The effect of laparoscopic salpingectomy for ectopic pregnancy on ovarian reserve.

BACKGROUND: Salpingectomy may damage ovarian reserve by direct vascular interruption to the ovary or thermal vascular injury from electrosurgery. It is plausible that this risk may increase in the context of salpingectomy conducted for ectopic pregnancy due to the distension of the fallopian tube and vascular changes associated with pregnancy. AIM: To report anti-Müllerian hormone (AMH) concentrations before and after laparoscopic salpingectomy for ectopic pregnancy as an indicator of change in ovarian reserve. MATERIALS AND METHODS: Women aged 18-44 years scheduled for salpingectomy for tubal ectopic pregnancy were prospectively recruited. Serum AMH concentrations were measured immediately prior to surgery, then repeated four months post-operatively. In all cases, salpingectomy was conducted laparoscopically using bipolar electrosurgery and mechanical scissors. A group of women scheduled for uterine curettage for first trimester miscarriage was recruited to ensure any observed change in AMH concentration in the women undergoing salpingectomy was secondary to surgery, rather than an effect of pregnancy. RESULTS: Paired pre- and post-operative serum AMH concentrations were obtained from 32 women with tubal ectopic pregnancy. The mean age of the women was 33.6 ± 4.6 years. There was no significant difference in the median pre- and post-operative AMH concentrations (13.00 pmol/L (range 5-67 pmol/L) vs 15.25 pmol/L (range 3-96 pmol/L), P = 0.575). Median AMH concentrations also remained stable in women experiencing a first trimester miscarriage (10.40 pmol/L (range 3.9-37.8 pmol/L) vs 13.67 pmol/L (range 2.8-30.5 pmol/L), P = 0.185). CONCLUSION: Laparoscopic salpingectomy using electrosurgery and mechanical scissors does not damage ovarian reserve. AMH concentrations do not fluctuate from baseline in the first trimester of pregnancy.

The safety and efficacy of controlled ovarian hyperstimulation for fertility preservation in women with early breast cancer: a systematic review.

STUDY QUESTION: Can controlled ovarian hyperstimulation (COH) for fertility preservation be effectively conducted in women with breast cancer without worsening their prognosis? SUMMARY ANSWER: COH with co-administration of letrozole suppresses oestradiol levels without significantly impacting oocyte yield or decreasing disease-free survival rates. WHAT IS KNOWN ALREADY: Oestradiol has the capacity to stimulate the proliferation of breast cancer cells. COH can cause oestradiol levels to rise by an order of magnitude above physiological levels. Concern exists regarding the effect of supra-physiological oestradiol levels in women with a recent diagnosis of breast cancer. STUDY DESIGN, SIZE, DURATION: A systematic review of the literature was performed using MEDLINE (PubMed database), EMBASE and the Cochrane Library. The search was restricted to articles written in English. No restrictions regarding the date of publication were applied. Safety was assessed in terms of relapse rates and cancer-related mortality rates. Peak oestradiol concentrations were recorded for different stimulation protocols. Efficacy was measured in terms of the total number of oocytes collected and proportion of mature oocytes. The primary outcome was mortality/recurrence in premenopausal women with Stage I-IIIB breast cancer who underwent COH in the immediate post-operative period, prior to chemotherapy. PARTICIPANTS/MATERIALS, SETTING, METHODS: This is a systematic review of randomized control trials (RCTs), case control and cohort studies reporting on the primary outcome of mortality/recurrence after COH in women with early breast cancer, or secondary outcomes of oocyte yield and peak oestrogen concentration. Owing to the small number of RCTs available, other study types were included. The last electronic search was run in April 2016. Two prospective non-randomized studies reported relapse and breast cancer-related mortality rates in 397 women with breast cancer, of whom 149 underwent COH. Twelve studies reported the peak oestradiol concentrations of 882 women undergoing COH with letrozole co-administration. Four studies compared the oocyte yield of 248 women who underwent COH plus letrozole with 254 women who underwent standard COH. Two studies compared peak oestradiol concentrations and oocyte yield in 61 women who underwent COH with tamoxifen co-administration and 49 women who underwent COH without tamoxifen. One study compared letrozole and tamoxifen co-administration, and another study compared the co-administration of letrozole and anastrozole. MAIN RESULTS AND THE ROLE OF CHANCE: The search identified 1002 records of which 15 were included in the final analysis. There was no evidence of a decline in relapse-free survival rates in the two studies of women with breast cancer who received COH with letrozole co-administration compared with women who did not undergo fertility preservation procedures. The largest of these studies reported recurrences in 6/120 (5.0%) women who received COH plus letrozole compared with 12/217 (5.5%) women who did not undergo COH (mean follow-up 5.0 versus 6.9 years; hazard ratio for recurrence 0.77, 95%CI 0.28-2.13). Conclusions regarding women with breast cancer who received tamoxifen during COH could not be made due to insufficient data. Peak oestradiol concentrations (338-829 pg/ml) were suppressed by letrozole when commenced on Days 2-3, with no decrease in oocyte yield. Tamoxifen does not suppress oestradiol concentrations, but may convey protection via its inhibitory action on the oestrogen receptor. LIMITATIONS, REASONS FOR CAUTION: Any statements regarding the safety of COH in women with breast cancer are based on a limited number of observational studies. High quality evidence is unlikely to become available for ethical and practical reasons. Whilst available data do not indicate a decline in disease-free survival, a small effect cannot be excluded. Breast cancers are heterogeneous in their genetic profile and receptor status, making the results of studies difficult to generalize to individual cases. The implication of alterations in other hormone levels such as androgens, progestins or vascular endothelial growth factor secondary to COH in women with breast cancer has not been quantified. WIDER IMPLICATIONS OF THE FINDINGS: The co-administration of 5 mg of letrozole daily commencing on Day 2 and continuing throughout COH is recommended as it reduces peak oestradiol concentrations without significantly decreasing oocyte yield. The use of a GnRH agonist trigger is beneficial as oestradiol concentrations rapidly decrease post-administration and rates of ovarian hyperstimulation are lower than with an hCG trigger, without a corresponding reduction in clinical pregnancy or live birth rates in cryopreservation cycles. The protective effect of tamoxifen has not been evaluated although theoretically may be of benefit due to its action on the oestrogen receptor. STUDY FUNDING/COMPETING INTEREST(S): None. REGISTRATION NUMBER: None.

Reliability of visual diagnosis of endometriosis.

OBJECTIVE: To determine whether accuracy of visual diagnosis of endometriosis at laparoscopy is determined by stage of disease. DESIGN: Prospective longitudinal cohort study (Canadian Task Force classification II-2). SETTING: Tertiary referral centers in three Australian states. PATIENTS: Of 1439 biopsy specimens, endometriosis was proved in at least one specimen in 431 patients. INTERVENTIONS: Laparoscopy with visual diagnosis and staging of endometriosis followed by histopathologic analysis and confirmation. Operations were performed by five experienced laparoscopic gynecologists. MEASUREMENTS AND MAIN RESULTS: Histopathologic confirmation of visual diagnosis of endometriosis adjusted for significant covariates. Endometriosis was accurately diagnosed in 49.7% of American Society for Reproductive Medicine (ASRM) stage I, which was significantly less accurate than for other stages of endometriosis. Deep endometriosis was more likely to be diagnosed accurately than superficial endometriosis (adjusted odds ratio, 2.51; 95% confidence interval, 1.50-4.18; p < .01). Lesion volume was also predictive, with larger lesions diagnosed more accurately than smaller lesions. In general, lesion site did not greatly influence accuracy except for superficial ovarian lesions, which were more likely to be incorrectly diagnosed visually as endometriosis (adjusted odds ratio, 0.16; 95% confidence interval, 0.06-0.41; p < .01). There was no statistically significant difference in accuracy between the gynecologic surgeons. CONCLUSION: The accuracy of visual diagnosis of endometriosis was substantially influenced by American Society of Reproductive Medicine stage, the depth and volume of the lesion, and to a lesser extent the location of the lesion.

Mental health care provision in the U.K. armed forces.

Like the United States, the United Kingdom (U.K.) population expresses ongoing interest in the mental health of their nation's armed forces and veterans. Current U.K. military mental health research efforts center on the work of military and civilian academics based at King's College London. These academics work closely with NATO partners, in particular the United States, in planning for future research. Conscious of the cultural dimensions to mental health among military personnel, considerable efforts have been made to strengthen informal support mechanisms including the training of lay Trauma Risk Management (TRiM) practitioners and other welfare services. Formal healthcare support provision comes from primary care providers and Departments of Community Mental Health, which provide local case management and appropriate escalation to in-patient services where required. Although veteran's healthcare is provided by the National Health Service, considerable efforts have been made to ensure their services best meet the needs of veterans and their families.

Relevance of gastrointestinal symptoms in endometriosis.

BACKGROUND: Endometriosis commonly presents with a range of symptoms none of which are particularly specific for the condition, often resulting in misdiagnosis or delay in diagnosis. AIM: To investigate gastrointestinal symptoms in women with endometriosis and compare their frequency with that of the classical gynaecological symptoms. METHODS: Systematic exploration of symptoms in a consecutive series of 355 women undergoing operative laparoscopy for suspected endometriosis. RESULTS: Endometriosis was confirmed by histology in 290 women (84.5%). Bowel lesions were present in only 7.6%. Ninety per cent of women had gastrointestinal symptoms, of which bloating was the most common (82.8%), but 71.3% also had other bowel symptoms. All gastrointestinal symptoms were similarly predictive of histologically confirmed endometriosis. Seventy-six women (21.4%) had previously been diagnosed with irritable bowel syndrome and 79% of them had endometriosis confirmed. CONCLUSION: Gastrointestinal symptoms are nearly as common as gynaecological symptoms in women with endometriosis and do not necessarily reflect bowel involvement.

Bowel resection for severe endometriosis: an Australian series of 177 cases.

BACKGROUND: Colorectal resection for severe endometriosis has been increasingly described in the literature over the last 20 years. AIMS: To describe the experiences of three gynaecological surgeons who perform radical surgery for colorectal endometriosis. METHODS: The records of three surgeons were reviewed. Relevant information was extracted and complied into a database. RESULTS: One hundred and seventy-seven women were identified as having undergone surgery between February 1997 and October 2007. The primary reason for presentation was pain in the majority of women (79%). Eighty-one segmental resections were performed, 71 disc excisions, ten appendicectomies and multiple procedures in ten women. The majority of procedures (81.4%) were performed laparoscopically. Histology confirmed the presence of disease in 98.3% of cases. A further 124 procedures to remove other sites of endometriosis were conducted, along with an additional 44 procedures not primarily for endometriosis. A total of 16 unintended events occurred. CONCLUSIONS: Our study adds to the growing body of literature describing colorectal resection for severe endometriosis. Overall, the surgery appeared to be well tolerated, demonstrating the role for this surgery.

Fertility and pain outcomes following laparoscopic segmental bowel resection for colorectal endometriosis: a review.

Intestinal involvement in endometriosis is thought to occur in up to 12% of all endometriosis cases. While colorectal resection is being increasingly advocated as a feasible management option in patients with severe disease, there still remains significant resistance towards this surgery. This article aims to review the current literature to determine the pain and fertility outcomes following segmental bowel resection for colorectal endometriosis.

A prospective multi-centre study of major complications experienced during excisional laparoscopic surgery for endometriosis.

OBJECTIVE: To clarify the rate of major intra-operative and post-operative complications experienced during excisional surgery for endometriosis. DESIGN: Prospective multi-centre observational study set in two University teaching hospitals and three private hospitals in Sydney, Australia. All consecutive subjects undergoing laparoscopic excisional surgery for minimal to severe endometriosis were recruited (790 subjects). Complications were recorded intra-operatively or post-operatively on a secure computerised patient database. Major intra- and post-operative complications i.e. inadvertent visceral or vascular injury or other complications directly related to surgery that either significantly prolonged the operating time, delayed discharge or necessitated re-admission. RESULTS: Seven hundred and ninety subjects were recruited over a 3-year period. Seven major complications were experienced (8.8/1000); four bowel injuries, one cystotomy, one ureteric transection, and one major vascular injury. All visceral or vascular injuries were diagnosed prior to completion of the surgery. No significant longterm sequelae were experienced. CONCLUSION: The incidence of major complications in this study of 8.8/1000 compares favourably with other similar reports. In view of the potential symptom relief obtained, the authors continue to believe the benefits of such surgery significantly outweigh the risks of subsequent operative-related morbidity.

Impact of biomarkers on clinical trial risk.

The last decade has witnessed the cost of drug development rise dramatically; concurrently, the number of new drug approvals has declined. Clinical trial failure rates have contributed significantly to this 'innovation' crisis and are directly related to clinical trial risk. One strategy that is often touted to resolve this challenge depends on embracing a personalized medicine approach where treatment is tailored to a patient's unique genetic background. We highlight a new risk-based paradigm of clinical trial risk that evaluates the utility of biomarkers in drug development and their risk mitigation benefits. Furthermore, examples elucidating the current state of biomarker integration during clinical trials and the potential risks posed by doing so will be discussed.

Laparoscopic transabdominal cervico-isthmic cerclage: a minimally invasive approach.

BACKGROUND: While the traditional approach to management of cervical insufficiency has been the insertion of a transvaginal cerclage during pregnancy, a transabdominal cervico-isthmic suture is indicated in certain patients. This procedure is traditionally performed via laparotomy. Laparoscopic transabdominal cervico-isthmic cerclage (LTCC) placement, however, confers the benefit of the low morbidity associated with laparoscopy. AIMS: To describe the technique and outcomes of LTCC in three cases. METHODS: LTCC was performed using Mersilene tape at the level of the internal cervical os in the prepregnancy period in three patients: one with previous cervical amputation and two with previous failed cervical cerclage. Procedures were performed at a tertiary level endoscopic unit, Sydney, Australia. RESULTS: The laparoscopic approach enabled placement of a suture with no morbidity, and rapid patient recovery in these cases. CONCLUSIONS: Laparoscopic cervical cerclage proved technically feasible and safe for a surgeon trained in laparoscopic suturing methods.