Assisted Conception Unit, Guy's and St Thomas' Hospitals Trust, Lambeth Palace Road, London SE1 7EH, UK
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Abstract |
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Key words: fertilization/globozoospermia/intracytoplasmic sperm injection/male factor infertility
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Introduction |
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Case report |
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His partner had extensive endometriosis but patent Fallopian tubes and a normal uterine cavity. Ovulatory progesterone concentration was noted and early follicular phase hormonal profile was normal.
The couple proceeded to ICSI. The ovaries were stimulated using a long protocol of buserelin nasal spray and follicle stimulating hormone (FSH, Metrodin®; Serono, Welwyn Garden City, Herts, UK). Of 12 oocytes retrieved under ultrasound guidance, 10 were injected with globe-headed spermatozoa. Nine oocytes remained intact and four fertilized normally. A total of three embryos (two 4-cell embryos with no fragmentation and one 3-cell embryo with minimal fragmentation) was transferred 48 h later. A pregnancy did not ensue.
Likewise, a second attempt at ICSI 2 months later did not result in a pregnancy, as out of 11 oocytes, only one fertilized normally and was transferred at the 4-cell stage.
In the third attempt at ICSI, 19 out of 21 oocytes retrieved were micro-injected with globe-headed spermatozoa, of which 15 remained intact and eight fertilized normally. Three 4-cell embryos were transferred 48 h after micro-injection. This attempt was successful. A singleton clinical pregnancy resulted, culminating in a spontaneous vaginal delivery of a live female infant. The pregnancy was complicated by pre-eclampsia, necessitating induction of labour at 36 weeks gestation. The infant's birth weight was 2.3 kg.
Spare embryos were cryopreserved for future use.
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Discussion |
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Biochemically, the spermatozoa are characterized by the absence, or reduced activity, of acrosin (acrosome protease) and of calicin (a cytoskeletal protein) (Florke-Gerloff et al., 1984). The globic heads are associated with rounded or other abnormally shaped nuclei with large vacuolar regions (Figure 2
). The chromatin is often spherically arranged, surrounded by varying amounts of cytoplasm. The mid-pieces and tails often exhibit structural abnormalities and abnormal mitochondria. Two types of globozoospermia have been described (Singh, 1992
). Type I is characterized by complete lack of acrosome and acrosomal enzymes. These spermatozoa are unable to penetrate the zona pellucida, causing primary infertility. Type II has some acrosomal covering with a conical nucleus, which may be surrounded by large droplets of cytoplasmic material indicating secondary degenerative changes. It is thought that the infertility in this type is caused by subsequent poor motility (Singh, 1992
).
In 1984 Syms et al. demonstrated that globic spermatozoa were able to undergo nuclear decondensation when incubated with crushed hamster ova. Lanzendorf et al. (1988) found decondensation and pronuclear formation after direct injection into hamster eggs. Thus, if the inability to penetrate the oocytes is by-passed, fertilization could take place. This was made possible in humans with the introduction of ICSI (Palermo et al., 1992) in 1992.
Following the first livebirth resulting from ICSI treatment in a case of globozoospermia (Trokoudes et al., 1995), there have been a number of globozoospermic cases described in which fertilization has been attempted using ICSI. These have been of varying success and in general it appears that fertilization rates following ICSI with round-headed spermatozoa are much lower than with morphologically normal spermatozoa (Liu et al., 1995
; Battaglia et al., 1997
; Rybouchkin et al., 1998
). This is demonstrated in our case.
The lower fertilization rate implies that there are further factors contributing to the infertility. Failed ICSI has been associated with a higher rate of premature chromosome condensation (PCC) compared with in-vitro fertilization (IVF; Schmiady et al., 1996). PCC occurs after sperm injection, if the oocyte is not activated but remains arrested at metaphase II. The ooplasmic chromosome condensing factors migrate into the sperm nucleus and induce PCC. Different degrees of condensation have been noted which may be related to the degree of sperm membrane damage caused during sperm immobolization. Edirisinghe et al. (1998) demonstrated a higher rate of PCC in round-headed spermatozoa after ICSI compared with normal spermatozoa. They suggested that this type of spermatozoon may be more susceptible to this form of damage.
Various other theories have been put forward for the lower fertilization rate of round-headed spermatozoa, including the inability of the spermatozoa to support post fertilization embryonic development, genetic or environmental defects or incapability of the globic spermatozoa to activate the oocytes after ICSI. Failure of activation and the consequent failure of the oocyte to complete meiosis is likely to contribute to the high rate of PCC noted in round-headed spermatozoa (Edirisinghe et al., 1998). Failure of activation has been tested in a number of studies. Battaglia et al. (1997) treated 14 oocytes with calcium ionophore to induce activation after failed fertilization with ICSI. Nine of these reached the embryo 24-cell stage at 38 h. They postulated that spermatozoa from patients with this condition may be deficient in oscillin, a factor which is normally expressed by fertilizing spermatozoa. It causes the release of calcium ions, which are needed for oocyte activation during fertilization, from intracellular stores in the oocyte (Swann and Ozil, 1994
). Rybouchkin et al. (1996, 1997) have also reported deficient oocyte activation capacity in globozoospermia, possibly secondary to the absence or down-regulation of the sperm-associated oocyte-activating factor but to a varying degree in different patients. They have developed a mouse model, which enables testing of spermatozoa to assess oocyte-activating capacity. This may be useful as a preliminary study of globozoospermic patients before ICSI, with or without assisted oocyte activation (Rybouchkin et al., 1998
).
Our patient exhibited features of type I globozoospermia with a complete absence of acrosome (Figure 2). The variable fertilization rates in the three attempts at ICSI in our case are consistent with other reports in the literature demonstrating the variation in the fertilizing capabilities of globe-headed spermatozoa within one individual. To our knowledge, this is the third live birth described in the literature in successful cases of fertilization with globozoospermia without assisted oocyte activation.
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Acknowledgments |
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Notes |
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References |
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Submitted on July 22, 1999; accepted on September 27, 1999.