Status epilepticus in pregnancy: a literature review and a protocol proposal.

INTRODUCTION: Status epilepticus (SE) in pregnancy represents a life-threatening medical emergency for both mother and fetus. Pregnancy-related pharmacokinetic modifications and the risks for fetus associated with the use of antiseizure medications (ASMs) and anesthetic drugs complicate SE management. No standardized treatment protocol for SE in pregnancy is available to date. AREAS COVERED: In this review, we provide an overview of the current literature on the management of SE in pregnancy and we propose a multidisciplinary-based protocol approach. EXPERT OPINION: Literature data are scarce (mainly anecdotal case reports or small case series). Prompt treatment of SE during pregnancy is paramount and a multidisciplinary team is needed. Benzodiazepines are the drugs of choice for SE in pregnancy. Levetiracetam and phenytoin represent the most suitable second-line agents. Valproic acid should be administered only if other ASMs failed and preferably avoided in the first trimester of pregnancy. For refractory SE, anesthetic drugs are needed, with propofol and midazolam as preferred drugs. Magnesium sulfate is the first-line treatment for SE in eclampsia. Termination of pregnancy, via delivery or abortion, is recommended in case of failure of general anesthetics. Further studies are needed to identify the safest and most effective treatment protocol.

Bone health and hormonal contraception.

INTRODUCTION: Short-term and long-term steroid contraceptive systems are widely employed in adolescents and premenopausal women; they could induce variation in bone metabolism, but whether these changes increase the overall fracture risk is not yet clear. EVIDENCE ACQUISITION: A systematic search of scientific publications about "hormonal contraceptives" and "bone metabolism" in reproductive age women was conducted. EVIDENCE SYNTHESIS: In adolescent girl, combined oral contraceptives could have a deleterious effect on bone health when their onset is within three years after menarche and when they contain ethinyl estradiol at the dose of 20 mcg. In perimenopausal women, steroid contraceptives seem not influence bone health nor increase osteoporotic fractures risk in menopause. The oral progestogens intake is not related to negative effects on skeletal health. Depot medroxyprogesterone acetate (DMPA) induce a prolonged hypoestrogenism with secondary detrimental effect on healthy bone; the higher bone loss was observed at the DMPA dose of 150 mg intramuscular such as after long-term DMPA-users. Progestin-based implants and intrauterine devices have not negative effect on bone health. CONCLUSIONS: Since sex-steroid drugs induce variations in hormonal circulating concentrations, they may negatively affect bone metabolism. Contraceptive choice should be tailored evaluating any possible effect on bone health. Clinicians should always perform a precontraceptive counselling to identify any coexisting condition that may affect bone health. Further randomized studies are needed to confirm these results.

Safety and Benefits of Contraceptives Implants: A Systematic Review.

Progestin-only contraceptive implants provide long-acting, highly effective reversible contraception. We searched the medical publications in PubMed, CENTRAL, and EMBASE for relevant articles on hormonal implants published in English between 1990 and 2021. Levonorgestrel (LNG) 6-capsule subdermal implants represented the first effective system approved for reversible contraception. The etonogestrel (ENG) single rod dispositive has been widely employed in clinical practice, since it is a highly effective and safe contraceptive method. Abnormal menstrual bleeding is a common ENG side effect, representing the main reason for its premature discontinuation. Emerging evidence demonstrated that it is possible to extend the use of the ENG implant beyond the three-year period for which it is approved. The ENG implant could be an effective and discrete alternative to the IUD in young girls, such as post-partum/post-abortion. Implants should be inserted by trained skilled clinicians who previously provide adequate counselling about their contraceptive effect, benefits, and any possible adverse events. More studies are needed to validate the extended use of the ENG implant for up to 5 years.

In-bag manual versus uncontained power morcellation for laparoscopic myomectomy: randomized controlled trial.

OBJECTIVE: To evaluate whether manualin-bag morcellation could be efficiently proposed as alternative to the uncontained power technique. DESIGN: Randomized controlled trial. SETTING: Academic hospital. PATIENT(S): One hundred fifty-two premenopausal women eligible for myomectomy were screened, and 104 were randomized. INTERVENTION(S): Patients were randomized into two groups. In the experimental group, "in-bag" protected morcellation was performed. In the control group, patients were treated by uncontained power myoma removal. MAIN OUTCOME MEASURE(S): The primary endpoint was the comparison of morcellation operative time (MOT). The secondary endpoints were the comparisons of total operative time (TOT), simplicity of morcellation (as defined by the surgeon using a visual analogue scale scale), intraoperative blood loss, rate of complications, and postoperative outcomes. RESULT(S): A sample size of 51 per group (n = 102) was planned. Between March 2014 and January 2015, patients were randomized as follows: 53 to the experimental group and 51 to the control group. Most demographic characteristics were similar across groups. MOT was observed to be similar in both study groups (16.18 ± 8.1 vs. 14.35 ± 7.8 minutes, in the experimental and control groups, respectively). Fibroid size was identified as the principal factor influencing morcellation time (Pearson coefficient 0.484 vs. 0.581, in the experimental and control groups, respectively). No significant difference in TOT, simplicity of morcellation, delta Hb, postoperative pain, and postoperative outcomes were observed between groups. CONCLUSION(S): The protected manual in-bag morcellation technique represents a time-efficient and feasible alternative, which does not interfere with surgical outcomes in women undergoing laparoscopic myomectomy. CLINICAL TRIAL REGISTRATION: NCT02086435.

Prophylactic bilateral salpingectomy for the prevention of ovarian cancers: What is happening in Italy?

In 2011, the Society of Gynecologic Oncology of Canada encouraged physicians to discuss with their patients the risks and benefits of prophylactic bilateral salpingectomy (PBS) at the time of hysterectomy or tubal ligation for prevention of ovarian cancers (OCs). The aim of this study was to examine obstetrician-gynaecologists' knowledge, opinions and practice patterns relating to opportunistic salpingectomy in the general population. An anonymous electronic survey was sent to residents, academic and hospital staff in Italian OBGYN departments. The survey included questions on demographics, knowledge and attitudes in terms of the implementation of PBS in women at average population risk of OC. At least 80% of the 479 respondents reported performing PBS during hysterectomy for benign indications, chiefly with the intent of OC risk reduction but also to decrease the risk of reoperation and subsequent tubal pathologies. Among the 86 colleagues who do not routinely perform PBS, more than 50% stated that they have doubts regarding the benefits associated with the procedure. Most of the respondents declared that they were familiar with the literature on the topic and were aware of the data reporting the safety of the procedure, and only 21 (4.53%) had never heard of PBS. Over 40% of the respondents worked in hospitals in southern Italy. PBS as a prophylactic measure to reduce the incidence of OC is a well-known strategy among the Italian OBGYNs interviewed. Given the unequal distribution of respondents, however, wider educational initiatives should be undertaken, at least in Italy, to increase the implementation of salpingectomy among OBGYNs.

Wide excision of soft tissues adjacent to the ovary and fallopian tube does not impair the ovarian reserve in women undergoing prophylactic bilateral salpingectomy: results from a randomized, controlled trial.

OBJECTIVE: To study the effects of the wide excision of soft tissues adjacent to the ovary and fallopian tube on ovarian function and surgical outcomes in women undergoing laparoscopic bilateral prophylactic salpingectomy. DESIGN: Randomized, controlled trial. SETTING: Teaching hospital. PATIENT(S): One hundred eighty-six women undergoing laparoscopic surgery for uterine myoma (n = 143) or tubal surgical sterilization (n = 43). INTERVENTION(S): Patients were randomly divided into two groups. In group A (n = 91), standard salpingectomy was performed. In group B (n = 95), the mesosalpinx was removed within the tubes. Prior to and 3 months after surgery, antimüllerian hormone (AMH), FSH, three-dimensional antral follicle count (AFC), vascular index (VI), flow index (FI), vascular-flow index (VFI), and OvAge were recorded for each patient. MAIN OUTCOME MEASURE(S): Ovarian reserve modification (Δ) before and after surgery was assessed as the primary outcome. Operative time, variation of the hemoglobin level (ΔHb), postoperative hospital stay, postoperative return to normal activity, and complication rate were assessed as secondary outcomes. RESULT(S): No significant difference was observed between groups for ΔAMH, ΔFSH, ΔAFC, ΔVI, ΔFI, ΔVFI, and ΔOvAge. Moreover, the groups were similar for operative time, ΔHb, postoperative hospital stay, postoperative return to normal activity, and complication rate. CONCLUSION(S): Even when the surgical excision includes the removal of the mesosalpinx, salpingectomy does not damage the ovarian reserve. Moreover, wide salpingectomy with excision of the mesosalpinx did not alter blood loss, hospitalization stay, or return to normal activities. CLINICAL TRIAL REGISTRATION NUMBER: NCT02086370.

Polycystic ovary syndrome: chemical pharmacotherapy.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disease among women of childbearing age. The clinical features are heterogeneous and vary in intensity. Hirsutism, menstrual disorders and infertility are the most frequent conditions observed; however, long-term complications (dyslipidemia, hypertension, cardiovascular disease, type 2 diabetes mellitus, endometrial cancer) are also often described. Each disorder may be managed by tailored strategies, employing sequential or combined pharmacological and/or non-pharmacological treatment. AREAS COVERED: The authors review the drugs used for PCOS management and discuss new approaches. A systematic MEDLINE search regarding the randomized controlled trials, retrospective and observational studies about medical treatments of PCOS, the Cochrane library for reviews and also search for registered trials on ClinicalTrials.gov is performed. EXPERT OPINION: A uniform treatment for PCOS patients does not exist. Clinicians should perform an accurate evaluation of patients' characteristics, identifying the phenotypic target and, subsequently, the best-tailored treatment to manage one or more clinical issues. Lifestyle intervention should always be the first recommended approach unless other issues indicate that drug or hormonal interventions are superior.

Sonographic findings in postmenopausal women with a prior endometrial ablation: interpretation and management of women with endometrial thickening and bleeding.

OBJECTIVE: To understand the meaning of endometrial thickening and bleeding in postmenopausal women who had previously undergone endometrial ablation (EA). DESIGN: Retrospective observational study. Canadian Task Force III. SETTING: Obstetrics and Gynecology Unit, Magna Graecia University, Catanzaro, Italy. PATIENTS: Sixty-three postmenopausal women who had previously undergone EA. INTERVENTIONS: A retrospective evaluation of clinical charts of postmenopausal women who had a follow-up visit after EA between January 2000 and August 2014. MEASUREMENTS AND MAIN RESULTS: The rates of endometrial thickening (with or without bleeding), endometrial atrophy, and cancer were determined. Postmenopausal bleeding was reported in 9 patients (14.3%). Endometrial thickening was observed in 51 patients (80.9%; mean ± SD endometrial thickness, 7.7 ± 3.0 mm). A significantly (p < .05) greater number of patients with an endometrial thickness of 5 to 10 mm was observed compared with those with an endometrial thickness of <5 mm or >10 mm. A significant (p = .001) difference in increase in endometrial thickness was observed between patients with and without bleeding. Overall, hysteroscopy plus endometrial biopsy was scheduled in 24 patients. In all bleeding women, a histological diagnosis of endometrial atrophy was demonstrated. Concerning bleeding-free women, in 14 patients with endometrial thickening of >10 mm, mucosal atrophy was detected. The only bleeding-free patient in whom an endometrial echogenic fluid collection was detected had a histological diagnosis of endometrioid endometrial cancer. Thus, patients who underwent hysteroscopy had a 95.8% rate of mucosal atrophy and a 4.2% rate of endometrial cancer. The overall cancer rate in our global population (menopause with previous EA) was 1.6%. CONCLUSION: Postmenopausal bleeding and sonographic detection of endometrial thickening in patients with previous EA are not necessarily related to a malignant disease. Nonetheless, ultrasound visualization of endometrial thickening plus an echogenic endometrial fluid collection in these patients always warrants an invasive diagnostic procedure regardless of whether or not bleeding is reported.

Adjuvant use of platelet gel for wound breakdown prevention in advanced vulvar cancer surgery: a retrospective study.

OBJECTIVE: The aggressive surgical strategy adopted for vulvar cancer is related to a high complication rate, usually consisting in infections and wound breakdown. Considering that platelet gel concentrate improves reparation of cutaneous lesions, the aim of the current retrospective study was to evaluate the efficacy of platelet gel application in women who had undergone radical surgery for vulvar cancer. MATERIALS AND METHODS: We retrospectively analyzed record charts of 25 women referred to our academic departments with a diagnosis of vulvar cancer and who had undergone radical vulvectomy plus inguinofemoral lymphadenectomy between January 2007 and December 2011. During the reconstructive phase, a platelet gel was placed on the vaginal breach in 10 women (group A). In the remaining 15 patients, only surgical strategies were performed (group B). Primary outcomes were wound infection, necrosis, and/or breakdown of wounds rates; secondary outcomes were postoperative fever, hospital stay, and lastly, wound healing. RESULTS: Compared to surgery alone, the platelet gel application was related to a significant decrease in wound infection (P = 0.032), necrosis of vaginal wounds (P = 0.096), and breakdown wound (P = 0.048) rates. In addition, in group A, reduction in postoperative fever rate (P < 0.001) and hospital stay (P < 0.001) were also detected. Compared to surgery alone, a faster wound healing in patients who had undergone surgery plus platelet (P < 0.001) were lastly observed. CONCLUSION: In conclusion, platelet gel application before vulvar reconstruction represents an effective strategy to prevent wound breakdown after local advanced vulvar cancer surgery. However, further prospective data are needed to confirm these preliminary results.

Improvement in chronic pelvic pain after gonadotropin releasing hormone analogue (GnRH-a) administration in premenopausal women suffering from adenomyosis or endometriosis: a retrospective study.

The aim of this study was to evaluate the improvement in catamenial chronic pelvic pain (CPP) after Gonadotropin Releasing Hormone analogue (GnRH-a) administration in women affected by adenomyosis or endometriosis. We retrospectively analysed clinical data of 63 premenopausal women with clinical suspect of adenomyosis (15 women, Group A) or endometriosis (48 women, Group B), which received GnRH-a in order to reduce CPP intensity during the time on surgery waiting list. Main outcome measures were variation of CPP intensity, numbers of days requiring analgesics and lost work productivity before and three months after GnRH-a administration. Compared to baseline, a significant decrease in CPP intensity (p < 0.05) was observed in both groups, even if this reduction was significantly higher in Group A than in Group B (p < 0.001). In both groups, moreover, a significant reduction in number of days requiring analgesics (p < 0.05) and lost work productivity (p < 0.05) was detected. In conclusion, GnRH-a administration in women with clinical suspect of adenomyosis induces a greater reduction in CPP when compared to women with endometriosis, thus representing a potential ex adiuvantibus criteria, helping TV-US in the clinical diagnosis of adenomyosis.

Changes in androgens and insulin sensitivity indexes throughout pregnancy in women with polycystic ovary syndrome (PCOS): relationships with adverse outcomes.

BACKGROUND: Given the high rate of pregnancy and perinatal complications recently observed in patients with polycystic ovary syndrome (PCOS) and the lack of data on the serum variations in androgens and insulin sensitivity indexes in pregnant women with PCOS, the current study was aimed to assess these changes and their potential effect on pregnancy outcomes in a population of women with PCOS. METHODS: Forty-five pregnant patients with ovulatory PCOS (PCOS group) and other 42 healthy pregnant women (control group) were studied assaying serum androgen levels and insulin sensitivity indexes throughout pregnancy serially, and recording obstetrical outcomes. RESULTS: Serum androgen levels and insulin resistance indexes were significantly (p < 0.05) higher in PCOS than in control group at study entry, these differences were sustained throughout pregnancy, and their changes resulted significantly (p < 0.05) different between PCOS and control group. In PCOS patients, women who had a complicated pregnancy showed serum androgen levels and insulin sensitivity indexes significantly (p < 0.05) worse in comparison to subjects without any pregnancy and/or neonatal complications. CONCLUSIONS: PCOS patients have impaired changes in serum androgen levels and insulin sensitivity indexes during pregnancy. These alterations could be implicated in the pregnancy and neonatal complications frequently observed in women affected by PCOS.

Serum and follicular anti-Mullerian hormone levels in women with polycystic ovary syndrome (PCOS) under metformin.

BACKGROUND: No data regarding metformin effects on follicular fluid anti-Müllerian hormone (AMH) levels were to date available in literature. The aim of the present study was to evaluate in patients with polycystic ovary syndrome (PCOS) whether metformin administration affects serum and follicular AMH levels, and whether this is related to ovarian response to the treatment. METHODS: Twenty young patients with PCOS who had received metformin were enrolled. Ten patients were anovulatory (Met-anov group), whereas the other 10 were ovulatory (Met-ov group) but had failed to conceive. Further untreated PCOS (PCOS controls, n. 10) and healthy controls (non-PCOS controls, n. 10) who were scheduled for laparoscopic surgery were enrolled. In each subjects, clinical and biochemical evaluations were performed. AMH concentrations in blood and antral follicular fluid were assayed. RESULTS: In both Met-anov and Met-ov groups, and without difference between them, serum androgens and AMH, and indices of insulin resistance were significantly (p < 0.05) improved after treatment. On the other hand, significant differences (p < 0.05) between the two groups were detected with respect to the same biochemical parameters in antral follicular fluid. In the Met-anov group, no significant correlation was observed between AMH concentrations in the follicular fluid and variation in serum androgens, AMH and insulin resistance indexes; whereas in Met-ov group significant correlations were detected between AMH levels in the follicular fluid and variation in serum androgens, AMH and insulin resistance indexes. CONCLUSIONS: Metformin administration in patients with PCOS exerts a differential action on the ovarian AMH levels on the basis of ovulatory response. Changes in AMH levels in antral follicular fluid during metformin treatment could be involved in the local mechanisms mediating the ovulatory restoration.

Ultra-conservative fertility-sparing strategy for bilateral borderline ovarian tumours: an 11-year follow-up.

BACKGROUND: This is a prospective long-term extension study of a randomized controlled trial aimed to assess the risk-benefit ratio of an ultra-conservative fertility-sparing approach in patients with bilateral borderline ovarian tumours (BOTs). METHODS: The experimental group (n = 15) was treated with an ultra-conservative surgical approach consisting of bilateral cystectomy, whereas the control group (n = 17) received a less conservative surgery consisting of oophorectomy plus controlateral cystectomy alone. All patients received a complete laparoscopic staging followed by a fertility enhancement programme. Patients who completed childbearing were treated with a non-conservative standard treatment at the first recurrence. RESULTS: After a follow-up period of 128 (9 interquartile range (IQR); 115-150 range) and 132 (7 IQR; 117-152 range) months for the experimental and control groups, respectively (P = 0.25), the time to first baby-in-arm (P < 0.02) and the relative rate (RR) of baby-in-arm (8.05 [95% confidence interval (CI), 1.20-9.66; P < 0.01]) were significantly lower and higher, respectively, for the experimental compared with the control group. Although the time to first recurrence was significently (P < 0.01) shorter for the experimental group, in the regression analysis the difference did not reach the statistic significance (P = 0.14), and the RR of recurrence (1.23 [95% CI, 0.62-3.17; P = 0.41]) was not significant. Finally the number needed to treat for pregnancy was three, the number needed to harm for radical surgery was only two. CONCLUSIONS: The ultra-conservative fertility-sparing approach is more effective than the standard approach in terms of reproductive outcomes, but presents a higher oncological risk.