Disclosures

Should we still perform instead of • No conflict of interest regarding the contents of this lecture at the time of female ?

Paloma Lobo Abascal Hospital Universitario Infanta Sofía. San Sebastián de los Reyes, Madrid. Spain. Universidad Europea. Madrid. Spain

Female sterilization prevalence Tubal sterilization failure rate. The CREST study

• CumulativeCONCLUSIONS: 10-year probability of depends on • Although tubal sterilization is highly effective, the risk of sterilization failure is higher than generally reported. • Female sterilization is the most common • Sterilization• Technique (parcial salpingectomy, silicone rings, bipolar coagulation…) • Age Theof the risk patient persists for years after the procedure and varies by method of tubal occlusion and age. method of contraception worldwide, • used by 19 percent of all women ages Time from the procedure 15 to 49 years who are married or in a relationship union. Dependent on remaining years of potential • Reliance on female sterilization is highest Age- dependent in Asia (23.4 %) and Latin America and the Caribbean (26%), and lowest in Africa (1.7%) and Europe (3.8%).

Salpingectomy as primary method of sterilization A shift in the paradigm of ovarian cancer

p53 signature

Until the past few years salpingectomy was reserved for individuals in w hom sterilization fails and it has been considered the preferred method to ensure definitive treatm ent. STIC

Seeding of cells

1 Epithelial ovarian cancer Epithelial ovarian cancer What did we know? What did we know?

LowerFor many risk with epithelial pregnancy, malignancies breast feeding the and cell origin is Lowerwell defined risk with pregnancy,(colon, cervical breast feeding cancer…) and Usually COC use. COC use. High grade diagnosed at an serous carcinoma advanced stage represents 70% (III, IV) The gonadotropin hypothesis: overstimulation of of epithelial This is not the case for ovarian epithelial cancer ovarian surface epithelium by FSH and LH leads to Incessant ovulation hypothesis proposed ovarian cancers High mortality proliferationMany theories and have risk beenof malignant proposed transformation. to understand the cells of origin and bythe Fathallamechanisms in1971 of carcinogenesis.

These and other theories have been proposed to understand how coelomic epithelium undergo metaplasia and Traditionally epithelial ovarian cancer has been assumed to arise from the epithelial surface of the ( dysplasia Higher risk in PCOS, nulliparous, and coelomic epithelium) Higher risk in PCOS patients • Benign ovarian cystadenomas can progress into a borderline tumor and later to a low grade malignancy. postmenopausal women. • Endometriosis is linked to endometrioid and clear cell cancers

• The progression from low grade to high grade serous carcinomas is extremely rare. Ovulation Coelomic Develof Cortical opment Inflammatio metMül apl ler as ian ia of Dysplasia Follicular epithelial inclusion damagen DNA the coelomic and rupture damage cysts (CICs) epithelium Cancer Traditional theories do not explain the pathogenesis of High grade serous carcinoma

Tubal origin of ovarian high grade serous carcinoma Shifting the paradigm

STIC “serous tubal intraepithelial carcinoma” Prophylactic tubal removal in BRCA 1 Anatomical close relationship of Epithelial stratification carriers or women who belong to families with the ovary at Nucl ear at ypi a with high risk of ovarian cancer the time of ovulation Acti ve prol i f erati on development. Ovulation: the ovarian surface ruptures with expulsion and transfer of P53 signature: the oocytefimbria. to the Nucl ear enlargement P53 mut at i on Lack of cilia

Tubal epithelial cells from the fimbria are dislodged and implant on the denuded surfacein the of formationthe ovary resultingof an inclusion cyst.

PiekAfterJMJ, closeJ Pathol examination2001;195:451 of tubal-59 segments these hyperplastic and dysplastic lesion resembled high-grade serous ovarian cancer without invasion.

The Origin and Pathogenesis of Epithelial Ovarian Cancer The Origin and Pathogenesis of Epithelial Ovarian Cancer A Proposed Unifying Theory: Serous carcinoma. A Proposed Unifying Theory: Endometrioid and clear cell carcinoma. High grade serous carcinoma: Direct dissemination or shedding of Low grade serous STICcarcinoma”cells “serous tubal onto intraephitelial the ovarian carcinoma: surface. Mutation KRAS/BRAF/ERRB2 From an inclusion cyst Often develops from a serous borderline tumor which arises Endometrial tissue by a from a serous cystadenoma. process of retrograde Serous tumors menstruation implants on the very similar to ovarian surface to form an endometrioid cyst from which Endometrioid and a LG endometrioid or clear clear cells tumors fallopian tube cell carcinoma can develop. High grade serous epithelium very similar to carcinoma: Mutati on TP53 From an inclusion cyst

Kurman Rj. Am J Surg Pathol 2010; 34:433-443. Kurman Rj. Am J Surg Pathol 2010; 34:433-443.

2 Why salpingectomy for sterilization? Expanded dualistic model of ovarian carcinogenesis Evidences

Bilateral tubal interruption confers some protection towards developing ovarian cancer. • Effects on ovarian vascularization that may affect its function • Acts as mechanical barriers against • Ascending vaginal carcinogens • Ascending proximal tubal and endometrial cells. Cibula D. Acta Obstet Gynecol Scand 2011;90:559-63.

• 60-75% of high grade serous ovarian carcinomas are associated with tubal intraephitelial carcinoma (STIC).

The precursor lesions are Salpingectomy Low grade High grade located in the distal portion should confer Slow growing Evolve rapidly of the fallopian tube. more protection Borderline precursors No precursors in the ovary

Kurman RJ. Am J Pathol 2016, 186: 733-747 Jones PM. Frontiers in Oncology. 2013 | Volume 3 | Article 217

Tubal ligation and risk of ovarian cancer Tubal ligation and risk of ovarian cancer Review and meta-analysis Pooled analysis of case-control studies

34% 19% 52% 48%

These data support the theory that these cancers originate from exfoliated endometrial cells. The magnitude of risk reductionConversely, was significantlyHGSC appear greater to arise for predominantly in the distal tube. endometrioid and clear cell cancers than for HGSC. Protection persist 10-14 years after the procedure Therefore, to substantially reduce the risk of invasive serous cancer, the distal tube must be ablated or removed. Confirmed for Endometrioid and serous cancer Sieh W. Int Journal of Epidemiol. 2013;42:579-589. Cibula D. Hum Reprod 2011;17:55-67.

Salpingectomy for ovarian cancer prevention Salpingectomy Recommendations and ovarian cancer risk reduction

Low risk 35% population 50% 28%

• When counseling women about laparoscopic sterilization methods, clinicians can communicate that bilateral salpingectomy can be consider a method that provides effective contraception. Results: • Population-based cohort study in Sweden. • Prophylactic salpingectomy may offer clinicians the opportunity to prevent ovarian cancer in their patients. ••ThereConclusion:251.465 was awomen statistically with significantly previous surgery lower riskon forbenign ovarian indication cancer among (sterilization, women salpingectomy, with previous salpingectomy ,(HR and = bilateral0.65, 95% salpingo CI = 0.52- to oophorectomy0.81) when compared [BSO], with hysterectomy) the unexposed compared population. with the unexposed population (n = 5.449.119) between 1973 and 2009. • Randomized controlled trials are needed support the validity of this approach to reduce the incidence of • Salpingectomy on benign indication is associated with reduced risk of ovarian cancer. “Theovarian approach cancer. to sterilization should not be influenced by the theoretical benefit of salpingectomy” ••There•DataThese was were a datastatistically analyzed support withsignificant theCox hypothesisregression risk reductions models. that among a substantial women with fraction previous of sterilization ovarian cancer(HR = arises0.72, 95% in theCI = fallopian 0.64 to 0.81). tube. • Bilateral• These salpingectomy data suggest was that associated removal with of a the 50% fallopian decrease tubes in risk byof ovarianitself, or cance concomitantlyrcompared with with the other unilateral benign procedure (HR = ACOG Committee Opinion 620-January 2015. •0.35,Thesurgery, 95% effects CI = of is0.17 onean toeffective- and0.73, two and -measuresided 0.71, salpingectomy95% to CI reduce= 0.56 to wereovarian 0.91, considered respectively). cancer inrisk a subin the-analysis. general population.

Falconer H. JNCI 2015;107(2): dju410

3 Salpingectomy…only for ovarian cancer prevention? Complications of tubal interruption

• Bilateral salpingectomy provide the best immediate and long-term contraceptive efficacy best immediate

• W e should explain to women • Fistula or recannulation Unintended pregnancy

• Hidrosalpinx Consultations, interventions

The differences in The risk of • in th e tu b al re m n an t pregnancy risk The potential The impact over operative and after tubal complications of the ovarian reserve perioperative interruption or tubal interruption of the different complications of the • The 10-year cumulative probability of ectopic pregnancy for all methods of tubal sterilization combined was 7.3 per 1000 procedures. salpingectomy and salpingectomy techniques different techniques • The cumulative probability varied substantially according to the method of sterilizationand the woman’s age at the time of sterilization. • Women s t er il iz ed by bipolar tubal coagulation before the age of 30 years had a probability of ectopic pregnancy that was 27 times as high as that among women of similar age who underwent postpartum partial salpingectomy.

Peterson HB.N Engl J Med 1997;336:762-7

Impact of extent of excision in ovarian reserve Risk and complication of salpingectomy versus tubal ligation

The opportunistic salpingectomy do not increase the risk of operative/perioperative complications and appears both feasible and safe.

• Tubal• Salpingectomy: sterilization cohort: open Salpingectomyversus laparoscopic v tubal approach ligation ••AdditionalAdditional surgical surgical time: time: 10 14 minutes minutes ••NoSignificantly differences more in blood blood loos transfusions Results: No significant difference was observed between groups for ∆AMH, ∆FSH, ∆AFC, ∆VI, ∆FI, ∆VFI, and ∆OvAge. Moreover, the • Longer• Length length of hospitalof hospital stay stay ( 3 days; 70% postpartum) • • Methods:groups were Patients similar forwere operative randomly time, divided ∆Hb, postoperativeinto two groups. hospital In group stay, postoperativeA (n=91), standard return salpingectomyto normal activity, was and performed. complication In grouprate. B HigherHospital hospital readmission readmission (nConclusions: = 95), the mesosalpinxEven when the was surgical removed excision within includes the tubes. the removalPrior to ofand the 3 ,months after salpingectomy surgery, antimullerian does not damagehormone the (AMH), ovarian FSH , threereserve.-dimensional Moreover, wideantral salpingectomy follicle count with(AFC), excision vascular of the index mesosalpinx (VI), flow didindex not (FI), alter vascular blood loss,-flow hospitalization index (VFI), and stay, OvAge or return wereto normalrecorded foractivities. each patient.

Venturella R. Fertil&Steril 2015;104:1332-9. n=15.n=2.492 288 McAlpine JN. AJOG 2014;210:471. e1-e11.

Salpingectomy for permanent contraception Do we have reasons for changing our practice?

TheWhy question we are notshould offering not be women focused a chance only on for ovarian near 100% cancer efficacy prevention; by removing rather, the moreFallopian important tube question Operative time shouldcompletely be: for sterilization? • Why we are not offering women a chance for near 100% efficacy by removing the Fallopian tube completely for sterilization? Perioperative complications

Lower failure rate Effect on ovarian reserve To avoid surgical risks? • Salpingectomy is safe and feasible and do not confer higher surgical risk compared with tubal interruption Ovarian cancer risk reduction No option for tubal reversal

To avoid risk of regret? • The younger the woman, the more likely she will regret choosing a permanent form of contraception. • For women who are not certain, LARC methods offer equal to or greater efficacy than tubal interruption procedures and women should be counseled more carefully about LARC rather than a less effective sterilization method that also has a risk of ectopic and ectopic pregnancy.

Creinin MD. Obstet & Gynecol 2014;124:596-9

4 Tubal sterilization Do we have reasons for changing our practice? Recommendations ( to take home)

Yes we have!! Operative time • For women undergoing surgical sterilization, all options for sterilization should be discussed, including complete salpingectomy, and we must communicate that sterilization by salpingectomy • It is not reversible Perioperative complications • Has higher efficacy than tubal interruption • According to the actual evidence may confer greater protection against most subtypes of ovarian cancer Ovarian cancer risk reduction including High grade serous carcinomas Effect on ovarian reserve • The available data regarding minimal added surgical time and risk of morbidity should be share with the women. • Opportunistic salpingectomy for permanent sterilization should be offered both in cases of interval tubal Lower failure rate sterilization and at the time of cesarean section.

Thank you very much for your attention!! Köszönöm szépen!!

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