Naama Srebnik | The Hebrew University of Jerusalem (original) (raw)

Papers by Naama Srebnik

ABSTRACTIn IVF treatments, accurate assessment of the developmental potential of embryos to impla... more ABSTRACTIn IVF treatments, accurate assessment of the developmental potential of embryos to implant is essential for reaching reasonable pregnancy rates while shortening time-to-pregnancy. Hence, clinical guidelines recommend extended incubation to blastocyst transfers, which provide better evaluation of embryo developmental potential. However, cleavage stage transfer is often favored owing to various clinical considerations. To improve embryo assessment of cleavage stage embryos without extended incubation, we present a computational strategy for forecasting future morphokinetic events. Motivated by the advances in language modeling, we adapt generative pre-training to forecast future morphokinetic events based on the sequence of present events. We demonstrate < 12% forecasting error in forecasting up to three consecutive events. A new policy is proposed that combines morphokinetic forecasting and assessment of the risk of embryo developmental arrest. Using this policy, we demon...

BMC Medicine, Feb 6, 2023

Human Reproduction, Jul 1, 2021

Study question Do preimplantation genetic testing (PGT) pregnancies have higher pregnancy and del... more Study question Do preimplantation genetic testing (PGT) pregnancies have higher pregnancy and delivery complications compared to naturally conceived (NC) pregnancies? Summary answer PGT pregnancies do not have increase pregnancy complications but do have increased post-partum complications. What is known already There is limited data about the outcome of PGT cycles regarding pregnancy complications. Previous reports show that PGT pregnancies are similar to NC pregnancies regarding birth weight and preterm delivery rate. Patients performing PGT are less likely to have infertility as a background problem, and therefore it is important to evaluate pregnancy complications in this specific population. Study design, size, duration A retrospective cohort study, between 2008–2020 in Shaare Zedek Medical center (SZMC). Demographic, background variables, treatment cycle information, and delivery data were collected from computerized hospital databases and patient files. Participants/materials, setting, methods All patients aged 18–45 that conceived following PGT treatment in the IVF unit and gave birth in SZMC were included in the study. We used two control groups: (1) women with spontaneous pregnancies (SP) who gave birth in SZMC. We used four “neighborhood control” for each PGT patient (two women delivered before and two after the case delivery). (2) pregnancies following ICSI with four neighborhood control for each. Main results and the role of chance 135 deliveries following PGT, 924 ICSI, and 4199 NC. Demographic variables were similar except PGT, and ICSI women were slightly older (30.93 ±4.33 PGT, 31.70±4.98 ICSI, 28.75±5.69 spontaneous, p &amp;lt; 0.01). PGT pregnancies had similar rates of placental complications (hypertensive disorder, preeclampsia (PET), placental abruption) as NC (p = 0.8), while ICSI pregnancies had significantly higher rates of gestational hypertension (p &amp;lt; 0.01) and abruption (p = 0.05). We found a higher rate of preterm delivery &amp;lt;37 weeks in both PGT and ICSI pregnancies (23.7%, 22.7%, 12.1%, p &amp;lt; 0.01 for PGT, ICSI, NC respectively), but only in ICSI was preterm delivery &amp;lt; 34 weeks increased (2.2% vs. 2.1%, p = 0.9, for PGT and NC, 4.3% for ICSI p &amp;lt; 0.01). Post-partum complications were more prevalent in both PGT and ICSI: longer third stage of labor (13.27±12.81, 12.58±10.08, 10.58±8.14, p &amp;lt; 0.05), manual lysis of placenta (6.7%, 2.3%, 1.4% p &amp;lt; 0.05), post-partum hemorrhage (PPH) (5.9%, 4.2%, 2.5% p = 0.02) and need for blood products (3.7%, 4.5%, 1.3% p = 0.02) for PGT, ICSI, NC respectively. The aOR for composite post-partum complications (PPH, hemoglobin drop&amp;gt;3 gram, revision or lysis) was 2.4, 95%CI [1.6–3.7]. We did not find any difference between fresh and frozen cycles in either placental complications, preterm delivery, or post-partum complications in the PGT group. Limitations, reasons for caution A single-center retrospective study. Included only pregnancies both conceived and delivered in SZMC. Wider implications of the findings: Physicians should be aware of PGT pregnancies as risk factors for post-partum placental complications and handle the third stage of the delivery with caution. Trial registration number 0351–18-SZMC

European Journal of Cancer, May 1, 2021

Breastfeeding Medicine, Feb 1, 2023

American Journal of Medical Genetics Part A

Current published guidelines for routine care of women with Prader–Willi syndrome (PWS) do not in... more Current published guidelines for routine care of women with Prader–Willi syndrome (PWS) do not include recommendations for gynecologic examinations. We describe our experience with gynecological examinations in women with PWS and offer recommendations for routine health care for these patients. Data were collected on all 41 PWS females ages ≥12 year, followed in our national Israeli multidisciplinary clinic between the years 2011 and 2022. Menstrual data and findings on external gynecological examination, including evaluation of the vulva and hymen were recorded at yearly visits. During the gynecological evaluation the topic of sexual education was discussed. Pelvic ultrasound, specifically for antral follicular count, was performed for those visiting the clinic during 2020–2022. Blood samples for luteinizing hormone (LH), follicular stimulating hormone (FSH), and estradiol were obtained routinely and DEXA scans for bone density were done when indicated. Of the 41 women, (median age...

Journal of Assisted Reproduction and Genetics

Purpose Our objective was to design an automated deep learning model that extracts the morphokine... more Purpose Our objective was to design an automated deep learning model that extracts the morphokinetic events of embryos that were recorded by time-lapse incubators. Using automated annotation, we set out to characterize the temporal heterogeneity of preimplantation development across a large number of embryos. Methods To perform a retrospective study, we used a dataset of video files of 67,707 embryos from four IVF clinics. A convolutional neural network (CNN) model was trained to assess the developmental states that appear in single frames from 20,253 manually-annotated embryos. Probability-weighted superposition of multiple predicted states was permitted, thus accounting for visual uncertainties. Superimposed embryo states were collapsed onto discrete series of morphokinetic events via monotonic regression of whole-embryo profiles. Unsupervised K-means clustering was applied to define subpopulations of embryos of distinctive morphokinetic profiles. Results We perform automated asse...

Journal of Clinical Medicine

Objective: Neonatal intensive care unit (NICU) admission among term neonates is associated with s... more Objective: Neonatal intensive care unit (NICU) admission among term neonates is associated with significant morbidity and mortality, as well as high healthcare costs. A comprehensive NICU admission risk assessment using an integrated statistical approach for this rare admission event may be used to build a risk calculation algorithm for this group of neonates prior to delivery. Methods: A single-center case–control retrospective study was conducted between August 2005 and December 2019, including in-hospital singleton live born neonates, born at ≥37 weeks’ gestation. Analyses included univariate and multivariable models combined with the machine learning gradient-boosting model (GBM). The primary aim of the study was to identify and quantify risk factors and causes of NICU admission of term neonates. Results: During the study period, 206,509 births were registered at the Shaare Zedek Medical Center. After applying the study exclusion criteria, 192,527 term neonates were included in ...

BMC Medicine

Background Neonatal intensive care unit (NICU) admission among term neonates is a rare event. The... more Background Neonatal intensive care unit (NICU) admission among term neonates is a rare event. The aim of this study was to study the association of the NICU admission of term neonates on the risk of long-term childhood mortality. Methods A single-center case–control retrospective study between 2005 and 2019, including all in-hospital ≥ 37 weeks’ gestation singleton live-born neonates. The center perinatal database was linked with the birth and death certificate registries of the Israeli Ministry of Internal Affairs. The primary aim of the study was to study the association between NICU admission and childhood mortality throughout a 15-year follow-up period. Results During the study period, 206,509 births were registered; 192,527 (93.22%) term neonates were included in the study; 5292 (2.75%) were admitted to NICU. Throughout the follow-up period, the mortality risk for term neonates admitted to the NICU remained elevated; hazard ratio (HR), 19.72 [14.66, 26.53], (p < 0.001). For ...

Journal of Assisted Reproduction and Genetics

The majority of human embryos, whether naturally or in vitro fertilized (IVF), do not poses the c... more The majority of human embryos, whether naturally or in vitro fertilized (IVF), do not poses the capacity to implant within the uterus and reach live birth. Hence, selecting the embryos with the highest developmental potential to implant is imperative for improving pregnancy rates without prolonging time to pregnancy. The developmental potential of embryos can be assessed based on temporal profiling of the discrete morphokinetic events of preimplantation development. However, manual morphokinetic annotation introduces intra- and inter-observer variation and is time-consuming. Using a large clinically-labeled multicenter dataset of video recordings of preimplantation embryo development by time-lapse incubators, we trained a convolutional neural network and developed a classifier that performs fully automated, robust, and standardized annotation of the morphokinetic events with R-square 0.994 accuracy. To delineate the morphokinetic heterogeneity of preimplantation development, we perf...

Human Reproduction, 2021

What are the success rates of social oocyte cryopreservation (SOC) at advanced age? In this study... more What are the success rates of social oocyte cryopreservation (SOC) at advanced age? In this study, one in four women who underwent SOC above age 35 had a delivery. While SOC is gaining popularity, reports on delivery rates are limited due to low utilization rates. Retrospective data collection of all woman who underwent SOC between 2011–2018, and presented for treatment using cryopreserved oocytes until January 2021. Participants/materials, setting, methods: Review of patient records (including both IVF and antenatal/postnatal) and laboratory data in a university affiliated hospital-based IVF unit. Main results and the role of chance: A total of 448 women underwent SOC during 2011–2018. 50 (11.2%) women returned to use these oocytes until the end of January 2021. Women who returned to use their oocytes underwent cryopreservation at mean age of 38.2±2.2. 46 (92%) of participants were above 35 at time of cryopreservation. Number of oocytes cryopreserved was 11.3±9.7. Mean time from cr...

Reproductive BioMedicine Online, 2021

RESEARCH QUESTION What are the reproductive choices and retrospective reflections of women at lea... more RESEARCH QUESTION What are the reproductive choices and retrospective reflections of women at least 4 years after planned oocyte cryopreservation (POC)? DESIGN This was an internet survey, using the REDCap application, of women who underwent POC, at a single-centre university-affiliated IVF unit, 4-8 years before the survey. The questionnaire addressed reproductive choices and outcomes following POC. RESULTS Seventy-nine women who underwent POC during 2011-2014 were invited to participate, and 70 (89%) responded. Mean age at cryopreservation was 37.1 ± 2.4 (range 30-41) years, mean age at study participation 42.6 ± 2.6 (range 35-48) years, and mean time from first cryopreservation cycle to study participation 5.5 ± 1.3 (range 4-8) years. The main retrospectively reported reason for POC was not wanting to become pregnant without a partner (59, 84%). During the follow-up period, 44 women (63%) attempted to conceive either naturally or by assisted reproductive technology using fresh or cryopreserved oocytes. Of those, 28 women achieved a live birth (64% of those who tried to conceive). Fourteen respondents (20% of all respondents) reported using their cryopreserved oocytes, and three (21%) achieved a birth using those oocytes. Fifteen women (34%) of those who tried to conceive used donor spermatozoa. CONCLUSIONS The most common reasons for not using frozen oocytes were achieving pregnancy without frozen oocytes or preferring not to have a child without a partner. A considerable proportion of women who had POC and were not interested in being a single parent by choice eventually try to conceive using donor spermatozoa several years later.

Reproductive BioMedicine Online, 2019

Fertility and Sterility, 2015

Journal of Clinical Medicine

Background and Aim: Polyhydramnios is associated with an increased risk of various adverse pregna... more Background and Aim: Polyhydramnios is associated with an increased risk of various adverse pregnancy outcomes, yet complications during labor have not been sufficiently studied. We assessed the labor and perinatal outcomes of idiopathic polyhydramnios during term labor. Methods: Retrospective cohort study at a tertiary medical center between 2010 and 2014. Women with idiopathic polyhydramnios defined as an amniotic fluid index (AFI) greater than 24 cm or a deep vertical pocket (DVP) > 8 cm (cases) were compared with women with a normal AFI (5–24 cm) (controls). Statistics: Descriptive, means ± SDs, medians + IQR. Comparisons: chi-square, Fisher’s exact test, Mann–Whitney Test, multivariate logistic models. Results: During the study period 11,065 women had ultrasound evaluation completed by a sonographer within two weeks of delivery. After excluding pregnancies complicated by diabetes (pre-gestational or gestational), fetal anomalies, IUFD, multifetal pregnancies, elective cesarea...

Obstetrical & Gynecological Survey

ABSTRACTIn IVF treatments, accurate assessment of the developmental potential of embryos to impla... more ABSTRACTIn IVF treatments, accurate assessment of the developmental potential of embryos to implant is essential for reaching reasonable pregnancy rates while shortening time-to-pregnancy. Hence, clinical guidelines recommend extended incubation to blastocyst transfers, which provide better evaluation of embryo developmental potential. However, cleavage stage transfer is often favored owing to various clinical considerations. To improve embryo assessment of cleavage stage embryos without extended incubation, we present a computational strategy for forecasting future morphokinetic events. Motivated by the advances in language modeling, we adapt generative pre-training to forecast future morphokinetic events based on the sequence of present events. We demonstrate < 12% forecasting error in forecasting up to three consecutive events. A new policy is proposed that combines morphokinetic forecasting and assessment of the risk of embryo developmental arrest. Using this policy, we demon...

BMC Medicine, Feb 6, 2023

Human Reproduction, Jul 1, 2021

Study question Do preimplantation genetic testing (PGT) pregnancies have higher pregnancy and del... more Study question Do preimplantation genetic testing (PGT) pregnancies have higher pregnancy and delivery complications compared to naturally conceived (NC) pregnancies? Summary answer PGT pregnancies do not have increase pregnancy complications but do have increased post-partum complications. What is known already There is limited data about the outcome of PGT cycles regarding pregnancy complications. Previous reports show that PGT pregnancies are similar to NC pregnancies regarding birth weight and preterm delivery rate. Patients performing PGT are less likely to have infertility as a background problem, and therefore it is important to evaluate pregnancy complications in this specific population. Study design, size, duration A retrospective cohort study, between 2008–2020 in Shaare Zedek Medical center (SZMC). Demographic, background variables, treatment cycle information, and delivery data were collected from computerized hospital databases and patient files. Participants/materials, setting, methods All patients aged 18–45 that conceived following PGT treatment in the IVF unit and gave birth in SZMC were included in the study. We used two control groups: (1) women with spontaneous pregnancies (SP) who gave birth in SZMC. We used four “neighborhood control” for each PGT patient (two women delivered before and two after the case delivery). (2) pregnancies following ICSI with four neighborhood control for each. Main results and the role of chance 135 deliveries following PGT, 924 ICSI, and 4199 NC. Demographic variables were similar except PGT, and ICSI women were slightly older (30.93 ±4.33 PGT, 31.70±4.98 ICSI, 28.75±5.69 spontaneous, p &amp;lt; 0.01). PGT pregnancies had similar rates of placental complications (hypertensive disorder, preeclampsia (PET), placental abruption) as NC (p = 0.8), while ICSI pregnancies had significantly higher rates of gestational hypertension (p &amp;lt; 0.01) and abruption (p = 0.05). We found a higher rate of preterm delivery &amp;lt;37 weeks in both PGT and ICSI pregnancies (23.7%, 22.7%, 12.1%, p &amp;lt; 0.01 for PGT, ICSI, NC respectively), but only in ICSI was preterm delivery &amp;lt; 34 weeks increased (2.2% vs. 2.1%, p = 0.9, for PGT and NC, 4.3% for ICSI p &amp;lt; 0.01). Post-partum complications were more prevalent in both PGT and ICSI: longer third stage of labor (13.27±12.81, 12.58±10.08, 10.58±8.14, p &amp;lt; 0.05), manual lysis of placenta (6.7%, 2.3%, 1.4% p &amp;lt; 0.05), post-partum hemorrhage (PPH) (5.9%, 4.2%, 2.5% p = 0.02) and need for blood products (3.7%, 4.5%, 1.3% p = 0.02) for PGT, ICSI, NC respectively. The aOR for composite post-partum complications (PPH, hemoglobin drop&amp;gt;3 gram, revision or lysis) was 2.4, 95%CI [1.6–3.7]. We did not find any difference between fresh and frozen cycles in either placental complications, preterm delivery, or post-partum complications in the PGT group. Limitations, reasons for caution A single-center retrospective study. Included only pregnancies both conceived and delivered in SZMC. Wider implications of the findings: Physicians should be aware of PGT pregnancies as risk factors for post-partum placental complications and handle the third stage of the delivery with caution. Trial registration number 0351–18-SZMC

European Journal of Cancer, May 1, 2021

Breastfeeding Medicine, Feb 1, 2023

American Journal of Medical Genetics Part A

Current published guidelines for routine care of women with Prader–Willi syndrome (PWS) do not in... more Current published guidelines for routine care of women with Prader–Willi syndrome (PWS) do not include recommendations for gynecologic examinations. We describe our experience with gynecological examinations in women with PWS and offer recommendations for routine health care for these patients. Data were collected on all 41 PWS females ages ≥12 year, followed in our national Israeli multidisciplinary clinic between the years 2011 and 2022. Menstrual data and findings on external gynecological examination, including evaluation of the vulva and hymen were recorded at yearly visits. During the gynecological evaluation the topic of sexual education was discussed. Pelvic ultrasound, specifically for antral follicular count, was performed for those visiting the clinic during 2020–2022. Blood samples for luteinizing hormone (LH), follicular stimulating hormone (FSH), and estradiol were obtained routinely and DEXA scans for bone density were done when indicated. Of the 41 women, (median age...

Journal of Assisted Reproduction and Genetics

Purpose Our objective was to design an automated deep learning model that extracts the morphokine... more Purpose Our objective was to design an automated deep learning model that extracts the morphokinetic events of embryos that were recorded by time-lapse incubators. Using automated annotation, we set out to characterize the temporal heterogeneity of preimplantation development across a large number of embryos. Methods To perform a retrospective study, we used a dataset of video files of 67,707 embryos from four IVF clinics. A convolutional neural network (CNN) model was trained to assess the developmental states that appear in single frames from 20,253 manually-annotated embryos. Probability-weighted superposition of multiple predicted states was permitted, thus accounting for visual uncertainties. Superimposed embryo states were collapsed onto discrete series of morphokinetic events via monotonic regression of whole-embryo profiles. Unsupervised K-means clustering was applied to define subpopulations of embryos of distinctive morphokinetic profiles. Results We perform automated asse...

Journal of Clinical Medicine

Objective: Neonatal intensive care unit (NICU) admission among term neonates is associated with s... more Objective: Neonatal intensive care unit (NICU) admission among term neonates is associated with significant morbidity and mortality, as well as high healthcare costs. A comprehensive NICU admission risk assessment using an integrated statistical approach for this rare admission event may be used to build a risk calculation algorithm for this group of neonates prior to delivery. Methods: A single-center case–control retrospective study was conducted between August 2005 and December 2019, including in-hospital singleton live born neonates, born at ≥37 weeks’ gestation. Analyses included univariate and multivariable models combined with the machine learning gradient-boosting model (GBM). The primary aim of the study was to identify and quantify risk factors and causes of NICU admission of term neonates. Results: During the study period, 206,509 births were registered at the Shaare Zedek Medical Center. After applying the study exclusion criteria, 192,527 term neonates were included in ...

BMC Medicine

Background Neonatal intensive care unit (NICU) admission among term neonates is a rare event. The... more Background Neonatal intensive care unit (NICU) admission among term neonates is a rare event. The aim of this study was to study the association of the NICU admission of term neonates on the risk of long-term childhood mortality. Methods A single-center case–control retrospective study between 2005 and 2019, including all in-hospital ≥ 37 weeks’ gestation singleton live-born neonates. The center perinatal database was linked with the birth and death certificate registries of the Israeli Ministry of Internal Affairs. The primary aim of the study was to study the association between NICU admission and childhood mortality throughout a 15-year follow-up period. Results During the study period, 206,509 births were registered; 192,527 (93.22%) term neonates were included in the study; 5292 (2.75%) were admitted to NICU. Throughout the follow-up period, the mortality risk for term neonates admitted to the NICU remained elevated; hazard ratio (HR), 19.72 [14.66, 26.53], (p < 0.001). For ...

Journal of Assisted Reproduction and Genetics

The majority of human embryos, whether naturally or in vitro fertilized (IVF), do not poses the c... more The majority of human embryos, whether naturally or in vitro fertilized (IVF), do not poses the capacity to implant within the uterus and reach live birth. Hence, selecting the embryos with the highest developmental potential to implant is imperative for improving pregnancy rates without prolonging time to pregnancy. The developmental potential of embryos can be assessed based on temporal profiling of the discrete morphokinetic events of preimplantation development. However, manual morphokinetic annotation introduces intra- and inter-observer variation and is time-consuming. Using a large clinically-labeled multicenter dataset of video recordings of preimplantation embryo development by time-lapse incubators, we trained a convolutional neural network and developed a classifier that performs fully automated, robust, and standardized annotation of the morphokinetic events with R-square 0.994 accuracy. To delineate the morphokinetic heterogeneity of preimplantation development, we perf...

Human Reproduction, 2021

What are the success rates of social oocyte cryopreservation (SOC) at advanced age? In this study... more What are the success rates of social oocyte cryopreservation (SOC) at advanced age? In this study, one in four women who underwent SOC above age 35 had a delivery. While SOC is gaining popularity, reports on delivery rates are limited due to low utilization rates. Retrospective data collection of all woman who underwent SOC between 2011–2018, and presented for treatment using cryopreserved oocytes until January 2021. Participants/materials, setting, methods: Review of patient records (including both IVF and antenatal/postnatal) and laboratory data in a university affiliated hospital-based IVF unit. Main results and the role of chance: A total of 448 women underwent SOC during 2011–2018. 50 (11.2%) women returned to use these oocytes until the end of January 2021. Women who returned to use their oocytes underwent cryopreservation at mean age of 38.2±2.2. 46 (92%) of participants were above 35 at time of cryopreservation. Number of oocytes cryopreserved was 11.3±9.7. Mean time from cr...

Reproductive BioMedicine Online, 2021

RESEARCH QUESTION What are the reproductive choices and retrospective reflections of women at lea... more RESEARCH QUESTION What are the reproductive choices and retrospective reflections of women at least 4 years after planned oocyte cryopreservation (POC)? DESIGN This was an internet survey, using the REDCap application, of women who underwent POC, at a single-centre university-affiliated IVF unit, 4-8 years before the survey. The questionnaire addressed reproductive choices and outcomes following POC. RESULTS Seventy-nine women who underwent POC during 2011-2014 were invited to participate, and 70 (89%) responded. Mean age at cryopreservation was 37.1 ± 2.4 (range 30-41) years, mean age at study participation 42.6 ± 2.6 (range 35-48) years, and mean time from first cryopreservation cycle to study participation 5.5 ± 1.3 (range 4-8) years. The main retrospectively reported reason for POC was not wanting to become pregnant without a partner (59, 84%). During the follow-up period, 44 women (63%) attempted to conceive either naturally or by assisted reproductive technology using fresh or cryopreserved oocytes. Of those, 28 women achieved a live birth (64% of those who tried to conceive). Fourteen respondents (20% of all respondents) reported using their cryopreserved oocytes, and three (21%) achieved a birth using those oocytes. Fifteen women (34%) of those who tried to conceive used donor spermatozoa. CONCLUSIONS The most common reasons for not using frozen oocytes were achieving pregnancy without frozen oocytes or preferring not to have a child without a partner. A considerable proportion of women who had POC and were not interested in being a single parent by choice eventually try to conceive using donor spermatozoa several years later.

Reproductive BioMedicine Online, 2019

Fertility and Sterility, 2015

Journal of Clinical Medicine

Background and Aim: Polyhydramnios is associated with an increased risk of various adverse pregna... more Background and Aim: Polyhydramnios is associated with an increased risk of various adverse pregnancy outcomes, yet complications during labor have not been sufficiently studied. We assessed the labor and perinatal outcomes of idiopathic polyhydramnios during term labor. Methods: Retrospective cohort study at a tertiary medical center between 2010 and 2014. Women with idiopathic polyhydramnios defined as an amniotic fluid index (AFI) greater than 24 cm or a deep vertical pocket (DVP) > 8 cm (cases) were compared with women with a normal AFI (5–24 cm) (controls). Statistics: Descriptive, means ± SDs, medians + IQR. Comparisons: chi-square, Fisher’s exact test, Mann–Whitney Test, multivariate logistic models. Results: During the study period 11,065 women had ultrasound evaluation completed by a sonographer within two weeks of delivery. After excluding pregnancies complicated by diabetes (pre-gestational or gestational), fetal anomalies, IUFD, multifetal pregnancies, elective cesarea...

Obstetrical & Gynecological Survey