Review question
Cochrane researchers reviewed the evidence for the effect of surgical removal of the womb (hysterectomy) together with the fallopian tubes (salpingectomy) versus hysterectomy without salpingectomy for ovarian cancer prevention.
Background
Ovarian cancer is the deadliest form of cancer of the female reproductive system. Screening for ovarian cancer is not effective, so preventive measures are needed. From previous studies, we learned that most types of ovarian cancer arise in the fallopian tubes. For that reason, the removal of the fallopian tubes (salpingectomy) during hysterectomy could lower the risk of ovarian cancer. The fallopian tubes have no function after completion of childbearing and salpingectomy is simple to perform.
Because salpingectomy is a preventive measure, it should not have serious side effects or risks. When considering possible risks of salpingectomy, it might lead to a higher complication rate because an extra surgical step has to be performed. Another possible risk could be an earlier onset of menopause. The ovaries and fallopian tubes lie close together and, in part, share their blood supply. Surgery to the fallopian tube could thus damage part of the blood supply to the ovaries. This damage could result in an earlier age of menopause. Ovarian reserve can be measured with the concentration of Anti-Müllerian hormone (AMH) in the blood. As women get older and come closer to menopause, the AMH concentration decreases.
To investigate the effectiveness and safety of salpingectomy for prevention of ovarian cancer, we compared the risks and benefits of hysterectomy with salpingectomy to hysterectomy without salpingectomy.
Study characteristics
We found seven randomised controlled trials comparing hysterectomy with salpingectomy to hysterectomy without salpingectomy. They included a total of 350 women undergoing a hysterectomy for benign conditions of the female reproductive tract. The evidence is current to January 2019.
Key results
We found no studies that reported ovarian cancer incidence after hysterectomy with salpingectomy to hysterectomy without salpingectomy.
The number of complications that occur after hysterectomy is generally very low. This means that only a few complications occurred in the trials included in this review and we were unable to make a good comparison of complication rates.
We found no evidence for any difference in onset of menopause after hysterectomy with salpingectomy. Our results suggest that the AMH concentrations after hysterectomy with salpingectomy would be between 1.89 pmol/L lower and 0.01 pmol/L higher than after hysterectomy without salpingectomy. The minimum difference in AMH concentration (0.01 pmol/L) represents no difference in the onset of menopause. The maximum difference in AMH concentration (1.89 pmol/L) shows that menopause could occur up to 20 months earlier after hysterectomy with salpingectomy compared to hysterectomy without salpingectomy. This result is calculated from the average decline of AMH per year.
Quality of the evidence
The evidence was of very low to low quality. The main limitations in the evidence were a low number of complications, meaning no comparison could be made, and differences in outcome measures of the included studies. Also, the total numbers of included studies and included women were low.
There were no eligible studies reporting on one of our primary outcomes - the incidence of ovarian cancer specifically after hysterectomy with or without opportunistic salpingectomy. In our meta-analyses we found insufficient data to assess whether there was any difference in surgical adverse events, with a very low number of events in women undergoing hysterectomy with and without opportunistic salpingectomy. For postoperative hormonal status we found no evidence of a difference between the groups. The maximum difference in time to menopause, calculated from the lower limit of the 95% CI and the natural average AMH decline, would be approximately 20 months, which we consider to be not clinically relevant. However, the results should be interpreted with caution and even more so in very young women for whom a difference in postoperative hormonal status is potentially more clinically relevant. Therefore, there is a need for research on the long-term effects of opportunistic salpingectomy during hysterectomy, particularly in younger women, as results are currently limited to six months postoperatively. This limit is especially important as AMH, the most frequently used marker for ovarian reserve, recovers over the course of several months following an initial sharp decline after surgery. In light of the available evidence, addition of opportunistic salpingectomy should be discussed with each woman undergoing a hysterectomy for benign indication, with provision of a clear overview of benefits and risks.
Ovarian cancer has the highest mortality rate of all gynaecological malignancies with an overall five-year survival rate of 30% to 40%. In the past two decades it has become apparent and more commonly accepted that a majority of ovarian cancers originate in the fallopian tube epithelium and not from the ovary itself. This paradigm shift introduced new possibilities for ovarian cancer prevention. Salpingectomy during a hysterectomy for benign gynaecological indications (also known as opportunistic salpingectomy) might reduce the overall incidence of ovarian cancer. Aside from efficacy, safety is of utmost importance, especially due to the preventive nature of opportunistic salpingectomy. Most important are safety in the form of surgical adverse events and postoperative hormonal status. Therefore, we compared the benefits and risks of hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy.
To assess the effect and safety of hysterectomy with opportunistic salpingectomy versus hysterectomy without salpingectomy for ovarian cancer prevention in women undergoing hysterectomy for benign gynaecological indications; outcomes of interest include the incidence of epithelial ovarian cancer, surgery-related adverse events and postoperative ovarian reserve.
The Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two clinical trial registers were searched in January 2019 together with reference checking and contact with study authors.
We intended to include both randomised controlled trials (RCTs) and non-RCTs that compared ovarian cancer incidence after hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications. For assessment of surgical and hormonal safety, we included RCTs that compared hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications.
We used standard methodological procedures recommended by Cochrane. The primary review outcomes were ovarian cancer incidence, intraoperative and short-term postoperative complication rate and postoperative hormonal status. Secondary outcomes were total surgical time, estimated blood loss, conversion rate to open surgery (applicable only to laparoscopic and vaginal approaches), duration of hospital admission, menopause-related symptoms and quality of life.
We included seven RCTs (350 women analysed). The evidence was of very low to low quality: the main limitations being a low number of included women and surgery-related adverse events, substantial loss to follow-up and a large variety in outcome measures and timing of measurements.
No studies reported ovarian cancer incidence after hysterectomy with opportunistic salpingectomy compared to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications. For surgery-related adverse events, there were insufficient data to assess whether there was any difference in both intraoperative (odds ratio (OR) 0.66, 95% confidence interval (CI) 0.11 to 3.94; 5 studies, 286 participants; very low-quality evidence) and short-term postoperative (OR 0.13, 95% CI 0.01 to 2.14; 3 studies, 152 participants; very low-quality evidence) complication rates between hysterectomy with opportunistic salpingectomy and hysterectomy without opportunistic salpingectomy because the number of surgery-related adverse events was very low. For postoperative hormonal status, the results were compatible with no difference, or with a reduction in anti-Müllerian hormone (AMH) that would not be clinically relevant (mean difference (MD) -0.94, 95% CI -1.89 to 0.01; I2 = 0%; 5 studies, 283 participants; low-quality evidence). A reduction in AMH would be unfavourable, but due to wide CIs, the postoperative change in AMH can still vary from a substantial decrease to even a slight increase.