Aetiological pattern of infertility cases managed at the University of Ilorin Teaching Hospital in Ilorin, North-Central Nigeria: a 3-year retrospective study

Abstract

Objective

The aetiological pattern of infertility in most African countries appeared to differ from that in developed countries. The aim of this study was to identify significant causes of infertility among infertile women attending the gynaecological clinics of the University of Ilorin Teaching Hospital.

Materials and methods

It was a hospital-based retrospective cross-sectional study of infertility cases managed at the gynaecology clinics of the hospital between 2016 and 2018. A total of 797 infertile women were recruited for the study. Aetiologic factors and patterns of infertility data were extracted from the participants’ case files. Chi-square test of association and logistic regression analyses were done to assess the significant association between studied aetiological factors and the pattern of infertility among them.

Results

The mean age of the participants was 32.9 ± 6 years. About a third of the participants had at least one form of menstrual disorder (35%), and fewer of them had PID (20.8%), obesity (14.2%), and hypertension (3.6%). More than half of them were with male partners with abnormal seminal fluid analysis results (55%). Regression analysis revealed that the most significant aetiological factor for the type of infertility among the patients studied was history of having had dilatation and curettage procedure (P < 0.001).

Conclusion

The predominant aetiologic factor in the study was male factor infertility with more than half of the women married to men with abnormal seminal fluid parameters. This finding underscores the growing significance of male factor in the aetiology of infertility among Nigerian women.

Introduction

Infertility is characterized by failure to achieve a clinical pregnancy after twelve months of regular and unprotected sexual intercourse. [1] It is a disease of the male or female or both reproductive systems and it is a common form of presentation in gynaecological clinics. [1] A 2023 World Health Organisation (WHO) publication reported a life-time prevalence of infertility of 17.5% among adult population globally, with no significant inter-regional differences. [2] However, a 2020 systematic review and meta-analysis of infertility in Africa reported a considerably higher pooled prevalence of infertility of 49%.³ This significant difference in the reported prevalence might be because of difference in methodology used in the calculation, and it might also be because of the reported higher level of poverty and pelvic inflammatory diseases in the continent. [3, 4].

Considering the epidemiology of infertility in Nigeria, the prevalence of secondary infertility of 55%, and primary infertility of 45% has been reported in a hospital-based study in South-Eastern Nigeria. [5] The overall prevalence of infertility in the study was 26.8%. [5] In another study in South-South Nigeria, the overall prevalence of infertility reported was 32%. [6] A similar study done in Kano, North-Western Nigeria, reported an overall prevalence of infertility of 16%, of which 53% had secondary infertility and 47% had primary infertility. [7] From these Nigerian studies, the overall prevalence of infertility in the country is between 16% and 32%. Most of the studies reporting infertility prevalence in Nigeria, are single-centred institutional studies, highlighting the need for more national and community studies.

In most African communities, infertility is wrongly assumed to be women’s problem alone. However, about 43.6% of the causes of the infertility were related to male factors while only about 10.4% of the cases were medically unexplained. [3].

Commonly identified causes of female infertility in Nigeria, like in most African countries are; tubal factors, uterine factors, and ovarian factors, accounting for 39.5%, 30%, and 13% respectively.⁸ In addition, hormone disorders like hyperprolactinemia has also been reported as a cause of female infertility in about 7% of the women. [9] Male infertility is a primary or contributory cause of infertility in about 50% of couples, and more recent data from Africa has reported prevalence of male infertility as high as 53.1%. [10, 11] The cause of male infertility can be congenital, acquired or idiopathic factors that impair spermatogenesis. [3] For both women and men, however, environmental and lifestyle factors such as smoking, excessive alcohol intake, obesity and exposure to environmental pollutants have been associated with lower fertility rates. [2].

The psychosocial impact of infertility is tremendous on the infertile women and in most African communities leading to them having lower psychosocial and total quality of life when compared with fertile women as reported in a recent Nigerian study. [12] Therefore, most adults have over the years tended to recognize or associate some clinical and socio-demographic features with infertility. [13] In a community study done among married adults in Ilorin, over 60% of the respondents rightfully identified lack of regular menstrual flow and poor ejaculation of semen as important causes of infertility. [13] This indicates a high level of some knowledge about the aetiopathogenesis of infertility among them.

Despite several reports from Nigeria, few recent data exist from North-Central Nigeria on the aetiology and pattern of infertility among women attending a tertiary hospital. This study is therefore, done with the aim of identifying important causes of infertility, and to model how these factors differentiate primary from secondary infertility among the studied population to develop recommendations towards prevention and management of infertility cases in the hospital.

Methodology

Study design

The study was a retrospective study of all infertile women managed at the gynaecology clinics of the University of Ilorin Teaching Hospital (UITH) between 2016 and 2018. Ilorin is the capital city of Kwara State, in the North-central region of Nigeria, in West Africa. The approval to conduct the study was received from the Ethical Review Committee of the University of Ilorin Teaching Hospital, Ilorin, Kwara State, Nigeria on the 9th of November 2022. Although the study was retrospective in design, all efforts were made to protect the privacy of the patients studied. All unique patients’ identifiers like names, address, etc., were not captured in the study. The study was conducted in accordance with the Declaration of Helsinki guiding research in human subjects. There was no direct interaction with human subjects so there was no need for a written informed consent to participate in the study.

The inclusion criteria were all female infertility cases managed at the clinics between 2016 and 2018 whose hospital records were complete and assessable during the study period. The seminal fluid analysis of male partners of the infertile women attending the clinic is one of the basic routine tests done in the evaluation of the aetiology of infertility in the gynaecology clinics of UITH. The results were interpreted and documented based on the WHO 2010, 5th Edition Manual for the Examination and Processing of Human Semen criteria, which was being used exclusively during the study period. [14] Therefore, these results and other important male partner information are available in the women’s hospital records. Those whose hospital records were missing, or incomplete, were excluded.

A team of five medical interns trained by the researchers and working independently went through all 797 eligible patients’ hospital folders and their investigation results sheets after detailed selection and sorting by the hospital records staff. The required data were extracted from the folders using a specially designed pre-tested data capture form. The data capture form used was divided into the following four sections:

1. Socio-demographic data: age, gender, marital status, level of education, occupation, tribe, and religion.

2. Obstetrics and gynaecological history: menstrual history, presence of hirsutism, voice changes, galactorrhoea, breast changes, gravidity, and parity.

3. Aetiologic factors of infertility: menstrual disorders, history of sexually transmitted diseases (STI), pelvic inflammatory diseases (PID), smoking, alcohol and other substance abuse, diabetes mellitus (DM), hypertension (HTN), dilatation and curettage procedure, ectopic pregnancy surgery, myomectomy, use of contraceptives, obesity, and sperm abnormalities.

4. Pattern of infertility.

The validity and reliability of the data collected was ensured and verified by a Consultant Obstetrics and Gynaecologist and an expert in data science. In addition, inter-rater reliability testing was done among the five to assess if there was a significant difference between their documentation of studied categorical variables (Aetiological factors, presence of infertility, and type of infertility). The inter-rater reliability was tested using Fleiss’s kappa (k), which is appropriate for assessing agreement among more than two raters on categorical variables. The Fleiss’s kappa demonstrated substantial agreement (k = 0.74, 95% CI: 0.68–0.86, p < 0.01).

Data analysis

The collected data were exported into IBM SPSS™ version 21 software (International Business Machine Corporation, New York, USA) for analysis. Descriptive statistics of the socio-demographic, obstetrics and gynaecology, infertility aetiological factors data, and the pattern of infertility of the studied group were analysed and presented in tables. Chi-square test of association was done to assess the level of association between studied aetiological factors and the pattern of infertility recorded among them. The level of statistical significance was set at P-value < 0.05.

All relevant and supportive data used in this study are available upon request from the corresponding author.

Funding declaration

We declared that the authors did not receive funding for this research except their personal contributions. All authors also declared no conflict of interests for this study.

Results

Socio-demographic Characteristics

The mean age of the studied patients was 32.9 ± 6 years and the highest percentage of them were between 30 and 39 years (48.7%). The majority of the patients were Yoruba by tribe (89.8%), practiced Islamic religion (66.5%), and 53.3% of them had at least tertiary level of education. The results are shown in Table 1.

Table 1.

Socio-demographic Characteristics of the patients (N = 797)

Variables	Frequency (n)	Percentage (%)
Age groups (years)
<20	4	0.5
20-29	317	39.8
30-39	388	48.7
≥40	88	11.0
Mean (SD)	32.9 (6.0)
Range	18-56
Ethnicity
Yoruba	716	89.8
Hausa	15	1.9
Igbo	21	2.6
Others	45	5.6
Religion
Islam	530	66.5
Christianity	267	33.5
Highest education level
Tertiary	425	53.3
Secondary	261	32.7
Primary	96	12
No formal education	15	1.9
Occupation
Civil servants	179	22.5
Self-employed	162	20.3
Private companies employed	53	6.6
Traders	270	33.9
unemployed	133	16.7
Marital status
Married	767	96.2
Not married	30	3.8

N = Total number of participants

n = Number of participants in a group

SD = Standard deviation of the mean

Gynaecological characteristics

The mean age at menarche among the patients was 14.3 ± 1.7 years. A large majority of them started menstruating between 12 and 14 years (69.8%). The mean menstrual cycle days among them was every 28.6 ± 4.7 days, and majority of them had menstrual flow lasting between 4 and 6 days (80.3%). Furthermore, only very few of them had features of hormonal imbalance such as excess body hair (3.4%) and voice changes (0.9%). The results are presented in Table 2.

Table 2.

Gynaecological characteristics of the patients (N = 797)

Variables	Frequency (n)	Percentage (%)
Age at menarche (years)
19-11	89	11.2
12-14	556	69.8
≥15	152	19
Mean (SD)	14.3 (1.7)
Range	9-23
Menstrual cycle (days)
<21	10	1.2
21-25	82	10.3
26-30	670	84.1
>30	35	4.4
Mean (SD)	28.6 (4.7)
Range	4-90
Menstrual cycle flow (days)
≤3	150	18.8
4-6	640	80.3
≥7	7	0.9
Mean (SD)	4.5 (1.6)
Range	1-28
Hirsutism
Yes	27	3.4
No	770	96.6
Voice changes
Yes	7	0.9
No	790	99.1

N = Total number of participants

n = Number of participants in a group

SD = Standard deviation of the mean

Aetiological factors for infertility

About a third of the patients had at least one form of menstrual disorders (35%), fewer of them had PID (20.8%), obesity (14.2%), smoking (0.3%), alcohol use (1.8%), diabetes (0.8%), and hypertension (3.6%). More than half of the patients had male partners with abnormal seminal fluid analysis results (55%). All the results are presented in Table 3.

Table 3.

Aetiological factors of infertility among the patients (N = 797)

Variables	Frequency (n)	Percentage (%)
Menstrual disorders
Yes	279	35
No	518	65
Pelvic Inflammatory Diseases
Yes	166	20.8
No	631	79.2
Obesity
Yes	113	14.2
No	684	85.8
Smoking
Yes	2	0.3
No	795	99.7
Alcohol
Yes	14	1.8
No	783	98.2
Diabetes
Yes	6	0.8
No	791	99.2
Hypertension
Yes	29	3.6
No	768	96.4
Dilatation and Curettage
Yes	213	26.7
No	584	73.3
Myomectomy
Yes	51	6.4
No	746	93.6
Tubal ectopic surgery
Yes	21	2.6
No	776	97.4
Seminal fluid analysis
Normal	359	45.0
Abnormal	438	55.0

N = Total number of participants

n = Number of participants in a group

SD = Standard deviation of the mean

Association between type of infertility and studied aetiological factors

The studied patients who were obese (X² = 7.192, OR = 7.6, P = 0.007), hypertensive (X² = 5.077, OR = 5.9, P = 0.024), those who had dilatation and curettage procedure (X² = 99.183, OR = 121.4, P < 0.001), and those who had ectopic tubal surgery (X² = 5.432, OR = 6.6, P = 0.020) had statistically significant associations and likelihood of developing secondary infertility rather than primary infertility. The results are available in Table 4.

Table 4.

Association between type of infertility and studied aetiologic factors

Variables	Infertility Primary [n (%)]	Type Secondary [n (%)]	X2	Odds	P-value
Menstrual disorders			0.101	0.1	0.750
Yes	94(35.6)	185(34.7)
No	170(64.4)	348(65.3)
PID			1.457	1.8	0.483
Yes	60(22.7)	106(19.9)
No	204(77.3)	427(80.1)
Obesity			7.192	7.6	0.007
Yes	25(9.5)	88(16.5)
No	239(90.5)	445(83.5)
Smoking			0.993	1.6	0.319
Yes	0(0.0)	2(0.4)
No	264(100.0)	531(99.6)
Alcohol			2.283	2.6	0.131
Yes	2(0.8)	12(2.3)
No	262(99.2)	521(97.7)
Diabetes			0.777	0-7	0.378
Yes	3(1.1)	3(0.6)
No	261(98.9)	530(99.4)
Hypertension			5.077	5.9	0.024
Yes	4(1.5)	25(4.7)
No	260(98.5)	508(95.3)
Dilatation and Curettage			99.183	121.4	<0.001
Yes	12(4.5)	201(37.7)
No	252(95.5)	332(62.3)
Myomectomy			2.466	2.4	0.116
Yes	22(8.3)	29(5.4)
No	242(91.7)	504(94.6)
Tubal surgery			5.432	6.6	0.020
Yes	2(0.8)	19(3.6)
No	262(99.2)	514(96.4)
Seminal fluid analysis			0.032	0.0	0.858
Normal	164(45.8)	195(54.3)
Abnormal	237(54.2)	201(55.5)

X2 = Chi-square

n = Number of participants in a group

Binomial logistic regression for significant aetiological factors for infertility

A binomial logistic regression analysis was performed to identify independent predictors of the significant aetiological factors in the bivariate analysis. Entry criterion into the multivariate model was variables with P-value < 0.05. Therefore, the covariates evaluated were presence of obesity, presence of hypertension, history of having had dilatation and curettage (D & C) procedure, and history of previous tubal ectopic surgery. The model was fitted using the enter method, and the model assumptions were assessed prior to interpretation. There was no evidence of multicollinearity (all Variance Inflation Factors are < 2), and the Hosmer-Lemeshow test indicated good model calibration (P = 0.45).

After correcting for confounders, the binomial logistic regression results revealed that the most significant aetiological factor for secondary infertility among the studied patients was history of having had dilatation and curettage (D & C) procedure. It also has the greatest odds compared to other factors, with those women who had D & C procedure having greater than 12 times odds of developing secondary rather than primary infertility (r = 2.530, OR = 12.6, 95% CI: 6.8–23.0, P < 0.001). The model explained 22.1% of the variation in the outcome (Nagelkerke R² = 0.221), indicating a moderate predictive ability. The results are shown in Table 5.

Table 5.

Binomial logistic regression for significant aetiological factors for secondary infertility among the patients

Aetiological factors	Regression (r)	Odds ratio (OR)	95% CI	P-value (P)
Presence of obesity	0.623	1.9	1.1-3.1	0.014
Presence of hypertension	0.700	2.0	0.6-6.4	0.234
History of dilatation and curettage procedure	2.530	12.6	6.8-23.0	<0.001
History of tubal ectopic surgery	1.786	6.0	1.4- 26.3	0.018

CI Confidence interval

Discussion

This retrospective study described the associated causes and pattern of infertility over a three-year period among women attending the gynaecological clinics of UITH for evaluation and management of infertility. The wide age range of the participants reflected the importance attached to having biological children among them, and that the search for viable pregnancy extended beyond the traditional reproductive years. The mean age of the infertile women in this study is close to the 33.5 years reported earlier by Olarinoye et al. in the same study site, and comparable to 34.5 years reported by Oladeji et al. in Ogbomoso, South-Western Nigeria. [15, 16].

More than half of the infertile women in this study had tertiary level of education which is consistent with various reports over the years that female level of education is significantly inversely proportional to their fertility in all the geopolitical zones in Nigeria. [17] The major reported reason for this observation was the delay in getting married and starting a family due to pursuit of academic and career related education. [17] Nigeria is a secular but highly religious country with the majority of the citizens practicing Islam or Christianity as reflected in this study. There is a strong religious restriction on extra-marital sexual relationships and having children out of wedlock. Therefore, most Nigerian women will not present for evaluation for infertility unless they are married. However, the trend appeared to be changing over the years as reported in this study where a small percentage of them presented for infertility as single women.

The mean age at menarche reported among infertile women in this study is considerably higher than the 12.9 years and 12.8 years reported among adolescent girls in both Northern and Southern Nigeria respectively. [18, 19] Late onset of menarche defined as menstruation starting when a woman was greater than 13 years old in a large population study has been shown to be associated with a slightly increased risk of infertility. [20] Furthermore, the higher mean age at menarche in this study could also be explained by the documented decline in the age of menarche over the last decades in Nigeria. [21] Majority of the women studied had menstrual cycle length and flow days which are similar to that of fertile women. Furthermore, only small percentages of the participants had features of hormonal imbalance like hirsutism and voice changes.

The top three female causes of infertility among the studied women were menstrual disorders, history of having had D & C, and history of having treatments for PID. These findings are comparable to those reported in Nigeria, other African countries, and India. [22–25] More than half of the women had associated male factor infertility which is similar to 50% reported by Agarwa et al. in India. [10] The increasing role of the male factor as a combined cause of infertility has been linked to declining male reproductive health globally. [26].

Overall, 33.1% of the women had primary infertility while the remaining 66.9% had secondary infertility. This 1:2 ratio of primary infertility to secondary infertility cases is consistent with previous reports from Nigeria but different from reports from Sudan, India and Iran where primary infertility cases were predominant. [16, 17, 19, 26, 27, 28].

Out of all the studied aetiologic factors of infertility in this study, only the presence of obesity (Odds ratio = 7.6, P = 0.007), systemic hypertension (Odds ratio = 5.9, P = 0.024), history of undergoing D & C procedure (Odds ratio = 121.4, P < 0.001) and history of having had tubal surgery (Odds ratio = 6.6, P = 0.020), had statistically significant associations with secondary rather than primary infertility. The odds ratio of the women with any of the above conditions or history having secondary rather than primary infertility was at least 5 times greater. Significant association of obesity and systemic hypertension to secondary infertility could be explained by pregnancy associated weight gain and rise in blood pressure so that women who had been pregnant before were more likely to have higher weights and higher blood pressure measurements than nulliparous women. The most common reason for undergoing dilatation and curettage procedure among the women in the study population, like in most places in Nigeria, was for illegal termination of unwanted pregnancy. [29] The procedure is usually done secretly in unhygienic places and by unqualified or poorly trained health care workers because voluntary termination of pregnancy without any medical justification is prohibited in Nigeria. [29] The common indications for tubal surgeries in Nigeria were mainly for the management of complicated tubal ectopic pregnancies and also for relieving of blocked fallopian tubes occasionally. [30] The latter indication is dwindling in practice in Nigeria due to relatively poor success rate. [30].

Confounder analysis with binomial logistic regression revealed that the greatest significant predictor of secondary infertility among the studied aetiologic factors was history of having undergone D & C procedure with more than 12 times odds that such women would have secondary rather than primary infertility (Odds ratio = 12.6, P < 0.001). This aetiologic association had been established previously by Okonofua in Ile-Ife, South-Western Nigeria. [31] This study has further provided evidence of direct association between undergoing D & C procedure and secondary infertility, and we hypothesized that it might also be the sole cause of infertility in the affected women due to uterine scarring. In another Nigerian study by Adesiyun et al., complicated D & C procedure was found to be the commonest cause of uterine scarring and adhesion among Nigerian women, it was also found to cause the greatest percentage of irreversible infertility among them. [32] However, reports from developed countries suggested rare complications from dilatation and curettage procedure which might be because of better hygienic facilities and stricter regulations. [33].

The presence of obesity and history of having undergone tubal surgery also remained significant predictors of secondary infertility but not systemic hypertension after the analysis. The risk of infertility has been reported to be three times higher in obese compared to non-obese women and that they also have worse pregnancy outcomes in natural as well as assisted conception. [34, 35].

This study has reported that more than half of the infertile women evaluated were married to men with abnormal seminal fluid parameters, making it the most single important aetiologic factor of infertility among them. This finding is particularly significant in African populations where infertility is usually perceived as a solely women problem. The most common cause of sperm abnormalities leading to male infertility in Africa is the relatively higher rates of sexually transmitted infections among them compared to men from other regions . [3, 8] It is a known fact that African men and women are more exposed to sexually transmitted infections and more likely to develop complications from the disease compared to people from other regions due to various reasons like high rates of sociopolitical unrest, poverty, ignorance, and poor health seeking behaviours. [3] So therefore, the most common cause of sperm abnormalities and tubal blockage in Africans are infections.[3] The study was also able to classify the aetiologic factors based on their propensity to cause secondary infertility or not. Aetiologic factors of infertility such as menstrual disorders, PID, smoking, alcohol, diabetes, hypertension, history of myomectomy surgery and abnormal seminal fluid were closely associated to both primary and secondary infertility. However, aetiologic factors like history of undergoing D & C, history of tubal surgery, and having obesity were shown to have at least two-fold statistically significant propensity to cause secondary rather than primary infertility after logistic regression analysis.

One of the limitations of this study was its retrospective design therefore the researchers were limited to only the information documented in the women’s paper records. Also, some of the paper files were damaged by wear and tears over the years and those with incomplete data had to be excluded from those studied. In addition, this study is a single-center hospital-based study, therefore, findings may not be generalizable to the wider community.

The most common aetiologic factor among the studied women was male factor infertility with more than half of the women married to men with abnormal seminal fluid parameters. This was followed by the top three female aetiologic factors in the study: menstrual disorders, history of dilatation and curettage, and history of treatments for PID. The significant aetiologic predictors for secondary infertility among the studied group were the history of having dilatation and curettage procedure, history of tubal surgery, and being obese. The study has provided further evidence of the increasing importance of male factor in the aetiology of infertility in Nigeria, emphasizing the need for a more detailed evaluation of the male partner of infertile women. There is also the need for stricter regulation of D & C procedures in the country towards a reduction of its complications.

Abbreviations

D & C

Dilation and curettage

DM

Diabetes

HTN

Hypertension

OR

Odds ratio

P

Probability value

PID

Pelvic inflammatory diseases

r

Regression coefficient

STI

Sexually transmitted infection

UITH

University of Ilorin Teaching Hospital, Ilorin

WHO

World Health Organization

Authors’ contributions

1. Odeigah LO: Conceptualization of the research ideas and design, expert review of the manuscript.2. Owolabi BO: Literature review, data collection, manuscript writing.3. Obalowu IA: Data collection, data analysis, manuscript writing.4. Mutalub YB: Data analysis, manuscript writing, and review.5. Agede OA: Manuscript writing and review6. Jimoh AAG: Expert review of the final manuscript.

Funding

We declared that the authors did not receive funding for this research except their personal contributions.

Data availability

All the data presented in this work and other supportive data are available upon request from the corresponding author.

Declarations

Ethics approval and consent to participate

The approval to conduct the study was received from the Ethical Review Committee of the University of Ilorin Teaching Hospital. The study was a retrospective one with no direct interaction with human subjects so the need for a written informed consent to participate in the study was waived by the ethical approval received. The study was conducted in accordance with the Declaration of Helsinki guiding research in human subjects.

Consent for publication

This is not applicable to this manuscript. All potential identifiers like the names and the hospital numbers of the patients are not included in the manuscript.

Competing interests

All authors declared no conflict of interests for this study.