Type and Location of Adenomyosis in Women with Recurrent Pregnancy Loss: A Transvaginal Ultrasonographic Assessment.

The current knowledge on adenomyosis as a risk factor for RPL is very scant. Overall 120 women were included in this retrospective observational study. They were divided in three groups each of which consisted of 40 subjects: Group 1: women with RPL who were diagnosed to have adenomyosis on transvaginal ultrasound (TVS); Group 2: patients with RPL without ultrasonographic findings of adenomyosis; Group 3: patients with ultrasound diagnosis of adenomyosis without RPL and at least one live birth pregnancy. The copresence of endometriosis was also investigated. Among women with RPL, patients with adenomyosis (Group 1) had higher number of pregnancy losses (p = 0.03) and lower age at first pregnancy loss (p = 0.03) than women without adenomyosis (Group 2). Moreover, they had more frequently primary RPL (p = 0.008). Adenomyosis of the inner myometrium was found more frequently (p = 0.04) in patients of Group 1 than in patients of Group 3 in which adenomyosis was mainly in the outer myometrium (p= 0.02). No differences were found in the severity of adenomyosis between these two groups of women. TVS findings for endometriosis were observed more frequently in women with adenomyosis without RPL (Group 3) than in the other two groups of patients. Adenomyosis can be a factor involved in RPL. Differences in adenomyosis localization are associated with different risks for RPL. Patients with RPL should be investigated for the presence of adenomyosis and also for the type and localization of the disease in the different myometrial layers.

Assessing ovarian stimulation with letrozole and levonorgestrel intrauterine system after combined fertility-sparing approach for atypical endometrial lesions: a retrospective case-control study.

RESEARCH QUESTION: Is ovarian stimulation with levonorgestrel intrauterine system (LNG-IUS) in situ and co-treatment with letrozole safe and effective in patients undergoing fertility-sparing combined treatment for atypical endometrial hyperplasia (AEH) or early endometrial cancer limited to the endometrium? DESIGN: Retrospective case-control study recruiting women who had undergone fertility-sparing 'combined' treatment and ovarian stimulation with letrozole and LNG-IUS in situ. The 'three steps' hysteroscopic technique was used. Once complete response was achieved, the ovaries were stimulated, and mature oocytes cryopreserved. The LNG-IUS was removed, and embryos transferred. A comparative analysis was conducted between the two control groups of the initial outcomes of ART (number of oocytes and MII oocytes retrieved): healthy infertile women undergoing ovarian stimulation for IVF/ICSI (control group A); and patients diagnosed with breast cancer who underwent ovarian stimulation with letrozole (control group B). RESULTS: Of the 75 patients analysed, 15 underwent oocyte cryopreservation after achieving a complete response to fertility-sparing treatment (study group); 30 patients in control group A and B, respectively. No statistically significant differences were observed in retrieved oocytes and mature oocytes between the study and control groups. In the nine patients who underwent embryo transfer, clinical pregnancy (55.6%), cumulative live birth (44.4%) and miscarriage (20%) rates were reported. In three patients with AEH, recurrence occurred (12%) at 3, 6 and 16 months after removing the LNG-IUS to attempt embryo transfer, respectively. CONCLUSION: Fertility-sparing hysteroscopic combined treatment and subsequent ovarian stimulation with letrozole and LNG-IUS in situ could be suggested to women with AEH or early endometrial cancer who ask for future fertility preservation.

Laparoscopic oocyte retrieval for fertility preservation in a patient with squamous cell carcinoma of the vagina.

OBJECTIVE: To describe a feasible fertility preservation strategy in a woman with vaginal carcinoma. DESIGN: Video case report demonstrating the diagnostic work-up and laparoscopic oocyte retrieval performed under regional anesthesia. SETTING: University tertiary care hospital. PATIENT(S): A 35-year-old nulliparous woman presented with vaginal bleeding and foul-smelling vaginal discharge. After a comprehensive diagnostic work-up, a final diagnosis of squamous cell carcinoma of the vagina stage II (Federation International Obstetrics and Gynecology classification) was made. As per the patient's desire, before undergoing chemoradiotherapy, the patient underwent oocyte cryopreservation. Transvaginal retrieval of oocytes was not feasible because of stenosis of the vaginal introitus and the potential risk of intracavitary tumor cell spillage. Transabdominal ultrasound-guided oocyte retrieval was not possible because of the body's habitus. INTERVENTION(S): The patient underwent ovarian stimulation for in vitro fertilization. To minimize estrogen levels, letrozole was used during controlled ovarian stimulation. Laparoscopic oocyte retrieval was performed under spinal anesthesia. MAIN OUTCOME MEASURE(S): Successful laparoscopic egg retrieval and cryopreservation in a woman with squamous cell carcinoma of the vagina. RESULT(S): A total follicular count of nine was estimated before the oocyte retrieval. Eight oocytes were retrieved at laparoscopy, and eight mature oocytes were successfully cryopreserved. No complications were encountered, and the patient was discharged on the same day of surgery. CONCLUSION(S): To our knowledge, this is the first published case of fertility preservation using the laparoscopic approach in a patient with vaginal cancer. Letrozole is a valuable strategy to reduce high estrogen in patients with gynecological cancer undergoing controlled ovarian stimulation. Laparoscopy oocyte retrieval, performed under regional anesthesia, can be performed in an ambulatory setting and should be considered an effective fertility preservation strategy in patients with large vaginal tumors.

Ovarian reserve in patients with multiple sclerosis: A systematic review and meta-analysis.

OBJECTIVE: To summarize recent evidence about ovarian reserve markers in women affected by multiple sclerosis (MS) compared with healthy controls, as women with MS seem to be characterized by lower anti-Müllerian hormone (AMH) levels. METHODS: The research was conducted using PubMed (MEDLINE), Scopus, ClinicalTrial.gov, OVID and Cochrane Library from inception of each database to June 30, 2022. Studies comparing ovarian reserve markers between women with MS and healthy controls were considered eligible for inclusion. The primary outcome was serum AMH (ng/mL) levels. Results were reported as pooled odds ratio (OR) for categorical outcomes and as mean difference (MD) for continuous variables, with their 95% confidence intervals (CIs). The random effect model of DerSimonian and Laird was adopted for all analyses. A P-value less than 0.05 was considered significant. RESULTS: Serum AMH circulating levels were not significantly different (MD -0.25, 95% CI -0.83 to 0.32; P = 0.390), as well as blood levels of follicle-stimulating hormone or ovarian volume. However, antral follicle count (AFC) and estradiol blood levels were significantly lower, and luteinizing hormone (LH) levels were significantly higher in women with MS than in controls. CONCLUSION: A significant difference in AFC, estradiol and LH levels was observed, but not for AMH levels.

The impact of COVID-19 pandemic on obstetrics and gynecology hospitalization rate and on reasons for seeking emergency care: a systematic review and meta-analysis.

BACKGROUND: During the lockdown due to COVID-19 pandemic, utilization of emergency care units has been reported to be reduced for obstetrical and gynaecological reasons. The aim of this systematic review is to assess if this phenomenon reduced the rate of hospitalizations for any reason and to evaluate the main reasons for seeking care in this subset of the population. METHODS: The search was conducted using the main electronic databases from January 2020 to May 2021. The studies were identified with the use of a combination of: "emergency department" OR "A&E" OR "emergency service" OR "emergency unit" OR "maternity service" AND "COVID-19" OR "COVID-19 pandemic" OR "SARS-COV-2" and "admission" OR "hospitalization". All the studies that evaluated women going to obstetrics & gynecology emergency department (ED) during the COVID-19 pandemic for any reason were included. RESULTS: The pooled proportion (PP) of hospitalizations increased from 22.7 to 30.6% during the lockdown periods, in particular from 48.0 to 53.9% for delivery. The PP of pregnant women suffering from hypertensive disorders increased (2.6 vs 1.2%), as well as women having contractions (52 vs 43%) and rupture of membranes (12.0 vs 9.1%). Oppositely, the PP of women having pelvic pain (12.4 vs 14.4%), suspected ectopic pregnancy (1.8 vs 2.0), reduced fetal movements (3.0 vs 3.3%), vaginal bleeding both for obstetrical (11.7 vs 12.8%) and gynecological issues (7.4 vs 9.2%) slightly reduced. CONCLUSION: During the lockdown, an increase in the proportion of hospitalizations for obstetrical and gynecological reasons has been registered, especially for labor symptoms and hypertensive disorders.

Use of artificial intelligence in obstetrics: not quite ready for prime time.

Artificial intelligence is finding several applications in healthcare settings. This study aimed to report evidence on the effectiveness of artificial intelligence application in obstetrics. Through a narrative review of literature, we described artificial intelligence use in different obstetrical areas as follows: prenatal diagnosis, fetal heart monitoring, prediction and management of pregnancy-related complications (preeclampsia, preterm birth, gestational diabetes mellitus, and placenta accreta spectrum), and labor. Artificial intelligence seems to be a promising tool to help clinicians in daily clinical activity. The main advantages that emerged from this review are related to the reduction of inter- and intraoperator variability, time reduction of procedures, and improvement of overall diagnostic performance. However, nowadays, the diffusion of these systems in routine clinical practice raises several issues. Reported evidence is still very limited, and further studies are needed to confirm the clinical applicability of artificial intelligence. Moreover, better training of clinicians designed to use these systems should be ensured, and evidence-based guidelines regarding this topic should be produced to enhance the strengths of artificial systems and minimize their limits.

Does Intrauterine Injection of hCG Improve IVF Outcome? A Systematic Review and a Meta-Analysis.

Various interventions have been proposed to improve embryo implantation in IVF. Among these, intrauterine injections of human chorionic gonadotropin seem to have promising results. Consequently, we conducted a review and meta-analysis to assess IVF outcomes by comparing couples who underwent intrauterine hCG injection transfer versus those who underwent embryo transfer with intrauterine injection of placebo, or without any additional intervention. The primary outcome was the clinical pregnancy rate. Secondary outcomes were the implantation rate, miscarriage rate, and live birth rate. A meta-analysis was conducted using the random effects model, while bias within studies was detected using the Cochrane risk of bias tool. Ectopic pregnancies and stillbirths were also assessed. The clinical pregnancy (RR 1.38, 95% CI 1.17−1.62, p < 0.0001) and implantation rate (RR 1.40, 95% CI 1.12−1.75, p = 0.003) were significantly higher in women who underwent hCG injection than in the control group. These significant effects persisted only in women who underwent cleavage-stage embryo transfer. No significant differences between groups were observed in the other secondary outcomes. In conclusion, our systematic review and meta-analysis demonstrate that intrauterine injection of hCG could be a valuable approach in women who undergo cleavage-stage embryo transfer. Given the lack of data about the live birth rate, caution should be exercised in interpreting these data.

Ovarian Hyperstimulation Syndrome after GnRH Agonist Triggering and Freeze-All Protocol? Never Not, Hardly Ever: A Systematic Review of Case Reports.

INTRODUCTION: Ovarian hyperstimulation syndrome (OHSS) is a severe complication associated with controlled ovarian stimulation (COS). GnRH agonist (GnRH-a) triggering is considered an efficient strategy to prevent OHSS in the high-risk patient. METHODS: We performed a review of 11 cases of early and severe OHSS following GnRH-a triggering and freeze-all protocol. Electronic databases were searched from inception of each database until October 2021, to identify case reports and case series that reported OHSS after GnRH-a triggering and freeze-all approach describing patient demographics, COS protocol, and patient outcomes. RESULTS: From the literature review, it is possible to suggest that (1) following GnRH-a triggering, the risk of early and severe OHSS is not totally cancelled; (2) despite it is not possible to predict the event, polycystic ovary syndrome is the most common risk factor; (3) the use of GnRH antagonist starting from the day of PU may represent a valid strategy for preventing OHSS in women with high-risk profile; (4) following the unexpected onset of OHSS, measuring serum levels of human chorionic gonadotropin (hCG) is helpful to exclude an inadvertent exogenous administration or a pregnancy. CONCLUSION: The statement that OHSS risk is eliminated when GnRH-a triggering, a freeze-all strategy, and no hCG in the luteal phase may generate the idea that this event cannot occur. Although rare, these cases have been observed in a relatively short period of time.

COVID-19 vaccine and pregnancy outcomes: A systematic review and meta-analysis.

OBJECTIVES: To explore perinatal outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-vaccinated pregnant women compared with unvaccinated counterparts. METHODS: Search was conducted using Web of Science, Scopus, ClinicalTrial.gov, MEDLINE, Embase, OVID, and Cochrane Library as electronic databases. We included observational studies evaluating pregnant women undergoing SARS-CoV-2 vaccination and compared pregnancy and perinatal outcomes with those in unvaccinated women. Categorical variables were assessed using odds ratio (OR) with 95% confidence interval (CI), whereas for continuous variables, the results were expressed as mean difference with their 95% CI. All analyses were performed by adopting the random effect model of DerSimonian and Laird. RESULTS: There was no difference in the probability of having a small-for-gestational-age fetus (OR 0.97, 95% CI 0.85-1.09; P = 0.570), but we observed a reduced probability of a non-reassuring fetal monitoring, a reduced gestational age at delivery, and a reduced probability of premature delivery in vaccinated pregnant women versus unvaccinated ones. CONCLUSION: The probability of small for gestational age is similar between vaccinated and unvaccinated pregnant women, and the former also had a slightly reduced rate of premature delivery.

Meningioma during pregnancy: what can influence the management? A case series and review of the literature.

Purpose: Meningioma is a benign tumor, more frequent in female population. During pregnancy, distinguishing a meningioma from other common conditions presenting with similar symptoms (headache, vomiting, visual impairment) is challenging. Moreover, the management must consider not only maternal but also fetal health. The rarity of the condition does not allow to define the features to which look in order to stratify the risk for the need of surgery during pregnancy. We reported three cases of meningioma in pregnant women treated at our department and reviewed those previously reported in the literature. The aim of this review is to evaluate which factors are more determinant in such management.Methods: Electronic databases were searched from year 2000 until June 2020, to identify clinical studies on management of meningioma diagnosed during pregnancy. The primary outcome was surgical timing. Secondary outcomes were delivery methods, maternal and neonatal outcomes.Results: Surgery after pregnancy is more frequently performed in PR + tumor (p-value 0.038) and with HA (p-value 0.0445), as well as in meningioma diagnosed during the third trimester, compared to those diagnosed before (p-value 0.0012). Surgery during pregnancy was more frequent in patients with visual loss (p-value 0.006). No significant differences were found in surgical management, according to age, WHO grade, tumor location, lesion diameter and ER positivity. Delivery method is independent from both hormonal receptor status and main symptoms, but women who had neurosurgery during pregnancy delivered more frequently with spontaneous vaginal delivery (p-value <0.01).Conclusion: The decision regarding surgical timing of meningioma diagnosed during pregnancy depends on PR + and impending symptoms as visual loss or headache. It seems that timing of neurosurgery does not affect the delivery method. A multidisciplinary approach is always useful to perform a rapid and appropriate diagnosis and to better evaluate pros and cons of surgery during pregnancy and following management both for maternal and fetal wellness.

Reproductive function of long-term treated patients with hepatic onset of Wilson's disease: a prospective study.

RESEARCH QUESTION: Wilson's disease (WD) is a disorder of copper metabolism that can cause hormonal alterations. The impact of WD and its therapies on fertility is not well defined. The aim of this study was to evaluate ovarian reserve and sperm parameters in long-term treated WD patients with hepatic onset. DESIGN: WD patients with hepatic onset treated for at least 5 years were compared with healthy controls. Men underwent spermiogram and sperm DNA fragmentation (SDF) analysis. Women were tested for serum FSH, anti-Müllerian hormone (AMH) and sonographic antral follicle count (AFC) in the early follicular phase. Ovulation was monitored with ultrasound and progesterone serum concentrations in the luteal phase. RESULTS: The WD group included 26 patients (12 males), the control group 19 subjects (9 males). All patients apart from four (one male) were responders to WD treatment. Sperm count and morphology were comparable between cases and controls. Sperm motility (total and after 1 h) was significantly lower in cases (44.78 ± 21.65%; 47.85 ± 21.52%) than controls (61.88 ± 11.03; 69.44 ± 11.02%, P = 0.03 and 0.01, respectively). The only non-responder had severe oligo-astheno-teratozoospermia. SDF values were normal in cases and controls. AMH, AFC and FSH did not differ between cases and controls. LH was significantly lower in cases (3.36 ± 1.65 mIU/ml) than controls (6.25 ± 1.03 mIU/ml, P < 0.0001). A non-responder woman who developed neurological signs had a 7-year history of infertility. CONCLUSIONS: WD patients with hepatic onset, diagnosed early and treated, have no impairment in fertility potential even if males show reduced sperm motility and females lower LH values. Only patients with poor disease control have some evidence of impaired fertility.

Luteal Phase Support Using Subcutaneous Progesterone: A Systematic Review.

Luteal phase support (LPS) is crucial in assisted reproductive technology (ART) cycles when the luteal phase has been found to be defective. Such deficiency is most likely related to the supraphysiological steroid levels that usually occurr in stimulated cycles which, in turn, could severely affect luteinizing hormone (LH) secretion and function, thereby negatively influencing the luteal phase. A number of different medications and routes have been successfully used for LPS in ART. Although an optimal protocol has not yet been identified, the existing plethora of medications offer the opportunity to personalize LPS according to individual needs. Subcutaneous administration progesterone has been proposed for LPS and could represent an alternative to a vaginal and intramuscular route. The aim of the present systematic review is to summarize the evidence found in the literature concerning the application of subcutaneous progesterone in ARTs, highlighting the benefits and limits of this novel strategy. With this aim in mind, we carried out systematic research in the Medline, ISI Web of Knowledge, and Embase databases from their inception through to November 2020. Randomized controlled trials (RCTs) were preferred by the authors in the elaboration of this article, although case-control and cohort studies have also been considered. According to our findings, evidence exists which supports that, in women with a good prognosis undergoing a fresh in vitro fertilization (IVF) cycle, subcutaneous Pg is not inferior to vaginal products. In the Frozen-thawed embryo transfer (FET) cycle, data concerning efficacy is mixed with an increased miscarriage rate in women undergoing a subcutaneous route in oocyte donor recipients. Data concerning the acceptance of the subcutaneous route versus the vaginal route are encouraging despite the different scales and questionnaires which were used. In addition, a cost-effective analysis has not yet been conducted.

Severe Ovarian Hyperstimulation Syndrome in a Woman With Breast Cancer Under Letrozole Triggered With GnRH Agonist: A Case Report and Review of the Literature.

We report a rare case of ovarian hyperstimulation syndrome (OHSS) in a 28-year-old woman with breast cancer and with a history of polycystic ovary syndrome (PCOS) despite treatment with letrozole and gonadotropin-releasing hormone agonist (GnRH-a) triggering in a GnRH antagonist (GnRH-ant) protocol without the administration of any human chorionic gonadotropin (hCG) for luteal-phase support. The patient, who underwent controlled ovarian syndrome (COS)-oocyte cryopreservation before chemotherapy, required hospitalization. Complete recovery was achieved after treatment with volume expanders, human albumin, and cabergoline. Based on our case and literature review, it is possible to establish that estradiol (E2) modulation with letrozole and GnRH-a triggering does not eliminate the risk of OHSS. Furthermore, it is advisable to postpone GnRH-a depot to minimize the risk of OHSS after the suspension of letrozole, following menstruation or at least 7-8 days after triggering. It would be desirable to identify high-risk patients, also on a genetic basis, in order to avoid delays in oncologic treatments that could strongly impact life expectancy.