The actual impact of SARS-CoV-2/COVID-19 pandemic on IVF activity: a survey across Italian ART centers.

PURPOSE: Since the end of February 2020, SARS-CoV-2 dramatically spread in Italy. To ensure that most of National Health System (NHS) resources were employed to control the pandemic, non-urgent medical procedures (including IVF) were suspended in March 2020. Here, we aimed at assessing the impact of the restrictive measures on Italian IVF activity. METHODS: In May 2020, the Italian ART Register launched an online survey (multiple choices and open answers) across ART centers (89.0% response rate; N = 170/191) to investigate how they were facing the emergency and estimate the reduction in their activity. In February 2022, the official data of the whole 2020 were published and retrospectively analyzed. The ART cycles conducted in Italy in 2020 (67,928 by 57,423 patients) were then compared to those conducted in 2019 (82,476 by 67,633 patients). The estimates formulated through the survey were compared to the actual reduction. RESULTS: In 2020, 14,548 less IVF cycles were conducted with respect to 2019 (- 17.6% reduction). This led to 2539 fewer live births (- 19.8%) than 2019. If the reduction unveiled by the survey launched in May 2020 (i.e., - 35%) would have persisted throughout 2020, a significantly larger impact was expected (4200 less newborns). Instead, the activity was gradually recovered, and it compensated the months of greatest emergency, thus fulfilling the most optimistic scenario. CONCLUSIONS: Italy suffers from the lowest birth rate in Europe, and COVID-19 impact on IVF-derived live births testified how key ART is for Italian demographics. The government should support access to these treatments with dedicated actions.

Hysteroscopic findings in women with menorrhagia.

STUDY OBJECTIVE: To describe the hysteroscopic findings in patients complaining of menorrhagia to establish any significant association between menorrhagia and benign/malignant intrauterine disorders. DESIGN: Prospective cohort study (Canadian Task Force classification II). SETTING: University La Sapienza, Rome, Italy. PATIENTS: One hundred eighteen premenopausal women undergoing office hysteroscopy for menorrhagia (group A) and 344 premenopausal patients undergoing office hysteroscopy for other indications (noncyclic abnormal uterine bleeding, infertility, ultrasonographic abnormalities, etc) (group B). INTERVENTIONS: Office hysteroscopy. MEASUREMENT AND MAIN RESULTS: Data on the prevalence of hysteroscopic findings (cervical polyps, endometrial polyps, submucous myomas, low-grade hyperplasia and high-grade hyperplasia/endometrial carcinoma) were compared between group A and group B. The total prevalence, as well as the prevalence of type 0 and type I myomas (totally or >50% intracavitary, respectively), and the mean number per patients with submucous myomas was significantly higher in group A compared with group B (p = .0001, p = .024, and p = .017, respectively). Multivariable logistic regression analysis showed a statistically significant association between age (odds ratio 4.15, 95% confidence interval 1.55-11.1 in the 40- to 49-year age group), presence of submucous myomas (odds ratio 2.76, 95% confidence interval 1.52-5.00), and menorrhagia. CONCLUSIONS: Menorrhagia seems to be associated with aging, the presence and number of submucous myomas, and with the degree of their intracavitary development.

Feasibility and complications in bipolar resectoscopy: preliminary experience.

OBJECTIVE: To evaluate whether the new bipolar resectoscope (BR) 22 Fr (Karl Storz) represents a reliable improvement in operative hysteroscopy and to compare the new device to the 26 Fr BR (Karl Storz). MATERIAL AND METHODS: A prospective observational study. From June 2010 through May 2011, 158 consecutive patients treated with bipolar resectoscope 22 Fr and 26 Fr for endocavitary pathologies were registered. Data analysis included patients'characteristics, surgical indications, operative time and complications. 140 patients were eligible. RESULTS: 115/140 (82.1%) patients were treated by BR 22; 55 (39.2%) metroplastics, 34 (24.2%) polipectomies, 25 (17.8%) myomectomies and one (0.71%) sinechiolisis were performed. 25/140 (17.8%) patients were treated by BR 26; 6 (4.2%) polipectomies and 19 (13.5%) myomectomies were performed. Mean time of cervical dilatation by Hegar series was 57 sec for BR 22 Fr and 102 sec for BR 26 Fr (p = 0.034). 4/25 (16%) with 26BR and 1/115 (0.8%) with 22BR complications were observed (p = 0.002) : One uterine perforation, two post operative bleedings > 7 days, one intravasation syndrome and one cervical laceration. CONCLUSION: Bipolar resectoscopy is feasible and safe. The new device BR 22 Fr is preferable to 26 Fr because it requires lower cervical dilatation limiting operative time and complications.

Low-dose spinal anesthesia with hyperbaric bupivacaine with intrathecal fentanyl for operative hysteroscopy: a case series study.

STUDY OBJECTIVE: To estimate the efficacy and tolerability of low dose spinal anesthesia during operative hysteroscopy in a group of patients with high surgical risks. DESIGN: Case series study (Canadian Task Force Classification II-2). SETTING: Tertiary centers for women health care. PATIENTS: A total of 47 women affected by endometrial polyps (n = 32), myomas (n = 8), and abnormal uterine bleeding (n = 7) scheduled for inpatient operative hysteroscopy. INTERVENTIONS: Transvaginal ultrasonography; office diagnostic hysteroscopy; preoperative evaluation of American Society of Anesthesiologist (ASA) classification; inpatient operative hysteroscopy; low-dose spinal anesthesia with hyperbaric bupivacaine; compilation of a questionnaire. MAIN OUTCOME MEASURES: Practicability and patients' subjective experiences with spinal anesthesia; duration of cervical dilation and for operative hysteroscopy; infusion volume needed; incidence of surgical complications. RESULTS: Resectoscopy was performed in all patients, with the exception of 1 woman (2.1%) in which spinal anesthesia was unsuccessful. No statistically significant differences were noted among groups in terms of intra- and peri-operative findings. Sensory block induced by spinal anesthesia was suitable for surgery in all patients, and side effects occurred far less frequently than mentioned in the literature. Data reported in the questionnaire revealed that 93.5% of women would choose a spinal anesthesia again for a potential operative hysteroscopy in the future, since for 89.1% of them long lasting anesthesia is of relevance. CONCLUSIONS: Low-dose spinal anesthesia is a feasible technique in the inpatient setting for operative hysteroscopy in women with high surgical risks.

Fertility counseling in women with hereditary cancer syndromes.

Hereditary cancer syndromes are a heterogeneous group of genetic conditions that are associated with an increased risk of developing cancer during lifespan. In affected women, parenthood may be accompanied by concerns for the offspring, considering the common autosomal dominant inheritance. Moreover, fertility preservation to prevent the detrimental effects of cancer treatments differs compared to other clinical contexts. The necessity to preserve gametes is indeed predictable and expected to be common. For these reasons, we advocate a personalized and early fertility counseling. Carriers should be aware of the risk of transmission. The possibility to perform elective oocytes cryopreservation, either before (previvors) or after (survivors) cancer diagnosis should be discussed. Finally, they should be informed about the options of preimplantation genetic test (PGT) and oocytes donation. In conclusion, physicians engaged in oncofertility should personalize the counseling for women with hereditary cancer syndromes, being aware of their peculiar needs.

Cytoplasmic expression of estrogen receptor beta (ERß) predicts poor clinical outcome in advanced serous ovarian cancer.

OBJECTIVE: In this study we investigated the prognostic value of estrogen receptor α (ERα), ERß and progesterone receptor (PR) expression in 58 untreated advanced serous ovarian cancer patients. The study also included 12 macroscopically and histopathologically normal ovaries. MATERIALS AND METHODS: Protein expression was evaluated by immunohistochemistry, and antibody staining detected in both the nuclear and cytoplasmic compartments was taken into account. Immunopositivity was analyzed in relation to tumor clinicopathological variables, disease-free survival (DFS), and overall survival (OS). RESULTS: Epithelial cells in ovarian cancer tissue showed significantly lower levels of nuclear ERß and PR, but not ERα, than in normal ovarian tissue. In the case of ERß, however, while normal ovarian epithelium exhibited almost exclusively strong nuclear staining, ovarian cancer tissue mostly showed cytoplasmic immunopositivity. Nuclear ERα and ERß expression were not associated with clinical outcome. Conversely, any cytoplasmic ERß expression was an independent unfavorable prognostic factor for DFS, a finding approaching statistical significance also for OS. These data suggest that, in advanced serous ovarian cancer, cytoplasmic ERß signaling may be more important for patient survival than its nuclear signaling. In the case of PR, positivity was an independent favorable prognostic factor for DFS. CONCLUSIONS: These novel findings, that need to be confirmed in a large prospective trial, suggest that additional prognostic, and possibly therapeutic opportunities may be available in advanced serous ovarian cancer.

Single-port access laparoscopic assisted vaginal hysterectomy in a case of uterine ventrofixation using a new reusable device.

Vaginal hysterectomy may at times prove difficult and require laparoscopic assistance to ensure safety of operations. This article reports a case in which single port laparoscopic assistance enabled vaginal hysterectomy in a patient with severe uterine ventrofixation. The use of an innovative device and tips to be applied are described.

Minilaparotomy in spinal anaesthesia: a surgical choice in treatment of benign gynaecologic disease.

PURPOSE: Minilaparotomic access in spinal anaesthesia represents an example of mininvasive surgery and could be a valid cost-benefit alternative in the surgical treatment of benign gynaecologic diseases. METHODS: The study is a randomized study. We analyzed a consecutive series of 80 patients treated for benign gynaecological diseases with spinal (group A) or with general anaesthesia (group B). RESULTS: The median length of incision was 5 cm. The average operating time was 40.5 +/- 9.39 min, without differences between groups. The average hospital stay was 0.71 days shorter (p < or = 0.0001) and the postoperative pain was lower at 2 and 6 h from the surgery and at 10 p.m. in the group A (p < or = 0.0001). CONCLUSIONS: Minilaparotomy in spinal anaesthesia carries advantages from economic point of view with reduction of length of stay in hospital which is an important parameter for the evaluation of the quality of surgical treatments.

Correlation between oocyte preincubation time and pregnancy rate after intracytoplasmic sperm injection.

BACKGROUND AND AIM: Both nuclear and cytoplasmic maturation of oocytes have to be completed in a coordinated manner to ensure optimal conditions for fertilization. This is well known for in vitro fertilization, but is debated for intracytoplasmic sperm injection (ICSI). It has been reported that preincubation of oocytes prior to ICSI is associated with improved maturation of oocytes, fertilization and embryo quality. Therefore, in the present study, we evaluated the fertilization rate, embryo quality and pregnancy rate in relation to incubation times of metaphase-II oocytes before ICSI. METHOD: We analyzed 135 selected ICSI cycles. Subjects were assigned to six groups according to oocyte incubation time before ICSI: 2-4 h, 5 h, 6 h, 7 h, 8 h and 9-12 h. RESULTS: We observed that the fertilization rate increased slightly at short (2 to 6 h) and then decreased at longer preincubation times (7 to 12 h). Concomitantly, cleavage rate increased up to 6 h of preincubation and decreased significantly in the groups in which ICSI was carried out after 7 to 12 h of incubation. With regard to clinical pregnancy rate, we observed a significant increase from 2 to 5 h of preincubation, when this parameter reached its maximum value (35%), tapering to 33% after 6 h and then dropping sharply to 12 h. CONCLUSIONS: These data confirm that the most appropriate incubation time for mature oocytes before ICSI is 5-6 h. This time improves embryo quality and pregnancy rate in ICSI cycles.

A multicenter, double-blind, randomized, placebo-controlled study to assess whether antibiotic administration should be recommended during office operative hysteroscopy.

We did a double-blind, randomized, placebo-controlled study to assess the incidence of infectious complications and the protective effect of antibiotic administration during operative hysteroscopic procedures in an office setting. A total of 1046 consecutively enrolled women with intrauterine lesions were randomly allocated to the reference group (523 patients administered with 1 g of cefazolin intramuscularly) and the study group (523 patients administered with 10 mL of isotonic sodium chloride solution), and treated in office setting by operative hysteroscopy for endometrial polypectomy, uterine septa, submucosal myomas, and intrauterine adhesions. The primary outcome measure was the computation of difference between groups in postsurgical infectious complications occurring in the 5 days after the procedures. The time spent in performing the various procedures did not differ significantly (P > .05) between the groups. With respect to the overall rate of postsurgical infection, we found that 12 (1.15%) of 1046 patients referred with symptoms related to infective complications, 7 (1.3% of 523 women) in the study--untreated--group and 5 (1.0% of 523 women) in the reference group. Such incidences did not differ significantly between the groups (P > .05). Antibiotics were prescribed in all cases of postsurgical infection and the infective process resolved in few days. None of these patients developed serious infections with adnexal involvement, as confirmed by clinical and ultrasounds evaluation. The results of the current study would support the American College of Obstetricians and Gynecologists recommendation not to prescribe routine antibiotic administration in the case of hysteroscopic surgery.

Three-step model course to teach intracorporeal laparoscopic suturing.

BACKGROUND: Laparoscopy requires a set of skills such as intracorporeal stitching and knotting. The aim of this study is to present an effective specialized training course for the laparoscopic suturing technique. MATERIALS AND METHODS: We designed a specialized 5-day training course for laparoscopic suturing skills with theoretical and practical sessions on inanimate pelvic training. The "gladiator rule" was the method used to teach intracorporeal suturing using the right and left hand from a lateral and suprapubic access. Data on sense of depth, coordination, dexterity, traction power, and posture at the beginning and at the end of the course were compiled. Three practical evaluations were performed by each course participant. Follow-up on subsequent live laparoscopic application of intracorporeal suturing was obtained. RESULTS: We enrolled 44 consecutive trainees: 33 men and 11 women. We found a significant statistical improvement during the course in coordination (P=.001), dexterity (P=.000), traction power (P=.002), and posture (P=.003). Men were better than women in coordination (P=.002), dexterity (P=.000), and traction power (P=.014). No significant statistical difference in suturing skill was found in relation to age, gender, previous courses, surgical training (surgeon or resident), and dominant hand. Twenty-nine of 40 (72.5%) trainees after the course began to apply intracorporeal sutures in vivo. CONCLUSIONS: The present study demonstrates the utility of a 5-day suturing course in teaching laparoscopic suturing technique. The "gladiator rule" is a useful and reproducible theory to teach intracorporeal knotting. The three-step model allows the majority of the trainees to apply laparoscopic suturing in vivo.

Clinical outcomes associated with surgical treatment of endometrioma coupled with resection of the posterior broad ligament.

OBJECTIVE: To evaluate clinical outcomes associated with the resection of both endometrioma and posterior broad ligament (PBL) among women with PBL adhesion associated with endometrioma. METHODS: Between January 2007 and December 2009 at the Villanova Hospital, Florence, Italy, a prospective trial was conducted on 99 consecutive patients with unilateral or bilateral endometrioma who underwent laparoscopic ovarian cystectomy by a stripping technique and homolateral PBL resection where PBL adhesion was associated with endometrioma. The prevalence of PBL adhesion and endometriosis, the association between PBL endometriosis and pain, and the recurrence of endometrioma and pain were evaluated. All data were analyzed with Prism software. RESULTS: Among 124 endometriomas treated by concomitant PBL resection, the PBL was not affected by adhesions in only 2% of patients. PBL endometriosis was superficial in 36 (29.5%) and deep in 86 (70.5%) of the histologic preparations; deep endometriosis correlated with preoperative pain. At 1-year follow-up, endometrioma had recurred in 7 patients; the main symptom reported was mid-cycle pain (24 patients, 24%; P=0.0007). CONCLUSION: Ovarian endometriosis was often (98%) associated with PBL endometriosis; deep endometriosis of PBL correlated with pain symptoms. Although PBL resection increased the incidence of mid-cycle pain, it was associated with low recurrence of endometrioma.

The practicability and surgeons' subjective experiences with vaginal danazol before an operative hysteroscopy.

This randomized, double blind, placebo-controlled study compared the usefulness of danazol 400mg vaginally versus 600mg orally in women as a preoperative preparation for hysteroscopic surgery. Ninety-one fertile women were randomly allocated to Group A (46 patients received 400mg of danazol placed into the posterior vaginal fornix and three oral tablets of commercially available folic acid as a placebo), and Group B [45 women treated with 600mg of danazol orally (200mg three times daily) and two vaginal tablets of Lactobacillus rhamnosus as a placebo]. The patients underwent an operative hysteroscopy, transvaginal sonography, blood tests, and a histological assay. A visual analog scale (VAS) score to compute the degree of the surgeon's satisfaction was used. The outcome measures were as follows: an evaluation of the changes in the endometrial thickness, the prevalence of endometrial atrophy, changes in the blood tests, any collateral effects, the degree of difficulty and view, the duration of the surgical procedure, any complications during the operative hysteroscopy and associated side effects, and the surgeon's satisfaction with the endometrial preparation. The vaginal administration route was associated with a more pronounced effect on the endometrial thickness. Significantly more patients receiving vaginal danazol (45/46) had a hypotrophic endometrium than those receiving oral danazol (37/45, P<0.01). In addition, the patients receiving danazol vaginally had a shorter operating time, lower infusion volume, fewer side effects, and a higher surgeon satisfaction. Vaginal danazol adequately prepares the endometrium for an operative hysteroscopy by thinning the endometrium effectively with few side effects and little impact on the metabolic parameters.

Single access laparoscopy for adnexal pathologies using a novel reusable port and curved instruments.

OBJECTIVE: To present our initial experience using single access laparoscopic surgery for the treatment of benign adnexal pathologies. METHODS: Sixteen patients with benign adnexal pathologies underwent salpingoophorectomy (n=9), ovarian cyst enucleation (n=5), or salpingectomy (n=2) using a laparoendoscopic single site approach with a new multiport reusable trocar and flexible and curved-as well as standard-laparoscopic instruments. RESULTS: Conversion to a multi-access standard laparoscopic technique was not required in any patient and no intraoperative complications were observed. Postoperatively, one umbilical scar infection was detected. Mean operative time was 42 minutes. CONCLUSION: Laparoscopic single site enucleation for adnexal pathologies is feasible, safe, and effective, and has good results for cosmetic appearance and postoperative pain. Use of specialized instruments and standardization of the technique affect surgical ergonomy and operating time.

Intracytoplasmic sperm injection and pregnancy with decapitated sperm.

OBJECTIVE: To perform intracytoplasmic sperm injection (ICSI) in couples with primary infertility owing to sperm defects causing total immotility. DESIGN: Case report. SETTING: Couple Sterility Center, University of Siena. PATIENT(S): Two infertile couples, the male members of which had "detached tail" genetic sperm defect. MAIN OUTCOME MEASURE(S): Physical and hormonal assays, semen analysis by light and electron microscopy, Y microdeletion screening, immunofluorescence, fluorescence in situ hybridization analysis of sperm nuclei, and PCR for partial sequences of AKAP4/AKAP3 binding regions were performed. The couples then underwent ICSI. RESULT(S): Transmission electron microscopic analysis showed that the cause of sterility was "detached tail" genetic sperm defect. Immunofluorescence staining confirmed sperm structural alterations. Screening of Y microdeletions, partial sequences of AKAP4/AKAP3 binding regions, and fluorescence in situ hybridization did not show any sperm nucleus abnormalities. Three and two ICSI cycles were performed in the two couples. One pregnancy was achieved and a healthy baby with a normal female karyotype was born. CONCLUSION(S): One couple successfully underwent ICSI with "detached tail" sperm and gave birth to a healthy baby, suggesting that this structural abnormality may be bypassed by injecting sperm with a normal centriolar region.

ICSI for treatment of human immunodeficiency virus and hepatitis C virus-serodiscordant couples with infected male partner.

BACKGROUND: Assisted reproductive technology with semen washing can offer a significant reduction in risk of sexual and vertical transmission of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in serodiscordant couples with infected male partner. METHODS: Among couples coming to our centre for reproductive problems from January 2001 to December 2003, we selected 43 couples with seropositive male and seronegative female: 25 couples with HIV-seropositive males, 10 couples with HIV/hepatitis C virus (HCV)-seropositive males and eight couples with HCV-seropositive males. Sperm samples were washed and used for ICSI. RESULTS: Seventy-eight cycles of ICSI were performed. The mean fertilization rate was 70.34 +/- 20.14% (mean +/- SD). A mean number of 3.55 +/- 1.11 (range: 1-5) embryos of good quality was transferred for each patient. We obtained 22 pregnancies (21 singletons and one twin), with a pregnancy rate per transfer of 28.2% and an implantation rate per transfer of 15.2%. The cumulative pregnancy rate was 51.2%. At follow-up, no seroconversion was detected in any patient. CONCLUSIONS: Our data suggest that sperm wash and ICSI could be useful for reducing the risk of HIV and/or HCV transmission in serodiscordant couples with infected male wishing to have a child, irrespective of their fertility status.