{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:52:05Z","timestamp":1792515125808,"version":"4.5.0"},"reference-count":38,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Treatments for men seeking fertility care are limited. Antioxidant supplements have been widely studied as a new treatment option, but these studies have had conflicting results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess whether treatment of men seeking fertility care with an antioxidant supplement can improve semen quality and pregnancy rates compared with a placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>The SUMMER trial was a multicenter, double-blind, placebo-controlled randomized clinical trial conducted in 21 hospitals and private fertility clinics in the Netherlands. Male patients in these centers were enrolled between May 2018 and February 2024, and follow-up of the primary outcome was completed in December 2024. Eligible participants were men aged 18 to 50 years with female partners aged 18 to 43 years, who sought fertility care and were advised to undergo expectant management, treatment with intrauterine insemination, in vitro fertilization (IVF), or intracytoplasmic sperm injection (ICSI). Couples treated with ovulation induction only or IVF for bilateral tubal pathology were excluded. The men were randomly assigned to receive an antioxidant supplement or a placebo. Intention-to-treat analysis was performed for all outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>\n                      The antioxidant supplement (Impryl) was a tablet to be taken daily for 6 months. It contained betaine (200 mg), L-cystine (200 mg), niacin (16 mg), zinc (10 mg), vitamin B\n                      <jats:sub>6<\/jats:sub>\n                      (1.4 mg), vitamin B\n                      <jats:sub>2<\/jats:sub>\n                      (1.4 mg), folic acid (400 \u00b5g), and vitamin B\n                      <jats:sub>12<\/jats:sub>\n                      (2.5 \u00b5g). The placebo tablet and its packaging were identical to those of the antioxidant supplement. All participating couples received standard infertility care.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>The primary outcome was ongoing pregnancy conceived within 6 months after randomization. Secondary outcomes included semen parameters, sperm DNA fragmentation, fertilization and embryo utilization rates after IVF or ICSI, biochemical and clinical pregnancy rates, first-trimester pregnancy loss, ectopic pregnancy rate, cumulative number of pregnancies, time to pregnancy, and adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 1171 men (median [IQR] age, 34 [31-38] years; female partners\u2019 median [IQR] age, 32 [30-35] years) were included in the data analysis, of whom 591 were in the antioxidant supplement group and 580 were in the placebo group. Ongoing pregnancy rate within 6 months was not significantly different between the 2 groups (193 of 571 [33.8%] vs 208 of 555 [37.5%]; adjusted odds ratio [AOR], 0.85 [95% CI, 0.66-1.09];\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.20). Within the window of optimal treatment effect between 4 and 6 months (considering a spermatogenesis cycle of 72 days), ongoing pregnancy rate was significantly lower in the antioxidant supplement group compared with the placebo group (69 of 446 [15.5%] vs 95 of 442 [21.5%]; AOR, 0.66 [95% CI, 0.47-0.94];\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.02). There were no significant between-group differences for the secondary outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>This randomized clinical trial found that ongoing pregnancy rates did not improve with the antioxidant supplement compared with a placebo. Therefore, the investigators do not support its use in men seeking fertility care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT03337360?intr=NCT03337360&amp;amp;amp;rank=1\">NCT03337360<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.32405","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T15:31:06Z","timestamp":1758814266000},"page":"e2532405","source":"Crossref","is-referenced-by-count":15,"title":["Antioxidant Treatment and the Chance to Conceive in Men Seeking Fertility Care"],"prefix":"10.1001","volume":"8","author":[{"given":"Wiep R.","family":"de Ligny","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, the Netherlands"},{"name":"Department of Obstetrics and Gynecology, Jeroen Bosch Hospital, \u2018s-Hertogenbosch, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Peter","family":"de Bruin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Jeroen Bosch Hospital, \u2018s-Hertogenbosch, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roos M.","family":"Smits","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilse G. 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