Sperm aneuploidy and recurrent pregnancy loss: A systematic review and meta-analysis

Figures & data

Table 1. Search strategy.(Web of science)

#1	TS = (“ sperm aneuploids ” or “ sperm aneuploidies ”or “sperm aneuploid ” or “ sperm aneuploidy”)
#2	TS = (“Habitual Abortion ”or “Habitual Abortions ”or “Miscarriage, Recurrent ”or “Recurrent Miscarriage ”or “Recurrent Miscarriages ”or “Abortion, Recurrent” or “Recurrent Abortion”or “Recurrent Abortions ” or “Recurrent Early Pregnancy Loss” or “recurrent spontaneous abortion”)
#1 AND #2

Unless otherwise declared, terms used in search strategy were free text terms. TS, topic

Table 2. Characters of included studiesTable2:Characters of included studies

Author time	Study type	RSA (n)	Control(n)	Sperm chromosome	Definition of RSA	Study reported results
Rubio et al. (1999)	Prospective	12	14	13/18/21/sex	≥2	(2); (4); (5); (9)
Rubio et al. (2001)	Retrospective	40	9	13/18/21/sex	3.0 ± 0.3(average)	(2); (4); (5); (9)
Carrell, Wilcox, et al., (2003)	Case control	24	10	13/18/21/sex	≥3	(1); (3); (4); (5)
Bernardini et al. (2004)	Case control	8	6	4/7/12/13/15/21/22/sex	≥3	(2); (3); (5); (6); (7); (8)
Al-Hassan et al. (2005)	Case control	14	5	13/18/21/sex	≥3	(2)
Collodel et al. (2009)	Retrospective	22	25	18/sex	≥3	(2); (4); (6); (7); (8); (9)
Neusser et al. (2015)	Case control	11	3	1-22/sex	≥3	(1); (2); (3); (4); (5); (6); (7); (8); (9)
Ramasamy et al. (2015)	Retrosrective	140	5(140 semensamples)20	13/18/21/sex	Recurrent miscarriage/inability to achieve a pregnancywithIVF/ICSI	qualitative analysis; a lack of standard deviation data
Zidi-Jrah et al. (2016)	Descriptive	22		18/sex	≥2	(2); (4); (6); (7); (8); (9)
Esquerré-Lamare et al. (2018)	Prospective case control	33	27	18/sex	≥3	(1); (4); (6); (7); (8)

(1)total sperm aneuploidy; (2)sperm diploidy; (3)Disomy13; (4)Disomy18;

(5):Disomy21;(6)DisomyX;(7)DisomyY;(8)DisomyXY;(9):Disomy sex chromosome

Figure 1. Flow chart of the meta-analysis

Table 3. Assessment of risk of bias based on Newcastle-Ottawa Scale

Author	Selection	Conparability^a	Exposure/Outcome	Total
Rubio et al. (1999)	**	**	***	7
Rubio et al. (2001)	***	**	***	8
Carrell, Wilcox, et al.,(2003)	**	**	**	6
Bernardini et al. (2004)	**	*	**	5
Al-Hassan et al. (2005)	*	**	**	5
Collodel et al. (2009)	**	*	**	5
Neusser et al. (2015)	**	**	**	6
Ramasamy et al. (2015)	***	**	**	7
Zidi-Jrah et al. (2016)	**	**	**	6
Esquerré-Lamare et al. (2018)	**	***	***	8

Table 4. Meta results of the included studies

Outcomes	Studies(n)	heterogeneity	effects model	Combined SMD and 95%CI	Combined OR and 95%CI	P value
total sperm aneuploidy	3	I^2 = 69% P = 0.04	random	1.07(0.39–1.75)	-	P < 0.01
sperm diploidy	5 2	I^2 = 89% P < 0.01 I^2 = 96% P < 0.01	random random	1.57(0.12–3.03)	0.66 (0.55–0.78)	P = 0.03 P < 0.01
Disomy13	3	I^2 = 53% P =  0.12	random	0.8 (−0.06–1.72)	-	P = 0.07
disomy18	5 2	I^2 = 85% P < 0.01 I^2 = 0% P =  0.59	random random	0.98 (0.12–1.84)	0.42 (0.27–0.65)	P = 0.03 P < 0.01
disomy 21	5 2	I^2 = 85% P < 0.01 I^2 = 0% P =  0.49	random random	2.24(0.03–4.45)	0.51(0.40–0.66)	P = 0.03 P < 0.01
disomy X	5	I^2 = 93% P < 0.01	random	0.70(−0.67–2.07)	-	P = 0.31
disomy Y disomy XY disomy sex chromosome	5 5 2	I^2 = 91% P < 0.01 I^2 = 72% P < 0.01 I^2 = 92% P < 0.01	random random random	0.83(−0.34–2.00) 0.87(0.21–1.53) 1.48(1.27–1.73)	-	P = 0.16 P < 0.01 P < 0.01

Heterogeneity include I² and P value

Figure 2. Forest plot of sperm aneuploidy

Figure 3. Forest plot of sperm diploidy/disomy 13/18/21

Figure 4. Forest plot of sperm disomy X/Y/XY

Figure 5. Forest plot of sperm dipoidy/disomy 18/21/sex chromosome

Figure 6. Funnel plots. (a) Sperm aneupoidy. (b) Sperm diploidy/disomy 13/18/21. (c) Sperm disomy X/Y/XY. (d) Sperm dipoidy/disomy 18/21/sex chromosome

Carrell, D. T., Wilcox, A. L., Lowy, L., Peterson, C. M., Jones, K. P., Erickson, L., Campbell, B., Branch, D. W., & Hatasaka, H. H. (2003). Elevated sperm chromosome aneuploidy and apoptosis in patients with unexplained recurrent pregnancy loss. Obstetrics and Gynecology, 101(6), 1229–1235. https://doi.org/10.1016/s0029-7844(03)00339-9

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Rubio, C., Gil-Salom, M., Simon, C., Vidal, F., Rodrigo, L., Minguez, Y., Remohí, J., & Pellicer, A. (2001). Incidence of sperm chromosomal abnormalities in a risk population: Relationship with sperm quality and ICSI outcome. Human Reproduction, 16(10), 2084–2092. https://doi.org/10.1093/humrep/16.10.2084

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Bernardini, L. M., Costa, M., Bottazzi, C., Gianaroli, L., Magli, M. C., Venturini, P. L., Francioso, R., Conte, N., & Ragni, N. (2004). Sperm aneuploidy and recurrent pregnancy loss. Reproductive Biomedicine Online, 9(3), 312–320. https://doi.org/10.1016/s1472-6483(10)62147-5

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Al-Hassan, S., Hellani, A., Al-Shahrani, A., Al-Deery, M., Jaroudi, K., & Coskun, S. (2005). Sperm chromosomal abnormalities in patients with unexplained recurrent abortion. Archives of Andrology, 51(1), 69–13. https://doi.org/10.1080/014850190518062

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Collodel, G., Giannerini, V., Antonio Pascarelli, N., Federico, M. G., Comodo, F., & Moretti, E. (2009). TEM and FISH studies in sperm from men of couples with recurrent pregnancy loss. Andrologia, 41(6), 352–360. https://doi.org/10.1111/j.1439-0272.2009.00936.x

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Neusser, M., Rogenhofer, N., Durl, S., Ochsenkuhn, R., Trottmann, M., Jurinovic, V., Steinlein, O., von Schönfeldt, V., Müller, S., & Thaler, C. J. (2015). Increased chromosome 16 disomy rates in human spermatozoa and recurrent spontaneous abortions. Fertility and Sterility, 104(5), 1130–1137. https://doi.org/10.1016/j.fertnstert.2015.07.1160

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Ramasamy, R., Scovell, J. M., Kovac, J. R., Cook, P. J., Lamb, D. J., & Lipshultz, L. I. (2015). Fluorescence in situ hybridization detects increased sperm aneuploidy in men with recurrent pregnancy loss. Fertility and Sterility, 103(4), 906–909. https://doi.org/10.1016/j.fertnstert.2015.01.029

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Zidi-Jrah, I., Hajlaoui, A., Mougou-Zerelli, S., Kammoun, M., Meniaoui, I., Sallem, A., Brahem, S., Fekih, M., Bibi, M., Saad, A., & Ibala-Romdhane, S. (2016). Relationship between sperm aneuploidy, sperm DNA integrity, chromatin packaging, traditional semen parameters, and recurrent pregnancy loss. Fertility and Sterility, 105(1), 58–64. https://doi.org/10.1016/j.fertnstert.2015.09.041

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Esquerré-Lamare, C., Walschaerts, M., Chansel-Debordeaux, L., Moreau, J., Bretelle, F., Isus, F., Karsenty, G., Monteil, L., Perrin, J., Papaxanthos-Roche, A., & Bujan, L. (2018). Sperm aneuploidy and DNA fragmentation in unexplained recurrent pregnancy loss: A multicenter case-control study. Basic and Clinical Andrology, 28(1), 4. https://doi.org/10.1186/s12610-018-0070-6

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