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New developments in reproductive surgery
Best Practice & Research Clinical Obstetrics & Gynaecology, 3, 27, pages 431 - 440
The introduction of in-vitro fertilisation within reproductive medicine has prompted questions to be asked about the relevance of reproductive surgery. Reproductive surgery is more than a competing discipline; it is complementary to the techniques of in-vitro fertilisation. As a complementary discipline, reproductive surgery covers the field of tubal and ovarian pathology and correction of uterine alterations. In recent decades, more attention has been paid to the importance of the uterus in the process of conception and implantation. The place of reproductive surgery and the existing controversies in the treatment of uterine congenital and acquired pathology, tubal, and ovarian surgery are discussed. Continuous training and accreditation programmes for reproductive technologies and surgery are more important than ever.
Keywords: surgery, laparoscopy, myoma, congenital uterine malformations, tubal anastomosis, hydrosalpinges, IVF, endometriosis, ovarian drilling.
With the introduction of assisted reproductive technologies (ART) to the field of reproductive medicine, the role of reproductive surgery has recently been questioned. It has frequently been argued that ART and reproductive surgery compete for the same outcomes, and therefore reproductive surgery no longer plays a viable role. Instead, the preferred approach to fertility problems is in-vitro fertilisation (IVF). 1
Although both techniques aim to achieve the same outcome, their approaches are completely different: IVF aims to bypass the problems and reproductive surgery aims to resolve the pathology and to restore normal function wherever possible.
Competition exists to a certain extent, but there is nothing wrong with competition. When a fair choice can be made between the two treatment modalities, both deserve our full attention. For patient benefit, both disciplines need expertise; however, expertise is frequently lacking in the field of reproductive surgery. Choice between treatment modalities is then made on the basis of ‘lack of expertise’. Once such a negatively driven choice has been made, competition no longer exists but rather exclusion of participation.
The introduction of ART has affected the place and future of reproductive surgery because it has opened up the possibility of liberal referrals to IVF. These mostly result from lack of expertise and understanding, or lack of availability of reproductive surgical services. In a recent survey conducted by the European Society of Human Reproduction and Embryology on management of fertility units in 2010, 32% of the 212 participating centres worldwide were stand-alone units offering only ART. Although referral to reproductive surgery units is a possibility, the absence of a reproductive surgeon within the unit precludes an open discussion on the best treatment option for an individual couple. As expertise declines, practitioners tend to bypass reproductive surgery. 1a
Other reasons for bypassing reproductive surgery include increased female age and the need to speed up the reproductive process (hence direct referrals to an IVF programme), avoidance of surgery-related risks, the broadening indications for ART, the cost-benefit for the centres and practitioners, and the country-related legislations on reimbursement of ART procedures favouring referral to IVF.
The positive influence of ART on reproductive surgery is that it offers an alternative treatment modality (competition). Initially, in women with tubo-ovarian pathology, microsurgical interventions were the only treatments available for achieving a pregnancy. Now, the results of reproductive surgery have to be balanced against the results of ART. Where initially only retrospective studies were conducted on surgical procedures, now prospective randomised-controlled trials comparing different treatment modalities are needed, as well as research projects, for a better understanding of the place of reproductive surgery.
Reproductive surgery as a complementary treatment is obvious in cases of hydrosalpinges and uterine submucous myoma; however, controversies still exist in cases of ovarian endometriosis, congenital uterine malformations and intramural myomas.
In women suffering from cancer and desirous of fertility preservation, however, the dual approach of both disciplines works well.
The role of the uterus has been underestimated for many years. The uterus is now believed to be a key player in conception and pregnancy outcome. Recent developments in non-invasive indirect imaging techniques, such as three-dimensional and four-dimensional ultrasound, will contribute greatly to the careful examination of the uterus. 2
Hysteroscopy as a minimal invasive ambulatory procedure still offers the advantage of direct visualisation of the uterine cavity and the exploration of the aspect of the endometrium. 3 In a recent study of the importance of the junctional zone and its role in conception and obstetric outcome, the investigators recommended exploration of the junctional as part of the exploration of the uterus. 4
Congenital uterine anomalies
The prevalence of uterine anomalies varies from 0.06% of women in the general population to 13% in women with a history of recurrent spontaneous miscarriages.5, 6, and 7In an extended prospective study of women who had experienced three or more spontaneous miscarriages, uterine septa or arcuata 8 were been observed in 90% of cases. 9
Several other studies have confirmed a direct correlation between septate uterus, spontaneous miscarriages, and fetal malpresentations.6 and 10Hysteroscopic metroplasty dramatically improves pregnancy outcome, reducing the miscarriage rate and increasing term deliveries.11 and 12
In one study, Homer et al. 13 compared reproductive outcome before and after hysteroscopic metroplasty. The miscarriage rate before the procedure was 88% compared with 14% after the procedure; live birth rate increased from 3% before the procedure to 80% after it. Although the role of metroplasty in infertility remains controversial, the investigators reported an overall crude pregnancy rate of 48% after metroplasty.
In a prospective study, the probability of conception in women after removal of a uterine septum was significantly higher than in those with unexplained infertility. 14
In a recent study, Ghi et al. 15 included 24 women with the incidental diagnosis of an abnormal uterus in the first trimester of pregnancy. Only 33% had a live birth, whereas 54.2% miscarried early, and 12.5% miscarried late, between 14 and 22 weeks.
The occurrence of normal pregnancies and the lack of properly conducted randomised-controlled studies on the effect of congenital abnormalities on conception and obstetric outcome is feeding the discussion on the importance of these anomalies and the necessity of surgical correction.
The lack of standardisation of diagnostic modalities and measurements has caused confusion, resulting in a rather subjective interpretation of these anomalies.
In an attempt to clarify the importance of these anomalies, a joint task force was established between the European Society for Gynaecological Endoscopy and the European Society of Human Reproduction and Embryology. The use of a new and easy-to-use classification system, 16 and the standardisation of diagnostic procedures, should finally clarify the importance of these pathologies and the necessity of surgical correction.
The frequency of uterine fibroids in women seeking fertility treatment is estimated to be between 5 and 10%. 17 It is the sole factor identified in about 2–4% of women.
The divergence in published data 17 is a result of the heterogeneity of the available data, lack of standardisation in size, number and location of myoma, and the different end points (e.g. pregnancy rates, abortion rates and obstetric outcomes). A meta-analysis conducted by Pritts et al. 18 showed that myectomy caused negative outcomes in pregnancy rates and an improvement in submucous myoma. No negative effects could be found in cases of subserous myoma. Data on intramural myoma are inconsistent. Some studies show a negative effect, whereas others show no influence.19, 20, 21, 22, 23, and 24
Hart et al. 22 reported a negative effect if the intramural myoma was larger than 5 cm; however, in a study by Khalaf et al., 25 a negative effect of small intramural myomas was found, with a reduction of 40% in pregnancy rates in each cycle of IVF.
In a prospective-controlled study, Casini et al. 26 highlight the importance of the location of the myoma. Pregnancy rates after myomectomy in cases of submucosal and submucosal-intramural myoma were 43.3% and 40%, respectively, compared with only 27.7% and 15% in cases of expectant management. These differences in pregnancy rates were less significant, as the myomas were located further from the cavity.
Several mechanisms have been claimed to be responsible for the lower pregnancy rates in cases of uterine myoma: encroachment on tubal ostium, deformation of uterine cavity, longer distance of sperm to travel, vascular changes, and abnormal endometrial maturation.
A plausible mechanism for intramural fibroids not distorting the cavity has been observed in the possible disruption of the junctional zone within the myometrial layer. Uterine peristaltic activity originates exclusively from this junctional zone. 27 Yoshino et al.,28 and 29linked decreased pregnancy rates to disturbed uterine peristalsis, highlighting the absence of pregnancies in women with high uterine peristalsis and intramural myomas. When low uterine peristalsis was recorded, however, pregnancy rates of 34% were shown. They also reported that, after myomectomy in the high peristaltic group, peristalsis normalised in 14 out of the 15 women, and a pregnancy rate of 40% was recorded.
All these data show that uterine myoma affects implantation and pregnancy rates because of their location in the uterine cavity and junctional zone. The disturbance of uterine peristalsis may also be a contributing factor.
The inner myometrium or junctional zone is ontogenetic, unlike the outer myometrium. Hormonal sensitivity is responsible for the cyclic differences in uterine peristalsis, and we believe that more attention should be paid to the location of the myoma in relation to their distance or encroachment on the junctional zone.30 and 31
Myomectomy is a safe procedure and does not carry the intrinsic risks of postoperative adhesion formation and uterine rupture. Therefore, the advantages for and against myomectomy should be well balanced.
Proximal tubal disease
The introduction of microsurgical techniques and the principles of gentle tissue handling have dramatically improved pregnancy rates after tubal surgery. Reported pregnancy rates after tubal microsurgical anastomosis are between 70 and 80%.32, 33, 34, and 35
In the absence of any other fertility-impairing factors, microsurgical tubal anastomosis by laparotomy or laparoscopy in cases of tubal sterilisation should be the first treatment option in women younger than 37 years. 36 Older women can be directly referred to IVF, although pregnancy rates of 30–40% have been reported. 37
Laparoscopic-related difficulties prompted surgeons to simplify the procedure to a one-layer technique, with only one or two sutures, or use glue or clips instead of sutures.38 and 39This simplification has resulted in lower pregnancy rates. Surgeons using the same two-layer microsurgical approach through the laparoscope40 and 41have reported similar results.
Recently, robotically assisted laparoscopy has been proposed as a possible valid alternative. It is a promising technique that overcomes the practical difficulties inherent in tubal microsurgical laparoscopic anastomosis.42 and 43
Distal tubal pathology
The beneficial effect of salpingectomy on IVF outcome in cases of thick-walled hydrosalpinges or ultrasonographically visible hydrosalpinges has been reported in several studies.44, 45, and 46In a Cochrane review, 47 salpingectomy before IVF was found to yield 1.75- to 2.13-fold higher odds of pregnancy and live birth, respectively. The removal of hydrosalpinges before treatment has a positive effect on pregnancy rates after IVF, and has led to systematic removal before starting IVF.
In various studies, however, it has clearly been shown that, in a selected group of women with hydrosalpinges, salpingostomy achieves acceptable intrauterine pregnancy rates. When salpingoscopy can exclude the presence of intratubal mucosal adhesions, a subgroup with more than 50% intrauterine pregnancy rates and less than 5% ectopic rates after reconstructive surgery can be identified.48, 49, 50, 51, and 52Salpingoscopic exploration of the tube, however, has not gained widespread acceptance. With the development of transvaginal endoscopy, salpingoscopy can now be carried out easily, thereby avoiding excessive manipulation of the tubes.53 and 54Systematic removal of all hydrosalpinges, however, will prevent spontaneous conception in some women.
Functional restoration surgery is indicated in women with a good prognosis who have thin walled hydrosalpinges, with minimal or no mucosal adhesions and absence of severe tubo-ovarian adhesions.
The visibility of hydrosalpinges on ultrasound is not a pathognomonic sign of severely damaged tubes; it is highly probable that thick-walled hydrosalpinges will be difficult to visualise on ultrasound; however, hydrosalpinges should be removed as the probability of pregnancy in this subcategory is remote.
If salpingectomy is carried out, the plane of dissection should be close to the base of the tube so as not to damage the ovarian blood supply. In cases of frozen pelvis, where the anatomy between tube and ovary is hardly distinguishable, a proximal tubal ligation could be indicated instead of a salpingectomy to avoid harming the ovarian blood supply. Hysteroscopic sterilisation can be an alternative as long as the applied procedure does not interfere with implantation and obstetric outcome. 55
Surgical treatment of minimal and mild endometriosis in infertility remains controversial. Paradoxically, the efficiency of surgery in endometriosis-associated infertility is higher in women with severe rather than minimal or mild endometriosis. 56
In a retrospective study of women with unexplained infertility, Akande et al. 57 found that in women with minimal or mild endometriosis that was left untreated, the time to natural conception was significantly prolonged. Results of the Canadian Collaborative Study Group on the ablation of minimal and mild endometriosis 58 showed an increased monthly fecundity rate from 3.2 to 6.1, but failed to restore normal fertility. A smaller Italian randomised-controlled study could not confirm these findings 59 ; however, a recent meta-analysis 60 combining the results of both trials showed that surgical treatment is more favourable than expectant management (odds ratio for pregnancy 1.7; 95% confidence interval 1.1 to 2.5).
Over the past few decades, the treatment for ovarian endometriosis has remained unchanged. A contradiction exists between those who favour cystectomy and those who favour ablative surgery.
In a 2008 Cochrane review, Hart et al. 61 concluded that cystectomy for endometriomas results in lower recurrence rates and higher spontaneous pregnancy rates compared with drainage and ablation. This analysis was based on three randomised-controlled trials using bipolar coagulation without prospective evaluation of the ovarian reserve.
Although reported recurrence rates differ between centres, they are lower after cystectomy, but with a higher risk of postoperative adhesion formation.62, 63, and 64Ablative surgery offers advantages over excision of the cyst, mainly in better preservation of the ovarian reserve and probably less adhesion formation. The ablation technique differs from fenestration and drainage because of its access through the site of inversion and resection of the fibrotic ring. 65
Sampson 66 was the first to suggest that ovarian endometriotic cysts originate from the outside of the ovary and are caused by adhesions and bleeding of surrounding peritoneal implants. Donnez et al. 67 suggested that ovarian endometriomas result from mesothelial metaplasia, and invagination of the ovarian cortex. As such, the ovarian endometrioma differs from other benign ovarian cysts by extra-ovarian localisation. According to Muzii et al., 68 the inadvertent excision of ovarian tissue, together with the fibrotic pseudo-capsule of the endometrioma, carries the highest risk of removal of follicles at the hilus.
Exacoustos 69 showed that cystectomy for benign ovarian dermoid cyst did not result in decreased ovarian volume, but a statistical reduction occurred after cystectomy for endometriomas.
Although ablative and excisional surgery can both result in diminished ovarian reserve, it has been shown that ovarian volume, antral follicle count and anti-Müllerian hormone were more negatively affected after cystectomy compared with ablative surgery.70, 71, 72, 73, and 74
Donnez et al. 75 suggested a modified technique involving a partial cystectomy of the lateral walls and ablative coagulation at the hilus. Recently, Roman et al. 72 described a less harmful effect of the ablation technique in the preservation of ovarian potential by using plasma energy. In his experience, cystectomy showed a statistically significant decrease in ovarian volume and reduction in antral follicle count compared with the ablation technique.
In some studies, oocytes and fertilisation rates have decreased in women with endometriosis; however, pregnancy rates after IVF have been reported to be the same as rates in women without endometriosis.76 and 77
In a meta-analysis, Tsoumpou et al. 78 concluded that no statistically significant differences were found in pregnancy or clinical pregnancy rates per cycle after IVF in between women undergoing surgery for endometriomas and women with endometriomas without surgery.
A number of studies, however, have shown a negative effect of endometriosis on fertilisation rates, pregnancy rates and live birth rates, with a higher effect in women with stage III and IV endometriosis.79, 80, 81, and 82A possible oocyte factor can play a major role in this process, as oocytes of endometriosis-positive donors result in lower pregnancy rates compared with oocytes from control participants without endometriosis. 83
The above-mentioned controversies are a reflection of the complexity of the disease and of the complexity of the surgery that can hardly be simplified to excision or ablation.
Surgery for ovarian endometrioma carries the intrinsic risk of damaging the ovarian reserve and should, therefore, be carried out with the highest precision and expertise to keep the ovarian damage to a minimum. In the hands of experienced surgeons, the effect on ovarian function seems to be comparable regardless of whether excision or ablation is used. It is likely that, in the hands of inexperienced surgeons, ovarian damage will be greater if cystectomy is carried out.
Clinicians should also be aware of the possible association and increased risk of ovarian carcinoma in women with endometriosis. 84 An indication of why endometriosis could be a precursor to some ovarian cancers, especially clear cell and endometroid cancers, can be found in some common histological and genetic alterations. 85
Surgery has a major role to play in the treatment of endometriomas, despite ART. Surgery can offer women the possibility of spontaneous conception.86 and 87Treatment should be individualised, and size of the endometriotic cyst, unilateral or bilateral localisation, recurrence, age, pain, and the wish to conceive, should all be taken into account.
Transvaginal ovarian capsule drilling
About 7% of women 88 are affected by polycystic ovary syndrome (PCOS). Infertility caused by chronic anovulation is the most common reason for women to seek medical assistance. About 20% of women with PCOS are resistant to ovulation induction with clomiphene citrate, and will remain anovulatory, 89 and 50% of those with ovulatory cycles will fail to conceive. 90
As an alternative to standard laparoscopy, transvaginal laparoscopy has been described as a first-line procedure in the exploration of infertile women.95 and 96The technique is based on transvaginal access, using a needle-puncture technique of the pouch of Douglas with the use of a watery medium for distension.
Routine vaginal examination and vaginal ultrasound under anaesthesia is mandatory in each woman to exclude pathology of the pouch of Douglas, hence to avoid complications. Although rectal perforation is a potential complication of the transvaginal access, the transvaginal approach is safe. In a recent overview of 13,360 procedures, the reported incidence of rectal perforation was 0.37% and the incidence of pelvic infection 0.007%. 99 In contrast to standard laparoscopy, rectal perforation at transvaginal access can be considered to be a minor complication, as it is directly diagnosed and not treated conservatively with antibiotics.
Transvaginal ovarian capsule drilling is carried out with a miniaturised bipolar needle, with a diameter of 0.2 mm, and causes minimal trauma to the ovarian cortex. Despite this, our results are comparable with those obtained after standard laparoscopic procedures, 100 with a reported in-vivo pregnancy rate of 57%. Comparable results were reported in several other studies.101, 102, and 103
Adhesion formation is one of the possible complications and major concerns after ovarian surgery. The minimal trauma caused by the bipolar needle, and the fact that the entire procedure is carried out under water, can minimise the risk of postoperative adhesion formation.
Second-look transvaginal laparoscopy in women who have had ovarian transvaginal drilling 8 months earlier has shown the presence of only filmy and locally non-connecting adhesions on the ovarian surface, with some neovascularisation inside the adhesions. 100
Restoration of monofollicular cycles, avoidance of the risks of ovarian hyperstimulation, reduction of multiple pregnancies, and decreased incidence of miscarriages are factors in favour of the surgical management of PCOS in women resistant to clomiphene.
A multicentre, prospectively randomised clinical trial, recently revealed that the total treatment cost of an ongoing pregnancy is the same, regardless of whether electrocautery or ovulation induction with recombinant follicle-stimulating hormone was carried out. Because of a lower incidence of multiple pregnancies, however, the electrocautery strategy reduces the cost.104 and 105The even lower cost of the transvaginal approach (i.e. lower morbidity, less work incapacity) is a supplementary benefit.
The role of surgery in reproduction is twofold: competing and complementary.
In a well-selected group of women, reproductive surgery offers the possibility of spontaneous conception in consecutive cycles and for consecutive pregnancies. As such, it favours high cumulative pregnancy rates. Second, it adds complementary value in ameliorating pregnancy rates and live birth rates in women referred to IVF in cases of hydrosalpinges and congenital or acquired uterine pathology. Although controversy still exists about the added value of surgery in cases of ovarian endometriosis, spontaneous pregnancy rates after surgery have been reported to be around 50%. In this complex disease and complex surgery, a simple pro or con answer cannot be given, and each treatment has to be individualised. Surgery in ovarian endometriosis is difficult and challenging, and requires the necessary expertise.
In-vitro fertilisation costs are high. In several developed countries, the budget, in some instances, has been lowered for the reimbursement of IVF treatments by restricting the numbers of reimbursed cycles, lowering the age limit or by reducing the financial reimbursement per cycle.
Certainly, in countries where IVF is not reimbursed, and therefore not affordable to many people, reproductive surgery can play an important role by offering the potential of conception in consecutive cycles.
Cost-savings can be made in selected women by directing them immediately to reproductive surgery, thereby avoiding more costly IVF procedures. The most accurate treatment for individual couples can only be achieved if each reproductive medicine centre can also offer reproductive surgery carried out by well-trained surgeons. Continuous training and accreditation programmes are mandatory to reach the highest standards in reproductive surgery.
- Systematic removal of all hydrosalpinges before IVF will prevent a number of women from conceiving naturally.
- Transvaginal salpingoscopy offers the possibility of easy tubal access and a salpingoscopy can help evaluate the tubal mucosa.
- Ovarian endometrioma is most frequently an extra-ovarian cyst and differs as such from other benign ovarian cysts.
- Ovarian endometriosis surgery caries an intrinsic risk of ovarian damage, and should be carried out by experienced surgeons.
- Transvaginal access for drilling of the ovarian capsule is currently favoured because of the safety of transvaginal access and its advantage in obese women; the reduced risk of postoperative adhesion formation; and the low morbidity of the procedure.
- Standardisation of diagnostic procedures in the diagnosis of uterine congenital anomalies is urgently needed.
- The importance of the junctional zone and the localisation of intramural myomas needs to be evaluated.
- Prospective randomised studies of surgical treatment of ovarian endometrioma are needed.
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