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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.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.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.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.

Thyroid screening is recommended during pregnancy with serum thyrotropin (TSH) as the primary test. However, since human chorionic gonadotropin, the serum hallmark of pregnancy, has TSH-like effects, the adequacy of TSH as a screening tool in this constellation requires further study. This study aimed to evaluate the relationship between TSH and thyroid hormones during pregnancy in order to determine if TSH is an adequate screening tool. This was a retrospective study utilizing the Clalit Health Service, Jerusalem district database between 2006–2017 in which we analyzed TSH, FT4 and FT3 measurements from 32430 pregnancies resulting in live birth. We grouped FT4 and FT3 levels by trimester and by the following TSH levels: (1) below 0.1/0.2/0.3 mIU/l, (2) 0.1–2.5/0.2–3.0/0.3–3.0 mIU/l, (3) 2.6–4.0/3.1–4.0 mIU/l, (4) 4.1–10.0 mIU/l and (5) above 10.0 mIU/l. In the first trimester, the most important for fetal brain development, FT3 was below normal, defined as below the 2.5th percentile for the population, in only 15.3% of tests with TSH over 10 mIU/l. FT4 was below normal in only 12.8% of such tests. Similar findings were noted for the second and third trimesters. As expected, there were far less abnormal tests when lower TSH cutoff levels were tested. In conclusion, TSH levels beyond the range accepted as normal do not, in most cases, reflect abnormal thyroid hormone levels during pregnancy. TSH is not a good screen for overt hypothyroidism in pregnancy. This may be due, at least in the first trimester, to thyrotropic effects of HCG.

To identify risk factors for increasing severity of OASI and evaluate its possible correlation with two known risk factors-birth weight (BW) and neonatal head circumference (HC).We performed a retrospective cohort study at a university affiliated hospital between 2003 and 2019. We compared five groups of patients - according to presence and degree of perineal laceration - 3a, 3b, 3c and 4 and patients without OASI. Additionally, four parameters were defined to assess their relation to the severity of OASI: (1) BW ≥ 90th and HC 90th percentiles; (2) BW 90th and HC ≥ 90th percentile; (3) BW and HC ≥ 90th percentile and (4) BW and HC 90th percentiles.During the study period, 150,221 deliveries were evaluated. Parturients were allocated according to OASI severity - 455 patients had a 3rd (3a, 3b or 3c) or 4th degree perineal tear, while 110,966 patients had no OASI. Allocation to subgroups according to offspring anthropomorphic measures showed that as fetal size parameters increased, the rate of more severe tears increased, particularly in women delivering neonates with HC ≥ 90th percentile. Multinomial regression analysis was performed for each 3rd degree OASI subgroup. This analysis demonstrated the odds for OASI gradually increase with tear severity for BW ≥ 90th percentile and the combined BW and HC ≥ 90th percentile parameters, as compared with neonates with HC and BW 90th percentile.Birth weight and head circumference above the 90th percentile are correlated with increased degree of OASI severity.

Dilation and Curettage (DC) may be performed with or without transabdominal ultrasound guidance. We aimed to evaluate the association between the use of ultrasound guidance during DC for first-trimester missed abortion (MA) and DC related complication rates.A retrospective cohort study including women in the age of 20-45 years, who underwent DC for first-trimester MA in a hospital-based setting between 2013-2019. The study population was divided into two groups - the study group which included women who underwent DC with ultrasound guidance (US group) and the control group, which included women who underwent DC without ultrasound guidance (N-US group). Gynecologic, obstetric and operative related data were collected from electronic medical records.Three-hundred and seventy-eight women were included in the study, 86 women in the US group and 292 women in N-US group. Baseline maternal characteristics and procedure-related characteristics did not differ between the groups. No significant difference between the US group and N-US group was shown when comparing DC related complications - retained products of conception rate (2.3% vs. 5.5%, respectively; p=0.385), uterine perforation rate (1.2% vs. 0.3%, respectively; p=0.404), and the total complication rate (8.1% vs. 12.3%, respectively; p=0.338). In a multivariate analysis, the use of ultrasound guidance during DC was not found to be associated with lower complication rate (adjusted Odds Ratio (aOR) 95% confidence interval (CI) 1.468 (0.578-3.729), p=0.419).Performance of DC under ultrasound guidance for first-trimester MA, in a hospital-based setting, was not associated with lower complication rate, suggesting that the common practice of performing DC without the use of ultrasound is an acceptable approach.

Obstetric anal sphincter injury (OASI) is a debilitating complication of vaginal delivery. The aim of this study was to identify risk factors for OASI in women with a previous vaginal delivery. We further attempted to detect specific risk factors for severe OASI in this subgroup. We conducted a retrospective cohort study between 2003 and 2019. The study group included women who had a singleton, live, vertex, vaginal delivery at term and who also had at least one previous vaginal delivery. The control group included women with at least one previous vaginal delivery without OASI. General medical history, obstetric history, and ante-, intra- and post-partum data were collected and compared between groups. Following implementation of the inclusion criteria, 79,176 women were included. Allocation to study groups was according to OASI occurrence: 135 patients (0.2%) had a third- or fourth-degree perineal tear, while 79,041 patients (99.8%) had no such injury. Multivariate analysis revealed that one previous vaginal delivery, birthweight ≥ 3900 g (90th percentile), vacuum-assisted vaginal delivery and episiotomy were associated with increased risk of OASI. Comparison of more severe OASI (3C and 4th-degree) cases to the control group showed similar results with the addition of prolonged second stage and younger age to risk factors associated with severe OASI while episiotomy was no longer significant. In women with a previous vaginal delivery, one vs. two or more previous vaginal deliveries, increased birthweight, vacuum-assisted vaginal delivery and episiotomy are risk factors for OASI.

Obstetric anal sphincter injury (OASI) is a complication with substantial maternal morbidity. The aim of this study was to develop a machine learning model that would allow a personalized prediction algorithm for OASI, based on maternal and fetal variables collected at admission to labor. We performed a retrospective cohort study at a tertiary university hospital. Included were term deliveries (live, singleton, vertex). A comparison was made between women diagnosed with OASI and those without such injury. For formation of a machine learning-based model, a gradient boosting machine learning algorithm was implemented. Evaluation of the performance model was achieved using the area under the receiver-operating characteristic curve (AUC). Our cohort comprised 98,463 deliveries, of which 323 (0.3%) were diagnosed with OASI. Applying a machine learning model to data recorded during admission to labor allowed for individualized risk assessment with an AUC of 0.756 (95% CI 0.732–0.780). According to this model, a lower number of previous births, fewer pregnancies, decreased maternal weight and advanced gestational week elevated the risk for OASI. With regard to parity, women with one previous delivery had approximately 1/3 of the risk for OASI compared to nulliparous women (OR = 0.3 (0.23–0.39), p

Medical second-trimester abortion in women with prior cesarean section (CS) is becoming an increasingly common phenomenon. However, data about the safety of the procedure are limited. This study addresses this issue. Retrospective cohort single-center study, done in Hadassah Medical Center in Jerusalem, a tertiary-care university hospital. This study included 779 women who needed pregnancy termination between 13 and 26 gestational weeks. 128 women had at least one previous CS (study group), whereas 651 had no CS (reference group). Protocols used were: (1) misoprostol tablets, 800 mcg vaginally followed by 400 mcg orally every 3 h up to four oral doses, (2) Oxytocin drip. Nearly one-fourth of the women received mifepristone as a preliminary treatment for cervical ripening. The outcomes assessed included the following complications: retained placenta, bleeding with or without requiring blood transfusion, infection, cervical lacerations, uterine adhesions and uterine ruptures. Previous CS does not appear to increase the incidence of complications, excluding clinical bleeding without requiring blood transfusions (p value 0.05), which has a minimal clinical significance. Oxytocin protocol had 3.44 OR for complications, compared to misoprostol (p value 0.03, CI; 1.12- 10.52). No significant correlation was found between Misoprostol dosage and complications (Mann–Whitney U test, p value 0.057). Medical second-trimester abortions for women with prior CS should be considered a safe and effective procedure, with a low complication rate. The most serious complication is uterine rupture, which is uncommon; we recorded one case only. Misoprostol protocol should be preferred. IRB 0177-17-HMO, 5/2014.

Background It is unclear whether sperm origin, either ejaculated or testicular, in couples diagnosed with male factor infertility, affects the timing of the embryo's developmental events evaluated by time-lapse monitoring and implantation rates. Objective To examine the effect of sperm origin on embryo morphokinetics in couples diagnosed with male factor infertility. Materials and methods This study included a retrospective analysis of morphokinetic parameters performed by time-lapse monitoring between 2013 and 2017. The developmental processes and morphokinetic parameters of 419 embryos obtained from couples with male factor infertility attributed to oligo-astheno-teratozoospermia, 158 embryos derived from surgically extracted testicular spermatozoa from couples diagnosed with non-obstructive azoospermia, and 190 embryos from couples with normal ejaculated spermatozoa and female mechanical factor-related infertility, were evaluated. A comparison of morphokinetic parameters, implantation, and clinical pregnancy rates was performed between the groups with additional analysis in accordance with implantation status. Results Embryos from the normal ejaculated spermatozoa and oligo-astheno-teratozoospermia patients reached the later morphokinetic milestones-synchronous division (S3) and time to morula (tM)-faster than embryos obtained from testicular spermatozoa. Implantation rate was similar in the normal ejaculated spermatozoa and oligo-astheno-teratozoospermia groups (41.9% vs. 45.8%, NS), with higher implantation rate in the oligo-astheno-teratozoospermia group compared to the testicular spermatozoa group (45.8% vs. 33.6%, p = 0.02). Comparison of Known Implantation Data (KID) positive (KIDp) and KID negative (KIDn) embryos in each group revealed more rapid development in KIDp embryos in the normal ejaculated spermatozoa and the oligo-astheno-teratozoospermia groups, while in the testicular spermatozoa group implanted embryos reached the late morphokinetic milestones (time to 8 cell stage-t8, ECC3, S3, and tM) significantly faster than embryos that failed to implant. In a multivariate logistic regression analysis of the male factor infertility population, (oligo-astheno-teratospermia) (OR = 2.54, p = 0.003) and t8 (OR = 0.95, p = 0.027) were predictive of successful implantation. Male factor infertility embryos that reached the t8 milestone within 48-56 h had favorable implantation rates (p Discussion The study results may highlight another pathophysiology by means of which sperm origin affects embryo developmental kinetics. Selecting embryos demonstrating a faster developmental rate at t8 and specifically the 48- to 56 h interval following time of pronuclei fading (tPNf) may improve implantation rates in cases of male factor infertility. Conclusion This study showed that ejaculated spermatozoa is associated with faster late cell divisions, more rapid compaction, and higher implantation rates compared to testicular spermatozoa. Additionally, t8 is an important predictor for implantation in the male factor infertility population.

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?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.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.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.

To investigate the effect of birth weight (BW) and maternal pre-pregnancy BMI (mBMI) on blood pressure (BP) in adolescence. A Population-based cohort of 11,729 births in Jerusalem during 1974–1976, with archival data on maternal and birth characteristics was performed. Measurements at age 17 were assessed and linear regression models were used to evaluate the associations of birth characteristics with BP outcomes. BW was inversely associated with both systolic (SBP) and diastolic (DBP) BP at age 17 (SBP: B = − 0.829, p = 0.002; DBP: B = − 0.397, p = 0.033). The interaction term between BW and weight at age 17 was significant for DBP (p = 0.017) and pulse pressure (p = 0.005). mBMI yielded significant positive associations with BP, independent of BW. Our findings indicate that there are at least two distinct pathways linking early life characteristics with subsequent BP: Intrauterine growth, as reflected by BW and other genetic or environmental factors, reflected by mBMI and maternal education, contribute to offspring adolescent BP. These results warrant replication in other birth cohorts and underline the need to explore specific mechanisms that account for these associations.

Unintentional extension of uterine incision is a known complication during cesarean delivery estimated to occur in 4-8% of cesarean deliveries. The aim of this study was to examine risk factors associated with unintentional uterine incision extension and to assess which of them are independent risk factors for this condition.We conducted a retrospective cohort study at a large public university tertiary referral center between 2003 and 2017. Included were women who underwent cesarean delivery during this time period. Demographic, medical, obstetrical and surgical data were collected. The primary outcome was the presence of uterine incision extension during cesarean delivery. Secondary outcomes included detection of risk factors associated with uterine incision extension. A multivariate analysis was additionally performed to identify general and labor related risk factors for unintentional extension of uterine incision among patients that underwent cesarean delivery during second stage of labor.During the study period, 25,879 cesarean deliveries performed in our medical center were assessed. Out of them, 731 (2.8%) cases of unintended uterine incision extension were identified. Women in this group had high rates of full cervical dilatation and increased maternal hemorrhage. Assessment of incision extension direction revealed that two-thirds of extensions were lateral, mostly unilateral. Median size of the extension was 2.7 ± 1.2 cm.Independent parameters associated with unintended uterine incision extension included nulliparity, vertex presentation, epidural anesthesia and cesarean section indication. Further analysis including cesarean deliveries performed during the second stage of labor revealed 397 (15.3%) cesarean deliveries in which incision extension was noted and 2205 (84.7%) cesarean deliveries without incision extension. Following multivariate analysis performed in women who underwent cesarean delivery during second stage of labor, two independent parameters associated with unintended uterine incision extension remained significant - past cesarean delivery and failed vacuum attempt.Vacuum extraction attempt and previous cesarean delivery are independent risk factors for uterine incision extension in women undergoing cesarean delivery during the second stage of labor. We also showed the majority of these extensions to be lateral.

SummaryA time-lapse monitoring system provides a complete picture of the dynamic embryonic development process and simultaneously supplies extensive morphokinetic data. The objective of this study was to investigate whether the use of the morphokinetic parameter of time of starting blastulation (tSB) can improve the implantation rate of day-5 transferred blastocyst selected based on morphological parameters. In this retrospective study we analyzed the morphokinetics of 196 day-5 transferred blastocysts, selected solely based on morphological parameters. The interval time from intracytoplasmic sperm injection (ICSI) to time of starting blastocyst formation (tSB) was calculated for each embryo. The overall implantation rate of transferred blastocyst, selected based only on morphological parameters, was 49.2%. Implantation rate, determined retrospectively, was significantly higher (58.8% versus 42.6%, P = 0.02) for embryos with a short interval time to tSB (78–95.9 h) compared with embryos with a longer timeframe (96–114 h). Time of expanded blastocyst (tEB) post-ICSI was also significantly associated with implantation; however, this parameter was not available for all the embryos at time of transfer. When we tested only high ranked KIDScore day-3 sub-group embryos, the implantation rate was significantly higher in short interval time embryos compared with longer interval time embryos (62.2% vs. 45.5%, respectively, P = 0.02).These observations emphasize the importance of the timing of starting blastulation over blastocyst morphological parameters and may provide a preferable criterion for good morphology day-5 blastocyst selection.

While obstetric anal sphincter injury (OASI) is less frequent in parous compared to nulliparous women, it remains a major concern affecting quality of life of women worldwide. The aim of this study was to evaluate the association between birthweight (BW) difference between deliveries and risk of OASI in parous women.We performed a retrospective case-control study including parous women with at least one previous vaginal delivery who were diagnosed with OASI. The control group consisted of parous women who did not have OASI during vaginal delivery. Controls were matched in a 1:2 ratio by year of birth, maternal age, and parity. Medical history, obstetric background, and current labor-related data were compared. Further univariate and multivariable analyses were performed, assessing for risk factors for OASI.One hundred eight parous women who had a diagnosis of OASI and a control group of 216 parturients who delivered without OASI were included in the final analysis. Differences between the current BW and the preceding and maximal previous BW were evaluated. There were significantly higher rates of women who had a larger neonate with500 g difference between the current and previous BW in the OASI group than in those with no OASI (28.7% vs. 12.30%, respectively; p0.001). Following a multivariable analysis for the dependent parameter of OASI, the following parameters were found to be independently associated with OASI outcome: previous operative vaginal delivery, BW ≥ 90th percentile, and current BW ≥ 500 g compared to previous maximal BW.In parous women, neonatal BW increase between deliveries of500 g is associated with OASI.

BACKGROUND Many variables, including woman's age, embryo quality and endometrial receptivity, influence the success rate of either fresh embryo transfer (ET) or frozen-thawed ET (FT-ET) cycles. This study aims to examine whether the results of a fresh in-vitro fertilization (IVF) cycle correlate with its frozen-thawed embryos transfer outcomes. METHODS A retrospective cohort study conducted in a tertiary medical center single IVF unit between 2014-2017. The study population was comprised of women who underwent fresh ET with the remaining embryos frozen using vitrification and at least one consecutive FT-ET cycle. Comparison of FT-ET cycle's details and outcomes were assessed in relation to the outcome of preceding fresh ET cycle. RESULTS A total of 599 women underwent fresh ET and at least one consecutive FT-ET cycle. Significantly higher rates of successful FT-ET cycle outcomes were observed in the group of patients with a successful fresh cycle compared to the group with an unsuccessful fresh cycle (48.9% vs. 20.8%, P

PURPOSE: To assess the effect of high ovarian response on oocyte quality and ovarian stimulation cycle outcomes. METHODS: A retrospective cohort study conducted at three IVF units. The high ovarian response (HOR) and polycystic ovary syndrome (PCOS) with HOR (PCOS HOR) groups included 151 and 13 women who underwent controlled ovarian stimulation (COS) resulting in more than 15 retrieved oocytes, for a total of 1863 and 116 cultured embryos, respectively. The normal ovarian response (NOR) group comprised 741 women with 6–15 retrieved oocytes, resulting in 4907 cultured embryos. Data collected included fresh cycle data and pregnancy rates, in addition to annotation of morphokinetic events from time of pronuclei fading to time of initiation of blastocyst formation of embryos cultured in a time lapse incubator, including occurrence of direct unequal cleavage at first cleavage (DUC-1) (less than 5 h from two to three blastomeres). Comparison was made between morphokinetic parameters between the 3 groups. Cycle outcomes were compared in the high vs. normal ovarian response groups. RESULTS: Oocyte maturation rate was significantly lower in the HOR vs. NOR groups (56.5% vs. 90.0%, p

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 p = 0.012) to be independent risk factors for OASI. Conclusion Adolescents have similar risk for OASI compared to adults but differ in risk factors leading to OASI. Head circumference ≥ 90th percentile was found to be associated with OASI in this age group.

AIM: This study aims to examine whether early-life factors are associated with adult ovarian reserve, measured by anti-Müllerian hormone (AMH) levels. METHODS: The work is based on the Jerusalem Perinatal Study (JPS), an extensive birth cohort with detailed information on all pregnancies and deliveries in Jerusalem between 1974 and 1976. A subset of individuals participated in a follow-up study that took place between 2007 and 2009 in which they completed questionnaires and were physically examined at mean age of 32. A blood sample was additionally drawn from each participant, and AMH was measured in a sample of 239 women. The associations between each early-life factors, including birth weight, maternal pre-pregnancy weight, gestational weight gain (GWG), socioeconomic position at birth, and parental smoking during pregnancy, were assessed with AMH levels at the age of 32.Multivariable regression models were used to examine the associations with AMH, adjusting for potential confounders at birth and at the age of 32. RESULTS: Low birth weight was significantly associated with lower ovarian reserve reflected by lower levels of AMH at age 32 (range 30–36), independent of other early-life factors and after adjusting for confounders (β = 0.180, p = 0.03). CONCLUSIONS: This prospective study demonstrates the association of birth weight and adult ovarian reserve. Underlying mechanisms are yet to be fully understood.

Background Retained products of conception following delivery or early pregnancy failure are often treated by operative hysteroscopy. We aimed to evaluate reproductive and obstetric outcomes following operative hysteroscopy for treatment of retained products of conception. We also investigated the effect of time interval between operative hysteroscopy and pregnancy on these outcomes. Methods A retrospective cohort study conducted at the gynecology department of a tertiary teaching hospital between January 2012 and December 2016. Included were women who underwent operative hysteroscopy for treatment of retained products of conception and became pregnant following the procedure. Reproductive and obstetric data were retrieved from electronic medical records and by telephone questionnaire. The effect of time interval between operative hysteroscopy and pregnancy on reproductive outcomes was also evaluated by comparing women who conceived 6 months or less and women who conceived more than 6 months following surgery. Results Seventy-nine women who underwent operative hysteroscopy for treatment of retained products of conception and who conceived later were included. Mean time from women's attempt to conceive to conception was 4.6 (SD=6.4) months. Conception rate was 84.8% at 6 months and reached 92.4% at 12 months postsurgery. Miscarriage rate for the consecutive pregnancy following hysteroscopy was 15.2% and delivery rate was 84.8%. Two cases of obstetric complications including one case of retained placenta and one case of post-partum hemorrhage were noted. Time interval between operative hysteroscopy and pregnancy did not affect reproductive or obstetric outcomes. Conclusions Women treated by operative hysteroscopy for retained products of conception have no negative reproductive and obstetric outcomes. Time interval between the procedure and pregnancy has no effect on these outcomes.

Study question Does human oocytes in-vitro maturation (IVM) effectiveness change throughout childhood, adolescence and adulthood in girls and women undergoing fertility preservation via ovarian tissue cryopreservation (OTC) prior to chemo-radiotherapy exposure? Summary answer The optimal age for IVM is from menarche to 25 years, while pre-menarche girls and women older than 30 years have extremely low maturation rates. What is known already In vitro maturation of oocytes from antral follicles seen during tissue harvesting is a fertility preservation technique with potential advantages over 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 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. Study design, size, duration 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 between 2003 and 2020 in a university affiliated tertiary center. Participants/materials, setting, methods A total of 133 chemotherapy naïve patients aged 1–35 years with attempted IVM were included in the study. The primary outcome was IVM rate in the different age groups – pre-menarche (1–5 years and ≥6 years), post-menarche (menarche–17 years), young adults (18–24 years) and adults (25–29 and 30–35 years). Comparison between paired groups for significant difference in the IVM rate parameter was done using the Tukey’s Studentized Range (HSD) Test. Main results and the role of chance A gradual increase in mean IVM rate was demonstrated in the age groups over 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 Limitations, reasons for caution Data regarding ovarian reserve evaluation was not available for most of the patients, due to our pre-op OTC procedures protocol. None of our patients have used their frozen in-vitro matured oocytes, as such further implications of age on in-vitro matured oocytes quality and implantation potential has yet to be evaluated. Wider implications of the findings: Our finding of extremely low success rates in those very young (under 6 years) and older (≥30 years) patients suggest that IVM of oocyte retrieved during OTC prior to chemotherapy should not be attempted in these age group. Trial registration number N/A

Study question Does high ovarian response to controlled ovarian stimulation (COS) have a negative effect on oocyte quality? Summary answer High ovarian response is associated with reduced oocyte quality manifested as higher fraction of immature oocytes and higher rate of direct uneven cleavage (DUC) embryos. What is known already The literature regarding the effect of ovarian hyperstimulation on oocyte quality is limited and controversial. Results from several studies suggest that hyper response to controlled ovarian stimulation has a detrimental effect on oocyte and embryo quality, while others failed to confirm the existence of a direct toxic effect on oocyte and embryo quality. The association between temporal embryonal milestones and implantation rate has been previously demonstrated ,offering an additive tool by which oocyte quality, represented by embryo dynamics, can be evaluated. None of the aforementioned studies, however, used time lapse monitoring (TLM) system to evaluate oocyte and embryo quality. Study design, size, duration This study included a retrospective assessment of morphokinetic parameters performed by TLM from three university affiliated medical centers between January 2014 and December 2019. The developmental process and kinetics of 1863 embryos obtained from the study group, referred as the “ high ovarian response” (HOR) group, was compared to 4907 embryos from the control group - the “normal ovarian response” (NOR) group. Participants/materials, setting, methods The study included patients younger than 38 years who underwent COS with consecutive aspiration of either more than 15 oocytes (the HOR group) or 6–15 oocytes (the NOR group). A comparison was made between the groups regarding morphokinetic parameters, including the rate of embryos manifesting direct uneven cleavage (DUC) at first cleavage (DUC–1), as well as implantation and pregnancy rates. Logistic regression was conducted to assess the association between patients’ characteristics and implantation rate. Main results and the role of chance Oocyte maturation rate was significantly lower, and the DUC–1 embryos rate was significantly higher in the high ovarian response group compared to the normal ovarian response group (56.5% Vs 90.0%, p Limitations, reasons for caution The groups were not homogenous in their basic characteristics. Important information regarding the maximal dose of GT obtained, previous IVF response and ovarian reserve testing was lacking Wider implications of the findings: Higher oocyte quantity might have an effect on oocyte quality manifested as higher fraction of incompetent oocytes and higher rate of DUC–1 embryos. Once beyond the preliminary developmental stages, embryos from both groups reach the morphokinetic milestones at a similar rate and display similar implantation and pregnancy rates. Trial registration number Not applicable

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.This study aimed to examine the association between the booster dose of the SARS CoV-2 vaccination during pregnancy and obstetrical outcomes.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.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.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.

Obstetric anal sphincter injury (OASI) is a debilitating complication of vaginal delivery. The aim of this study was to identify risk factors for OASI in women with a previous vaginal delivery. We further attempted to detect specific risk factors for severe OASI in this subgroup.We conducted a retrospective cohort study between 2003 and 2019. The study group included women who had a singleton, live, vertex, vaginal delivery at term and who also had at least one previous vaginal delivery. The control group included women with at least one previous vaginal delivery without OASI. General medical history, obstetric history, and ante-, intra- and post-partum data were collected and compared between groups.Following implementation of the inclusion criteria, 79,176 women were included. Allocation to study groups was according to OASI occurrence: 135 patients (0.2%) had a third- or fourth-degree perineal tear, while 79,041 patients (99.8%) had no such injury. Multivariate analysis revealed that one previous vaginal delivery, birthweight ≥ 3900 g (90th percentile), vacuum-assisted vaginal delivery and episiotomy were associated with increased risk of OASI. Comparison of more severe OASI (3C and 4th-degree) cases to the control group showed similar results with the addition of prolonged second stage and younger age to risk factors associated with severe OASI while episiotomy was no longer significant.In women with a previous vaginal delivery, one vs. two or more previous vaginal deliveries, increased birthweight, vacuum-assisted vaginal delivery and episiotomy are risk factors for OASI.

Objective To assess the impact of the COVID-19 pandemic on the activity of a tertiary fertility service and compare telemedicine and face-to-face meetings during this time. Methods This was a retrospective cohort study conducted in a university affiliated tertiary medical center. Included were patients scheduled for an appointment in the in-vitro fertilization (IVF) unit between March 18th and April 15th. A comparison was made between patients who chose telemedicine as opposed to face-to-face meetings. Additionally, the population of patients who chose to cancel their appointment was characterized. IVF cycle outcomes were additionally compared between the groups. Results Overall, 90 IVF clinic appointments were scheduled during the study period. Thirty-four (37.8 %) patients chose to arrive to the clinic in spite of the COVID 19 pandemic and partial quarantine, 27 (30.0 %) patients chose to avoid in person meeting and scheduled a telemedicine appointment and 29 (32.2 %) patients cancelled their appointment. On comparison between patients who chose telemedicine vs. face-to-face meeting, the telemedicine group had lower prevalence of primary infertility (20.0 % vs. 47.1 %, p = 0.037) and higher rates of preimplantation genetic testing indication for in-vitro fertilization (48.2 % vs. 20.6 %, p = 0.026). Rate of a first-ever clinic visit was higher in patients that arrived for a face-to-face meeting, as compared to telemedicine encounter (55.9 % vs. 28.0 %, respectively; p = 0.036). Patients that opted to avoid attending the clinic or meeting via telemedicine had higher rates of medical comorbidities compared to patients who chose to attend their appointment (51.7 % vs. 29.5 %, p = 0.016). Rate of appointments that led to fresh or frozen-thawed embryo transfer and these transfers' outcomes (clinical pregnancy rate) were similar in the telemedicine and face-to-face meeting groups (72.2 % vs. 88.0 % and 30.8 % vs. 31.8 %, p = 0.73 and p = 1.00; respectively). Conclusion Telemedicine is a valuable tool for delivering fertility care during the COVID-19 pandemic. There is need to determine which patients will benefit most from this modality.

PURPOSE: To assess oocyte quality in young patients with decreased ovarian response to controlled ovarian stimulation using time-lapse analysis. METHODS: A retrospective cohort study conducted at five medical centers between 2013 and 2017. The “decreased ovarian response” (DOR) group consisted of 241 women who underwent controlled ovarian stimulation with ≤ 5 retrieved oocytes and 519 cultured embryos. The “normal response” (NOR) group consisted of 667 women with ≥ 6 retrieved oocytes resulting in 3633 embryos. Data included annotation of morphokinetic events of embryos cultured in a time-lapse incubator from time of pronuclei appearance to time of starting blastocyst formation (tSB). Comparison was made between morphokinetic parameters of DOR and NOR patients with additional subgroup analysis according to the implantation status. RESULTS: Implantation and clinical pregnancy rates were significantly higher in the NOR group compared with the DOR group (44.5% vs. 31.6% and 51.5% vs. 37.7%, respectively; p < 0.05). Embryos from the DOR group reached the morphokinetic milestones later than embryos obtained from NOR patients. In the DOR group, implanted embryos reached starting blastocyst formation (tSB) faster than embryos which failed to be implanted, however, manifested a protracted course compared with implanted embryos from the NOR group. In a multivariate analysis—decreased ovarian response, nulliparity, number of transferred embryos, and t4, and were predictive for implantation. CONCLUSIONS: The quantitative decrease in ovarian response is associated with reduced oocyte quality, reflected by a slower developmental rate and lower implantation and pregnancy rates. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02113-4.

Urinary bladder injury during cesarean delivery is an uncommon complication with substantial maternal morbidity. The aim of this study was to identify possible risk factors for bladder injury during cesarean delivery and to describe the role of retrograde bladder filling in the assessment of bladder wall integrity. A retrospective cohort study at a large tertiary referral center. Women who underwent cesarean delivery between 2003 and 2017 were included. Women diagnosed with urinary bladder injury were compared to women who did not have such injuries. Data retrieved included demographic characteristics, general medical history, obstetric history and intra-partum and intra-operative data. Information regarding use of retrograde bladder filling intra-operatively was retrieved as well. During the study period, 21,177 cesarean deliveries were performed of which 68 (0.3%) cases of urinary bladder injury were identified. Two-thirds of injuries were located at the urinary bladder dome with the remaining third located at the posterior bladder wall. Most injuries were formed during uterine incision extension (60.0%) followed by peritoneal entry (22.0%). Following uni- and multivariate analyses, three parameters remained independent risk factors for bladder injury: urinary bladder adhesions, failed vacuum attempt prior to cesarean delivery and size of the uterine incision extension. In 15.4% of cases in which retrograde bladder filling was utilized following bladder repair, leakage of fluid was evident. Urinary bladder adhesions, failed vacuum attempt prior to cesarean delivery and size of uterine incision extension are independent risk factors for urinary bladder injury during cesarean delivery.

Obstetric anal sphincter injury (OASI) is a complication with substantial maternal morbidity. The aim of this study was to develop a machine learning model that would allow a personalized prediction algorithm for OASI, based on maternal and fetal variables collected at admission to labor.We performed a retrospective cohort study at a tertiary university hospital. Included were term deliveries (live, singleton, vertex). A comparison was made between women diagnosed with OASI and those without such injury. For formation of a machine learning-based model, a gradient boosting machine learning algorithm was implemented. Evaluation of the performance model was achieved using the area under the receiver-operating characteristic curve (AUC).Our cohort comprised 98,463 deliveries, of which 323 (0.3%) were diagnosed with OASI. Applying a machine learning model to data recorded during admission to labor allowed for individualized risk assessment with an AUC of 0.756 (95% CI 0.732-0.780). According to this model, a lower number of previous births, fewer pregnancies, decreased maternal weight and advanced gestational week elevated the risk for OASI. With regard to parity, women with one previous delivery had approximately 1/3 of the risk for OASI compared to nulliparous women (OR = 0.3 (0.23-0.39), p 0.001), and women with two previous deliveries had 1/3 of the risk compared to women with one previous delivery (OR = 0.35 (0.21-0.60), p 0.001).Our machine learning-based model stratified births to high or low risk for OASI, making it an applicable tool for personalized decision-making upon admission to labor.

Subgaleal hemorrhage (SGH) is a rare neonatal condition, mainly associated with instrumental delivery, mainly vacuum extractor (VE). The aim of this study was to develop a machine learning model that would allow a personalized prediction algorithm for Subgaleal hemorrhage (SGH) following vacuum extraction (VE), based on maternal and fetal variables collected during the first stage of labor.A retrospective cohort study on data from a university affiliated hospital, recorded between January 2013 and February 2017. Balanced random forest algorithm was used to develop a machine learning model to predict personalized risk of the neonate developing SGH, in the eventuality that vacuum extraction was used during delivery.During the study period, 35,552 term, singleton spontaneous or induced trials of labor deliveries were included in this study. Neonatal SGH following vacuum extraction (SGH-VE) occurred in 109 cases (0.3%). Two machine learning models were developed: a proof of concept model (model A), based on a cohort limited to the (n=2955) instances of vacuum extraction, and the clinical support model (model B), based on all spontaneous or induced trials of labor (n=35,552). The models stratified parturients into high- and low-risk groups for development of SGH-VE. Model A showed a 2-fold increase in the high-risk group of parturients compared to the low risk group (OR=2.76, CI 95% 1.85-4.11). In model B, a 4-fold increase in the odds of SGH was observed in the high-risk group of parturients compared to the low risk group (OR=4.2, CI 2.2-8.1), while identifying 90.8% (99/109) of the SGH cases.Our machine learning-based model stratified births to high or low risk for SGH, making it an applicable tool for personalized decision-making during labor regarding the application of VE. This model may contribute to improved neonatal outcomes.

While the ratio of male to female births (sex-ratio at birth [SRB]) in humans is remarkably stable on the population level, there are many families with multiple same-sex offspring.To identify a putative sub-population with skewed SRB and explore potential factors affecting the SRB.A retrospective cohort study including 66,054 families with up to nine same-sex offspring evaluated between 2003 and 2015 at Hadassah-Hebrew University Medical Center. Outcome measures were observed prevalence and SRB of families with up to nine same-sex offspring in a single family. Analyses included the effect of parity, month and year of delivery, inter-delivery interval, and presence of a sequence of previous same-sex offspring on the SRB.The study comprised 193,411 live-born babies with SRB of 1.057 in favor of males. The proportion of SRB in families with up to nine same-sex offspring did not differ from the calculated presumed proportion. Furthermore, none of the tested factors (parity, month and year of delivery, inter-delivery interval, and the sequence of previous same-sex offspring) were significantly associated with SRB.SRB was not associated with any of the tested demographic characteristics. We could not identify a skew in SRB even in families with up to nine consecutive same sex offspring. This finding suggests that in the majority of the population the chance of a male or female fetus in each pregnancy remains similar in every pregnancy, regardless of any of the tested variables.

Urinary bladder injury during cesarean delivery is an uncommon complication with substantial maternal morbidity. The aim of this study was to identify possible risk factors for bladder injury during cesarean delivery and to describe the role of retrograde bladder filling in the assessment of bladder wall integrity.A retrospective cohort study at a large tertiary referral center. Women who underwent cesarean delivery between 2003 and 2017 were included. Women diagnosed with urinary bladder injury were compared to women who did not have such injuries. Data retrieved included demographic characteristics, general medical history, obstetric history and intra-partum and intra-operative data. Information regarding use of retrograde bladder filling intra-operatively was retrieved as well.During the study period, 21,177 cesarean deliveries were performed of which 68 (0.3%) cases of urinary bladder injury were identified. Two-thirds of injuries were located at the urinary bladder dome with the remaining third located at the posterior bladder wall. Most injuries were formed during uterine incision extension (60.0%) followed by peritoneal entry (22.0%). Following uni- and multivariate analyses, three parameters remained independent risk factors for bladder injury: urinary bladder adhesions, failed vacuum attempt prior to cesarean delivery and size of the uterine incision extension. In 15.4% of cases in which retrograde bladder filling was utilized following bladder repair, leakage of fluid was evident.Urinary bladder adhesions, failed vacuum attempt prior to cesarean delivery and size of uterine incision extension are independent risk factors for urinary bladder injury during cesarean delivery.

Objectives To determine if PF-88, a reverse thermo-responsive polymer designed to create a gel at body temperature and liquefy at a lower temperature (21°C) can reversibly occlude the fallopian tubes in rabbits. Study design Mature female New Zealand White rabbits underwent laparotomy and placement of 22-gage catheter into the lumen of the distil uterine horns for evaluation of tubal patency by fluoroscopy using radio opaque contrast and treatment with PF-88. In the Acute Phase group (n = 5) after PF-88 treatment we immediately cooled the serosal surface of the tube with ice for 90 seconds to liquify the gel then reassessed patency. In the Survival Phase groups, animals recovered from the initial surgery and then underwent a second procedure for evaluation of tubal occlusion and reversibility at 4 (n = 3), 14 (n = 2), and 28 (n = 3) weeks after the initial procedure. We compared the histologic appearance of the treated fallopian tubes to untreated controls (n = 3). Results In the Acute Phase, we found all 10 fallopian tubes patent on initial evaluation, occluded following treatment with PF88, and patent following re-liquification by chilling. Animals in the Survival Group, all but one of the treated tubes appeared blocked at follow-up and patent following chilling. The treatment failure occurred in an animal in the 4-week group. Tubes treated with PF88 showed no histologic evidence of residual material or damage after removal of the polymer. Conclusion The PF-88 reverse thermo-responsive polymer demonstrated the ability to reversibly block fallopian tubes for up to 28 weeks. Implications The demonstration of reversible occlusion of the fallopian tube of rabbits using PF-88, a thermo-responsive reverse polymer, support additional studies to evaluate the potential of this polymer as a contraceptive in women.

Background: Many variables, including woman`s age, embryo quality and endometrial receptivity, influence the success rate of either fresh embryo transfer (ET) or frozen-thawed ET (FT-ET) cycles. The aim of this study is to examine whether the results of a fresh in-vitro fertilization (IVF) cycle correlates with its frozen-thawed embryos transfer outcomes. Methods: A retrospective cohort study conducted in a tertiary medical center single IVF unit between 2014 and 2017. The study population was comprised of women who underwent fresh ET with the remaining embryos frozen using vitrification and at least one consecutive FT-ET cycle. Comparison of FT-ET cycle's details and outcomes were assessed in relation to the outcome of the preceding fresh ET cycle . Results: A total of 599 women underwent fresh ET and at least one consecutive FT-ET cycle. Significantly higher rates of successful FT-ET cycle outcomes were observed in the group of patients with a successful fresh cycle compared to the group with an unsuccessful fresh cycle (48.9% vs. 20.8%, p

Sperm quality in lymphoma patients may be reduced even prior to initiation of chemotherapy. The objective of this study was to examine the relationship between lymphoma prognostic factors and sperm quality prior to chemotherapy. A retrospective cohort study was conducted in a Hadassah Medical Center sperm bank and the Hematology department. The cohort included 101 Hodgkin's and 90 non-Hodgkin's lymphoma patients that underwent sperm cryopreservation before chemotherapy between 1998 and 2015. Known lymphoma prognostic factors were compared between patients with normal and impaired sperm parameters. The Prognostic Score Ratio (PSR), an index representing the number of negative lymphoma prognostic measures that found in a lymphoma patient, was additionally calculated and compared between the groups. Among the prognostic factors of lymphoma, the following factors were found to be associated with impaired sperm parameters-low albumin (p < 0.001) and haemoglobin (p < 0.001) levels, B symptoms (p = 0.021) and PSR (p < 0.001). Logistic regression showed significant association of albumin and haemoglobin with reduced sperm quality (OR = 2.7 and OR = 13.5, p < 0.05; respectively). To conclude, low albumin and haemoglobin levels are related to reduced sperm quality. The linkage between these prognostic factors and sperm quality may be related to a general inflammatory status.

In euthyroidism, as thyroid Stimulating hormone (TSH) levels increase, the free triiodothyronine (FT3) to free thyroxine (FT4) ratio increases. The aim of this study was to assess if beyond the euthyroid range of TSH levels FT3/FT4 ratio continues to increase and if levothyroxine treatment reduces this ratio, possibly through TSH suppression. This cross sectional retrospective study included a total of 77 832 patients [age 22.76±15.17 years (4 days to 112 years)] evaluated and treated in community clinics between January 2009 and September 2013. Blood samples drawn in community clinics for which TSH, FT4, FT3, age, and gender were available were included. Tests with TSH below 0.5 IU/l were excluded as were samples taken during pregnancy. The FT3/FT4 ratio continued to increase significantly even with TSH above 50 mIU/l (p for trend