Unique Patient Issues

Early Interventions and Management

Catherine Combelles, M.H., Ph.D.


Semin Reprod Med. 2012;30(3):243-252. 

In This Article

Abstract and Introduction


Patient cases that present with recurring fertilization failure or complete abnormality in either the oocytes or sperm before fertilization are uncommon, yet they are devastating. This review presents several such instances, including oocyte maturation blocks, empty follicle syndrome, oocyte activation failures, defects in sperm phospholipase C isoform ζ, sperm structural anomalies, spontaneous oocyte activation, and unexplained cases. Diagnostic efforts have not only provided insight into possible etiologies but also have helped manage such challenging cases. Interventions may comprise cellular, molecular, or genetic analyses of gametes, as well as functional assays and/or modified treatment strategies. Consequently, infertility professionals can increasingly rely on evidence-based counseling with respect to prognosis and treatment options.


Every assisted reproductive technology (ART) laboratory has experienced unique patient cases in which the oocytes and/or sperm prove abnormal and failed fertilization ensues. This review focuses on total recurrent issues within a couple; single instances of total failure are excluded because these may be due to a laboratory or clinical failure and/or random variability in response to ovarian stimulation within any single cycle due to the disparate follicular origin following ovarian stimulation. The present discussion thus remains focused on unusual repeated instances with a uniform defect in the entire cohort.

It is worth acknowledging that these unique cases are not always reported, yet they likely occasionally occur in all clinics and are important to document. Even if not prevalent, such cases are obviously devastating and most challenging not only to patients but also to the laboratory and clinicians. An improved understanding of functional abnormalities in gametes may be instrumental in patient counseling. Therefore, instances when such knowledge benefited cycle management are discussed. Cases include a spectrum of abnormalities with developmental defects in gametes occurring before and during the fertilization process (Fig. 1).

Figure 1.

Schematic of refractory cases with unique aberrations either during oocyte or sperm development or at fertilization (shown in grayed boxes). A detailed presentation of these unusual cases is found in the text. GV, germinal vesicle; MI, metaphase I; MII, metaphase II; 2 PN, 2 PB, two pronuclei and two polar and two pronuclei).


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.