Fluorescent in situ hybridization FISH: Alterations in Sperm Cells

By (gynecologist), (embryologist), (gynecologist), (gynecologist) and (biochemist).
Last Update: 11/27/2023

Fluorescent in situ hybridization (FISH) is a cytogenetic technique that consists of applying DNA probes specific to certain chromosomal regions. In the usual analysis, chromosomes 13, 18, 21, X and Y are evaluated. It is possible, however, to extend this study to other chromosomes.

The aim of this technique is to detect the chromosome endowment, i.e. the number of copies of each chromosome in the sperm. Thus, a normal result can be obtained or a pathological result with a greater probability of generating embryos with chromosomal alterations.

FISH is especially indicated in couples with repeated miscarriages or implantation failures and in men with low sperm quality. It is also recommended for men with an altered karyotype.

Errors in spermatogenesis

During the process of formation of sperm called spermatogenesis, errors can occur in some of the stages of meiosis. This meiosis is a process of cell division in that the number of chromosomes is divided in half and haploid sperm are obtained with 23 chromosomes. If this process does not occur properly, the chromosomes are not equally distributed and gametes with chromosomal abnormalities are generated.

Meiosis consists of a cell division process that involves two divisions, obtaining four daughter cells with a chromosomal endowment reduced by half. Therefore, haploid cells are generated with a single set of chromosomes.

Men may have a percentage of sperm with a number of chromosomes other than 23. However, if this percentage is within reference values, it will be considered normal. Normal sperm, since they have a better quality, are more likely to reach the egg and fertilize it.

On the contrary, if the percentage of sperm cells with numbers of chromosomes different to 23 surpass the reference values, there will be a greater risk of passing on chromosomal anomalies to their children.

Definition of FISH

Fluorescent in situ hybridization or FISH is a cytogenetic analysis technique based on the use of fluorescent DNA probes. Its purpose is the study of some specific chromosomes of the spermatozoa. These chromosomes are found inside the nucleus at the head of the sperm and are at the interface, i.e. the phase of the cell cycle in which the chromosomes are not compacted.

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This is a diagnostic test where the tube marked with fluorescence must hybridize with the sperm DNA. Therefore, this test provides important information on the seminal quality of the male, beyond the concentration, mobility and morphology of the spermatozoa, since it analyzes their genetic content.

In addition, the usual chromosomes that are analyzed with the FISH technique are 13, 18, 21, X and Y, because they are more likely to have abnormalities.

FISH allows us to determine the percentage of spermatozoa with chromosomal alterations in the male semen. Such alterations pose a risk of producing embryos carrying chromosomal alterations, which will have a low probability of implanting and a high miscarriage rate.

As Dr Sergio Rogel, an OB/GYN specialising in assisted reproduction, tell us:

The aim of FISH of sperm cells is to evulate the percentage of normal spermatazoa, genetically speaking. To perform this analysis we need a sufficient number of sperm cells.

Then by looking at one chromosome in particular, we ensure that the sperm only have one copy of this particular chromosome. Thus ensuring the correct genetic complement of the sperm, that it is not too little or too much.

Step-by-step process for FISH

As already above mentioned, the FISH technique consists of carrying out an indirect analysis of the chromosomal content in the interphase nucleus of the spermatozoa.

For this, the patient must obtain a semen sample with a minimum abstinence of 2 days, which will be delivered to the laboratory for analysis.

The FISH procedure performed in the laboratory is divided into several stages:

1. Fixation of the spermatozoa, preparation of a dilution and extension on a slide.

2. Chromatin decondensation due to the small size of the sperm head and the compaction of the chromatin inside the nucleus. This is the substance that is located in the nucleus of cells forming the chromosomal material during the interphase. It consists of DNA and proteins.

3. Denaturation and hybridization with specific probes for each chromosome to be studied. The most commonly used probes are for the visualization of chromosomes 13, 18, 21, X and Y.

4. Chromatin detection.

5. Visualization and interpretation of hybridization signals by comparing the results with the values of samples from a control population. The visualization is carried out with a fluorescence microscope and the signal of a large number of sperm is observed. Normal sperm are those with a single fluorescent signal for each chromosome analysed.

When to perform FISH

In a male fertility study it is not common to routinely perform FISH on sperm. This test is usually requested when there are previous implantation failures, repeated miscarriages or when there is a suspicion that the genetic content of the sperm is altered.

Other cases where FISH is also recommended for male sperm are the following:

  • Patients undergoing oncological treatment.
  • Previous pregnancy with some chromosomal alteration.
  • Alterations in the karyotype.
  • Sterility of unknown origin.
  • Advanced age.

In addition, FISH is recommended in males with seminal alterations such as, for example, oligozoospermia, asthenozoospermia and/or teratozoospermia.

Treatments after a pathological FISH

Once the result is obtained, the patient is given error rates in the meiosis of their sperm. If these rates are within normal range, FISH indicates that the man has sperm with a normal genetic content in his ejaculate.

If, on the other hand, some alteration is observed that indicates a greater proportion of spermatozoa with a certain chromosomal alteration, it would be advisable to resort to some of the following options:

  • Perform a preimplantation genetic diagnosis (PGD) to check that the embryo does not present alterations and perform the embryo transfer with those who have a greater probability of implanting and evolving, since they are genetically normal.
  • Make a prenatal diagnosis in case of gestation.
  • Use a treatment with donor sperm in cases of very serious alterations.

Therefore, the FISH technique is not a sperm selection method but a diagnostic test that helps to choose the best reproductive option based on the results obtained

FAQs from users

What is sperm FISH?

By Blanca Paraíso M.D., Ph.D., M.Sc. (gynecologist).

FISH is a cytogenetic analysis technique that allows the identification of sperm chromosomes in an ejaculate or testicular biopsy sample. It determines the chromosomal endowment, expressing the percentage of spermatozoa that present alterations.

Usually 5 chromosomes are analyzed, 13, 18, 21, X and Y, as they are the most frequently affected chromosomes that can give rise to viable gestations. However, this study can be extended to other chromosomes.

Are sperm fragmentation test and FISH the same thing?

By Mónica Aura Masip M.D., M.Sc. (gynecologist).

No. These are two diagnostic tests that are performed on the male to complete the male fertility workup, but they are not routine tests.
Read more

In which patients is sperm FISH indicated?

By Blanca Paraíso M.D., Ph.D., M.Sc. (gynecologist).

Multiple indications have been proposed for performing sperm FISH, including repeated miscarriages, implantation failure, advanced paternal age, history of chemotherapy treatment, seminal alterations, infertility of unknown origin, genetic anomalies, etc. However, not all of them are linked to a high percentage of patients with an altered FISH.
Read more

What consequences can be expected after a pathological FISH?

By Marta Barranquero Gómez B.Sc., M.Sc. (embryologist).

The consequences that can be expected after a pathological FISH result are a lower implantation rate, a lower gestation rate, a higher abortion rate, and an increased risk of malformation.

Are there strict evaluation criterias in FISH testing?

By Marta Barranquero Gómez B.Sc., M.Sc. (embryologist).

Yes, in sperm FISH defined and not superimposed contours must be evaluated and all hybridization signals must be perfectly located inside the nucleus.

In addition, in cases where more than one signal is detected for each chromosome analysed, all signals must be of equal intensity.

What is the price of the FISH technique?

By Marta Barranquero Gómez B.Sc., M.Sc. (embryologist).

The price to perform a FISH depends on each clinic or center, but is usually around 200-300 euros.

If you want to learn more about the process of sperm formation, you can visit the following article: How are sperm cells formed?

We also have mentioned that a possible solution would be to carry out a PGD. You can read more about this here: What is PGD used for?

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References

Kowalski RK, Cejko BI. Sperm quality in fish: Determinants and affecting factors. Theriogenology. 2019 Sep 1;135:94-108. doi: 10.1016/j.theriogenology.2019.06.009 (View)

Rodrigo L, Meseguer M, Mateu E, Mercader A, Peinado V, Bori L, Campos-Galindo I, Milán M, García-Herrero S, Simón C, Rubio C. Sperm chromosomal abnormalities and their contribution to human embryo aneuploidy. Biol Reprod. 2019 Jul 18. pii: ioz125. doi: 10.1093/biolre/ioz125 (View)

Salvarci A, Zamani A. Evaluation of sexual function and micro- testicular sperm extraction in men with mosaic Turner syndrome. Natl Med J India. 2018 Sep-Oct;31(5):274-278. doi: 10.4103/0970-258X.261196 (View)

Sarrate et al. The use of fluorescence in situ hybridization analysis on sperm: indications to perform and assisted reproduction technology outcomes. J AssistReprod Genet. 2019 Aug 8. doi: 10.1007/s10815-019-01554-2 (View)

FAQs from users: 'What is sperm FISH?', 'Are sperm fragmentation test and FISH the same thing?', 'In which patients is sperm FISH indicated?', 'What consequences can be expected after a pathological FISH?', 'Are there strict evaluation criterias in FISH testing?' and 'What is the price of the FISH technique?'.

Read more

Authors and contributors

 Blanca Paraíso
Blanca Paraíso
M.D., Ph.D., M.Sc.
Gynecologist
Bachelor's Degree in Medicine and Ph.D from the Complutense University of Madrid (UCM). Postgraduate Course in Statistics of Health Sciences. Doctor specialized in Obstetrics & Gynecology, and Assisted Procreation. More information about Blanca Paraíso
License: 454505579
 Marta Barranquero Gómez
Marta Barranquero Gómez
B.Sc., M.Sc.
Embryologist
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
 Mónica  Aura Masip
Mónica Aura Masip
M.D., M.Sc.
Gynecologist
Dr. Mónica Aura has a degree in Medicine and General Surgery from the Autonomous University of Barcelona (UAB). She is also a specialist in Gynecology and Obstetrics from the Hospital de Santa Creu y Sant Pau and has a Master's degree in Human Assisted Reproduction from the University Juan Carlos I of Madrid and another in Health Center Management from the UB. More information about Mónica Aura Masip
Licence number: 31588
 Sergio Rogel Cayetano
Sergio Rogel Cayetano
M.D.
Gynecologist
Bachelor's Degree in Medicine from the Miguel Hernández University of Elche. Specialist in Obstetrics & Gynecology via M. I. R. at Hospital General de Alicante. He become an expert in Reproductive Medicine by working at different clinics of Alicante and Murcia, in Spain, until he joined the medical team of IVF Spain back in 2011. More information about Sergio Rogel Cayetano
License: 03-0309100
Adapted into english by:
 Michelle Lorraine Embleton
Michelle Lorraine Embleton
B.Sc. Ph.D.
Biochemist
PhD in Biochemistry, University of Bristol, UK, specialising in DNA : protein intereactions. BSc honours degree in Molecular Biology, Univerisity of Bristol. Translation and editing of scientific and medical literature.
More information about Michelle Lorraine Embleton

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