Uterine cervical stenosis: from classification to advances in management. Overcoming the obstacles to access the uterine cavity.

BACKGROUND: To date hysteroscopy is the gold standard technique for the evaluation and management of intrauterine pathologies. The cervical canal represents the access route to the uterine cavity. The presence of cervical stenosis often makes entry into the uterine cavity difficult and occasionally impossible. Cervical stenosis has a multifactorial etiology. It is the result of adhesion processes that can lead to the narrowing or total obliteration of the cervical canal. PURPOSE: In this review, we summarize the scientific evidence about cervical stenosis, aiming to identify the best strategy to overcome this challenging condition. METHODS: The literature review followed the scale for the quality assessment of narrative review articles (SANRA). All articles describing the hysteroscopic management of cervical stenosis were considered eligible. Only original papers that reported data on the topic were included. RESULTS: Various strategies have been proposed to address cervical stenosis, including surgical and non-surgical methods. Medical treatments such as the preprocedural use of cervical-ripening agents or osmotic dilators have been explored. Surgical options include the use of cervical dilators and hysteroscopic treatments. CONCLUSIONS: Cervical stenosis can present challenges in achieving successful intrauterine procedures. Operative hysteroscopy has been shown to have the highest success rate, particularly in cases of severe cervical stenosis, and is currently considered the gold standard for managing this condition. Despite the availability of miniaturized instruments that have made the management of cervical stenosis more feasible, it remains a complex task, even for experienced hysteroscopists.

Fertility and anatomical outcomes following hysteroscopic adhesiolysis: An 11-year retrospective cohort study to validate a new classification system for intrauterine adhesions (Urman-Vitale Classification System).

OBJECTIVE: To propose a new classification system (Urman-Vitale Classification System) for intrauterine adhesions (IUAs) and to evaluate anatomical and fertility outcomes after hysteroscopic adhesiolysis accordingly. METHODS: A retrospective analysis of consecutive patients treated over 11 years by a single operator in a tertiary care hospital. Women with sonographic suspicion of IUAs were scheduled for hysterosalpingography (HSG) and hysteroscopy for confirmation and treatment. IUAs were divided into five classes according to symptoms, ultrasound, HSG findings, and postsurgical hysteroscopic appearance. Hysteroscopic adhesiolysis was performed using a bipolar cutting electrode in an office setting. Evaluated outcomes were restoration of the uterine cavity, clinical pregnancy, pregnancy loss, and live birth rates. RESULTS: A total of 227 patients (479 procedures) were included. Mean number of hysteroscopies increased in frequency with class of adhesions from Class 1 to Class 5 (1.0 ± 0.2 vs 2.3 ± 0.5; P = 0.001). Full restoration of the cavity was achieved in 100% of patients with Class 1 compared with 18.5% for Class 5 (43/43 vs 5/27; P = 0.001). Clinical pregnancy (Class 1 vs Class 4: P = 0.034; 1 vs 5: P = 0.006; 2 vs 5: P = 0.024) and live birth (Class 1 vs Class 4: P = 0.001; 1 vs 5: P = 0.006; 2 vs 4: P = 0.007; 2 vs 5: P = 0.0208) rates decreased with increasing severity of IUAs. Pregnancy loss rate was related to IUA severity (Class 1 vs Class 4: P = 0.012; 1 vs 5: P = 0.003: 2 vs 4: P = 0.014; 2 vs 5: P = 0.021). CONCLUSION: A classification based on symptoms, imaging findings, and postsurgical macroscopic appearance of the uterine cavity could be useful in predicting prognosis and fertility in women with IUAs.

Maternal serum Sortilin-1 level as a potential biomarker for intrahepatic cholestasis of pregnancy.

Objective: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease related to pregnancy in women. Sortilin-1 is a sorting receptor belonging to the vacuolar protein sorting 10 (Vps10p) domain family, and recent studies have shown that Sortilin-1 has a distinct role in the pathogenesis of biliary fibrosis and cirrhosis. We aimed to evaluate maternal serum Sortilin-1 level as a potential biomarker in pregnant women with intrahepatic cholestasis.Materials and methods: A prospective observational cohort study was conducted. We enrolled 80 pregnant women, 49 with the diagnosis of intrahepatic cholestasis of pregnancy and 31 healthy controls. Then, we measured maternal serum Sortilin-1 levels using an enzyme-linked immunosorbent assay method and compared them between groups.Results: The mean Sortilin-1 level in the ICP group was higher than control group (3.3 ± 1.7 ng/mL vs. 2.0 ± 0.6 ng/mL, respectively, p < .001). The receiver operating characteristic curve (ROC) analysis based on maternal serum Sortilin-1 levels to predict the presence of ICP was 85.3% controls [area under the curve (AUC), 0.853; 95% CI, 0.738-0.938, p < .001]. The optimal cutoff value of Sortilin-1 was 2.24 ng/mL (71.4% sensitivity and 74.2% specificity) to detect intrahepatic cholestasis of pregnancy.Conclusion: Elevated maternal serum Sortilin-1 levels are associated with ICP and can be used as a disease biomarker. Sortilin-1 levels can be combined with total bile acids, transaminases, and blood coagulation profile in the follow-up of ICP.

Does Oocyte Retrieval Performance in Mono-follicular Cycles Differ by Physician Experience?

Oocyte pick-up (OPU) is considered as a minor surgical procedure and complications are very rare when performed by trained physicians. However, data on training standards are limited and assessment of proficiency is challenging. The aim of this study was to show the impact of physician experience on OPU performance in mono-follicular in vitro fertilization (IVF) cycles, using two measurable outcome parameters: successful oocyte retrieval and operative time. Senior physicians (n = 6) had over 15 years of experience and novice physicians (n = 4) had at least 30 procedures under supervision. The study population included 226 mono-follicular cycles. Oocyte retrieval was successful in 179 out 226 procedures (79.2%); seniors and novices achieved similar oocyte retrieval rates (74.1%, 43/58 vs 80.9%, 136/168, p = 0.270). The mean duration of the procedure was 513.4 ± 163.1 (126-769) s. It was significantly shorter with a mean difference of - 117.9 s (95% CI: - 164.4 to - 71.3, p = 0.0001, Hedges g = 1.3) for senior physicians when compared to novices (425.8 ± 146.2 versus 543.7 ± 157.9 s). Novices who start performing OPU independently after 30 supervised procedures perform well in collecting the single oocyte grown in mono-follicular cycles; however, the mean duration of the procedure is relatively longer compared to seniors. After initial training period, physicians have few opportunities to compare themselves with their seniors and peers; periodical reassessment of the technique-which should also cover managing the operation time-would help confirm their own practices.

What is the optimum number of follicular flushes in mono-follicular in-vitro fertilization cycles in a poor responder population?

OBJECTIVE: Assessment of the optimal number of follicular flushes on retrieval rate and quality of oocytes in mono-follicular in-vitro fertilization (IVF) cycles. MATERIAL AND METHODS: A retrospective analysis of 246 oocyte pick-up procedures in mono-follicular IVF cycles of 226 poor responder women was performed. The primary endpoint was oocyte retrieval rate in the initial aspirate versus subsequent flushing episodes. The secondary endpoints were oocyte maturity, fertilization rates and embryo cleavage. RESULTS: The procedure was successful in 187 cycles (76%), of which 160 metaphase-II oocytes were retrieved. Retrieval rates were similar for natural and modified natural cycles (p=0.595). The initial aspirate provided 54% of the total yield and the rest was obtained from up to four episodes of flushing. Follicular flushing increased oocyte recovery rate from 41.1% to 76%. None of the oocytes retrieved after three flushes fertilized. Oocyte maturity, fertilization and embryo cleavage rates were comparable for oocytes from the initial aspirate and one or two episodes of flushing. Oocytes obtained after the third flushing episode developed into poor quality embryos. CONCLUSION: Flushing confers a benefit for oocyte recover rates in mono-follicular IVF cycles in poor responder women. However, more than three attempts at flushing were not associated with good outcome.

A promising novel biomarker for early-onset preeclampsia: soluble trigger receptor expressed on myeloid cells-1 (sTREM-1).

BACKGROUND: We aimed to explore TREM-1 activation in pregnant women who has preeclampsia through the measurement of its soluble form sTREM. METHODS: A prospective cohort study was conducted. Participants were recruited from antenatal clinic between 1 May 2019 and 31 August 2019, and they all provided written informed consent for participation. Women between 18 and 42 years of age who were diagnosed with early or late-onset preeclampsia (LOP) were offered participation if they did not have any known systemic disease (chronic hypertension, diabetes, hypothyroidism, chronic renal-liver diseases, etc.); autoimmune disorders; multiple pregnancies; presence of fetal structural and chromosomal anomalies; placenta previa; cholestasis of pregnancy; preterm delivery; evidence of chronic and active infection. The primary outcome of the study was to assess any difference between groups in terms of the diagnostic value of sTREM level. RESULTS: A total of 80 patients were enrolled; proven early-onset preeclampsia (EOP) (n = 20), LOP (n = 30), and control (n = 30) groups. There was no significant difference among the groups in terms of age and BMI. Mean gestational age at diagnosis of EOP; 30 ± 1.9 and LOP; 34.7 ± 1.9 weeks gestation. The mean sTREM level was 160.130 ± 1.65 pg/ml in the EOP group, 119.337 ± 2.04 pg/ml in LOP group, and 87.764 ± 1.69 pg/ml in the control group. According to subgroup analysis, sTREM levels were significantly higher in EOP group than control group. CONCLUSIONS: sTREM might be a promising biomarker for early detection of EOP. However, future studies are necessary to confirm this hypothesis.

Prevalence of T-shaped uterus among fertile women based on ESHRE/ESGE and Congenital Uterine Malformation by Experts (CUME) criteria.

RESEARCH QUESTION: What is the prevalence of T-shaped uteri among fertile women based on ESHRE/ESGE and Congenital Uterine Malformation by Experts (CUME) criteria? DESIGN: A prospective cohort study of 258 women of reproductive age with a history of at least one natural pregnancy resulting in live birth. Participants were recruited from the family planning clinic between January 2018 and March 2020. The ESHRE/ESGE classification of congenital anomalies of the female genital tract was used for describing abnormal findings. CUME criteria were also used for diagnosing T-shaped uterus. Uterine cavity volume was measured. RESULTS: Mean age of participants was 35.4 ± 6.2 years. Participants were diagnosed with the following: congenital uterine abnormality (n = 9 [3.6%]); partial septate uterus (n = 5 [2.0%]) and hemiuterus (n = 2 [0.8%]). Two women (0.8%) were diagnosed with T-shaped uterus and borderline T-shaped uterus based on the ESHRE/ESGE criteria and CUME. Mean lateral indentation angle, lateral indentation depth and T-angle were 156.2° ± 9.53°, 2.85 ± 0.93 mm and 73.3° ± 9.85° in patients with normal uterine cavity. In patients with T-shaped and borderline T-shaped uteri, respective figures were 115° versus 121°, 10 mm versus 7.6 mm and 27.5° versus 70°. Median volume of the uterine cavity in patients with normal uterine cavity and T-shaped uterus was 3.71 ml (minimum 2.0 to maximum 9.03 ml, interquartile range 1.93) and 3.2 ml (2.9 and 3.62 ml), respectively. CONCLUSIONS: The prevalence of T-shaped uteri in fertile women is low, which corresponds to previous reports of women with poor reproductive history.

A Survey of Women Who Cryopreserved Oocytes for Non-medical Indications (Social Fertility Preservation).

To evaluate the expectations, experiences, and fertility awareness status of women who underwent social oocyte cryopreservation. Cohort survey study was conducted at an academic medical center. All women who underwent social oocyte cryopreservation between January 2015 and June 2016 were recruited. One hundred thirty-three women were contacted by phone to participate in a survey. The questionnaire investigated the initial motivation towards freezing, intentions to use cryopreserved oocytes, treatment experience, awareness of fertility and knowledge about chances of having a live birth with their frozen oocytes. The mean age at the time of oocyte freezing was 38.5 ± 2.68 years. The average number of mature oocytes cryopreserved was 5.48 ± 6.6 (1-16). Two major motivations were absence of a male partner (40%) and an anticipated age-related fertility decline (42%). Almost 60% overestimated the chances of natural conception, as well as the success of IVF at the age of 40 years. Half of the oocyte bankers reported that fertility declined between ages 35 and 39, but only 28% of patients estimated the live birth rate per cryopreserved oocyte correctly. Overall 98.8% stated that they would recommend oocyte cryopresevation to a friend, and 72% felt more secure in terms of reproductive potential. Despite comprehensive personalized counseling prior to the start of ovarian stimulation, many women do not seem to have a realistic understanding of reproductive aging. Even though gamete cryopreservation provides some insurance, overestimating the effectiveness of oocyte cryopreservation can also lead to a false sense of security. Clinical Trial Registration: 2016.086.IRB1.006.

Anogenital distance in newborn infants conceived by assisted reproduction and natural conception.

RESEARCH QUESTION: Does anogenital distance (AGD) differ in newborn infants conceived through assisted reproduction technology (ART) compared with those conceived naturally? DESIGN: This case-control study looked at anthropometric and anogenital measurements in 247 male and 200 female newborns born after ART (n = 121) or natural conception (n = 326), within 24 h of birth. Anogenital measurements included distance from the centre of the anus to the anterior clitoris (AGDAC) and to the posterior fourchette (AGDAF) in female infants, and from the centre of the anus to the posterior base of the scrotum (AGDAS) and to the anterior base of the penis (AGDAP) in male infants. RESULTS: ART mothers were older, more likely to be nulliparous and delivered by Caesarean section at an earlier gestational week. AGDAS of male infants was approximately twice the AGDAF of female infants (17.6 ± 5.0 versus 9.1 ± 3.6 mm). AGDAF in female infants conceived by ART compared with those conceived naturally was not significantly different (8.8 ± 3.6 versus 9.3 ± 3.6 mm; P = 0.404). AGDAC were also comparable for both groups (27.4 ± 6.3 versus 27.7 ± 7.1 mm; P = 0.770). In male infants, no significant difference was seen between ART and natural conception groups in terms of AGDAS (17.4 ± 4.6 versus 17.7 ± 5.2 mm, P = 0.742) and AGDAP (37.5 ± 6.6 versus 38.0 ± 6.7 mm, P = 0.589). When adjusted for gestational age, weight, length and head circumference, mode of conception was not associated with differences in any of the anogenital measurements. CONCLUSIONS: AGD measurements in infants conceived by ART are no different from those of infants conceived naturally.

Predictive Value of Malignancy Risk Indices for Ovarian Masses in Premenopausal and Postmenopausal Women.

BACKGROUND: To evaluate the predictive role of a risk of malignancy index in discriminating between benign and malignant adnexal masses preoperatively. MATERIALS AND METHODS: A total of 408 patients with adnexal masses managed surgically between January 2010 and February 2014 were included. The risk of malignancy indices (RMI) 1, 2, 3 and 4 were calculated using findings for ultrasonography, menopausal status, and CA125 levels. Histopathologic results were the end point. ROC analysis was used for the sensitivity and the specificity of the models. RESULTS: Some 37.6 % of the cases were malignant in the postmenopausal group while 7.9 % were malignant in the premenopausal group. Pelvic pain was the most common complaint, and the majority of the cases were diagnosed at stage 3. The RMI 1, 2, 3 and 4 yielded percentage sensitivities of 76.1, 79.1, 76.1 and 76.1 and specificities of 91.5, 89.1, 90.6, 88.6, respectively. RMI 1 was the most reliable test in the general population according to AUC levels and Kappa statistics. From ROC analysis results of post/ premenopausal women, the RMI 1 (cut off: 200) yielded sensitivities of 84.0/60.9 and specificities of 87.7/92.5. With RMI 2 they were 88.6/60.9 and 80.0/91.0, with RMI 3 84.0/ 60.9 and 87.7/91.8, and with RMI 4 (cut off:400) 81.8/47.8 and 83.6 /44.0. Although test performance of RMI methods were good in a general population and postmenopausal women, the RMI inter-agreement validity was only moderate or fair in premenopausal women. CONCLUSIONS: Our study confirms the effectiveness of RMI algorithms in postmenopausal women. However, more sensitive tests are needed for premenopausal women.