Olivier Donnez

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.

Long-term treatment of uterine fibroids with ulipristal acetate ☆

OBJECTIVE To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids. DESIGN Repeated intermittent open-label UPA courses, each followed by randomized double-blind norethisterone acetate (NETA) or placebo. SETTING European clinical gynecology centers. PATIENT(S) Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding. INTERVENTION(S) Patients received up to four 3-month courses of UPA 10 mg daily, immediately followed by 10-day double-blind treatment with NETA (10 mg daily) or placebo. MAIN OUTCOME MEASURE(S) Amenorrhea, fibroid volume, endometrial histology. RESULT(S) After the first UPA course, amenorrhea occurred in 79% of women, with median onset (from treatment start) of 4 days (interquartile range, 2-6 days). Median fibroid volume change was -45% (interquartile range, -66%; -25%). Amenorrhea rates were 89%, 88%, and 90% for the 131, 119, and 107 women who received treatment courses 2, 3, and 4, respectively. Median times to amenorrhea were 2, 3, and 3 days for treatment courses 2, 3, and 4, respectively. Median fibroid volume changes from baseline were -63%, -67%, and -72% after treatment courses 2, 3, and 4, respectively. All endometrial biopsies showed benign histology without hyperplasia; NETA did not affect fibroid volume or endometrial histology. CONCLUSION(S) Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov (www.clinicaltrials.gov) registration numbers NCT01156857 (PEARL III) and NCT01252069 (PEARL III extension).

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.

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.

Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids.

OBJECTIVE To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. DESIGN Double-blind, randomized administration of two 12-week courses of ulipristal acetate. SETTING Gynecology centers. PATIENT(S) A total of 451 patients with symptomatic uterine fibroid(s) and heavy bleeding. INTERVENTION(S) Two repeated 12-week treatment courses of daily 5 or 10 mg of ulipristal acetate. MAIN OUTCOME MEASURE(S) Amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), pain. RESULT(S) In the 5- and 10-mg treatment groups (62% and 73% of patients, respectively) achieved amenorrhea during both treatment courses. Proportions of patients achieving controlled bleeding during two treatment courses were >80%. Menstruation resumed after each treatment course and was diminished compared with baseline. After the second treatment course, median reductions from baseline in fibroid volume were 54% and 58% for the patients receiving 5 and 10 mg of ulipristal acetate, respectively. Pain and QoL improved in both groups. Ulipristal acetate was well tolerated with less than 5% of patients discontinuing treatment due to adverse events. CONCLUSION(S) Repeated 12-week courses of daily oral ulipristal acetate (5 and 10 mg) effectively control bleeding and pain, reduce fibroid volume, and restore QoL in patients with symptomatic fibroids. CLINICAL TRIAL REGISTRATION NUMBER NCT01629563 (PEARL IV).

Long-term medical management of uterine fibroids with ulipristal acetate

OBJECTIVE To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. DESIGN Double-blind, randomized administration of four 12-week courses of ulipristal acetate. SETTING Gynecology centers. PATIENT(S) Four hundred fifty-one subjects with symptomatic uterine fibroid(s) and heavy menstrual bleeding. INTERVENTION(S) Four repeated 12-week treatment courses of daily 5 or 10 mg ulipristal acetate. MAIN OUTCOME MEASURE(S) Endometrial safety and general safety, laboratory parameters, amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), and pain. RESULT(S) Efficacy results, such as bleeding control and fibroid volume reduction, were in line with previously published data. Pain and QoL showed marked improvements from screening, even during the off-treatment intervals. The safety profile of ulipristal acetate was confirmed, and repeated treatment courses did not increase the occurrence of adverse reactions. There were no significant changes in laboratory parameters during the study. The percentage of subjects with endometrial thickness ≥ 16 mm was 7.4% (all subjects) after the first treatment course and returned to below screening levels (4.9%) in subsequent treatment courses. As in previous studies, ulipristal acetate did not increase the occurrence of endometrial features of concern. The frequency of nonphysiological changes did not increase with repeated treatment. They were observed in 17.8% and 13.3% of biopsies after treatment courses 2 and 4, respectively, and were reversible after treatment cessation. CONCLUSION(S) The results of this study demonstrate the efficacy and further support the safety profile of repeated intermittent treatment of symptomatic fibroids with ulipristal acetate. CLINICAL TRIAL REGISTRATION NUMBER NCT01629563.

Deep neuromuscular block improves surgical conditions during laparoscopic hysterectomy: a randomised controlled trial.

BACKGROUND The benefit of inducing deep neuromuscular block to improve laparoscopic surgical conditions is controversial. OBJECTIVE The goal of this study was to determine the depth of neuromuscular block needed to guarantee excellent operating conditions during laparoscopic hysterectomy. DESIGN A randomised controlled trial. SETTING A single-centre study performed between February 2011 and May 2012. PATIENTS One hundred and two women of ASA physical status 1 or 2 gave consent to participate and were allocated randomly to one of two groups. INTERVENTION Under desflurane general anaesthesia, patients in Group S (shallow block), neuromuscular blockade was induced by administration of rocuronium 0.45 mg kg−1 followed by spontaneous recovery or a rescue bolus dose of 5 mg if surgical conditions were unacceptable. In Group D (deep block), neuromuscular block was induced by administration of rocuronium 0.6 mg kg−1 and maintained by bolus doses of 5 mg if the train-of-four count exceeded two, using adductor pollicis electromyography. MAIN OUTCOME MEASURES With a stable pneumoperitoneum (13 mmHg), the surgeon scored the quality of the surgical field every 10 min as excellent (1), good but not optimal (2), poor but acceptable (3) or unacceptable (4). The groups were compared using the Cochran–Armitage trend test. The level of neuromuscular blockade was recorded each time the surgical field score exceeded 1. RESULTS For groups S and D, respectively, the maximum surgical field scores were 1 in 21 and 34 patients, 2 in 11 and 11 patients, 3 in 4 and 5 patients and 4 in 14 and 0 patients. A trend towards higher scores was demonstrated in group S (P < 0.001). Surgical field scores of 2, 3 and 4 occurred only when the train-of-four count was at least 1, 2 and 3, respectively. CONCLUSION Inducing deep neuromuscular block (train-of-four count <1) significantly improved surgical field scores and made it possible to completely prevent unacceptable surgical conditions.

A series of 400 laparoscopic hysterectomies for benign disease: a single center, single surgeon prospective study of complications confirming previous retrospective study

Please cite this paper as: Donnez O, Donnez J. A series of 400 laparoscopic hysterectomies for benign disease: a single centre, single surgeon prospective study of complications confirming previous retrospective study. BJOG 2010; DOI: 10.1111/j.1471‐0528.2010.02520.x.

With the advent of selective progesterone receptor modulators, what is the place of myoma surgery in current practice?

Uterine fibroids are the most common benign uterine tumors. This review examines the different management strategies, involving mainly surgery, and evaluates them in the light of new developments with selective progesterone receptor modulators. On the one hand, hysteroscopic and laparoscopic (or minilaparotomic) myomectomy is the treatment of choice in women who wish to preserve their uterus, and hysterectomy has long been considered the standard surgical approach in symptomatic women who no longer wish to conceive. On the other hand, recent studies have demonstrated the efficacy of ulipristal acetate in the medical management of myomas. Analyzing the respective advantages of both medical and surgical therapy, we propose new guidelines for the management of fibroids that take into account the most important symptoms (bleeding, infertility) and the age of the patients.

Oxidative stress in the pelvic cavity and its role in the pathogenesis of endometriosis.

Endometriosis is a disorder associated with a general inflammatory response in the peritoneal cavity. Oxidative stress is a potential factor involved in the pathophysiology of this disease, and reactive oxygen species (ROS) are implicated in this process. Indeed, in healthy individuals, ROS and antioxidants are in balance, but when balance is tipped toward an overabundance of ROS, oxidative stress occurs and can impact the entire reproductive lifespan of a woman. Reactive oxygen species are intermediaries produced by normal oxygen metabolism but are known to have deleterious effects. Excessive release of ROS induces cellular damage and alters cellular function by regulating protein activity and gene expression, leading to harmful effects. To protect themselves, cells have developed antioxidant systems to limit production of ROS, inactivate them, and repair cell damage. Understanding of the control of hemoglobin, heme, and iron-induced redox balance in endometriosis led us to propose a number of hypotheses to explain why oxidative stress is induced in case of pelvic endometriosis. Erythrocytes, apoptotic endometrial tissue, and cell debris transplanted into the peritoneal cavity by menstrual reflux and macrophages have all been cited as potential inducers of oxidative stress. Erythrocytes are likely to release pro-oxidant and proinflammatory factors, such as hemoglobin and its highly toxic by-products heme and iron, into the peritoneal environment. Iron and heme are essential to living cells, but unless appropriately chelated, free iron, and to a lesser extent heme, play a key role in the formation of deleterious ROS.