Case reports to suggest an algorithm for management of total fertilisation failure prior to use of donor gametes

Abstract

Purpose Total fertilisation failure (TFF), even with intracytoplasmic sperm injection (ICSI), occurs in approximately 3 % of cycles, can be recurrent and the exact cause is difficult to elucidate. Differentiation between oocyte and sperm-related cause of TFF is possible using mouse oocyteactivation techniques, but is not an option within most clinical settings. Therefore, the management of these couples is clinically driven, and the endpoint, if recurrent, is often the use of donor gametes. However, with the invariable lack of a definitive cause of TFF, any decision between the use of donor sperm or oocytes remains an emotive one. We present two case reports demonstrating the importance of appropriate investigation, activation techniques (mechanical and chemical) and clinical management options to develop a clinical algorithm prior to the use of donor gametes. Methods This study is composed of two case reports of assisted reproduction investigation and treatment within an assisted conception unit for couples with recurrent total fertilisation failure. Results Using appropriate investigation (endocrine, urological and embryological) and treatments (ICSI, IMSI, oocyteactivation techniques), a fertilisation rate of 48 % was achieved in two cycles in couples following a total of nine previous cycles (and 200 previously collected eggs) with TFF.Conclusions Oocyte activation requires the triggering of intracellular calcium oscillations by the release of a spermspecific factor (phospholipase C zeta (PLCζ)) into the oocyte cytoplasm. Although, PLCζ deficiencies have been demonstrated as putative causes of failed activation, impaired oocyte responsiveness may also be a factor. The use of donor gametes is often recommended and is often the required endpoint of treatment. However, these reports outline a clinical algorithm that potentially offers success without donation, and also offers a systematic approach to help decide whether donor oocytes or sperm should be recommended.

Artificial Egg Activation Using Calcium Ionophore

“…ICSI fertilization rates (defined as proportion of mature oocytes injected with 2PN and 2PB the day after microinjection) are expected to be 65 to 80% 29 ; however, 5 to 8% IVF cycles and 1 to 3% ICSI cycles are affected by TFF, where no eggs are fertilized. 30 Although TFF is rare, its effect is devastating. Potential causes include technical problems affecting the injection of sperm or laboratory equipment malfunction, although these events are fortunately rare.…”

SPERM FACTORS AND EGG ACTIVATION: Phospholipase C zeta (PLCZ1) and the clinical diagnosis of oocyte activation deficiency

“…Indeed, the HFEA currently considers AOAs as a treatment add-on and has placed AOA treatment on their ‘Amber’ list, thus implying that there is insufficient evidence relating to the efficiency and safety of AOAs ( HFEA 2017 ). Only a small proportion of infertility clinics perform AOA; those that do only consider treatment according to a history of fertilization failure after ICSI or the suspicion of OAD ( Tesarik et al 2002 , Montag et al 2012 , Nicopoullos et al 2015 ). Van Blerkom et al expressed significant concern over the fact that AOA treatment might become more frequently used for ICSI cycles to ensure appropriate pronuclear formation and to eliminate the potential for fertilization failure ( Van Blerkom et al 2015 ).…”