Heavy menstrual bleeding (HMB) is a common clinical condition affecting adolescent and adult women and compromising their quality of life. Primary hemostasis disorders, affecting platelet plug formation, can be the underlying cause of HMB. They comprise a heterogeneous group of diseases with Von Willebrand disease (VWD) being the most commonly diagnosed; other disorders in this group that have been linked to HMB include (a) Glanzmann thrombasthenia, (b) Bernard–Soulier syndrome, (c) Hermansky–Pudlak syndrome, (d) immune thrombocytopenia (ITP), and (e) Ehlers–Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD). Diagnosing these diseases can be challenging, as the basic laboratory investigations can be within the normal range. Thus, identification of specific clinical features and a thorough hematologic workup can be very important, providing the correct diagnosis. Proper diagnosis of the underlying disorder is important, as management may vary accordingly. Although disease-specific management guidelines exist for some of these disorders such as VWD and ITP, due to the rarity of most primary hemostasis disorders, the best approach for the management of HMB in these women remains elusive. The goal of this study was to create an informative, comprehensive review of the primary hemostasis disorders that have been linked to HMB. This study provides a summary of the basic published information regarding epidemiology, pathophysiology, clinical phenotype, diagnosis, and treatment of HMB in those diseases and serves as a reference guide for further reading.

Clotting Factor deficiencies are rare disorders with variations in clinical presentation and severity of symptoms ranging from asymptomatic to mild to life-threatening bleeding. Thus, they pose a diagnostic and therapeutic challenge, mainly for the primary health care providers, general practitioners, and gynecologists who are more likely to first encounter these patients. An additional diagnostic challenge arises from the variable laboratory presentations, as PT, PTT, and BT are not always affected. The morbidity is higher among women of reproductive age since Abnormal Uterine Bleeding–specifically Heavy Menstrual Bleeding–is one of the most prevalent manifestations of these disorders, and in some cases of severe deficiencies has led to life-threatening episodes of bleeding requiring blood transfusions or even immediate surgical intervention. Physician awareness is important as, in the case of some of these disorders–i.e., Factor XIII deficiency–prophylactic treatment is available and recommended. Although uncommon, the potential for rare bleeding disorders and for hemophilia carrier states should be considered in women with HMB, after more prevalent causes have been excluded. Currently, there is no consensus on the management of women in these instances and it is reliant on the physicians’ knowledge.

Data on patients with immune-mediated rheumatic diseases (IMRDs) undergoing assisted reproductive technology (ART) remain limited. We searched PubMed, Scopus, Cochrane Library, and Google Scholar up to 22/11/2025, for cohort or case-control studies comparing ART outcomes between women with IMRDs and controls, or case series of women with IMRDs undergoing ART. Our primary outcomes were live birth (per cycle, per embryo transfer (ΕΤ), and per couple) and miscarriage. We pooled odds ratios (ORs), mean differences (MDs), and Freeman-Tukey transformed proportion estimates using random-effects models. Twelve studies were included, covering Sjögren's disease (SjD), undifferentiated connective tissue disease (UCTD), systemic lupus erythematosus and/or antiphospholipid syndrome (SLE/APS), rheumatoid arthritis (RA), and familial Mediterranean fever (FMF). Live birth per ET was significantly lower in SjD (OR 0.49 (95 % CI 0.26-0.91)) and RA (OR 0.71 (95 % CI 0.61 - 0.83)). Live birth rates per couple were lower in all diseases. We found significant reductions in live birth rates per cycle, ET, and couple in the overall IMRD analysis. The pooled live birth rates per ET were 24 % in SjD, 24 % in SLE/APS, 18 % in RA, 38 % in FMF, and 26 % in the overall IMRD analysis. Very low to low-certainty evidence showed lower live birth rates per ET in SjD and RA and lower live birth rates per couple in all diseases. Effect sizes may have been influenced by confounding. More large-scale, high-quality data and consistent documentation of baseline characteristics and treatment regimens are needed to draw reliable conclusions regarding the effect of IMRDs on ART outcomes.