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Oocyte development and fertilization are largely influenced by the microenvironment of the follicular fluid (FF), and the exploration of its molecular/metabolic composition may help in improving in vitro fertilization (IVF) outcomes.... more
Oocyte development and fertilization are largely influenced by the microenvironment of the follicular fluid (FF), and the exploration of its molecular/metabolic composition may help in improving in vitro fertilization (IVF) outcomes. Here, the concentrations of molecules related to oxidative stress/inflammation were measured in FF from follicles at oocyte retrieval during IVF. Here, the FF antioxidant potential was correlated with the number of retrieved/mature oocytes and the number of fertilized ones. FF collected from the follicles of normal fertilized oocytes presented an elevated antioxidant capability, lower levels of pro-inflammatory molecules (i.e., IL-6, IL-8, IL-12, TGF-β, and HIF-1α), and a higher IL-10 concentration. FF samples from follicles at oocyte retrieval that resulted in top-quality embryos displayed a peculiar antioxidant capability and a further decrease in proinflammatory molecules when compared with FF, giving rise to poor-quality embryos. Finally, pro-inflam...
An abnormal endometrial microbiota has been suggested to impair the process of embryo implantation, thus leading to repeated implantation failure (RIF) in women undergoing in vitro fertilization (IVF). However, the molecular mechanisms... more
An abnormal endometrial microbiota has been suggested to impair the process of embryo implantation, thus leading to repeated implantation failure (RIF) in women undergoing in vitro fertilization (IVF). However, the molecular mechanisms linking uterine microbiota and IVF out-comes are still an open question. The aim of this cohort study was to outline the relationship between endometrial microbiota, inflammation and IVF outcomes. To this purpose, endometrial microbiota and selected components of the “cytokine network” were analyzed in women presenting RIF and divided between eubiosis and dysbiosis groups, according to the percentage of endometrial lactobacilli (≥90% or <90%, respectively). The Dysbiosis group presented significantly higher tissue concentrations of the inflammatory markers (IL-6, IL-1β, HIF-1α and COX-2) and significantly lower levels of the anti-inflammatory/well-being factors, IL-10 and IGF-1, with respect to women with eubiosis. Moreover, the Lactobacillus perce...
Polycystic ovary syndrome (PCOS) is an endocrine systemic disorder mainly characterized by a hormonal and metabolic disbalance that leads to oligo/anovulation, hyperandrogenism and the formation of ovarian cysts. Despite the progress that... more
Polycystic ovary syndrome (PCOS) is an endocrine systemic disorder mainly characterized by a hormonal and metabolic disbalance that leads to oligo/anovulation, hyperandrogenism and the formation of ovarian cysts. Despite the progress that has been reached in its diagnosis and management, little is known about the molecular mechanisms and signaling pathways underlying the pathogenic mechanisms. In this sense, recent research has suggested that the influence of multiple factors, including age, environment, lifestyle and the disease state environment can change the clinical presentation of PCOS via epigenetic modifications. Variants in the genes encoding for proteins involved in steroidogenesis and glucose homeostasis play a crucial role in the development of the disease. Other genes involved in inflammation and cell proliferation seem to undergo an epigenetic control. Moreover, lifestyle factors influence the PCOS course and prognosis, including diet and physical activity, which are f...
Recently, the importance of bioenergetics in the reproductive process has emerged. For its energetic demand, the oocyte relies on numerous mitochondria, whose activity increases during embryo development under a fine regulation to limit... more
Recently, the importance of bioenergetics in the reproductive process has emerged. For its energetic demand, the oocyte relies on numerous mitochondria, whose activity increases during embryo development under a fine regulation to limit ROS production. Healthy oocyte mitochondria require a balance of pyruvate and fatty acid oxidation. Transport of activated fatty acids into mitochondria requires carnitine. In this regard, the interest in the role of carnitines as mitochondrial modulators in oocyte and embryos is increasing. Carnitine pool includes the un-esterified l-carnitine (LC) and carnitine esters, such as acetyl-l-carnitine (ALC) and propionyl-l-carnitine (PLC). In this review, carnitine medium supplementation for counteracting energetic and redox unbalance during in vitro culture and cryopreservation is reported. Although most studies have focused on LC, there is new evidence that the addition of ALC and/or PLC may boost LC effects. Pathways activated by carnitines include an...
Purpose Endometriosis is a benign gynecological disease affecting women in their Reproductive age and characterized by chronic pelvic pain and infertility. Previous studies have demonstrated the role of neurotrophins (in particular... more
Purpose Endometriosis is a benign gynecological disease affecting women in their Reproductive age and characterized by chronic pelvic pain and infertility. Previous studies have demonstrated the role of neurotrophins (in particular brain-derived neurotrophic factor) in the pain pathway and in inflammation processes, which both characterize endometriosis. Our previous study revealed higher brain-derived neurotrophic factor levels in patients suffering from endometriosis than in healthy women during the follicular phase of the menstrual cycle, thus suggesting a neuroprotective role of this particular neurotrophin in response to a neuro-inflammatory reaction. The aim of this study is to assess whether the diurnal variation of brain-derived neurotrophic factor and the circadian rhythm of cortisol are preserved in this kind of patient. Methods We enrolled 11 healthy women (age range 20 to 30, BMI range 20.6 to 29.3), and 11 women suffering from endometriosis (age range 25 to 35, BMI rang...
Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of... more
Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent deacylation and the ADP-ribosylation of mitochondrial proteins, thereby modulating gene expression and activities of enzymes involved in oxidative metabolism and stress responses. In this context, mitochondrial sirtuins (mtSIRTs) act in synergistic or antagonistic manners to protect from aging and aging-related metabolic abnormalities. In this review, we focus on the role of mtSIRTs in the biological competence of reproductive cells, organs, and embryos. Most studies are focused on SIRT3 in female reproduction, providing evidence that SIRT3 improves the competence of oocytes in humans and animal models. Moreover, SIRT3 protects oocytes, early embryos, and ovaries against stress c...
Endometriosis (EMS) pathogenesis has been related to the release of inflammatory mediators in peritoneal fluid, creating an altered microenvironment that leads to low-grade oocyte/embryos and to the reduction of implantation rates. The... more
Endometriosis (EMS) pathogenesis has been related to the release of inflammatory mediators in peritoneal fluid, creating an altered microenvironment that leads to low-grade oocyte/embryos and to the reduction of implantation rates. The Epithelial–Mesenchymal Transition (EMT), an inflammation-related process, can be a further contributing factor to EMS. This study aimed to investigate, among various cytokines and EMT markers (Cadherins, TGF-β, HIF-1α), diagnostic markers of EMS and prognostic factors of in vitro fertilization (IVF) outcomes. Herein, EMS patients manifested higher serum levels of the inflammatory molecules IL-6, IL-8, and IL-12 and a decrease in the concentrations of the anti-inflammatory IL-10. Moreover, biochemical markers associated with the EMT process were more elevated in serum and follicular fluid (FF) of EMS patients than in controls. At the end, the number of good-quality embryos was inversely related to serum IL-6 and EMT markers. Interestingly, serum IL-6 a...
Purpose Endometriosis is one of the most common benign gynecological diseases affecting women of reproductive age; it is characterized by the presence and growth of ectopic endometrial tissue outside the endometrial cavity. This complex... more
Purpose Endometriosis is one of the most common benign gynecological diseases affecting women of reproductive age; it is characterized by the presence and growth of ectopic endometrial tissue outside the endometrial cavity. This complex disease is frequently associated with infertility and pelvic pain. Given the relationship and the apparent importance of the role that neurotrophins play in the reproductive system, and in particular brain-derived neurotrophic factor (BDNF) which is involved in both the central and peripheral pain pathways, we were interested in determining whether the presence of endometriosis is associated and correlated with plasma and follicular fluid variation of BDNF. Methods We determined BDNF level in plasma and in follicular fluid from infertile women with endometriosis and fertile women without the disease. Results BDNF plasma levels were significantly higher in endometriotic patients than in control women (p<0.001). After surgery this level decreased si...
The advent of robot-assisted laparoscopy (RAL) represents an important innovation and has opened new perspectives for treatment of endometriosis, in particular in deep infiltrating endometriosis (DIE). RAL could offer several technical... more
The advent of robot-assisted laparoscopy (RAL) represents an important innovation and has opened new perspectives for treatment of endometriosis, in particular in deep infiltrating endometriosis (DIE). RAL could offer several technical advantages in treating this complex disease, such as 3D vision, tremor filtration and better surgical ergonomy, would be able to improve surgical performances without increasing in surgical time, blood loss, intra- and postoperative complications and it reduces the rates of conversion to laparotomy. Additionally thanks to its reduced learning curve compared to conventional laparoscopy, facilitates the training of less experienced surgeons. For these reason DIE might be one of the best indications for robot assisted laparoscopy in gynecologic surgery. However, very few retrospective studies, small cases series and only a randomized clinical trial were reported. Further randomized control trial comparing CL to RAL for different stage of endometriosis an...
In the last years, the practice of surgery is evolved thanks to the introduction of videolaparoscopic and robotic techniques. Laparoscopic surgery has revolutionized the concept of minimally invasive surgery in the last decades but it... more
In the last years, the practice of surgery is evolved thanks to the introduction of videolaparoscopic and robotic techniques. Laparoscopic surgery has revolutionized the concept of minimally invasive surgery in the last decades but it presents limitations due to the normal mechanism of the human hand. The robotic-assisted surgery is designed to overcome these limitations. In comparison with laparoscopic surgery, the robotic technique presents many advantages such as 3-dimensional vision, a decrease of surgeon’s fatigue and tremors, and an increase of wrist motion improved dexterity and greater surgical precision. Many procedures have already been performed with this technique in urology, cardiac surgery and general surgery. Nowadays the use of the robotic technique is becoming more frequent also in gynaecological surgery and it is preferred to conventional laparoscopy for the treatment of gynaecological malignancies and most of the benign disease of certain complexity, such as hyste...
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The “resistant” or “insensitive” ovary syndrome is a well-known cause of hypergonadotropic amenorrhea. Ovaries appear normal and contain primordial follicles. However, the primordial follicles fail to respond to human gonadotropins. It... more
The “resistant” or “insensitive” ovary syndrome is a well-known cause of hypergonadotropic amenorrhea. Ovaries appear normal and contain primordial follicles. However, the primordial follicles fail to respond to human gonadotropins. It can be defined as a condition similar to the premenopause hormonal situation, with an ovarian low response to the pituitary stimulation that has been found in women under 45 years of age. This hormonal situation frequently is an indication of total hormonal ovarian failure, which can be verified during the postmenopausal period.
Ovarian folliculogenesis is regulated by a fine balance between endocrine and intraovarian factors. In this review, we focus on the role of growth factors in physiological folliculogenesis and in polycystic ovaries. Recent evidence shows... more
Ovarian folliculogenesis is regulated by a fine balance between endocrine and intraovarian factors. In this review, we focus on the role of growth factors in physiological folliculogenesis and in polycystic ovaries. Recent evidence shows that the main systems implicated in polycystic ovary folliculogenesis are the growth hormone and insulin-like growth factor system, vascular endothelial growth factor, and the transforming growth factor-β family. Growth hormone and the insulin-like growth factor system could affect follicular development and oocyte maturation if their balance was altered, while vascular endothelial growth factor is implied in follicular dominance by providing an increasing vascular supply. The transforming growth factor-β family is composed of various molecules, which have different roles in cellular proliferation. Finally, a series of different factors seem to be involved in altered polycystic ovary follicular growth.
... of drugs and laboratory tests [9]. Paolo Giovanni Artini1, Francesca Papini1, Maria Ruggiero1, Giulia Scaravelli2, Olga Maria Di Berardino1, Giovanna Simi1 and Vito Cela†1 1Department of Reproductive Medicine and Child ...
One of the aims of assisted reproduction technologies (ART) is the recruitment of multiple follicles ensuring the recovery of good-quality oocytes upon controlled ovarian hyperstimulation (COH). In recent years, the number of patients in... more
One of the aims of assisted reproduction technologies (ART) is the recruitment of multiple follicles ensuring the recovery of good-quality oocytes upon controlled ovarian hyperstimulation (COH). In recent years, the number of patients in whom few oocytes are obtained in response to COH is increasing. This phenomenon mainly is probably related to the postponement of childbearing to the fourth decade of life. In this group of patients, multifollicular response to COH remains a challenge, but the optimisation of laboratory strategies may help to maximise their chances of pregnancy. Ovarian response to COH varies widely among patients and is strictly dependent on the size of the ovarian pool of resting follicles, the so-called ovarian reserve [1]. In women with a reduced ovarian reserve, a poor ovarian response results in a low number of retrieved oocytes despite the high dose of gonadotropins administered. Hence, although tests for predicting ovarian reserve are available [2], the parameter that best categorises a woman as a ‘poor responder’ remains the ovarian response itself. The incidence of poor ovarian response (POR) is estimated between 9 and 24 % [3–5]. This value increases with age [3, 5] reaching about 50 % in women over 40 years [6]. Women who respond poorly to COH have pregnancy rates that vary from 7.6 to 17.5 %, while in normal responders, they vary from 25.9 to 36.7 %. Female age plays a distinct role in predicting poor response to COH; in fact, older poor responders have lower pregnancy rates (ranging between 1.5 and 12.7 %) compared with younger poor responders (ranging between 13.0 and 35 %) [2]. A second predicting factor of pregnancy outcome in poor responders is the degree of poor response. A lower number of retrieved oocytes results in fewer embryos to transfer and a lower chance of pregnancy, in addition to the expected negative effect of poor ovarian function on oocyte quality.
Poor response to ovarian stimulation (POR) usually indicates a reduction in follicular response to ovarian stimulation during in vitro fertilization (IVF) cycles resulting in a reduced number of retrieved oocytes. In recent years, mainly... more
Poor response to ovarian stimulation (POR) usually indicates a reduction in follicular response to ovarian stimulation during in vitro fertilization (IVF) cycles resulting in a reduced number of retrieved oocytes. In recent years, mainly due to the postponement of childbearing and the consequent decrease of ovarian reserve, often a POR occurs during IVF despite the high dose of gonadotropins administered. Incidence of POR has been reported from 9 to 24 % [1, 2], and even if this condition may occur unexpectedly, its prevalence increases with age, and it is >50 % in patients over 40 years [3]. Patients with POR are defined as poor responders.
Thyroid autoimmunity is the most prevalent autoimmune state that affects up to 5-20% of women during the age of fertility. Prevalence of thyroid autoimmunity is significantly higher among infertile women, especially when the cause of... more
Thyroid autoimmunity is the most prevalent autoimmune state that affects up to 5-20% of women during the age of fertility. Prevalence of thyroid autoimmunity is significantly higher among infertile women, especially when the cause of infertility is endometriosis or polycystic ovary syndrome. Presence of thyroid autoimmunity does not interfere with normal embryo implantation and have been observed comparable pregnancy rates after assisted reproduction techniques in patients with or without thyroid autoimmunity. Instead, the risk of early miscarriage is substantially raised with the presence of thyroid autoimmunity, even if there was a condition of euthyroidism before pregnancy. Furthermore the controlled ovarian hyperstimulation, used as preparation for assisted reproduction techniques, can severely impair thyroid function increasing circulating estrogen levels. Systematic screening for thyroid disorders in women with a female cause of infertility is controversial but might be important to detect thyroid autoimmunity before to use assisted reproduction techniques and to follow-up these parameters in these patients after controlled ovarian hyperstimulation and during pregnancy.
Premature ovarian failure is a complex disorder that results in the early loss of ovarian function; however this disease must be separated from early menopause because these patients can sporadically ovulate and in literature are... more
Premature ovarian failure is a complex disorder that results in the early loss of ovarian function; however this disease must be separated from early menopause because these patients can sporadically ovulate and in literature are described pregnancies. The aetiology and the patho-physiology of premature ovarian failure are still matter of debate, but is commonly accepted that genetic factors play an important role. This review is aimed to present an overview of known inherited factor implied in the pathogenesis of this disorder to help physician in the counselling of affected pregnant women.
Polycystic ovary syndrome is an endocrine disorder often characterized by insulin resistance and hyperinsulinemia, especially in overweight/obese women. Among insulin sensitizers, the positive role of inositols has been increasingly... more
Polycystic ovary syndrome is an endocrine disorder often characterized by insulin resistance and hyperinsulinemia, especially in overweight/obese women. Among insulin sensitizers, the positive role of inositols has been increasingly established in recent years. The action of inositols not only concerns the metabolic parameters of these patients, but also the hormonal profile, resulting in beneficial effects on ovarian function. For this reason, many studies have tried to recognize their role in PCOS infertile women who underwent in vitro fertilization (IVF) procedures.
Follicular fluid (FF) levels of immuno reactive beta-Endorphin (i.r. beta-EP), i.r. gamma-Endorphin (i.r. gamma-EP), i.r. alpha-melanocyte-stimulating hormone (i.r. alpha-MSH), androgens and estrogens were measured in 76 preovulatory... more
Follicular fluid (FF) levels of immuno reactive beta-Endorphin (i.r. beta-EP), i.r. gamma-Endorphin (i.r. gamma-EP), i.r. alpha-melanocyte-stimulating hormone (i.r. alpha-MSH), androgens and estrogens were measured in 76 preovulatory follicles obtained, after gonadotropin stimulation from 19 women undergoing in vitro fertilization (IVF). The aim of the study was to investigate the relationships existing between peptide contents of FF and both oocyte-cumulus-corona-complex (OCCC) maturity and the success of IVF. Peptides and steroids were measured by RIA after FF extraction with liquid chromatography and ethyl-ether, respectively. Out of the total of 76 oocytes, 52 were fertilized in vitro and 35 of them underwent normal cleavage and were transferred. Among the three peptides, only i.r. beta-EP levels were higher in FF from follicles which contained oocytes that were subsequently fertilized (127.6 +/- 16.2 pmol/L mean +/- SE) than in FF from follicles which contained oocytes that did not subsequently fertilized (62.9 +/- 8.4, p less than 0.04). Independent of subsequent fertilization, i.r. alpha-MSH values in FF were 5 times higher than those of i.r. beta-EP and i.r. gamma-EP. In the presence of a morphologically mature oocyte, FF i.r. gamma-EP levels (165.2 +/- 45.3 pmol/L) were higher than in FF from follicles yielding immature (63.6 +/- 13.5, p less than 0.01) or luteinized (32.7 +/- 9.2, p less than 0.01) oocytes. Steroid levels in FF did not change in relation to oocyte maturity or subsequent oocyte fertilization.(ABSTRACT TRUNCATED AT 250 WORDS)
In the authors' centers, fresh saphenous veins (FSV) procured from routine saphenectomies have been preferred to synthetic prostheses in cases of difficult vascular accesses (VA) for dialysis. The need for veins of different... more
In the authors' centers, fresh saphenous veins (FSV) procured from routine saphenectomies have been preferred to synthetic prostheses in cases of difficult vascular accesses (VA) for dialysis. The need for veins of different lengths and diameters prompted them to preserve SV by instantaneous freezing in liquid nitrogen since November 1987. Until now, 59 patients have received 35 FSV and 32 cryopreserved SV (CSV). Actuarial patency rates after 1 year are 82% and 72%, respectively. The 6-keto prostaglandin F1 alpha measured on punches of both veins showed residual production of prostacyclin even in CSV, but this was unresponsive to stimulation by arachidonic acid and bradykinin, or to inhibition by aspirin. In the authors' opinion, despite marked endothelial damage, satisfactory clinical results can be obtained by this very simple and cheap method of storing biologic prostheses for dialysis VA.
A consistent body of in vivo and in vitro evidence suggests that insulin-like growth factor-I (IGF-I) and possibly growth hormone (GH) play a stimulatory role in the regulation of the ovarian follicular cycle. Administration of GH in... more
A consistent body of in vivo and in vitro evidence suggests that insulin-like growth factor-I (IGF-I) and possibly growth hormone (GH) play a stimulatory role in the regulation of the ovarian follicular cycle. Administration of GH in protocols of induction of superovulation gave promising results. In the present study, 10 patients with a previously normal response to gonadotrophins were administered s.c. GH-releasing factor (GRF) combined with gonadotrophins for superovulation induction in an in-vitro fertilization/embryo transfer-gamete intra-Fallopian transfer (IVF/ET-GIFT) programme. Administration of GRF was followed by shortening of the stimulatory cycle and reduction of the total number of gonadotrophin ampoules utilized per patient relative to a previous stimulatory cycle with gonadotrophins alone. A significant increase of both follicular fluid IGF-I levels (compared to the previous cycle) and plasma GH levels immediately following GRF administration throughout the GRF cycle suggest that GRF supported the ovarian response to gonadotrophins through stimulation of the GH-IGF-I axis. A possible direct effect of GRF is discussed. Before employing GRF for superovulation in infertile patients, the pituitary GH response to provocative stimuli should be evaluated on an individual basis.
A patient with hypothalamic amenorrhoea and a poor response in terms of pituitary growth hormone (GH) to acute administration of growth hormone-releasing factor has been treated with pulsatile gonadotrophin-releasing hormone (GnRH)... more
A patient with hypothalamic amenorrhoea and a poor response in terms of pituitary growth hormone (GH) to acute administration of growth hormone-releasing factor has been treated with pulsatile gonadotrophin-releasing hormone (GnRH) combined with GH to induce ovulation. GH was administered daily until signs of ovulation were detected. The luteal phase was supported by pulsatile GnRH only. Combined treatment gave an improved follicular recruitment, higher plasma levels of 17 beta-oestradiol and an earlier ovulation, compared to the previous cycle with pulsatile GnRH only. The result was a twin pregnancy which ended with the birth of two healthy male babies. The role of GH in potentiating the ovarian response to gonadotrophins, as well as the GH secretion abnormalities associated with dysfunctions of the hypothalamic - pituitary - gonadal axis, might provide a rationale for combined GH and pulsatile GnRH treatment in such patients.
To analyze the results obtain in cancer patients who receive the same controlled ovarian stimulation protocol, started in two different moments of the menstrual cycle, follicular or luteal phase. The stimulation is performed before cancer... more
To analyze the results obtain in cancer patients who receive the same controlled ovarian stimulation protocol, started in two different moments of the menstrual cycle, follicular or luteal phase. The stimulation is performed before cancer treatment in order to preserve fertility through oocytes cryopreservation. The study is a retrospective analysis about 25 cancer patients at our centre, Department of Reproductive Medicine of University of Pisa, in order to preserve their fertility before cancer treatment. Patients are divided into two groups depending on the menstrual cycle phase, follicular or luteal phase, at the moment of first examination. Standard stimulation protocol with gonadotropins is administered in the follicular group, whereas in the second group we use GnRH (gonadotropin-releasing hormone) antagonist before gonadotropins administration in order to have a rapid luteolysis. The outcome measures are the number of days needed before starting procedure, duration of stimul...
Retrograde ejaculation is an uncommon form of male infertility. It may occur in diabetics from neuropathy involving the sympathetic fibers innervating the bladder neck. Treatment of infertility in these cases is with artificial homologous... more
Retrograde ejaculation is an uncommon form of male infertility. It may occur in diabetics from neuropathy involving the sympathetic fibers innervating the bladder neck. Treatment of infertility in these cases is with artificial homologous insemination. Several techniques for semen recovery from the bladder have been proposed. This paper describes a case of twin pregnancy following direct intraperitoneal insemination (DIPI) of semen retrieved from a diabetic man with retrograde ejaculation. Retrieval of semen was performed in this case by spontaneous voiding of urine after the introduction of a suitable medium into the bladder and before ejaculation. The quality of the semen was examined after spontaneous urination before DIPI. The poor quality of the spermatozoa induced us to introduce into the bladder a suitable medium before ejaculation and sperm recovery.
One-hundred-and-twenty couples with male factor, cervical factor, unexplained or immunological infertility underwent direct intraperitoneal insemination (DIPI) of capacitated spermatozoa, combined with ovarian stimulation for a total of... more
One-hundred-and-twenty couples with male factor, cervical factor, unexplained or immunological infertility underwent direct intraperitoneal insemination (DIPI) of capacitated spermatozoa, combined with ovarian stimulation for a total of 254 cycles. Pregnancy occurred in 47 cycles, resulting in an overall pregnancy rate of 40.5% per patient (two pregnancies occurred in two patients) and a cycle fecundity of 18.5%. Of the patients, 23 have delivered live infants (one twins, 22 singletons), 15 (32%) miscarried and 9 have ongoing pregnancies. The cycle fecundity rates increased with increasing sperm concentration and total progressive motile count, both before and after sperm preparation (r = 0.8161, r = 0.8717 and r = 0.759, r = 0.795, respectively). However, there were two pregnancies where the inseminates had a count of 0.1 x 10(6) total motile spermatozoa. DIPI as an outpatient, in-vivo conception procedure offers encouraging results and is recommended before attempting more costly and invasive assisted reproduction techniques.
Follicular fluid sex-steroids, insulin-like growth factor-I (IGF-I), IGF-I binding protein (IGF-I-BP) and epidermal growth factor were investigated in patients with polycystic ovaries and normally ovulating women, following ovulation... more
Follicular fluid sex-steroids, insulin-like growth factor-I (IGF-I), IGF-I binding protein (IGF-I-BP) and epidermal growth factor were investigated in patients with polycystic ovaries and normally ovulating women, following ovulation induction with gonadotrophins or growth hormone plus gonadotrophins. Growth hormone supplementation enhanced the ovarian response to gonadotrophins, and significantly increased follicular fluid IGF-I in both groups, without affecting follicular fluid epidermal growth factor; growth hormone supplementation significantly decreased follicular fluid androstenedione in both groups.
Follicular fluid concentrations of growth hormone (GH), insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF) and oestradiol were related to diversities in oocyte maturation and fertilization among oocytes obtained for... more
Follicular fluid concentrations of growth hormone (GH), insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF) and oestradiol were related to diversities in oocyte maturation and fertilization among oocytes obtained for in-vitro fertilization (IVF). Follicular fluid GH, IGF-I and oestradiol concentrations were significantly correlated with increasing follicular size. Follicles with immature oocytes had concentrations of oestradiol that were significantly lower when compared to follicles with intermediate and mature oocytes. Follicular fluid EGF concentration was similar for all oocyte maturational stages. In follicular fluids with mature oocytes we found IGF-I and GH concentrations were significantly higher compared to those of follicular fluid with atretic oocytes. Follicular fluids with immature and intermediate oocytes had similar concentrations of GH and IGF-I to follicular fluid containing mature oocytes and higher concentrations than follicular fluid with atretic oocytes. No statistically significant difference was found between fertilized and unfertilized oocytes. We conclude that maturation of oocytes is associated with higher concentrations of GH, IGF-I and oestradiol, but follicular fluid IGF-I and GH concentrations cannot serve as a predictor for IVF.
Controlled ovarian stimulation (COS) leading to ovulation of multiple follicles is a crucial aspect of biomedical infertility care. Nevertheless, biomarkers useful for COS management are still lacking. Peroxisome proliferator-activated... more
Controlled ovarian stimulation (COS) leading to ovulation of multiple follicles is a crucial aspect of biomedical infertility care. Nevertheless, biomarkers useful for COS management are still lacking. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors relevant to steroid metabolism in granulosa cells (GCs). We investigated whether PPARs and their steroidogenic targets were differentially expressed in GCs differentiated under different recombinant or urinary gonadotropin preparations. GCs from women subjected to COS with r-hFSH, r-hFSH/r-hLH, or hMG-HP were processed to assess expression of PPARα, PPARβ/δ, PPARγ, and steroidogenic enzymes under PPAR modulation. As an evidence of their activation, all PPAR isotypes with their coactivators, the retinoic-X-receptors (RXRs), localized in the nucleus. When GCs from r-hFSH/r-hLH group were compared with r-hFSH, a significant reduction of PPARα protein was observed. By contrast, an increase of PPARβ/δ at both...
ABSTRACT
To investigate intrafollicular insulin-like growth factor II (IGF-II) in patients affected with polycystic ovary syndrome (PCOS) in comparison with normal women. Insulin-like growth factor-II was determined in 103 follicular fluids (FF)... more
To investigate intrafollicular insulin-like growth factor II (IGF-II) in patients affected with polycystic ovary syndrome (PCOS) in comparison with normal women. Insulin-like growth factor-II was determined in 103 follicular fluids (FF) from normally ovulating women and in 102 FF from patients with PCOS. Ribonucleic acid was extracted from granulosa cells of follicles obtained from control and PCOS patients and from tissue from polycystic ovaries. Procedures were performed in a university laboratory. Twenty-nine normally ovulating women and 19 patients with PCOS underwent ovulation induction for IVF-ET with LH-releasing hormone (LH-RH) analog and gonadotropins. Eleven of them, 4 to 8 months later, underwent ovulation induction with approximately the same dosage of gonadotropins plus a standard dosage of GH. Intrafollicular IGF-II, IGF-I, epidermal growth factor (EGF), transforming growth factor beta 2, (TGF-beta 2), inhibin, and steroids were evaluated by appropriate RIA, immunoenzymatic assay (EIA), and ELISA assays. The expression of the gene encoding IGF-II was analyzed by Northern blot. Intrafollicular IGF-II was lower in PCOS than in controls. Accordingly, IGF-II messenger RNA expression was lower in PCO than in normal granulosa cells. Several differences in FF IGF-I, EGF, inhibin, and TGF-beta 2 concentrations were observed between PCOS and controls. Both IGF-II and IGF-I were reduced in PCOS, confirming a possible role of an IGF imbalance in the development of this disease.
To assess tubal patency by color Doppler hysterosalpingography (HSG). Comparative study of color Doppler HSG with roentgenogram HSG and chromolaparoscopy in infertile women of childbearing age. Clinical environment. Sixty female patients... more
To assess tubal patency by color Doppler hysterosalpingography (HSG). Comparative study of color Doppler HSG with roentgenogram HSG and chromolaparoscopy in infertile women of childbearing age. Clinical environment. Sixty female patients (22 to 39 years) with long-lasting infertility problems. Sterile saline was transcervically injected into the uterine cavity through a catheter and color Doppler HSG was performed. All the patients were submitted to roentgenogram HSG and chromolaparoscopy. The diagnostic efficacy of color Doppler HSG and its concordance with "gold standard" chromolaparoscopy were analyzed. Correlation between color Doppler HSG and roentgenogram HSG with chromolaparoscopy occurred in 86% versus 93% of all women studied. Color Doppler HSG with its accuracy and safety results a promising alternative technique to roentgenogram HSG in diagnosing tubal status in infertile patients.
Reproductive dysfunction with ageing has been so far extensively characterized in terms of depletion of ovarian follicles and reduced ability to produce gametes competent for fertilization. Nevertheless, molecular mechanisms underlying... more
Reproductive dysfunction with ageing has been so far extensively characterized in terms of depletion of ovarian follicles and reduced ability to produce gametes competent for fertilization. Nevertheless, molecular mechanisms underlying this process are still poorly understood. In the present study we addressed the hypothesis that methylglyoxal (MG), a major precursor of Advanced Glycation Endproducts (AGE), may contribute to molecular damage occurring during ovarian ageing. Our results showed that the biochemical activity of glyoxalase 1, the main component of the MG scavenging system, is significantly decreased in ovaries from reproductively-aged mice in comparison with the young group. This effect was associated with decreased expression at protein and RNA level of this enzyme and increased intraovarian level of MG. MG-arginine adducts argpyrimidine as detected with a specific antibody was found to accumulate with ageing in specific ovarian compartments. Separation of ovarian prot...
Proteolytic enzymes, like urokinase (uPA) and plasminogen activator inhibitor type-1 (PAI-1), are involved in remodelling tissues during invasion and metastasis of tumor cells. The purpose of the study is to evaluate the expression and... more
Proteolytic enzymes, like urokinase (uPA) and plasminogen activator inhibitor type-1 (PAI-1), are involved in remodelling tissues during invasion and metastasis of tumor cells. The purpose of the study is to evaluate the expression and the prognostic significance of these enzymes in endometrial hyperplasia and cancer. We used immunohistochemical staining to localize uPA and PAI-1 antigens and evaluate their expression, and the enzyme-linked immunosorbent assay (ELISA) to measure their levels during the progression of endometrial carcinoma. The results show that the levels of uPA and PAI-1 detection are systematically weak in simplex hyperplasia and are moderate in complex hyperplasia. In the endometrial carcinoma a very strong reaction was observed in the most aggressive variant of epithelial tumors. A positive signal for uPA was found only in the cytoplasm of normal and hyperplastic cells while, in tumors, uPA was present also in the cellular areas surrounding the neoplastic glands...
To evaluate the immunoactivity of human follicular fluids (FFs) of ovaries stimulated with exogenous gonadotropins. Follicular fluids and peripheral blood mononuclear cells (PBMCs) were obtained at the time of ovum pick-up from 15 women... more
To evaluate the immunoactivity of human follicular fluids (FFs) of ovaries stimulated with exogenous gonadotropins. Follicular fluids and peripheral blood mononuclear cells (PBMCs) were obtained at the time of ovum pick-up from 15 women (25 to 34 years of age) undergoing gonadotropin stimulation for GIFT. The evaluation of the blastic response of PBMC to phytohemagglutinin (PHA), PHA plus recombinant interleukin (IL)-2, and recombinant IL-2 alone was performed by measuring 3H-thymidine (3H-TdR) incorporation by the cells cultured in media with or without FF. The percentage of CD25 expression on PHA-stimulated T lymphocytes was evaluated by flow cytofluorometry. The levels of IL-1 alpha and IL-2 in supernatants from PHA-stimulated PBMC were evaluated by an ELISA. The PBMC blastic response to PHA, to recombinant IL-2 alone, and to PHA plus recombinant IL-2 was suppressed by the addition of FF. However, the percentage of inhibition of 3H-TdR incorporation induced by FF in cultures perf...
ABSTRACT
To assess the roles of instrument diameter (5.0- or 3.5-mm external sheath), uterine distention medium (carbon dioxide [CO(2)] or saline solution), and hysteroscopist experience in diagnostic hysteroscopy. Prospective, randomized,... more
To assess the roles of instrument diameter (5.0- or 3.5-mm external sheath), uterine distention medium (carbon dioxide [CO(2)] or saline solution), and hysteroscopist experience in diagnostic hysteroscopy. Prospective, randomized, multicenter trial (Canadian Task Force classification I). Two university medical centers in Italy. One hundred eighty-four women attending an infertility clinic. Patients were randomly assigned to undergo conventional hysteroscopy (group 1, n = 92) or minihysteroscopy (group 2, n = 92) with CO(2) or saline solution as distention medium. The procedures were performed by hysteroscopists with varying degrees of experience. Patient discomfort was analyzed using the visual analog score. Procedure complications and patient satisfaction rate were also recorded. Independent of hysteroscopist experience, less pain, fewer complications, and higher satisfaction rates were observed with minihysteroscopy. In addition, procedures in which saline solution was used resulted in less pain and fewer complications than those in which CO(2) was used, but only when performed by inexperienced hysteroscopists. Instrument diameter and hysteroscopist experience, but not the distention medium, seem to be the primary variables that affect the perception of discomfort during office hysteroscopy.
Follicular fluid (FF) lipoprotein content was evaluated in an in vitro fertilization/embryo transfer and gamete--intrafallopian--transfer program and correlated to follicular and oocyte maturation. Moreover, the in vitro progesterone... more
Follicular fluid (FF) lipoprotein content was evaluated in an in vitro fertilization/embryo transfer and gamete--intrafallopian--transfer program and correlated to follicular and oocyte maturation. Moreover, the in vitro progesterone response of granulosa-luteal cells from 10 patients to high-density lipoprotein (HDL) and to low-density lipoprotein (LDL) was assessed. Most FFs contained only HDL. Sixteen out of 97 FFs contained also very low levels of LDL and very-low-density lipoprotein (VLDL). The presence of LDL was associated to features of follicle and oocyte hypermaturity. LDL alone induced a much more potent increase of progesterone (P) release by granulosa-luteal cells than HDL alone, and the HDL partially reversed the potent effect of LDL. It is concluded that in late follicular phase HDL maintains P release by granulosa cells at a low rate and prevents a potent stimulation of P production by LDL which might cross the maturating blood-follicle barrier, until increasing passage of LDL in FF decreases the HDL:LDL ratio and the action of LDL becomes prominent.
As it has been hypothesized that IGF-binding proteins (IGFBPs) may have a role as autocrine/paracrine factors in regulating the local actions of the insulin-like growth factors (IGFs) in the ovary, we studied the production of the IGFBPs... more
As it has been hypothesized that IGF-binding proteins (IGFBPs) may have a role as autocrine/paracrine factors in regulating the local actions of the insulin-like growth factors (IGFs) in the ovary, we studied the production of the IGFBPs by human granulosa cells (GC) in culture and the role of IGFBP-3 in the modulation of ovarian cell responsiveness to IGF-I and FSH. To this purpose, human luteinizing GC were cultured in serum-free conditions for 24 h and subsequently submitted to increasing concentrations (2-8 nmol/l) of recombinant non-glycosylated or partially glycosylated IGF-BP-3 for 48 h, in the presence or absence of IGF-I, des(1-3)IGF-I- a truncated analog of human IGF-I with markedly reduced binding ability to IGFBPs - and FSH (5-20 mIU/ml). The results demonstrate that human GC release IGFBP-1-2 and -3 into the medium, and that FSH is able to inhibit this release, while GH is clearly inhibitory on IGFBP-1 and stimulatory on IGFBP-3. Both IGF-I and des(1-3)IGF-I significantly (p < 0.001) stimulate E2 production by human GC in culture in a manner comparable to that of FSH in the dose range used. Preincubation for 2 h at 22 C with IGFBP-3, to allow the formation of the IGF-IGFBP complex, drastically reduced the stimulatory effect of IGF-I but not that of des(1-3)IGF-I. IGFBP-3 was also able to inhibit the stimulatory effect of FSH. These data show that: i) the IGF peptide is less active when bound to IGFBP-3; ii) as IGFBP-3 does not affect the potency of des(1-3)IGF-I, its inhibitory action is exerted upstream of the membrane receptor binding; iii) as the action of IGFBP-3 is exerted by binding the IGF peptide, its inhibitory effect on FSH points out the role of the locally produced IGF-II in potentiating the FSH action on human GC.
The use of luteal phase support has been demonstrated in patients undergoing IVF/ET in cycles stimulated after pituitary desensitization with gonadotrophin releasing hormone agonists. However, it is still not clear which is the most... more
The use of luteal phase support has been demonstrated in patients undergoing IVF/ET in cycles stimulated after pituitary desensitization with gonadotrophin releasing hormone agonists. However, it is still not clear which is the most suitable kind of supplementation. This study was designed to compare the absorption and the efficacy of three different luteal support. We randomly administered progesterone i.m. (50 mg/day), human chorionic gonadotrophin (hCG) (2000 IU every three days), progesterone vaginal cream (100 mg/day) or nothing (controls) to 176 women treated for assisted procreation. We were not able to show any statistical differences for the percentage of pregnancy rate between groups. The serum progesterone (P) and 17-beta-estradiol (E2) and E2/P ratio levels of the luteal phase were compared with the control not supplemented group. All the treatments were able to increase significantly the luteal P values versus controls (p < 0.01). Moreover, vaginal cream and natural P im significantly decreased E2/P ratio (p < 0.05). Serum P levels were more steady with P vaginal cream than im injection. Vaginal cream for better bioavailability and acceptance appear the most suitable and comfortable method for luteal phase support.
Hippocampus plays an important role in cognition, neuroendocrine function and sexual behaviour. Changes of hippocampal neuropeptide and neurotransmitter concentrations are associated to behavioural changes occurring throughout... more
Hippocampus plays an important role in cognition, neuroendocrine function and sexual behaviour. Changes of hippocampal neuropeptide and neurotransmitter concentrations are associated to behavioural changes occurring throughout reproductive life. The present study focused the attention on the presence of a neurosteroid, 5 alpha-pregnan-3 alpha-ol-20-one (termed allopregnanolone) in hippocampus. In particular, hippocampal allopregnanolone concentration in male and female prepubertal rats and in female rats throughout estrous cycle were evaluated. Hippocampal extracts were eluted on high pressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Prepubertal male and female rats (15 days old) showed highest values which significantly decreased with advancing age (25 and 60 days) (p < 0.01); the lowest hippocampal concentration of allopregnanolone was found in adult rats. Female rats on proestrus morning and afternoon showed an hippocampal allopregnanolone concentration significantly higher than on diestrus or on estrus (p < 0.01), while rats on estrus showed hippocampal allopregnanolone concentration significantly lower than during other days of estrus cycle (p < 0.01). These data indicate differences in hippocampal concentration of allopregnanolone between prepubertal and adult rats and throughout estrous cycle in female rats. This finding suggest a putative role of neurosteroids in the modulation of behavioral changes occurring throughout reproductive life.
GH therapy increases the ovarian response to gonadotropin stimulation in women presenting with ovaries that are relatively resistant to conventional gonadotropin therapy. As it is not completely certain whether GH modulates the actions of... more
GH therapy increases the ovarian response to gonadotropin stimulation in women presenting with ovaries that are relatively resistant to conventional gonadotropin therapy. As it is not completely certain whether GH modulates the actions of FSH on granulosa cells directly or via insulin-like growth factor-I (IGF-I) production, we studied its effect on steroid release by human granulosa cells obtained from subjects affected by unexplained or male factor infertility. In all subjects, superovulation for in vitro fertilization/embryo transfer was induced by treatment with gonadotropins or GH plus gonadotropins combined. The effects of the different in vivo treatments were evaluated in the conditioned medium obtained after the first 24 h of incubation; granulosa cells from patients treated with GH released higher amounts of estradiol and progesterone into the medium than did granulosa cells from patients treated with gonadotropins alone. When the release of steroid due to the in vivo treatment was exhausted, cells were subjected to increasing concentrations of GH in the presence or absence of 200 nmol anti-IGF Sm 1.2 monoclonal antibody (MoAb) or the antitype I receptor alpha IR3 MoAb. The results revealed that GH stimulates estradiol production in a dose-dependent fashion, and the presence of the MoAbs drastically reduces the GH effect. These data demonstrate that the established stimulatory effect of GH on ovarian function is dependent not only on the increased levels of circulating IGF-I, but also on a direct effect of GH on granulosa cells, which seems to be mediated at least in part by the autocrine action of IGF, particularly IGF-II. In fact, chromatographic analysis of medium conditioned by human granulosa cells revealed that these cells clearly produce IGF-II and IGF-binding proteins and only small amounts of IGF-I. Since GH appears to be able to increase the in vitro effect of both IGF-I and IGF-II, we can hypothesize a sensitization of the granulosa cells to the IGF-II produced by the cells themselves, which acts through the IGF-I receptor.
Relationships between immune and endocrine systems seem to occur in ovarian follicular fluids (FF). Lymphomonocytes have been found in preovulatory follicles and their specific products, cytokines [interleukin-1 (IL1), IL2], were... more
Relationships between immune and endocrine systems seem to occur in ovarian follicular fluids (FF). Lymphomonocytes have been found in preovulatory follicles and their specific products, cytokines [interleukin-1 (IL1), IL2], were demonstrated to inhibit steroidogenesis. Ovarian steroids, in turn, reduce the cytokine production from immune-competent cells. In the present study we evaluated whether lymphomonocytes are present in FF, and if both their subset distribution and their IL1 alpha and IL2 secretions, after activation with phytohemagglutinin (PHA), are similar to those of peripheral blood. Interferences of IL1 alpha and IL2 production by FF lymphomonocytes caused by isolated granulosa cells were also evaluated. The study was performed on 86 FFs obtained from follicles containing mature oocytes that were aspirated at the time of ovum pickup from 27 women undergoing controlled ovarian hyperstimulation with exogenous gonadotropins for an in vitro fertilization (IVF) program [IVF-embryo transfer (IVF-ET) or gamete intrafallopian transfer (GIFT)]. Lymphocytes were found in FF. The distribution of CD8+ and CD3+ lymphocyte subsets is equal to that in peripheral blood, but the percentage of CD11b+, CD16+, and CD4+ cells (its trend) is higher in FF than in peripheral blood. The amount of IL2 and IL1 alpha deriving from PHA-activated FF lymphomonocytes is similar to that of peripheral blood PHA-activated lymphomonocytes. Granulosa cells significantly blunt IL2 and IL1 alpha production by FF lymphomonocytes. These results suggest that preovulation, a migration of lymphomonocytes from the peripheral compartment to the follicle occurs. However, unfavorable effects of IL2 and IL1 alpha, cytotoxic and antisteroidogenetic activities, are counteracted by the products of granulosa cells. The higher amounts of CD11b+, CD16+, and CD4+ in FF suggest that they could be involved in other immune processes.
This study compares the results of three ovulation induction protocols in polycystic ovarian disease (PCOD) patients undergoing an in vitro fertilization-embryo transfer (IVF-ET) program. A total of 85 cycles was studied. The patients... more
This study compares the results of three ovulation induction protocols in polycystic ovarian disease (PCOD) patients undergoing an in vitro fertilization-embryo transfer (IVF-ET) program. A total of 85 cycles was studied. The patients were treated with clomiphene citrate (CC) plus human menopausal gonadotropin (hMG) (CC/hMG group), with purified menofollitropin (pFSH) plus hMG (pFSH/hMG group), and with pFSH/hMG plus gonadotropin releasing hormone analogue (GnRH-a) (analogue group). In the analogue group the suppression of luteinizing hormone (LH) with GnRH-a decreased the number of follicles < 12 mm on the day of human chorionic gonadotropin (hCG) administration and the number and percentage of immature oocytes retrieved and increased the percentage of mature oocytes retrieved. However, fertilization rates of oocytes, cleaved embryo rates, pregnancy rates following replacement, and pregnancy outcomes were not different. Although the suppression of the hypothalamic-pituitary-ovarian axis with GnRH-a in PCOD patients improved follicular synchrony and oocyte maturity, none of the ovulation induction protocols was superior to the others with respect to pregnancy rates and pregnancy outcomes.
Pregnancy-induced hypertension (PIH) is a relatively common complica-tion of pregnancy. In the present study we evaluated the role of Doppler ultra-sound in the management of 36 patients with the disorder. Ultrasound assess-ment of... more
Pregnancy-induced hypertension (PIH) is a relatively common complica-tion of pregnancy. In the present study we evaluated the role of Doppler ultra-sound in the management of 36 patients with the disorder. Ultrasound assess-ment of amiotic fluid was performed on alternate ...
We aimed to examine the behaviour of the angiogenetic factor vascular endothelial growth factor (VEGF) and its soluble receptor (sVEGFR-1) in polycystic ovary patients undergoing In vitro fertilisation (IVF) compared with respect to... more
We aimed to examine the behaviour of the angiogenetic factor vascular endothelial growth factor (VEGF) and its soluble receptor (sVEGFR-1) in polycystic ovary patients undergoing In vitro fertilisation (IVF) compared with respect to normally ovulating controls. Levels of VEGF and sVEGFR-1 were compared in follicular fluid and serum, both on the day of human choriogonadotropin (hCG) administration and on the day of oocyte retrieval (OR), in controls and polycystic ovarian syndrome (PCOS) patients undergoing IVF cycles. The bioactivity of VEGF (VEGF/sVEGFR-1 ratio) in the two groups was calculated. Thirty PCOS patients and 20 controls referring to the IVF Centre of the University of Pisa (Italy) were enrolled. In each patient, blood samples were collected on the day of hCG and on the day of OR administration, and follicular fluid samples. VEGF and sVEGFR-1 were measured by Enzyme Linked Immuno Sorbant Assay (ELISA). Serum VEGF bioactivity markedly increased in both groups after hCG administration. Serum and follicular fluid VEGF bioactivity was greater in PCOS patients than in controls on the day of OR. The increase in VEGF bioactivity in PCOS patients undergoing IVF was not only because of increasing levels of VEGF but also to decreasing levels of its soluble receptor. We believe that additional studies will clarify their role in the pathogenesis of ovarian hyperstimulation syndrome, which most often occurs in patients with PCOS.
Vascular endothelial growth factor (VEGF) is a powerful mediator for vessel permeability and it is strongly implicated in angiogenesis, stimulating endothelial cell proliferation as well as capillary permeability. We studied 30 women... more
Vascular endothelial growth factor (VEGF) is a powerful mediator for vessel permeability and it is strongly implicated in angiogenesis, stimulating endothelial cell proliferation as well as capillary permeability. We studied 30 women undergoing in vitro fertilization (IVF) programs and evaluated, on the day of oocyte retrieval, VEGF levels in plasma and follicular fluid and related such concentrations to the amount of follicle-stimulating hormone (FSH) administered. Furthermore, the correlation between the number of oocytes retrieved and the VEGF concentrations both in plasma and in follicular fluid were also investigated. Results indicate that follicular fluid VEGF concentrations and the amount of pure FSH administered were directly proportional (p < 0.05). On the day of oocyte retrieval, the VEGF plasma concentrations and the number of oocytes collected were directly proportional (p < 0.05). VEGF plasma levels increased after human chorionic gonadotropin (hCG) administration (30.37 +/- 18.60 pg/ml up to 52.62 +/- 43.63 pg/ml). In conclusion, this study demonstrates that the doses of pure FSH administered to women undergoing IVF cycles have a crucial role in hCG-dependent VEGF production.
We report a case of general hypersensitivity-like allergic reactions to intramuscular injections of highly purified urinary follicle stimulating hormone (uFSH-HP) successfully managed by using intramuscular recombinant FSH (rFSH). The... more
We report a case of general hypersensitivity-like allergic reactions to intramuscular injections of highly purified urinary follicle stimulating hormone (uFSH-HP) successfully managed by using intramuscular recombinant FSH (rFSH). The patient underwent a first cycle of in vitro fertilization (IVF) and controlled ovarian hyperstimulation (COH) was achieved with a combination of gonadotropin releasing hormone against (GnRH-a) and uFSH-HP. Because, after oocyte recovery, no fertilization occurred, the couple subsequently entered an intracytoplasmic sperm injection (ICSI) program. During the COH, the woman developed general hypersensitivity-like allergic reactions with itching, redness and swelling. Although there was regular follicular growth, the allergic symptoms worsened and, on day 8 of COH, the stimulation cycle was suspended. A few months later, the patient entered a new ICSI cycle. COH was achieved by using a combination of GnRH-a and rFSH. The cycle was completed and the patient did not report any allergic reaction. To avoid allergic reaction to the protein components of the urine-derived FSH preparations, the use of rFSH is suggested in those patients who present local and/or general hypersensitivity-like allergic reactions.
The aim of the study was to evaluate the plasma thromboxane and plasma viscosity in relation with Doppler flow parameters in postmenopausal patients treated with hormone replacement therapy. Thirty-two postmenopausal (follicle-stimulating... more
The aim of the study was to evaluate the plasma thromboxane and plasma viscosity in relation with Doppler flow parameters in postmenopausal patients treated with hormone replacement therapy. Thirty-two postmenopausal (follicle-stimulating hormone > 40 IU/l and estradiol < 100 pmol/l) women (mean age +/- SD, 54.7 +/- 2.9 years) participated in the study and were submitted to continuous estradiol transdermal supplementation and 12-day courses of medroxyprogesterone acetate every second month. Doppler resistances at the level of the uterine and internal carotid arteries, thromboxane plasma levels and plasma viscosity were analyzed in basal condition and after 1, 3 and 6 months. During hormone supplementation, the pulsatility index significantly decreased at the level of the analyzed arteries. Similarly, plasma thromboxane levels and plasma viscosity were significantly reduced. Significant correlations were found between thromboxane plasma concentrations, plasma viscosity and uterine artery resistances. Thus hormone replacement therapy seems to be responsible for both direct and indirect modifications at the level of the vessel wall physiology.
The aim of this study was to evaluate whether patients with partial bilateral polycystic ovaries show different ovarian and uterine blood flow to those with complete bilateral polycystic ovaries, and to investigate whether there is a... more
The aim of this study was to evaluate whether patients with partial bilateral polycystic ovaries show different ovarian and uterine blood flow to those with complete bilateral polycystic ovaries, and to investigate whether there is a correlation between ultrasonographic and hormonal parameters. Fifteen patients with partial polycystic ovaries and eighteen patients with complete bilateral polycystic ovaries underwent clinical, biochemical, gray-scale and color Doppler ultrasonographic evaluation. Hormonal (luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH concentration ratio, estradiol, prolactin, androstenedione, testosterone), clinical (body mass index, Ferriman-Gallwey score), ultrasonographic (ovarian volume, number and distribution of subcapsular follicles, stromal score) and Doppler (uterine artery and intraparenchymal vessels pulsatility index, ovarian stromal vascularization) parameters were evaluated, in the early follicular phase (cycle day 3-5) in oligomenorrheic patients, or at random in amenorrheic patients. Significantly higher androstenedione plasma levels and LH/FSH concentration ratios were observed in complete bilateral polycystic ovaries. In partial polycystic ovaries, gray-scale and color Doppler ultrasonography showed different features in affected and unaffected areas of the ovary, similar to polycystic and normal ovary appearance respectively. In conclusion, PCOS does not predetermine a single ultrasonographic or Doppler pattern.
Estradiol and estrone concentrations in ovarian follicular fluid change according to the ovulatory cycle, but no studies on the possible presence and/or changes of estriol are available. The aim of the present study was to evaluate... more
Estradiol and estrone concentrations in ovarian follicular fluid change according to the ovulatory cycle, but no studies on the possible presence and/or changes of estriol are available. The aim of the present study was to evaluate whether estriol is measurable in follicular fluid and how its concentration changes according to the volume of ovarian follicles and to the maturational stage of oocytes. A group of women (n = 39) undergoing a program of induction of ovulation was included in this study and divided into three groups according to the causes of infertility: those with unexplained infertility (n = 11); those with endocrine disturbances (n = 5); and normal ovulatory women (n = 23) (controls). The follicles recruited (n = 116) on the basis of morphology and the appearance of the oocyte cumulus-corona complex were divided into: mature (n = 22); intermediate (n = 75); immature (n = 11); and atretic (n = 8). Ovarian follicles were also divided according to the diameter of each: < 1.5 cm (n = 38); 1.6-2.4 cm (n = 66); and > 2.5 cm (n = 12). Ovarian follicular fluids were aspirated under ultrasound guidance and a blood specimen was collected from each subject. Estriol and estradiol concentrations were evaluated by radioimmunoassay in serum and follicular fluid following an ether extraction. Estriol was found in high concentration in each sample of follicular fluid, significantly higher than in the respective serum sample (p < 0.01). Although the estradiol concentration was significantly lower in follicles containing immature and atretic oocytes than in intermediate or mature follicles (p < 0.01), the estriol concentration did not depend upon the maturational stage. In addition, the follicular fluid estriol concentration did not differ according to the causes of infertility. Follicular fluid and serum estradiol concentrations showed significant correlation (p < 0.01), whereas no significant correlation was observed between serum and follicular estriol concentrations. The present data show that follicular fluid contains a high concentration of estriol and that its changes are independent of the ovulatory cycle and estradiol concentrations, supporting an independent origin and suggesting a different function for estriol.
The aim of this study was to compare the costs and effects of two different controlled ovarian hyperstimulation treatments: a starting dose of recombinant follicle stimulating hormone (FSH) followed by highly purified urinary FSH; or... more
The aim of this study was to compare the costs and effects of two different controlled ovarian hyperstimulation treatments: a starting dose of recombinant follicle stimulating hormone (FSH) followed by highly purified urinary FSH; or highly purified urinary FSH alone. Forty-six infertile patients, after being given luteal gonadotropin-releasing hormone (GnRH) agonist, were randomly assigned to the two stimulation protocols. During the ovarian stimulation regimen the patients underwent transvaginal ultrasonographic evaluation of follicular number and size. The retrieved oocytes were classified on the basis of the criteria of Acosta and colleagues. To study the impact of embryo quality on implantation, the embryos were graded morphologically before replacement. Pregnancy rates were ascertained and the costs of the two different protocols were analyzed. The number of days of FSH stimulation and the cost of gonadotropin treatment were similar in both groups. The number of follicles > 17 mm in size, the number of collected oocytes, and pregnancy rate per cycle were significantly higher in the group partially treated with recombinant gonadotropin. We conclude from these results that the use of recombinant FSH in the early phase of controlled ovarian hyperstimulation leads to significant improvements in pregnancy rate per cycle without increasing the costs of treatment.
The effects of hormone-replacement therapy on the Doppler flow parameters of the ophthalmic artery in postmenopausal women were studied and compared with those registered at the level of the internal carotid and uterine arteries.... more
The effects of hormone-replacement therapy on the Doppler flow parameters of the ophthalmic artery in postmenopausal women were studied and compared with those registered at the level of the internal carotid and uterine arteries. Fifty-seven postmenopausal patients were submitted to continuous estradiol transdermal supplementation and 12-day courses of medroxyprogesterone acetate. During the estrogen phase of hormone-replacement therapy all patients underwent (at 1, 3 and 6 months after the beginning of hormone-replacement therapy) transvaginal ultrasonographic evaluation of the pelvic organs and of endometrial thickness. On the same day, they underwent color Doppler analysis of the blood flow impedance of the uterine, internal carotid and ophthalmic arteries. Estradiol plasma concentrations were assayed on the day that ultrasonographic and Doppler examinations took place. The pulsatility index of all the arteries improved, from baseline values, during the therapy and attained stable values compared to those after the first month of treatment. Furthermore, at the level of the internal carotid and ophthalmic arteries, a significant increase of the peak systolic blood flow velocity (Vmax) was observed over the 6 months of therapy. Doppler studies of the ophthalmic artery are capable of affording specific and precise pathophysiologic information to assess peripheral intracranial blood flow variations. Furthermore, such studies may be useful in monitoring hormone-replacement therapy effects on cerebral perfusion.
The objective of this study was to determine whether amenorrheic women have more severe blood flow variations and clinical-endocrinological patterns in comparison with oligomenorrheic polycystic ovary syndrome (PCOS) patients. Twenty... more
The objective of this study was to determine whether amenorrheic women have more severe blood flow variations and clinical-endocrinological patterns in comparison with oligomenorrheic polycystic ovary syndrome (PCOS) patients. Twenty oligomenorrheic women (cycle length > 35 days; Group I), and 20 amenorrheic women (no vaginal bleeding for at least 6 months; Group II) were submitted to ultrasonographic evaluation of ovarian volume, follicle distribution, number and diameter, color Doppler analysis of uterine and intraovarian blood flow, hormonal assay of different compartments, and plasma evaluation of lipid profile. The number of subcapsular small-sized follicles, and the ovarian volume, androstenedione and luteinizing hormone (LH) plasma levels, and the LH/follicle-stimulating hormone (FSH) ratio were significantly higher in the amenorrheic group compared with the oligomenorrheic patients. Furthermore, significantly lower high-density lipoprotein (HDL) and HDL/total cholesterol ratio were observed in Group II compared with Group I. In addition, in Group II, higher resistance in the uterine arteries and lower impedance to blood flow in the intraovarian arteries have been shown. The assessment of ovarian morphology by transvaginal ultrasound and Doppler flow analysis of both intraovarian and uterine arteries in patients with PCOS may provide an insight into the pathological state and the degree of progression of the disease.
The aim of this study was to compare the uterine blood flow variations induced by chemical castration and spontaneous menopause. Thirty infertile patients were studied in the early follicular phase (day 5-7) and then treated with... more
The aim of this study was to compare the uterine blood flow variations induced by chemical castration and spontaneous menopause. Thirty infertile patients were studied in the early follicular phase (day 5-7) and then treated with gonadotropin releasing hormone agonists (GnRH-a). On day 25 from GnRH-a injection, the suppressive effect was checked. The values obtained were compared with those found in 18 postmenopausal women (menopause < 5 years). All the subjects underwent transvaginal ultrasonography, Doppler analysis of uterine arteries, hormonal assay and evaluation of hematological and biochemical parameters. In all infertile patients, the GnRH-a suppressive effect was shown at the 25th day from the injection. Endometrium thickness decreased from 0.6 +/- 0.1 mm to 0.3 +/- 0.1 mm (p < 0.05) and the pulsatility index increased from 2.52 +/- 0.31 to 3.02 +/- 0.25 (p < 0.05). The plasma estradiol level fell from 48.2 +/- 4.4 pg/ml to 13.6 +/- 7.9 pg/ml (p < 0.05). No other hormonal and biochemical parameters were significantly modified by GnRH-a. In postmenopausal women, the values of the studied parameters were similar to those found in the infertile GnRH-a-suppressed patients. These data show that GnRH-a induces vascular modifications similar to those induced by early post-menopause and that both are probably exclusively related to hypoestrogenism.
The aim of this study was to evaluate how, in patients with polycystic ovary syndrome, the number of small subcapsular follicles correlates with uterine and ovarian blood flow and with specific hormonal parameters. At an ultrasonographic... more
The aim of this study was to evaluate how, in patients with polycystic ovary syndrome, the number of small subcapsular follicles correlates with uterine and ovarian blood flow and with specific hormonal parameters. At an ultrasonographic evaluation, 30 patients with polycystic ovary syndrome showed 5-10 (group I; n = 14) or > 10 (group II; n = 16) small follicles. These patients underwent ultrasonographic (ovarian volume and stroma echodensity; number, diameter and distribution of follicles) and color Doppler (uterine and intraovarian vessels) analyses, and hormonal assay. In group II, significantly lower pulsatility index values than in group I were observed in the ovarian stromal arteries. The Ferriman-Gallwey score, plasma androstenedione level and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio results were significantly higher in group II than in group I. Androstenedione plasma levels correlated with the number of small follicles. Furthermore, the LH/FSH ratio correlated with both the number of small follicles and the stromal artery pulsatility index. The combined assessment of ovarian morphology by transvaginal ultrasound and color Doppler may provide insight into the pathological state of polycystic ovary syndrome.
The efficacy of combined growth hormone (GH)-gonadotropin treatment has been studied in patients previously resistant to sole gonadotropins for induction of superovulation. Eleven patients (aged 26-41) with a mechanical cause of... more
The efficacy of combined growth hormone (GH)-gonadotropin treatment has been studied in patients previously resistant to sole gonadotropins for induction of superovulation. Eleven patients (aged 26-41) with a mechanical cause of infertility were treated. All were given the same dosage of gonadotropins as in previous cancelled cycles (6-17 ampules/cycle of menofollitropin; 34-80 ampules/cycle of human menopausal gonadotropin) plus a standard dosage of GH (0.1 IU per kg body weight, daily). Younger patients (n = 6, age 26-36) showed a considerable improvement of ovarian response in terms of number of mature follicles aspirated by laparoscopy (performed on day 11-13). Older patients (n = 5, age 39-41) did not show any significant improvement of ovarian response with combined treatment and all had their stimulatory cycle cancelled. Follicular fluid (FF) levels of GH, 17 beta-estradiol (E2) and progesterone (P) were significantly higher in the group of younger GH-treated patients (n = 53 follicles) than in 4 controls treated with gonadotropins only (n = 32 follicles). FF insulin-like growth factor-I (IGF-I) did not significantly differ between the two groups. A significant positive linear correlation has been found between FF GH and IGF-I in the GH-treated group. In conclusion, GH-gonadotropin combined treatment considerably improves ovarian response in protocols for superovulation induction in younger gonadotropin-resistant patients. A local action of GH and IGF-I in the ovaries may be hypothesized.
The aim of the present study was to evaluate the effect of progesterone and of various synthetic progestins on hypothalamic gonadotropin-releasing hormone (GnRH) and on pituitary and plasma LH and prolactin (Prl) concentrations in... more
The aim of the present study was to evaluate the effect of progesterone and of various synthetic progestins on hypothalamic gonadotropin-releasing hormone (GnRH) and on pituitary and plasma LH and prolactin (Prl) concentrations in ovariectomized rats. Groups of 6 rats were treated for 2 weeks with a pharmacological dose of progesterone, desogestrel, medroxyprogesterone acetate or norethisterone enanthate (NET). The same treatment was also repeated in association with estradiol benzoate (EB). Groups of ovariectomized rats were also treated with EB only or vehicle. Ovariectomized rats showed hypothalamic concentrations of GnRH significantly higher than control rats. Progesterone and NET significantly increased GnRH concentrations and reversed the EB-induced changes. Rats treated with progesterone and NET also showed reduced pituitary LH concentration, with high plasma LH levels. All progestins blocked the increase of pituitary LH induced by EB, but were inactive in influencing the inhibitory effect of EB on plasma LH levels. The administration of progesterone and progestins did not induce significant changes of pituitary or plasma Prl, but reversed the EB-induced increase. These results showed that progesterone and progestins have a marked effect on hypothalamic and pituitary hormone secretion and that they modulate estrogen-induced effects.
To evaluate the association between the vulnerability to stress and the treatment outcome of couples undergoing IVF-ET. Controlled, prospective clinical study. The Assisted Reproduction Unit of the Department of Obstetrics and Gynecology,... more
To evaluate the association between the vulnerability to stress and the treatment outcome of couples undergoing IVF-ET. Controlled, prospective clinical study. The Assisted Reproduction Unit of the Department of Obstetrics and Gynecology, University of Modena. Forty-nine infertile women consecutively admitted to standard superovulation treatment. Mean age was 33.9 years, duration of infertility was 6.3 years. Reasons for assisted reproduction were mechanical factor in 22 cases, sperm problem in 9 cases, and endocrine disorder in 6 cases. In 12 cases, infertility was unexplained. More than 55% already had an IVF-ET attempt. The day of oocyte pick-up, subjects were submitted to Stroop Color and Word test, a task measuring the ability to cope with a cognitive stressor, involving attentional and sympathoadrenal systems. Systolic (SBP) and diastolic blood pressure, as well as heart rate (HR) were measured at baseline, during the test, and 10 minutes after the end of testing. The evidence of a biochemical pregnancy (beta-hCG value 12 days after ET) define the success and failure groups. Sixteen women (33%) had a biochemical pregnancy, 12 also had ultrasound evidence. Eight gave birth to healthy infants. Age, education, causes, and duration of infertility were similar in the success and failure groups. The latter were more involved in a job outside home than the former. Moreover, they had a lower number of both fertilized oocytes and transferred embryos. In response to the Stroop test, every subject reported an increase of cardiovascular parameters. However, women becoming pregnant showed a lower response of both SBP and HR than women who failed. Both a major cardiovascular vulnerability to stress and working outside home are associated to a poor outcome of IVF-ET treatment.
The follicular fluid (FF) content of androgens, estrogens and epidermal growth factor (EGF) has been evaluated in a group of patients with policystic ovary disease (PCO) and in one of normally-ovulating infertile women (NOW) in an IVF/ET... more
The follicular fluid (FF) content of androgens, estrogens and epidermal growth factor (EGF) has been evaluated in a group of patients with policystic ovary disease (PCO) and in one of normally-ovulating infertile women (NOW) in an IVF/ET program. The in vitro response to follicle-stimulating hormone (FSH) has been also evaluated in granulosa luteal cells from the same patients. PCO patients showed significantly higher FF androstenedione (delta 4) and testosterone (T) and similar FF estrone (E1) and 17 beta-estradiol (E2) levels compared to controls. In vitro production of E1 and E2 by granulosa luteal cells from PCO patients and from controls were overlapping and their response to FSH was similar. These data indicate a normal intrinsic potential aromatase activity in ovaries from PCO patients stimulated with gonadotropins and suggest that PCOs do not derive from inherent ovarian aromatase deficiency. Increased FF androgen content following gonadotropin stimulation may result from theca cell hyperactivity and androgen accumulation in the follicular antrum of rescued hyperandrogenic follicles as well as from inhibitory factors that may inhibit aromatase activation in vivo, partially counteracting the effect of gonadotropins. FF EGF levels were significantly higher in the group of PCO patients compared to those of NOW. EGF may play a role in blunting the in vivo response of granulosa cells to gonadotropins.
Thyroid function and gonadal axis are related throughout a woman's fertile period. Modifications of thyroid hormone levels have been... more
Thyroid function and gonadal axis are related throughout a woman's fertile period. Modifications of thyroid hormone levels have been reported as a consequence of controlled ovarian stimulation for infertility. A 28-year-old woman with regular menses and previous evidence of euthyroidism underwent controlled ovarian hyperstimulation (COH) for assisted reproductive technology (ART). Free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and autoantibodies against thyroperoxidase and thyroglobulin (TPOAb and TgAb, respectively) were measured before COH. FT4, FT3, and TSH were re-evaluated 6 days, 2 weeks (during oocyte retrieval), and 1 month after the beginning of the procedure. The baseline evaluation revealed subclinical autoimmune hypothyroidism. The patient was hypothyroidic at 6 days and 2 weeks and spontaneously returned to euthyroidism 1 month after COH. This is the first case of a woman with an unknown subclinical autoimmune hypothyroidism who developed overt and transient hypothyroidism as a consequence of COH. Careful thyroid evaluation is advised for women undergoing COH.
ABSTRACT Aim: Angiogenesis is an important factor in tumoral progression, metastasis and invasion. More recently, it has also been found to play a particular role in hematological malignancies. Methods: In this study, 45 patients... more
ABSTRACT Aim: Angiogenesis is an important factor in tumoral progression, metastasis and invasion. More recently, it has also been found to play a particular role in hematological malignancies. Methods: In this study, 45 patients harboring hematological malignancies (15 acute myeloid leukemia (AML), 10 acute lymphoblastic leukemia (ALL), 10 multiple myeloma (MM), 10 chronic myeloid leukemia (CML)) were compared with 20 healthy individuals matched according to age and sex, regarding serum vascular endothelial growth factor (VEGF, a marker for angiogenesis) levels. Results: The difference between serum VEGF levels of the study group (338.4 ± 587.6 pg/mL) and the control group (69.9 ± 24.4 pg/mL) was statistically significant (p<0.05). The highest serum VEGF level (1099.7±906.8 pg/mL) was found in CML subgroup. Conclusion: Serum VEGF levels of the patients with hematological malignancies were significantly higher compared to controls. Further studies are needed to determine the exact role of VEGF in the development and progression of the hematological malignancies and therapeutic implications of this finding.
In the current study the efficacy of maternal hyperoxygenation on growth-retarded fetuses was evaluated. Thirty-six pregnant women with intrauterine growth retardation were studied. The patients were divided in oxygen-treated (n = 17) and... more
In the current study the efficacy of maternal hyperoxygenation on growth-retarded fetuses was evaluated. Thirty-six pregnant women with intrauterine growth retardation were studied. The patients were divided in oxygen-treated (n = 17) and untreated (n = 19) groups. Doppler analysis of the fetal circulation was performed on the arrival to the hospital, after 12 hours, and thereafter on alternate days until delivery. Fetal blood was sampled by cordocentesis for immediate blood gas analysis at entrance to the study and the day of delivery. Significant improvement in Doppler flow patterns in treated patients were found when compared with untreated women. The Doppler variations were associated with complementary modifications in fetal blood gas. These differences resulted in a significant modification in perinatal mortality with an incidence of 29% and 68% (p less than 0.01) in treated and untreated groups, respectively. Our data suggest a benefit of maternal hyperoxygenation in the treatment of fetal growth retardation.
Our purpose was to evaluate whether intraovarian and uterine blood flow variations are associated with clinical, ultrasonographic, and endocrine polycystic ovary syndrome findings. Thirty-two hirsute, oligomenorrheic patients and 18... more
Our purpose was to evaluate whether intraovarian and uterine blood flow variations are associated with clinical, ultrasonographic, and endocrine polycystic ovary syndrome findings. Thirty-two hirsute, oligomenorrheic patients and 18 volunteer women underwent in the early follicular phase ultrasonographic evaluation of ovarian volume, echodensity, and follicle number; transvaginal color Doppler measurement of the uterine and intraovarian vessel variations; and radioimmunologic dosage of luteinizing hormone, follicle-stimulating hormone, estradiol, progesterone, testosterone, androstenedione, and other hormonal compartments. In the patients with polycystic ovary syndrome (increased luteinizing hormone/follicle-stimulating hormone ratio, elevated androstenedione levels, high number of subcapsular follicles by ultrasonography-augmented ovarian volume and echodensity) (n = 22) we observed, at Doppler analysis, significantly elevated uterine artery pulsatility index values associated with a typical low resistance index of stromal ovary vascularization. The pulsatility index was positively correlated with the luteinizing hormone/follicle-stimulating hormone ratio, and the resistance index was negatively correlated. The elevated uterine artery resistance was correlated with androstenedione levels. Doppler analysis can be a valuable additional tool for the diagnosis of polycystic ovary syndrome.
To evaluate the hemorrheological modifications in post-term pregnant women. Pregnant women (n = 48) at > 280 days' gestation, were tested on alternate days by nonstress test; ultrasound assessment of amniotic fluid volume,... more
To evaluate the hemorrheological modifications in post-term pregnant women. Pregnant women (n = 48) at > 280 days' gestation, were tested on alternate days by nonstress test; ultrasound assessment of amniotic fluid volume, placental grading, hourly measurement of fetal urine production, and maternal fetal Doppler analysis. We further recorded maternal: plasma viscosimetry, red blood cells, hemoglobin, hematocrit, platelet count, mean platelet volume, fibrinogen, antithrombin III, creatinine, uric acid, plasma calcium, hPL, and estriol. We analyzed the last values obtained within 48 hours prior to delivery. The subjects were divided into Group I (40 wks to 40 wks+3 days; n = 16); Group II (40 wks+4 days to 41 wks; n = 16); Group III (> 41 wks; n = 16). The time-averaged maximum velocity of the fetal descending thoracic aorta was lower at Doppler analysis in Group III (29.0 +/- 3.5 cm/s) than in Group I (34.0 +/- 4.3 cm/s; p < 0.05). A decrease of the middle cerebral/umbilical pulsatility index ratio (1.75 in the Group I vs 1.52 in the Group III; p < 0.05) was shown. Furthermore, the incidence of oligohydramnios; Grannum placental grade III; plasma viscosity and coagulation parameters were significantly higher in Group III patients. The plasma viscosity resulted positively correlated with uric acid, and inversely correlated with fibrinogen, antithrombin III and platelet number values. From the present data we conclude that post-term pregnancy may mimic a mild 'fetal growth restriction'.
Doppler ultrasound is a non-invasive technique for investigating artery blood flow variations. In 39 normoovulatory patients we investigated the correlation between bladder distension and uterine/ovarian blood flow resistance. The... more
Doppler ultrasound is a non-invasive technique for investigating artery blood flow variations. In 39 normoovulatory patients we investigated the correlation between bladder distension and uterine/ovarian blood flow resistance. The patients were scanned transabdominally or transvaginally both with full and emptied bladders. Pulsatility Index was significantly higher in patients with a full bladder than in the same group after they had emptied their bladders. The present study showed that the full bladder modifying pelvic anatomy and/or increasing sympathetic tone is responsible of a high blood flow resistance in the uterine artery.
A fetal abdominal wall mass was detected by ultrasound and analyzed by duplex Doppler showing a low resistance to blood flow through its vessels. The antenatal diagnosis of cavernous hemangioma was confirmed after birth.
Thyroid autoimmunity is the most prevalent autoimmune state that affects up to 5-20% of women during the age of fertility. Prevalence of thyroid autoimmunity is significantly higher among infertile women, especially when the cause of... more
Thyroid autoimmunity is the most prevalent autoimmune state that affects up to 5-20% of women during the age of fertility. Prevalence of thyroid autoimmunity is significantly higher among infertile women, especially when the cause of infertility is endometriosis or polycystic ovary syndrome. Presence of thyroid autoimmunity does not interfere with normal embryo implantation and have been observed comparable pregnancy rates after assisted reproduction techniques in patients with or without thyroid autoimmunity. Instead, the risk of early miscarriage is substantially raised with the presence of thyroid autoimmunity, even if there was a condition of euthyroidism before pregnancy. Furthermore the controlled ovarian hyperstimulation, used as preparation for assisted reproduction techniques, can severely impair thyroid function increasing circulating estrogen levels. Systematic screening for thyroid disorders in women with a female cause of infertility is controversial but might be important to detect thyroid autoimmunity before to use assisted reproduction techniques and to follow-up these parameters in these patients after controlled ovarian hyperstimulation and during pregnancy.