Pregnancy of unknown location (PUL) is a temporary pathologic or physiologic phenomenon of early pregnancy that requires follow up to determine the final pregnancy outcome. Evidence indicated that PUL patients suffer a remarkably higher rate of adverse pregnancy outcomes, represented by ectopic gestation and early pregnancy loss, than the general population. In the past few decades, discussion about PUL has never stopped, and a variety of markers have been widely investigated for the early and accurate evaluation of PUL, including serum biomarkers, ultrasound imaging features, multivariate analysis, and the diagnosis of ectopic pregnancy based on risk stratification. So far, machine learning (ML) methods represented by M4 and M6 logistic regression have gained a level of recognition and are continually improving. Nevertheless, the heterogeneity of PUL markers, mainly caused by the limited sample size, the differences in population and technical maturity, etc., have hampered the management of PUL. With the advancement of multidisciplinary integration and cutting-edge technologies (e.g. artificial intelligence, prediction model development, and telemedicine), novel markers, and strategies for the management of PUL are expected to be developed. In this review, we summarize both conventional and novel markers (represented by artificial intelligence) for PUL assessment and management, investigate their advancements, limitations and challenges, and propose insights on future research direction and clinical application.

Background/Objectives: There are indications that the microbial composition of the maternal mucosal surfaces is associated with adverse events during pregnancy. The aim of this review is to investigate the link between vaginal microbiome alterations and gestational complication risk. Methods: This comprehensive literature review was performed using Medline and Scopus databases. The following search algorithm was used, \"Pregnancy Complications\" [Mesh] AND (Vagin*), and after the literature screening, 44 studies were included in the final review. Results: The studies that were included investigated the association between vaginal microbial composition and preterm birth, miscarriage, preeclampsia, ectopic pregnancy, gestational diabetes mellitus, chorioamnionitis, and preterm premature rupture of membranes. In most of the studies, it was well established that increased microbial diversity is associated with these conditions. Also, the depletion of Lactobacillus species is linked to most of the gestational complications, while the increased relative abundance and especially Lactobacillus crispatus may exert a protective effect in favor of the pregnant woman. Several pathogenic taxa including Gardnerella, Prevotella, Sneathia, Bacterial Vaginosis-Associated Bacteria-2, Atopobium, and Megasphera seem to be correlated to higher maternal morbidity. Conclusions: Vaginal microbiome aberrations seem to have an association with pregnancy-related adverse events, but more high-quality homogenous studies are necessary to reliably verify this link.

UNASSIGNED: Cervical ectopic pregnancy is a relatively rare type of ectopic pregnancy and has no standardized guidelines for management.
UNASSIGNED: This systematic review is based on the collection of case reports, published in PubMed/MEDLINE about the resolution of ectopic cervical pregnancies over the last decade and the presentation of a case managed in our healthcare unit. Studies involving cervical pregnancy in the first trimester with the presence of a viable embryo and β-hCG in the serum below 100.000 mIU/mL were included, while heterotopic pregnancies were excluded.
UNASSIGNED: Nineteen articles reporting twenty-three case reports are demonstrated explicitly emphasizing on the management techniques. There is no established approach for the management of this type of ectopic pregnancy.
UNASSIGNED: It is important to consider the conservative approaches as first-line treatment in all cases of cervical pregnancy preserving fertility. Minimally invasive methods are also described and preferred as second-line treatment, as reported in our literature review.
UNASSIGNED: Gimdos kaklelio negimdinis nėštumas yra palyginti retas negimdinio nėštumo tipas, kuriam nėra standartizuotų gydymo gairių.
UNASSIGNED: Ši sisteminė apžvalga paremta PubMed/MEDLINE publikuotų atvejų aprašymų apie negimdinio gimdos kaklelio nėštumo sprendimą per pastarąjį dešimtmetį rinkiniu ir mūsų sveikatos priežiūros skyriuje tvarkyto atvejo pristatymu. Buvo įtraukti tyrimai, susiję su gimdos kaklelio nėštumu pirmąjį trimestrą, kai yra gyvybingas embrionas ir β-hCG serume yra mažesnis nei 100 000 mIU/ml, o heterotopinis nėštumas nebuvo įtrauktas.
UNASSIGNED: Įvertinti devyniolika straipsnių, kuriuose pateikti dvidešimt trijų atvejų aprašymai, kuriuose aiškiai pabrėžiami gydymo metodai. Nėra nusistovėjusio šio tipo negimdinio nėštumo gydymo metodo.
UNASSIGNED: Svarbu, kad visais vaisingumą išsaugančio gimdos kaklelio nėštumo atvejais konservatyvūs metodai būtų laikomi pirmos eilės gydymo metodais. Minimaliai invaziniai metodai taip pat aprašyti ir jiems teikiama pirmenybė kaip antros eilės gydymui, kaip nurodyta mūsų literatūros apžvalgoje.

BACKGROUND: Non-tubal ectopic pregnancies account for < 10% of all ectopic pregnancies. Due to its rarity and wide variation in clinical practice, there is no guideline or consensus for its management. We reported our 20-year experience in the management of non-tubal ectopic pregnancies in a tertiary hospital.
METHODS: This is a retrospective review of all women admitted for non-tubal ectopic pregnancies from January 2003 to December 2022 in a tertiary hospital. Women with non-tubal ectopic pregnancies diagnosed by ultrasound or operation were included for analysis.
RESULTS: Within the study period, 180 women were diagnosed to have non-tubal ectopic pregnancies at a mean gestation of 6.8 weeks. 16.7% (30/180) were conceived via assisted reproduction. Medical treatment was the first-line management option for 81 women, of which 75 (92.1%) women received intralesional methotrexate administered under transvaginal ultrasound guidance. The success rate of intralesional methotrexate ranges from 76.5% to 92.3%. Intralesional methotrexate was successful even in cases with a positive fetal pulsation or with high human chorionic gonadotrophin levels up to 252605U/L. Twenty seven women were managed expectantly and 40 underwent surgery. Nine (11.1%), two (6.1%), and one (2.3%) women required surgery due to massive or recurrent bleeding following medical, expectant, or surgical treatment. Hysterotomy and uterine artery embolization were necessary to control bleeding in one Caesarean scar and one cervical pregnancy.
CONCLUSIONS: Intralesional methotrexate is more effective than systemic methotrexate and should be considered as first line medical treatment for non-tubal ectopic pregnancies. It has a high success rate in the management of unruptured non-tubal ectopic pregnancies even in the presence of fetal pulsations or high human chorionic gonadotrophin levels, but patients may require a prolonged period of monitoring. Close surveillance and readily available surgery were required due to the risk of heavy post-procedural intra-abdominal bleeding.

OBJECTIVE: Existing evidence of the relationship between induced abortion and ectopic pregnancy has not been assessed rigorously. This systematic review provides a comprehensive evaluation to examine whether induced abortion (IA) can increase the rate of ectopic pregnancy (EP).
METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane, CNKI, WanFang, and Sinomed databases since their inception until February 2023. Eligibility criteria included case-control studies and cohort studies that analyzed induced abortion associated with ectopic pregnancy. Data analyses were conducted by using R-studio Version 1.1.383 software.
RESULTS: A total of 33 case-control studies and 7 cohort studies involving 132,926 participants were included. In case-control studies, there was a significant association between induced abortion and ectopic pregnancy by using single-factor analysis data (OR = 2.32, 95% CI = 1.81-2.98). Subgroup analysis by region suggested no statistical significance in the Americas (OR = 1.15, 95% CI = 0.92-1.43) and Eastern Mediterranean (OR = 3.64, 95% CI = 0.88-15.18). The relationship was significant by using multiple regression analysis data (OR = 1.97, 95% CI = 1.38-2.80). In cohort studies, statistical significance was found (OR = 1.42, 95% CI = 1.001-2.018) after omitting one study in sensitivity analysis. The combined results of the two types of studies suggested that induced abortion would increase the risk of ectopic pregnancy to some degree, but the conclusion needs to be considered with caution.
CONCLUSIONS: This study indicated that IA could increase the risk of EP to some degree and the times of IA had a negative impact on the risk. Safe abortion and avoiding repeat abortion due to unintended pregnancy could protect women\'s fertility.

Heterotopic pregnancy (HP) is the coexistence of living or dead intrauterine pregnancy, single or multiple, and extrauterine pregnancy located in the oviduct, ovary, uterine corner, cervix or peritoneal cavity. This condition is very rare (1:30 000 pregnancies). HP constitutes a rare obstetric condition. Its occurrence after natural conception is sparsely documented in the literature. Here in, we present a case of a 27-year-old primeparous women who presented at 18 weeks with features of ruptured ectopic pregnancy. Initial ultrasonographic imaging showed an intrauterine pregnancy corresponding to 18 weeks. It also revealed a floating fetus with significant collection of fluid in the pouch of Douglas, retroceacal recess and both hepatocellular recess. An emergency explorative laparotomy was done where right salpingectomy was performed. She was later followed up to term and delivered by elective cesarean section successfully. A brief narrative of the challenges in the management, clinical presentation and limitation in the management is highlighted in the present case report. Key message: Heterotopic pregnancy can occur in natural conception irrespective of usage of ovulation induction. Routine early pregnancy ultrasound can promote early detection with prompt surgical intervention to mitigate its complications.

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.

Ectopic pregnancy (EP) constitutes 1%-2% of all pregnancies and is one of the leading causes of maternal morbidity and mortality. The most common site of ectopic pregnancy is the ampulla. Ectopic ovarian pregnancy (EOP) is one of the rare events, with an incidence of 0.5%-3% of all pregnancies. The incidence is higher in intrauterine device users or assisted reproductive techniques. The precise aetiology and pathogenesis of EOP remain elusive. Clinically, EOP mirrors the presentation of tubal pregnancy or a ruptured luteal cyst, often leading to life-threatening hypovolemic shock. Transvaginal sonography is the primary diagnostic tool. Still pinpointing the exact location early on poses challenges, and it\'s usually misinterpreted as a tubo-ovarian mass, hemorrhagic cyst, or luteal cyst. Furthermore, while a suboptimal rise in serum beta-human chorionic gonadotropin (β-hCG) levels may indicate pregnancy, it doesn\'t definitively confirm EOP. Only histopathological examination offers a conclusive diagnosis. This paper discusses an EOP case in a young woman who experienced five months of amenorrhea and exhibited no traditional risk factors, underscoring the significant challenges inherent in preoperative diagnosis.

UNASSIGNED: Abdominal ectopic pregnancy (AEP) located at hepatic region and pelvic-wall ectopic pregnancy (EP) are rare entities, that provoking a potentially life-threatening condition. Due to insufficient data, a proper management of non-specific types remains a challenge for all gynecologists worldwide.
METHODS: Two child-bearing age women were hospitalized due to delayed menstruation and a urine pregnancy test was positive without a determination of intrauterine pregnancy. The first EP case was located at the pelvic wall which identified incidentally during laparoscopy for a presumed tubal ectopic pregnancy on ultrasonography throughout. The second EP case was found at the hepatic region due to intermittent pain rising from the right upper quadrant region and serial ultrasonic findings. In our management, both cases were successfully assessed by laparoscopy and laparotomy without requiring further intervention, respectively.
UNASSIGNED: An accurate diagnosis of EP location at liver and pelvic wall is totally difficult since its uncommon location. An initial assessment should be based on clinical symptoms and the treatment remains controversial. The surgical management including laparotomy and laparoscopy depends on clinical evaluation, experience of surgeon, and interdisciplinary team. Thus, these abnormal sites of ectopic pregnancy ought to take into consideration for all gynecologists in an emergency condition with a major hemorrhage.
CONCLUSIONS: In reproductive age women, primary EP at liver and pelvic wall should be considered with high index of suspicion if intrauterine pregnancy is totally excluded. Timely diagnosis, rational management by surgical excision, and a multidisciplinary team can reduce substantially adverse outcomes.

UNASSIGNED: Ectopic pregnancy (EP), reflecting a fertilized ovum implanted outside the normal uterine cavity, represents a frequent cause of morbidity and possibly mortality in women of reproductive age.
UNASSIGNED: To summarize the diagnosis and treatment of EP after in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET).
UNASSIGNED: The medical records of patients who were diagnosed with EP after embryo transfer from 2017 to 2019, in a tertiary hospital were reviewed.
UNASSIGNED: Of the 24 cases analyzed, 21 (87.5%) had fallopian tube involvement, while 2 (8.3%) and 1 (4.2%) had cornual and cervical pregnancies, respectively. Clinical manifestations included vaginal bleeding (58.3%) and lower abdominal pain (16.7%); 9 (42.9%) cases had no symptoms. One cornual pregnancy was misdiagnosed as acute appendicitis and later correctly diagnosed by laparoscopic exploration. There were 2 cases of multiple-site EP and 2 of heterotopic pregnancy, including one with an intrauterine pregnancy with double chorionic and four amniotic sacs and right tubal ampullary pregnancy. Five of the 21 cases with fallopian tube involvement received conservative treatment, while the remaining 16 underwent surgeries, including laparoscopic ipsilateral salpingostomy and ipsilateral salpingectomy.
UNASSIGNED: Ectopic pregnancy after embryo transfer, mainly involving the fallopian tube, is very complex and is with diverse manifestations. Even with the pregnancy sac observed in the uterus, the pelvic cavity should be scanned thoroughly after embryo transfer.