow-up of endometriosis in baboons, which is one of the primate species that develop spontaneous endometriosis. Forty-one baboons were checked for the presence of spontaneous endometriosis. We then attempted to induce endometriosis in 30 of them by endocervical canal resection. SETTING Institute of Primate Research, Nairobi, Kenya, and Catholic University of Louvain, Brussels, Belgium. ANIMAL(S) Forty-one baboons were checked for spontaneous endometriosis and 30 of them were used to develop a model of induced endometriosis. INTERVENTION(S) A total of 41 baboons underwent diagnostic laparoscopy for 10 months. In a first step, 30 of this number subsequently underwent endocervical canal resection. In a second step, 20 of the 30 underwent uterine horn resection. MAIN OUTCOME MEASURE(S) Follow-up by laparoscopy. RESULT(S) Two of the 41 baboons were diagnosed with spontaneous endometriosis (4.8%). Twelve months after the surgical procedure to induce endometriosis, 8 of 29 animals presented with endometriotic lesions diagnosed by using laparoscopy and confirmed by histologic examination. The incidence of induced endometriosis in our model was thus 27.6%. In 2 baboons, endometriosis disappeared over time, resulting in a final rate of 20.7% (6/29). CONCLUSION(S) The rate of spontaneous endometriosis is very low (4.8%). Endometriosis can be induced (with a rate of just 27.6%) by endocervical canal resection to stimulate retrograde menstruation.

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.

Live birth after allografting of ovarian cortex between monozygotic twins with Turner syndrome (45,XO/46,XX mosaicism) and discordant ovarian function.

OBJECTIVE To report the restoration of ovarian function in a woman with Turner syndrome by allografting ovarian cortex from her monozygotic twin. DESIGN Case report. SETTING Gynecology research unit in a university hospital. PATIENT(S) A 37-year-old woman with Turner syndrome who had suffered premature ovarian failure (POF) at the age of 15. INTERVENTION(S) In this woman, we performed ovarian cortex transplantation. The donor was her monozygotic twin who had not experienced POF and who had had two normal deliveries. MAIN OUTCOME MEASURE(S) Restoration of ovarian activity and pregnancy. RESULT(S) Restoration of ovarian function was achieved 3 months after transplantation. After 7 months of regular cycles, spontaneous pregnancy occurred. The patient delivered a healthy baby girl weighing 2,850 g at 38 weeks of gestation. CONCLUSION(S) Girls with Turner syndrome suffer accelerated loss of ovarian follicles and only 2%-5% experience spontaneous menses with the potential to achieve pregnancy without medical intervention. This manuscript reports the first live birth after allografting between monozygotic twins with 45,XO/46,XX mosaicism and discordant growth pattern and ovarian function.

Minimally invasive gynecologic procedures.

Purpose of review To evaluate different surgical options for the treatment of endometriomas. A heated debate is currently under way between advocates of excisional surgery and the ablative approach. With papers increasingly focusing on ovarian reserve after endometrioma surgery, a review was mandatory. Recent findings Excisional and ablative surgery are well known procedures. This paper describes a combined technique that allows preservation of ovarian volume and antral follicle count. The question of postoperative ovarian reserve is widely discussed and the risk of malignancy is addressed. Summary Some previously published reviews have probably too hastily concluded that excision is a better option than ablation. They failed to analyze the ovarian reserve, which is often significantly decreased after excisional surgery. This manuscript clearly explains the crucial importance of preserving the ovarian blood supply, as well as the ovarian cortex containing all primordial follicles, during surgery.

Profile of vintafolide (EC145) and its use in the treatment of platinum-resistant ovarian cancer.

Objective Our aim was to review the profile of vintafolide (EC145) and its rationale for use in platinum-resistant ovarian cancer. First we investigated the folate receptors (FRs), folate’s pathway into cells, and its expression in normal and cancerous cells, before detailing the mechanism of action of vintafolide, its clinical applications, and the results of different study phases. Materials and methods A literature search was conducted through PubMed/Medline, Google, ClinicalTrials.gov and websites of pharmaceutical companies. Only articles in English were selected. All articles investigating folate receptor expression in ovarian cancer were selected first, than articles reviewing platinum resistance. Papers about vintafolide were collected, while those talking about synthesis and biochemistry concerns were excluded. The different Phase I and II studies were read, and an update on the website of pharmaceuticals companies were added. Results FR is a bundle-membrane receptor that is expressed normally in some normal tissues on the apical surface of cells, but highly expressed in ovarian cancer cells (>80%). It collects folate through endocytosis. Chemotherapy does not modify its expression in ovarian cancer cells, and its expression appears to be mostly associated with a poor prognosis and platinum resistance. Vintafolide is a folate-desacetylvinblastine monohydrazide conjugate, allowing a liberation of the drug into the cytoplasm of cancerous cells via the FR-α (FRα) and endocytosis, with high specificity. Phase I studies showed a 2.5 mg bolus dose to be nontoxic, with moderately adverse events. Phase II clinical trials for the first time demonstrated a statistically significant improvement in disease-free survival in patients with platinum-resistant ovarian cancer, and in those with a very poor prognosis who had already received three to four lines of systemic chemotherapy. The greater benefits were observed in patients with highly expressed FRα. Conclusion Vintafolide is a promising targeted agent for recurrent platinum-resistant ovarian cancer, first, thanks to its mechanism of action and the characteristics of FRα in ovarian cancer, and, second, because of the favorable results observed in the first clinical trials on platinum-resistant ovarian cancer. Phase III clinical trials are currently ongoing and are expected to confirm these results.