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Condition

Globozoospermia

Globozoospermia is a rare, severe sperm morphology disorder in which sperm have abnormally round heads and lack a normal acrosome, the structure needed for normal interaction with and activation of the egg. It is an important genetic cause of male infertility and is commonly associated with fertilization failure, even when sperm count and motility are otherwise relatively preserved.

Also known as: Round-headed sperm syndrome, Round head sperm syndrome, Round-headed spermatozoa, Acrosomeless sperm syndrome, Acrosome-deficient sperm, Globozoospermia syndrome, Total globozoospermia, Complete globozoospermia, Partial globozoospermia, Round sperm heads

Symptoms8 listed
ICD-10N46.9
TreatableYes
DE
Medically reviewed by Dr. Elif Yılmaz, MD, FECSM
Last reviewed 23 August 2026
✓ Clinician reviewed
Globozoospermia✓ Clinician-reviewed information
Key takeaways
  • Globozoospermia is a rare sperm morphology disorder characterized by round-headed sperm with an absent or severely abnormal acrosome.
  • It accounts for less than approximately 0.1% of male infertility cases.
  • Genetic abnormalities are common, particularly involving the DPY19L2 gene.
  • The absence of the acrosome and abnormalities in sperm-mediated oocyte activation can cause severe fertilization failure.
  • IVF with ICSI is usually required, and assisted oocyte activation may be considered in carefully selected cases, although evidence and safety considerations should be discussed with an experienced reproductive medicine team.

Overview

Globozoospermia is a rare and severe form of teratozoospermia, meaning that sperm have a characteristic structural abnormality.

The classic sperm cell normally has an oval-shaped head containing:

  • The paternal genetic material

  • A specialized structure called the acrosome

The acrosome forms a cap over the front portion of the sperm head and contains proteins involved in normal fertilization.

In globozoospermia, the sperm head becomes characteristically:

  • Round

  • Acrosome-deficient

  • Structurally abnormal

The WHO laboratory manual specifically describes globozoospermia as the round-head defect caused by failure of normal acrosome development.

What is the acrosome?

The acrosome is a specialized organelle that develops over the head of a mature sperm.

It contributes to the sperm's ability to interact with and penetrate the structures surrounding the egg.

Sperm affected by globozoospermia either:

  • Completely lack an acrosome

  • Have severe acrosomal hypoplasia or malformation

The abnormality therefore affects much more than appearance.

It can directly interfere with fertilization.

Why does globozoospermia cause infertility?

Several mechanisms may contribute.

Failure of normal egg penetration

Acrosome-deficient sperm cannot interact normally with the zona pellucida surrounding the oocyte.

This makes conventional fertilization extremely difficult.

Oocyte activation deficiency

Even when ICSI bypasses the need for the sperm to penetrate the egg naturally, fertilization may still fail.

One reason is that globozoospermic sperm may have reduced levels or abnormal localization of proteins involved in activating the oocyte after sperm injection.

An important example is phospholipase C zeta (PLCζ).

Oocyte activation failure is a major reason why conventional ICSI alone can produce poor fertilization in some globozoospermic patients.

Is globozoospermia genetic?

Very often.

Globozoospermia is considered a genetically heterogeneous disorder, meaning several different genes may cause a similar sperm phenotype.

The most important gene is:

DPY19L2

DPY19L2 abnormalities are among the most frequently identified genetic causes of complete globozoospermia.

Other genes reported in association with the condition include:

  • SPATA16

  • PICK1

  • GGN

  • SPACA1

  • ZPBP

  • CCDC62

  • CCNB3

and additional candidate genes continue to be investigated.

A systematic review therefore recommends considering genetic evaluation as part of the clinical assessment of affected men.

What does DPY19L2 do?

DPY19L2 plays an important role during sperm-head development.

During normal spermiogenesis, the developing acrosome must remain attached to the sperm nucleus.

Loss of normal DPY19L2 function interferes with this process, resulting in:

  • Acrosome loss

  • Failure of normal sperm-head elongation

  • Round-headed sperm

Large deletions or pathogenic variants affecting DPY19L2 have been identified in many men with complete globozoospermia.

Types of globozoospermia

Complete Globozoospermia
Complete or total globozoospermia is the classic and most severe form. Virtually 100% of sperm have round heads and lack a normal acrosome.
Partial Globozoospermia
Only a proportion of sperm demonstrate the characteristic round-headed/acrosomal abnormality. Other sperm may show more normal morphology or partial acrosomal development.
DPY19L2-Associated Globozoospermia
A pathogenic deletion or variant affecting the DPY19L2 gene is identified. This is one of the best-characterized genetic forms.
Non-DPY19L2 Globozoospermia
No pathogenic DPY19L2 abnormality is detected. Other genetic causes may be involved, including variants affecting SPATA16, PICK1, and additional genes involved in sperm-head and acrosome development.
How common is it?
Globozoospermia is extremely rare and is estimated to account for less than 0.1% of male infertility cases.
Source: pubmed.ncbi.nlm.nih.gov

Symptoms

Difficulty conceiving
Abnormal sperm morphology
Round-headed sperm on semen analysis
Absence of normal acrosomes
Fertilization failure during IVF
Low fertilization after conventional ICSI
Repeated assisted-reproduction failure in some couples
Associated abnormalities in sperm motility or DNA integrity in some patients

Causes

DPY19L2 deletion
Other pathogenic DPY19L2 variants
SPATA16 mutations
PICK1 mutations
GGN abnormalities
SPACA1 abnormalities
ZPBP abnormalities
CCDC62 abnormalities
CCNB3 abnormalities
Other genetic defects affecting acrosome formation
Abnormal spermiogenesis
Defective sperm-head remodeling

Risk factors

Family history of severe male infertility
Consanguinity in some genetic pedigrees
Known pathogenic variants affecting sperm development
Previous semen analysis demonstrating monomorphic round-headed sperm
Previous unexplained total fertilization failure
Previous ICSI failure associated with oocyte activation deficiency

How it is diagnosed

Diagnosis begins with a carefully performed semen analysis and detailed sperm morphology assessment.

Semen analysis

Standard semen analysis evaluates:

  • Sperm concentration

  • Total sperm count

  • Motility

  • Morphology

  • Vitality when appropriate

In globozoospermia, the characteristic finding is a high proportion of sperm with:

  • Round heads

  • Absent acrosomes

  • Abnormal sperm-head morphology

WHO guidance specifically emphasizes that distinctive monomorphic sperm abnormalities such as round-headed/acrosomeless sperm should be recognized and reported.

Morphology assessment

An experienced andrology laboratory examines stained sperm under high magnification.

The embryologist evaluates:

  • Head shape

  • Acrosome

  • Midpiece

  • Tail

  • Proportion of sperm showing the same abnormal phenotype

When virtually all sperm share the characteristic round-headed abnormality, complete globozoospermia is suspected.

Acrosome assessment

Specialized laboratory staining or microscopy can demonstrate absence or severe abnormality of the acrosome.

This may help distinguish true globozoospermia from other causes of round-headed or abnormal sperm morphology.

Genetic testing

Genetic evaluation is important, particularly in complete globozoospermia.

Testing may include:

  • DPY19L2 deletion analysis

  • DPY19L2 sequencing

  • Targeted genetic panels

  • Broader infertility gene panels in selected cases

Additional genes may be investigated when DPY19L2 testing is negative.

Genetic counselling

Genetic counselling can be valuable before assisted reproduction because some forms of globozoospermia are inherited.

The implications depend on:

  • Specific gene involved

  • Inheritance pattern

  • Partner genetics

  • Planned reproductive treatment

Sperm DNA and chromatin testing

Some studies have identified increased sperm DNA fragmentation or abnormal chromatin packaging in affected men.

These tests are not universally required for every patient but may be considered in specialist fertility centers when the result would influence management.

When to see a doctor
  • A semen analysis reports round-headed sperm.
  • The laboratory suspects globozoospermia.
  • Nearly all sperm have abnormal round heads.
  • You and your partner have unexplained infertility.
  • Fertilization failed despite apparently adequate sperm numbers.
  • A previous ICSI cycle resulted in total or near-total fertilization failure.
  • You have been advised that sperm lack normal acrosomes.
  • A DPY19L2 mutation or deletion has been identified.
  • There is a family history of severe male infertility.
  • You want genetic counselling before IVF/ICSI.
Reducing your risk
  • Obtain expert semen morphology analysis when severe teratozoospermia is reported.
  • Consider genetic testing in complete globozoospermia.
  • Seek genetic counselling when a pathogenic variant is identified.
  • Discuss assisted reproduction with a specialist experienced in severe male-factor infertility.
  • Review previous fertilization outcomes before subsequent IVF/ICSI cycles.
  • Consider fertility-center evaluation when conventional ICSI results in very low or absent fertilization.

Common questions

What is globozoospermia?
Globozoospermia is a rare sperm disorder characterized by round-headed sperm that lack a normal acrosome. The abnormality can prevent normal fertilization and is an important cause of severe male infertility.
Why are the sperm round?
The sperm-head remodeling process during spermatogenesis does not occur normally. In many cases, abnormalities affecting genes such as DPY19L2 prevent normal acrosome attachment and sperm-head elongation.
What is the acrosome?
The acrosome is a specialized cap-like structure located at the front of a normal sperm head. It contains molecules involved in fertilization and is important for normal sperm-oocyte interaction.
Can a sperm fertilize an egg without an acrosome?
Natural fertilization is severely impaired because the acrosome is involved in interaction with and penetration of the structures surrounding the egg. ICSI bypasses this physical barrier by injecting sperm directly into the oocyte. However, fertilization can still fail because globozoospermic sperm may also have defects in oocyte activation.
Is globozoospermia genetic?
Frequently, yes. DPY19L2 is the most commonly identified gene, although several other genetic abnormalities have also been associated with the condition.
What is DPY19L2?
DPY19L2 is a gene involved in normal sperm-head and acrosome development. Pathogenic deletions or mutations can cause complete globozoospermia.
Can globozoospermia be treated with medication?
There is currently no established medication that can correct the underlying sperm-head/acrosome defect. Treatment generally focuses on assisted reproduction.
Can supplements fix globozoospermia?
No supplement has been shown to reverse the characteristic structural defect of true genetic globozoospermia. General health optimization may support fertility care but does not replace specialist treatment.
Can a man with globozoospermia have biological children?
Yes. Biological fatherhood may be possible using assisted reproduction. ICSI is commonly used, sometimes together with additional laboratory techniques depending on previous fertilization results and the underlying sperm activation defect.
Does IVF alone work for globozoospermia?
Conventional IVF is generally ineffective in complete globozoospermia because affected sperm cannot normally penetrate and fertilize the egg. ICSI is generally required.
What is ICSI?
ICSI stands for intracytoplasmic sperm injection. An embryologist selects a sperm and injects it directly into an oocyte, bypassing the sperm's inability to penetrate the egg normally.
Does ICSI always work in globozoospermia?
No. Even after direct sperm injection, fertilization can remain poor because the sperm may fail to trigger normal oocyte activation. Published studies report substantially reduced fertilization with conventional ICSI in some affected patients.
What is assisted oocyte activation?
Assisted oocyte activation (AOA) is a laboratory technique intended to trigger activation of the egg after ICSI. Chemical activation with calcium ionophores is one method that has been studied. It may be considered in selected cases of globozoospermia or previous fertilization failure.
Does assisted oocyte activation improve fertilization?
Several observational studies report improved fertilization in globozoospermic patients when AOA is added to ICSI. However, broader systematic reviews emphasize that high-quality randomized evidence and long-term safety data remain limited, so AOA should be offered selectively after specialist counselling rather than presented as universally proven therapy.
What is complete globozoospermia?
Complete globozoospermia means essentially all sperm demonstrate the characteristic round-headed, acrosome-deficient phenotype. It is generally associated with more severe fertilization impairment.
What is partial globozoospermia?
Partial globozoospermia means only a proportion of sperm have the characteristic abnormality. The reproductive significance varies depending on how many sperm are affected and whether morphologically and functionally usable sperm remain.
Can sperm selection improve outcomes?
Specialized sperm selection techniques may be considered in some fertility laboratories, but their effectiveness depends on the phenotype and available expertise. They should not be presented as guaranteed to overcome the underlying genetic defect.
Is sperm DNA abnormal in globozoospermia?
Some studies report increased sperm DNA fragmentation and abnormal chromatin packaging in affected men. This does not mean every sperm carries damaged DNA, but it is one reason specialist reproductive evaluation may be appropriate.
Can globozoospermia be passed to children?
Some genetic forms can be inherited. The exact reproductive risk depends on the gene and inheritance pattern. Genetic counselling is therefore recommended when a pathogenic variant is identified.
Is donor sperm always necessary?
No. Many affected men may be able to pursue biological parenthood using ICSI and, when appropriate, assisted oocyte activation. Donor sperm is one reproductive option, not an automatic requirement.
Which doctor treats globozoospermia?
Evaluation is best coordinated by: Andrologist Reproductive urologist Reproductive endocrinologist Clinical embryologist Clinical geneticist or genetic counsellor when appropriate Management usually requires collaboration between male-infertility and IVF specialists.

Sources

  1. WHO Laboratory Manual for the Examination and Processing of Human Semen, Sixth Edition https://www.who.int/publications/i/item/9789240030787
  2. Molecular cytogenetic and genetic aspects of globozoospermia: a review https://pubmed.ncbi.nlm.nih.gov/22571172/
  3. Globozoospermia: A Case Report and Systematic Review of Literature https://pubmed.ncbi.nlm.nih.gov/36047070/
  4. Globozoospermia is mainly due to DPY19L2 deletion https://pubmed.ncbi.nlm.nih.gov/22653751/
  5. Assisted oocyte activation overcomes fertilization failure in globozoospermic patients regardless of DPY19L2 status https://pubmed.ncbi.nlm.nih.gov/23411621/
  6. Assisted Oocyte Activation Systematic Review https://pubmed.ncbi.nlm.nih.gov/39168919/