Yoel Shufaro - Academia.edu (original) (raw)

Papers by Yoel Shufaro

The aging of the human ovary and the depletion of the oocyte pool have traditionally been the mar... more The aging of the human ovary and the depletion of the oocyte pool have traditionally been the marker of the ending fecundity. The availability of assisted reproduction and the associated technologies such as cryopreservation and egg donation has significantly extended the possibility to conceive quite far beyond the natural human fecundity. Such pregnancies in women of advanced age raise serious medical and ethical concerns regarding the welfare of both the mother and child. The adverse effect of advanced maternal age (AMA) on offspring health has been studied extensively and is currently well recognized. Here we will describe the dilemmas for setting up an age limit for conception attempts, how to screen the candidates in the narrow path of safety, and how to manage these pregnancies.

Journal of Psychosomatic Obstetrics & Gynecology, Feb 12, 2023

International Journal of Andrology, Aug 18, 2022

Molecular human reproduction, Dec 9, 2009

To study possible effects of assisted reproductive technologies (ART) on epigenetic reprogramming... more To study possible effects of assisted reproductive technologies (ART) on epigenetic reprogramming, we have analyzed the DNA methylation levels of differentially methylated regions (DMRs) of seven imprinted genes (H19, MEG3, LIT1, MEST, NESP55, PEG3 and SNRPN) as well as the promoter regions of the pluripotency gene NANOG and the tumor suppressor gene APC in chorionic villus samples (CVS) of 42 spontaneous miscarriages and stillbirths after ART and 29 abortions/stillbirths after spontaneous conception. We did not find an increased rate of faulty methylation patterns after ART, but significant and trend differences (ROC curve analysis, Wilcoxon test) in the methylation levels of LIT1 (P ¼ 0.006) and H19 (P ¼ 0.085) between ART and non-ART samples. With the possible exception of NANOG, we did not observe a gestational age effect on the methylation levels of the studied genes. The frequency of extreme methylation values in PEG3 and APC was markedly higher than in the other studied genes, indicating an increased susceptibility of some genes to epigenetic alterations. Most methylation abnormalities in CVS represented either hypermethylated DMRs of paternally and maternally imprinted genes or hypomethylated promoters of non-imprinted genes. The observed methylation abnormalities (mosaicism) are consistent with methylation reprogramming defects during early embryogenesis.

Human Reproduction, Jun 1, 2023

Research Square (Research Square), May 26, 2022

BACKGROUND: Pulmonary aspiration is a potentially lethal perioperative complication related to ga... more BACKGROUND: Pulmonary aspiration is a potentially lethal perioperative complication related to gastric size and contents. Several perioperative factors are believed to increase gastric size, while others are less studied. Therefore, this study aimed to investigate the effect of anxiety, hormone-induced ovarian stimulation, and prolonged face mask ventilation (FMV) on gastric size via measuring antral crosssectional area (CSA) using ultrasound. METHODS: This prospective observational study was conducted in Rabin Medical Center, Israel. We recruited 49 female patients undergoing hormone-induced ovarian stimulation and oocyte retrieval for invitro fertilization. Preoperatively, they ranked anxiety level on a visual numeric anxiety score (VNS). In the operation room, pre-and postoperative gastric ultrasound examinations were performed. Anesthesia was induced intravenously, followed by FMV with a peak inspiratory pressure of 15 cm H 2 O. RESULTS: There was no substantial correlation between pre-operative VNS anxiety and antral CSA (p=0.697). Moreover, the number of follicles, blood estradiol, and progesterone levels did not correlate with antral CSA (p=0.590, p=0.104, and p=0.511, respectively). The median duration of FMV was 13 minutes [IQR 18 to 8.5] and did not correlate with the antral CSA delta (p=0.312). CONCLUSIONS: Neither preoperative anxiety nor extensive ovarian stimulation affects gastric size. Moreover, prolonged FMV with a peak inspiratory pressure of 15 cm H2O did not increase the gastric size by insu ation. These ndings add to a growing body of literature on this topic. Furthermore, it provides new evidence that FMV is still safe even in a relatively short procedure.

Andrology

BackgroundIntra‐uterine insemination is an essential component in the treatment of infertility. S... more BackgroundIntra‐uterine insemination is an essential component in the treatment of infertility. Success rates are dependent on clinical factors of the female partner, sperm quality, and preparation technique. The effect of the time interval between the end of sperm preparation in the lab, and its injection into the uterine cavity (lab‐to‐uterus time) is yet to be determined.AimTo investigate the association between the lab‐to‐uterus time and the pregnancy rate.Materials and methodsPartner and donor spermatozoa intra‐uterine insemination cycles were included. Preparation for intra‐uterine insemination of partners’ fresh ejaculate or donor thawed spermatozoa was identical. The time interval from the completion of this stage to the actual intra‐uterine injection was recorded. The lab‐to‐uterus intervals were divided into groups A (0–29 min), B (30–59 min), C (60–89 min), and D (90–180 min). Pregnancy was defined as two adequate consecutive doubling levels of hCG and the pregnancy rates...

European Journal of Obstetrics & Gynecology and Reproductive Biology

American Journal of Obstetrics and Gynecology

Human Fertility, 2021

The association between fresh embryo transfer (ET) outcome and the subsequent frozen-thawed (FET)... more The association between fresh embryo transfer (ET) outcome and the subsequent frozen-thawed (FET) cycles that follow is not clear, mainly because of incomplete embryo cohort utilization. The aim of this study was to determine if the outcome of a fresh ET affects the frozen cumulative clinical pregnancy (CP) and live birth (LB) rates resulting from the utilization of all surplus embryos from sibling oocytes. Outcome measures were the FET cumulative CP and LB rates. Multivariate logistic regression was performed for the frozen cumulative CP rate and adjusted for age, the number of oocytes, fresh ET outcome and other confounders. A total of 1313 cycles met the inclusion criteria. The FET cumulative CP and LB rates were not affected by the outcome of the fresh ET. The FET cumulative CP rate increased with the number of oocytes collected regardless of whether a pregnancy was achieved in the fresh cycle or not. In multivariate analysis, age (OR = 0.96, 95% CI 0.94-0.98), protocol (OR = 0.13, 95% CI 0.03-0.57) and the number of oocytes (OR = 1.05, 95% CI 1.02-1.07) were associated with the frozen cumulative CP rate. It is concluded that fresh ET does not impact the outcome of the vitrified-thawed embryos from the same oocyte cohort.

Placenta, 2020

In a recent study of 10,011 pregnant women, 95% of miscarriages occurred before routine ultrasoun... more In a recent study of 10,011 pregnant women, 95% of miscarriages occurred before routine ultrasound scan at 11-14 weeks. Our study aimed to identify early first trimester parameters which may predict miscarriage before 10 weeks of gestation for in vitro fertilization (IVF) pregnancies. Methods: A cohort of 115 healthy IVF patients with a singleton viable embryo in early first trimester were studied in a tertiary university-affiliated medical center (April 2017-June 2018). Calculations included gestational age (GA); ultrasound evaluation of crown-rump length (CRL), mean gestational sac diameter (GSD) and volume (GSV), mean yolk sac diameter (YSD) and volume (YSV); fetal heart rate (FHR), mean uterine arteries pulsatility index (UtA-PI); and maternal blood placental protein 13 (PP13) levels. Patients were divided into three groups by GA; and early miscarriage versus ongoing pregnancy after GA 10 weeks. Results: Early fetal loss occurred in 14.8% of patients; miscarriage group had higher discrepancy between calculated and measured GA (P < 0.001), lower GSD and GSV (P = 0.005 and P = 0.02, respectively), significantly different YSD and YSV, and lower GSD/YSD and GSV/YSV ratios (P = 0.001 and P = 0.003, respectively). UtA-PI/CRL ratio was higher in patients with miscarriage at GA 46-48 days and GA >48 days (P = 0.034 and P = 0.026, respectively). PP13/CRL ratio was higher in patients with miscarriage at GA >48 days (P = 0.041). Discussion: In IVF pregnancies with live embryo at first ultrasound scan, high UtA-PI/CRL and maternal blood PP13/CRL ratios may indicate impaired placentation preceded early pregnancy loss. A larger cohort is needed to further verify these predictions.

Archives of Gynecology and Obstetrics, 2021

Third stage of labor complications are more prevalent following singleton vaginal deliveries of g... more Third stage of labor complications are more prevalent following singleton vaginal deliveries of gestations conceived through in vitro fertilization (IVF) and fresh embryo transfer. This study aimed to evaluate these complications in pregnancies conceived through frozen-thawed embryo transfer (FET), in which endometrial preparation differs from fresh cycles. A cohort study of all singleton pregnancies conceived through IVF-FET who delivered vaginally at a tertiary medical center during 2007–2017. The study group consisted of 88 IVF-FET gestations (cases) that were matched to 176 spontaneous pregnancies based on age, gravidity, parity and gestational week at delivery (controls). The association between mode of conception and third stage of labor complication rate was examined. Baseline characteristics were similar between groups, except for a lower prevalence of induction of labor in the control group (23.3% vs. 36.3%, p = 0.03). The rate of post-partum hemorrhage (PPH), manual lysis and revision of the uterine cavity were all higher in pregnancies conceived through IVF-FET versus spontaneously (13.6% vs. 5.7%, p = 0.018; 17% vs. 2.3%, p < 0.001; and 21.6% vs. 6.8%, p < 0.001, respectively). Multivariate analysis adjusting for age, previous cesarean section, induction of labor, neonatal weight and use of analgesia demonstrated that deliveries following IVF-FET were independently associated with an increased risk for third stage of labor complications (estimated OR = 3.45, p = 0.0002). IVF-FET is an independent risk factor for PPH, need for manual lysis and revision of the uterine cavity. Precautionary measures should be undertaken in the third stage in deliveries following IVF-FET, even if no other risk factors are present.

Journal of Assisted Reproduction and Genetics, 2020

Purpose To compare fertility preservation (FP) outcomes among adolescent transgender males with t... more Purpose To compare fertility preservation (FP) outcomes among adolescent transgender males with those of cisgender females. Methods This retrospective cohort study included nine adolescent transgender males and 39 adolescent cisgender females who underwent FP between January 2017-April 2019 and September 2013-April 2019, respectively. The transgender males were referred before initiating testosterone, and the cisgender females were referred due to cancer diagnosis before starting anticancer treatment. Statistical analyses compared assisted reproductive technology (ART) data and FP outcomes between two groups. Results Basal FSH levels (5.4 ± 1.7 mIU/mL) and AFC (19.8 ± 5.6) of all transgender males were normal compared with standard references. The mean age of transgender males and cisgender females was similar (16.4 ± 1.1 vs 15.5 ± 1.3 years, respectively, P = 0.064). The amount of FSH used for stimulation was significantly lower among the former compared with the latter (2416 ± 1041 IU vs 4372 ± 1877 IU, P < 0.001), but the duration of stimulation was similar (12.6 ± 4.0 and 10.1 ± 2.8 days, P = 0.086). Peak estradiol level was significantly higher among transgender males compared with cisgender females (3073 ± 2637 pg/mL vs 1269 ± 975 pg/mL, respectively, P = 0.018), but there were no significant differences in number of retrieved oocytes between the two groups (30.6 ± 12.8 vs 22 ± 13.2, P = 0.091), number of MII oocytes (25.6 ± 12.9 vs 18.8 ± 11.2, P = 0.134), or maturity rates (81.5 ± 10.0% vs 85.4 ± 14.6%, P = 0.261). Conclusions Adolescent transgender males have an excellent response to ovulation stimulation before initiating testosterone treatment. Oocyte cryopreservation is, therefore, a feasible and effective way for them to preserve their fertility for future biological parenting.

Reproductive BioMedicine Online, 2018

Embryos from in-vitro-matured metaphase I oocytes have a different morphokinetic profile from the... more Embryos from in-vitro-matured metaphase I oocytes have a different morphokinetic profile from their sibling oocytes aspirated at the metaphase II stage after completing maturation in-vivo. This finding supports their low priority status for embryo transfer. The clinical significance should be prospectively studied in treatments when only such embryos are present.

Fertility and Sterility, 2016

PLOS ONE, Oct 20, 2009

Background and Aims: microRNAs (miRNAs) are small noncoding RNAs that regulate cognate mRNAs post... more Background and Aims: microRNAs (miRNAs) are small noncoding RNAs that regulate cognate mRNAs post-transcriptionally. miRNAs have been implicated in regulating gene expression in embryonic developmental processes, including proliferation and differentiation. The liver is a multifunctional organ, which undergoes rapid changes during the developmental period and relies on tightly-regulated gene expression. Little is known regarding the complex expression patterns of both mRNAs and miRNAs during the early stages of human liver development, and the role of miRNAs in the regulation of this process has not been studied. The aim of this work was to study the impact of miRNAs on gene expression during early human liver development. Methods: Global gene and miRNA expression were profiled in adult and in 9-12w human embryonic livers, using highdensity microarrays and quantitative RT-PCR. Results: Embryonic liver samples exhibited a gene expression profile that differentiated upon progression in the developmental process, and revealed multiple regulated genes. miRNA expression profiling revealed four major expression patterns that correlated with the known function of regulated miRNAs. Comparison of the expression of the most regulated miRNAs to that of their putative targets using a novel algorithm revealed a significant anti-correlation for several miRNAs, and identified the most active miRNAs in embryonic and in adult liver. Furthermore, our algorithm facilitated the identification of TGFb-R1 as a novel target gene of let-7. Conclusions: Our results uncover multiple regulated miRNAs and genes throughout human liver development, and our algorithm assists in identification of novel miRNA targets with potential roles in liver development.