Subserosal pregnancy: Systematic review with proposal of new diagnostic criteria and ectopic pregnancy classification.

Ectopic pregnancy (EP) is a pregnancy where the growing blastocyst implants outside the endometrial cavity. EP account approximately for 0.5-1% of all pregnancies, and extrauterine implant is the leading cause of woman mortality in the first trimester of gestation. Non-tubal pregnancies (NTP) account for less than 5% of all EP. NTP are accompanied by a 7-8 times higher risk of maternal mortality when compared to tubal pregnancies, and their treatment might sometimes be very challenging. Subserosal pregnancy (SP) has been defined as rare variant of intramural pregnancy, where a portion of the gestational sac was surrounded only by the serosa of the uterus. Whereas the treatment of the ectopic pregnancies is crucial for patients' lives and for adequate fertility sparing and considering the need for surgical treatment in many cases, an early diagnosis is important; thus we believe it g might be useful to define some criteria to guide subserosal pregnancy identification, and to distinguish it from other types of non-tubal ectopic pregnancy. A systematic review on Pubmed, Scopus, Web of Science and Google Scholar was performed. Case reports, randomized controlled trials, prospective controlled studies, prospective cohort studies, retrospective studies, and case series were considered eligible. In all databases mentioned were considered manuscripts published from 1990 up to March 2023. Only four articles were eligible for inclusion in this review. All patients underwent to surgical management in laparoscopy. The main risk factors for this type of ectopic pregnancy were previous uterine surgery with opening of the endometrial cavity and assisted reproductive techniques procedures. Considering our results, we propose new classification and diagnostic criteria for subserosal pregnancy, to distinguish it from other types of non-tubal ectopic pregnancies with the aim to preserve fertility following the most correct management.

The Use of Methotrexate and Mifepristone for Treatment of Interstitial Pregnancies: An Overview of Effectiveness and Complications.

Interstitial pregnancy is an unusual and potentially life-threatening form of ectopic pregnancy, accounting for approximately 1-6% of all ectopic pregnancies, with a maternal mortality rate of 2-2.5%. Implantation happens in the proximal portion of the fallopian tube as it passes through the myometrium. The resolution of interstitial pregnancy after medical treatment should be assessed by a decline in serum ß-hCG, which occurs in about 85-90% of cases. Nonetheless, its effectiveness and consequences have been presented through case reports and case series. However, few cases of interstitial pregnancies treated totally medically with the use of methotrexate and mifepristone have been presented in the literature. Complications of this medical treatments have also never been reviewed before. In the present manuscript, we present a case of interstitial pregnancy treated with methotrexate and mifepristone. The patient after treatment developed a uterine arteriovenous malformation, treated with uterine artery embolization. Furthermore, we performed a systematic review of the literature using Scopus, PubMed and Google Scholar. A total of 186 papers were found, and 7 papers which included 10 cases were assessed for eligibility. The systemic medical treatment with the use of methotrexate and mifepristone was effective in 7 of the 10 cases. Two cases of hemoperitoneum following combined methotrexate and mifepristone treatment were reported. The applicability of this medical conservative treatment should be tailored to the patient, taking into account their obstetric history, gestational age at diagnosis and desire for future pregnancies. Complete resolution after this treatment was achieved in most of the cases reported without major complications. The appearance of uterine arteriovenous malformation can be managed conservatively, and we propose uterine artery embolization as an effective treatment of this rare complication.

Maternal and fetal outcomes of intraplacental choriocarcinoma complicated by fetomaternal hemorrhage: a systematic review.

INTRODUCTION: Intraplacental choriocarcinoma is a gestational trophoblastic neoplasia located within the placenta. Due to the usual silent presentation, more than half of the cases are diagnosed incidentally. It has been demonstrated that this pathology is linked to feto-maternal hemorrhage (FMH), stillbirth, and intrauterine growth restriction. The aim of our review was to establish if there are recurrent signs that might lead to an early diagnosis and better management in cases complicated by FMH. MATERIALS AND METHODS: We performed a systematic review of the literature from 2000 up to March 2023. The adopted research strategy included the following terms: (gestational choriocarcinoma obstetrics outcome) AND (intraplacental choriocarcinoma) AND (gestational choriocarcinoma). The MEDLINE (PubMed), Google Scholar, and Scopus databases were searched. RESULTS: The research strategy identified 19 cases of FMH coexisting with intraplacental choriocarcinoma (IC), as described in 17 studies. The perinatal mortality rate was 36.8%. In eight cases, histological diagnosis of IC was made post-delivery. Metastatic lesions were found in 75% (6/8) of described cases. One case of maternal death has been described. Chemotherapy was necessary in seven cases. Sporadical prenatal ultrasound signs were described. DISCUSSION: The diagnosis of IC is usually delayed, mostly due to aspecific symptoms and signs. Histological analysis of the placenta, when not routinely performed, should be performed when warning symptoms are encountered. The maternal prognosis was good, with a mortality rate of 5.5%. A fertility-sparing approach is always possible even in the presence of metastasis. Chemotherapy seems to be useful in cases of maternal and neonatal metastasis.

Placental Chorangiocarcinoma a Specific Histological Pattern of Uncertain Incidence and Clinical Impact: Systematic Review of the Literature.

Chorangiocarcinoma is a very rare and misdiagnosed placental neoplasm. The unique morphologic features of the lesion distinguish it from other trophoblastic tumors and vascular abnormalities. We present a systematic review of the literature to provide clarity on chorangiocarcinoma entity and biology. A literature search was carried out in December 2022 using the keywords "Placental chorangiocarcinoma", "Chorangioma", "Placenta", and "Throphoblast proliferation". Articles published from 1988 to 2022 were obtained from Scopus, Google Scholar, and PUBMED. In our review, we examined maternal age, gestational age at the time of delivery, parity, type of pregnancy, placental weight, ultrasound features of the placenta, macroscopic examination and tumor size, microscopic examination, immunostaining, maternal beta-human chorionic gonadotropin, fetal and maternal outcome. Eight manuscripts were detected. They are all case reports. The macroscopic characteristics of the lesions were represented by the presence of a grey-yellow-white color well-demarcated round nodule. Microscopically, all the authors described typical aspects of malignancy as a high rate of mitosis, nuclear atypia and necrotic areas. In some cases, the presence of AE1/AE3 cytoplasmic positivity, p63 nuclear staining, and beta-human chorionic gonadotropin (BHCG) were reported. A good fetal outcome was reported in all cases of newborns with normal birth weight, except one with fetal growth restriction. Maternal outcome was good in all cases except one with maternal lung metastasis three months after delivery. The clinical course has probably underestimated the real incidence of the pathology. Only greater knowledge of its histology and its clinical course will allow us to evaluate the real prevalence of the disease.

New Topical Therapy for Provoked Vestibulodynia: Improvement of Psychological and Sexual Well-Being.

Vulvodynia is a vulvar discomfort that occurs in the absence of any specific, clinically identifiable disorder. Few therapies have shown to be effective for the treatment of vulvodynia. In our recently published study, we tested a drug-free gel in women affected by vulvar vestibulitis. It is a cosmetic gel which acts locally without any metabolic, pharmacological or immunological effect. In order to further promote the validity of this new product, in this manuscript we analyzed the results obtained from the administration of four questionnaires in the same two groups of women affected by PVD and treated with a placebo and the new product. The questionnaires used: Female Sexual Function Index Scoring (FSFI), Female Sexual Distress Scale (FSDS), Hospital Anxiety and Depression Scale (HADS), and health-related quality of life measured by SF-36 (SF-36). The results obtained by this current analysis showed that the new gel has also proven benefits on women's quality of life and sexual function, including improvements in arousal, desire, orgasm and satisfaction.

Hysteroscopic Removal of Intrauterine Device in Pregnancy: A Scoping Review to Guide Personalized Care.

Background and objectives: Pregnancies that occur with an intrauterine device (IUD) in situ are at increased risk for developing severe conditions which may affect the fetus and the mother. The incidence of such adverse consequences significantly drops after device removal. A scoping review of the literature was performed to highlight the risks, benefits, and outcomes of hysteroscopic removal of intrauterine devices in early pregnancy. Materials and Methods: PubMed, Scopus, and Web of Science were searched. The review included all reports from 1990 to October 2022. The research strategy adopted included different combinations of the following terms: ("hysteroscopy") AND ("pregnancy") AND ("intrauterine device" or "IUD") AND ("intrauterine system" or "IUS"). A scoping review of the hysteroscopic removal of IUDs during pregnancy was performed. All studies identified were listed by citation, title, authors, and abstract. Duplicates were identified by an independent manual screening performed by two researchers and then removed. For the eligibility process, two authors independently screened the titles and abstracts of all non-duplicated papers and excluded those not pertinent to the topic. Results: PRISMA guidelines were followed. Nine manuscripts were detected, accounting for 153 patients. Most IUD removals occurred during the first trimester of pregnancy. Most of the time, the procedure was safe and without consequences. Conclusions: This review highlights the safety and efficacy of operative hysteroscopy as a method of IUD removal in early pregnancy. We recommend using a 3 to 5 mm hysteroscope, avoiding cervical dilation, and maintaining low infusion pressure during the procedure to avoid potential damage to the gestational sac and IUD fragment displacement. Heating the distension media to 30 °C should be considered.

Caesarean Section on Maternal Request-Ethical and Juridic Issues: A Narrative Review.

In recent decades, the rate of caesarean deliveries has increased worldwide. The reasons for this trend are still largely misunderstood and controversial among researchers. The decision often depends on the obstetrician, his beliefs and experience, the characteristics of the patients, the hospital environment and its internal protocols, the increasing use of induction of labor, the medico-legal implications, and, finally, the mother's ability to request delivery by caesarean section without medical indication. This review aims to describe the reasons behind the increasing demand for caesarean sections by patients (CDMR) and strategies aimed at reducing caesarean section rates and educating women about the risks and benefits of CS.

Hysteroscopic Resection Followed by Adjuvant Radiotherapy: Report of a New Therapeutic Approach to Primary Cervical Diffuse Large B-Cell Lymphoma.

The female genital tract can be involved as a secondary manifestation of disseminated lymphomas or leukemia but can rarely be the primary site of so-called extranodal lymphomas. Primary lymphomas of the female genital tract can affect the uterine corpus, uterine cervix, vulva, vagina or adnexa. Only about 0.008% of all cervical tumors are primary malignant lymphomas. The presenting symptoms are unspecific and also refer to much more common diseases of the female genital tract. Cervical cytology is usually negative. Preoperative diagnosis requires deep cervical biopsy. To date there is no consensus regarding optimal treatment. Radiotherapy, chemotherapy and surgery are used in different association. We report the first case reported in literature managed with an urgent hysteroscopic resection of a primary cervical diffuse large B-cell lymphoma, followed by adjuvant radiotherapy. Relevant literature was reviewed. Our conservative approach needs to be validated in the future, especially for women with pregnancy desire and for those with low performance status. To date, after 24 months from diagnosis, our patient is still disease-free.

Umbilical Cord Knots: Is the Number Related to Fetal Risk?

True knots of the umbilical cord (UC) are a rare occurrence and are reported in 0.4-1.2% of deliveries. The compression of true knot of the UC can cause obstruction of the fetal circulation, leading to intra-uterine growth retardation or fetal death. Predisposing factors for the genesis of the true UC knot are numerous and include all the conditions, which lead to a relatively large uterine volume. This situation may predispose to free and excessive fetal movements. Although not all true knots lead to perinatal complications, they have been associated with adverse pregnancy outcomes, including fetal distress, fetal hypoxia, intra-uterine growth restriction (IUGR), long-term neurological damage, caesarean delivery and stillbirth. We present a rare case of operative delivery with vacuum in a multiparous woman at term of pregnancy with a double true knot of the UC. As in most cases, the diagnosis was made after delivery, as there were no fetal symptoms during pregnancy. Some authors assume that 3D power sonography may be useful in the diagnosis of true UC knots. However, 3D power Doppler cannot be considered as a definitive method. There are no specific prenatal indications to induce the physician to look for ultrasound signs suggestive of umbilical true knot. Some studies argue that cases of fetal death and fetal risk are directly related to the number of knots. We also support this thesis, even if further observational and retrospective studies are needed to demonstrate it.

Fetal disseminated intravascular coagulopathy, hydrops and massive umbilical vein thrombosis consequence of a rare placental condition: multifocal chorangiomatosis.

Purpose: Villous capillary lesions are rare abnormal placental developmental conditions which include chorangiosis, chorangiomatosis, chorangioma and a rare variant of the latter called multiple chorangioma syndrome. The causes of villous capillary lesion are not completely clear but appear to involve excessive angiogenesis. MATERIALS AND METHODS: In this paper we start illustrating our experience of multifocal chorangiomatosis with the newborn affected by massive umbilical vein thrombosis, disseminated intravascular coagulopathy and hydrops, going to a literature review of cases available.Results: Two other similar cases have been previously published in literature. Comparing clinical characteristics and fetal outcomes, we confirm the association with unfavorable neonatal outcome mentioned in literature. Our case is the first characterized by severe hemolytic anemia, thrombocytopenia, heart congestion with the overlap of disseminated intravascular coagulopathy and massive umbilical vein thrombosis and congenital anomalies. CONCLUSIONS: Our clinical case and the review of literature highlight how multifocal chorangiomatosis, within the three subgroups identified, is the rarer form with distinct placental features and the worst outcomes for neonates. No cases of multifocal chorangiomatosis have never been described prenatally and, for further studies, could be reasonable investigate the involvement of some growth factors like vascular endothelial growth factor and placental growth factor that could lead to a detection of a subgroup of patient at higher risk to manifest placental vascular lesions and the follow fetal and maternal complications.

Ladylift® non-ablative laser technology for the treatment of menopausal vestibulodynia and genitourinary syndrome.

Introduction: Genitourinary syndrome of menopause (GSM) affects up to 48% of pre-menopause women and up to 90% of menopausal women. Many menopausal women with dyspareunia have significant vestibular tenderness due to oestrogen deficiency, which increases the density of sensory nerve fibres in the vulva and the vagina. For this reason, GSM is recognized as one of the causes of provoked vestibulodynia. Few therapies have proven to be effective for provoked vestibulodynia. Many studies have shown the efficacy of laser CO2 therapy, proving its cost-effectiveness and safety for vaginal health. Material and methods: In this article we tested a new non-ablative solid-state laser: Ladylift®. The main difference between Ladylift® and other laser technologies is the use of a non-ablative laser wavelength of 1470 nm, without causing ablative thermal injury on the surface of the mucosa. We enrolled 18 post- menopausal women presenting to a private clinic with GSM symptoms and provoked vulvodynia. Results: The treatment protocol consists of 4 sessions of laser, 2 weeks apart, of the duration of 4 minutes. Benefits to menopause symptoms, reported with a numeric rating scale, and to epithelium trophism reported with the vaginal health index were apparent since the first session. Patients undergoing laser therapy have had evident benefit both from the point of view of pain and from that of vaginal health. Conclusions: All the women tolerated the therapy well without any adverse effects. However, the beneficial effect tended to gradually decrease over time, suggesting the need to perform more therapy sessions.

A New Therapy for Uncomplicated Vulvovaginal Candidiasis and Its Impact on Vaginal Flora.

Background: An estimated 75% of women will have one episode of vulvovaginal candidiasis (VCC) during their lifetime, and 40-50% of these will experience further episodes. The high incidence of vulvovaginal candidiasis, combined with the problems of azole resistance and toxicity, highlights the necessity for new strategies for the treatment of this condition. In this context, natural compounds represent promising alternatives. Methods: We enrolled, between January 2020 and April 2021, forty women affected by uncomplicated vulvovaginal candidiasis. Women were divided into two groups. In the first group, we treated 20 women with clotrimazole daily administration for six days. In the second group, 20 women were treated with clotrimazole associated with Unilen® Microbio+, a new product containing Saccharomyces cerevisiae, melatonin, and GLA-14. Women underwent a check at days 15, 30, and 90. A clinical and cultural examination were performed to establish the effect of the treatments on vaginal flora. Results: In the group treated with Unilen® Microbio+, clinical and microbiological cure at 15 and 30 days was observed in 18 women (90%), compared with 16 women (80%) in the group treated only with clotrimazole. The efficacy of the association between clotrimazole and Unilen® Microbio+ in these uncomplicated forms was therefore not inferior to the azole treatment alone. Only four women (20%) in the Unilen® Microbio+ group presented symptomatic recurrences within the 3 months, compared with eight women (40%) in the clotrimazole-only group. Microscopic wet mount analysis at 1 and 3 months demonstrated a significant increase in lactobacillus count and a reduction in the polymorphonucleate cells in the Unilen® Microbio+ group. Conclusions: Unilen® Microbio+ supplementation was demonstrated to cure uncomplicated vulvovaginal candidiasis with clotrimazole, reducing recurrence and improving vaginal flora better than clotrimazole treatment alone.

Postcoital Vaginal Perforation and Evisceration in Women with No Prior Pelvic Surgery: Laparoscopic Management and Systematic Review of the Literature.

OBJECTIVE: to evaluate risk factors, causes, management and surgical therapy of postcoital vaginal perforation and evisceration in women with no prior pelvic surgery. DATA SOURCES: We used MEDLINE (PubMed), Scopus, Embase and Web of Science for our research. Our review includes all reports from 1980 to November 2020. The research strategy adopted included different combinations of the following terms: (intercourse) AND (coitus) AND (vaginal perforation). METHODS OF STUDY SELECTION: we report a case of vaginal evisceration after consensual intercourse in a young and healthy woman. In addition, we performed a systematic review of vaginal perforations with or without evisceration in women without prior surgery or any other predisposing disease. All studies identified were listed by citation, title, authors and abstract. Duplicates were identified by an independent manual screening, performed by one researcher and then removed. For the eligibility process, two authors independently screened the title and abstracts of all non-duplicated papers and excluded those not pertinent to the topic. TABULATION, INTEGRATION AND RESULTS: We have followed the PRISMA guidelines. Five manuscripts were detected through the references of the works that had been identified with the research on MEDLINE (PubMed), Scopus, Embase and Web of Science. We found 16 cases between 1980 and 2020. The young age and the virginal status represent the principal risk factors and all the lacerations occurred in the posterior vaginal fornix. The most common surgical technique was the laparotomic approach and, in the remaining cases, the laparoscopic and vaginal route was performed. CONCLUSIONS: Post-coital vaginal perforation and evisceration in women with no prior pelvic surgery is a rare condition in the clinical practice and, when it is associated with evisceration it is a surgical emergency. Usually, these injuries are not life-threatening conditions but, a delay in diagnosis, can lead to severe complications. In consideration of the high heterogeneity of the data in the literature, it is essential to define a diagnostic-therapeutic management for the patients with vaginal perforation. With our review, we try to identify the associated risk factors, the best and fastest diagnosis, and the best surgical approach. We believe that a combined vaginal and laparoscopic approach can be the best surgical treatment, useful to diagnose injuries of the abdominal organs and to improve postoperative outcome.

The Rare, Unexpected Condition of a Twisted Leiomyoma in Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome: Etiopathogenesis, Diagnosis and Management. Our Experience and Narrative Review of the Literature.

Uterine leiomyomas are a common finding in medical practice, but their frequency changes drastically when contextualized in a syndrome, as in the following case. A 50-year-old woman with a known Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome presented at our clinic with abdominal pain located in the lower quadrants and scarcely responsive to analgesic therapy. A twisted gynecological pelvic mass was diagnosed, and management for prompt resolution was adopted. Histologically the mass was described as a leiomyoma. The aim of the present study is to share our experience and to review the literature to compare different manifestation of the disease and different approach used in the various centers. The additional novelty of the paper is the immunohistochemical study we carried out on the leiomyoma that is contrasted with the current etiopathogenetic theories.

The singular case of multiple chorangioma syndrome in an IVF pregnancy. Analysis of the case and review of literature.

The redacted classification of placental lesions identifies in the group of fetal-stromal vascular lesions a subgroup called villous capillary lesions. The causes of villous capillary lesions appear to involve excessive angiogenesis. These conditions include chorangiosis, chorangiomatosis, chorangioma and a rare variant of the latter called multiple chorangioma syndrome where multiple chorangiomas, ranging from very small early precursor lesions to typical macroscopic chorangioma, occupy up to 80% of the total placental parenchyma. We present the first case of multiple chorangioma syndrome in an oncologic patient who obtained the pregnancy by egg donation, comparing the clinical case with ones available in literature. Fifteen cases have been previously published in literature but only 11 were eligible for the present review. We compared clinical characteristics and fetal outcomes with our clinical case, to highlight similarities and differences useful for a better understanding of this rare and partially unknown disease. Multiple chorangioma syndrome is a rare villous capillary lesion associated with poor fetal condition. All cases analyzed have been conceived naturally and our case is the first described in an IVF pregnancy. We believe that in our case the advanced maternal age, the method of conception and the previous chemo-therapeutic treatments might have played an important role in determining the manifestation of this rare placental condition. However, there is not appropriate literature supporting our consideration and, for future studies, it could be reasonable investigate the incidence of this condition, or even the incidence of all cluster of villous capillary lesions, in oncologic and IVF patients.

Semaphorin 3F expression is reduced in pregnancy complicated by preeclampsia. An observational clinical study.

BACKGROUND AND OBJECTIVE: Preeclampsia is a systemic disorder, affecting 2-10% of pregnancies, characterized by a deregulated pro- and anti-angiogenic balance. Semaphorin 3F is an angiogenesis inhibitor. We aimed to investigate whether semaphorin 3F expression is modulated in preeclampsia. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We performed two observational single center cohort studies between March 2013 and August 2014. In the first we enrolled 110 consecutive women, undergoing an elective cesarean section; in the second we included 150 consecutive women undergoing amniocentesis for routine clinical indications at 16-18 week of gestation. Semaphorin 3F concentration was evaluated in maternal peripheral blood, venous umbilical blood and amniotic fluid, along with its placenta protein expression at the time of delivery in the first study group and in the amniotic fluid at 16-18 weeks of gestation in the second study group. RESULTS: In the first study 19 patients presented at delivery with preeclampsia. Semaphorin 3F placenta tissue expression was significantly reduced in preeclampsia. In addition, semaphorin 3F level at delivery was significantly lower in serum, amniotic fluid and venous umbilical blood of preeclamptic patients compared with normal pregnant women. In the prospective cohort study 14 women developed preeclampsia. In this setting, semaphorin 3F amniotic level at 16-18 weeks of gestation was reduced in women who subsequently developed preeclampsia compared to women with a normal pregnancy. ROC curve analysis showed that semaphorin 3F amniotic levels could identify women at higher risk of preeclampsia. CONCLUSIONS: Semaphorin 3F might represent a predictive biomarker of preeclampsia.