Riccardo Marana

Correlation between the American Fertility Society * classifications of adnexal adhesions and distal tubal occlusion, salpingoscopy, and reproductive outcome in tubal surgery

OBJECTIVE To compare the prognostic value of salpingoscopy with a current classification system of adnexal adhesions and distal tubal occlusion in patients with tubal infertility undergoing reconstructive tubal surgery. DESIGN Prospective clinical study. SETTING Department of Obstetrics and Gynecology of the Catholic University, a tertiary care University Center in Rome, Italy. PATIENTS Fifty-five infertile patients with either adnexal adhesions (29 patients) or hydrosalpinx (26 patients) undergoing reconstructive tubal surgery. INTERVENTIONS Salpingoscopy performed concomitantly to salpingo-ovariolysis or salpingoneostomy at the time of either operative laparoscopy or laparotomy using microsurgical techniques. MAIN OUTCOME MEASURES Salpingoscopic findings were compared with a current classification system of adnexal adhesions and distal tubal occlusion. The patients were followed for a mean follow-up of 49 months; the pregnancy rates achieved were correlated with the salpingoscopic findings and the classification system used. RESULTS There was a significant correlation between the salpingoscopic grade and the occurrence of a term pregnancy for both the salpingo-ovariolysis and salpingoneostomy groups of patients. There was no significant correlation between the classification system used and the occurrence of a term pregnancy for both groups of patients. CONCLUSION Salpingoscopy plays an important role in selecting the patients who may benefit the most from reconstructive tubal surgery.

The impact of preoperative gonadotropin-releasing hormone agonist treatment on laparoscopic excision of ovarian endometriotic cysts

OBJECTIVE To compare surgical performance and recurrence rates in patients submitted to laparoscopy for endometrioma excision following GnRH agonist (GnRH-a) treatment versus no preoperative medical treatment. DESIGN Controlled clinical study. SETTING A tertiary care university hospital. PATIENTS Twenty patients with unilateral endometriomas underwent operative laparoscopy after 3-month GnRH-a treatment, whereas 21 patients underwent laparoscopic excision of endometriomas without preoperative medical treatment. INTERVENTIONS Operative laparoscopy was performed with the stripping technique using a four-puncture approach. MAIN OUTCOME MEASURE A blinded videotape review was undertaken to evaluate the duration and complexity of the different phases of surgery. Recurrence rates were evaluated at 1-year follow-up ultrasonography. RESULTS No significant difference was found between the two groups in total operative time, cyst excision time, time needed for cyst capsule stripping and coagulation of ovarian parenchyma, and the complexity of the latter phases; recurrence rates also were comparable. CONCLUSION Preoperative GnRH-a treatment for endometriomas does not seem to offer any advantage in terms of subsequent surgical performance.

Male fertility and reduction in semen parameters: A single tertiary-care center experience

Background. Infertility is both a clinical and a public problem, affecting the life of the couple, the healthcare services, and social environment. Standard semen analysis is the surrogate measure of male fertility in clinical practice. Objective. To provide information about the relationship between semen parameters and spontaneous conception. Methods. We evaluated retrospectively 453 pregnancies that occurred among 2935 infertile couples evaluated at an infertility clinic of a tertiary-care university hospital, between 2004 and 2009. Results. Normal semen analysis was present only in 158 patients; 295 subfertile patients showed alterations in at least one seminal parameter. A reduction in all seminal parameters was observed in 41 patients. Etiological causes of male infertility were identified in 314 patients. Conclusion. Our data highlights the possibility of a spontaneous conception with semen parameters below WHO reference values. Therefore, we support the importance of defining reference values on a population of fertile men. Finally, we analyzed the related ethical issues.

Proteomic approach in the identification of fertility pattern in seminal plasma of fertile men

OBJECTIVE To identify a panel of common seminal proteins in human seminal plasma by fertile men that might be involved in successful reproduction. DESIGN Experimental study. SETTING University hospital. PATIENT(S) Five fertile men who conceived within 3 months before the start of the study. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Proteomic analysis performed by an Ultimate 3000 Nano/Micro-HPLC apparatus equipped with an FLM-3000-Flow manager module and coupled with an LTQ Orbitrap XL hybrid mass spectrometer; gene ontology analysis. RESULT(S) From 919 to 1,487 unique proteins were identified per individual subject sample. Among these proteins, 83 proteins were present in all samples, including some proteins that might be involved in male fertility, such as semenogelin I, semenogelin II, olfactory receptor 5R1, lactoferrin, hCAP18, spindling, and clusterin. The gene ontology annotation analysis provided further information in describing common pattern in male fertility. CONCLUSION(S) The identification of common seminal plasma proteome in fertile men could provide better insight into the physiology of male fertility and might identify novel markers of male infertility.

GnRH analogue treatment before hysteroscopic resection of submucous myomas: A prospective, randomized, multicenter study

OBJECTIVE To evaluate the efficacy of GnRH analogue treatment before hysteroscopic resection of submucous myomas in patients with abnormal uterine bleeding. DESIGN Multicenter, prospective, randomized, clinical study. SETTING Tertiary-care university hospitals. PATIENT(S) Thirty-nine consecutive patients with submucous myomas graded as G0 or G1 according to the European Society for Gynecological Endoscopy classification (myoma size 10-35 mm). INTERVENTION(S) Patients were randomized to either direct surgery or 2 months of GnRH analogues before undergoing hysteroscopic resection of the submucous myoma. MAIN OUTCOME MEASURE(S) Operating times, fluid absorption, difficulty of the operation, surgeon satisfaction with the procedure, intra- and postoperative complications, postoperative pain, and patient satisfaction were recorded. RESULT(S) Patients treated with GnRH analogue had significantly shorter operative times (15.9+/-3.1 minutes vs. 21.3+/-4.0 minutes) and significantly reduced fluid absorption (378+/-137 mL vs. 566+/-199 mL) compared with no preoperative medical treatment. Operative difficulty and overall surgeon satisfaction were significantly better in the GnRH analogue group. Patient satisfaction was similar in the two groups. CONCLUSION(S) GnRH analogue treatment before hysteroscopic resection of G0-G1 10-35 mm submucous myomas was effective in reducing operative times, fluid absorption, and difficulty of the procedure.

Laparoscopy versus microsurgery by laparotomy for excision of ovarian cysts in patients with moderate or severe endometriosis

STUDY OBJECTIVE To compare the efficacy of laparoscopy versus microsurgery by laparotomy in the treatment of ovarian endometriomas. DESIGN Retrospective study with historical controls. SETTING A tertiary university hospital. PATIENTS One hundred thirty-two women under 40 years of age with ovarian endometriotic cysts at least 3 cm in diameter (stage III and IV endometriosis, R-AFS classification). Interventions. A single surgeon (RM) treated 83 patients by laparoscopy for excision of ovarian endometriomas by the stripping technique and 49 by microsurgery at laparotomy. MEASUREMENTS AND MAIN RESULTS Data regarding recurrence of ovarian cysts, symptomatic improvement, and reproductive outcome were comparable for the two groups. Postoperative febrile morbidity and length of hospitalization were significantly less for the laparoscopy group than for the laparotomy group (p <0.0005). CONCLUSIONS Operative laparoscopy for excision of ovarian endometrial cysts by the stripping technique is as effective as microsurgery by laparotomy. It is associated with less febrile morbidity and a shorter hospitalization.

Antiphospholipid Antibodies Affect Human Endometrial Angiogenesis

Antiphospholipid antibodies (aPL) represent an important risk factor for thrombosis and recurrent miscarriage in patients with antiphospholipid syndrome (APS). The mechanisms of aPL-mediated pregnancy failure have been researched. Previous studies demonstrated that aPL bind trophoblast cells, reducing proliferation, human chorionic gonadotrophin release, and in vitro invasiveness. Recent data suggest that aPL are also able to react with human decidual cells, inducing a proinflammatory phenotype. Decidua, a newly formed tissue on the maternal side of the human placenta, is characterized by active angiogenesis and structural modifications of the spiral arteries in early pregnancy. Since angiogenesis is a critical component of normal placentation, the purpose of our study was to evaluate the role of aPL on human endometrial angiogenesis. For this reason, we investigated the effect of aPL on in vitro endometrial endothelial cell (HEEC) angiogenesis, VEGF secretion by ELISA, matrix metalloproteinases (MMPs) activity by gelatin zymography, and DNA binding activity of NFKB by a sensitive multiwell colorimetric assay. Furthermore, we performed experiments to study whether aPL affects in vivo angiogenesis in a murine model. We found that aPL significantly decrease the number and the total length of the tubules formed by HEEC on in vitro Matrigel assay and reduce newly formed vessels in aPL-inoculated mice. Moreover, aPL reduce significantly both VEGF and MMPs production and, at the nuclear level, NFKB DNA binding activity. From our results, it appears that aPL are associated with an inhibition of angiogenesis, suggesting further additional mechanisms to explain the defective placentation in the APS.

Sevoflurane improves the neuroendocrine stress response during laparoscopic pelvic surgery

PurposeStress response to surgery is modulated by several factors, including magnitude of the injury type of procedure (e.g., laparoscopy vs laparotomy) and type of anesthesia. Our purpose was to compare intra- and postoperative hormonal changes during isoflurane vs sevoflurane anesthesia, in a clinical model of well defined operative stress (laparoscopic pelvic surgery).MethodIn this prospective randomized clinical study, 20 women requiring laparoscopic pelvic surgery for benign ovarian cysts received either a standard isoflurane plus fentanyl (Group A) or sevoflurane plus fentanyl anesthesia (Group B). Blood samples were collected preoperatively 30 min after the beginning of surgery, at the end of surgery after extubation, and “two and four hours after the end of surgery. Intra- and postoperative plasma levels of norepinephrine, epinephrine, adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH) and prolactin (PRL) were measured.ResultsCatecholamine levels and postoperative pain were similar in both groups. Nonetheless, in comparison to Group A, Group B showed a significant decrease of ACTH, cortisol and GH levels (A vs B at the end of surgery: ACTH 160 ± 45 vs 100 ± 40 pg·mL−1; cortisol 45 ± 8 vs 23 ± 7 μg·dL−1; GH 3 ± 2 vs 0.8 ± 0.4 ng·mL−1; P < 0.001 for all), but enhanced PRL levels (A vs B, at 30 min after the beginning of surgery: 139 ± 54 vs 185 ± 22 ng·mL−1; at the end of surgery: 100±27 vs 141 ± 45 ng·mL−1; P < 0.001 for both).ConclusionsIn the clinical setting of low stress laparoscopic surgery, the type of volatile anesthetic significantly affected the stress response; the changes associated with sevoflurane suggested a more favourable metabolic and immune response compared to isoflurane.RésuméObjectifLa réaction au stress chirurgical dépend, entre autres, de l’importance du traumatisme chirurgical, du type d’intervention (laparoscopie vs laparotomie) et d’anesthésie. Nous voulions comparer les changements hormonaux pendant et après l’opération sous anesthésie à l’isoflurane, ou au sévoflurane, selon un modèle clinique bien défini de stress opératoire (intervention chirurgicale par laparoscopie pelvienne).MéthodeL’étude clinique, prospective et randomisée, a été faite auprès de 20 femmes devant subir une intervention par laparoscopie pelvienne pour des kystes bénins de l’ovaire. Les patientes ont reçu, soit une anesthésie normale à l’isoflurane avec du fentanyl (groupe A), soit au sévoflurane avec du fentanyl (groupe B). Le sang a été prélevé avant l’opération, 30 min après le début, à la fin après l’extubation et, deux et quatre heures après l’opération. Les niveaux plasmatiques peropératoire et postopératoire de noradrénaline, d’adrénaline, d’hormone adrénocorticotrope (ACTH), de cortisol, d’hormone de croissance GH) et de prolactine (PRL) ont été mesurés.RésultatsLes niveaux de catécholamine et la douleur postopératoire ont été similaires dans les deux groupes. Néanmoins, comparé au groupe A, le groupe B a affiché une baisse significative d’ACTH, de cortisol et de GH (A vs B à la fin de l’opération: ACTH 160 ± 45 vs 100 ±40 pg·mL−1; cortisol 45 ±8 vs 23 ±7 μg·dL−1; GH 3 ± 2 vs 0,8 ± 0,4 ng·mL−1; P < 0,001 pour toutes), et une hausse de PRL (A vs B, 30 min après le début de l’opération: 139 ± 54 vs 185 ± 22 ng·mL−1; à la fin de l’opération: 100 ± 27 vs 141 ± 45 ng·m−1; P < 0,001 pour les deux).ConclusionDans le cadre clinique d’une intervention laparoscopique de faible stress, le type d’anesthésique volatil utilisé a un effet significatif sur la réaction de stress; les changements associés au sévoflurane montrent une réaction immunitaire et métabolique plus favorable qu’avec l’isoflurane.

Decreased expression of heparin-binding epidermal growth factor-like growth factor as a newly identified pathogenic mechanism of antiphospholipid-mediated defective placentation

OBJECTIVE Heparin-binding epidermal growth factor-like growth factor (HB-EGF) plays a role in blastocyst implantation and is down-regulated in preeclampsia and in hypertensive pregnancy disorders associated with defective extravillous trophoblast invasion. Defective placentation and severe preeclampsia are also features of the antiphospholipid syndrome (APS). The purpose of this study was to investigate whether abnormal HB-EGF expression plays a pathogenic role in antiphospholipid antibody (aPL)-mediated defective placentation. METHODS HB-EGF expression in placental tissue was evaluated by Western blotting and messenger RNA analysis in normal and APS placentae. Polyclonal IgG fractions or monoclonal beta(2)-glycoprotein I-dependent aPL and their respective controls were investigated for the following 4 features: their binding to human trophoblast monolayers, as determined by cell enzyme-linked immunosorbent assay (ELISA); their effect on HB-EGF expression by Western blotting in trophoblast cell extracts as well as by ELISA as a protein secreted in the culture supernatants; their inhibitory effect on in vitro trophoblast invasiveness, as evaluated by Matrigel assay; and their inhibitory effect on matrix metalloproteinase (MMP) levels, as measured by gelatin zymography. Experiments were also performed in the presence of serial concentrations of heparin or recombinant HB-EGF. RESULTS Placental APS tissue displayed reduced expression of HB-EGF. Polyclonal and monoclonal aPL bound to trophoblast monolayers and significantly reduced the in vitro synthesis and secretion of HB-EGF. Heparin inhibited aPL binding and restored HB-EGF expression in a dose-dependent manner. Addition of recombinant HB-EGF reduced the in vitro aPL-induced inhibition of Matrigel invasiveness as well as MMP-2 levels. CONCLUSION These preliminary findings suggest that the reduction of aPL-mediated HB-EGF represents an additional mechanism that is responsible for the defective placentation associated with APS and that heparin protects from aPL-induced damage by inhibiting antibody binding.

Histologic analysis of specimens from laparoscopic endometrioma excision performed by different surgeons: Does the surgeon matter?

OBJECTIVE To evaluate whether the amount of ovarian tissue inadvertently removed along with the endometrioma cyst wall at laparoscopy differs in relation to the operating surgeons level of expertise. DESIGN Multicenter, prospective trial. SETTING Four tertiary care university hospitals. PATIENT(S) Fifty patients, aged 25 to 40 years, with monolateral ovarian endometriomas who underwent laparoscopic excision. INTERVENTION(S) Operation with the stripping technique by surgeons with specific expertise in endometriosis surgery in four centers (groups A, B, C, and D) and by residents with average training in laparoscopic surgery (group E). MAIN OUTCOME MEASURE(S) Histologic examination for the evaluation of the mean thickness of the cyst wall from each specimen, and the mean thickness and morphologic characteristics of any ovarian tissue removed. RESULT(S) No statistically significant differences were present in the rate of presence of ovarian tissue in the endometrioma wall specimens from the different groups (44%, 45%, 55%, 56%, and 60% in groups A, B, C, D, and E, respectively). For groups A+B+C+D versus group E, a statistically significant difference was found in the mean thickness of the tissue specimens (1.51 mm vs. 1.91 mm, respectively) and in the mean thickness of ovarian tissue inadvertently excised (0.49 mm vs. 0.97 mm, respectively). CONCLUSION(S) Level of expertise in endometriosis surgery is inversely correlated with inadvertent removal of healthy ovarian tissue along with the endometrioma capsule.