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Surgical management of tubal disease and infertility
Review
Surgical management of tubal disease and infertility
the risk of persistent tubal damage leading to infertility is approximately 8–12%. This risk doubles with each subsequent episode of PID so that infertility affects approximately 24% of patients following two documented episodes of PID, and approximately 54% of patients after three episodes. Prior abdominal surgeries, septic abortions, appendicitis associated with rupture, endometriosis, or other inflammatory pelvic and abdominal processes have also been implicated in causing tubal disease. Some of the causes of tubal blockage are listed in Table 1. While assisted reproductive technology (ART) results are improving, operative endoscopy has advanced tremendously in recent years ensuring an ongoing place in the management of infertility. The quality of the laparoscopic image improved dramatically with fibreoptic technology, better light sources and cameras. The feasibility of laparoscopic suturing has allowed many reconstructive procedures that traditionally required a laparotomy to be accomplished safely with laparoscopy on a day surgery basis with lower costs, shorter hospital stay and faster recovery times. Unlike ART that bypasses pelvic pathologies, surgical approaches improve fertility by correcting them and so, can potentially improve a patient’s related symptoms of pelvic pain and abnormal menstruation. Successful tubal surgery can provide a permanent cure. Couples can have unlimited attempts to conceiving naturally without being subjected to the side-effects of multiple pregnancies and ovarian hyperstimulation syndrome. In-vitro fertilisation (IVF) is a stressful and time-consuming treatment and each attempt offers only a single chance of pregnancy, unless embryos are available to freeze for future use.
C Coughlan T C Li
Abstract A spectrum of tubal disease of varying severity is recognised at laparoscopy. Pathology may vary from peritubal adhesions, damaged fimbriae or distorted tubal anatomy to tubal blockage or hydrosalpinx (a fluid-filled distension of the fallopian tube in the presence of distal tubal occlusion). Reproductive surgery remains an important option and complement to assisted reproductive technologies. Reproductive surgery should be considered as first-line treatment: when the correction of infertility pathology is achievable and a good result is expected; when the pathology is causing the patient pain or discomfort; and when if left uncorrected infertility pathology will compromise the results or increase the risks of assisted reproductive technology. The success of surgical infertility treatment depends on the careful selection of cases using appropriate investigative techniques, with procedures performed in centres with sufficient expertise. For both specialised reproductive and general gynaecological surgery, it is paramount to carefully follow the microsurgical principles to avoid adhesion formation and conserve normal tubal and ovarian tissues.
Diagnosis of tubal disease
Keywords endometriosis; fibroids; polycystic ovarian syndrome; tubal
There are currently many diagnostic tests available for evaluating tubal patency but our ability to evaluate tubal function is limited,
disease
Introduction
Some of the causes of tubal blockage
Tubal and peritoneal factors account for 30–40% of cases of female infertility. Tubal factors include damage to or obstruction of the fallopian tubes, usually related to previous pelvic inflammatory disease (PID) or pelvic or tubal surgery. PID is unquestionably the largest contributor to tubal infertility. When salpingitis occurs, luminal endothelial damage destroys the ciliated cells lining the ampullary and infundibular portions of the fallopian tube. These ciliated cells, responsible for transport of the gametes and embryo to their proper location, often do not recover after resolution of the infection. Loss of or compromise to ciliated cells leads to fibrosis both within the tube and distally, causing occlusion and possibly pelvic adhesions. Chlamydial salpingitis has a long incubation period and is likely to be asymptomatic. As a result, it is likely to lead to a prolonged, untreated infection causing permanent endothelial damage. Despite successful antibiotic treatment of laparoscopically confirmed PID,
Causes
Proximal tubal blockage
Pelvic inflammatory disease Salpingitis isthmica nodosa – nodular thickening of the isthmic portion of the tube Endometriosis – endometriosis of the tubes can occur in the serosa or the mucosa Obliterative fibrosis – in this condition, dense collagenous connective tissue replaces the lumen and the lamina propria of the tube, and involves the transmural segment of the tube Mucus, polyps and intramural debris – these are reversible causes of tubal blockage via tubal flushing Salpingitis – a polymicrobial aetiology in most cases Endometriosis Surgery – peri-tubular adhesions distort anatomy/sterilisation
Mid/distal tubal blockage
C Coughlan MRCOG MRCPI is Clinical Research Fellow at the Centre for Reproductive Medicine, Jessop Wing, Royal Hallamshire Hospital, Sheffield S10 2SF, UK. T C Li MRCP FRCOG MD PhD is a Professor at Sheffield Teaching Hospitals NHS trust, The Jessop Wing, Tree Root Walk, Sheffield S10 2SF, UK.
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Site of blockage
Table 1
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effect of tubal and ovarian adhesions on fertility was investigated by an early controlled study that evaluated the effect of salpingoovariolysis on subsequent fertility. The cumulative pregnancy rate in the group that underwent salpingo-ovariolysis was three times higher than in the non-treated group (32% vs 11% at 12 months and 45% vs 16% at 24 months). This study confirmed that pregnancies can occur spontaneously in a small proportion of women with periadnexal adhesions and patent tubes and established the therapeutic value of salpingo-ovariolysis in such cases. When the adhesions are mild and filmy, adhesiolysis will result in good cumulative conception rates (60% in 24 months). However, dense adhesions carry a worse prognosis than fine, filmy adhesions. Studies have shown that de novo adhesion formation was greater following laparotomy as compared with laparoscopy. The degree of magnification achieved during laparoscopy permits equivalent ease of surgery as with open microsurgery and the initial access to adherent pelvic organs is more easily achieved, without the need for macro-dissection. Laparoscopic salpingoovariolysis for periadnexal adhesions, when compared with laparotomy and adhesiolysis, has several advantages both in terms of lower cost and speedier postoperative recovery. Adhesiolysis can frequently be performed at the time of the routine diagnostic laparoscopy during investigation of infertility providing preoperative consent has been obtained from the patient. Laparoscopic lysis of dense adhesions may be difficult, particularly for thick, vascular and extensive dense adhesions between the adnexa and bowel. It is debatable as to whether microsurgery via laparotomy may occasionally be useful to lyse such adhesions as these patients have a very poor prognosis after surgery and are best referred for IVF. Other considerations prior to surgery include female age as IVF success rates decline with advancing age and in women above the age of 40 years, it is prudent to progress to IVF quickly rather than wait for tubal surgery to prove successful. The couple will have been investigated thoroughly before the decision is made to proceed with tubal surgery and if there are coexisting fertility problems – for example sperm dysfunction – IVF should be recommended. Patients who have had prior attempts at surgical tubal repair and patients with multifocal tubal disease have a very poor prognosis and, therefore, are not surgical candidates. Contraindications to tubal surgery are female age of 43 years, follicle stimulating hormone levels ≥15, inoperable tubal disease and abnormal semen analysis.
and tubal patency does not necessarily equate to satisfactory tubal function. We currently judge the degree of tubal damage mainly by tubal patency and the extent of peritubal adhesions, as determined by the American Fertility Scoring System rather than by the functional status of the tubal mucosa. Although current technology – such as salpingoscopy or fertiloscopy – now enables us to examine tubal mucosa in greater detail, it is still not possible to determine the intricate physiological function of the fallopian tube just by mere macroscopic inspection. Investigations for tubal disease can be divided into radiological tests, microbiological tests and surgical tests (see Table 2). The National Institute for Clinical Excellence (NICE) recommend that women who are not known to have comorbidities (such as pelvic inflammatory disease, previous ectopic pregnancy (EP) or endometriosis) should be offered hysterosalpingography (HSG) to screen for tubal occlusion. HSG is a reliable test for excluding tubal occlusion, and it is less invasive and makes more efficient use of resources than laparoscopy. For women who are not known to have co-morbidities and where the appropriate expertise is available, hysterosalpingo-contrastultrasonography may also be considered. However, if women are thought to have co-existing pathology, it is preferable to offer laparoscopy and dye transit test to allow tubal and other pelvic pathology to be assessed at the same time.
Tubal disease and surgery Peritubal adhesiolysis Peritubal adhesions interfere with ovum pick-up and tubal transport, while periovarian adhesions may inhibit ovulation. The
A summary of the diagnostic tests available for tubal disease Investigation
Description
Hysterosalpingogram
Injection of contrast media cervically and x-rays taken to illustrate the contour of the uterus and patency of the tubes ‘Gold Standard’ for tubal evaluation – involves laparoscopy and injection of methylene blue cervically to test tubal patency Ultrasound-guided procedure galactose microparticles are injected into the uterine cavity, air bubbles are followed into the uterine cavity and used to assess tubal patency Transvaginal microendoscopy – a fine endoscope is used to visualise the entire fallopian tube Combination of transvaginal hydrolaparoscopy, dye test, fimbrioscopy or salpingoscopy and hysteroscopy Blood test for Chlamydia antibodies
Laparoscopy and dye
Hysterocontrastsonography (HyCoSy)
Falloposcopy
Fertiloscopy
Chlamydia testing
Proximal tubal disease The narrow lumen of the proximal tube and its thick muscular wall with the physiological constrictor mechanism renders it prone to blockage by mucus or uterine debris. Spasm of the uterotubal sphincter is the most common reason for bilateral proximal tubal occlusion encountered during HSG. Spasm can result simply from the increased intrauterine pressure in response to the transcervical injection of methylene blue dye. The description of pain during the procedure should raise the suspicion that the inability of dye to enter the interstitial portion of the fallopian tube may be physiological. This problem may be resolved by the slow and gentle injection of dye into the uterine cavity, exercising care to minimise the abrupt increase in intrauterine pressure. Alternatively, the administration of a smooth muscle relaxant such as buscopan before the procedure may reduce the
Table 2
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children with a new partner. Procedures that destroy the least amount of tube have the highest success rates after reversal. Filshie clips and Falope rings generally have the best chance of success following surgical repair. In our unit, a pregnancy rate of 81% has been achieved in women who had a Filshie-clip sterilisation and reversal using microsurgical techniques. Tubal cautery destroys a large amount of the tube and is associated with a much lower success rate. The success of tubal re-anastomosis is dependent not only on the method of sterilisation, but the site of anastomosis, length of tube remaining and the presence of other infertility factors. Higher pregnancy rates and a lower median interval between surgery and pregnancy are expected with a longer remaining tube. If less than 4 cm of viable tube is available for anastomosis, the chances for subsequent pregnancy are quite poor. The location of the anastomosis also plays a role, with isthmic– isthmic re-anastomosis giving the best outcomes. The success rates also diminish when the anastomotic sites differ significantly in diameter. The length of time between sterilisation and reversal is not generally regarded as important, but one study noted an increased risk of damaged mucosa with flattening of epithelium and polyp formation in the proximal portion of the tube after 5 years of sterilisation. Currently, laparotomy and magnification with either loupes or an operative microscope offer the best chance of successful reversal. Important surgical techniques should be employed such as gentle tissue handling, meticulous haemostasis, minimising tissue injury, careful anatomical reconstruction and constant irrigation to avoid desiccation to allow the greatest chance of success. While open laparotomy and microsurgical tubal reconstruction are still standard practice, laparoscopic sterilisation reversal in the hands of experienced laparoscopic surgeons has excellent results. Prior to scheduling a patient for reversal of tubal sterilisation, the patient’s ovarian function, tubal condition and male fertility factors need to be assessed in order to counsel the patient appropriately as to the likelihood of future fertility following reversal. Laparoscopy may be necessary to assess surgical prognostic factors if they are not apparent from the history.
incidence of spasm. Selective transcervical cannulation of the fallopian tube with injection of dye may help to differentiate spasm from pathology. HSG delineates the uterine cavity and the fallopian tubes. It is important that the procedure is performed by an experienced radiologist who is able both to position the cannula into the cervical canal and to inject the contrast medium gently while imaging the pelvis to get a dynamic view of the passage of dye. A watersoluble contrast medium is usually used and will be absorbed after an hour approximately. However, the use of lipoidol has been shown in randomised controlled trials (RCTs) to improve chances of post-HSG pregnancy but the potential consequences of extravasations of oil-soluble contrast media into the pelvic cavity and fallopian tubes may be associated with anaphylaxis and lipogranuloma. Sometimes the cause of an apparent blockage is a mucus plug, which might be flushed through the tube by the contrast medium. There are reports of an increased chance of pregnancy in the 2 or 3 months that follow either HSG or laparoscopic insufflation of the tubes. Clinical pelvic infection following HSG has been reported. Prophylactic antibiotics are effective in reducing this risk and should be considered. Both doxycycline and azithromycin are effective prophylaxis and treatment for Chlamydia. Surgical options in the treatment of proximal tubal block include both microsurgical tubal anastomosis and tubal cannulation. Tubal catheterisation/cannulation can be performed using either a radiographic approach (selective salpingography combined with tubal cannulation) or a hysteroscopic approach. Selective salpingography can provide information about proximal and distal tubal obstruction. An advantage of selective salpingography combined with tubal cannulation is the ‘see and treat’ approach for proximal tubal obstruction in appropriately selected patients. Tubal perforation has been reported as a complication of tubal cannulation. In the NICE published guidelines in 2004, it was recommended that selective salpingography plus tubal catheterisation, or hysteroscopic tubal cannulation, should be considered as treatment options for women with proximal tubal obstruction because these treatments improve the chance of pregnancy. Microsurgical tubocornual anastomosis has been regarded as the standard treatment for proximal tubal blockage. A case series study reported that 27%, 47% and 53% of women with proximal tubal blockage who had microsurgical tubocornual anastomosis achieved a livebirth within 1, 2 and 3.5 years of surgery, respectively. Adverse prognostic factors on future fertility include reduced residual length of tube, significant intramural damage and evidence of pelvic infection/inflammation. Success rates with tubal surgery are also thought to depend upon the severity of the tubal damage, as well as the age of the woman, the duration of infertility and other associated infertility factors. Specialised training, experience and availability of equipment have a major effect on the outcome of tubal surgery.
Distal tubal disease The terminal portion of tube is involved in several infertilityrelated disorders ranging from thin, filmy adhesions to complete occlusion of its distal pole with distortion of anatomic relationships and resulting hydrosalpinx. The inflammatory response may be limited to the serosal surface of the fallopian tube or may cause extensive destruction of mucosal folds and the microscopic cilia that line the ampullary portion. The tubal epithelium with its secretions provides a unique nurturing environment that enhances oocyte maturation and sperm function leading to improved fertilisation, and is essential for early embryo development during the first 3–4 days mainly in the ampulla. It was observed in both animal and human studies that fertility diminishes in a linear fashion with the shortening or mucosal damage of the ampulla. Patency alone does not reflect the full functional roles of fallopian tubes. Fimbrioplasty is the lysis of fimbrial adhesions or dilatation of fimbrial strictures while neosalpingostomy is the creation of a new tubal opening in a fallopian tube with a distal occlusion.
Sterilisation reversal Between 0.2% and 3% of women who have had surgical tubal sterilisation will request a reversal procedure. The younger the patient at the time of a tubal sterilisation, the more likely it is that she will later regret her decision. The most frequently cited reason for requesting a reversal procedure is the desire for more
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levels after the above treatments. Serum hCG monitoring enables the timely detection of inadequately declining serum hCG concentrations following treatment. Whether salpingostomy or salpingectomy should be performed has not been properly examined in RCTs and is, therefore, still subject to debate. The inherent drawbacks of salpingostomy, that is, the risk of persistent trophoblast and repeat tubal EP, which both generate additional costs, are only justified if this would result in a higher spontaneous IUP rate, thereby saving on the costs of subsequent infertility treatment after salpingectomy. A review of cohort studies – published by Clausen in 1996 and Mol et al. in 1996 – comparing fertility outcome after salpingostomy and salpingectomy for tubal EP showed no significant beneficial effect of conservative surgery on IUP rates. However, the risk of repeat EPs was increased, although not significantly. Methodological limitations of these cohort studies were differences in duration of follow-up, failure to report on the desire for pregnancy and how subsequent pregnancies were achieved. Retrospective comparative studies, addressing these issues and reporting on life table analysis, showed a beneficial effect of salpingostomy compared with salpingectomy for tubal EP towards fertility outcome in women with contralateral tubal pathology and in women with previous infertility factors. In 2008, Mol et al. systematically reviewed the current evidence on surgery, systemic methotrexate and expectant management in the treatment of tubal EP. Following their review of 15 RCTs laparoscopic salpingostomy was found to be significantly less successful than the open surgical approach due to a higher persistent trophoblast rate, but was significantly less costly. However, a prophylactic single intramuscular injection of methotrexate given immediately postoperatively, significantly reduced persistent trophoblast after laparoscopic salpingostomy. This meta-analysis showed that laparoscopic surgery is the most cost-effective treatment for tubal EP and systemic methotrexate is a good alternative in selected patients with low serum hCG concentrations. Systemic administration of methotrexate has gained acceptance in selected patients. Women considered to be appropriate candidates for this treatment include those with a serum hCG below 3000 iu/l, and with minimal symptoms. The presence of cardiac activity in an EP is associated with a reduced chance of success and is considered to be a contraindication to medical treatment. Systemic methotrexate can only be recommended for haemodynamically stable women with an unruptured tubal EP and no signs of active bleeding presenting with serum hCG concentrations <3000 iu/l. If this treatment is offered, women should be given clear information both verbally but also in writing about the possible need for further treatment and possible adverse effects including abdominal pain, conjunctivitis, stomatitis and gastrointestinal upset. Women should be advised to avoid sexual intercourse during treatment, to maintain ample fluid intake and to use reliable contraception for 3 months after treatment because of the teratogenic risk associated with methotrexate. Expectant management has been advocated based on the knowledge that the natural course of many early EPs is a self-limiting process, ultimately resulting in tubal abortion or re-absorption. The Royal College of Obstetricians and Gynaecologists (RCOG) published guidelines regarding the management of tubal pregnancy in 2004. In this guideline, it was advocated
Results for distal tubal surgery vary widely, mainly because of bias in case selection in the absence of standardised assessment of the extent of tubal damage, especially the mucosal state. The degree of tubal damage can be assessed both pre- and intraoperatively and tubal disease can generally be categorised as mild, moderate or severe based on certain criteria. Mild disease is defined as absent or small hydrosalpinx (15 mm) with easily recognised fimbriae when tubal patency was restored, no significant peritubal or periovarian adhesions, and HSG demonstrating normal rugal folds. Up to 80% of these patients achieve intrauterine pregnancy (IUP) following surgical treatment. Tubal surgery for patients with moderate-to-severe disease tends to have a much worse prognosis. Not only is the prognosis poor, but should a patient conceive spontaneously, the risk of EP is also increased. Both laparoscopy and laparotomy have similar success rates for repair of distal tubal occlusion. Singhal et al. reviewed the outcome of microsurgical salpingostomy in 97 patients in our unit. An IUP rate of 34% was obtained and a livebirth rate of 29%, demonstrating that IVF has not rendered salpingostomy obsolete today. It is reasonable to perform laparoscopic fimbrioplasty or salpingostomy and resort to IVF should conception not occur within a certain time period. The chief determinant of results is patient selection. Careful pre- and intra-operative assessments are important to identify those patients who are most likely to benefit from surgery. If HSG films are obtainable, evidence of proximal disease, ampullary mucosal folds, strictures, intratubal adhesions and spillage, and dispersion of the contrast medium should be specifically looked for. When distal and proximal obstruction are both present (bipolar disease), surgical success rate is 5% or less. At laparoscopy direct inspection of the crucial distal one-third of the tubal lumen can be carried out by salpingoscopy using either a rigid hysteroscope or fine flexible endoscope capable of visualising intratubal adhesions or loss of normal landmarks. EP With improved awareness and earlier detection of EPs, the treatment focus has largely evolved from saving lives to preserving fertility. To date, therapeutic options for women with tubal EP are surgery, medical treatment or expectant management. Laparoscopy is the accepted approach to perform salpingostomy or salpingectomy. Laparoscopic surgery has been compared with open surgery in 228 women in three RCTs. Laparoscopic procedures were associated with shorter operation times, less intra-operative blood loss, shorter hospital stays and lower analgesic requirements resulting in a more cost-effective procedure. In women who desired future fertility, the subsequent IUP rates were similar and there was a trend toward lower repeat EP rates if a laparoscopic approach was used. However, laparoscopic salpingostomy was less successful than an open approach in elimination of the tubal pregnancy, reflected in a trend towards higher rates of persistent trophoblast. Persistent trophoblast may lead to recurrence of clinical symptoms and is an indication for additional treatment. Persistent trophoblast is a well-recognised hazard following salpingostomy, systemic methotrexate treatment and expectant management and units should have follow-up protocols in place for monitoring serum human chorionic gonadotrophin (hCG)
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improves the chance of a livebirth. While care should be taken not to compromise ovarian blood supply, there is no evidence for an impairment of ovarian response in subsequent IVF. Options other than salpingectomy have been considered. Transvaginal aspiration of hydrosalpinges has not been shown to be beneficial for a number of reasons. The underlying pathology is not altered and fluid will rapidly re-accumulate. The procedure is associated with a risk of infection and efficacy is not proven. Another option is proximal tubal ligation performed laparoscopically. This procedure is a reasonable option if salpingectomy is not technically possible due to the presence of pelvic adhesions but may result in pain and discomfort for the patient if hydrosalpinx is exacerbated due to both distal and proximal occlusion of the tube. Hydrosalpinges have a detrimental effect on the outcome of IVF and salpingectomy prior to IVF restores the likelihood of a successful outcome in a well-defined group of patients with ultrasound-visible hydrosalpinges. However, not every woman with hydrosalpinges should undergo salpingectomy as some fallopian tubes may be amenable to surgical repair. Preserved tubal mucosa indicates a good prognosis for tubal surgery, therefore, an appropriate mucosal assessment should be routine prior to deciding upon further management. Reconstructive tubal surgery should be preferred to salpingectomy in mild-to-moderate tubal disease. As salpingectomy is a definitive procedure it should be performed when the hydrosalpinges are beyond repair or in cases of IVF failure. Prophylactic salpingectomy and IVF are complementary to each other in the treatment of hydrosalpinges-related infertility.
that expectant management is an option for clinically stable women with minimal symptoms and a pregnancy of unknown location. In the management of suspected EP there is a serum hCG level at which it is assumed that all viable IUPs will be visualised by transvaginal ultrasound. This level is dependent on the quality of the ultrasound equipment and the experience of the ultrasonographer. A level of 1500 iu/l is usually acceptable. Five observational studies have shown that 44–69% of pregnancies of unknown location resolve spontaneously with expectant management. Expectant management is also an option for clinically stable asymptomatic women with an ultrasound diagnosis of EP and a decreasing serum hCG, initially less than serum 1000 iu/l. Women selected for conservative management must be counselled about the importance of compliance with follow-up and should be within easy access to the hospital. In accordance with RCOG Guideline No. 22, it is recommended that anti-D immunoglobulin be administered to all non-sensitised women who are rhesus-negative and who have an EP. Hydrosalpinx IVF is a treatment for infertility that bypasses the fallopian tubes. However, numerous retrospective studies in the 1990s suggested that the presence of extensive tubal disease, especially hydrosalpinx, might have a deleterious effect on the outcome of IVF. These reports were summarised in two meta-analyses, which showed that pregnancy rates are reduced by half and rates of spontaneous miscarriage are more than doubled in the presence of hydrosalpinx. Animal and in-vitro studies have demonstrated that hydrosalpingeal fluid can inhibit sperm motility and is embryotoxic. Endometrium in women with a hydrosalpinx expressed significantly lower levels of integrin than women without hydrosalpinx, with normal expression restored after removal. Leukaemia inhibitory factor expression in the mid-luteal phase endometrium of infertile women (n = 10) with hydrosalpinges was significantly lower than control fertile subjects. Salpingectomy resulted in an increase of leukaemia inhibitory factor expression in eight of 10 subjects with hydrosalpinges. Therefore, there is evidence of impaired endometrial receptivity in women with hydrosalpinges. A Cochrane review of three prospective randomised trials showed that laparoscopic salpingectomy for hydrosalpinges prior to IVF increased pregnancy (odds ratio (OR) 1.75, 95% confidence interval (CI) 1.07, 2.86) and livebirth (OR 2.13, 95% CI 1.24, 3.65) rates. In the subset of women with hydrosalpinges visible on ultrasound and those affected bilaterally, in one study, salpingectomy increased the delivery rates by more than 2-fold and 3.5-fold, respectively. Despite these data, there are concerns about the potentially negative impact of salpingectomy on ovarian function. Though early retrospective studies reported no immediate adverse effects on ipsilateral or contralateral ovarian function, some suggested that salpingectomy, when not properly performed close to the tube, may disrupt the normal blood flow to the ovary, resulting in fewer oocytes being retrieved from the side of operation during IVF cycle in comparison with the side with intact adnexa. However, the NICE published guidelines in 2004 regarding assessment and treatment for people with fertility problems and it was advised to offer salpingectomy to women with hydrosalpinges, preferably by laparoscopy, before IVF treatment because this
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Other fertility–enhancing surgical procedures Endometriosis and endometrioma Endometriosis is a common finding in women of reproductive age who commonly present with pelvic pain and infertility. While both medical and surgical treatments are effective in treatment of endometriosis-associated pain, the surgical approach is associated with lower recurrence rates as disease is removed rather than suppressed as in medical therapy. For patients with infertility, however, medical treatment is ineffective in enhancing fertility, while its role as an adjuvant therapy for ART remains debatable. Earlier studies indicated that women with moderate or severe disease would have improved fecundity with the removal of endometriotic implants. Surgery for severe and deep endometriosis is unpredictably difficult and may be associated with severe complications. Therefore, a preoperative ultrasound, contrast enema and intravenous pyelography may be required in many cases, together with a full preoperative bowel preparation. Surgery should be carefully planned and may require collaboration with a urologist or a colorectal surgeon. The RCOG published guidelines regarding the investigation and management of endometriosis in 2000 and it was advised that severe cases of endometriosis should be referred to centres where relevant clinical expertise would be available. Increasing evidence, including meta-analyses of non-randomised studies and a randomised study in Canada, showed significant increase in fecundity when implants in mild disease were removed. It is reasonable to conclude that laparoscopic resection or ablation of minimal and mild endometriosis using either bipolar diathermy or laser energy enhances fecundity in infertile women. 102
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Myomectomy is a major procedure with potential risks to the integrity and viability of the uterus. It is associated with risks of significant morbidity, including: infection; blood transfusion; risk of uterine rupture in pregnancy; and an increased likelihood of Caesarean section. Adhesion formation compromising future fertility may occur following both laparoscopic and open myomectomy. Preoperative treatment with a gonadotrophin-releasing hormone agonist for 6–8 weeks will cause significant shrinkage of the fibroids and reduce vascularity and blood loss during surgery. Patients should be advised to consider carefully the risks and benefits of myomectomy before proceeding to surgery. Studies have demonstrated a significant decrement in ongoing IVF pregnancy rates in patients with other intracavitary lesions such as intrauterine adhesions, uterine septum, and endometrial polyps. With the advent of hysteroscopic resection, such fibroids and other intrauterine lesions such as uterine septa can be easily removed via a relatively minor surgical procedure with reduced risks, shortened hospitalisation, reduced costs and better results. Hysteroscopic myomectomy has provided successful surgery in more than 90%, with persistence of disease in 10% of patients, especially those with significant intramural component. In the latter, two-stage operations under laparoscopic guidance may be advisable; with the removal of the remaining lesion during the second operation being possible in up to 98% of cases. In patients with recurrent pregnancy loss and infertility resulting from intrauterine adhesions, hysteroscopic adhesiolysis restored normal menstrual flow in 81% and achieved a favourable obstetric outcome in up to 71% of the pregnancies.
ART is effective in the treatment of infertility in patients with endometriosis. Although the ART pregnancy rates in patients with endometriosis in general are comparable with women with tubal disease, the results for the latter may be suboptimal due to the presence of hydrosalpinx. There are reports of poorer ovarian responses to stimulation and poorer outcomes of ART cycles in women with advanced endometriosis, especially those with endometrioma. Superovulation during ART cycles can worsen the disease and the patient’s symptoms, with the risk of infection increased during egg collection in the presence of an endometrioma. Medical suppression of endometriosis or the removal or destruction of an endometriotic cyst should be considered prior to commencing IVF treatment. Both approaches have been shown to improve the ovarian response to ovarian superovulation and to improve the pregnancy rates. Various strategies have been used to treat endometrioma including aspiration, cystectomy and coagulation of cyst capsules. Medical therapy or simple aspiration and irrigation of endometrioma are ineffective, with recurrence rates greater than 80% at 6-month follow-up. Ultrasound-guided aspiration will result in leaking of endometriotic fluid in the pelvis, which in turn causes pelvic infections and abscess formation. Removal of the cyst lining, by either stripping or sharp excision of the capsule results in a complete treatment. Following adhesiolysis, irrigation and suction procedure, the ovarian capsule is incised around the cyst opening. Once the plane of cleavage is found, the cyst wall is stripped from the ovary. Closure of the ovary is not considered to be necessary. It has been suggested that ovarian cystectomy may result in inadvertent removal or destruction of primordial follicles at the same time and, thus, reduce ovarian volume and reserve resulting in a negative effect on fertility. Therefore, it has been proposed to replace cystectomy by fenestration and coagulation of the inner wall of the endometriotic ovarian cyst. However, the treatment may be superficial and result in inadequate treatment. For larger cysts, a two-stage treatment is proposed. At the first operation, a large window is made in the cyst wall, followed by irrigation, some focal treatment and postoperatively 3 months of gonadotrophin-releasing hormone agonist treatment is prescribed. If ultrasound confirms the persistence of the cyst or its reformation, a second surgery will excise it. If there is no ultrasound evidence of the cyst and in the absence of pain or infertility, the benefit of a second surgery is unclear. This two-stage treatment allows the first operation to be scheduled as a day case without bowel preparation, whereas the need for a bowel preparation will be known prior to the second intervention.
Polycystic ovarian syndrome Polycystic ovarian syndrome (PCOS) is a multifaceted disease characterised by clinical and biochemical features with the identification of polycystic ovaries on ultrasonography. PCOS affects up to 20% of women in their reproductive age and is the most prominent cause of ovulatory defect. Medical treatment, in the form of the anti-oestrogen clomifene citrate, has been advocated as first-line treatment for anovulation in these women. Clomifene citrate will induce gonadotrophin release by occupying the oestrogen receptors in the hypothalamus, thereby interfering with the normal feedback mechanisms, increasing gonadotrophins and so stimulating the ovary to produce more follicles. As a result the adverse effects of this medication include ovarian hyperstimulation, abdominal discomfort and multiple pregnancies, NICE published guidelines in 2004 regarding the assessment and treatment for people with fertility problems. In these guidelines, it was recommended that women with PCOS should be offered treatment with clomifene citrate as the first-line of treatment for up to 12 months. It was also recommended that women prescribed clomifene should be offered ultrasound monitoring during at least the first cycle of treatment to ensure that they receive a dose that minimises the risk of a multiple pregnancy. Although up to 80% of women ovulate in response to clomifene, only 40–50% of women conceive. The NICE guidelines recommended that anovulatory women with PCOS who have not responded to clomifene and who have a body mass index of more than 25 should be offered metformin combined with clomifene citrate because this increases ovulation and pregnancy rates. Metformin is an oral biguanide insulin-sensitising agent
Uterine-fibroid and endometrial lesions Uterine fibroids are found in 25% of women older than 35 years with common symptoms ranging from excessive uterine bleeding, pelvic pressure, recurrent pregnancy loss and infertility; the latter appears mostly related to submucous or intramural myomas that distort the uterine cavity. Until recently it was thought that fibroids should only be removed if they are causing a significant distortion of the uterine cavity or if they are blocking the cornual region of the tube. There is increasing evidence that intramural fibroids affect implantation, even when there is no distortion of the uterine cavity.
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widely used in the treatment of type-2 diabetes. Several systematic reviews and a meta-analysis have evaluated the efficacy of metformin in the treatment of anovulation due to PCOS. The conclusion of these reviews was that metformin monotherapy represents a safe and valid therapeutic option for improving ovulation in PCOS patients. Clomifene citrate tends to work more quickly but incurs the risk of multiparity. Metformin has been administered in association with clomifene citrate in order to improve the efficacy of clomifene in clomifene-resistant patients. Siebert et al. confirmed the efficacy of metformin in improving ovulation in a population of clomifene citrate resistant PCOS women with an OR of 6.82 (95% CI 3.59–12.96, p < 0.00001). In 2008, Palomba et al. performed a systematic review and meta-analysis of the available RCTs comparing clomifene citrate and metformin. They concluded that in PCOS patients with anovulatory infertility and not previously treated, the administration of metformin plus clomifene citrate is no better than monotherapy (metformin alone or clomifene citrate alone). Those who fail to ovulate with clomifene and metformin would require intensive treatment using gonadotrophin either in the form of ovulation induction or hyperstimulation for IVF. The ovarian response to gonadotrophin in this group of patients can be highly unpredictable and difficult to control. They may either not develop any large follicles or hyper-respond with a significant risk of hyperstimulation syndrome and multiple pregnancy. The need for prolonged stimulation and intensive monitoring, and the high cancellation and miscarriage rate can be extremely stressful to these patients. Surgical methods of ovulation induction for women with clomifene citrate resistant PCOS include laparoscopic ovarian drilling with diathermy. This technique has replaced the more invasive and damaging technique of ovarian wedge resection. Laparoscopic ovarian surgery is free of the risks of multiple pregnancy and ovarian hyperstimulation and does not require intensive ultrasound monitoring. Surgery does, of course, carry its own risks and must be performed only with the use of proper techniques. The dose finding studies by Amer et al. suggested that four punctures per ovary with application of diathermy current via a specially designed needle (ovarian diathermy needle, Rocket of London), set at 30 watts for 5 seconds, should produce optimal results. The use of an excessive amount of electrical energy may lead to ovarian atrophy. Diathermy should be followed by instilling Hartmann’s solution or Adept into the pouch of Douglas, which, by cooling the ovaries, prevents heat injury to adjacent tissues and reduces adhesion formation. In a review of 27 studies with a total of 729 patients who underwent ovarian drilling, 84.2% ovulated and 55.7% conceived. One long-term follow-up study reported that most women became ovulatory soon after the surgery and 74% were still ovulating when studied 18–20 years later. In addition, ovarian drilling also renders patients with PCOS more responsive to either clomifene or gonadotrophin. Further research is needed to evaluate the effect of ovarian drilling on the formation of adhesions and the longterm health consequences of this procedure. ◆
Donesky BW, Adashi EY. Surgically induced ovulation in the polycystic ovary syndrome: wedge resection revisited in the age of laparoscopy. Fertil Steril 1995; 63: 438–443. Dover RW, Torode H. Endometriomas: a review of modern management. Gynaecol Endoscopy 2000; 9: 219–226. Forsey JP, Caul EO, Paul ID, Hull MG. Chlamydia trachomatis, tubal disease and the incidence of symptomatic and asymptomatic infection following hysterosalpingography. Hum Reprod 1990; 5: 444–447. Johnson N, Vandekerckhove P, Watson A, Lilford R, Harada T, Hughes E. Tubal flushing for subfertility. Cochrane Database Syst Rev 2002(3): CD003718. Johnson NP, Mak W, Sowter MC. Laparoscopic salpingectomy for women with hydrosalpinges enhances the success of IVF: a Cochrane Review. Hum Reprod 2002; 17: 543–548. Marcoux S, Maheux R, Berube S. The Canadian Collaborative Group on Endometriosis. Laparoscopic surgery in infertile women with minimal or mild endometriosis. N Engl J Med 1997; 337: 217–222. Mol F, Mol BW, Ankum WM, van der Veen F, Hajenius PJ. Current evidence on surgery, systemic methotrexate and expectant management in the treatment of tubal ectopic pregnancy: a systematic review and metaanalysis. Hum Reprod Update 2008; 14: 309–319. National Institute for Clinical Excellence. Fertility: assessment and treatment for people with fertility problems. Clinical guideline. London: NICE, February 2004. Palomba S, Pasquali R, Orio F, Nestler JE. Clomifene citrate, metformin or both as first-step approach in treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS): a systematic review of head-to-head randomized controlled studies and metaanalysis. Clin Endocrinol 2008 Aug 7 [Epub ahead of print]. Parker J, Bisits A, Proietto AM. A systematic review of single-dose intramuscular methotrexate for the treatment of ectopic pregnancy. Aust N Z J Obstet Gynaecol 1998; 38: 145–150. Posaci JC, Camus M, Osmanagaoglu K, Devroey P. Tubal surgery in the era of assisted reproductive technology: clinical options. Hum Reprod 1999; 14(Suppl. 1): 120–136. Pritts E. Fibroids and infertility: a systematic review of the evidence. Obstet Gynecol Surv 2001; 56: 483–491. Royal College of Obstetricians and Gynaecologists. Guideline no. 25. The investigation and management of endometriosis. London: RCOG, October 2000. Siebert TI, Kruger TF, Steyn DW, Nosarka S. Is the addition of metformin efficacious in the treatment of clomiphene citrateresistant patients with polycystic ovary syndrome? A structured literature review. Fertil Steril 2006; 86: 1432–1437. Spielvogel K, Shwayder J, Coddington CC. Surgical management of adhesions, endometriosis, and tubal pathology in the woman with infertility. Clin Obstet Gynecol 2000; 43: 916–928. Voorhis Van, Bradley J. Comparison of tubal ligation reversal procedures. Clin Obstet Gynecol 2000; 43: 641–649. Yao M, Tulandi T. Current status of surgical and non-surgical treatment of ectopic pregnancy. Fertil Steril 1997; 67: 421–433.
Practice points • Microsurgical and fertility-conserving principles should be followed in all gynaecological operations involving patients during their reproductive years
Further reading Bajekal N, Li TC. Fibroids, infertility and pregnancy wastage. Hum Reprod Update 2000; 6: 614–620.
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• Laparoscopic surgery produces less de novo adhesion formation compared with laparotomy • Tubal patency does not equate with normal tubal function • Tubo-ovarian adhesiolysis may improve fertility • Tubal re-anastomosis for proximal obstruction or reversal of sterilisation is highly successful. The method and site of sterilisation, length of tube remaining and the presence of other infertility factors are important factors affecting the end result • For surgical treatment of EP, linear salpingostomy if technically feasible should be used in haemodynamically stable women who wish to preserve their fertility
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• In distal tubal disease, proper selection according to objective assessment criteria including mucosal health is critical in triaging these patients to IVF or surgical management • Surgical treatment of endometriosis is effective in promoting both fertility and pain reduction; caution is needed to avoid adhesion formation and ovarian injury that may compromise subsequent fertility • Endometrial or uterine pathologies affecting the endometrial cavity impair ART results. Many of these lesions can be corrected safely with operative hysteroscopic approaches with good results
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Surgical management of tubal disease and infertility
the risk of persistent tubal damage leading to infertility is approximately 8–12%. This risk doubles with each subsequent episode of PID so that infertility affects approximately 24% of patients following two documented episodes of PID, and approximately 54% of patients after three episodes. Prior abdominal surgeries, septic abortions, appendicitis associated with rupture, endometriosis, or other inflammatory pelvic and abdominal processes have also been implicated in causing tubal disease. Some of the causes of tubal blockage are listed in Table 1. While assisted reproductive technology (ART) results are improving, operative endoscopy has advanced tremendously in recent years ensuring an ongoing place in the management of infertility. The quality of the laparoscopic image improved dramatically with fibreoptic technology, better light sources and cameras. The feasibility of laparoscopic suturing has allowed many reconstructive procedures that traditionally required a laparotomy to be accomplished safely with laparoscopy on a day surgery basis with lower costs, shorter hospital stay and faster recovery times. Unlike ART that bypasses pelvic pathologies, surgical approaches improve fertility by correcting them and so, can potentially improve a patient’s related symptoms of pelvic pain and abnormal menstruation. Successful tubal surgery can provide a permanent cure. Couples can have unlimited attempts to conceiving naturally without being subjected to the side-effects of multiple pregnancies and ovarian hyperstimulation syndrome. In-vitro fertilisation (IVF) is a stressful and time-consuming treatment and each attempt offers only a single chance of pregnancy, unless embryos are available to freeze for future use.
C Coughlan T C Li
Abstract A spectrum of tubal disease of varying severity is recognised at laparoscopy. Pathology may vary from peritubal adhesions, damaged fimbriae or distorted tubal anatomy to tubal blockage or hydrosalpinx (a fluid-filled distension of the fallopian tube in the presence of distal tubal occlusion). Reproductive surgery remains an important option and complement to assisted reproductive technologies. Reproductive surgery should be considered as first-line treatment: when the correction of infertility pathology is achievable and a good result is expected; when the pathology is causing the patient pain or discomfort; and when if left uncorrected infertility pathology will compromise the results or increase the risks of assisted reproductive technology. The success of surgical infertility treatment depends on the careful selection of cases using appropriate investigative techniques, with procedures performed in centres with sufficient expertise. For both specialised reproductive and general gynaecological surgery, it is paramount to carefully follow the microsurgical principles to avoid adhesion formation and conserve normal tubal and ovarian tissues.
Diagnosis of tubal disease
Keywords endometriosis; fibroids; polycystic ovarian syndrome; tubal
There are currently many diagnostic tests available for evaluating tubal patency but our ability to evaluate tubal function is limited,
disease
Introduction
Some of the causes of tubal blockage
Tubal and peritoneal factors account for 30–40% of cases of female infertility. Tubal factors include damage to or obstruction of the fallopian tubes, usually related to previous pelvic inflammatory disease (PID) or pelvic or tubal surgery. PID is unquestionably the largest contributor to tubal infertility. When salpingitis occurs, luminal endothelial damage destroys the ciliated cells lining the ampullary and infundibular portions of the fallopian tube. These ciliated cells, responsible for transport of the gametes and embryo to their proper location, often do not recover after resolution of the infection. Loss of or compromise to ciliated cells leads to fibrosis both within the tube and distally, causing occlusion and possibly pelvic adhesions. Chlamydial salpingitis has a long incubation period and is likely to be asymptomatic. As a result, it is likely to lead to a prolonged, untreated infection causing permanent endothelial damage. Despite successful antibiotic treatment of laparoscopically confirmed PID,
Causes
Proximal tubal blockage
Pelvic inflammatory disease Salpingitis isthmica nodosa – nodular thickening of the isthmic portion of the tube Endometriosis – endometriosis of the tubes can occur in the serosa or the mucosa Obliterative fibrosis – in this condition, dense collagenous connective tissue replaces the lumen and the lamina propria of the tube, and involves the transmural segment of the tube Mucus, polyps and intramural debris – these are reversible causes of tubal blockage via tubal flushing Salpingitis – a polymicrobial aetiology in most cases Endometriosis Surgery – peri-tubular adhesions distort anatomy/sterilisation
Mid/distal tubal blockage
C Coughlan MRCOG MRCPI is Clinical Research Fellow at the Centre for Reproductive Medicine, Jessop Wing, Royal Hallamshire Hospital, Sheffield S10 2SF, UK. T C Li MRCP FRCOG MD PhD is a Professor at Sheffield Teaching Hospitals NHS trust, The Jessop Wing, Tree Root Walk, Sheffield S10 2SF, UK.
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Site of blockage
Table 1
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effect of tubal and ovarian adhesions on fertility was investigated by an early controlled study that evaluated the effect of salpingoovariolysis on subsequent fertility. The cumulative pregnancy rate in the group that underwent salpingo-ovariolysis was three times higher than in the non-treated group (32% vs 11% at 12 months and 45% vs 16% at 24 months). This study confirmed that pregnancies can occur spontaneously in a small proportion of women with periadnexal adhesions and patent tubes and established the therapeutic value of salpingo-ovariolysis in such cases. When the adhesions are mild and filmy, adhesiolysis will result in good cumulative conception rates (60% in 24 months). However, dense adhesions carry a worse prognosis than fine, filmy adhesions. Studies have shown that de novo adhesion formation was greater following laparotomy as compared with laparoscopy. The degree of magnification achieved during laparoscopy permits equivalent ease of surgery as with open microsurgery and the initial access to adherent pelvic organs is more easily achieved, without the need for macro-dissection. Laparoscopic salpingoovariolysis for periadnexal adhesions, when compared with laparotomy and adhesiolysis, has several advantages both in terms of lower cost and speedier postoperative recovery. Adhesiolysis can frequently be performed at the time of the routine diagnostic laparoscopy during investigation of infertility providing preoperative consent has been obtained from the patient. Laparoscopic lysis of dense adhesions may be difficult, particularly for thick, vascular and extensive dense adhesions between the adnexa and bowel. It is debatable as to whether microsurgery via laparotomy may occasionally be useful to lyse such adhesions as these patients have a very poor prognosis after surgery and are best referred for IVF. Other considerations prior to surgery include female age as IVF success rates decline with advancing age and in women above the age of 40 years, it is prudent to progress to IVF quickly rather than wait for tubal surgery to prove successful. The couple will have been investigated thoroughly before the decision is made to proceed with tubal surgery and if there are coexisting fertility problems – for example sperm dysfunction – IVF should be recommended. Patients who have had prior attempts at surgical tubal repair and patients with multifocal tubal disease have a very poor prognosis and, therefore, are not surgical candidates. Contraindications to tubal surgery are female age of 43 years, follicle stimulating hormone levels ≥15, inoperable tubal disease and abnormal semen analysis.
and tubal patency does not necessarily equate to satisfactory tubal function. We currently judge the degree of tubal damage mainly by tubal patency and the extent of peritubal adhesions, as determined by the American Fertility Scoring System rather than by the functional status of the tubal mucosa. Although current technology – such as salpingoscopy or fertiloscopy – now enables us to examine tubal mucosa in greater detail, it is still not possible to determine the intricate physiological function of the fallopian tube just by mere macroscopic inspection. Investigations for tubal disease can be divided into radiological tests, microbiological tests and surgical tests (see Table 2). The National Institute for Clinical Excellence (NICE) recommend that women who are not known to have comorbidities (such as pelvic inflammatory disease, previous ectopic pregnancy (EP) or endometriosis) should be offered hysterosalpingography (HSG) to screen for tubal occlusion. HSG is a reliable test for excluding tubal occlusion, and it is less invasive and makes more efficient use of resources than laparoscopy. For women who are not known to have co-morbidities and where the appropriate expertise is available, hysterosalpingo-contrastultrasonography may also be considered. However, if women are thought to have co-existing pathology, it is preferable to offer laparoscopy and dye transit test to allow tubal and other pelvic pathology to be assessed at the same time.
Tubal disease and surgery Peritubal adhesiolysis Peritubal adhesions interfere with ovum pick-up and tubal transport, while periovarian adhesions may inhibit ovulation. The
A summary of the diagnostic tests available for tubal disease Investigation
Description
Hysterosalpingogram
Injection of contrast media cervically and x-rays taken to illustrate the contour of the uterus and patency of the tubes ‘Gold Standard’ for tubal evaluation – involves laparoscopy and injection of methylene blue cervically to test tubal patency Ultrasound-guided procedure galactose microparticles are injected into the uterine cavity, air bubbles are followed into the uterine cavity and used to assess tubal patency Transvaginal microendoscopy – a fine endoscope is used to visualise the entire fallopian tube Combination of transvaginal hydrolaparoscopy, dye test, fimbrioscopy or salpingoscopy and hysteroscopy Blood test for Chlamydia antibodies
Laparoscopy and dye
Hysterocontrastsonography (HyCoSy)
Falloposcopy
Fertiloscopy
Chlamydia testing
Proximal tubal disease The narrow lumen of the proximal tube and its thick muscular wall with the physiological constrictor mechanism renders it prone to blockage by mucus or uterine debris. Spasm of the uterotubal sphincter is the most common reason for bilateral proximal tubal occlusion encountered during HSG. Spasm can result simply from the increased intrauterine pressure in response to the transcervical injection of methylene blue dye. The description of pain during the procedure should raise the suspicion that the inability of dye to enter the interstitial portion of the fallopian tube may be physiological. This problem may be resolved by the slow and gentle injection of dye into the uterine cavity, exercising care to minimise the abrupt increase in intrauterine pressure. Alternatively, the administration of a smooth muscle relaxant such as buscopan before the procedure may reduce the
Table 2
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children with a new partner. Procedures that destroy the least amount of tube have the highest success rates after reversal. Filshie clips and Falope rings generally have the best chance of success following surgical repair. In our unit, a pregnancy rate of 81% has been achieved in women who had a Filshie-clip sterilisation and reversal using microsurgical techniques. Tubal cautery destroys a large amount of the tube and is associated with a much lower success rate. The success of tubal re-anastomosis is dependent not only on the method of sterilisation, but the site of anastomosis, length of tube remaining and the presence of other infertility factors. Higher pregnancy rates and a lower median interval between surgery and pregnancy are expected with a longer remaining tube. If less than 4 cm of viable tube is available for anastomosis, the chances for subsequent pregnancy are quite poor. The location of the anastomosis also plays a role, with isthmic– isthmic re-anastomosis giving the best outcomes. The success rates also diminish when the anastomotic sites differ significantly in diameter. The length of time between sterilisation and reversal is not generally regarded as important, but one study noted an increased risk of damaged mucosa with flattening of epithelium and polyp formation in the proximal portion of the tube after 5 years of sterilisation. Currently, laparotomy and magnification with either loupes or an operative microscope offer the best chance of successful reversal. Important surgical techniques should be employed such as gentle tissue handling, meticulous haemostasis, minimising tissue injury, careful anatomical reconstruction and constant irrigation to avoid desiccation to allow the greatest chance of success. While open laparotomy and microsurgical tubal reconstruction are still standard practice, laparoscopic sterilisation reversal in the hands of experienced laparoscopic surgeons has excellent results. Prior to scheduling a patient for reversal of tubal sterilisation, the patient’s ovarian function, tubal condition and male fertility factors need to be assessed in order to counsel the patient appropriately as to the likelihood of future fertility following reversal. Laparoscopy may be necessary to assess surgical prognostic factors if they are not apparent from the history.
incidence of spasm. Selective transcervical cannulation of the fallopian tube with injection of dye may help to differentiate spasm from pathology. HSG delineates the uterine cavity and the fallopian tubes. It is important that the procedure is performed by an experienced radiologist who is able both to position the cannula into the cervical canal and to inject the contrast medium gently while imaging the pelvis to get a dynamic view of the passage of dye. A watersoluble contrast medium is usually used and will be absorbed after an hour approximately. However, the use of lipoidol has been shown in randomised controlled trials (RCTs) to improve chances of post-HSG pregnancy but the potential consequences of extravasations of oil-soluble contrast media into the pelvic cavity and fallopian tubes may be associated with anaphylaxis and lipogranuloma. Sometimes the cause of an apparent blockage is a mucus plug, which might be flushed through the tube by the contrast medium. There are reports of an increased chance of pregnancy in the 2 or 3 months that follow either HSG or laparoscopic insufflation of the tubes. Clinical pelvic infection following HSG has been reported. Prophylactic antibiotics are effective in reducing this risk and should be considered. Both doxycycline and azithromycin are effective prophylaxis and treatment for Chlamydia. Surgical options in the treatment of proximal tubal block include both microsurgical tubal anastomosis and tubal cannulation. Tubal catheterisation/cannulation can be performed using either a radiographic approach (selective salpingography combined with tubal cannulation) or a hysteroscopic approach. Selective salpingography can provide information about proximal and distal tubal obstruction. An advantage of selective salpingography combined with tubal cannulation is the ‘see and treat’ approach for proximal tubal obstruction in appropriately selected patients. Tubal perforation has been reported as a complication of tubal cannulation. In the NICE published guidelines in 2004, it was recommended that selective salpingography plus tubal catheterisation, or hysteroscopic tubal cannulation, should be considered as treatment options for women with proximal tubal obstruction because these treatments improve the chance of pregnancy. Microsurgical tubocornual anastomosis has been regarded as the standard treatment for proximal tubal blockage. A case series study reported that 27%, 47% and 53% of women with proximal tubal blockage who had microsurgical tubocornual anastomosis achieved a livebirth within 1, 2 and 3.5 years of surgery, respectively. Adverse prognostic factors on future fertility include reduced residual length of tube, significant intramural damage and evidence of pelvic infection/inflammation. Success rates with tubal surgery are also thought to depend upon the severity of the tubal damage, as well as the age of the woman, the duration of infertility and other associated infertility factors. Specialised training, experience and availability of equipment have a major effect on the outcome of tubal surgery.
Distal tubal disease The terminal portion of tube is involved in several infertilityrelated disorders ranging from thin, filmy adhesions to complete occlusion of its distal pole with distortion of anatomic relationships and resulting hydrosalpinx. The inflammatory response may be limited to the serosal surface of the fallopian tube or may cause extensive destruction of mucosal folds and the microscopic cilia that line the ampullary portion. The tubal epithelium with its secretions provides a unique nurturing environment that enhances oocyte maturation and sperm function leading to improved fertilisation, and is essential for early embryo development during the first 3–4 days mainly in the ampulla. It was observed in both animal and human studies that fertility diminishes in a linear fashion with the shortening or mucosal damage of the ampulla. Patency alone does not reflect the full functional roles of fallopian tubes. Fimbrioplasty is the lysis of fimbrial adhesions or dilatation of fimbrial strictures while neosalpingostomy is the creation of a new tubal opening in a fallopian tube with a distal occlusion.
Sterilisation reversal Between 0.2% and 3% of women who have had surgical tubal sterilisation will request a reversal procedure. The younger the patient at the time of a tubal sterilisation, the more likely it is that she will later regret her decision. The most frequently cited reason for requesting a reversal procedure is the desire for more
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levels after the above treatments. Serum hCG monitoring enables the timely detection of inadequately declining serum hCG concentrations following treatment. Whether salpingostomy or salpingectomy should be performed has not been properly examined in RCTs and is, therefore, still subject to debate. The inherent drawbacks of salpingostomy, that is, the risk of persistent trophoblast and repeat tubal EP, which both generate additional costs, are only justified if this would result in a higher spontaneous IUP rate, thereby saving on the costs of subsequent infertility treatment after salpingectomy. A review of cohort studies – published by Clausen in 1996 and Mol et al. in 1996 – comparing fertility outcome after salpingostomy and salpingectomy for tubal EP showed no significant beneficial effect of conservative surgery on IUP rates. However, the risk of repeat EPs was increased, although not significantly. Methodological limitations of these cohort studies were differences in duration of follow-up, failure to report on the desire for pregnancy and how subsequent pregnancies were achieved. Retrospective comparative studies, addressing these issues and reporting on life table analysis, showed a beneficial effect of salpingostomy compared with salpingectomy for tubal EP towards fertility outcome in women with contralateral tubal pathology and in women with previous infertility factors. In 2008, Mol et al. systematically reviewed the current evidence on surgery, systemic methotrexate and expectant management in the treatment of tubal EP. Following their review of 15 RCTs laparoscopic salpingostomy was found to be significantly less successful than the open surgical approach due to a higher persistent trophoblast rate, but was significantly less costly. However, a prophylactic single intramuscular injection of methotrexate given immediately postoperatively, significantly reduced persistent trophoblast after laparoscopic salpingostomy. This meta-analysis showed that laparoscopic surgery is the most cost-effective treatment for tubal EP and systemic methotrexate is a good alternative in selected patients with low serum hCG concentrations. Systemic administration of methotrexate has gained acceptance in selected patients. Women considered to be appropriate candidates for this treatment include those with a serum hCG below 3000 iu/l, and with minimal symptoms. The presence of cardiac activity in an EP is associated with a reduced chance of success and is considered to be a contraindication to medical treatment. Systemic methotrexate can only be recommended for haemodynamically stable women with an unruptured tubal EP and no signs of active bleeding presenting with serum hCG concentrations <3000 iu/l. If this treatment is offered, women should be given clear information both verbally but also in writing about the possible need for further treatment and possible adverse effects including abdominal pain, conjunctivitis, stomatitis and gastrointestinal upset. Women should be advised to avoid sexual intercourse during treatment, to maintain ample fluid intake and to use reliable contraception for 3 months after treatment because of the teratogenic risk associated with methotrexate. Expectant management has been advocated based on the knowledge that the natural course of many early EPs is a self-limiting process, ultimately resulting in tubal abortion or re-absorption. The Royal College of Obstetricians and Gynaecologists (RCOG) published guidelines regarding the management of tubal pregnancy in 2004. In this guideline, it was advocated
Results for distal tubal surgery vary widely, mainly because of bias in case selection in the absence of standardised assessment of the extent of tubal damage, especially the mucosal state. The degree of tubal damage can be assessed both pre- and intraoperatively and tubal disease can generally be categorised as mild, moderate or severe based on certain criteria. Mild disease is defined as absent or small hydrosalpinx (15 mm) with easily recognised fimbriae when tubal patency was restored, no significant peritubal or periovarian adhesions, and HSG demonstrating normal rugal folds. Up to 80% of these patients achieve intrauterine pregnancy (IUP) following surgical treatment. Tubal surgery for patients with moderate-to-severe disease tends to have a much worse prognosis. Not only is the prognosis poor, but should a patient conceive spontaneously, the risk of EP is also increased. Both laparoscopy and laparotomy have similar success rates for repair of distal tubal occlusion. Singhal et al. reviewed the outcome of microsurgical salpingostomy in 97 patients in our unit. An IUP rate of 34% was obtained and a livebirth rate of 29%, demonstrating that IVF has not rendered salpingostomy obsolete today. It is reasonable to perform laparoscopic fimbrioplasty or salpingostomy and resort to IVF should conception not occur within a certain time period. The chief determinant of results is patient selection. Careful pre- and intra-operative assessments are important to identify those patients who are most likely to benefit from surgery. If HSG films are obtainable, evidence of proximal disease, ampullary mucosal folds, strictures, intratubal adhesions and spillage, and dispersion of the contrast medium should be specifically looked for. When distal and proximal obstruction are both present (bipolar disease), surgical success rate is 5% or less. At laparoscopy direct inspection of the crucial distal one-third of the tubal lumen can be carried out by salpingoscopy using either a rigid hysteroscope or fine flexible endoscope capable of visualising intratubal adhesions or loss of normal landmarks. EP With improved awareness and earlier detection of EPs, the treatment focus has largely evolved from saving lives to preserving fertility. To date, therapeutic options for women with tubal EP are surgery, medical treatment or expectant management. Laparoscopy is the accepted approach to perform salpingostomy or salpingectomy. Laparoscopic surgery has been compared with open surgery in 228 women in three RCTs. Laparoscopic procedures were associated with shorter operation times, less intra-operative blood loss, shorter hospital stays and lower analgesic requirements resulting in a more cost-effective procedure. In women who desired future fertility, the subsequent IUP rates were similar and there was a trend toward lower repeat EP rates if a laparoscopic approach was used. However, laparoscopic salpingostomy was less successful than an open approach in elimination of the tubal pregnancy, reflected in a trend towards higher rates of persistent trophoblast. Persistent trophoblast may lead to recurrence of clinical symptoms and is an indication for additional treatment. Persistent trophoblast is a well-recognised hazard following salpingostomy, systemic methotrexate treatment and expectant management and units should have follow-up protocols in place for monitoring serum human chorionic gonadotrophin (hCG)
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improves the chance of a livebirth. While care should be taken not to compromise ovarian blood supply, there is no evidence for an impairment of ovarian response in subsequent IVF. Options other than salpingectomy have been considered. Transvaginal aspiration of hydrosalpinges has not been shown to be beneficial for a number of reasons. The underlying pathology is not altered and fluid will rapidly re-accumulate. The procedure is associated with a risk of infection and efficacy is not proven. Another option is proximal tubal ligation performed laparoscopically. This procedure is a reasonable option if salpingectomy is not technically possible due to the presence of pelvic adhesions but may result in pain and discomfort for the patient if hydrosalpinx is exacerbated due to both distal and proximal occlusion of the tube. Hydrosalpinges have a detrimental effect on the outcome of IVF and salpingectomy prior to IVF restores the likelihood of a successful outcome in a well-defined group of patients with ultrasound-visible hydrosalpinges. However, not every woman with hydrosalpinges should undergo salpingectomy as some fallopian tubes may be amenable to surgical repair. Preserved tubal mucosa indicates a good prognosis for tubal surgery, therefore, an appropriate mucosal assessment should be routine prior to deciding upon further management. Reconstructive tubal surgery should be preferred to salpingectomy in mild-to-moderate tubal disease. As salpingectomy is a definitive procedure it should be performed when the hydrosalpinges are beyond repair or in cases of IVF failure. Prophylactic salpingectomy and IVF are complementary to each other in the treatment of hydrosalpinges-related infertility.
that expectant management is an option for clinically stable women with minimal symptoms and a pregnancy of unknown location. In the management of suspected EP there is a serum hCG level at which it is assumed that all viable IUPs will be visualised by transvaginal ultrasound. This level is dependent on the quality of the ultrasound equipment and the experience of the ultrasonographer. A level of 1500 iu/l is usually acceptable. Five observational studies have shown that 44–69% of pregnancies of unknown location resolve spontaneously with expectant management. Expectant management is also an option for clinically stable asymptomatic women with an ultrasound diagnosis of EP and a decreasing serum hCG, initially less than serum 1000 iu/l. Women selected for conservative management must be counselled about the importance of compliance with follow-up and should be within easy access to the hospital. In accordance with RCOG Guideline No. 22, it is recommended that anti-D immunoglobulin be administered to all non-sensitised women who are rhesus-negative and who have an EP. Hydrosalpinx IVF is a treatment for infertility that bypasses the fallopian tubes. However, numerous retrospective studies in the 1990s suggested that the presence of extensive tubal disease, especially hydrosalpinx, might have a deleterious effect on the outcome of IVF. These reports were summarised in two meta-analyses, which showed that pregnancy rates are reduced by half and rates of spontaneous miscarriage are more than doubled in the presence of hydrosalpinx. Animal and in-vitro studies have demonstrated that hydrosalpingeal fluid can inhibit sperm motility and is embryotoxic. Endometrium in women with a hydrosalpinx expressed significantly lower levels of integrin than women without hydrosalpinx, with normal expression restored after removal. Leukaemia inhibitory factor expression in the mid-luteal phase endometrium of infertile women (n = 10) with hydrosalpinges was significantly lower than control fertile subjects. Salpingectomy resulted in an increase of leukaemia inhibitory factor expression in eight of 10 subjects with hydrosalpinges. Therefore, there is evidence of impaired endometrial receptivity in women with hydrosalpinges. A Cochrane review of three prospective randomised trials showed that laparoscopic salpingectomy for hydrosalpinges prior to IVF increased pregnancy (odds ratio (OR) 1.75, 95% confidence interval (CI) 1.07, 2.86) and livebirth (OR 2.13, 95% CI 1.24, 3.65) rates. In the subset of women with hydrosalpinges visible on ultrasound and those affected bilaterally, in one study, salpingectomy increased the delivery rates by more than 2-fold and 3.5-fold, respectively. Despite these data, there are concerns about the potentially negative impact of salpingectomy on ovarian function. Though early retrospective studies reported no immediate adverse effects on ipsilateral or contralateral ovarian function, some suggested that salpingectomy, when not properly performed close to the tube, may disrupt the normal blood flow to the ovary, resulting in fewer oocytes being retrieved from the side of operation during IVF cycle in comparison with the side with intact adnexa. However, the NICE published guidelines in 2004 regarding assessment and treatment for people with fertility problems and it was advised to offer salpingectomy to women with hydrosalpinges, preferably by laparoscopy, before IVF treatment because this
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Other fertility–enhancing surgical procedures Endometriosis and endometrioma Endometriosis is a common finding in women of reproductive age who commonly present with pelvic pain and infertility. While both medical and surgical treatments are effective in treatment of endometriosis-associated pain, the surgical approach is associated with lower recurrence rates as disease is removed rather than suppressed as in medical therapy. For patients with infertility, however, medical treatment is ineffective in enhancing fertility, while its role as an adjuvant therapy for ART remains debatable. Earlier studies indicated that women with moderate or severe disease would have improved fecundity with the removal of endometriotic implants. Surgery for severe and deep endometriosis is unpredictably difficult and may be associated with severe complications. Therefore, a preoperative ultrasound, contrast enema and intravenous pyelography may be required in many cases, together with a full preoperative bowel preparation. Surgery should be carefully planned and may require collaboration with a urologist or a colorectal surgeon. The RCOG published guidelines regarding the investigation and management of endometriosis in 2000 and it was advised that severe cases of endometriosis should be referred to centres where relevant clinical expertise would be available. Increasing evidence, including meta-analyses of non-randomised studies and a randomised study in Canada, showed significant increase in fecundity when implants in mild disease were removed. It is reasonable to conclude that laparoscopic resection or ablation of minimal and mild endometriosis using either bipolar diathermy or laser energy enhances fecundity in infertile women. 102
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Myomectomy is a major procedure with potential risks to the integrity and viability of the uterus. It is associated with risks of significant morbidity, including: infection; blood transfusion; risk of uterine rupture in pregnancy; and an increased likelihood of Caesarean section. Adhesion formation compromising future fertility may occur following both laparoscopic and open myomectomy. Preoperative treatment with a gonadotrophin-releasing hormone agonist for 6–8 weeks will cause significant shrinkage of the fibroids and reduce vascularity and blood loss during surgery. Patients should be advised to consider carefully the risks and benefits of myomectomy before proceeding to surgery. Studies have demonstrated a significant decrement in ongoing IVF pregnancy rates in patients with other intracavitary lesions such as intrauterine adhesions, uterine septum, and endometrial polyps. With the advent of hysteroscopic resection, such fibroids and other intrauterine lesions such as uterine septa can be easily removed via a relatively minor surgical procedure with reduced risks, shortened hospitalisation, reduced costs and better results. Hysteroscopic myomectomy has provided successful surgery in more than 90%, with persistence of disease in 10% of patients, especially those with significant intramural component. In the latter, two-stage operations under laparoscopic guidance may be advisable; with the removal of the remaining lesion during the second operation being possible in up to 98% of cases. In patients with recurrent pregnancy loss and infertility resulting from intrauterine adhesions, hysteroscopic adhesiolysis restored normal menstrual flow in 81% and achieved a favourable obstetric outcome in up to 71% of the pregnancies.
ART is effective in the treatment of infertility in patients with endometriosis. Although the ART pregnancy rates in patients with endometriosis in general are comparable with women with tubal disease, the results for the latter may be suboptimal due to the presence of hydrosalpinx. There are reports of poorer ovarian responses to stimulation and poorer outcomes of ART cycles in women with advanced endometriosis, especially those with endometrioma. Superovulation during ART cycles can worsen the disease and the patient’s symptoms, with the risk of infection increased during egg collection in the presence of an endometrioma. Medical suppression of endometriosis or the removal or destruction of an endometriotic cyst should be considered prior to commencing IVF treatment. Both approaches have been shown to improve the ovarian response to ovarian superovulation and to improve the pregnancy rates. Various strategies have been used to treat endometrioma including aspiration, cystectomy and coagulation of cyst capsules. Medical therapy or simple aspiration and irrigation of endometrioma are ineffective, with recurrence rates greater than 80% at 6-month follow-up. Ultrasound-guided aspiration will result in leaking of endometriotic fluid in the pelvis, which in turn causes pelvic infections and abscess formation. Removal of the cyst lining, by either stripping or sharp excision of the capsule results in a complete treatment. Following adhesiolysis, irrigation and suction procedure, the ovarian capsule is incised around the cyst opening. Once the plane of cleavage is found, the cyst wall is stripped from the ovary. Closure of the ovary is not considered to be necessary. It has been suggested that ovarian cystectomy may result in inadvertent removal or destruction of primordial follicles at the same time and, thus, reduce ovarian volume and reserve resulting in a negative effect on fertility. Therefore, it has been proposed to replace cystectomy by fenestration and coagulation of the inner wall of the endometriotic ovarian cyst. However, the treatment may be superficial and result in inadequate treatment. For larger cysts, a two-stage treatment is proposed. At the first operation, a large window is made in the cyst wall, followed by irrigation, some focal treatment and postoperatively 3 months of gonadotrophin-releasing hormone agonist treatment is prescribed. If ultrasound confirms the persistence of the cyst or its reformation, a second surgery will excise it. If there is no ultrasound evidence of the cyst and in the absence of pain or infertility, the benefit of a second surgery is unclear. This two-stage treatment allows the first operation to be scheduled as a day case without bowel preparation, whereas the need for a bowel preparation will be known prior to the second intervention.
Polycystic ovarian syndrome Polycystic ovarian syndrome (PCOS) is a multifaceted disease characterised by clinical and biochemical features with the identification of polycystic ovaries on ultrasonography. PCOS affects up to 20% of women in their reproductive age and is the most prominent cause of ovulatory defect. Medical treatment, in the form of the anti-oestrogen clomifene citrate, has been advocated as first-line treatment for anovulation in these women. Clomifene citrate will induce gonadotrophin release by occupying the oestrogen receptors in the hypothalamus, thereby interfering with the normal feedback mechanisms, increasing gonadotrophins and so stimulating the ovary to produce more follicles. As a result the adverse effects of this medication include ovarian hyperstimulation, abdominal discomfort and multiple pregnancies, NICE published guidelines in 2004 regarding the assessment and treatment for people with fertility problems. In these guidelines, it was recommended that women with PCOS should be offered treatment with clomifene citrate as the first-line of treatment for up to 12 months. It was also recommended that women prescribed clomifene should be offered ultrasound monitoring during at least the first cycle of treatment to ensure that they receive a dose that minimises the risk of a multiple pregnancy. Although up to 80% of women ovulate in response to clomifene, only 40–50% of women conceive. The NICE guidelines recommended that anovulatory women with PCOS who have not responded to clomifene and who have a body mass index of more than 25 should be offered metformin combined with clomifene citrate because this increases ovulation and pregnancy rates. Metformin is an oral biguanide insulin-sensitising agent
Uterine-fibroid and endometrial lesions Uterine fibroids are found in 25% of women older than 35 years with common symptoms ranging from excessive uterine bleeding, pelvic pressure, recurrent pregnancy loss and infertility; the latter appears mostly related to submucous or intramural myomas that distort the uterine cavity. Until recently it was thought that fibroids should only be removed if they are causing a significant distortion of the uterine cavity or if they are blocking the cornual region of the tube. There is increasing evidence that intramural fibroids affect implantation, even when there is no distortion of the uterine cavity.
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widely used in the treatment of type-2 diabetes. Several systematic reviews and a meta-analysis have evaluated the efficacy of metformin in the treatment of anovulation due to PCOS. The conclusion of these reviews was that metformin monotherapy represents a safe and valid therapeutic option for improving ovulation in PCOS patients. Clomifene citrate tends to work more quickly but incurs the risk of multiparity. Metformin has been administered in association with clomifene citrate in order to improve the efficacy of clomifene in clomifene-resistant patients. Siebert et al. confirmed the efficacy of metformin in improving ovulation in a population of clomifene citrate resistant PCOS women with an OR of 6.82 (95% CI 3.59–12.96, p < 0.00001). In 2008, Palomba et al. performed a systematic review and meta-analysis of the available RCTs comparing clomifene citrate and metformin. They concluded that in PCOS patients with anovulatory infertility and not previously treated, the administration of metformin plus clomifene citrate is no better than monotherapy (metformin alone or clomifene citrate alone). Those who fail to ovulate with clomifene and metformin would require intensive treatment using gonadotrophin either in the form of ovulation induction or hyperstimulation for IVF. The ovarian response to gonadotrophin in this group of patients can be highly unpredictable and difficult to control. They may either not develop any large follicles or hyper-respond with a significant risk of hyperstimulation syndrome and multiple pregnancy. The need for prolonged stimulation and intensive monitoring, and the high cancellation and miscarriage rate can be extremely stressful to these patients. Surgical methods of ovulation induction for women with clomifene citrate resistant PCOS include laparoscopic ovarian drilling with diathermy. This technique has replaced the more invasive and damaging technique of ovarian wedge resection. Laparoscopic ovarian surgery is free of the risks of multiple pregnancy and ovarian hyperstimulation and does not require intensive ultrasound monitoring. Surgery does, of course, carry its own risks and must be performed only with the use of proper techniques. The dose finding studies by Amer et al. suggested that four punctures per ovary with application of diathermy current via a specially designed needle (ovarian diathermy needle, Rocket of London), set at 30 watts for 5 seconds, should produce optimal results. The use of an excessive amount of electrical energy may lead to ovarian atrophy. Diathermy should be followed by instilling Hartmann’s solution or Adept into the pouch of Douglas, which, by cooling the ovaries, prevents heat injury to adjacent tissues and reduces adhesion formation. In a review of 27 studies with a total of 729 patients who underwent ovarian drilling, 84.2% ovulated and 55.7% conceived. One long-term follow-up study reported that most women became ovulatory soon after the surgery and 74% were still ovulating when studied 18–20 years later. In addition, ovarian drilling also renders patients with PCOS more responsive to either clomifene or gonadotrophin. Further research is needed to evaluate the effect of ovarian drilling on the formation of adhesions and the longterm health consequences of this procedure. ◆
Donesky BW, Adashi EY. Surgically induced ovulation in the polycystic ovary syndrome: wedge resection revisited in the age of laparoscopy. Fertil Steril 1995; 63: 438–443. Dover RW, Torode H. Endometriomas: a review of modern management. Gynaecol Endoscopy 2000; 9: 219–226. Forsey JP, Caul EO, Paul ID, Hull MG. Chlamydia trachomatis, tubal disease and the incidence of symptomatic and asymptomatic infection following hysterosalpingography. Hum Reprod 1990; 5: 444–447. Johnson N, Vandekerckhove P, Watson A, Lilford R, Harada T, Hughes E. Tubal flushing for subfertility. Cochrane Database Syst Rev 2002(3): CD003718. Johnson NP, Mak W, Sowter MC. Laparoscopic salpingectomy for women with hydrosalpinges enhances the success of IVF: a Cochrane Review. Hum Reprod 2002; 17: 543–548. Marcoux S, Maheux R, Berube S. The Canadian Collaborative Group on Endometriosis. Laparoscopic surgery in infertile women with minimal or mild endometriosis. N Engl J Med 1997; 337: 217–222. Mol F, Mol BW, Ankum WM, van der Veen F, Hajenius PJ. Current evidence on surgery, systemic methotrexate and expectant management in the treatment of tubal ectopic pregnancy: a systematic review and metaanalysis. Hum Reprod Update 2008; 14: 309–319. National Institute for Clinical Excellence. Fertility: assessment and treatment for people with fertility problems. Clinical guideline. London: NICE, February 2004. Palomba S, Pasquali R, Orio F, Nestler JE. Clomifene citrate, metformin or both as first-step approach in treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS): a systematic review of head-to-head randomized controlled studies and metaanalysis. Clin Endocrinol 2008 Aug 7 [Epub ahead of print]. Parker J, Bisits A, Proietto AM. A systematic review of single-dose intramuscular methotrexate for the treatment of ectopic pregnancy. Aust N Z J Obstet Gynaecol 1998; 38: 145–150. Posaci JC, Camus M, Osmanagaoglu K, Devroey P. Tubal surgery in the era of assisted reproductive technology: clinical options. Hum Reprod 1999; 14(Suppl. 1): 120–136. Pritts E. Fibroids and infertility: a systematic review of the evidence. Obstet Gynecol Surv 2001; 56: 483–491. Royal College of Obstetricians and Gynaecologists. Guideline no. 25. The investigation and management of endometriosis. London: RCOG, October 2000. Siebert TI, Kruger TF, Steyn DW, Nosarka S. Is the addition of metformin efficacious in the treatment of clomiphene citrateresistant patients with polycystic ovary syndrome? A structured literature review. Fertil Steril 2006; 86: 1432–1437. Spielvogel K, Shwayder J, Coddington CC. Surgical management of adhesions, endometriosis, and tubal pathology in the woman with infertility. Clin Obstet Gynecol 2000; 43: 916–928. Voorhis Van, Bradley J. Comparison of tubal ligation reversal procedures. Clin Obstet Gynecol 2000; 43: 641–649. Yao M, Tulandi T. Current status of surgical and non-surgical treatment of ectopic pregnancy. Fertil Steril 1997; 67: 421–433.
Practice points • Microsurgical and fertility-conserving principles should be followed in all gynaecological operations involving patients during their reproductive years
Further reading Bajekal N, Li TC. Fibroids, infertility and pregnancy wastage. Hum Reprod Update 2000; 6: 614–620.
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• Laparoscopic surgery produces less de novo adhesion formation compared with laparotomy • Tubal patency does not equate with normal tubal function • Tubo-ovarian adhesiolysis may improve fertility • Tubal re-anastomosis for proximal obstruction or reversal of sterilisation is highly successful. The method and site of sterilisation, length of tube remaining and the presence of other infertility factors are important factors affecting the end result • For surgical treatment of EP, linear salpingostomy if technically feasible should be used in haemodynamically stable women who wish to preserve their fertility
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• In distal tubal disease, proper selection according to objective assessment criteria including mucosal health is critical in triaging these patients to IVF or surgical management • Surgical treatment of endometriosis is effective in promoting both fertility and pain reduction; caution is needed to avoid adhesion formation and ovarian injury that may compromise subsequent fertility • Endometrial or uterine pathologies affecting the endometrial cavity impair ART results. Many of these lesions can be corrected safely with operative hysteroscopic approaches with good results
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