Genetic infertility: causes, diagnosis and treatment

By (gynecologist), (embryologist), (embryologist) and (psychologist).
Last Update: 01/26/2022

Genetic infertility is infertility caused by some alteration in the DNA sequence of the man or woman who is trying to have a child.

Depending on the type of genetic anomaly, it is possible to differentiate between:

numerical or structural alterations of the chromosomes.
Genetic mutations
defects in one or more genes.

Sometimes, prospective parents are not aware that they are carriers of a genetic disorder until they begin to have difficulties in achieving pregnancy.

Genetic male infertility

Although apparently, they do not show other symptoms that affect their health, men affected by or carrying a genetic pathology may suffer sterility.

In the following list, we will describe the most common causes of this genetic sterility in the male:

Klinefelter's syndrome
these males have an extra X chromosome (47,XXY). As a consequence, spermatogenesis is defective and they do not produce spermatozoa, being the most important genetic cause of secretory azoospermia.
Y chromosome microdeletions
this is a small loss of genetic material on the Y chromosome. The consequence of this is also a secretory azoospermia in the male.
Mutations in the cystic fibrosis gene (CFTR)
these defects give rise to the well-known congenital bilateral absence of the vas deferens. As a consequence, sperm cannot exit through the urethra with ejaculation and is the main genetic cause of obstructive azoospermia.

Thanks to assisted reproduction, these men have been able to have children by obtaining sperm from the testicle with a biopsy and performing in vitro fertilization (IVF). However, it should be noted that there is a risk of transmitting this genetic infertility to offspring.

Genetic alterations in spermatozoa

It is also possible that the man has no alteration in his genetic material, but his spermatozoa do. This would result in fertilization failure, implantation failure, or recurrent miscarriages.

The origin of these genetic faults lies in the process of sperm formation and maturation that occurs in the testes. It is possible that it may occur:

  • Sperm DNA fragmentation
  • Diploid spermatozoa (with two chromosomes instead of one)
  • Nullisomic spermatozoa (no genetic material)
  • Spermatozoa with structural abnormalities in chromosomes

Unfortunately, in the present, there are no techniques to separate genetically healthy spermatozoa from those with abnormalities in their DNA. Therefore, the only option for these couples is to resort to preimplantation genetic diagnosis (PGD) or donor sperm.

Genetic female infertility

In the case of females, the most relevant chromosomal disease-causing sterility is Turner syndrome. This disorder is due to the presence of a single-sex chromosome (45,X0).

Women with Turner syndrome have defined characteristics such as short stature or short neck, in addition to other fertility-related alterations, such as lack of sexual development, ovarian failure, absence of menstruation, etc.

However, there are females who present Turner syndrome in mosaicism. This means that some cells in your body are normal, while others are missing an X chromosome.

Women with mosaic Turner syndrome often find out about this condition when they have trouble conceiving and have genetic testing.

Other disorders that can cause female sterility of genetic origin are hereditary thrombophilias, such as mutation of the MTHFR gene. Defects in blood clotting can lead to repeated miscarriages.

Finally, as in the case of sperm, eggs can also carry numerical or structural chromosomal abnormalities caused in the process of meiosis.

Genetic alterations in the embryo

There is a possibility that, although the couple's eggs and sperm are healthy and free of genetic alterations, the embryos resulting from fertilization may not be viable.

During fertilization, the female nucleus of the egg must fuse with the male nucleus of the sperm, and the new chromosomal endowment of the embryo is established. Any error in this process will result in aneuploid embryos that cannot implant or if they do, will result in miscarriage or the birth of a sick baby.

The main cause of these genetic alterations in embryos is poor oocyte quality due to advanced maternal age.

How is genetic infertility diagnosed?

In most cases, genetic infertility is not diagnosed until more specific fertility tests are done. A simple seminogram, ultrasound or hormone analysis cannot detect genetic alterations.

Below, we will discuss the most common tests for genetic diagnosis of infertility.

Karyotype analysis

The karyotype refers to the set of chromosomes found within each cell. In the human species, the karyotype consists of 22 pairs of autosomal chromosomes and one pair of sex chromosomes that define the sex of the individual:


Therefore, karyotype analysis is used to study whether a person has the chromosomal load that corresponds to him or, on the other hand, presents some type of translocation, trisomy, monosomy, etc.

The karyotype is performed on both members of the couple and has an approximate cost of about 100-2000$. More and more fertility clinics are indicating the performance of a karyotype at the first visit to make a more personalized diagnosis.

FISH of spermatozoa

Fluorescent in situ hybridization or FISH is another technique used to analyze possible abnormalities in the number or structure of chromosomes.

As it can be performed on spermatozoa, this diagnostic test provides more information about the male's reproductive capacity.

The chromosomes analyzed are those most likely to be altered: 13, 18, 21, X, and Y, although in cases of recurrent miscarriages chromosomes 16 and 22 are also analyzed.

However, after analysis, these spermatozoa cannot be used in any assisted reproduction technique to achieve pregnancy, so it is not possible to select or separate viable spermatozoa from those with chromosomal alterations.

You will find all the information about this genetic test in the following post: FISH in spermatozoa.

Preimplantation genetic diagnosis

Preimplantation genetic diagnosis or PGD is a genetic analysis performed on the embryos resulting from the fertilization of the couple's eggs and sperm. Therefore, PGD is the only technique that ensures the pregnancy of a healthy baby, free of any genetic alteration coming from the parents.

To perform PGD, it is necessary for the couple to undergo in vitro fertilization (IVF) treatment and thus obtain the embryos in the laboratory. An embryo biopsy is then performed to collect one or more cells from each embryo, which will be analyzed.

Once the PGD results are obtained, genetically viable embryosare selected. This means that embryos that are genetically healthy will be transferred and embryos that have any aneuploidy or genetic mutation will be discarded.

If you want more information about this complimentary technique, you can read the following article: What is the preimplantation genetic diagnosis?

Prenatal tests

If there is a risk of having children with genetic pathologies and a PGD has not been performed to ensure a viable pregnancy, there are prenatal genetic tests that can be performed on the fetus during the course of gestation.

If the result of these prenatal tests is not favorable, the woman or couple will have to choose whether to terminate the pregnancy in order to avoid the birth of a sick baby.

The different types of prenatal genetic testing are as follows:

Fetal DNA blood test
this is a non-invasive prenatal test, since it analyzes the DNA of the fetus found in the maternal blood.
Chorionic biopsy
through an abdominal or vaginal puncture, a sample of the chorionic villi of the placenta is obtained to perform the genetic study.
amniotic fluid is obtained through an abdominal puncture and the fetal cells suspended in it are analyzed.

We recommend you to read the following article if you are interested in knowing more information about this topic: Types of prenatal diagnostic tests.

FAQs from users

Is it advisable to perform PGD whenever there is a risk of aneuploidy?

By Concha Leal Cariñena M.D. (gynecologist).

Yes, it is the only technique that allows embryos with normal chromosomal endowment to be transferred to the uterus, without chromosomal aneuploidy.

What is genetic counseling?

By Zaira Salvador B.Sc., M.Sc. (embryologist).

Genetic counseling or genetic counseling is a service to provide all the information and support to couples who suffer from or are at risk of transmitting a genetic disorder.

In the consultation, the geneticist analyzes all the family history of the patients and the genetic studies performed in order to be able to inform about the genetic risks that exist, as well as to recommend the most appropriate treatment in each case.

When is it necessary to perform a karyotype?

By Zaira Salvador B.Sc., M.Sc. (embryologist).

The karyotype is indicated in all couples who attend an assisted reproduction consultation due to infertility problems. However, there are clinics that only send it in the following cases:

  • Azoospermia
  • Severe oligozoospermia
  • Repeated implantation failures
  • Repeat abortions

In addition to everything discussed throughout this article, there are also hereditary genetic diseases that, although they do not cause sterility, prospective parents do not want to pass on to their children. Therefore, PGD will also be necessary to avoid these pathologies: What genetic or chromosomal diseases can PGD detect?

On the other hand, you can learn more about the tests that are performed during pregnancy in order to ensure the health of both the baby and the mother-to-be in the following article: Prenatal pregnancy control.

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Flannigan R, Schlegel PN. Genetic diagnostics of male infertility in clinical practice. Best Pract Res Clin Obstet Gynaecol. 2017 Oct;44:26-37.

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Hendriks S, Peeraer K, Bos H, Repping S, Dancet EAF. The importance of genetic parenthood for infertile men and women. Hum Reprod. 2017 Oct 1;32(10):2076-2087.

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FAQs from users: 'Is it advisable to perform PGD whenever there is a risk of aneuploidy?', 'What is genetic counseling?' and 'When is it necessary to perform a karyotype?'.

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Authors and contributors

 Concha Leal Cariñena
Concha Leal Cariñena
Bachelor's Degree in Medicine from the University of Zaragoza. She has an extensive career as a gynaecologist specialising in assisted reproduction and is also an associate lecturer in the Department of Surgery, Gynaecology and Obstetrics at the University of Zaragoza More information about Concha Leal Cariñena
License: 5008547
 Marta Barranquero Gómez
Marta Barranquero Gómez
B.Sc., M.Sc.
Graduated in Biochemistry and Biomedical Sciences by the University of Valencia (UV) and specialized in Assisted Reproduction by the University of Alcalá de Henares (UAH) in collaboration with Ginefiv and in Clinical Genetics by the University of Alcalá de Henares (UAH). More information about Marta Barranquero Gómez
License: 3316-CV
 Zaira Salvador
Zaira Salvador
B.Sc., M.Sc.
Bachelor's Degree in Biotechnology from the Technical University of Valencia (UPV). Biotechnology Degree from the National University of Ireland en Galway (NUIG) and embryologist specializing in Assisted Reproduction, with a Master's Degree in Biotechnology of Human Reproduction from the University of Valencia (UV) and the Valencian Infertility Institute (IVI) More information about Zaira Salvador
License: 3185-CV
Adapted into english by:
 Cristina  Algarra Goosman
Cristina Algarra Goosman
B.Sc., M.Sc.
Graduated in Psychology by the University of Valencia (UV) and specialized in Clinical Psychology by the European University Center and specific training in Infertility: Legal, Medical and Psychosocial Aspects by University of Valencia (UV) and ADEIT.
More information about Cristina Algarra Goosman
Member number: CV16874

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