TY - JOUR
T1 - Multicentric, prospective observational data show sperm capacitation predicts male fertility, and cohort comparison reveals a high prevalence of impaired capacitation in men questioning their fertility
AU - Sharara, Fady
AU - Seaman, Eric
AU - Morris, Randy
AU - Schinfeld, Jay
AU - Nichols, Jennifer
AU - Sobel, Michael
AU - Lee, Annette
AU - Somkuti, Stephen
AU - Hirshberg, Steven
AU - Budinetz, Tara
AU - Barmat, Larry
AU - Palermo, Gianpiero
AU - Rosenwaks, Zev
AU - Bar-Chama, Natan
AU - Bodie, Joshua
AU - Nichols, John
AU - Payne, John
AU - McCoy, Travis
AU - Tarnawa, Edward
AU - Whitman-Elia, Gail
AU - Weissmann, Lauren
AU - Doukakis, Maria
AU - Hurwitz, Joshua
AU - Leondires, Mark
AU - Murdock, Cynthia
AU - Ressler, Ilana
AU - Richlin, Spencer
AU - Williams, Shaun
AU - Wosnitzer, Matthew
AU - Butcher, Michael
AU - Kashanian, James
AU - Ahlering, Peter
AU - Aubuchon, Mira
AU - Ostermeier, G. Charles
AU - Travis, Alexander J.
N1 - Funding Information:
The authors are grateful to doctors and clinics who used the assay but did not meet the criteria for authorship, the patients and staff at all participating clinics, and the technical staff in Androvia's laboratory, particularly C. Cardona, B. Kloos, R. Mendoza, M. Moody and A. Simpson. Androvia LifeSciences supported costs associated with performing the Cap-Score and maintaining its database, individual clinics supported their own participation, and Cornell University supported A. J. Travis.
Publisher Copyright:
© 2020 The Author(s)
PY - 2020/7
Y1 - 2020/7
N2 - Research questions: Can a previously defined relationship between sperm capacitation and the probability of a man generating pregnancy within three cycles, prospectively predict male fertility in diverse clinical settings? A second study asked, what is the prevalence of impaired sperm fertilizing ability in men questioning their fertility (MQF), and does this relate to traditional semen analysis metrics? Design: In the multicentric, prospective observational study, data (n = 128; six clinics) were analysed to test a published relationship between the percentage of fertilization-competent, capacitated spermatozoa (Cap-Score) and probability of generating pregnancy (PGP) within three cycles of intrauterine insemination. Logistic regression of total pregnancy outcomes (n = 252) assessed fit. In the cohort comparison, Cap-Scores of MQF (n = 2155; 22 clinics) were compared with those of 76 fertile men. Results: New outcomes (n = 128) were rank-ordered by Cap-Score and divided into quintiles (25–26 per group); chi-squared testing revealed no difference between predicted and observed pregnancies (P = 0.809). Total outcomes (n = 252; 128 new + 124 previous) were pooled and the model recalculated, yielding an improved fit (P < 0.001). Applying the Akaike information criterion found that the optimal model used Cap-Score alone. Cap-Scores were performed on 2155 men (with semen analysis data available for 1948). To compare fertilizing ability, men were binned by PGP (≤19%, 20–29%, 30–39%, 40–49%, 50–59%, ≥60%). Distributions of PGP and the corresponding Cap-Scores were significantly lower in MQF versus fertile men (P < 0.001). Notably, 64% of MQF with normal volume, concentration and motility (757/1183) had PGP of 39% or less (Cap-Scores ≤31), versus 25% of fertile men. Conclusions: Sperm capacitation prospectively predicted male fertility. Impaired capacitation affects many MQF with normal semen analysis results, informing diagnosis versus idiopathic infertility.
AB - Research questions: Can a previously defined relationship between sperm capacitation and the probability of a man generating pregnancy within three cycles, prospectively predict male fertility in diverse clinical settings? A second study asked, what is the prevalence of impaired sperm fertilizing ability in men questioning their fertility (MQF), and does this relate to traditional semen analysis metrics? Design: In the multicentric, prospective observational study, data (n = 128; six clinics) were analysed to test a published relationship between the percentage of fertilization-competent, capacitated spermatozoa (Cap-Score) and probability of generating pregnancy (PGP) within three cycles of intrauterine insemination. Logistic regression of total pregnancy outcomes (n = 252) assessed fit. In the cohort comparison, Cap-Scores of MQF (n = 2155; 22 clinics) were compared with those of 76 fertile men. Results: New outcomes (n = 128) were rank-ordered by Cap-Score and divided into quintiles (25–26 per group); chi-squared testing revealed no difference between predicted and observed pregnancies (P = 0.809). Total outcomes (n = 252; 128 new + 124 previous) were pooled and the model recalculated, yielding an improved fit (P < 0.001). Applying the Akaike information criterion found that the optimal model used Cap-Score alone. Cap-Scores were performed on 2155 men (with semen analysis data available for 1948). To compare fertilizing ability, men were binned by PGP (≤19%, 20–29%, 30–39%, 40–49%, 50–59%, ≥60%). Distributions of PGP and the corresponding Cap-Scores were significantly lower in MQF versus fertile men (P < 0.001). Notably, 64% of MQF with normal volume, concentration and motility (757/1183) had PGP of 39% or less (Cap-Scores ≤31), versus 25% of fertile men. Conclusions: Sperm capacitation prospectively predicted male fertility. Impaired capacitation affects many MQF with normal semen analysis results, informing diagnosis versus idiopathic infertility.
KW - Andrology
KW - Assisted reproduction
KW - Diagnostic
KW - Infertility
KW - Pregnancy
KW - Real world data
KW - Real world evidence
UR - http://www.scopus.com/inward/record.url?scp=85085742310&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85085742310&partnerID=8YFLogxK
U2 - 10.1016/j.rbmo.2020.03.011
DO - 10.1016/j.rbmo.2020.03.011
M3 - Article
C2 - 32505543
AN - SCOPUS:85085742310
SN - 1472-6483
VL - 41
SP - 69
EP - 79
JO - Reproductive BioMedicine Online
JF - Reproductive BioMedicine Online
IS - 1
ER -