Dr G D Reid

 

In 1999, I ran a workshop on “Alternatives to Hysterectomy”. This followed a similar seminar conducted by the American Association of Gynecologic Laparoscopists in the previous year, which was hugely successful. Attendance at these meetings attests to the fact that the search for alternative managements for dysfunctional uterine bleeding is “alive and well”.

 

In 2000 I was asked to write an article for a General Practice journal. This was a response to a statement made by an epidemiologist, that too many hysterectomies were performed in Australia. There are approximately 30,000 (1.6/1,000) hysterectomies performed annually in Australia compared with 600,000 (2.4/1,000) in the United States of America.

 

My response was based upon the fact that hysterectomy rates are consumer driven, and that demand can reasonably be expected to vary between countries. Women’s lives have changed and they no longer accept the inconvenience of dysfunctional bleeding. Quite appropriately they seek a solution – and this drives the search for less invasive procedures.

 

 Abnormal uterine bleeding affects around 20% of women between the ages of 30 – 50 years. Around 10% of these will have malignant or pre-malignant pathology, 30% will have uterine myomata and another 20% will have uterine polyps. A small number will be found to have medical conditions contributing to their bleeding tendency, such as thyroid disease or various blood dyscrasias.  This leaves around 40% of women who will have a normal uterine cavity with documented degrees of abnormal bleeding – or true “dysfunctional uterine bleeding”. This is a diagnosis of exclusion, and classical teaching has been to treat such women with available medical therapies.

 

Medical therapies have not changed greatly over the last 20 years, with the exception of hormonal implants. Approaches to dysfunctional bleeding include the use of non-steroidal anti-inflammatory agents such as mefanamic acid, naproxen and ibuprofen. These have all been shown to reduce menstrual blood loss, as has tranexamic acid, an antifibrinolytic agent. Potent synthetic progestogens such as danocrine have also shown to be efficacious, and parenteral administration of high dose parenteral oestrogen remains useful for acute dysfunctional bleeding. These drugs all have significant side effects, and are frequently not tolerated by patients in the long term.

 

Hormonal implants such as “Mirena” probably offer the greatest hope for management of dysfunctional uterine bleeding, as their local action on the endometrium with minimal systemic side effects is generally well tolerated.

 

These deficiencies and disadvantages of medical therapies led to great interest in endometrial ablation procedures when they became popularised in the late 1980’s. Hysteroscopy led to the accurate diagnosis of intrauterine pathology, and provided an opportunity for the delivery of potentially effective intrauterine therapies. Magos et al¹ introduced trans-cervical resection of the endometrium (TCRE) into the UK in 1989, and the procedure became popularised.  There followed great interest in endometrial ablation as a new operation, and its ability to impact upon hysterectomy rates around the world. In Australia, the peak utilization of endometrial ablation occurred in 1992. There followed a general disillusionment with the outcome of the operation, and a progressive abandonment of its utilization.

 

Why did this occur?  I believe there were three main reasons. First, hysteroscopic surgery was relatively new, and many Gynaecologists felt obliged to perform this new and popular procedure before their level of training and skill permitted good results. Conventional endometrial ablation, by both resection and roller-ball technique, is a highly skill dependent procedure, and this was underrated.  Secondly, the importance of patient selection was undervalued. Patients with large uteri, and other uterine pathology, especially adenomyosis, demonstrated poor outcomes. Thirdly, laparoscopic hysterectomy was gaining in popularity as a real alternative to the treatment of dysfunctional bleeding.

 

With good patient selection, and procedures performed by skilled operators, TCRE provided around an 85% patient satisfaction rate. About half of these patients developed amenorrhoea, and the rest were hypomenorrhoeic. Patients in the older age range tended to have the highest long-term satisfaction rates.

 

Inevitably, complications were reported. These included intraoperative fluid overload, uterine perforation, postoperative bleeding, infection and subsequent pregnancy. Morbidity rates of around 3% were reported and Macdonald et al² reported a mortality rate of 0.02% (1/4038), following a survey of members of the British Society for Gynaecological Endoscopy in 1992.

 

On July 18, 1996 the New England Journal of Medicine published an editorial stating: “it is only a matter of time before ablation is superseded by less invasive procedures such as balloon heating…” Four years before, in an editorial in Gynaecological Endoscopy, Loffer³ wrote: “It can be anticipated that in the future other simpler and more efficacious methods of applying thermal energy to the endometrial surface will become available.”

 

The medical technology industry responded to this call and produced a wide range of devices. The concept of less skill dependent, global ablation of the endometrium for a common problem was addressed with enthusiasm.  Many devices were introduced, and we are presently in a situation of addressing which will prove to be most efficacious and safe.

 

Some, such as Novasure and Vestablate delivered electrosurgical energy to the endometrium in a global fashion. Other technologies deliver thermal energy to achieve endometrial destruction. These include the Thermachoice balloon, the Cavaterm balloon and the HydroThermAblator, which circulates heated saline freely within the uterine cavity. All these devices aimed to achieve uniform endometrial destruction with skill levels much reduced from those required for classical ablation. There have been many reports comparing various global systems against classical ablation (by skilled operators), showing comparable results. Parkin⁴ highlighted the importance of such studies in his editorial report in 2000. There is evidence that the outcome of global systems compare favourably with conventional resection / ablation.  What is required, however, is a comparison between the global systems, and unfortunately this is not available.

 

 There are considerable capital costs involved in the installation of these systems, and considerable disposable item costs. Many companies will amortize the cost of controller devices against the costs of disposables, but ultimately all the equipment must be paid for by one means or another. Institutions need comparative and efficacy data to assist in these decisions. Available data is further hampered by variable length of follow-up, patient populations and criteria for reporting results and adverse outcomes. This led Morris Wortman⁵ to highlight that the time has come to set standards for comparison of these technologies. He summarised some available published data, but no clear conclusions could be drawn regarding the superiority of one system over another.

 

Let us consider some of the global ablation systems available and the published results. I shall restrict my review to those systems currently available for commercial use in Australia, and which have current FDA approval in the USA.

 

The Thermachoice (Gynecare) device has been marketed for the longest period of time. This is a latex balloon that is inflated with 5% dextrose within the uterine cavity to a pressure of approximately 180mmHg. The balloon contains a central heating element through which the fluid is heated by an electronic controller to 87°C for 8 minutes. Optimal pre-treatment regimens have not been defined, but the compressive effect of the balloon pressure on the endometrium probably makes endometrial pre-treatment unnecessary. Global thermal destruction of the endometrium occurs. Unless the pressure can be stabilized, within the confines of the uterine cavity, the treatment cycle cannot be started. Fall of pressure below a certain level, e.g. with rupture of the balloon, will shut down the treatment cycle.

 

Neuwirth conducted the initial laboratory development and peri-hysterectomy studies of this device in 1988, having previously described the use of the urological resectoscope for classical endometrial resection in 1983⁶. Pilot clinical studies were conducted by Singer and Neuwirth in 1990, and pressure studies by Haber and Vilos in 1994. An international multicentre study was established in 1994, to gather data for FDA approval. 541 cases had been entered on this study by 1996.  The first 300 of these patients followed up at 3 and/or 6 and/or 12 months was published by Amso et al⁵ was published in 1998. At 12 months 163 patients were available for follow-up. 15% were amenorrhoeic, 48% were hypomenorrhoeic and 25% were eumenorrhoeic. 12% reported menorrhagia. There were no intraoperative complications, and postoperatively there was one case of cystitis, six patients with febrile morbidity (presumed endometritis) and two patients who developed hematometra. No major complications were reported.

 

Potential problems with this device include conformity to the uterine cavity, and in particular accommodation to deep cornual horns. Furthermore there is a fall in temperature from the central heating element to the surface of the endometrium. This may account for Amso et al’s⁷ findings that treatment outcomes are improved in patients with a smaller uterine cavity, as temperature degradation is greater in the larger uterus. Recognition of this problem has led the manufacturer to explore methods of circulation of fluid within the balloon. Thermachoice devices including circulation enhancement are not yet available in Australia.

 

The second thermal balloon device available at present is the Cavaterm (Wallsten Medical) system. This differs from the Thermachoice device in having an adjustable balloon length, as well as having a circulation system for the contained fluid. A series of 32 patients with 18-28 months of follow-up was reported by Friberg B, Persson BR et al⁸ in 1998. They reported amenorrhoea rates of 31%, hypomenorrhoea rates of 41%, eumenorrhoea rates of 19% and failure rates of 9%. Again, no complications were reported.

 

 A novel approach to thermal ablation was adopted with the HydroThermAblator (HTA). This system approaches the shortcomings of contained balloon therapy by circulating thermo-destructive saline freely within the uterine cavity. This overcame the problem of balloon conformity to the uterine shape, and expanded thermo-ablation technology to septate uteri, or those with deep cornual horns.

 

Why does saline, heated to near boiling point, not escape from the fallopian tube and cause serious operative morbidity? This is always the first question asked. It is poorly appreciated that the pressure required to achieve uterine distension for diagnostic hysteroscopy is around 25-35mmHg. Tubal opening pressure is around 70mmHg, and the HTA operates in a pressure range of 40-50mmHg. Fluid does not escape from the fallopian tube under these conditions.

 

The HTA is a device that circulates heated saline within the uterine cavity under gravity (pole height) adjustable pressure. Instilled fluid is scavenged by a suction pump, so no positive pressure (beyond gravity) is applied. Free circulation of fluid occurs, and the equipment shuts down if 10ml fluid loss occurs. The treatment cycle will abort whether fluid is lost through the fallopian tube, the cervix or a uterine perforation. This is fairly foolproof technology.

 

By necessity, this procedure must be performed under direct hysteroscopic visualization. This permits the sheath tip to be positioned at the internal cervical os, for maximal ablative efficiency. This detracts slightly from the procedure, as a minimal amount of hysteroscopic skill is required. Nevertheless, the advantage of real time visualization of a surgical procedure, verses a blind global ablation procedure must be accepted.

 

Unlike the balloon devices with their endometrial compression, pre-operative endometrial thinning is absolutely essential with free circulating saline. The depth of endometrial destruction is a time – temperature effect, so the prescribed protocol will not destroy a thick endometrium. Mechanical thinning (curettage) at the time of the procedure results in bleeding which inteferes with closed system volume monitoring –an integral safety feature of the system.

 

Efficacy and safety data requirements led to the establishment of an international multi-centre study to assess HTA. 650 patients were enrolled from 16 treatment centres. At 12 months this data produced an amenorrhoea rate of 44.4%, a hypomenorrhoea rate of 37.5% and a eumenorrhoea rate of 13.8%. HTA results were then published in a number of individual series, such as Romer and Muller⁹ who reported amenorrhoea rates of 50%, hypomenorrhoea rates of 39% and eumenorrhoea rates of 5.5%. Botacini das Dores and Richart et al¹⁰ reported results on 26 women undergoing the HTA procedure. 87.5% of women were amenorrhoeic or hypomenorrhoeic at 12 months.

 

Let us return to Morris Wortman’s assessment of global ablation systems. With his stringent requirements for ammenorrhoea as an endpoint, Thermachoice provided a 20.6% and 15.2% incidence in the two papers studied. Vestablate provided a 31.8% rate and HTA a 50% rate. This compared with a 25-40% rate for classical resection or ablation. None of this was statistically significant.

 

I believe there are three conclusions that can be drawn from all this data.

 

1.      Global ablation systems have been compared with classical endometrial ablation / resection and the clinical results in the short term are not statistically different.

2.      The various global ablation systems available show no statistically significant difference in their short-term outcomes, with a trend for Thermachoice to show a lower ammenorrhoea rate than the other systems.

3.      All the global systems have a low morbidity rate.

 

At this point of time, and until emerging clinical data places one system clearly more efficacious than another, logical appraisal must prevail. In theory, a procedure which allows free access of the thermo-destructive agent to all areas of the uterine cavity, which is conducted under direct hysteroscopic vision and which has inbuilt mechanisms to terminate the procedure in the event of fluid loss is attractive.

 

What is needed is a randomised study of various global techniques. This will be most difficult to undertake, as none of the manufacturers wish to expose themselves to the risk of sub-optimal outcomes.

 

Kremer and Duffy¹¹ considered these issues in an editorial in the British Journal of Obstetrics and Gynaecology in December 2000. They assessed all the current generation methods of endometrial ablation. They were critical that insufficient data was available to assess global endometrial ablation. They did acknowledge that these global ablation systems seemed safe, and called for an assessment of cost effectiveness.

 

These are important issues, and they continue to be addressed by those interested in endometrial ablation and alternative approaches. In my view, there is no doubt that endometrial ablative procedures have a place in the management of dysfunctional uterine bleeding. The high skill level required with classical ablation was a problem, and the global systems have addressed this. These are simple systems, and they are safe. Outcomes between one system and another cannot at present be determined. Logically, the HydroThermAblator has an advantage, but the evolution of evidence will provide the ultimate answer. 

 

 

References:

 

1.      Magos A, Baumann R, et al. Transcervical resection of the endometrium in women with menorrhagia. Br Med J. 1989; 298:1209-1212.

2.      Macdonald R, Phipps J, Singer A. Endometrial Ablation: a safe procedure. Gynaecological Endoscopy. 1992; 1:7-9.

3.      Loffer F. Endometrial ablation – where do we stand? Gynaecological Endoscopy. 1992; 1:175-179.

4.      Parkin DE. Endometrial resection and ablation: past, present and future. Gynaecological Endoscopy. 2000; 9:1-7. 

5.      Wortman M. Minimally Invasive Surgery for Menorrhagia and Intractable Uterine Bleeding: Time to Set Standards. JAAGL. 1999; 6(4):369-373

6.      Neuwirth RS. Hysteroscopic management of symptomatic submucous fibroids. Obstetrics and Gynecology. 1983; 62:509-511.

7.      Amso NN, Stabinsky SA et al. Uterine thermal balloon therapy for the treatment of menorrhagia: the first 300 patients from a multi-centre study. Br J Obstet Gynaecol. 1998; 105:517-523.

8.       Friberg B, Persson BR et al. Endometrial destruction by thermal coagulation: evaluation of a new form of treatment for menorrhagia. Gynaecological Endoscopy. 1998; 7:73-78.

9.      Romer T, Muller J. A Simple Method of Coagulating Endometrium in Patients with Therapy-Resistant, Recurring Hypermenorrhoea. JAAGL. 1999;6(3):265-268.

10.  Botacini das Dores G, Richart RM et al. Evaluation of HydroThermAblator for Endometrial Destruction in Patients with Menorrhagia. JAAGL. 1999; 6(3): 275-284.

11.   Kremer C, Duffy S. Endometrial ablation: the next generation. Br J Obstet Gynaecol