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Globozoospermia Syndrome: an Update

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Globozoospermia Syndrome: an Update Received: 16 July 2019 | Revised: 17 September 2019 | Accepted: 21 September 2019 DOI: 10.1111/and.13459 INVITED REVIEW Globozoospermia syndrome: An update Farzaneh Fesahat1 | Ralf Henkel2,3 | Ashok Agarwal3 1Reproductive Immunology Research Center, Shahid Sadoughi University of Abstract Medical Sciences, Yazd, Iran Among the factors involved in male infertility, there is a rare morphology disorder 2 Department of Medical called "globozoospermia" that is classified into total globozoospermia and partial Bioscience, University of the Western Cape, Bellville, South Africa globozoospermia (type I and type II, respectively). This syndrome is primarily char‐ 3American Center for Reproductive acterised by the presence of round‐headed spermatozoa with cytoskeleton defects Medicine, Cleveland Clinic, Cleveland, OH, USA around the nucleus and no acrosome. Current data support the negative correlation between globozoospermia and conventional intracytoplasmic sperm injection (ICSI) Correspondence Ashok Agarwal, American Center for outcomes, revealing the need for the management of patients undergoing assisted Reproductive Medicine, Cleveland Clinic, reproduction technology (ART) through more effective treatment techniques. This Cleveland, OH, USA. Email: [email protected] review highlights the most important characteristics of globozoospermia such as sperm parameters, DNA/chromatin integrity and sperm DNA fragmentation (SDF), as well as genetic features based on the latest knowledge. Additionally, we looked into current progress on fertilisation potential and possible treatment strategies for patients presenting with globozoospermia. KEYWORDS DNA fragmentation, globozoospermia, human, intracytoplasmic sperm injection, morphology, spermatozoa 1 | INTRODUCTION causes primary male infertility (Singh, 1992). Contrary, men with type II globozoospermia have both normal and round‐headed sperm Among the factors involved in male infertility, there is a rare mor‐ cells with large CDs, which impair motility. In this type of globozo‐ phology disorder called "globozoospermia", first described by Wolff, ospermia, 20%–90% of spermatozoa have no acrosome; therefore, Schill, and Moritz (1976). Globozoospermia is primarily characterised it is also known as partial globozoospermia (Dam et al., 2006, 2011). by the presence of round‐headed spermatozoa without acrosome, The findings of one study demonstrated that partial globozoosper‐ cytoskeleton defects around the nucleus, the absence of a post‐ac‐ mia was actually an oligoasthenoteratozoospermia (OAT) with an rosomal sheath and the separation of nuclear membranes (Figure 1) increased percentage of acrosome‐less spermatozoa (>25%), thus (Han et al., 2017). Another important characteristic of globozoosper‐ showing no uniform pathology (Vicari et al., 2002). mic spermatozoa is their coiled tails (Dam et al., 2006). Furthermore, maturation defects, such as the presence of cytoplasmic droplets (CDs) surrounding the nucleus or intermediate piece, have been fre‐ 2 | PATHOGENESIS AND EPIDEMIOLOGY quently reported (Dam et al., 2006). Singh (1992) classified globozoospermia into type I and type II So far, no clear explanation has been provided for the pathogenesis (Singh, 1992). Accordingly, in type I globozoospermia, also known as of globozoospermia. The morphological characteristics of globozoo‐ total or classic globozoospermia, or true round‐head only syndrome, spermic spermatozoa are formed during spermiogenesis and due to a 100% of the spermatozoa have a small, round and acrosome‐free defect in one or more of the sperm nuclear remodelling mechanisms, head. Since round‐headed spermatozoa are unable to penetrate the especially during the formation of the acrosome and the integra‐ zona pellucida because of having no acrosome, this kind of disorder tion of its vesicles, and sperm elongation (Dam et al., 2006, 2011; Andrologia. 2019;00:e13459. wileyonlinelibrary.com/journal/and © 2019 Blackwell Verlag GmbH | 1 of 13 https://doi.org/10.1111/and.13459 2 of 13 | FESAHAT et AL. (a) (b) (c) (d) (e) (f) FIGURE 1 Human sperm morphology. Schematic view of normal spermatozoa (a) and sperm cell with globozoospermia (b) primarily characterised by the presence of round‐headed spermatozoa without acrosome. Diff‐Quik (c) and Papanicolaou (d–f) staining were applied to evaluate morphological features for spermatozoa. Stained spermatozoon with normal as well as abnormal round‐headed globozoospermia was seen as dark and colour arrows respectively Wolff et al., 1976). Other morphological features of globozoosper‐ needed to clarify the epidemiology of both total and partial globozo‐ mic samples include cytoskeleton defects such as the round nucleus, ospermia in different populations. the absence of a posterior acrosomal sheath, separation of nuclear membranes and coiled tails, and the presence of a cluster of differ‐ entiation surrounding the middle piece (Courtot, 1991). The separate 3 | SPERM PARAMETERS development of the acrosome from the Golgi apparatus, the lack of acrosome vesicle fusion and the poor performance of the Golgi ap‐ Some of the human studies indicated that the quality of vari‐ paratus can be mentioned as possible mechanisms for the absence ous semen parameters in globozoospermic men was differentially of acrosomes in globozoospermic spermatozoa (Courtot, 1991). The changed (Table 1). A retrospective study on semen parameters of prevalence of this disorder among infertile men is estimated to be 72 globozoospermic patients collected from all papers published on <0.05%–0.1% in different studies (Kalahanis et al., 2002; Karaca, globozoospermia from 1965 to January 2006 concluded that the Akpak, Oral, Durmus, & Yilmaz, 2015; Kim, Cha, Park, & Gye, 2001). average ejaculatory volume and sperm concentration were normal Round‐headed spermatozoa are also found in normal ejaculates, despite 100% morphological abnormalities in these sperm cells ac‐ but there is no definite threshold for the natural population of these cording to WHO standards (≤1999). However, the average sperm sperm cells in an individual normal ejaculate. In a study conducted motility was decreased by 39% (Dam et al., 2006). In fact, the major‐ on 233 semen samples from infertile men, the percentage of round‐ ity of each included case report in the aforementioned review (Dam headed spermatozoa was estimated to be 0.1%–0.8% (Andrade‐ et al., 2006) showed that the patients with globozoospermia rep‐ Rocha, 2001). Kalahanis et al. reported that globozoospermic sperm resented normal sperm concentrations and semen volume, but the rates were significantly higher in infertile men compared with fertile total sperm motility was in abnormal but admissible range (Larson subjects (2.3 ± 0.5% vs. 0.5% ± 0.1% respectively) (Kalahanis et al., et al., 2001; Vicari et al., 2002). 2002). In contrast, Dam et al. (2011) reported that sperm concentration, Despite little knowledge about the effect of environmental fac‐ progressive motility and normal morphology in globozoospermic tors such as smoking on increasing the number of round‐headed samples were significantly decreased compared with normozoosper‐ sperm cells in individual ejaculates, it is believed that environmental mic controls. In a case–controled study, Eskandiari and colleagues factors might be effective indicators for globozoospermia, especially reported significantly reduced sperm concentration and motility in for the partial type (Rubes et al., 1998). More detailed research is globozoospermic men compared with controls (68.60 and 53.20 vs. FESAHAT et AL. | 3 of 13 TABLE 1 List of key findings on semen parameters of globozoospermic men in recent studies Total motility Semen parameters Volume (ml) Count (106/ml) (%) Normal morphology (%) Dam et al. (2006) 3.7 (N = 43) 67 (N = 67) 39 (N = 64) 0I Systematic review (WHO ≤1999) Varied based on morphological (Results collected from all papers published on assessmentsII globozoospermia from 1965 to January 2006) Different assessment was used in (N = 75) each study Cases: types I and II Egashira et al. (2009) 2.6 43 32.6 0 (Case report) (reference criteria was not mentioned) Simple light microscopic observa‐ (N = 1) tion was used Case: type I Sermondade et al. (2011) NA 35 30 0 (Case report) (WHO, 2010) Both Harris–Shorr coloration and (N = 1) motile sperm organelle morphol‐ Case: type I ogy examination (MSOME) were used Brahem et al. (2011) 2.1 115 53 0 (Case–control) (WHO, 1992) Methodology was not indicated (N = 2 vs., 20 respectively) Cases: types I and II Dam et al. (2011) 2 (N = 3)I 70I 38I 0A/E & D‐Q, I (Case–control) (WHO, 1999) 2.9 (N = 10)II 21II 22II 28A/E,II, 1D‐Q, II (N = 13 vs., 9 respectively) A/E and D‐Q were used Cases: types I and II Vozdova et al. (2014) 6.2 243 48 0 (Case report) (WHO, 2010) D‐Q and Spermac were used (N = 1) Case: type I Hosseinifar et al. (2015) NA 37.82 18.08 0 (Case–control) ¥ Papanicolaou was used (N = 20 vs., 40 respectively) Case: infertile men with more than 90% globozoospermia Ghasemzadeh et al. (2015) 3.24I 78.07I 33.93I 0I (Case–control) (WHO, 2010) Papanicolaou was used (N = 15 vs., 21 respectively) Case: type I Karaca et al. (2015) 3.2 14 57.33 0 (Case report) (WHO, 2010) D‐Q and TEM were used (N = 1) Case: type I Talebi et al. (2018) 3.3I 86.9I 38.96I 0I (Case–control) (WHO, 2010) 2.6II 38.8II 24.01II 0.19 (min = 0‐max = 3)II (N = 27 vs., 30 respectively) Papanicolaou was used Cases: types I and II Ghazavi et al. (2018) NA 58.5 34.5 0 (Case–control) (WHO, 2010)¥ Methodology was not indicated (N = 6 vs., 1 respectively)
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