Causes and Treatment of Infertility

Term Paper, 2020

47 Pages, Grade: c



List of Tables


1.1 Background of Infertility
1.2 Main causes of infertility
1.3 Constraints with Infertility
1.4 Genetics of human Male Infertility
1.5 Genetics of human Female Infertility

Aim of the Research

3.1 Search strategy and identification of studies
3.1.1 Other resources
3.2 Criteria for considering studies for this review
3.2.1 Inclusion Criteria
3.2.2 Exclusion Criteria

4.1 Screening of Articles
4.2 Findings from MEDLINE Website
4.3 Findings from UM (University of Michigan) LIBRARY DATABASE
4.4 Findings from Cochrane Library
4.5 Findings from AGORA Website
4.6 Discussion



List of Figures

List of Tables

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Infertility is a qualification of a situation where couple has tried to achieve pregnancy for more than one year without success. The basic work-up doesn’t find a reason for the failure in more than 30 percent cases. Many of the defects related to infertility is still unknown. The aim of this research was to perform a systematic review of literature to determine the causes and treatment aspects. This review also aimed to interpret the findings in the context of recent clinical practices and suggest optimal treatment and management aspects regarding this infertility. A comprehensive review where the literature was searched for causes and treatment of infertility/subfertility” at library website of University by using a cross-search of different medical databases besides the relevant printed medical articles, journals, periodicals and book chapters. MEDLINE, UM Library including EMBASE, AGORA, Cochrane database of systematic reviews were searched for relevant publications in between 1970 to 2020. In this review process, total 15 articles were included related to infertility. The outcomes of this review highlight on the criteria used to define infertility and causes of infertility in male and female. This review focused on different factors including ovulatory factor, utero-tubal peritoneal factor, semen migration factor and male factor. More than 40% cases of infertile couples exhibit a combination of factors and nearly 15% cases may not display any specific factors. Some of these infertile conditions treated as unexplained infertility problems in some extent. This review process deploys a new strategy to translate the recent research findings and evidence-based causes into a simplified focused cause of male and female infertility. The development of molecular biology and biotechnology as well as genetics has profound influence on infertility study on causes, assessment and treatment process.

Keywords: Infertility, genetics, causes, treatment, management



1.1 Background of Infertility

Infertility is a disease in reproductive system which encompasses a wide range of circumstances that affects the ability of an individual to reproduce naturally (Yatsenko and Rajkovic, 2019). It is also a graver concern affecting the lifestyle and status of the couples. The World Health Organization (WHO) defines the infertility as the incapability to conceive after 12 months of regular unprotected intercourse of a couple (Faraj et al., 2016). Regular sexual intercourse is taken to mean every 2-3 days (NICE, 2013). For every 100 couples who are trying to conceive naturally, 84 will conceive within 12 months, 92 will conceive within 24 months and 93 will conceive within the 36 months, the likelihood of pregnancy occurring within the next is 25% or less (NHS Choices, 2014). Researchers confirms that, male are to be responsible either fully or partially for 35-40% cases, whereas female are responsible for nearly 35-40% and the remaining 20-30% is the combined factors and unexplained cases (Orbiclinic, 2011).

A diagnosis of Infertility defined as the inability of a couple to conceive naturally after 12 months of regular unprotected sexual intercourse (Kamal, 2010; Anwar and Anwar, 2016). It is a common occurrence in clinical difficulties which affects 13% to 15% of couples worldwide (WHO, 1983). In developing countries due to the limited investigational resource and treatment the occurrence varies widely in comparison with the developed countries (Cates et al., 1985). In the United Kingdom, approximately 17% couples have infertility issues (Zargar et al., 1997).

In addition, subfertility generally describes any form of reduced fertility with prolonged time of unwanted non-conception. The major factor affecting the individuals spontaneously pregnancy prospect is the time of unwanted non-conception which specify the grading of infertility. Most of the pregnancy occurs during the first six cycles with intercourse of the fertile phases (80%). Then, acute subfertility must be assumed in every second couple (10%) although after 12 unsuccessful cycles untreated live birth rates are nearly 55% in the next 36 months among these couples. In addition, nearly 5% couples are definitive infertile with no chance of spontaneous pregnancies in the upcoming future. The cumulative probabilities of conception decline because heterogeneity in fecundity increases due to higher proportion of infertile couples. The couples have unexplained infertility need to encourage waiting because even with treatment they do not have better chance of conceiving (Gnoth et al., 2005)

Table 1 Published definitions by different organizations and scientists

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aZegers-Hochschild et al., 2009; b PCASRM, 2008; cNICE guideline (UK), 2004;d Larsen, 2005.

1.2 Main causes of infertility

The main causes of infertility issues in couples can be triggered by the factors associated with the men, women or both. Statistics show a same frequency, with 30% of the cases having a male origin, and another 30% occur due to female factors. The remaining 20% occurs for combined causes and 20% due to unexplained causes (Fig. 01). The combined or mixed infertility causes mean that both partners are responsible for this situation, while the unexplained cases refers to the impossibility of the cause to be detected in spite of running the specific medical information or tests (Rodrigo et al., 2019).

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Figure 1 The main causes of male and female infertility (Rodrigo et al., 2019)1

The term infertility and sterility refer to the inability to have any offspring. Although these two terms often used synonymously, but their inherit meaning is not exactly the same. On the other hand, subfertility is defined as the condition of being capable of conceiving, yet less fertile than normal. The basic difference between being infertile and being sterile lie in the precise moment when the issue prevents pregnancy. A sub fertile couple is not infertile, but can find conception in more difficult way. The term subfertility defined as the inability to achieve pregnant due to the fusion between the egg and the sperm where fertilization never occurs. Infertility is the inability to carry a pregnancy due to fertilization problems that already taken place. In this case, egg sperm binding does occur, but the resulting embryo is unable to implant or cannot develop till the end of the pregnancy (Fig. 02).

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Figure 2 Difference between sterility and infertility (Rodrigo et al., 2019)2

The purpose of having a baby cannot be fulfilled in all these cases. The chance of having a baby is a little bit higher in infertility than in cases of sterility. The concept of sterility and infertility can be split into two different types as primary and secondary cases. Primary sterility defied as the couple whose gametes have never been able to cause a pregnancy whereas, secondary refers as a couple have been able to have children previously, but conception does not occur in further cases. On the other hand, the primary infertility occurs when a couple never achieved a full-term pregnancy whilst, the secondary refers as a couple have already had a child, but unable to achieve another full-term pregnancy. In addition, by the term subfertility refers to a couple being unable to achieve a successful pregnancy, but with more difficulty faced by the female partner (Fig. 03) (Rodrigo et al., 2019).

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Figure 3 The difference between the infertility and subfertility issues. (Rodrigo et al., 2019)3

1.3 Constraints with Infertility

Infertility is considered not only as a problem affecting the couple’s life but also a problem influencing social environment (Whitman et al., 2001). Depressions, humiliation, guilt, grief, inadequacy with social isolation are the feelings experienced by the infertile couple (Irvine, 2004). Genetic, endocrine, physiological, anatomical, and immunological abnormalities and factors of the reproductive system can affect the woman’s likelihood of becoming pregnant (Yatsenko and Rajkovic, 2019). The causes of infertility vary from one region to another region on the basis of etiology associated with reproductive behaviors, such as age at marriage, environmental pollution, smoking, alcohol abuse, changing in life style, and diet (Macaluso et al., 2010).

In developing countries, pattern of infertility is quite different from those in developed countries. Many cases of infertility require sophisticated and expensive treatment and management procedure. Therefore, addressing the infertility issue appears to be one of the priority tasks in this middle-developing country. In general, the major focuses of infertility in the past have been the female partners. But, the chance of infertility is same in male and female cases. There are more than three million couples in Bangladesh are infertile and increasing the rate rapidly due to various reasons. Unfortunately, female partners are mostly blamed albeit husbands are responsible for 60% cases (Bashed et al., 2012).

There are ample of literature can be found on the issues on human infertility, women or men infertility, causes of these infertile conditions and treatment process of different infertility issues (Yatsenko and Rajkovic, 2019; Allam et al., 2019; Faraj et al., 2016; Leaver, 2016; Gurunath et al., 2011). However, infertility studies are rather new and few scientific literatures are available in Bangladesh (Nahar, 2010, 2012; Nahar and Richters, 2011; Bashed et al., 2012; Sultana et al., 2014; Hosen et al., 2015).

1.4 Genetics of human Male Infertility

The multifactorial complex disease with highly heterogeneous phenotypic demonstration called as male infertility. At least fifteen percent cases related to known genetic disorders including both chromosomal and single gene alterations. In about forty percent cases of primary testicular failure, the etiology remains unknown and a portion caused by unidentified genetic anomalies. There is rare variant burden in men with impaired spermatogenesis (Krausz et al., 2015). The causes are known in less than fifty percent cases whereas, the major factor includes as genetic or inherited disease and specific abnormalities in the Y-chromosome. The innovation of molecular technologies has provided profound insight into the genetics of the male infertility. Yet, the understanding of the male genetic causes remains limited in some extent (Poongothai et al., 2009).

1.5 Genetics of human Female Infertility

The female reproduction system is regulated by a large number of genes which are essential for differentiation of highly specialized cells, complex intra- and intercellular signing and dynamic tissue specific and organ specific interactions among hypothalamus, pituitary and the reproductive tract etc. (Yatsenko and Rajkovic, 2019). The ovarian functions depend on transcription of genes and controlled by the non-coding regulatory DNA sequences (Dangle et al., 2017; Portnoi et al., 2018; Verdin et al., 2013), microRNAs (Zaho and Rajkovic, 2008; Ahn et al., 2010; Sirotkin et al., 2010), and small non-coding RNA molecules (Sirotkin, 2010). This ovarian dysgenesis and primary ovarian insufficiently are the outcomes of homozygous or biallelic pathogenic variants. The polygenic inheritance may responsible for developmental failure in embryos or incompetence of an embryo or fetus to develop postfertilization due to biparental polygenic problem (Yatsenko and Rajkovic, 2019).

The frequent cause of ovarian dysgenesis is the large X chromosome. A simple phenotype manifesting and reduced fetal viability can be seen in females with balanced rearrangements, submicroscopic alternations, and single gene defects. The reproductive potentiality with genomic alterations and syndrome conditions greatly depends on diagnosis, genes affected and concomitant manifestations (Yatsenko and Rajkovic, 2019). Different causative genes are displayed beneath the key biological process affecting several stage of oocyte developments


Aim of the Research

The objective of this research was to perform a systematic review of literature to determine the criteria used to define the infertility assessing the causes and management issues. In addition, this study aimed to interpret the findings in the context of recent clinical practices and suggest optimal treatment and management aspects regarding this infertility.



3.1 Search strategy and identification of studies

The systematic review on the observational studies of the infertility/sterility/subfertility including the causes and treatment aspects were followed. This review aimed to identify the prevalence and management issues of infertility. Owing to the nature of this research question, this review expected to identify the causes and the management aspects related with the infertility. The following electronic resource and database were investigated during this systematic review for relevant population-based prevalence research from 1970 to 2020.

MEDLINE (PubMed including Medline) ( - Medical Literature Analysis and Retrieval System Online,

UM Library including EMBASE ( -,

Cochrane library (,


This comprehensive review deploys a new strategy to convert the research findings and evidence-base recommendations into the simplified focused guide. This aim of this approach is to disseminate the causes of infertility. To perform this review, the literature was searched for the keywords of “infertility”, “sterility”, “subfertility”, “causes of infertility”, “causes of subfertility”, “management of infertility”, “treatment of infertility”, “management of subfertility”, “treatment of subfertility” at some library website of AGORA-research life by using a cross-search of different medical databases such as BIOSIS Previews on Web of Knowledge and Web of Science, in addition to the relevant printed, open-access and paid medical journals, articles and periodicals.

The available and reliable infertility cause with treatment and management aspects retrieved from the best evidence reviews including the America College of Obstetricians and Gynecologists (ACOG, American Society for Reproductive Medicine (ASRM-, Canadian Fertility and Andrology Society (CFAS-, European Society of Human Reproduction and Embryology (ESHRE-, Human Fertilization and Embryology Authority (HFEA-, Royal College of Obstetricians and Gynecologists (RCOG- and the World Health Organization (WHO- followed by Kamel, 2010.

3.1.1 Other resources

Science-direct website, Wiley online and Google scholar were also searched using the earlier mentioned search terms. Conference proceeding of the American Society of Reproductive Medicine (ASRM) and the European Society of Human Reproduction and Embryology were also done during this review process


1 Rodrigo, Andrea, et al. “What’s the Difference between Infertility, Sterility & Subfertility?” Digital image. InviTRA,

2 Rodrigo, Andrea, et al. “What’s the Difference between Infertility, Sterility & Subfertility?” Digital image. InviTRA,

3 Rodrigo, Andrea, et al. “What’s the Difference between Infertility, Sterility & Subfertility?” Digital image. InviTRA,

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Causes and Treatment of Infertility
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causes, treatment, infertility, male factor, female factor
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Marzina Ajrin (Author)Priyanka Debnath (Author), 2020, Causes and Treatment of Infertility, Munich, GRIN Verlag,


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