caesarean scar niche/isthmocele and fibroids

Question 1

Definition (international Niche Taskforce) and incidence

Answer 1

An indentation at the site of the caesarean scar with a depth of at least 2mm and visible by means of a TVUSS.

Prev definition used 1mm.
It is a myometrial defect that forms because of imperfect healing.
~50-60% of women with a history of a caesarean section will have a niche.

Question 2

Associated symptoms

Answer 2

Asymptomatic
Postmenstrual spotting.
Prolonged menses.
dysmenorrhoea and chronic pelvic pain.
Vaginal discharge.
May also cause secondary infertility.

Question 3

Theoretical impact on fertility

Answer 3

Accumulation of blood, mucus and fluid in the niche
Impaired myometrial contractility

Can lead to:
Impaired sperm migration and viability
Hostile uterine environment for implantation
Change the microbiome/cause chronic endometritis or inflammation

Question 4

Evidence of impact on secondary infertility.

Answer 4

CS reduced probability of a subsequent pregnancy by 10% relative to a vaginal birth but none looked specifically at uterine niche.

Retrospective study showed women undergoing their first IVF cycle reported significantly lower live birth rates in those with a previous CS cf a previous vaginal birth.

Retrospective study meta-analysis in F&S November 2023 -
P - Women undergoing IVF cycle
I - Isthmocele
C - Those with a CS without isthmocele and those with a vaginal birth
O - Isthmocele associated with a lower live birth rate than both women with a previous CS without isthmocele and those with a vaginal birth
Results more significant for those who have intra-cavity fluid, if no ICF seen then results were similar to that of no isthmocele

Question 5

Risks associated

Answer 5

Obstetric:
Casearean scar ectopic
Placenta praevia, accreta, increta and percreta
Scar dehiscence
Uterine rupture
*secondary infertility

Question 6

Options for management

Answer 6

Nil/conservative
Medical management - mentrual suppression
Surgical repair -
- Hysteroscopic
- Laparoscopic
- Vaginal
- Laparotomy
Hysterectomy

Question 7

Risk factors for developing a CSD

Answer 7

increasing number of CS
Longer duration of labour
Dilatation beyond 5 cm
Peripartum infection
Increased BMI
Low versus high hysterotomy

Question 8

Fibroids - indication for myomectomy in infertile women (RANZCOG guideline the same as ACCEPT guideline 2011)

Answer 8

Fibroid size, number and location within the uterus may impact on the utility of myomectomy, and this will need to be considered in the management plan for an individual patient.
The indications for myomectomy in infertile women may be summarized as follows:
* Infertile women and those women undergoing ART who have a demonstrated SM fibroid(s). (level 2 evidence, consensus grade alpha)
* Infertile women with symptomatic fibroid(s), such as heavy vaginal bleeding or pressure symptoms, even though trial evidence does not show clear fertility benefit, the presence of symptoms may justify the intervention. (level 4 evidence, consensus grade beta)
* Couples presenting with multiple failed cycles ART where the female partner has IM fibroids. (level 4 evidence, consensus grade alpha)

Question 9

Treatment that should only be done in a research setting

Answer 9

1. Uterine artery ligation (temporary or permanent)
2. Uterine artery embolisation
3. Magentic resonance guided focused ultrasound surgery (MRgFUS)
4. Myolysis - application of an energy source directed at the fibroids intending to stop blood flow and cause necrosis whilst not damaging the surrounding tissues (laser myolysis or cryomyolysis are examples)
5. Radio-frequency ablation

Question 10

Medical management of fibroids in the context of research setting

Answer 10

Delays efforts to conceive and not recommended.
Can be considered for:
Short term use of GnRH analogue considered for preoperative correction of anaemia or short term reduction in fibroid volume.
Ulipristil acetate is not recommended due to the risk of significant adverse effects (liver failure)

Question 11

FIGO classification system for AUB in reproductive years

Answer 11

PALM COEIN

Polyp
Adenomyosis
Leiomyomoa (submucous and other)
Malignancy and hyperplasia

Coagulopathy
Ovulatory dyfunction
Endometrial
Iatrogenic
Not otherwise classified

Question 12

FIGO classification for leiomyoma

Answer 12

Combination of TVUS and TA USS to identify leiomyomas
Subclassification requires determination of relationship of the endometrium with the leiomyoma (contact or not) - done with TVUS, contrast sonohysterography, hysteroscopy or MRI.
Tertiary subclassification requires the clinican to clarify the relationship of the leiomyomas with the endometrium, endometrial cavity, myometrium and uterine serosa.

Question 13

Proposed MoA for fibroids affecting fertility.

Answer 13

Thicker capsule - A capsule that surrounds the fibroid can be considered a separate entity. This pseudocapsule consists of compressed
myometrium and contains nerves. An increasein pseudocapsule
thickness may increase the number of neuroendocrine fibers,
influencing muscle contractility and uterine peristalsis.

Question 14

Cochrane review 2017 GnRHa pretreatment prior to surgery for uterine fibroids

Answer 14

GnRHa resulted in:
reduction in uterine and fibroid volumes.
Increase in preoperative Hb
Resulted in higher rate of adverse events (hot flushes etc)

Hysterectomy - reduced operative time, less operative blood loss, fewer blood transfusions, fewer postoperative complications.

Myomectomy - reduced intraoperative blood loss

Note: Whether pretreatment prior to IVF for intramural fibroids improves LBR has not be studied.

Question 15

Cochrane 2020 Surgical treatment of fibroids for subfertility.

Answer 15

four RCTs with 442 participants.
Very low-quality with the main limitations being due to serious imprecision, inconsistency and indirectness.
There is limited evidence to determine the role of myomectomy for infertility in women with fibroids as only one trial compared myomectomy with no myomectomy.

Question 16

Risk factors for fibroids

Answer 16

Increasing incidence with age
Black women > white women
Family history of fibroids x3 RR

Question 17

Fibroid pathology

Answer 17

Monoclonal tumours predominantly composed of smooth muscle cells with variable amounts of connective tissues.
Can undergo atrophy, internal haemorrhage, fibrosis or calcification. Can also undergo degeneration.

Question 18

Radiographic features of fibroids

Answer 18

Ultrasound:
Well defined, solid, concentric, hypoechoic mass with variable amount of acoustic shadowing.
Hypoechoic (can be iso or hyperechoic)
Discrete lesion/lesions
Can see calcification (echogenic focus), cystic areas of necrosis can also be seen.
Venetian blind artifact may be seen but edge shadowing +/- sense posterior shadowing can also b seen.

Question 19

Causes of fibroid growth

Answer 19

Benign tumours – monoclonal (single cell) with expansion of surrounding extra-cellular matrix under influence of ovarian hormones.

1. Hormonally dependent
   o Increased ERa receptors – allow permissive effect for P to act
   o Increased PR receptors – cause fibroid growth due to paracrine effects
   o Anti-progestins or AI’s stop fibroid growth, E alone not enough to stimulate fibroid growth
2. Cytokine & Growth factors
   o b-catenin and TGF-b pathways alter stem cell differentiation
3. Genetics
   o Fumurate hydratase deficiency: predisposes ♀ to multiple fibs
   o MED12 & HMGA2 mutations – transforms myometrial stem cells to fibroid stem cell
4. Epigenetic effects
   o DNA methylation
   o Histone modification
   o miRNA alterations

Question 20

Reasons for difficulty in interpreting fibroid evidence

Answer 20

Poor quality
Many studies uncontrolled (or historically controlled)
Small sample size
Heterogeny in patient population - age, length of infertility, suspected aetiology are not stated or not controlled for.
Heterogeny in fibroids - varying size, number, location
Heterogeny in fibroid assessment - no uniformity in the metho of uterine cavity assessment.
Prior to FIGO classification no clear classification system for fibroids

Question 21

UAE concerns from a fertility perspective

Answer 21

Concerns for developing POI - inadvertant passage of embolic particles into the utero-ovarian anastomoses
Synechia development from small diameter particles lodging in the endometrial vasculature
Increased spon miscarriage, preterm delivery, abnormal placentation, caesarean section and post partum haemorrhage (case reports)

Question 22

MRgFUS

Answer 22

Magnetic resonance guided focussed ultrasound surgery - employs real time MRI guidance to direct high-intentisty ultrasound waves intot he body of a myoma causing protein denaturation, irreversible cell damage and coagulative necrosis.
While successful pregnancies have been reported it should still only be performed in a research setting.

Question 23

Myolysis

Answer 23

Placement of probes within the fibroid, usually by laparoscopy, followed by the use of bipolar or monopolar heat, cold (cryomyolysis) or laser to destroy the tissue. Potentially effective at reducing fibroid volume -pregnancy outcomes are unclear.

Question 24

Radiofrequency thermal ablation

Answer 24

USS or laparoscopy guided needle electrode to heat fibroid tissue and cause necorsis. again reproductive parameters unknown.

Question 25

Uterine artery ligation

Answer 25

Permanent uterine artery ligation. Targeted surgical occlusion of the uterine vessels has been trialled as an alternative to uterine artery embolisation (UAE) because it may avoid collateral damage to ovarian vasculature. There is limited data on pregnancy outcomes after laparoscopic uterine artery occlusion, so safe use in women wishing to
maintain their fertility has not yet been established.
Temporary uterine artery occlusion. A Doppler ultrasound guided transvaginal clamp which is left in situ for 6 h has yielded success in terms of symptom reduction and reduction in fibroid size. This technique is based on the theory that fibroids are exquisitely susceptible to ischaemia
because of their tenuous blood supply, while normal myometrium is more resilient. This too is a novel technique for which long-term outcomes are not known.

Question 26

Tubal reanastomosis surgery - surgical steps

Answer 26

Surgical steps:
1. Preoperative identification of appropriate surgical candidate
2. Informed consent including discussion of alternatives (IVF)
3. Performed laparoscopically under operative microscope
4. Safe laparoscopic entry
5. Anatomy identification and assessment of tubal injury. Identification if reanastomosis possible.
6. Instil vasopressin into mesosalpinx
7. Tubal stump preparation:
8. Identify point of ligation and excise occluded ends (remove filshie clip if not fallen off; dissect off occluded ends to expose fresh tissue)
9. Refresh edges of tubes – to ensure adequate blood supply and removal of fibrotic tissue
10. Confirmation of tubal patency on both sides done with instillation of methylene blue or manual examination
11. Anastomosis -
a. Dissect tubes to allow mobilisation and end to end anastomosis with no tension
b. Perform anastomosis: bring mesosalpinx together first for tensionless repair on tube. Using 6/0 vicryl with a two layer technique; using 4 quadrant sutures
12 - patency confirmed at end with methylene blue and then postoperative with HSG

Question 27

Factors influencing reanastomosis success

Answer 27

Factors influencing success:
- age of patient
- type of sterilisation (41 percent of women with a previous electrocautery procedure, 50 percent of those who had a Pomeroy tubal ligation, 75 percent of women with rings, and 84 percent of those with clips, 0% in those with salpingectomy)
- tubal length (75 percent in women with residual tubal length of 4 cm or more, but only 19 percent in those with shorter tubes)

Overall chance of success
- 90-98% success in achieving patent fallopian tubes
- Pregnancy rates 40-70% (maternal age clear confounder)
- Ectopic rate 6%

Question 28

Fimbrioplasty

Answer 28

Performed for the treatment of partial obstruction of distal fallopian tube (often the tube is patent but there are adhesive bands that surround the terminal end).
- Procedure aims to divide the peritoneal adhesive bands that surround the fimbria
– gentle alligator laparoscopic forceps are placed into the tubal ostium followed by opening and withdrawal of the of the forceps to stretch the tube and release minor degrees of fimbrial agglutination.
- Pregnancy rate following this procedure is 20-60%
-Ectopic rate is at 15%

Question 29

Terminal salpingostomy

Answer 29

Procedure to relieve tubal obstruction associated with hydrosalpinx
- However the chance of improving fertility depends on tubal wall thickness, ampullary dilation, presence of mucosal folds, percentage of ciliated cells in the fimbrial end and peritubal adhesions
- Pregnancy rate following salpingostomy is approx. 30% and ectopic pregnancy rate of 10%
- However pregnancy rate can be 0% if the tube is thick and rigid without rugae

Question 30

Proximal tubal occlusion and options

Answer 30

Proximal tubal occlusion
- low incidence of true cornual occlusion, typically diagnosed at
hysterosalpingographic findings interpretation of proximal tubal obstruction on imaging should be done with caution as sensitivity and specificity of imaging is approx. 65% and 83% respectively

Causes:
Acute/chronic salpingitis
Salingitis isthmica nodosa
cornual fibroids
Endometriosis
Prior ectopic pregnancy
Tubal polyps
Mucus plugs

Tubal catheterisation (non surgical)
- if proximal tubal occlusion is present, in selective patients tubal catheterisation can be considered with tubal patency rate of 60-80% and pregnancy rates of 20-60%
- half of the reported pregnancies occurred in the first 12 months
-none of the studies had control groups

Tubocornual anastomosis
- performed in patients with true cornual obstruction cornual portion of the tube is resected followed by anastomosis
- IUP rates vary from 16-55% and ectopic pregnancy rates from 7-30%.
- Overall this procedure can be done by laparoscopy (small number of reported cases)or laparotomy but IVF is preferred over surgery