{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:59:22Z","timestamp":1780981162307,"version":"3.54.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Female infertility affects approximately one in six couples worldwide and disproportionately impacts women aged 30\u201342 years, yet evidence on which interventions improve clinically meaningful outcomes (live birth and safety) is heterogeneous.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim of this study was to synthesize evidence on interventions that restore or improve fertility in women aged 30\u201342 years, grouped by etiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence review<\/jats:title>\n                    <jats:p>We conducted a PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses)-compliant systematic review (PROSPERO CRD420251109428). PubMed and Scopus were searched for English\/Spanish studies (1 January 2020 to 31 July 2025). Eligible designs were randomized trials and non-randomized interventional and observational studies. We aligned outcomes to the infertility core outcome set, prioritizing live birth per woman, then ongoing\/clinical pregnancy and prespecified safety endpoints. Risk of bias used RoB 2 [randomized controlled trials (RCTs)], ROBINS-I (non-randomized), and JBI (observational). When pooling was not feasible, we applied SwiM (Synthesis Without Meta-analysis) and summarized by etiology and intervention class.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>A total of 21 studies met inclusion criteria for synthesis, and two additional randomized protocols were summarized narratively (23 records tracked overall). Interventions spanned hormonal therapies, assisted reproductive technologies (ART) strategies, surgical procedures, lifestyle and psychosocial programs, and investigational adjuncts. Across etiologies, several interventions were associated with improved pregnancy-related outcomes\u2014such as myo-inositol, clomiphene with sildenafil, selected luteal support regimens, structured stress management, and specific ART strategies\u2014whereas live-birth effects were supported by only moderate-certainty evidence, limited by small samples, heterogeneity, and indirectness. Diagnostic and prognostic approaches (e.g., serum progesterone profiling, BAP-EB receptivity assay, and endometrial T-bet\/GATA3 ratio) showed predictive value but no therapeutic effect. Safety reporting was limited; few studies reported ovarian hyperstimulation syndrome, multiple gestation, or neonatal outcomes, and patient-reported outcomes were seldom assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and relevance<\/jats:title>\n                    <jats:p>For women aged 30\u201342 years, established hormonal and ART strategies improve pregnancy outcomes; however, certainty for live birth and safety remains limited. Clinical care should prioritize standard therapies and shared decision-making, acknowledging evidence gaps. Future trials must center on live birth, adopt standardized core outcomes, and consistently report maternal\u2013neonatal safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n                      , identifier CRD420251109428.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1741198","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:30:47Z","timestamp":1780979447000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Evidence-based interventions to restore or improve female fertility in women aged 30\u201342 years: a systematic review by etiology and evidence level"],"prefix":"10.3389","volume":"17","author":[{"given":"Maria Jimena","family":"Barroso Alverde","sequence":"first","affiliation":[{"name":"Anahuac University of North Mexico","place":["Huixquilucan de Degollado, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sion","family":"Yu","sequence":"additional","affiliation":[{"name":"Anahuac University of North Mexico","place":["Huixquilucan de Degollado, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Pascal Pont\u00f3n","sequence":"additional","affiliation":[{"name":"Avida Fertility","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise Niza","family":"Benardete Harari","sequence":"additional","affiliation":[{"name":"Avida Fertility","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Elias","family":"Tesone Lasman","sequence":"additional","affiliation":[{"name":"Avida Fertility","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13048-025-01629-y","article-title":"Association of age at menarche and different causes of infertility: a retrospective study of 7634 women undergoing assisted reproductive technology","volume":"18","author":"Chen","year":"2025","journal-title":"J Ovarian Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2023.03.018","article-title":"Association of endometriosis and adenomyosis with pregnancy and infertility","volume":"119","author":"Vercellini","year":"2023","journal-title":"Fertil Steril"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2021.1958310","article-title":"Polycystic ovarian syndrome and infertility: overview and insights of the putative treatments","volume":"37","author":"Coll\u00e9e","year":"2021","journal-title":"Gynecol Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/advances\/nmab141","article-title":"Nutritional supplements and complementary therapies in polycystic ovary syndrome","volume":"13","author":"Alesi","year":"2022","journal-title":"Adv Nutr"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.23736\/S2724-606X.24.05552-0","article-title":"Impact of endometriosis on oocyte quality in women undergoing assisted reproduction","volume":"76","author":"Chinta","year":"2024","journal-title":"Minerva Obstet Gynecol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12958-020-0567-7","article-title":"Smoke, alcohol and drug addiction and female fertility","volume":"18","author":"de Angelis","year":"2020","journal-title":"Reprod Biol Endocrinol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/medicina59091551","article-title":"Adenomyosis and infertility: a literature review","volume":"59","author":"Pados","year":"2023","journal-title":"Medicina (Kaunas)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/nu14081556","article-title":"The influence of diet on ovulation disorders in women\u2014a narrative review","volume":"14","author":"Jurczewska","year":"2022","journal-title":"Nutrients"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoad007","article-title":"Infertility in women of reproductive age in China: prevalence and risk factors","volume":"2023","author":"Zhou","year":"2023","journal-title":"Hum Reprod Open"},{"key":"B10","volume-title":"Fertility problems: assessment and treatment. 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