Are sperm chromatin and DNA defects relevant in the clinic?

Figures & data

Table 1.  Selected Diagnostic Properties of Studies on Sperm DNA Damage and Natural Pregnancy.

Study	n	Assay	%hDD	Sens	Spec	PPV	NPV	OR	(95% CI)
Evenson et al. 1999	144	SCSA	7	0.19	0.96	0.60	0.81	6.54	(1.72, 24.92)
Spano et al. 2000	215	SCSA	13	0.23	0.96	0.86	0.55	7.59	(2.54, 22.67)
Giwercman et al. 2010	257	SCSA	12	0.21	0.96	0.83	0.58	6.82	(2.52, 18.47)

Abbreviations: %hDD = proportion of samples with high sperm DNA damage; Sens = sensitivity; Spec = specificity; PPV = positive predictive value; NPV = negative predictive value; OR = odds ratio; SCSA = sperm chromatin structure assay.

Table 2.  Selected Diagnostic Properties of 11 Studies on Sperm DNA Damage and Pregnancy After IVF.

Study	n	Assay	%hDD	Sens	Spec	PPV	NPV	OR	(95% CI)
Filatov et al. 1999	176	CC	41	0.46	0.88	0.96	0.21	6.34	(1.82, 22.08)
Host et al. 2000	175	TUNEL	30	0.34	0.79	0.77	0.37	1.92	(0.92, 4.04)
Henkel et al. 2003	208	TUNEL	69	0.35	0.81	0.81	0.35	2.24	(1.09, 4.58)
Huang et al. 2005	217	TUNEL	19	0.22	0.83	0.50	0.57	1.30	(0.66, 2.56)
Boe-Hansen et al. 2006	139	SCSA	5	0.06	0.97	0.86	0.29	2.43	(0.28, 20.83)
Borini et al. 2006	82	TUNEL	16	0.17	0.89	0.85	0.23	1.66	(0.33, 8.28)
Lin et al. 2008	137	SCSA	16	0.15	0.83	0.45	0.51	0.88	(0.35, 2.19)
Benchaib et al. 2007	84	TUNEL	10	0.07	0.86	0.50	0.32	0.46	(0.11, 2.00)
Bungum et al. 2007	388	SCSA	16	0.17	0.86	0.71	0.34	1.24	(0.69, 2.26)
Frydman et al. 2008	117	TUNEL	44	0.58	0.68	0.64	0.35	2.97	(1.39, 6.32)
Tarozzi et al. 2009	82	CMA3	17	0.22	0.97	0.97	0.28	10.86	(0.62, 191.5)

Abbreviations: %hDD = proportion of samples with high sperm DNA damage; Sens = sensitivity; Spec = specificity; PPV = positive predictive value; NPV = negative predictive value; OR = odds ratio; CC = chromatin compaction; TUNEL = terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling; SCSA = sperm chromatin structure assay; CMA3 = chromomycin A3.

Table 3.  Selected Characteristics of 11 Studies on Sperm DNA Damage and Pregnancy After IVF.

Study	Population	Outcome	Design	Female factors	Cutoff based on
Filatov et al. 1999	Unselected	CP	Unspecified	Unspecified	Large population
Host et al. 2000	Unselected	BP	Prospective	Unspecified	Fertile population
Henkel et al. 2003	Unselected	CP	Prospective	Unspecified	ROC analysis
Huang et al. 2005	Unselected	CP	Retrospective	Unspecified	Unspecified
Boe-Hansen et al. 2006	Unselected	CP	Prospective	FSH<10	Evenson et al. 1999
Borini et al. 2006	Unselected	CP	Unspecified	Unspecified	Benchaib et al. 2007
Lin et al. 2008	Normal semen	CP	Prospective	<40 years, FSH<15	Evenson et al. 1999
Benchaib et al. 2007	Unselected	CP	Prospective	Unspecified	IVF & ICSI results
Bungum et al. 2007	Female factor	BP	Prospective	<40 years, FSH<12	Evenson et al. 1999
Frydman et al. 2008	Unselected	CP	Prospective	<38 years, FSH<10	Median value
Tarozzi et al. 2009	Male factor	CP	Unspecified	Unspecified	ROC analysis

Abbreviations: CP = clinical pregnancy; BP = biochemical pregnancy; ROC = receiver operating characteristics.

Table 4.  Selected Diagnostic Properties of 14 Studies on Sperm DNA Damage and Pregnancy After ICSI.

Study	n	Assay	%hDD	Sens	Spec	PPV	NPV	OR	95% CI
Hammadeh et al. 1996	60	ABlue	44	0.50	0.71	0.82	0.35	2.40	(0.72, 7.96)
Host et al. 2000	61	TUNEL	59	0.57	0.38	0.58	0.36	0.79	(0.28, 2.25)
Henkel et al. 2003	54	TUNEL	48	0.68	0.63	0.79	0.50	3.67	(1.12, 12.0)
Gandini et al. 2004	22	SCSA	41	0.31	0.44	0.44	0.31	0.36	(0.06, 2.08)
Huang et al. 2005	86	TUNEL	57	0.64	0.50	0.55	0.60	1.80	(0.76, 4.27)
Zini et al. 2005	60	SCSA	18	0.17	0.81	0.46	0.51	0.87	(0.23, 3.22)
Check et al. 2005	104	SCSA	28	0.29	0.76	0.72	0.34	1.34	(0.52, 3.43)
Boe-Hansen et al. 2006	47	SCSA	38	0.36	0.57	0.67	0.28	0.76	(0.21, 2.72)
Borini et al. 2006	50	TUNEL	60	0.71	0.75	0.90	0.45	7.36	(1.67, 32.4)
Benchaib et al. 2007	218	TUNEL	17	0.19	0.87	0.72	0.37	1.55	(0.70, 3.41)
Bungum et al. 2007	223	SCSA	33	0.29	0.61	0.52	0.37	0.65	(0.37, 1.14)
Lin et al. 2008	86	SCSA	24	0.26	0.77	0.52	0.52	1.21	(0.45, 3.23)
Micinski et al. 2009	50	SCSA	35	0.40	0.85	0.91	0.28	3.73	(0.74, 18.77)
Tarozzi et al. 2009	50	CMA3	56	0.49	0.27	0.61	0.18	0.34	(0.09, 1.29)

Abbreviations: %hDD = proportion of samples with high sperm DNA damage; Sens = sensitivity; Spec = specificity; PPV = positive predictive value; NPV = negative predictive value; OR = odds ratio; ABlue = aniline blue; TUNEL = terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling; SCSA = sperm chromatin structure assay; CMA3 = chromomycin A3.

Table 5.  Selected Characteristics of 14 Studies on Sperm DNA Damage and Pregnancy After ICSI.

Study	Population	Outcome	Design	Female factors	Cutoff based on
Hammadeh et al. 1996	Male factor	CP	Prospective	Unspecified	ROC analysis
Host et al. 2000	Male factor	CP	Prospective	Unspecified	Fertile population
Henkel et al. 2003	Unselected	CP	Prospective	Unspecified	Large population
Gandini et al. 2004	Unselected	CP	Prospective	Unspecified	Evenson et al. 1999
Huang et al. 2005	Unselected	CP	Retrospective	Unspecified	Unspecified
Zini et al. 2005	Unselected	CP	Prospective	Unspecified	Evenson et al. 1999
Check et al. 2005	IVF failures	CP	Unspecified	Unspecified	Evenson et al. 1999
Boe-Hansen et al. 2006	Unselected	CP	Prospective	Unspecified	Large population
Borini et al. 2006	Unselected	CP	Unspecified	Unspecified	Benchaib et al. 2007
Benchaib et al. 2007	Unselected	CP	Prospective	Unspecified	IVF & ICSI results
Bungum et al. 2007	Male factor	CP	Prospective	<40 years, FSH<12	Evenson et al. 1999
Lin et al. 2008	Male factor	CP	Prospective	<40 years, FSH<15	Evenson et al. 1999
Micinski et al. 2009	Unselected	CP	Prospective	<38 years	Filatov et al. 1999
Tarozzi et al. 2009	Male factor	CP	Unspecified	Unspecified	ROC analysis

Abbreviations: CP = clinical pregnancy; ROC = receiver operating characteristics.

Table 6.  Selected Diagnostic Properties of Studies on Sperm DNA Damage and Pregnancy Loss (PL) After IVF and IVF/ICSI.

Study	n	ART	Assay	PL (%)	Ab Test* (%)	Sens	Spec	PPV	NPV	OR (95% CI)
Check et al. 2005	104	ICSI	SCSA	47	24	0.31	0.83	0.63	0.58	2.27 (0.45, 11.59)
Zini et al. 2005	60	ICSI	SCSA	16	19	0.40	0.85	0.33	0.88	3.67 (0.46, 29.42)
Borini et al. 2006	82	IVF	TUNEL	6	11	0.91	0.94	0.50	0.99	160 (0.18,144708)
Borini et al. 2006	50	ICSI	TUNEL	25	25	0.97	0.99	0.97	0.99	2700 (0.38, 2×10^7)
Benchaib et al. 2007	84	IVF	TUNEL	15	15	0.50	0.91	0.50	0.91	10.0 (0.87, 114.8)
Benchaib et al. 2007	218	ICSI	TUNEL	12	15	0.38	0.88	0.30	0.91	4.54 (0.89, 23.28)
Bungum et al. 2007	388	IVF	SCSA	24	14	0.11	0.85	0.19	0.76	0.73 (0.23, 2.33)
Bungum et al. 2007	223	ICSI	SCSA	19	40	0.50	0.63	0.24	0.84	1.69 (0.63, 4.49)
Frydman et al. 2008	117	IVF	TUNEL	19	32	0.64	0.75	0.37	0.90	5.25 (1.31, 21.11)
Lin et al. 2008	137	IVF	SCSA	10	17	0.29	0.84	0.17	0.92	2.16 (0.37, 12.72)
Lin et al. 2008	86	ICSI	SCSA	18	23	0.50	0.83	0.40	0.88	5.00 (0.97, 25.77)

Abbreviations: ART = assisted reproductive technology; PL = pregnancy loss; Ab Test = proportion of abnormal sperm DNA test amongst documented pregnancies; Sens = sensitivity; Spec = specificity; PPV = positive predictive value; NPV = negative predictive value; OR = odds ratio.

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