Etiology And Diagnosis Of Abnormal Fertilization

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Fertilization abnormalities mostly result from deficiencies of sperm-derived oocyte-activating factor of those of the oocyte cytoplasmic systems that have to generate an adequate response to the sperm factor (also refer to section "Normal Versus Abnormal Fertilization''). In either situation, the signaling events implicated in nuclear and cytoplasmic reprogramming required for the gamete-to-embryo transition are failing. In other cases, fertilization problems are caused by sperm centriole abnormalities which lead to disturbances of the MTOC function which is required for pronuclear apposition, nuclear syngamy, and the subsequent cleavage divisions.

Many of the conditions underlying abnormal fertilization can now be analyzed, but this is mostly possible only with the use of systems which imply irreversible cell damage or destruction. In practice, however, maximum information possible needs to be drawn from noninvasive observations on living spermatozoa, oocytes, and zygotes.

Many abnormalities can be detected by noninvasive examination of zygote pronuclei (also refer to section "Predictive Potential of Zygote Noninvasive Evaluation"). However, pronuclear alterations are nonspecific and can be caused by both sperm-borne factors (50) and by those derived from the oocyte (51). Hence, the identification of the gamete of origin can only be evaluated indirectly, by putting together observations on zygotes and embryos from the present and the past assisted reproduction trials and analyzing them in the overall clinical context of each case.

Sperm-derived, paternal factors are responsible both for abnormalities of fertilization and for defective preimplantation development. The most serious paternal deficiencies can cause complete fertilization failure or a failure of the male pronuclear development. Such conditions can be detected by diagnostic tests using heterologous ICSI with the patient's spermatozoa to mouse, hamster, rabbit, or bovine oocytes (52-54). As mentioned previously, functional abnormalities of the sperm centriole can be revealed by cytochemical visualization of microtubuli in newly formed asters after het-erologous ICSI using bovine oocytes (28).

On the other hand, paternal factors often cause much more subtle anomalies. If the two pronuclei fail to get in apposition, the sperm centriole is mostly to be blamed. As to other abnormalities, concerning pronuclear size, orientation, and internal structure, the distinction of the male and the female origin is virtually impossible.

Yet the gamete responsible for fertilization abnormality in question can sometimes be suggested by the clinical context. In an oocyte donation program, for instance, an abnormally high frequency of fertilization abnormalities is likely to be of sperm origin, especially if the infertile couple has experienced a history of similar problems with the patient's own oocytes.

On the other hand, oocyte-derived origin of fertilization abnormalities can be suspected in cases of abnormal hormonal profiles recorded during controlled ovarian stimulation (51). Lack of evidence for a sperm deficiency from a heterologous ICSI test (see above) can further substantiate such a conclusion.

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A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

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