{"paper_id":"bc352b1f-6013-4fd4-b4af-12ea368a6c7f","body_text":"Submit Manuscript | http://medcraveonline.com\nIntroduction\nInfertility has been described as a “ disease” of male or female \nreproductive system defined by failure to achieve a pregnancy after \ntwelve months or more of regular, unprotected sexual intercourse. 1 \nIt is estimated that, globally, as low as 48 million and as high as \n186 million individuals are affected by infertility. 2-4 A range of extra \nuterine (endocrine, abnormalities of the ovaries), intrauterine (uterus, \nfallopian tubes), intracavitary (abnormalities within the uterine \ncavity) and infectious diseases (Tuberculosis, hepatitis) among other, \nmay be responsible for female infertility, which could be primary \n(never achieved pregnancy) or secondary (had achieved pregnancy \nat least once). Adequate clinical fertility management includes \nprevention, diagnosis of hindrances to get pregnant and removal of \nsuch hindrances and application of appropriate treatment to reverse \ninfertility. According to WHO, equal and equitable access to fertility \ncare remains a challenge in most countries; particularly in low and \nmiddle-income countries.1 certain conditions constitute hindrances to \nfertility, either as causative or as co-morbidity with infertility or both. \nAmong these are certain chronic medical diseases such as hypertension \nand diabetes. For example, chronic high blood pressure prior to \npregnancy has also been linked with (i) poor egg quality (ii) excessive \nproduction of estrogen (iii) difficulty in embryo implantation and (iv) \nmiscarriage. Those that high blood pressure can contribute to their \ninfertility or lower their chances of getting pregnant are women who \nare (i) aged above 35 years, (ii) overweight or (iii) obese. 5 In a study \non Infertility and risk of hypertension, Farland et al., 6 reported no \napparent increase in hypertension risk among infertile women or those \nwho previously underwent fertility.6 Another chronic illness that can \ncause infertility is diabetes of either type. Although a woman may get \nPregnancy & Child Birth. 2022;8(3):71‒78. 71\n©2022 Olamijulo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which \npermits unrestricted use, distribution, and build upon your work non-commercially.\nGynecological co-morbidity, chronic illnesses and \ninfectious diseases among black African women \nwith primary or secondary infertility: should we be \nworried about hepatitis?\nVolume 8 Issue 3 - 2022\nJoseph Ayodeji Olamijulo,1 Joseph Agboeze,2  \nBamgboye M. Afolabi3,4 \n1Department of Obstetrics and Gynecology, Lagos University \nT eaching Hospital, Nigeria\n2Department of Obstetrics and Gynecology, Alex Ekwueme \nFederal University T eaching Hospital, Nigeria\n3Nigerian Institute of Medical Research, Nigeria\n4Health, Environment and Development Foundation, Nigeria\nCorrespondence: Dr. Bamgboye M Afolabi, Health, \nEnvironment and Development Foundation 18 Ogunfunmi \nStreet, Surulere, Lagos, Nigeria, Email \nReceived: May 10, 2022 | Published: Aug 04, 2022\nAbstract\nIntroduction: Female infertility may not occur alone but could be associated with other \nhealth conditions. Overlooking these health conditions during clinical assessment of \nwomen who present with primary or secondary infertility may not bring desired results of \nachieved pregnancy. \nObjective:  To determine the frequency and relative risks of certain chronic illnesses such \nas hypertension and diabetes, infectious diseases such as hepatitis and other gynecological \ndiseases such as uterine fibroid and endometriosis in women with primary and secondary \ninfertility taking into consideration their age groups and body mass index.\nStudy design: This was a retrospective study carried out at a tertiary health care facility in \nLagos Nigeria. \nMethods:  Records of patients who consulted for the management of infertility were \nretrieved for analysis. \nResult: The overall prevalence of hypertension, diabetes, cancer and asthma in all patients \nwere 9.6%, 6.8%, 0.8% and 0.4% respectively. Among the infectious diseases, hepatitis B \noccurred most frequently at 19.1%, more among women with SI (28.0%) than PI (13.9%). \nThe most prevalent gynecological diseases as co-morbidity were uterine fibroid (32.7%) and \nendometriosis (11.2%). Pooled analysis showed that there was a significant variation in the \ndistribution of Polycystic ovarian syndrome (PCOS) (Pearson’s χ²=10.14, P-value=0.02) \nrelative to age, no significant distribution of any disease relative to body mass index (BMI) \nin Kg/m2, significant distribution of intrauterine adhesion relative to age (years) and BMI \namong those with PI (Pearson’s χ²=9.80, P-value=0.04) but not in SI. Significant correlations \nwere observed between infertility and hepatitis (r=0.17, P-value=0.006, 95% CI= 0.06, \n0.36) and between infertility and fibroid (r=0.1868, P-value=0.003, 95% CI=0.07, 0.32). \nConclusion: Through this study it is concluded that women with history of primary \ninfertility are more at risk of diabetes, endometriosis and PCOS more than those with \nSI; conversely, those with SI are more at risk of hypertension, hepatitis, fibroid and \nadenomyosis. Gynecologists and fertility experts in sub-Saharan Africa should probe for \nthese diseases in each patient who presents with infertility, after excluding male factor \nas contributing to female infertility. Early diagnosis of these diseases and others among \ninfertile or sub-fertile women can minimize pain and reduce cost of hospitalization and also \nminimize the number of patients with unexplained infertility.\nKey words: hypertension, diabetes mellitus, hepatitis b, uterine fibroid, endometriosis; \ninfertility, black women, sub-saharan africa\nInternational Journal of Pregnancy & Child Birth\nResearch article\n Open Access\n\n\nGynecological co-morbidity, chronic illnesses and infectious diseases among black African women with \nprimary or secondary infertility: should we be worried about hepatitis?\n72\nCopyright:\n©2022 Olamijulo et al.\nCitation: Olamijulo JA, Agboeze J, M. Afolabi B. Gynecological co-morbidity, chronic illnesses and infectious diseases among black African women with primary \nor secondary infertility: should we be worried about hepatitis?Pregnancy & Child Birth. 2022;8(3):71‒78. DOI: 10.15406/ipcb.2022.08.00264\npregnant with proper control with gycemic medications, remaining \npregnant for the entire duration may pose a major problem, especially \nif she has had diabetes for a prolonged period.7 \nDiabetes is known to impact female and male fertility by causing \nhormonal disturbances with delayed or failed implantation and/or \nconception as consequences as well as poor sperm and embryo quality \nand damaged genetic mutations and deletions8  A study reported a 20% \ngreater risk of developing diabetes among women with a history of \ninfertility compared with those without such a history, after adjusting \nfor adjusting for age, lifestyle factors, marital status, oral contraceptive \nuse, family history of diabetes and BMI.9 Other health conditions that \nmay cause infertility are uterine fibroid and endometriosis. Uterine \nfibroid is present in about 33% of women of reproductive age10 and in \nNigeria; there is a relatively high prevalence of symptomatic fibroid \nin women who presented with infertility.11 \nDespite the fact that between 5% to 10% of female infertility \nlinked with uterine fibroid, uterine fibroid is reckoned to be the \nexclusive constituent for infertility in only 1% to 3% of cases. 12,13 \nEndometriosis, the presence of endometrial-like tissue (glands and \nstroma) outside the uterus, which induces a chronic inflammatory \nreaction, scar tissue, and adhesions that may distort a woman’s \npelvic anatomy and primarily found in young slender women. 14 An \nenigmatic disease, endometriosis, impacts about 10% of women in \nchild-bearing age causing pain and infertility. Approximately 50% \nof women diagnosed with endometriosis are infertile 15 while about \n20% of infertile women have endometriosis. 16 Further, Polycystic \novarian syndrome (PCOS), an endocrine disorder in which women \nhave higher than normal levels of testosterone (hyperandrogenism), is \na common condition that can reduce or prevent female fertility. It is a \ncondition in which a large number of cysts develop on the ovaries and \nis associated with irregular periods (oligomenorrhea) or absent periods \n(secondary amenorrhea) thus an ovulation or irregular ovulation. 17 \nPCOS is particularly associated with obesity  and type 2 diabetes. \nThe prevalence of PCOS in the Chinese community population was \n5.6%18 and it occurs in one in six infertile Nigerian women.19 \nObesity plays a vital role in hyperandrogenism, hyperinsulinemia, \nand the development of PCOS,20 Infectious diseases, such as Hepatitis \nB virus (HBV),  have also been known to negatively affect fertility. The \nWorld Health Organization (WHO) documents that African, Asian, \nand South American countries have carrier rates as high as 8%, with \nAfrica, south of the Sahara responsible for 20% of the global burden.21 \nFor example, one source suggested that HBV infection in either \npartner is associated with tubal infertility and that HBV infection in \neither partner probably increases the risk of pelvic infection in female \npartner through impaired immune response to sexually transmitted \ninfections, with consequent tubal damage and infertility.22 \nHBV infection in women has been associated with increased \nrisk of tubal and uterine infertility and in men, it has been linked with \nincreased risk of tubal infertility in their partner, due to the HBV virus \nlowering the woman’s immune system and increasing the chance of \npelvic infection.23 It might not be too challenging for gynecologists \nto diagnose infertility in sub-Saharan Africa but exploring definitive \ncause(s) and risk factors for infertility, and removing cause and \nameliorating the condition such that the patient becomes pregnant may \nbe a Herculean task. Considering the many causes of female infertility \nwhich a woman can be exposed to and considering the dearth of \nlocal data on some of these conditions, the study aimed to calculate \nthe risk of co-morbidity with other gynecological illnesses, chronic \nillnesses and infectious diseases that co-exist with either primary or \nsecondary infertility among Black Women in sub-Sahara Africa. The \nstudy intended to list diseases most prevalent in primary or secondary \ninfertility relative to age and body mass index and to evaluate the \ncorrelation and linear regression of primary and secondary infertility \nagainst these diseases for any significant association.\nMaterials and methods\nIn 2018 and 2019, a total of 1421 and 1590 gynecological cases \nwere seen, respectively, making a total of 3011. In each of these years, \n202 (14.2%) and 206 (13.0%) cases (408, 13.6%) of female infertility \nwere recorded at a tertiary health facility in Nigeria. Of this number, \n251 (61.5%) cases of female patients attending weekly gynecology \nclinic were randomly selected and analyzed in this study. The tertiary \nhealth facility serves a population of approximately 5 million people \nnot only for obstetrics and Gynecology but for all other clinical, sub-\nclinical and biomedical departments. Patients patronizing this facility \nare from all strata of the society. Patients are also referred from other \nprimary, secondary or private health facilities to this tertiary health \nfacility. \nType of study:  This was a retrospective study in which hospital \nrecords of female patients who presented for management of infertility \nwere retrieved by simple random sampling. \nInclusion criteria: Those included in the study were Black women, \nNigerians by nationality, resident in the country and not visiting. Also \nincluded were those who had complete medical and gynecological \nrecords.\nExclusion criteria: Non-Nigerians, Caucasians, those on admission, \nthose with fulminant neoplasm or with any severe illness were \nexcluded. \nClinical examination and laboratory investigations: All patients \nwere investigated appropriately. The attending gynecologists took \nrelevant medical, gynecological and social histories from each \npatient. At the initial consultation and subsequently on each visit, \neach patient’s systolic and diastolic blood pressure was measured in \na sitting position; fasting or random blood sugar or other appropriate \ninvestigation for the analysis of blood sugar was assessed. Where \nnecessary, laparoscopy and appropriate gynecological procedures \nwere conducted using standard methods in operation theatre or \nother designated places, especially for endometriosis. Evidence \nof endometriosis was based on the presence of chocolate ovarian \ncyst among other. Uterine fibroid was initially suspected based on \npalpation informative of enlarged irregular uterine configuration on \nexamination of the pelvis after which a confirmatory diagnosing by \nUltrasonography (USS) examination was made. \nUltrasonography was also used for the confirmation of other \ngynecological diseases. Venous blood was aseptically taken into \nappropriate containers and sent to the laboratory for investigations \nof hepatitis, HIV among other and for relevant endocrine profile \nof the patients. Data extracted from hospital records of the patients \nincluded their socio-demographic information, history medical and \ngynecological illnesses, and social history including consumption \nof alcohol, traditional medicinal herbal tea, cigarette smoking and \nuse of tobacco. History of sexually transmitted diseases such as \nGonorrhea, Human Immuno-deficient Virus (HIV) and Hepatitis were \nalso extracted. Furthermore investigations that the patients had done \nand the results of such investigations, the diagnosis, prognosis and \npossible causative agents of their illnesses, these data were extracted \nby two trained research assistants into a pro-forma questionnaire \ndesigned by two of the three authors (JA, BMA) and verified by the \nthird author (JAO). The data extraction was supervised and verified \n\nGynecological co-morbidity, chronic illnesses and infectious diseases among black African women with \nprimary or secondary infertility: should we be worried about hepatitis?\n73\nCopyright:\n©2022 Olamijulo et al.\nCitation: Olamijulo JA, Agboeze J, M. Afolabi B. Gynecological co-morbidity, chronic illnesses and infectious diseases among black African women with primary \nor secondary infertility: should we be worried about hepatitis?Pregnancy & Child Birth. 2022;8(3):71‒78. DOI: 10.15406/ipcb.2022.08.00264\nby one of the authors (JAO). Age was categorized into <26 years, \n26-35 years, 36-45 years and >45 years. Body Mass Index (BMI) was \ncalculated as body weight in kilograms (kg) by height (squared) in \nmeters or Kg/m 2 before BMI was stratified as <18.5 (underweight), \n18.5-24.9 (normal), 25.0-29.9 (overweight) and ≥30 (obese).  The \nextracted data were then transferred into Excel spreadsheet, verified, \ncleaned and imported into statistical software for analysis.\nStatistical analysis\nStatistical analysis was performed by using NCSS 2021 (Kaysville, \nUtah, USA). Age (years) was categorized as ≤25, 26-35, 36-45 and \n>45, BMI (Kg/m 2) was segregated into <18.5, 18.5-24.9, 25.0-29.9 \nand ≥30. 24 Infertility was stratified as primary and secondary. The \nchi-square was used to test the significance of differences between \ntwo proportions while Pearson’s χ² was used to test the significance \nbetween more than two proportions in a pooled analysis. T-test \nwas used to evaluate significant differences in means between two \ngroups while one-way ANOV A were used to compare more than two \nsamples. Relative risk, odds ratio (OR) and 95% confidence interval \n(CI) as well as Correlation and Linear Regression Analysis were \ndetermined using appropriate commands. Data were presented as \nnumber (percent) or mean ± SD, Tables and Figures. P-value≤0.05 \nwas considered significant. \nResults\nFrequency distribution of and relationship between \nage (years), Body Mass Index (Kg/m2) and types of \ninfertility (T able 1, Figures 1a, b)\nThose aged 26-35 (117, 46.6%) and those with BMI≥30 Kg/m 2 \n(131, 52.2%) formed the bulk of the study population. There was no \nstudy subject with BMI <18.5 Kg/m 2. In all, the proportion of those \nwith primary infertility (PI) (158, 62.9%) was higher than that of \nthose with secondary infertility (SI) (93, 37.1%). Pearson’s chi square \nanalysis shows that PI or SI was significantly associated with age \n(Pearson’s χ²=14.89, P-value=0.001) but not with BMI (Pearson’s \nχ²=0.15, P-value=0.93). This assertion is illustrated in Figure 1a \nwhich elaborates the proportion of study subjects with primary or \nsecondary infertility relative to their age and in Figure 1b which \nshows the same proportion relative to their BMI. Women in age-group \nof 26-35 years were approximately 2½ times more likely to present \nwith PI (χ²=10.47, P-value=0.001, COR=2.39, 95% CI= 1.40, 4.07) \nwhile those aged >45 years were roughly 2½ times more likely to \npresent with SI (χ²=5.30, P-value=0.02, COR=2.57, 95% CI= 1.13, \n5.86). (Table 1)\nT able 1 Frequency distribution of and relationship between age (years), Body Mass Index (Kg/m2) and types of infertility among study subjects\nVariable Item n %\nInfertility\nχ² P-value\nPrimary infertility Secondary infertility\nPrimary \n(n=158, \n62.9%) \nSecondary \n(n=93, \n37.1%)   \nCOR 95% CI COR 95% CI\nAge \n(years)\n≤25 10 4 8 (5.1) 2  (2.1) 0.65* 0.42 2.43 0.50, 11.68 0.41 0.09, 1.98\n26-35 117 46.6 86  (54.4) 31 (33.3) 10.47 0.001 2.39 1.40, 4.07 0.42 0.25, 0.71\n36-45 98 39 53 (33.5) 45 (48.4) 5.42 0.02 0.54 0.32, 0.91 1.86 1.10, 3.14\n>45 26 10.4 11 (7.0) 15 (16.1) 5.3 0.02 0.39 0.17, 0.89 2.57 1.13, 5.86\nMean (±sd) 34.5 (6.6) 37.7 (7.3) t-test = \n-3.59 0.0004 - - - -\nPearson’s Chi-square=14.89, P-value=0.001 (H0 is rejected: Primary/Secondary Infertility and Age are associated)\nBMI (Kg/\nm2)\n<18.5 - - - - - - - - - -\n18.5-\n24.9 35 13.9 21 (13.3) 14 (15.1) 0.15 0.7 0.86 0.42, 1.80 1.16 0.56, 2.40\n25.0-\n29.9 85 33.9 54 (34.2) 31 (33.3) 0.02 0.89 1.03 0.60, 1.79 0.96 0.56, 1.66\n≥30 131 52.2 83 (52.5) 48 (51.6) 0.02 0.89 1.04 0.62, 1.73 0.96 0.58, 1.61\nPearson’s Chi-square=0.15, P-value=0.93 (H0 is not rejected: Primary/Secondary Infertility and BMI  are not associated)\n *Fisher’s Exact T est; COR, crude odds ratio; No patient was underweight with BMI<18.5 Kg/m2.\nFigure 1a  Pearson’s Chi-square=14.89, P-value=0.001 (H0 is rejected: \nPrimary/Secondary Infertility and Age are associated).\nFigure 1b Pearson’s Chi-square=0.15, P-value=0.93 (H0 is not  rejected : \nPrimary/Secondary Infertility and BMI  are not associated).\n\n\nGynecological co-morbidity, chronic illnesses and infectious diseases among black African women with \nprimary or secondary infertility: should we be worried about hepatitis?\n74\nCopyright:\n©2022 Olamijulo et al.\nCitation: Olamijulo JA, Agboeze J, M. Afolabi B. Gynecological co-morbidity, chronic illnesses and infectious diseases among black African women with primary \nor secondary infertility: should we be worried about hepatitis?Pregnancy & Child Birth. 2022;8(3):71‒78. DOI: 10.15406/ipcb.2022.08.00264\nFrequency distribution and risks of chronic illnesses, \ninfectious diseases and other gynecological diseases \nrelative to type of infertility among study subjects \n(T able 2)\nIn all, hypertension (HT) was the most prevalent chronic illness \namong the study subjects (24, 9.6%) followed by diabetes mellitus \n(DM) (17, 6.8%). Hypertension was more prevalent (10/93, 10.8%) \nand had higher relative risk (χ²=0.24, P-value=0.62, RR=1.21, 95% \nCI=0.56, 2.62) among those with SI  than among those with PI \n(14/158, 8.9%), while DM was more prevalent (13/158, 8.2%) and had \nhigher relative risk (χ²=0.87, P-value=0.35, RR=1.91, 95% CI=0.64, \n5.70) among those with PI  than those with SI (4/93, 4.3%). Hepatitis \nwas the commonest infectious disease (48/251, 19.1%) with a higher \nrelative risk among those with SI (χ²=7.45, P-value=0.006, RR=2.01, \n95% CI=1.21, 3.33) compared to those with PI (22/158, 13.9%). \nHowever, the prevalence of Human Immunodeficiency Virus (HIV) \n(9/251, 3.6%) was more common in PI than in SI subjects. In all, \nuterine fibroid (82/251, 32.7%) ranked highest as a co-morbidity with \ninfertility, and most prevalent in SI (41/93, 44.1%) than in PI (41/158, \n26.0%). The overall individual prevalence of other gynecological \ndiseases as co-morbidity with infertility were endometriosis (28/251, \n11.2%), Endometriosis (28/251, 11.2%), Polycystic ovarian syndrome \n(24/251, 9.6%), Uterine polyps (13/251, 5.2%), Intrauterine adhesion \n(12/251, 4.8%), Adenomyosis (9/251, 3.6%), and Ovarian tumor \n(8/251, 3.2%). Of these, those with SI had a higher relative risk of \nadenomyosis (χ²=2.32, P-value=0.13, RR=3.40, 95% CI=0.87, \n13.27) while those with PI had a higher relative risk of ovarian tumor \n(χ²=0.12, P-value=0.73, RR=1.77, 95% CI=0.36, 8.57). (Table 2)\nT able 2 Frequency distribution and risks of chronic illnesses, infectious diseases and other gynecological diseases relative to type of infertility among study \nsubjects\nVariable Item\nAll \nFreq.\n(%)\nT ype of infertility\nχ² P-value\nPrimary infertility Secondary infertility\nPrimary \n(n=158) \nSecondary \n(n=93) RR 95%CI RR 95%CI\nChronic illness\nHypertension 24 (9.6) 14 (8.9) 10 (10.8) 0.24 0.62 0.82 0.38, 1.78 1.21 0.56, 2.62\nDiabetes \nmellitus 17 (6.8) 13 (8.2) 4 (4.3) 0.87 0.35 1.91 0.64, 5.70 0.52 0.18, 1.56\nCancer 2 (0.8) 1 (0.6) 1 (1.1) 0 1 0.59 0.04, 9.23 1.64 0.10, 26.50\nAsthma 1 (0.4) 1 (0.6) 0 (0.0) 0 1 undefined undefined\nInfectious \ndisease\nGonorrhea 3 (1.2) 1 (0.6) 2 (2.2) 0.22 0.64 0.29 0.03, 3.20 3.4 0.31, 36.96\nHIV 9 (3.6) 7 (4.4) 2 (2.2) 0.34 0.56 2.06 0.43, 9.71 0.49 0.10, 2.29\nHepatitis B 48 (19.1) 22 (13.9) 26 (28.0) 7.45 0.006 0.5 0.30, 0.83 2.01 1.21, 3.33\nPID 1 (0.4) 1 (0.6) 0 (0.0) 0 1 undefined undefined\nOther \ngynecological \ndiseases\nUterine \nfibroid 82 (32.7) 41 (26.0) 41 (44.1) 8.75 0.003 0.59 0.42, 0.83 1.7 1.20, 2.41\nOvarian \ntumor 8 (3.2) 6 (3.8) 2 (2.2) 0.12 0.73 1.77 0.36, 8.57 0.57 0.12, 2.75\nEndometriosis 28 (11.2) 18 (11.4) 10 (10.8) 0.02 0.88 1.06 0.51, 2.20 0.94 0.46, 1.96\nPCOS 24 (9.6) 16 (10.1) 8 (8.6) 0.16 0.69 1.18 0.52, 2.64 0.85 0.38, 1.91\nAdenomyosis 9 (3.6) 3 (1.9) 6 (6.5) 2.32 0.13 0.29 0.08, 1.15 3.4 0.87, 13.27\nIUA 12 (4.8) 7 (4.4) 5 (5.4) 0.001 0.97 0.82 0.27, 2.52 1.21 0.40, 3.71\nPolyps 13 (5.2) 8 (5.1) 5 (5.4) 0 1 0.94 0.32, 2.79 1.06 0.36, 3.15\nPrevalence of different diseases among women with \nprimary or secondary infertility relative to age group \n(years) (T able 3)\nPooled analysis shows no significant difference in the distribution \nof any of the chronic illnesses or infectious diseases by age distribution \nin PI or SI, though there were marginally significant divergence in \nthe spread of endometriosis (Pearson’s χ² = 7.59, P-value = 0.05) and \nmomentous variation in PCOS (Pearson’s χ² =10.14, P-value = 0.02). \nHypertension (5/10, 50.0%) and DM (6/33, 11.3%) were observed \nmore in PI aged >45 and 36-45 years respectively. Hepatitis was \nmost prevalent in SI aged 36-45 years (14/45, 31.1%) and in PI aged \n<25 years (2/8, 25.0%) while uterine fibroid was more commoner in \nSI aged >45 years (6/15, 40.0%) and in PI aged 35-45 years (20/53, \n37.4%).\nPrevalence of different diseases among women with \nprimary or secondary infertility relative to body mass \nindex of study subjects (Table 4)\nThere was also no significant difference in the spread of chronic \nillnesses, infectious diseases and other gynecological diseases relative \nto BMI and type of infertility. However, it is pertinent to observe \nthat HT was more prevalent in obese (BMI ≥30 kg/m 2) women with \nSI (10/48, 20.8%) than those with PI (9/83, 10.8%) while DM was \nmore common in obese women with PI (6/83, 7.2%) than in obese \nwomen with SI (3/48, 6.2%). The highest prevalence of hepatitis \n(6/14, 42.9%) was observed in normal weight women with SI. Among \nthose with PI, hepatitis was more common (4/21, 19.0%) in those with \nnormal weight (Table 4). \n\nGynecological co-morbidity, chronic illnesses and infectious diseases among black African women with \nprimary or secondary infertility: should we be worried about hepatitis?\n75\nCopyright:\n©2022 Olamijulo et al.\nCitation: Olamijulo JA, Agboeze J, M. Afolabi B. Gynecological co-morbidity, chronic illnesses and infectious diseases among black African women with primary \nor secondary infertility: should we be worried about hepatitis?Pregnancy & Child Birth. 2022;8(3):71‒78. DOI: 10.15406/ipcb.2022.08.00264\nT able 3 Prevalence of different diseases among women with primary or secondary infertility relative to age groups (years)\nVariable Item\nT ype of infertility\nPearson’s χ² df P-value\nPrimary (n=158) Secondary (n=93)\nAge (years)\n<25 (n=8) 26-35 \n(n=86)\n36-45 \n(n=53)\n>45 \n(n=10)\n<25 \n(n=2)\n26-35 \n(n=31)\n36-45 \n(n=45)\n>45 \n(n=15)\nChronic illness\nHypertension 1 (12.5) 4 (4.6) 4 (7.5) 5 (50.0) 0 (0.0) 4 (12.9) 6 (13.3) 0 (0.0) 5.9 3 0.12\nDiabetes \nmellitus 0 (0.0) 6 (7.0) 6 (11.3) 1 (10.0) 0 (0.0) 1 (3.2) 2 (4.4) 1 (6.7) 1.12 2 0.57\nCancer 0 (0.0) 0 (0.0) 1 (1.9) 0 (0.0) 0 (0.0) 1 (3.2) 0 (0.0) 0 (0.0) 2 1 0.16\nAsthma 0 (0.0) 0 (0.0) 1 (1.9) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) - - -\nInfectious \ndisease\nGonorrhea 0 (0.0) 0 (0.0) 1 (1.9) 0 (0.0) 0 (0.0) 1 (3.2) 1 (2.2) 0 (0.0) 0.75 1 0.39\nHIV 1 (12.5) 4 (4.6) 2 (3.8) 0 (0.0) 0 (0.0) 2 (6.4) 0 (0.0) 0 (0.0) 1.29 2 0.53\nHepatitis 2 (25.0) 10 (11.6) 9 (17.0) 1 (9.1) 0 (0.0) 8 (25.8) 14 \n(31.1) 4 (26.7) 4.81 3 0.13\nPID 0 (0.0) 1 (1.2) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) - - -\nOther \ngynecological \ndiseases\nFibroid 0 (0.0) 17 (19.8) 20 (37.4) 4 (36.4) 0 (0.0) 13 \n(41.9)\n22 \n(48.9) 6 (40.0) 1.03 2 0.6\nOvarian tumor 1 (12.5) 3 (3.5) 1 (1.9) 1 (9.1) 1 \n(50.0) 1 (3.2) 0 (0.0) 0 (0.0) 1.33 3 0.72\nEndometriosis 0 (0.0) 12 (13.9) 5 (9.4) 1 (9.1) 1 \n(50.0) 2 (6.4) 4 (8.9) 3 (20.0) 7.59 3 0.05\nPCOS 6 (75.0) 8 (9.3) 2 (3.8) 0 (0.0) 1 \n(50.0) 1 (3.2) 4 (8.9) 2 (13.3) 10.14 3 0.02\nAdenomyosis 0 (0.0) 2 (2.3) 1 (1.9) 0 (0.0) 0 (0.0) 1 (3.2) 4 (8.9) 1 (6.7) 2.4 2 0.3\nIUA 1 (12.5) 5 (5.8)  1 (1.9) 0 (0.0) 0 (0.0) 1 (3.2) 1 (2.2) 3 (20.0) 6.51 3 0.09\nPolyps 0 (0.0) 6 (7.0) 2 (3.8) 0 (0.0) 0 (0.0) 3 (9.7) 2 (4.4) 0 (0.0) 0.32 1 0.57\nDistribution of different diseases among women with \nprimary infertility in different age groups relative to \nbody mass index of study subjects (Table 5)\nAmong all those with PI in all categories of BMI, none in age \ngroup of ≤25 years presented a chronic disease. The only exception \nwas among overweight women among whom one subject (1/5, 20%) \npresented with hypertension. Among those with PI, the highest \nprevalence of HT (4/7, 57.1%) was observed in obese women aged \n>45 years, of DM (2/12, 16.7%) was observed among overweight \nwomen, of hepatitis (3/8, 37.5%) was observed among normal weight \nwomen. Endometriosis was commoner (3/11, 27.3%) in normal weight \nwomen aged 26-35 years. In a pooled analysis, there was a noticeable \ndifference (Pearson’s χ²=9.80, P-value=0.04) in the distribution of \nIUA relative to BMI and age. \nDistribution of different diseases among women with \nsecondary infertility in different age groups relative to \nbody mass index of study subjects (Table 6)\nAmong those with SI, HT was most prevalent (4/13, 30.8%) in \nobese women aged 26-35 years, DM in overweight women aged \n>45 years (1/5, 20.0%), hepatitis in normal weight women aged 36-\n45 years (2/4, 50.0%) and aged >45 years (2/4, 50.0%). The most \nprevalent gynecological co-morbidity was uterine fibroid, observed in \nobese women in the age-group of 36-45 years (17/29, 58.6%).\nCorrelation and Linear regression analysis of infertility \n(primary and secondary as dependent variables) \nagainst various other conditions as independent \nvariables (Figures 2a-2j)\nFigures 2a-j show significant correlations between infertility and \nhepatitis (r=0.17, P-value=0.006, 95% CI= 0.06, 0.36) and between \ninfertility and fibroid (r=0.1868, P-value=0.003, 95% CI=0.07, 0.32). \nNo other variable showed any significant correlation with infertility \nthough adenomyosis approached a level of marginal significance \n(r=0.12, P-value=0.06, 95% CI= -0.01, 0.62).\nDiscussion\nThis retrospective study used data of women in child-bearing \nage group attending weekly clinic at a tertiary hospital in south of \nNigeria between 2018 and 2019 to investigate the most prevalent \ntype of female infertility and assess chronic medical, infectious \nand other gynecological illnesses that could exist as co-morbidity \nwith either form of infertility. This approach is very relevant since \nsocial, environmental and other factors can elicit health conditions \nthat may trigger or be linked with primary or secondary infertility. At \nany rate, at the clinic, gynecologists, physicians or fertility experts \nshould be able to identify any co-morbidity with female infertility \nand provide satisfactory management of not only infertility but also \nco-morbidity. There are some key findings in the study that warrant \n\nGynecological co-morbidity, chronic illnesses and infectious diseases among black African women with \nprimary or secondary infertility: should we be worried about hepatitis?\n76\nCopyright:\n©2022 Olamijulo et al.\nCitation: Olamijulo JA, Agboeze J, M. Afolabi B. Gynecological co-morbidity, chronic illnesses and infectious diseases among black African women with primary \nor secondary infertility: should we be worried about hepatitis?Pregnancy & Child Birth. 2022;8(3):71‒78. DOI: 10.15406/ipcb.2022.08.00264\nfurther discussion. First and foremost, before going through co-\nmorbidity factors, the issues of age and BMI come to the forefront. \nAge is a definitive factor that has been known to predispose a woman \nin reproductive age to a higher risk of infertility in that the quality \nand also quantity of a woman’s eggs gradually reduce with age such \nthat by about 35 years of age, speed of follicle loss is faster, leading \nto possibility of fewer and poorer eggs, difficulty in conceiving and \nhigher risk of miscarriage. In this facility-based study, prevalence \nof female primary infertility was 62.9%, a figure that is higher than \nthe 51.4% reported by Maheshwari et al., 25 but lesser than the 68.9% \nreported from Khartoum, Sudan26 or the 78.0% reported from Henan \nProvince in China.27 \nFigures 2a-2j Correlation and Linear regression analysis of infertility (primary and secondary as dependent variables) against various other conditions as \nindependent variables.\n\n\nGynecological co-morbidity, chronic illnesses and infectious diseases among black African women with \nprimary or secondary infertility: should we be worried about hepatitis?\n77\nCopyright:\n©2022 Olamijulo et al.\nCitation: Olamijulo JA, Agboeze J, M. Afolabi B. Gynecological co-morbidity, chronic illnesses and infectious diseases among black African women with primary \nor secondary infertility: should we be worried about hepatitis?Pregnancy & Child Birth. 2022;8(3):71‒78. DOI: 10.15406/ipcb.2022.08.00264\nThis might be due to modern Nigerian women in reproductive age \nwanting to have an income, be independent of men or want to establish \na corporate identity in various industries in which early pregnancy \nmay deny them the opportunity of self-establishment. Another \npossible reason is that men are not ready to get married because of \nunemployment and scarce income to support a family. Studies have \nactually reported that more men in the country are having fewer or no \nsperm cells.28,29  The 46.6% prevalence of primary infertility in the age \ngroup of 26-35 years is similar to the 46.0% reported in the same age \ngroup from an Indian study 30 but the 48.4% prevalence of secondary \ninfertility among those aged 36-45 years in this study in this much \nhigher than the 21.6% reported in the same Indian study. \nThe submission of Cates et al., 31 that African couples were more \nlikely, than those from elsewhere, to have secondary infertility \nor longer duration appears paradoxical, though it should still be \nconsidered in the context of a population-based and not facility-based \nstudy. Another key finding is that there was no significant difference \nin the effect of Body Mass Index in primary or secondary infertility. \nMany studies have reported the influence of BMI on infertility. For \nexample Zhu et al predicted that the relationship between infertility \nand BMI presented a U-shaped curve and that underweight and obese \nBMI tended to predict infertility. 32 In this study, the proportion of \nwomen that were obese (52.2%) or overweight (33.9%) was higher \nthan the respective 46.4% or 39.4% reported from a study in Algeria.33 \nHowever, there was no significant difference of the effect of BMI \non primary and secondary infertility, though further studies on factors \nnot considered in this study, such as insulin-sensitizing adipokines \nand abundance of adipose tissues34 may demonstrate potential effects \nof BMI on the two types of infertility. Stratification by BMI showed \nthat hypertension was most prominent in obese women, regardless of \nthe type of infertility while diabetes was most prominent in normal \nweight women with primary infertility as well as in obese women with \nsecondary infertility. Although there was no significant difference in \nthe proportion of women with primary or secondary infertility who \npresented with hypertension or diabetes, still overall, hypertension \nwas more prevalent in those with secondary infertility, with a slightly \nhigher risk, while diabetes was seen more in those with primary \ninfertility, with about twice the risk compared to secondary infertility. \nHowever when stratified by age, women with primary infertility, \naged over 45 years, were most likely to present with hypertension. \nThe insignificantly higher prevalence of hypertension in secondary \ninfertility may be due to the normal degenerative process as those \nwith secondary infertility were significantly older than those with \nprimary infertility. \nLack of regular exercise, increased sodium salt intake and obesity \nmay also be responsible as risk factors for the hypertension found in \nboth primary and secondary infertility. Plasma leptin concentration 35 \nmay be raised in women with secondary more than those with primary \ninfertility, though this needs further study. Ghafarzadeh et al had linked \ninfertility in women with the development of metabolic syndrome \nsuch as dyslipidemia, hypertension, insulin resistance, and obesity \nand various cardiovascular abnormalities. 36 in obesity-associated \ndiabetes, cytokines released from adipocytes; adipokines - especially \nadiponectin - probably play significant roles in reciprocally modulating \nlevels of glucose and insulin, among other things. 37 Further, lowered \nconcentration of high molecular adiponectin has been found to be \nlinked with cardiovascular disorder in type II diabetic patients.38 \nThis calls for further studies on adiponectin among infertile Black \nAfrican women in sub-Saharan Africa that present with primary or \nsecondary infertility and with overweight or obesity, hypertension and/\nor diabetes. A major key finding in this paper is the high prevalence \nof Hepatitis B, more in those with secondary, with twice the relative \nrisk, compared to those with primary infertility. The overall 19.1% \nprevalence of HBV in this study was higher than the 2.9%, 3.9% and \n6.9% reported among pregnant women attending antenatal clinic in \nUganda,39 northern part of Nigeria 40 and in Ethiopia 41 respectively. \nPossibly, HBV is a cause of idiopathic infertility, an issue that should \nbe explored further in infertility clinics in Africa. Another report \nobserves that individuals with HBV are 1.59 times more likely to \nexperience infertility than individuals who are not infected. 42 the \noverall number of women with Gonorrhea, HIV and PID were too few \nto make a meaningful deduction, though the relative risk of gonorrhea \nwas about 3½ higher in secondary than in primary infertility. Finally, \nthe 9.6% prevalence of PCOS reported in this study is lower than \nthe 13.8% reported from the Benin City in South-south Nigeria, 43 \nthe 18.1% documented in Enugu, South-east Nigeria 44 and 33.0% \nreported in Iraq45  respectively.\nLimitations\nThere are few limitations in this study that need consideration, \nthe first of which is the sampling size which may be insufficient to \ngeneralize to the Nigerian population and the sampling method which \nmay introduce bias. Also, the study was conducted in the tropical \nforest region of the south and may not reflect the true picture in the \narid Savannah region of the north. Further, this was a retrospective \nstudy and, though very remote, there might have been some error in \ndata records, a phenomenon that is common to most retrospective \nstudies. \nConclusion\nIn the analysis of this study, the proportion of women in the \nreproductive age who presented with primary infertility was higher \nthan those who presented with secondary infertility. The study also \nobserved that, confirming what has been reported, age and infertility are \nassociated with both primary and secondary infertility whereas Body \nMass Index has the same association with either primary or secondary \ninfertility. Hypertension and Diabetes were almost equally distributed \nin both types of infertility though the risk of hypertension was higher \nin women with secondary than in those with primary infertility. \nConversely, the risk of diabetes was higher in women with primary \nthan in those with secondary infertility. The most prominent infectious \ndisease was Hepatitis B virus (HBV) which was more prominent in \nthose with secondary than in primary infertility. The study also found \nthat uterine fibroid was the most common co-morbidity, especially \nin those with secondary infertility. Endometriosis, Polycystic ovarian \nsyndrome (PCOS), Intrauterine adhesion and polyps also featured \nprominently as co-morbidity, the former two in primary and the latter \ntwo in secondary infertility.  Significant correlation was observed \nbetween infertility and hepatitis. Screening for hepatitis should be \nincorporated and aggressively pursued as one of the run-ups for female \ninfertility examination in sub-Saharan Africa. Further, a nationwide, \npopulation-based survey of hepatitis in Nigeria should be undertaken \nand reviewed on four-year basis.\nFunding\nNone\nConflicts of interest\nThe authors declared no potential conflict of interest.\nAcknowledgment\nNone\n\nGynecological co-morbidity, chronic illnesses and infectious diseases among black African women with \nprimary or secondary infertility: should we be worried about hepatitis?\n78\nCopyright:\n©2022 Olamijulo et al.\nCitation: Olamijulo JA, Agboeze J, M. Afolabi B. Gynecological co-morbidity, chronic illnesses and infectious diseases among black African women with primary \nor secondary infertility: should we be worried about hepatitis?Pregnancy & Child Birth. 2022;8(3):71‒78. DOI: 10.15406/ipcb.2022.08.00264\nReferences\n1. Geneva. International classification of diseases, 11th revision (ICD-11). \nWorld Health Organization. 2018.\n2. Mascarenhas MN, Flaxman SR, Boerma T, et al. 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