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.

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.

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.