Centromeric AA motif in KIR as an optimal surrogate marker for precision definition of alloimmune reproductive failure.

Throughout pregnancy, the decidua is predominantly populated by NK lymphocytes expressing Killer immunoglobulin-like receptors (KIR) that recognize human leukocyte antigen-C (HLA-C) ligands from trophoblast cells. This study aims to investigate the association of KIR-HLA-C phenotypes in couples facing infertility, particularly recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), in comparison to a reference population and fertile controls. This observational, non-interventional retrospective case-control study included patients consecutively referred to our Reproductive Immunology Unit from 2015 to 2019. We analyzed the frequencies of KIR and HLA-C genes. As control groups, we analyzed a reference Spanish population for KIR analysis and 29 fertile controls and their male partners for KIR and HLA-C combinations. We studied 397 consecutively referred women with infertility and their male partners. Among women with unexplained RPL (133 women) and RIF (176 women), the centromeric (cen)AA KIR genotype was significantly more prevalent compared to the reference Spanish population (p = 0.001 and 0.02, respectively). Furthermore, cenAA was associated with a 1.51-fold risk of RPL and a 1.2-fold risk of RIF. Conversely, the presence of BB KIR showed a lower risk of reproductive failure compared to non-BB KIR (OR: 0.12, p < 0.001). Women and their partners with HLA-C1C1/C1C1 were significantly less common in the RPL-Group (p < 0.001) and RIF-Group (p = 0.002) compared to the control group. Moreover, the combination of cenAA/C1C1 in women with C1C1 partners was significantly higher in the control group than in the RPL (p = 0.009) and RIF (p = 0.04) groups, associated with a 5-fold increase in successful pregnancy outcomes. In our cohort, the cenAA KIR haplotype proved to be a more accurate biomarker than the classic AA KIR haplotype for assessing the risk of RPL and RIF, and might be particularly useful to identify women at increased risk among the heterogeneous KIR AB or Bx population. The classification of centromeric KIR haplotypes outperforms classical KIR haplotypes, making it a better indicator of potential maternal-fetal KIR-HLA-C mismatch in patients.

Lack of Improvement of Sperm Characteristics in Obese Males After Obesity Surgery Despite the Beneficial Changes Observed in Reproductive Hormones.

BACKGROUND: Even though obesity surgery normalizes circulating testosterone concentrations in males with obesity-associated secondary hypogonadism, its impact on spermatogenesis remains controversial. We aimed to evaluate sperm characteristics in obese men after bariatric surgery as well as changes in reproductive hormones. METHODS: Twenty severely obese men (body mass index (BMI) ≥ 35 kg/m2) were evaluated before and 2 years after bariatric surgery. The serum was assayed for insulin, leptin, kisspeptin, and inhibin B, among other hormones. Homeostasis model assessment of insulin resistance (HOMA-IR) was estimated. We used World Health Organization reference values for sperm analysis. RESULTS: After surgery, serum total testosterone, calculated free testosterone, inhibin B, and kisspeptin increased, whereas fasting insulin, HOMA-IR, and leptin concentrations decreased. Despite these improvements, sperm volume showed a small decrease after surgery, while the rest of sperm characteristics remained mostly unchanged. Abnormal sperm concentration persisted in 60% of the patients. CONCLUSIONS: Sperm characteristics may not improve after bariatric surgery despite the beneficial changes of reproductive hormones.

Morbid obesity-related changes in the expression of lipid receptors, transporters, and HSL in human sperm.

OBJECTIVE: To study the location and expression of receptors (SR-BI/CLA-1, SR-BII, and LDLr) and transporter (ABCA1) involved in uptake and efflux of cholesterol in human spermatozoa and assess whether obesity alters its location/expression and whether this could be related to infertility. DESIGN: Observational study. SETTING: None PATIENT(S): Ten controls and 20 obese patients. INTERVENTION(S): Anthropometric parameters. Serum and semen samples were collected. MAIN OUTCOME MEASURE(S): Spermatozoon concentration, immunolocalization, and protein expression in semen. RESULTS: Spermatozoon concentration and motility was decreased in morbidly obese patients. SR-BI/CLA-1, SR-BII, LDLr, and ABCA1 are located in the spermatozoon cell membrane and the localization does not change between obese patients and controls. Control spermatozoa showed high SR-BI expression, and less expression for the rest of the receptors analyzed, indicating that SR-BI/CLA-1 is relevant in human spermatozoon cholesterol uptake/efflux. On the contrary, spermatozoa of obese patients showed less SR-BI/CLA-1 expression than controls, and more intense positive staining for SR-BII, LDLr, and ABCA1. Finally, human sperm expresses the 130- and 82-kDa hormone-sensitive lipase (HSL) isoforms. The 130-kDa isoform is expressed in the control sperm, and the expression disappears in the obese patients. CONCLUSION(S): The presence of lipid receptors/transporters and HSL in human spermatozoa suggests their role in the process of maturation/capacitation. The changes in the expression of lipid receptors/transporters and the lack of the 130-kDa HSL isoform in obese patients prevent the hydrolysis of cholesterol esters internalized by these receptors, and favor their accumulation in the cytoplasm of the spermatozoa that could contribute to lipotoxicity and infertility.

Subcutaneous implant with etonogestrel (Implanon®) for catamenial exacerbations in a patient with cystic fibrosis: a case report.

BACKGROUND: Cystic Fibrosis (CF) is a genetic disease with equal prevalence across sexes. However, women present worse lung function with faster function decline, earlier onset of bacterial colonization, more frequent pulmonary exacerbations (PE), greater bronchial hyper-responsiveness, and higher mortality rates after puberty than men. The etiology of this gender disparity remains elusive but female hormones have been implicated in several studies. CASE PRESENTATION: A 20-year-old female with CF with severe recurrent PE, always related to the menstrual cycle since menarche, combined with lung function decline requiring multiple courses of intravenous antibiotics. We report the cessation of PE and recovery of pulmonary function following the insertion of a subcutaneous implant with 68 mg of etonogestrel (Implanon®, Organon Española S.A. Laboratories, Madrid, Spain). CONCLUSION: Our case report supports the key role of female hormones in the development of PE and in the decline of lung function in a woman with CF. When appropriate, hormonal manipulation through contraceptive methods should be considered as potential treatment.

[Requests for utilization of a semen bank among oncological patients. Semen cryopreservation prior to chemotherapy, radiotherapy and surgery]. / Demanda y utilización de un banco de semen en pacientes oncológicos. Criopreservacion de semen pre-quimioterapia, pre-radioterapia y pre-cirugía.

OBJECTIVES: Oncological therapies, either surgery, radiotherapy or chemotherapy, may cause irreversible subfertiliy/infertility. Both chemotherapy and radiotherapy have cytotoxic effects on gametogenesis and there are not preventive alternatives currently available. The objective of this article is to review current criteria for semen cryopreservation and its usefulness as a method for preservation of fertility in patients with cancer. METHODS/RESULTS: We reviewed a large group of recent original articles and systematic reviews on the issue with a common feature: evaluation of fertility status after oncological therapy. CONCLUSIONS: Every male patient in fertile age who could wish future fatherhood should be offered the option to storage cryopreserved semen samples before starting oncological therapies, with the exception of patients with azoospermia at the time of diagnosis.