The 100 most cited articles in ectopic pregnancy: a bibliometric analysis

Ectopic pregnancy (EP) remains a major gynecological emergency and is a cause of morbidity or even mortality in women. As a consequence, top citation analysis of EP research in database of the Science Citation Index Expanded is needed to assess the publication trends of leading countries/territories and institutes as well as the research hotspots of EP. A total of 4881 articles relevant to EP were retrieved in the database of the Science Citation Index Expanded from 1965 to present, in which the 100 top-cited articles were selected for further analysis. The number of citations ranged from 81 to 482 (131.57 ± 69.76), with a time span of 40 years between 1969 and 2009. These citation classics came from 14 countries, and 65 of the articles came from the United States. Yale University in Connecticut led the list of classics with six papers. The 100 top-cited articles were published in 32 journals, in which the journal of Fertility and Sterility published the most (23 papers). Stovall TG and Ling FW published the highest number of studies (6 papers each). Articles that originated in the United States and that were published in high-impact journals were most likely to be cited in the field of EP research. Bibliometric analysis was used to provide a historical perspective on the progress in EP research over the past 50 years. Citation analysis is a feasible tool to comprehensively recognize the advances of EP research in the past and future research.


Background
Ectopic pregnancy (EP), which is the implantation of a fertilized ovum outside the endometrial cavity and has an approximate incidence of 1.5-2.0 % in all pregnancies, is a potentially life-threatening disease (Chang et al. 2003). With increasing in vitro fertilization (IVF) procedures, there is an increase of Eps (Ramer et al. 2016;Sisti et al. 2016). Currently, it remains a major problem in contemporary gynecological practice and continues to be an important cause of morbidity and mortality in women. EP is also a clinical manifestation of poor fertility prognosis and adverse outcomes in subsequent pregnancies (Musa et al. 2009). Although oviduct inflammation, the history of tubal pregnancy and tubal surgery, the application of assisted reproductive technology (ART) and so on are known as the pathogenesis of EP by now. However, the definite mechanism of it is still missing. Therefore, many specialists and researchers have focused their efforts on EP to gain a better understanding of the mechanism of this disease and develop new methods for the diagnosis and treatment of this issue.
Citation is an author's reference to a previous work that acknowledges the relevance of that work in contributing to the completion of the author's current paper (Kavanagh et al. 2013). While number of citations is not the only factor in determining an article's relevance, it is arguably our best marker for articles that have been influential in the field (Baldwin et al. 2013). Citation analysis involves ranking and evaluating an article or journal based on the frequency of citation that it receives (Murray et al. 2012). The frequency of citation has significant implications for authors, journals, institutions and even nations (Moed 2009). Citation analysis is the bibliometric process that is used to examine the citation history of a particular paper by examining the citations attributed to that publication. Usually, it involves ranking and evaluating an article or journal based on the number of citations that it has received.
To systematically review the citation classics dedicated to EP, we evaluated the current literature for the 100 most frequently cited articles in an attempt to provide a bibliometric perspective of the progress in this field. To our knowledge, this is the first study to quantify and analyze the most frequently cited papers to review the history of EP.

Methods
The database (Web of Science Expanded citation index) of the Institute for Scientific Information (ISI) from 1965 to 2015 was searched using the keyword "ectopic pregnanc*" to identify the citation classics. This database includes peer-reviewed publications indexed from more than 10,000 high-impact journals worldwide. Only papers that had been published as an "article" were selected for further study and no language restriction criteria was applied in our study. Each article in the top 100 cited list was reviewed, and the information including number of citations, authorship, journals, institution and country of origin, and year of publication was retrieved. Country of origin was defined based on the first author's address. The addresses of other authors were noted to determine whether international collaboration was involved.

Results
The 100 most frequently cited articles related to EP were identified using Science Citation Index Expanded (SCIexpanded). A total of 6872 papers were identified in the period from 1965 to 2015, with 4881 classified as "article", 384 classified as "review", 499 classified as "letter", 245 classified as "proceeding paper", 410 classified as "meeting abstract"; the remaining were classified as "other". The selection process of the articles is shown in Fig. 1, and the top 100 cited articles composing our final list are shown in Table 1. By reading the abstract or full text of the original 100 most cited articles, a total of 15 articles like the 15th paper written by Gaydos et al. (1998) and the 25th one contributed by Conway et al. (1997) were eliminated because of its minor relevance to EP.
The most cited paper was contributed by Kalman et al. (1999) with 482 citations, whereas the 100th paper by Chegini and Flanders (1992) was cited 86 times. The mean number of citations was 132 (SD 69.76). The oldest citation classic on the list was ranked at position 62 and was published in 1969 by Kobayashi et al. (1969) (96 citations), and the most recent paper was at position 82 and was published in 2009 (88 citations) by Schumacher et al. (2009). In analyzing the list by publishing decade, most of the top 100 papers were published in the 1990s, and no top 100 paper was published in the 2010s (Fig. 2).
Several authors published multiple papers in the top 100 list ( Fig. 3; Table 2). Both Stovall TG and Ling FW, who published six papers, appeared at the top of the list, followed by Decherney AH, Pouly JL and Buster JE with five papers. In regard to the first author and corresponding author, Stovall TG appeared at the top of the list with four papers, followed by Decherney AH also with four first author papers, in which Barnhart was the corresponding author as well.
The journal of Fertility and Sterility published the highest number of papers (23), followed closely by Obstetrics and Gynecology (15), American Journal of Obstetrics and Gynecology (10), New England Journal of Medicine (6) and JAMA-Journal of The American Medical Association (6). The detailed results are shown in Table 3.
Of the top 100 articles, 65 papers were from the United States, followed by the United Kingdom and France (Table 4). In regard to institution contribution (Table 5), Yale University in Connecticut contributed seven papers, whereas the Center for Disease Control and Prevention in Atlanta, Georgia published six papers each. Of all of the articles, 36 resulted from multi-institutional collaboration, 4 from multinational collaboration, and 64 from individual institutions.
Additionally, high-frequency keywords that appeared more than ten times in the 100 most cited articles, including EP, treatment, risk factors, methotrexate, diagnosis, tubal pregnancy, Chlamydia trachomatis infections, human chorionic gonadotropin (HCG), pelvic inflammatory disease, ultrasound, were screened to determine the hot topics in EP research (Table 6).

Discussion
The term "citation classics" was first introduced by Eugene Garfield in 1987 in a study to identify the 100 most-cited JAMA articles (Garfield 1987). Since then, citation classics have been studied by many authors in various fields. The number of times that an article is cited is a good way of measuring the impact that the article has on a specific field or topic and, in turn, allows both the author and the journal to be evaluated (Garfield 1972). In our study, the SCI-expanded was used to identify the 100 most cited papers in EP to produce a list of citation classics in this field. This list provides us with a source of great value in terms of the authors and topics that have had a profound influence in the area of EP over the past 50 years.
The present study summarizes several features of influential articles in EP research over the past 50 years. For instance, we found that half of the 100 most cited papers were published in the 1990s, which suggests that older papers are cited more (Picknett and Davis 1999). The articles in 1990s were neither too old to have some outdated opinions nor too early to have time to be proven or cited. In fact, it has been found that the true impact and importance of an article cannot often be precisely assessed for at least two decades after it is published (Baltussen and Kindler 2004).
A high citation frequency also demonstrates that other authors have formulated opinions on the topic and that it has generated discussion and debate (Nason et al. 2013). In our study, these top 100 articles were published in 32 peer-reviewed journals of high quality, as demonstrated by their impact factor (mean 10.421, range 1.535-55.873). The impact factor of a journal is generally accepted as a representation of the scientific quality of a publication. With further analysis, we found that most of the top-cited articles were published in high-impact journals, which is consistent with the results of other reviews. It is generally presumed that articles that are published in high-impact journals are more likely to have an extensive popularity among readers and thus have a greater potential for citation, which in turn maintains the high impact factor of these journals. This factor also supports the well-known paradigm that top-cited articles are often published in journals topping the impact factor list, which in turn maintains the high impact factor of these journals (Garfield 2006). Additionally, it was found that American authors tended to cite local papers (Campbell 1990), and that US reviewers had a significant preference to accept papers written by native researchers (Link 1998).
Additionally, we found that all of the papers in the top 100 were written in the English language and that a majority of them were from the United States. One of the underlying reasons might be due to the large population of senior researchers, adequate research budgets and superior scientific research conditions for scientific investigation. Besides, because of the powerful influence of English-speaking countries like USA, UK and so on and the fact that English is the official language using by most countries and is the world's most extensive second language, English is widely used all over the word. Collaboration has increased at the author, institution and country levels, which is supported by many earlier studies (Kliegl and Bates 2011). Of the top 100 cited papers, 64 came from individual institutions, 36 came from multi-institutional collaboration, and 4 came from multinational collaboration. This finding reflects that teamwork awareness, in some cases, is of great importance and that scientific collaboration plays an indispensable role in the progress of scientific research.    1986-1990. Fertil Steril. 1995 (4) EP has been defined as pregnancy that develops after implantation of the blastocyst anywhere other than the endometrium lining of the uterine cavity. It remains a major gynecological problem in contemporary gynecological practice and continues to be an important cause of morbidity and mortality in women. Therefore, many studies have targeted the pathogenesis, diagnosis or treatment application to improve future prognosis. According to the implantation site of the blastocyst, EP is divided into tubal pregnancy, ovarian pregnancy, abdominal pregnancy, or intraligamentary pregnancy. Among the sites of EP, more than 95 % of EPs occur in the fallopian tubes. Some special-site EPs such as cesarean scar pregnancy (Godin et al. 1997;Hemminki and Merilainen 1996;Jurkovic et al. 2003;Seow et al. 2004;Sorbi et al. 2013), interstitial pregnancy (Lau and Tulandi 1999), cornual pregnancy (Timortritsch et al. 1992), and cervical pregnancy (Frates et al. 1994) were discussed in the 100 most cited papers.
The risks of an EP vary across women. Among the 100 articles, more than a quarter of them emphasized the risk factors of EP, among which the relationship between  (9) Table 2 List of authors who published more than 3 of most 100 cited papers in ectopic pregnancy The first authors with more articles took precedence and then the corresponding author and at last the initials according to the order of the alphabet in the situation of equal numbers of articles  Chlamydia trachomatis infection and EP was discussed mostly (Brunham et al. 1986;Cates and Wasserheit 1991;Chow et al. 1990;Egger et al. 1998;Hillis et al. 1997; Van-Voorhis et al. 1997). Additionally, the authors focused on other risk factors that can lead to EP, such as pelvic inflammatory disease (PID), smoking, in vitro fertilization (IVF), the use of intrauterine contraceptive devices (IUD), and vaginal douching (Aral et al. 1992;Castles et al. 1999;Hillis et al. 1993;Logerotlebrun et al. 1995;Ory 1981;Rogers 2009;Westrom et al. 1992;Zhang et al. 1997). The phenomenon reminds us that the etiology and pathogenesis of EP for clinical and basic research has attracted close attention from many senior researchers. The diagnosis of EP has been a hot topic in research across the world. A timely, early diagnosis can help patients obtain better pregnancy outcomes. Ultrasonography and β-hCG levels are important in the early diagnosis of EP (Crochet et al. 2013). Moreover, the combined application of ultrasound and β-hCG levels has great value in a precise diagnosis (Cacciatore et al. 1990;Kadar et al. 1981). We also found that the articles relating to early diagnosis were mainly cited before the 1990s, indicating that the effect of early diagnosis of EP on clinical practice and basic research still needs to be explored.
The treatment of EP has drawn attention from modern researchers. The treatments presented in the classic articles include expectant management and medical and surgical protocols. The focus of treatment is to select a safer and more effective method to preserve reproductive potential. Methotrexate treatment, especially single-dose methotrexate, is thought to reduce the potential cost and morbidity of hospitalization and surgery, which is discussed mostly as well (Glock et al. 1994;Stovall and Ling 1993;Stovall et al. 1991). Following EP, fertility is another topic that is commonly discussed in these classic articles (Sherman et al. 1982) which show improved intrauterine pregnancy after an ectopic pregnancy. Besides, ESEP study and DEMETER study show high rate of 2 years intrauterine pregnancy after an ectopic pregnancy which match the conclusion (Fernandez et al. 2013;Mol et al. 2014).
Although the top 100 articles have proved to be most useful to the vastly larger population of practicing scientists, some limitations are existed in our study (Van Noorden et al. 2014). First, the top-cited articles were always the older papers because of the limited life span of literature. Therefore, some points need to be updated, and such updates are likely to identify trends in research patterns (Garfield 1972). Another important problem Table 4 List of countries that published the 100 top-cited articles in ectopic pregnancy TP refers to all the co-authors originating from the same country or territory contributed to the number of the 100 most cited articles in EP; TC refers to the number of 100 top-cited articles published by the first author originating from each country or territory; SP refers to single country or territory articles; CP refers to internationally collaborative articles. Rank: according to the order of TP, TC, SP, CP and the order of the alphabet of the initials  with this type of analysis is the "obliteration by incorporation" phenomenon (Garfield 1987). This issue describes the process in which information from truly classic papers becomes cited less frequently and is absorbed into the body of current knowledge (Kelly et al. 2010). Second, the words that we used as subject terms were only "ectopic pregnancy" and "ectopic pregnancies", which may miss some citations related to our analysis such as those indexed with extrauterine pregnancy or heterotopic pregnancy. Furthermore, the only database that we searched was the SCI-expanded, and those articles published before 1965 were excluded from our study. Therefore, some "classic" articles from other databases or before 1965 may have also been missed in this analysis. Additionally, self-citation, journal bias and language bias were not controlled for in our study, and these issues may have affected our research, whereas citation analysis is still a feasible tool to comprehensively recognize the advances of EP research in the past and future research.

Conclusions
Bibliometric analysis was used to provide a historical perspective on the progress in EP research over the past 50 years. The citation increases as time goes by, and it reaches its peak in the 1990s. Articles originating from the United States and published in high-impact journals were most likely to be cited in the field of EP research. The risk factors of EP like Chlamydia trachomatis infections and the treatment of EP especially like methotrexate medical management were screened to present the hotspots of EP research.