Ultrasound in Obstetrics & Gynecology, Sep 1, 2017
Short oral presentation abstracts Objectives: To investigate pregnancy outcome for fetuses with n... more Short oral presentation abstracts Objectives: To investigate pregnancy outcome for fetuses with nuchal translucency (NT) ≥ 3.5 mm but normal karyotype and CMA.
Fetal phenotypeA couple of Ashkenazi Jewish descent was referred for an early anatomy scan at 14 ... more Fetal phenotypeA couple of Ashkenazi Jewish descent was referred for an early anatomy scan at 14 + 2 weeks of gestation following a previous pregnancy termination due to posterior encephalocele and enlarged kidneys. The index pregnancy was also positive for several fetal abnormalities, including enlarged kidneys with cystic dysplasia and abnormal cerebellar morphology highly suggestive of Joubert syndrome.Genetic diagnostic test performed, result, and interpretationTrio exome sequencing revealed compound heterozygosity for variants in the TMEM67 gene: a known pathogenic maternally inherited variant found in trans with a paternal intronic variant of unknown significance. RNA analysis revealed that the intronic variant creates a cryptic acceptor splice site in intron 12, leading to the insertion of 22 bp and causing a frameshift with a premature stop codon. This analysis enabled the reclassification of the intronic variant to likely pathogenic.Implications and noveltyThis information ...
This article is protected by copyright. All rights reserved. This article is protected by copyrig... more This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Background: HNF1B deletion/intragenic mutations are the most commonly identified genetic cause of... more Background: HNF1B deletion/intragenic mutations are the most commonly identified genetic cause of congenital anomalies of the kidney and urinary tract (CAKUT) suggested by fetal ultrasound findings such as: parenchymal hyperechogenicity, overt cystic changes or gross morphological urinary system (UT) abnormalities. The postnatal evolution of these 17q12 deletions encompassing the HNF1B gene-associated findings has not been assessed in depth. Methods: In this observational study, we present postnatal follow-up findings in 5 of 6 cases (one pregnancy was terminated on parental request) of fetal-onset cystic/hyperechogenic kidneys eventually diagnosed with 17q12 microdeletion encompassing the HNF1B gene between 2009 and 2017. Results: Complete normalization of kidney parenchymal abnormalities and of depressed neonatal renal function was observed in 4/5 and 5/5 patients within 2-4.9 years and 1.5-8 months, respectively. All 5 patients had preserved normal renal function at 3-11 years of follow-up. The evolving later-onset renal features included: hypomagnesemia, hyperuricemia, urinary tract infection (UTI), and bilateral grade 3-4 vesicoureteral reflux and bladder diverticula in 3, 3, 2, and 1 patient, respectively. HNF1B gene deletionassociated extra-renal manifestations with delayed presentation were global developmental delay/autistic spectrum disorder (ASD), rolandic-type seizures, overweight, and borderline fasting hyperglycemia observed in 1-2 patients each. Family history was positive for small-size or asymptomatic cystic kidneys with normal function, diabetes mellitus, seizures, and mental/psychiatric problems in 3/6 cases. Conclusions: Fetal-onset HNF1B deletion-associated kidneys' parenchymal abnormalities confirmed postnatally with initially depressed renal function might undergo complete resolution within several years and few months, respectively. However, later-onset urinary tract, metabolic, and neurodevelopmental features of this mutation might appear over years. Therefore, genetic molecular evaluation/diagnosis and continuous follow-up for evolving features are mandatory in affected children.
Journal of Medical Statistics and Informatics, 2019
Background: The purpose of this research was to calculate the minimum sample size needed to obtai... more Background: The purpose of this research was to calculate the minimum sample size needed to obtain reliable results from crowdsourced retrospective online surveys of IVF clinics, where the sample was IVF cycles performed annually per clinic-a new metric that may offer more survey flexibility than number of clinics or respondents. Methods: This analysis used two statistical formulas to calculate sample sizes and confidence intervals, initially assessing a published self-report survey conducted online by IVF-Worldwide of global IVF practices. The survey covered 592,900 IVF cycles from 795 clinics worldwide. A subset of 275,600 European IVF cycles was used as a test sample population, which was compared statistically with the actual survey population. To validate results, two additional geographic subsets (North America and Asia) from the initial survey and three additional previously published surveys were also evaluated in same fashion. Only one survey entry was accepted per clinic. Results: Results showed that to obtain reliable survey outcomes, the estimated minimum sample size was 35,000 cycles. Given a 99% confidence level, 0.5 probability, and a 5% estimation error, the minimum sample size for Europe was 35,340. Similarly, sample sizes for earlier surveys and other continent subsets were between 35,280 and 35,340. Conclusions: Surveyors often strive for small sample sizes to savecost, effort, time and/or management overhead. Currently, however, sample size standards for online surveys do not exist. The results presented here suggest that sample sizes below 35,000 may lead to unreliable results. Finding the right sample size for multiple-choice crowdsourced surveys will save cost and effort, accelerate research, and empower surveys originally deemed too difficult and/or expensive due to inordinate sample sizes required. Surveys that count number of IVF cycles as the survey population may offer researchers more options for how to conduct and analyze surveys. Further research is required to apply findings to other areas of medicine, such as surveying using the number of procedures performed by clinic.
Journal of Assisted Reproduction and Genetics, 2019
Purpose This research sought to understand IVF-physicians' knowledge of, experience with, and att... more Purpose This research sought to understand IVF-physicians' knowledge of, experience with, and attitudes toward fertility preservation for cancer patients. Methods A 35-question, self-report survey request was emailed to IVF providers who were registered on the IVF-Worldwide. com network (3826 clinics). Physicians submitted responses on the IVF-Worldwide.com website. Survey results were reported as a proportion of the responding clinics. Results Survey responses were completed by 321 (8.4%) globally distributed IVF clinics, representing 299,800 IVF cycles. Of these clinics, 86.6% (278) performed fertility preservation, treating approximately 6300 patients annually. However, 18.4% of the centers reported that patients sought advice independently, without an oncologist's referral. Ovarian tissue cryopreservation was performed by 37.7% of the clinics, yet 52.6% considered the procedure experimental. IVM was performed by 16.5% of responding clinics. A majority (63.6%) of the clinics selected treatment protocols based on each patient's malignancy. Most respondents (76.3%) disagreed that fertility preservation was not yet successful enough to make it an available option. However, 44.2% believed that pregnancy rates following oocyte cryopreservation could not be determined because not enough oocyte cryopreservation patients had completed embryo transfer. Conclusions Most clinics performed fertility preservation, tailoring protocols to each patient's disease and condition. Almost 20% of patients sought advice independently, indicating that more effort is needed to encourage oncologists to refer patients. Most survey respondents believed that data was not yet available on either live birth outcomes or the best protocol for each disease. Therefore, long-term study must continue, with the establishment of interim milestones and an outcome-tracking registry.
Objective: To evaluate whether endometrial receptivity is compromised in patients with premature ... more Objective: To evaluate whether endometrial receptivity is compromised in patients with premature ovarian failure (POF) due to Turner's syndrome who undergo oocyte donation. Design: Retrospective analysis. Setting: In vitro fertilization-ET units, anonymous oocyte donation program. Patients: The study included 53 patients with POF who underwent oocyte donation. These included 7 patients with Turner's syndrome (45,X) who underwent 22 ET cycles, 15 women with Turner variants (mosaics, deletions, or isochromosomes) who underwent 36 ET cycles, and 31 other patients with POF and a normal karyotype who underwent 69 oocyte donation cycles. Intervention: All patients on standby for donation were treated with E2 valerate 6 mg/d until oocytes became available; then P 100 mg/d was added. Oocyte donors were healthy women <34 years who underwent IVF themselves. Main Outcome Measures: Clinical pregnancy rates (PRs), biochemical pregnancies, early abortions, and delivery rates were evaluated. Results: Turner's syndrome patients had a significantly higher rate of biochemical pregnancies (22.7% versus 4.3%), a lower clinical PR (22.7% versus 33.3%), a significantly higher rate of early abortions (60% versus 8.7%), and a significantly lower rate of deliveries per pregnancy (20.0% versus 73.1%) compared with non-Turner patients. Conclusions: Patients with a complete or partial deficiency of an X chromosome have reduced PRs and an increase in early implantation failure after oocyte donation. This may indicate an inherent endometrial abnormality, possibly associated with a deficiency of X-linked genes regulating endometrial receptivity.
American Journal of Obstetrics and Gynecology, 2017
gain significantly more weight than control (wildtype; WT) mice when fed a high-fat diet. We hypo... more gain significantly more weight than control (wildtype; WT) mice when fed a high-fat diet. We hypothesized that this increased weight gain was due to the role of hepatic Npas2 in regulating satiety. STUDY DESIGN: Npas2 cKO (n¼62) and control mice (WT, n¼49) were generated for this study. At weaning mice were placed onto high fat diet (HFD, 42% fat) and weighed biweekly. A subset of cKO (n¼5) and control (n¼4) mice were placed in comprehensive lab animal monitoring system (CLAMS) at 16 weeks post-weaning to monitor feeding behavior, activity, and energy expenditure. RESULTS: Male cKO mice on a HFD had significantly increased mass when compared to HFD-fed WT starting at 16 weeks post-weaning (p<0.01; Fig.1). Despite their mass increase, no difference in daily food intake or energy expenditure was observed (p¼0.25 and 0.40 respectively). However, satiety was significantly different. While the liver specific Npas2 cKO ate fewer meals than WTmice (cKO: 61, WT: 80, p¼0.04), the average meal size significantly greater (0.056g versus 0.046g; p¼0.03, Fig.2). We also found that cKO mice averaged longer meal times (61 seconds per meal (spm)) than WT mice (39 spm, p¼0.02). CONCLUSION: We have deleted a circadian gene only in the neonatal liver, leaving it intact in the brain, and shown with in depth analysis of feeding behavior a significant impact on satiety with HFD feeding. These findings indicate for the first time that Npas2 expression in the neonatal liver plays a crucial role in regulating satiety signaling under metabolic stress. These data underscore the importance of the neonatal hepatic Npas2 circadian responses in orchestrating both hunger and satiety signals and how disruptions to Npas2 expression during fetal development may lead to metabolic disease in children and adults.
American Journal of Obstetrics and Gynecology, 2017
We have previously identified risk factors for acute fetal demise (<24 hours after procedure) aft... more We have previously identified risk factors for acute fetal demise (<24 hours after procedure) after fetoscopic laser procedure (FLP) for twin twin transfusion syndrome (TTTS). There is a gap in knowledge in perinatal outcomes between FLP and selective reduction (SR). We aim to compare procedure-to-delivery interval and perinatal survival between patients with single fetal survival following FLP to planned SR in complicated monochorionic twin pregnancies. STUDY DESIGN: This was a secondary analysis of prospectively collected data in complicated monochorionic twin pregnancies from two fetal centers from 2008-2015. The selection of procedure was dependent upon provider and patient preference. Group 1 was defined as women undergoing FLP for TTTS with an idiopathic single fetal demise within 24 hours of the procedure. Group 2 consisted of women undergoing planned SR for TTTS, and Group 3 was SR for indications other than TTTS, such as discordant anomalies, twin reverse arterial perfusion (TRAP), and selective IUGR. Baseline demographics and perinatal outcomes were compared among the three groups using comparative statistics. Kaplan-Meier survival analysis and Cox-proportional hazard model was performed to compare gestational age (GA) at delivery and procedure to delivery time. RESULTS: In Group 1, 77/1043 (7%) had a single fetal demise within 24 hours of FLP, of which 59 (76%) were donor fetal demise and 18 (24%) were recipient demise. Group 2 included 15 patients, of which 13 (87%) donor fetuses and 2 (13%) recipient fetuses were selectively reduced. Relevant outcomes among the three groups are illustrated in Table below. Survival of the co-twin was highest in the Group 1 (p¼0.04). Although no differences were found in the mean GA at delivery and procedure to delivery time among the groups, on K-M plot with Cox-proportional hazard model, there was significant difference among groups (Figure 1; p¼0.01). On multivariate analysis with cox-proportional hazard model, GA at procedure (Hazard ratio [HR]: 1.1; p¼0.04) and FLP for TTTS (HR: 2.1; p¼0.04) were the only factors found independently associated with GA at delivery. CONCLUSION: When single fetal demise occurs following fetoscopic laser photocoagulation, the other twin is more likely to survive to delivery, but more likely to deliver at an earlier GA compared to selective reduction for TTTS.
Objective: To assess the effect of the duration of uterine preparation with E2 on pregnancy rates... more Objective: To assess the effect of the duration of uterine preparation with E2 on pregnancy rates (PRs) in oocyte donation. Design.: A retrospective study. Setting: IVF-ET Unit, oocyte donation program. Patients: Four hundred eleven patients undergoing 865 ET cycles after oocyte donation. Uterine preparation consisted of6 mg/d E2 valerate. The duration of treatment varied according to the availability of the oocytes for donation. Progesterone, 100 mg/d, was added upon oocyte retrieval. Patients were divided into seven groups according to the duration of uterine preparation with E2, in 5-day ranks. Main Outcome Measures: Pregnancy rates per ET according to the duration of uterine preparation. Results: No differences were noted in the mean age, number of oocytes received, fertilization rates, or number of embryos transferred when comparing all groups. Pregnancy rates ranged from 19% to 27% for E2 treatment of 5 to 35 days. Conclusion: Endometrial preparation in anonymous oocyte donation programs is achieved with continuous administration of E2 until oocytes become available. Our results show that this treatment may be extended for as long as 5 weeks with no significant decrease in PRs.
To evaluate regulation of follicle-stimulating hormone (FSH) receptor expression in the mouse ova... more To evaluate regulation of follicle-stimulating hormone (FSH) receptor expression in the mouse ovary during different stages of an artificially induced ovulatory cycle. Follicular maturation was achieved in pubertal female mice by pregnant mares' serum gonadotropin (PMSG). Ovulation was induced 48 hours later by human chorionic gonadotropin (hCG). Ovaries were harvested before treatment, at 24 and 48 hours after PMSG and at 3, 9 and 12 hours after hCG. RNA was extracted using a single-step isolation method and used for reverse transcription. The cDNA was amplified by polymerase chain reaction (PCR) using primers designed to amplify a 512-basepair product corresponding to the extracellular fragment of the FSH receptor. PCR products, resolved by electrophoresis on agarose gels, showed four bands corresponding to four discrete, alternatively spliced forms of the FSH receptor. Expression of the various transcripts varied at different stages of the ovulatory cycle such that the larger...
Introduction: Preimplantation genetic diagnosis (PGD) is reserved for couples at risk of transmit... more Introduction: Preimplantation genetic diagnosis (PGD) is reserved for couples at risk of transmitting a genetic disease, and hence avoids undesirable therapeutic abortion. Materials and methods: From February 2003 through February 2005, we performed polymerase chain reactionbased PGD for 10 couples at risk for Duchenne's muscular dystrophy (DMD), OTC deficiency, osteogenesis imperfecta (OI), epidermolysis bullosa (EB), lactic acidosis, SMA and LCHAD deficiency. Results: Embryo biopsy was performed on 157 embryos. All embryos were successfully biopsied. Successful diagnosis rate was 94.9% (149/157) and 73 embryos (49.0%) were diagnosed as unaffected. Among them, 38 embryos were transferred in 14 cycles, resulting in five clinical pregnancies (35.7% per transfer) in cases of DMD, OTC deficiency, OI and SMA. There was no clinical abortion or miscarriage in the pregnancies. All pregnancies were confirmed by amniocentesis and neonatal diagnosis. Conclusions: PGD is an efficient alternative method of having children for couples at risk of transmitting genetic diseases.
BackgroundA monochorionic‐diamniotic placenta (MCDAP) is rare in dizygotic (DZ) twinning. All rep... more BackgroundA monochorionic‐diamniotic placenta (MCDAP) is rare in dizygotic (DZ) twinning. All reported cases have been documented in pregnancies achieved by the induction of ovulation alone or during the IVF cycle.Methods and ResultsWe report a spontaneous pregnancy in a 39‐year‐old patient with evidence of MCDAP in DZ twins, discordant for trisomy 21. The first and second‐trimester sonographic scans indicated male twins with MCDAP. Amniocentesis, performed because of advanced maternal age, revealed a normal karyotype in one fetus, and trisomy 21 in the other. Molecular studies, performed in order to confirm the zygosity and chorionicity, demonstrated that the fetuses were DZ. In order to identity the affected twin, a detailed sonographic examination was repeated, but no abnormal findings associated with Down syndrome were demonstrated in any of the fetuses. Therefore, umbilical cord blood samples were obtained from both fetuses. Chromosomal analysis revealed in both fetuses two cel...
Letters to the Editor Sertoli cell only syndrome Dear Sir, Sertoli cell only syndrome was first d... more Letters to the Editor Sertoli cell only syndrome Dear Sir, Sertoli cell only syndrome was first described by Del Castillo et al. (1947). According to the original description it has been used when no spermatogenic cells have been seen in a testicular biopsy specimen. It is therefore unfortunate that the name of this syndrome has been misused in Human Reproduction in connection with cases where Sertoli cell only has been a diagnostic failure by a pathologist (Devroey et al, 1995; Silber et al, 1995). If spermatogenic cells, spermatogonia, spermatocytes, spermatids or spermatozoa are found "in the testis, although in minimal numbers, the state is not Sertoli cell only, but hypospermatogenesis or spermatogenic arrest (maturation arrest). The aetiology of low numbers of tubules with spermatogenesis can be genetic, infection, toxic agent, radiation, or something else. In these cases it is possible to use intracytoplasmic sperm injection (ICSI) with spermatozoa or spermatids obtained from testicular aspiration or biopsy knowing that in genetic cases there is a risk of mediating the defect to male offspring. In cases of true Sertoli cell only syndrome, ICSI is not possible, because there is a total lack of spermatogenic cells.
There are numerous studies concerning pregnancy rates in oocyte donation, yet only a handful repo... more There are numerous studies concerning pregnancy rates in oocyte donation, yet only a handful report the obstetric outcome in such pregnancies. The purpose of this study was to assess factors that influence pregnancy rates, to determine the incidence of complications, and to evaluate obstetric outcome in pregnancies resulting from oocyte donation. This study included 423 oocyte recipients who underwent 1001 oocyte donation cycles at the Oocyte Donation Programme, In-Vitro Fertilization (IVF)-Embryo Transfer Unit, Herzlia Medical Center, Israel. Donors were all healthy women <34 years old who underwent IVF themselves. In 873 cycles, fertilization occurred and embryo transfer was performed, resulting in 194 clinical pregnancies. Pregnancy rates (PR) significantly declined with the increase in number of previous attempts, and with increasing age of recipient (36.8%/embryo transfer in patients ഛ30 compared to 17.8% in patients >40 years old). A significant increment in PR was noted with the increasing number of embryos transferred. The overall PR was 22.2%/ embryo transfer. However, in young amenorrhoeic patients with normal karyotypes undergoing their first cycle, PR was 52.2%; the 'take home baby' rate was 38.3% per patient undergoing embryo transfer and 17.8% per embryo transfer cycle. A significant increase in the incidence of pregnancy-induced hypertension and a higher proportion of abortions were noted in older patients. A significantly higher incidence of prematurity and low birthweight was observed in multiple pregnancies.
Objective: The aim of our study was to evaluate whether intracardiac echogenic foci (ICEFs) may b... more Objective: The aim of our study was to evaluate whether intracardiac echogenic foci (ICEFs) may be associated with increased risk for structural cardiac anomalies in the low-risk population. Methods: During a 24-month period, 3,744 low-risk patients were prospectively screened for ICEFs by prenatal sonography. The study group was composed of 138 fetuses (3.7%) with ICEF. The control group was composed of 167 fetuses without ICEF. In all fetuses a complete echocardiographic evaluation was performed. Results: Among the 138 fetuses in the study group, 108 (78%) ICEFs were found in the left ventricle, 25 (18%) were found in the right ventricle, and 5 (4%) were found to be bilateral. No statistically significant difference was found between the study and the control group regarding the presence of cardiac anomalies. Only 1 case (0.7%) of pulmonic stenosis was found in the study group, compared to 1 case (0.6%) of bicuspid aortic valve in the control group. Conclusions: We conclude that I...
Ultrasound in Obstetrics & Gynecology, Sep 1, 2017
Short oral presentation abstracts Objectives: To investigate pregnancy outcome for fetuses with n... more Short oral presentation abstracts Objectives: To investigate pregnancy outcome for fetuses with nuchal translucency (NT) ≥ 3.5 mm but normal karyotype and CMA.
Fetal phenotypeA couple of Ashkenazi Jewish descent was referred for an early anatomy scan at 14 ... more Fetal phenotypeA couple of Ashkenazi Jewish descent was referred for an early anatomy scan at 14 + 2 weeks of gestation following a previous pregnancy termination due to posterior encephalocele and enlarged kidneys. The index pregnancy was also positive for several fetal abnormalities, including enlarged kidneys with cystic dysplasia and abnormal cerebellar morphology highly suggestive of Joubert syndrome.Genetic diagnostic test performed, result, and interpretationTrio exome sequencing revealed compound heterozygosity for variants in the TMEM67 gene: a known pathogenic maternally inherited variant found in trans with a paternal intronic variant of unknown significance. RNA analysis revealed that the intronic variant creates a cryptic acceptor splice site in intron 12, leading to the insertion of 22 bp and causing a frameshift with a premature stop codon. This analysis enabled the reclassification of the intronic variant to likely pathogenic.Implications and noveltyThis information ...
This article is protected by copyright. All rights reserved. This article is protected by copyrig... more This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Background: HNF1B deletion/intragenic mutations are the most commonly identified genetic cause of... more Background: HNF1B deletion/intragenic mutations are the most commonly identified genetic cause of congenital anomalies of the kidney and urinary tract (CAKUT) suggested by fetal ultrasound findings such as: parenchymal hyperechogenicity, overt cystic changes or gross morphological urinary system (UT) abnormalities. The postnatal evolution of these 17q12 deletions encompassing the HNF1B gene-associated findings has not been assessed in depth. Methods: In this observational study, we present postnatal follow-up findings in 5 of 6 cases (one pregnancy was terminated on parental request) of fetal-onset cystic/hyperechogenic kidneys eventually diagnosed with 17q12 microdeletion encompassing the HNF1B gene between 2009 and 2017. Results: Complete normalization of kidney parenchymal abnormalities and of depressed neonatal renal function was observed in 4/5 and 5/5 patients within 2-4.9 years and 1.5-8 months, respectively. All 5 patients had preserved normal renal function at 3-11 years of follow-up. The evolving later-onset renal features included: hypomagnesemia, hyperuricemia, urinary tract infection (UTI), and bilateral grade 3-4 vesicoureteral reflux and bladder diverticula in 3, 3, 2, and 1 patient, respectively. HNF1B gene deletionassociated extra-renal manifestations with delayed presentation were global developmental delay/autistic spectrum disorder (ASD), rolandic-type seizures, overweight, and borderline fasting hyperglycemia observed in 1-2 patients each. Family history was positive for small-size or asymptomatic cystic kidneys with normal function, diabetes mellitus, seizures, and mental/psychiatric problems in 3/6 cases. Conclusions: Fetal-onset HNF1B deletion-associated kidneys' parenchymal abnormalities confirmed postnatally with initially depressed renal function might undergo complete resolution within several years and few months, respectively. However, later-onset urinary tract, metabolic, and neurodevelopmental features of this mutation might appear over years. Therefore, genetic molecular evaluation/diagnosis and continuous follow-up for evolving features are mandatory in affected children.
Journal of Medical Statistics and Informatics, 2019
Background: The purpose of this research was to calculate the minimum sample size needed to obtai... more Background: The purpose of this research was to calculate the minimum sample size needed to obtain reliable results from crowdsourced retrospective online surveys of IVF clinics, where the sample was IVF cycles performed annually per clinic-a new metric that may offer more survey flexibility than number of clinics or respondents. Methods: This analysis used two statistical formulas to calculate sample sizes and confidence intervals, initially assessing a published self-report survey conducted online by IVF-Worldwide of global IVF practices. The survey covered 592,900 IVF cycles from 795 clinics worldwide. A subset of 275,600 European IVF cycles was used as a test sample population, which was compared statistically with the actual survey population. To validate results, two additional geographic subsets (North America and Asia) from the initial survey and three additional previously published surveys were also evaluated in same fashion. Only one survey entry was accepted per clinic. Results: Results showed that to obtain reliable survey outcomes, the estimated minimum sample size was 35,000 cycles. Given a 99% confidence level, 0.5 probability, and a 5% estimation error, the minimum sample size for Europe was 35,340. Similarly, sample sizes for earlier surveys and other continent subsets were between 35,280 and 35,340. Conclusions: Surveyors often strive for small sample sizes to savecost, effort, time and/or management overhead. Currently, however, sample size standards for online surveys do not exist. The results presented here suggest that sample sizes below 35,000 may lead to unreliable results. Finding the right sample size for multiple-choice crowdsourced surveys will save cost and effort, accelerate research, and empower surveys originally deemed too difficult and/or expensive due to inordinate sample sizes required. Surveys that count number of IVF cycles as the survey population may offer researchers more options for how to conduct and analyze surveys. Further research is required to apply findings to other areas of medicine, such as surveying using the number of procedures performed by clinic.
Journal of Assisted Reproduction and Genetics, 2019
Purpose This research sought to understand IVF-physicians' knowledge of, experience with, and att... more Purpose This research sought to understand IVF-physicians' knowledge of, experience with, and attitudes toward fertility preservation for cancer patients. Methods A 35-question, self-report survey request was emailed to IVF providers who were registered on the IVF-Worldwide. com network (3826 clinics). Physicians submitted responses on the IVF-Worldwide.com website. Survey results were reported as a proportion of the responding clinics. Results Survey responses were completed by 321 (8.4%) globally distributed IVF clinics, representing 299,800 IVF cycles. Of these clinics, 86.6% (278) performed fertility preservation, treating approximately 6300 patients annually. However, 18.4% of the centers reported that patients sought advice independently, without an oncologist's referral. Ovarian tissue cryopreservation was performed by 37.7% of the clinics, yet 52.6% considered the procedure experimental. IVM was performed by 16.5% of responding clinics. A majority (63.6%) of the clinics selected treatment protocols based on each patient's malignancy. Most respondents (76.3%) disagreed that fertility preservation was not yet successful enough to make it an available option. However, 44.2% believed that pregnancy rates following oocyte cryopreservation could not be determined because not enough oocyte cryopreservation patients had completed embryo transfer. Conclusions Most clinics performed fertility preservation, tailoring protocols to each patient's disease and condition. Almost 20% of patients sought advice independently, indicating that more effort is needed to encourage oncologists to refer patients. Most survey respondents believed that data was not yet available on either live birth outcomes or the best protocol for each disease. Therefore, long-term study must continue, with the establishment of interim milestones and an outcome-tracking registry.
Objective: To evaluate whether endometrial receptivity is compromised in patients with premature ... more Objective: To evaluate whether endometrial receptivity is compromised in patients with premature ovarian failure (POF) due to Turner's syndrome who undergo oocyte donation. Design: Retrospective analysis. Setting: In vitro fertilization-ET units, anonymous oocyte donation program. Patients: The study included 53 patients with POF who underwent oocyte donation. These included 7 patients with Turner's syndrome (45,X) who underwent 22 ET cycles, 15 women with Turner variants (mosaics, deletions, or isochromosomes) who underwent 36 ET cycles, and 31 other patients with POF and a normal karyotype who underwent 69 oocyte donation cycles. Intervention: All patients on standby for donation were treated with E2 valerate 6 mg/d until oocytes became available; then P 100 mg/d was added. Oocyte donors were healthy women <34 years who underwent IVF themselves. Main Outcome Measures: Clinical pregnancy rates (PRs), biochemical pregnancies, early abortions, and delivery rates were evaluated. Results: Turner's syndrome patients had a significantly higher rate of biochemical pregnancies (22.7% versus 4.3%), a lower clinical PR (22.7% versus 33.3%), a significantly higher rate of early abortions (60% versus 8.7%), and a significantly lower rate of deliveries per pregnancy (20.0% versus 73.1%) compared with non-Turner patients. Conclusions: Patients with a complete or partial deficiency of an X chromosome have reduced PRs and an increase in early implantation failure after oocyte donation. This may indicate an inherent endometrial abnormality, possibly associated with a deficiency of X-linked genes regulating endometrial receptivity.
American Journal of Obstetrics and Gynecology, 2017
gain significantly more weight than control (wildtype; WT) mice when fed a high-fat diet. We hypo... more gain significantly more weight than control (wildtype; WT) mice when fed a high-fat diet. We hypothesized that this increased weight gain was due to the role of hepatic Npas2 in regulating satiety. STUDY DESIGN: Npas2 cKO (n¼62) and control mice (WT, n¼49) were generated for this study. At weaning mice were placed onto high fat diet (HFD, 42% fat) and weighed biweekly. A subset of cKO (n¼5) and control (n¼4) mice were placed in comprehensive lab animal monitoring system (CLAMS) at 16 weeks post-weaning to monitor feeding behavior, activity, and energy expenditure. RESULTS: Male cKO mice on a HFD had significantly increased mass when compared to HFD-fed WT starting at 16 weeks post-weaning (p<0.01; Fig.1). Despite their mass increase, no difference in daily food intake or energy expenditure was observed (p¼0.25 and 0.40 respectively). However, satiety was significantly different. While the liver specific Npas2 cKO ate fewer meals than WTmice (cKO: 61, WT: 80, p¼0.04), the average meal size significantly greater (0.056g versus 0.046g; p¼0.03, Fig.2). We also found that cKO mice averaged longer meal times (61 seconds per meal (spm)) than WT mice (39 spm, p¼0.02). CONCLUSION: We have deleted a circadian gene only in the neonatal liver, leaving it intact in the brain, and shown with in depth analysis of feeding behavior a significant impact on satiety with HFD feeding. These findings indicate for the first time that Npas2 expression in the neonatal liver plays a crucial role in regulating satiety signaling under metabolic stress. These data underscore the importance of the neonatal hepatic Npas2 circadian responses in orchestrating both hunger and satiety signals and how disruptions to Npas2 expression during fetal development may lead to metabolic disease in children and adults.
American Journal of Obstetrics and Gynecology, 2017
We have previously identified risk factors for acute fetal demise (<24 hours after procedure) aft... more We have previously identified risk factors for acute fetal demise (<24 hours after procedure) after fetoscopic laser procedure (FLP) for twin twin transfusion syndrome (TTTS). There is a gap in knowledge in perinatal outcomes between FLP and selective reduction (SR). We aim to compare procedure-to-delivery interval and perinatal survival between patients with single fetal survival following FLP to planned SR in complicated monochorionic twin pregnancies. STUDY DESIGN: This was a secondary analysis of prospectively collected data in complicated monochorionic twin pregnancies from two fetal centers from 2008-2015. The selection of procedure was dependent upon provider and patient preference. Group 1 was defined as women undergoing FLP for TTTS with an idiopathic single fetal demise within 24 hours of the procedure. Group 2 consisted of women undergoing planned SR for TTTS, and Group 3 was SR for indications other than TTTS, such as discordant anomalies, twin reverse arterial perfusion (TRAP), and selective IUGR. Baseline demographics and perinatal outcomes were compared among the three groups using comparative statistics. Kaplan-Meier survival analysis and Cox-proportional hazard model was performed to compare gestational age (GA) at delivery and procedure to delivery time. RESULTS: In Group 1, 77/1043 (7%) had a single fetal demise within 24 hours of FLP, of which 59 (76%) were donor fetal demise and 18 (24%) were recipient demise. Group 2 included 15 patients, of which 13 (87%) donor fetuses and 2 (13%) recipient fetuses were selectively reduced. Relevant outcomes among the three groups are illustrated in Table below. Survival of the co-twin was highest in the Group 1 (p¼0.04). Although no differences were found in the mean GA at delivery and procedure to delivery time among the groups, on K-M plot with Cox-proportional hazard model, there was significant difference among groups (Figure 1; p¼0.01). On multivariate analysis with cox-proportional hazard model, GA at procedure (Hazard ratio [HR]: 1.1; p¼0.04) and FLP for TTTS (HR: 2.1; p¼0.04) were the only factors found independently associated with GA at delivery. CONCLUSION: When single fetal demise occurs following fetoscopic laser photocoagulation, the other twin is more likely to survive to delivery, but more likely to deliver at an earlier GA compared to selective reduction for TTTS.
Objective: To assess the effect of the duration of uterine preparation with E2 on pregnancy rates... more Objective: To assess the effect of the duration of uterine preparation with E2 on pregnancy rates (PRs) in oocyte donation. Design.: A retrospective study. Setting: IVF-ET Unit, oocyte donation program. Patients: Four hundred eleven patients undergoing 865 ET cycles after oocyte donation. Uterine preparation consisted of6 mg/d E2 valerate. The duration of treatment varied according to the availability of the oocytes for donation. Progesterone, 100 mg/d, was added upon oocyte retrieval. Patients were divided into seven groups according to the duration of uterine preparation with E2, in 5-day ranks. Main Outcome Measures: Pregnancy rates per ET according to the duration of uterine preparation. Results: No differences were noted in the mean age, number of oocytes received, fertilization rates, or number of embryos transferred when comparing all groups. Pregnancy rates ranged from 19% to 27% for E2 treatment of 5 to 35 days. Conclusion: Endometrial preparation in anonymous oocyte donation programs is achieved with continuous administration of E2 until oocytes become available. Our results show that this treatment may be extended for as long as 5 weeks with no significant decrease in PRs.
To evaluate regulation of follicle-stimulating hormone (FSH) receptor expression in the mouse ova... more To evaluate regulation of follicle-stimulating hormone (FSH) receptor expression in the mouse ovary during different stages of an artificially induced ovulatory cycle. Follicular maturation was achieved in pubertal female mice by pregnant mares' serum gonadotropin (PMSG). Ovulation was induced 48 hours later by human chorionic gonadotropin (hCG). Ovaries were harvested before treatment, at 24 and 48 hours after PMSG and at 3, 9 and 12 hours after hCG. RNA was extracted using a single-step isolation method and used for reverse transcription. The cDNA was amplified by polymerase chain reaction (PCR) using primers designed to amplify a 512-basepair product corresponding to the extracellular fragment of the FSH receptor. PCR products, resolved by electrophoresis on agarose gels, showed four bands corresponding to four discrete, alternatively spliced forms of the FSH receptor. Expression of the various transcripts varied at different stages of the ovulatory cycle such that the larger...
Introduction: Preimplantation genetic diagnosis (PGD) is reserved for couples at risk of transmit... more Introduction: Preimplantation genetic diagnosis (PGD) is reserved for couples at risk of transmitting a genetic disease, and hence avoids undesirable therapeutic abortion. Materials and methods: From February 2003 through February 2005, we performed polymerase chain reactionbased PGD for 10 couples at risk for Duchenne's muscular dystrophy (DMD), OTC deficiency, osteogenesis imperfecta (OI), epidermolysis bullosa (EB), lactic acidosis, SMA and LCHAD deficiency. Results: Embryo biopsy was performed on 157 embryos. All embryos were successfully biopsied. Successful diagnosis rate was 94.9% (149/157) and 73 embryos (49.0%) were diagnosed as unaffected. Among them, 38 embryos were transferred in 14 cycles, resulting in five clinical pregnancies (35.7% per transfer) in cases of DMD, OTC deficiency, OI and SMA. There was no clinical abortion or miscarriage in the pregnancies. All pregnancies were confirmed by amniocentesis and neonatal diagnosis. Conclusions: PGD is an efficient alternative method of having children for couples at risk of transmitting genetic diseases.
BackgroundA monochorionic‐diamniotic placenta (MCDAP) is rare in dizygotic (DZ) twinning. All rep... more BackgroundA monochorionic‐diamniotic placenta (MCDAP) is rare in dizygotic (DZ) twinning. All reported cases have been documented in pregnancies achieved by the induction of ovulation alone or during the IVF cycle.Methods and ResultsWe report a spontaneous pregnancy in a 39‐year‐old patient with evidence of MCDAP in DZ twins, discordant for trisomy 21. The first and second‐trimester sonographic scans indicated male twins with MCDAP. Amniocentesis, performed because of advanced maternal age, revealed a normal karyotype in one fetus, and trisomy 21 in the other. Molecular studies, performed in order to confirm the zygosity and chorionicity, demonstrated that the fetuses were DZ. In order to identity the affected twin, a detailed sonographic examination was repeated, but no abnormal findings associated with Down syndrome were demonstrated in any of the fetuses. Therefore, umbilical cord blood samples were obtained from both fetuses. Chromosomal analysis revealed in both fetuses two cel...
Letters to the Editor Sertoli cell only syndrome Dear Sir, Sertoli cell only syndrome was first d... more Letters to the Editor Sertoli cell only syndrome Dear Sir, Sertoli cell only syndrome was first described by Del Castillo et al. (1947). According to the original description it has been used when no spermatogenic cells have been seen in a testicular biopsy specimen. It is therefore unfortunate that the name of this syndrome has been misused in Human Reproduction in connection with cases where Sertoli cell only has been a diagnostic failure by a pathologist (Devroey et al, 1995; Silber et al, 1995). If spermatogenic cells, spermatogonia, spermatocytes, spermatids or spermatozoa are found "in the testis, although in minimal numbers, the state is not Sertoli cell only, but hypospermatogenesis or spermatogenic arrest (maturation arrest). The aetiology of low numbers of tubules with spermatogenesis can be genetic, infection, toxic agent, radiation, or something else. In these cases it is possible to use intracytoplasmic sperm injection (ICSI) with spermatozoa or spermatids obtained from testicular aspiration or biopsy knowing that in genetic cases there is a risk of mediating the defect to male offspring. In cases of true Sertoli cell only syndrome, ICSI is not possible, because there is a total lack of spermatogenic cells.
There are numerous studies concerning pregnancy rates in oocyte donation, yet only a handful repo... more There are numerous studies concerning pregnancy rates in oocyte donation, yet only a handful report the obstetric outcome in such pregnancies. The purpose of this study was to assess factors that influence pregnancy rates, to determine the incidence of complications, and to evaluate obstetric outcome in pregnancies resulting from oocyte donation. This study included 423 oocyte recipients who underwent 1001 oocyte donation cycles at the Oocyte Donation Programme, In-Vitro Fertilization (IVF)-Embryo Transfer Unit, Herzlia Medical Center, Israel. Donors were all healthy women <34 years old who underwent IVF themselves. In 873 cycles, fertilization occurred and embryo transfer was performed, resulting in 194 clinical pregnancies. Pregnancy rates (PR) significantly declined with the increase in number of previous attempts, and with increasing age of recipient (36.8%/embryo transfer in patients ഛ30 compared to 17.8% in patients >40 years old). A significant increment in PR was noted with the increasing number of embryos transferred. The overall PR was 22.2%/ embryo transfer. However, in young amenorrhoeic patients with normal karyotypes undergoing their first cycle, PR was 52.2%; the 'take home baby' rate was 38.3% per patient undergoing embryo transfer and 17.8% per embryo transfer cycle. A significant increase in the incidence of pregnancy-induced hypertension and a higher proportion of abortions were noted in older patients. A significantly higher incidence of prematurity and low birthweight was observed in multiple pregnancies.
Objective: The aim of our study was to evaluate whether intracardiac echogenic foci (ICEFs) may b... more Objective: The aim of our study was to evaluate whether intracardiac echogenic foci (ICEFs) may be associated with increased risk for structural cardiac anomalies in the low-risk population. Methods: During a 24-month period, 3,744 low-risk patients were prospectively screened for ICEFs by prenatal sonography. The study group was composed of 138 fetuses (3.7%) with ICEF. The control group was composed of 167 fetuses without ICEF. In all fetuses a complete echocardiographic evaluation was performed. Results: Among the 138 fetuses in the study group, 108 (78%) ICEFs were found in the left ventricle, 25 (18%) were found in the right ventricle, and 5 (4%) were found to be bilateral. No statistically significant difference was found between the study and the control group regarding the presence of cardiac anomalies. Only 1 case (0.7%) of pulmonic stenosis was found in the study group, compared to 1 case (0.6%) of bicuspid aortic valve in the control group. Conclusions: We conclude that I...
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Papers by Yuval Yaron