What about gr/gr deletions and male infertility? Systematic review and meta-analysis.

Katrien Stouffs, Willy Lissens, Herman Tournaye, Josiane Van Der Elst, Ingeborg Liebaers, Patrick Haentjens

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52 Citations (Scopus)

Abstract

Introduction: There has been a debate about the impact of gr/gr deletions on male fertility. These partial deletions of the AZFc region of the Y chromosome have been detected more frequently in subfertile patients than in control groups. However, few individual studies have been able to demonstrate a statistically significant association. In this systematic review, we aimed to quantify the strength of the association between gr/gr deletions and male subfertility, and to explore potential sources of heterogeneity including ethnicity, geographical location, and definition of infertility and control status.
Materials and methods: Medline was searched up to December 31 2007 for full articles concerning case-control studies in which the prevalence of gr/gr deletions was investigated in subfertile and control men. From each eligible study we abstracted data into 2 x 2 tables and calculated the odds ratio (OR) and the corresponding 95% confidence interval (95% CI). The pooled summary OR was estimated by the DerSimonian and Laird random-effects model since clinical heterogeneity was anticipated. Between-study heterogeneity was assessed by the Cochran's Q test, and quantified by the I2 statistic. We identified, a priori, the following potential sources of heterogeneity: publication year, total sample size, baseline prevalence of gr/gr deletions among controls, ethnicity, country of study, and geographic region defined according to the categories of the Global Burden of Disease (GBD) 2000 World Health Organization member states project. In this regard we performed categorical and meta-regression analyses. We further postulated, also a priori, that the findings would be affected by predetermined subgroup characteristics. To this end, we constructed separate 2 x 2 tables for studies providing separate data pertaining to cases with azoospermia, cases with oligozoospermia, and controls with normozoospermia, and conducted subgroup meta-analyses accordingly.
Results: Eighteen case-control studies including 5777 cases and 4481 controls met our inclusion criteria. In the individual studies gr/gr deletions varied from 2.1% to 30.1% among cases, and from 0.2% to 33.9% among controls. The individual ORs varied from 0.62 to 21.41. Pooled estimates indicated that gr/gr deletions were present in 4.94% (95% CI, 4.38-5.55) of cases and 3.47% (0-8.92) of controls. The association between gr/gr deletions and infertility was significant (P ¼ 0.005), with a pooled random-effects OR of 1.62 (1.15-2.27). The test for heterogeneity among studies was also significant (Q test P ¼ 0.029) with an I2 value of 43%, indicating moderate heterogeneity. The association between gr/gr deletions and subfertility was dependent on the geographic region: the pooled OR was significant in Europe (2.96; 1.54-5.70), but not in the Americas (1.33; 0.49-3.65), Southeast Asia (0.98; 0.24-4.04), the Eastern Mediterranean (1.23; 0.42-3.58), and the Western Pacific regions (1.38; 0.80- 1.62). The predefined subgroup meta-analysis including 7 studies providing data on cases with azoospermia versus controls with normozoospermia showed an increased but statistically non-significant pooled OR of 1.56 (0.80-3.02). No between-study heterogeneity was observed (Q test P ¼ 0.63, I2 ¼ 0%). By contrast, for the predefined subgroup meta-analysis of the 6 studies providing data on cases with oligozoospermia versus controls with normozoospermia, the pooled OR of 2.19 (1.19 to 4.01) was statistically significant (P ¼ 0.011). Again, there was no heterogeneity between studies. (Q test P ¼ 0.42, I2 ¼ 0%).
Conclusions: Our meta-analysis comprising more than 10 000 men analyzed for the presence of gr/gr deletions demonstrates that these partial AZFc deletions occur more frequently in subfertile than in control men. When comparing normozoospermic control men to azoospermic or oligozoospermic patients, a significantly higher occurence of gr/gr deletions is observed only in patients with oligozoospermia. These findings suggest that gr/gr deletions may cause a reduction in sperm concentration. In azoospermic men, and part of oligozoospermic men, at least one other factor must be involved.
Original languageEnglish
Pages (from-to)112-113
Number of pages2
JournalHum Reprod
Volume23
Publication statusPublished - 2008
EventFinds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet - Stockholm, Sweden
Duration: 21 Sep 200925 Sep 2009

Keywords

  • male infertility

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