Failure of fertilization after intracytoplasmic sperm injection in a patient with Kartagener's syndrome and totally immotile spermatozoa: Case Report

Antoine Abu-Musa1,3, Antoine Hannoun1, Antoun Khabbaz1 and Paul Devroey2

1 Department of Obstetrics and Gynaecology, American University of Beirut – Medical Centre, Beirut, Lebanon and 2 Centre for Reproductive Medicine, University Hospital, Dutch-speaking Brussels Free University, Laarbeeklaan 101, B-1090 Brussels, Belgium


    Abstract
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
Patients with Kartagener's syndrome (KS) are invariably infertile with totally immotile spermatozoa. Intracytoplasmic sperm injection (ICSI) is considered to be the treatment of choice for patients with immotile spermatozoa. We report the second KS case in the literature from whom immotile spermatozoa from the ejaculate failed to fertilize mature oocytes after ICSI. The role of micromanipulation in the treatment of KS patients is discussed.

Key words: ICSI/immotile spermatozoa/Kartagener's syndrome


    Introduction
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
Kartagener's syndrome (KS) is characterized by the classic triad of chronic sinusitis, bronchiectasis and situs inversus. Male patients are invariably infertile, presenting with totally immotile spermatozoa (Yokota et al., 1993Go; Wolf et al., 1994Go). This syndrome is believed to be caused by ultrastructural defects mainly in the dynein arms of both cilia and spermatozoa leading to immotility or occasionally to an abnormal motility pattern (Eliasson et al., 1977; Pederson and Mygind, 1980Go).

Intracytoplasmic sperm injection (ICSI) provides an effective treatment modality for patients even with the severest forms of male factor infertility. Previous reports have shown that totally immotile spermatozoa have the capacity to fertilize an oocyte after ICSI (Nijs et al., 1996Go). Pregnancies and healthy births using immotile spermatozoa and ICSI have also been reported (Nijs et al., 1996Go; Kahraman et al., 1997Go). In this report, a patient with KS and totally immotile spermatozoa that failed to fertilize the wife's oocytes in vitro is presented. The role of micromanipulation in the treatment of these patients is discussed.


    Case report
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 Abstract
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 Case report
 Discussion
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A 30 year old woman presented with primary infertility of 8 years duration. Her infertility work-up was essentially negative except for mild elevation in dehydroepiandrosterone. Her husband was 36 years of age. He was diagnosed as a case of KS with situs inversus and a history of recurrent respiratory infections, chronic cough, production of mucopurulent sputum, sinusitis and rhinorrhoea. His semen analysis repeatedly showed totally immotile spermatozoa. The couple were referred to the Centre for Reproductive Medicine, Dutch-speaking Brussels Free University, Belgium for ICSI. After an ovarian stimulation cycle using the long protocol of gonadotrophin-releasing hormone analogue/human menopausal gonadotrophin (GnRHa/HMG), six oocytes were retrieved. A semen sample was collected by masturbation into a sterile cup. Initial evaluation revealed a sperm concentration of 58x106/ml, 0% motility and 9% normal morphology (WHO, 1992). After two-layered Percoll gradient preparation, spermatozoa were again observed without motility. The procedure for sperm preparation for ICSI has been described elsewhere (Vandervorst et al., 1997Go). Although immotile, tails of the spermatozoa were touched before the ICSI procedure, and the oolemma was aspirated before injection of the spermatozoon into the oocyte to facilitate oocyte activation. Oocyte handling and ICSI procedures have been extensively described elsewhere (Van Steirteghem et al., 1995Go). Four metaphase II oocytes were injected, but none fertilized.


    Discussion
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 Case report
 Discussion
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Afzelius (1976) was the first to recognize that the relationship of KS to male infertility was due to immotility of spermatozoa (Afzelius, 1976Go). This immotility is due to defects in the dynein arms present in sperm tails. The protein dynein exhibits adenosine triphosphatase activity necessary for ciliary and tail motility, since it induces sliding of adjacent microtubule doublets (Fawcett, 1977Go). Because of this, men with KS are invariably thought to be infertile. However, a few patients with KS who were fertile have been reported (Jonsson et al., 1982Go; Conraads et al., 1992Go). This has been attributed to the heterogeneous ultrastructural defects of the axonema, which will not necessarily result in immobilization but rather in the absence of effective movement. Kartagener's syndrome is thus regarded as a subgroup of primary ciliary dyskinesia that includes asynchronous ciliary beating, reduced or excessive motility, rotating or vibrating movement or random ciliary orientation. All of this could result in unco-ordinated movement of respiratory cilia and contribute to impaired mucociliary clearance; however, this co-ordination is not needed in swimming spermatozoa. This could explain the paradoxical association between bronchopulmonary disease and normal fertility in some patients with KS.

Our patient had always had totally immotile spermatozoa. ICSI is now the treatment of choice in such a condition. The ability of an immotile spermatozoon to fertilize an oocyte is well documented. Non-viable spermatozoa have been injected into aged oocytes (Georon et al., 1995) and fertilization and early cleavage observed. Fertilization and development have been obtained after injecting totally immotile spermatozoa stored for 2 days at 4°C (Ghunaim et al., 1995Go). Recently, clinical pregnancies and a healthy birth after ICSI using immotile spermatozoa were reported (Nijs et al., 1996Go; Kahraman et al., 1997Go). In our patient, none of the oocytes fertilized after ICSI. The centre where ICSI was done has consistently reported a high fertilization rate after ICSI (Van Steirteghem et al., 1993Go); thus the failed fertilization was not due to a low ICSI proficiency. Although other authors reported no fertilization after ICSI with totally immotile spermatozoa (Liu et al., 1995Go), this is probably due to a technical problem rather than the fertilizing potential of the spermatozoa. Even though the spermatozoa are immotile, it is still necessary to immobilize them before injection. Destabilization of the plasma membranes leads to the release of an activating factor `oscillion' into the ooplasm (Dozortsev et al., 1995Go; Parrington et al., 1996Go) and it is necessary for ooplasmic enzymes to reach the sperm nucleus in order to start chromatin decondensation (Tesarik et al., 1994Go).

To our knowledge, this is the second case reported in the literature of a patient with KS whose immotile spermatozoa failed to fertilize oocytes after ICSI. One KS patient whose spermatozoa were used for both ICSI and subzonal insemination (SUZI) has been reported (Nijs et al., 1996Go). None of the oocytes fertilized after ICSI, but some did after SUZI, leading to embryo replacement and a live birth. A pregnancy achieved after SUZI in a patient with KS has also been reported (Wolf et al., 1993Go). To explain the difference in fertilization rates between SUZI and ICSI in patients with KS, it was pointed out that in the ejaculate of these patients dead spermatozoa could also be present (Nijs et al., 1996Go). Therefore, when performing ICSI, no distinction can be made between the dead spermatozoa and the viable but immotile ones. When SUZI is applied, the theoretical probability that one mature live spermatozoon is present amongst the >10 spermatozoa injected is obviously higher than when only one spermatozoon is retrieved for ICSI. The use of the swelling test (Van der Ven et al., 1986Go) might be of help in identifying those spermatozoa that are viable. In addition, the use of testicular spermatozoa in these patients needs to be evaluated. Nijs et al. (1996) demonstrated that the fertilizing capacity of totally immotile testicular spermatozoa is better than that of totally immotile ejaculated spermatozoa. This has been attributed to the long transit time the spermatozoa spend in the epididymes. This increases the risk of senescent degeneration of spermatozoa (Bedford, 1994Go). These aged spermatozoa contain fragile DNA, the protamine packaging has become unstable and pronucleus formation is subsequently hampered. Because only two cases of KS with failed fertilization after ICSI have been reported so far, the number of tested oocytes in the literature is very small. The fertilizing capacity of immotile spermatozoa from patients with KS can be further evaluated by performing experimental ICSI on a large number of animal oocytes.


    Notes
 
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    References
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
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Submitted on February 15, 1999; accepted on June 17, 1999.