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Background/Objectives: Hodgkin lymphoma (HL) primarily affects individuals of reproductive age, making gonadal dysfunction after chemotherapy a critical survivorship concern. While fertility preservation options including gamete and gonadal tissue cryopreservation are available before treatment, evidence-based counseling requires regimen-specific risk estimates accounting for patient age and sex. Therefore, a meta-analysis was performed to assess presumed infertility in HL patients, stratified by chemotherapy regimen, age, and sex. Methods: This systematic review and meta-analysis, conducted within the FertiTOX project, included studies published between 2000 and February 2024. Eligible studies reported gonadal function outcomes ≥ 1 year after chemotherapy, excluding patients who received pelvic radiotherapy or stem cell transplantation, or had recurrent disease. Presumed infertility was defined by surrogate markers, including amenorrhea, premature ovarian failure, or abnormal hormonal levels in women, and azoospermia, oligozoospermia, or abnormal hormonal levels in men. Results: Of 2376 screened studies, 50 were included (meta-analysis: 43 studies; 5564 female and 1631 male patients). Overall presumed infertility prevalence was 21% in women (95% CI: 0.14–0.29) and 45% in men (95% CI: 0.29–0.62). The highest prevalence occurred after BEACOPP (women 38%; men 81%), while ABVD was associated with the lowest (6% each in women and men). Childhood/adolescent HL treatment resulted in lower prevalence in women (8%) but remained high in men (67%). Conclusions: Fertility risk depends on regimen, age, and sex, requiring tailored counseling. For female children/adolescents and all patients receiving ABVD, post-treatment fertility evaluation and treatment may suffice. However, pre-treatment fertility preservation is strongly recommended for male adolescents and patients receiving other regimens.

Background: Chronic endometritis (CE) is a subtle, often asymptomatic endometrial inflammation marked by CD138+ plasma cell infiltration and linked to recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), and unexplained infertility. Emerging evidence implicates endometrial microbiome dysbiosis in CE. Objective: To systematically review and conduct meta-analysis on the association between CE and endometrial microbiome alterations and their reproductive implications. Methods: We searched MEDLINE, Embase, Web of Science, Scopus, Cochrane CENTRAL, and Google Scholar for studies diagnosing CE via CD138 immunostaining, assessing microbiota with molecular techniques. Data extraction, quality assessment, and meta-analysis were performed. Results: Twenty-two studies including 4022 women were analyzed. CE was associated with reduced prevalence of Lactobacillus-dominated microbiota and increased detection of non-Lactobacillus species, particularly Streptococcus spp., Enterococcus spp., Escherichia coli, Staphylococcus spp., Ureaplasma spp., and Gardnerella vaginalis. In the meta-analysis (2947 women), Enterococcus spp. and Ureaplasma spp. were significantly more prevalent in women with CE, whereas Streptococcus spp., E. coli, Staphylococcus spp. and G. vaginalis showed non-significant trends. Only E. coli and Streptococcus spp. showed significant heterogeneity between-studies. Conclusions: CE is linked to microbial dysbiosis with reduced Lactobacillus dominance and enrichment of potentially pathogenic taxa, notably Enterococcus and Ureaplasma spp. These findings suggest that the endometrial microbiome contributes to chronic inflammation and adverse reproductive outcomes, yet heterogeneity and limited evidence call for standardized diagnostics and robust trials before clinical implementation.

Background: The presence of ectopic endometrial glands within the uterine myometrium in patients with adenomyosis has been associated with adverse fertility outcomes. UP (Uterine Peristalsis), a movement of contractions at the junctional zone of the non-pregnant uterus, can be impacted by an altered architecture of uterine layers. Abnormal contractility patterns could impact both uterotubal sperm transport as well as embryo implantation. Because of this potential influence on clinical symptoms and reproduction in patients with adenomyosis, studies have been analyzing the feasibility of diagnostic techniques in assessing uterine peristalsis. Objective: This systematic review and meta-analysis aimed to detect an alteration in patterns of UP in patients with adenomyosis. Methods: A systematic literature search of Medline, Embase, Cochrane, CENTRAL databases and Google Scholar was conducted up to June 2025, including studies evaluating UP and adenomyosis. Clinical studies evaluating uterine contractility were included, excluding those potentially affected by therapeutic interventions. The meta-analysis pooled data from studies to compare uterine contractility direction between patients with adenomyosis and control groups. Results: In seven included studies (442 women), uterine contractility varied significantly in association with menstrual cycle phases and pathological conditions. The meta-analysis revealed two statistically significant findings: women with adenomyosis showed significantly reduced uterine contraction frequency (SMD −1.81, 95% CI: −3.04 to −0.58, p = 0.0039) and fewer antegrade contractions (OR 0.35, 95% CI: 0.13–0.96, p = 0.0423) compared to controls. Other contractility patterns showed non-significant trends with substantial heterogeneity. Conclusions: Our findings show a significant difference in uterine contraction patterns in patients with adenomyosis compared to controls, namely a decrease in frequency and an increased number of retrograde uterine contractions in the adenomyosis group. The remarkable heterogeneity of the results highlighted the need for larger study cohorts in the future, especially to address the main diagnostic possibilities and treatments in order to improve reproductive outcomes.

Wesentlich ist die korrekte Indikation für oder gegen fertilitätsprotektive Maßnahmen, um eine optimale Versorgung der Patienten gewährleisten und eine Über- bzw. Untertherapie vermeiden zu können. Die Beurteilung der Indikation folgt allgemeingültigen Kriterien, muss aber zusätzlich auch krankheitsspezifisch und individuell gestellt werden. Zur Verfügung stehen sowohl medikamentöse Maßnahmen als auch die Kryokonservierung von Gameten und Gonadengewebe. Die Wahl der Technik richtet sich nach den Risiken einer Sterilität, dem verfügbaren Zeitrahmen für die Maßnahmen, dem Alter der Patientin bzw. des Patienten und der Erkrankung per se. Fertilitätsprotektive Maßnahmen sollten nur im Verbund mit onkologischen und anderen spezialisierten Zentren und versierten reproduktionsmedizinischen Zentren durchgeführt werden.

Background Uterine contractions, also known as peristalsis, have been shown to affect fertility. However, despite previous studies, most clinicians have not paid sufficient attention to uterine peristalsis. Recent studies have recognised its importance and evaluated contractility parameters prior to embryo transfer. Method A systematic literature search was conducted in Medline, Embase and Cochrane CENTRAL up to January 2024. Inclusion criteria were studies involving patients undergoing in vitro fertilization (IVF) or other infertility treatments in which uterine contractility was assessed. Studies were excluded if they included therapeutic interventions that affected contractility, or if they focused on uterine pathologies such as adenomyosis or fibroids. The meta-analysis included trials with IVF treatments that compared clinical pregnancy rates in women with high versus low frequent uterine contractions. Results A total of 2587 women (17 studies) were included in the systematic review, of whom 1134 (43.1%) (5 studies) underwent embryo transfer and were eligible for meta-analysis. The review found that elevated contractility on the day of embryo transfer is associated with a negative impact on pregnancy rates. The meta-analysis showed that women with two or more uterine contractions at the time of the embryo transfer had a significantly lower clinical pregnancy rate than with women with two or fewer contractions (OR 0.52, 95% CI: 0.38- 0.69). There was moderate heterogeneity between studies (I 2  = 55, p  < 0.01). Conclusions The lower clinical pregnancy rate in women with high uterine contractility, highlights the role of uterine peristalsis around the time of embryo implantation. However, due to the limited and heterogeneous data available, the influence of uterine peristalsis on reproductive outcomes such as live birth rates remains unclear.

Purpose Fertility preservation methods are playing an increasing role in women up to the age of 40 years because of rising survival rates in those affected by cancer. However, balanced practical recommendations concerning all relevant fertility preservation, to support doctors in counselling and treating patients, are still rare. Methods These recommendations were prepared by the network FertiPROTEKT ( http://www.fertiprotect.eu ), a collaboration of around 70 centres in Germany, Switzerland and Austria. The recommendations were developed by specialists in reproductive medicine, reproductive biology and oncology, which gave a comprehensive overview of all named techniques as well as their benefits and risks. Furthermore, practice-orientated recommendations for the individual use of fertility preservation methods for various indications such as breast cancer, Hodgkin’s lymphoma and borderline ovarian tumours are given. Results Various options such as ovarian stimulation and cryopreservation of unfertilised or fertilised oocytes, cryopreservation and transplantation of ovarian tissue, GnRH-agonist administration and transposition of the ovaries can be offered. All the techniques can be performed alone or in combination within a maximum of 2 weeks with low risk and different success rates. Conclusions Fertility preservation in women has become an option with realistic chances to become pregnant after cytotoxic therapies. The information provided allows a well balanced and realistic counselling and treatment.

Up until now, the measurement of Quality of Life (QoL) was based on validated subjective rating tools rather than objective measurement. To become more independent of the self-assessment of probands, a way to objectively measure QoL should be found. A monocenter, cross-sectional, observational, non-interventional trial was performed from 2012 to 2014 at Inselspital Bern to evaluate the bio-functional status (BFS), a complex, generic, non-invasive, sex- and age-validated assessment tool, in a wide range of areas. A standardized battery of assessments was performed on 464 females and 166 males, ages 18 to 65 (n = 630). In addition to the survey of the BFS, participants replied—among others—to the validated questionnaire SF-36 for health-related QoL (n = 447, subgroup 1). Since the accepted cut-off value for BFA calculation is age ≥ 35 years, subgroup 2 included 227 subjects (all participants aged ≥ 35 years out of subgroup 1). In order to be able to compare the eight SF-36 subscales to BFS parameters, a comparable score set of single BFS items had to be constructed. Subsequently, we aimed to statistically identify BFS item combinations that best represented each SF-36 subscale. All eight SF-36 subscales were significantly represented by various different combinations of BFS items. A total of 24 single BFS items significantly correlated with SF-36 subscales, of which 15 were objective and nine were subjective. All eight SF-36 subscales were significantly represented by various different combinations of BFS items leading to stronger correlations (range five to nine BFS items), and overall, sex and age did not affect these associations, but in the SF-36 subscales ‘bodily pain’ (sex) and ‘role limitations due to physical health problems’ (age in men). To our knowledge, we are the first to correlate a validated set of 34 objective and 9 subjective parameters with subjectively evaluated SF-36 subscales. This first study on the objectifiability of the SF-36 questionnaire demonstrated that questions on quality of life can be answered independently of a subjective assessment by subjects in future scientific studies.

PurposeIn addition to guidelines focusing on scientific evidence, practical recommendations on fertility preservation are also needed.MethodsA selective literature search was performed based on the clinical and scientific experience of the authors. This article (Part II) focuses on fertility preservation techniques. Part I, also published in this journal, provides information on disease prognosis, disease-specific therapy, and risks for loss of fertility.ResultsOvarian stimulation including double stimulation and freezing of oocytes is the best-established therapy providing live birth chances in women < 35 years with high ovarian reserve of around 30 40%. Ovarian tissue freezing is especially useful in young women with good ovarian, if spontaneous conception is favoured and if < 1 week until chemotherapy is provided. Data on success rates are still limited, but this further evolving technique will possibly reach similar success rates as ovarian stimulation. GnRH agonists seem to reduce the risk of premature ovarian failure up to 50%; however, the effect is possibly not long-lasting. Ovarian transposition can easily be combined with freezing of ovarian tissue and is the preferred technique before pelvic radiotherapy. Other techniques, such as in vitro maturation, are limited to women with high ovarian reserve and remain less effective. In addition, procedures such as in vitro growth of follicles, etc. are still experimental.ConclusionsFertility preservation in women provides realistic chances of becoming pregnant. The choice of technique needs to be based on the time required, the woman s age, its risks and efficacy, and the individual preference of the patient.

Background: The incidence of colorectal cancer (CRC) is increasing in the population under 50 years of age, with more than 10% of cases occurring in young adults. Fertility preservation counseling has therefore received increased attention in this younger patient population. The treatment of CRC is often based on multimodal therapies, including surgery, radiotherapy, chemotherapy, and, more recently, immunotherapy, which makes it difficult to estimate the expected effect of treatment on fertility. We, therefore, systematically analyzed the published literature on the gonadotoxic effects of CRC treatments to better advise patients on the risk of infertility and the need for fertility preservation measures. This systematic review and meta-analysis are part of the FertiTOX project, which aims to reduce the data gap regarding the gonadotoxicity of oncological therapies. Objectives: The aim of this review and meta-analysis is to evaluate the potential impact of CRC therapies on gonadal function to allow more accurate counseling regarding the risk of clinically relevant gonadotoxicity and the need for fertility preservation measures before oncological treatment. Materials and Methods: A systematic literature search was conducted in Medline, Embase, the Cochrane database of systematic reviews, and CENTRAL in March 2024. A total of 22 out of 4420 studies were included in the review. Outcomes were defined as clinically relevant gonadotoxicity, indicated by elevated follicle-stimulating hormone (FSH) and/or undetectable anti-Müllerian hormone (AMH) levels and/or the need for hormone replacement therapy in women and azoo-/oligozoospermia and/or low inhibin B levels in men. Studies with fewer than nine patients were excluded from the meta-analysis. Results: The qualitative analysis included 22 studies with 1634 subjects (775 women, 859 men). Treatment consisted of active surveillance after surgery (37.7%), chemotherapy (12.7%), radiation (0.2%), or radiochemotherapy (53.9%). In 0.5%, the therapy was not clearly described. The meta-analysis included ten studies and showed an overall prevalence of clinically relevant gonadotoxicity of 23% (95% CI: 13–37%). In women, the prevalence was 27% (95% CI: 11–54%), and in men, 18% (95% CI: 13–26%). A subanalysis by type of CRC was only possible for rectal cancer, with a prevalence of relevant gonadotoxicity of 39% (95% CI: 20–64%). In patients undergoing chemotherapy exclusively, the prevalence was 4% (95% CI: 2–10%). In those receiving only radiotherapy, the prevalence was 23% (95% CI: 10–44%); in contrast, it reached 68% (95% CI: 40–87%) in patients who received radiochemotherapy. Conclusions: This first meta-analysis of the clinically relevant gonadotoxicity of CRC therapies provides a basis for counseling on the risk of infertility and the need for fertility preservation measures. Despite the low prevalence of gonadotoxicity in cases receiving chemotherapy alone, fertility preservation is still recommended due to the uncertainty of subsequent therapy and the lack of large longitudinal data on individual treatment effects. Further prospective studies are needed to investigate the impact of CRC treatment on gonadal function and estimate the effect of new treatment modalities, such as immunotherapies.