Tisotumab vedotin, sold under the brand name Tivdak, is an antibody-drug conjugate used to treat cervical cancer. It is a combination of tisotumab, a monoclonal antibody against tissue factor, and monomethyl auristatin E (MMAE), a potent inhibitor of cell division. Tisotumab vedotin was approved for medical use in the United States in September 2021. It is administered by infusion into a vein every 3 weeks.Tisotumab vedotin is the international nonproprietary name (INN). Adverse effects
In the United States, Tivdak carries a black box warning for ocular toxicity, which occurs in up to 60% of treated patients. In clinical trials, the most common forms of ocular toxicity were dry eye, conjunctivitis, corneal damage, and blepharitis.To prevent eye damage, premedication with three different types of eye drops—a topical corticosteroid, a vasoconstrictor,  and artificial tears—is recommended before each infusion, as well as the use of cold packs over the eyes.Other very common adverse effects include bleeding (occurring in approximately 60% of patients, most often nosebleed) and peripheral neuropathy (42% of patients). Like all drugs containing MMAE, tisotumab vedotin can cause inflammation of the lungs. Mechanism of action
The antibody portion of tisotumab vedotin (tisotumab) binds to and forms a complex with tissue factor, a molecule expressed on the surface of cancer cells. This complex is then taken up into the cell, where tisotumab vedotin is broken down by proteolytic cleavage, releasing MMAE, which stops the cell cycle and kills the cell by apoptosis.
This makes the sperm completely unable to penetrate the zona pellucida. The sperm in Type 2 globozoospermia has some acrosomal covering surrounded by large droplets of cytoplasmic material, suggesting secondary degenerative changes. There is also a conical nucleus. It is thought that infertility in this type of globozoospermia is due to incorrect chromatin packaging which prevents proper fertilization. Symptoms
Aside from the effect on fertility globozoospermia is symptomless. People with globozoospermia have normal physical and mental development, normal clinical features and normal hormonal profile. Genetics
Table 1: Gene mutations that have been identified in globozoospermia and the impact these mutations have on sperm function and successful fertilization. Diagnosis
The presence of round headed sperm in a semen analysis sample confirms the diagnosis of globozoospermia. The lack of acrosome can be ascertained by either morphology staining or immunofluorescence. Treatment
Until 1995, the only options for people with globozoospermia who wished to conceive were adoption or sperm donation. With the advancement of assisted reproductive techniques (ART) it is now possible for those with globozoospermia to conceive using their own sperm. The main technique used is intracytoplasmic sperm injection (ICSI) where fertilisation is achieved by a single sperm being injected into the egg. Some studies have shown it is possible for a viable embryo to be created with this technique alone, however others have found it necessary to also use calcium ionophore treatment for fertilisation to be successful. Calcium ionophore treatment is used to artificially activate the oocyte.