Factors associated with female infertility in Ethiopia: A systematic review and meta-analysis.

Infertility defined clinically as inability to become pregnant after one year of unprotected regular sexual intercourse [ 1 , 2 ]. From the perspective of the demographer, infertility is defined as the inability to have a live birth in a woman of reproductive age (15–49 years) with regular unprotected sexual intercourse [ 3 ]. It can be classified as either primary or secondary [ 4 ]. Primary infertility refers to women who have never conceived, while secondary infertility applies to women who have had at least one successful pregnancy but are unable to conceive again [ 5 ]. Globally, infertility affects approximately 60–80 million women [ 2 ], and the prevalence rate has increased by 0.37% annually from 1990 to 2017 [ 6 ]. A recent meta-analysis reported a global pooled prevalence of infertility at 46.25% [ 5 ]. In Africa, the pooled prevalence of primary and secondary infertility was found to be 49.91% and 49.79%, respectively [ 3 ]. In Ethiopia, the prevalence of infertility ranges from 24.2% [ 7 ] to 27.6% [ 8 ]. Various studies have identified several factors associated with infertility, including polycystic ovary syndrome, hormonal imbalances, thyroid disorders, premature ovarian failure, fallopian tube obstructions, congenital malformations, luteal phase defects, endometritis, endometrial polyps, leiomyomas, Asherman’s syndrome, chronic systemic diseases, and certain social and personal habits, such as the use of illicit drugs [ 9 , 10 ]. Infertility has significant gynecological, social, and public health consequences [ 2 , 9 , 11 ]. These consequences can include marital instability, social isolation, sexual abuse, stigma, intimate partner violence, stress, depression, anxiety, and, in some cases, suicide [ 1 , 12 – 14 ]. In Ethiopia, the impacts of infertility are further worsened by factors such as limited access to healthcare services, high costs of fertility treatments, cultural stigmas surrounding infertility, and inadequate infrastructure for diagnosis and treatment [ 15 ]. Women facing infertility may seek alternative solutions, such as visiting spiritualists, traditional healers, or witchcraft practitioners, before resorting to modern medicine [ 16 , 17 ]. Additionally, infertility may lead individuals to engage in extramarital sex as a test of fertility, which exposes them to the risk of sexually transmitted infections [ 16 ]. While several primary studies in Ethiopia have investigated factors associated with female infertility, their findings have often been inconsistent and inconclusive [ 7 , 15 , 18 – 21 ]. Some studies have reported a strong association between factors like having multiple sexual partner [ 8 ] and infertility, while others have not [ 20 ]. Similarly, results regarding the impact of having a Khat-abusive partner, an alcohol-abusing partner, and rural residency have been contradictory. These inconsistencies make it difficult to draw definitive conclusions about the factors associated with female infertility in Ethiopia. Given these gaps in the literature, this study aimed to synthesize available evidence and identify the key factors associated with female infertility in Ethiopia. Specifically, we sought to answer two key research questions: (1) What are the factors associated with female infertility in Ethiopia? (2) How consistent are the relationships between these associated factors and infertility across different studies, and what areas of agreement or divergence exist? By pooling data from multiple studies, we aimed to provide a comprehensive and reliable understanding of the factors associated with female infertility in Ethiopia. Our findings will help clarify the inconsistencies in the existing literature, highlight specific associated factors that require further investigation, and identify unique contextual factors in Ethiopia that influence infertility. Ultimately, this study may inform targeted interventions and public health strategies to address infertility in the region.

A total of 57 articles were searched from different databases and search engines (PubMed = 10, google scholar = 4, EBSCO = 5, DOAJ = 1, and AJOL = 37). Additionally, 2 grey literature sources (master’s theses) were found in the institutional repositories of Ethiopian universities. Out of the total articles, 8 articles were removed from screening due to duplication. A total of 33 studies were excluded from the review because of irrelevant or unrelated titles and 12 studies were excluded due to different outcomes of interest. Finally, six studies were included to determine the associated factors of female infertility in Ethiopia ( Fig 1 ). The list of all identified articles and the reasons for the exclusion of each study are provided as supplementary data in supplementary Table 4 ( S4 Table ). A total of six studies were included to identify the factors associated with female infertility in Ethiopia. Among these, four studies were published in different journals, while two studies were grey literature, which are found in Debre Birhan and Bahir Dar University institutional repositories. Regarding study design, three studies were cross-sectional studies, whereas three studies were case-control studies. Regarding the region where the studies were conducted, two studies were in Addis Ababa, one study from the Oromia region, two studies from the Amhara region, and one study based on EDHS data. A total of 7794 samples were included in this meta-analysis ( Table 2 ). N/A: Not applicable (grey literature) Egger’s regression test was employed to evaluate publication biases, and the results indicated no publication bias or small study effects for having a history of multiple sexual partners (p-value = 0.873), STDs (p-value = 0.918), and having an alcohol-abusive partner (p-value = 0.658). However, only two studies were available to assess the pooled effect of maternal age over 35 years and having a khat-abusive partner, so Egger’s regression test was not conducted for these variables. This systematic review and meta-analysis focuses on associated factors that were consistently studied and reported across the primary research, with a minimum of two occurrences. While we recognize the significance of immune system function, drug use, lifestyle, diet, psychological stress, socio-economic determinants, hormonal factors (e.g., thyroid disorders, premature ovarian failure, hyperprolactinemia, and polycystic ovary syndrome), and cigarette smoking, these factors were not included in our analysis due to their limited representation in the primary studies. Six studies reported one or more factors associated with female infertility. The most frequently reported factors were having multiple sexual partners, having alcohol-abusing partner, and having a history of sexually transmitted disease ( Table 3 ). Having multiple sexual partner and infertility : Three studies have examined the association between female infertility and having multiple sexual partners [ 8 , 15 , 19 ]. A meta-analysis combining these studies found a significant association: women with a history of multiple sexual partners were 4.31 times more likely to experience female infertility compared to those with only one sexual partner (OR = 4.31, 95% CI = 3.46, 5.16). A random-effects model was used to assess this association, revealing high heterogeneity across the studies (I 2  = 77.9). The results of this meta-analysis is illustrated in Fig 2 . The association between having alcohol-abusing partner and female infertility: three studies found significant association between having alcohol-abusing partner and female infertility [ 7 , 8 , 19 ]. This meta-analysis also found a significant association between female infertility and having an alcohol-abusing partner. Specifically, women with alcohol-abusing partners were 1.57 times more likely to experience infertility compared to those whose partners did not abuse alcohol (OR = 1.57, 95% CI = 1.25, 1.89). A random-effects model was used to assess the pooled effect, with moderate heterogeneity observed across the studies (I 2  = 71.39). This findings are presented in Fig 3 . Association between history of STD and female infertility: Three studies have reported the association between a history of STD and female infertility [ 15 , 19 , 20 ]. Our meta-analysis also found a significant association between infertility and history of STD. Accordingly, those woman who had a history of STD were 2.76 times more likely to have female infertility as compared to their counterpart (OR = 2.76, 95%CI = 1.61, 3.91). High heterogeneity was detected across the studies (I 2  = 87.12). The result is shown in Fig 4 . Association between infertility and women’s age greater than 35 years: Two studies have reported a significant association between women’s age over 35 years and infertility [ 7 , 20 ]. This meta-analysis also found a significant association between women’s age greater than 35 years and infertility. Accordingly, those women whose age > 35 years were 2.07 times more likely to have infertility (OR = 2.07, 95% CI = 1.32–2.81). High heterogeneity was observed between the studies (I 2  = 83.43). The result is shown in Fig 5 The association between female infertility and having Khat-abusive partner : A significant association was also noted between female infertility and having khat-abusive partner [ 7 , 19 ]. Those women who had khat abusive partner were 1.85 times more likely to have infertility as compared to their counterpart (OR = 1.85, 95%CI = 1.36, 2.35). Moderate heterogeneity was observed between the studies. The result is shown in Fig 6 . The association between residency and female infertility: Two studies have reported a significant association between being rural residency and infertility [ 7 , 18 ]. However, our meta-analysis found no significant association between rural residency and infertility (OR = 2.51, 95%CI = -0.37, 5.39). The result is presented in Fig 7 .

Having multiple sexual partners, a history of sexually transmitted infections (STIs), an alcohol-abusing partner, a khat-abusing partner, and being over the age of 35 are significantly associated with female infertility in Ethiopia. Encouraging safe sexual practices, regular screening for STIs, avoiding harmful substances like khat, and limiting alcohol consumption can help reduce the burden of infertility and improve the chances of successful conception. The findings also highlight the need for further research on understudied factors contributing to female infertility in Ethiopia, including immune function, psychological health, environmental exposures, as well as endocrinological and gynecological conditions. Finally, since the primary studies included in this meta-analysis did not distinguish between factors associated with primary and secondary infertility, future research should differentiate these factors. Such an approach would yield more nuanced insights into the distinct risk factors of each type, ultimately guiding targeted interventions tailored to the specific needs of affected individuals.

The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to conduct this meta-analysis [ 22 ]. The PRISMA checklist is provided as supplementary material in supplementary table 1 ( S1 Table ). The protocol has been registered in PROSPERO under the registration number CRD42024525437, which can be accessed at https://www.crd.york.ac.uk/PROSPERO . The literature search was conducted independently by two authors, DA and BB. Both authors adhered to a standardized protocol that included predefined keywords. The search was carried out across various databases, including PubMed, African Journals Online, EBSCO, Google Scholar, and the Directory of Open Access Journals. Additionally, studies were sourced from the institutional repositories of Ethiopian universities. The reference lists of all included primary studies were also examined to identify any potentially missed studies. To refine their search techniques and locate pertinent studies, the authors employed the Condition, Context, and Population (CoCoPop) framework, with detailed criteria outlined under the inclusion criteria. The searching strategies for PubMed database were ((“Infertility, Female”[ 23 ] OR “female infertility”[All Fields] OR “infertility in women”[All Fields] OR “women’s infertility”[All Fields]) AND (“Risk Factors”[ 23 ] OR “determinants”[All Fields] OR “causes”[All Fields] OR “factors”[All Fields] OR “risk factors”[All Fields]) AND (“Ethiopia”[ 23 ] OR Ethiopia[All Fields])). The search period spanned from January 1, 2000, to March 20, 2024. Detailed information about the literature search strategies and the search results are provided in Supplementary Table 2 ( S2 Table ). Condition (Co): Studies that examined the association between different variables and female infertility were included. Context (Co): Studies that were conducted in Ethiopia were included. Population (Pop): Studies that were done among reproductive age couples were included. Study Design: Observational studies (cross-sectional, case-control, and cohort studies) were included. Publication Condition: Both published and unpublished studies were included. Language: All studies written in English were included. Studies with a different outcome of interest were excluded. Studies with irrelevant or unrelated titles were excluded Studies with a different study population were excluded. Studies that missed important information, such as the adjusted odds ratio (AOR) with a 95% confidence interval for significant variables, were excluded. Studies with a low quality assessment score (less than 7 out of 10 for cross-sectional studies and 7 out of 9 for case-control studies, using the Newcastle-Ottawa Quality Assessment Scale) were excluded. The data selection process consisted of several key steps. First, all studies obtained from various databases and the institutional repositories of Ethiopian universities were imported into EndNote 7 reference management software. Any duplicate studies were identified and removed using this software. Two authors, WY and DA, then independently reviewed the remaining studies based on pre-defined inclusion and exclusion criteria. Following this initial review, they convened to discuss their findings, presenting their justifications for including or excluding specific studies while referencing the established criteria. Through this open dialogue, they aimed to reach a consensus regarding the included and excluded studies. In cases where they could not achieve agreement, a third author was consulted to provide an objective perspective. Ultimately, decisions were made collaboratively, ensuring that both authors were aligned on the final list of studies included in the review. Finally, the quality of the selected studies was assessed independently by WY and DA using the Newcastle-Ottawa Quality Assessment Scale (NOS) [ 24 ]. Based on the NOS, articles were considered high quality and included in the review when a study scored at least 7 points out of 10 for cross-sectional studies and 7 out of 9 points for case-control studies. The results of the quality assessment are provided as supplementary data in supplementary table 3 ( S3 Table ). After the screening, all pertinent variables were extracted from the included studies by two authors (DA and BB) separately using Microsoft Excel. The authors extracted the name of the first author, the publication status, the year of publication, the study design, the study period, the study region, the sample size, the sampling design, and the adjusted odds ratio (AOR) with a 95% CI for significant factors ( Table 1 ). Missing data were handled with care to ensure the robustness, accuracy, and replicability of our findings. For studies with missing outcome data or incomplete reporting of relevant statistics (e.g., adjusted odds ratio and 95% confident interval for significant factors), we made efforts to contact the original study authors via email to request the missing information. If we were unable to obtain the missing data after reaching out to the authors, we excluded those specific studies or data points from the meta-analysis, as appropriate. The decision to exclude studies or data points was based on the extent and nature of the missing data; studies with substantial missing data were excluded entirely, while studies with minor missing data were included, provided the missing data did not critically impact the overall analysis. Alcohol-abusing partners refers to a pattern of alcohol consumption in which an individual regularly consumes more than two standard drinks of alcohol per day [ 8 ]. Khat-abusive partner refers to an individual who intentionally ingests khat, a psycho-stimulant substance, at least once per day [ 18 ]. Stata 17 was used for the data analysis. The studies’ quality was evaluated using the Newcastle-Ottawa quality assessment tool. The assessments of heterogeneity and publication bias were conducted using I-squared statistics and Egger’s regression tests, respectively [ 25 , 26 ]. To specify the degree of heterogeneity, we employed the following cut points: I-squared (I 2 ) = 0 indicates no heterogeneity; values of 25%, 50%, and 75% indicate moderate, high, and large heterogeneity, respectively. A random effects model was selected to determine the associated factors of female infertility [ 27 ]. Since our study was a systematic review and meta-analysis, ethical approval, consent to participate, and consent for publication are not applicable. However, this meta-analysis has been conducted with careful attention to ethical standards and transparency in data handling and analysis. We ensure that all data included are accurate and reliable by critically evaluating each study’s methodological quality and identifying any potential biases. Additionally, the results was presented honestly, highlighting both strengths and limitations, and discussing their implications for practice and future research.

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