P-039 Pregnancy outcomes and genetic analysis of globozoospermic patients: A case series and review of the literature
Authors: Bendayan M , Clémenceau M , Saïs E , Kherraf Z E , Lefeuve F , Alter L , Paillusson B , Fathallah K , Ray P , Boitrelle F 
Published: June 2023

Abstract

Study question
How should men with globozoospermia be managed in Assisted Reproductive Technologies (ART)?

Summary answer
IMSI (intracytoplasmic morphologically selected sperm injection), without oocyte activators (OA) allows to obtain a live birth, even when there is a mutation of DPY19L2 gene.

What is known already
Globozoospermia is a rare syndrome found in less than 0.1% of the infertile population. It is characterized by the presence of spermatozoa with round heads devoid of acrosomes. Two main genes are involved in the transmission of the disease: SPATA 16 and DPY19L2. Only Assisted Reproductive Technologies (ART) such as ICSI (intra-cytoplasmic sperm injection) and IMSI, with or without OA allow these couples to obtain pregnancies. There are no live births described after IMSI without OA in patients with a DPY19L2 mutation.

Study design, size, duration
Four infertile couples followed in the Department of ART at the Poissy Hospital Center, were studied between 2011 and 2022.All patients had total globozoospermia. Three patients were tested for the DPY19L2 gene mutation. Patients were managed in ART with the IMSI technique without the use of OA.

Participants/materials, setting, methods
The first patient had a homozygous mutation of the DPY19L2 gene. Two live births were obtained after IMSI.
The second patient was not DPY19L2 mutated. 2 IMSI were performed, resulting in a biochemical pregnancy.
The third patient had a homozygous mutation of the DPY19L2 gene. An IMSI was performed without obtaining a pregnancy, a second attempt is scheduled soon.
The fourth patient refused genetic testing and IMSI management. Sperm donation was performed without achieving pregnancy.

Main results and the role of chance
In this case series, we present the management of four globozoosperm couples in the Reproductive Biology and Andrology Department at the Poissy Hospital Center. We also present the first two live births after performing an IMSI, without OA, in a globozoospermic patient with a homozygous mutation of DPY19L2 gene. In fact, according to our review of the literature, 53 case reports or articles of patients having benefited from ART with or without OA have been reported in globozoospermic patients. In these couples, 60 children were born. However, no live births had been reported until now in couples managed in IMSI without OA, where men had globozoospermia with DPY19L2 mutation.

Limitations, reasons for caution
The use of OA to increase the membrane permeability of oocyte to calcium and increase fertilization rates. The highest number of live births in the globozoosperm population occurs after ICSI or IMSI with OA. There is no described live birth without the use of OA in a DPY19L2 mutated patient.

Wider implications of the findings
The use of OA remains debated and is not authorized in some countries. Although our study found low fertilization rates after IMSI, it’s possible to obtain live births. The selection of spermatozoa with an acrosome outline at high magnification is thus an interesting alternative to the use of oocyte activators.

Trial registration number
not applicable