Pub Date : 2026-03-20DOI: 10.1016/j.fertnstert.2026.03.023
Daniel M Green,Kendrick Li,Raymond W Ke,Angela Delaney,Christine H Yu,Lu Xie,Kari Bjornard,DeoKumar Srivastava,William H Kutteh,Megan E Ware,Kyla C Shelton,Siddhant Taneja,Kirsten K Ness,John T Lucas,Gregory T Armstrong,Leslie L Robison,Melissa M Hudson
OBJECTIVETo study the long-term dose-response relationship of alkylating agents (AA) on azoospermia and oligospermia among adult childhood cancer survivors treated with or without platinating agents or epipodophyllotoxins.DESIGNRetrospective cohort with longitudinal follow-up SUBJECTS: Male survivors of childhood cancer ≥18 years of age and five or more years after diagnosis at the time of semen analysis EXPOSURE: Alkylating agents, platinating agents, epipodophyllotoxins, anthracyclines. No radiation therapy. AA exposure was estimated using the cyclophosphamide equivalent dose (CED). Platinating agent exposure was categorized using the cisplatin equivalent dose (CiED). Etoposide exposure was categorized using cumulative dose median.MAIN OUTCOME MEASURESParticipants were categorized as azoospermic, oligospermic (sperm concentration > 0 and < 15 million/ml), or normospermic (sperm concentration ≥ 15 million/ml).RESULTS22.1% of childhood cancer survivors had azoospermia, 26.7% oligospermia, and 51.1% normospermia. The odds of azoospermia or oligospermia increased by 1.111 (95% CI, 1.053 to 1.173) for each 1000 mg/m2 increase in CED, by 9.683 (95% CI 2.048 to 45.792) for CiED > 500 mg/m2, and by 4.738 (95% CI, 2.274 to 9.871) for treatment with etoposide > 10000 mg/m2. Risk for azoospermia and oligospermia among those not treated with a platinating agent was best distinguished from risk for normospermia using a CED cutoff of 7200 mg/m2 based on the Youden Index.CONCLUSIONNearly half of those who received AA without radiation therapy experience oligospermia or azoospermia. CED, CiED, and treatment with etoposide are significantly associated with azoospermia and oligospermia. These results will inform pre-treatment counseling of patients and therapeutic study design.
{"title":"Semen parameters in unirradiated, alkylating agent exposed childhood cancer survivors in the St. Jude Lifetime Cohort Study.","authors":"Daniel M Green,Kendrick Li,Raymond W Ke,Angela Delaney,Christine H Yu,Lu Xie,Kari Bjornard,DeoKumar Srivastava,William H Kutteh,Megan E Ware,Kyla C Shelton,Siddhant Taneja,Kirsten K Ness,John T Lucas,Gregory T Armstrong,Leslie L Robison,Melissa M Hudson","doi":"10.1016/j.fertnstert.2026.03.023","DOIUrl":"https://doi.org/10.1016/j.fertnstert.2026.03.023","url":null,"abstract":"OBJECTIVETo study the long-term dose-response relationship of alkylating agents (AA) on azoospermia and oligospermia among adult childhood cancer survivors treated with or without platinating agents or epipodophyllotoxins.DESIGNRetrospective cohort with longitudinal follow-up SUBJECTS: Male survivors of childhood cancer ≥18 years of age and five or more years after diagnosis at the time of semen analysis EXPOSURE: Alkylating agents, platinating agents, epipodophyllotoxins, anthracyclines. No radiation therapy. AA exposure was estimated using the cyclophosphamide equivalent dose (CED). Platinating agent exposure was categorized using the cisplatin equivalent dose (CiED). Etoposide exposure was categorized using cumulative dose median.MAIN OUTCOME MEASURESParticipants were categorized as azoospermic, oligospermic (sperm concentration > 0 and < 15 million/ml), or normospermic (sperm concentration ≥ 15 million/ml).RESULTS22.1% of childhood cancer survivors had azoospermia, 26.7% oligospermia, and 51.1% normospermia. The odds of azoospermia or oligospermia increased by 1.111 (95% CI, 1.053 to 1.173) for each 1000 mg/m2 increase in CED, by 9.683 (95% CI 2.048 to 45.792) for CiED > 500 mg/m2, and by 4.738 (95% CI, 2.274 to 9.871) for treatment with etoposide > 10000 mg/m2. Risk for azoospermia and oligospermia among those not treated with a platinating agent was best distinguished from risk for normospermia using a CED cutoff of 7200 mg/m2 based on the Youden Index.CONCLUSIONNearly half of those who received AA without radiation therapy experience oligospermia or azoospermia. CED, CiED, and treatment with etoposide are significantly associated with azoospermia and oligospermia. These results will inform pre-treatment counseling of patients and therapeutic study design.","PeriodicalId":12275,"journal":{"name":"Fertility and sterility","volume":"7 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147495007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-18DOI: 10.1016/j.fertnstert.2026.03.022
Nataly Del Aguila,Francisco Jose Sanz,Patricia Sebastian-Leon,Mónica Romeu,Asunta Martinez-Martinez,Antonio Parraga-Leo,Ana Monzó,Maria Del Carmen Vidal,Immaculada Sanchez-Ribas,Marcos Ferrando,Rebeca Esteve-Moreno,Antonio Pellicer,Patricia Diaz-Gimeno
OBJECTIVETo evaluate endometrial epigenetic age acceleration (EEAA)-the difference between epigenetic and chronological age-in endometrial tissue from patients undergoing in vitro fertilization (IVF), using Horvath's DNA-methylation-based clock.DESIGNCross-sectional observational study with prospective, multicentre data collection.SUBJECTSNinety-one Caucasian women aged 28.45-49.99 years undergoing IVF. All the participants followed a standardized hormone-replacement protocol (oral estradiol valerate and vaginal progesterone) and met the following inclusion criteria: BMI 19-29.9 kg/m2, endometrial thickness > 6.5 mm, and absence of systemic or interfering conditions.EXPOSUREEndometrial biopsies collected in the mid-secretory phase.MAIN OUTCOME MEASURESEEAA in an IVF population measured using Horvath's epigenetic clock.RESULTSEndometrial epigenetic age in this population was 46.45 years, 5.79 years significantly higher than chronological age (p = 1.31 × 10-14 EEAA significantly decreased with increasing age: 12.29 years in women aged ≤ 35 years, 10.31 years in those aged 36-40, 7.60 years in the group aged 41-45, and 3.40 years in women aged > 45 (p = 3.89×10-7).CONCLUSIONThe endometrium of women undergoing IVF shows significant epigenetic age acceleration, which is most pronounced at younger maternal ages. Although further studies linking EEAA to clinical outcomes are needed, EEAA may serve as a biomarker of endometrial health and fertility potential.
{"title":"Epigenetic clock timing in the endometrium of women undergoing IVF.","authors":"Nataly Del Aguila,Francisco Jose Sanz,Patricia Sebastian-Leon,Mónica Romeu,Asunta Martinez-Martinez,Antonio Parraga-Leo,Ana Monzó,Maria Del Carmen Vidal,Immaculada Sanchez-Ribas,Marcos Ferrando,Rebeca Esteve-Moreno,Antonio Pellicer,Patricia Diaz-Gimeno","doi":"10.1016/j.fertnstert.2026.03.022","DOIUrl":"https://doi.org/10.1016/j.fertnstert.2026.03.022","url":null,"abstract":"OBJECTIVETo evaluate endometrial epigenetic age acceleration (EEAA)-the difference between epigenetic and chronological age-in endometrial tissue from patients undergoing in vitro fertilization (IVF), using Horvath's DNA-methylation-based clock.DESIGNCross-sectional observational study with prospective, multicentre data collection.SUBJECTSNinety-one Caucasian women aged 28.45-49.99 years undergoing IVF. All the participants followed a standardized hormone-replacement protocol (oral estradiol valerate and vaginal progesterone) and met the following inclusion criteria: BMI 19-29.9 kg/m2, endometrial thickness > 6.5 mm, and absence of systemic or interfering conditions.EXPOSUREEndometrial biopsies collected in the mid-secretory phase.MAIN OUTCOME MEASURESEEAA in an IVF population measured using Horvath's epigenetic clock.RESULTSEndometrial epigenetic age in this population was 46.45 years, 5.79 years significantly higher than chronological age (p = 1.31 × 10-14 EEAA significantly decreased with increasing age: 12.29 years in women aged ≤ 35 years, 10.31 years in those aged 36-40, 7.60 years in the group aged 41-45, and 3.40 years in women aged > 45 (p = 3.89×10-7).CONCLUSIONThe endometrium of women undergoing IVF shows significant epigenetic age acceleration, which is most pronounced at younger maternal ages. Although further studies linking EEAA to clinical outcomes are needed, EEAA may serve as a biomarker of endometrial health and fertility potential.","PeriodicalId":12275,"journal":{"name":"Fertility and sterility","volume":"14 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVETo examine intra-patient variability in retrieved oocyte numbers across consecutive in-vitro fertilization (IVF) ovarian stimulation (OS) cycles with an identical OS protocol.DESIGNCross-continental, multi-center retrospective cohort study.SUBJECTSPatients undergoing OS for IVF (2014-2024) with ≥2 OS cycles within six-months using the same OS protocol, gonadotropin type, and initial and daily dose; all underwent freeze-all-cycles and had ≥1 oocyte retrieved in each of the two consecutive cycles. For each patient, the earliest consecutive pair meeting criteria was analyzed.EXPOSUREOocyte yield in the first versus consecutive OS cycle.MAIN OUTCOME MEASURESPrimary outcomes included: i) average percentage change in oocyte yield between cycles (higher divided by lower oocyte yield); and ii) 25th, 50th (median), and 75th percentiles of oocyte-yield percentage change, overall and by age groups (≤30, 31-35, 36-39, ≥40 years). Secondary outcomes included: i) coefficient of determination (R2) between each cycle's oocyte count and the patient's average oocyte count across both cycles, representing the extent of variation explained by the patient's baseline profile; ii) shifts between ovarian response categories--poor (1-3 oocytes), suboptimal (4-9), normal (10-14), and hyper-response (≥15); (iii) average and median percentage change in mature-oocyte-yield.RESULTSOverall, 801 cycle pairs met inclusion criteria. Mean daily gonadotropin dosage was 361.5±112.6 IU; with comparable demographic and cycle characteristics between cycles. Overall, the average percentage change in oocyte yield was 62.7%; the 25th, 50th (median), and 75th percentiles were 16.7%, 40%, and 80%, respectively. Fifty-percent of patients showed >33% difference in retrieved oocytes, and 381/801 (47.57%) shifted ovarian response categories, with 29/381 (7.61%) shifting across two categories. Median oocyte yield percentage change was 44.4% in women ≥40 versus 33.3% in those ≤30 years. The (R2) between each cycle and the average of the two cycles was 0.834, representing the optimal performance any prediction model could achieve when predicting oocyte yield given baseline characteristics alone. The average percentage change in mature oocyte yield was 74.5%, with a median of 50%, CONCLUSION: Cycle-to-cycle variations in retrieved oocyte yield exist despite the same cycle conditions, across all age groups, reflecting fluctuations in ovarian follicular readiness and response, challenging ovarian response categorization based on oocyte yield and stressing the importance of key performance indicators in IVF OS cycles.
{"title":"Intra-Patient Variability in the Number of Retrieved Oocytes and Ovarian Response Categories Between Consecutive IVF Cycles.","authors":"Alyssa Hochberg,Shachar Reuvenny,Nevo Itzhak,Almog Luz,Rohi Hourvitz,Eden Moran,Nikolaos P Polyzos,Eduardo Hariton,Wenjing Zheng,Thomas D'Hooghe,Ettie Maman,Micha Baum,Michal Youngster,Ariel Hourvitz","doi":"10.1016/j.fertnstert.2026.03.020","DOIUrl":"https://doi.org/10.1016/j.fertnstert.2026.03.020","url":null,"abstract":"OBJECTIVETo examine intra-patient variability in retrieved oocyte numbers across consecutive in-vitro fertilization (IVF) ovarian stimulation (OS) cycles with an identical OS protocol.DESIGNCross-continental, multi-center retrospective cohort study.SUBJECTSPatients undergoing OS for IVF (2014-2024) with ≥2 OS cycles within six-months using the same OS protocol, gonadotropin type, and initial and daily dose; all underwent freeze-all-cycles and had ≥1 oocyte retrieved in each of the two consecutive cycles. For each patient, the earliest consecutive pair meeting criteria was analyzed.EXPOSUREOocyte yield in the first versus consecutive OS cycle.MAIN OUTCOME MEASURESPrimary outcomes included: i) average percentage change in oocyte yield between cycles (higher divided by lower oocyte yield); and ii) 25th, 50th (median), and 75th percentiles of oocyte-yield percentage change, overall and by age groups (≤30, 31-35, 36-39, ≥40 years). Secondary outcomes included: i) coefficient of determination (R2) between each cycle's oocyte count and the patient's average oocyte count across both cycles, representing the extent of variation explained by the patient's baseline profile; ii) shifts between ovarian response categories--poor (1-3 oocytes), suboptimal (4-9), normal (10-14), and hyper-response (≥15); (iii) average and median percentage change in mature-oocyte-yield.RESULTSOverall, 801 cycle pairs met inclusion criteria. Mean daily gonadotropin dosage was 361.5±112.6 IU; with comparable demographic and cycle characteristics between cycles. Overall, the average percentage change in oocyte yield was 62.7%; the 25th, 50th (median), and 75th percentiles were 16.7%, 40%, and 80%, respectively. Fifty-percent of patients showed >33% difference in retrieved oocytes, and 381/801 (47.57%) shifted ovarian response categories, with 29/381 (7.61%) shifting across two categories. Median oocyte yield percentage change was 44.4% in women ≥40 versus 33.3% in those ≤30 years. The (R2) between each cycle and the average of the two cycles was 0.834, representing the optimal performance any prediction model could achieve when predicting oocyte yield given baseline characteristics alone. The average percentage change in mature oocyte yield was 74.5%, with a median of 50%, CONCLUSION: Cycle-to-cycle variations in retrieved oocyte yield exist despite the same cycle conditions, across all age groups, reflecting fluctuations in ovarian follicular readiness and response, challenging ovarian response categorization based on oocyte yield and stressing the importance of key performance indicators in IVF OS cycles.","PeriodicalId":12275,"journal":{"name":"Fertility and sterility","volume":"7 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17DOI: 10.1016/j.fertnstert.2026.03.019
Yannick Hurni,Francesco La Torre,Nuria Barbany-Freixa,Maria A Lequerica-Cabello,Maria Angela Pascual,Betlem Graupera,Francesc Tresserra,Sandra García-Martínez,Silvia Cabrera,Pere N Barri-Soldevila
{"title":"Intraoperative Transvaginal Ultrasound for Rectosigmoid Endometriosis: A Feasibility Study.","authors":"Yannick Hurni,Francesco La Torre,Nuria Barbany-Freixa,Maria A Lequerica-Cabello,Maria Angela Pascual,Betlem Graupera,Francesc Tresserra,Sandra García-Martínez,Silvia Cabrera,Pere N Barri-Soldevila","doi":"10.1016/j.fertnstert.2026.03.019","DOIUrl":"https://doi.org/10.1016/j.fertnstert.2026.03.019","url":null,"abstract":"","PeriodicalId":12275,"journal":{"name":"Fertility and sterility","volume":"11 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17DOI: 10.1016/j.fertnstert.2026.03.018
Rachel L Babcock,Allan Haynes,Jannette M Dufour
Infertility impacts roughly one in six adults globally, where 50% of infertility cases are due to male factors. It is estimated that up to 15% of male infertility cases are due to disruption of testicular immune regulation. Thus, understanding mechanisms of immune privilege dysregulation resulting in blood-testis-barrier (BTB) disruption and germ cell loss could bring us one step closer to identifying ways to address infertility issues. In this views and reviews article, we introduce how testicular immune privilege is established at the BTB through junction proteins between adjacent Sertoli cells and surrounding testicular and immune cells, and discuss how immune protection fails due to infections, cancers, and traumas. Finally, we discuss clinical considerations when immune privilege has failed, including attention for clinical counseling, infertility workups, and fertility preservation approaches.
{"title":"Testicular Immune Privilege Revisited: When Protection Fails.","authors":"Rachel L Babcock,Allan Haynes,Jannette M Dufour","doi":"10.1016/j.fertnstert.2026.03.018","DOIUrl":"https://doi.org/10.1016/j.fertnstert.2026.03.018","url":null,"abstract":"Infertility impacts roughly one in six adults globally, where 50% of infertility cases are due to male factors. It is estimated that up to 15% of male infertility cases are due to disruption of testicular immune regulation. Thus, understanding mechanisms of immune privilege dysregulation resulting in blood-testis-barrier (BTB) disruption and germ cell loss could bring us one step closer to identifying ways to address infertility issues. In this views and reviews article, we introduce how testicular immune privilege is established at the BTB through junction proteins between adjacent Sertoli cells and surrounding testicular and immune cells, and discuss how immune protection fails due to infections, cancers, and traumas. Finally, we discuss clinical considerations when immune privilege has failed, including attention for clinical counseling, infertility workups, and fertility preservation approaches.","PeriodicalId":12275,"journal":{"name":"Fertility and sterility","volume":"12 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17DOI: 10.1016/j.fertnstert.2026.03.021
Yiming Sun,Xiaoxi Sun,Kristina Gemzell-Danielsson
IMPORTANCEManagement of low responders is a challenge in the field of assisted reproduction. A number of trials comparing frozen versus fresh embryo transfer have been published and are mainly restricted to high and normal responders. Current studies on the suitability of frozen embryo transfer in low responders are limited and yielded mixed results.OBJECTIVETo investigate whether cryopreservation of all embryos and subsequent frozen embryo transfer produces better reproductive outcomes compared with fresh embryo transfer in low responders.EVIDENCE REVIEWWe searched PubMed, Embase, Cochrane Library, Web of Science Core Collection and Scopus from inception to December 2025. After de-duplication, titles and abstracts of 4423 articles were screened, and 154 full-text articles were assessed for eligibility. One randomized controlled trial and 14 non-randomized studies were included in the systematic review. Data extraction was performed for the primary outcome of live birth rate and secondary outcomes.FINDINGSHigh certainty evidence from one randomized controlled trial showed that frozen embryo transfer resulted in a reduction in live birth (RR 0.79, 95% CI 0.65-0.94), clinical pregnancy (RR 0.83, 95% CI 0.71-0.97) and cumulative live birth rate (RR 0.86, 95% CI 0.75-0.99), while non-randomized studies provided very uncertain evidence that there was no significant difference in the two groups including live birth rate (RR 1.00, 95% CI 0.65-1.55). A lower miscarriage rate favoring fresh embryo transfer was found in women fulfilling the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number criteria (RR 1.31, 95% CI 1.11-1.56). Consistent evidence indicated that frozen embryo transfer did not produce significant improvements in other reproductive outcomes.CONCLUSION AND RELEVANCEOur results suggested that the 'freeze-all' strategy did not produce better reproductive outcomes compared with fresh embryo transfer in low responders. Reproductive outcomes may be improved by performing fresh embryo transfer, which could be explained by a more physiological endometrium or better embryo quality without injury caused by cryopreservation. These findings should be further explored in randomized trials.
低应答者的管理是辅助生殖领域的一个挑战。一些比较冷冻和新鲜胚胎移植的试验已经发表，主要局限于高反应和正常反应。目前关于低应答者冷冻胚胎移植的适用性的研究是有限的，并且得出了混合的结果。目的探讨低应答者所有胚胎冷冻保存后冷冻胚胎移植是否比新鲜胚胎移植有更好的生殖效果。我们检索了PubMed， Embase, Cochrane Library， Web of Science Core Collection和Scopus从成立到2025年12月。删除重复后，筛选了4423篇文章的标题和摘要，并评估了154篇全文文章的合格性。系统评价纳入1项随机对照试验和14项非随机研究。对主要终点活产率和次要终点进行数据提取。一项随机对照试验的高确定性证据表明，冷冻胚胎移植导致活产（RR 0.79, 95% CI 0.65-0.94）、临床妊娠（RR 0.83, 95% CI 0.71-0.97）和累积活产率（RR 0.86, 95% CI 0.75-0.99）的降低，而非随机研究提供了非常不确定的证据，表明两组的活产率没有显著差异（RR 1.00, 95% CI 0.65-1.55）。在满足以患者为导向的策略包括个体化卵母细胞数量标准的妇女中，发现更低的流产率有利于新鲜胚胎移植（RR 1.31, 95% CI 1.11-1.56）。一致的证据表明，冷冻胚胎移植对其他生殖结果没有显著改善。结论和相关性我们的研究结果表明，与低应答者的新鲜胚胎移植相比，“冷冻全部”策略并没有产生更好的生殖结果。进行新鲜胚胎移植可能会改善生殖结果，这可能是由于子宫内膜更生理性或胚胎质量更好，而没有低温保存造成的损伤。这些发现应该在随机试验中进一步探索。
{"title":"Frozen versus fresh embryo transfer in low responders: a systematic review.","authors":"Yiming Sun,Xiaoxi Sun,Kristina Gemzell-Danielsson","doi":"10.1016/j.fertnstert.2026.03.021","DOIUrl":"https://doi.org/10.1016/j.fertnstert.2026.03.021","url":null,"abstract":"IMPORTANCEManagement of low responders is a challenge in the field of assisted reproduction. A number of trials comparing frozen versus fresh embryo transfer have been published and are mainly restricted to high and normal responders. Current studies on the suitability of frozen embryo transfer in low responders are limited and yielded mixed results.OBJECTIVETo investigate whether cryopreservation of all embryos and subsequent frozen embryo transfer produces better reproductive outcomes compared with fresh embryo transfer in low responders.EVIDENCE REVIEWWe searched PubMed, Embase, Cochrane Library, Web of Science Core Collection and Scopus from inception to December 2025. After de-duplication, titles and abstracts of 4423 articles were screened, and 154 full-text articles were assessed for eligibility. One randomized controlled trial and 14 non-randomized studies were included in the systematic review. Data extraction was performed for the primary outcome of live birth rate and secondary outcomes.FINDINGSHigh certainty evidence from one randomized controlled trial showed that frozen embryo transfer resulted in a reduction in live birth (RR 0.79, 95% CI 0.65-0.94), clinical pregnancy (RR 0.83, 95% CI 0.71-0.97) and cumulative live birth rate (RR 0.86, 95% CI 0.75-0.99), while non-randomized studies provided very uncertain evidence that there was no significant difference in the two groups including live birth rate (RR 1.00, 95% CI 0.65-1.55). A lower miscarriage rate favoring fresh embryo transfer was found in women fulfilling the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number criteria (RR 1.31, 95% CI 1.11-1.56). Consistent evidence indicated that frozen embryo transfer did not produce significant improvements in other reproductive outcomes.CONCLUSION AND RELEVANCEOur results suggested that the 'freeze-all' strategy did not produce better reproductive outcomes compared with fresh embryo transfer in low responders. Reproductive outcomes may be improved by performing fresh embryo transfer, which could be explained by a more physiological endometrium or better embryo quality without injury caused by cryopreservation. These findings should be further explored in randomized trials.","PeriodicalId":12275,"journal":{"name":"Fertility and sterility","volume":"89 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17DOI: 10.1016/j.fertnstert.2026.01.027
Catherine Racowsky Ph.D.
{"title":"The dilemma: is it reasonable to freeze immature oocytes and, if so, when?","authors":"Catherine Racowsky Ph.D.","doi":"10.1016/j.fertnstert.2026.01.027","DOIUrl":"https://doi.org/10.1016/j.fertnstert.2026.01.027","url":null,"abstract":"","PeriodicalId":12275,"journal":{"name":"Fertility and sterility","volume":"81 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-16DOI: 10.1016/j.fertnstert.2026.03.015
Eve C. Feinberg MD, Marcelle I. Cedars MD
This Views and Reviews brings together experts to evaluate and summarize the evidence on optimization of fertility using lifestyle interventions, surgical restoration of anatomy, menstrual cycle tracking, and comparative data between these methods and IVF. In summarizing the evidence, it becomes apparent that knowledge gaps exist and that all stakeholders must work collaboratively to prioritize women’s health and personalization of care to optimize health and time to pregnancy for all women. The need for additional research in women’s health and fertility is evident.
{"title":"Data driven analysis of fertility optimization","authors":"Eve C. Feinberg MD, Marcelle I. Cedars MD","doi":"10.1016/j.fertnstert.2026.03.015","DOIUrl":"https://doi.org/10.1016/j.fertnstert.2026.03.015","url":null,"abstract":"This Views and Reviews brings together experts to evaluate and summarize the evidence on optimization of fertility using lifestyle interventions, surgical restoration of anatomy, menstrual cycle tracking, and comparative data between these methods and IVF. In summarizing the evidence, it becomes apparent that knowledge gaps exist and that all stakeholders must work collaboratively to prioritize women’s health and personalization of care to optimize health and time to pregnancy for all women. The need for additional research in women’s health and fertility is evident.","PeriodicalId":12275,"journal":{"name":"Fertility and sterility","volume":"33 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-16DOI: 10.1016/j.fertnstert.2026.03.017
Sarah A. Robertson PhD, David J. Sharkey PhD
Seminal fluid is more than a vehicle for sperm transport. It contains a complex mix of immune-regulatory cytokines that, together with other bioactive factors, influence sperm generation and survival, and interact with female reproductive tract cells and tissues to facilitate conception and stimulate female receptivity to pregnancy. Cytokines are synthesized in the seminal vesicles, prostate, and other male accessory glands. They contact sperm at ejaculation, and upon intromission are delivered to the cervix and uterus in soluble form, as cargo of seminal extracellular vesicles, or in physical association with sperm. The relative concentrations of different cytokines vary between individual men and can fluctuate over time – in response to local and systemic viral or bacterial infection, acute and chronic inflammatory and metabolic disorders such as varicocele, prostatitis and diabetes, and environmental exposures including heat stress, chemical toxin exposures, and smoking. While seminal fluid cytokines in healthy men promote fertility through permissive effects on embryo development and implantation, elevated abundance of certain pro-inflammatory cytokines is linked with infertility and subfertility. Emerging insight on the identity and biological functions of key permissive and inhibitory seminal fluid cytokines indicates potential clinical applications in evaluating and managing male and female infertility, and for developing improved assisted reproduction techniques. However, knowledge gaps on the significance of cytokines in reproductive biology and pathophysiology, the most informative cytokines and their normal ranges, and technical challenges regarding optimal assay platforms and protocols, must first be overcome.
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