According to World Health Organisation (WHO) , Infertility is a disease of the reproductive systemdefined by the failure to achieve a clinical pregnancy after 12 months or more of regularun protected sexual intercourse. There are multiple factors which can contribute to infertility like hormonal, related to age, obesity or infectious disease ; it can be immunological, psychological, result from surgery or blockage, or be associated with defined abnormalities in gametes. Also there are various known genetic alterations that causes infertility like chromosomal aberrations, single gene variants and phenotypes with multifactorial inheritance. Genetic association studies are performed to identify and characterize natural variants or polymorphisms within genes that might be associated with fertility phenotypes. Chromosomal aberrations can be identified using karyotypingand fluorescence in situ hybridization analysis whereas sequencing methods can be used to identify gene mutations.


Female infertility is defined as the inability to conceive naturally or to carry a pregnancy to full term. Female infertility can be caused by genetic, hormonal or environmental factors.

Polycystic ovarian syndrome (PCOS)

is a complex and heterogeneous endocrine disorder. Aside of obesity and type 2 diabetes mellitus common symptoms of PCOS is irregular menstruation ,polycystic ovaries, secondary amenorrhea, hirsutism and reduced fertility due to oversized and dysfunctional follicles. Several genetic variants have been reported that shows relationship with PCOS , studies of multiple candidate gene including StAR , CYP11A , P450 17α- hydroxylase/ 17,20- desmolase), HSD17B1–3 ACTR1 , ACTR2A–B , FS (follistatin), INHA (inhibin alpha), INHC (inhibin C),LHCGR (luteinizing hormone/chorionic gonadotropin receptor), FSHR (folliclestimulating hormone receptor), MADH4, AR (androgen receptor), MC4R (melanocortin 4 receptor), OB (leptin), OBR (leptin receptor), POMC (pro-opiomelanocortin), UCP2+3 (uncoupling proteins 2 + 3), IGF1R (insulin-like growth factor receptor I), IGFBPI1+3 (insulin-like growth factor binding proteins 1 + 3), IR (insulin receptor), INSL (Leydig insulin-like protein) and PPARG (Jakubowski et al., 2005) . A direct relationship of INSR gene and and PCOS has been found in Chinese population which identified 3 additional PCOS loci i.e 2p16.3, 2p21,9q33.3.

Primary ovarian failure (POF)

also known as primary ovarian insufficiency (POI) is defined as either complete or incomplete failure of ovarian function. General symptoms of POF are amenorrhea due to hyperestrogenism, elevated gonadotrophin levels and other menopause related symptoms. There are number of genes which show relationship with POF /POI. X-linked genes includes FMR1 and bone morphogenic protein 15 (BMP15) located at Xp11.2 region. Several other genes have been studied in POF patients, and mutation in FSH, INHA, FOXO3A(forkhead boxO3),FOXL2 (Fork head box L2) has ben shown to cause POF.


is a complex disease characterised by inflammation and bleeding of the endometrium. Often there is infertility and pain due to endometrial tissue in the pelvic region
outside of the uterus. A number of genes have been studied for their association with endometriosis includes glutathione S-transferase (GST) and the cytochrome P450 (CYP) gene families which have been investigated for association with endometriosis.


also known as fibroids, are benign tumours found in myometrium (smooth muscle layer) of uterus. The common symptoms of leiomyomas is irregular bleeding and pain. In terms of estrogen and progesterone concentration, both the estrogen receptors (ER’s) (at 6q25.1 and 14q) and progesterone receptors (PR’s) (at 11q22) were greater in leiomyomata than the myometrium. X inactivation studies in term of leiomyomas have revealed that inactivation of one X-chromosome in normal female cells, have demonstrated that leiomyomas develop as clonal lesions. X-chromosomelinked phospho glycerokinase (PGK) showed that all studied leiomyomas had a single type of inactive allele and were of unicellular origin but independently generated in the uterus.


There are many factors that contributes to male infertility including irregular sperm production , functioning of undescended testicles, genetic abnormalities, psychological or health issues like diabetes, infections (gonorrhea, HIV) and some unexplained reasons. Genetic abnormalities like cystic fibrosis, absence of vas deferens , the androgen insensitivity syndrome and spermatogenic damage may result into infertility. According to WHO , Spermatogenic failure or defects often referred as azoospermia , oligospermia , teratospermia , asthenozoospermia. Azoospermia is a medical condition of a man whose seminal fluid lacks sperms produced during orgasm. The sex chromosome (Y) consists of (Yp) and (Yq) arms. In the Y chromosome, Yq microdeletions are detected with spermatogenic
failure. Three azoospermia factor (AZF) regions (AZFa, AZFb, and AZFc) are defined on Yq11. However, deletions of AZF regions are caused by non allelic homologous recombination.

Cystic Fibrosis

is caused by unusual secretions of lungs, pancreas, intestines and liver. These abnormal secretions results in the formation of plugs that obstruct the ductal lumens in organs, which leads to dilatations, frequent infections, and fibrosis. This abnormality is caused due to mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes for chloride channel protein. Even though, the role of CFTR is essential in both males and females. The presence of CFTR gene is necessary for sperm maturation in the epididymis, as it is necessary for fluid absorption and the facilitation of sperm capacitation for fertilization ability. Patients with CF, testicular histology indicates normal spermatogenesis, exhibit impaired spermatogenesis, and such impairment may be attributed to the role of the CFTR protein in gametogenesis , abnormal sperm morphology has also been described and attributed as defective spermiogensis due to a lack of CFTR protein, which is also expressed in spermatozoa.

Globozoospermia or Teratozoospermia

is characterized by round-headed acrosomeless sperm, which is a rare and severe form of teratozoospermia. Two DPY19L2 heterozygous deletions and three point mutations are the main cause of globozoospermia and indicating that DPY19L2 gene signals the protein which is responsible for making the sperm cells.

Klinefelter syndrome (KS) , 47 (XXY)

,this medical condition of Hypogonadism is a disorder of males born with extra X chromosome instead of XY chromosomes. The failure of chromosome to separate at anaphase during meiosis I, meiosis II or mitosis giving rise to cells with an aberrant number of chromosomes. Hypogonadism doesn’t show any symptoms until onset of puberty. However , there are prevalent symptoms like delayed puberty , loss of lobido, that indicates that the male is born with Klinefelter syndrome.

Androgen insensitivity syndrome (AI)

is a condition that affects sexual development during puberty. Males with this condition are genetically male(XY sex chromosomes). But , because their bodies do not respond to sex hormone called androgens, they mostly acquire female external sex characters. This medical condition is inherited in an X-linked recessive pattern , if the mutated gene causing this disorder is located on the X chromosome. In genetic males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In genetic females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. Thus, due to this unusual gene binding and response to the specific hormone , males with this syndromes are infertile.


Karyotyping , In case of females, three most common classes of abnormalities are 45X, trisomy and polyploidy ; the risk of occurrence increases with maternal age. These type of chromosomal aberrations significantly impact fertility and the risk to miscarriage , therefore karyotype analysis is always advisable. However , in case of male infertility, microdeletions of Y chromosome can only be seen with fluorescent in situ hybridisation (FISH).

Expanded carrier screening (ECS)

is the practice of screening all individuals from dozens to hundreds of diseases, some with lower frequencies to some with high severity grades. The main objective of ECS in individual/couples is to inform them about possible genetic disease risk for their future offsprings and their possible reproductive options in order to foster autonomous reproductive choices.

Preimplantation genetic

testing is a screening test for numerical chromosome abnormalities (aneuploidy) within the embryos resulting from parents with a chromosomal composition presumed to be normal. Most common indication for PG testing are recurrent miscarriages and abortions, advanced maternal age repeat implantation failure and several male factor.

Non invasive prenatal testing

involves analysing the cell-free foetal DNA (cffDNA) present in a sample of maternal blood to determine the likelihood of a foetal aneuploidy.


In most of the cases problems related to reproductive systems remains undiscovered until diagnosed. It has been explained that there are many genetic factors that leads to infertility in both males and females. Female factors like Polycystic ovarian syndrome (PCOS), primary ovarian failure (POF) , endometriosis , leiomyomas and Male factors like Androgen insensitivity syndrome (AI) , spermatogenic failure , cystic fibrosis , globozoospermia , Klinefelter syndrome (KS). However , these genetic alterations directly effects the fertility of the couple. Furthermore , these genetic factors can be considered as beneficial tool for studying the genetic screening of ART patients to direct the fertility treatment through various processes like Karyotyping , Preimplantation genetic testing and non invasive prenatal testing.

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