Israeli men's attitudes toward posthumous reproduction and prior consent amid ongoing armed conflict.

Background: From October 7, 2023, until August 28, 2024, 187 posthumous sperm retrieval (PSR) procedures have been conducted on deceased men, 171 of whom are soldiers. PSR was predominantly initiated by parents to cope with their profound loss. However, the attitudes of Israeli men toward this procedure are unknown.

IVF outcomes pre- and post-anti-COVID-19 vaccination - Are there any differences?

Since the beginning of the SARS-CoV-2 pandemic, there have been rising concerns about the virus's possible ability to affect male and female fertility. Although effective vaccines were introduced and the vaccination rate of the general population is high, some reproductive-age individuals are still hesitant to receive the vaccine, because of an unestablished belief that the vaccine might impair fertility. In this single-center retrospective study, encompassing data from 387 medical files of in-vitro fertilization (IVF) patients we compared IVF cycle outcomes and sperm characteristics in vaccinated couples before and after vaccination, as well as between vaccinated patients and a control group of individuals who were neither vaccinated nor infected with COVID-19 before or during the cycles.

Impact of pre-treatment in GnRH-antagonist cycles triggered with GnRH agonist on reproductive outcomes.

Objective: Pre-treatment (PT) therapies in IVF are known to be used as pre-stimulation modality to improve cycle outcomes. This study aims to assess whether PT in GnRH antagonist cycles triggered with GnRH-agonist impact oocyte maturation response.

Methods: Data were retrospectively collected for patients who underwent GnRH antagonist cycle with agonist triggering with and without PT.

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.

Differentiation of uniparental human embryonic stem cells into granulosa cells reveals a paternal contribution to gonadal development.

Genomic imprinting underlies the mammalian requirement for sexual reproduction. Nonetheless, the relative contribution of the two parental genomes during human development is not fully understood. Specifically, a fascinating question is whether the formation of the gonad, which holds the ability to reproduce, depends on equal contribution from both parental genomes.

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.

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.

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.

Leukocyte Telomere Length Correlates with Extended Female Fertility.

Current social trends of delayed reproduction to the fourth and fifth decade of life call for a better understanding of reproductive aging. Demographic studies correlated late reproduction with general health and longevity. Telomeres, the protective ends of eukaryotic chromosomes, were implicated in various aging-associated pathologies and longevity.

Hypogonadism in Women with Prader-Willi Syndrome-Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion.

Prader-Willi syndrome (PWS) is a rare neuroendocrine genetic syndrome. Characteristics of PWS include hyperphagia, hypotonia, and intellectual disability. Pituitary hormone deficiencies, caused by hypothalamic dysfunction, are common and hypogonadism is the most prevalent.

Identifying regulators of parental imprinting by CRISPR/Cas9 screening in haploid human embryonic stem cells.

In mammals, imprinted genes are regulated by differentially methylated regions (DMRs) that are inherited from germ cells, leading to monoallelic expression in accordance with parent-of-origin. Yet, it is largely unknown how imprinted DMRs are maintained in human embryos despite global DNA demethylation following fertilization. Here, we explored the mechanisms involved in imprinting regulation by employing human parthenogenetic embryonic stem cells (hpESCs), which lack paternal alleles.

DMPK hypermethylation in sperm cells of myotonic dystrophy type 1 patients.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant muscular dystrophy that results from a CTG expansion (50-4000 copies) in the 3' UTR of the DMPK gene. The disease is classified into four or five somewhat overlapping forms, which incompletely correlate with expansion size in somatic cells of patients. With rare exception, it is affected mothers who transmit the congenital (CDM1) and most severe form of the disease.

'Why have women not returned to use their frozen oocytes?': a 5-year follow-up of women after planned oocyte cryopreservation.

Research Question: What are the reproductive choices and retrospective reflections of women at least 4 years after planned oocyte cryopreservation (POC)?

Design: This was an internet survey, using the REDCap application, of women who underwent POC, at a single-centre university-affiliated IVF unit, 4-8 years before the survey. The questionnaire addressed reproductive choices and outcomes following POC.

Results: Seventy-nine women who underwent POC during 2011-2014 were invited to participate, and 70 (89%) responded.

Hypogonadism in Adult Males with Prader-Willi Syndrome-Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion.

Prader-Willi syndrome (PWS) is a complex genetic syndrome characterized by hyperphagia, intellectual disability, hypotonia and hypothalamic dysfunction. Adults with PWS often have hormone deficiencies, hypogonadism being the most common. Untreated male hypogonadism can aggravate PWS-related health issues including muscle weakness, obesity, osteoporosis, and fatigue.

Expanded clinical validation of Haploseek for comprehensive preimplantation genetic testing.

Purpose: We previously developed Haploseek, a method for comprehensive preimplantation genetic testing (PGT). However, some key features were missing, and the method has not yet been systematically validated.

Methods: We extended Haploseek to incorporate DNA from embryo grandparents and to allow testing of variants on chromosome X or in regions where parents share common haplotypes.

Preimplantation genetic testing (PGT) for copy number variants of uncertain significance (CNV- VUS) in the genomic era: to do or not to do?

Purpose: To review cases of couples presented to our PGT-unit with copy number variants (CNVs) classified as variants of uncertain significance (VUS) in order to better understand their needs.

Methods: Retrospective cohort study conducted in a tertiary medical-center, 2014-2019. We reviewed files of all couples applying for genetic counseling with CNVs classified as VUS.

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.

Cancer in IVF patients treated at age 40 years and older: long term follow-up.

Research Question: Current knowledge of cancer risk among women who undergo IVF is based mainly on studies of women treated in their thirties, frequently with short follow-up periods. Therefore, information about cancer risk among infertile menopausal women is limited. We aimed to evaluate the risk of cancer among IVF patients treated at age 40 years and older, followed up for an extended period.

Global Characterization of X Chromosome Inactivation in Human Pluripotent Stem Cells.

Dosage compensation of sex-chromosome gene expression between male and female mammals is achieved via X chromosome inactivation (XCI) by employing epigenetic modifications to randomly silence one X chromosome during early embryogenesis. Human pluripotent stem cells (hPSCs) were reported to present various states of XCI that differ according to the expression of the long non-coding RNA XIST and the degree of X chromosome silencing. To obtain a comprehensive perspective on XCI in female hPSCs, we performed a large-scale analysis characterizing different XCI parameters in more than 700 RNA high-throughput sequencing samples.

The effect of repeated biopsy on pre-implantation genetic testing for monogenic diseases (PGT-M) treatment outcome.

Purpose: To study the outcome of repeated biopsy for pre-implantation genetic testing in case of failed genetic diagnosis in the first biopsy.

Methods: The study group included 81 cycles where embryos underwent re-biopsy because there were no transferable embryos after the first biopsy: in 55 cycles, the first procedure was polar body biopsy (PBs) and the second cleavage-stage (BB); in 26 cycles, the first was BB and the second trophectoderm (BLAST) biopsy. The control group included 77 cycles where embryos underwent successful genetic diagnosis following the first biopsy, matched by maternal age, egg number, genetic inheritance type, and embryonic stage at the first biopsy.

Noninvasive paternal exclusion testing for cystic fibrosis in the first five to eight weeks of gestation.

Prenatal genetic testing is not generally applicable to the very early stages of pregnancy (prior to week 8 gestation), a time period that is crucial to pregnant couples with high risk for transmission of genetic disease to their fetus. Therefore, we developed a new ultra-sensitive targeted next generation sequencing method for noninvasive haplotype-based paternal allele exclusion testing of the cystic fibrosis-associated gene, CFTR. This new method was compared to a conventional library prep and sequencing analysis method and all test results were validated by amniotic fluid testing at later stages of pregnancy.

Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial.

Study Question: Does preimplantation genetic testing for aneuploidy (PGT-A) by comprehensive chromosome screening (CCS) of the first and second polar body to select embryos for transfer increase the likelihood of a live birth within 1 year in advanced maternal age women aged 36-40 years planning an ICSI cycle, compared to ICSI without chromosome analysis?

Summary Answer: PGT-A by CCS in the first and second polar body to select euploid embryos for transfer does not substantially increase the live birth rate in women aged 36-40 years.

What Is Known Already: PGT-A has been used widely to select embryos for transfer in ICSI treatment, with the aim of improving treatment effectiveness. Whether PGT-A improves ICSI outcomes and is beneficial to the patients has remained controversial.

Forty years of IVF.

This monograph, written by the pioneers of IVF and reproductive medicine, celebrates the history, achievements, and medical advancements made over the last 40 years in this rapidly growing field.

Incomplete methylation of a germ cell tumor (Seminoma) in a Prader-Willi male.

Background: Prader-Willi syndrome (PWS) is a multisystem genetic disorder characterized by lack of satiety leading to morbid obesity, variable degrees of mental retardation, behavior disorders, short stature, and hypogonadism. The underlying genetic cause for PWS is an imprinting defect resulting from a lack of expression of several paternally inherited genes embedded within the 15q11.2-q13 region.