Meena P.1, Bhojwani P2, Verma G.S.3
1Dr. Pragati Meena, 2Dr. Poonam Bhojwani, 3Dr. Gajendra Singh Verma, all authors are affiliated with Department of Obstetrics Gynecology, NIMS Medical College and Hospital, Shobha Nagar, Delhi Highway Jaipur, Rajasthan, India
Corresponding Author: Dr. Poonam Bhojwani, Email: drpragati02@gmail.com
Abstract
Ectopic pregnancy is a major health issue in reproductive age group female. Incidence of primary ovarian ectopic pregnancy as mentioned in literature of India is variable from 0.001% to 0.014% of normal pregnancies. Only 0.15% to 3.0% of all ectopic pregnancy occurs in ovary and it is 2ndmost common site of ectopic pregnancy after fallopian tube. Annual incidence of extra uterine cavity pregnancy is rising over past 3 yrs. The aim of ourpresent study isto find out the incidence of ovarian ectopic pregnancy, role of USG in pre-operative diagnosisand risk factors, feasibility of conservative management with medical method or conservative management e.g. minimal invasive surgery in developing countries like India. We analysed the incidence, management of ovarian pregnancy & reviewed the literature, risk factors and clinical presentation of ovarian ectopic pregnancies managed at NIMS Medical College and Hospital jaipur. According to Spielberg criteria, it is a diagnostic challenge to obstetrician. Diagnosis of ectopic pregnancy can be missed radio logically and intra operatively. It Should be suspected in patients presented with rupturedectopic pregnancy, ultrasound features suggestive of normal bilateralfallopian tube with hemo peritoneum with breached ovarian surface. Conservative surgical approach is preferred, now days Medical management is preferred for unruptured ectopic pregnancy. Confirmation of ovarian pregnancy done only after histopathological report. Now daysMedical management with single dose of Methotrexate is very successful for un ruptured ovarian pregnancy
Keywords- Ectopic pregnancy, Laparotomy, Salpingoophorectomy, Methotrexate
Manuscript received: 08th December 2017, Reviewed: 14th December 2017
Author Corrected: 20th December 2017, Accepted for Publication: 31st December 2017
Introduction
The Incidence of ectopic pregnancy is 1.2 -1.4%.Incidence of primaryovarian ectopic pregnancy is, as mentioned in literature of India is variable from 0.001% to 0.014% of normal pregnancies.Only 0.15% to 3.0% of all ectopic pregnancy occurs in ovary and it is 2ndmost common site of ectopic pregnancy after fallopian tube [1]. Extrauterine pregnancy or ectopic ovarian pregnancy a Greek word originated from “EKTOPOS” which means out of place. Ectopic refer to implantation of blasto cyst outside of uterine cavity[1]. Primary ovarian ectopic pregnancy is very rare clinical presentation of extra uterine pregnancy &a life threatening emergencyalso if not diagnosed timely. Fallopian tube is most common site of ectopic pregnancy, comprises to 95% of total ectopic pregnancies. Incidence increasing with ART procedures and IUCD insertion. Ovarian pregnancy is gestational sac implantation in the ovary.First case of ovarian pregnancy is reported by St. Maurice in 1689[2]. Its diagnosis is very difficult & based on clinical diagnosis, intra operative finding and on Histopathology examination report. Definite management of ruptured ovarian pregnancy is surgical. Approximately 75% pregnancies terminate in early gestation,1 2.5% patients terminate in the second trimester & 12.5 %patients reached till term. Ovarian pregnancy in 1624, suggested first by Mercerus[3,4].
Incidence of ectopic pregnancy is-
1. Tubal pregnancy- 90-95.5%
2. Ovary-1.5- 3%
3. Abdomen-1.3%
4. Cervical -0.15%
5. Heterotopic 1-2%
6. Caesarean -6%
7. Interstitial -2.5%
Case Report- A 28 years old female, presented with 6weeks amenorrhea with severe right sided lower abdominal pain with no history of vaginal bleeding came to our hospital emergency corresponds to 6 weeks and 3 days of gestational period. According to her, his previous menstrual history was normal. There was no history of PID, ART procedure, Tuberculosis and any Infertility treatment. On her examination, her vitals were BP-90/60 mm of Hg, PR-110 /min, clinical features suggestive of haemorrhagic shock were present. On her P/A examination - soft distension was present and tenderness present in RIF.P/V examination revealed –uterus mobile and non-tender, cervical motion tenderness present,2.8x2.8 cm adnexal mass felt in right fornix. Patient investigated, her UPT +ve,Hb% 8gm,TLC 10,600/ cumm, rest hemogram was normal,USG findings Shows Empty uterine cavity &bulky ET-19 mm ,2.8x2.8 cm right adnexal massseen without fetal pole, free fluid present in POD.
Image No-1: Ultrasound showing ovarian ctopic pregnancy
Our provisional diagnosis was ruptured ectopic pregnancy was made & patient was prepared for laparotomy, her intra operative findings were-
Hemoperitoneum of 200 cc was present
Uteruswas bulky
B/L fallopian tubes normal &left ovary normal
Rt ovary enlarged by a 2.8 ×2.8 cm sized adnexal mass in situ which visible as bluish red color with oozing frombreached ovarian surface.
Right salpingo - oophorectomy done and Left fallopian tubal ligation done by modified pomeroy,s method and tissue sent for histopathological examination. Her postoperative period was uneventful. Her histopathology report shows corpus luteum with trophoblastic villi in the ovarian tissue. Histopathological report of her D&C tissue shows absence of villous or fetal tissue.
Image No-2: Intraoperative finding showing ovarian pregnancy
Histopathology report & her intra operative findings were satisfied with the Spielberg criteria. Her immediate and long term postoperative course was uneventful. Patient followed up in OPD after 1 week of surgery.Her serial β hcg was on D5 -500miu/ml,D12 -30miu/ml, D19- undetectable.
Discussion and Review of Literature- Clinical presentation of ovarian ectopic pregnancy is variable and it is a life-threatening emergency. Etiology of ovarian ectopic pregnancy still remains obscure. A study done by Goyal et. al concluded that incidence of ovarian pregnancy is 4.8% of all pregnancies.94% patients diagnosed inearly first trimester, 11% cases diagnosed preoperatively [4,5].Incidence Increases with ART procedures [due to increase progesterone from corpus luteum, ovarian hypervascularity due to hyperstimulation], PID, previous pelvic surgery, PCOD,fibroid uterus. IUCD is found in 15-32% of patients of non ovarian ectopic pregnancy and 60-92% of patient of ovarian ectopic pregnancy. Grimes et. al studied 24 cases of ovarian pregnancy & concluded that ≥ 50% cases had infertility orhistory of failed ART[5,6].
Cigarette smoking interferes with tubal motility and ovum pickup. There is usually delay in diagnosis because of Gestation sac of ovarian ectopic pregnancy in ultrasound mimics to haemorrhagic cyst of ovary, corpusluteal cyst and endometrioma of ovary. Diagnosis confirmed by TVS and CT scan. Ovarian pregnancy carries higher risk of morbidity and mortality then tubal pregnancies because ovarian pregnancy located at the most vascularised site of female pelvis. Uterine artery and ovarian anastomosis of blood vessels eroded by developing chorionic villi, that leads to severe haemorrhage and patientmay went into haemorrhagicshock[7,8].
Ovarian ectopic pregnancies diagnosed intra operatively & histo-pathologically except few exceptions according to Spielberg criteria. Ovarian ectopic pregnancy should be differentiated from ampullary /infundibulam tubal pregnancy, in these cases ovaries may involve secondarily after tubal abortion or rupture[9].
Criteria includes:
1. Gestation sac should occupy the normal position of the ovary.
2. Gestation sac and uterus connected with each other by utero-ovarian ligament.
3. Affected side fallopian tube with its fimbria should be intact and separate from ovary.
4. Ovarian tissue (tunica albugenia) must be present in the specimen or in the wall of gestational sac.
5. Empty uterine cavity and evidence of amniotic cavity within follicle.
3D ultrasound (TVS) help to differentiate from haemorrhagic corpus luteal cyst (8).Diagnostic features of ovarian pregnancy are-.
Sensitivity is 85%-92% and specificity is 99.98%
1. Double echogenic ring found within hypoechoic latero-uterine mass & echogenicity of ring is more than ovary itself (inhomogenous mass). Wide echogenic ring with an internal echolucent areas on superficial ovarian surface are also found.
2. Gestational sac found adjacent to the ovary.
3. All around mass follicles & corpus luteum is present as a part of ovarian cortex.
4. Empty uterine cavity & free fluid in peritoneal cavity(mild fluid in pod is physiological)
5. Ovarian ectopic pregnancywill move with ovary on pressure applied with transvaginal probe.
Gestation sac visualized by trans- abdominal scan at β-hCG discriminatory zone ≥6500miu/ml in 1981.Discriminatory zone for Transvaginal ultrasound upto 1000 to 2000 miu/ml
Com shock et. al studied ultra sonographic appearance of ovarian ectopic pregnancy and they concluded ovarian pregnancy is rarely identified correctlyby sonography andit is even very difficult to diagnose intra operatively.[9,10].
Heterotopic pregnancy is Ectopic pregnancy coexist with an intrauterine pregnancy but it is very rare with incidence 1/40000, diagnosis is very difficult. It is common with assisted conception.
Benauereaf et. al suggested that transducer frequency from 7MHZ to 10MHZ is help fulin improving diagnostic accuracy[10] ovarian ectopic pregnancy classified into two types –
1. Intra follicular pregnancy-In this ovum trapped inside the follicle, mature ovum not picked up or expelled from its follicle. Sperm fertilize the egg after entering into follicle various theories are given for explanation
Hormonal causes
Thickened tunica albugenia of the ovary
Defect in ovum pick up due to inadequate fimbria on ovarian surface
2. Extra follicular pregnancy-mature ovum fertilized outside of ovary, implant on ovarian surface because of endometrial decidual reaction.
Few hypotheses suggested inflammatory thickened tunica albugenia and malfunctioning of tubes, interference of release of mature ovum from follicle. The sign and symptom of primary ovarian pregnancy are very similar to tubal ectopic pregnancy. Very difficult to differentiate clinically from chocolate cyst, haemorrhagiccyst, tubal pregnancy.
Tropho blastic cells invade the ovarian tissue on6thday, followed by the invasion of the ovarian artery. Although ovarian pregnancies rupture by the 40th gestational day, reports of those progressing into the 3rd trimester even to live births have been established.
Most of primary ectopic pregnancy usually ruptured in first trimester of pregnancy. Recurrent ectopic pregnancy is not reported yet, in contrast to tubal pregnancy, 15% recurrence noted in primigravida patients. A study done by Savita et al. according to them out of 104 patients only 94patients had ectopic proved by histopathology and remaining had either haemorrhagic cyst or corpus lutealhematoma. out of 94 patients only four had ovarian pregnancy who fulfilled spigelberg criteria. Future fertility after surgery is unaffected [10].
Our retrospective cross – sectional study on ovarian pregnancies at NIMS Medical college & hospital Jaipur, we studied risk factor, incidence, diagnosis and management of ovarian pregnancy.
Table No-1: Risk factor for ovarian pregnancy
|
S.No. |
Age |
POG-weeks |
O/H |
Past
history |
USG
finding |
Management |
|
1 |
20 |
9 wk |
G4P2L2A1 |
IUCD-3yr |
FF in POD |
Excision
of sac& B/L salpingectomy |
|
2 |
23 |
- |
G1 |
1*infertility |
FF in POD |
Excision
of sac& B/L salpingectomy |
|
3 |
24 |
7wk |
G5P2L2A2 |
IUCD-2yr |
Βhcg-2000 |
Excision
of sac& B/L salpingectomy |
|
4 |
25 |
Nil |
P3L3 |
IUCD-5yr |
4×4cm,adnexal |
Rt
oopherectomy |
|
5 |
24 |
34wk |
G4P3L2 |
MTP |
Placenta previa |
Laprotomy
with Exicion of placenta delivery of baby and oophorectomy |
|
6 |
33 |
9wk |
G3P1L1A1 |
-- |
FF
in POD,βhcg-1800 |
Excision
of sac ,repair |
|
7 |
24 |
8wk |
G2A1 |
-- |
Lt
adnexal mass,FF + |
Lt
oophorectomy |
|
8 |
35 |
7wk |
G4P2L3 |
IUCD-4yr |
Ltovarian G. Sac,βhcg-2000 |
Excision
of sac |
|
9 |
24 |
8wk |
G1 |
Infertility |
FF in POD |
Excision
of sac |
|
10 |
31 |
Nil |
P3L3 |
-- |
Rt adnexal mass βhcg-3000 |
Excision
of sac & repair |
A study done by Savita et al concluded out of 4 patient 3 patient had history ofrisk factor like IUCD was present[11].
Management- Expectant Management-Success rate is 48%-100%.
Inclusion criteria –
• Asymptomatic women with stable vitals
• Β-hCG<1000miu/ml
• Ultrasound findings –Size ≤ 2cm and GA < 6 weeks, Cardiac activity absent,YoIk sac and fetal polealso absent, Free fluid in pouch of douglas<100CC.
• Serum progesterone level <3.1 ng/ml
• Cooperative patient willing for follow up
These patients followed twice weeklyon Day 3,7.
If β-hcg fall >50%within a week, continue expectant management
If β-hcg fall <50%within a week, consider medical /surgical management.
It is most useful when initial β-hC Glevel is ≤1000 iu/l with un ruptured ectopic pregnancy. Success rate is between 50-80%.According to one prospective observational study, in which 118 patients are on expectant management out of them 88% recovered successfully. They hadβ-hCG ≤ 200 mIU/mL and patients with β-hCG level≥ 2000 mIU/ml only 26% recovered. Favourable factors for success of expectant management areserum β-hCG level≤200, gestational age ≤ 6 weeks & progesterone level below 10 nmol/L.
Expectant management to be stop pedif the patient is having if the β-hCG level increases or Persistently increasing abdominal pain. To avoid rupture of ectopic pregnancy, avoid vigorous physical activity sexual activity & pelvic examination.
Medical Management- Mittal et. al first time used injection methotrexate directly into gestational sac of ovary[12]. Kudo et. Al reported first successful use of methotrexate in ovarian pregnancy [13].
Gabbur et al. Done a retrospective analysis on MTX use in unruptured ovarian ectopicand concluded that after single MTX injection on D7 β-hcg levels only, predict a need of surgery or successful treatment not Day 4 β hcg level[13,14] Patient selection is very important. Methotrexate is antagonist of folic acid that impairs cellreplication & DNA synthesis. In 1982, Methotrexate first time used for medical management and its mode of action iskill rapidly dividing cytotrophoblasts cells at the site of implantation[15].
Table No-2: Contraindication of Methotrexate treatment in ectopic pregnancy
|
Absolute |
Relative |
|
i.
Hypersensitivity ii.
Thrombocytopenia(<
1 lac/µl) iii.
Liver dysfunction
> 2 fold.Alcoholic liver disorders. iv.
Pulmonary and peptic
ulcer disease v.
Hematological
dysfunction with bone marrowdepression. TLC < 1500/µl vi.
Heterotopic pregnancy vii.
Ruptured ectopic
pregnancy viii.
Lactating mothers ix.
Moderate to severe
anemia creatinine clearance < 50 mL per minute per 1.73 m2 |
i.
Β-hCG>5000miu/ml ii. Ectopic mass > 4 cm iii. Fetal
cardiac activity present iv. Poor
complaint patient |
Patient should instruct to stop taking prenatal vitamins, Alcohol, non steroidal anti-inflammatory drugs& avoid excessive sunlight(to avoid MTX induced dermatitis) and folate supplementation, as folate will counteract action of injection methotrexate. Rh status of patient must be known to determine further need of immunoglobin the rapyin Rh negative patient. A meta-analysis on single and multiple dose regimens done by Barnhart et al. They concluded multidose regimen is more effective (90%) then single dose (80%)[13,14,15].
If β hCG is ≥ 5000 treatment failure rate is 40%. If 15% decrease occurs b/w Day 4 and Day 7, β-hCG level smonitored weekly tillreach zero. This will take at least five to seven weeks.
Levin et al. done astudy and concluded, out of 69 women of study group 45 patient was treated successfully with single dose of injection methotrexate[13].
Predictors of successful medical treatment before single dose of methotrexate good are-
If β-hCG level≤ 1600 iu/landincrease ≤14% , in a day or 24 hr.
Single dose regimen associated with least side effects.
Table No-3: Single dose of methotreaxate treatment protocol
|
|
0 |
4 |
7 |
|
1. Investigations 2. Medical
management |
Βhcg CBC ABOrh LFT RFT Methotreaxate in dose of 50mg/m2 of
body surface area is given by IM route |
Βhcg Methotreaxate in dose of 50mg/m2 of
body surface area is given by IM route |
Βhcg i.
If Decrease in βhcg
>15% between from day 4 to day 7. Monitor βhcg weekly till zero. ii.
If βhcg decrease<
15%between day 4 to day 7 give methotreaxate |
Two dose regimes of methotrexate of ectopic pregnancy-
Bran hart was only one whofirst described Double dose regimen. Hossam et al concluded that double dose protocol is better than single dose regimen [16,17].
Table No-4: Multiple dose of methotreaxate treatment protocol
|
|
0 |
4 |
7 |
11 |
14 |
|
Investigation Medical management |
CBC Abo, Rh LFT RFT βhcg Methotreaxate
in dose of 50mg/m2 of body surface area is given by IM route. |
Βhcg Methotreaxate in dose
of 50mg/m2 of body surface area is given by IM route. |
Βhcg If
Decrease in βhcg >15% between from day 4 to day 7. Moniter βhcg weekly till
zero. If
βhcg decrease< 15%between day 4 to day 7.give methotreaxate. |
Βhcg If
Decrease in βhcg >15% between from day 7 to day 11. Moniter βhcg weekly
till zero. If
βhcg decrease<15%between day 7 to day 11.give methotreaxate |
Βhcg If
Decrease in βhcg >15% between from day 11 to day 14. Moniter βhcg weekly
till zero. If
βhcg decrease< 15%between day 11 to day 14 Refer to surgery |
Multiple dose regime of methotrexate in ectopic pregnancy-Krik et al concluded that multiple dose regimen is more effective then single and double dose protocol with sensitivity 94%, specificity 86% [1,17,18].Success rate of treatment with β- hCG ≤1000miu/ml is 87%.Failure rate is 40 % with level ≥5000miu/ml.
Surgical Management- Primary management of Ovarian ectopic pregnancy is surgical. According to 3 prospective randomized trial laparoscopic approach is superior then laparotomy in view of less blood loss & pain, shorter hospital stays and there is no significant difference in recurrence, subsequent intrauterine pregnancy[18,19].
Laparoscopic surgery has become preferred method & gold standard nowdays.Conservative surgical technique like ovarian wedge resection, nucleation are also in trend now days.
80% cases managedby conservative management and radical oophorectomy done in 13% cases only. John et al. Was performed first laparotomy for ovarian ctopic pregnancy in 1759.In 1884Robert et al. Ligated bleeding blood vessels first time during laparotomy [4]. Shapiro and Adler introducedfirst time a laparoscopic approach in 1973[20,21].According to Cochrane review 2007, there is no significant difference b/w systematic methotrexate and conservative surgery if β -hCG level ≤1500miu/ml
Corpus lutealcystectomy for tropho blast, curettage of trophoblast by coagulation and hemostatic suture of the bed.These are totally conservative surgeries. In case of advanced ectopic pregnancy oophorectomy or ovariectomy [22,23,24].Recurrence of ovarian pregnancy in literature till now. Only single case reported has been reported in contrast to tubal ectopic pregnancy recurrence rate isup to 15 %[25-30].
Conclusion and Perspective- According to Spielberg criteria, it is a diagnostic challenge to obstetrician. diagnosis can be missed radiologically, intra operatively. Ovarian pregnancy can occur evenin Nulliparous female without risk factors like IUCD,PID, ART. Now days Medical management with single dose of Methotrexate is very successful for unruptured ovarian pregnancy.
Should be suspected in patients presented with ruptured ectopic pregnancy, ultrasound features suggestive of normal fallopian tube with hemoperitoneum with breached ovarian surface. Conservative surgical approach is preferred. Confirmation of ovarian pregnancy done only after histo-pathologicalreport.
Conflict of Interest: Not declared, Funding: Nil
Source of supply: Nil
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How to cite this article?
Meena P., Bhojwani P, Verma G. S. Ovarian ectopic pregnancy:a review article. Obg Rev:J obstet Gynecol 2017;3(4):68- 75.doi:10.17511/jobg.2017.i4.06.