This retrospective case-control study was conducted over a 5-month period (February 1 to June 30, 2023), reviewing data from 10 years (January 1, 2013 to December 31, 2022). The study took place in the Obstetrics and Gynecology departments of two tertiary referral hospitals in Douala, Cameroon: Douala General Hospital (DGH) and Gyneco-Obstetrics and Pediatric Hospital of Douala (GOPHD). Both hospitals provide comprehensive reproductive health services, including medical and surgical (laparotomy and laparoscopy) management of ectopic pregnancies, and are involved in medical training and research.

The minimum sample size was calculated using the Schlesselman formula, with a 1:2 case-to-control ratio. Based on a previous Cameroonian study reporting an odds ratio (OR) of 13.18 (95% CI: 6.19 - 27.42) for pelvic inflammatory disease as a risk factor for ectopic pregnancy, the calculated minimum sample size was 39 cases and 78 controls (total 117).

The following cases were excluded:

Cases and controls were matched by age group, gravidity, and study site (1:2 ratio).

Data were collected from birth registers, operative notes, and medical records, including demographic, gynecological, obstetrical, surgical, medical, and toxicological information.

Data were analyzed using EPI Info 3.5.4 and Microsoft Excel 2007. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess associations between variables. Logistic regression was used to control for confounding variables. Chi-square and Fisher’s exact tests were used as appropriate.

Ethical approval was obtained from the Ethics Committee of Universite des Montagnes (No. 2023/267/Udm/PR/CIE). Patient confidentiality and safety were maintained throughout the study.

Table 1 below summarizes the comparison of socio-demographic factors between the cases and the controls. Women in the (31 - 35) and >40 age groups had the highest odds of having ectopic pregnancy, while those in the age group (26 - 30) had the lowest. Regarding profession, being a housewife carried the highest risk of having EP. Both tobacco and alcohol use were significantly associated with an increased risk of ectopic pregnancy.

As shown in Table 2 , women with a gravidity of four or more pregnancies have a significantly higher risk of ectopic pregnancy (EP) (OR = 6.00, p = 0.040). However, no significant association was found between parity and the risk of EP. In terms of abortions, a history of one to four voluntary abortions was significantly linked to an increased risk of EP (OR = 2.23, p = 0.000). A history of pelvic inflammatory disease (PID), particularly when associated with Chlamydia trachomatis infection, was also identified as a significant risk factor for EP (OR =2.12, p = 0.000).

Other risk factors included the use of Medroxyprogesterone Acetate (MPA) (OR = 3.33, p = 0.030), intrauterine devices (IUDs) (OR = 5.29, p = 0.000), natural contraceptive methods (OR = 2.30, p = 0.050), and a previous ectopic pregnancy (OR = 43.45, p = 0.000). On the other hand, condom use (OR = 0.59, p = 0.010) and practicing safe sexual behavior (defined as having fewer than five sexual partners) (OR = 0.49, p = 0.000) were found to have a protective effect against the occurrence of EP.

The most significant finding in Table 3 is the strong association between a previous surgery for ectopic pregnancy and the increased risk of future ectopic pregnancies (OR = 38.28, p = 0.000). Other surgical histories, including myomectomy, cystectomy, cesarean section, pelvic abscess drainage, and appendectomy, did not show a statistically significant association with the risk of EP.

All factors that showed significant association with the occurrence of EP were included in the multivariate regression models to study the independence of their effects. Table 4 presents the results of a multivariate logistic regression analysis that evaluates the adjusted odds ratios (aOR) for various factors associated with the risk of ectopic pregnancy (EP). Age > 30 years, past history of EUP, surgery for EUP, tobacco use, and number of voluntary abortions (1 - 4) all emerged as significant risk factors for ectopic pregnancy in this analysis. Natural methods of contraception also showed a significant association with an increased risk of EP. Alcohol consumption, cumulative number of sexual partners, and past history of PID were not significant in the final multivariate model, indicating that other factors may better explain the risk of EP.

The average age of the population in the case group was (31.26 ± 5.81) years, with an age above 30 years being a significant risk factor for EP. This relatively young age has been observed in several studies conducted in low- and middle-income countries (LMICs) [8] [17] [18] and was also noted by Abdullah Karaer in Türkiye [19] . While few authors did not find a significant age difference between the EP and intra-uterine pregnancy groups, our findings underscore the importance of considering age-related physiological changes when providing reproductive health counseling.

Induced abortions, especially repeated ones, were strong independent predictors of EP in our study. This could be attributed to restrictive abortion laws in the region, which often lead to unsafe abortions carried out by untrained individuals. These unsafe procedures can result in ascending infections, ultimately leading to salpingitis and narrowing the lumen of the fallopian tubes. This reduces the movement of the fertilized ovum towards the uterine cavity, contributing to the risk of EP [8] . Similar findings have been reported both in developed countries [5] [13] and LMICs [9] [18] - [21] .

In line with previous scientific literature, our study identified the past history of EP and past history of tubal surgery as key predictors of EP. Tubal damage and adhesions resulting from the surgical management of EP or tubal surgery are primary pathophysiological mechanisms leading to the occurrence of EP [22] . Studies from both high-income countries and African nations have consistently identified these factors as significant predictors of EP [23] - [25] .

Furthermore, a past history of pelvic inflammatory disease (PID) was associated with the occurrence of EP, with the association being stronger when PID was caused by Chlamydia trachomatis, even though not statistically significant. The role of PID and sexually transmitted infections (STIs) in the development of EP has been well-documented globally [7] [13] [26] [27] . The high incidence of PID, combined with suboptimal treatment due to poverty in our setting, is a notable contributor to this condition. Tubal damage caused by PID reduces the peristaltic movement of the ovum and impedes sperm migration, which can explain this association.

The use of intrauterine devices (IUDs) was found to increase the risk of EP by 5.29 times. Other hormonal contraceptives, such as Medroxyprogesterone Acetate (MPA), were also identified as risk factors for EP but without. Although our findings differ from the results of Mindjah et al. in Cameroon [8] and Parashi et al. in India, who did not find a significant association between Depo-Provera use and EP risk [28] , this discrepancy may be due to the possibility of early conception occurring immediately after discontinuation of MPA. This phenomenon has also been described for other contraceptive methods, such as the Levonorgestrel implant [29] . The association of natural contraception with increased EP risk remains controversial in the literature. While authors like Karaer et al. and Zhang et al. corroborate our findings, others like McQueen report no such link [30] . The potential explanation for this increased risk with natural methods of contraception is the higher likelihood of unintended pregnancies, which may result in ectopic pregnancies.

Other factors, such as the number of lifetime sexual partners, early onset of sexual intercourse, being single, and a past history of appendectomy—described by several authors—were not present in our study.

Tobacco smoking was identified as a predictor of EP in this study, whereas alcohol consumption showed no significant relationship. The link between cigarette smoking and EP due to the harmful effects of nicotine on the cilia of the fallopian tubes, and consequently on the occurrence of EP, has been well-established in European and American studies [16] . Our finding was somewhat surprising, as women in our study population typically claim abstention from smoking. This may suggest the impact of passive smoking or the presence of nicotine in other substances consumed in the population’s diet.

This retrospective study may be subject to recall bias, particularly when gathering reproductive and surgical history. Additionally, its regional scope and the relatively small sample size limit the ability to generalize the findings to the broader population of the nation or continent.

1. Age:

2. Nationality: Cameroonian /

1 = Yes 2 = No If not, specify your origin:

3. Region of Origin:

1 = West 2 = Centre 3 = Littoral 4 = North

5 = North-West 6 = South-West 7 = South 8 = Far North

9 = Adamawa 10 = East

4. Marital Status:

1 = Single 2 = Married 3 = Widow 4 = Divorced

5 = Open relationship

5. Profession:

1 = Public sector 2 = Private sector 3 = Parapublic sector

4 = Trader 5 = Pupil 6 = Student

7 = Housewife

Obstetrical

6. Number of pregnancies:

Number of children delivered at term:

7. Number of induced abortions: Number of spontaneous abortions:

8. Past history of ectopic pregnancy:

1 = Yes (If yes, specify number: )

2 = No

9. Fertility treatment history:

1 = Yes (Specify: Clomiphene citrate □ Others □ )

2 = No

10. In vitro fertilization (IVF) history:

1 = Yes 2 = No

Gynecological

11. Number of cumulative sexual partners:

12. Endometriosis history:

1 = Yes 2 = No

13. Tubal pathology history:

1 = Yes 2 = No

14. Contraceptive use history:

1 = Intrauterine contraceptive device (IUD) 2 = Progesterone-only pills

3 = Condoms 4 = Others (Specify: )

15. Pelvic inflammatory disease (PID) history:

1 = Chlamydia with IgG ≥ 128 2 = Others (Specify: ) 3 = No

Surgical

16. Surgical history: (Check all applicable)

□ Surgery for ectopic pregnancy □ Myomectomy

□ Cystectomy □ Cesarean section (If yes, number: )

□ Drainage of pelvic abscess □ Others (Specify: )

Toxicology

17. Tobacco use:

1 = Yes (If yes, specify number of pack-years: ) 2 = No

18. Alcohol consumption:

1 = Yes (Check one: □ Absolutely □ Occasionally □ Frequently)

2 = No

19. Other past history:

1 = Yes (If yes, specify: ) 2 = No

20. Amenorrhea:

1 = Yes 2 = No

21. Pelvic pain:

1 = Yes 2 = No

22. Per vaginal bleeding:

1 = Yes 2 = No

23. Gestational age (in days):

1 = ≤42 2 = 42 - 49 3 = ≥49

24. Tubal location:

1 = Yes (If yes, specify: □ Left □ Right □ Ampullary □ Isthmic □ Fimbrial □ Interstitial □ Unknown)

2 = No

25. Ovarian location:

1 = Yes 2 = No

26. Abdominal location:

1 = Yes 2 = No

27. Heterotopic location:

1 = Yes 2 = No

28. Ectopic pregnancy state:

1 = Ruptured 2 = Non-ruptured 3 = Fissurated

29. Homolateral tube state:

1 = Normal 2 = Abnormal 3 = Absent 4 = Unknown

30. Contralateral tube state:

1 = Normal 2 = Abnormal 3 = Absent 4 = Unknown

31. Associated pathologies:

1 = Hydrosalpinx 2 = Uterine fibroid 3 = Ovarian cyst

4 = Chlamydia cyst 5 = Adhesions 6 = None

32. Medical treatment with methotrexate:

1 = Yes 2 = No

33. Route of methotrexate administration:

1 = Parenteral 2 = Local

34. Methotrexate protocol:

1 = Single dose 2 = Multi-dose

35. Adjuvant treatment with folate:

1 = Yes 2 = No

36. Surgical treatment:

1 = Yes 2 = No

37. Surgical route:

1 = Laparotomy 2 = Laparoscopy

38. Radical surgical management:

1 = Yes 2 = No

39. If yes, specify:

1 = Total salpingectomy 2 = Adnexectomy 3 = Unknown

40. Conservative surgical treatment:

1 = Yes 2 = No

41. If yes, specify:

1 = Partial salpingectomy

2 = Tubal expression

3 = Salpingotomy

4 = Partial oophorectomy

5 = Partial salpingectomy plus end-to-end anastomosis

6 = Unknown