Pub Date : 2025-12-01Epub Date: 2025-06-17DOI: 10.1016/j.xfnr.2025.100095
Anisha R. Chada M.D. , Kerri E. Andre M.D. , Noor Al-Shibli M.D. , Heather S. Hipp M.D.
<div><h3>Objective</h3><div>Human immunodeficiency virus (HIV) has transformed from an almost universally terminal diagnosis to that of a chronic manageable condition over the last 4 decades. Patients of reproductive age make up the largest proportion of those with HIV. Our aim in this scoping review was to investigate how HIV sequelae, comorbidities, and antiretroviral treatment affect both male fertility and female fertility.</div></div><div><h3>Evidence Review</h3><div>A scoping review identified relevant articles on HIV, fertility, assisted reproductive technology, and HIV treatment. Included articles had one of the following study designs: prospective; retrospective; controlled; randomized controlled; or observational. Articles were excluded if they were of inappropriate study design or published in a non-English language. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines were used to assess eligibility of studies identified through PubMed, and manuscripts were reviewed independently by 2 reviewers.</div></div><div><h3>Results</h3><div>Fifty-nine manuscripts were included in the final qualitative synthesis, including 9 prospective studies, 14 retrospective studies, 35 observational studies, and 1 clinical trial. Articles on male fertility (n = 10) mainly focused on effects of HIV and/or antiretrovirals on semen quality, finding some level of abnormality in semen parameters compared with controls. Small observational studies (n = 4) found statistically significant effects of antiretroviral therapy on semen parameters. Large observational studies (n = 2) examining outcomes for serodiscordant couples pursuing intrauterine insemination with HIV+ male partner showed pregnancy outcomes comparable to those of controls. In studies examining outcomes of in vitro fertilization for serodiscordant couples with HIV+ male partner (n = 5), pregnancy outcomes were comparable to those of controls. In female patients with HIV (n = 7), HIV infection was associated with ovarian dysfunction and/or oligomenorrhea or prolonged amenorrhea. Markers of severe disease, such as a low CD4 count or viremia, were shown to be correlated with lower antimüllerian hormone levels. Three studies illustrated how the effects of comorbidities such as history of smoking, drug use, or pelvic infections can also compound infertility in these patients. Several cohort studies (n = 13) showed increased time to pregnancy, decreased pregnancy rates with and without in vitro fertilization, and an increased risk of spontaneous abortion. Given that the current backbone of preconception and antepartum management of HIV includes dual therapy with nucleoside reverse transcriptase inhibitors (NRTIs), most of the studies (n = 7) focused on NRTI’s potential toxicities such as mitochondrial depletion in gametes. In vitro and animal studies (n = 3) have shown negative implications on oocyte fertilizability and genomic disturbances in offs
{"title":"Fertility considerations in individuals affected by human immunodeficiency virus: a scoping review","authors":"Anisha R. Chada M.D. , Kerri E. Andre M.D. , Noor Al-Shibli M.D. , Heather S. Hipp M.D.","doi":"10.1016/j.xfnr.2025.100095","DOIUrl":"10.1016/j.xfnr.2025.100095","url":null,"abstract":"<div><h3>Objective</h3><div>Human immunodeficiency virus (HIV) has transformed from an almost universally terminal diagnosis to that of a chronic manageable condition over the last 4 decades. Patients of reproductive age make up the largest proportion of those with HIV. Our aim in this scoping review was to investigate how HIV sequelae, comorbidities, and antiretroviral treatment affect both male fertility and female fertility.</div></div><div><h3>Evidence Review</h3><div>A scoping review identified relevant articles on HIV, fertility, assisted reproductive technology, and HIV treatment. Included articles had one of the following study designs: prospective; retrospective; controlled; randomized controlled; or observational. Articles were excluded if they were of inappropriate study design or published in a non-English language. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines were used to assess eligibility of studies identified through PubMed, and manuscripts were reviewed independently by 2 reviewers.</div></div><div><h3>Results</h3><div>Fifty-nine manuscripts were included in the final qualitative synthesis, including 9 prospective studies, 14 retrospective studies, 35 observational studies, and 1 clinical trial. Articles on male fertility (n = 10) mainly focused on effects of HIV and/or antiretrovirals on semen quality, finding some level of abnormality in semen parameters compared with controls. Small observational studies (n = 4) found statistically significant effects of antiretroviral therapy on semen parameters. Large observational studies (n = 2) examining outcomes for serodiscordant couples pursuing intrauterine insemination with HIV+ male partner showed pregnancy outcomes comparable to those of controls. In studies examining outcomes of in vitro fertilization for serodiscordant couples with HIV+ male partner (n = 5), pregnancy outcomes were comparable to those of controls. In female patients with HIV (n = 7), HIV infection was associated with ovarian dysfunction and/or oligomenorrhea or prolonged amenorrhea. Markers of severe disease, such as a low CD4 count or viremia, were shown to be correlated with lower antimüllerian hormone levels. Three studies illustrated how the effects of comorbidities such as history of smoking, drug use, or pelvic infections can also compound infertility in these patients. Several cohort studies (n = 13) showed increased time to pregnancy, decreased pregnancy rates with and without in vitro fertilization, and an increased risk of spontaneous abortion. Given that the current backbone of preconception and antepartum management of HIV includes dual therapy with nucleoside reverse transcriptase inhibitors (NRTIs), most of the studies (n = 7) focused on NRTI’s potential toxicities such as mitochondrial depletion in gametes. In vitro and animal studies (n = 3) have shown negative implications on oocyte fertilizability and genomic disturbances in offs","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 2","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The use of gonadotropin-releasing hormone (GnRH) antagonist protocols in assisted reproductive technology provides various options for achieving final follicular maturation. The choice of agent should be tailored to the patient characteristics and the mechanism of action of the triggers. The two primary agents used for this purpose are human chorionic gonadotropin, which acts as a luteinizing hormone analogue, and GnRH agonist, which induces the release of internal gonadotropin stores. Although these agents aim to achieve the same goal, they differ in the mechanism of action and downstream effects. Human chorionic gonadotropin binds to the luteinizing hormone receptors in the ovarian follicles and promotes oocyte maturation and ovulation through continuous luteotropic activity. This prolonged effect can increase the risk of ovarian hyperstimulation syndrome. GnRH agonists trigger ovulation by stimulating an endogenous gonadotropin surge. This process more closely resembles natural ovulation but is transient because of the short half-life. Another option is the dual trigger approach, when human chorionic gonadotropin is combined with GnRH agonist with the aim to optimize oocyte maturation while balancing safety and efficacy. Understanding the underlying mode of action of the triggers is crucial for tailoring individualized treatment protocols, achieving optimal oocyte yield and quality, enhancing clinical outcomes while appropriately mitigating the risks. With this manuscript, we aim to provide an in-depth review of each ovulation trigger agent and their combination and summarize recommendations on the basis of the most common patient characteristics.
{"title":"Final oocyte maturation for in vitro fertilization: a comprehensive review with investigators’ recommendations","authors":"Evelina Manvelyan M.D. , Agnes Manvelyan M.D. , Kathryn Coyne M.D. , Rebecca Flyckt M.D. , Rachel Weinerman M.D.","doi":"10.1016/j.xfnr.2025.100096","DOIUrl":"10.1016/j.xfnr.2025.100096","url":null,"abstract":"<div><div>The use of gonadotropin-releasing hormone (GnRH) antagonist protocols in assisted reproductive technology provides various options for achieving final follicular maturation. The choice of agent should be tailored to the patient characteristics and the mechanism of action of the triggers. The two primary agents used for this purpose are human chorionic gonadotropin, which acts as a luteinizing hormone analogue, and GnRH agonist, which induces the release of internal gonadotropin stores. Although these agents aim to achieve the same goal, they differ in the mechanism of action and downstream effects. Human chorionic gonadotropin binds to the luteinizing hormone receptors in the ovarian follicles and promotes oocyte maturation and ovulation through continuous luteotropic activity. This prolonged effect can increase the risk of ovarian hyperstimulation syndrome. GnRH agonists trigger ovulation by stimulating an endogenous gonadotropin surge. This process more closely resembles natural ovulation but is transient because of the short half-life. Another option is the dual trigger approach, when human chorionic gonadotropin is combined with GnRH agonist with the aim to optimize oocyte maturation while balancing safety and efficacy. Understanding the underlying mode of action of the triggers is crucial for tailoring individualized treatment protocols, achieving optimal oocyte yield and quality, enhancing clinical outcomes while appropriately mitigating the risks. With this manuscript, we aim to provide an in-depth review of each ovulation trigger agent and their combination and summarize recommendations on the basis of the most common patient characteristics.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 2","pages":"Article 100096"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-04-24DOI: 10.1016/j.xfnr.2025.100091
John Coté M.D. , Remington Coté C.P.T. , Isabella Zent B.S. , Kate Woods B.S. , Katherine Kedeshian B.S. , Mya Hendry B.S. , Kaylee Dykstal M.D. , Ryan W. Walters Ph.D.
Objective
To synthesize and compare measurable parameters researchers have used in the different immunocompetent mouse models of endometriosis.
Evidence Review
A systematic literature search of English language studies within PubMed/MEDLINE, Scopus, and Google Scholar from inception until January 2024 was performed. We included studies that reported an immunocompetent mouse model of intra-abdominal endometriosis and recorded at least one quantifiable lesion measurement with associated SDs or standard errors.
Results
The systematic search retrieved 1,421 studies, of which 236 underwent a full text review. A total of 163 studies met inclusion criteria for the meta-analysis. Within the suture (n = 76 studies) and injection (n = 88 studies) models there were multiple outcomes evaluated. The overall effect for lesion weight (33.1 mg, 95% confidence interval [CI], 23.8–45.9), lesion volume (15.6 mm3, 95% CI, 12.2–19.9), lesion area (8.6 mm2, 95% CI, 5.6–13.4), lesion diameter (3.8 mm, 95% CI, 2.8–5.2), and lesion number (3.33, 95% CI, 2.8–3.8). Significant heterogeneity was observed for all outcomes. Meta-regression showed BALB/c strain, days of disease, and receiving estrogen affected lesion weight, injection, days of disease, and autologous donor/recipient affected lesion volume, days of disease affected lesion area, days of disease, and myometrium plus endometrium affected lesion diameter and BALB/c, receiving estrogen, and autologous donor/recipient affected lesion number.
Conclusion
The degree of heterogeneity, risk of bias, and low quality of evidence emphasize the need for a call to action. Model standardization, agreed on by the clinical and translational research community, would improve reproducibility and allow for evidenced-based translational outcomes, especially in the setting of preclinical endometriosis studies.
{"title":"Immunocompetent mouse models of endometriosis: a systematic review and meta-analysis","authors":"John Coté M.D. , Remington Coté C.P.T. , Isabella Zent B.S. , Kate Woods B.S. , Katherine Kedeshian B.S. , Mya Hendry B.S. , Kaylee Dykstal M.D. , Ryan W. Walters Ph.D.","doi":"10.1016/j.xfnr.2025.100091","DOIUrl":"10.1016/j.xfnr.2025.100091","url":null,"abstract":"<div><h3>Objective</h3><div>To synthesize and compare measurable parameters researchers have used in the different immunocompetent mouse models of endometriosis.</div></div><div><h3>Evidence Review</h3><div>A systematic literature search of English language studies within PubMed/MEDLINE, Scopus, and Google Scholar from inception until January 2024 was performed. We included studies that reported an immunocompetent mouse model of intra-abdominal endometriosis and recorded at least one quantifiable lesion measurement with associated SDs or standard errors.</div></div><div><h3>Results</h3><div>The systematic search retrieved 1,421 studies, of which 236 underwent a full text review. A total of 163 studies met inclusion criteria for the meta-analysis. Within the suture (n = 76 studies) and injection (n = 88 studies) models there were multiple outcomes evaluated. The overall effect for lesion weight (33.1 mg, 95% confidence interval [CI], 23.8–45.9), lesion volume (15.6 mm<sup>3</sup>, 95% CI, 12.2–19.9), lesion area (8.6 mm<sup>2</sup>, 95% CI, 5.6–13.4), lesion diameter (3.8 mm, 95% CI, 2.8–5.2), and lesion number (3.33, 95% CI, 2.8–3.8). Significant heterogeneity was observed for all outcomes. Meta-regression showed BALB/c strain, days of disease, and receiving estrogen affected lesion weight, injection, days of disease, and autologous donor/recipient affected lesion volume, days of disease affected lesion area, days of disease, and myometrium plus endometrium affected lesion diameter and BALB/c, receiving estrogen, and autologous donor/recipient affected lesion number.</div></div><div><h3>Conclusion</h3><div>The degree of heterogeneity, risk of bias, and low quality of evidence emphasize the need for a call to action. Model standardization, agreed on by the clinical and translational research community, would improve reproducibility and allow for evidenced-based translational outcomes, especially in the setting of preclinical endometriosis studies.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 2","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Endometriosis is a common gynecological disorder affecting 10% of reproductive-aged women, characterized by ectopic endometrial-like tissue exhibiting malignant-like behaviors including invasiveness and angiogenesis. Growing evidence identifies recurrent somatic mutations in cancer driver genes (KRAS, ARID1A, PIK3CA, and PTEN) within endometriotic lesions, suggesting their potential role in disease pathogenesis. This narrative review examines the contribution of somatic mutations to endometriosis development and fibrogenesis, their biomarker potential, and therapeutic implications. We conducted a comprehensive literature search (PubMed, Scopus, and Cochrane, encompassing all publications from the earliest available records of each database up to May 2025) focusing on next-generation sequencing–based studies of endometriotic lesions, particularly analyzing fibrotic remodeling and oxidative stress mechanisms.
Analysis of 15 key studies revealed the following: somatic mutations across all lesion subtypes (ovarian, deep infiltrating, and peritoneal); oxidative stress from retrograde menstruation and iron overload as likely mutagenic drivers promoting fibrogenesis; distinct mutational patterns between epithelial and stromal components indicating oligoclonal origins; and lesion-specific mutation profiles within individual patients suggesting independent clonal evolution. Notably, although these mutations mirror those in cancers, endometriosis typically remains benign, implying microenvironmental constraints on malignant transformation.
Somatic mutations appear actively involved in endometriosis pathogenesis and fibrogenesis rather than being incidental findings. Their detection in benign lesions underscores the disease’s molecular complexity. Further research should focus on mutation-microenvironment interactions to develop molecular classifications and targeted therapies, potentially revolutionizing endometriosis management through personalized approaches.
{"title":"The role of somatic mutations in endometriosis: pathogenesis, progression, and fibrogenesis (narrative review)","authors":"Leila Adamyan Ph.D. , Laura Pivazyan M.D. , Maria Yurkanova M.D. , Evdokiya Zarova M.D. , Maria Kuznetsova Ph.D. , Karina Mailova Ph.D. , Dmitry Trofimov Ph.D. , Assia Stepanian Ph.D.","doi":"10.1016/j.xfnr.2025.100098","DOIUrl":"10.1016/j.xfnr.2025.100098","url":null,"abstract":"<div><div>Endometriosis is a common gynecological disorder affecting 10% of reproductive-aged women, characterized by ectopic endometrial-like tissue exhibiting malignant-like behaviors including invasiveness and angiogenesis. Growing evidence identifies recurrent somatic mutations in cancer driver genes (<em>KRAS</em>, <em>ARID1A</em>, <em>PIK3CA</em>, and <em>PTEN</em>) within endometriotic lesions, suggesting their potential role in disease pathogenesis. This narrative review examines the contribution of somatic mutations to endometriosis development and fibrogenesis, their biomarker potential, and therapeutic implications. We conducted a comprehensive literature search (PubMed, Scopus, and Cochrane, encompassing all publications from the earliest available records of each database up to May 2025) focusing on next-generation sequencing–based studies of endometriotic lesions, particularly analyzing fibrotic remodeling and oxidative stress mechanisms.</div><div>Analysis of 15 key studies revealed the following: somatic mutations across all lesion subtypes (ovarian, deep infiltrating, and peritoneal); oxidative stress from retrograde menstruation and iron overload as likely mutagenic drivers promoting fibrogenesis; distinct mutational patterns between epithelial and stromal components indicating oligoclonal origins; and lesion-specific mutation profiles within individual patients suggesting independent clonal evolution. Notably, although these mutations mirror those in cancers, endometriosis typically remains benign, implying microenvironmental constraints on malignant transformation.</div><div>Somatic mutations appear actively involved in endometriosis pathogenesis and fibrogenesis rather than being incidental findings. Their detection in benign lesions underscores the disease’s molecular complexity. Further research should focus on mutation-microenvironment interactions to develop molecular classifications and targeted therapies, potentially revolutionizing endometriosis management through personalized approaches.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 2","pages":"Article 100098"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-15DOI: 10.1016/j.xfnr.2025.100099
Ida Behrendt Møller M.D. , Kilian Vomstein Dr. med. habil. , Maria Christine Krog Ph.D. , Ruth Bunker Lathi Ph.D. , Henriette Svarre Nielsen D.M.Sc
Many clinicians suspect immune problems when treating women with unexplained recurrent pregnancy loss (RPL); however, we lack evidence that immunotherapy helps. Although immune tolerance is crucial for successful pregnancy, distinguishing immunologic from nonimmunologic causes of RPL continues to be a major hurdle. Apart from antiphospholipid syndrome (APS), decades of studying immune markers have yielded no reliable diagnostic tests. This diagnostic uncertainty has led to widespread off-label use of immunomodulatory treatments without strong evidence of a positive effect on pregnancy outcomes. This review examines current data on frequently used immune therapies including corticosteroids, intravenous immunoglobulin, lymphocyte immunotherapy, calcineurin inhibitors, anticoagulants, and granulocyte colony–stimulating factor. Small studies with diverse demographics and contradictory findings make up most of the information available. There are only a few high-quality randomized controlled trials, frequently demonstrating no significant treatment benefit. Designing such trials is particularly challenging because of the heterogeneous nature of RPL, which may involve patients with genetic, anatomical, endocrine, and immunologic risk factors. Ideally, such trials only include patients with similar underlying pathologies to generate robust and reliable evidence. Current evidence does not support routine use of these expensive and potentially dangerous therapies. Future progress requires identifying trustworthy biomarkers that can distinguish immune-mediated RPL from other causes to identify women who potentially could benefit from immune modulation and conducting appropriately powered randomized controlled trials in well-defined patient populations.
{"title":"The evidence-practice gap in immunotherapy for recurrent pregnancy loss: a critical narrative review of current treatments","authors":"Ida Behrendt Møller M.D. , Kilian Vomstein Dr. med. habil. , Maria Christine Krog Ph.D. , Ruth Bunker Lathi Ph.D. , Henriette Svarre Nielsen D.M.Sc","doi":"10.1016/j.xfnr.2025.100099","DOIUrl":"10.1016/j.xfnr.2025.100099","url":null,"abstract":"<div><div>Many clinicians suspect immune problems when treating women with unexplained recurrent pregnancy loss (RPL); however, we lack evidence that immunotherapy helps. Although immune tolerance is crucial for successful pregnancy, distinguishing immunologic from nonimmunologic causes of RPL continues to be a major hurdle. Apart from antiphospholipid syndrome (APS), decades of studying immune markers have yielded no reliable diagnostic tests. This diagnostic uncertainty has led to widespread off-label use of immunomodulatory treatments without strong evidence of a positive effect on pregnancy outcomes. This review examines current data on frequently used immune therapies including corticosteroids, intravenous immunoglobulin, lymphocyte immunotherapy, calcineurin inhibitors, anticoagulants, and granulocyte colony–stimulating factor. Small studies with diverse demographics and contradictory findings make up most of the information available. There are only a few high-quality randomized controlled trials, frequently demonstrating no significant treatment benefit. Designing such trials is particularly challenging because of the heterogeneous nature of RPL, which may involve patients with genetic, anatomical, endocrine, and immunologic risk factors. Ideally, such trials only include patients with similar underlying pathologies to generate robust and reliable evidence. Current evidence does not support routine use of these expensive and potentially dangerous therapies. Future progress requires identifying trustworthy biomarkers that can distinguish immune-mediated RPL from other causes to identify women who potentially could benefit from immune modulation and conducting appropriately powered randomized controlled trials in well-defined patient populations.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 2","pages":"Article 100099"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145527805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Breast cancer is the most common malignancy in adolescent and young adult women and poses a high risk of infertility because of gonadotoxic chemotherapy and prolonged endocrine therapy-associated ovarian aging. Although embryo and oocyte cryopreservation are standard approaches, technical limitations (e.g., insufficient oocyte yield) as well as nontechnical barriers, including limited accessibility, cost, and concerns about oncologic outcomes, restrict their use. Ovarian tissue cryopreservation, a backup strategy, also faces the challenge of substantial follicle loss during processing. These gaps underscore the urgent need for pharmacologic ovarian protective agents. Mechanistic target of rapamycin (mTOR) inhibitors, approved for advanced/recurrent breast cancer treatment, have emerged as promising dual-purpose agents that preserve ovarian reserve while enhancing antitumor efficacy. In preclinical models, mTOR inhibition mitigates follicular loss induced by chemotherapy, aging, and ovarian tissue cryopreservation and transplantation. Moreover, mTOR inhibitors may act as endometrial protectants by reducing tamoxifen-induced endometrial hyperplasia. Despite compelling preclinical evidence, clinical application of mTOR inhibitors for fertility preservation remains unexplored. Dedicated trials with coprimary endpoints of ovarian function and oncologic outcomes are warranted. Alternatively, post hoc analyses of existing (neo)adjuvant breast cancer trials could rapidly assess fertility-protective effects. Teratogenic risk appears low, and ovarian-protective doses may be lower than antitumor doses, potentially minimizing toxicity. This narrative review integrates preclinical findings, examines translational challenges, and outlines future directions. Further research on mTOR inhibitors could improve fertility and quality of life for adolescent and young adult survivors.
{"title":"Mechanistic target of rapamycin inhibitors for fertility preservation in breast cancer: a narrative review","authors":"Yuji Tanaka M.D., Ph.D., Tsukuru Amano M.D., Ph.D., Ayako Inatomi M.D., Ph.D., Tetsuro Hanada M.D., Ph.D., Akimasa Takahashi M.D., Ph.D., Shunichiro Tsuji M.D., Ph.D.","doi":"10.1016/j.xfnr.2025.100097","DOIUrl":"10.1016/j.xfnr.2025.100097","url":null,"abstract":"<div><div>Breast cancer is the most common malignancy in adolescent and young adult women and poses a high risk of infertility because of gonadotoxic chemotherapy and prolonged endocrine therapy-associated ovarian aging. Although embryo and oocyte cryopreservation are standard approaches, technical limitations (e.g., insufficient oocyte yield) as well as nontechnical barriers, including limited accessibility, cost, and concerns about oncologic outcomes, restrict their use. Ovarian tissue cryopreservation, a backup strategy, also faces the challenge of substantial follicle loss during processing. These gaps underscore the urgent need for pharmacologic ovarian protective agents. Mechanistic target of rapamycin (mTOR) inhibitors, approved for advanced/recurrent breast cancer treatment, have emerged as promising dual-purpose agents that preserve ovarian reserve while enhancing antitumor efficacy. In preclinical models, mTOR inhibition mitigates follicular loss induced by chemotherapy, aging, and ovarian tissue cryopreservation and transplantation. Moreover, mTOR inhibitors may act as endometrial protectants by reducing tamoxifen-induced endometrial hyperplasia. Despite compelling preclinical evidence, clinical application of mTOR inhibitors for fertility preservation remains unexplored. Dedicated trials with coprimary endpoints of ovarian function and oncologic outcomes are warranted. Alternatively, post hoc analyses of existing (neo)adjuvant breast cancer trials could rapidly assess fertility-protective effects. Teratogenic risk appears low, and ovarian-protective doses may be lower than antitumor doses, potentially minimizing toxicity. This narrative review integrates preclinical findings, examines translational challenges, and outlines future directions. Further research on mTOR inhibitors could improve fertility and quality of life for adolescent and young adult survivors.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 2","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-06-04DOI: 10.1016/j.xfnr.2025.100093
Kyle Le M.D. , Atoosa Ghofranian M.D. , Kate Devine M.D.
Some transgender and gender-diverse individuals desire biological children; however, only a small percentage of these individuals preserve their fertility. There are many barriers preventing such patients from accessing assisted reproductive technologies. Many of them are not informed regarding fertility preservation options before initiation of gender-affirming hormonal therapy (GAHT). Transgender women and transfeminine individuals have worse semen parameters than cisgender men, even without exposure to GAHT. For those who seek GAHT, estradiol and/or antiandrogens may negatively impact semen parameters. Although a hiatus from GAHT before sperm cryopreservation may be considered, this may impose hardship. Transgender men and transmasculine individuals on GAHT have similar oocyte retrieval outcomes compared with transgender men not on GAHT and cisgender women. Multiple reports have indicated positive outcomes even in those who continue their testosterone through the oocyte stimulation cycle. Ideally, transgender and gender-diverse individuals should see a reproductive endocrinologist for a discussion of fertility preservation options and, if desired, should ideally complete fertility preservation before starting GAHT. Still, for several reasons, patients may decline or omit this step before initiating medical transition and then decide later that they wish to pursue fertility preservation or treatment. Thankfully for transgender males, data indicates that successful fertility preservation is possible even after medical transition. For transgender females, estradiol may reduce fertility potential, and outcomes after medical transition can be more limited.
{"title":"Fertility care in transgender and gender-diverse individuals: the possibility of oocyte and sperm cryopreservation after medical transition","authors":"Kyle Le M.D. , Atoosa Ghofranian M.D. , Kate Devine M.D.","doi":"10.1016/j.xfnr.2025.100093","DOIUrl":"10.1016/j.xfnr.2025.100093","url":null,"abstract":"<div><div>Some transgender and gender-diverse individuals desire biological children; however, only a small percentage of these individuals preserve their fertility. There are many barriers preventing such patients from accessing assisted reproductive technologies. Many of them are not informed regarding fertility preservation options before initiation of gender-affirming hormonal therapy (GAHT). Transgender women and transfeminine individuals have worse semen parameters than cisgender men, even without exposure to GAHT. For those who seek GAHT, estradiol and/or antiandrogens may negatively impact semen parameters. Although a hiatus from GAHT before sperm cryopreservation may be considered, this may impose hardship. Transgender men and transmasculine individuals on GAHT have similar oocyte retrieval outcomes compared with transgender men not on GAHT and cisgender women. Multiple reports have indicated positive outcomes even in those who continue their testosterone through the oocyte stimulation cycle. Ideally, transgender and gender-diverse individuals should see a reproductive endocrinologist for a discussion of fertility preservation options and, if desired, should ideally complete fertility preservation <em>before</em> starting GAHT. Still, for several reasons, patients may decline or omit this step before initiating medical transition and then decide later that they wish to pursue fertility preservation or treatment. Thankfully for transgender males, data indicates that successful fertility preservation is possible even after medical transition. For transgender females, estradiol may reduce fertility potential, and outcomes after medical transition can be more limited.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 2","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-06-04DOI: 10.1016/j.xfnr.2025.100094
Dean E. Morbeck Ph.D. , Michael P. Diamond M.D.
There is an urgent global need to improve in vitro fertilization success rates and expand access to services. Specific to the in vitro fertilization laboratory, challenges such as standardization and a shortage of trained embryologists hinder quality and limit service availability. Current standards for product approval rely on demonstrating comparable pregnancy rates, requiring extensive patient involvement and time-consuming trials, which may be further hindered by patient reluctance to participate in clinical trials. Efficient assessment of new protocols and devices for assessing human assisted reproductive technology requires considering intermediate endpoints and markers to complement conventional endpoints. This review explores blastocyst development as a potential surrogate marker for pregnancy. It examines the correlation between blastocyst development and implantation potential, evaluates how culture conditions and other factors affect outcomes, and discusses the evidence supporting an absence of adverse effects of embryo culture on perinatal and offspring health. The conclusion strongly suggests that blastocyst development could serve as a valuable surrogate for establishing equivalency of pregnancy and live births in new assisted reproductive technology protocols. This review underscores the need for a surrogate marker of quality and presents evidence supporting the utility of blastocyst use rate as a sufficient indicator.
{"title":"Blastocyst development in assisted reproductive technologies: a narrative review evaluating its role as a surrogate marker for pregnancy outcomes and live birth success","authors":"Dean E. Morbeck Ph.D. , Michael P. Diamond M.D.","doi":"10.1016/j.xfnr.2025.100094","DOIUrl":"10.1016/j.xfnr.2025.100094","url":null,"abstract":"<div><div>There is an urgent global need to improve in vitro fertilization success rates and expand access to services. Specific to the in vitro fertilization laboratory, challenges such as standardization and a shortage of trained embryologists hinder quality and limit service availability. Current standards for product approval rely on demonstrating comparable pregnancy rates, requiring extensive patient involvement and time-consuming trials, which may be further hindered by patient reluctance to participate in clinical trials. Efficient assessment of new protocols and devices for assessing human assisted reproductive technology requires considering intermediate endpoints and markers to complement conventional endpoints. This review explores blastocyst development as a potential surrogate marker for pregnancy. It examines the correlation between blastocyst development and implantation potential, evaluates how culture conditions and other factors affect outcomes, and discusses the evidence supporting an absence of adverse effects of embryo culture on perinatal and offspring health. The conclusion strongly suggests that blastocyst development could serve as a valuable surrogate for establishing equivalency of pregnancy and live births in new assisted reproductive technology protocols. This review underscores the need for a surrogate marker of quality and presents evidence supporting the utility of blastocyst use rate as a sufficient indicator.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 2","pages":"Article 100094"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2024-10-30DOI: 10.1016/j.xfnr.2024.100080
{"title":"Retraction notice to ‘The impact of an endometrial receptivity array on personalizing embryo transfer for patients with infertility: a meta-analysis’ (F S Rev 2022;3:157-73)","authors":"","doi":"10.1016/j.xfnr.2024.100080","DOIUrl":"10.1016/j.xfnr.2024.100080","url":null,"abstract":"","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2024-11-06DOI: 10.1016/j.xfnr.2024.100081
Ana K. Rosen Vollmar Ph.D. , Shruthi Mahalingaiah M.D. , Anne Marie Jukic Ph.D.
Some medical professional organizations have advocated for including the menstrual cycle as a vital sign in adolescence but not in adulthood. However, documenting menstrual cycle patterns is not routine clinical or research practice. Vital signs are used to predict health outcomes, indicate needed treatment, and monitor a clinical course. They can help identify pathologies, affirm wellness, and are responsive to exposures. Here, we review the scientific evidence showing how the menstrual cycle meets these criteria and should, therefore, be treated as a vital sign. Using key words and controlled vocabulary terms, we performed multiple literature searches, prioritizing the inclusion of systematic reviews, meta-analyses, and clinical practice guidelines. This review describes how the menstrual cycle is a health indicator, how it cyclically can impact health conditions, and its associations with long-term postmenopausal health outcomes. We review exposures influencing the menstrual cycle, evidence underlying its use to optimize wellness, and available tools for documenting cycles. Supplemental materials include patient handouts on menstrual cycle tracking and an index of related clinical practice guidelines and reviews by subject. The menstrual cycle is a vital sign from menarche through menopause, an underused but powerful tool for understanding gynecological and general health.
{"title":"The menstrual cycle as a vital sign: a comprehensive review","authors":"Ana K. Rosen Vollmar Ph.D. , Shruthi Mahalingaiah M.D. , Anne Marie Jukic Ph.D.","doi":"10.1016/j.xfnr.2024.100081","DOIUrl":"10.1016/j.xfnr.2024.100081","url":null,"abstract":"<div><div>Some medical professional organizations have advocated for including the menstrual cycle as a vital sign in adolescence but not in adulthood. However, documenting menstrual cycle patterns is not routine clinical or research practice. Vital signs are used to predict health outcomes, indicate needed treatment, and monitor a clinical course. They can help identify pathologies, affirm wellness, and are responsive to exposures. Here, we review the scientific evidence showing how the menstrual cycle meets these criteria and should, therefore, be treated as a vital sign. Using key words and controlled vocabulary terms, we performed multiple literature searches, prioritizing the inclusion of systematic reviews, meta-analyses, and clinical practice guidelines. This review describes how the menstrual cycle is a health indicator, how it cyclically can impact health conditions, and its associations with long-term postmenopausal health outcomes. We review exposures influencing the menstrual cycle, evidence underlying its use to optimize wellness, and available tools for documenting cycles. Supplemental materials include patient handouts on menstrual cycle tracking and an index of related clinical practice guidelines and reviews by subject. The menstrual cycle is a vital sign from menarche through menopause, an underused but powerful tool for understanding gynecological and general health.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100081"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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