Raoul Orvieto | Tel Aviv University (original) (raw)

Papers by Raoul Orvieto

Research paper thumbnail of The role of patient mobilization after embryo transfer in in vitro fertilization programs

American Journal of Obstetrics and Gynecology, 1995

Research paper thumbnail of Cytokines — Involvement in reproduction

International Journal of Gynecology & Obstetrics, 1993

To relay the current knowledge on the interaction between the immune and reproductive systems tha... more To relay the current knowledge on the interaction between the immune and reproductive systems that results from sharing certain lymphohematopoietic cytokines and their receptors. Major studies related to this topic have been identified through MEDLINE searches and through the published literature. Those that have reported on the role of cytokines in the neuroendocrine events of reproduction, ovarian function, placenta, and the developing embryo. The field of growth factor and cytokines and their effects on reproduction is a rapidly growing new area of investigation. Immune cells and related cytokines have been shown to affect the neuroendocrine events of reproduction, ovarian function, placenta, and the developing embryo. Furthermore, it is now becoming apparent that these relationships are reciprocal in that the different cellular components of the neuroendocrine and reproductive systems and the developing embryo can modulate the production of cytokine by the immune system and can also produce certain cytokines. The presence of lymphocytes and macrophages in the female reproductive system, together with the fact that these cells may secrete soluble factors influencing embryo development and trophoblast growth, might suggest that cytokines may play a fundamental role in the mechanisms of immunological reproductive failure. In addition, different mixtures of these mediators, generated by immune cells, the developing embryo, or other maternal cells, may modulate the fine tuning of these activities. Current knowledge indicates a close interaction between the immune and reproductive functions. Further understanding of these interactions may lead to new concepts in fertility regulation.

Research paper thumbnail of Ovarian cysts and cyclic hormone replacement therapy: is there an association?

Acta Obstetricia Et Gynecologica Scandinavica, Jun 1, 1997

Research paper thumbnail of Asymptomatic postmenopausal intrauterine fluid accumulation; characterization and significance

The aims of the study were to characterize those postmenopausal women who develop intrauterine fl... more The aims of the study were to characterize those postmenopausal women who develop intrauterine fluid accumulation and to evaluate its significance. All asymptomatic postmenopausal women who were referred for routine transvaginal ultrasonographic examination between 1 January 1995 and 31 March 1996 were included in the study. Demographic and ultrasonographic parameters were recorded on a prospectively created computerized database. When intrauterine fluid accumulation was identified, the women was referred for endometrial sampling. A total of 1175 consecutive, asymptomatic postmenopausal women were evaluated; intrauterine fluid accumulation was identified sonographically in 166 (14.1%). Women with intrauterine fluid accumulation were older, had experienced more years since the menopause, and had smaller uterine volume indices, thinner endometria and smaller indices of ovarian area, compared to those without intrauterine fluid accumulation (all at a significant level of p < 0.0005). The prevalences of hormone replacement therapy use were 6.6% in the 'accumulating fluid' women and 43% in the 'non-accumulating fluid' group (p < 0.0005). Of the 166 women with intrauterine fluid accumulation, 91 had an endometrial biopsy, of which 70% were insufficient for evaluation and 30% were normal on histology. Postmenopausal intrauterine fluid accumulation is a common, mostly benign phenomenon that typically occurs in the late postmenopausal age subgroups. It may be postulated that it represents part of the atrophic mechanism that takes place at this stage of life. Hormone replacement therapy appears to be a 'protection' against this phenomenon.

Research paper thumbnail of The poor-responder patient in an in vitro fertilization-embryo transfer (IVF-ET) program

The purpose of this article is to review the methods and evaluate the 'avenues' t... more The purpose of this article is to review the methods and evaluate the 'avenues' that are open to patients and physicians in their search for improvement of in vitro fertilization-embryo transfer (IVF-ET) treatment results. The option of egg donation, although very important and viable in the treatment of poor responders, is not described here.

Research paper thumbnail of FMR6 may play a role in the pathogenesis of fragile X-associated premature ovarian insufficiency

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, Jan 11, 2015

The aim of this study was to evaluate whether long noncoding RNA accumulation play a role in the ... more The aim of this study was to evaluate whether long noncoding RNA accumulation play a role in the pathophysiology of fragile X-associated premature ovarian insufficiency (FXPOI). The study population consisted of 22 consecutive fragile X mental retardation 1 (FMR1) premutation carriers (CGGn 55-199 repeats) undergoing in vitro fertilization and pre-implantation genetic diagnosis (IVF-PGD) treatment. The control group consists of 11 patients, with <55 CGG repeats, undergoing IVF-ICSI for male factor infertility, matched by age, treated in the same period. After oocyte retrieval, granulosa cells from follicular fluid were washed and stored at -80 °C. RNA was transcribed to generate cDNA and the RNA levels were measured using RT-PCR. Transcripts levels in granulosa cells of long noncoding RNA's FMR4 and FMR6 were measured. In FMR1 premutation carriers there was a significant nonlinear association between the number of CGG repeats and the levels of FMR6 (p = 0.03), but not FMR4. T...

Research paper thumbnail of Albumin in the Prevention of Severe Ohss. Authors' Reply

Research paper thumbnail of Vascular endothelial growth factor production by circulating immune cells is elevated in ovarian hyperstimulation syndrome. Author's reply

Obstet Gynecol Surv, Jun 1, 2007

Research paper thumbnail of The sperm chemoattractant secreted from human cumulus cells is progesterone

Human Reproduction, 2008

BACKGROUND: Human spermatozoa appear to be guided by chemotaxis to the oocyte in the female genit... more BACKGROUND: Human spermatozoa appear to be guided by chemotaxis to the oocyte in the female genital tract. While one of the sources of sperm chemoattractants is the cumulus cells that surround the oocyte, the identity of the chemoattractant secreted from them is unknown. Progesterone, recognized to be secreted from cumulus cells, was demonstrated, at the pM concentration range, to be

Research paper thumbnail of Cervical pregnancy — a conservative stepwise approach

Research paper thumbnail of A novel approach to normal responder patient with repeated implantation failures - a case report

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, Jan 3, 2015

We describe a case of normal responder patients with repeated implantation failure who was offere... more We describe a case of normal responder patients with repeated implantation failure who was offered the combination of the ultrashort GnRH-ag/ GnRH-ant COH protocol, followed by endometrial injury and a subsequent natural cycle frozen-thawed embryos transfer. The patient conceived following the natural FET cycle that was supported by luteal daily progesterone, with the additional single injection of HCG and GnRH-agonist, on day of ET and 4 days later, respectively. This combined approach seems to be a valuable tool in the armamentarium for treating normal responder patients with repeated implantation failures and should be further examined in large randomized controlled trials.

Research paper thumbnail of Perinatal outcome after fetal reduction from twin to singleton: to reduce or not to reduce?

Fertility and sterility, 2015

To determine whether reduction of twin gestation to singleton pregnancy is associated with improv... more To determine whether reduction of twin gestation to singleton pregnancy is associated with improved perinatal outcome. A retrospective cohort study. Single tertiary care medical center. A cohort of 63 singleton pregnancies after reduction from dichorionic-diamniotic twins gestation and 62 dichorionic-diamniotic nonreduced twins. Fetal reduction between 11 and 14 weeks of gestation. Obstetric outcome. The rates of preterm delivery at <34 weeks (1.6% in pregnancies after reduction vs. 11.7% in nonreduced twins) and at <37 weeks of gestation (9.5% vs. 56.7%) were significantly lower in patients whose pregnancies were reduced to singletons. The rates of miscarriage of one twin (0% vs. 4.8%) and early pregnancy loss before 24 weeks of gestation as well as the rates of gestational diabetes (11.1% vs. 10%), hypertensive diseases of pregnancy (6.3% vs. 15%), and intrauterine growth restriction (0% vs. 3.3%) were similar in both groups. Fetal reduction of twins to singleton is associat...

Research paper thumbnail of Interleukin-2 and SOCS-1 proteins involvement in the pathophysiology of severe ovarian hyperstimulation syndrome-a preliminary proof of concept

Journal of ovarian research, Jan 26, 2014

BackgroundOvarian hyperstimulation syndrome (OHSS), is characterized by marked ovarian enlargemen... more BackgroundOvarian hyperstimulation syndrome (OHSS), is characterized by marked ovarian enlargement and acute third space fluid sequestration that almost always develops after hCG administration or in early pregnancy. OHSS is similar to vascular leak syndrome (VLS), which may be attributable to the massive increase in systemic inflammatory cytokines. In the present pilot exploratory case series, we sought to evaluate interleukin (IL)-2 and suppressor of cytokine signaling (SOCS)-1 expressions in the peripheral blood mononuclear cells (PBMCs) of patients suffering from severe ovarian hypertimulation syndrome (OHSS), and to examine whether their expressions differ when compared to PBMCs originated from normal early pregnant women (without OHSS).MethodsInterleukin-2 and SOCS-1 mRNA expressions were examined in PBMCs of 5 women who were hospitalized due to severe OHSS (OHSS group) and 5 women with early IVF pregnancies and without OHSS (control group).ResultsInterleukin-2 mRNA levels in ...

Research paper thumbnail of Should zygote intrafallopian transfer be offered to all patients with unexplained repeated in-vitro fertilization cycle failures?

Journal of ovarian research, 2014

One of the suggest strategy for patients with repeated implantation failure (RIF) is zygote intra... more One of the suggest strategy for patients with repeated implantation failure (RIF) is zygote intrafallopian transfer (ZIFT). However, no data exist regarding to the issue of when and under which circumstances should ZIFT be offered to patients with RIF? We therefore aimed to examine whether repeated implantation failure (RIF) patients characteristics or their previous controlled ovarian hyperstimulation (COH) variables may differentiate between those who will conceive following a ZIFT cycle and those who will not. Forty seven consecutive women admitted to our IVF unit during a 7 year period, who underwent ZIFT for RIF, were included. Ovarian stimulation characteristics, number of oocytes retrieved and number and quality of zygotes/embryos transferred were assessed and compared between the ZIFT cycle and the previous IVF/ICSI cycle and between those who conceived following the ZIFT cycle and those who did not. Twelve clinical pregnancies (clinical pregnancy rate- 25.5%) were recorded ...

Research paper thumbnail of Does preejaculatory penile secretion originating from Cowper's gland contain sperm?

Journal of assisted reproduction and genetics, 2003

To determine if spermatozoa are present in the preejaculatory penile secretion, originating from ... more To determine if spermatozoa are present in the preejaculatory penile secretion, originating from Cowper's gland. Prospective clinical and laboratory study. Andrology and Sex Counseling Unit, Department of Obstetrics and Gynecology, Academic Teaching Hospital. Five patients referred for premature ejaculation, three for excessive fluid secreted during foreplay and four normal healthy volunteers. Glass slide smears of preejaculatory Cowper's gland secretion obtained during foreplay from at least two different occasions, and semen samples after masturbation. Microscopic examination of air-dried smears, and routine semen analyses. None of the preejaculatory samples contained sperm. All the patients had sperm in routine sperm analyses. Preejaculatory fluid secreted at the tip of the urethra from Cowper's gland during sexual stimulation did not contain sperm and therefore cannot be responsible for pregnancies during coitus interruptus.

Research paper thumbnail of Is severe OHSS associated with adverse pregnancy outcomes? Evidence from a case–control study

Reproductive BioMedicine Online, 2014

Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially life-threatening complicati... more Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially life-threatening complication of fertility treatment. This study evaluated pregnancy outcomes of women hospitalized for severe OHSS. A case-control study was performed of 125 women who were hospitalized due to severe OHSS compared with a control group, consisting of 156 women matched by age and aetiology of infertility, who conceived via IVF and did not develop OHSS. Among women with singleton pregnancies, patients with severe OHSS delivered significantly earlier (37.96 versus 39.11 weeks) and had smaller babies (2854 g versus 3142 g) compared with the matched controls. Similarly, rates of preterm delivery (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;34 weeks of gestation: 8.9% versus 0%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;37 weeks of gestation: 20.5% versus 5.1%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) were significantly increased among patients in the study group. There were no between-group differences in the rates of gestational diabetes, gestational hypertension and intrauterine growth restriction. In contrast, twin pregnancies following OHSS were not significantly different from matched control twins, with regard to the rates of delivery &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;34 weeks and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;37 weeks of gestation, gestational diabetes, gestational hypertension and intrauterine growth restriction. In conclusion, severe OHSS at early gestation is associated with adverse pregnancy outcome only in singleton gestations.

Research paper thumbnail of Pregnancy outcome in women with primary renal disease

The Israel Medical Association journal : IMAJ, 2000

The preconception and intraconception parameters that are relevant to outcome in women with under... more The preconception and intraconception parameters that are relevant to outcome in women with underlying renal disease remain controversial. To analyze the types and frequencies of short- and long-term (2 years after delivery) maternal and neonatal complications in 38 patients with primary renal disease (46 pregnancies), most of them with mild renal insufficiency. Logistic regression models were formulated to predict successful outcome. Successful pregnancy outcome (live, healthy infant without severe handicap 2 years after delivery) was observed in 98% of the patients with primary renal disease. Factors found to be significantly predictive of successful outcome were absence of pre-existing hypertension, in addition to low preconception serum uric acid level. Most women with primary renal disease who receive proper prenatal care have a successful pregnancy outcome. Worse pregnancy outcome was observed in women with moderate or severe renal failure. Fitted logistic models may provide u...

Research paper thumbnail of Interleukin-2 production by cultured human granulosa cells

International journal of fertility and women's medicine

To determine whether cultured human granulosa cells (GC) produce Interleukin (IL)-2 and whether t... more To determine whether cultured human granulosa cells (GC) produce Interleukin (IL)-2 and whether this GC IL-2 production may be regulated by human chorionic gonadotropin (hCG). Human GC derived from preovulatory follicles during in vitro fertilization (IVF) cycles were cultured in the absence or presence of hCG. Interleukin-2 was measured in tissue-culture medium by an enzyme-linked immunosorbent assay (ELISA) system. Cultured GCs were demonstrated to produce IL-2 in vitro. Moreover, a positive, but not statistically significant, dose-response effect was demonstrated between culture supernatant IL-2 levels and hCG concentration. Our data indicate that human GC produce IL-2 and that this production might be regulated by hCG. These results lend credence to the theory that IL-2 might be involved in the events leading to ovarian hyperstimulation syndrome (OHSS).

Research paper thumbnail of Elevated Levels of FMR1 mRNA in Granulosa Cells Are Associated with Low Ovarian Reserve in FMR1 Premutation Carriers

PLoS ONE, 2014

To assess the role of mRNA accumulation in granulosa cells as the cause of low ovarian response a... more To assess the role of mRNA accumulation in granulosa cells as the cause of low ovarian response among FMR1 premutation carriers undergoing pre-implantation genetic diagnosis (PGD). Case control study in an academic IVF unit. Twenty-one consecutive FMR1 premutation carriers and 15 control women were included. After oocyte retrieval the granulosa cells mRNA levels of FMR1 was measured using RT-PCR. In FMR1 premutation carriers, there was a significant non-linear association between the number of CGG repeats and the number of retrieved oocytes (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and a trend to granulosa cells FMR1 mRNA levels (p = 0.07). The lowest number of retrieved oocytes and the highest level of mRNA were seen in women with mid-size CGG repeats (80-120). A significant negative linear correlation was observed between the granulosa cells FMR1 mRNA levels and the number of retrieved oocytes (R2 linear = 0.231, P = 0.02). We suggest that there is a no-linear association between the number of CGG repeats and ovarian function, resulting from an increased granulosa cells FMR1 mRNA accumulation in FMR1 carriers in the mid-range (80-120 repeats).

Research paper thumbnail of Anti Müllerian Hormone (AMH) level and expression in mural and cumulus cells in relation to age

Journal of Ovarian Research, 2014

Serum AMH is declining with age and is highly associated with ovarian follicular reserve and diso... more Serum AMH is declining with age and is highly associated with ovarian follicular reserve and disordered folliculogenesis. However, the precise role of AMH in the process of human follicular aging has still to be determined. This study investigates AMH level in the follicular fluid (FF) and mRNA expression pattern in cumulus and mural granulosa cells of human ovarian follicles in relation to age. We conducted a prospective study. Sixty-eight women undergoing In vitro fertilization (IVF) treatment were enrolled in the study. We obtained FF, mural and cumulus granulosa cells from large preovulatory follicles (17-20 mm) of 21-35 years old women (n = 40) and 40-45 years old women (n = 28) during oocyte pickup. Higher level of AMH mRNA expression in cumulus cells was observed in the older age group compared to the younger (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). In accordance with AMH mRNA expression results, FF AMH protein levels were significantly higher in the older group than in the younger group (4.7 ± 1.1 ng\ml and 2.3 ± 0.2 ng\ml respectively, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.002). AMH is highly expressed and secreted from cumulus GCs of advanced age patients. This remarkable correlation between AMH mRNA levels in cumulus cells in respect to age suggests that AMH may be involved in follicular aging process.

Research paper thumbnail of The role of patient mobilization after embryo transfer in in vitro fertilization programs

American Journal of Obstetrics and Gynecology, 1995

Research paper thumbnail of Cytokines — Involvement in reproduction

International Journal of Gynecology & Obstetrics, 1993

To relay the current knowledge on the interaction between the immune and reproductive systems tha... more To relay the current knowledge on the interaction between the immune and reproductive systems that results from sharing certain lymphohematopoietic cytokines and their receptors. Major studies related to this topic have been identified through MEDLINE searches and through the published literature. Those that have reported on the role of cytokines in the neuroendocrine events of reproduction, ovarian function, placenta, and the developing embryo. The field of growth factor and cytokines and their effects on reproduction is a rapidly growing new area of investigation. Immune cells and related cytokines have been shown to affect the neuroendocrine events of reproduction, ovarian function, placenta, and the developing embryo. Furthermore, it is now becoming apparent that these relationships are reciprocal in that the different cellular components of the neuroendocrine and reproductive systems and the developing embryo can modulate the production of cytokine by the immune system and can also produce certain cytokines. The presence of lymphocytes and macrophages in the female reproductive system, together with the fact that these cells may secrete soluble factors influencing embryo development and trophoblast growth, might suggest that cytokines may play a fundamental role in the mechanisms of immunological reproductive failure. In addition, different mixtures of these mediators, generated by immune cells, the developing embryo, or other maternal cells, may modulate the fine tuning of these activities. Current knowledge indicates a close interaction between the immune and reproductive functions. Further understanding of these interactions may lead to new concepts in fertility regulation.

Research paper thumbnail of Ovarian cysts and cyclic hormone replacement therapy: is there an association?

Acta Obstetricia Et Gynecologica Scandinavica, Jun 1, 1997

Research paper thumbnail of Asymptomatic postmenopausal intrauterine fluid accumulation; characterization and significance

The aims of the study were to characterize those postmenopausal women who develop intrauterine fl... more The aims of the study were to characterize those postmenopausal women who develop intrauterine fluid accumulation and to evaluate its significance. All asymptomatic postmenopausal women who were referred for routine transvaginal ultrasonographic examination between 1 January 1995 and 31 March 1996 were included in the study. Demographic and ultrasonographic parameters were recorded on a prospectively created computerized database. When intrauterine fluid accumulation was identified, the women was referred for endometrial sampling. A total of 1175 consecutive, asymptomatic postmenopausal women were evaluated; intrauterine fluid accumulation was identified sonographically in 166 (14.1%). Women with intrauterine fluid accumulation were older, had experienced more years since the menopause, and had smaller uterine volume indices, thinner endometria and smaller indices of ovarian area, compared to those without intrauterine fluid accumulation (all at a significant level of p &lt; 0.0005). The prevalences of hormone replacement therapy use were 6.6% in the &#39;accumulating fluid&#39; women and 43% in the &#39;non-accumulating fluid&#39; group (p &lt; 0.0005). Of the 166 women with intrauterine fluid accumulation, 91 had an endometrial biopsy, of which 70% were insufficient for evaluation and 30% were normal on histology. Postmenopausal intrauterine fluid accumulation is a common, mostly benign phenomenon that typically occurs in the late postmenopausal age subgroups. It may be postulated that it represents part of the atrophic mechanism that takes place at this stage of life. Hormone replacement therapy appears to be a &#39;protection&#39; against this phenomenon.

Research paper thumbnail of The poor-responder patient in an in vitro fertilization-embryo transfer (IVF-ET) program

The purpose of this article is to review the methods and evaluate the &#39;avenues&#39; t... more The purpose of this article is to review the methods and evaluate the &#39;avenues&#39; that are open to patients and physicians in their search for improvement of in vitro fertilization-embryo transfer (IVF-ET) treatment results. The option of egg donation, although very important and viable in the treatment of poor responders, is not described here.

Research paper thumbnail of FMR6 may play a role in the pathogenesis of fragile X-associated premature ovarian insufficiency

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, Jan 11, 2015

The aim of this study was to evaluate whether long noncoding RNA accumulation play a role in the ... more The aim of this study was to evaluate whether long noncoding RNA accumulation play a role in the pathophysiology of fragile X-associated premature ovarian insufficiency (FXPOI). The study population consisted of 22 consecutive fragile X mental retardation 1 (FMR1) premutation carriers (CGGn 55-199 repeats) undergoing in vitro fertilization and pre-implantation genetic diagnosis (IVF-PGD) treatment. The control group consists of 11 patients, with <55 CGG repeats, undergoing IVF-ICSI for male factor infertility, matched by age, treated in the same period. After oocyte retrieval, granulosa cells from follicular fluid were washed and stored at -80 °C. RNA was transcribed to generate cDNA and the RNA levels were measured using RT-PCR. Transcripts levels in granulosa cells of long noncoding RNA's FMR4 and FMR6 were measured. In FMR1 premutation carriers there was a significant nonlinear association between the number of CGG repeats and the levels of FMR6 (p = 0.03), but not FMR4. T...

Research paper thumbnail of Albumin in the Prevention of Severe Ohss. Authors' Reply

Research paper thumbnail of Vascular endothelial growth factor production by circulating immune cells is elevated in ovarian hyperstimulation syndrome. Author's reply

Obstet Gynecol Surv, Jun 1, 2007

Research paper thumbnail of The sperm chemoattractant secreted from human cumulus cells is progesterone

Human Reproduction, 2008

BACKGROUND: Human spermatozoa appear to be guided by chemotaxis to the oocyte in the female genit... more BACKGROUND: Human spermatozoa appear to be guided by chemotaxis to the oocyte in the female genital tract. While one of the sources of sperm chemoattractants is the cumulus cells that surround the oocyte, the identity of the chemoattractant secreted from them is unknown. Progesterone, recognized to be secreted from cumulus cells, was demonstrated, at the pM concentration range, to be

Research paper thumbnail of Cervical pregnancy — a conservative stepwise approach

Research paper thumbnail of A novel approach to normal responder patient with repeated implantation failures - a case report

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, Jan 3, 2015

We describe a case of normal responder patients with repeated implantation failure who was offere... more We describe a case of normal responder patients with repeated implantation failure who was offered the combination of the ultrashort GnRH-ag/ GnRH-ant COH protocol, followed by endometrial injury and a subsequent natural cycle frozen-thawed embryos transfer. The patient conceived following the natural FET cycle that was supported by luteal daily progesterone, with the additional single injection of HCG and GnRH-agonist, on day of ET and 4 days later, respectively. This combined approach seems to be a valuable tool in the armamentarium for treating normal responder patients with repeated implantation failures and should be further examined in large randomized controlled trials.

Research paper thumbnail of Perinatal outcome after fetal reduction from twin to singleton: to reduce or not to reduce?

Fertility and sterility, 2015

To determine whether reduction of twin gestation to singleton pregnancy is associated with improv... more To determine whether reduction of twin gestation to singleton pregnancy is associated with improved perinatal outcome. A retrospective cohort study. Single tertiary care medical center. A cohort of 63 singleton pregnancies after reduction from dichorionic-diamniotic twins gestation and 62 dichorionic-diamniotic nonreduced twins. Fetal reduction between 11 and 14 weeks of gestation. Obstetric outcome. The rates of preterm delivery at <34 weeks (1.6% in pregnancies after reduction vs. 11.7% in nonreduced twins) and at <37 weeks of gestation (9.5% vs. 56.7%) were significantly lower in patients whose pregnancies were reduced to singletons. The rates of miscarriage of one twin (0% vs. 4.8%) and early pregnancy loss before 24 weeks of gestation as well as the rates of gestational diabetes (11.1% vs. 10%), hypertensive diseases of pregnancy (6.3% vs. 15%), and intrauterine growth restriction (0% vs. 3.3%) were similar in both groups. Fetal reduction of twins to singleton is associat...

Research paper thumbnail of Interleukin-2 and SOCS-1 proteins involvement in the pathophysiology of severe ovarian hyperstimulation syndrome-a preliminary proof of concept

Journal of ovarian research, Jan 26, 2014

BackgroundOvarian hyperstimulation syndrome (OHSS), is characterized by marked ovarian enlargemen... more BackgroundOvarian hyperstimulation syndrome (OHSS), is characterized by marked ovarian enlargement and acute third space fluid sequestration that almost always develops after hCG administration or in early pregnancy. OHSS is similar to vascular leak syndrome (VLS), which may be attributable to the massive increase in systemic inflammatory cytokines. In the present pilot exploratory case series, we sought to evaluate interleukin (IL)-2 and suppressor of cytokine signaling (SOCS)-1 expressions in the peripheral blood mononuclear cells (PBMCs) of patients suffering from severe ovarian hypertimulation syndrome (OHSS), and to examine whether their expressions differ when compared to PBMCs originated from normal early pregnant women (without OHSS).MethodsInterleukin-2 and SOCS-1 mRNA expressions were examined in PBMCs of 5 women who were hospitalized due to severe OHSS (OHSS group) and 5 women with early IVF pregnancies and without OHSS (control group).ResultsInterleukin-2 mRNA levels in ...

Research paper thumbnail of Should zygote intrafallopian transfer be offered to all patients with unexplained repeated in-vitro fertilization cycle failures?

Journal of ovarian research, 2014

One of the suggest strategy for patients with repeated implantation failure (RIF) is zygote intra... more One of the suggest strategy for patients with repeated implantation failure (RIF) is zygote intrafallopian transfer (ZIFT). However, no data exist regarding to the issue of when and under which circumstances should ZIFT be offered to patients with RIF? We therefore aimed to examine whether repeated implantation failure (RIF) patients characteristics or their previous controlled ovarian hyperstimulation (COH) variables may differentiate between those who will conceive following a ZIFT cycle and those who will not. Forty seven consecutive women admitted to our IVF unit during a 7 year period, who underwent ZIFT for RIF, were included. Ovarian stimulation characteristics, number of oocytes retrieved and number and quality of zygotes/embryos transferred were assessed and compared between the ZIFT cycle and the previous IVF/ICSI cycle and between those who conceived following the ZIFT cycle and those who did not. Twelve clinical pregnancies (clinical pregnancy rate- 25.5%) were recorded ...

Research paper thumbnail of Does preejaculatory penile secretion originating from Cowper's gland contain sperm?

Journal of assisted reproduction and genetics, 2003

To determine if spermatozoa are present in the preejaculatory penile secretion, originating from ... more To determine if spermatozoa are present in the preejaculatory penile secretion, originating from Cowper's gland. Prospective clinical and laboratory study. Andrology and Sex Counseling Unit, Department of Obstetrics and Gynecology, Academic Teaching Hospital. Five patients referred for premature ejaculation, three for excessive fluid secreted during foreplay and four normal healthy volunteers. Glass slide smears of preejaculatory Cowper's gland secretion obtained during foreplay from at least two different occasions, and semen samples after masturbation. Microscopic examination of air-dried smears, and routine semen analyses. None of the preejaculatory samples contained sperm. All the patients had sperm in routine sperm analyses. Preejaculatory fluid secreted at the tip of the urethra from Cowper's gland during sexual stimulation did not contain sperm and therefore cannot be responsible for pregnancies during coitus interruptus.

Research paper thumbnail of Is severe OHSS associated with adverse pregnancy outcomes? Evidence from a case–control study

Reproductive BioMedicine Online, 2014

Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially life-threatening complicati... more Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially life-threatening complication of fertility treatment. This study evaluated pregnancy outcomes of women hospitalized for severe OHSS. A case-control study was performed of 125 women who were hospitalized due to severe OHSS compared with a control group, consisting of 156 women matched by age and aetiology of infertility, who conceived via IVF and did not develop OHSS. Among women with singleton pregnancies, patients with severe OHSS delivered significantly earlier (37.96 versus 39.11 weeks) and had smaller babies (2854 g versus 3142 g) compared with the matched controls. Similarly, rates of preterm delivery (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;34 weeks of gestation: 8.9% versus 0%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;37 weeks of gestation: 20.5% versus 5.1%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) were significantly increased among patients in the study group. There were no between-group differences in the rates of gestational diabetes, gestational hypertension and intrauterine growth restriction. In contrast, twin pregnancies following OHSS were not significantly different from matched control twins, with regard to the rates of delivery &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;34 weeks and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;37 weeks of gestation, gestational diabetes, gestational hypertension and intrauterine growth restriction. In conclusion, severe OHSS at early gestation is associated with adverse pregnancy outcome only in singleton gestations.

Research paper thumbnail of Pregnancy outcome in women with primary renal disease

The Israel Medical Association journal : IMAJ, 2000

The preconception and intraconception parameters that are relevant to outcome in women with under... more The preconception and intraconception parameters that are relevant to outcome in women with underlying renal disease remain controversial. To analyze the types and frequencies of short- and long-term (2 years after delivery) maternal and neonatal complications in 38 patients with primary renal disease (46 pregnancies), most of them with mild renal insufficiency. Logistic regression models were formulated to predict successful outcome. Successful pregnancy outcome (live, healthy infant without severe handicap 2 years after delivery) was observed in 98% of the patients with primary renal disease. Factors found to be significantly predictive of successful outcome were absence of pre-existing hypertension, in addition to low preconception serum uric acid level. Most women with primary renal disease who receive proper prenatal care have a successful pregnancy outcome. Worse pregnancy outcome was observed in women with moderate or severe renal failure. Fitted logistic models may provide u...

Research paper thumbnail of Interleukin-2 production by cultured human granulosa cells

International journal of fertility and women's medicine

To determine whether cultured human granulosa cells (GC) produce Interleukin (IL)-2 and whether t... more To determine whether cultured human granulosa cells (GC) produce Interleukin (IL)-2 and whether this GC IL-2 production may be regulated by human chorionic gonadotropin (hCG). Human GC derived from preovulatory follicles during in vitro fertilization (IVF) cycles were cultured in the absence or presence of hCG. Interleukin-2 was measured in tissue-culture medium by an enzyme-linked immunosorbent assay (ELISA) system. Cultured GCs were demonstrated to produce IL-2 in vitro. Moreover, a positive, but not statistically significant, dose-response effect was demonstrated between culture supernatant IL-2 levels and hCG concentration. Our data indicate that human GC produce IL-2 and that this production might be regulated by hCG. These results lend credence to the theory that IL-2 might be involved in the events leading to ovarian hyperstimulation syndrome (OHSS).

Research paper thumbnail of Elevated Levels of FMR1 mRNA in Granulosa Cells Are Associated with Low Ovarian Reserve in FMR1 Premutation Carriers

PLoS ONE, 2014

To assess the role of mRNA accumulation in granulosa cells as the cause of low ovarian response a... more To assess the role of mRNA accumulation in granulosa cells as the cause of low ovarian response among FMR1 premutation carriers undergoing pre-implantation genetic diagnosis (PGD). Case control study in an academic IVF unit. Twenty-one consecutive FMR1 premutation carriers and 15 control women were included. After oocyte retrieval the granulosa cells mRNA levels of FMR1 was measured using RT-PCR. In FMR1 premutation carriers, there was a significant non-linear association between the number of CGG repeats and the number of retrieved oocytes (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and a trend to granulosa cells FMR1 mRNA levels (p = 0.07). The lowest number of retrieved oocytes and the highest level of mRNA were seen in women with mid-size CGG repeats (80-120). A significant negative linear correlation was observed between the granulosa cells FMR1 mRNA levels and the number of retrieved oocytes (R2 linear = 0.231, P = 0.02). We suggest that there is a no-linear association between the number of CGG repeats and ovarian function, resulting from an increased granulosa cells FMR1 mRNA accumulation in FMR1 carriers in the mid-range (80-120 repeats).

Research paper thumbnail of Anti Müllerian Hormone (AMH) level and expression in mural and cumulus cells in relation to age

Journal of Ovarian Research, 2014

Serum AMH is declining with age and is highly associated with ovarian follicular reserve and diso... more Serum AMH is declining with age and is highly associated with ovarian follicular reserve and disordered folliculogenesis. However, the precise role of AMH in the process of human follicular aging has still to be determined. This study investigates AMH level in the follicular fluid (FF) and mRNA expression pattern in cumulus and mural granulosa cells of human ovarian follicles in relation to age. We conducted a prospective study. Sixty-eight women undergoing In vitro fertilization (IVF) treatment were enrolled in the study. We obtained FF, mural and cumulus granulosa cells from large preovulatory follicles (17-20 mm) of 21-35 years old women (n = 40) and 40-45 years old women (n = 28) during oocyte pickup. Higher level of AMH mRNA expression in cumulus cells was observed in the older age group compared to the younger (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). In accordance with AMH mRNA expression results, FF AMH protein levels were significantly higher in the older group than in the younger group (4.7 ± 1.1 ng\ml and 2.3 ± 0.2 ng\ml respectively, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.002). AMH is highly expressed and secreted from cumulus GCs of advanced age patients. This remarkable correlation between AMH mRNA levels in cumulus cells in respect to age suggests that AMH may be involved in follicular aging process.