Prevalence and Risk factors of Infertility in a Mongolian Population

Background: Worldwide, the median prevalence of infertility is 9%, but rates in different countries vary from 3.5% to 16.7%. Infertility, which is dened by the World Health Organization (WHO) as the failure to conceive after 12 months of unprotected regular sexual intercourse, is not considered a medical condition but carries a social stigma and can greatly impact a couple’s self-esteem and wellbeing. There are a number of risk factors associated with infertility such as: genetic background, age, socio-economic factors, and health care including treatment of sexually transmitted diseases. We have achieved the rst population-based study on the prevalence of infertility in reproductive aged women in Mongolia, and the factors that inuence it. Method: We conducted a population-based, cross sectional study in 4 regions of Mongolia and the capital city, Ulaanbaatar: East, West, Central Khangai, Central, and Ulaanbaatar. Our questionnaire consisted of categories that inuenced infertility such as: socio-economic status, lifestyle factors, health, reproductive history, present status and sexual function. Trained staff conducted face-to-face interviews with the participants. Results: A total of 1,920 couples residing in 4 regions of Mongolia and the capital city, Ulaanbaatar were studied. The median prevalence rate was 7.2%, which is similar to the worldwide infertility rate of 9%. Primary and secondary infertility was 2.5% and 5% respectively. Sexual transmitted diseases (STIs) contributed to secondary infertility. Our study showed that the most important risk factors for infertility were rural living and low levels of education. Only 14.8% of infertile patients received hormone therapy, and even fewer infertile patients (0.8%) received in vitro fertilization (IVF) treatment. Conclusions: Our study shows that two most signicant risk factors for infertility were: reliving in rural communities and having a low level of education. Occupational conditions, and monthly household income were not signicant risk factors for infertility. Since this is the rst population-based study in Mongolia we were not able to measure trends in infertility prevalence but intend to do so in


Plain English Summary
Infertility is one of the most important and underappreciated reproductive health problems and carries a stigma that can affect the wellbeing of a couple, and lead to depression and low self-esteem. The World Health Organization (WHO) de nes infertility as the failure to conceive after at least 12 months of regular unprotected intercourse. The average prevalence of infertility worldwide is 9%, although it varies from country to country depending on a number of risk factors. Relevant risk factors are the socio-economic conditions of a country and its health care.
We studied infertility amongst married couples living in 4 regions of Mongolia as well as in the capital city, Ulaanbaatar. In Mongolia the average infertility rate was 7.2%, which is similar to the average infertility rate worldwide. We found that in Mongolia infertility prevalence was signi cantly higher in rural communities and with couples who had lower levels of education. These two risk factors were often Page 4/17 associated. Besides these two risk factors age and history reproductive system diseases posed risks.
Furthermore, Assisted Reproductive Technologies (ART) for the treatment of infertile is rare in Mongolia. Background Infertility, as de ned by WHO, is the failure to conceive after at least 12 months of regular unprotected sexual intercourse (1) . Infertility is a medical issue that also carries a social stigma and leads to a decrease in the quality of life, emotional instability, and low self-esteem, especially in women (2).
There are wide-ranging estimates of infertility prevalence depending on the study and de nition of infertility (3) (4,5). A global study estimated the 12-month infertility prevalence to be 9%. With rates, ranging from 3.5-16.7% in more developed nations and from 6.9-9.3% in less-developed nations (6). There are around 186 million married women in developing countries (excluding China) between the ages of 15 and 49 with primary and secondary infertility (7). The differences between the developed and developing world have been increasing because of the availability, accessibility in infertility care and differing socio-cultural values for procreation and childlessness (8).
The only available data on infertility in Mongolia was represented demographically with a primary infertility occurrence of 1-1.99% while secondary infertility was 13% (9). In certain regions of the world including developing countries unsafe abortion, poor maternity care and sexually transmitted infections contribute to the higher rate of secondary infertility compared to primary infertility (10). Mongolia has one of the highest rates of secondary infertility (9) and this may largely be attributed to high rates of sexually transmitted infections (STIs). For instance, the rate of gonorrhea among women and men in Mongolia was 3.3% and 2.9%, and chlamydia was 19.5% and 15.6% respectively (11). Mongolia has an unregulated growth of the private healthcare sector and poor enforcement of standards and technical guidelines for safe abortion (12).
Mongolian based studies on infertility such as Bayasgalan et al 2004, are in a clinically based they found a female infertility rate of 45.8%, and a male infertility rate of 25.6%, unexplained infertility was 9.8% and the combined rate for couples was 18.8%. In Mongolia, the major factors in uencing female infertility were tubal adhesions and endocrinal factors, while in the male they were varicocele, azoospermia and testicular damage (13).
Infertility studies in Mongolia have mainly been hospital-based with limited epidemiological studies. Therefore, accurate assessment of infertility using epidemiological study methods are crucial in order to provide high quality assessment, treatment, and management. The aim of this study was to provide the rst 12-month prevalence rate of infertility with a population-based study, including causative factors leading to infertility in women of a reproductive age in Mongolia.

Study population and sampling
We conducted a population-based cross-sectional study from September 2016 to November 2018 in the four regions of Mongolia as well as the capital city of Ulaanbaatar. Mongolia is divided into four regions based on geographical and economic factors (Eastern, Western, Central and Khangai) while the capital city Ulaanbaatar is viewed as a separate region. Each region is made up of provinces with a total of 21 provinces in all.
The appropriate sample size for the study was calculated by taking the average international rates of infertility of around 8-10%. International infertility rates were used to calculate the appropriate sample size since there were no previous infertility studies undertaken in Mongolia. With an allowable error of 5% and a con dence level of 95%, a total sample size of 2000 couples was required for the study. Incomplete questionnaires (80 respondents) were excluded resulting in a total 1920 couples participating in the study giving in a response rate of 96%.
This was a nation-wide study that involved one or two provinces within each region randomly selected by a multi-stage strati ed cluster sampling design. We calculated the study sample of reproductive-age couples in each of four main regions (Govi-Altai province (n = 300) from Western region, Khuvsgul (n = 200) and Orkhon (n = 218) provinces from the Northern region Darkhan (n = 174) and Umnugovi (n = 150) provinces from the Central region and Ulaanbaatar (n = 695) region.
For the study we selected married couples who were citizens of Mongolia and who had been living together at least one year at a permanent residence in one of the selected regions. The women were between 20-45 years of age while there was no age selection for men. Couples excluded from the study were those who had lived apart for longer than three months, used birth control in any form, were presently breastfeeding, or those women in early menopause. After participants agreed to take part in the study, they were asked to sign a consent form. The Mongolian National University of Medical Sciences approved these studies (No 16/3/2016-16).
We randomly approached eligible couples with assistance from the local family healthcare centers from each Sum (territorial administrative unit of Mongolia) and District, the couples that agreed to participate were interviewed at the local family healthcare center. In some cases, participants were not able to come to the local healthcare center, so we conducted the survey in their homes.
A pretested standardized and structured questionnaire was used to gather data from the participants. As precaution to possible di culties arising from illiteracy and cultural miscommunication errors, we conducted a verbal interview in accordance with the questionnaire. In order to protect the participants privacy and to gather accurate information a trained interviewer conducted the interview individually with each person in a private setting.
Our questionnaire assessed general demographic and socio-economic status, medical history, toxin exposure, reproductive history, female reproductive health (e.g. age of menarche, last menstrual period, menstrual regularity, menstrual cycle, menstrual blood volume, medical history, operative history), marriage and child bearing status (e.g. length of marriage and cohabitation, pregnancy history including information concerning live births, miscarriage, induced abortions and stillbirths, frequency of sexual intercourse) and past medical consultation on infertility. We also conducted anthropometrics measurements. For gauging alcohol consumption, tobacco use and physical activity we based our questions on WHO STEPS Instrument's NCD (non-communicable disease) risk factor questionnaire (14).
For our study we used WHO's de nition of infertility as "a disease of the reproductive system de ned by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse" (15). Primary female infertility is de ned as a woman who has never before been diagnosed with a clinical pregnancy and meets the criteria of being classi ed as having infertility", while "secondary female infertility is de ned as a woman currently unable to establish a clinical pregnancy but who has previously been diagnosed with a clinical pregnancy" (16). Since infertility is usually de ned by the female population we calculated the epidemiology of infertility solely based on female data (4).
Data analysis was performed using the Statistical Program for Social Sciences (SPSS v 20, IBM). Missing data for the variables analyzed were excluded. Continuous measurements were shown as mean standard deviation (SD) and categorical variables were expressed as percentages. For statistical analysis distributions were compared using Pearson's chi-square test and Fisher's exact test when appropriate. Binary logistic regression analyses were then performed within each subgroup, adjusting for confounders. For comparison of variables t-test and ANOVA test were used; 95% con dence interval was considered statistically signi cant p < 0.05.

Study population
Our study population of 1920 participants consisted of residents of Ulaanbaatar city and four regions of Mongolia (Western, Eastern, Central and Khangai). The demographic and socio-economic characteristics of the participants are shown in Table 1.

Prevalence of infertility and patterns of region
Our study showed an infertility incidence of 7.2% (n=138), with primary infertility at 2.4% (n=46) and secondary infertility at 4.8% (n=92). Geographically the prevalence rate was as follows: Central region (8.2%, n=30), Khangai region (12.4%, n=49), Western region (7%, n=21), Eastern region (8%, n=13), Capital city Ulaanbaatar (3.6%, n=25) ( Figure 1). In comparison with the sole urban area of Ulaanbaatar, the prevalence of infertility is signi cantly higher (p<0.001) amongst the rural population. As it is the only territory with a city status in Mongolia, we viewed it as the sole urban area.

Age related patterns of infertility
Our results show that there is a trend of secondary and overall infertility that increases with the women's age. However, the same trend is present in primary infertility ( Furthermore, when we map the prevalence of infertility as individual ages instead of groups, we notice a slow decline from ages 30-36 and then a sudden spike at ages 36-39 followed by a plateau until age 45. (Figure 2).

Risk factors for infertility
We then divided our participants into two groups of either infertile or fertile females. Adjusting for age we calculated for the association between infertility and risk factors among women.
We calculated the risk of infertility compared to the 20-24-year age group. Among the risk factors age was the most signi cant risk factor, with the risk increasing by 4 to 8-fold with each progressing age group. Social factors, such as: occupational conditions and monthly household income were not signi cent risk factors for infertility however alcohol consumption, obesity, rural living and lower levels of education were signi cant risk factors (Table 3) We used the participant's self-reported gynecological history to calculate the risks it imposed. We found the following risks associated with infertility: abnormal menstrual cycles 1.

Clinical consultations for infertile couples
Of the total infertile participants (n=138), 77.5% (n=107) had sought clinical consultation regarding their infertility, while 22.5% (n=31) never sought any type of clinical consultation. Among the group that sought clinical consultation 29.7% (n=41) of the women had received some form of treatment, with hormonal therapy being most commonly used at 14.3%, followed by timing therapy at 4.5%, IUI therapy 0% and assisted reproductive technology ART at 0.8% (n=1) was scarce.

Discussion
Mongolia is a land locked nation that borders the People's Republic China to the south and the Russian Federation to the north. It is comprised of 21 provinces distributed in 4 regions (Khangai, Central, Eastern and Western) and Ulaanbaatar city. Globally it ranks 6th for the least densely populated country at approximately 1.7 persons per squared kilometer.
The Mongolian Government's policy on population development between 2016-2025 is to create favorable conditions for sustainable population growth.
Until now there has not been population-based studies on infertility and its risk factors in Mongolia.
Researchers used the number of couples and females with infertility in a certain time and location in relation to the total population to calculate the prevalence rate of infertility. The prevalence of infertility can be de ned as the total number of women or couples who experience infertility within a given period of time and in a given place, in proportion to the total population in the same time and place(3). Our study was done using this de nition, for the population of Ulaanbaatar and the four regions of Mongolia. We found an infertility prevalence of 7.2% which is in agreement with similar studies from around the world that had a median infertility prevalence ranging from 6.9-9.3% [4]. Mongolia is a developing country and our result of 7.2% was similar to the global rate of infertility in developing countries at 6.9-9.3%(9).
Larsen et al.'s study of primary and secondary infertility in sub-Saharan Africa showed a prevalence of primary and secondary infertility of 3% and 5% respectively (17). This was in keeping with our study, which showed a prevalence of primary and secondary infertility of 2.4% and 4.8% respectively. However, their de nition of infertility as "5 years or more of failure to conceive" was not the same as our de nition of infertility, which was 12 months of failed conception. Both Mongolia and the Sub-Saharan region had a high rate of gonorrhea and chlamydia(11) (18), which are risk factors for secondary infertility that could explain the similar results of the two studies. A study done in a fellow low-and middle-income country, Nigeria had a prevalence rate of infertility rate of 31.1% (19). This is much higher than the infertility rate we measured in Mongolia but it may be due to a different study design. A population-based study conducted in our neighboring country China, had a prevalence of 15.5% (20). Although both studies used the same de nition of infertility and study methods, we believe the contrasting result of 7.2% is due to governmental policy on reproduction (China's one-child policy), inclusion criteria, the age of the participants, socio-economic values and other factors. Recent meta-analysis study results in Iran showed a very similar result to our own with a total infertility prevalence of 7.8% to our 7.2%. However, these studies had primary and secondary infertility rates of 3.9% and 2.18% while our data showed 2.4% and 4.8% respectively. (21) There are numerous risk factors that contribute to female subfertility and it is important to diagnose each carefully in order to treat patients appropriately (22). Risk factors which vary between different regions of the world, include: the genetics of the population, socio-economic factors, differences in government policy, health care, nutrition, age of the participants, and STIs. High levels of STIs present in the population contribute to secondary infertility (23). Our study shows that important risk factors for infertility in Mongolia are age of the woman, alcohol consumption, obesity, rural living, and the level of education of the couple In women, the quantity and quality of oocytes is known to decline with age, with the resulting decline in fecundity becoming clinically relevant by the mid 30s (24). Interestingly our results showed a steady decline in fertility through the ages of 30-36 followed by a sudden spike then plateauing until age 45. Another possible contributing factor for infertility increasing with age in women is that susceptibility to infection also increases with age. A Scottish fertility clinic study found that women over 35 were more likely to be diagnosed with tubal factor infertility than younger women (OR 2.2, CI 1.7-2.7) (25). In a study conducted in Turkey infertility was signi cantly higher among women aged between 35 and 49 (p < 0.01)(26).
In our study a women's level of education was one of the factors affecting female infertility. This is agreement with a study China which showed that increasing levels of education was inversely correlated with a decreased the risk of infertility(27). This may be due to a link between higher levels od education healthier lifestyles and better healthcare.
We also found that obesity contributed to infertility which may be related to abnormal metabolism. Clinical studies de nitively demonstrate an impact of obesity on the risk of subfertility(28). Cohort studies showed that there is an increased risk of anovulation in extremely heavy exercisers (> 60 min/day), but vigorous exercise of 30-60 min/day was associated with reduced risk of anovulatory infertility(29).
We attribute the higher rates of infertility in rural areas compared to urban areas due to limited the access to healthcare. For instance, all 6 of the fertility clinics in Mongolia are located in the city of Ulaanbaatar. Among the infertile women in our study, only 0.8% had undergone IVF therapy, compared to China's 5.6% IVF therapy and 29.4% traditional Chinese medicine rates. (27) Furthermore with only 14.3% of our infertile participants who received hormone therapy had poor access to advanced fertility treatment.
Infertility is expected to change in populations over time. In a US National Health report it was shown that infertility fell from 8.5% in 1982 to 7.4% in 2002(30). Further declines in infertility were seen in 2006 (31). These declines in infertility may be due to improved nutrition and general health of the population and improvements in assisted reproductive techniques (ART). In Mongolia we were unable to look for these trends as this was our rst report, but we hope in the future to conduct further studies on infertility.
Our study calls for further quantitative and qualitative research speci cally designed to identify the causes of declining fertility, the socio-demographic and medical factors contributing to infertility and the links between infertility and the use of ART in Mongolia. Furthermore, we hope our results can help highlight the need for legislation and policies to increase ART accessibility and availability to patients in rural areas.

Strengths And Limitations
We used a population-based method to study infertility in 4 regions of Mongolia and the city Ulaanbaatar. The sample size and methods were rigorous for this study. We used only one de nition to determine infertility, which limited us to using strict inclusion criteria. We used a self-reporting method to assess infertility and this can be subject to bias.

Conclusions
In conclusion, the overall 12 months prevalence of infertility was 7.2% and primary and secondary infertility was 2.4% and 4.8%. Our study shows the most signi cant risk factors for infertility were: age, obesity alcohol consumption, rural living and having a low level of education. An unfavorable gynecological history also posed a risk to fertility. Occupational conditions, and monthly household income were not signi cant risk factors for infertility. Since this is the rst population-based study in Mongolia we were not able to measure trends in infertility prevalence but intend to do so in the future.  Figure 1 Infertility prevalence by region. Note: The designations employed and the presentation of the material on this map do not imply the expression of any opinion whatsoever on the part of Research Square concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. This map has been provided by the authors. Infertility prevalence by age

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