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

Fady Sharara, Eric Seaman, Randy Morris, Jay Schinfeld, Jennifer Nichols, Michael Sobel, Annette Lee, Stephen Somkuti, Steven Hirshberg, Tara Budinetz, Larry Barmat, Gianpiero Palermo, Zev Rosenwaks, Natan Bar-Chama, Joshua Bodie, John Nichols, John Payne, Travis McCoy, Edward Tarnawa, Gail Whitman-EliaLauren Weissmann, Maria Doukakis, Joshua Hurwitz, Mark Leondires, Cynthia Murdock, Ilana Ressler, Spencer Richlin, Shaun Williams, Matthew Wosnitzer, Michael Butcher, James Kashanian, Peter Ahlering, Mira Aubuchon, G. Charles Ostermeier, Alexander J. Travis

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)69-79
Number of pages11
JournalReproductive BioMedicine Online
Volume41
Issue number1
DOIs
StatePublished - Jul 2020

Bibliographical note

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.

Keywords

  • Andrology
  • Assisted reproduction
  • Diagnostic
  • Infertility
  • Pregnancy
  • Real world data
  • Real world evidence

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