Bullous hemorrhagic dermatosis (BHD) is a rare cutaneous manifestation characterized by tense hemorrhagic bullae that appear at sites distant from low molecular weight heparin (LMWH) injections, typically within seven days of exposure. As of March 2022, only 94 cases have been reported. It most commonly affects elderly males with predisposing factors for thromboembolism, such as carcinoma, and usually involves the extremities.

This case highlights the importance of maintaining a high index of suspicion for bullous hemorrhagic dermatosis (BHD) in patients receiving low molecular weight heparin, even beyond the typical 7-day window and in demographics not commonly affected. Early recognition and prompt discontinuation of the offending agent, as demonstrated in this atypical presentation involving a Filipino elderly woman with multiple comorbidities and no malignancy, can lead to favorable outcomes. Clinicians should be aware of this rare but reversible complication to avoid misdiagnosis and ensure appropriate management.

Human ; Female ; Aged: 65-79 Yrs Old ; Affect ; Aged ; Blister ; Carcinoma ; Causality ; Demography ; Diagnostic Errors ; Enoxaparin ; Extremities ; Heparin ; Heparin, Low-molecular-weight ; Index ; Injections ; Lead ; Male ; Molecular Weight ; Neoplasms ; Patients ; Research Report ; Skin Diseases ; Thromboembolism ; Women

OBJECTIVE: To assess the feasibility of first polar body transfer (PB1T) combined with preimplantation mitochondrial genetic testing for blocking the transmission of a pathogenic mitochondrial DNA 8993T>G mutation. METHODS: A Chinese family affected with Leigh syndrome which had attended the Reproductive Medicine Centre of the First Affiliated Hospital of Anhui Medical University in September 2021 was selected as the study subject. Controlled ovarian hyperstimulation was carried out for the proband after completing the detection of the mitochondrial DNA 8993T>G mutation load among the pedigree members. Mature MII oocytes were inseminated by intracytoplasmic sperm injection (ICSI), cultured in vitro for 5 to 6 days to the blastocyst stage, and trophoblastocytes were obtained by microbiopsy. Mitochondrial DNA testing (PGT-MT) and chromosomal aneuploidy (PGT-A) analyses were carried out after whole-genome amplification, and the embryos with zero mutation load were selected for transfer. Amniotic fluid and umbilical cord blood samples were collected during middle pregnancy and after birth respectively for mitochondrial DNA testing to verify the reliability of embryo screening. As an attempt, PB1 with good morphology of MII oocytes was selected for transfer into the enucleated oocytoplasm from healthy donors, followed by ICSI fertilization, blastocyst culture and PGT of embryos using the same procedure. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University (No. 2021zhyx-B12). RESULTS: An antagonist protocol was used for ovarian stimulation, and a total of 19 oocytes were obtained, of which 14 MII were fertilized by ICSI, and 2 had developed into blastocysts. PGT-MT was carried out on biopsied trophoblastocytes, in which the mitochondrial DNA 8993T>G mutation load was not detected in one embryo, the other was 100% mutated, and the mutation loads of the remaining unfertilized eggs and developmentally arrested embryos ranged from 0% ~ 100%, presenting a clear biased distribution. With fully informed consent, one PGT-MT zero mutation load blastocyst was transferred and clinical pregnancy was achieved. Mitochondrial DNA and chromosomal testing of amniotic fluid cells during middle pregnancy had revealed no abnormalities. The proband had delivered a healthy boy through Caesarean section at 39⁺⁵ weeks of gestation, and no mutation was detected in the cord blood sample. Five well-formed PBs from 14 eggs were selected for PB1 transfer, followed by ICSI and culture, and two of the reconstituted embryos had formed blastocysts, with none of the above mutations detected in the biopsied samples. CONCLUSION The PGT-MT technology can help families affected with mitochondrial diseases to have healthy offspring. PB1 transfer in combination with ICSI and PGT-MT holds the promise of turning waste into treasure and providing an alternative means of fertility for such families.
Humans ; Preimplantation Diagnosis/methods* ; Female ; DNA, Mitochondrial/genetics* ; Genetic Testing/methods* ; Pregnancy ; Mitochondrial Diseases/genetics* ; Polar Bodies ; Adult ; Feasibility Studies ; Sperm Injections, Intracytoplasmic/methods* ; Embryo Transfer/methods* ; Mutation ; Male ; Blastocyst/metabolism* ; Pedigree

OBJECTIVE: To investigate the association between SPAG17 gene variant and Familial severe asthenozoospermia, and to assess its impact on the outcome of intracytoplasmic sperm injection (ICSI). METHODS: Two siblings (Probands 1 and 2) with severe asthenozoospermia from a Chinese family who presented at the Reproductive Medicine Center II of Gansu Maternity and Child Health Care Hospital (Gansu Provincial Central Hospital) in May 2023 were selected as study subjects. Clinical data were collected, and sperm morphology and ultrastructure (assessed by transmission electron microscopy) were analyzed. Pathogenic variants were screened using whole exome sequencing (WES) and verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of Gansu Maternity and Child Health Care Hospital (Ethics No.: 2023GSFYLS78). RESULTS: Probands 1 and 2 had primary infertility for 10 and 3 years, respectively, and both exhibited normal semen concentration, but the percentage of progressive motile sperm (PR) was significantly lower than the normal reference value (> 32.00%), measuring 2.33% ± 0.58% and 0.80% ± 0.45%, respectively. Additionally, the percentage of sperms with normal morphology was slightly below the reference range (> 4.00%), with the values of 3.36% ± 0.35% and 2.93% ± 1.36%. Both probands were found to harbor homozygous c.2188C>T (p.Q730*) nonsense variant of the SPAG17 gene (NM_206996.4), for which their mother was a heterozygous carrier (their father had already deceased). Both sibs underwent ICSI treatment using a long gonadotropin-releasing hormone agonist protocol during the follicular phase combined with assisted oocyte activation (AOA). The wife of Proband 1 ultimately gave birth to a healthy girl, whilst the wife of Proband 2 delivered two healthy girls. CONCLUSION The homozygous c.2188C>T (p.Q730*) nonsense variant of the SPAG17 gene is closely related with the severe asthenozoospermia phenotype. Live births can be achieved through ICSI combined with AOA technology, though the overall utilizable embryo rate may be relatively low.
Humans ; Male ; Asthenozoospermia/genetics* ; Adult ; Sperm Injections, Intracytoplasmic ; Pedigree ; Spermatozoa ; Female ; Exome Sequencing

Nonobstructive azoospermia (NOA) is the most challenging and complex clinical scenario for infertile men. Besides circumstances such as hypogonadotropic hypogonadism, surgical sperm retrieval is typically necessary, and microdissection testicular sperm extraction (micro-TESE) is the procedure of choice for men with NOA desiring to father children with their own gametes. Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection (ICSI) in comparison to all other techniques for surgical sperm retrieval in men with NOA. Several factors may affect sperm retrieval rate and ICSI outcomes, including the patient's age, testicular volume, histopathological and genetic profile, and serum hormone levels. This article aims to review the medical literature describing predictors of successful micro-TESE and the outcomes of ICSI in men with NOA.
Humans ; Azoospermia/surgery* ; Male ; Sperm Injections, Intracytoplasmic ; Sperm Retrieval ; Treatment Outcome ; Testis/pathology* ; Female ; Microdissection

One major challenge in male factor infertility is nonobstructive azoospermia (NOA), which is characterized by spermatozoa-deficient semen without physical duct blockage. This review offers a thorough overview of the histopathology of the testes in NOA cases, clarifying its complex etiology and emphasizing the possible value of histopathology inspection for both diagnosis and treatment. Variable histopathological findings have been linked to NOA, such as tubular hyalinization, Sertoli cell-only syndrome, hypospermatogenesis, and germ cell arrest. Understanding the pathophysiology and forecasting the effectiveness of treatment are further enhanced by both morphometric and ultrastructural analyses. The potential significance of testicular biopsy in forecasting reproductive outcomes is assessed, especially concerning assisted reproductive technologies like intracytoplasmic sperm injection (ICSI). Besides, testicular microlithiasis, serum hormone profiles, and testicular size are investigated concerning NOA histopathology. It is concluded that understanding the histopathological patterns in NOA is crucial for its accurate diagnosis and appropriate management. Further research is still warranted to improve understanding of the complex pathophysiology underlying NOA.
Humans ; Azoospermia/etiology* ; Male ; Testis/pathology* ; Sertoli Cell-Only Syndrome/pathology* ; Sperm Injections, Intracytoplasmic

Nonobstructive azoospermia (NOA) is considered the most challenging clinical scenario for infertile men and current treatments leave many men unsuccessful at being able to achieve a pregnancy with their partner using their own sperm. Microdissection testicular sperm extraction (micro-TESE) is the choice for men with NOA desiring to father children with their own gametes. Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection. With suboptimal micro-TESE success rates of sperm retrieval and then pregnancy and live birth using the retrieved sperm with in vitro fertilization/intracytoplasmic sperm injection, advances to improve outcomes are necessary. This article comprehensively reviews the technologies investigated to date to improve the outcomes for men undergoing micro-TESE.
Humans ; Male ; Sperm Retrieval ; Azoospermia/surgery* ; Pregnancy ; Female ; Sperm Injections, Intracytoplasmic ; Microdissection/methods* ; Fertilization in Vitro ; Testis/surgery*

Peyronie's disease (PD) presents a multifaceted challenge in contemporary urological practice, marked by penile deformity, pain, and the potential for erectile dysfunction. We meticulously explored the existing literature of intralesional/topical interventions, aiming to provide clinicians with a nuanced understanding of available options for comprehensive PD management. To conduct this review, we performed a systematic search using the PubMed, Scopus, and ScienceDirect databases, including the keywords of combination of the "Peyronie's disease/plastic induration of the penis (PIP) and intralesional/topical treatments". The study selection was based on adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, resulting in the inclusion of 16 articles. We delve into the effectiveness and safety profiles of collagenase Clostridium histolyticum (CCH), interferon, platelet-rich plasma (PRP), hyaluronic acid, botulinum toxin, stem cell, extracorporeal shock wave therapy (ESWT), and traction therapy, assessing their impact on penile curvature, length improvement, and patient-reported symptoms and outcomes. The best options evaluated are intralesional injections of CCH and penile traction devices, alone or in combination. Despite PD remains a challenge for urologists, the objective of this review is to contribute to the evolving landscape of PD management, fostering informed decision-making, and personalized care for individuals grappling with this challenging condition.
Humans ; Male ; Administration, Topical ; Botulinum Toxins/administration & dosage* ; Extracorporeal Shockwave Therapy ; Hyaluronic Acid/administration & dosage* ; Injections, Intralesional ; Interferons/administration & dosage* ; Microbial Collagenase/administration & dosage* ; Penile Induration/therapy* ; Platelet-Rich Plasma ; Stem Cell Transplantation ; Traction

Peyronie's disease (PD) is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages. In this study, we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD: transforming growth factor-β1 (TGF-β1), fibrin, sodium tetradecyl sulfate (STS) combined with TGF-β1, and polidocanol (POL) combined with TGF-β1. The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature. The STS + TGF-β1 combination resulted in both histological and morphological alterations, but with a high incidence of localized necrosis that led to animal death. The POL + TGF-β1 combination produced pathological changes and curvature comparable to STS + TGF-β1 and led to fewer complications. In conclusion, fibrin, STS + TGF-β1, and POL + TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats. The POL + TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.
Animals ; Male ; Penile Induration/drug therapy* ; Rats ; Transforming Growth Factor beta1/metabolism* ; Disease Models, Animal ; Fibrin ; Penis/drug effects* ; Polidocanol/administration & dosage* ; Rats, Sprague-Dawley ; Polyethylene Glycols/administration & dosage* ; Injections

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.
Humans ; Female ; Pregnancy ; Male ; Chromosomes, Human, Y/genetics* ; Adult ; Chromosome Deletion ; Pregnancy Outcome/genetics* ; Infertility, Male/genetics* ; Spermatozoa/physiology* ; Semen Analysis ; Sex Chromosome Disorders of Sex Development/genetics* ; Sperm Injections, Intracytoplasmic ; Azoospermia/genetics* ; Sex Chromosome Aberrations