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Abstract Background To date, the association between retained placenta and treatment success rate of misoprostol for early pregnancy failure has yet to be evaluated. The aim of this study was to evaluate this association and further investigated the connection between medical, clinical and sonographic parameters and treatment success. Methods We conducted a retrospective cohort study of women with early pregnancy failure treated with misoprostol from 2006 to 2021. The success rate of misoprostol treatment was compared between patients with history of retained placenta including women who underwent manual lysis of the placenta following delivery or patients who were found to have retained products of conception during their post-partum period (study group) and patients without such history (controls). Demographic, clinical, and sonographic characteristics as well as treatment outcomes were compared between the groups. Results A total of 271 women were included in the study (34 women in the study group compared to 237 women in the control group). Two-hundred and thirty-three women (86.0%) presented with missed abortion, and 38 (14.0%) with blighted ovum. Success rates of misoprostol treatment were 61.8% and 78.5% for the study and control groups, respectively (p = 0.032). Univariate analysis performed comparing successful vs. failed misoprostol treatment showed advanced age, gravidity, parity and gestational sac size (mm) on TVUS were associated with higher misoprostol treatment failure rate. Following a multivariate logistic regression model these variables did not reach statistical significance. Conclusion Women who have an event of retained placenta following childbirth appear to have decreased success rate of treatment with misoprostol for early pregnancy failure. Larger studies are needed to confirm this finding.

Abstract Research question Clinicians involved in fertility preservation (FP) are often required to make prompt and consequential decisions despite the absence of evidence-based data. We established a collaborative professional online consultation group for fertility preservation issues. We sought to determine the main controversial clinical issues in FP as raised by participants of this group. Design Content analysis of a dedicated community of practice interacting via a messaging application (WhatsApp) and a survey of group participants. Results Between January 2019 and July 2022, group members posed 39 clinical questions which were discussed and debated by the group. Common themes included management of oncofertility cases (33%), potential gonadotoxicity of various therapies (23%), fertility preservation in women and girls with premature ovarian insufficiency (POI) (18%), and technical aspects of ovarian tissue cryopreservation (10%). All but one query received prompt response (mean time for first response for 95% of queries 7.1 ± 9.0 min) from a mean of 5.4 ± 3.2 members. An anonymous online survey of group members was conducted during August 2022 (n = 31, response rate 94%). The majority of respondents stated they gained knowledge and assistance in clinical decision making from participation in the discussion group (90% and 58% of respondents, respectively). Conclusions Management of clinical oncofertility cases, potential gonadotoxic effect of therapeutics and fertility preservation in women and girls with POI were the most common controversial issues in our fertility preservation community of practice. Intra-professional collaborative communication via a messaging application can aid in clinical management of fertility preservation and augment clinician’s knowledge.

Abstract Background Trial of labor after cesarean delivery (TOLAC) in twin gestations has been associated with decreased rates of successful vaginal delivery compared to singleton pregnancies, with mixed results regarding maternal and neonatal morbidity. However, induction of labor (IOL) in this unique population has not yet been fully evaluated. Objective To assess success rates and maternal and neonatal outcomes in women with a twin gestation and a previous cesarean delivery undergoing IOL. Methods A retrospective cohort study including women with a twin gestation and one previous cesarean delivery undergoing a trial of labor between the years 2009–2020. Patients requiring IOL were compared to those with a spontaneous onset of labor. Results There were 53 patients who met the inclusion criteria: 31 had a spontaneous onset of labor (58%) and 22 required an IOL. Baseline characteristics were comparable between the groups apart from a history of labor arrest which was more common in the IOL group (40.9% vs. 9.6%, P = 0.006). A successful vaginal delivery occurred in all (100%) women with a spontaneous labor compared to 81% in the IOL group (p = 0.02). Secondary outcomes were comparable. A history of no previous vaginal delivery, maternal obesity, and IOL were associated with TOLAC failure. Conclusions IOL after cesarean delivery in twin gestation is associated with an increased risk of TOLAC failure compared to spontaneous onset of labor. However, no adverse neonatal or maternal outcomes were found. IOL in this high-risk population is feasible but patients should be counseled about the lower rate of success.

Abstract Background Induction of labor in women with a previous cesarean section (CS) is associated with increased rates of uterine rupture and failed attempt for vaginal delivery. Prostaglandins use is contraindicated in this population, limiting available options for cervical ripening. Objective To evaluate the efficacy and safety of artificial rupture of membranes (AROM) as a mode of Induction of labor (IOL) in women with a previous cesarean section. Methods A retrospective cohort study conducted in a single tertiary care center between January 2015 and October 2020. Women with one previous cesarean section and a current singleton term pregnancy requiring IOL, with an unfavorable cervix, were included. The primary outcome was a successful vaginal delivery (VBAC); secondary outcomes were rates of chorioamnionitis, uterine rupture and low Apgar score ( 12 h after AROM) administration, there were no significant changes in the rates of successful VBAC or of chorioamnionitis. Conclusion AROM as a single mode of IOL in women with a previous CS is a safe and efficient practice with high rates of successful VBAC. When spontaneous labor does not develop, there is no advantage to delay the administration of oxytocin.

Abstract Background Women undergoing in-vitro fertilization (IVF) treatments are at increased risk for maternal and neonatal complications compared to women who conceive spontaneously. Though spontaneous pregnancies of young women and adolescents have an increased risk for adverse maternal and neonatal outcomes, pregnancy outcomes of this age group, following IVF treatment have been scarcely reported. The aim of this study was to report maternal and neonatal outcomes of young women who conceived following IVF compared to women in the same age group with spontaneous conception. Methods We performed a multicenter case–control study. The study group included women aged 17–25 years who conceived by IVF with an ongoing singleton pregnancy. For the purpose of the study, a control group matched (1:2 ratio) for maternal age at delivery and parity was constructed. Demographic, medical history, pregnancy related characteristics and maternal and neonatal outcomes were compared between groups. Finally, factors associated with spontaneous vaginal delivery were assessed for the entire cohort using a univariate and multivariate logistic regression model. Results Between 2005 and 2021, we identified 80 women aged 19–25 years who conceived by IVF. A control group of 160 women was matched to the study group by age and parity. The unmatched maternal characteristics and pregnancy associated complications were similar among the groups. However, the IVF group had a significantly higher rate of induction of labor (48.1% vs. 26.6%, p = 0.001), meconium-stained amniotic fluid (27.6% vs. 14.1%, p = 0.025), prolonged second stage of labor (26.0% vs. 7.3%, p = 0.001) and operative vaginal delivery (22.5% vs.12.5%, p = 0.048). Neonatal outcomes were for the most part comparable; nevertheless, we found a higher rate of neonates with an umbilical artery pH

Pre-pubertal oocytes are still dormant. They are arrested in a GV state and do not undergo meiotic divisions naturally. A multitude of molecular pathways are changed and triggered upon initiation of puberty. It is not yet clear which epigenetic events occur in oocytes upon pubertal transition, and how significant these epigenetic events may be. We evaluated epigenetic marker levels in mouse pre-pubertal and post-pubertal female oocytes. In addition, we evaluated H3K9me2 levels in human oocytes collected from fertility preservation patients, comparing the levels between pre-pubertal patients and post-pubertal patients. The chromatin structure shows a lower number of chromocenters in mouse post-pubertal oocytes in comparison to pre-pubertal oocytes. All heterochromatin marker levels checked (H3K9me2, H3K27me3, H4K20me1) significantly rise across the pubertal transition. Euchromatin markers vary in their behavior. While H3K4me3 levels rise with the pubertal transition, H3K27Ac levels decrease with the pubertal transition. Treatment with SRT1720 [histone deacetylase (HDAC) activator] or overexpression of heterochromatin factors does not lead to increased heterochromatin in pre-pubertal oocytes. However, treatment of pre-pubertal oocytes with follicle-stimulating hormone (FSH) for 24 h - changes their chromatin structure to a post-pubertal configuration, lowers the number of chromocenters and elevates their histone methylation levels, showing that hormones play a key role in chromatin regulation of pubertal transition. Our work shows that pubertal transition leads to reorganization of oocyte chromatin and elevation of histone methylation levels, thus advancing oocyte developmental phenotype. These results provide the basis for finding conditions for in-vitro maturation of pre-pubertal oocytes, mainly needed to artificially mature oocytes of young cancer survivors for fertility preservation purposes.

Abstract Background There is conflicting evidence regarding an association between gonadotropin releasing hormone analogue (GnRHa) therapy and polycystic ovary syndrome (PCOS). This study aimed to compare the prevalence of endocrine disorders, primarily PCOS, between women who had been treated with GnRHa for central precocious puberty (CPP) and those who were not treated. Methods This was a retrospective cohort study, including women diagnosed with central precocious puberty between 1989 and 2011 in a university affiliated tertiary medical center. Data collected included demographic data, medical background, clinical presentation at diagnosis and duration of treatment (zero for non-treated). Gynecologic and endocrine long-term outcomes were compared by treatment group. Results Fifty-one women were included in the study, 27/51 had been treated with gonadotropin releasing hormone analogue (GnRHa). Overall prevalence of PCOS was 19.6%. No statistically significant difference in prevalence of PCOS was demonstrated between the treated and non-treated groups. Similarly, overall prevalence of either clinical or laboratory hyper-androgenism, was 29.4% and 33.3%, for the treatment and non-treatment groups respectively (p = non-significant). Conclusions GnRHa treatment for precocious puberty is not associated with increased risk of polycystic ovary syndrome.

Abstract Background Obstetric anal sphincter injury (OASI) is a debilitating complication of vaginal delivery which has yet to receive ample attention in adolescents. The aim of this study was to describe risk for OASI in adolescent mothers compared to adults. We further attempted to compare risk factors for OASI between these two age groups. Methods We performed a retrospective cohort study between 2003 and 2019. Primiparous women who delivered vaginally, 21 years and younger were compared to women ages 26–35. Excluded were preterm, multifetal, non-vertex, cesarean deliveries as well as intrauterine fetal death. Rate of OASI as well as obstetric and labor characteristics of women with OASI, were compared between groups. Finally, risk factors were assessed for each group separately. Univariate and multivariate logistic regression model were performed. Results Final analysis was performed on 5113 nulliparous adolescents and 13,845 nulliparous in the 26–35 age group. Allocation to study groups was according to OASI – Sixty-seven adolescents (1.3%) had a 3rd or 4th degree perineal tear and were defined as the OASI group, while 5046 patients (98.7%) did not have such a tear. In the adult group, 199 out of 13,845 patients (1.4%) were diagnosed with OASI. Occurrence of OASI did not differ between groups (p = 0.510). Comparison of women with OASI in the adolescent group vs. adult group found differences with regard to operative vaginal delivery, (20.9% vs. 36.2%, respectively; p = 0.023) and meconium stained amniotic fluid (9.1% vs. 21.3%, respectively; p = 0.027). Following multivariate analysis the only parameter independently associated with OASI in the adolescent age group was head circumference ≥ 90th percentile with an adjusted odds ratio of 3.08 (CI 1.48–6.38, p = 0.003). In the adult group the similar analysis revealed operative vaginal delivery (OR = 2.44, CI 1.72–3.47, p

Abstract Background Endometrial thickness (ET) has previously been shown to positively correlate with implantation and clinical pregnancy rates. Pregnancies achieved using in-vitro fertilization (IVF) technique are prone to higher rates of early miscarriage. The aim of this study was to compare the effects of expectant management, medical treatment (Misoprostol) and dilation and curettage (D&C) for early miscarriage following IVF cycles on the subsequent cycle outcomes - endometrial thickness and reproductive outcomes. Methods A retrospective cohort study of women who underwent embryo transfer, conceived and had first trimester miscarriage with at least one subsequent embryo transfer. ET measurements during fresh or frozen-thawed IVF cycles were assessed for each patient. Comparisons of ET differences between the miscarriage and the subsequent cycles, as well as reproductive outcomes, were performed according to the initial miscarriage management approach. Results A total of 223 women were included in the study. Seventy-eight women were managed conservatively, 61 were treated with Misoprostol and 84 women underwent D&C. Management by D&C, compared to conservative management and Misoprostol treatment was associated with higher prevalence of a significant (> 2 mm) ET decrease (29.8%% vs. 14.1and 6.6%, respectively; p

Abstract Background The sterilizing effect of cancer treatment depends mostly on the chemotherapy regimen and extent of radiotherapy. Prediction of long-term reproductive outcomes among cancer survivors according to chemo-radiotherapy regimen may improve pre-treatment fertility preservation counseling and future reproductive outcomes. Methods The aim of this study was to evaluate long term reproductive outcomes in cancer survivors according to gonadotoxicity risk estimation of the chemo-radiotherapy regimens utilized. This retrospective cohort study was comprised of post-pubertal female patients referred for fertility preservation during 1997 and 2017 was performed. Eligible adult patients were addressed and asked to complete a clinical survey regarding their ovarian function, menstruation, reproductive experience and ovarian tissue auto-transplantation procedures. Results were stratified according to the gonadotoxic potential of chemotherapy and radiotherapy they received—low, moderate and high-risk, defined by the regimen used, the cumulative dose of chemotherapy administered and radiation therapy extent. Results A total of 120 patients were eligible for the survey. Of those, 92 patients agreed to answer the questionnaire. Data regarding chemotherapy regimen were available for 77 of the 92 patients who answered the questionnaire. Menopause symptoms were much more prevalent in patients undergoing high vs moderate and low-risk chemotherapy protocol. (51.4% vs. 27.3% and 16.7%, respectively; p

Abstract Background Pelvic hematoma is a common finding following hysterectomy which at times may become infected causing substantial morbidity. The aim of this study was to describe the incidence, clinical manifestation and identify risk factors for infected pelvic hematoma. We also attempted to identify specific bacterial pathogens which may cause this phenomenon. Methods We conducted a retrospective cohort study at a tertiary university teaching hospital. Included were all women who underwent hysterectomy and were diagnosed with a pelvic hematoma following surgery from 2013 to 2018. In an attempt to assess possible risk factors for infected pelvic hematoma women with asymptomatic pelvic hematoma were compared to women with an infected pelvic hematoma. Results During the study period 648 women underwent hysterectomy at our medical center. Pelvic hematoma was diagnosed by imaging in 50 women (7.7%) including 41 women who underwent vaginal hysterectomy and 9 women who underwent abdominal hysterectomy. In 14 (2.2%) cases the hematoma became infected resulting in need for readmission and further treatment. Women who underwent vaginal surgery were more likely to return with infected pelvic hematoma compared to women who underwent open abdominal or laparoscopic surgery (4.5% vs. 1.1%, p

In vitro maturation of oocytes from antral follicles seen during tissue harvesting is a fertility preservation technique with potential advantages over ovarian tissue cryopreservation (OTC), as mature frozen and later thawed oocyte used for fertilization poses decreased risk of malignant cells re-seeding, as compared to ovarian tissue implantation. We previously demonstrated that in vitro maturation (IVM) performed following OTC in fertility preservation patients, even in pre-menarche girls, yields a fair amount of oocytes available for IVM and freezing for future use. We conducted a retrospective cohort study, evaluating IVM outcomes in chemotherapy naïve patients referred for fertility preservation by OTC that had oocyte collected from the medium with attempted IVM. A total of 133 chemotherapy naïve patients aged 1–35 years were included in the study. The primary outcome was IVM rate in the different age groups – pre-menarche (1–5 and ≥6 years), post-menarche (menarche-17 years), young adults (18–24 years) and adults (25–29 and 30–35 years). We demonstrate a gradual increase in mean IVM rate in the age groups from 1 to 25 years [4.6% (1–5 years), 23.8% (6 years to menarche), and 28.4% (menarche to 17 years)], with a peak of 38.3% in the 18–24 years group, followed by a decrease in the 25–29 years group (19.3%), down to a very low IVM rate (8.9%) in the 30–35 years group. A significant difference in IVM rates was noted between the age extremes – the very young (1–5 years) and the oldest (30–35 years) groups, as compared with the 18–24-year group (p < 0.001). Importantly, number of oocytes matured, percent of patients with matured oocytes, and overall maturation rate differed significantly (p < 0.001). Our finding of extremely low success rates in those very young (under 6 years) and older (≥30 years) patients suggests that oocytes retrieved during OTC prior to chemotherapy have an optimal window of age that shows higher success rates, suggesting that oocytes may have an inherent tendency toward better maturation in those age groups.

Abstract Background Uterine leiomyomas are often discovered during early pregnancy and in most cases will have no effect on pregnancy outcomes. However, in rare cases uterine leiomyomas may lead to obstetric complications. The aim of the study was to evaluate rate of uterine leiomyoma growth in the 3 trimesters of pregnancy. Methods We conducted a retrospective cohort study. Included were women who were diagnosed with uterine leiomyoma during pregnancy and had at least two sonographic measurements in different trimesters. Data regarding leiomyoma growth, recorded by ultrasound examination, during 1st 2nd and 3rd trimesters were collected from electronic patient records. Results Two-hundred forty-eight uterine leiomyomas were included in the study. Leiomyoma area increased substantially in size between the 1st and 2nd trimesters (54.5% ± 75.9%, p = .007) and to a lesser degree between the 2nd and 3rd trimesters (17.9% ± 59.7%, NS). Evaluation of the change in size throughout the pregnancy – between 1st and 3rd trimesters revealed a significant increase of 95.9% ± 191.3% (p