Ovarian ectopic pregnancy: a review article

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 2 most common site of ectopic pregnancy after fallopian tube. Annual incidence of extra uterine cavity pregnancy is rising over past 3 yrs. The aim of our present study isto find outthe incidence of ovarian ectopic pregnancy, role of USG in pre-operative diagnosis and 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 andclinical presentation of ovarian ectopic pregnancies managed at NIMS Medical College and Hospital jaipur. According to Spielbergcriteria, it is a diagnostic challenge to obstetrician. Diagnosis of ectopic pregnancy can be missed radio logically and intraoperatively. 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 days Medical management with single dose of Methotrexate is very successful for unruptured ovarian pregnancy KeywordsEctopic pregnancy, Laparotomy, Salpingoophorectomy, Methotrexate ......................................................................................................................................................................................................... Introduction The Incidence of ectopic pregnancy is 1.2-1.4%. Incidence of primary ovarian ectopic pregnancy is, as mentioned in literature of Indiais 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 2 most common site of ectopic pregnancy after fallopian tube [1]. Extra uterine pregnancy or ectopic ovarian pregnancy a Greek word originated from “EKTOPOS” which means out of place. Ectopic refer toimplantation of blasto cyst outside of uterine cavity [1]. Primary ovarian ectopic pregnancy is very rare clinical presentation of extra uterine pregnancy & a life threatening emergency also if not diagnosed timely. Fallopian tube is most common site of ectopic pregnancy, comprises to 95% of total ectopic pregnancies. Incidence increasing with ART proceduresand IUCD insertion. Ovarian pregnancy is gestational sac implantation in the ovary. First case of Manuscript received: 08 December 2017 Reviewed: 14 December 2017 Author Corrected: 20 December 2017 Accepted for Publication: 31 December 2017 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, 12.5% patients terminate in the second trimester & 12.5 % patients reached till term. Ovarian pregnancyin 1624, suggested first by Mercerus[3,4]. Incidence of ectopic pregnancy is1. Tubal pregnancy90-95.5% 2. Ovary-1.53% 3. Abdomen-1.3% 4. Cervical -0.15% 5. Heterotopic 1-2% 6. Caesarean -6% 7. Interstitial -2.5% October December, 2017/ Vol 3/ Issue 4 Print ISSN: 2581-4389, Online ISSN: 2455-5444 Review Article Obsgyne Review: Journal of Obstetrics and Gynecology Available online at : www.medresearch.in 64 | P a g e Case Report A 28 years old female, presented with 6 weeks 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/Aexamination soft distension was present and tenderness presentin RIF. P/V examination revealed – uterusmobile 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 , 2.8x2.8cm 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 pregnancywas 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 redcolor with oozing frombreached ovarian surface. Right salpingo oophorectomy done and Left fallopian tubal ligation done by modified pomeroys 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 October December, 2017/ Vol 3/ Issue 4 Print ISSN: 2581-4389, Online ISSN: 2455-5444 Review Article Obsgyne Review: Journal of Obstetrics and Gynecology Available online at : www.medresearch.in 65 | P a g e 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, D19undetectable. Discussion and Review of LiteratureClinical presentation of ovarian ectopic pregnancy is variable and it is a lifethreatening 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 1532% 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 haemorrhagic shock [7,8]. Ovarian ectopic pregnancies diagnosed intraoperatively & histo-pathologically except few exceptions according to Spielbergcriteria. 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 andseparate 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 (in homogenous mass). Wide echogenic ring with an internalecholucent 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 visualizedby 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 ultrasonographic appearance of ovarian ectopic pregnancy and they concluded ovarian pregnancyis rarely identified correctlyby sonographyandit is evenvery difficultto diagnose intra operatively. [9,10]. Heterotopic pregnancyis 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 helpfulin improving diagnostic accuracy[10] ovarianectopic pregnancy classifiedinto two types – October December, 2017/ Vol 3/ Issue 4 Print ISSN: 2581-4389, Online ISSN: 2455-5444 Review Article Obsgyne Review: Journal of Obstetrics and Gynecology Available online at : www.medresearch.in 66 | P a g e 1. Intrafollicular pregnancyIn this ovum trapped inside the follicle, mature ovum not picked up or expelled from its follicle. Sperm fertilizethe 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. Trophoblastic cells invade theovarian tissue on 6 day, followed by the invasion of the ovarian artery. Although ovarian pregnancies rupture by the 40 gestational day, reports of those progressing into the 3 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 totubal pregnancy, 15% recurrence noted in primigravida patients. A study done by Savita et al. according to them out of 104 patients only 94 patients had ectopic proved by histopathology and remaininghad either haemorrhagic cyst or corpus lutealhematoma.out of 94 patients only four hadovarian pregnancy who fulfilled spigelberg criteria. Future fertility after surgery is unaffected [10]. Ourretrospectivecross – sectional study onovarian pregnancies at NIMSMedical college &hospitalJaipur, westudied 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,βhcg1800 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]. ManagementExpectant ManagementSuccess rate is 48%-100%. October December, 2017/ Vol 3/ Issue 4 Print ISSN: 2581-4389, Online ISSN: 2455-5444 Review Article Obsgyne Review: Journal of Obstetrics and Gynecology Available online at : www.medresearch.in 67 | P a g e 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 ofdouglas<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 expectantmanagement If β-hcg fall <50%within a week,consider medical /surgical management. It is most useful when initial β-hCGlevel is ≤1000 iu/l with unruptured 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 had β-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 stoppedif the patient is having if the β-hCG level increases or Persistently increasing abdominal pain. To avoid rupture of ectopic pregnancy, avoidvigorous physical activity sexual activity & pelvic examination. Medical ManagementMittal 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 injectionon D7 β-hcg levels only, predict aneed 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 andits 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 m 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, nonsteroidal 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 therapy in Rh negative patient. A meta-analysison 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 levelsmonitored weekly tillreach zero. Thiswill takeat leastfive to sevenweeks. October December, 2017/ Vol 3/ Issue 4 Print ISSN: 2581-4389, Online ISSN: 2455-5444 Review Article Obsgyne Review: Journal of Obstetrics and Gynecology Available online at : www.medresearch.in 68 | P a g e Levin et al.done astudy and concluded,out of 69 women of study group 45 patient was treated successfully withsingle dose of injection methotrexate [13]. Predictors of successfulmedical treatmentbefore single dose of methotrexategood areIf β-hCG level≤ 1600 iu/landincrease ≤14% , in a day or 24 hr. Single dose regimen associatedwith 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/m of body surface area is given by IM route Βhcg Methotreaxate in dose of 50mg/m 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 pregnancyBranhart was only one who first 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/m of body surface area is given by IM route. Βhcg Methotreaxate in dose of 50mg/m 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 pregnancyKrik 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 βhCG ≤1000miu/ml is 87%. Failure rate is 40% with level ≥5000miu/ml. October December, 2017/ Vol 3/ Issue 4 Print ISSN: 2581-4389, Online ISSN: 2455-5444 Review Article Obsgyne Review: Journal of Obstetrics and Gynecology Available online at : www.medresearch.in 69 | P a g e Surgical ManagementPrimary 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 1884 Robert 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 surgeryif β -hCG level ≤1500miu/ml Corpus lutealcystectomy for trophoblast, 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 ofovarian 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 PerspectiveAccording to Spielbergcriteria, it is a diagnostic challenge to obstetrician. diagnosis can be missed radiologically, intraoperatively. Ovarian pregnancy canoccur even in 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. Funding: Nil, Conflict of interest: Nil Permission from IRB: Yes References 1. Joseph RJ, Irvine LM. Ovarian ectopic pregnancy: aetiology, diagnosis, and challenges in surgical management. J Obstet Gynaecol. 2012 Jul; 32 (5):472-4. doi: 10.3109/01443615.2012.673039. 2. Mehmood SA, Thomas JA. Primary ectopic ovarian pregnancy (report of three cases). J Postgrad Med 1985; 31: 219. 3. Rana P, Kazmi I, Singh R, Afzal M, Al-Abbasi FA, Aseeri A, Singh R, Khan R, Anwar F. Ectopic pregnancy: a review. Arch Gynecol Obstet. 2013 Oct; 288 (4): 74757. doi:10. 1007 /s00404 -013-2929-2. Epub 2013 Jun 21. 4. Krik E, Bourne T . Ectopic pregnancy. Obstet gynecol Reprod Med 2011;21(7):207-211,2011. 5. Goyal Lajya Devi, Tondon Rimpy, Goel Poonam and Sehgal Alka. Ovarian ectopic pregnancy: A 10 years’ experience and review of literature. Iran J Reprod Med. 2014 December; 12(12): 825–830. 6. Fritz MA, Speroff L. Clinical gynecologic endocrinology and infertility, 8th edn. Wolters Kluwer Health/ Lippincott Williams & Wilkins, Philadelphia. 2011. 7. Hallatt JG. Primary ovarian pregnancy: a report of twenty-five cases. Am J Obstet Gynecol. 1982;143:55–60. PMID: 7081312.doi.org/10.1016/0002-9378(90)90685-Z. 8. Panelli Danielle M , H. Phillips Catherine , Brady Paula C. Incidence, diagnosis and management of tubal and nontubal ectopic pregnancies: a review. Fertility Research and Practice 2015; 1:15,2015. DOI:10.1186/s40738-0150008. 9. Vanitha N Sivalingam,W Colin Duncan; Emma Kirk, Lucy A Shephard, Andrew W Horne. Diagnosis and Management of Ectopic Pregnancy. J Fam Plann Reprod Health Care. 2011; 37(4): 231-240,2011. doi:10.1136/ jfprhc2011-0073. 10. Comstock C, Huston K, Lee W. The ultra sonographic appearance of ovarianectopic pregnancies. Obstet Gynecol. 2005 Jan;105(1):42-5. 11. Chang FW, Chen CH, Liu JY. Early diagnosis of ovarian pregnancy by ultrasound. Int J Gynecol Obstet. 2004; 85:186–187. 12. Juan YC, Wang PH, Chen CH, Ma PC, Liu WM. Successful treatment of ovarian pregnancy with laparoscopy-assisted local injection of etoposide. Fertil Steril . 2008;90:1200 October December, 2017/ Vol 3/ Issue 4 Print ISSN: 2581-4389, Online ISSN: 2455-5444 Review Article Obsgyne Review: Journal of Obstetrics and Gynecology Available online at : www.medresearch.in 70 | P a g e 13. Mittal S, Dadhwal V, Baurasi P. Successful medical management of ovarian pregnancy. Int J Gynecol Obstet. 2003;80:309–310. 14. Buster JE, Carson SA. Ectopic pregnancy: newadvances in diagnosis and treatment. Curr Opin Obstet Gynecol. 1995 Jun;7(3):168-76. 15. Gabbur N, Sherer DM, Hellmann M . Do serum betahuman chorionic gonadotropin levels on day 4 following methotrexate treatment of patients with ectopic pregnancy predict successful single-dose therapy? Am J Perinatol. 2006. 23:193–196. 16. Barnhart KT, Gosman G, Ashby R, Sammel M. The medicalmanagement of ectopic pregnancy: a metaanalysis comparing "single dose" and "multidose" regimens. Obstet Gynecol. 2003 Apr;101(4):778-84. 17. Barnhart K, Hummel AC, Sammel MD, Menon S, Jain J, Chakhtoura N. Use of "2-dose" regimen of methotrexate to treat ectopic pregnancy. Fertil Steril. 2007 Feb;87(2):250-6. Epub 2006 Nov 13. 18. Hamed HO, Ahmed SR, Alghasham AA. Comparison of doubleand single-dosemethotrexateprotocols for treatment of ectopic pregnancy. Int J Gynaecol Obstet. 2012 Jan; 116(1):67-71. doi: 10.1016/j.ijgo.2011.08.009. Epub 2011 Oct 28. 19. Kirk E, Condous G, Van Calster B, Haider Z, Van Huffel S, Timmerman D, Bourne T. A validation of the most commonly used protocol to predict the success of single-dose methotrexate in the treatment of ectopic pregnancy. Hum Reprod. 2007 Mar;22(3):858-63. Epub 2006 Nov 6. 20. Bagga R, Suri V, Verma P, Chopra S, Kalra J. Failed Medical Management in Ovarian Pregnancy Despite Favorable Prognostic Factors-A Case Report. Med Gen Med. 2006;8:35.PMID:16926774. 21. Habbu J, Read MD. Ovarian pregnancy successfully treated with methotrexate. J Obstet Gynaecol. 2006 Aug;26(6):587-8. 22. Shapiro HI, Adler DH. Excision of an ectopic pregnancy through the laparoscope. Am J Obstet Gynecol. 1973;117:290-1. PMID: 4269637. 23. Ayakannu T, Rogers J, Wordsworth S, Jayagopal N, Vine S. Conservative laparoscopic approach with systemic medical management of an ovarianectopic gestation. J Obstet Gynaecol. 2007; 27:449–50. https:/ /doi. org/10. 1080/014436 10701360009. 24. Mittal S, Dadhwal V, Baurasi P. Successful medical management of ovarian pregnancy. Int J Gynaecol Obstet. 2003 Mar;80(3):309-10. 25. O. Birge, M. M. Erkan, E. G. Ozbey, and D. Arslan. Medical management of an ovarian ectopic pregnancy: a case report. Journal of Medical Case Reports. , 2015; vol. 9:1, article no. 774. 26. G. Scutiero, P. Di Gioia, A. Spada, and P. Greco. Primary ovarian pregnancy and its management,” Journal of the Society of Laparo-endoscopic Surgeons.2012 ; vol. 16:3,492–494. 27. Y. Koo, H. Choi, K. Im, H. Jung, and Y. Kwon. Pregnancy outcomes after surgical treatment of ovarian pregnancy. International Journal of Gynecology & Obstetrics.2011;vol. 114:,97–100,2011. 28. Chatburn Luke, Sanghani Reesha , Chatburn Luke, et al. An Alternative Treatment for the Ovarian Ectopic Pregnancy. J Womens Health Gyn. 2015; Vol2: 102. 29. Odejinmi F, Rizzuto MI, Macrae R, Olowu O, Hussain M. Diagnosis and laparoscopicmanagement of 12consecutivecases of ovarian pregnancy and review of literature. J Minim Invasive Gynecol. 2009 May-Jun;16 (3): 354-9. doi: 10.1016/j.jmig.2009.01.002. 30. Nadarajah S, Sim LN, Loh SF. Laparoscopic management of an ovarian pregnancy. Singapore Med J. 2002 Feb;43(2):095-6. .......................................... How to cite this article? Meena P., Bhojwani P, Verma G. S. Ovarian ectopic pregnancy:a review article. Obs Rev:J obstet Gynecol 2017;3(4):6370.doi:10.17511/joog.2017.i04.06. .........................................................................................................................................................................................................


Introduction
The Incidence of ectopic pregnancy is 1.2-1.4%. Incidence of primary ovarian ectopic pregnancy is, as mentioned in literature of Indiais 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 2 nd most common site of ectopic pregnancy after fallopian tube [1].
Extra uterine pregnancy or ectopic ovarian pregnancy a Greek word originated from "EKTOPOS" which means out of place. Ectopic refer toimplantation of blasto cyst outside of uterine cavity [1]. Primary ovarian ectopic pregnancy is very rare clinical presentation of extra uterine pregnancy & a life threatening emergency also if not diagnosed timely. Fallopian tube is most common site of ectopic pregnancy, comprises to 95% of total ectopic pregnancies.
Incidence increasing with ART proceduresand IUCD insertion. Ovarian pregnancy is gestational sac implantation in the ovary. First case of

Case Report
A 28 years old female, presented with 6 weeks 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/Aexamination -soft distension was present and tenderness presentin RIF. P/V examination revealed -uterusmobile 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 , 2.8x2.8cm 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 pregnancywas made & patient was prepared for laparotomy, her intra operative findings were- 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 lifethreatening 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 haemorrhagic shock [7,8].
Ovarian ectopic pregnancies diagnosed intraoperatively & histo-pathologically except few exceptions according to Spielbergcriteria. 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 andseparate 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.
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 (in homogenous mass). Wide echogenic ring with an internalecholucent 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.
Heterotopic pregnancyis 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 helpfulin improving diagnostic accuracy [10] ovarianectopic pregnancy classifiedinto two types -1. Intrafollicular pregnancy-In this ovum trapped inside the follicle, mature ovum not picked up or expelled from its follicle. Sperm fertilizethe 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.
Trophoblastic cells invade theovarian tissue on 6 th day, followed by the invasion of the ovarian artery. Although ovarian pregnancies rupture by the 40 th gestational day, reports of those progressing into the 3 rd 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 totubal pregnancy, 15% recurrence noted in primigravida patients. A study done by Savita et al. according to them out of 104 patients only 94 patients had ectopic proved by histopathology and remaininghad either haemorrhagic cyst or corpus lutealhematoma.out of 94 patients only four hadovarian pregnancy who fulfilled spigelberg criteria. Future fertility after surgery is unaffected [10].

Review Article
Obsgyne Review: Journal of Obstetrics and Gynecology Available online at : www.medresearch.in
It is most useful when initial β-hCGlevel is ≤1000 iu/l with unruptured 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 had β-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 stoppedif the patient is having if the β-hCG level increases or Persistently increasing abdominal pain. To avoid rupture of ectopic pregnancy, avoidvigorous 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 injectionon D7 β-hcg levels only, predict aneed 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 andits mode of action iskill rapidly dividing cytotrophoblasts cells at the site of implantation [15].  [13].