Ectopic Olufemi

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CURRENT CONCEPTS IN MANAGEMENT : 

CURRENT CONCEPTS IN MANAGEMENT Olufemi Aworinde

Outline : 

Outline Introduction History Risk factors Pathology Clinical presentation Diagnosis Treatment Future fertility Conclusion 12/11/2010 13:41 Ectopic Pregnancy 2

Introduction : 

Introduction Derived from the Greek word ektopos, meaning “out of place”. Implantation of a fertilized ovum outside the endometrial lining of the uterus 2% of all pregnancies and is the most common cause of pregnancy-related mortality in the first trimester. Incidence of ectopic pregnancy has been rising in many countries due to increased incidence of PID, ART and early diagnosis. 12/11/2010 13:41 Ectopic Pregnancy 3

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Common life-threatening surgical emergency Reported incidence 2.7% of deliveries in Ibadan 2.3% “ “ Benin 1.6% “ “ Jos 2.0% “ “ Sokoto In Ile-Ife, incidence quadrupled btw 1987 and 1997 with 97% ruptured. Contribution to maternal mortality 6.5% - Ilorin 8.6% - Lagos

History : 

History The survival rate in the early 19th century was dismal with only 1 of 6 patients surviving surgery. Early 20th century, great improvements in anaesthesia, antibiotics, and bld transfusion there was decrease in the MMR (1-2/50 patients) 1970; 4.5/1000 preg in US; 1992  19.7/1000. Case-fatality rate decrsd by 90% from 197092 However, in developing countries, both the prevalence and case fatality rates remain high. 5

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Diagnosis was previously at post mortem Later it was diagnosed before death but expectant mgt was done with 70% mortality. The reduction in case fatality seen now is due to the improvement in diagnostic methods, aiding early diagnosis; and better ways of treatment. This does not only ensure that the woman remains alive but gives her the chance of reproducing her kind, which is the dream of most women. 6

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1693– Busiere first recognised Ectopic Preg 1759 -John Bard reported the first successful surgical intervention. 1884 -- Robert Lawson Tait of Birmingham performed the first successful Salpingectomy 1953 – Stromme – Salpingostomy 1973 – Shapiro & Adler – Laparoscopic Salpingectomy 1991 – Young et al – Laparoscopic Salpingotomy

Risk factors : 

Risk factors Congenital - Tubal Hypoplasia , Tortuosity , Congenital diverticuli , Accessory ostia , Partial stenosis ACQUIRED: Inflammatory: PID, Septic Abortion, Puerperal Sepsis Surgical: Tubal surgery Miscellaneous: IUCD , ART (IVF & GIFT), Endometriosis, Previous ectopic, Smoking, exposure to DES inutero, infertility, Early age at intercourse, Multiple partners 12/11/2010 13:41 Ectopic Pregnancy 8

Pathology : 

Ampullary (A 55-70%). Isthmic segment of the tube (B 12-25%). Fimbrial (C 5 - 10%). Interstitial (D 2%). Non-tubal sites are rare (3-5%) Abdominal pregnancies (E 1.4%) Ovarian (F 0.2%). Cervical (G0.2%). Previous c/s scars, or in a rudimentary uterine horn 9 About 80% of ectopics are found on the same side as the corpus luteum Pathology

Clinical presentation : 

Clinical presentation Symptoms are usually not seen until it ruptures then presents in either of two ways - Acute &. Chronic; features depend upon the evolution of the pathology Ruptured ectopic pregnancy Chronic ectopic (slow-leaking) pregnancy Early un-ruptured ectopic pregnancy

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“Pregnancy in the fallopian tube is a black cat on a dark night. It may make its presence felt in subtle ways or leap at you or it may slip past unobserved. Although it is difficult to distinguish from cats of other colours in darkness, illumination clearly identifies it.” Mc. Fadyen 12/11/2010 13:41 Ectopic Pregnancy 11 Diagnosis

Before.....before : 

12/11/2010 13:41 Ectopic Pregnancy 12 Before.....before Urine hcg value values -500-800miu/L Serial PCV measurement Ultrasound- Poor resolution TAB Serum progesterone: Single value Culdocentesis—false positive[26%]; false negative [10-14%] Dilatation and curretage

Now…………. : 

Now…………. Radioimmunoassay utilising monoclonal antibodies to beta HCG (serum 5-10iu/L; urine 20-50iu/L) Ultrasound scanning – High Resolution abdominal and vaginal ultrasound and Colour Doppler Laparoscopy- diagnostic and therapeutic 12/11/2010 13:41 Ectopic Pregnancy 13

Beta HCG : 

Beta HCG In early healthy intrauterine pregnancies, serum levels of bhCG double approximately every 2 days (1.4-2.1 d), lower limit is 66%. Increase in bhCG <66% is associated with an abnormal intrauterine pregnancy or an extrauterine pregnancy. 15% of healthy intrauterine pregnancies do not increase by 66%; 13% of all ectopic and 64% of very early ectopic pregnancies rise normally. Serial measurement is needed; positive result alone does not tell location and carries risk of rupture while waiting. 12/11/2010 13:41 Ectopic Pregnancy 14

uss : 

uss TVS can visualise a gestational sac as early as 4-5 weeks from LMP. During this time the lowest serum beta HCG is 1000 IU/L (6000 IU/L for TAB) i.e discriminatory zone When beta HCG level is greater than this and there is an empty uterine cavity, ectopic pregnancy is suspected. 12/11/2010 13:41 Ectopic Pregnancy 15

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12/11/2010 13:41 Ectopic Pregnancy 16

Doppler USS : 

Doppler USS Improves diagnostic sensitivity and specificity of TVS. Use of DUS, compared with TVS alone, increases the sensitivity from 71-87% for ectopic preg. Aids early diagnosis and eliminate delays caused by using serial levels of bhCG for diagnosis. Used to identify involuting ectopic preg that may be candidates for expectant management. The vascular colour in a xteristic placental shape (ring of fire pattern or flame sign) is seen outside the uterine cavity; UC is cold. 12/11/2010 13:41 Ectopic Pregnancy 17

Note… : 

12/11/2010 13:41 Ectopic Pregnancy 18 Note… The sensitivity of ultrasound depends on quality of scan machine, experience and skill of the operator. difficulty in differentiating between interstial ectopic and intra-uterine pregnancy Non – cystic adnexal mass, fluid in pouch of Douglas and empty uterus - positive predictive value of 94% Definitive diagnosis: gestational sac with a fetal pole exhibiting cardiac activity

Laparoscopy : 

Laparoscopy Reduced need for use for diagnosis The whole length of the tubes should be outlined Allows assessment of the pelvic structures, size and exact location of ectopic pregnancy, presence of haemoperitoneum, and presence of other conditions. Provides the option to treat once confirmed. Routine use on all patients may lead to unnecessary risks, morbidity, and costs. Can miss up to 4% of early ectopic pregnancies 12/11/2010 13:41 Ectopic Pregnancy 19

Other investigations. : 

Other investigations. Other serum markers under investigations: Serum estriol Inhibin Pregnancy associated plasma protein A Creatine kinase Quadruple screen of serum progesterone, bhcg, estriol and alpha-fetoprotein

Management : 

Management Depends on the type of ectopic and the condition of the patient at diagnosis. Options- Surgery – Laparoscopy / Laparotomy Medical – Administration of drugs at the site / systemically Expectant – Observation and monitoring 12/11/2010 13:41 Ectopic Pregnancy 21

Acute ectopic pregnancy : 

Acute ectopic pregnancy Hospitalisation Resuscitation-Treatment of shock, Analgesics, Blood transfusion Surgery should be done early. If blood is not available, auto-transfusion can be done. Aim is resuscitation and laparotomy, not sequential. 12/11/2010 13:41 Ectopic Pregnancy 22

Chronic ectopic pregnancy : 

Chronic ectopic pregnancy Serial quantitative beta HCG level USS- usually haematocele is found Laparoscopy Surgery 12/11/2010 13:41 Ectopic Pregnancy 23

Unruptured ectopic pregnancy : 

Unruptured ectopic pregnancy Surgery Surgically administered medical treatment Medical treatment Expectant management 12/11/2010 13:41 Ectopic Pregnancy 24

Surgery : 

Surgery Carried out either by Laparoscopy / Laparotomy. The procedures are: - Salpingectomy / Cornual resection / Excision Conservative surgery (in cases of Infertility & desire for pregnancy) Linear salpingostomy Linear salpingotomy Segmental resection and anastomosis Milking of the tube 12/11/2010 13:41 Ectopic Pregnancy 25

Surgery : 

Surgery 12/11/2010 13:41 Ectopic Pregnancy 26 LAPAROTOMY? VS. LAPAROSCOPY? SALPINGECTOMY? VS SALPINGOSTOMY / SALPINGOTOMY? The debate goes on

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12/11/2010 13:41 Ectopic Pregnancy 27 Laparotomy vs laparoscopy L’tomy L’scopy Hospital cost More? Less? Post operative adhesions More Less Risk of future ectopic Same Same Future fertility Same Same Experience of Surgeon Trained Special Instruments General Special

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12/11/2010 13:41 Ectopic Pregnancy 28 Salpingectomy vs salpingostomy / salpingotomy All tubal pregnancies can be treated by partial or total Salpingectomy Salpingostomy / Salpingotomy is indicated when: The patient desires to conserve her fertility Patient is haemodynamically stable Tubal pregnancy is accessible Unruptured and < 5cm in size Contralateral tube is absent or damaged

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12/11/2010 13:41 Ectopic Pregnancy 29 The choice of surgical treatment does not influence the post treatment fertility, but prior history of infertility is associated with a marked reduction in fertility after treatment Making the choice – Chapron et al (1993) have described a scoring system, based on the patient’s previous gynaecological history and the appearance of the pelvic organs, to decide between salpingostomy / salpingotomy and salpingectomy. The rationale behind the scoring system is to decide the risk of recurrent ectopic pregnancy.

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12/11/2010 13:41 Ectopic Pregnancy 30 Fertility reducing factor Score Antecedent one Ectopic pregnancy 2 Additional antecedent Ectopic pregnancy 1 Antecedent Adhesiolysis 1 Antecedent Tubal micro surgery 2 Antecedent Salpingitis 1 Solitary tube 2 Homolateral Adhesions 1 Contralateral Adhesions 1 Conservative surgery is indicated with a score of 1-4 only, while radical treatment is to be performed if the score is 5 or more

Persistent ectopic pregnancy (PEP) : 

Persistent ectopic pregnancy (PEP) Complication of conservative surgery when residual trophoblast continues to survive bcos of incomplete evacuation of the ectopic pregnancy. Diagnosis is made because of a raised or plateau postoperative serum HCG If untreated, can cause life threatening hemorage Risk factors: Early Rx <42days mentrual cycle; sac <2cm; >3000iu/L and site medial to salpingostomy incision. Treatment is by- Reoperation and further evacuatn /Salpingectomy Administration of IM / oral MTX in a single dose of 50 mg/m2 of body surface 12/11/2010 13:41 Ectopic Pregnancy 31

SAM treatment : 

SAM treatment Aim- trophoblastic destruction without systemic SE Technique- Injection of trophotoxic substance into the ectopic pregnancy sac or into the affected tube by- Laparoscopy or USS guidance or with Falloposcopy. Trophotoxic substances used include Methotrexate, KCl, Mifepristone (RU 486), PGF2, Actinomycin D &Hyper osmolar glucose solution 12/11/2010 13:41 Ectopic Pregnancy 32

Medical treatment : 

Selection criteria: Clinically stable GS < 3.5cm No collections in POD Show no cardiac activity bhcg level should be <3000iu/l Patient should be compliant & return for ff up No contraindication to use of methotrexate Medical treatment 33

Methotrexate : 

Methotrexate Can be given IV/IM/Oral The multidose protocol involves giving 1mg/kg i.m on days 0, 2, 4 and 6 followed by leucovorin (folinic acid) 0.1mg/kg on days 1, 3, 5, 7 Recent concept is to use a single dose of 50mg/m2 without Folinic acid. If serum HCG does not fall to 15% of value of day4 by day7, then a second dose is given and resolution confirmed by HCG estimation. Treatment effects of methotrexate:Increase abdominal pain and bhcg during first 1-3days of treatment, Vaginal bleeding, Spotting. 12/11/2010 13:41 Ectopic Pregnancy 34

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Before Rx blood samples to be taken for: Baseline bhcg Renal, hepatic and marrow function Blood group and Rhesus Repeat blood samples for bhcg days 4days & 7days after methotrexate injection Monitor patient’s bhcg levels weekly until they become undetectable

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Contraindications to use of methotrexate: Breast feeding immunodeficiency, Alcoholism peptic ulcer disease Liver disease active pulmonary disease Blood dyscrasias anaemia, leucopenia, thrombocytopenia renal, hepatic and haematological dysfunction.

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Advantages – Minimal Hospitalisation. Usually outpatient treatment Quick recovery 90% success if cases are properly selected Disadvantages- Side effects like GI Monitoring is essential- Total blood count, LFT & serum HCG once weekly till it becomes negative (< 5-10miu/L) 12/11/2010 13:41 Ectopic Pregnancy 37

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Failure of medical Rx occurs when bhcg levels increase, plateau, or fail to decrease by 15% from days 4-7 post injection Surgical intervention may be indicated Medical Rx is an option when ectopic pregnancy is located on the cervix, ovary, interstitial or cornual portion of the tube Surgical Rx of these cases is often associated with haemorrhage often resulting in hysterectomy or oophorectomy 12/11/2010 13:41 Ectopic Pregnancy 38

Other pharmarcological Rx : 

Other pharmarcological Rx Mifepristone (RU486): Not successful in treating ectopic pregnancy as single agent; Combined with methotrexate success rates are improved Actinomycin D: More potent chemotherapy than methotrexate especially in advanced gestations (bhcg levels >10000miu/ml in which methotrexate has a higher failure rate KCL: Injected into the fetal heart in advanced ectopic pregnancy. May have a role in treating heterotopic pregnancy

Expectant treatment : 

Expectant treatment Tubal Pregnancies are known to Abort / Resolve Before the advent of salpingectomy in 1884, ectopic pregnancies were being treated expectantly with 70% mortality. Today only selected cases are managed expectantly, screened and identified by high resolution ultrasound scanner and monitored with serial serum HCG assay 12/11/2010 13:41 Ectopic Pregnancy 40

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Identification criteria (Ylostalo et al , 1993)- Diameter of ectopic pregnancy <4 Cm. No sign of intrauterine pregnancy No sign of rupture by TVS No sign of acute bleeding by TVS HCG <1000miu/L (?200miu/L) Falling level of serum HCG at 2 day intervals If any deviation from the above criteria occurs, then emergency treatment is necessary. Prolonged follow-up: Anxiety to patient and clinician 12/11/2010 13:41 Ectopic Pregnancy 41

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OUTCOME: 72% - Spontaneous resolution occurs spontaneous resolution may take 4 – 67 days (mean 20 days) for the serum HCG to return to non pregnant level. 28% - will need laparoscopic salpingostomy The % fall in serum HCG by day 7 is a better indicator than the percentage fall by day 2. Warning:- Tubal pregnancies have been known to rupture even when serum HCG levels are low. 42

Follow up Rx : 

Follow up Rx Weekly bhcg assay until the level is zero The average time for bhcg to clear in the system is about 2-3weeks up to 6weeks may be required Administration of prophylactic dose of methotrexate have been suggested after conservative Rx to reduce risk of persistent ectopic pregnancy

Ectopic in other sites : 

Ectopic in other sites Heterotopic: No room for expectant or medical mgt Ovarian Oophorectomy (localised surgical resection with preservation of the ovary if detected early) Cervical * Hysterectomy Tamponade with inflated Foley's catheter MTX administration avoids severe haemorrhage Abdominal: Diagnostic challenge; Surgery done. Placenta at laparotomy (Leave or remove) Give MTX or don’t give if placenta is left

Ovarian ectopic (Spiegelberg’s criteria) : 

Ovarian ectopic (Spiegelberg’s criteria) Tube on the affected side must be intact Gestational sac must be located in the ovarian fossa Must be connected to the uterus by the ovarian ligament Ovarian tissue must be found on it s wall on histology 12/11/2010 13:41 Ectopic Pregnancy 45

Cervical ectopic criteria (Clinical) : 

Cervical ectopic criteria (Clinical) Soft, enlarged cervix equal to or larger than the uterus Painless uterine bleeding following amenorrhea Products of conception entirely confined within and attached to the endocervix Closed internal os with partially opened external os. 12/11/2010 13:41 Ectopic Pregnancy 46

Cervical ectopic criteria (Rubins) : 

12/11/2010 13:41 Ectopic Pregnancy 47 Cervical ectopic criteria (Rubins) Cervical gland must be present opposite placental attachment. Attachment of placental to cervix must be intimate Placental must be below the entrance of uterine vessels or below the peritoneal reflection on the anterioposterior uterine surface

Abdominal ectopic criteria (Studdiford) : 

12/11/2010 13:41 Ectopic Pregnancy 48 Abdominal ectopic criteria (Studdiford) Normal ovaries and tubes. Absence of uteroperitoneal fistula GS should be related exclusively to the peritoneal surface and early enough to eliminate 10 implantation in tube.

Differential diagnosis : 

Differential diagnosis Abortion: Threatened, Inevitable, Incomplete, Complete, Missed Appendicitis Degenerating fibroid  PID Typhoid enteritis Intestinal obstruction Ruptured corpus luteum cyst, Ovarian torsion Cornual myoma or abscess Ovarian tumor 11/12/2010 49

Prevention : 

Prevention Early detection and treatment of STIs Clean and safe delivery Effective post – abortion care Community sensitization on need for early presentation in pregnancy

Future fertility : 

Future fertility Chances of intrauterine pregnancy after an ectopic pregnancy is 50% - 80% Chance of intra-uterine pregnancy post – salpingectomy – 40% post – conservative surgery – 60% post – medical treatment – 87% Recurrent ectopic pregnancy rates (10-20%) similar for all treatment modalities; 15% after 1st, 25% after 2 ectopics

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In Ile-Ife; the records of 108 patients who had at least 1 year of follow-up 35.9% subsequently conceived, 13.9% had recurrent ectopic pregnancy, 19.4% delivered at term, and 37% remained secondarily infertile. Thirty patients were sterilized or using contraception as of the time of review. Previous history of ectopic preg seen in 3.45% of infertile women, compared to 2.1% of pregnant women. 12/11/2010 13:41 Ectopic Pregnancy 52

Reinforcement of current concepts : 

Reinforcement of current concepts Serial Serum β-hCG measurements Transvaginal ultrasound Conservative laparoscopic surgery Systemic methotrexate therapy 12/11/2010 13:41 Ectopic Pregnancy 53

Conclusion : 

Conclusion Over the last decade, the management of ectopic pregnancy has evolved from a radical operative approach (salpingectomy) to a more conservative surgical or medical treatment. This has been possible due to early diagnosis, advanced laparoscopic techniques and ability to monitor the patient after conservative management. This has resulted in a fall in maternal mortality despite an increase in its incidence. 12/11/2010 13:41 Ectopic Pregnancy 54

Slide 55: 

Thank you!

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