Rescue intrauterine insemination in women failing to retrieve oocytes at ovum pick-up: report of a case series.

PURPOSE: Failure to collect oocytes at the time of oocyte pick-up is an unfavorable outcome of in vitro fertilization (IVF) cycles. In these cases, prompt intrauterine insemination (IUI) could be an option (rescue IUI), but this possibility has been poorly studied. METHODS: Rescue IUI is routinely offered in our unit in women failing to retrieve oocytes, provided that they have at least one patent tube, normal male semen analysis, and the total number of developed follicles is ≤ 3. We therefore reviewed all oocyte retrievals performed from 2006 to 2022 in our unit to identify these cases. As a comparator, we referred to preplanned IUI performed during the same study period. The 95% confidence interval (95% CI) of proportions was calculated using a binomial distribution model. RESULTS: Rescue IUI was performed in 96 out of 3531 oocyte retrievals (2.7%; 95% CI 2.2-3.3%). Six live births were obtained, corresponding to 6.2% (95% CI 2.3-13.1). All pregnancies were singletons. CONCLUSIONS: Rescue IUI in women failing to retrieve oocytes is a possible option that may be considered in selected cases. The efficacy is low, but the procedure is simple, and without significant risks. Generalizability to a conventional IVF protocol setting is however limited.

The role of microbiota in female fertility and infertility.

In recent years, the introduction of advanced technologies has led to a new scientific revolution: the discovery of the human microbiota. Next-generation sequencing allowed the identification of microbial communities in all districts of the human body and, among these, 9% are distributed in the genitourinary system. The microbiota plays a key role in controlling the homeostasis, therefore dysbiosis can lead to an alteration of the physiological state of health. An alteration of female reproductive microbial communities may affect fertility due to an alteration of the vaginal and endometrial ecosystem. A perturbation of the vaginal, cervical or endometrial flora may also have an impact on the outcome of assisted reproductive technology procedures, particularly in vitro fertilization and embryo transfer. This review examines the role of microbiota in human reproduction and its contribution to infertility. In addition we investigate the role of endometrial bacteria in recurrent implantation failure.

Structural Variations of Vaginal and Endometrial Microbiota: Hints on Female Infertility.

Microbiota are microorganismal communities colonizing human tissues exposed to the external environment, including the urogenital tract. The bacterial composition of the vaginal microbiota has been established and is partially related to obstetric outcome, while the uterine microbiota, considered to be a sterile environment for years, is now the focus of more extensive studies and debates. The characterization of the microbiota contained in the reproductive tract (RT) of asymptomatic and infertile women, could define a specific RT microbiota associated with implantation failure. In this pilot study, 34 women undergoing personalized hormonal stimulation were recruited and the biological samples of each patient, vaginal fluid, and endometrial biopsy, were collected immediately prior to oocyte-pick up, and sequenced. Women were subsequently divided into groups according to fertilization outcome. Analysis of the 16s rRNA V4-V5 region revealed a significant difference between vaginal and endometrial microbiota. The vaginal microbiota of pregnant women corroborated previous data, exhibiting a lactobacilli-dominant habitat compared to non-pregnant cases, while the endometrial bacterial colonization was characterized by a polymicrobial ecosystem in which lactobacilli were exclusively detected in the group that displayed unsuccessful in vitro fertilization. Overall, these preliminary results revisit our knowledge of the genitourinary microbiota, and highlight a putative relationship between vaginal/endometrial microbiota and reproductive success.

Could art cycles have a detrimental effect on ovarian reserve? A retrospective case control study.

BACKGROUND: Even if it is supposed damage of repeated ART (assisted reproductive technology) cycles on oocyte pool, there is still no evidence in literature. Aim of the study is to investigate whether infertile women who undergo to several ART cycles can show a lower ovarian reserve measured by AMH (Anti-Mullerian hormone) levels. METHODS: The study includes 282 infertile women, between 18 and 42 years, and allocated into two groups: 159 women previously submitted to two or more ART cycles (group A) and 123 women never submitted naïve to-ART cycles (group B). We tested whether AMH, FSH, LH and E2 levels were significantly different between the two groups, stratifying according to age. RESULTS: Regardless to the age ranges bands, the AMH in group A was statistically significant lower than in group B with a statistical significance (P=0.047). In particular women aged over 35 previously submitted to one or more ART cycles showed lower AMH levels, than those paired with age, which had never been treated with ART. CONCLUSIONS: Despite the limitations of the study, our data demonstrate a reduced AMH levels in women aged over 35 previously submitted to two or more repeated ART-cycles compared to patients never treated before. The strength of this study is the actuality of the topic that has not been discussed before in detail.

What About Fertility Staff Emotions? An Explorative Analysis of Healthcare Professionals' Subjective Perspective.

Infertility-related psychological research is traditionally oriented to analyze the wellbeing of couples undergoing Assisted Reproductive Technologies (ART), than to study the job-related effects on the healthcare fertility staff. This piece of research aims at understanding the subjective perspective of the fertility professionals and contribute to identify their emotional dynamics in their work environment. An in-depth explorative research study was conducted on 12 healthcare professionals of an Italian ART hospital clinic. Structured interviews with open-ended questions were administered to explore their deep feelings about their professional experience. Emotional text analysis was then conducted to analyze the textual corpus of their narratives to grasp their affective symbolizations. Statistical multidimensional techniques were used to detect some thematic domains (cluster analysis) and latent factors organizing the contraposition between them (multiple correspondence analysis). Five thematic domains were detected which refer to different emotional dimensions, as follows: performance anxiety (Cluster 1), ambivalence between omnipotence and powerlessness (Cluster 2), care burden (Cluster 3), feeling of duty (Cluster 4), and sense of interdependence (Cluster 5). Then, four latent factors were identified dealing with the laborious attempt to remedy, the realistic sense of limitation, the incumbent feeling of pressure and the restorative sense of justice, respectively. The results are discussed based on the existing literature and some useful recommendations for staff education, training and clinical supervision are provided accordingly.

Alpha lipoic acid in obstetrics and gynecology.

Alpha-Lipoic acid (ALA) is a natural antioxidant synthetized by plants and animals, identified as a catalytic agent for oxidative decarboxylation of pyruvate and α-ketoglutarate. In this review, we analyzed the action of ALA in gynecology and obstetrics focusing in particular on neuropathic pain and antioxidant and anti-inflammatory action. A comprehensive literature search was performed in PubMed and Cochrane Library for retrieving articles in English language on the antioxidant and anti-inflammatory effects of ALA in gynecological and obstetrical conditions. ALA reduces oxidative stress and insulin resistance in women with polycystic ovary syndrome (PCOS). The association of N-acetyl cysteine (NAC), alpha-lipoic acid (ALA), and bromelain (Br) is used for prevention and treatment of endometriosis. In association with omega-3 polyunsaturated fatty acids (n-3 PUFAs) with amitriptyline is used for treatment of vestibulodynia/painful bladder syndrome (VBD/PBS). A promising area of research is ALA supplementation in patients with threatened miscarriage to improve the subchorionic hematoma resorption. Furthermore, ALA could be used in prevention of diabetic embryopathy and premature rupture of fetal membranes induced by inflamation. In conclusion, ALA can be safely used for treatment of neuropatic pain and as a dietary support during pregnancy.

Current management of ovarian endometriomas.

The choice of treatment in case of ovarian endometriomas is one of the most discussed topics in Reproductive Medicine. Management options include expectancy, medical treatment, surgery, in vitro fertilization (IVF), or a combination of the above. The main presenting symptom, i.e. pain or infertility, usually guide the choice of treatment. Medical treatment is usually preferred as the first line option when pain is the associated symptom, whereas surgery or IVF are preferred in case of associated infertility. In most cases, however, the symptoms may overlap, and often a patient with infertility complains also of chronic pelvic pain, and vice versa. In addition, in many cases the patient may be asymptomatic, usually presenting with the incidental diagnosis of an ovarian endometrioma. Therefore, a strict categorization in two separate pathways of either associated pain or associated infertility, as the one outlined in current guidelines, may not represent the real clinical scenario. In this context, a personalized approach, taking into account several additional variables that are not considered in guidelines, is mandatory. In the present review, a symptom-driven approach to the management of ovarian endometriomas, that goes beyond the pain/infertility categorization, is described, considering additional parameters that guide the choice of treatment, with a patient-centered, personalized approach.

Ultrasonography reappraisal of tubal patency in assisted reproduction technology patients: comparison between 2D and 3D-sonohysterosalpingography. A pilot study.

BACKGROUND: The aim of this study was to compare 2D and 3D-sonohysterosalpingography (2D-3D-HyFoSy) with previous diagnostic laparoscopy in the diagnosis of tubal patency, and compare each procedure in terms of procedure's time, perceived pain and complication rate. METHODS: We prospectively recruited infertile women, previously submitted to laparoscopy and randomly allocated into 2D-HyFoSy (group I) and 3D-HyFoSy (group II). We analyzed the results in term of sensitivity, specificity, positive predictive value and negative predictive value in tubal patency evaluation of both procedures in comparison with laparoscopy. RESULTS: We enrolled 50 women, 25 in group I and 25 in group II. 2D-HyFoSy findings obtained in group I, were concordant with laparoscopy in 81% of cases, with a sensitivity of 80% and a specificity of 92%. In group II, a correspondence was present in 88% of examinations, with a sensitivity and specificity of 98% and 91.4% respectively. 3D-HyFoSy was found to be faster and less painful than 2D (P<0.001). CONCLUSIONS: In the diagnosis of tubal occlusion, in the high-risk population, it seems advisable to us using the 3D-HyFoSy as the first-level examination, while, in low-risk patients, if the tubes appear obstructed in 2D-HyFoSy, the 3D-HyFoSy should be indicated before submitting patients to operative laparoscopy.

Efficacy of carboxymethyl beta-glucan in cervical intraepithelial neoplasia: a retrospective, case-control study.

BACKGROUND: Persistent human papillomavirus (HPV) infection constitutes the principal risk factor for the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. For this reason, new drugs have been studied to support the host immune system against the HPV infection. The aim of this retrospective, case-control study was to detect the efficacy and safety of carboxymethyl ß-glucan (Colpofix®) gel as adjuvant therapy in HPV infection. METHODS: The medical records of patients attending the Colposcopy Service of four hospitals in Rome from 2011 to 2013 were collected. Case arm consisted of patients submitted to local therapy with Colpofix®. Control arm comprised patients who did not receive this therapy. A total of 999 patients were included, divided into four groups, according to their cytological and histological specimens, colposcopy and subsequent management. RESULTS: Local therapy with Colpofix® gel resulted effective with respect to no therapy for the regression of low-grade CIN (CIN1) in patients submitted to follow up (P=0.0204), while it was no effective for the regression of CIN1 submitted to ablative therapy and high-grade CIN (CIN 2+) (P value not significant). CONCLUSIONS: In conclusion, Colpofix® gel represents a valid alternative to "wait and see" strategy in patients affected by CIN1. Further prospective studies are warranted to confirm these results.

Role of 3.0 Tesla magnetic resonance hysterosalpingography in the diagnostic work-up of female infertility.

BACKGROUND: Imaging evaluation plays a crucial role in the diagnostic work-up of female infertility. In recent years, the possibility to evaluate tubal patency using 1.5 Tesla magnetic resonance (1.5T MR) has been studied. PURPOSE: To assess the feasibility of 3.0 Tesla magnetic resonance (3.0T MR) hysterosalpingography and its role in the diagnostic work-up of female infertility and to evaluate if this fast "one-stop-shop" imaging approach should be proposed as a first-line examination. MATERIAL AND METHODS: A total of 116 infertile women were enrolled in this prospective study; all underwent 3.0T MR hysterosalpingography. After standard imaging of the pelvis, tubal patency was assessed by acquiring 3D dynamic time-resolved T1-weighted (T1W) sequences during manual injection of 4-5 mL of contrast solution consisting of gadolinium and normal sterile saline. Images were evaluated by two radiologists with different experience in MR imaging (MRI). RESULTS: The examination was successfully completed in 96.5% of cases, failure rate was 3.5%. Dynamic sequences showed bilateral tubal patency in 64.3%, unilateral tubal patency in 25.9%, and bilateral tubal occlusion in 9.8%. Extratubal abnormalities were found in 69.9% of patients. Comprehensive analysis of morphological and dynamic sequences showed extratubal abnormalities in 43.1% of patients with bilateral tubal patency. CONCLUSION: 3.0T MR hysterosalpingography is a feasible, simple, fast, safe, and well-tolerated examination, which allows evaluation of tubal patency and other pelvic causes of female infertility in a single session, and it may thus represent a "one-stop-shop" solution in female infertility diagnostic work-up.

Water-soluble carboranyl-phthalocyanines for BNCT. Synthesis, characterization, and in vitro tests of the Zn(II)-nido-carboranyl-hexylthiophthalocyanine.

The zinc(II) complex of the octa-anionic 2,3,9,10,16,17,23,24-octakis-(7-methyl-7,8-dicarba-nido-undeca-boran-8-yl)hexyl-thio-6,13,20,27-phthalocyanine (nido-[ZnMCHESPc]Cs8, 7) has been obtained in the form of caesium salt through mild deboronation of the neutral precursor, the closo-[ZnMCHESPc] complex, 6, with CsF. 6 has been synthesized, in turn, by heating a finely ground mixture of the appropriate phthalonitrile and zinc(II) acetate at 180.0 °C. The complexes have been characterized by elemental analyses, FT-IR, UV-visible absorption and fluorescence emission spectroscopy, and their structures were assessed by (1)H, (13)C, (11)B, and two-dimensional homo- and hetero-correlated NMR spectroscopy experiments. 7 showed appreciable solubility in water solution, together with a marked tendency to aggregate. Aggregation of 7 in the hydrotropic medium resulted in significant fluorescence quenching. Instead, fluorescence quantum yields (Φ(F)) of 0.14 and 0.08, and singlet oxygen quantum yields (Φ(Δ)) of 0.63 and 0.24 were obtained for 6 and 7, respectively, in a DMF solution. In vitro boron neutron capture therapy (BNCT) experiments, employing boron imaging techniques as implemented in qualitative and quantitative neutron autoradiography methods, showed that 7 is capable of increasing the boron concentration of two selected cancerous cell lines, the DHD/K12/TRb of rat colon adenocarcinoma and UMR-106 of rat osteosarcoma, with the large-size Cs(+) counter-ions used to neutralize the negatively charged carborane polyhedra not presenting a significant obstacle to the process. Taken together, BNCT and photophysical measurement results indicated that 7 is potentially suitable for bimodal or multimodal anticancer therapy.

Symmetrically substituted nido-carboranylphthalocyanines: facile synthesis, characterization, and solution properties. Evidence for intra- and intermolecular H+/K+ exchange.

The direct, non ex post synthesis of a novel phthalocyanine decorated with eight thiohexyl-nido-carborane functions, nido-[H(2)MCHESPc]K(8), where the anionic polyhedra are in the form of K(+) salt, is reported and discussed. The solution properties of this compound, including the unprecedented exchange between the pyrrolic protons and the peripheral alkali-metal ions, are also analyzed.

Mass spectrometric evidence for collisionally induced removal of H(2) from monoanions of (10)B nido-carborane derivatives investigated by electrospray ionization quadrupole linear ion trap and Fourier transform ion cyclotron resonance mass spectrometry.

Some newly synthesized (10)B nido-carborane derivatives, i.e., 7,8-dicarba-nido-undecaborane monoanions ([7-Me-8-R-C(2)B(9)H(10)](-)K(+), R = H, butyl, hexyl, octyl and decyl), have been fully characterised and examined by electrospray ionization and Fourier transform ion cyclotron resonance mass spectrometry with liquid chromatographic separation (LC/ESI-FTICR-MS). These boron-containing compounds exhibit abundant molecular ions ([M](-)) at m/z 140.22631 [C(3) (10)B(9)H(14)](-), m/z 196.28883 [C(7) (10)B(9)H(22)](-), m/z 224.32032 [C(9) (10)B(9)H(26)](-), m/z 252.35133 [C(11) (10)B(9)H(30)](-) and m/z 280.38354 [C(13) (10)B(9)H(34)](-) at the normal tube lens voltage setting of -90 V, which was an instrumental parameter value selected in the tuning operation. Additional [M-nH(2)](-) (n = 1-4) ions were observed in the mass spectra when higher tube lens voltages were applied, i.e., -140 V. High-resolution FTICR-MS data revealed the accurate masses of fragment ions, bearing either an even or an odd number of electrons. Collision-induced dissociation of the [M-nH(2)](-) ions (n = 0-4) in the quadrupole linear ion trap (LTQ) analyzer confirmed the loss of hydrogen molecules from the molecular ions. It is suggested that the loss of H(2) molecules from the alkyl chain is a consequence of the stabilization effect of the nido-carborane charged polyhedral skeleton.

Electrochemical and spectroscopic behavior of iron(III) porphyrazines in Langmuir-Schafer films.

Thin films of a newly synthesized iron(III) porphyrazine, LFeOESPz ( L = ClEtO, OESPz = ethylsulfanylporphyrazine), have been deposited by the Langmuir-Schafer (LS) technique (horizontal lifting) on ITO or gold substrates. Before deposition, the floating films have been investigated at the air-water interface by pressure/area per molecule (pi/ A) experiments, Brewster angle microscopy (BAM) and UV-vis reflection spectroscopy (RefSpec). The complex reacts with water subphase (pH 6.2) forming the mu-oxo dimer, which becomes the predominant component of the LS films ( LS-Fe) as indicated by optical, IR, XPS, and electrochemical data. LS-Fe multilayers exhibit, between open circuit potential (OCP) and +0.90 V (vs SCE), two independent peak pairs with formal potentials, E surf (I) and E surf(II) of +0.56 V and +0.78 V, respectively. According to dynamic voltammetric and coulometric experiments the peak pair at +0.56 V is attributed to one-electron process at the iron(III) centers on the monomer, while the peak pair at +0.78 V is associated to a four-electron process involving mu-oxo-dimer oligomers. LS-Fe films prove to be quite stable electrochemically between OCP and +0.90 V. The electrochemical stability decreases, however, when the potential range is extended both anodically and cathodically outside these limits, due to formation of new species. Upon incubation with TCA solutions, LS-Fe films show remarkable changes in the UV-vis spectra, which are consistent with a significant mu-oxo dimer --> monomer conversion. Addition of TCA to the electrochemical cell using a LS-Fe film as working electrode, results in a linear increase of a cathodic current peak near -0.40 V as the TCA concentration varies in the 0.1-2.0 mM range. This behavior is interpreted in terms of TCA inducing a progressive change in the composition of the LS-Fe films in favor of the monomeric iron(III) porphyrazine, which is responsible for the observed increase in the cathodic current near -0.40 V.

Insertion of a magnesium(II)-octacarboranyl(hexylsulfanyl) porphyrazine into liposomes: a physico-chemical study.

The synthesis, characterization and liposome insertion of a novel magnesium(II) carboranyl-porphyrazine, i.e. [2,3,7,8,12,13,17,18-octakis-(1,2-dicarba-closo-dodecaboranyl)-hexylthio-5,10,15,20-porphyrazine]magnesium(II) complex, MgHECSPz, are described. MgHECSPz was designed to improve the potentiality in multiple approach anticancer therapy. Liposomal formulations with different surface charge were prepared as delivering agents. The obtained loaded vectors were characterized by DLS, SAXS, SANS and zeta potential measurements in order to define the overall properties and structural details of loaded liposomes.

Small angle scattering and zeta potential of liposomes loaded with octa(carboranyl)porphyrazine.

In this work, the physicochemical characterization of liposomes loaded with a newly synthesized carboranyl porphyrazine (H2HECASPz) is described. This molecule represents a potential drug for different anticancer therapies, such as boron neutron capture therapy and for photodynamic therapy or photothermal therapy. Different loading methods and different lipid mixtures were tested. The corresponding loaded vectors were studied by small angle scattering, light scattering, and zeta potential. The combined analysis of structural data at various lengths of scales and the measurement of the surface charge allowed us to obtain a detailed characterization of the investigated systems. The mechanisms underlying the onset of differences in relevant physicochemical parameters (size, polydispersity, and charge) were also critically discussed.