Evaluating the heterogeneous effect of extended culture to blastocyst transfer on the implantation outcome via causal inference in fresh ICSI cycles.

PURPOSE: In IVF treatments, extended culture to single blastocyst transfer is the recommended protocol over cleavage-stage transfer. However, evidence-based criteria for assessing the heterogeneous implications on implantation outcomes are lacking. The purpose of this work is to estimate the causal effect of blastocyst transfer on implantation outcome. METHODS: We fit a causal forest model using a multicenter observational dataset that includes an exogenous source of variability in treatment assignment and has a strong claim for satisfying the assumptions needed for valid causal inference from observational data. RESULTS: We quantified the probability difference in embryo implantation if transferred as a blastocyst versus cleavage stage. Blastocyst transfer increased the average implantation rate; however, we revealed a subpopulation of embryos whose implantation potential is predicted to increase via cleavage-stage transfer. CONCLUSION: Relative to the current policy, the proposed embryo transfer policy retrospectively improves implantation rate from 0.2 to 0.27. Our work demonstrates the efficacy of implementing causal inference in reproductive medicine and motivates its utilization in medical disciplines that are dominated by retrospective datasets.

The White Blood Cell Count in Laboring Women at Term Is Associated with Neonatal Macrosomia.

BACKGROUND: Fetal weight estimation at term is a challenging clinical task. OBJECTIVES: To evaluate the association between peripheral white blood cell (WBC) count of the laboring women and neonatal birth weight (BW) for term uncomplicated pregnancies. METHODS: We conducted a single-center, retrospective cohort study (2006-2021) of women admitted in the first stage of labor or planned cesarean delivery. Complete blood counts were collected at admission. BW groups were categorized by weight (grams): < 2500 (group A), 2500-3499 (group B), 3500-4000 (group C), and > 4000 (group D). Two study periods were used to evaluate the association between WBC count and neonatal BW. RESULTS: There were a total of 98,632 deliveries. The dataset analyses showed a lower WBC count that was significantly and linearly associated with a higher BW; P for trend < 0.001 for women in labor. The most significant association was noted for the > 4000-gram newborns; adjusted odds ratio 0.97, 95% confidence interval 0.96-0.98; P < 0.001; adjusted for hemoglobin level, gestational age, and fetal sex. The 2018-2021 dataset analyses revealed WBC as an independent predictor of macrosomia with a significant incremental predictive value (P < 0.0001). The negative predictive value of the WBC count for macrosomia was significantly high, 93.85% for a threshold of WBC < 10.25 × 103/µl. CONCLUSIONS: WBC count should be considered to support the in-labor fetal weight estimation, especially valuable for the macrosomic fetus.

Neonatal intensive care admission for term neonates and subsequent childhood mortality: a retrospective linkage study.

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 all term neonates, the mortality rate was 0.16% (n = 311); 47.9% (n = 149) of those had records of a NICU admission. The mortality rate by time points (ratio1:10,0000 births) related to the age at death during the follow-up period was as follows: 29, up to 7 days; 20, 7-28 days; 37, 28 days to 6 months; 21, 6 months to 1 year; 19, 1-2 years; 9, 2-3 years; 10, 3-4 years; and 27, 4 years and more. Following the exclusion of congenital malformations and chromosomal abnormalities, NICU admission remained the most significant risk factor associated with mortality of the study population, HRs, 364.4 [145.3; 913.3] for mortality in the first 7 days of life; 19.6 [12.1; 32.0] for mortality from 28 days through 6 months of life and remained markedly elevated after age 4 years; HR, 7.1 [3.0; 17.0]. The mortality risk related to the NICU admission event, adjusted for admission diagnoses remained significant; HR = 8.21 [5.43; 12.4]. CONCLUSIONS: NICU admission for term neonates is a pondering event for the risk of long-term childhood mortality. This group of term neonates may benefit from focused health care.

The importance of gynecological examination in adolescent girls and adult women with Prader-Willi syndrome.

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 at start of follow-up 17 years, range [12.3-39], BMI 30.4 kg/m2 [IQR 23.5-37.1]), 39 women agreed to external gynecological examination. Eleven women (27%) had spontaneous menses, with menarche at the age of 14 to as late as 31 years. The hymen was intact in all except one. Poor hygiene was observed in eight women, three women with vulvovaginitis, and five with irritated vulva related to poor hygiene. Gynecological ultrasound was performed in 27 women. In 22, endometrial thickness was less than 5 mm. The median antral follicular count (AFC) was 6 (<10th percentile for age). No correlation between AFC and menstruation or BMI was found. Mean FSH level was 5.7 ± 3.6 IU, LH was 2.29 ± 2.23, and estradiol was 128 ± 76 pmol/L. Data on DEXA measurements were available in 25 women aged 16-39. Median spine T score was -1.3 (range between 0.5 and -3.7), and hip T score was -1.2 (range between 0.8 and -3.3). A negative correlation was found between endometrial thickness and the presence of osteopenia or osteoporosis (r = -0.5, p = 0.013). Despite our recommendations, only eight of 14 women agreed to hormonal treatment or contraception. One woman who received treatment had a thromboembolic event. Routine health care for women with PWS should include gynecological examinations. The gynecological evaluation should include external genital examination, assessment of hygiene, obtaining a blood sample for hormone levels, and documenting a history of sexual experience or sexual abuse. Hormonal treatment or contraception should be offered when appropriate.

PGT pregnancies have a similar risk for post-partum complications as naturally conceived pregnancies.

RESEARCH QUESTION: Do preimplantation genetic testing (PGT) pregnancies have higher post-partum complications compared with naturally conceived pregnancies? DESIGN: Retrospective cohort study conducted in 2008-2020 at the Shaare Zedek Medical Center (SZMC), including all patients aged 18-45 years old who conceived following PGT with a singleton live birth >24 weeks. Data were collected from computerized hospital databases and patient files. There were two control groups: (i) pregnancies following IVF-ICSI (intracytoplasmic sperm injection); (ii) four neighbourhood controls for each case delivery (two women delivered before and two after) of women with naturally conceived pregnancies. RESULTS: Overall, 120 PGT, 779 IVF-ICSI and 3507 naturally conceived deliveries were included. Demographic variables were similar apart from slightly higher age in the PGT (P = 0.003) and ICSI (P = 0.002) groups (31.07 ± 4.38 PGT, 31.66 ± 5.03 ICSI, 28.77 ± 5.72 naturally conceived). Composite post-partum placental-related complications (manual lysis of placenta, revision of uterine cavity, haemoglobin drop ≥3 g/dl, post-partum haemorrhage, need for blood transfusion) were more prevalent in both the PGT and IVF-ICSI groups as opposed to naturally conceived (20.0% versus 18.9% versus 10.3%, respectively, P < 0.001, P = 0.007). In a multivariate regression model PGT was not found to be independently associated with composite post-partum placental-related complications (adjusted odds ratio [aOR] 1.44, 95% confidence interval [CI] 0.83-2.15), while IVF-ICSI pregnancies had increased risk (aOR 1.52, 95% CI 1.20-1.97) compared with natural conception. No difference was found between fresh and frozen cycles or between day 3 and day 5 embryo transfer. CONCLUSIONS: PGT pregnancies have a comparable risk of post-partum placental-related complications to naturally conceived pregnancies, unlike IVF-ICSI pregnancies. It is possible that infertility itself is the main mediator for post-partum complications in IVF-ICSI pregnancies.

Embryo classification beyond pregnancy: early prediction of first trimester miscarriage using machine learning.

PURPOSE: First trimester miscarriage is a major concern in IVF-ET treatments, accounting for one out of nine clinical pregnancies and for up to one out of three recognized pregnancies. To develop a machine learning classifier for predicting the risk of cleavage-stage embryos to undergo first trimester miscarriage based on time-lapse images of preimplantation development. METHODS: Retrospective study of a 4-year multi-center cohort of 391 women undergoing intra-cytoplasmatic sperm injection (ICSI) and fresh single or double embryo transfers. The study included embryos with positive indication of clinical implantation based on gestational sac visualization either with first trimester miscarriage or live-birth outcome. Miscarriage was determined based on negative fetal heartbeat indication during the first trimester. Data were recorded and obtained in hospital setting and research was performed in university setting. RESULTS: A minimal subset of six non-redundant morphodynamic features were screened that maintained high prediction capacity. Features that account for the distribution of the nucleolus precursor bodies within the small pronucleus and pronuclei dynamics were highly predictive of miscarriage outcome as evaluated using the SHapley Additive exPlanations (SHAP) methodology. Using this feature subset, XGBoost and random forest models were trained following a 100-fold Monte-Carlo cross validation scheme. Miscarriage was predicted with AUC 0.68 to 0.69. CONCLUSION: We report the development of a decision-support tool for identifying the embryos with high risk of miscarriage. Prioritizing embryos for transfer based on their predicted risk of miscarriage in combination with their predicted implantation potential is expected to improve live-birth rates and shorten time-to-pregnancy.

Delineating the heterogeneity of embryo preimplantation development using automated and accurate morphokinetic annotation.

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 assessment of single-frame embryo states with 97% accuracy and demonstrate whole-embryo morphokinetic annotation with R-square 0.994. High quality embryos that had been valid candidates for transfer were clustered into nine subpopulations, as characterized by distinctive developmental dynamics. Retrospective comparative analysis of transfer versus implantation rates reveals differences between embryo clusters as marked by poor synchronization of the third mitotic cell-cleavage cycle. CONCLUSIONS: By demonstrating fully automated, accurate, and standardized morphokinetic annotation of time-lapse embryo recordings from IVF clinics, we provide practical means to overcome current limitations that hinder the implementation of morphokinetic decision-support tools within clinical IVF settings due to inter-observer and intra-observer manual annotation variations and workload constrains. Furthermore, our work provides a platform to address embryo heterogeneity using dimensionality-reduced morphokinetic descriptions of preimplantation development.

Extended fertility at highly advanced reproductive age is not related to anti-Müllerian hormone concentrations.

RESEARCH QUESTION: Is extended fertility at the advanced reproductive age of 43-47 years associated with high anti-Müllerian hormone (AMH) concentrations? DESIGN: Prospective cohort study including 98 women aged 43-47 years old with a spontaneous conception who were tested for AMH concentrations 1-4 days and 3-11 months post-partum. AMH concentrations at 3-11 months post-partum were further compared with AMH concentrations in healthy age-matched controls that last gave birth at ≤42 years old. Women with current use of combined hormonal contraceptives (CHC), ovarian insult or polycystic ovary syndrome were excluded. Power analysis supported the number of participating women. RESULTS: Median AMH concentrations did not differ between the extended fertility (n = 40) and control (n = 58) groups (0.50 versus 0.45 ng/ml, P = 0.51). This remained when analysing by age (≥ or <45 years old). AMH concentrations and women's age did not correlate within the extended fertility group (r = 0.017, P = 0.92); a weak negative correlation was found within the control group (r = -0.23, P = 0.08). AMH was significantly higher 3-11 months post-partum (0.50 ng/ml [0.21-1.23]) than 1-4 days post-partum (0.18 ng/ml [0.06-0.40]), P < 0.001. The two results for each participant were highly correlated (r = 0.82, P < 0.001). The extended fertility and control groups were similar regarding age, age at menarche, past CHC use and history of fertility concern. Parity differed but showed no significant correlation with AMH. CONCLUSIONS: Serum AMH concentrations that reflect ovarian reserve do not seem to predict reproductive potential at highly advanced age. Thus, additional factors such as oocyte quality should also be considered in evaluating reproductive potential. AMH suppression that is associated with pregnancy at 1-4 days post-partum recovers at 3-11 months post-partum in women of highly advanced reproductive age.

Clinical outcome of planned oocyte cryopreservation at advanced age.

PURPOSE: To report outcome of planned oocyte cryopreservation (POC) in the first 8 years of this treatment in our center. METHODS: A retrospective study in a university-affiliated medical center. RESULTS: A total of 446 women underwent POC during 2011-2018. Fifty-seven (13%) women presented to use these oocytes during the study period (until June 2021). POC was performed at a mean age of 37.9 ± 2.0 (range 33-41). Age at thawing was 43.3 ± 2.1 (range 38-49). A total of 34 (60%) women transferred their oocytes for thawing at other units. Oocyte survival after thawing was significantly higher at our center than following shipping to ancillary sites (78 vs. 63%, p = 0.047). Forty-nine women completed their treatment, either depleting their cryopreserved oocytes without conceiving (36) or attaining a live birth (13)-27% live birth rate per woman. Only one of eleven women who cryopreserved oocytes aged 40 and older had a live birth using thawed oocytes. CONCLUSION: Women should be advised to complete planned oocyte cryopreservation before age 40, given low success rates in women who underwent cryopreservation at advanced reproductive age. In this study, oocyte shipping was associated with lower survival rate. These findings may be relevant for women considering POC and utilization of cryopreserved oocytes.

Intrapartum fetal monitoring and perinatal risk factors of neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) in term infants, is a major cause of neonatal mortality and severe neurologic disability. OBJECTIVES: To identify in labor fetal monitoring characteristic patterns and perinatal factors associated with neonatal HIE. STUDY DESIGN: Single-center retrospective case-control study between 2010 and 2017. Cases clinically diagnosed with neonatal HIE treated by therapeutic hypothermia according to strict criteria (HIE-TH) were compared to a group of neonates born in the same period, gestational age-matched diagnosed with fetal distress according to fetal monitoring interpretation that was followed by prompt delivery, without subsequent HIE or therapeutic hypothermia (No-HIE). The primary outcome of the study was the electronic fetal monitoring (EFM) pattern during 60 min prior to delivery; the secondary outcome was the identification of perinatal associated factors. RESULTS: 54 neonates with HIE were treated by therapeutic hypothermia. EFM parameters most predictive of HIE-TH were indeterminate baseline heart rate OR = 47.297, 95% (8.17-273.76) p < 0.001, bradycardia OR = 15.997 95% (4.18-61.18) p < 0.001, low variability OR = 10.224, 95% (2.71-38.45) p < 0.001, higher baseline of the fetal heart rate calculated for each increment of 1 BPM OR = 1.0547, 95% (1.001-1.116) p = 0.047. Rupture of a previous uterine cesarean scar and placental abruption were characteristic of the HIE-TH group 14.8% vs. 1% p < 0.05; and 16.7% vs. 6% p < 0.05, respectively. Adverse neonatal outcomes also differed significantly: HIE-TH had a higher rate of neonatal seizures 46.2% vs. 0% p < 0.001 and mortality 7.7% vs. 0% p < 0.001. CONCLUSIONS: Characteristic fetal monitoring pattern prior to delivery together with acute obstetric emergency events are associated with neonatal HIE, neurological morbidity, and mortality.

Recognizing the unique prenatal phenotype of Prader-Willi Syndrome (PWS) indicates the need for a diagnostic methylation test.

OBJECTIVES: Prader-Willi syndrome (PWS) is a neurogenetic disorder characterized by mental retardation, morbid obesity, and endocrine and behavior disorders. We previously showed in a small group of patients that PWS may have a unique prenatal phenotype. We aimed to characterize clinical and ultrasonic features in a larger series of pregnancies with a PWS fetus. METHODS: We retrospectively interviewed all mothers of children with PWS followed in the Israel national multidisciplinary PWS clinic. We compared details of the PWS pregnancy with the pregnancies of healthy siblings and with data from the general population. Medical records including ultrasound reports, obstetric records, and genetic results were analyzed. RESULTS: Distinct prenatal features of PWS pregnancies included abnormal fetal growth [fetal growth restriction (FGR) (37.3%), increased head to abdominal circumference ratio (44.8%), decreased abdominal circumference (49.2%)], markedly decreased fetal movements (DFM) (80.4%), and polyhydramnios (42.0%) (P < 0.001 for all). The combination of abnormal growth accompanied by polyhydramnios or DFM was highly suggestive for PWS. CONCLUSIONS: Recognition of the unique PWS phenotype should alert obstetricians to consider the possibility of PWS, perform the diagnostic methylation test, provide appropriate counseling, and plan optimal management of the affected pregnancy.

Recurrent intrauterine growth restriction: characteristic placental histopathological features and association with prenatal vascular Doppler.

PURPOSE: Intrauterine growth restriction (IUGR) is a leading cause of perinatal morbidity and mortality, carrying a 20% recurrence rate. The placental disease is a cardinal factor among IUGR underlying processes. This study describes placental histopathological features (HPf) characteristic of recurrent IUGR (rIUGR) and assesses association with antenatal Doppler studies. METHODS: We conducted a retrospective case-control study, between the years 2005-2016, evaluating 34 placentae of 17 women with rIUGR, and 59 placentae of a gestational age-matched control. Doppler studies within a week prior to delivery were analyzed for the rIUGR group. RESULTS: Placental HPf characteristic of rIUGR is maternal and fetal vascular malperfusion lesions; maternal accelerated villous maturation and villous infarcts, repetitive feature rate 88.8% (95% CI 37.2-97), and fetal chorionic plate/stem villous thrombi, repetitive feature rate 66.6% (95% CI 30-90.3). Among women with abnormal Doppler, 83.3% had a placenta HPf of maternal vascular malperfusion lesions and 66.7% presented with a hypertensive disorder. CONCLUSIONS: Women with rIUGR are a unique group of patients characterized by repetitive placental HPf of both maternal and fetal vascular malperfusion lesions. Specifically, maternal vascular malperfusion lesions are associated with abnormal Doppler findings. In conclusion, characteristic placental HPf may serve as predictors of future IUGR recurrence, thus offering early recognition of pregnancies that require "high-risk" antenatal care.

Invasive Prenatal Diagnostic Testing Recommendations are Influenced by Maternal Age, Statistical Misconception and Perceived Liability.

Funding policy and medico-legal climate are part of physicians' reality and might permeate clinical decisions. This study evaluates the influence of maternal age and government funding on obstetrician/gynecologist recommendation for invasive prenatal testing (i.e. amniocentesis) for Down syndrome (DS), and its association with the physician's assessment of the risk of liability for medical malpractice unless they recommend amniocentesis. Israeli physicians (N = 171) completed a questionnaire and provided amniocentesis recommendations for women at 18 weeks gestation with normal preliminary screening results, identical except aged 28 and 37. Amniocentesis recommendations were reversed for the younger ('yes' regardless of testing results: 6.4%; 'no' regardless of testing results: 31.6%) versus older woman ('yes' regardless of testing results: 40.9%; 'no' regardless of testing results: 7.0%; χ2 = 71.55, p < .01). About half of the physicians endorsed different recommendations per scenario; of these, 65.6% recommended amniocentesis regardless of testing results for the 37-year-old woman. Physicians routinely performing amniocentesis and those advocating for amniocentesis for all women ≥ age 35 were approximately twice as likely to vary their recommendations per scenario. Physicians who perceived risk of liability for malpractice as large were nearly one-and-a-half times more likely to vary recommendations. The results indicate physicians' recommendations are influenced by maternal age, though age is already incorporated in prenatal DS risk evaluations. The physician's assessment of the risk that they will be sued unless they recommend amniocentesis may contribute to this spurious influence.

The association between ABO blood group and obstetric hemorrhage.

UNLABELLED: Whether intra- and early post-partum hemorrhage is influenced by ABO blood groups remains unknown. Therefore, we compared women with O to non-O blood groups with regard to maternal post-partum hemorrhage and transfusion need. This retrospective study was conducted in a single tertiary center between 2005 and 2014. For the purpose of the study, parturients were categorized as O and non-O blood groups. Data included all deliveries but excluded patients with missing blood grouping or hemoglobin values, and/or stillbirth. Drop in hemoglobin was defined as hemoglobin concentration at admission for delivery minus lowest hemoglobin concentration post-delivery. Study outcomes were postpartum hemorrhage, hemoglobin drop >2-7 g/dL inclusive, and packed red blood cells transfusion. STATISTICS: descriptive, χ(2) (p < 0.05 significant) and multivariable regression models [odds ratio (OR), 95 % confidence interval (CI), p value]. 125,768 deliveries were included. After multivariable analysis, women with O blood type relative to women with non-O blood type had significantly higher odds of postpartum hemorrhage (OR 1.14; 95 % CI 1.05-1.23, p < 0.001), higher odds of statistically significant hemoglobin decreases of >2, 3, or 4 g/dL (OR 1.07; 95 % CI 1.04-1.11, p < 0.001, OR 1.08; 95 % CI 1.03-1.14, p = 0.002, OR 1.14; 95 % CI 1.05-1.23, p = 0.001; respectively), and higher odds, albeit not statistically significant of 5, 6, or 7 g/dL decreases in hemoglobin (OR 1.13; 95 % CI 1.00-1.29, p = 0.055, OR 1.05; 95 % CI 0.84-1.32, p = 0.66, OR 1.15; 95 % CI 0.79-1.68, p = 0.46; respectively), but no difference in blood products transfusion (OR 1.03; 95 % CI 0.92-1.16, p = 0.58). In conclusion, women with blood type O may be at greater risk of obstetrical hemorrhage.

How Many Embryos should be Transferred? The Relevance of Parity and Obstetric History.

BACKGROUND: Fertility treatments are responsible for the rise in high order pregnancies in recent decades and their associated complications. Reducing the number of embryos returned to the uterus will reduce the rate of high order pregnancies. OBJECTIVES: To explore whether obstetric history and parity have a role in the clinician's decision making regarding the number of embryos transferred to the uterus during in vitro fertilization (IVF). METHODS: In a retrospective study for the period August 2005 to March 2012, data of twin deliveries > 24 weeks were collected, including parity, mode of conception (IVF vs. spontaneous), gestational age at delivery, preeclampsia, birth weight, admission to the neonatal intensive care unit (NICU), and Apgar scores. RESULTS: A total of 1651 twin deliveries > 24 weeks were record- ed, of which 959 (58%) were at term (> 37 weeks). The early preterm delivery (PTD) rate (< 32 weeks) was significantly lower with increased parity (12.6%, 8.5%, and 5.6%, in women with 0, 1, and ≥ 2 previous term deliveries, respectively). Risks for PTD (< 37 weeks), preeclampsia and NICU admission were significantly higher in primiparous women compared to those who had one or more previous term deliveries. Primiparity and preeclampsia, but not IVF, were significant risk factors for PTD. CONCLUSIONS: The risk for PTD in twin pregnancies is significantly lower in women who had a previous term delivery and decreases further after two or more previous term deliveries. This finding should be considered when deciding on the number of embryos to be transferred in IV.

BRCA mutation carriers do not have compromised ovarian reserve.

UNLABELLED: Controversy exists about the impact of BRCA1/2 mutations on female fertility. Previous studies are small or based on indirect parameters (eg, self-reported infertility), which depend on additional factors unrelated to true fertility potential. Most of the previous studies did not use strict fertility markers. OBJECTIVE: The aim of this study is to evaluate the relation between carrying a BRCA1/2 mutation and fertility using the level of anti-müllerian hormone (AMH), which has been previously shown to be an accurate marker of ovarian reserve and fertility potential. PATIENTS AND METHODS: Forty-one healthy BRCA1/2 mutation carriers, aged 26 to 40 years, attending a multidisciplinary breast and ovarian cancer surveillance clinic, were tested for AMH levels using a 2-site ELISA. Levels were compared with those of our general population and with well-established normograms of the general population. RESULTS: The mean age of carriers was 33.2 years (26-39 years; SD, 3.99 years). The mean parity of carriers was 1.97 (0-7; SD, 1.49). All women carried at least 1 Ashkenazi Jewish founder mutation. The AMH levels for most carriers were in the reference range, 2.71 ± 0.59 ng/mL (approximately 50th percentile of normograms). These levels were similar to those in the control group, in which the AMH levels were 2.02 ± 0.12 ng/mL (P = 0.27). CONCLUSIONS: The AMH levels of healthy BRCA1/2 mutation carriers are similar to those of noncarrier women matched for age; therefore, their ovarian reserve is comparable. This is the only study, to the best of our knowledge, that directly examines ovarian reserve in a relatively large group of carriers with an accurate marker. The results of this study may possibly give reassurance to female carriers concerning fertility potential.

Elective induction of labor in women with gestational diabetes mellitus: an intervention that modifies the risk of cesarean section.

AIM: To evaluate the effect of elective induction at term for women with gestational diabetes mellitus (GDM) on the risk for cesarean delivery. STUDY DESIGN: This is a retrospective case-control matched study, based on a single-center computerized database, 2005-2011. The medical records were reviewed for GDM management and glycemic control. For the study, two groups were defined: Group 1, women diagnosed with GDM with an estimated fetal weight <4,000 g, electively induced at term; Group 2, women induced due to Term-PROM, an indication for term induction in normoglycemic women with uncomplicated pregnancies, matched for age and parity (ratio 1:2). The primary outcome was cesarean delivery and secondary outcomes included other maternal and neonatal events. Descriptive analyses and multivariate analyses models were fitted. RESULTS: GDM was diagnosed in 1,873 (2.6 %) women of 72,374 births; 227 (12.1 %) were eligible for inclusion in Group 1 and matched with 454 women in Group 2. GDM management included diet in 103 (45.4 %), insulin in 81 (35.7 %), and oral hypoglycemic agents in 43 (18.9 %).The cesarean delivery rate was significantly higher in Group 1, 17.1 vs. 11.2 % (p = 0.02). Three out of four births complicated by shoulder dystocia and BW <4,000 g, occurred in Group 1 (p = 0.076) and were associated with no glycemic control. Other obstetrical-related outcomes such as instrumental birth, severe perineal tears, early postpartum hemorrhage and peripartum transfusion were similar between groups. CONCLUSION: Elective induction at term for women with GDM is associated with an increased risk for cesarean delivery as compared to other elective induction of labor.

Impact of first-trimester mechanical cervical dilatation during curettage on maternal and neonatal outcomes: A retrospective comparative study.

OBJECTIVE: Earlier studies have indicated a potential link between dilatation and curettage (D&C) and subsequent preterm delivery, possibly attributed to cervical damage. This study examines outcomes in pregnancies subsequent to first-trimester curettage with and without cervical dilatation. METHODS: A retrospective cohort study was conducted on women who conceived after undergoing curettage due to a first trimester pregnancy loss. Maternal and neonatal outcomes of the subsequent pregnancy were compared between two groups: women who underwent cervical dilatation before their curettage and those who had curettage without dilatation. The primary outcome assessed was the rate of preterm delivery at the subsequent pregnancy, and secondary outcomes included other adverse maternal and neonatal outcomes. Univariate analysis was performed, followed by multiple logistic regression models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Among the 1087 women meeting the inclusion criteria during the study period, 852 (78.4 %) underwent first-trimester curettage with cervical dilatation, while 235 (21.6 %) opted for curettage only. No significant maternal or neonatal different outcomes were noted between the study groups, including preterm delivery (5.5 % vs. 3.5 %, p = 0.16), fertility treatments, placental complications, and mode of delivery. However, deliveries following D&C were associated with higher rates of small for gestational age neonates (7.6 % vs. 3.8 %, p = 0.04). Multivariate analysis revealed that cervical dilation before curettage was not significantly linked to preterm delivery [adjusted odds ratio 0.64 (0.33-1.26), p = 0.20]. CONCLUSION: The use of cervical dilatation during a curettage procedure for first trimester pregnancy loss, does not confer additional risk of preterm delivery. Further studies are needed to reinforce and validate these results.

Time-Lapse Incubation for Embryo Culture-Morphokinetics and Environmental Stability May Not Be Enough: Results from a Pilot Randomized Controlled Trial.

Background: Does the Time-lapse Incubator (TLI) add value to reproductive outcomes when its two components, undisturbed culturing and morphokinetic embryo grading, are separated. Methods: A prospective pilot, randomized, controlled, double-blinded, single-center study was conducted during the years 2016-2020. In total, 102 patients were randomized into three groups: (1) conventional incubation with morphological evaluation only (n = 34), (2) TLI with both morphological and morphokinetic evaluations (n = 32), and (3) TLI with morphological evaluation only (n = 36). All arms were cultured in ESCO-MIRI® incubators. A total of 1061 injected mature oocytes were evaluated (420 in arm 1, 285 in arm 2, and 356 in arm 3). The primary outcome was live birth rates. Secondary outcomes included clinical and cumulative pregnancy rates as well as embryo quality. Embryos in arm 3 were retrospectively evaluated for their morphokinetic score. Results: No significant difference was found in the live birth rate for single embryo transfer cycles (SET) (35% vs. 31.6% vs. 24%, p = 0.708) or double embryo transfer (DET) cycles (41.7% vs. 38.5% vs. 36.4%, p = 0.966). Comparable pregnancy rates, clinical pregnancy rates, and cumulative pregnancy were found for similar top-quality embryos for days 2, 3, and blastocyst stages across groups. A similar number of embryos were suitable for either transfer or cryopreservation within the different groups. For 62.8% of the embryos in arm 3, the morphokinetic and morphologic evaluations were similar. In only 2/36 (5.6%) treatment cycles, the use of morphokinetic scoring may have helped the patient avoid undergoing an additional treatment cycle. In the other cases, morphokinetic scoring would not have changed the end point of pregnancy. Conclusions: The two components of the TLI system-undisturbed culturing and morphokinetic embryo grading-do not appear to have a significant additional value in reproductive outcome, although these results should be validated by an RCT.

Physician recommendation for invasive prenatal testing: the case of the 'precious baby'.

STUDY QUESTION: Do clinicians manage pregnancies conceived by assisted reproductive technologies (ART) differently from spontaneous pregnancies? SUMMARY ANSWER: Clinicians' decisions about prenatal testing during pregnancy depend, at least partially, on the method of conception. WHAT IS KNOWN ALREADY: Research thus far has shown that patients' decisions regarding prenatal screening are different in ART pregnancies compared with spontaneous ones, such that ART pregnancies may be considered more valuable or 'precious' than pregnancies conceived without treatment. STUDY DESIGN, SIZE AND DURATION: In this cross-sectional study, preformed during the year 2011, 163 obstetricians and gynecologists in Israel completed an anonymous online questionnaire. PARTICIPANTS, SETTING, METHODS: Clinicians were randomly assigned to read one of two versions of a vignette describing the case of a pregnant woman. The two versions differed only with regard to the method of conception (ART; n = 78 versus spontaneous; n = 85). Clinicians were asked to provide their recommendations regarding amniocentesis. MAIN RESULTS AND THE ROLE OF CHANCE: The response rate among all clinicians invited to complete the questionnaire was 16.7%. Of the 85 clinicians presented with the spontaneous pregnancy scenario, 37 (43.5%) recommended amniocentesis. In contrast, of the 78 clinicians presented with the ART pregnancy scenario, only 15 (19.2%) recommended the test. Clinicians were 3.2 (95% confidence interval [CI]: 1.6-6.6) times more likely to recommend amniocentesis for a spontaneous pregnancy than for an ART pregnancy. LIMITATIONS AND REASONS FOR CAUTION: The study is limited by a low response rate, the relatively small sample and the hypothetical nature of the decision, as clinician recommendations may have differed in an actual clinical setting. WIDER IMPLICATIONS OF THE FINDINGS: Our findings show that fertility history and use of ART may affect clinicians' recommendations regarding amniocentesis following receipt of screening test results. This raises the question of how subjective factors influence clinicians' decisions regarding other aspects of pregnancy management. STUDY FUNDING AND COMPETING INTEREST: There was no funding source to this study. The authors declare no conflicts of interest.