Oocyte development and fertilization are largely influenced by the microenvironment of the follic... 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 implantatio... 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 horm... 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 energe... 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... 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... 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 per... 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 ... 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 ... 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 videolaparosc... 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...
The “resistant” or “insensitive” ovary syndrome is a well-known cause of hypergonadotropic amenor... 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.
Expert Review of Endocrinology & Metabolism, 2007
Ovarian folliculogenesis is regulated by a fine balance between endocrine and intraovarian factor... 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... more ... of drugs and laboratory tests [9]. Paolo Giovanni Artini1, Francesca Papini1, Maria Ruggiero1, Giulia Scaravelli2, Olga Maria Di Berardino1, Giovanna Simi1 and Vito Cela1 1Department of Reproductive Medicine and Child ...
One of the aims of assisted reproduction technologies (ART) is the recruitment of multiple follic... 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 t... 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.
Oocyte development and fertilization are largely influenced by the microenvironment of the follic... 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 implantatio... 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 horm... 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 energe... 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... 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... 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 per... 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 ... 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 ... 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 videolaparosc... 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...
The “resistant” or “insensitive” ovary syndrome is a well-known cause of hypergonadotropic amenor... 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.
Expert Review of Endocrinology & Metabolism, 2007
Ovarian folliculogenesis is regulated by a fine balance between endocrine and intraovarian factor... 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... more ... of drugs and laboratory tests [9]. Paolo Giovanni Artini1, Francesca Papini1, Maria Ruggiero1, Giulia Scaravelli2, Olga Maria Di Berardino1, Giovanna Simi1 and Vito Cela1 1Department of Reproductive Medicine and Child ...
One of the aims of assisted reproduction technologies (ART) is the recruitment of multiple follic... 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 t... 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.
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