Cognitive achievements in school-age children born following assisted reproductive technology treatments: A prospective study.

Background: While assisted reproductive technology is increasingly prevalent, there is concern amid conflicting findings reported regarding the long-term outcomes of children born following these treatments. The aim of this research was to investigate aspects of cognitive development in early school-age Israeli children born following assisted reproductive technology (ART) treatments, compared to those spontaneously conceived (SC).

Method: This prospective follow-up study was based on an Israeli cohort recruited from June 2006 to December 2008, that included 561 women whose pregnancies were achieved by ART treatments and 600 women whose pregnancies were SC.

How Are They Doing? Neurodevelopmental Outcomes at School Age of Children Born Following Assisted Reproductive Treatments.

Objective: The purpose of this study was to assess major neurodevelopmental aspects of children conceived by assisted reproductive treatments compared to spontaneously conceived children during the early school years.

Material & Methods: In this follow-up study, mothers of 358 children born following assisted reproductive treatments and 401 spontaneously-conceived children were interviewed by telephone regarding their children's health and development, when the children were 7-8 years old. The main outcomes were maternal responses to 4 questionnaires: Developmental Coordination Disorder Questionnaire, Short Sensory Profile, Autism Spectrum Screening Questionnaire, and the Attention-deficit hyperactive disorder (ADHD) Child Symptom Inventory-4 subscale.

The effect of body mass index (BMI) and gestational weight gain on adverse obstetrical outcomes in pregnancies following assisted reproductive technology as compared to spontaneously conceived pregnancies.

Objective: To compare the effect of pre-pregnancy body mass index (BMI) and inappropriate gestational weight gain (GWG) on adverse obstetrical outcomes among women undergoing assisted reproductive technology (ART) treatments as compared to spontaneously-conceived (SC) pregnancies.

Methods: This prospective cohort study included 1058 pregnant women from two medical centres; 504 women who conceived following ART treatments and 554 who conceived spontaneously. The women were recruited at 8 weeks of gestation and follow-up telephone interviews were conducted 6 weeks after delivery.

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.

Possible risk for cancer among children born following assisted reproductive technology in Israel.

Background: Among children conceived by assisted reproductive technology (ART), increased risk of adverse birth outcomes has been observed, including multiple births, preterm births, and congenital malformations. Regarding cancer among ART-conceived children, findings are discrepant.

Methods: This is a historical cohort of 9,042 ART-conceived children and 211,763 spontaneously conceived (SC) children born from 1997 through 2004.

The Dual Role of PEDF in the Pathogenesis of OHSS: Negating Both Angiogenic and Inflammatory Pathways.

Context: Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of assisted reproductive technologies. This complex syndrome is known to involve massive angiogenesis and inflammation. We have previously established the anti-angiogenic involvement of pigment epithelium-derived factor (PEDF) in the pathophysiology and treatment of OHSS.

Pigment epithelium-derived factor regulation by human chorionic gonadotropin in granulosa cells.

Human chorionic gonadotropin (hCG) is a known trigger of ovarian hyperstimulation syndrome (OHSS), a potentially life-threatening complication of assisted reproduction. Administration of hCG results in the release of vascular endothelial growth factor (VEGF) from the ovary. We have previously shown that expression of pigment epithelium-derived factor (PEDF) in granulosa cell line is regulated by hCG, reciprocally to VEGF, and that the PEDF-VEGF balance is impaired in OHSS.

GnRH Agonist Triggering Modulates PEDF to VEGF Ratio Inversely to hCG in Granulosa Cells.

Context: GnRH agonist (GnRH-a) triggering is associated with a reduced risk of ovarian hyperstimulation syndrome (OHSS) compared with human chorionic gonadotropin (hCG) in assisted reproduction technology cycles. We have shown that ovarian pigment epithelium derived factor (PEDF), a potent antiangiogenic factor, counteracts vascular endothelial growth factor (VEGF) expression and that OHSS is correlated with hCG-induced impaired PEDF to VEGF ratio.

Objective: The objective of the study was to explore whether GnRH-a triggering could directly modulate PEDF/VEGF balance in granulosa cells.

Ploidy of spermatogenic cells of men with non-mosaic Klinefelter's syndrome as measured by a computerized cell scanning system.

Purpose: This study aims to characterize the origin of testicular post-meiotic cells in non-mosaic Klinefelter's syndrome (KS).

Methods: The study included testicular tissue specimens from 11 non-mosaic KS patients, with (6 positive) and without (5 negative) spermatozoa presence. The obtained testicular cells were affixed and stained for morphology followed by fluorescence in situ hybridization (FISH) for centromeric probes X, Y, and 18.

Pigment epithelium-derived factor exerts antioxidative effects in granulosa cells.

Objective: To determine whether supplementing granulosa cells cultures with pigment epithelium-derived factor (PEDF) can protect them from oxidative stress.

Design: We used either granulosa cell line or human primary granulosa cell culture from women undergoing in vitro fertilization (IVF) treatments.

Setting: University research facilities.

Human oocyte-derived sperm chemoattractant is a hydrophobic molecule associated with a carrier protein.

Objective: To characterize the nature of the human oocyte-derived chemoattractant.

Design: Laboratory in vitro study.

Setting: Academic research institute.

The effect of two distinct levels of oxygen concentration on embryo development in a sibling oocyte study.

Purpose: This prospective randomized study used sibling oocytes of 258 women with ≥8 oocytes to compare the effect of 5 % O(2) versus 20 % O(2) concentrations on embryo development and clinical outcome.

Methods: Oocytes of each case were divided between incubators with either 5 % or 20 % O(2) concentration. Outcome measures were fertilization, cleavage, embryo quality, blastocyst formation, and implantation, pregnancy and live birth rates.

Intracytoplasmic sperm injection outcome of ejaculated versus extracted testicular spermatozoa in cryptozoospermic men.

Objective: To compare intracytoplasmic sperm injection (ICSI) outcome of patients with cryptozoospermia after use of ejaculated versus testicular sperm in different cycles of the same patients.

Design: Retrospective cohort study.

Setting: University-affiliated infertility center.

Preimplantation genetic diagnosis in genomic regions with duplications and pseudogenes: long-range PCR in the single-cell assay.

Long-range PCR is generally employed for the analysis of disease-causing mutations in genes with homologous pseudogene copies. However, long-range PCR is challenging when performed on single cells, as in preimplantation genetic diagnosis (PGD) of monogenic disorders. PGD on single cells requires concurrent analysis of a mutation together with multiple linked polymorphic markers from closely related family members to prevent misdiagnosis.

The role of pigment epithelium-derived factor in the pathophysiology and treatment of ovarian hyperstimulation syndrome in mice.

Context: Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of assisted reproduction. OHSS is induced by an ovarian release of vasoactive, angiogenic substances that results in vascular hyperpermeability, leakage, and shift of fluids from blood vessels into the extravascular space with consequent ascites and edema that are attributed to vascular endothelial growth factor (VEGF).

Objective: Our objective was to examine a physiological approach for preventing and treating OHSS, based on negating the VEGF network.

Conventional IVF versus ICSI in sibling oocytes from couples with endometriosis and normozoospermic semen.

Purpose: This study compares the fertilization rate and embryonic development of oocytes randomly inseminated by conventional IVF or ICSI in patients with endometriosis and normozoospermic semen during IVF cycles.

Methods: Sibling oocytes were randomized to be inseminated either by ICSI or IVF. Rates of fertilization, cleavage, blastulation and embryonic morphology were assessed.

Hormonal regulation of pigment epithelium-derived factor (PEDF) in granulosa cells.

Angiogenesis is critical for the development of ovarian follicles. Blood vessels are abrogated from the follicle until ovulation, when they invade it to support the developing corpus luteum. Granulosa cells are known to secrete anti-angiogenic factors that shield against premature vascularization; however, their molecular identity is yet to be defined.

Computerized cell-scanning system for evaluating human spermatogenesis in non-obstructive azoospermic patients.

There may be incompatibility between testicular histopathological evaluation and testicular sperm extraction (TESE) outcome. Assessment for sperm presence and different pathological disturbances of non-obstructive azoospermia (NOA) remains challenging. An assay for maximal sampling and accurate identification of testicular cells from NOA patients undergoing TESE and autopsied fertile controls was developed.

Ovarian response to stimulation for fertility preservation in women with malignant disease: a systematic review and meta-analysis.

Objective: To evaluate the current available data regarding ovarian performance of patients diagnosed with malignant disease undergoing controlled ovarian hyperstimulation (COH) for fertility preservation, before radio/chemotherapy, compared with age-matched, healthy patients undergoing COH for in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI).

Design: Meta-analysis of the data available from a systematic review of the literature.

Setting: Academic centers of infertility and IVF.

Nationwide use of postmortem retrieved sperm in Israel: a follow-up report.

A follow-up study of the subsequent use of all postmortem frozen sperm samples during 2003-2010 is reported. Only the sister of one of the 10 unmarried deceased men was in contact with the bank. Four widows elected to discard the frozen sperm and all of the remaining spouses were uninterested in its fate.

The effect of medical clowning on pregnancy rates after in vitro fertilization and embryo transfer.

This experimental prospective quasi-randomized study examining the impact of a medical clowning encounter after embryo transfer (ET) after in vitro fertilization (IVF) found that the pregnancy rate in the intervention group was 36.4%, compared with 20.2% in the control group (adjusted odds ratio, 2.

In vitro fertilization surrogacy in rare coexisting Mayer-Rokitansky-Kuster-Hauser syndrome and triple X karyotype.

Objective: To report the responses to IVF surrogacy attempts in a female with a heretofore never described combination of Mayer-Rokitansky-Kuster-Hauser (MRHK) syndrome and triple X karyotype.

Design: Case report.

Setting: Reproductive unit of a university-affiliated medical center.

Preimplantation genetic diagnosis (PGD) for SHOX-related haploinsufficiency in conjunction with trisomy 21 detection by molecular analysis.

Purpose: Development of a molecular PGD protocol for a male with an X-linked deletion in the SHOX gene region, located in the pseudoautosomal region of the X/Y chromosomes. Due to excessive recombination in this region, the deletion can be found in male offspring.

Methods: We developed a 13 marker multiplex fluorescent PCR protocol: 3 markers within the deleted SHOX region, 5 flanking markers, 3 informative markers on chromosome 21 (advanced maternal age) and 2 markers for sex determination.

Using sperm posthumously: national guidelines versus practice.

Under pressure from involved families and time limitations, Israeli judges tend to authorize postmortem sperm retrieval and freezing, even in unmarried men and in contradiction to current, albeit non-legally binding, guidelines of the Attorney General. Postmortem sperm retrieval in our institution (2003 to June 2009) was successful in 17 cases, motile sperm was found in 16/17, and cryopreservation was performed in 15/16: no application for use of any of the postmortem frozen samples has been performed thus far.

Outcome of IVF pregnancies following severe OHSS.

Because severe ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening iatrogenic complication, much effort is made to prevent it and the anticipated pregnancy naturally becomes of secondary importance. There are many publications on OHSS, but very few on pregnancy outcomes. This work is to review the effect of OHSS on pregnancy outcome along the pregnancy course.