Carolien Vermeulen

This thesis addresses various aspects of pelvic floor dysfunction in women following hysterectomy, divided into two main parts: prevalence and treatment. The first part contains the prevalence of prolapse, pelvic floor symptoms, and central sensitisation syndrome after hysterectomy, while the second part focuses on the treatment of post-hysterectomy vaginal apical prolapse.

Chapter 1 introduces the topics covered in this thesis and provides background information necessary for interpreting the content. The following research questions are addressed:
- What is the prevalence of prolapse and pelvic floor symptoms in the long term after laparoscopic versus vaginal hysterectomy? (Chapters 2 and 3)
- Is central sensitisation syndrome more common in women where pelvic floor complaints cannot be explained by POP? (Chapter 4)
- How is vaginal vault prolapse treated in clinical practice in the Netherlands; is there practice pattern variation? (Chapter 5)
- Is laparoscopic uterosacral ligament suspension, with or without hysterectomy, an effective and safe treatment for apical prolapse? (Chapter 6)

PART I

In Chapter 2, the prevalence of pelvic organ prolapse (POP) after laparoscopic versus vaginal hysterectomy is investigated (POP-UP study). Many studies have indicated that hysterectomy increases the risk of POP, particularly based on data from vaginal and abdominal hysterectomies. Nowadays, hysterectomy is more frequently performed laparoscopically than vaginally. This study aims to determine whether there is a difference in the prevalence of POP between laparoscopic and vaginal hysterectomy. Women who had undergone laparoscopic or vaginal hysterectomy more than 10 years ago were invited to participate. A total of 406 women completed a questionnaire on pelvic floor symptoms, risk factors, and prolapse treatment, with 247 women also undergoing a physical examination for POP (POP-Q examination), on average 16 years post-hysterectomy. Women were classified into three different groups: LH group (N=90 women after laparoscopic hysterectomy), VH-1 group (N=51 women after vaginal hysterectomy for non-POP indications), and VH-2 group (N=106 women after vaginal hysterectomy for POP). Overall, 62% of women had anatomical prolapse: 42% in the LH group, 51% in the VH-1 group, and 84% in the VH-2 group. Vaginal vault prolapse was present in 13% of women: 4.4% in the LH group, 5.8% in the VH-1 group, and 23% in the VH-2 group. The composite outcome measure (prolapse > hymen, POP surgery, and/or vaginal bulge sensation) occurred in 30% of women.
Conclusion: no differences were found between the LH group and VH-1 group. However, women in the VH-2 group had a significantly increased risk of POP in all outcome measures.

Chapter 3 presents a secondary analysis of the POP-UP study, focusing on the nature and severity of pelvic floor symptoms per type of POP. POP can manifest with various pelvic floor symptoms, with vaginal bulge sensation being the primary complaint. However, women often experience atypical symptoms, sometimes related to the prolapsed compartment. This study analysed the symptom pattern per compartment to better assess which symptoms can be resolved with POP treatment and which cannot. In total, 47% of all women post-hysterectomy had moderate to severe pelvic floor symptoms, with or without POP. Only 35% of women with prolapse >= stage 2 reported vaginal bulge sensation. A significant association was found between anterior POP and voiding symptoms. The most commonly reported symptoms in women with POP were flatus incontinence, frequent urination, and urge urinary incontinence. The only two symptoms significantly associated with severe POP (prolapse beyond the hymen) were vaginal bulge sensation and having to manually complete micturition. Urinary incontinence was significantly more common in women without POP. Among women without POP, 39% had moderate to severe pelvic floor symptoms, with stress urinary incontinence, obstructive defecation, and residual defecation being the most frequently reported.
Conclusion: this study demonstrates that pelvic floor symptoms are very common in women after hysterectomy, regardless of the presence of POP. Anterior POP was significantly associated to voiding symptoms; this association was not found between posterior POP and defecation symptoms. Healthcare providers should be aware that resolving the POP does not always result in symptom resolution. Women undergoing hysterectomy should be counselled about pelvic floor symptoms and be informed about preventive lifestyle measures.

In Chapter 4, we focus on the group of women with pelvic floor symptoms without POP. Hypothetically, central sensitisation syndrome (CSS) could play a role in the experience of these symptoms. This syndrome is an overarching term for conditions where bothersome symptoms are experienced without somatically identifiable causes, possibly due to changes in afferent nerve pathways. A follow-up study was conducted to assess the prevalence of CSS in women with pelvic floor symptoms without POP (group 1, N=42) compared to women without pelvic floor symptoms and/or POP (groups 2-4, N=93). The results showed significant differences. CSS was present in 37% of women in group 1, while it was only 12% in groups 2-4. Additionally, women in group 1 were more likely to have a passive coping style and were more affected by somatisation, anxiety, stress, and depression. These findings highlight an important aspect of urogynaecology. Studies indicate that women with CSS are less satisfied after POP surgery and are more likely to develop postoperative pain syndrome. Therefore, caution is warranted in women with disproportionate symptoms relative to the degree of POP.
Conclusion: CSS was significantly more prevalent in women who experience pelvic floor symptoms without having evident POP. Appropriate patient selection for POP surgery remains essential. Alternative therapies have not been adequately studied, leaving a significant knowledge gap for future research.

PART II

In the Netherlands, various treatments for apical POP after hysterectomy (vaginal vault prolapse) are performed. Chapter 5 investigated clinical practice variation through a questionnaire. Most gynaecologists first attempt a pessary before opting for surgery. The most commonly performed surgeries were sacrospinous fixation and laparoscopic sacrocolpopexy. The combination of these two techniques was mentioned by 66% of the respondents as their first and second choice, indicating significant practice variation. Other surgeries mentioned included abdominal sacrocolpopexy, robotic sacrocolpopexy, vaginal mesh, and colpocleisis.
Conclusion: This study reveals a lack of consensus regarding the treatment of vaginal vault prolapse. Based on literature, developing guidelines is not yet feasible. Treatment decisions are currently individualised based on patient characteristics and the preferences of the attending physician.

Chapter 6 presents a systematic review and meta-analysis of laparoscopic uterosacral ligament suspension (LUSLS) as a treatment for apical POP. This laparoscopic technique involves shortening and attaching the uterosacral ligaments to the vaginal apex or cervix and can be performed with or without concomitant hysterectomy. This review examined the effectiveness and safety of this technique. Thirteen studies with 933 patients, with an average follow-up of 22 months, were included. The anatomical success rate was 90%, and the subjective success rate (satisfaction/absence of symptoms) was 90.5%. In women with uterus preservation, the anatomical success rate was 83.4%, compared to 96.6% in women with concomitant hysterectomy; however, this difference was not statistically significant. There was no difference in subjective success between these two groups. The complication risk was low.
Conclusion: LUSLS appears to be an effective and safe treatment for apical POP. Nevertheless, these results are based on retrospective and prospective cohort studies. Large prospective trials and randomised controlled trials are needed before implementing this technique on a large scale.

Chapter 7 summarises the general findings of this thesis, the clinical implications, and suggestions for future research. The conclusions drawn from this thesis are as follows:
1. The long-term risk of POP after hysterectomy does not depend on the route of hysterectomy (laparoscopic versus vaginal), but on the indication for hysterectomy. The composite outcome (prolapse beyond the hymen, bulging or POP surgery) occurred in 16% of women after laparoscopic hysterectomy (LH), 24% after vaginal hysterectomy for non-prolapse indication (VH-1), and 45% after vaginal hysterectomy for POP (VH-2).
2. Vaginal vault prolapse (apical POP >= stage 2 or apical POP surgery) does not occur frequently after hysterectomy for non-POP indication (4.4-5.8% after LH and VH-1). After VH-2, vaginal vault prolapse occurred in 23%.
3. In a group of post-hysterectomy women who did not actively seek help, 47% experienced problematic pelvic floor symptoms, independent of the presence or absence of an anatomic POP.
4. Central sensitisation syndrome is more prevalent in women with pelvic floor symptoms without relevant POP. More awareness of central sensitisation syndrome and valid individual counselling may lead to higher patient satisfaction and help in setting realistic expectations.
5. According to a survey among all members of the Dutch Society for Urogynaecology, there is no standard treatment of vaginal vault prolapse in the Netherlands and the practice pattern variation is high. The surgical approach depends on individual patient characteristics and doctors’ preference.
6. The laparoscopic uterosacral ligament suspension (with or without uterus preservation) seems to be an effective and safe treatment for women with apical POP, but long-term prospective trials and RCTs are necessary before it can be implemented in clinical practice.