The association between history of retained placenta and success rate of misoprostol treatment for early pregnancy failure.

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.

Induction of labor in twin pregnancy in patients with a previous cesarean delivery.

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.

Prior exposure to chemotherapy does not reduce the in vitro maturation potential of oocytes obtained from ovarian cortex in cancer patients.

STUDY QUESTION: Does chemotherapy exposure affect IVM potential of immature oocytes retrieved from the ovarian cortex following ovarian tissue cryopreservation (OTC) for fertility preservation? SUMMARY ANSWER: The IVM potential of oocyte retrieved from ovarian cortex following OTC is not affected by prior exposure to chemotherapy but primarily dependent on patient's age, while successful retrieval of immature oocytes from the ovarian tissue is negatively affected by chemotherapy and its timing. WHAT IS KNOWN ALREADY: The potential and feasibility of IVM in premenarche patients was previously demonstrated, in smaller studies. The scarce data that exist on the IVM potential of oocytes retrieved during OTC following chemotherapy support the feasibility of this process, however, this was not previously shown in the premenarche cancer patients population or in larger cohorts. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study evaluating 229 cancer patients aged 1-39 years with attempted retrieval of oocytes from the ovarian tissue and the medium following OTC in a university affiliated fertility preservation unit between 2002 and 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 172 chemotherapy naïve and 57 chemotherapy exposed patients aged 1-39 years underwent OTC in university affiliated tertiary infertility and IVF center. OTC and IVM outcomes were compared between the chemotherapy naïve and exposed groups. The main outcome measure was mean IVM rate per patient in the chemotherapy naïve and exposed groups, with subgroup analysis of a 1:1 chemotherapy exposed group matched for age at OTC and type of malignancy. We additionally analyzed premenarche and postmenarche patients' outcomes separately and investigated the effect of time from chemotherapy to IVM, malignancy type and chemotherapy regimen on oocyte number and IVM outcomes in the chemotherapy exposed group. MAIN RESULTS AND THE ROLE OF CHANCE: While the number of retrieved oocytes and percentage of patients with at least one oocyte retrieved was higher in the chemotherapy naïve group (8.7 ± 7.9 versus 4.9 ± 5.6 oocytes and 87.2% versus 73.7%, P < 0.001 and P = 0.016, respectively), IVM rate and number of mature oocytes were comparable between the groups (29.0 ± 25.0% versus 28. 9 ± 29.2% and 2.8 ± 3.1 versus 2.2 ± 2.8, P = 0.979 and P = 0.203, respectively). Similar findings were shown in subgroup analyses for premenarche and postmenarche groups. The only parameter found to be independently associated with IVM rate in a multivariable model was menarche status (F = 8.91, P = 0.004). Logistic regression models similarly showed that past chemotherapy exposure is negatively associated with successful retrieval of oocytes while older age and menarche are predictive of successful IVM. An age and the type of malignancy matched (1:1) chemotherapy naïve and exposed groups were created (25 patients in each group). This comparison demonstrated similar IVM rate (35.4 ± 30.1% versus 31.0 ± 25.2%, P = 0.533) and number of matured oocytes (2.7 ± 3.0. versus 3.0 ± 3.9 oocytes, P = 0.772). Type of malignancy and chemotherapy regimen including alkylating agents were not associated with IVM rate. LIMITATIONS, REASONS FOR CAUTION: This study's inherited retrospective design and the long study period carries the possible technological advancement and differences. The chemotherapy exposed group was relatively small and included different age groups. We could only evaluate the potential of the oocytes to reach metaphase II in vitro but not their fertilization potential or clinical outcomes. WIDER IMPLICATIONS OF THE FINDINGS: IVM is feasible even after chemotherapy broadening the fertility preservation options of cancer patients. The use of IVM for fertility preservation, even after exposure to chemotherapy, should be further studied for optimal postchemotherapy timing safety and for the in vitro matured oocytes potential for fertilization. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study by any of the authors. The authors report that no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Artificial rupture of membranes as a mode for induction of labor in women with a previous cesarean section- a retrospective cohort study.

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 (< 7). RESULTS: Of the 665 women who met the inclusion criteria, 492 (74%) did not receive subsequent oxytocin and 173 (26%) did. There were significant differences in the baseline characteristics between these two groups, including maternal age, cervical dilation at presentation, parity, and a history of a previous VBAC. Among women who were induced solely by AROM the rate of a successful TOLAC was higher (81.3% vs 73.9%), total time of IOL was shorter (mean 8.7 h vs.16.1 h) and the risk of chorioamnionitis was lower (7.3% vs 18.4%). When subdividing the women who received oxytocin into early (< 12 h after AROM) vs late (> 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.

Sperm quality is not affected by the BNT162b2 mRNA SARS-CoV-2 vaccine: results of a 6-14 months follow-up.

PURPOSE: We aimed to investigate the possible effect of SARS-CoV-2 vaccination on sperm quality by evaluating semen analyses of men prior to vaccination and 6-14 months after vaccination. METHODS: This was a retrospective cohort study, conducted in a university-affiliated in vitro fertilization center between October 2021 and March 2022, including men not previously infected with the SARS-CoV-2 virus who received at least 2 doses of the Pfizer-BioNTech (BNT162b2) SARS-CoV-2 vaccine. Semen analyses of samples given pre-vaccination and 6-14 months post-vaccination were analyzed for the parameters of volume, concentration, motility, morphology, and total motile count (TMC) and compared. These parameters were also compared separately for men who received a third (booster) dose and for men with pre-vaccination normal and abnormal sperm. Correlations between time from vaccination and post-vaccination sperm parameters were also assessed. RESULTS: Fifty-eight men were included in the final analysis. Semen volume (2.9 ± 1.4 vs. 2.9 ± 1.6 ml), sperm concentration (42.9 ± 37.9 vs. 51.5 ± 46.2 million/ml), motility (42.5 ± 23.1 vs. 44.3 ± 23.4 percent), morphology (8.8 ± .16.6 vs. 6.6 ± 8.8 percent), and TMC (55.7 ± 57.9 vs. 71.1 ± 77.1 million) were comparable between the pre- and post-vaccination samples. This was true for the entire study cohort, for the subgroup of men who received a third dose and for the subgroups of men with a pre-vaccination normal and abnormal semen samples. No correlation was found between time from vaccination and post-vaccination sperm parameters. CONCLUSIONS: The Pfizer-BioNTech (BNT162b2) SARS-CoV-2 vaccine does not impair any of the sperm parameters over a relatively long-time interval of 6 to 14 months from vaccination.

Pfizer SARS-CoV-2 BNT162b2 mRNA vaccination (BNT162b2) has no adverse effect on elective oocyte cryopreservation outcomes.

RESEARCH QUESTION: Do elective oocyte cryopreservation outcomes in women 1-13 months after SARS-CoV-2 vaccination alter compared with unvaccinated women and do different time intervals between vaccination and ovarian stimulation impact these outcomes? DESIGN: This retrospective cohort study, conducted in a university-affiliated IVF centre, included 232 elective oocyte cryopreservation cycles of vaccinated and unvaccinated patients, without previous infection with the SARS-CoV-2 virus, between December 2020 and January 2022. Two control groups - pre-pandemic (January 2019 to February 2020) and intra-pandemic (December 2020 to January 2022) unvaccinated groups - were compared with the vaccinated group, further divided into four subgroups (under 3, 3-6, 6-9 and 9-13 months). The primary outcome was the elective oocyte cryopreservation cycle outcomes - number of retrieved and number of mature oocytes. RESULTS: The vaccinated group demonstrated comparable outcomes with regards to number of retrieved and mature oocytes compared with the pre-pandemic and intra-pandemic unvaccinated groups (12.6 ± 8.0 versus 13.0 ± 8.2 and 12.5 ± 7.4 retrieved and 10.1 ± 6.9 versus 9.5 ± 6.4 and 10.1 ± 6.3 mature oocytes, respectively; not significant for both). Similar results were noted in a comparison between the intra-pandemic unvaccinated group and the four vaccinated subgroups. No correlation was found between the parameter of days from vaccination and cycle outcomes. Similarly, analysis of covariance showed no association between vaccination status and timing and number of mature oocytes. CONCLUSIONS: The SARS-CoV-2 vaccination does not alter the outcomes of elective oocyte cryopreservation procedures. This is true even in a relatively long time interval of 9 to 13 months from vaccination.

Safety of third SARS-CoV-2 vaccine (booster dose) during pregnancy.

BACKGROUND: COVID-19 during pregnancy is associated with adverse outcomes for both the mother and fetus. SARS-CoV-2 vaccination has significantly reduced the risk for symptomatic disease. Several studies have reported on the safety of SARS-CoV-2 vaccination during pregnancy, with no adverse effects on the obstetrical outcomes. However, data regarding the obstetrical outcomes following a booster dose of the SARS CoV-2 vaccination during pregnancy have not yet to be published. OBJECTIVE: This study aimed to examine the association between the booster dose of the SARS CoV-2 vaccination during pregnancy and obstetrical outcomes. STUDY DESIGN: This was a retrospective cohort study of women who delivered between July and October 2021 at a large tertiary medical center. We compared women who received the booster vaccination dose during pregnancy with women who were not vaccinated and with those who only received 2 vaccination doses. Primary outcomes were the incidence of preterm labor and of small for gestational age neonates. Secondary outcomes were other maternal and neonatal complications. A secondary analysis investigating the association between the time from vaccination to delivery and the outcomes was also performed. Multivariable logistic regression models were used to adjust for potential confounders. RESULTS: There were 6507 women who met the inclusion criteria: 294 women received 3 doses of the vaccination, 2845 women received only 2 doses, and 3368 were unvaccinated. Patients receiving 3 doses of the vaccine were older and more likely to smoke than unvaccinated patients. No differences were noted among the triple-vaccinated, twice-vaccinated, and unvaccinated groups with regards to preterm birth and the incidence of small for gestational age neonates. Regarding the secondary outcomes, women in the triple-vaccinated group had higher rates of postpartum hemorrhage (9.5% vs 3.21%; P<.001) and gestational diabetes mellitus (12.2% vs 8.3%; P=.02) and were less likely to have hypertensive disorders of pregnancy (0% vs 1.4%; P=.041) than the unvaccinated group. Compared with the twice-vaccinated patients, patients with 3 doses of the vaccine were more likely to experience postpartum hemorrhage (9.5% vs 3.5%; P<.001) and were less likely to have a low umbilical artery pH (0.7% vs 6.1%; P<.001). In the sensitivity analysis comparing patients who delivered within 2 weeks of the third vaccination dose (n=53) with those who delivered at least 6 weeks after vaccination (n=96), there were no differences in the rates of small for gestational age neonates, preterm birth, postpartum hemorrhage, or cesarean delivery. CONCLUSION: Receiving the booster dose of the SARS-CoV-2 vaccination during pregnancy was not associated with adverse obstetrical outcomes when compared with unvaccinated or twice-vaccinated women. However, higher rates of postpartum hemorrhage were observed. Further studies on a larger scale are needed to confirm these findings.

Safety of SARS-CoV-2 vaccination during pregnancy- obstetric outcomes from a large cohort study.

BACKGROUND: COVID-19 during pregnancy is associated with adverse outcomes for mother and fetus. SARS-CoV-2 vaccination has significantly reduced the risk of symptomatic disease. Several small studies have reported the safety of SARS-CoV-2 vaccination during pregnancy, with no adverse effect on obstetric outcomes. OBJECTIVE: To examine the association between SARS-CoV-2 vaccination during pregnancy and maternal and neonatal outcomes in a large cohort study. Furthermore, to evaluate if timing of vaccination during pregnancy is related to adverse outcomes. METHODS: A retrospective cohort study of women who delivered between December 2020 and July 2021 at a large tertiary medical center. Excluded were women with multiple pregnancy, vaccination prior to pregnancy, COVID-19 infection during or before pregnancy, or unknown timing of vaccination. Primary outcomes were the incidence of preterm labor and of small for gestational age. Secondary outcomes were other maternal and neonatal complications. A secondary analysis investigating the association between time of vaccination and outcomes was also performed. Multivariable logistic regression models were used to adjust for potential confounders. RESULTS: There were 5618 women who met the inclusion criteria: 2,305 (41%) women were vaccinated and 3,313 (59%) were unvaccinated. There were no differences between vaccinated and non-vaccinated patients with respect to primary outcomes. The rate of preterm birth was 5.5% in the vaccinated group compared to 6.2% in the unvaccinated group (p = 0.31). Likewise, the rates of small for gestational age were comparable between the two groups (6.2% vs. 7.0% respectively, p = 0.2). In a secondary analysis focusing on time of vaccination and its relationship with outcomes, patients vaccinated in the second trimester (n = 964) and in the third trimester (n = 1329) were independently compared to their unvaccinated counterparts. Women who were vaccinated in the second trimester were more likely to have a preterm birth (8.1% vs. 6.2%, p < 0.001). This association persisted after adjusting for potential confounders (adjusted odds ratio 1.49, 95%CI 1.11, 2.01). CONCLUSIONS: SARS-CoV-2 vaccine appears to be safe during pregnancy with no increase in incidence of preterm labor and small for gestational age compared to unvaccinated women. However, in women vaccinated during the second trimester there may be an increase in the rate of preterm birth.

Oxytocin Regulates the Expression of Selected Colostrum-derived microRNAs.

OBJECTIVE: The highly expressed microRNAs (miRNAs) in milk are known as beneficial miRNAs, such as mir148a-3p, which is related to immune system development and disease prevention. There is a need to study their expression and secretion regulatory mechanism in breast milk. We hypothesize that oxytocin can be involved in the regulation of expression and secretion of milk-derived miRNAs. METHODS: Initially, oxytocin's effect on miRNA expression in human mammary cells was analyzed. Secondly, the expression of selected miRNAs in mothers' colostrum treated or not with oxytocin before, during, or after labor was compared. MiRNA expression was analyzed by quantitative real-time PCR. RESULTS: The expression of miR-148a was significantly upregulated, and miR-320 downregulated in oxytocin-treated mammary cells as well as their secreted extracellular vesicles to the media, compared with untreated cells. MiR-148a was found to be upregulated, and miR-320 was downregulated in the human colostrum of exogenous oxytocin-treated mothers. Moreover, miR-320 was highly expressed compared with miR-148a in the colostrum of mothers that did not receive exogenous oxytocin. In contrast, in the milk of mothers who received exogenous oxytocin, the expression of miRNA-148-3p was highly expressed compared with miR-320. CONCLUSIONS: This study shows that oxytocin modulates the expression of main milk-derived miRNAs. Our findings provide a novel insight into oxytocin's role in milk composition by regulating miRNA expression. Our results implicate that oxytocin increases miRNA expression in mammary epithelial cells and human milk, affecting human milk composition and may contribute to further infant health.

Recurrent Tubal Ectopic Pregnancy Management and the Risk of a Third Ectopic Pregnancy.

STUDY OBJECTIVE: To evaluate the rate of a third ectopic pregnancy according to the modality of treatment of the second ectopic pregnancy. DESIGN: Retrospective cohort study. SETTING: University-affiliated tertiary medical center. PATIENTS: One hundred eleven women who had 2 ectopic pregnancies and a third consecutive pregnancy between 2003 and 2018. INTERVENTIONS: Surgery or medical treatment as required. MEASUREMENTS AND MAIN RESULTS: With regard to the modality of treatment of the second ectopic pregnancy, the patients were divided into 3 groups: expectant management, medical treatment with methotrexate, and laparoscopic salpingectomy. Univariate and multivariate analyses were conducted to assess the association of various parameters of the second ectopic pregnancy with the occurrence of a third ectopic pregnancy in the consecutive pregnancy. Twenty women (18.0%) were managed expectantly, 55 (49.6%) were treated with methotrexate, and 36 (32.4%) underwent surgery. Expectant management resulted in significantly higher rates of a third ectopic pregnancy compared with treatment with methotrexate or surgical intervention (50.0% vs 18.2% and 13.8%, respectively; p = .005). In the cases of 2 ipsilateral ectopic pregnancies, the interventional approach (medical or surgical treatment) resulted in lower recurrence rates compared with expectant management (25.7% vs 60.0%, respectively; p = .043). CONCLUSION: The risk of a third episode of an ectopic pregnancy after expectant management of a second ectopic pregnancy is extremely high. An interventional approach by treatment with methotrexate or salpingectomy is therefore preferred for recurrent ectopic pregnancy management, especially in ipsilateral recurrences.

Laparoscopic uterosacral ligament suspension versus vaginal colposuspension using the Uphold Lite™ mesh system: clinical outcome and patient satisfaction.

INTRODUCTION AND HYPOTHESIS: The objective was to compare clinical and anatomical outcomes between laparoscopic uterosacral ligament suspension (LUSLS) and vaginal colposuspension using the Uphold Lite™ mesh system for the treatment of apical prolapse. METHODS: We performed a comparative, retrospective cohort study. All women who underwent either vaginal colposuspension with the Uphold Lite™ System or LUSLS for treatment of apical prolapse between 2010 and 2019 were included. The groups were compared with regard to demographic, pre-operative, intra-operative, and post-operative data. Outcome measures included clinical and anatomical cure, as well as a composite outcome. The PGI-I questionnaire was used to determine patient satisfaction. RESULTS: One-hundred and nineteen women met the inclusion criteria, including 70 women who underwent LUSLS and 49 women who underwent vaginal colposuspension with the Uphold Lite™ mesh system. At a mean follow-up of 31.7 (SD = 18.1) months, the clinical cure rate was high for both groups, reaching 98.6% in the LUSLS group compared with 89.8% in the Uphold group (NS). Anatomical cure rate was 83.6% in the LUSLS group compared with 69.7% for the Uphold group (NS). With regard to the composite outcome, no difference was found, although a trend towards a higher success rate was noted in the LUSLS group (83.6% vs 66.7%, p = 0.055). Patient satisfaction measured using the PGI-I questionnaire was high, at 98.6% in the LUSLS group and 87.8% in the Uphold group (NS). CONCLUSION: Laparoscopic uterosacral ligament suspension and vaginal colposuspension using the Uphold Lite™ mesh system both have high clinical cure rates.