Postgraduate Training Course in Reproductive Health 2004

Worldwide incidence of ectopic pregnancy
A protocol for a systematic review

Dr. Esra Esim Buyukbayrak
Kartal Education and Research Hospital
Istanbul, Turkey

See also presentation

Background

Ectopic pregnancy (EP) is defined as a pregnancy in which the implantation of the fertilized egg occurs outside the uterine cavity, most frequently in the fallopian tube. Ectopic pregnancy presents as an acute emergency and a life-threatening event, accounting for up to 10% of all maternal deaths (1). This condition could be considered a public health indicator in developing countries, providing an overall picture of the capacity of a health system to deal with the diagnosis and treatment of emergency situations.
Although advances in early diagnosis have led to decreased mortality rates and conservative laparoscopic treatments have enabled improved outcomes, EP remains a leading cause of maternal mortality and accounts for a sizeable proportion of infertility and ectopic recurrence, so its immediate and delayed sequela must not be underestimated. Ectopic pregnancy is responsible for thousands of hospital admissions, surgical interventions and blood transfusions. Moreover, in developing countries, where transport facilities are poor, diagnosis and interventions are delayed, the majority of patients are diagnosed after rupture and morbidity, transfusion requirements and time of hospital stay are increased.
The main risk factors associated with EP are previous EP, previous tubal surgery, documented tubal pathology, in utero diethylstilbestrol (DES) exposure, previous genital infections (pelvic inflammatory disease (PID), chlamydia, gonorrhoea), infertility, smoking, current intrauterine device use and more than one lifetime sexual partners (2). Ectopic pregnancy is a well-known risk of in vitro fertilisation (IVF). Patients who undergo IVF often have a number of underlying factors, like previous tubal surgery or PID, and are also at high risk for EP after natural conception. The proportion of EP after IVF ranges from 4% to 11% of pregnancies (3). As the number of IVF attempts steadily rises throughout the world, all centres are confronted with the problem of diagnosis, treatment and prevention of EP.
Reported incidence of EP varies widely between developed and developing countries. A review by Liskin suggested an increase in incidence of EP from 1960s until the middle of 1980s. This review pointed at the highest EP incidence rates in African countries (0.5-2.3% of live births) whereas low incidence rates were reported in Asia and Middle East during the same time period (0.4-0.6% of live births) (4). Incidence of EP in England-Wales is reported as 12.4 per 1000 reported pregnancies between 1994-1996(5). Incidence of EP in Beijing-China is reported as 0.50 per 1000 women of reproductive age (6). Whereas in Nigeria incidence of EP is reported as 1.7% of total births and in Ghana incidence of EP is reported as 4%(7). It has been estimated that in the United States, about 40 women die annually as a result of EP, about 0.8 deaths per 1000 cases. Moreover, this relative risk of death is 10 times the risk of death from childbirth and 50 times the risk of legally induced abortion (8).
Due to individual definitions of the denominator reported, the incidence of EP has been expressed in various ways (e.g. per reported pregnancies, deliveries, women aged 15-44 years, live births) that result in widely differing estimates which are difficult to compare. Underestimation of EP rate can result from the sizeable percentage of spontaneous abortions or chemical pregnancies that may actually represent self-resolving extrauterine gestations. Overestimation of EP rate can result from high rate of pregnancies illegally terminated and unreported. The best denominator for comparing the public health impact of EP involves a given population’s fixed subset of reproductive-aged women because this constant denominator remains the same and is unaffected by fluctuations in spontaneous or induced abortions (5). But this requires population based studies which are not always easy to conduct.
The global incidence of EP is difficult to determine because of variation in availability of medical surveillance resources. In developing countries, maternal deaths are frequently underreported, resulting in the omission of numerous patients who died before receiving any treatment, including those who died due to EP. For maternal deaths associated with EP particularly, if women did not undergo surgery, the principal risk of confusion is misclassification as an induced abortion. Another problem is that, many reports have been based upon samples not representative of the population from which they are drawn and thus it has been difficult to determine the true incidence of EP in a general population.
Epidemiological studies of the incidence of EP provide estimates of the burden of this condition that are vital in informing and planning of public health policies and medical care. The information is dispersed widely in the literature and comparisons are difficult to make. For this reason, we will conduct a systematic review to summarise all available information on the prevalence and incidence of ectopic pregnancy.

Objective

To determine an updated information on the worldwide prevalence and incidence of ectopic pregnancy.

Methodology

Study Design

Any study design providing prevalence or incidence rates for EP in any population will be assessed. Ectopic pregnancy is diagnosed either clinically, by laboratory examination or self-reported.

Selection Criteria

/Inclusion criteria: studies that report incidence/prevalence of ectopic pregnancies, irrespective of the language, and published from 1997 to 2002.
Exclusion criteria: studies with no data, studies with fewer than a total of 200 participants, studies without any source of data that can be tracked, reports referring to data collected from before 1990 and studies where no dates for data collection periods are provided.

Type of participants

Women who are pregnant or within 42 days of termination of pregnancy or women of reproductive age.

Type of outcome

Ectopic pregnancy.

Search strategy

All relevant studies, irrespective of language, published from 1997 to 2002 will be included by; electronic databases will be searched (Medline, Popline, CAB Abstracts, Sociofile, CINAHL, Econlit, EMBASE, BIOSIS, PAIS International, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effectiveness, Cochrane Controlled Trials Register and regional WHO online databases); other electronic searches (existing web pages from ministries of health in all countries and other internet search including google with the term 'maternal mortality'); hand and reference lists searching personal contacts and specific strategies.

Description of studies

A table with the characteristics of the included studies will be prepared containing the methods, participants and outcomes studied. This table will show the studies listed chronologically by year of publication. Within each year, the order will be alphabetically by country and within each country, the order will be alphabetically by first author.

Methods of the review

Reference manager bibliographic software will be used to store the studies identified and reports retrieved from other sources will be entered. A screening form will be designed and all identified studies will be evaluated according to the criteria on the screening form initially by titles and abstracts. Articles that pass this stage will be evaluated as full text. A data extraction form will be developed and completed for included studies. A second reviewer will be available for discussion when data cannot be extracted by the first reviewer. Data extraction form will be designed so that the differences in the study characteristics regarding the study designs, sampling, characteristics of the population studied and of setting can be discerned.

References

1. Kamwendo F, Forslin L, Bodin L, Danielsson D. Epidemiology of ectopic pregnancy during a 28 year period and the role of pelvic inflammatory disease. Sex Transm Infect. 2000 Feb;76(1):28-32.[PubMed]
2. Ankum W, Mol BW, Van der Veen F, Bossuyt P. Risk factors for ectopic pregnancy: a meta-analysis.Fertil Steril. 1996 Jun;65(6):1093-9.[PubMed]
3. Dubuisson JB, Aubriot FX, Mathieu L, Foulot H, Mandelbrot L, de Joliere JB. Risk factors for ectopic pregnancy in 556 pregnancies after in vitro fertilization: implications for preventive management. Fertil Steril. 1991 Oct;56(4):686-90. [PubMed]
4. Goyaux N, Leke R, Keita N, Thonneau P. Ectopic pregnancy in African developing countries. Acta Obstet Gynecol Scand. 2003 Apr;82(4):305-12.[PubMed]
5. Rajkhowa M, Glass MR, Rutherford AJ, Balen AH, Sharma V, Cuckle HS. Trends in the incidence of ectopic pregnancy in England and Wales from 1966 to 1996. BJOG. 2000 Mar;107(3):369-74. [PubMed]
6. Zhang Z, Weng L, Zhang Z, Jin X, Jing X, Zhang L, Lian S, Cui Y. An epidemiological study on the relationship of ectopic pregnancy and the use of contraceptives in Beijing--the incidence of ectopic pregnancy in the Beijing area. Beijing Collaborating Study Group for Ectopic Pregnancy. [PubMed]
7. Gharoro EP, Igbafe AA. Ectopic pregnancy revisited in Benin City, Nigeria: analysis of 152 cases. Acta Obstet Gynecol Scand. 2002 Dec;81(12):1139-43. [PubMed]
8. Doyle MB, DeCherney AH, Diamond MP. Epidemiology and etiology of ectopic pregnancy. Obstet Gynecol Clin North Am. 1991 Mar;18(1):1-17.[PubMed]